High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2013-05-01

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

Retinal nerve fiber layer reflectance for early glaucoma diagnosis.

PubMed

Liu, Shuang; Wang, Bingqing; Yin, Biwei; Milner, Thomas E; Markey, Mia K; McKinnon, Stuart J; Rylander, Henry G

2014-01-01

Compare performance of normalized reflectance index (NRI) and retinal nerve fiber layer thickness (RNFLT) parameters determined from optical coherence tomography (OCT) images for glaucoma and glaucoma suspect diagnosis. Seventy-five eyes from 71 human subjects were studied: 33 controls, 24 glaucomatous, and 18 glaucoma-suspects. RNFLT and NRI maps were measured using 2 custom-built OCT systems and the commercial instrument RTVue. Using area under the receiver operating characteristic curve, RNFLT and NRI measured in 7 RNFL locations were analyzed to distinguish between control, glaucomatous, and glaucoma-suspect eyes. The mean NRI of the control group was significantly larger than the means of glaucomatous and glaucoma-suspect groups in most RNFL locations for all 3 OCT systems (P<0.05 for all comparisons). NRI performs significantly better than RNFLT at distinguishing between glaucoma-suspect and control eyes using RTVue OCT (P=0.008). The performances of NRI and RNFLT for classifying glaucoma-suspect versus control eyes were statistically indistinguishable for PS-OCT-EIA (P=0.101) and PS-OCT-DEC (P=0.227). The performances of NRI and RNFLT for classifying glaucomatous versus control eyes were statistically indistinguishable (PS-OCT-EIA: P=0.379; PS-OCT-DEC: P=0.338; RTVue OCT: P=0.877). NRI is a promising measure for distinguishing between glaucoma-suspect and control eyes and may indicate disease in the preperimetric stage. Results of this pilot clinical study warrant a larger study to confirm the diagnostic power of NRI for diagnosing preperimetric glaucoma.

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

PubMed Central

Howell, Gareth R.; Soto, Ileana; Zhu, Xianjun; Ryan, Margaret; Macalinao, Danilo G.; Sousa, Gregory L.; Caddle, Lura B.; MacNicoll, Katharine H.; Barbay, Jessica M.; Porciatti, Vittorio; Anderson, Michael G.; Smith, Richard S.; Clark, Abbot F.; Libby, Richard T.; John, Simon W.M.

2012-01-01

Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. PMID:22426214

A Framework for Detecting Glaucomatous Progression in the Optic Nerve Head of an Eye using Proper Orthogonal Decomposition

PubMed Central

Balasubramanian, Madhusudhanan; Žabić, Stanislav; Bowd, Christopher; Thompson, Hilary W.; Wolenski, Peter; Iyengar, S. Sitharama; Karki, Bijaya B.; Zangwill, Linda M.

2009-01-01

Glaucoma is the second leading cause of blindness worldwide. Often the optic nerve head (ONH) glaucomatous damage and ONH changes occur prior to visual field loss and are observable in vivo. Thus, digital image analysis is a promising choice for detecting the onset and/or progression of glaucoma. In this work, we present a new framework for detecting glaucomatous changes in the ONH of an eye using the method of proper orthogonal decomposition (POD). A baseline topograph subspace was constructed for each eye to describe the structure of the ONH of the eye at a reference/baseline condition using POD. Any glaucomatous changes in the ONH of the eye present during a follow-up exam were estimated by comparing the follow-up ONH topography with its baseline topograph subspace representation. Image correspondence measures of L1 and L2 norms, correlation, and image Euclidean distance (IMED) were used to quantify the ONH changes. An ONH topographic library built from the Louisiana State University Experimental Glaucoma study was used to evaluate the performance of the proposed method. The area under the receiver operating characteristic curves (AUC) were used to compare the diagnostic performance of the POD induced parameters with the parameters of Topographic Change Analysis (TCA) method. The IMED and L2 norm parameters in the POD framework provided the highest AUC of 0.94 at 10° field of imaging and 0.91 at 15° field of imaging compared to the TCA parameters with an AUC of 0.86 and 0.88 respectively. The proposed POD framework captures the instrument measurement variability and inherent structure variability and shows promise for improving our ability to detect glaucomatous change over time in glaucoma management. PMID:19369163

Sensitivity and specificity for detecting early glaucoma in eyes with high myopia from normative database of macular ganglion cell complex thickness obtained from normal non-myopic or highly myopic Asian eyes.

PubMed

Nakanishi, Hideo; Akagi, Tadamichi; Hangai, Masanori; Kimura, Yugo; Suda, Kenji; Kumagai, Kyoko Kawashima; Morooka, Satoshi; Ikeda, Hanako Ohashi; Yoshimura, Nagahisa

2015-07-01

We aimed to determine the sensitivity and specificity of the normative database of non-myopic and highly myopic eyes of the macular ganglion cell complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes. Forty-seven highly myopic eyes (axial length ≥26.0 mm) of 47 subjects were studied. The SD-OCT images were used to determine the mGCC thickness within a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of the non-myopic database were compared to that of the highly myopic database for distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The mGCC scans were classified as abnormal if at least one of the eight sectors of the significance map was < 1 % of the normative thickness. Twenty-one eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. . The average mGCC thickness was significantly thinner (80.9 ± 8.5 μm) in the early glaucoma group than in the non-glaucomatous group (91.2 ± 7.5 μm; p <1 × 10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non-myopic database was used, and the sensitivity was 92.3 % and the specificity was 90.5 % when the highly myopic database was used. The difference in the specificity was significant (p < 0.01). The significantly higher specificity of the myopic normative database for detecting early glaucoma in highly myopic eyes will lead to fewer false positive diagnoses. The database obtained from highly myopic eyes should be used when evaluating the mGCC thickness of highly myopic eyes.

Color Doppler imaging of the retrobulbar circulation in progressive glaucoma optic neuropathy.

PubMed

Magureanu, Marineta; Stanila, Adriana; Bunescu, Liviu Valentin; Armeanu, Cristina

2016-01-01

It is known that elevated intraocular pressure (IOP) is the primary risk factor for glaucoma. Recently, more and more evidences have shown that the vascular deficit also plays an important role in the pathogenesis and progressions of glaucomatous optic neuropathy. This issue is backed up by glaucomatous optic neuropathy (GON) cases drug compensated in which the progression of the disease in one or both eyes is ascertained despite a normal and relatively constant IOP. The present study evaluated the hemodynamic parameters in the retrobulbar circulation in patients with progressive glaucomatous optic neuropathy in one eye, who received compensated medication. The hemodynamic parameters (PSV, EDV, IR) were measured by using color Doppler ultrasound and progression was evaluated by a repeated automated perimetry. The obtained values were statistically analyzed and compared with those obtained for the stable eye.

Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa.

PubMed

Wang, Bo; Lucy, Katie A; Schuman, Joel S; Sigal, Ian A; Bilonick, Richard A; Lu, Chen; Liu, Jonathan; Grulkowski, Ireneusz; Nadler, Zachary; Ishikawa, Hiroshi; Kagemann, Larry; Fujimoto, James G; Wollstein, Gadi

2018-05-08

The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.

Nerve Fiber Flux Analysis Using Wide-Field Swept-Source Optical Coherence Tomography.

PubMed

Tan, Ou; Liu, Liang; Liu, Li; Huang, David

2018-02-01

To devise a method to quantify nerve fibers over their arcuate courses over an extended peripapillary area using optical coherence tomography (OCT). Participants were imaged with 8 × 8-mm volumetric OCT scans centered at the optic disc. A new quantity, nerve fiber flux (NFF), represents the cross-sectional area transected perpendicular to the nerve fibers. The peripapillary area was divided into 64 tracks with equal flux. An iterative algorithm traced the trajectory of the tracks assuming that the relative distribution of the NFF was conserved with compensation for fiber connections to ganglion cells on the macular side. Average trajectory was averaged from normal eyes and use to calculate the NFF maps for glaucomatous eyes. The NFF maps were divided into eight sectors that correspond to visual field regions. There were 24 healthy and 10 glaucomatous eyes enrolled. The algorithm converged on similar patterns of NFL tracks for all healthy eyes. In glaucomatous eyes, NFF correlated with visual field sensitivity in the arcuate sectors (Spearman ρ = 0.53-0.62). Focal nerve fiber loss in glaucomatous eyes appeared as uniform tracks of NFF defects that followed the expected arcuate fiber trajectory. Using an algorithm based on the conservation of flux, we derived nerve fiber trajectories in the peripapillary area. The NFF map is useful for the visualization of focal defects and quantification of sector nerve fiber loss from wide-area volumetric OCT scans. NFF provides a cumulative measure of volumetric loss along nerve fiber tracks and could improve the detection of focal glaucoma damage.

A generalised porous medium approach to study thermo-fluid dynamics in human eyes.

PubMed

Mauro, Alessandro; Massarotti, Nicola; Salahudeen, Mohamed; Romano, Mario R; Romano, Vito; Nithiarasu, Perumal

2018-03-22

The present work describes the application of the generalised porous medium model to study heat and fluid flow in healthy and glaucomatous eyes of different subject specimens, considering the presence of ocular cavities and porous tissues. The 2D computational model, implemented into the open-source software OpenFOAM, has been verified against benchmark data for mixed convection in domains partially filled with a porous medium. The verified model has been employed to simulate the thermo-fluid dynamic phenomena occurring in the anterior section of four patient-specific human eyes, considering the presence of anterior chamber (AC), trabecular meshwork (TM), Schlemm's canal (SC), and collector channels (CC). The computational domains of the eye are extracted from tomographic images. The dependence of TM porosity and permeability on intraocular pressure (IOP) has been analysed in detail, and the differences between healthy and glaucomatous eye conditions have been highlighted, proving that the different physiological conditions of patients have a significant influence on the thermo-fluid dynamic phenomena. The influence of different eye positions (supine and standing) on thermo-fluid dynamic variables has been also investigated: results are presented in terms of velocity, pressure, temperature, friction coefficient and local Nusselt number. The results clearly indicate that porosity and permeability of TM are two important parameters that affect eye pressure distribution. Graphical abstract Velocity contours and vectors for healthy eyes (top) and glaucomatous eyes (bottom) for standing position.

Progression of Patterns (POP): A Machine Classifier Algorithm to Identify Glaucoma Progression in Visual Fields

PubMed Central

Goldbaum, Michael H.; Lee, Intae; Jang, Giljin; Balasubramanian, Madhusudhanan; Sample, Pamela A.; Weinreb, Robert N.; Liebmann, Jeffrey M.; Girkin, Christopher A.; Anderson, Douglas R.; Zangwill, Linda M.; Fredette, Marie-Josee; Jung, Tzyy-Ping; Medeiros, Felipe A.; Bowd, Christopher

2012-01-01

Purpose. We evaluated Progression of Patterns (POP) for its ability to identify progression of glaucomatous visual field (VF) defects. Methods. POP uses variational Bayesian independent component mixture model (VIM), a machine learning classifier (MLC) developed previously. VIM separated Swedish Interactive Thresholding Algorithm (SITA) VFs from a set of 2,085 normal and glaucomatous eyes into nine axes (VF patterns): seven glaucomatous. Stable glaucoma was simulated in a second set of 55 patient eyes with five VFs each, collected within four weeks. A third set of 628 eyes with 4,186 VFs (mean ± SD of 6.7 ± 1.7 VFs over 4.0 ± 1.4 years) was tested for progression. Tested eyes were placed into suspect and glaucoma categories at baseline, based on VFs and disk stereoscopic photographs; a subset of eyes had stereophotographic evidence of progressive glaucomatous optic neuropathy (PGON). Each sequence of fields was projected along seven VIM glaucoma axes. Linear regression (LR) slopes generated from projections onto each axis yielded a degree of confidence (DOC) that there was progression. At 95% specificity, progression cutoffs were established for POP, visual field index (VFI), and mean deviation (MD). Guided progression analysis (GPA) was also compared. Results. POP identified a statistically similar number of eyes (P > 0.05) as progressing compared with VFI, MD, and GPA in suspects (3.8%, 2.7%, 5.6%, and 2.9%, respectively), and more eyes than GPA (P = 0.01) in glaucoma (16.0%, 15.3%, 12.0%, and 7.3%, respectively), and more eyes than GPA (P = 0.05) in PGON eyes (26.3%, 23.7%, 27.6%, and 14.5%, respectively). Conclusions. POP, with its display of DOC of progression and its identification of progressing VF defect pattern, adds to the information available to the clinician for detecting VF progression. PMID:22786913

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

PubMed

Naka, Maiko; Kanamori, Akiyasu; Tatsumi, Yasuko; Fujioka, Miyuki; Nagai-Kusuhara, Azusa; Nakamura, Makoto; Negi, Akira

2009-01-01

To evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD> or =-6 dB; moderate, -12 dB< or =MD<-6 dB; advanced, MD<-12 dB). Among structure-function relationships in all subjects, the highest correlation determination (R) was MD with RNFLT (=0.298). CIGTS score showed better R than MD or AGIS score with rim area, but these values were not higher than any R with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.

Retinoschisis and neurosensory detachment in advanced focal glaucoma.

PubMed

Arranz-Márquez, E; Jarrín Hernández, E; Pastor, A; García Gil de Bernabé, J

2017-10-01

A 71-year-old woman with normotensive primary open-angle glaucoma presented with an asymptomatic temporal peripapillary retinoschisis, associated with serous retinal detachment in the eye with the more advanced glaucoma. It was located at the inferior pole of the optic disc, in the proximity of a glaucomatous focal disc defect. Although congenital optic pits are strongly related with juxta-papillary retinoschisis, retinoschisis can also arise from acquired defects in the proximity of glaucomatous optic discs. As symptoms depend on the extent of the retinoschisis, the prevalence of this complication could be greater than that reported in glaucomatous eyes. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging.

PubMed

Wang, Ke; Johnstone, Murray A; Xin, Chen; Song, Shaozhen; Padilla, Steven; Vranka, Janice A; Acott, Ted S; Zhou, Kai; Schwaner, Stephen A; Wang, Ruikang K; Sulchek, Todd; Ethier, C Ross

2017-09-01

The purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements. Postmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm's canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward. The elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018). TM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy.

PubMed

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-12-01

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

PubMed Central

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-01-01

Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes. PMID:23060026

Neurophthalmological conditions mimicking glaucomatous optic neuropathy: analysis of the most common causes of misdiagnosis.

PubMed

Dias, Diego Torres; Ushida, Michele; Battistella, Roberto; Dorairaj, Syril; Prata, Tiago Santos

2017-01-10

To analyze the most common neurophthalmological conditions that may mimic glaucomatous optic neuropathy and to determine which most often lead to misdiagnosis when evaluated by a glaucoma specialist. We reviewed the charts of consecutive patients with optic neuropathies caused by neurophthalmological conditions screened in a single Eye Clinic within a period of 24 months. Within these enrolled patients, we selected the eyes whose fundoscopic appearance could resemble glaucoma based in pre-defined criteria (vertical cup-to-disc ratio ≥0.6, asymmetry of the cup-to-disc ratio ≥0.2 between eyes, presence of localized retinal nerve fiber layer and/or neuroretinal rim defects, and disc haemorrhages). Then, color fundus photographs and Humphrey Visual Field tests (HVF) of these eyes were mixed with tests from 21 consecutive glaucomatous patients (42 eyes with normal tension glaucoma). These images were mixed randomly and a masked glaucoma specialist was asked to distinguish if each set of exams was from a patient with glaucoma or with a neurophthalmologic condition. Among the 101 eyes (68 patients) enrolled with neurophthalmological diseases, 16 (15.8%) were classified as conditions that could mimic glaucoma. The most common diagnoses were ischemic optic neuropathy (25%), compressive optic neuropathy (18.7%) and hereditary optic neuropathy (18.7%). Based on the analysis of fundus photographs and HVF tests, 25% of these were misdiagnosed as glaucoma (two ischemic optic neuropathies and two congenital optic disc anomalies). Conversely, 11.9% of the glaucomatous neuropathies were misdiagnosed as neurophthalmological disorders. Overall, the glaucoma specialist correctly diagnosed 84.5% of the eyes. Some neurophthalmological disorders can mimic glaucoma. In our study, isquemic and compressive optic neuropathies were the ones that most often did so. Almost one quarter of the eyes were misdiagnosed when evaluated by a glaucoma specialist, which can lead to inadequate management and influence the prognosis of these patients.

Ocular characteristics associated with the location of focal lamina cribrosa defects in open-angle glaucoma patients.

PubMed

Park, H-Yl; Hwang, Y S; Park, C K

2017-04-01

PurposeTo investigate the clinical characteristics according to the location of focal lamina cribrosa (LC) defects and its associated ocular features.Patients and methodsA total of 139 open-angle glaucoma patients underwent Spectralis optical coherence tomography (OCT) with enhanced depth imaging. Alterations in the contour of the LC were investigated to find focal LC defects. The location of the visible LC defect from the neural canal wall (far-peripheral and mid-peripheral) and clock-hour position (superotemporal, temporal and inferotemporal) were classified. Disc ovality ratio and disc-foveal angle were measured from disc and retinal nerve fiber layer (RNFL) photographs. The disc tilt degree was measured using a Heidelberg Retina Tomograph (HRT) III system. The en face OCT image of the disc scans was registered to the disc and RNFL photographs, to determine whether the focal LC defects corresponded spatially to the glaucomatous damage location.ResultsEyes with far-peripheral LC defects were significantly myopic and had a higher disc ovality ratio. The disc tilt degree obtained by HRT revealed significant temporal disc tilt in eyes with temporal LC defects (P<0.001). Eyes with inferotemporal LC defects had a significantly larger disc-foveal angle (P=0.027). The inferotemporal LC defects corresponded to the location of glaucomatous damage in 81.6%; however, only 46.2% of eyes with a superotemporal LC defect and 3.2% of eyes with a temporal LC defect corresponded spatially with the glaucomatous damage location.ConclusionsThe clinical characteristics and association with glaucomatous damage location were different according to the location of focal LC defect.

Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa

NASA Astrophysics Data System (ADS)

Vilupuru, Abhiram S.; Rangaswamy, Nalini V.; Frishman, Laura J.; Smith, Earl L., III; Harwerth, Ronald S.; Roorda, Austin

2007-05-01

The lamina cribrosa has been postulated from in vitro studies as an early site of damage in glaucoma. Prior in vivo measures of laminar morphology have been confounded by ocular aberrations. In this study the lamina cribrosa was imaged after correcting for ocular aberrations using the adaptive optics scanning laser ophthalmoscope (AOSLO) in normal and glaucomatous eyes of rhesus monkeys. All measured laminar morphological parameters showed increased magnitudes in glaucomatous eyes relative to fellow control eyes, indicating altered structure. The AOSLO provides high-quality images of the lamina cribrosa and may have potential as a tool for early identification of glaucoma.

Comparison of RNFL thickness and RPE-normalized RNFL attenuation coefficient for glaucoma diagnosis

NASA Astrophysics Data System (ADS)

Vermeer, K. A.; van der Schoot, J.; Lemij, H. G.; de Boer, J. F.

2013-03-01

Recently, a method to determine the retinal nerve fiber layer (RNFL) attenuation coefficient, based on normalization on the retinal pigment epithelium, was introduced. In contrast to conventional RNFL thickness measures, this novel measure represents a scattering property of the RNFL tissue. In this paper, we compare the RNFL thickness and the RNFL attenuation coefficient on 10 normal and 8 glaucomatous eyes by analyzing the correlation coefficient and the receiver operator curves (ROCs). The thickness and attenuation coefficient showed moderate correlation (r=0.82). Smaller correlation coefficients were found within normal (r=0.55) and glaucomatous (r=0.48) eyes. The full separation between normal and glaucomatous eyes based on the RNFL attenuation coefficient yielded an area under the ROC (AROC) of 1.0. The AROC for the RNFL thickness was 0.9875. No statistically significant difference between the two measures was found by comparing the AROC. RNFL attenuation coefficients may thus replace current RNFL thickness measurements or be combined with it to improve glaucoma diagnosis.

Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork

PubMed Central

Last, Julie A.; Pan, Tingrui; Ding, Yuzhe; Reilly, Christopher M.; Keller, Kate; Acott, Ted S.; Fautsch, Michael P.; Murphy, Christopher J.; Russell, Paul

2011-01-01

Purpose. Elevated intraocular pressure (IOP) is a risk factor for glaucoma. The principal outflow pathway for aqueous humor in the human eye is through the trabecular meshwork (HTM) and Schlemm's canal (SC). The junction between the HTM and SC is thought to have a significant role in the regulation of IOP. A possible mechanism for the increased resistance to flow in glaucomatous eyes is an increase in stiffness (increased elastic modulus) of the HTM. In this study, the stiffness of the HTM in normal and glaucomatous tissue was compared, and a mathematical model was developed to predict the impact of changes in stiffness of the juxtacanalicular layer of HTM on flow dynamics through this region. Methods. Atomic force microscopy (AFM) was used to measure the elastic modulus of normal and glaucomatous HTM. According to these results, a model was developed that simulated the juxtacanalicular layer of the HTM as a flexible membrane with embedded pores. Results. The mean elastic modulus increased substantially in the glaucomatous HTM (mean = 80.8 kPa) compared with that in the normal HTM (mean = 4.0 kPa). Regional variation was identified across the glaucomatous HTM, possibly corresponding to the disease state. Mathematical modeling suggested an increased flow resistance with increasing HTM modulus. Conclusions. The data indicate that the stiffness of glaucomatous HTM is significantly increased compared with that of normal HTM. Modeling exercises support substantial impairment in outflow facility with increased HTM stiffness. Alterations in the biophysical attributes of the HTM may participate directly in the onset and progression of glaucoma. PMID:21220561

Sensitivity and specificity of scanning laser polarimetry using the GDx.

PubMed

Munkwitz, S; Funk, J; Loeffler, K U; Harbarth, U; Kremmer, S

2004-09-01

To determine the sensitivity and the specificity of the GDx in the detection of (1) advanced glaucoma, (2) early glaucoma, and (3) nerve fibre bundle defects (NFBD). Group A comprised 20 eyes with reproducible glaucomatous visual field defects confirmed by octopus perimetry, group B consisted of 10 eyes with normal visual fields but either glaucomatous NFBD or deterioration of the disc over time clearly visible upon flicker comparison, and group C included 16 eyes with glaucomatous or non-glaucomatous NFBD clearly visible on red free photographs. Forty four eyes of 22 healthy volunteers served as controls. The GDx printouts of all subjects were evaluated by three independent observers in a masked fashion and without the clinical picture of the optic disc. Two of the three observers (SK, UH) were GDx experts, one (KUL) was an untrained GDx user. Among the GDx experts, sensitivity/specificity was 100%/100% (SK) and 90%/100% (UH) in detecting advanced glaucoma, and 100%/100% (SK) and 90%/100% (UH) in detecting early glaucoma. The sensitivity in detecting NFBD was only 37.5% (SK and UH). For the untrained GDx user the corresponding values were 50%/100% (group A), 20%/100% (group B), and 12.5%/91% (group C). Detection of (early) glaucoma damage by the GDx, evaluated by trained experts, can be extremely high. To optimise its benefit in clinical routine training in interpreting GDx printouts is highly recommended. Detection of localised NFBD is crucial, even for experts.

Automated 3D segmentation of intraretinal layers from optic nerve head optical coherence tomography images

NASA Astrophysics Data System (ADS)

Antony, Bhavna J.; Abràmoff, Michael D.; Lee, Kyungmoo; Sonkova, Pavlina; Gupta, Priya; Kwon, Young; Niemeijer, Meindert; Hu, Zhihong; Garvin, Mona K.

2010-03-01

Optical coherence tomography (OCT), being a noninvasive imaging modality, has begun to find vast use in the diagnosis and management of ocular diseases such as glaucoma, where the retinal nerve fiber layer (RNFL) has been known to thin. Furthermore, the recent availability of the considerably larger volumetric data with spectral-domain OCT has increased the need for new processing techniques. In this paper, we present an automated 3-D graph-theoretic approach for the segmentation of 7 surfaces (6 layers) of the retina from 3-D spectral-domain OCT images centered on the optic nerve head (ONH). The multiple surfaces are detected simultaneously through the computation of a minimum-cost closed set in a vertex-weighted graph constructed using edge/regional information, and subject to a priori determined varying surface interaction and smoothness constraints. The method also addresses the challenges posed by presence of the large blood vessels and the optic disc. The algorithm was compared to the average manual tracings of two observers on a total of 15 volumetric scans, and the border positioning error was found to be 7.25 +/- 1.08 μm and 8.94 +/- 3.76 μm for the normal and glaucomatous eyes, respectively. The RNFL thickness was also computed for 26 normal and 70 glaucomatous scans where the glaucomatous eyes showed a significant thinning (p < 0.01, mean thickness 73.7 +/- 32.7 μm in normal eyes versus 60.4 +/- 25.2 μm in glaucomatous eyes).

Ability of Cirrus™ HD-OCT Optic Nerve Head Parameters to Discriminate Normal from Glaucomatous Eyes

PubMed Central

Mwanza, Jean-Claude; Oakley, Jonathan D; Budenz, Donald L; Anderson, Douglas R

2010-01-01

Purpose To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus™ HD-OCT to discriminate between normal and glaucomatous eyes and to compare them to the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus™ HD-OCT. Design Evaluation of diagnostic test or technology. Participants Seventy-three subjects with glaucoma and one hundred and forty-six age-matched normal subjects. Methods Peripapillary ONH parameters and RNFL thickness were measured in one randomly selected eye of each participant within a 200×200 pixel A-scan acquired with Cirrus™ HD-OCT centered on the ONH. Main Outcome Measures ONH topographic parameters, peripapillary RNFL thickness, and the area under receiver operating characteristic curves (AUCs). Results For distinguishing normal from glaucomatous eyes, regardless of disease stage, the six best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (RA, 0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951) and average RNFL thickness (0.950). The AUC for distinguishing between normal and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), RA (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893) and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (p > 0.05). Conclusions Cirrus™ HD-OCT ONH parameters are able to discriminate between eyes that are normal from those with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus™ OCT, to distinguish between normal and glaucomatous eyes. PMID:20920824

Effect of spectrum bias on the diagnostic accuracy of spectral-domain optical coherence tomography in glaucoma.

PubMed

Rao, Harsha L; Kumbar, Tukaram; Addepalli, Uday K; Bharti, Neha; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2012-02-29

To evaluate the influence of a control group on the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) in early glaucoma. In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no findings suspicious for glaucoma (control cohort 1); 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal but with physiological variations in their optic nerves (control cohort 2); and 65 eyes of 46 early-glaucoma patients (cases) underwent imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) by SD-OCT. Areas under the receiver operating characteristic curves (AUC) of ONH parameters discriminating glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (P < 0.001) than those discriminating glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters discriminating glaucomatous eyes from normal eyes of control cohorts 2 and 1 were comparable. Although the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume in control cohort 2 (0.684 and 0.671. respectively) were significantly less (P < 0.05) than in control cohort 1 (0.881 and 0.841, respectively). The effectiveness of most SD-OCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant control group with suspicious-looking optic nerves compared with that against a control group consisting of normal subjects with no findings suspicious for glaucoma.

Pattern-reversal electroretinograms in unilateral glaucoma.

PubMed

Wanger, P; Persson, H E

1983-06-01

Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded from 11 patients with unilateral glaucoma. All glaucomatous eyes had reduced amplitudes both compared to the opposite eye in the same patient and to reference values. In 10 of the 11 cases this reduction was below the level of normal variation. The difference in pattern-reversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant. No differences were observed in flash ERGs or OPs. The histopathologic correlate to the visual field defects in glaucoma is retinal ganglion cell degeneration. The present electrophysiologic findings support the view, based on results from animal experiments, that the pattern-reversal ERG reflects ganglion cell activity.

Pulsar perimetry in the diagnosis of early glaucoma.

PubMed

Zeppieri, Marco; Brusini, Paolo; Parisi, Lucia; Johnson, Chris A; Sampaolesi, Roberto; Salvetat, Maria Letizia

2010-01-01

To assess the ability of Pulsar perimetry (Pulsar) in detecting early glaucomatous visual field (VF) damage in comparison with Frequency Doubling Technology (FDT), Scanning Laser Polarimetry (SLP, GDx VCC), and Heidelberg Retina Tomography (HRT). Prospective observational cross-sectional case study. This multicenter study included: 87 ocular hypertensives (OHT); 67 glaucomatous optic neuropathy (GON) patients; 75 primary open-angle glaucoma (POAG) patients; and 90 normals. All patients underwent standard automated perimetry (SAP) HFA 30-2, Pulsar T30W, FDT N-30, HRT II, and GDx VCC. Area under Receiver Operating Characteristic Curves (AROCs) for discriminating between healthy and glaucomatous eyes and agreement among instruments were determined. The best parameters for Pulsar, FDT, HRT, and GDx were, respectively: loss variance square root; no. of areas with P< 5%; Cup-Shape-Measure; and Nerve Fiber Indicator (NFI). In detecting POAG eyes, Pulsar (AROC, 0.90) appeared comparable with FDT (0.89) and significantly better than HRT (0.82) and GDx (0.79). For GON, Pulsar ability (0.74) was higher than GDx (0.69) and lower than FDT (0.80) and HRT (0.83). The agreement among instruments ranged from 0.12 to 0.56. Pulsar test duration was significantly shorter than SAP and FDT (P< .001). Pulsar T30W test is a rapid and easy perimetric method, showing higher sensitivity than SAP in detecting early glaucomatous VF loss. Its diagnostic ability is good for detecting early perimetric POAG eyes and fair for GON eyes. Pulsar performance was comparable with FDT, HRT, and GDx, even if the agreement between instruments was poor to fair. Copyright 2010 Elsevier Inc. All rights reserved.

Bilateral Glaucomatous Optic Neuropathy Caused by Eye Rubbing.

PubMed

Savastano, Alfonso; Savastano, Maria Cristina; Carlomusto, Laura; Savastano, Silvio

2015-01-01

In this report, we describe a particular condition of a 52-year-old man who showed advanced bilateral glaucomatous-like optic disc damage, even though the intraocular pressure resulted normal during all examinations performed. Visual field test, steady-state pattern electroretinogram, retinal nerve fiber layer and retinal tomographic evaluations were performed to evaluate the optic disc damage. Over a 4-year observational period, his visual acuity decreased to 12/20 in the right eye and counting fingers in the left eye. Visual fields were severely compromised, and intraocular pressure values were not superior to 14 mm Hg during routine examinations. An accurate anamnesis and the suspicion of this disease represent a crucial aspect to establish the correct diagnosis. In fact, our patient strongly rubbed his eyes for more than 10 h per day. Recurrent and continuous eye rubbing can induce progressive optic neuropathy, causing severe visual field damage similar to the pathology of advanced glaucoma.

Comparison of matrix frequency-doubling technology perimetry and standard automated perimetry in monitoring the development of visual field defects for glaucoma suspect eyes.

PubMed

Hu, Rongrong; Wang, Chenkun; Racette, Lyne

2017-01-01

Perimetry is indispensable for the clinical management of glaucoma suspects. Our goal is to compare the performance of standard automated perimetry (SAP) and Matrix frequency-doubling technology (FDT) perimetry in monitoring the development of visual field (VF) defects in glaucoma suspect eyes. Longitudinal data of paired SAP and FDT from 221 eyes of 155 glaucoma suspects enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. All eyes had glaucomatous optic neuropathy or ocular hypertension, but normal SAP and FDT results at baseline. The development of glaucomatous VF defects was defined as the presence of a cluster of ≥ 3 (less conservative) or ≥ 4 (more conservative) locations confirmed on ≥ 2 additional consecutive tests. Risk factors for the development of VF defects were analyzed by COX proportional hazard models. After conversion into common logarithmic units, the rates of change of global VF indices were fitted with linear mixed models. FDT detected more eyes that developed VF defects than SAP using the less conservative criterion, and no significant difference was observed using the more conservative criterion. For those eyes detected by both SAP and FDT, FDT detected the development of VF defects either earlier than SAP or simultaneously in most cases. Baseline structural measurements were not significantly associated with an increased risk for the development of glaucomatous VF defects on either SAP or FDT. Older age was significantly associated with the development of VF defects on FDT but not on SAP. Both SAP and FDT detected a progressing worsening trend of pattern standard deviation over time with a similar rate of change between these test types. Matrix FDT would be useful to monitor the onset of VF defects in glaucoma suspects and may outperform SAP in the early stage of glaucomatous VF damage.

Glaucoma Diagnostic Ability of the Optical Coherence Tomography Angiography Vessel Density Parameters.

PubMed

Chung, Jae Keun; Hwang, Young Hoon; Wi, Jae Min; Kim, Mijin; Jung, Jong Jin

2017-11-01

To investigate the glaucoma diagnostic abilities of vessel density parameters as determined by optical coherence tomography (OCT) angiography in different stages of glaucoma. A total of 113 healthy eyes and 140 glaucomatous eyes were enrolled. Diagnostic abilities of the OCT vessel density parameters in the optic nerve head (ONH), peripapillary, and macular regions were evaluated by calculating the area under the receiver operation characteristic curves (AUCs). AUCs of the peripapillary vessel density parameters and circumpapillary retinal nerve fiber layer (RNFL) thickness were compared. OCT angiography vessel densities in the ONH, peripapillary, and macular regions in the glaucomatous eyes were significantly lower than those in the healthy eyes (P < 0.05). Among the vessel density parameters, the average peripapillary vessel density showed higher AUC than the ONH and macular region (AUCs: 0.807, 0.566, and 0.651, respectively) for glaucoma detection. The peripapillary vessel density parameters showed similar AUCs with the corresponding sectoral RNFL thickness (P > 0.05). However, in the early stage of glaucoma, the AUCs of the inferotemporal and temporal peripapillary vessel densities were significantly lower than that of the RNFL thickness (P < 0.05). The glaucomatous eyes showed decreased vessel density as determined by OCT angiography. Although the peripapillary vessel density parameters showed similar glaucoma diagnostic ability with circumpapillary RNFL thickness, in the early stage, the vessel density parameters showed limited clinical value.

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes.

PubMed

Ara, Mirian; Ferreras, Antonio; Pajarin, Ana B; Calvo, Pilar; Figus, Michele; Frezzotti, Paolo

2015-01-01

To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression.

The retinal nerve fibre layer thickness in glaucomatous hydrophthalmic eyes assessed by scanning laser polarimetry with variable corneal compensation in comparison with age-matched healthy children.

PubMed

Hložánek, Martin; Ošmera, Jakub; Ležatková, Pavlína; Sedláčková, Petra; Filouš, Aleš

2012-12-01

To compare the thickness of the retinal nerve fibre layer (RNFL) in hydrophthalmic glaucomatous eyes in children with age-matched healthy controls using scanning laser polarimetry with variable corneal compensation (GDxVCC). Twenty hydrophthalmic eyes of 20 patients with the mean age of 10.64 ± 3.02 years being treated for congenital or infantile glaucoma were included in the analysis. Evaluation of RNFL thickness measured by GDxVCC in standard Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was performed. The results were compared to TSNIT values of an age-matched control group of 120 healthy children published recently as referential values. The correlation between horizontal corneal diameter and RNFL thickness in hydrophthalmic eyes was also investigated. The mean ± SD values in TSNIT Average, Superior Average, Inferior Average and TSNIT SD in hydrophthalmic eyes were 52.3 ± 11.4, 59.7 ± 17.1, 62.0 ± 15.6 and 20.0 ± 7.8 μm, respectively. All these values were significantly lower compared to referential TSNIT parameters of age-matched healthy eyes (p = 0.021, p = 0.001, p = 0.003 and p = 0.018, respectively). A substantial number of hydrophthalmic eyes laid below the level of 5% probability of normality in respective TSNIT parameters: 30% of the eyes in TSNIT average, 50% of the eyes in superior average, 30% of the eyes in inferior average and 45% of the eyes in TSNIT SD. No significant correlation between enlarged corneal diameter and RNFL thickness was found. The mean values of all standard TSNIT parameters assessed using GDxVCC in hydrophthalmic glaucomatous eyes in children were significantly lower in comparison with referential values of healthy age-matched children. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Steady-state pattern electroretinogram and short-duration transient visual evoked potentials in glaucomatous and healthy eyes.

PubMed

Amarasekera, Dilru C; Resende, Arthur F; Waisbourd, Michael; Puri, Sanjeev; Moster, Marlene R; Hark, Lisa A; Katz, L Jay; Fudemberg, Scott J; Mantravadi, Anand V

2018-01-01

This study evaluates two rapid electrophysiological glaucoma diagnostic tests that may add a functional perspective to glaucoma diagnosis. This study aimed to determine the ability of two office-based electrophysiological diagnostic tests, steady-state pattern electroretinogram and short-duration transient visual evoked potentials, to discern between glaucomatous and healthy eyes. This is a cross-sectional study in a hospital setting. Forty-one patients with glaucoma and 41 healthy volunteers participated in the study. Steady-state pattern electroretinogram and short-duration transient visual evoked potential testing was conducted in glaucomatous and healthy eyes. A 64-bar-size stimulus with both a low-contrast and high-contrast setting was used to compare steady-state pattern electroretinogram parameters in both groups. A low-contrast and high-contrast checkerboard stimulus was used to measure short-duration transient visual evoked potential parameters in both groups. Steady-state pattern electroretinogram parameters compared were MagnitudeD, MagnitudeD/Magnitude ratio, and the signal-to-noise ratio. Short-duration transient visual evoked potential parameters compared were amplitude and latency. MagnitudeD was significantly lower in glaucoma patients when using a low-contrast (P = 0.001) and high-contrast (P < 0.001) 64-bar-size steady-state pattern electroretinogram stimulus. MagnitudeD/Magnitude ratio and SNR were significantly lower in the glaucoma group when using a high-contrast 64-bar-size stimulus (P < 0.001 and P = 0.010, respectively). Short-duration transient visual evoked potential amplitude and latency were not significantly different between the two groups. Steady-state pattern electroretinogram was effectively able to discern between glaucomatous and healthy eyes. Steady-state pattern electroretinogram may thus have a role as a clinically useful electrophysiological diagnostic tool. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Patterns of Progressive Ganglion Cell-Inner Plexiform Layer Thinning in Glaucoma Detected by OCT.

PubMed

Shin, Joong Won; Sung, Kyung Rim; Park, Sun-Won

2018-04-25

To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Longitudinal, retrospective, observational study. Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Spatial characteristics and patterns of progressive GCIPL thinning. Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

EFFECTS OF TOPICAL CORTICOSTEROID ADMINISTRATION ON INTRAOCULAR PRESSURE IN NORMAL AND GLAUCOMATOUS CATS

PubMed Central

Gosling, Allyson A; Kiland, Julie A; Rutkowski, Lauren E; Hoefs, Adam; Ellinwood, N Matthew; McLellan, Gillian J

2016-01-01

Objective to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG). Animals studied 5 normal and 11 FCG cats were studied in 2 cohorts. Procedures IOP was measured by a single, masked observer, once daily 3–5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; Balanced salt solution (BSS) applied to the contralateral eye, served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively. Results 8/11 FCG cats responded to topical CCS after 1–5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). 2/5 normal cats responded to topical CCS with appreciable but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg). Conclusions our data indicate that the incidence of steroid induced IOP elevation in cats is lower than previously published feline studies suggest. Cats with pre-existing compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats. PMID:26876736

Retinal Nerve Fiber Layer and Peripapillary Choroidal Thicknesses in Non-Glaucomatous Unilateral Optic Atrophy Compared with Unilateral Advanced Pseudoexfoliative Glaucoma.

PubMed

Kucukevcilioglu, Murat; Ayyildiz, Onder; Aykas, Seckin; Gokce, Gokcen; Koylu, Mehmet Talay; Ozgonul, Cem; Ozge, Gokhan; Mumcuoglu, Tarkan; Yumusak, Erhan

2017-02-01

To investigate retinal nerve fiber layer thickness (RNFL-T) and peripapillary choroidal thickness (PC-T) in non-glaucomatous optic atrophy (OA) patients in comparison with unaffected and control eyes, furthermore, to compare thickness profiles with unilateral pseudoexfoliative advanced glaucoma. Thirty-three eyes with OA (Group A), 33 unaffected fellow eyes (Group B), 25 right eyes of 25 control subjects (Group C), and 15 eyes with advanced glaucoma (Group D) were enrolled. RNFL-T was measured in six regions by spectral-domain optical coherence tomography. Enhanced depth imaging optical coherence tomography was obtained to evaluate PC-T in corresponding regions. RNFL-T was significantly lower in Group A than in Groups B and C globally and at all peripapillary regions (all p < 0.001). P-CT in Group A was significantly lower globally (p = 0.03) and in three regions (temporal, p = 0.001; temporal-superior, p = 0.01; and nasal-inferior, p = 0.037) versus Group C. However, it was significantly thinner than in Group B in all regions (temporal, p = 0.02; temporal-superior, p = 0.013; nasal-superior, p = 0.044; nasal, p = 0.02; nasal-inferior, p < 0.001; and temporal-inferior, p < 0.001) and globally (p < 0.001). In Group A RNFL-T (thicker superiorly and inferiorly; thinner temporally and nasally) and PC-T (superior > temporal > nasal > inferior) profiles were almost identical to that in unaffected fellow eyes and control eyes. However, Group D showed different patterns with less regional differences in RNFL-T, and the greatest value of PC-T in nasal quadrant. Besides retinal nerve fiber layer thinning, non-glaucomatous OA is associated with choroidal thinning. The RNFL-T and PC-T profiles in advanced glaucoma eyes differed from the common patterns seen among OA eyes, unaffected fellow eyes, and control eyes.

Symptoms related to glaucomatous visual field abnormalities among male Japanese workers in a population-based setting.

PubMed

Tatemichi, Masayuki; Nakano, Tadashi; Hayashi, Takeshi; Tanaka, Katsutoshi; Hiro, Hisanori; Miyamoto, Toshiaki; Aratake, Miho; Nishinoue, Norihide; Yamazaki, Akira; Nakadate, Toshio; Sugita, Minoru

2012-09-01

To identify symptoms potentially related to glaucomatous visual field abnormalities (VFAs) in a population-based setting, and to assess the applicability of using these symptoms to identify persons at risk of developing glaucoma. In this study, 10,214 Japanese male general workers (mean age, 45.3±8.8 years) filled out a self-administered questionnaire and underwent frequency doubling technology (FDT) perimetry testing. The questionnaire inquired about whether the participant was suffering from any of nine symptoms, with scores for each response graded on a four-item Likert scale: 0 (none), 1 (rarely), 2 (sometimes), and 3 (always). Results from the questionnaire were compared among three groups: participants without any VFAs (9767), participants with VFAs as determined by the FDT test (FDT-VFA; 447), and 227 participants (of the 447 FDT-VFA participants) with glaucomatous VFAs who were newly diagnosed by ophthalmologic examinations. The mean summed scores for the total items were significantly (p<0.01) higher in FDT- and glaucomatous VFA groups than in normal subjects. In particular, responses citing the symptoms 'feeling of something in the front of the eye' and 'feeling of hardness to see in dark places' were significantly (p<0.05) more frequent in subjects with FDT- and glaucomatous VFAs than among normal participants. However, the respective areas under the receiver operating characteristic curve of summed scores for the nine total items and for the two items which showed significant differences for the glaucoma groups were 0.57 (95% confidence interval=0.53-0.60) and 0.58 (95% confidence interval=0.54-0.61). Although the symptoms 'feeling of hardness to see in dark places' and 'feeling of something in the front of the eye' could be associated with glaucomatous VFA in a population-based setting, inquiring about symptoms is of little aid in identifying subjects with glaucomatous VFA as a strategy for public health. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Acquired color vision and visual field defects in patients with ocular hypertension and early glaucoma.

PubMed

Papaconstantinou, Dimitris; Georgalas, Ilias; Kalantzis, George; Karmiris, Efthimios; Koutsandrea, Chrysanthi; Diagourtas, Andreas; Ladas, Ioannis; Georgopoulos, Gerasimos

2009-01-01

To study acquired color vision and visual field defects in patients with ocular hypertension (OH) and early glaucoma. In a prospective study we evaluated 99 eyes of 56 patients with OH without visual field defects and no hereditary color deficiencies, followed up for 4 to 6 years (mean = 4.7 +/- 0.6 years). Color vision defects were studied using a special computer program for Farnsworth-Munsell 100 hue test and visual field tests were performed with Humphrey analyzer using program 30-2. Both tests were repeated every six months. In fifty-six eyes, glaucomatous defects were observed during the follow-up period. There was a statistically significant difference in total error score (TES) between eyes that eventually developed glaucoma (157.89 +/- 31.79) and OH eyes (75.51 +/- 31.57) at the first examination (t value 12.816, p < 0.001). At the same time visual field indices were within normal limits in both groups. In the glaucomatous eyes the earliest statistical significant change in TES was identified at the first year of follow-up and was -20.62 +/- 2.75 (t value 9.08, p < 0.001) while in OH eyes was -2.11 +/- 4.36 (t value 1.1, p = 0.276). Pearson's coefficient was high in all examinations and showed a direct correlation between TES and mean deviation and corrected pattern standard deviation in both groups. Quantitative analysis of color vision defects provides the possibility of follow-up and can prove a useful means for detecting early glaucomatous changes in patients with normal visual fields.

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Ara, Mirian; Pajarin, Ana B.

2015-01-01

Objective. To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. Methods. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. Results. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. Conclusions. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression. PMID:26185762

Glaucomatous patterns in Frequency Doubling Technology (FDT) perimetry data identified by unsupervised machine learning classifiers.

PubMed

Bowd, Christopher; Weinreb, Robert N; Balasubramanian, Madhusudhanan; Lee, Intae; Jang, Giljin; Yousefi, Siamak; Zangwill, Linda M; Medeiros, Felipe A; Girkin, Christopher A; Liebmann, Jeffrey M; Goldbaum, Michael H

2014-01-01

The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters. FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age. FDT mean deviation was -1.00 dB (S.D. = 2.80 dB) and -5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G1 and G2 combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G1 and G2 the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity. VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.

Glaucoma evolution in patients with diabetes.

PubMed

Apreutesei, Nicoleta Anton; Chiselita, D; Motas, O I

2014-01-01

Glaucoma and diabetes are two chronic diseases with a long suspected pathogenic relationship. Screening for glaucoma in patients with diabetes. A retrospective study on 92 eyes from 46 patients with primitive open angle glaucoma (POAG) (normal and hypertensive) and intraocular hypertension (OHT) receiving medication and/or surgery associated with diabetes mellitus (DM) (type I, type II, mixed) is presented. Participants were divided into two groups as following: 16 eyes with glaucoma and diabetic retinopathy changes (group 1) and 76 eyes with glaucoma and without diabetic retinopathy changes (group 2). The following parameters were analysed: ocular pressure (Goldmann aplanotonometry), perimeter development (computerized perimetry) and fundus condition (absence, presence or progression of diabetic retinopathy). In patients with glaucoma and diabetic retinopathy (8 patients) we found a mean difference between treated intraocular pressure (IOP) and IOP last untreated control of 4.95 mmHg; a depreciation of the MD by 4.18 dB and an average number of glaucoma medications used of 0.889 +/- 1.054. Predominant changes in proliferative diabetic retinopathy were mild. In patients with glaucoma in the absence of diabetic retinopathy, the average difference between untreated IOP and IOP under treatment at the last check-up was 1.63 mmHg, the MD depreciation was by 0.65 dB and the average number of glaucoma medications used was 0.795 +/- 0.978. No statistically significant differences in terms of initial and final pressure were found. No statistically significant differences in the evolution of changes in perimeter between the two groups were observed. The presence of non-proliferating diabetic retinopathy influenced (only marginally statistically) the glaucomatous disease progression. Large comparative prospective studies are needed for the long-term follow up.

Exploring eye movements in patients with glaucoma when viewing a driving scene.

PubMed

Crabb, David P; Smith, Nicholas D; Rauscher, Franziska G; Chisholm, Catharine M; Barbur, John L; Edgar, David F; Garway-Heath, David F

2010-03-16

Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of 'point-of-regard' of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive.

Exploring Eye Movements in Patients with Glaucoma When Viewing a Driving Scene

PubMed Central

Crabb, David P.; Smith, Nicholas D.; Rauscher, Franziska G.; Chisholm, Catharine M.; Barbur, John L.; Edgar, David F.; Garway-Heath, David F.

2010-01-01

Background Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). Methodology/Principal Findings The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of ‘point-of-regard’ of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. Conclusions/Significance Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive. PMID:20300522

Eye Disease in Patients with Diabetes Screened with Telemedicine.

PubMed

Park, Dong-Wouk; Mansberger, Steven L

2017-02-01

Telemedicine with nonmydriatic cameras can detect not only diabetic retinopathy but also other eye disease. To determine the prevalence of eye diseases detected by telemedicine in a population with a high prevalence of minority and American Indian/Alaskan Native (AI/AN) ethnicities. We recruited diabetic patients 18 years and older and used telemedicine with nonmydriatic cameras to detect eye disease. Two trained readers graded the images for diabetic retinopathy, age-related macular degeneration (ARMD), glaucomatous features, macular edema, and other eye disease using a standard protocol. We included both eyes for analysis and excluded images that were too poor to grade. We included 820 eyes from 424 patients with 72.3% nonwhite ethnicity and 50.3% AI/AN heritage. While 283/424 (66.7%) patients had normal eye images, 120/424 (28.3%) had one disease identified; 15/424 (3.5%) had two diseases; and 6/424 (1.4%) had three diseases in one or both eyes. After diabetic retinopathy (104/424, 24.5%), the most common eye diseases were glaucomatous features (44/424, 10.4%) and dry ARMD (24/424, 5.7%). Seventeen percent (72/424, 17.0%) showed eye disease other than diabetic retinopathy. Telemedicine with nonmydriatic cameras detected diabetic retinopathy, as well as other visually significant eye disease. This suggests that a diabetic retinopathy screening program needs to detect and report other eye disease, including glaucoma and macular disease.

Optical coherence tomography for glaucoma diagnosis: An evidence based meta-analysis.

PubMed

Kansal, Vinay; Armstrong, James J; Pintwala, Robert; Hutnik, Cindy

2018-01-01

Early detection, monitoring and understanding of changes in the retina are central to the diagnosis of glaucomatous optic neuropathy, and vital to reduce visual loss from this progressive condition. The main objective of this investigation was to compare glaucoma diagnostic accuracy of commercially available optical coherence tomography (OCT) devices (Zeiss Stratus, Zeiss Cirrus, Heidelberg Spectralis and Optovue RTVue, and Topcon 3D-OCT). 16,104 glaucomatous and 11,543 normal eyes reported in 150 studies. Between Jan. 2017 and Feb 2017, MEDLINE®, EMBASE®, CINAHL®, Cochrane Library®, Web of Science®, and BIOSIS® were searched for studies assessing glaucoma diagnostic accuracy of the aforementioned OCT devices. Meta-analysis was performed pooling area under the receiver operating characteristic curve (AUROC) estimates for all devices, stratified by OCT type (RNFL, macula), and area imaged. 150 studies with 16,104 glaucomatous and 11,543 normal control eyes were included. Key findings: AUROC of glaucoma diagnosis for RNFL average for all glaucoma patients was 0.897 (0.887-0.906, n = 16,782 patient eyes), for macula ganglion cell complex (GCC) was 0.885 (0.869-0.901, n = 4841 eyes), for macula ganglion cell inner plexiform layer (GCIPL) was 0.858 (0.835-0.880, n = 4211 eyes), and for total macular thickness was 0.795 (0.754-0.834, n = 1063 eyes). The classification capability was similar across all 5 OCT devices. More diagnostically favorable AUROCs were demonstrated in patients with increased glaucoma severity. Diagnostic accuracy of RNFL and segmented macular regions (GCIPL, GCC) scans were similar and higher than total macular thickness. This study provides a synthesis of contemporary evidence with features of robust inclusion criteria and large sample size. These findings may provide guidance to clinicians when navigating this rapidly evolving diagnostic area characterized by numerous options.

Acquired color vision and visual field defects in patients with ocular hypertension and early glaucoma

PubMed Central

Papaconstantinou, Dimitris; Georgalas, Ilias; Kalantzis, George; Karmiris, Efthimios; Koutsandrea, Chrysanthi; Diagourtas, Andreas; Ladas, Ioannis; Georgopoulos, Gerasimos

2009-01-01

Purpose: To study acquired color vision and visual field defects in patients with ocular hypertension (OH) and early glaucoma. Methods: In a prospective study we evaluated 99 eyes of 56 patients with OH without visual field defects and no hereditary color deficiencies, followed up for 4 to 6 years (mean = 4.7 ± 0.6 years). Color vision defects were studied using a special computer program for Farnsworth–Munsell 100 hue test and visual field tests were performed with Humphrey analyzer using program 30–2. Both tests were repeated every six months. Results: In fifty-six eyes, glaucomatous defects were observed during the follow-up period. There was a statistically significant difference in total error score (TES) between eyes that eventually developed glaucoma (157.89 ± 31.79) and OH eyes (75.51 ± 31.57) at the first examination (t value 12.816, p < 0.001). At the same time visual field indices were within normal limits in both groups. In the glaucomatous eyes the earliest statistical significant change in TES was identified at the first year of follow-up and was −20.62 ± 2.75 (t value 9.08, p < 0.001) while in OH eyes was −2.11 ± 4.36 (t value 1.1, p = 0.276). Pearson’s coefficient was high in all examinations and showed a direct correlation between TES and mean deviation and corrected pattern standard deviation in both groups. Conclusion: Quantitative analysis of color vision defects provides the possibility of follow-up and can prove a useful means for detecting early glaucomatous changes in patients with normal visual fields. PMID:19668575

Automated determination of cup-to-disc ratio for classification of glaucomatous and normal eyes on stereo retinal fundus images

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Nakagawa, Toshiaki; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2011-09-01

Early diagnosis of glaucoma, which is the second leading cause of blindness in the world, can halt or slow the progression of the disease. We propose an automated method for analyzing the optic disc and measuring the cup-to-disc ratio (CDR) on stereo retinal fundus images to improve ophthalmologists' diagnostic efficiency and potentially reduce the variation on the CDR measurement. The method was developed using 80 retinal fundus image pairs, including 25 glaucomatous, and 55 nonglaucomatous eyes, obtained at our institution. A disc region was segmented using the active contour method with the brightness and edge information. The segmentation of a cup region was performed using a depth map of the optic disc, which was reconstructed on the basis of the stereo disparity. The CDRs were measured and compared with those determined using the manual segmentation results by an expert ophthalmologist. The method was applied to a new database which consisted of 98 stereo image pairs including 60 and 30 pairs with and without signs of glaucoma, respectively. Using the CDRs, an area under the receiver operating characteristic curve of 0.90 was obtained for classification of the glaucomatous and nonglaucomatous eyes. The result indicates potential usefulness of the automated determination of CDRs for the diagnosis of glaucoma.

Rate and Pattern of Rim Area Loss in Healthy and Progressing Glaucoma Eyes

PubMed Central

Hammel, Na’ama; Belghith, Akram; Bowd, Christopher; Medeiros, Felipe A.; Sharpsten, Lucie; Mendoza, Nadia; Tatham, Andrew J.; Khachatryan, Naira; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Zangwill, Linda M.

2015-01-01

Objective To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African descent (AD) and European descent (ED). Design Prospective longitudinal study. Subjects 296 eyes of 157 healthy subjects (88 AD and 69 ED) and 73 progressing glaucoma eyes of 67 subjects (24 AD and 43 ED) from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) were included. Methods Global and sectoral rim area was measured using confocal laser scanning ophthalmoscopy (CSLO). Progression of glaucomatous optic disc damage was determined by masked stereophoto review. The rates of absolute rim area loss and percent rim area loss in healthy and progressing glaucomatous eyes were compared using multivariable nested mixed-effects models. Main Outcome Measures Rate of rim area loss over time. Results The median (inter-quartile range) follow-up time was 5.0 years (2.0–7.4) for healthy eyes and 8.3 years (7.5–9.9) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucoma eyes compared with healthy eyes for both rim area loss (−10.2 ×10−3 mm2/year vs. −2.8 ×10−3 mm2/year, respectively, P<.001) and percent rim area loss (−1.1 %/year vs. −0.2 %/year, respectively, P<.001), but there was considerable overlap between the two groups. 63% of progressing glaucoma eyes had a rate of change faster than the 5th quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percent rim area loss was similar; it tended to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in AD and ED progressing eyes. Conclusions Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percent rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss due to glaucoma. PMID:26746597

Diagnostic capability of scanning laser polarimetry with and without enhanced corneal compensation and optical coherence tomography.

PubMed

Benítez-del-Castillo, Javier; Martinez, Antonio; Regi, Teresa

2011-01-01

To compare the abilities of the current commercially available versions of scanning laser polarimetry (SLP) and optical coherence tomography (OCT), SLP-variable corneal compensation (VCC), SLP-enhanced corneal compensation (ECC), and high-definition (HD) OCT, in discriminating between healthy eyes and those with early-to-moderate glaucomatous visual field loss. Healthy volunteers and patients with glaucoma who met the eligibility criteria were consecutively enrolled in this prospective, cross-sectional, observational study. Subjects underwent complete eye examination, automated perimetry, SLP-ECC, SLP-VCC, and HD-OCT. Scanning laser polarimetry parameters were recalculated in 90-degree segments (quadrants) in the calculation circle to be compared. Areas under the receiver operating characteristic curve (AUROCs) were calculated for every parameter in order to compare the ability of each imaging modality to differentiate between normal and glaucomatous eyes. Fifty-five normal volunteers (mean age 59.1 years) and 33 patients with glaucoma (mean age 63.8 years) were enrolled. Average visual field mean deviation was -6.69 dB (95% confidence interval -8.07 to -5.31) in the glaucoma group. The largest AUROCs were associated with nerve fiber indicator (0.880 and 0.888) for the SLP-VCC and SLP-ECC, respectively, and with the average thickness in the HD-OCT (0.897). The best performing indices for the SLP-VCC, SLP-ECC, and HD OCT gave similar AUROCs, showing moderate diagnostic accuracy in patients with early to moderate glaucoma. Further studies are needed to evaluate the ability of these technologies to discriminate between normal and glaucomatous eyes.

Initial Arcuate Defects within the Central 10 Degrees in Glaucoma

PubMed Central

Raza, Ali S.; de Moraes, Carlos Gustavo V.; Odel, Jeffrey G.; Greenstein, Vivienne C.; Liebmann, Jeffrey M.; Ritch, Robert

2011-01-01

Purpose. To better understand the relationship between the spatial patterns of functional (visual field [VF] loss) and structural (axon loss) abnormalities in patients with glaucomatous arcuate defects largely confined to the central 10° on achromatic perimetry. Methods. Eleven eyes (9 patients) with arcuate glaucomatous VF defects largely confined to the macula were selected from a larger group of patients with both 10-2 and 24-2 VF tests. Eyes were included if their 10-2 VF had an arcuate defect and if the 24-2 test was normal outside the central 10° (i.e., did not have a cluster of three contiguous points within a hemifield). For the structural analysis, plots of retinal nerve fiber layer (RNFL) thickness of the macula were obtained with frequency-domain optical coherence tomography (fdOCT). The optic disc locations of the RNFL defects were identified on peripapillary fdOCT scans. Results. The VF arcuate defects extended to within 1° of fixation on the 10-2 test and were present in the superior hemifield in 10 of the 11 eyes. The arcuate RNFL damage, seen in the macular fdOCT scans of all 11 eyes, involved the temporal and inferior temporal portions of the disc on the peripapillary scans. Conclusions. Glaucomatous arcuate defects of the macula's RNFL meet the disc temporal to the peak of the main arcuate bundles and produce a range of macular VF defects from clear arcuate scotomas to a papillofoveal horizontal step (“pistol barrel scotoma”). If RGC displacement is taken into consideration, the RNFL and VF defects can be compared directly. PMID:20881293

Optical coherence tomography for glaucoma diagnosis: An evidence based meta-analysis

PubMed Central

Armstrong, James J.; Pintwala, Robert; Hutnik, Cindy

2018-01-01

Purpose Early detection, monitoring and understanding of changes in the retina are central to the diagnosis of glaucomatous optic neuropathy, and vital to reduce visual loss from this progressive condition. The main objective of this investigation was to compare glaucoma diagnostic accuracy of commercially available optical coherence tomography (OCT) devices (Zeiss Stratus, Zeiss Cirrus, Heidelberg Spectralis and Optovue RTVue, and Topcon 3D-OCT). Patients 16,104 glaucomatous and 11,543 normal eyes reported in 150 studies. Methods Between Jan. 2017 and Feb 2017, MEDLINE®, EMBASE®, CINAHL®, Cochrane Library®, Web of Science®, and BIOSIS® were searched for studies assessing glaucoma diagnostic accuracy of the aforementioned OCT devices. Meta-analysis was performed pooling area under the receiver operating characteristic curve (AUROC) estimates for all devices, stratified by OCT type (RNFL, macula), and area imaged. Results 150 studies with 16,104 glaucomatous and 11,543 normal control eyes were included. Key findings: AUROC of glaucoma diagnosis for RNFL average for all glaucoma patients was 0.897 (0.887–0.906, n = 16,782 patient eyes), for macula ganglion cell complex (GCC) was 0.885 (0.869–0.901, n = 4841 eyes), for macula ganglion cell inner plexiform layer (GCIPL) was 0.858 (0.835–0.880, n = 4211 eyes), and for total macular thickness was 0.795 (0.754–0.834, n = 1063 eyes). Conclusion The classification capability was similar across all 5 OCT devices. More diagnostically favorable AUROCs were demonstrated in patients with increased glaucoma severity. Diagnostic accuracy of RNFL and segmented macular regions (GCIPL, GCC) scans were similar and higher than total macular thickness. This study provides a synthesis of contemporary evidence with features of robust inclusion criteria and large sample size. These findings may provide guidance to clinicians when navigating this rapidly evolving diagnostic area characterized by numerous options. PMID:29300765

Characteristics of eyes with inner retinal cleavage.

PubMed

Hwang, Young Hoon; Kim, Yong Yeon; Kim, Hwang Ki; Sohn, Yong Ho

2015-02-01

Inner retinal cleavage can be misdiagnosed as a glaucomatous retinal nerve fiber layer (RNFL) defect. This study was performed to characterize eyes with inner retinal cleavage. Inner retinal cleavage is defined as the appearance of a dark spindle-shaped space between the nerve fibers. Patients who presented at our institution with inner retinal cleavage were enrolled in the study. All participants were evaluated by fundus examination, visual field testing with standard automated perimetry, and optical coherence tomography (OCT) imaging. A total of 15 eyes of 11 subjects with inner retinal cleavage were included in the study. The median age of the subjects was 57 years (age range, 30-67 years). In each case, inner retinal cleavage was located adjacent to retinal blood vessels. Tissue bridging the cleavage area was observed in ten eyes. Six eyes had epiretinal membranes (ERMs), two eyes had glaucoma, and one eye had ERM in addition to glaucoma. Six eyes with inner retinal cleavage without combined ocular abnormalities had highly myopic refractive error (-6.50 to -8.50 diopters). Cross-sectional OCT images of the areas of inner retinal cleavage demonstrated defects with irregular margins and empty spaces in the inner layers of the retina. During the follow-up period, no eye showed changes in inner retinal layer cleavage or visual field sensitivity. Inner retinal cleavage was found in eyes with high myopia or ERMs. Inner retinal cleavage was associated with structural changes distinct from those associated with glaucomatous RNFL defects.

Eye-Tracking as a Tool to Evaluate Functional Ability in Everyday Tasks in Glaucoma.

PubMed

Kasneci, Enkelejda; Black, Alex A; Wood, Joanne M

2017-01-01

To date, few studies have investigated the eye movement patterns of individuals with glaucoma while they undertake everyday tasks in real-world settings. While some of these studies have reported possible compensatory gaze patterns in those with glaucoma who demonstrated good task performance despite their visual field loss, little is known about the complex interaction between field loss and visual scanning strategies and the impact on task performance and, consequently, on quality of life. We review existing approaches that have quantified the effect of glaucomatous visual field defects on the ability to undertake everyday activities through the use of eye movement analysis. Furthermore, we discuss current developments in eye-tracking technology and the potential for combining eye-tracking with virtual reality and advanced analytical approaches. Recent technological developments suggest that systems based on eye-tracking have the potential to assist individuals with glaucomatous loss to maintain or even improve their performance on everyday tasks and hence enhance their long-term quality of life. We discuss novel approaches for studying the visual search behavior of individuals with glaucoma that have the potential to assist individuals with glaucoma, through the use of personalized programs that take into consideration the individual characteristics of their remaining visual field and visual search behavior.

Eye-Tracking as a Tool to Evaluate Functional Ability in Everyday Tasks in Glaucoma

PubMed Central

Black, Alex A.

2017-01-01

To date, few studies have investigated the eye movement patterns of individuals with glaucoma while they undertake everyday tasks in real-world settings. While some of these studies have reported possible compensatory gaze patterns in those with glaucoma who demonstrated good task performance despite their visual field loss, little is known about the complex interaction between field loss and visual scanning strategies and the impact on task performance and, consequently, on quality of life. We review existing approaches that have quantified the effect of glaucomatous visual field defects on the ability to undertake everyday activities through the use of eye movement analysis. Furthermore, we discuss current developments in eye-tracking technology and the potential for combining eye-tracking with virtual reality and advanced analytical approaches. Recent technological developments suggest that systems based on eye-tracking have the potential to assist individuals with glaucomatous loss to maintain or even improve their performance on everyday tasks and hence enhance their long-term quality of life. We discuss novel approaches for studying the visual search behavior of individuals with glaucoma that have the potential to assist individuals with glaucoma, through the use of personalized programs that take into consideration the individual characteristics of their remaining visual field and visual search behavior. PMID:28293433

Enhanced Insight into the Autoimmune Component of Glaucoma: IgG Autoantibody Accumulation and Pro-Inflammatory Conditions in Human Glaucomatous Retina

PubMed Central

Gramlich, Oliver W.; Beck, Sabine; von Thun und Hohenstein-Blaul, Nadine; Boehm, Nils; Ziegler, Anika; Vetter, Jan M.; Pfeiffer, Norbert; Grus, Franz H.

2013-01-01

Background There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. Methods and Results Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group). A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007). Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004). CD27+ cells and CD27+/IgG+ plasma cells were observed in all glaucomatous subjects, but not in controls. Conclusion This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an immunological involvement comparable to other neurodegenerative diseases, but also shows a multifactorial pathomechanism, which diverges and might be linked to the specific nature of both eye and retina. PMID:23451242

Visual field changes after cataract extraction: the AGIS experience.

PubMed

Koucheki, Behrooz; Nouri-Mahdavi, Kouros; Patel, Gitane; Gaasterland, Douglas; Caprioli, Joseph

2004-12-01

To test the hypothesis that cataract extraction in glaucomatous eyes improves overall sensitivity of visual function without affecting the size or depth of glaucomatous scotomas. Experimental study with no control group. One hundred fifty-eight eyes (of 140 patients) from the Advanced Glaucoma Intervention Study with at least two reliable visual fields within a year both before and after cataract surgery were included. Average mean deviation (MD), pattern standard deviation (PSD), and corrected pattern standard deviation (CPSD) were compared before and after cataract extraction. To evaluate changes in scotoma size, the number of abnormal points (P < .05) on the pattern deviation plot was compared before and after surgery. We described an index ("scotoma depth index") to investigate changes of scotoma depth after surgery. Mean values for MD, PSD, and CPSD were -13.2, 6.4, and 5.9 dB before and -11.9, 6.8, and 6.2 dB after cataract surgery (P < or = .001 for all comparisons). Mean (+/- SD) number of abnormal points on pattern deviation plot was 26.7 +/- 9.4 and 27.5 +/- 9.0 before and after cataract surgery, respectively (P = .02). Scotoma depth index did not change after cataract extraction (-19.3 vs -19.2 dB, P = .90). Cataract extraction caused generalized improvement of the visual field, which was most marked in eyes with less advanced glaucomatous damage. Although the enlargement of scotomas was statistically significant, it was not clinically meaningful. No improvement of sensitivity was observed in the deepest part of the scotomas.

Do pattern deviation values accurately estimate glaucomatous visual field damage in eyes with glaucoma and cataract?

PubMed

Matsuda, Aya; Hara, Takeshi; Miyata, Kazunori; Matsuo, Hiroshi; Murata, Hiroshi; Mayama, Chihiro; Asaoka, Ryo

2015-09-01

To study the efficacy of pattern deviation (PD) values in the estimation of visual field compensating the influence of cataract in eyes with glaucoma. The study subjects comprised of 48 eyes of 37 glaucoma patients. Mean total deviation value (mTDs) on Humphrey Field Analyzer after cataract surgery was compared with mean PD (mPD) before the surgery. Visual field measurements were carried out ≤6 months before (VF(pre)) and following (VF(post)) successful cataract surgery. The difference between the mPD or mTD values in the VF(pre) and mTD values in the VF(post) (denoted as εmPD/ΔmTD) was calculated, and the influence of the extent of 'true' glaucomatous visual field damage or cataract (as represented by εmPD and ΔmTD, respectively) on this difference was also investigated. There was a significant difference between mTD in the VF(pre) and mTD in the VF(post) (p<0.001, repeated measures analysis of variance). There was not a significant difference between mPD in the VF(pre) and mTD in the VF(post) (p=0.06); however, εmPD was significantly correlated with the mTD in VF(post) and also ΔmTD (R(2)=0.56 and 0.27, p<0.001, Pearson's correlation). The accurate prediction of the mTD in the VF(post) can be achieved using the pattern standard deviation (PSD), mTD and also visual acuity before surgery. Clinicians should be very careful when reviewing the VF of a patient with glaucoma and cataract since PD values may underestimate glaucomatous VF damage in patients with advanced disease and also overestimate glaucomatous VF damage in patients with early to moderate cataract. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.

PubMed

Chang, Diane T W; Herceg, Michael C; Bilonick, Richard A; Camejo, Larissa; Schuman, Joel S; Noecker, Robert J

2009-01-01

To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score +/- SD in nonglaucomatous eyes was 1.3 +/- 0.8 in control and 0.8 +/- 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 +/- 0.7 in control and 0.9 +/- 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes.

Comparison of Ethnic-specific Databases in Heidelberg Retina Tomography-3 to Discriminate Between Early Glaucoma and Normal Chinese Eyes.

PubMed

Tan, Xiu Ling; Yap, Sae Cheong; Li, Xiang; Yip, Leonard W

2017-01-01

To compare the diagnostic accuracy of the 3 race-specific normative databases in Heidelberg Retina Tomography (HRT)-3, in differentiating between early glaucomatous and healthy normal Chinese eyes. 52 healthy volunteers and 25 glaucoma patients were recruited for this prospective cross-sectional study. All underwent standardized interviews, ophthalmic examination, perimetry and HRT optic disc imaging. Area under the curve (AUC) receiver operating characteristics, sensitivity and specificity were derived to assess the discriminating abilities of the 3 normative databases, for both Moorfields Regression Analysis (MRA) and Glaucoma Probability Score (GPS). A significantly higher percentage (65%) of patients were classified as "within normal limits" using the MRA-Indian database, as compared to the MRA-Caucasian and MRA-African-American databases. However, for GPS, this was observed using the African-American database. For MRA, the highest sensitivity was obtained with both Caucasian and African-American databases (68%), while the highest specificity was from the Indian database (94%). The AUC for discrimination between glaucomatous and normal eyes by MRA-Caucasian, MRA-African-American and MRA-Indian databases were 0.77 (95% CI, 0.67-0.88), 0.79 (0.69-0.89) and 0.73 (0.63-0.84) respectively. For GPS, the highest sensitivity was obtained using either Caucasian or Indian databases (68%). The highest specificity was seen with the African-American database (98%). The AUC for GPS-Caucasian, GPS-African-American and GPS-Indian databases were 0.76 (95% CI, 0.66-0.87), 0.77 (0.67-0.87) and 0.76 (0.66-0.87) respectively. Comparison of the 3 ethnic databases did not reveal significant differences to differentiate early glaucomatous from normal Chinese eyes.

Diagnostic ability of macular ganglion cell-inner plexiform layer thickness in glaucoma suspects.

PubMed

Xu, Xiaoyu; Xiao, Hui; Guo, Xinxing; Chen, Xiangxi; Hao, Linlin; Luo, Jingyi; Liu, Xing

2017-12-01

The purpose is to assess the diagnostic ability for early glaucoma of macular ganglion cell-inner plexiform layer (GCIPL) thickness in a Chinese population including glaucoma suspects.A total of 367 eyes with primary open-angle glaucoma (168 early glaucoma, 78 moderate glaucoma, and 121 advanced glaucoma), 52 eyes with ocular hypertension (OHT), 59 eyes with enlarged cup-to-disc ratio (C/D), and 225 normal eyes were included. GCIPL thickness (average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal), retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured using Cirrus high-definition optical coherence tomography (OCT) and compared. The diagnostic ability of OCT parameters was assessed by area under receiver operating characteristic curve (AUROC) in 3 distinguishing groups: normal eyes and eyes with early glaucoma, normal eyes and eyes with glaucoma regardless of disease stage, and nonglaucomatous eyes (normal eyes, eyes with OHT, and enlarged C/D) and early glaucomatous eyes.Glaucomatous eyes showed a significant reduction in GCIPL thickness compared with nonglaucomatous eyes. In all 3 distinguishing groups, best-performing parameters of GCIPL thickness, RNFL thickness, and ONH parameters were minimum GCIPL thickness (expressed in AUROC, 0.899, 0.952, and 0.900, respectively), average RNFL thickness (0.904, 0.953, and 0.892, respectively), and rim area (0.861, 0.925, and 0.824, respectively). There was no statistical significance of AUROC between minimum GCIPL thickness and average RNFL thickness (all P > .05).GCIPL thickness could discriminate early glaucoma from normal and glaucoma suspects with good sensitivity and specificity. The glaucoma diagnostic ability of GCIPL thickness was comparable to that of RNFL thickness. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Racial Differences in Selective Laser Trabeculoplasty Efficacy.

PubMed

Goosen, Emil; Coleman, Kate; Visser, Linda; Sponsel, William E

2017-01-01

Sub-Saharan Africa has a population of 1 billion, with one ophthalmologist per million people. Basic ophthalmic support services are virtually absent for all but a few urban populations. Minimally invasive laser treatment may help. This study reports our initial experience using selective laser trabeculoplasty (SLT) in a mixed-racial population of adult glaucoma patients in Durban, South Africa. Institution Review Board approved the 5-year chart review. Consecutive glaucomatous adults underwent SLT (Lumenis Selecta) on one or both eyes applying 360° treatment of 120 to 140 closely spaced burns (400 urn spot size for 3 ns; range 1.1-1.4 mJ). Significance of change in intraocuar pressure (IOP) from baseline at 1, 3, 6, and 12 months was assessed by two-tailed paired t-test. Among 148 eyes of 84 patients (60 African, 21 Indian, 3 Caucasian), 69 had already undergone glaucoma therapy, and 15 untreated (de novo). Among all eyes, mean IOP was reduced by >32% with mean IOP < 15 mm Hg from baseline at all four study intervals (p < 0.0001). A 20% reduction in IOP was sustained at 12 months in 90% of African eyes but in only 50% of Indian eyes. Selective laser trabeculoplasty was effective in producing clinically significant IOP reduction among South African adults with or without prior medical or surgical anti-glaucoma therapy. Socioeconomically comparable individuals of Indian ancestry showed good therapeutic responses, but significantly less efficacious than those observed among Black subjects. Programs to provide first-line SLT management of glaucoma in Africa, where 90% of patients are unable to sustain prescribed medical therapy, appear to be a very appropriate option. Goosen E, Coleman K, Visser L, Sponsel WE. Racial Differences in Selective Laser Trabeculoplasty Efficacy. J Curr Glaucoma Pract 2017;11(1):22-27.

Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography.

PubMed

Wu, Zhichao; Weng, Denis S D; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C

2018-04-01

To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROI M ), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROI A ), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm 2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test-retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. On average, the longitudinal SNR for the global thickness, ROI A and ROI M methods were -0.90 y -1 , -0.91 y -1 , and -1.03 y -1 , respectively, and was significantly more negative for the ROI M compared with the global thickness ( P = 0.003) and ROI A methods ( P = 0.021). Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage.

Patterns of glaucomatous visual field loss in sita fields automatically identified using independent component analysis.

PubMed

Goldbaum, Michael H; Jang, Gil-Jin; Bowd, Chris; Hao, Jiucang; Zangwill, Linda M; Liebmann, Jeffrey; Girkin, Christopher; Jung, Tzyy-Ping; Weinreb, Robert N; Sample, Pamela A

2009-12-01

To determine if the patterns uncovered with variational Bayesian-independent component analysis-mixture model (VIM) applied to a large set of normal and glaucomatous fields obtained with the Swedish Interactive Thresholding Algorithm (SITA) are distinct, recognizable, and useful for modeling the severity of the field loss. SITA fields were obtained with the Humphrey Visual Field Analyzer (Carl Zeiss Meditec, Inc, Dublin, California) on 1,146 normal eyes and 939 glaucoma eyes from subjects followed by the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. VIM modifies independent component analysis (ICA) to develop separate sets of ICA axes in the cluster of normal fields and the 2 clusters of abnormal fields. Of 360 models, the model with the best separation of normal and glaucomatous fields was chosen for creating the maximally independent axes. Grayscale displays of fields generated by VIM on each axis were compared. SITA fields most closely associated with each axis and displayed in grayscale were evaluated for consistency of pattern at all severities. The best VIM model had 3 clusters. Cluster 1 (1,193) was mostly normal (1,089, 95% specificity) and had 2 axes. Cluster 2 (596) contained mildly abnormal fields (513) and 2 axes; cluster 3 (323) held mostly moderately to severely abnormal fields (322) and 5 axes. Sensitivity for clusters 2 and 3 combined was 88.9%. The VIM-generated field patterns differed from each other and resembled glaucomatous defects (eg, nasal step, arcuate, temporal wedge). SITA fields assigned to an axis resembled each other and the VIM-generated patterns for that axis. Pattern severity increased in the positive direction of each axis by expansion or deepening of the axis pattern. VIM worked well on SITA fields, separating them into distinctly different yet recognizable patterns of glaucomatous field defects. The axis and pattern properties make VIM a good candidate as a preliminary process for detecting progression.

Scanning Laser Polarimetry with Variable and Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Sehi, Mitra; Guaqueta, Delia C.; Feuer, William J.; Greenfield, David S.

2007-01-01

Purpose To investigate whether correction for atypical birefringence pattern (ABP) using scanning laser polarimetry with enhanced corneal compensation (SLP-ECC) reduces the severity of ABP compared with variable corneal compensation (SLP-VCC), and improves the correlation with visual function. Design Prospective observational study. Methods Normal and glaucomatous eyes enrolled from 4 clinical sites underwent complete examination, automated perimetry, SLP-ECC and SLP-VCC. Eyes were characterized in 3 groups based upon the typical scan score (TSS): normal birefringence pattern (NBP) was defined as TSS 80, mild ABP as TSS 61–79, moderate-severe ABP as TSS 60. For each of 4 SLP parameters the area under the ROC curve (AUROC) was calculated to compare the ability of SLP-ECC and SLP-VCC to discriminate between normal and glaucomatous eyes. Results Eighty-four normal volunteers and 45 glaucoma patients were enrolled. Mean TSS was significantly (p<0.001) greater using SLP-ECC (98.0 ± 6.6) compared to SLP-VCC (83.4 ± 22.5). The frequency of moderate-severe ABP images was significantly (p<0.001, McNemar test) higher using SLP-VCC (18 of 129, 14%) compared to SLP-ECC (1 of 129, 0.8%). Two SLP-ECC parameters (TSNIT average and inferior average) had significantly (p=0.01, p<0.001) higher correlation (r=0.45, r=0.50 respectively) with MD compared to SLP-VCC (r=0.34, r=0.37). Among eyes with moderate-severe ABP (N = 18), inferior average obtained using SLP-ECC had significantly (p=0.03) greater AUROC (0.91 ± 0.07) compared with SLP-VCC (0.78 ± 0.11). Conclusions SLP-ECC significantly reduces the frequency and severity of ABP compared to SLP-VCC and improves the correlation between RNFL measures and visual function. PMID:17157800

Detecting early functional damage in glaucoma suspect and ocular hypertensive patients with the multifocal VEP technique.

PubMed

Thienprasiddhi, Phamornsak; Greenstein, Vivienne C; Chu, David H; Xu, Li; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2006-08-01

To determine whether the multifocal visual evoked potential (mfVEP) technique can detect early functional damage in ocular hypertensive (OHT) and glaucoma suspect (GS) patients with normal standard achromatic automated perimetry (SAP) results. Twenty-five GS patients (25 eyes), 25 patients with OHT (25 eyes), and 50 normal controls (50 eyes) were enrolled in this study. All GS, OHT and normal control eyes had normal SAP as defined by a pattern standard deviation and mean deviation within the 95% confidence interval and a glaucoma hemifield test within normal limits on the Humphrey visual field 24-2 program. Eyes with GS had optic disc changes consistent with glaucoma with or without raised intraocular pressure (IOP), and eyes with OHT showed no evidence of glaucomatous optic neuropathy and IOPs >or=22 mm Hg. Monocular mfVEPs were obtained from both eyes of each subject using a pattern-reversal dartboard array with 60 sectors. The entire display had a radius of 22.3 degrees. The mfVEPs, for each eye, were defined as abnormal when either the monocular or interocular probability plot had a cluster of 3 or more contiguous points with P<0.05 and at least 2 of these points with P<0.01. The mfVEP results were abnormal in 4% of the eyes from normal subjects. Abnormal mfVEPs were detected in 20% of the eyes of GS patients and 16% of the eyes of OHT patients. Significantly more mfVEP abnormalities were detected in GS patients than in normal controls. However, there was no significant difference in mfVEP results between OHT patients and normal controls. The mfVEP technique can detect visual field deficits in a minority of eyes with glaucomatous optic disks and normal SAP results.

Effect of experimental glaucoma on the non-image forming visual system.

PubMed

de Zavalía, Nuria; Plano, Santiago A; Fernandez, Diego C; Lanzani, María Florencia; Salido, Ezequiel; Belforte, Nicolás; Sarmiento, María I Keller; Golombek, Diego A; Rosenstein, Ruth E

2011-06-01

Glaucoma is a leading cause of blindness worldwide, characterized by retinal ganglion cell degeneration and damage to the optic nerve. We investigated the non-image forming visual system in an experimental model of glaucoma in rats induced by weekly injections of chondroitin sulphate (CS) in the eye anterior chamber. Animals were unilaterally or bilaterally injected with CS or vehicle for 6 or 10 weeks. In the retinas from eyes injected with CS, a similar decrease in melanopsin and Thy-1 levels was observed. CS injections induced a similar decrease in the number of melanopsin-containing cells and superior collicular retinal ganglion cells. Experimental glaucoma induced a significant decrease in the afferent pupil light reflex. White light significantly decreased nocturnal pineal melatonin content in control and glaucomatous animals, whereas blue light decreased this parameter in vehicle- but not in CS-injected animals. A significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was observed in glaucomatous animals. General rhythmicity and gross entrainment appear to be conserved, but glaucomatous animals exhibited a delayed phase angle with respect to lights off and a significant increase in the percentage of diurnal activity. These results indicate the glaucoma induced significant alterations in the non-image forming visual system. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Longitudinal analysis of progression in glaucoma using spectral-domain optical coherence tomography.

PubMed

Wessel, Julia M; Horn, Folkert K; Tornow, Ralf P; Schmid, Matthias; Mardin, Christian Y; Kruse, Friedrich E; Juenemann, Anselm G; Laemmer, Robert

2013-05-01

To compare the longitudinal loss of RNFL thickness measurements by SD-OCT in healthy individuals and glaucoma patients with or without progression concerning optic disc morphology. A total of 62 eyes, comprising 38 glaucomatous eyes with open angle glaucoma and 24 healthy controls, were included in the study (Erlangen Glaucoma Registry, NTC00494923). All patients were investigated annually over a period of 3 years by Spectralis SD-OCT measuring peripapillary RNFL thickness. By masked comparative analysis of photographs, the eyes were classified into nonprogressive and progressive glaucoma cases. Longitudinal loss of RNFL thickness was compared with morphological changes of optic disc morphology. Mixed model analysis of annual OCT scans revealed an estimated annual decrease of the RNFL thickness by 2.12 μm in glaucoma eyes with progression, whereas glaucoma eyes without progression in optic disc morphology lost 1.18 μm per year in RNFL thickness (P = 0.002). The rate of change in healthy eyes was 0.60 μm and thereby also significantly lower than in glaucoma eyes with progression (P < 0.001). The intrasession variability of three successive measurements without head repositioning was 1.5 ± 0.7 μm. The loss of mean RNFL thickness exceeded the intrasession variability in 60% of nonprogressive eyes, and in 85% of progressive eyes after 3 years. LONGITUDINAL MEASUREMENTS OF RNFL THICKNESS USING SD-OCT SHOW A MORE PRONOUNCED REDUCTION OF RNFL THICKNESS IN PATIENTS WITH PROGRESSION COMPARED WITH PATIENTS WITHOUT PROGRESSION IN GLAUCOMATOUS OPTIC DISC CHANGES. (www.clinicaltrials.gov number, NTC00494923.).

Relationship between Scanning Laser Polarimetry with Enhanced Corneal Compensation and with Variable Corneal Compensation

PubMed Central

Kim, Kyung Hoon; Choi, Jaewan; Lee, Chang Hwan; Cho, Beom-Jin; Kook, Michael S.

2008-01-01

Purpose To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. Methods Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. Results In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). Conclusions The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP. PMID:18323701

Measurement of amino acid levels in the vitreous humor of rats after chronic intraocular pressure elevation or optic nerve transection.

PubMed

Levkovitch-Verbin, Hana; Martin, Keith R G; Quigley, Harry A; Baumrind, Lisa A; Pease, Mary Ellen; Valenta, Danielle

2002-10-01

To investigate whether the levels of free amino acids and protein in the vitreous of rat eyes are altered with chronic intraocular pressure (IOP) elevation or after optic nerve transection. The concentrations of 20 amino acids in the vitreous humor were measured by high-performance liquid chromatography in both eyes of 41 rats with unilateral IOP elevation induced by translimbal photocoagulation. Eyes were studied 1 day and 1, 2, 4, and 9 weeks after initial IOP elevation. The same amino acids were measured in 41 rats 1 day and 2, 4, and 9 weeks after unilateral transection of the orbital optic nerve. The intravitreal protein level was assayed in additional 22 rats with IOP elevation and 12 rats after nerve transection. Two masked observers evaluated the amount of optic nerve damage with a semiquantitative, light-microscopic technique. In rats with experimental glaucoma, amino acid concentrations were unchanged 1 day after treatment. At 1 week, 4 of 20 amino acids (aspartate, proline, alanine, and lysine) were higher than in control eyes ( < or = 0.01), but this difference was nonsignificant after Bonferroni correction for multiple simultaneous amino acid comparisons (none achieved < 0.0025). No amino acid was significantly different from control in the nerve transection groups (all > 0.05). Vitreous protein level was significantly higher in glaucomatous eyes than their paired controls at 1 day ( < 0.0001) and 1 week ( < 0.002). One day and 1 week after optic nerve transection, vitreal proteins were significantly elevated compared with control eyes from untreated animals ( < 0.0020 and < 0.0022, respectively), though not compared with their fellow eyes ( = 0.25 and 0.10). Chronic experimental glaucoma and transection of the optic nerve increase the amount of protein in the rat vitreous above control levels. In the vitreous of rats with experimental glaucoma, a number of free amino acids were transiently elevated to a modest degree, but no significant difference in vitreous glutamate concentration was detected ( > 0.01).

Agreement of glaucoma specialists and experienced optometrists in gonioscopy and optic disc evaluation

PubMed Central

Kumar, Addepalli U.; Jonnadula, Ganesh B.; Garudadri, Chandrasekhar; Rao, Harsha L.; Senthil, Sirisha; Papas, Eric B.; Sankaridurg, Padmaja; Khanna, Rohit C.

2013-01-01

Purpose To compare the diagnostic performance of glaucoma specialists and experienced optometrists in gonioscopy and optic disc assessment. Methods This study was done to validate the diagnostic performance of two experienced optometrists for using their skills of detecting glaucoma using gonioscopy and optic disc assessment in a major epidemiological study, the L V Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). Gonioscopic findings for 150 eyes were categorized as 0, 1 and 2 for open angle, primary angle closure suspect (PACS) and primary angle closure (PAC) respectively. Optic disc findings for 200 eyes were categorized as 0, 1 and 2 for normal, suspects and glaucomatous respectively. Weighted kappa (κ) and diagnostic accuracy parameters were calculated. Two optometrists (#1 and #2) participated in the study. Results Agreement between glaucoma specialists and optometrist for interpretation of gonioscopy to discriminate PACS and PAC from open angles and for interpretation of optic disc to discriminate glaucomatous and suspicious discs from normal, the kappa (κ) was 0.92 and 0.84 and 0.90 and 0.89 for optometrists #1 and #2 respectively. Sensitivities and specificities were above 90% for gonioscopy. Optic disc evaluation had specificities greater than 95% to discriminate normal from glaucomatous discs while the sensitivities were 83% and 93% for optometrists #1 and #2 respectively. Conclusion Agreement between optometrists and glaucoma specialists, in diagnostic performance of gonioscopy and optic assessment was excellent with high sensitivity and specificity. Hence, we conclude that the experienced optometrists can detect glaucoma accurately in the LVPEI-GLEAMS.

[The 8-year follow-up study for clinical diagnostic potentials of frequency-doubling technology perimetry for perimetrically normal eyes of open-angle glaucoma patients with unilateral visual field loss].

PubMed

Fan, X; Wu, L L; Xiao, G G; Ma, Z Z; Liu, F

2018-03-11

Objective: To analyze potentials of frequency-doubling technology perimetry (FDP) for diagnosing open-angle glaucoma (OAG) in perimetrically normal eyes of OAG patients diagnosed with standard automated perimetry (SAP) and relating factors from abnormalities on FDP to visual field loss on SAP. Methods: A prospective cohort study. Sixty-eight eyes of 68 OAG patients visiting the ophthalmic clinic of Peking University Third Hospital during November 2003 and October 2007 [32 primary open-angle glaucoma patients and 36 normal tension glaucoma patients, 32 males and 36 females, with an average age of (59±13) years] with unilateral field loss detected by SAP (Octopus101 tG2 program) were examined with the FDP N-30 threshold program (Humphrey Instruments) at baseline. Two groups, FDP positive group and FDP negative group, were divided based on the FDP results, and visual field examinations were followed by a series of SAP examinations for the perimetrically normal eyes over 8 years. During the follow-up, the difference of the converting rate of SAP tests between the two groups was analyzed. Differences between "convertors" and "non-convertors" of SAP tests in the FDP positive group, such as the cup-to-disk ratio and glaucomatous optic neuropathy rate, were also compared with the independent-sample t test or Wilcoxon two-sample test for continuous variable data and the χ(2) test or Fisher exact test for classified variable data and rates. Results: Forty-eight perimetrically normal eyes of 48 participants had complete data and a qualifying follow-up. Baseline FDP results were positive in 33 eyes and negative in 15 eyes. Of the eyes with positive FDP results, 22 eyes developed abnormal SAP results after 4.0 to 90.0 months (median 14.5 months) , whereas none of the eyes with negative FDP results developed abnormal SAP results. For perimetrically normal eyes in the FDP positive group, "converters" showed a greater cup-to-disk ratio (0.73±0.09 vs . 0.63±0.14, Wilcoxon two-sample test, P= 0.011) and more eyes with glaucomatous optic neuropathy (19/22 vs . 4/11, Fisher exact test, P= 0.006). Conclusions: In perimetrically normal eyes of OAG patients, FDP could detect visual field loss of these eyes and predict to some extent future visual field loss on SAP. Severity of glaucomatous optic neuropathy at baseline is related to converting from abnormalities on FDP to visual field loss on SAP. (Chin J Ophthalmol, 2018, 54: 177-183) .

Heidelberg retina tomograph measurements of the optic disc and parapapillary retina for detecting glaucoma analyzed by machine learning classifiers.

PubMed

Zangwill, Linda M; Chan, Kwokleung; Bowd, Christopher; Hao, Jicuang; Lee, Te-Won; Weinreb, Robert N; Sejnowski, Terrence J; Goldbaum, Michael H

2004-09-01

To determine whether topographical measurements of the parapapillary region analyzed by machine learning classifiers can detect early to moderate glaucoma better than similarly processed measurements obtained within the disc margin and to improve methods for optimization of machine learning classifier feature selection. One eye of each of 95 patients with early to moderate glaucomatous visual field damage and of each of 135 normal subjects older than 40 years participating in the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) were included. Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Dossenheim, Germany) mean height contour was measured in 36 equal sectors, both along the disc margin and in the parapapillary region (at a mean contour line radius of 1.7 mm). Each sector was evaluated individually and in combination with other sectors. Gaussian support vector machine (SVM) learning classifiers were used to interpret HRT sector measurements along the disc margin and in the parapapillary region, to differentiate between eyes with normal and glaucomatous visual fields and to compare the results with global and regional HRT parameter measurements. The area under the receiver operating characteristic (ROC) curve was used to measure diagnostic performance of the HRT parameters and to evaluate the cross-validation strategies and forward selection and backward elimination optimization techniques that were used to generate the reduced feature sets. The area under the ROC curve for mean height contour of the 36 sectors along the disc margin was larger than that for the mean height contour in the parapapillary region (0.97 and 0.85, respectively). Of the 36 individual sectors along the disc margin, those in the inferior region between 240 degrees and 300 degrees, had the largest area under the ROC curve (0.85-0.91). With SVM Gaussian techniques, the regional parameters showed the best ability to discriminate between normal eyes and eyes with glaucomatous visual field damage, followed by the global parameters, mean height contour measures along the disc margin, and mean height contour measures in the parapapillary region. The area under the ROC curve was 0.98, 0.94, 0.93, and 0.85, respectively. Cross-validation and optimization techniques demonstrated that good discrimination (99% of peak area under the ROC curve) can be obtained with a reduced number of HRT parameters. Mean height contour measurements along the disc margin discriminated between normal and glaucomatous eyes better than measurements obtained in the parapapillary region. Copyright Association for Research in Vision and Ophthalmology

Heidelberg Retina Tomograph Measurements of the Optic Disc and Parapapillary Retina for Detecting Glaucoma Analyzed by Machine Learning Classifiers

PubMed Central

Zangwill, Linda M.; Chan, Kwokleung; Bowd, Christopher; Hao, Jicuang; Lee, Te-Won; Weinreb, Robert N.; Sejnowski, Terrence J.; Goldbaum, Michael H.

2010-01-01

Purpose To determine whether topographical measurements of the parapapillary region analyzed by machine learning classifiers can detect early to moderate glaucoma better than similarly processed measurements obtained within the disc margin and to improve methods for optimization of machine learning classifier feature selection. Methods One eye of each of 95 patients with early to moderate glaucomatous visual field damage and of each of 135 normal subjects older than 40 years participating in the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) were included. Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Dossenheim, Germany) mean height contour was measured in 36 equal sectors, both along the disc margin and in the parapapillary region (at a mean contour line radius of 1.7 mm). Each sector was evaluated individually and in combination with other sectors. Gaussian support vector machine (SVM) learning classifiers were used to interpret HRT sector measurements along the disc margin and in the parapapillary region, to differentiate between eyes with normal and glaucomatous visual fields and to compare the results with global and regional HRT parameter measurements. The area under the receiver operating characteristic (ROC) curve was used to measure diagnostic performance of the HRT parameters and to evaluate the cross-validation strategies and forward selection and backward elimination optimization techniques that were used to generate the reduced feature sets. Results The area under the ROC curve for mean height contour of the 36 sectors along the disc margin was larger than that for the mean height contour in the parapapillary region (0.97 and 0.85, respectively). Of the 36 individual sectors along the disc margin, those in the inferior region between 240° and 300°, had the largest area under the ROC curve (0.85–0.91). With SVM Gaussian techniques, the regional parameters showed the best ability to discriminate between normal eyes and eyes with glaucomatous visual field damage, followed by the global parameters, mean height contour measures along the disc margin, and mean height contour measures in the parapapillary region. The area under the ROC curve was 0.98, 0.94, 0.93, and 0.85, respectively. Cross-validation and optimization techniques demonstrated that good discrimination (99% of peak area under the ROC curve) can be obtained with a reduced number of HRT parameters. Conclusions Mean height contour measurements along the disc margin discriminated between normal and glaucomatous eyes better than measurements obtained in the parapapillary region. PMID:15326133

Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography

PubMed Central

Weng, Denis S. D.; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C.

2018-01-01

Purpose To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. Methods One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROIM), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROIA), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test–retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. Results On average, the longitudinal SNR for the global thickness, ROIA and ROIM methods were −0.90 y−1, −0.91 y−1, and −1.03 y−1, respectively, and was significantly more negative for the ROIM compared with the global thickness (P = 0.003) and ROIA methods (P = 0.021). Conclusions Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. Translational Relevance These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage. PMID:29616153

Recognizing patterns of visual field loss using unsupervised machine learning

NASA Astrophysics Data System (ADS)

Yousefi, Siamak; Goldbaum, Michael H.; Zangwill, Linda M.; Medeiros, Felipe A.; Bowd, Christopher

2014-03-01

Glaucoma is a potentially blinding optic neuropathy that results in a decrease in visual sensitivity. Visual field abnormalities (decreased visual sensitivity on psychophysical tests) are the primary means of glaucoma diagnosis. One form of visual field testing is Frequency Doubling Technology (FDT) that tests sensitivity at 52 points within the visual field. Like other psychophysical tests used in clinical practice, FDT results yield specific patterns of defect indicative of the disease. We used Gaussian Mixture Model with Expectation Maximization (GEM), (EM is used to estimate the model parameters) to automatically separate FDT data into clusters of normal and abnormal eyes. Principal component analysis (PCA) was used to decompose each cluster into different axes (patterns). FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results, recruited from a university-based, longitudinal, multi-center, clinical study on glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1 contained 94% normal fields (94% specificity) and clusters 2 and 3 combined, contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA successfully separated FDT fields from healthy and glaucoma eyes and identified familiar glaucomatous patterns of loss.

Diagnostic Ability of Automated Pupillography in Glaucoma.

PubMed

Rao, Harsha L; Kadambi, Sujatha V; Mehta, Pooja; Dasari, Srilakshmi; Puttaiah, Narendra K; Pradhan, Zia S; Rao, Dhanraj A S; Shetty, Rohit

2017-05-01

To evaluate the diagnostic ability of automated pupillography measurements in glaucoma and study the effect of inter-eye asymmetry in glaucomatous damage on the diagnostic ability. In an observational, cross-sectional study, 47 glaucoma patients and 42 control subjects underwent automated pupillography using a commercially available device. Diagnostic abilities of the pupillary response measurements were evaluated using area under receiver operating characteristic (ROC) curves (AUC) and sensitivities at fixed specificities. Influence of inter-eye asymmetry in glaucoma [inter-eye mean deviation (MD) difference on visual fields (VF)] on the diagnostic ability of pupillography parameters was evaluated by ROC regression approach. The AUCs of automated pupillography parameters ranged from 0.60 (amplitude score with peripheral blue stimulus) to 0.82 (amplitude score with full field white stimulus, Amp-FF-W). Sensitivity at 95% specificity ranged between 5% (amplitude score with full field blue stimulus) and 45% (amplitude score with full field green stimulus). Inter-eye MD difference significantly affected the diagnostic performance of automated pupillography parameters (p < 0.05). AUCs of Amp-FF-W at inter-eye MD difference of 0 dB, 5 dB, 10 dB and 15 dB were 0.71, 0.80, 0.87 and 0.93, respectively, according to the regression model. The corresponding sensitivities at 95% specificity were 20%, 34%, 50% and 66%, respectively. The diagnostic abilities of even the best automated pupillography parameters were only moderate in glaucoma. The performance of these pupillography measurements in detecting glaucoma significantly increased with greater inter-eye asymmetry in the glaucomatous damage.

3D modeling to characterize lamina cribrosa surface and pore geometries using in vivo images from normal and glaucomatous eyes

PubMed Central

Sredar, Nripun; Ivers, Kevin M.; Queener, Hope M.; Zouridakis, George; Porter, Jason

2013-01-01

En face adaptive optics scanning laser ophthalmoscope (AOSLO) images of the anterior lamina cribrosa surface (ALCS) represent a 2D projected view of a 3D laminar surface. Using spectral domain optical coherence tomography images acquired in living monkey eyes, a thin plate spline was used to model the ALCS in 3D. The 2D AOSLO images were registered and projected onto the 3D surface that was then tessellated into a triangular mesh to characterize differences in pore geometry between 2D and 3D images. Following 3D transformation of the anterior laminar surface in 11 normal eyes, mean pore area increased by 5.1 ± 2.0% with a minimal change in pore elongation (mean change = 0.0 ± 0.2%). These small changes were due to the relatively flat laminar surfaces inherent in normal eyes (mean radius of curvature = 3.0 ± 0.5 mm). The mean increase in pore area was larger following 3D transformation in 4 glaucomatous eyes (16.2 ± 6.0%) due to their more steeply curved laminar surfaces (mean radius of curvature = 1.3 ± 0.1 mm), while the change in pore elongation was comparable to that in normal eyes (−0.2 ± 2.0%). This 3D transformation and tessellation method can be used to better characterize and track 3D changes in laminar pore and surface geometries in glaucoma. PMID:23847739

Diagnostic Value of Ganglion Cell-Inner Plexiform Layer Thickness in Glaucoma With Superior or Inferior Visual Hemifield Defects.

PubMed

Kim, Ho Soong; Yang, Heon; Lee, Tae Heon; Lee, Kyung Heon

2016-06-01

To determine the diagnostic value of the ganglion cell-inner plexiform layer (GCIPL) thickness in glaucomatous eyes with superior or inferior visual hemifield defects. Eighty-five patients with glaucoma (42 isolated superior hemifield defects and 43 isolated inferior hemifield defects) and 46 normal subjects were enrolled. All patients underwent Cirrus high-definition optical coherence tomography and standard automated perimetry. The area under the receiver operating characteristic curve (AUC) was calculated to determine the diagnostic ability of the GCIPL and peripapillary retinal nerve fiber layer (pRNFL). In the superior hemifield defect glaucoma group, the best parameters for discriminating normal eyes from glaucomatous eyes were the inferotemporal GCIPL thickness (0.942), inferior quadrant RNFL thickness (0.974), and 7 o'clock sector RNFL thickness (0.999). For diagnosing inferior hemifield defect glaucoma, the AUCs of all GCIPL parameters (0.331 to 0.702) were significantly lower than that of the superior quadrant RNFL thickness (0.866, P<0.05). The diagnostic ability of GCIPL parameters was similar to that of the pRNFL parameters in superior hemifield defect glaucoma. However, the diagnostic performance of the GCIPL parameters was significantly inferior to those of the pRNFL parameters in eyes with inferior hemifield defect glaucoma.

Rho-associated kinase inhibitors: a novel glaucoma therapy.

PubMed

Inoue, Toshihiro; Tanihara, Hidenobu

2013-11-01

The rho-associated kinase (ROCK) signaling pathway is activated via secreted bioactive molecules or via integrin activation after extracellular matrix binding. These lead to polymerization of actin stress fibers and formation of focal adhesions. Accumulating evidence suggests that actin cytoskeleton-modulating signals are involved in aqueous outflow regulation. Aqueous humor contains various biologically active factors, some of which are elevated in glaucomatous eyes. These factors affect aqueous outflow, in part, through ROCK signaling modulation. Various drugs acting on the cytoskeleton have also been shown to increase aqueous outflow by acting directly on outflow tissue. In vivo animal studies have shown that the trabecular meshwork (TM) actin cytoskeleton in glaucomatous eyes is more disorganized and more randomly oriented than in non-glaucomatous control eyes. In a previous study, we introduced ROCK inhibitors as a potential glaucoma therapy by showing that a selective ROCK inhibitor significantly lowered rabbit IOP. Rho-associated kinase inhibitors directly affect the TM and Schlemm's canal (SC), differing from the target sight of other glaucoma drugs. The TM is affected earlier and more strongly than ciliary muscle cells by ROCK inhibitors, largely because of pharmacological affinity differences stemming from regulatory mechanisms. Additionally, ROCK inhibitors disrupt tight junctions, result in F-actin depolymerization, and modulate intracellular calcium level, effectively increasing SC-cell monolayer permeability. Perfusion of an enucleated eye with a ROCK inhibitor resulted in wider empty spaces in the juxtacanalicular (JCT) area and more giant vacuoles in the endothelial cells of SC, while the endothelial lining of SC was intact. Interestingly, ROCK inhibitors also increase retinal blood flow by relaxing vascular smooth muscle cells, directly protecting neurons against various stresses, while promoting wound healing. These additional effects may help slow progressing visual field loss in glaucoma patients, making ROCK inhibitors an even more desirable anti-glaucoma agent. All evidence indicates that aqueous humor outflow is affected by cytoskeleton physiology and this information may provide valuable insight into understanding glaucoma pathology and treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

PubMed

Hoesl, Laura Maria; Tornow, Ralf P; Schrems, Wolfgang A; Horn, Folkert K; Mardin, Christian Y; Kruse, Friedrich E; Juenemann, Anselm G M; Laemmer, Robert

2013-01-01

To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.

Morphological and functional differences between normal-tension and high-tension glaucoma.

PubMed

Häntzschel, Janek; Terai, Naim; Sorgenfrei, Friederike; Haustein, Michael; Pillunat, Karin; Pillunat, Lutz E

2013-08-01

To compare visual field (VF) and nerve fibre loss in patients with normal-tension (NTG) and high-tension glaucoma (HTG) at an equal level of glaucomatous structural damage of the optic nerve head (ONH). In a retrospective, pair-matched, comparative study, 126 eyes with NTG and 126 eyes with HTG were matched according to the same glaucomatous ONH damage based on rim volume, rim area and disc size measured by the Heidelberg Retina Tomograph (HRT III). Visual field by Humphrey perimetry and nerve fibre layer thickness measured by scanning laser polarimetry (GdxVCC) were compared between both groups. Based on the HRT, NTG and HTG displayed comparable structural damage of the ONH without a statistically significant difference between both groups (mean, NTG/HTG: disc area 2.32/2.32 mm², p =0.342; rim area 1.03/1.00 mm², p = 0.279; rim volume 0.2/0.19 mm³; p = 0.274). Eyes with NTG had significantly less VF damage than eyes with HTG (mean, NTG/HTG: mean deviation (MD) -3.69/-9.77 dB, p = 0.0001; pattern standard deviation (PSD) 4.80/7.17 dB, p = 0.0001). The nerve fibre layer of NTG patients was thicker than that of HTG patients (mean, NTG/HTG: GDx total: 46.9/44.0 μm, p = 0.073; GDx superior: 57.2/49.9 μm, p = 0.0001; GDx inferior: 54.9/49.7 μm, p = 0.001). At an equal level of glaucomatous structural damage of the ONH indicated by cupping, rim area and rim volume, NTG patients seem to have a less affected visual field and a better preserved nerve fibre layer than HTG patients. © 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.

Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure: Findings from the Maracaibo Aging Study.

PubMed

Melgarejo, Jesús D; Lee, Joseph H; Petitto, Michele; Yépez, Juan B; Murati, Felipe A; Jin, Zhezhen; Chávez, Carlos A; Pirela, Rosa V; Calmón, Gustavo E; Lee, Winston; Johnson, Matthew P; Mena, Luis J; Al-Aswad, Lama A; Terwilliger, Joseph D; Allikmets, Rando; Maestre, Gladys E; De Moraes, C Gustavo

2018-06-01

To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. Observational cross-sectional study. A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Assessment of conditions affecting surgical success of Ahmed glaucoma valve implants in glaucoma secondary to different uveitis etiologies in adults.

PubMed

Sungur, G; Yakin, M; Eksioglu, U; Satana, B; Ornek, F

2017-10-01

PurposeThere is little known about the long-term efficacy and safety of Ahmed glaucoma valve (AGV) implant and about the conditions affecting surgical success in uveitic glaucoma (UG).Patients and methodsThe charts of adult patients with UG who underwent AGV implantation from 2006 to 2015 were reviewed retrospectively.ResultsData of 46 eyes of 39 patients were evaluated. Mean follow-up was 51.93±23.08 months. Mean preoperative IOP was 37.05±9.62 mm Hg and mean number of preoperative topical anti-glaucomatous medications was 2.98±0.27. One eye (2%) was defined as failure because of implant extraction surgery. In the rest of the eyes, intraocular pressure (IOP) was under control with or without anti-glaucomatous medications during follow-up. The cumulative probability of complete success (IOP control without medications) was 78% at 6 months, 76% at 1 year, 71% at 2 years, 66% at 3 years, and 63% at 4 years (95% confidence interval, 61.24-87.81). The cumulative probability of eyes without complication was 64% at 6 months, 48% at 12 months, 44% at 24 months, 41% at 36 months, and 38% at 48 months (95% confidence interval, 34.64-62.85). Complete success was lower in eyes with previous ocular surgery than the eyes without (P=0.061) and it was lower in eyes with active inflammation at the time of surgery than the eyes without (P=0.011).ConclusionAGV implantation is an effective and safe alternative method in the management of UG, especially when it is performed as a primary surgical option and when no inflammation is present preoperatively.

Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma.

PubMed

Chen, Monica F; Chui, Toco Y P; Alhadeff, Paula; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Hood, Donald C

2015-01-08

To better understand the nature of glaucomatous damage of the macula, especially the structural changes seen between relatively healthy and clearly abnormal (AB) retinal regions, using an adaptive optics scanning light ophthalmoscope (AO-SLO). Adaptive optics SLO images and optical coherence tomography (OCT) vertical line scans were obtained on one eye of seven glaucoma patients, with relatively deep local arcuate defects on the 10-2 visual field test in one (six eyes) or both hemifields (one eye). Based on the OCT images, the retinal nerve fiber (RNF) layer was divided into two regions: (1) within normal limits (WNL), relative RNF layer thickness within mean control values ±2 SD; and (2) AB, relative thickness less than -2 SD value. As seen on AO-SLO, the pattern of AB RNF bundles near the border of the WNL and AB regions differed across eyes. There were normal-appearing bundles in the WNL region of all eyes and AB-appearing bundles near the border with the AB region. This region with AB bundles ranged in extent from a few bundles to the entire AB region in the case of one eye. All other eyes had a large AB region without bundles. However, in two of these eyes, a few bundles were seen within this region of otherwise missing bundles. The AO-SLO images revealed details of glaucomatous damage that are difficult, if not impossible, to see with current OCT technology. Adaptive optics SLO may prove useful in following progression in clinical trials, or in disease management, if AO-SLO becomes widely available and easy to use. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Glaucoma-Diagnostic Ability of Ganglion Cell-Inner Plexiform Layer Thickness Difference Across Temporal Raphe in Highly Myopic Eyes.

PubMed

Kim, Young Kook; Yoo, Byeong Wook; Jeoung, Jin Wook; Kim, Hee Chan; Kim, Hae Jin; Park, Ki Ho

2016-11-01

To evaluate the glaucoma-diagnostic ability of the ganglion cell-inner plexiform layer (GCIPL) thickness difference across the temporal raphe in highly myopic eyes. We consecutively enrolled a total of 195 highly myopic eyes (axial length [AL] >26.5 mm) of 195 subjects: 93 glaucoma patients along with and 102 nonglaucomatous subjects. Cirrus high-definition optical coherence tomography (OCT) was employed to scan all of the subjects' macular and optic discs. Using a MATLAB-based customized program (the GCIPL hemifield test), a positive test result was automatically declared if the following two conditions were met: (1) the horizontal line is detected for longer than one-half of the distance from the temporal inner elliptical annulus to the outer elliptical annulus, and (2) the average GCIPL thickness difference within 10 pixels of the reference line, both above and below, is 5 μm or more. The glaucoma-diagnostic ability was computed using the area under the receiver operating characteristic curve (AUC). Among the glaucomatous eyes, GCIPL hemifield test positivity was shown in 92.5% (86 of 93), significantly higher than that for the nonglaucomatous eyes (4.90%, 5 of 102; P <0.001). The value of AUC for the GCIPL hemifield test was excellent (0.938; sensitivity 92.50%, specificity 95.10%) and was the best compared with those for any of OCT parameters. In highly myopic eyes, determination of the presence or absence of GCIPL thickness difference across the temporal raphe via OCT macula scan can be a useful means of distinguishing the glaucomatous damage.

Imaging patients with glaucoma using spectral-domain optical coherence tomography and optical microangiography

NASA Astrophysics Data System (ADS)

Auyeung, Kris; Auyeung, Kelsey; Kono, Rei; Chen, Chieh-Li; Zhang, Qinqin; Wang, Ruikang K.

2015-03-01

In ophthalmology, a reliable means of diagnosing glaucoma in its early stages is still an open issue. Past efforts, including forays into fluorescent angiography (FA) and early optical coherence tomography (OCT) systems, to develop a potential biomarker for the disease have been explored. However, this development has been hindered by the inability of the current techniques to provide useful depth and microvasculature information of the optic nerve head (ONH), which have been debated as possible hallmarks of glaucoma progression. We reasoned that a system incorporating a spectral-domain OCT (SD-OCT) based Optical Microangiography (OMAG) system, could allow an effective, non-invasive methodology to evaluate effects on microvasculature by glaucoma. SD-OCT follows the principle of light reflection and interference to produce detailed cross-sectional and 3D images of the eye. OMAG produces imaging contrasts via endogenous light scattering from moving particles, allowing for 3D image productions of dynamic blood perfusion at capillary-level resolution. The purpose of this study was to investigate the optic cup perfusion (flow) differences in glaucomatous and normal eyes. Images from three normal and five glaucomatous subjects were analyzed our OCT based OMAG system for blood perfusion and structural images, allowing for comparisons. Preliminary results from blood flow analysis revealed reduced blood perfusion within the whole-depth region encompassing the Lamina Cribrosa in glaucomatous cases as compared to normal ones. We conclude that our OCT-OMAG system may provide promise and viability for glaucoma screening.

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma

PubMed Central

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-01-01

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma. PMID:29676314

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma.

PubMed

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-05-01

The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma.

Retinal nerve fiber layer thickness measured with optical coherence tomography is related to visual function in glaucomatous eyes.

PubMed

El Beltagi, Tarek A; Bowd, Christopher; Boden, Catherine; Amini, Payam; Sample, Pamela A; Zangwill, Linda M; Weinreb, Robert N

2003-11-01

To determine the relationship between areas of glaucomatous retinal nerve fiber layer thinning identified by optical coherence tomography and areas of decreased visual field sensitivity identified by standard automated perimetry in glaucomatous eyes. Retrospective observational case series. Forty-three patients with glaucomatous optic neuropathy identified by optic disc stereo photographs and standard automated perimetry mean deviations >-8 dB were included. Participants were imaged with optical coherence tomography within 6 months of reliable standard automated perimetry testing. The location and number of optical coherence tomography clock hour retinal nerve fiber layer thickness measures outside normal limits were compared with the location and number of standard automated perimetry visual field zones outside normal limits. Further, the relationship between the deviation from normal optical coherence tomography-measured retinal nerve fiber layer thickness at each clock hour and the average pattern deviation in each visual field zone was examined by using linear regression (R(2)). The retinal nerve fiber layer areas most frequently outside normal limits were the inferior and inferior temporal regions. The least sensitive visual field zones were in the superior hemifield. Linear regression results (R(2)) showed that deviation from the normal retinal nerve fiber layer thickness at optical coherence tomography clock hour positions 6 o'clock, 7 o'clock, and 8 o'clock (inferior and inferior temporal) was best correlated with standard automated perimetry pattern deviation in visual field zones corresponding to the superior arcuate and nasal step regions (R(2) range, 0.34-0.57). These associations were much stronger than those between clock hour position 6 o'clock and the visual field zone corresponding to the inferior nasal step region (R(2) = 0.01). Localized retinal nerve fiber layer thinning, measured by optical coherence tomography, is topographically related to decreased localized standard automated perimetry sensitivity in glaucoma patients.

En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography

NASA Astrophysics Data System (ADS)

Tan, Ou; Liu, Gangjun; Liang, Liu; Gao, Simon S.; Pechauer, Alex D.; Jia, Yali; Huang, David

2015-06-01

An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2×2 mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4±6.7 μl/min for healthy control and 34.7±7.6 μl/min for glaucomatous participants (p-value=0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement.

New approach to estimating variability in visual field data using an image processing technique.

PubMed Central

Crabb, D P; Edgar, D F; Fitzke, F W; McNaught, A I; Wynn, H P

1995-01-01

AIMS--A new framework for evaluating pointwise sensitivity variation in computerised visual field data is demonstrated. METHODS--A measure of local spatial variability (LSV) is generated using an image processing technique. Fifty five eyes from a sample of normal and glaucomatous subjects, examined on the Humphrey field analyser (HFA), were used to illustrate the method. RESULTS--Significant correlation between LSV and conventional estimates--namely, HFA pattern standard deviation and short term fluctuation, were found. CONCLUSION--LSV is not dependent on normals' reference data or repeated threshold determinations, thus potentially reducing test time. Also, the illustrated pointwise maps of LSV could provide a method for identifying areas of fluctuation commonly found in early glaucomatous field loss. PMID:7703196

Reference Standard Test and the Diagnostic Ability of Spectral Domain Optical Coherence Tomography in Glaucoma.

PubMed

Rao, Harsha L; Yadav, Ravi K; Addepalli, Uday K; Begum, Viquar U; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2015-08-01

To evaluate the relationship between the reference standard used to diagnose glaucoma and the diagnostic ability of spectral domain optical coherence tomograph (SDOCT). In a cross-sectional study, 280 eyes of 175 consecutive subjects, referred to a tertiary eye care center for glaucoma evaluation, underwent optic disc photography, visual field (VF) examination, and SDOCT examination. The cohort was divided into glaucoma and control groups based on 3 reference standards for glaucoma diagnosis: first based on the optic disc classification (179 glaucoma and 101 control eyes), second on VF classification (glaucoma hemifield test outside normal limits and pattern SD with P-value of <5%, 130 glaucoma and 150 control eyes), and third on the presence of both glaucomatous optic disc and glaucomatous VF (125 glaucoma and 155 control eyes). Relationship between the reference standards and the diagnostic parameters of SDOCT were evaluated using areas under the receiver operating characteristic curve, sensitivity, and specificity. Areas under the receiver operating characteristic curve and sensitivities of most of the SDOCT parameters obtained with the 3 reference standards (ranging from 0.74 to 0.88 and 72% to 88%, respectively) were comparable (P>0.05). However, specificities of SDOCT parameters were significantly greater (P<0.05) with optic disc classification as reference standard (74% to 88%) compared with VF classification as reference standard (57% to 74%). Diagnostic parameters of SDOCT that was significantly affected by reference standard was the specificity, which was greater with optic disc classification as the reference standard. This has to be considered when comparing the diagnostic ability of SDOCT across studies.

Progression of Local Glaucomatous Damage Near Fixation as Seen with Adaptive Optics Imaging.

PubMed

Hood, Donald C; Lee, Dongwon; Jarukasetphon, Ravivarn; Nunez, Jason; Mavrommatis, Maria A; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Chui, Toco Y P

2017-07-01

Deep glaucomatous defects near fixation were followed over time with an adaptive optics-scanning light ophthalmoscope (AO-SLO) to better understand the progression of these defects and to explore the use of AO-SLO in detecting them. Six eyes of 5 patients were imaged with an AO-SLO from 2 to 4 times for a range of 14.6 to 33.6 months. All eyes had open-angle glaucoma with deep defects in the superior visual field (VF) near fixation as defined by 10-2 VFs with 5 or more points less than -15 dB; two of the eyes had deep defects in the inferior VF as well. AO-SLO images were obtained around the temporal edge of the disc. In 4 of the 6 eyes, the edge of the inferior-temporal disc region of the retinal nerve fiber (RNF) defect seen on AO-SLO moved closer to fixation within 10.6 to 14.7 months. In 4 eyes, RNF bundles in the affected region appeared to lose contrast and/or disappear. Progressive changes in RNF bundles associated with deep defects on 10-2 VFs can be seen within about 1 year with AO-SLO imaging. These changes are well below the spatial resolution of the 10-2 VF. On the other hand, subtle thinning of regions with RNF bundles is not easy to see with current AO-SLO technology, and may be better followed with OCT. AO-SLO imaging may be useful in clinical trials designed to see very small changes in deep defects.

Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a prospective study

PubMed Central

Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2012-01-01

Purpose To test a framework that describes how the multifocal visual-evoked potential (mfVEP) technique is used in a particular glaucoma practice. Methods In this prospective, descriptive study, glaucoma suspects, ocular hypertensives and glaucoma patients were referred for mfVEP testing by a single glaucoma specialist over a 2-year period. All patients underwent standard automated perimetry (SAP) and mfVEP testing within 3 months. Two hundred and ten patients (420 eyes) were referred for mfVEP testing for the following reasons: (1) normal SAP tests suspected of early functional loss (ocular hypertensives, n = 43; and glaucoma suspects on the basis of suspicious optic disks, n = 52); (2) normal-tension glaucoma patients with suspected central SAP defects (n = 33); and (3) SAP abnormalities needing confirmation (n = 82). Results All the glaucoma suspects with normal SAP and mfVEP results remained untreated. Of those with abnormal mfVEP results, 68 % (15/22) were treated because the abnormal regions on the mfVEP were consistent with the abnormal regions seen during clinical examination of the optic disk. The mfVEP was abnormal in 86 % (69/80) of eyes with glaucomatous optic neuropathy and SAP damage, even though it did not result in an altered treatment regimen. In NTG patients, the mfVEP showed central defects in 44 % (12 of 27) of the eyes with apparently normal central fields and confirmed central scotomata in 92 % (36 of 39), leading to more rigorous surveillance of these patients. Conclusions In a clinical practice, the mfVEP was used when clinical examination and subjective visual fields provided insufficient or conflicting information. This information influenced clinical management. PMID:22476612

Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a prospective study.

PubMed

De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2012-08-01

To test a framework that describes how the multifocal visual-evoked potential (mfVEP) technique is used in a particular glaucoma practice. In this prospective, descriptive study, glaucoma suspects, ocular hypertensives and glaucoma patients were referred for mfVEP testing by a single glaucoma specialist over a 2-year period. All patients underwent standard automated perimetry (SAP) and mfVEP testing within 3 months. Two hundred and ten patients (420 eyes) were referred for mfVEP testing for the following reasons: (1) normal SAP tests suspected of early functional loss (ocular hypertensives, n = 43; and glaucoma suspects on the basis of suspicious optic disks, n = 52); (2) normal-tension glaucoma patients with suspected central SAP defects (n = 33); and (3) SAP abnormalities needing confirmation (n = 82). All the glaucoma suspects with normal SAP and mfVEP results remained untreated. Of those with abnormal mfVEP results, 68 % (15/22) were treated because the abnormal regions on the mfVEP were consistent with the abnormal regions seen during clinical examination of the optic disk. The mfVEP was abnormal in 86 % (69/80) of eyes with glaucomatous optic neuropathy and SAP damage, even though it did not result in an altered treatment regimen. In NTG patients, the mfVEP showed central defects in 44 % (12 of 27) of the eyes with apparently normal central fields and confirmed central scotomata in 92 % (36 of 39), leading to more rigorous surveillance of these patients. In a clinical practice, the mfVEP was used when clinical examination and subjective visual fields provided insufficient or conflicting information. This information influenced clinical management.

Thermo-mechanical mechanism of laser-assisted alteration and stabilization of micro pore structure in eye-sclera

NASA Astrophysics Data System (ADS)

Baum, Olga; Wachsmann-Hogiu, Sebastian; Sobol, Emil

2018-02-01

Thermo-mechanical effect of laser radiation is a basis of new method of normalization of intraocular pressure in glaucomatous eyes due to laser-assisted pore formation in eye sclera. Laser-induced creation of pores in sclera increases hydraulic permeability. Stability of laser-induced pore system is achieved via gas nano-bubbles arisen in the sclera under laser radiation as a result of temperature dependency of gas solubility. The stabilization of laser-induced gas and pore systems in the tissue is an important mechanism for a long lasting healing of glaucoma observed in clinical trials with one year follow-up.

Antiglaucomatous effects of the activation of intrinsic Angiotensin-converting enzyme 2.

PubMed

Foureaux, Giselle; Nogueira, José C; Nogueira, Bárbara S; Fulgêncio, Gustavo O; Menezes, Gustavo B; Fernandes, Simone O A; Cardoso, Valbert N; Fernandes, Renata S; Oliveira, Gabriel P; Franca, Juçara R; Faraco, André A G; Raizada, Mohan K; Ferreira, Anderson J

2013-06-21

To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats. DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy. The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor. Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin-angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma.

Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers

PubMed Central

2014-01-01

Background Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. Methods Two groups of adult Swiss mice were used: age-matched control (naïve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. Results The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. Conclusions Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology. PMID:25064005

Assessment of Filtration Bleb and Endplate Positioning Using Magnetic Resonance Imaging in Eyes Implanted with Long-Tube Glaucoma Drainage Devices.

PubMed

Sano, Ichiya; Tanito, Masaki; Uchida, Koji; Katsube, Takashi; Kitagaki, Hajime; Ohira, Akihiro

2015-01-01

To evaluate ocular fluid filtration and endplate positioning in glaucomatous eyes with long-tube glaucoma drainage devices (GDDs) using magnetic resonance imaging (MRI) and the effects of various factors on postoperative intraocular pressure (IOP). This observational case series included 27 consecutive glaucomatous eyes (18 men, 7 women; mean age ± standard error, 63.0±2.0 years) who underwent GDD implantation (n = 8 Ahmed Glaucoma Valves [AGV] and n = 19 Baerveldt Glaucoma Implants [BGI]). Tubes were inserted into the pars plana in 23 eyes and anterior chamber in 4 eyes. Six months postoperatively, high-resolution orbital images were obtained using 3-Tesla MRI with head-array coils, and the filtering bleb volume, bleb height, and distances between the anterior endplate edge and corneal center or limbus or between the endplate and orbital wall were measured. In MR images obtained by three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA) sequences, the shunt endplate was identified as low-intensity signal, and the filtering bleb was identified as high-intensity signals above and below the endplate in all eyes. The 6-month-postoperative IOP level was correlated negatively with bleb volume (r = -0.4510, P = 0.0182) and bleb height (r = -0.3954, P = 0.0412). The postoperative IOP was significantly (P = 0.0026) lower in BGI-implanted eyes (12.2±0.7 mmHg) than AGV-implanted eyes (16.7±1.2 mmHg); bleb volume was significantly (P = 0.0093) larger in BGI-implanted eyes (478.8±84.2 mm3) than AGV-implanted eyes (161.1±52.3 mm3). Other parameters did not differ. The presence of intraorbital/periocular accumulation of ocular fluid affects postoperative IOP levels in eyes implanted with long-tube GDDs. Larger filtering blebs after BGI than AGI implantations explain lower postoperative IOP levels achieved with BGI than AGV. The findings will contribute to better understanding of IOP reducing mechanism of long-tube GDDs.

Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.

PubMed

Ciolino, Joseph B; Ross, Amy E; Tulsan, Rehka; Watts, Amy C; Wang, Rong-Fang; Zurakowski, David; Serle, Janet B; Kohane, Daniel S

2016-10-01

To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. Preclinical efficacy study of 3 treatment arms in a crossover design. Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. Intraocular pressure. Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05). Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A 10-year follow-up to determine the effect of YAG laser iridotomy on the natural history of pigment dispersion syndrome: a randomized clinical trial.

PubMed

Gandolfi, Stefano A; Ungaro, Nicola; Tardini, Maria Grazia; Ghirardini, Stella; Carta, Arturo; Mora, Paolo

2014-12-01

Prospective long-term analyses of the role of drug-induced mydriasis and laser peripheral iridotomy (LPI) are needed to identify and manage the eyes of patients with pigment dispersion syndrome (PDS) at risk for progressing to ocular hypertension. To assess the 10-year incidence of increased intraocular pressure (IOP) in the 2 eyes of patients with PDS, with 1 eye that underwent LPI and the other that did not. In a randomized clinical trial in the glaucoma research unit at the University Hospital of Parma, Italy, 72 patients with PDS underwent phenylephrine testing. Of these 72 patients, 29 (58 eyes) tested positive for succeeding IOP elevation, and 43 (59 eyes) tested negative. For the 29 high-risk patients (all in both eyes), one eye was randomly assigned to LPI, and the fellow eye was left untreated. For the 43 low-risk patients, the affected eyes were left untreated. An IOP elevation of 5 mm Hg or higher vs baseline (daily phasing) was considered to be a significant increase (ie, an event). In the high-risk group, 3 of 21 eyes that underwent LPI (14.3%) and 13 of 21 untreated eyes (61.9%) showed an increase in IOP of 5 mm Hg or higher during the follow-up period; 4 of 35 low-risk eyes (11.4%) showed a similar increase. Event-free mean (SD) time was 7.99 (0.43) years for high-risk treated eyes, 3.89 (0.68) years for high-risk untreated eyes, and 7.16 (0.23) years for low-risk eyes. The log-rank test showed the following: P < .001 for treated high-risk eyes vs untreated high-risk eyes, P = .74 for treated high-risk eyes vs low-risk eyes, and P < .001 for untreated high-risk eyes vs low-risk eyes. At the end of the 10-year follow-up, (1) approximately one-third of the whole PDS patient population showed an IOP increase of 5 mm Hg or higher in at least 1 eye; (2) phenylephrine testing identified eyes at high risk for developing IOP elevation; and (3) LPI, when performed on high-risk eyes, reduced the rate of IOP elevation to the same level as the low-risk eyes. clinicaltrials.gov Identifier: NCT01053416.

Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes with glaucomatous optic neuropathy.

PubMed

De Moraes, Carlos Gustavo; Ketner, Scott; Teng, Christopher C; Ehrlich, Joshua R; Raza, Ali S; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2011-08-01

We investigated changes in multifocal visual evoked potential (mfVEP) responses due to beta-zone parapapillary atrophy (ßPPA). Patients with glaucomatous optic neuropathy (GON) with or without standard achromatic perimetry (SAP) abnormalities were referred for mfVEP testing during a 2-year period. Eyes with good quality optic disc stereophotographs and reliable SAP results were included. The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed. Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical equivalent (SE) were analyzed in the multivariate model. Generalized estimated equations were used for comparisons between groups after adjusting for inter-eye associations. Of 394 eyes of 200 patients, 223 (57%) had ßPPA. The ßPPA eyes were older (59.6 ± 13.7 vs. 56.5 ± 13.7 year, P = 0.02), more myopic (-4.0 ± 3.5 vs. -1.3 ± 3.5 D, P < 0.01), and had poorer SAP scores (MD: -4.9 ± 5.2 vs. -2.6 ± 5.2 dB, P < 0.01; PSD: 4.3 ± 2.9 vs. 2.5 ± 3.0 dB, P < 0.01). By univariate analysis, mean latencies were longer in ßPPA eyes (6.1 ± 5.3 vs. 4.0 ± 5.5 ms, P < 0.01). After adjusting for differences in SE, age, and SAP MD, there was no significant difference between the two groups (P = 0.09). ßPPA eyes had lower amplitude log SNR (0.49 ± 0.16 vs. 0.56 ± 0.15, P < 0.01), which lost significance (P = 0.51) after adjusting for MD and PSD. Although eyes with ßPPA had significantly lower amplitudes and prolonged latencies than eyes without ßPPA, these differences were attributable to differences in SAP severity, age, and refractive error. Thus, ßPPA does not appear to be an independent factor affecting mfVEP responses in eyes with GON.

Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes with glaucomatous optic neuropathy

PubMed Central

Ketner, Scott; Teng, Christopher C.; Ehrlich, Joshua R.; Raza, Ali S.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2015-01-01

We investigated changes in multifocal visual evoked potential (mfVEP) responses due to beta-zone parapapillary atrophy (βPPA). Patients with glaucomatous optic neuropathy (GON) with or without standard achromatic perimetry (SAP) abnormalities were referred for mfVEP testing during a 2-year period. Eyes with good quality optic disc stereophotographs and reliable SAP results were included. The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed. Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical equivalent (SE) were analyzed in the multivariate model. Generalized estimated equations were used for comparisons between groups after adjusting for inter-eye associations. Of 394 eyes of 200 patients, 223 (57%) had βPPA. The βPPA eyes were older (59.6 ± 13.7 vs. 56.5 ± 13.7 year, P = 0.02), more myopic (−4.0 ± 3.5 vs. −1.3 ± 3.5 D, P < 0.01), and had poorer SAP scores (MD: −4.9 ± 5.2 vs. −2.6 ± 5.2 dB, P < 0.01; PSD: 4.3 ± 2.9 vs. 2.5 ± 3.0 dB, P < 0.01). By univariate analysis, mean latencies were longer in βPPA eyes (6.1 ± 5.3 vs. 4.0 ± 5.5 ms, P < 0.01). After adjusting for differences in SE, age, and SAP MD, there was no significant difference between the two groups (P = 0.09). βPPA eyes had lower amplitude log SNR (0.49 ± 0.16 vs. 0.56 ± 0.15, P < 0.01), which lost significance (P = 0.51) after adjusting for MD and PSD. Although eyes with βPPA had significantly lower amplitudes and prolonged latencies than eyes without βPPA, these differences were attributable to differences in SAP severity, age, and refractive error. Thus, βPPA does not appear to be an independent factor affecting mfVEP responses in eyes with GON. PMID:21735265

Multifocal VEP and OCT findings in patients with primary open angle glaucoma: A cross-sectional study

PubMed Central

2012-01-01

Bakground To evaluate objectively the anatomical and functional changes of optic nerve in eyes with primary open angle glaucoma (POAG) by the joint use of optical coherence tomography (OCT) and multifocal visual evoked potentials (mfVEP). Methods 29 eyes with open angle glaucoma and visual field defects, as well as 20 eyes of 10 age-matched control normal subjects were tested. All participants underwent a complete ophthalmological examination. Moreover, Humphrey visual field test, OCT examination and recording of mfVEP were performed. Amplitude and implicit time of mfVEP, as well as RNFL thickness were measured. Differences in density components of mfVEP and in RNFL thickness among POAG eyes and control eyes were examined using Student’s t-test. Results In glaucomatous eyes the mean Retinal Response Density (RRD) was lower than normal in ring 1, 2 and 3 of mfVEP (p < 0.0001). Specifically the mean amplitude of mfVEP in POAG eyes was estimated at 34.2 ± 17.6 nV/deg2, 6.9 ± 4.8 nV/deg2 and 2.6 ± 1.6 nV/deg2 in rings 1, 2 and 3 respectively. In contrast the mean implicit time was similar to control eyes. In addition, the mean RNFL thickness in POAG eyes was estimated at 76.8 ± 26.6 μm in the superior area, 52.1 ± 16.3 μm in the temporal area, 75.9 ± 32.5 μm in the inferior area and 58.6 ± 19.4 μm in the nasal area. There was a statistically significant difference in RNFL thickness in all peripapillary areas (p < 0.0001) between POAG eyes and controls, with superior and inferior area to present the highest decrease. Conclusions Our study shows that, although Standard Automatic Perimetry is the gold standard to evaluate glaucomatous neuropathy, the joint use of mfVEP and OCT could be useful in better monitoring glaucoma progression. PMID:22856337

Diagnostic ability of macular ganglion cell asymmetry for glaucoma.

PubMed

Hwang, Young Hoon; Ahn, Sang Il; Ko, Sung Ju

2015-11-01

Using spectral-domain optical coherence tomography (OCT), this study aims to investigate the glaucoma diagnostic ability of macular ganglion cell asymmetry analysis. A cross-sectional study was conducted. This study was performed to investigate glaucoma diagnostic ability of macular ganglion cell asymmetry analysis in eyes with various degrees of glaucoma. We enrolled 181 healthy eyes and 265 glaucomatous eyes. Glaucomatous eyes were subdivided into pre-perimetric, early, moderate and advanced-to-severe glaucoma based on visual field test results. For each eye, macular ganglion cell-inner plexiform layer (GCIPL) thickness was measured using OCT. Average GCIPL thickness, GCIPL thicknesses in superior and inferior hemispheres, absolute difference in GCIPL thickness between superior and inferior hemispheres and GCIPL asymmetry index calculated as the absolute value of log10 (inferior hemisphere thickness/superior hemisphere thickness) were analysed. Areas under the receiver operating characteristics curves (AUCs) of GCIPL parameter were calculated and compared. All of the GCIPL parameters showed good glaucoma diagnostic ability (AUCs ≥ 0.817, P < 0.01). AUCs of average, superior and inferior GCIPL thickness increased as the severity of glaucoma increased. GCIPL thickness difference and asymmetry index showed the highest AUCs in early and moderate glaucoma and lower AUCs in pre-perimetric and advanced-to-severe glaucoma. GCIPL thickness difference and asymmetry index showed better glaucoma diagnostic ability than other GCIPL parameters only in early stage of glaucoma (P < 0.05); in other stages, these parameters had similar to or worse glaucoma diagnostic ability than other GCIPL parameters. Macular ganglion cell asymmetry analysis showed good glaucoma diagnostic ability, especially in early-stage glaucoma. However, it has limited usefulness in other stages of glaucoma. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Adjuvant effect of Chakshushya Rasayana with beta-blocker eye drops in the management of progressive glaucomatous optic neuropathy: An open-label randomized controlled trial.

PubMed

Dhiman, K S; Adhoor, Veeranagouda S; Agarwal, Riju; Mehta, Amit J

2016-01-01

Primary open angle glaucoma is an insidious and chronic vision-threatening eye ailment due to neuro-retino-optic nerve degeneration, which may be due to the raised intraocular pressure (IOP) or due to independent factors. Management of glaucoma is mainly concentrated on lowering IOP that requires lifetime topical medication, different ocular medicaments for lowering of IOP, and surgical interventions, but it has its own limitations to control the progression of glaucomatous optic neuropathy (GON), and this is the reason behind the use of alternative neuroprotective adjuvants. To evaluate the neuroprotective effect of Ayurvedic line of management of progressive GON. Ingredients of trial drug Vara Fort powder ( Chakshushya Rasayana ) were procured from the Institute Pharmacy, except Swarnamakshika Bhasma , which was purchased from Dhootapapeshwar Pharmaceuticals. The patients fulfilling inclusion criteria, attending outpatient and inpatient departments, irrespective of their sex, race, religion, occupation, etc., were selected and divided into two groups with open-labeled randomization. In Group A, in addition to betaxolol (0.1%) or timolol (0.5%) (non-iobrim), Chakshushya Rasayana 6 g/day orally with Triphala Ghrita and honey along with Koshtha-Shuddhi (body-microchannel clearing treatment) protocol was tried. Nasya (oleation through nasal route) with Jeevantyadi Taila and Tarpana (eye satiation) with Go-Ghrita were also performed. In Group B (control), brimonidine (iobrim) 0.2% eye drop was used for 3 months. Significant improvement was observed in subjective parameters in Group A such as blurred vision, frequent change of presbyopic glasses, and delayed dark adaptation. Chakshushya Rasayana , if administered in a systematic approach along with a modern topical betaxolol or timolol eye drops, has a definite role in improving the lost retinal sensitivity as much as up to 12 dB in 3 months duration.

Confocal Adaptive Optics Imaging of Peripapillary Nerve Fiber Bundles: Implications for Glaucomatous Damage Seen on Circumpapillary OCT Scans.

PubMed

Hood, Donald C; Chen, Monica F; Lee, Dongwon; Epstein, Benjamin; Alhadeff, Paula; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Chui, Toco Y P

2015-04-01

To improve our understanding of glaucomatous damage as seen on circumpapillary disc scans obtained with frequency-domain optical coherence tomography (fdOCT), fdOCT scans were compared to images of the peripapillary retinal nerve fiber (RNF) bundles obtained with an adaptive optics-scanning light ophthalmoscope (AO-SLO). The AO-SLO images and fdOCT scans were obtained on 6 eyes of 6 patients with deep arcuate defects (5 points ≤-15 db) on 10-2 visual fields. The AO-SLO images were montaged and aligned with the fdOCT images to compare the RNF bundles seen with AO-SLO to the RNF layer thickness measured with fdOCT. All 6 eyes had an abnormally thin (1% confidence limit) RNF layer (RNFL) on fdOCT and abnormal (hyporeflective) regions of RNF bundles on AO-SLO in corresponding regions. However, regions of abnormal, but equal, RNFL thickness on fdOCT scans varied in appearance on AO-SLO images. These regions could be largely devoid of RNF bundles (5 eyes), have abnormal-appearing bundles of lower contrast (6 eyes), or have isolated areas with a few relatively normal-appearing bundles (2 eyes). There also were local variations in reflectivity of the fdOCT RNFL that corresponded to the variations in AO-SLO RNF bundle appearance. Relatively similar 10-2 defects with similar fdOCT RNFL thickness profiles can have very different degrees of RNF bundle damage as seen on fdOCT and AO-SLO. While the results point to limitations of fdOCT RNFL thickness as typically analyzed, they also illustrate the potential for improving fdOCT by attending to variations in local intensity.

Cataract Surgery Outcomes in Glaucomatous Eyes: Results From the Veterans Affairs Ophthalmic Surgery Outcomes Data Project.

PubMed

Turalba, Angela; Payal, Abhishek R; Gonzalez-Gonzalez, Luis A; Cakiner-Egilmez, Tulay; Chomsky, Amy S; Vollman, David E; Baze, Elizabeth F; Lawrence, Mary; Daly, Mary K

2015-10-01

To compare visual acuity outcomes, vision-related quality of life, and complications related to cataract surgery in eyes with and without glaucoma. Retrospective cohort study. Cataract surgery outcomes in cases with and without glaucoma from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project were compared. We identified 608 glaucoma cases and 4306 controls undergoing planned cataract surgery alone. After adjusting for age, pseudoexfoliation, small pupil, prior ocular surgery, and anterior chamber depth, we found that glaucoma cases were more likely to have posterior capsular tear with vitrectomy (odds ratio [OR] 1.8, P = .03) and sulcus intraocular lens placement (OR 1.65, P = .03) during cataract surgery. Glaucoma cases were more likely to have postoperative inflammation (OR 1.73, P < .0001), prolonged elevated intraocular pressure (OR 2.96, P = .0003), and additional surgery within 30 days (OR 1.92, P = .03). Mean best-corrected visual acuity (BCVA) and Visual Function Questionnaire (VFQ) scores significantly improved after cataract surgery in both groups (P < .0001), but there were larger improvements in BCVA (P = .01) and VFQ composite scores (P < .0001) in the nonglaucoma vs the glaucoma group. A total of 3621 nonglaucoma cases (94.1%) had postoperative BCVA 20/40 or better, compared to 466 glaucoma cases (89.6%) (P = .0003). Eyes with glaucoma are at increased risk for complications and have more modest visual outcomes after cataract surgery compared to eyes without glaucoma. Despite this, glaucoma patients still experience significant improvement in vision-related outcomes after cataract extraction. Further study is needed to explore potential factors that influence cataract surgery outcomes in glaucomatous eyes. Published by Elsevier Inc.

Dichoptic stimulation improves detection of glaucoma with multifocal visual evoked potentials.

PubMed

Arvind, Hemamalini; Klistorner, Alexander; Graham, Stuart; Grigg, John; Goldberg, Ivan; Klistorner, Asya; Billson, Frank A

2007-10-01

To determine whether simultaneous binocular (dichoptic) stimulation for multifocal visual evoked potentials (mfVEP) detects glaucomatous defects and decreases intereye variability. Twenty-eight patients with glaucoma and 30 healthy subjects underwent mfVEP on monocular and dichoptic stimulation. Dichoptic stimulation was presented with the use of virtual reality goggles (recording time, 7 minutes). Monocular mfVEPs were recorded sequentially for each eye (recording time, 10 minutes). Comparison of mean relative asymmetry coefficient (RAC; calculated as difference in amplitudes between eyes/sum of amplitudes of both eyes at each segment) on monocular and dichoptic mfVEP revealed significantly lower RAC on dichoptic (0.003 +/- 0.03) compared with monocular testing (-0.02 +/- 0.04; P = 0.002). In all 28 patients, dichoptic mfVEP identified defects with excellent topographic correspondence. Of 56 hemifields (28 eyes), 33 had Humphrey visual field (HFA) scotomas, all of which were detected by dichoptic mfVEP. Among 23 hemifields with normal HFA, two were abnormal on monocular and dichoptic mfVEP. Five hemifields (five patients) normal on HFA and monocular mfVEP were abnormal on dichoptic mfVEP. In all five patients, corresponding rim changes were observed on disc photographs. Mean RAC of glaucomatous eyes was significantly higher on dichoptic (0.283 +/- 0.18) compared with monocular (0.199 +/- 0.12) tests (P = 0.0006). Dichoptic mfVEP not only detects HFA losses, it may identify early defects in areas unaffected on HFA and monocular mfVEP while reducing testing time by 30%. Asymmetry was tighter among healthy subjects but wider in patients with glaucoma on simultaneous binocular stimulation, which is potentially a new tool in the early detection of glaucoma.

Determination of cup-to-disc ratio of optical nerve head for diagnosis of glaucoma on stereo retinal fundus image pairs

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Nakagawa, Toshiaki; Sawada, Akira; Hatanaka, Yuji; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

2009-02-01

A large cup-to-disc (C/D) ratio, which is the ratio of the diameter of the depression (cup) to that of the optical nerve head (ONH, disc), can be one of the important signs for diagnosis of glaucoma. Eighty eyes, including 25 eyes with the signs of glaucoma, were imaged by a stereo retinal fundus camera. An ophthalmologist provided the outlines of cup and disc on a regular monitor and on the stereo display. The depth image of the ONH was created by determining the corresponding pixels in a pair of images based on the correlation coefficient in localized regions. The areas of the disc and cup were determined by use of the red component in one of the color images and by use of the depth image, respectively. The C/D ratio was determined based on the largest vertical lengths in the cup and disc areas, which was then compared with that by the ophthalmologist. The disc areas determined by the computerized method agreed relatively well with those determined by the ophthalmologist, whereas the agreement for the cup areas was somewhat lower. When C/D ratios were employed for distinction between the glaucomatous and non-glaucomatous eyes, the area under the receiver operating characteristic curve (AUC) was 0.83. The computerized analysis of ONH can be useful for diagnosis of glaucoma.

En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography

PubMed Central

Tan, Ou; Liu, Gangjun; Liang, Liu; Gao, Simon S.; Pechauer, Alex D.; Jia, Yali; Huang, David

2015-01-01

Abstract. An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2×2  mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4±6.7  μl/min for healthy control and 34.7±7.6  μl/min for glaucomatous participants (p-value=0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement. PMID:26062663

Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma.

PubMed

Mead, Ben; Hill, Lisa J; Blanch, Richard J; Ward, Kelly; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2016-04-01

Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a(+) RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Lipofuscin accumulation and autophagy in glaucomatous human lamina cribrosa cells.

PubMed

McElnea, Elizabeth M; Hughes, Emily; McGoldrick, Aloysius; McCann, Amanda; Quill, Barry; Docherty, Neil; Irnaten, Mustapha; Farrell, Michael; Clark, Abbot F; O'Brien, Colm J; Wallace, Deborah M

2014-12-02

Disease associated alterations in the phenotype of lamina cribrosa (LC) cells are implicated in changes occurring at the optic nerve head (ONH) in glaucoma. Lipofuscin, the formation of which is driven by reactive oxygen species (ROS), is an intralysosomal, non-degradable, auto-fluorescent macromolecule which accumulates with age and can affect autophagy - the lysosomal degradation of a cell's constituents. We aimed to compare the content of lipofuscin-like material and markers of autophagy in LC cells from normal and glaucoma donor eyes. The number and size of peri-nuclear lysosomes were examined by transmission electron microscopy (TEM). Cellular auto-fluorescence was quantified by flow cytometry. Cathepsin K mRNA levels were assessed by PCR. Autophagy protein 5 (Atg5) mRNA and protein levels were analysed by PCR and Western blot. Protein levels of subunits of the microtubule associated proteins (MAP) 1A and 1B, light chain 3 (LC3) I and II were analysed by Western blot. Immunohistochemical staining of LC3-II in ONH sections from normal and glaucomatous donor eyes was performed. A significant increase in the number of peri-nuclear lysosomes [4.1 × 10,000 per high power field (h.p.f.) ± 1.9 vs. 2.0 × 10,000 per h.p.f. ± 1.3, p = 0.002, n = 3] and whole cell auto-fluorescence (83.62 ± 45.1 v 41.01 ± 3.9, p = 0.02, n = 3) was found in glaucomatous LC cells relative to normal LC cells. Glaucomatous LC cells possessed significantly higher levels of Cathepsin K mRNA and Atg5 mRNA and protein. Enhanced levels of LC3-II were found in both LC cells and optic nerve head sections from glaucoma donors. Increased lipofuscin formation is characteristic of LC cells from donors with glaucoma. This finding confirms the importance of oxidative stress in glaucoma pathogenesis. Intracellular lipofuscin accumulation may have important effects on autophagy the modification of which could form the basis for future novel glaucoma treatments.

The Post-Illumination Pupil Response Is Reduced in Glaucoma Patients

PubMed Central

Kankipati, Laxmikanth; Girkin, Christopher A.; Gamlin, Paul D.

2011-01-01

Purpose. The post-illumination pupil response (PIPR), which is driven by the intrinsic response of melanopsin-containing, intrinsically photosensitive retinal ganglion cells, has previously been characterized in healthy eyes. The present study examined whether the PIPR is affected in patients with glaucoma compared with healthy subjects. Methods. Sixteen glaucoma patients (mean age, 63.7 years) were tested by presenting a 60°, 10-second light stimulus (13 log quanta/cm2/s retinal irradiance) of either 470 nm (blue) or 623 nm (red) to one eye after dilation. The consensual pupil response of the fellow undilated eye was recorded by infrared pupillometry for 50 seconds after light offset. These pupillary responses were compared with those of 19 age-matched controls (mean age, 59 years). Results. The glaucoma patients displayed a net PIPR (blue PIPR minus red PIPR) that was significantly (t-test, P < 0.001) smaller (0.6 mm, SEM 0.12; P < 0.05) than in age-matched controls (1.3 mm, SEM 0.16; P < 0.001). For the patient population, the magnitude of the net PIPR was inversely correlated with the measured visual field loss (mean deviation) of the tested eye. Conclusions. This study demonstrates that there is a significant decrease in the ipRGC-mediated PIPR in glaucomatous patients when compared to age-matched controls. As the severity of the glaucomatous neuropathy increases, there is a correlated decrease in the PIPR. Therefore, this test has the potential for use as a clinical tool in evaluating patients with glaucoma. PMID:21212172

Detecting glaucomatous change in visual fields: Analysis with an optimization framework.

PubMed

Yousefi, Siamak; Goldbaum, Michael H; Varnousfaderani, Ehsan S; Belghith, Akram; Jung, Tzyy-Ping; Medeiros, Felipe A; Zangwill, Linda M; Weinreb, Robert N; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

2015-12-01

Detecting glaucomatous progression is an important aspect of glaucoma management. The assessment of longitudinal series of visual fields, measured using Standard Automated Perimetry (SAP), is considered the reference standard for this effort. We seek efficient techniques for determining progression from longitudinal visual fields by formulating the problem as an optimization framework, learned from a population of glaucoma data. The longitudinal data from each patient's eye were used in a convex optimization framework to find a vector that is representative of the progression direction of the sample population, as a whole. Post-hoc analysis of longitudinal visual fields across the derived vector led to optimal progression (change) detection. The proposed method was compared to recently described progression detection methods and to linear regression of instrument-defined global indices, and showed slightly higher sensitivities at the highest specificities than other methods (a clinically desirable result). The proposed approach is simpler, faster, and more efficient for detecting glaucomatous changes, compared to our previously proposed machine learning-based methods, although it provides somewhat less information. This approach has potential application in glaucoma clinics for patient monitoring and in research centers for classification of study participants. Copyright © 2015 Elsevier Inc. All rights reserved.

Premise and Prediction – How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

PubMed Central

Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

We propose that age-related alterations in optic nerve head (ONH) biomechanics underlie the clinical behavior and increased susceptibility of the aged ONH to glaucomatous damage. The literature which suggests that the aged ONH is more susceptible to glaucomatous damage at all levels of intraocular pressure is reviewed. The relevant biomechanics of the aged ONH are discussed and a biomechanical explanation for why, on average, the stiffened peripapillary scleral and lamina cribrosa connective tissues of the aged eye should lead to a shallow (senile sclerotic) form of cupping is proposed. A logic for why age-related axon loss and the optic neuropathy of glaucoma in the aged eye may overlap is discussed. Finally, we argue for a need to characterize all forms of clinical cupping into prelaminar and laminar components so as to add precision to the discussion of clinical cupping which does not currently exist. Such characterization may lead to the early detection of ONH axonal and connective tissue pathology in ocular hypertension and eventually aid in the assessment of etiology in all forms of optic neuropathy including those that may be purely age-related. PMID:18552618

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage.

PubMed

Hood, D C; Harizman, N; Kanadani, F N; Grippo, T M; Baharestani, S; Greenstein, V C; Liebmann, J M; Ritch, R

2007-07-01

To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24-2 SAP tests. For the mfVEP and 24-2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice.

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

PubMed

Castany, Marta; Jordi, Isabel; Catala, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesus

2011-03-01

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Binocular Glaucomatous Visual Field Loss and Its Impact on Visual Exploration - A Supermarket Study

PubMed Central

Aehling, Kathrin; Heister, Martin; Rosenstiel, Wolfgang; Schiefer, Ulrich; Papageorgiou, Elena

2014-01-01

Advanced glaucomatous visual field loss may critically interfere with quality of life. The purpose of this study was to (i) assess the impact of binocular glaucomatous visual field loss on a supermarket search task as an example of everyday living activities, (ii) to identify factors influencing the performance, and (iii) to investigate the related compensatory mechanisms. Ten patients with binocular glaucoma (GP), and ten healthy-sighted control subjects (GC) were asked to collect twenty different products chosen randomly in two supermarket racks as quickly as possible. The task performance was rated as “passed” or “failed” with regard to the time per correctly collected item. Based on the performance of control subjects, the threshold value for failing the task was defined as μ+3σ (in seconds per correctly collected item). Eye movements were recorded by means of a mobile eye tracker. Eight out of ten patients with glaucoma and all control subjects passed the task. Patients who failed the task needed significantly longer time (111.47 s ±12.12 s) to complete the task than patients who passed (64.45 s ±13.36 s, t-test, p<0.001). Furthermore, patients who passed the task showed a significantly higher number of glances towards the visual field defect (VFD) area than patients who failed (t-test, p<0.05). According to these results, glaucoma patients with defects in the binocular visual field display on average longer search times in a naturalistic supermarket task. However, a considerable number of patients, who compensate by frequent glancing towards the VFD, showed successful task performance. Therefore, systematic exploration of the VFD area seems to be a “time-effective” compensatory mechanism during the present supermarket task. PMID:25162522

Binocular glaucomatous visual field loss and its impact on visual exploration--a supermarket study.

PubMed

Sippel, Katrin; Kasneci, Enkelejda; Aehling, Kathrin; Heister, Martin; Rosenstiel, Wolfgang; Schiefer, Ulrich; Papageorgiou, Elena

2014-01-01

Advanced glaucomatous visual field loss may critically interfere with quality of life. The purpose of this study was to (i) assess the impact of binocular glaucomatous visual field loss on a supermarket search task as an example of everyday living activities, (ii) to identify factors influencing the performance, and (iii) to investigate the related compensatory mechanisms. Ten patients with binocular glaucoma (GP), and ten healthy-sighted control subjects (GC) were asked to collect twenty different products chosen randomly in two supermarket racks as quickly as possible. The task performance was rated as "passed" or "failed" with regard to the time per correctly collected item. Based on the performance of control subjects, the threshold value for failing the task was defined as μ+3σ (in seconds per correctly collected item). Eye movements were recorded by means of a mobile eye tracker. Eight out of ten patients with glaucoma and all control subjects passed the task. Patients who failed the task needed significantly longer time (111.47 s ±12.12 s) to complete the task than patients who passed (64.45 s ±13.36 s, t-test, p < 0.001). Furthermore, patients who passed the task showed a significantly higher number of glances towards the visual field defect (VFD) area than patients who failed (t-test, p < 0.05). According to these results, glaucoma patients with defects in the binocular visual field display on average longer search times in a naturalistic supermarket task. However, a considerable number of patients, who compensate by frequent glancing towards the VFD, showed successful task performance. Therefore, systematic exploration of the VFD area seems to be a "time-effective" compensatory mechanism during the present supermarket task.

Antiglaucomatous Effects of the Activation of Intrinsic Angiotensin-Converting Enzyme 2

PubMed Central

Foureaux, Giselle; Nogueira, José C.; Nogueira, Bárbara S.; Fulgêncio, Gustavo O.; Menezes, Gustavo B.; Fernandes, Simone O. A.; Cardoso, Valbert N.; Fernandes, Renata S.; Oliveira, Gabriel P.; Franca, Juçara R.; Faraco, André A. G.; Raizada, Mohan K.; Ferreira, Anderson J.

2013-01-01

Purpose. To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats. Methods. DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy. Results. The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor. Conclusions. Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin–angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma. PMID:23702784

SOURCES OF BINOCULAR SUPRATHRESHOLD VISUAL FIELD LOSS IN A COHORT OF OLDER WOMEN BEING FOLLOWED FOR RISK OF FALLS (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

PubMed Central

Coleman, Anne Louise

2007-01-01

Purpose To determine the sources of binocular visual field loss most strongly associated with falls in a cohort of older women. Methods In the Study of Osteoporotic Fractures, women with severe binocular visual field loss had an increased risk of two or more falls during the 12 months following the eye examination. The lens and fundus photographs of the 422 women with severe binocular visual field loss, plus a random sample of 141 white women with no, mild, or moderate binocular visual field loss—47 white women with no binocular visual field loss, 46 white women with mild binocular visual field loss, and 48 white women with moderate binocular visual field loss —were evaluated for lens opacities, glaucomatous optic nerve damage, age-related macular degeneration, and diabetic retinopathy. Results Eighty-four percent of the women with severe binocular visual field loss had ocular disease in one or both eyes. Bilateral cataracts and glaucomatous optic nerve damage were the most common sources of this severe binocular visual field loss. Approximately 15.2% of women had no evidence of lens opacities, glaucomatous optic nerve damage, age-related macular degeneration, or diabetic retinopathy. Conclusion Severe binocular visual field loss due primarily to cataracts, glaucoma, and age-related macular degeneration explains 33.3% of the falls among women who fell frequently. Because binocular visual field loss may be treatable and/or preventable, screening programs for binocular visual field loss and subsequent referral for intervention and treatment are recommended as a strategy for preventing falls among the elderly. PMID:18427619

Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

PubMed Central

Mitra, Arijit; Ramakrishnan, R.; Kader, Mohideen Abdul

2014-01-01

A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

PubMed

Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul

2014-08-01

A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

Biometric Differences between Unilateral Chronic Primary Angle Closure Glaucoma and Fellow Non-Glaucomatous Eyes.

PubMed

Wang, Wei; Li, Xinyi; Chen, Shida; Huang, Wenbin; Zhang, Xiulan

2017-11-29

To compare biometric differences between eyes with unilateral chronic primary angle-closure glaucoma (PACG) and fellow non-glaucomatous eyes in the same patient. Clinical data and imaging records of 17 patients with unilateral PACG were retrospectively reviewed. The fellow eyes with primary angle-closure (PAC) or primary angle-closure suspected (PACS) were grouped in Group 1. The PACG eyes were set as Group 2. The biometric parameters of both eyes were measured by IOL-Master, anterior segment optical coherence tomography (AS-OCT), and swept source OCT. The iris area in Group 1 was significantly thicker than that in Group 2 (1.590 ± 0.267 versus 1.365 ± 0.352, P = 0.016). Choroidal thickness in the macular region was thicker in Group 1 than in Group 2, with statistical significance at inner temporal grid (282.7 ± 121.1 versus 191.6 ± 90.3, P = 0.036), central field (297.4 ± 130.6 versus 200.1 ± 96.3, P = 0.029), inner nasal grid (283.1 ± 128.3 versus 194.8 ± 91.8, P = 0.040), and average value (265.3 ± 105.6 versus 191.1 ± 87.0, P = 0.049). Group 1 also had thicker peripapillary choroidal thickness at 1 o'clock (141.4 ± 68.4 versus 101.8 ± 39.0, P = 0.025) and 12 o'clock (141.5 ± 82.3 versus 104.5 ± 44.6, P = 0.037) compared to Group 2. The multivariate logistic regression analyses showed that only intraocular pressure was independently associated with PACG and explained 58.3% variance of PACG. In unilateral PACG, there was significant inter-eye difference in anterior and posterior segment parameters. Longitudinal comparisons are required to further understand the differences in pathology of angle closures.

Glaucoma –state of the art and perspectives on treatment

PubMed Central

Wójcik-Gryciuk, Anna; Skup, Małgorzata; Waleszczyk, Wioletta J.

2015-01-01

Glaucoma is a chronic optic neuropathy characterized by progressive damage to the optic nerve, death of retinal ganglion cells and ultimately visual field loss. It is one of the leading causes of irreversible loss of vision worldwide. The most important trigger of glaucomatous damage is elevated eye pressure, and the current standard approach in glaucoma therapy is reduction of intraocular pressure (IOP). However, despite the use of effective medications or surgical treatment leading to lowering of IOP, progression of glaucomatous changes and loss of vision among patients with glaucoma is common. Therefore, it is critical to prevent vision loss through additional treatment. To implement such treatment(s), it is imperative to identify pathophysiological changes in glaucoma and develop therapeutic methods taking into account neuroprotection. Currently, there is no method of neuroprotection with long-term proven effectiveness in the treatment of glaucoma. Among the most promising molecules shown to protect the retina and optic nerve are neurotrophic factors. Thus, the current focus is on the development of safe and non-invasive methods for the long-term elevation of the intraocular level of neurotrophins through advanced gene therapy and topical eye treatment and on the search for selective agonists of neurotrophin receptors affording more efficient neuroprotection. PMID:26684267

The Location of the Deepest Point of the Eyeball Determines the Optic Disc Configuration.

PubMed

Kim, Yong Chan; Jung, Younhea; Park, Hae-Young Lopilly; Park, Chan Kee

2017-07-19

Tilted and rotated appearances are hallmarks of the myopic optic disc. As the eyeball grows axially, the posterior pole elongates not only globally but in a localized manner as well. In this process, the optic disc is pulled towards the deepest point of the elongated eyeball, which might result in a change in optic disc configuration. Thus, we hypothesized that analyzing the variation of posterior pole contour can play a major role in understanding optic disc configuration in myopic subjects. By analyzing consecutive images of swept source OCT coronal sections at the posterior pole, the deepest interface between Bruch's membrane and the choroid could be identified as the deepest point of the eyeball (DPE). The location and the properties of the DPE differed significantly between the 125 eyes of non-glaucomatous myopic group and the 40 eyes of non-glaucomatous emmetropic group classified based on 24 mm axial length. The results suggested that the larger disc to DPE angle and the larger disc to DPE depth strongly predicts the optic disc torsion degree and the optic disc tilt. Our findings suggest that identifying the posterior pole profile plays a major role in understanding the optic disc alterations found in myopic subjects.

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage

PubMed Central

Hood, D C; Harizman, N; Kanadani, F N; Grippo, T M; Baharestani, S; Greenstein, V C; Liebmann, J M; Ritch, R

2007-01-01

Aim To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. Methods Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24‐2 SAP tests. For the mfVEP and 24‐2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). Results Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. Conclusions The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice. PMID:17301118

Peripapillary Retinoschisis in Glaucoma Patients

PubMed Central

Bayraktar, Serife; Cebeci, Zafer; Kabaalioglu, Melis; Ciloglu, Serife; Kir, Nur; Izgi, Belgin

2016-01-01

Purpose. To investigate peripapillary retinoschisis and its effect on retinal nerve fiber layer (RNFL) thickness measurements by using spectral-domain optical coherence tomography (SD-OCT) in glaucomatous eyes. Methods. Circumpapillary RNFL (cpRNFL) B-scan images of 940 glaucoma patients (Group 1) and 801 glaucoma-suspect patients (Group 2) obtained by SD-OCT were reviewed. The structural and clinical characteristics of the retinoschisis were investigated. The RNFL thickness measurements taken at the time of retinoschisis diagnosis and at the follow-up visits were also compared. Results. Twenty-nine retinoschisis areas were found in 26 of the 940 glaucoma patients (3.1%) in Group 1 and seven areas were found in 801 patients (0.87%) in Group 2. In glaucomatous eyes, the retinoschisis was attached to the optic disc and overlapped with the RNFL defect. At the time of retinoschisis, the RNFL thickness was statistically greater in the inferior temporal quadrant when compared with the follow-up scans (p < 0.001). No macular involvement or retinal detachment was observed. Conclusion. The present study investigated 33 peripapillary retinoschisis patients. Increase in RNFL thickness measurements was observed at the time of retinoschisis. It is important to examine the cpRNFL B-scan images of glaucoma patients so that the RNFL thickness is not overestimated. PMID:27069674

Glaucoma Diagnostic Capability of Circumpapillary Retinal Nerve Fiber Layer Thickness in Circle Scans With Different Diameters.

PubMed

Ghassibi, Mark P; Chien, Jason L; Patthanathamrongkasem, Thipnapa; Abumasmah, Ramiz K; Rosman, Michael S; Skaat, Alon; Tello, Celso; Liebmann, Jeffrey M; Ritch, Robert; Park, Sung Chul

2017-04-01

To compare varying circumpapillary optical coherence tomographic (OCT) scan diameters for glaucoma diagnosis. Prospective, cross-sectional, observational study. Circumpapillary retinal nerve fiber layer thickness (RNFLT) was measured using spectral-domain OCT in 1 randomly selected eye. Scans with diameters of 3.5, 4.1, and 4.7 mm were obtained, each with 7 parameters: mean global (G) RNFLT and mean RNFLT for the temporal-inferior (TI), nasal-inferior (NI), temporal-superior (TS), nasal-superior (NS), nasal (N), and temporal (T) sectors. Areas under the receiver operating characteristic curve (AUCs) were calculated. Mean age was 55±18 years in 68 healthy eyes and 59±15 years in 95 glaucomatous eyes (P=0.12). Visual field mean deviation was -7.55±6.61 dB in glaucomatous eyes. In all 3 circle scans, mean TI RNFLT had the greatest AUC (0.974 to 0.983), followed by mean G RNFLT (0.949 to 0.956). The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean TI RNFLTs in the 4.7- (0.978; P=0.128) and 3.5-mm (0.974; P=0.049) scans. The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean G RNFLTs in the 3.5- (0.954; P=0.011), 4.1- (0.956; P=0.016), and 4.7-mm (0.949; P=0.011) scans. In 2 eyes with large parapapillary atrophy, RNFL segmentation error was noted only in the 3.5-mm scan in the area of parapapillary atrophy. Further investigations to find the spectral-domain OCT circle scan diameter with the best diagnostic capability and the least artifacts are warranted, especially focusing on larger-than-conventional circle scans.

The Impact of Retardance Pattern Variability on Nerve Fiber Layer Measurements over Time Using GDx with Variable and Enhanced Corneal Compensation

PubMed Central

Grewal, Dilraj S.; Sehi, Mitra; Cook, Richard J.

2011-01-01

Purpose. To examine the impact of retardance pattern variability on retinal nerve fiber layer (RNFL) measurements over time using scanning laser polarimetry with variable (GDxVCC) and enhanced corneal compensation (GDxECC; both by Carl Zeiss Meditec, Inc., Dublin, CA). Methods. Glaucoma suspect and glaucomatous eyes with 4 years of follow-up participating in the Advanced Imaging in Glaucoma Study were prospectively enrolled. All eyes underwent standard automated perimetry (SAP), GDxVCC, and GDxECC imaging every 6 months. SAP progression was determined with point-wise linear regression analysis of SAP sensitivity values. Typical scan score (TSS) values were extracted as a measure of retardance image quality; an atypical retardation pattern (ARP) was defined as TSS < 80. TSS fluctuation over time was measured using three parameters: change in TSS from baseline, absolute difference (maximum minus minimum TSS value), and TSS variance. Linear mixed-effects models that accommodated the association between the two eyes were constructed to evaluate the relationship between change in TSS and RNFL thickness over time. Results. Eighty-six eyes (51 suspected glaucoma, 35 glaucomatous) of 45 patients were enrolled. Twenty (23.3%) eyes demonstrated SAP progression. There was significantly greater fluctuation in TSS over time with GDxVCC compared with GDxECC as measured by absolute difference (18.40 ± 15.35 units vs. 2.50 ± 4.69 units; P < 0.001), TSS variance (59.63 ± 87.27 units vs. 3.82 ± 9.63 units, P < 0.001), and change in TSS from baseline (−0.83 ± 11.2 vs. 0.25 ± 2.9, P = 0.01). The change in TSS over time significantly (P = 0.006) influenced the TSNIT average RNFL thickness when measured by GDxVCC but not by GDxECC. Conclusions. Longitudinal images obtained with GDxECC have significantly less variability in TSS and retardance patterns and have reduced bias produced by ARP on RNFL progression assessment. PMID:21296821

Angle-closure glaucoma in an urban population in southern India. The Andhra Pradesh eye disease study.

PubMed

Dandona, L; Dandona, R; Mandal, P; Srinivas, M; John, R K; McCarty, C A; Rao, G N

2000-09-01

To assess the prevalence and features of angle-closure glaucoma (ACG) in an urban population in southern India. A population-based, cross-sectional study. A total of 2522 (85.4% of those eligible) persons of all ages, including 1399 persons 30 years of age or older, from 24 clusters representative of the population of Hyderabad city. The participants underwent an interview and detailed eye examination that included logarithm of minimum angle of resolution visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, and gonioscopy; pupil dilatation and stereoscopic fundus evaluation was performed if the risk of angle-closure as a result of dilatation was not believed to be imminent. Humphrey threshold 24-2 visual fields (Humphrey Instruments Inc., San Leandro, CA) were performed when indicated by standardized criteria for disc damage or if intraocular pressure (IOP) was 22 mmHg or more. An occludable angle was defined as pigmented posterior trabecular meshwork not visible by gonioscopy in three quarters or more of the angle circumference. Manifest primary angle-closure glaucoma (PACG) was defined as IOP of 22 mmHg or more or glaucomatous optic disc damage with visual field loss in the presence of an occludable angle. An IOP of 22 mmHg or more or glaucomatous optic disc damage in the presence of an occludable angle secondary to an obvious cause was defined as secondary ACG. Manifest PACG and occludable angles without ACG were present in 12 and 24 participants, respectively, with age- and gender-adjusted prevalence (95% confidence interval [CI]) of 0.71% (0.34%-1.31%) and 1.41% (0.73%-2.09%) in participants 30 years of age or older, and 1.08% (0.36%-1.80%) and 2.21% (1.15%-3.27%) in participants 40 years of age or older, respectively. With multivariate analysis, the prevalence of these two conditions considered together increased significantly with age (P < 0.001); although not statistically significant, these were more common in females (odds ratio 1.70; 95% CI, 0.82-3.54) and in those belonging to lower socioeconomic strata as compared with middle and upper strata (odds ratio, 1.82; 95% CI, 0.88-3.74). The odds of manifest PACG were higher in the presence of hyperopia of more than 2 diopters ([D]; odds ratio, 3.69; 95% CI, 0.89-15.2). Only four of 12 participants (33.3%) with manifest PACG had been previously diagnosed, and one of 12 (8.3%) had peripheral iridotomy performed previously. Manifest PACG had caused blindness in one or both eyes in five of these 12 participants (41.7%); best-corrected distance visual acuity less than 20/400 in one or both eyes in four patients, and acuity less than 20/200 in one eye in another patient. Most (83.3%) of those with manifest PACG could be classified as having chronic form of the disease. We may have underestimated manifest PACG because visual fields were per- formed only on those with clinical suspicion of optic disc damage. Secondary ACG was present in two participants. The prevalence of PACG in this urban population in southern India is close to that reported recently in a Mongolian population. A large proportion of the PACG in this population was undiagnosed and untreated. Because visual loss resulting from PACG is potentially preventable if peripheral iridotomy or iridectomy is performed in the early stage, strategies for early detection of PACG could reduce the high risk of blindness resulting from PACG seen in this urban population in India.

Automatic segmentation of the optic nerve head for deformation measurements in video rate optical coherence tomography

NASA Astrophysics Data System (ADS)

Hidalgo-Aguirre, Maribel; Gitelman, Julian; Lesk, Mark Richard; Costantino, Santiago

2015-11-01

Optical coherence tomography (OCT) imaging has become a standard diagnostic tool in ophthalmology, providing essential information associated with various eye diseases. In order to investigate the dynamics of the ocular fundus, we present a simple and accurate automated algorithm to segment the inner limiting membrane in video-rate optic nerve head spectral domain (SD) OCT images. The method is based on morphological operations including a two-step contrast enhancement technique, proving to be very robust when dealing with low signal-to-noise ratio images and pathological eyes. An analysis algorithm was also developed to measure neuroretinal tissue deformation from the segmented retinal profiles. The performance of the algorithm is demonstrated, and deformation results are presented for healthy and glaucomatous eyes.

Dry eye syndrome. Etiological and therapeutic aspects.

PubMed

Apostol, Silvia; Filip, M; Dragne, Carmen; Filip, A

2003-01-01

"Dry eye syndrome" is a common disorder of the tear film that results from inadequate tear production, excessive tear evaporation or abnormality in mucin or lipid components of the tear film. A number of 53 patients suffering from dry eye syndrome were followed up for a period of 18 months. The study group was heterogeneous, including a lot of conditions accompanied by dry eye syndrome: Syogren's syndrome, lupus erythematous, ocular rosacea, patients with systemic treatments with antidepressants, betablockers, diuretics, oral contraceptives, glaucomatous patients with topical beta-blockers, postmenopausal women, aging people, computer users and long-term contact lens wearers. The therapeutical options were dictated by the severity of the syndrome: substitution therapy, treatment of the underlying eyelid diseases, modifying of the environmental conditions and treatment of the complications in the most severe cases. The new pathological approach is innovative and it may provide a real therapeutical measure for this condition: topical A Cyclosporine and androgen drops.

Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

PubMed Central

Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

2014-01-01

Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

Comparison of manual & automated analysis methods for corneal endothelial cell density measurements by specular microscopy.

PubMed

Huang, Jianyan; Maram, Jyotsna; Tepelus, Tudor C; Modak, Cristina; Marion, Ken; Sadda, SriniVas R; Chopra, Vikas; Lee, Olivia L

2017-08-07

To determine the reliability of corneal endothelial cell density (ECD) obtained by automated specular microscopy versus that of validated manual methods and factors that predict such reliability. Sharp central images from 94 control and 106 glaucomatous eyes were captured with Konan specular microscope NSP-9900. All images were analyzed by trained graders using Konan CellChek Software, employing the fully- and semi-automated methods as well as Center Method. Images with low cell count (input cells number <100) and/or guttata were compared with the Center and Flex-Center Methods. ECDs were compared and absolute error was used to assess variation. The effect on ECD of age, cell count, cell size, and cell size variation was evaluated. No significant difference was observed between the Center and Flex-Center Methods in corneas with guttata (p=0.48) or low ECD (p=0.11). No difference (p=0.32) was observed in ECD of normal controls <40 yrs old between the fully-automated method and manual Center Method. However, in older controls and glaucomatous eyes, ECD was overestimated by the fully-automated method (p=0.034) and semi-automated method (p=0.025) as compared to manual method. Our findings show that automated analysis significantly overestimates ECD in the eyes with high polymegathism and/or large cell size, compared to the manual method. Therefore, we discourage reliance upon the fully-automated method alone to perform specular microscopy analysis, particularly if an accurate ECD value is imperative. Copyright © 2017. Published by Elsevier España, S.L.U.

Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

PubMed

Teng, Christopher C; De Moraes, Carlos Gustavo V; Prata, Tiago S; Tello, Celso; Ritch, Robert; Liebmann, Jeffrey M

2010-05-01

Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (<525 microm) had a weak but significant correlation with presence of beta-zone PPA (kappa = 0.13). Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Acute shallowing of the anterior chamber.

PubMed Central

Mapstone, R

1981-01-01

In aging eyes phenylephrine drops have no significant effect on the depth of the anterior chamber, whereas pilocarpine drops produce a significant shallowing. If both drugs are instilled simultaneously, a significantly greater decrease in anterior chamber depth occurs. The effect is seen in normal, glaucomatous, and hypertensive eyes, and in eyes with shallow anterior chambers. It did not occur in eyes that had had an iridectomy. During the course of a positive provocative test an acute reduction in anterior depth occurs which is reversed when the angle opens and pressure returns to normal levels. It is concluded that the depth of the anterior chamber is not a static dimension but that changes can occur which are rapid and transient. The mechanism of shallowing and deepening depends on an increase or a decrease in the pupil block force. It is a necessary consequence too that eyes with nonshallow anterior chambers can get closed-angle glaucoma and that this possibility cannot be detected by a conventional gonioscopic approach. PMID:6455153

Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.

PubMed

Martin, Keith R G; Levkovitch-Verbin, Hana; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Quigley, Harry A

2002-07-01

High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.

Relevance Vector Machine and Support Vector Machine Classifier Analysis of Scanning Laser Polarimetry Retinal Nerve Fiber Layer Measurements

PubMed Central

Bowd, Christopher; Medeiros, Felipe A.; Zhang, Zuohua; Zangwill, Linda M.; Hao, Jiucang; Lee, Te-Won; Sejnowski, Terrence J.; Weinreb, Robert N.; Goldbaum, Michael H.

2010-01-01

Purpose To classify healthy and glaucomatous eyes using relevance vector machine (RVM) and support vector machine (SVM) learning classifiers trained on retinal nerve fiber layer (RNFL) thickness measurements obtained by scanning laser polarimetry (SLP). Methods Seventy-two eyes of 72 healthy control subjects (average age = 64.3 ± 8.8 years, visual field mean deviation =−0.71 ± 1.2 dB) and 92 eyes of 92 patients with glaucoma (average age = 66.9 ± 8.9 years, visual field mean deviation =−5.32 ± 4.0 dB) were imaged with SLP with variable corneal compensation (GDx VCC; Laser Diagnostic Technologies, San Diego, CA). RVM and SVM learning classifiers were trained and tested on SLP-determined RNFL thickness measurements from 14 standard parameters and 64 sectors (approximately 5.6° each) obtained in the circumpapillary area under the instrument-defined measurement ellipse (total 78 parameters). Tenfold cross-validation was used to train and test RVM and SVM classifiers on unique subsets of the full 164-eye data set and areas under the receiver operating characteristic (AUROC) curve for the classification of eyes in the test set were generated. AUROC curve results from RVM and SVM were compared to those for 14 SLP software-generated global and regional RNFL thickness parameters. Also reported was the AUROC curve for the GDx VCC software-generated nerve fiber indicator (NFI). Results The AUROC curves for RVM and SVM were 0.90 and 0.91, respectively, and increased to 0.93 and 0.94 when the training sets were optimized with sequential forward and backward selection (resulting in reduced dimensional data sets). AUROC curves for optimized RVM and SVM were significantly larger than those for all individual SLP parameters. The AUROC curve for the NFI was 0.87. Conclusions Results from RVM and SVM trained on SLP RNFL thickness measurements are similar and provide accurate classification of glaucomatous and healthy eyes. RVM may be preferable to SVM, because it provides a Bayesian-derived probability of glaucoma as an output. These results suggest that these machine learning classifiers show good potential for glaucoma diagnosis. PMID:15790898

Difference in glaucoma progression between the first and second eye after consecutive bilateral glaucoma surgery in patients with bilateral uveitic glaucoma.

PubMed

Din, Norshamsiah Md; Talat, Lazha; Isa, Hazlita; Tomkins-Netzer, Oren; Barton, Keith; Lightman, Sue

2016-12-01

To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE). This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software. The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF. In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit.

Lower corneal hysteresis in glaucoma patients with acquired pit of the optic nerve (APON).

PubMed

Bochmann, Frank; Ang, Ghee S; Azuara-Blanco, Augusto

2008-05-01

Acquired pit-like changes of the optic nerve head (APON) are characteristic of glaucomatous damage and may be a sign of a localized susceptibility of the optic nerve. Thus, it is possible that biomechanical properties of the ocular tissues may play a pressure-independent role in the pathogenesis of glaucoma. Corneal hysteresis (CH) appears to provide information of the biomechanical properties of the ocular hull tissues. The purpose of this study was to compare CH of patients with primary open angle glaucoma (POAG) with and without APON. A prospective case control study was done. POAG patients with and without APON were measured using the Ocular Response Analyzer by masked investigators. Patients in both groups were matched for sex, age, corneal thickness, and type of glaucoma according to maximal IOP (NTG or POAG). Statistical analysis was done using ANOVA. Corneal hysteresis of 16 glaucomatous eyes with APON and 32 controls (glaucoma without APON) was measured. The mean (+/-SD) CH in the APON group was 8.89 (+/-1.53) and 10.2 (+/-1.05) in the control group. The difference is statistically significant (p=0.005). Corneal hysteresis in POAG patients with APON was significantly lower than in patients that did not have such structural changes of the optic disc. These findings may reflect pressure-independent mechanisms involved in the pathogenesis of such glaucomatous optic nerve changes.

Frequency-doubling technology perimetry and multifocal visual evoked potential in glaucoma, suspected glaucoma, and control patients

PubMed Central

Kanadani, Fabio N; Mello, Paulo AA; Dorairaj, Syril K; Kanadani, Tereza CM

2014-01-01

Introduction The gold standard in functional glaucoma evaluation is standard automated perimetry (SAP). However, SAP depends on the reliability of the patients’ responses and other external factors; therefore, other technologies have been developed for earlier detection of visual field changes in glaucoma patients. The frequency-doubling perimetry (FDT) is believed to detect glaucoma earlier than SAP. The multifocal visual evoked potential (mfVEP) is an objective test for functional evaluation. Objective To evaluate the sensitivity and specificity of FDT and mfVEP tests in normal, suspect, and glaucomatous eyes and compare the monocular and interocular mfVEP. Methods Ninety-five eyes from 95 individuals (23 controls, 33 glaucoma suspects, 39 glaucomatous) were enrolled. All participants underwent a full ophthalmic examination, followed by SAP, FDT, and mfVEP tests. Results The area under the curve for mean deviation and pattern standard deviation were 0.756 and 0.761, respectively, for FDT, 0.564 and 0.512 for signal and alpha for interocular mfVEP, and 0.568 and 0.538 for signal and alpha for monocular mfVEP. This difference between monocular and interocular mfVEP was not significant. Conclusion The FDT Matrix was superior to mfVEP in glaucoma detection. The difference between monocular and interocular mfVEP in the diagnosis of glaucoma was not significant. PMID:25075173

Longitudinal Changes of Angle Configuration in Primary Angle-Closure Suspects

PubMed Central

Jiang, Yuzhen; Chang, Dolly S.; Zhu, Haogang; Khawaja, Anthony P.; Aung, Tin; Huang, Shengsong; Chen, Qianyun; Munoz, Beatriz; Grossi, Carlota M.

2015-01-01

Objective To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes. Design Longitudinal cohort study. Participants Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial. Methods Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI. Main Outcome Measures Angle width in degrees was calculated from Shaffer grades assessed under static gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500, AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCT images. Results No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy (P = 0.18), AOD250 (P = 0.167) and ARA (P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8–1.6) in treated eyes and 1.6°/year (95% CI, 1.3–2.0) in untreated eyes (P<0.001). Conclusions Angle width of treated eyes increased markedly after LPI, remained stable for 6 months, and then decreased significantly by 18 months after LPI. Untreated eyes experienced a more consistent and rapid decrease in angle width over the same time period. PMID:24835757

Localized Glaucomatous Change Detection within the Proper Orthogonal Decomposition Framework

PubMed Central

Balasubramanian, Madhusudhanan; Kriegman, David J.; Bowd, Christopher; Holst, Michael; Weinreb, Robert N.; Sample, Pamela A.; Zangwill, Linda M.

2012-01-01

Purpose. To detect localized glaucomatous structural changes using proper orthogonal decomposition (POD) framework with false-positive control that minimizes confirmatory follow-ups, and to compare the results to topographic change analysis (TCA). Methods. We included 167 participants (246 eyes) with ≥4 Heidelberg Retina Tomograph (HRT)-II exams from the Diagnostic Innovations in Glaucoma Study; 36 eyes progressed by stereo-photographs or visual fields. All other patient eyes (n = 210) were non-progressing. Specificities were evaluated using 21 normal eyes. Significance of change at each HRT superpixel between each follow-up and its nearest baseline (obtained using POD) was estimated using mixed-effects ANOVA. Locations with significant reduction in retinal height (red pixels) were determined using Bonferroni, Lehmann-Romano k-family-wise error rate (k-FWER), and Benjamini-Hochberg false discovery rate (FDR) type I error control procedures. Observed positive rate (OPR) in each follow-up was calculated as a ratio of number of red pixels within disk to disk size. Progression by POD was defined as one or more follow-ups with OPR greater than the anticipated false-positive rate. TCA was evaluated using the recently proposed liberal, moderate, and conservative progression criteria. Results. Sensitivity in progressors, specificity in normals, and specificity in non-progressors, respectively, were POD-Bonferroni = 100%, 0%, and 0%; POD k-FWER = 78%, 86%, and 43%; POD-FDR = 78%, 86%, and 43%; POD k-FWER with retinal height change ≥50 μm = 61%, 95%, and 60%; TCA-liberal = 86%, 62%, and 21%; TCA-moderate = 53%, 100%, and 70%; and TCA-conservative = 17%, 100%, and 84%. Conclusions. With a stronger control of type I errors, k-FWER in POD framework minimized confirmatory follow-ups while providing diagnostic accuracy comparable to TCA. Thus, POD with k-FWER shows promise to reduce the number of confirmatory follow-ups required for clinical care and studies evaluating new glaucoma treatments. (ClinicalTrials.gov number, NCT00221897.) PMID:22491406

Development of the conceptual framework for the Eye-Drop Satisfaction Questionnaire (EDSQ) in glaucoma using a qualitative study.

PubMed

Nordmann, Jean-Philippe; Denis, Philippe; Vigneux, Marc; Trudeau, Elyse; Guillemin, Isabelle; Berdeaux, Gilles

2007-08-06

Compliance is a major issue in glaucoma care. It is usually poor in glaucomatous patients, and may ultimately result in an acceleration of the disease progression and a risk of blindness. Reasons for this poor compliance are complex and multifactorial, amongst which patient satisfaction can be counted. The objective of this study was to develop a questionnaire to assess patient satisfaction and compliance with eye-drop treatment. A qualitative study was carried out to develop the questionnaire. An interview guide was developed based on a literature review. Structured interviews of fifteen French and English patients with primary open-angle glaucoma or intraocular hypertension were conducted by trained interviewers of the native language of the interviewees. General concepts and subconcepts were identified from the transcripts. The questionnaire was developed using the patient verbatim, and submitted to six patients (French and English) for cognitive debriefing. Following patients' comments, items were modified and restructured, and a pilot questionnaire was designed. Analysis of data from the interviews with patients and clinicians resulted in the elicitation of concepts related to patient satisfaction and compliance with glaucomatous treatment. These were further refined and used to generate a test questionnaire, which consisted of 46 items grouped into 6 domains: patient characteristics, treatment characteristics, patient-clinician relationship, patient experience with the disease and the treatment, interaction between the patient and the treatment, and patient knowledge of the disease and the treatment. The Eye-Drop Satisfaction Questionnaire (EDSQ) conceptual framework and items were developed simultaneously in French and in English. This questionnaire could be used to evaluate patient satisfaction and compliance with eye-drop treatment and would facilitate the identification of patients at risk of being non-compliant prior to clinical trials or innovative device tests. A psychometric study is under way to validate the questionnaire.

Glaucoma Progression Detection by Retinal Nerve Fiber Layer Measurement Using Scanning Laser Polarimetry: Event and Trend Analysis

PubMed Central

Moon, Byung Gil; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S.

2012-01-01

Purpose To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Methods Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). Results Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. Conclusions RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression. PMID:22670073

Glaucoma progression detection by retinal nerve fiber layer measurement using scanning laser polarimetry: event and trend analysis.

PubMed

Moon, Byung Gil; Sung, Kyung Rim; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S

2012-06-01

To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression.

Optical Coherence Tomography Machine Learning Classifiers for Glaucoma Detection: A Preliminary Study

PubMed Central

Burgansky-Eliash, Zvia; Wollstein, Gadi; Chu, Tianjiao; Ramsey, Joseph D.; Glymour, Clark; Noecker, Robert J.; Ishikawa, Hiroshi; Schuman, Joel S.

2007-01-01

Purpose Machine-learning classifiers are trained computerized systems with the ability to detect the relationship between multiple input parameters and a diagnosis. The present study investigated whether the use of machine-learning classifiers improves optical coherence tomography (OCT) glaucoma detection. Methods Forty-seven patients with glaucoma (47 eyes) and 42 healthy subjects (42 eyes) were included in this cross-sectional study. Of the glaucoma patients, 27 had early disease (visual field mean deviation [MD] ≥ −6 dB) and 20 had advanced glaucoma (MD < −6 dB). Machine-learning classifiers were trained to discriminate between glaucomatous and healthy eyes using parameters derived from OCT output. The classifiers were trained with all 38 parameters as well as with only 8 parameters that correlated best with the visual field MD. Five classifiers were tested: linear discriminant analysis, support vector machine, recursive partitioning and regression tree, generalized linear model, and generalized additive model. For the last two classifiers, a backward feature selection was used to find the minimal number of parameters that resulted in the best and most simple prediction. The cross-validated receiver operating characteristic (ROC) curve and accuracies were calculated. Results The largest area under the ROC curve (AROC) for glaucoma detection was achieved with the support vector machine using eight parameters (0.981). The sensitivity at 80% and 95% specificity was 97.9% and 92.5%, respectively. This classifier also performed best when judged by cross-validated accuracy (0.966). The best classification between early glaucoma and advanced glaucoma was obtained with the generalized additive model using only three parameters (AROC = 0.854). Conclusions Automated machine classifiers of OCT data might be useful for enhancing the utility of this technology for detecting glaucomatous abnormality. PMID:16249492

Structure and function in patients with glaucomatous defects near fixation.

PubMed

Shafi, Asifa; Swanson, William H; Dul, Mitchell W

2011-01-01

To assess relations between perimetric sensitivity and neuroretinal rim area using high-resolution perimetric mapping in patients with glaucomatous defects within 10° of fixation. One eye was tested in each of 31 patients with open-angle glaucoma enrolled in a prospective study of perimetric defects within 10° of fixation. Norms were derived from 110 control subjects free of eye disease, aged 21 to 81 years. Perimetric sensitivity was measured using the 10-2 test pattern with the Swedish Interactive Threshold Algorithm (SITA) standard algorithm on the Humphrey Field Analyzer (HFA) II-i; Carl Zeiss Meditec), stimulus size III. Area of the temporal neuroretinal rim was measured using the Heidelberg retina tomograph 3. Decibel values were converted into linear units of contrast sensitivity averaged across locations corresponding to the temporal rim sector. Both measures were expressed as percent of mean normal, and the Bland-Altman method was used to assess agreement. Perimetric locations corresponding to the temporal sector were determined for six different optic nerve maps. Contrast sensitivity was moderately correlated with temporal rim area (r2 >30%, p < 0.005). For all six optic nerve maps, Bland-Altman analysis found good agreement between perimetric sensitivity and rim area with both measures expressed as fraction of mean normal and confidence limits for agreement that were consistent with normal between-subject variability in control eyes. By using high-resolution perimetric mapping in patients with scotomas within 10° of fixation, we confirmed findings of linear relations between perimetric sensitivity and area of temporal neuroretinal rim and showed that the confidence limits for agreement in patients with glaucoma were consistent with normal between-subject variability.

Structure and Function in Patients with Glaucomatous Defects Near Fixation

PubMed Central

Shafi, Asifa; Swanson, William H.; Dul, Mitchell W.

2010-01-01

Purpose To assess relations between perimetric sensitivity and neuroretinal rim area using high-resolution perimetric mapping in patients with glaucomatous defects within 10 degrees of fixation. Methods One eye was tested in each of 31 patients with open angle glaucoma enrolled in a prospective study of perimetric defects within 10 degrees of fixation. Norms were derived from 110 control subjects free of eye disease ages 21 – 81. Perimetric sensitivity was measured using the 10-2 test pattern with the SITA Standard algorithm (HFAII-i, Carl Zeiss Meditec), stimulus size III. Area of the temporal neuroretinal rim was measured using the Heidelberg Retinal Tomograph (HRT III). Decibel (dB) values were converted into linear units of contrast sensitivity averaged across locations corresponding to the temporal rim sector. Both measures were expressed as percent of mean normal and the Bland-Altman method was used to assess agreement. Perimetric locations corresponding to the temporal sector were determined for six different optic nerve maps. Results Contrast sensitivity was moderately correlated with temporal rim area (r2 > 30%, p < 0.005). For all six optic nerve maps, Bland-Altman analysis found good agreement between perimetric sensitivity and rim area with both measures expressed as fraction of mean normal, and confidence limits for agreement that were consistent with normal between-subject variability in control eyes. Conclusions Using high-resolution perimetric mapping in patients with scotomas within 10° of fixation, we confirmed findings of linear relations between perimetric sensitivity and area of temporal neuroretinal rim, and showed that the confidence limits for agreement in patients with glaucoma were consistent with normal between-subject variability. PMID:20935585

Spectral Domain Optical Coherence Tomography in Glaucoma: Qualitative and Quantitative Analysis of the Optic Nerve Head and Retinal Nerve Fiber Layer (An AOS Thesis)

PubMed Central

Chen, Teresa C.

2009-01-01

Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 μm and 3 μm, respectively. Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 μm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003–.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials. PMID:20126502

Globe penetration in a cat following maxillary nerve block for dental surgery.

PubMed

Perry, Rachel; Moore, Denise; Scurrell, Emma

2015-01-01

Dental treatment was carried out in an 8.5-year-old castrated male domestic shorthair cat found to have tooth resorption. Right mandibular, and right and left maxillary nerve blocks were administered using a 1 ml syringe attached to a 25 G x 5/8 inch needle and an intraoral technique. The following day the cat displayed blepharospasm of the right eye. The ocular signs progressed and 5 days later an ophthalmologist confirmed a blind, glaucomatous right eye. It was suspected that the eye had suffered a penetrating injury during dental surgery. Enucleation of the right eye was performed and gross and histopathological examination revealed a penetrating wound consistent with a needle tract injury. Complications arising from veterinary dental regional anaesthesia appear to be rare; however, it may be that they are under-reported. This case report highlights the risks involved and reviews the safest and most efficacious regional anaesthesia technique for the feline maxilla. © ISFM and AAFP 2015.

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.

PubMed

Yang, Hongli; Reynaud, Juan; Lockwood, Howard; Williams, Galen; Hardin, Christy; Reyes, Luke; Stowell, Cheri; Gardiner, Stuart K; Burgoyne, Claude F

2017-07-01

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal changes of angle configuration in primary angle-closure suspects: the Zhongshan Angle-Closure Prevention Trial.

PubMed

Jiang, Yuzhen; Chang, Dolly S; Zhu, Haogang; Khawaja, Anthony P; Aung, Tin; Huang, Shengsong; Chen, Qianyun; Munoz, Beatriz; Grossi, Carlota M; He, Mingguang; Friedman, David S; Foster, Paul J

2014-09-01

To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes. Longitudinal cohort study. Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial. Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI. Angle width in degrees was calculated from Shaffer grades assessed under static gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500, AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCT images. No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy (P = 0.18), AOD250 (P = 0.167) and ARA (P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8-1.6) in treated eyes and 1.6°/year (95% CI, 1.3-2.0) in untreated eyes (P<0.001). Angle width of treated eyes increased markedly after LPI, remained stable for 6 months, and then decreased significantly by 18 months after LPI. Untreated eyes experienced a more consistent and rapid decrease in angle width over the same time period. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effect of subretinal injection on retinal structure and function in a rat oxygen-induced retinopathy model.

PubMed

Becker, Silke; Wang, Haibo; Stoddard, Gregory J; Hartnett, M Elizabeth

2017-01-01

Subretinal injections are used to deliver agents in experimental studies of retinal diseases, often through viral vectors. However, few studies have investigated the effects of subretinal injections alone on the structure and function of the healthy or diseased retina, particularly in models of oxygen-induced retinopathy (OIR). We report on the effects of subretinal injections in a rat OIR model, which is used to study mechanisms of retinopathy of prematurity. Within 6 h of birth, neonatal rat pups were exposed to repeated cycles of oxygen between 50% and 10% O 2 every 24 h for 14 days and subsequently moved to room air. On postnatal day 8 (P8), animals were treated in both eyes with advancement of the injection needle into the vitreous (pilot-treated) or with a subretinal PBS injection (sPBS-treated) or were left untreated (untreated). Additional control animals were exposed to microscope light after eyelid opening only (light-treated). Retinal fundus images were recorded on P26. Areas of the avascular retina and intravitreal neovascularization were determined in flat mounted retinas stained with isolectin B4 on P32. Retinal function of the respective eyes was assessed with the Ganzfeld electroretinogram (ERG) on P31 or P32 and with focal ERG in the central retina on P28 or P29. The thickness of the retinal layers was measured with spectral domain optical coherence tomography (OCT) on P30 and in opsin- and TO-PRO 3-stained retinal cryosections from pups euthanized on P32. Two sections were analyzed in each pup. For each section, three images of three different locations were analyzed accounting for 18 thickness measurements per pup. Compared to untreated animals, the avascular area of the retina was greater in the pilot-treated (p<0.05) and sPBS-treated eyes (p<0.01), and the sPBS-treated eyes had a greater avascular retinal area compared to the pilot-treated eyes (p<0.01). The intravitreal neovascular area was larger in the sPBS-treated eyes compared to the untreated eyes (p<0.01). The outer nuclear and outer segment layers were thinner in the pilot- (p<0.01) and sPBS-treated eyes (p<0.05) compared to the untreated eyes as measured with OCT and immunohistochemical staining of the retinal cryosections. Compared to the untreated eyes, the amplitudes of the scotopic a- and b-waves in the Ganzfeld ERG were reduced in the pilot-treated eyes (p<0.001 and p<0.01, respectively), but only the a-wave was reduced in the sPBS-treated eyes (p<0.001). The a-wave amplitude in the focal ERG was reduced in the pilot- and sPBS-treated eyes, and no difference was seen in the b-wave amplitude between any of the groups. There was no difference between the light-treated and untreated eyes in the areas of the avascular retina or intravitreal neovascularization or Ganzfeld or focal ERG. Pilot injections alone without injection into the subretinal space resulted in an increased avascular retinal area, reduced thickness of the photoreceptors, and reduced ERG function compared to the untreated animals. Although subretinal PBS injections further increased the areas of avascular retina and intravitreal neovascularization and resulted in similar retinal thinning compared to the pilot treatment, inner retinal function was improved, as evidenced by higher Ganzfeld b-wave amplitudes. Differences in the Ganzfeld and focal ERGs may indicate that the peripheral retina is more susceptible to remote beneficial effects from potential protective mechanisms induced by subretinal injection. This study stresses the importance of appropriate controls in experiments with subretinal delivery of agents.

Assessment of β-zone peripapillary atrophy by optical coherence tomography and scanning laser ophthalmoscopy imaging in glaucoma patients

PubMed Central

Seidensticker, Florian; Reznicek, Lukas; Mann, Thomas; Hübert, Irene; Kampik, Anselm; Ulbig, Michael; Hirneiss, Christoph; Neubauer, Aljoscha S; Kernt, Marcus

2014-01-01

Purpose To assess β-zone peripapillary atrophy (β-PPA) using spectral domain optical coherence tomography (SD-OCT), scanning laser ophthalmoscopy (SLO), and fundus auto-fluorescence (FAF) imaging in patients with primary open-angle glaucoma with advanced glaucomatous visual field defects. Methods A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma were included in this study. All study participants underwent a full ophthalmic examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic nerve head and the peripapillary region. Results Eighty-four glaucomatous eyes were included in our prospective study. Correlation analyses for horizontally and vertically obtained β-PPA for all three imaging modalities (color SLO, FAF, and SD-OCT) revealed highest correlations between FAF and color SLO (Pearson correlation coefficient: 0.904 [P<0.001] for horizontal β-PPA and 0.786 [P<0.001] for vertical β-PPA). Bland–Altman plotting revealed highest agreements between color SLO and FAF, with −2.1 pixels ±1.96 standard deviation (SD) for horizontal β-PPA, SD: 10.5 pixels and 2.4 pixels ±1.96 SD for vertical β-PPA. Conclusion β-PPA can be assessed using en-face SLO and cross-sectional SD-OCT imaging. Correlation analyses revealed highest correlations between color SLO and FAF imaging, while correlations between SLO and SD-OCT were weak. A more precise structural definition of β-PPA is needed. PMID:25061270

Scanning laser polarimetry using variable corneal compensation in the detection of glaucoma with localized visual field defects.

PubMed

Kook, Michael S; Cho, Hyun-soo; Seong, Mincheol; Choi, Jaewan

2005-11-01

To evaluate the ability of scanning laser polarimetry parameters and a novel deviation map algorithm to discriminate between healthy and early glaucomatous eyes with localized visual field (VF) defects confined to one hemifield. Prospective case-control study. Seventy glaucomatous eyes with localized VF defects and 66 normal controls. A Humphrey field analyzer 24-2 full-threshold test and scanning laser polarimetry with variable corneal compensation were used. We assessed the sensitivity and specificity of scanning laser polarimetry parameters, sensitivity and cutoff values for scanning laser polarimetry deviation map algorithms at different specificity values (80%, 90%, and 95%) in the detection of glaucoma, and correlations between the algorithms of scanning laser polarimetry and of the pattern deviation derived from Humphrey field analyzer testing. There were significant differences between the glaucoma group and normal subjects in the mean parametric values of the temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and TSNIT standard deviation (SD) (P<0.05). The sensitivity and specificity of each scanning laser polarimetry variable was as follows: TSNIT, 44.3% (95% confidence interval [CI], 39.8%-49.8%) and 100% (95.4%-100%); superior average, 30% (25.5%-34.5%) and 97% (93.5%-100%); inferior average, 45.7% (42.2%-49.2%) and 100% (95.8%-100%); and TSNIT SD, 30% (25.9%-34.1%) and 97% (93.2%-100%), respectively (when abnormal was defined as P<0.05). Based on nerve fiber indicator cutoff values of > or =30 and > or =51 to indicate glaucoma, sensitivities were 54.3% (50.1%-58.5%) and 10% (6.4%-13.6%), and specificities were 97% (93.2%-100%) and 100% (95.8%-100%), respectively. The range of areas under the receiver operating characteristic curves using the scanning laser polarimetry deviation map algorithm was 0.790 to 0.879. Overall sensitivities combining each probability scale and severity score at 80%, 90%, and 95% specificities were 90.0% (95% CI, 86.4%-93.6%), 71.4% (67.4%-75.4%), and 60.0% (56.2%-63.8%), respectively. There was a statistically significant correlation between the scanning laser polarimetry severity score and the VF severity score (R2 = 0.360, P<0.001). Scanning laser polarimetry parameters may not be sufficiently sensitive to detect glaucomatous patients with localized VF damage. Our algorithm using the scanning laser polarimetry deviation map may enhance the understanding of scanning laser polarimetry printouts in terms of the locality, deviation size, and severity of localized retinal nerve fiber layer defects in eyes with localized VF loss.

How does glaucoma look?: patient perception of visual field loss.

PubMed

Crabb, David P; Smith, Nicholas D; Glen, Fiona C; Burton, Robyn; Garway-Heath, David F

2013-06-01

To explore patient perception of vision loss in glaucoma and, specifically, to test the hypothesis that patients do not recognize their impairment as a black tunnel effect or as black patches in their field of view. Clinic-based cross-sectional study. Fifty patients (age range, 52-82 years) with visual acuity better than 20/30 and with a range of glaucomatous visual field (VF) defects in both eyes, excluding those with very advanced disease (perimetrically blind). Participants underwent monocular VF testing in both eyes using a Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA; 24-2 Swedish interactive threshold algorithm standard tests) and other tests of visual function. Participants took part in a recorded interview during which they were asked if they were aware of their VF loss; if so, there were encouraged to describe it in their own words. Participants were shown 6 images modified in a variety of ways on a computer monitor and were asked to select the image that most closely represented their perception of their VF loss. Forced choice of an image best representing glaucomatous vision impairment. Participants had a range of VF defect severity: average HFA mean deviation was -8.7 dB (standard deviation [SD], 5.8 dB) and -10.5 dB (SD, 7.1 dB) in the right and left eyes, respectively. Thirteen patients (26%; 95% confidence interval [CI], 15%-40%) reported being completely unaware of their vision loss. None of the patients chose the images with a distinct black tunnel effect or black patches. Only 2 patients (4%; 95% CI, 0%-14%) chose the image with a tunnel effect with blurred edges. An image depicting blurred patches and another with missing patches was chosen by 54% (95% CI, 39%-68%) and 16% (95% CI, 7%-29%) of the patients, respectively. Content analysis of the transcripts from the recorded interviews indicated a frequent use of descriptors of visual symptoms associated with reported blur and missing features. Patients with glaucoma do not perceive their vision loss as a black tunnel effect or as black patches masking their field of view. These findings are important in the context of depicting the effects of glaucomatous vision loss and raising awareness for glaucoma detection. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Magnetic resonance in studies of glaucoma

PubMed Central

Fiedorowicz, Michał; Dyda, Wojciech; Rejdak, Robert; Grieb, Paweł

2011-01-01

Summary Glaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated. PMID:21959626

Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy.

PubMed

Cabrerizo, Javier; Livny, Eitan; Musa, Fayyaz U; Leeuwenburgh, Paulien; van Dijk, Korine; Melles, Gerrit R J

2014-10-01

The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED-affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. Compared with untreated FED-affected eyes, best spectacle-corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

PubMed

Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

2009-07-01

To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Laser-assisted formation of micropores and nanobubbles in sclera promote stable normalization of intraocular pressure

NASA Astrophysics Data System (ADS)

Baum, Olga; Wachsmann-Hogiu, Sebastian; Milner, Thomas; Sobol, Emil

2017-06-01

Pores in sclera enhance uveoscleral water outflow and can normalize intraocular pressure in glaucomatous eyes. The aims of this study are to demonstrate laser-induced formation of pores with a dendritic structure and to answer the questions: How is a pore system stable and can laser treatment provide a long-lasting pressure stabilization effect? Effect of 1.56 µm laser radiation on porcine eye sclera was studied using atomic force microscopy and super resolution structured irradiation microscopy with fluorescent markers. Results suggest that the pores with a complex spatial configuration can arise as a result of laser irradiation and that laser-generated stable gas nanobubbles coated with calcium ions allow pore stabilization in the sclera. Our results support a laser based approach for treatment of glaucoma.

A perspective of gene therapy in the glaucomas.

PubMed

Kaufman, P L; Jia, W W; Tan, J; Chen, Z; Gabelt, B T; Booth, V; Tufaro, F; Cynader, M

1999-06-01

Gene therapy in the anterior and posterior segment tissues may have the potential to favorably influence aqueous hydrodynamics and retinal ganglion cell biology, thereby preventing, delaying, or minimizing glaucomatous damage to the optic nerve. We demonstrated the feasibility of using a herpes viral vector (ribonucleotide reductase defective HSV-1, hrR3) to deliver the lacZ reporter gene to living cat and rat eyes. Cats received injections into the anterior chamber and rats into the vitreous cavity. In cats, lacZ expression was detectable at 1 to 2 days in the anterior outer portion of the ciliary muscle and the lining of the intertrabecular spaces of the corneoscleral and uveal meshwork. Rat eyes showed lacZ expression in the retinal pigment epithelium and photoreceptor outer segments 2 days after injection.

The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.

PubMed

Atchison, Elizabeth A; Wood, Kevin M; Mattox, Cynthia G; Barry, Catherine N; Lum, Flora; MacCumber, Mathew W

2018-05-01

To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. Database study. Patients seeing an ophthalmic provider who contributes to the database. We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

PubMed

Saarela, Ville; Falck, Aura; Airaksinen, P Juhani; Tuulonen, Anja

2012-03-01

To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT. © 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.

[The glaucoma pharmacological treatment and biomechanical properties of the cornea].

PubMed

Liehneová, I; Karlovská, S

2014-10-01

To evaluate and compare the impact of long-term use of intraocular pressure lowering medication on the biomechanical properties of the cornea. Group of 305 eyes of 154 patients newly diagnosed with primary open angle glaucoma (POAG, n = 68) or ocular hypertension (OH, n = 6) was enrolled in prospective cohort study. The control group was established of 80 untreated eyes of 40 patients with ocular hypertension and 80 eyes of 40 patients with no ocular pathology. Following parameters were evaluated: intraocular pressure (IOPg,IOPcc), hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT). The parameters were evaluated at baseline (untreated) and in follow up periods of 3, 6, 9 and 12 months. The same schedule was used for eyes in the control group. Eyes with POAG or OH were sorted into two groups depending on the type of applied medication: prostaglandin analogues, carboanhydrase inhibitors alone or combined with betablockers. We did not prove any statistically significant difference in hysteresis in patients with newly diagnosed POAG (yet untreated) in comparison with normal eyes in control group (p = 0.238). We proved significantly higher values of CRF (p = 0.032) and CCT (p = 0.013) in the control group of untreated patients with ocular hypertension. This result confirms higher number of patients with stiffer and thicker corneas. Statistically significant difference of CH and CRF was proved (p < 0.0001) in eyes treated by prostaglandin analogues during follow up period. In these eyes we also demonstrated reduction of CCT (p < 0.001). We did not record any other statistically significant change in remaining followed parameters. Increase of CH and CRF can show change of biomechanical properties of the cornea after long-term use of prostaglandin analogues. The biomechanical properties of the cornea were not impacted by carboanhydrase inhibitors. Further studies are required to establish the effect of long-term use prostaglandin analogues on accuracy of IOP measurements.

Baseline Risk Factors that Predict the Development of Open-angle Glaucoma in a Population: The Los Angeles Latino Eye Study

PubMed Central

Jiang, Xuejuan; Varma, Rohit; Wu, Shuang; Torres, Mina; Azen, Stanley P; Francis, Brian A.; Chopra, Vikas; Nguyen, Betsy Bao-Thu

2012-01-01

Objective To determine which baseline socio-demographic, lifestyle, anthropometric, clinical, and ocular risk factors predict the development of open-angle glaucoma (OAG) in an adult population. Design A population-based, prospective cohort study. Participants A total of 3,772 self-identified Latinos aged 40 years and older from Los Angeles, California who were free of OAG at baseline. Methods Participants from the Los Angeles Latino Eye Study had standardized study visits at baseline and 4-year follow-up with structured interviews and a comprehensive ophthalmologic examination. OAG was defined as the presence of an open angle and a glaucomatous visual field abnormality and/or evidence of glaucomatous optic nerve damage in at least one eye. Multivariate logistic regression with stepwise selection was performed to determine which potential baseline risk factors independently predict the development of OAG. Main Outcome Measure Odds ratios for various risk factors. Results Over the 4-year follow-up, 87 participants developed OAG. The baseline risk factors that predict the development of OAG include: older age (odds ratio [OR] per decade, 2.19; 95% confidence intervals [CI], 1.74-2.75; P<0.001), higher intraocular pressure (OR per mmHg, 1.18; 95% CI, 1.10-1.26; P<0.001), longer axial length (OR per mm, 1.48; 95% CI, 1.22-1.80; P<0.001), thinner central cornea (OR per 40 μm thinner, 1.30; 95% CI, 1.00-1.70; P=0.050) higher waist to hip ratio (OR per 0.05 higher, 1.21; 95% CI, 1.05-1.39; P=0.007) and lack of vision insurance (OR, 2.08; 95% CI, 1.26-3.41; P=0.004). Conclusions Despite a mean baseline IOP of 14 mmHg in Latinos, higher intraocular pressure is an important risk factor for developing OAG. Biometric measures suggestive of less structural support such as longer axial length and thin CCT were identified as important risk factors. Lack of health insurance reduces access to eye care and increases the burden of OAG by reducing the likelihood of early detection and treatment of OAG. PMID:22796305

Secondary pigmentary glaucoma in patients with underlying primary pigment dispersion syndrome.

PubMed

Sivaraman, Kavitha R; Patel, Chirag G; Vajaranant, Thasarat S; Aref, Ahmad A

2013-01-01

Primary pigment dispersion syndrome (PPDS) is a bilateral condition that occurs in anatomically predisposed individuals. PPDS may evolve into pigmentary glaucoma, but it is difficult to predict which patients will progress. Secondary pigment dispersion is more often unilateral and acquired as a result of surgery, trauma, or intraocular tumor, but can likewise lead to pigmentary glaucoma. We report two cases of patients with bilateral PPDS who developed secondary pigment dispersion and pigmentary glaucoma in one eye. Patients with PPDS who acquire a secondary mechanism of pigment dispersion may be at an increased risk of progression to pigmentary glaucoma, presumably due to an increased burden of liberated pigment. In addition to regular surveillance for progression to glaucoma from PPDS, secondary causes of pigmentary dispersion in these eyes should be considered when patients present with grossly asymmetric findings. When secondary pigment dispersion is identified in eyes with PPDS, we recommend prompt intervention to alleviate the cause of secondary pigment dispersion and/or aggressive control of intraocular pressure to limit glaucomatous damage.

Advanced pigment dispersion glaucoma secondary to phakic intraocular collamer lens implant.

PubMed

Ye, Clara; Patel, Cajal K; Momont, Anna C; Liu, Yao

2018-06-01

We report a case of pigment dispersion glaucoma secondary to uncomplicated phakic intraocular collamer lens (ICL) (Visian ICL™, Staar Inc., Monrovia, CA) implant that resulted in advanced visual field loss. A 50-year-old man presented for routine follow-up status post bilateral phakic intraocular collamer lens (ICL) placement 8 years earlier. He was incidentally found to have a decline in visual acuity from an anterior subcapsular cataract and elevated intraocular pressure (IOP) in the left eye. There were signs of pigment dispersion and no evidence of angle closure. Diffuse optic nerve thinning was consistent with advanced glaucomatous visual field defects. Pigment dispersion was also present in the patient's right eye, but without elevated IOP or visual field defects. The patient was treated with topical glaucoma medications and the phakic ICL in the left eye was removed concurrently with cataract surgery to prevent further visual field loss. Pigment dispersion glaucoma is a serious adverse outcome after phakic ICL implantation and regular post-operative monitoring may prevent advanced visual field loss.

Secondary pigmentary glaucoma in patients with underlying primary pigment dispersion syndrome

PubMed Central

Sivaraman, Kavitha R; Patel, Chirag G; Vajaranant, Thasarat S; Aref, Ahmad A

2013-01-01

Primary pigment dispersion syndrome (PPDS) is a bilateral condition that occurs in anatomically predisposed individuals. PPDS may evolve into pigmentary glaucoma, but it is difficult to predict which patients will progress. Secondary pigment dispersion is more often unilateral and acquired as a result of surgery, trauma, or intraocular tumor, but can likewise lead to pigmentary glaucoma. We report two cases of patients with bilateral PPDS who developed secondary pigment dispersion and pigmentary glaucoma in one eye. Patients with PPDS who acquire a secondary mechanism of pigment dispersion may be at an increased risk of progression to pigmentary glaucoma, presumably due to an increased burden of liberated pigment. In addition to regular surveillance for progression to glaucoma from PPDS, secondary causes of pigmentary dispersion in these eyes should be considered when patients present with grossly asymmetric findings. When secondary pigment dispersion is identified in eyes with PPDS, we recommend prompt intervention to alleviate the cause of secondary pigment dispersion and/or aggressive control of intraocular pressure to limit glaucomatous damage. PMID:23569351

Visual Acuity Improvement of Amblyopia in an Adult With Levodopa/Carbidopa Treatment.

PubMed

Orge, Faruk H; Dar, Suhail A

2015-09-09

Amblyopia is the leading cause of visual loss in children, affecting 2% to 3% of the population. Occlusion of the dominant eye is the primary and best treatment, although efficacy decreases after 6 years of age. As a result, levodopa/carbidopa has been explored as an adjunct to conventional therapy and has been shown to have an immediate impact on visual acuity. Several studies to date have shown mixed results on the benefit of supplementing occlusion therapy with levodopa/carbidopa, although they have primarily studied children. The authors describe the oldest patient (46 years old) documented in the literature to have shown improvement in visual acuity using levodopa/carbidopa. He was given a 16-week course at a dose in line with previous studies while being effectively occluded full time due to a glaucomatous right eye with no light perception. On 3-month follow-up, his left eye improved two lines and stabilized at 6 months. Copyright 2015, SLACK Incorporated.

Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats.

PubMed

Levkovitch-Verbin, Hana; Quigley, Harry A; Martin, Keith R G; Valenta, Danielle; Baumrind, Lisa A; Pease, Mary Ellen

2002-02-01

To develop and characterize a model of pressure-induced optic neuropathy in rats. Experimental glaucoma was induced unilaterally in 174 Wistar rats, using a diode laser with wavelength of 532 nm aimed at the trabecular meshwork and episcleral veins (combination treatment group) or only at the trabecular meshwork (trabecular group) through the external limbus. Intraocular pressure (IOP) was measured by a tonometer in rats under ketamine-xylazine anesthesia. Possible retinal vascular compromise was evaluated by repeated fundus examinations and by histology. The degree of retinal ganglion cell (RGC) loss was assessed by a masked, semiautomated counting of optic nerve axons. Effects of laser treatment on anterior ocular structures and retina were judged by light microscopy. After the laser treatment, IOP was increased in all eyes to higher than the normal mean IOP of 19.4 +/- 2.1 mm Hg (270 eyes). Peak IOP was 49.0 +/- 6.1 mm Hg (n = 108) in the combination group that was treated by a laser setting of 0.7 seconds and 0.4 W and 34.0 +/- 5.7 mm Hg (n = 46) in the trabecular group. Mean IOP after 6 weeks was 25.5 +/- 2.9 mm Hg in glaucomatous eyes in the combination group compared with 22.0 +/- 1.8 mm Hg in the trabecular group. IOP in the glaucomatous eyes was typically higher than in the control eyes for at least 3 weeks. In the combination group, RGC loss was 16.1% +/- 14.4% at 1 week (n = 8, P = 0.01), 59.7% +/- 25.7% at 6 weeks (n = 88, P < 0.001), and 70.9% +/- 23.6% at 9 weeks (n = 12, P < 0.001). The trabecular group had mean axonal loss of 19.1% +/- 14.0% at 3 weeks (n = 9, P = 0.004) and 24.3% +/- 20.2% at 6 weeks (n = 25, P < 0.001), increasing to 48.4% +/- 32.8% at 9 weeks (n = 12, P < 0.001). Laser treatment led to closure of intertrabecular spaces and the major outflow channel. The retina and choroid were normal by ophthalmoscopy at all times after treatment. Light microscopic examination showed only loss of RGCs and their nerve fibers. Increased IOP caused by a laser injury to the trabecular meshwork represents a useful and efficient model of experimental glaucoma in rats.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes.

PubMed

Wang, Qi; Grozdanic, Sinisa D; Harper, Matthew M; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Diagnostic accuracy of ganglion cell complex substructures in different stages of primary open-angle glaucoma.

PubMed

Elbendary, Amal M; Abd El-Latef, Mohamed Hafez; Elsorogy, Hisham I; Enaam, Kamal M

2017-08-01

To evaluate diagnostic accuracy of substructure of ganglion cell complex versus peripapillary nerve fiber layer (NFL) thickness using spectral domain optical coherence tomography (SD-OCT) in different stages of glaucoma. Thirty eyes were normal, 120 were glaucomatous. Glaucomatous eyes were classified into: early glaucoma (46), moderate glaucoma (48), and severe glaucoma (26). Perimetry and SD-OCT were done. Peripapillary NFL thickness, ganglion cell layer (GCL), macular NFL thickness, combined GCL and macular ganglion cell complex (GCC), were recorded. Area under receiver operating characteristic curves (AUCs) was used to verify performance of different OCT parameters. Peripapillary NFL, GCL, and GCC thickness values were significantly different in all stages of glaucoma. All comparisons were significantly different; normal versus early, early versus moderate and moderate versus severe. The best parameters that distinguished normal from early stage were: peripapillary NFL (AUC: 0.90), GCC (AUC: 0.75), early from moderate stage were: peripapillary NFL thickness (AUC: 0.85), GCL (0.81),GCC (0.81), moderate from severe stage were: GCC (AUC:0.95), macular NFL (AUC:0.91), GCL (AUC:0.89), and peripapillary NFL (AUC:0.88). Peripapllary NFL and GCC thinning showed paradoxical course. The most diagnosed parameter in early glaucoma was peripapillary NFL and in severe glaucoma was GCC. In severe glaucoma, macular NFL showed higher diagnostic power than GCL and peripapillary NFL. Ganglion cell complex mapping may provide good alternative to optic disc imaging in advanced glaucoma with poor fixation. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Quantitative comparison of disc rim color in optic nerve atrophy of compressive optic neuropathy and glaucomatous optic neuropathy.

PubMed

Nakano, Eri; Hata, Masayuki; Oishi, Akio; Miyamoto, Kazuaki; Uji, Akihito; Fujimoto, Masahiro; Miyata, Manabu; Yoshimura, Nagahisa

2016-08-01

The purpose was to investigate an objective and quantitative method to estimate the redness of the optic disc neuroretinal rim, and to determine the usefulness of this method to differentiate compressive optic neuropathy (CON) from glaucomatous optic neuropathy (GON). In our study there were 126 eyes: 40 with CON, 40 with normal tension glaucoma (NTG), and 46 normal eyes (NOR). Digital color fundus photographs were assessed for the redness of disc rim color using ImageJ software. We separately measured the intensity of red, green, and blue pixels from RGB images. Three disc color indices (DCIs), which indicate the redness intensity, were calculated through existing formulas. All three DCIs of CON were significantly smaller than those of NOR (P < 0.001). In addition, when compared with NTG, DCIs were also significantly smaller in CON (P < 0.05). A comparison of mild CON and mild NTG (mean deviation (MD) > -6 dB), in which the extent of retinal nerve fiber layer thinning is comparable, the DCIs of mild CON were significantly smaller than those of mild NTG (P < 0.05). In contrast, DCIs did not differ between moderate-to-severe stages of CON and NTG (MD ≤ -6 dB), though the retinal nerve fibers of CON were more severely damaged than those of NTG. To differentiate between mild CON and mild NTG, all AUROCs for the three DCIs were above 0.700. A quantitative and objective assessment of optic disc color was useful in differentiating early-stage CON from GON and NOR.

Glaucomatous retinal nerve fiber layer thickness loss is associated with slower reaction times under a divided attention task.

PubMed

Tatham, Andrew J; Boer, Erwin R; Rosen, Peter N; Della Penna, Mauro; Meira-Freitas, Daniel; Weinreb, Robert N; Zangwill, Linda M; Medeiros, Felipe A

2014-11-01

To examine the relationship between glaucomatous structural damage and ability to divide attention during simulated driving. Cross-sectional observational study. Hamilton Glaucoma Center, University of California San Diego. Total of 158 subjects from the Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76 similarly aged controls. Ability to divide attention was investigated by measuring reaction times to peripheral stimuli (at low, medium, or high contrast) while concomitantly performing a central driving task (car following or curve negotiation). All subjects had standard automated perimetry (SAP) and optical coherence tomography was used to measure retinal nerve fiber layer (RNFL) thickness. Cognitive ability was assessed using the Montreal Cognitive Assessment and subjects completed a driving history questionnaire. Reaction times to the driving simulator divided attention task. The mean reaction times to the low-contrast stimulus were 1.05 s and 0.64 s in glaucoma and controls, respectively, during curve negotiation (P < .001), and 1.19 s and 0.77 s (P = .025), respectively, during car following. There was a nonlinear relationship between reaction times and RNFL thickness in the better eye. RNFL thickness remained significantly associated with reaction times even after adjusting for age, SAP mean deviation in the better eye, cognitive ability, and central driving task performance. Although worse SAP sensitivity was associated with worse ability to divide attention, RNFL thickness measurements provided additional information. Information from structural tests may improve our ability to determine which patients are likely to have problems performing daily activities, such as driving. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs.

PubMed

Li, Zhixi; He, Yifan; Keel, Stuart; Meng, Wei; Chang, Robert T; He, Mingguang

2018-03-02

To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs. A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs. We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm. This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm. The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON. In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%). A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Deep Retinal Layer Microvasculature Dropout detected by the Optical Coherence Tomography Angiography in Glaucoma

PubMed Central

Suh, Min Hee; Zangwill, Linda M.; Manalastas, Patricia Isabel C.; Belghith, Akram; Yarmohammadi, Adeleh; Medeiros, Felipe A.; Diniz-Filho, Alberto; Saunders, Luke J.; Weinreb, Robert N.

2016-01-01

Purpose To investigate factors associated with dropout of the deep retinal layer microvasculature within the β-zone parapapillary atrophy (βPPA) assessed by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. Design Cross-sectional study. Participants Seventy-one eyes from 71 primary open angle glaucoma (POAG) patients with βPPA enrolled in the Diagnostic Innovations in Glaucoma Study. Methods βPPA deep layer microvasculature dropout was defined as a complete loss of the microvasculature located within deep retinal layer of the βPPA from OCT-A-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) was also calculated using OCT-A. Choroidal thickness and presence of the focal lamina cribrosa (LC) defect were determined using swept-source OCT. Main Outcome Measures Presence of the βPPA deep layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defect, βPPA area, and choroidal thickness were analyzed. Results βPPA deep layer microvasculature dropout was detected in 37 eyes (52.1%) of eyes with POAG. Eyes with dropouts had a higher prevalence of LC defect (70.3 vs. 32.4%), lower cpVD (52.7 vs. 58.8%), worse VF MD (-9.06 vs. -3.83dB), thinner total choroidal thickness (126.5 vs. 169.1/μm), longer axial length (24.7 vs. 24.0mm), larger βPPA (1.2 vs. 0.76mm2) and lower diastolic blood pressure (74.7 vs. 81.7mmHg) than those without dropouts (P< 0.05, respectively). In the multivariate logistic regression, higher prevalence of focal LC defect (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were significantly associated with the dropout. Conclusions Certain systemic and ocular factors such as focal LC defect, more advanced disease status, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the βPPA deep layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between βPPA deep layer dropout and these factors. PMID:27769587

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head

PubMed Central

Jones, H. J.; Girard, M. J.; White, N.; Fautsch, M. P.; Morgan, J. E.; Ethier, C. R.; Albon, J.

2015-01-01

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse. PMID:25808336

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head.

PubMed

Jones, H J; Girard, M J; White, N; Fautsch, M P; Morgan, J E; Ethier, C R; Albon, J

2015-05-06

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal-temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior-temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

Is LASIK for Me? A Patient's Guide to Refractive Surgery

MedlinePlus

... whether LASIK would be appropriate for you are: • dry eye syndrome . If dry eye is left untreated prior to surgery, patients may be disappointed with their LASIK results. If dry eye is diagnosed and adequately treated before surgery, you ...

Hypodense regions (holes) in the retinal nerve fiber layer in frequency-domain OCT scans of glaucoma patients and suspects.

PubMed

Xin, Daiyan; Talamini, Christine L; Raza, Ali S; de Moraes, Carlos Gustavo V; Greenstein, Vivienne C; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2011-09-09

To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 ± 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 ± 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields.

Rodent models of glaucoma and their applicability for drug discovery.

PubMed

Agarwal, Renu; Agarwal, Puneet

2017-03-01

Rodents have widely been used to represent glaucomatous changes both in the presence and absence of elevated intraocular pressure (IOP) as they offer clear advantages over other animal species. IOP elevation is commonly achieved by creating an obstruction in the aqueous outflow pathways, consequently leading to retinal ganglion cell and optic nerve (ON) damage, the hallmark of glaucoma. These changes may also be achieved in the absence of elevated IOP by directly inflicting injury to retina or ON. Areas covered: This paper presents a summary of currently used rodent models of glaucoma. The characteristics of these models from several studies are summarized. The benefits and shortcomings of these models are also discussed. Expert opinion: The choice of animal model that closely represents human disease is key for successful translational of preclinical research to clinical practice. Rodent models of rapid IOP elevation are likely to be least representative, whereas models such as steroid-induced glaucoma models more closely resemble the trabecular meshwork changes seen in glaucomatous human eyes. However, this model needs further characterization. Rodent models based on direct retinal and ON injury are also useful tools to investigate molecular mechanisms involved at the site of final common pathology and neuroprotective strategies.

Choice of Stimulus Range and Size Can Reduce Test-Retest Variability in Glaucomatous Visual Field Defects

PubMed Central

Swanson, William H.; Horner, Douglas G.; Dul, Mitchell W.; Malinovsky, Victor E.

2014-01-01

Purpose To develop guidelines for engineering perimetric stimuli to reduce test-retest variability in glaucomatous defects. Methods Perimetric testing was performed on one eye for 62 patients with glaucoma and 41 age-similar controls on size III and frequency-doubling perimetry and three custom tests with Gaussian blob and Gabor sinusoid stimuli. Stimulus range was controlled by values for ceiling (maximum sensitivity) and floor (minimum sensitivity). Bland-Altman analysis was used to derive 95% limits of agreement on test and retest, and bootstrap analysis was used to test the hypotheses about peak variability. Results Limits of agreement for the three custom stimuli were similar in width (0.72 to 0.79 log units) and peak variability (0.22 to 0.29 log units) for a stimulus range of 1.7 log units. The width of the limits of agreement for size III decreased from 1.78 to 1.37 to 0.99 log units for stimulus ranges of 3.9, 2.7, and 1.7 log units, respectively (F = 3.23, P < 0.001); peak variability was 0.99, 0.54, and 0.34 log units, respectively (P < 0.01). For a stimulus range of 1.3 log units, limits of agreement were narrowest with Gabor and widest with size III stimuli, and peak variability was lower (P < 0.01) with Gabor (0.18 log units) and frequency-doubling perimetry (0.24 log units) than with size III stimuli (0.38 log units). Conclusions Test-retest variability in glaucomatous visual field defects was substantially reduced by engineering the stimuli. Translational Relevance The guidelines should allow developers to choose from a wide range of stimuli. PMID:25371855

Choice of Stimulus Range and Size Can Reduce Test-Retest Variability in Glaucomatous Visual Field Defects.

PubMed

Swanson, William H; Horner, Douglas G; Dul, Mitchell W; Malinovsky, Victor E

2014-09-01

To develop guidelines for engineering perimetric stimuli to reduce test-retest variability in glaucomatous defects. Perimetric testing was performed on one eye for 62 patients with glaucoma and 41 age-similar controls on size III and frequency-doubling perimetry and three custom tests with Gaussian blob and Gabor sinusoid stimuli. Stimulus range was controlled by values for ceiling (maximum sensitivity) and floor (minimum sensitivity). Bland-Altman analysis was used to derive 95% limits of agreement on test and retest, and bootstrap analysis was used to test the hypotheses about peak variability. Limits of agreement for the three custom stimuli were similar in width (0.72 to 0.79 log units) and peak variability (0.22 to 0.29 log units) for a stimulus range of 1.7 log units. The width of the limits of agreement for size III decreased from 1.78 to 1.37 to 0.99 log units for stimulus ranges of 3.9, 2.7, and 1.7 log units, respectively ( F = 3.23, P < 0.001); peak variability was 0.99, 0.54, and 0.34 log units, respectively ( P < 0.01). For a stimulus range of 1.3 log units, limits of agreement were narrowest with Gabor and widest with size III stimuli, and peak variability was lower ( P < 0.01) with Gabor (0.18 log units) and frequency-doubling perimetry (0.24 log units) than with size III stimuli (0.38 log units). Test-retest variability in glaucomatous visual field defects was substantially reduced by engineering the stimuli. The guidelines should allow developers to choose from a wide range of stimuli.

Detecting Glaucoma With a Portable Brain-Computer Interface for Objective Assessment of Visual Function Loss.

PubMed

Nakanishi, Masaki; Wang, Yu-Te; Jung, Tzyy-Ping; Zao, John K; Chien, Yu-Yi; Diniz-Filho, Alberto; Daga, Fabio B; Lin, Yuan-Pin; Wang, Yijun; Medeiros, Felipe A

2017-06-01

The current assessment of visual field loss in diseases such as glaucoma is affected by the subjectivity of patient responses and the lack of portability of standard perimeters. To describe the development and initial validation of a portable brain-computer interface (BCI) for objectively assessing visual function loss. This case-control study involved 62 eyes of 33 patients with glaucoma and 30 eyes of 17 healthy participants. Glaucoma was diagnosed based on a masked grading of optic disc stereophotographs. All participants underwent testing with a BCI device and standard automated perimetry (SAP) within 3 months. The BCI device integrates wearable, wireless, dry electroencephalogram and electrooculogram systems and a cellphone-based head-mounted display to enable the detection of multifocal steady state visual-evoked potentials associated with visual field stimulation. The performances of global and sectoral multifocal steady state visual-evoked potentials metrics to discriminate glaucomatous from healthy eyes were compared with global and sectoral SAP parameters. The repeatability of the BCI device measurements was assessed by collecting results of repeated testing in 20 eyes of 10 participants with glaucoma for 3 sessions of measurements separated by weekly intervals. Receiver operating characteristic curves summarizing diagnostic accuracy. Intraclass correlation coefficients and coefficients of variation for assessing repeatability. Among the 33 participants with glaucoma, 19 (58%) were white, 12 (36%) were black, and 2 (6%) were Asian, while among the 17 participants with healthy eyes, 9 (53%) were white, 8 (47%) were black, and none were Asian. The receiver operating characteristic curve area for the global BCI multifocal steady state visual-evoked potentials parameter was 0.92 (95% CI, 0.86-0.96), which was larger than for SAP mean deviation (area under the curve, 0.81; 95% CI, 0.72-0.90), SAP mean sensitivity (area under the curve, 0.80; 95% CI, 0.69-0.88; P = .03), and SAP pattern standard deviation (area under the curve, 0.77; 95% CI, 0.66-0.87; P = .01). No statistically significant differences were seen for the sectoral measurements between the BCI and SAP. Intraclass coefficients for global and sectoral parameters ranged from 0.74 to 0.92, and mean coefficients of variation ranged from 3.03% to 7.45%. The BCI device may be useful for assessing the electrical brain responses associated with visual field stimulation. The device discriminated eyes with glaucomatous neuropathy from healthy eyes in a clinically based setting. Further studies should investigate the feasibility of the BCI device for home-based testing as well as for detecting visual function loss over time.

Deformation of the Early Glaucomatous Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation in 3-D Histomorphometric Reconstructions

PubMed Central

Yang, Hongli; Thompson, Hilary; Roberts, Michael D.; Sigal, Ian A.; Downs, J. Crawford

2011-01-01

Purpose. To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Methods. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n = 3), 30 (n = 3), or 45 (n = 3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Results. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. Conclusions. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants. PMID:20702834

Methylphenidate (Ritalin)-associated cataract and glaucoma.

PubMed

Lu, Chao-Kung; Kuang, Tung-Mei; Chou, Joe Ching-Kuang

2006-12-01

Methylphenidate hydrochloride (Ritalin) is the drug of choice for attention deficit hyperactivity disorder (ADHD). However, an association of Ritalin with glaucoma has been reported. We report a case of Ritalin-associated cataract and glaucoma. A 10-year-old boy was diagnosed with ADHD and had received methylphenidate hydrochloride, 60 mg/day for 2 years. He presented with blurred vision. Best-corrected visual acuity was 6/60 in both eyes. Ocular examinations revealed intraocular pressure (IOP) of 30 mmHg under medication, dense posterior subcapsular opacity of lens, pale disc with advanced cupping, and marked constriction of visual field. Despite maximal anti-glaucomatous medication, IOP still could not be controlled. The patient then received combined cataract and glaucoma surgery. Visual acuity improved and IOP was within normal limits in both eyes postoperatively. Large dose of methylphenidate may cause cataract and glaucoma. The mechanism remains unclear. Doctors should be aware of the possible ocular side effects of methylphenidate.

Correlation between corneal thickness and optic disc morphology in normal tension glaucoma using modern technical analysis.

PubMed

Coman, Laurenţiu; Costescu, Monica; Alecu, Mihail; Coman, Oana Andreia

2014-01-01

The purpose of this study was to evaluate the relationship between central corneal thickness (CCT) and optic disc morphology in normal tension glaucoma (NTG). Patients with NTG underwent eye examination, optic disc imaging with Heildelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. The morphological parameters of the optic discs were used to classify the eyes into four groups: generalized enlargement (GE) type, myopic glaucomatous (MY) type, focal ischemic (FI) type and senile sclerotic (SS) type. A correlation between CCT and optic disc morphology obtained by HRT II was calculated. Multiple comparison and post hoc tests were performed in order to determine the significance of the differences between the four groups. The strongest correlation was between CCT and the parameters of optic disc imaging obtained at HRT II in the GE type of optic disc.

Meibomian Gland Dysfunction and Treatment (Posterior Blepharitis)

MedlinePlus

... if left untreated, MGD can cause or exacerbate dry eye symptoms and eyelid inflammation. The oil glands become ... in permanent changes in the tear film and dry eyes. Symptoms include: ... Stickiness/ Crustiness Watering ...

Glaucomatous Retinal Nerve Fiber Layer Thickness Loss is associated with Slower Reaction Times under a Divided Attention Task

PubMed Central

Tatham, Andrew J.; Boer, Erwin R.; Rosen, Peter N.; Penna, Mauro Della; Meira-Freitas, Daniel; Weinreb, Robert N.; Zangwill, Linda M.; Medeiros, Felipe A.

2014-01-01

Purpose To examine the relationship between glaucomatous structural damage and ability to divide attention during simulated driving. Design Cross-sectional observational study. Methods Setting Hamilton Glaucoma Center, University of California San Diego. Patient Population 158 subjects from the Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76 similarly aged controls. Observation Procedure Ability to divide attention was investigated by measuring reaction times to peripheral stimuli (at low, medium or high contrast) while concomitantly performing a central driving task (car following or curve negotiation). All subjects had standard automated perimetry (SAP) and optical coherence tomography was used to measured retinal nerve fiber (RNFL) thickness. Cognitive ability was assessed using the Montreal Cognitive Assessment and subjects completed a driving history questionnaire. Main outcome measures Reaction times to the driving simulator divided attention task. Results The mean reaction times to the low contrast stimulus were 1.05 s and 0.64 s in glaucoma and controls respectively during curve negotiation (P <0.001), and 1.19 s and 0.77 s (P = 0.025) respectively during car following. There was a non-linear relationship between reaction times and RNFL thickness in the better eye. RNFL thickness remained significantly associated with reaction times even after adjusting for age, SAP mean deviation in the better eye, cognitive ability and central driving task performance. Conclusions Although worse SAP sensitivity was associated with worse ability to divide attention, RNFL thickness measurements provided additional information. Information from structural tests may improve our ability to determine which patients are likely to have problems performing daily activities, such as driving. PMID:25068641

Rates of glaucomatous visual field change in a large clinical population.

PubMed

Chauhan, Balwantray C; Malik, Rizwan; Shuba, Lesya M; Rafuse, Paul E; Nicolela, Marcelo T; Artes, Paul H

2014-06-10

To determine the rate of glaucomatous visual field change in routine clinical care. Mean deviation (MD) rate was computed in one randomly selected eye of all glaucoma patients and suspects with ≥5 examinations in a tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed in tertile groups by the number of examinations, baseline age, and MD. The MD rates were compared to the Canadian Glaucoma Study (CGS), a prospective study with IOP interventions mandated by visual field progression, by pairwise matching of patients by baseline MD. There were 2324 patients with median (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, -0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was 17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of fast and catastrophic progressors, with each tertile of increasing age. Worse MD rate was associated with lower follow-up IOP. Neither MD rate nor the number of fast and catastrophic progressors was significantly different in clinical care patients matched to CGS patients. Most patients under routine glaucoma care demonstrate slow rates of visual field progression. The MD rate in the current study was similar to an interventional prospective study, but considerably less negative compared to published studies with similar design. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

PubMed

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Comparison of glaucoma diagnostic accuracy of macular ganglion cell complex thickness based on nonhighly myopic and highly myopic normative database

PubMed Central

Chen, Henry Shen-Lih; Liu, Chun-Hsiu; Lu, Da-Wen

2016-01-01

Background/Purpose: To evaluate and compare the diagnostic discriminative ability for detecting glaucoma in highly myopic eyes from a normative database of macular ganglion cell complex (mGCC) thickness based on nonhighly myopic and highly myopic normal eyes. Methods: Forty-nine eyes of 49 participants with high myopia (axial length ≥ 26.0 mm) were enrolled. Spectral-domain optical coherence tomography scans were done using RS-3000, and the mGCC thickness/significance maps within a 9-mm diameter circle were generated using built-in software. We compared the difference of sensitivity, specificity, and diagnostic accuracy between the nonhighly myopic database and the highly myopic database for differentiating the early glaucomatous eyes from the nonglaucomatous eyes. Results: This study enrolled 15 normal eyes and 34 eyes with glaucoma. The mean mGCC thickness of the glaucoma group was significantly less than that of the normal group (p < 0.001). Sensitivity was 96.3%, and the specificity was 50.0% when using the nonhighly myopic normative database. When the highly myopic normative database was used, the sensitivity was 88.9%, and the specificity was 90.0%. The false positive rate was significantly lower when using the highly myopic normative database (p < 0.05). Conclusion: The evaluations of glaucoma in eyes with high myopia using a nonhighly myopic normative database may lead to a frequent misdiagnosis. When evaluating glaucoma in high myopic eyes, the mGCC thickness determined by the long axial length high myopic normative database should be applied. PMID:29018704

Biomechanics of the Human Posterior Sclera: Age- and Glaucoma-Related Changes Measured Using Inflation Testing

PubMed Central

Coudrillier, Baptiste; Tian, Jing; Alexander, Stephen; Myers, Kristin M.; Quigley, Harry A.; Nguyen, Thao D.

2012-01-01

Purpose. The objective of this study was to measure the biomechanical response of the human posterior sclera in vitro and to estimate the effects of age and glaucoma. Methods. Scleral specimens from 22 donors with no history of glaucoma and 11 donors with a history of glaucoma were excised 3 mm posterior to the equator and affixed to an inflation chamber. Optic nerve cross-sections were graded to determine the presence of axon loss. The time-dependent inflation response was measured in a series of pressure-controlled load–unload tests to 30 mm Hg and creep tests to 15 and 30 mm Hg. Circumferential and meridional strains were computed from the digital image correlation displacements, and midposterior stresses were determined from pressure and deformed geometry. Results. Among normal specimens, older age was predictive of a stiffer response and a thinner sclera. In the age group 75 to 93, diagnosed glaucoma eyes with axon damage were thicker than normal eyes. Both damaged and undamaged glaucoma eyes had a different strain response in the peripapillary sclera characterized by a stiffer meridional response. Undamaged glaucoma eyes had slower circumferential creep rates in the peripapillary sclera than normal eyes. Glaucoma eyes were not different from normal eyes in stresses and strains in the midposterior sclera. Conclusions. The observed differences in the biomechanical response of normal and glaucoma sclera may represent baseline properties that contribute to axon damage, or may be characteristics that result from glaucomatous disease. PMID:22395883

Visual field progression in glaucoma: total versus pattern deviation analyses.

PubMed

Artes, Paul H; Nicolela, Marcelo T; LeBlanc, Raymond P; Chauhan, Balwantray C

2005-12-01

To compare visual field progression with total and pattern deviation analyses in a prospective longitudinal study of patients with glaucoma and healthy control subjects. A group of 101 patients with glaucoma (168 eyes) with early to moderately advanced visual field loss at baseline (average mean deviation [MD], -3.9 dB) and no clinical evidence of media opacity were selected from a prospective longitudinal study on visual field progression in glaucoma. Patients were examined with static automated perimetry at 6-month intervals for a median follow-up of 9 years. At each test location, change was established with event and trend analyses of total and pattern deviation. The event analyses compared each follow-up test to a baseline obtained from averaging the first two tests, and visual field progression was defined as deterioration beyond the 5th percentile of test-retest variability at three test locations, observed on three consecutive tests. The trend analyses were based on point-wise linear regression, and visual field progression was defined as statistically significant deterioration (P < 5%) worse than -1 dB/year at three locations, confirmed by independently omitting the last and the penultimate observation. The incidence and the time-to-progression were compared between total and pattern deviation analyses. To estimate the specificity of the progression analyses, identical criteria were applied to visual fields obtained in 102 healthy control subjects, and the rate of visual field improvement was established in the patients with glaucoma and the healthy control subjects. With both event and trend methods, pattern deviation analyses classified approximately 15% fewer eyes as having progressed than did the total deviation analyses. In eyes classified as progressing by both the total and pattern deviation methods, total deviation analyses tended to detect progression earlier than the pattern deviation analyses. A comparison of the changes observed in MD and the visual fields' general height (estimated by the 85th percentile of the total deviation values) confirmed that change in the glaucomatous eyes almost always comprised a diffuse component. Pattern deviation analyses of progression may therefore underestimate the true amount of glaucomatous visual field progression. Pattern deviation analyses of visual field progression may underestimate visual field progression in glaucoma, particularly when there is no clinical evidence of increasing media opacity. Clinicians should have access to both total and pattern deviation analyses to make informed decisions on visual field progression in glaucoma.

Deep Retinal Layer Microvasculature Dropout Detected by the Optical Coherence Tomography Angiography in Glaucoma.

PubMed

Suh, Min Hee; Zangwill, Linda M; Manalastas, Patricia Isabel C; Belghith, Akram; Yarmohammadi, Adeleh; Medeiros, Felipe A; Diniz-Filho, Alberto; Saunders, Luke J; Weinreb, Robert N

2016-12-01

To investigate factors associated with dropout of the parapapillary deep retinal layer microvasculature assessed by optical coherence tomography angiography (OCTA) in glaucomatous eyes. Cross-sectional study. Seventy-one eyes from 71 primary open-angle glaucoma (POAG) patients with β-zone parapapillary atrophy (βPPA) enrolled in the Diagnostic Innovations in Glaucoma Study. Parapapillary deep-layer microvasculature dropout was defined as a complete loss of the microvasculature located within the deep retinal layer of the βPPA from OCTA-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) also was calculated using OCTA. Choroidal thickness and presence of focal lamina cribrosa (LC) defects were determined using swept-source optical coherence tomography. Presence of parapapillary deep-layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defects βPPA area, and choroidal thickness were analyzed. Parapapillary deep-layer microvasculature dropout was detected in 37 POAG eyes (52.1%). Eyes with microvasculature dropout had a higher prevalence of LC defects (70.3% vs. 32.4%), lower cpVD (52.7% vs. 58.8%), worse VF MD (-9.06 dB vs. -3.83 dB), thinner total choroidal thickness (126.5 μm vs. 169.1 μm), longer axial length (24.7 mm vs. 24.0 mm), larger βPPA (1.2 mm 2 vs. 0.76 mm 2 ), and lower diastolic blood pressure (74.7 mmHg vs. 81.7 mmHg) than those without dropout (P < 0.05, respectively). In the multivariate logistic regression analysis, higher prevalence of focal LC defects (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were associated significantly with the dropout. Systemic and ocular factors including focal LC defects more advanced glaucoma, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the parapapillary deep-layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between parapapillary deep-layer microvasculature dropout and systemic and ocular factors. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

[Investigations of the efficacy and bio-availability of different pilocarpine eye drops].

PubMed

Tapasztó, I; Boross, F

1982-01-01

The efficacy of three pilocarpine preparations in different concentrations (pilocarpine borate 0.5%, 1%, 2%; pilocarpine hydrochloride 0.5%, 1%, 2%; pilocarpine nitrate 1%, 2%) was investigated in 57 glaucomatous patients. Pilocarpine borate reduced intraocular pressure more effectively than either of the other pilocarpine solutions. The 2% concentration had a particularly prolonged effect. This finding corresponded well with pilocarpine levels in the aqueous humour of rabbits, as determined by spectrophotometric analysis. Pilocarpine borate 2% revealed an almost two-fold amount of drug compared to the 2% hydrochloride and nitrate solutions, and a detectable pilocarpine level was present for a longer period as well.

Trunk Accelerometry Reveals Postural Instability in Untreated Parkinson's Disease

PubMed Central

Mancini, Martina; Horak, Fay B.; Zampieri, Cris; Carlson-Kuhta, Patricia; Nutt, John G.; Chiari, Lorenzo

2017-01-01

While several studies have shown that subjects with advanced Parkinson's disease (PD) exhibit abnormalities in sway parameters during quiet standing, abnormalities of postural sway associated with untreated PD have not been reported. Although not clinically apparent, we hypothesized that spontaneous sway in quiet stance is abnormal in people with untreated PD. We examined 13 subjects, recently diagnosed with PD, who were not yet taking any anti-parkinsonian medications and 12 healthy, age-matched control subjects. Postural sway was measured with a linear accelerometer on the posterior trunk (L5 level) and compared with traditional forceplate measures of sway. Subjects stood for two minutes under two conditions: eyes open (EO) and eyes closed (EC). One of the most discriminative measures of postural changes in subjects with untreated PD was the increased ‘JERK’ of lower trunk in the EO condition, measured with the accelerometer. Root mean square and the frequency dispersion of postural sway in the EO condition also discriminated sway in untreated PD subjects compared to controls subjects. We conclude that accelerometer-based sway metrics could be used as objective measures of postural instability in untreated PD. Accelerometer-based analysis of spontaneous sway may provide a powerful tool for early clinical trials and for monitoring the effects of treatment of balance disorders in subjects with PD. PMID:21641263

Influence of optic disc leakage on objective optic nerve head assessment in patients with uveitis.

PubMed

Heinz, Carsten; Kogelboom, Katy; Heiligenhaus, Arnd

2016-02-01

Secondary glaucoma is a common complication in patients with uveitis. Heidelberg Retina Tomography (HRT) and retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) are widely used for examining optic nerve head changes. We evaluated these parameters in patients with uveitis and secondary glaucoma and with inflammatory papillary leakage on fluorescein angiography. Prospective single-center analysis of patients with uveitis, evaluating the impact of optic disc leakage on objective optic disc imaging parameters. Overall, 96 eyes of 59 patients were included. Papillary leakage was found in 42 eyes (43.8 %), and secondary glaucoma was found in 41 eyes (42.7 %). Glaucoma and papillary leakage were present in 12 (29 %) eyes with leakage and in 29 (54 %) eyes without leakage (p = 0.023). Neuroretinal rim area (p = 0.004), rim volume on HRT (p = 0.004), and RNFL thickness on OCT (p = 0.0008) were significantly increased in eyes with papillary leakage, while RNFL on HRT was unchanged (p = 0.255). When only eyes with normal IOP were examined, all objective parameters on OCT and HRT were significantly increased, whereas in eyes with secondary glaucoma, there was only a trend in the same direction, which did not reach significance. A comparison of eyes with secondary glaucoma and optic disc leakage to normal eyes with no glaucoma or leakage revealed no difference in any of the parameters. The objective parameters of optic nerve head imaging tools are significantly influenced by papillary leakage. In patients with secondary glaucoma and papillary leakage, these techniques are unable to detect and monitor glaucomatous damage.

Thick Prelaminar Tissue Decreases Lamina Cribrosa Visibility.

PubMed

Lucy, Katie A; Wang, Bo; Schuman, Joel S; Bilonick, Richard A; Ling, Yun; Kagemann, Larry; Sigal, Ian A; Grulkowski, Ireneusz; Liu, Jonathan J; Fujimoto, James G; Ishikawa, Hiroshi; Wollstein, Gadi

2017-03-01

Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05). The average prelaminar tissue thickness in regions of scans where the LC was analyzable (214 μm) was significantly thinner than in regions where the LC was not analyzable (569 μm; P < 0.001). Healthy eyes had significantly thicker average prelaminar tissue measurements than glaucoma or glaucoma suspect eyes (both P < 0.001), and glaucoma suspect eyes had significantly thicker average prelaminar tissue measurements than glaucoma eyes (P = 0.008). Significantly more of the ALC boundary was visible in glaucoma eyes (63% of ONH) than in healthy eyes (41%; P = 0.005). Thick prelaminar tissue was associated with impaired visualization of the LC. Healthy subjects generally had thicker prelaminar tissue, which potentially could create a selection bias against healthy eyes when comparing LC structures.

Lipid Neuroprotectants and Traumatic Glaucomatous Neurodegeneration

DTIC Science & Technology

2016-05-01

alter elastic TM, modulus and binding and functional assays with potential protein targets. Endogenous lipids, Aqueous humor, Trabecular meshwork...Intraocular pressure, sphingolipids, primary cell culture, elastic modulus, protein targets. Major goal 1. Test the hypothesis that selected lipids...glaucomatous TM with and without these lipids and atomic force microscope (AFM). Further elastic modulus using high flow and low flow areas of glaucomatous

An imaged-based inverse finite element method to determine in-vivo mechanical properties of the human trabecular meshwork.

PubMed

Pant, Anup D; Kagemann, Larry; Schuman, Joel S; Sigal, Ian A; Amini, Rouzbeh

2017-01-01

Previous studies have shown that the trabecular meshwork (TM) is mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is believed that elevated TM stiffness increases resistance to the aqueous humor outflow, producing increased intraocular pressure (IOP). It would be advantageous to measure TM mechanical properties in vivo , as these properties are believed to play an important role in the pathophysiology of glaucoma and could be useful for identifying potential risk factors. The purpose of this study was to develop a method to estimate in-vivo TM mechanical properties using clinically available exams and computer simulations. Inverse finite element simulation. A finite element model of the TM was constructed from optical coherence tomography (OCT) images of a healthy volunteer before and during IOP elevation. An axisymmetric model of the TM was then constructed. Images of the TM at a baseline IOP level of 11, and elevated level of 23 mmHg were treated as the undeformed and deformed configurations, respectively. An inverse modeling technique was subsequently used to estimate the TM shear modulus ( G ). An optimization technique was used to find the shear modulus that minimized the difference between Schlemm's canal area in the in-vivo images and simulations. Upon completion of inverse finite element modeling, the simulated area of the Schlemm's canal changed from 8,889 µm 2 to 2,088 µm 2 , similar to the experimentally measured areal change of the canal (from 8,889 µm 2 to 2,100 µm 2 ). The calculated value of shear modulus was found to be 1.93 kPa, (implying an approximate Young's modulus of 5.75 kPa), which is consistent with previous ex-vivo measurements. The combined imaging and computational simulation technique provides a unique approach to calculate the mechanical properties of the TM in vivo without any surgical intervention. Quantification of such mechanical properties will help us examine the mechanistic role of TM biomechanics in the regulation of IOP in healthy and glaucomatous eyes.

[Diode laser in "Malignant Glaucoma" treatment].

PubMed

Bresson Dumont, H; Ballereau, L; Lehoux, A; Santiago, P-Y

2006-05-01

Malignant glaucoma remains one of the most dramatic complications of ocular surgery. It can occur after glaucoma surgery but also after iridotomy, capsulotomy, or cataract extraction. However, the mechanisms remain unclear. to evaluate diode laser cyclodestruction as a complementary treatment in refractory malignant glaucoma. Seven women with malignant glaucoma with onset several months before (mean, 43 months; range, 12-96 months), in whom shallow anterior chamber and high IOP (25 mmHg +/- 5.5 treated with 2.86 +/- 0.9 topical and systemic medications) persisted despite prior surgical treatment (mean, 2; range, 1-5). Controlateral eyes had hyperopia (mean, +3.7 D, range, +1 to +6), five had shallow anterior chamber and high IOP. UBM detected plateau iris in four women. Seven eyes with malignant glaucoma and three controlateral eyes underwent cyclodestruction with diode laser (Viridis Twin Quantel Medical, laser, 810 nm), 22 burns around 270 degrees , 2 mm from the limbus for glaucomatous eyes and 15 inferior burns for controlateral eyes. Resolution of malignant glaucoma, with lower pressure (mean, 35%; range, 10%-70%), lower levels of medications (64%), final IOP at 13.2 mmHg (+/- 4.7), and deepening anterior chamber was achieved in all cases (mean follow-up, 18 months; range, 12-22). Cycloplegic topical treatment was stopped in 70% of cases. Diode laser cyclodestruction can help to resolve refractory malignant glaucoma. Larger UBM studies could help us to better understand the mechanisms of malignant glaucoma.

Relationship Between Anterior Lamina Cribrosa Surface Tilt and Glaucoma Development in Myopic Eyes.

PubMed

Lee, Eun Jung; Han, Jong Chul; Kee, Changwon

2017-05-01

To evaluate the anterior lamina cribrosa (LC) surface tilt angle in myopic eyes and associate it with glaucoma development. In this retrospective study, medical records of myopic patients referred for glaucoma examination from July 1, 2012 to March 30, 2016 were reviewed. Comprehensive ophthalmic examination including spectral-domain optical coherence tomography were performed. We measured the angle of anterior LC surface tilt against Bruch's membrane opening from optical coherence tomography images at the center of the clinical optic disc margin. In horizontal and vertical sections, the angles were defined as α and β, respectively. Patients were grouped according to the presence of glaucomatous damage and factors including optic nerve head morphologic parameters and LC tilt angles were compared between the 2 groups. Among 138 patients originally enrolled, 102 patients were finally analyzed. One eye from 1 patient was randomly chosen. Fifty-five eyes had glaucoma and 47 were normal. The degree of myopia and all optic nerve head morphologic parameters were not significantly different between the 2 groups. However, |α| and |β| were significantly larger in the glaucoma group (all P<0.001), and significances were maintained in multivariate analysis (P<0.001). Larger anterior LC surface tilt angles were related to the presence of glaucoma in normal-pressure myopic eyes. Angulation of the LC against Bruch's membrane opening plane might be associated with increased glaucoma susceptibility in myopic eyes. Further investigations are warranted before clinical utilization of LC tilt as glaucoma susceptibility biomarker.

Prevalence of myelinated retinal nerve fibres in adult Indians: the Central India Eye and Medical Study.

PubMed

Nangia, Vinay; Jonas, Jost B; Khare, Anshu; Bhate, Karishma; Agarwal, Shubhra; Panda-Jonas, Songhomitra

2014-05-01

To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population. The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination. Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58±0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03±0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p=0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p=0.11), best corrected visual acuity (logMAR; p=0.33), intraocular pressure (p=0.09), amount of nuclear cataract (p=0.93), optic disc area (p=0.60), presence of glaucomatous optic nerve atrophy (p=0.62), and early age-related macular degeneration (p=0.53). Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evaluation of a New Scoring System for Retinal Nerve Fiber Layer Photography Using HRA1 in 964 Eyes

PubMed Central

Hong, Samin; Moon, Jong Wook; Ha, Seung Joo; Kim, Chan Yun; Seong, Gong Je

2007-01-01

Purpose To evaluate retinal nerve fiber layer (RNFL) defect by a new scoring system for RNFL photography using the Heidelberg Retina Angiograph 1 (HRA1). Methods This retrospective study included 128 healthy eyes and 836 primary open-angle glaucoma eyes. The RNFL photography using HRA1 was interpreted using a new scoring system, and correlated with visual field indices of standard automated perimetry (SAP). Using the presence of RNFL defect, darkness, width, and location, we established the new scoring system of RNFL photos. Results The mean RNFL defect score I in the early, moderate, severe, and control groups were 7.3, 9.2, 10.4, and 3.6, respectively. The mean RNFL defect score II in the early, moderate, severe, and control groups were 14.5, 28.5, 43.4, and 3.4, respectively. Correlations between the RNFL defect score II and the mean deviation of SAP was the strongest of the various combinations (r=-0.675, P<.001). Conclusions Using a new scoring system, we propose a method for semi-quantitative interpretation of RNFL photographs. This scoring system may be helpful to distinguish between normal and glaucomatous eyes, and the score is associated with the severity of visual field loss. PMID:18063886

Inter-eye Asymmetry of Optical Coherence Tomography Angiography Vessel Density in Bilateral Glaucoma, Glaucoma Suspect, and Healthy Eyes.

PubMed

Hou, Huiyuan; Moghimi, Sasan; Zangwill, Linda M; Shoji, Takuhei; Ghahari, Elham; Manalastas, Patricia Isabel C; Penteado, Rafaella C; Weinreb, Robert N

2018-03-23

To investigate inter-eye retinal vessel density asymmetry in healthy, glaucoma suspect, and mild to moderate glaucoma subjects, and its potential utility for early detection of glaucomatous damage. Cross-sectional study. 153 subjects including 55 healthy, 32 glaucoma suspect, and 66 glaucoma subjects enrolled in the Diagnostic Innovations in Glaucoma Study(DIGS). Vessel density was obtained from optical coherence tomography angiography (OCT-A) macular and optic nerve head scans. Thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) was measured with spectral-domain optical coherence tomography (SD-OCT) scans. Inter-eye asymmetry was calculated by taking the absolute value of difference in vessel density and thickness between the right and left eyes. Inter-eye retinal vessel density asymmetry parameters were significantly different among the three groups. Glaucoma suspects had significantly higher peripapillary and macular inter-eye vessel density asymmetries compared to healthy groups in univariate (1.1% vs. 2.0%, P=0.014 and 1.2% vs. 2.5%, P=0.027, respectively) and multivariate analyses (P=0.007 and 0.038, respectively). No significant differences in asymmetry of thickness parameters were found between glaucoma suspect and healthy groups (all P> 0.718). However significant differences in asymmetry of thickness parameters between glaucoma suspects and glaucoma patients (P<0.01) were found for all parameters. Inter-eye vessel density asymmetry can be quantified by OCT-A measurement. Glaucoma suspects have significantly greater vessel density asymmetry than healthy eyes. Longitudinal studies are needed to better characterize the relationship of vessel density asymmetry with the development and progression of glaucoma. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of blotchy pigments in the anterior chamber angle as a sign of angle closure

PubMed Central

Rao, Harsha L; Mungale, Sachin C; Kumbar, Tukaram; Parikh, Rajul S; Garudadri, Chandra S

2012-01-01

Background: Blotchy pigments in the anterior chamber (AC) angle are considered diagnostic of primary angle closure (PAC). But there are no reports either on the prevalence of blotchy pigments in AC angles or the validity of this sign. Aims: To determine the prevalence of blotchy pigments in AC angles and to evaluate their relationship with glaucomatous optic neuropathy (GON) in eyes with occludable angles. Setting and Design: Cross-sectional, comparative study. Materials and Methods: Gonioscopy was performed in 1001 eyes of 526 subjects (245 eyes of 148 consecutive, occludable angle subjects and 756 eyes of 378 non-consecutive, open angle subjects), above 35 years of age. Quadrant-wise location of blotchy pigments was documented. Statistical Analysis: Odds of blotchy pigments in occludable angles against that in open angles were evaluated. Relationship of GON with blotchy pigments in occludable angle eyes was evaluated using a multivariate model. Results: Prevalence of blotchy pigments in occludable angles was 28.6% (95% CI, 22.9-34.3) and in open angles was 4.7% (95% CI, 3.2-6.3). Blotchy pigments were more frequently seen in inferior (16%) and superior quadrants (15%) of occludable angles, and inferior quadrant of open angles (4%). Odds of superior quadrant blotchy pigments in occludable angles were 33 times that in open angles. GON was seen in 107 occludable angle eyes. Blotchy pigments were not significantly associated with GON (odds ratio = 0.5; P = 0.1). Conclusions: Blotchy pigments were seen in 28.6% of occludable angle eyes and 4.7% of open angles eyes. Presence of blotchy pigments in the superior quadrant is more common in occludable angles. Presence of GON in occludable angle eyes was not associated with blotchy pigments. PMID:23202393

Pattern Electroretinography and Visual Evoked Potentials Provide Clinical Evidence of CNS Modulation of High- and Low-Contrast VEP Latency in Glaucoma

PubMed Central

Sponsel, William E.; Johnson, Susan L.; Trevino, Rick; Gonzalez, Alberto; Groth, Sylvia L.; Majcher, Carolyn; Fulton, Diane C.; Reilly, Matthew A.

2017-01-01

Purpose Both pattern electroretinography (PERG) and visual evoked potentials (VEP) can be performed using low- (15%; Lc) and high- (85%; Hc) contrast gratings that may preferentially stimulate the magno- and parvocellular pathways. We observed that among glaucomatous patients showing only one VEP latency deficit per eye, there appeared to be a very strong tendency for an Hc delay in one eye and an Lc delay in the other. Methods Diopsys NOVA-LX system was used to measure VEP Hc and Lc latency among a clinical glaucoma population to find all individuals with either a single Hc or Lc latency abnormality in each eye (group 1), or with greater than 0 and less than 4 Hc or Lc VEP latency abnormalities in the two eyes (group 2) to determine whether a significant inverse correlation existed for these values in either group. Hc and Lc PERG data were also evaluated to assess associated retinal ganglion cell responses. Results A strong inverse correlation (P = 0.0000003) was observed between the Hc and Lc VEP latency values among the 64 eyes in group 1. Group 2 provided a comparable result (n = 143; 286 eyes; P = 0.0005). PERG (n = 81; 162 eyes) also showed strong bilateral symmetry for magnitude values (P < 0.0001 for both Lc and Hc in groups 1 and 2). Conclusions Bilateral retention of both low-resolution/high-speed and high-resolution/low-speed function may persist with both eyes open despite symmetrically pathologic retinal ganglion cell PERG waveform asynchrony for Hc and Lc stimuli in the paired eyes. Translational Relevance Clinical electrophysiology strongly suggests binocular compensation for dynamic dysfunction operates under central nervous system (CNS) control in glaucoma. PMID:29134137

Evaluation of the Ganglion Cell Complex and Retinal Nerve Fiber Layer in Low, Moderate, and High Myopia: A Study by RTVue Spectral Domain Optical Coherence Tomography.

PubMed

Sezgin Akcay, Betul Ilkay; Gunay, Betul Onal; Kardes, Esra; Unlu, Cihan; Ergin, Ahmet

2017-01-01

To assess the effect of low, moderate, and high myopia on the thickness of the retinal nerve fiber layer (RNFL) and Ganglion cell complex (GCC) measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in non-glaucomatous subjects. The subjects were divided into three groups: low (n = 81, 35.6%), moderate (n = 79, 34.8%), and highly myopic eyes (n = 67, 29.5%). The RNFL thickness profile, including the average, superior, nasal, inferior, and temporal quadrant and each of the eight directional thicknesses, was measured. GCC parameters, including the average, superior, and inferior values, the focal loss volume (FLV), and the global loss volume (GLV), were measured. The correlation between the OCT measurements and the axial length was evaluated. The average, superior, inferior, and nasal RNFL thicknesses of low and moderate myopic eyes were found to be significantly higher than those of highly myopic eyes. The temporal RNFL thicknesses were not different among the three groups. The average, superior, and inferior ganglion cell complex values of low and moderate myopic eyes were significantly higher than those of highly myopic eyes. The FLV and GLV of low and moderate myopic eyes were significantly higher than those of highly myopic eyes (p = 0.001 for all). In the moderate and high myopia groups, the average RNFL thickness and GCC thickness were both negatively correlated with the axial length. Highly myopic subjects tend to have thinner RNFL and GCC thicknesses than subjects with low and moderate myopia.

Secondary glaucoma after pediatric cataract surgery

PubMed Central

Şahin, Alparslan; Çaça, Ihsan; Cingü, Abdullah Kürşat; Türkcü, Fatih Mehmet; Yüksel, Harun; Şahin, Muhammed; Çinar, Yasin; Ari, Şeyhmus

2013-01-01

AIM To determine the incidence and risk factors of secondary glaucoma after pediatric cataract surgery. METHODS Two hundred and forty nine eyes of 148 patients underwent cataract surgery without intraocular lens (IOL) implantation (group 1), and 220 eyes of 129 patients underwent cataract surgery with IOL implantation (group 2) retrospectively, were evaluated between 2000 and 2011. The outcome measure was the presence or absence of post-cataract surgery glaucoma, defined as an intraocular pressure (IOP) ≥26mmHg, as measured on at least two occasions along with corneal or optic nerve changes. RESULTS The mean follow-up periods of group 1 and 2 were (60.86±30.95) months (12-123 months) and (62.11±31.29) months (14-115 months) respectively. In group 1, 12 eyes of 8 patients (4.8%) developed glaucoma. None of the patients developed glaucoma after surgery in group 2. The mean age of the patients at the cataract surgery was (2.58±0.90) months (1 month-4 months) and the average period for glaucoma development after surgery was (9.50±4.33) months (4-16 months) in group 1. Three of the 12 glaucomatous eyes were controlled with antiglaucomatous medication and 9 eyes underwent trabeculectomy+mitomycin C surgery. One patient underwent a second trabeculectomy + mitomycin C operation for both of his eyes. CONCLUSION The incidence of glaucoma after pediatric cataract surgery is very low in patients in whom IOL is implanted. The aphakic eyes after pediatric cataract surgery are at an increased risk for glaucoma development particularly if they underwent surgery before 4 months of age. PMID:23638427

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome.

PubMed

Bourla, Dan Haim; Laron, Zvi; Snir, Moshe; Lilos, Pearl; Weinberger, Dov; Axer-Siegel, Ruth

2006-07-01

To evaluate the ocular dimensions in patients with primary growth hormone receptor insensitivity (Laron syndrome [LS]) and to study the effect of supplemental insulinlike growth factor I (IGF-I) on ocular growth. Retrospective case series. Twelve patients with LS, 8 untreated (LS group) and 4 treated (LS-T group) with supplemental IGF-I, and 30 healthy controls. Ocular dimensions and refraction were measured, and a full ophthalmologic examination was performed. Differences in the average ocular dimension data among IGF-I-treated patients, untreated ones, and controls. The average axial length of eyes in the LS group was 21.94 mm (standard deviation [SD], 0.81). Corresponding values for the LS-T and control group eyes were 22.53 mm (SD, 1.74) and 23.20 mm (SD, 1.35) respectively. The average anterior chamber depth of eyes in the LS group was 2.55 mm (SD, 0.26). Corresponding values for eyes in the LS-T and control groups were 3.48 mm (SD, 0.09) and 3.84 mm (SD, 0.16) respectively. The average lens thickness of eyes in the LS group was 4.56 mm (SD, 0.36). Corresponding values for the LS-T and control groups were 3.77 mm (SD, 0.23) and 3.51 mm (SD, 0.25), respectively. The average corneal curvature of eyes in the LS group was 46.9 diopters (D) (SD, 2.32). Corresponding values for the LS-T and control groups were 47.6 D (SD, 2.83) and 44.4 D (SD, 1.5), respectively. Insulinlike growth factor I seems to be an important regulator of ocular growth as documented in patients with primary growth hormone insensitivity. The mechanism of this observation should be investigated further.

Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency.

PubMed

Loma, Patricia; Guzman-Aranguez, Ana; Perez de Lara, Maria Jesus; Pintor, Jesus

2015-05-01

The effect of the dinucleotide P(1), P(4)-Di (adenosine-5') tetraphosphate (Ap4A) in improving adrenergic anti-glaucomatous delivery by modifying the tight junction proteins of the corneal epithelium was evaluated. Stratified human corneal epithelial cells (HCLE) were treated with Ap4A (100 μM) for 5 min and TJ protein levels and barrier function were analysed by western blotting and transepithelial electrical resistance (TEER), respectively. Western blot experiments showed a significant reduction at 2 h (45% reduction of ZO-1 and 65% reduction of occludin protein levels) as compared to non-treated (control) cells. Two hours after Ap4A treatment, TEER values were significantly reduced (65% as compared to control levels (p < 0.001)), indicating an increase in corneal barrier permeability. Topical application of Ap4A in New Zealand white rabbits two hours before the instillation of the hypotensor compounds (the α2-adrenergic receptor agonist, brimonidine and the β-adrenergic receptor antagonist, timolol), improved the delivery of these compounds to the anterior chamber as well as their hypotensive action on the intraocular pressure. The results obtained showed that, when Ap4A was topically applied two hours before the adrenergic compounds, the concentration of brimonidine in the aqueous humour increased from 64.3 ± 5.3 nM to 240.6 ± 8.6 nM and from 58.9 ± 9.2 nM to 183.7 ± 6.8 nM in the case of timolol, which also produces a more profound effect on IOP. Therefore, Ap4A treatment results in a better entrance of adrenergic anti-glaucomatous compounds within the eye and consequently improved therapeutic efficiency by increasing corneal epithelial barrier permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ocular surface changes in glaucomatous patients treated with and without preservatives beta-blockers.

PubMed

Iester, Michele; Telani, Serena; Frezzotti, Paolo; Motolese, Ilaria; Figus, Michele; Fogagnolo, Paolo; Perdicchi, Andrea

2014-08-01

To determine whether there were ocular surface changes in glaucomatous patients treated with preservatives beta-blockers who switched to preservative-free beta-blockers. This was a prospective, longitudinal, open-labeled study. One hundred thirty-two patients with primary open angle glaucoma treated with a preserved beta-blocker were enrolled. All the patients underwent perimetric and gonioscopic examination, complete ophthalmologic examination, intraocular pressure (IOP) measurements, evaluation of ocular surface, Schirmer's test, blood pressure and heart rate at baseline and 1-3 months after changing the medical treatment to a preservative-free timolol 0.1% (Timogel 0.1; Thea). At baseline, after 1 month and at the end of the study (3 months), all patients underwent a questionnaire on the visual quality and symptoms and on the quality of life (QoL). Data were analyzed by t-test when the distribution of the data was normal, by Mann-Whitney when the distribution was not normal. No significant difference was found for IOP before switching from preserved beta-blockers to preservative-free ones. No significant difference was found in blood pressure and heart rate. However, a statistically significant difference was found for abnormal fluorescein staining of the cornea and conjunctiva, eyelid erythema, conjunctival hyperemia, and follicular hyperplasia. A significant difference was found for break-up time (from 9.38±4.7 s at baseline to 10.64±4.7 s after 3 months) and Schirmer's test (from 12.9±5.96 mm at baseline to 14.2±5.87 mm after 3 months). The questionnaire showed that the patient improved the dryness and foreign body sensation. In glaucomatous patients, preservative-free 0.1 timolol treatment improved their QoL. Similar dry eye signs or symptoms improved after 3 months of treatment reducing dryness, hyperemia, follicular hyperplasia, and foreign body sensation.

Contrast Sensitivity Perimetry and Clinical Measures of Glaucomatous Damage

PubMed Central

Swanson, William H.; Malinovsky, Victor E.; Dul, Mitchell W.; Malik, Rizwan; Torbit, Julie K.; Sutton, Bradley M.; Horner, Douglas G.

2014-01-01

ABSTRACT Purpose To compare conventional structural and functional measures of glaucomatous damage with a new functional measure—contrast sensitivity perimetry (CSP-2). Methods One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. Results Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, −0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). Conclusions Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease. PMID:25259758

Contrast sensitivity perimetry and clinical measures of glaucomatous damage.

PubMed

Swanson, William H; Malinovsky, Victor E; Dul, Mitchell W; Malik, Rizwan; Torbit, Julie K; Sutton, Bradley M; Horner, Douglas G

2014-11-01

To compare conventional structural and functional measures of glaucomatous damage with a new functional measure-contrast sensitivity perimetry (CSP-2). One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, -0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease.

Non-destructive analysis of the conformational changes in human lens lipid and protein structures of the immature cataracts associated with glaucoma

NASA Astrophysics Data System (ADS)

Lin, Shan-Yang; Li, Mei-Jane; Liang, Run-Chu; Lee, Shui-Mei

1998-09-01

Previous study has supposed a possible mechanism of exacerbating cataract formation in cataractous human lens capsules induced by hypertension or glaucoma. To clarify the glaucoma-induced cataract formation of the eyes lens, changes in the human lens lipid and protein structures of immature cataractous patients with or without glaucoma were investigated. Two normal lenses, ten immature cataractous lenses without any complication and four immature cataractous lenses with glaucoma were used after surgical operation. Each de-capsulated human lens sample was sliced with a number 15 surgical blade. The intact nuclear lens regions were used for non-destructive analysis. The lens lipid and protein structures, as well as compositions of these lens samples, were determined using a Fourier transform infrared (FTIR) microspectroscopy with second-derivative, de-convolution and curve-fitting methods. The results indicate that the IR spectrum of glaucomatous lenses appeared as a shoulder only at 2853 cm -1, thus the composition of the symmetric CH 2 stretching band at 2853 (2852) cm -1 decreased more significantly in glaucomatous lens to only one half of that in normal and immature cataractous lenses. The composition of the asymmetric CH 3 stretching band at 2965 cm -1 for normal lens decreases markedly from 32 to 20% for immature cataractous lenses with or without glaucoma. The compositional ratio of component at 2965 cm -1 to component at 2928 (2930) cm -1 for normal lenses was about 0.702, and that ratio for cataractous lenses without glaucoma was 0.382 but for glaucomatous lenses was 0.377. The maximum peak position of amide I band for IR spectra of the normal lens, immature cataractous lenses without complications or glaucomatous lenses appeared respectively at 1632, 1630 or 1622 cm -1, assigned to β sheet structure. A marked difference in peak intensity of amide I band for the normal lenses and immature cataractous human lenses with or without glaucoma was observed. The peak intensity ratio of amide I /amide II (1632/1545 cm -1) for normal lenses was in the range of 2.20-2.33, whereas in the spectra of immature cataractous lenses without glaucoma this ratio (1630/1545 cm -1) was 1.28-1.41 but was 1.04-1.13 for glaucomatous lens in the intensity ratio of 1622/1545 cm -1. The intensity of the glycogen bands in the wavenumber region 1135-1076 and 1069-1032 cm -1 was found to increase for the immature cataractous lenses with or without glaucoma, as compared with the normal ones. The peaks ranging from 1633 to 1610 cm -1 assigned to β-sheet structure also exhibited a pronounced compositional difference, particularly in glaucomatous lenses. The human lens lipid and protein secondary structures were more affected by glaucoma. Higher protein side chains and reduced lipid content contributed predominantly to the CH stretching vibrations of normal lens structure, whereas high lipid content and less protein side chains dominated the CH stretching vibrations of cataractous lenses with or without glaucoma. Decrease α-helix and random coil structures but enhanced β-sheet structure in the immature cataractous human lens induced by glaucoma might result from the formation of intermolecular hydrogen-bonding insoluble protein aggregates that modify the secondary structure of protein in lenses.

Outcomes of Infantile-Onset Glaucoma Associated With Port Wine Birthmarks and Other Periocular Cutaneous Vascular Malformation.

PubMed

Reyes-Capó, Daniela; Cavuoto, Kara M; Chang, Ta C

2018-01-01

The incidence of infantile-onset secondary glaucoma associated with periocular cutaneous vascular malformations is high and the outcomes of these glaucomatous eyes have anecdotally been poor. The purpose of this study was to determine the anatomic and visual outcomes of affected eyes. Retrospective case series. Consecutive patients with early-onset (younger than 36 months of age) glaucoma associated with cutaneous vascular malformations from 1995‒2015 were included. Seventeen eyes of 13 patients with Sturge-Weber syndrome (SW, n = 10), Klippel-Trenaunay-Weber syndrome (KTW, n = 1), cutis marmorata telangiectatica congenita (CMTC, n = 1), and phakomatosis pigmentovascularis (PPV, n = 1) were included. Three SW and 1 KTW patient had bilateral glaucoma. At presentation, mean age was 6.5 ± 9.1 months and mean intraocular pressure was 27.2 ± 6.13 mm Hg. The average number of surgical procedures per eye increased from 1.0 ± 0.5 (range, 0‒2) at less than 5 years' follow-up (9 eyes) to 3.5 ± 2.3 (range, 1‒7) with at least 5 years' follow-up (8 eyes). Visual acuity was better than or equal to 20/70 in 2 of 6 eyes (33%) with less than 5 years' follow-up and in 3 of 7 eyes (43%) with at least 5 years' follow-up. Additionally, a higher number of baseline risk factors correlated with poorer visual outcome. After a mean follow-up of 6.6 years, visual outcome in infantile-onset secondary glaucoma associated with cutaneous periocular vascular malformation is guarded. Increased numbers of baseline risk factors and procedures are associated with poorer vision. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Thick Prelaminar Tissue Decreases Lamina Cribrosa Visibility

PubMed Central

Lucy, Katie A.; Wang, Bo; Schuman, Joel S.; Bilonick, Richard A.; Ling, Yun; Kagemann, Larry; Sigal, Ian A.; Grulkowski, Ireneusz; Liu, Jonathan J.; Fujimoto, James G.; Ishikawa, Hiroshi; Wollstein, Gadi

2017-01-01

Purpose Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). Methods The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. Results A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05). The average prelaminar tissue thickness in regions of scans where the LC was analyzable (214 μm) was significantly thinner than in regions where the LC was not analyzable (569 μm; P < 0.001). Healthy eyes had significantly thicker average prelaminar tissue measurements than glaucoma or glaucoma suspect eyes (both P < 0.001), and glaucoma suspect eyes had significantly thicker average prelaminar tissue measurements than glaucoma eyes (P = 0.008). Significantly more of the ALC boundary was visible in glaucoma eyes (63% of ONH) than in healthy eyes (41%; P = 0.005). Conclusions Thick prelaminar tissue was associated with impaired visualization of the LC. Healthy subjects generally had thicker prelaminar tissue, which potentially could create a selection bias against healthy eyes when comparing LC structures. PMID:28324116

Effects of 0.2% brimonidine and 0.2% brimonidine-0.5% timolol on intraocular pressure and pupil size in normal equine eyes.

PubMed

Von Zup, M; Lassaline, M; Kass, P H; Miller, P E; Thomasy, S M

2017-11-01

Brimonidine is an α 2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes. To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes. A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first). Pupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS). There were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important. Horses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma. Brimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP. © 2017 EVJ Ltd.

Vitiligo iridis and glaucoma: a rare sequelae of small pox.

PubMed

Kavitha, S; Patel, S R; Mohini, P; Venkatesh, R; Sengupta, S

2015-10-01

Vitiligo iridis refers to focal areas of iris atrophy as sequelae of small pox infection. We report a series of patients with unilateral vitiligo iridis, some of whom presented with secondary open-angle glaucoma. Three patients with vitiligo iridis underwent a comprehensive ophthalmic examination including intraocular pressure (IOP) measurement, slit lamp biomicroscopy, gonioscopy, and fundus evaluation. Patients' facial features were also documented and photographed. All patients were in their sixth decade. Two out the three had elevated IOP (52 mm Hg and 36 mm Hg) in the same eye as vitiligo iridis, at initial presentation. Gonioscopy showed patchy iris hyperpigmentation and fundus evaluation showed glaucomatous optic disc changes in the involved eye. One patient responded favourably to topical antiglaucoma medications, whereas the other was taken up for combined phacoemulsification-trabeculectomy with good results. The third patient had normal IOP in the involved eye. All three patients gave a history of small pox in childhood and had pitted facial scars typical of previous small pox infection. Vitiligo iridis may be associated with the secondary glaucoma as a long-term sequelae of small pox. It may be prudent to periodically follow-up such patients for development of raised IOP in the future.

Description of the Age-Related Eye Disease Study 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Ying, Gui-shuang; Maguire, Maureen G; Alexander, Judith; Martin, Revell W; Antoszyk, Andrew N

2009-09-01

To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.

Ablation of lens epithelial cells with a laser photolysis system: Histopathology, ultrastructure, and immunochemistry

PubMed Central

Mamalis, Nick; Grossniklaus, Hans E.; Waring, George O.; Werner, Liliana; Brubaker, Jacob; Davis, Don; Espandar, Ladan; Walker, Rudolf; Thyzel, Reinhardt

2010-01-01

PURPOSE To evaluate efficacy of a neodymium:YAG (Nd:YAG) laser photolysis system in removing lens epithelial cells (LECs) and characterize the effect of the laser on laminin and fibronectin involved in LEC adhesion and migration. METHODS Cadaver eyes were evaluated using the Miyake technique. The lenses were removed with phacoemulsification. The modified Nd:YAG laser was used to clean the LECs from the capsule. Only the fornix was cleaned in some eyes and the anterior subcapsular area in other eyes. Some areas were not treated and acted as controls. Standard irrigation/aspiration (I/A) removal of LECs was performed in additional eyes. The eyes were analyzed using light microscopy and immunohistochemical staining. RESULTS Histopathologic evaluation showed that the laser removed the LECs from the anterior lens capsule and from the fornix. Immunohistochemical staining showed fibronectin and laminin staining in the untreated areas that was absent in the treated areas. Standard I/A removal of the LECs showed absence of cells but persistent laminin and fibronectin. Electron microscopy showed epithelial cells in untreated areas with an absence of the LECs and debris in treated areas. CONCLUSIONS The laser photolysis system removed LECs from the anterior lens capsule and capsule fornix. Along with the cells, laminin, fibronectin, and cell debris remained in the untreated areas but were removed by the treatment. This treatment may be useful in preventing posterior capsule opacification. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. PMID:20494774

Increased Ap4A levels and ecto-nucleotidase activity in glaucomatous mice retina.

PubMed

Pérez de Lara, María J; Guzmán-Aranguez, Ana; Gómez-Villafuertes, Rosa; Gualix, Javier; Miras-Portugal, María Teresa; Pintor, Jesús

2018-06-08

The pathogenesis of glaucoma involves numerous intracellular mechanisms including the purinergic system contribution. Furthermore, the presence and release of nucleotides and dinucleotides during the glaucomatous damage and the maintenance of degradation machinery through ecto-nucleotidase activity are participating in the modulation of the suitable extracellular complex balance. The aim of this study was to investigate the levels of diadenosine tetraphosphate (Ap 4 A) and the pattern of ecto-nucleotidase activity expression in glaucomatous retinas during the progress the pathology. Ap 4 A levels were analyzed by HPLC in glaucomatous retinas from the DBA/2J mice at 3, 9, 15, and 23 months of age. For that, retinas were dissected as flattened whole-mounts and stimulated in Ringer buffer with or without 59 mM KCl. NPP1 expression was analyzed by RT-PCR and western blot and its distribution was assessed by immunohistochemistry studies examined under confocal microscopy. Glaucomatous mice exhibited Ap 4 A values, which changed in stimulated retinas as long as the pathology progressed varying from 0.73 ± 0.04 (3 months) to 0.170 ± 0.05 pmol/mg retina (23 months). Concomitantly, NPP1 expression was significantly increased (82.15%) in the DBA/2J mice at 15 months. Furthermore, immunohistochemical studies showed that NPP1 labeling was stronger in OPL and IPL labeling tangentially in the vitreal part of the retina and was upregulated at 15 months of age. Our findings demonstrate that Ap 4 A decreased levels may be related with exacerbated activity of NPP1 protein in glaucomatous degeneration and in this way contributing to elucidate different mechanisms involved in retinal impairment in glaucomatous degeneration.

Likelihood Ratios for Glaucoma Diagnosis Using Spectral Domain Optical Coherence Tomography

PubMed Central

Lisboa, Renato; Mansouri, Kaweh; Zangwill, Linda M.; Weinreb, Robert N.; Medeiros, Felipe A.

2014-01-01

Purpose To present a methodology for calculating likelihood ratios for glaucoma diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements from spectral domain optical coherence tomography (spectral-domain OCT). Design Observational cohort study. Methods 262 eyes of 187 patients with glaucoma and 190 eyes of 100 control subjects were included in the study. Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with preperimetric and perimetric glaucomatous damage were included in the glaucoma group. The control group was composed of healthy eyes with normal visual fields from subjects recruited from the general population. All eyes underwent RNFL imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma diagnosis were estimated for specific global RNFL thickness measurements using a methodology based on estimating the tangents to the Receiver Operating Characteristic (ROC) curve. Results Likelihood ratios could be determined for continuous values of average RNFL thickness. Average RNFL thickness values lower than 86μm were associated with positive LRs, i.e., LRs greater than 1; whereas RNFL thickness values higher than 86μm were associated with negative LRs, i.e., LRs smaller than 1. A modified Fagan nomogram was provided to assist calculation of post-test probability of disease from the calculated likelihood ratios and pretest probability of disease. Conclusion The methodology allowed calculation of likelihood ratios for specific RNFL thickness values. By avoiding arbitrary categorization of test results, it potentially allows for an improved integration of test results into diagnostic clinical decision-making. PMID:23972303

Normal versus High Tension Glaucoma: A Comparison of Functional and Structural Defects

PubMed Central

Thonginnetra, Oraorn; Greenstein, Vivienne C.; Chu, David; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2009-01-01

Purpose To compare visual field defects obtained with both multifocal visual evoked potential (mfVEP) and Humphrey visual field (HVF) techniques to topographic optic disc measurements in patients with normal tension glaucoma (NTG) and high tension glaucoma (HTG). Methods We studied 32 patients with NTG and 32 with HTG. All patients had reliable 24-2 HVFs with a mean deviation (MD) of −10 dB or better, a glaucomatous optic disc and an abnormal HVF in at least one eye. Multifocal VEPs were obtained from each eye and probability plots created. The mfVEP and HVF probability plots were divided into a central 10-degree (radius) and an outer arcuate subfield in both superior and inferior hemifields. Cluster analyses and counts of abnormal points were performed in each subfield. Optic disc images were obtained with the Heidelberg Retina Tomograph III (HRT III). Eleven stereometric parameters were calculated. Moorfields regression analysis (MRA) and the glaucoma probability score (GPS) were performed. Results There were no significant differences in MD and PSD values between NTG and HTG eyes. However, NTG eyes had a higher percentage of abnormal test points and clusters of abnormal points in the central subfields on both mfVEP and HVF than HTG eyes. For HRT III, there were no significant differences in the 11 stereometric parameters or in the MRA and GPS analyses of the optic disc images. Conclusions The visual field data suggest more localized and central defects for NTG than HTG. PMID:19223786

Thickness related textural properties of retinal nerve fiber layer in color fundus images.

PubMed

Odstrcilik, Jan; Kolar, Radim; Tornow, Ralf-Peter; Jan, Jiri; Budai, Attila; Mayer, Markus; Vodakova, Martina; Laemmer, Robert; Lamos, Martin; Kuna, Zdenek; Gazarek, Jiri; Kubena, Tomas; Cernosek, Pavel; Ronzhina, Marina

2014-09-01

Images of ocular fundus are routinely utilized in ophthalmology. Since an examination using fundus camera is relatively fast and cheap procedure, it can be used as a proper diagnostic tool for screening of retinal diseases such as the glaucoma. One of the glaucoma symptoms is progressive atrophy of the retinal nerve fiber layer (RNFL) resulting in variations of the RNFL thickness. Here, we introduce a novel approach to capture these variations using computer-aided analysis of the RNFL textural appearance in standard and easily available color fundus images. The proposed method uses the features based on Gaussian Markov random fields and local binary patterns, together with various regression models for prediction of the RNFL thickness. The approach allows description of the changes in RNFL texture, directly reflecting variations in the RNFL thickness. Evaluation of the method is carried out on 16 normal ("healthy") and 8 glaucomatous eyes. We achieved significant correlation (normals: ρ=0.72±0.14; p≪0.05, glaucomatous: ρ=0.58±0.10; p≪0.05) between values of the model predicted output and the RNFL thickness measured by optical coherence tomography, which is currently regarded as a standard glaucoma assessment device. The evaluation thus revealed good applicability of the proposed approach to measure possible RNFL thinning. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Heidelberg Retina Tomograph 3 machine learning classifiers for glaucoma detection

PubMed Central

Townsend, K A; Wollstein, G; Danks, D; Sung, K R; Ishikawa, H; Kagemann, L; Gabriele, M L; Schuman, J S

2010-01-01

Aims To assess performance of classifiers trained on Heidelberg Retina Tomograph 3 (HRT3) parameters for discriminating between healthy and glaucomatous eyes. Methods Classifiers were trained using HRT3 parameters from 60 healthy subjects and 140 glaucomatous subjects. The classifiers were trained on all 95 variables and smaller sets created with backward elimination. Seven types of classifiers, including Support Vector Machines with radial basis (SVM-radial), and Recursive Partitioning and Regression Trees (RPART), were trained on the parameters. The area under the ROC curve (AUC) was calculated for classifiers, individual parameters and HRT3 glaucoma probability scores (GPS). Classifier AUCs and leave-one-out accuracy were compared with the highest individual parameter and GPS AUCs and accuracies. Results The highest AUC and accuracy for an individual parameter were 0.848 and 0.79, for vertical cup/disc ratio (vC/D). For GPS, global GPS performed best with AUC 0.829 and accuracy 0.78. SVM-radial with all parameters showed significant improvement over global GPS and vC/ D with AUC 0.916 and accuracy 0.85. RPART with all parameters provided significant improvement over global GPS with AUC 0.899 and significant improvement over global GPS and vC/D with accuracy 0.875. Conclusions Machine learning classifiers of HRT3 data provide significant enhancement over current methods for detection of glaucoma. PMID:18523087

Fluctuation of Bacteria on Bleb Surface After Trabeculectomy With Adjunctive Mitomycin C.

PubMed

Takahashi, Nobumichi; Sawada, Akira; Mochizuki, Kiyofumi; Katada, Toshihiko; Yamamoto, Tetsuya

2016-05-01

To determine whether the bacterial and floral patterns on the bleb surface are affected by the season in eyes that had undergone trabeculectomy with adjunctive mitomycin C. Forty-four glaucoma patients who had an avascular or a hypovascular cystic filtering bleb were studied. Swabs of the bleb surface were taken 4 times in 1 year. The samples were cultured, and all organisms isolated were identified and tested for antibiotic sensitivity and resistance. Of the 176 specimens, 48 tested positive in cultures. Out of the 44 glaucoma eyes that had undergone trabeculectomy, 30 (68.2%) eyes were culture positive. A total of 58 strains were isolated. The organisms isolated were 22 strains of Staphylococcus epidermidis, 21 strains of Propionibacterium acnes, 8 strains of Corynebacterium sp., 5 strains of Staphylococcus sp., and 1 strain of both Neisseria sp., and Candida parapsilosis. Fifteen eyes had a positive culture ≥2 times, and in 10 of these eyes, the same strain was isolated. There was no resistance to vancomycin by S. epidermidis, P. acnes, and Corynebacterium sp. All of the isolates of S.epidermidis were sensitive to minocycline and amikacin. The rate of bacterial detection in the spring was 13.6%, summer was 20.5%, autumn was 45.5%, and winter was 29.5%. The increase in the incidence of bacterial presence during autumn was significant (P=0.006; the Fisher exact probability test). It is not rare to detect the bacterial organisms on the bleb surface in glaucomatous eyes that had undergone trabeculectomy. The prevalence varied with the season and was highest in the autumn.

Surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy combined with lensectomy for glaucomatous eyes with extremely shallow anterior chamber and cataract.

PubMed

Zhang, Zhaotian; Zhang, Shaochong; Jiang, Xintong; Qiu, Suo; Wei, Yantao

2016-01-04

Glaucoma combined with an extremely shallow anterior chamber and cataracts remains as a complex condition to deal with. And the emergence of microincision vitrectomy surgery (MIVS) system may provide an ideal option for the treatment of that. We report a clinical study of surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy (PPV) combined with lensectomy in the treatment of glaucomatous eyes with extremely shallow anterior chamber and cataract. Prospective, nonrandomized and noncomparative case series study. Consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited to have combined surgeries of 23-gauge transconjunctival pars plana vitrectomy and lensectomy. The main outcomes were best corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber depth (ACD), number of anti-glaucoma medications and surgery-associated complications. Seventeen consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited. The mean follow-up was 21.2 ± 8.8 months. Postoperatively, there was no significant improvement of BCVA (P = 0.25). The mean intraocular (IOP) decreased significantly from 43.14 ± 6.53 mmHg to 17.29 ± 1.80 mmHg (P < 0.001), and the mean depth of anterior chamber increased significantly from 0.507 ± 0.212 mm to 3.080 ± 0.313 mm (P < 0.001). The mean number of anti-glaucoma medications decreased from 4.1 ± 0.8 to 0.6 ± 0.8 (P < 0.001). No severe vision-threatening intra- or post-operative complications occurred. Glaucoma with an extremely shallow anterior chamber and cataract can be managed well with the combined surgeries of 23-gauge pars plana vitrectomy and lensectomy. The surgical procedure is an effective and safe method to resolve the pupillary block and deepen the anterior chamber.

Driving patterns in older adults with glaucoma.

PubMed

van Landingham, Suzanne W; Hochberg, Chad; Massof, Robert W; Chan, Emilie; Friedman, David S; Ramulu, Pradeep Y

2013-02-21

The ability to drive is important for ensuring quality of life for many older adults. Glaucoma is prevalent in this age group and may affect driving. The purpose of this study is to determine if glaucoma and glaucomatous visual field (VF) loss are associated with driving cessation, limitations, and deference to another driver in older adults. Cross-sectional study. Eighty-one glaucoma subjects and 58 glaucoma suspect controls between age 60 and 80 reported if they had ceased driving, limited their driving in various ways, or preferred another to drive. Twenty-three percent of glaucoma subjects and 6.9% of suspects had ceased driving (p = 0.01). Glaucoma subjects also had more driving limitations than suspects (2.0 vs. 1.1, p = 0.007). In multivariable models, driving cessation was more likely for glaucoma subjects as compared to suspects (OR = 4.0; 95% CI = 1.1-14.7; p = 0.03). The odds of driving cessation doubled with each 5 decibel (dB) decrement in the better-eye VF mean deviation (MD) (OR = 2.0; 95% CI = 1.4-2.9; p < 0.001). Glaucoma subjects were also more likely than suspects to report a greater number of driving limitations (OR = 4.7; 95% CI = 1.3-16.8; p = 0.02). The likelihood of reporting more limitations increased with the VF loss severity (OR = 1.6 per 5 dB decrement in the better-eye VF MD; 95% CI = 1.1-2.4; p = 0.02). Neither glaucoma nor VF MD was associated with other driver preference (p > 0.1 for both). Glaucoma and glaucomatous VF loss are associated with greater likelihood of driving cessation and greater limitation of driving in the elderly. Further prospective study is merited to assess when and why people with glaucoma change their driving habits, and to determine if their observed self-regulation of driving is adequate to ensure safety.

Variation in the vitreoretinal configuration of Stage 4 retinopathy of prematurity in photocoagulated and treatment naive eyes undergoing vitrectomy

PubMed Central

Gadkari, Salil Sharad; Deshpande, Madan

2017-01-01

Purpose: We sought to document the difference in the vitreoretinal configuration of Stage 4 retinopathy of prematurity (ROP) in photocoagulated and treatment naive eyes undergoing vitrectomy and to correlate it with surgical complexity. Methods: Consecutive eyes posted for vitrectomy with Stage 4 ROP were documented preoperatively using a RetCam for the presence of peripheral traction (PT), presence of central traction just outside the arcades, and presence of traction extending to the lens. A note was made of the following intraoperative events: lensectomy, intraoperative bleeding, and iatrogenic breaks. Wilcoxon rank-sum test was used for analysis. Results: From a total of 46 eyes, 16 and 30 eyes were from the treated and treatment naive group, respectively. More eyes in the treated group had central (P < 0.0001) and lenticular traction (P = 0.022). More eyes in the untreated group had PT (P < 0.0001). A significant number of eyes without photocoagulation needed lensectomy (P = 0.042), and no difference in intraoperative bleeding (P = 0.94) was demonstrable. Iatrogenic retinotomy occurred in three eyes, all naive. Notably, age at surgery was more in the untreated group (P = 0.00008). Conclusion: Vasoproliferative activity in all retinopathies occurs at the junction of the ischemic and nonischemic retina. In the natural course of ROP, this takes place peripherally, at the ridge. In photocoagulated eyes, this junction is displaced posteriorly due to peripheral ablation. Treated eyes manifested with posterior proliferative changes and were more amenable to lens-sparing vitrectomy. Naive eyes were older when they underwent surgery to relieve PT with greater chances of lensectomy and iatrogenic breaks. PMID:28905829

Compressed 3D and 2D digital images versus standard 3D slide film for the evaluation of glaucomatous optic nerve features.

PubMed

Sandhu, Simrenjeet; Rudnisky, Chris; Arora, Sourabh; Kassam, Faazil; Douglas, Gordon; Edwards, Marianne C; Verstraten, Karin; Wong, Beatrice; Damji, Karim F

2018-03-01

Clinicians can feel confident compressed three-dimensional digital (3DD) and two-dimensional digital (2DD) imaging evaluating important features of glaucomatous disc damage is comparable to the previous gold standard of stereoscopic slide film photography, supporting the use of digital imaging for teleglaucoma applications. To compare the sensitivity and specificity of 3DD and 2DD photography with stereo slide film in detecting glaucomatous optic nerve head features. This prospective, multireader validation study imaged and compressed glaucomatous, suspicious or normal optic nerves using a ratio of 16:1 into 3DD and 2DD (1024×1280 pixels) and compared both to stereo slide film. The primary outcome was vertical cup-to-disc ratio (VCDR) and secondary outcomes, including disc haemorrhage and notching, were also evaluated. Each format was graded randomly by four glaucoma specialists. A protocol was implemented for harmonising data including consensus-based interpretation as needed. There were 192 eyes imaged with each format. The mean VCDR for slide, 3DD and 2DD was 0.59±0.20, 0.60±0.18 and 0.62±0.17, respectively. The agreement of VCDR for 3DD versus film was κ=0.781 and for 2DD versus film was κ=0.69. Sensitivity (95.2%), specificity (95.2%) and area under the curve (AUC; 0.953) of 3DD imaging to detect notching were better (p=0.03) than for 2DD (90.5%; 88.6%; AUC=0.895). Similarly, sensitivity (77.8%), specificity (98.9%) and AUC (0.883) of 3DD to detect disc haemorrhage were better (p=0.049) than for 2DD (44.4%; 99.5%; AUC=0.72). There was no difference between 3DD and 2DD imaging in detecting disc tilt (p=0.7), peripapillary atrophy (p=0.16), grey crescent (p=0.1) or pallor (p=0.43), although 3D detected sloping better (p=0.013). Both 3DD and 2DD imaging demonstrates excellent reproducibility in comparison to stereo slide film with experts evaluating VCDR, notching and disc haemorrhage. 3DD in this study was slightly more accurate than 2DD for evaluating disc haemorrhage, notching and sloping. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Degenerative effects in rat eyes after experimental ocular hypertension.

PubMed

Scarsella, G; Nebbioso, M; Stefanini, S; Pescosolido, N

2012-10-08

This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC) 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs), by means of fluorescein isothiocyanate-coniugated dextran (FITC), the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP) revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF) was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

A hierarchical cluster analysis of normal-tension glaucoma using spectral-domain optical coherence tomography parameters.

PubMed

Bae, Hyoung Won; Ji, Yongwoo; Lee, Hye Sun; Lee, Naeun; Hong, Samin; Seong, Gong Je; Sung, Kyung Rim; Kim, Chan Yun

2015-01-01

Normal-tension glaucoma (NTG) is a heterogenous disease, and there is still controversy about subclassifications of this disorder. On the basis of spectral-domain optical coherence tomography (SD-OCT), we subdivided NTG with hierarchical cluster analysis using optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thicknesses. A total of 200 eyes of 200 NTG patients between March 2011 and June 2012 underwent SD-OCT scans to measure ONH parameters and RNFL thicknesses. We classified NTG into homogenous subgroups based on these variables using a hierarchical cluster analysis, and compared clusters to evaluate diverse NTG characteristics. Three clusters were found after hierarchical cluster analysis. Cluster 1 (62 eyes) had the thickest RNFL and widest rim area, and showed early glaucoma features. Cluster 2 (60 eyes) was characterized by the largest cup/disc ratio and cup volume, and showed advanced glaucomatous damage. Cluster 3 (78 eyes) had small disc areas in SD-OCT and were comprised of patients with significantly younger age, longer axial length, and greater myopia than the other 2 groups. A hierarchical cluster analysis of SD-OCT scans divided NTG patients into 3 groups based upon ONH parameters and RNFL thicknesses. It is anticipated that the small disc area group comprised of younger and more myopic patients may show unique features unlike the other 2 groups.

Alterations in molecular pathways in the retina of early experimental glaucoma eyes

PubMed Central

Cao, Li; Wang, Lin; Cull, Grant; Zhou, An

2015-01-01

Glaucoma is a multifactorial, neurodegenerative disease. The molecular mechanisms that underlie the pathophysiological changes in glaucomatous eyes, especially at the early stage of the disease, are poorly understood. Here, we report the findings from a quantitative proteomic analysis of retinas from experimental glaucoma (EG) eyes. An early stage of EG was modeled on unilateral eyes of five nonhuman primates (NHP) by laser treatment-induced elevation of intraocular pressure (IOP). Retinal proteins were extracted from individual EG eyes and their contralateral control eyes of the same animals, respectively, and analyzed by quantitative mass spectrometry (MS). As a result, a total, 475 retinal proteins were confidently identified and quantified. Results of bioinformatic analysis of proteins that showed an increase in the EG eyes suggested changes in apoptosis, DNA damage, immune response, cytoskeleton rearrangement and cell adhesion processes. Interestingly, hemoglobin subunit alpha (HBA) and Ras related C3 botulinum toxin substrate 1 (Rac1) were among the increased proteins. Results of molecular modeling of HBA- and Rac1-associated signaling network implicated the involvement of Mitogen-Activated Protein Kinase (MAPK) pathway in the EG, through which Rac1 may exert a regulatory role on HBA. This is the first observation of this potentially novel signaling network in the NHP retina and in EG. Results of Western blot analyses for Rac1, HBA and a selected MAPK pathway protein indicated synergistic changes in all three proteins in the EG eyes. Further, results of hierarchical cluster analysis of proteomes of control eyes revealed a clear age-proteome relationship, and such relationship appeared disrupted in the EG eyes. In conclusion, our results suggested an increased presence of a potentially novel signaling network at the early stage of glaucoma, and age might be one of the determinant factors in retinal proteomic characteristics under normal conditions. PMID:26069528

Glaucoma diagnostic accuracy of optical coherence tomography parameters in early glaucoma with different types of optic disc damage.

PubMed

Shin, Hye-Young; Park, Hae-Young Lopilly; Jung, Younhea; Choi, Jin-A; Park, Chan Kee

2014-10-01

To compare the initial visual field (VF) defect pattern and the spectral-domain optical coherence tomography (OCT) parameters and investigate the effects of distinct types of optic disc damage on the diagnostic performance of these OCT parameters in early glaucoma. Retrospective, observational study. A total of 138 control eyes and 160 eyes with early glaucoma were enrolled. The glaucomatous eyes were subdivided into 4 groups according to the type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile sclerotic (SS) group, and generalized enlargement (GE) group. The values of total deviation (TD) maps were analyzed, and superior-inferior (S-I) differences of TD were calculated. The optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. Comparison of diagnostic ability using area under the receiver operating characteristic curves (AUCs). The S-I and central S-I difference of the FI group were larger than those of the GE group. The rim area of the SS group was larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR) of the GE group was larger than that of the MY group. In addition, the minimum and inferotemporal GCIPL thicknesses of the FI group were smaller than those of the GE group. The AUC of the rim area (0.89) was lower than that of the minimum GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of the minimum GCIPL thicknesses of the FI and MY group were greater than those of the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE. The OCT parameters differed among the 4 groups on the basis of the distinct optic disc appearance and initial glaucomatous damage pattern. Clinicians should be aware that the diagnostic capability of OCT parameters could differ according to the type of optic disc damage in early glaucoma. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential objective perimetry for the diagnosis and early detection of glaucomatous field defects.

PubMed

Mousa, Mohammad F; Cubbidge, Robert P; Al-Mansouri, Fatima; Bener, Abdulbari

2014-02-01

Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively. The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

Evaluation of Hemifield Sector Analysis Protocol in Multifocal Visual Evoked Potential Objective Perimetry for the Diagnosis and Early Detection of Glaucomatous Field Defects

PubMed Central

Mousa, Mohammad F.; Cubbidge, Robert P.; Al-Mansouri, Fatima

2014-01-01

Purpose Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. Methods Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. Results Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively. Conclusions The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. PMID:24511212

Correlation between epithelial thickness in normal corneas, untreated ectatic corneas, and ectatic corneas previously treated with CXL; is overall epithelial thickness a very early ectasia prognostic factor?

PubMed

Kanellopoulos, Anastasios John; Aslanides, Ioannis M; Asimellis, George

2012-01-01

To determine and correlate epithelial corneal thickness (pachymetric) measurements taken with a digital arc scanning very high frequency ultrasound biomicroscopy (HF UBM) imaging system (Artemis-II), and compare mean and central epithelial thickness among normal eyes, untreated keratoconic eyes, and keratoconic eyes previously treated with collagen crosslinking (CXL). Epithelial pachymetry measurements (topographic mapping) were conducted on 100 subjects via HF UBM. Three groups of patients were included: patients with normal eyes (controls), patients with untreated keratoconic eyes, and patients with keratoconic eyes treated with CXL. Central, mean, and peripheral corneal epithelial thickness was examined for each group, and a statistical study was conducted. Mean, central, and peripheral corneal epithelial thickness was compared between the three groups of patients. Epithelium thickness varied substantially in the keratoconic group, and in some cases there was a difference of up to 20 μm between various points of the same eye, and often a thinner epithelium coincided with a thinner cornea. However, on average, data from the keratoconic group suggested an overall thickening of the epithelium, particularly over the pupil center of the order of +3 μm, while the mean epithelium thickness was on average +1.1 μm, compared to the control population (P = 0.005). This overall thickening was more pronounced in younger patients in the keratoconic group. Keratoconic eyes previously treated with CXL showed, on average, virtually the same average epithelium thickness (mean -0.7 μm, -0.2 μm over the pupil center, -0.9 μm over the peripheral zone) as the control group. This finding further reinforces our novel theory of the "reactive" component of epithelial thickening in corneas that are biomechanically unstable, becoming stable when biomechanical rigidity is accomplished despite persistence of cornea topographic irregularity. A highly irregular epithelium may be suggestive of an ectatic cornea. Our results indicate that the epithelium is thinner over the keratoconic protrusion, but to a much lesser extent than anticipated, and on average epithelium is thicker in this group of patients. This difference appears to be clinically significant and may become a screening tool for eyes suspected for ectasia.

Correlation between epithelial thickness in normal corneas, untreated ectatic corneas, and ectatic corneas previously treated with CXL; is overall epithelial thickness a very early ectasia prognostic factor?

PubMed Central

Kanellopoulos, Anastasios John; Aslanides, Ioannis M; Asimellis, George

2012-01-01

Purpose To determine and correlate epithelial corneal thickness (pachymetric) measurements taken with a digital arc scanning very high frequency ultrasound biomicroscopy (HF UBM) imaging system (Artemis-II), and compare mean and central epithelial thickness among normal eyes, untreated keratoconic eyes, and keratoconic eyes previously treated with collagen crosslinking (CXL). Methods Epithelial pachymetry measurements (topographic mapping) were conducted on 100 subjects via HF UBM. Three groups of patients were included: patients with normal eyes (controls), patients with untreated keratoconic eyes, and patients with keratoconic eyes treated with CXL. Central, mean, and peripheral corneal epithelial thickness was examined for each group, and a statistical study was conducted. Results Mean, central, and peripheral corneal epithelial thickness was compared between the three groups of patients. Epithelium thickness varied substantially in the keratoconic group, and in some cases there was a difference of up to 20 μm between various points of the same eye, and often a thinner epithelium coincided with a thinner cornea. However, on average, data from the keratoconic group suggested an overall thickening of the epithelium, particularly over the pupil center of the order of +3 μm, while the mean epithelium thickness was on average +1.1 μm, compared to the control population (P = 0.005). This overall thickening was more pronounced in younger patients in the keratoconic group. Keratoconic eyes previously treated with CXL showed, on average, virtually the same average epithelium thickness (mean −0.7 μm, −0.2 μm over the pupil center, −0.9 μm over the peripheral zone) as the control group. This finding further reinforces our novel theory of the “reactive” component of epithelial thickening in corneas that are biomechanically unstable, becoming stable when biomechanical rigidity is accomplished despite persistence of cornea topographic irregularity. Conclusion A highly irregular epithelium may be suggestive of an ectatic cornea. Our results indicate that the epithelium is thinner over the keratoconic protrusion, but to a much lesser extent than anticipated, and on average epithelium is thicker in this group of patients. This difference appears to be clinically significant and may become a screening tool for eyes suspected for ectasia. PMID:22701079

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

PubMed

Panchal, Shital S; Patidar, Rajesh K; Jha, Abhishek B; Allam, Ahmed A; Ajarem, Jamaan; Butani, Shital B

2017-01-01

Purpose . γ -Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods . Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF- α and IL-6. Structural damage in eye was examined by histopathological studies. Results . In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF- α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions . Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids.

PubMed

Galbis-Estrada, Carmen; Pinazo-Durán, Maria D; Cantú-Dibildox, Jorge; Marco-Ramírez, Carla; Díaz-Llópis, Manuel; Benítez-del-Castillo, Javier

2013-01-01

Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (-NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

2015-01-01

To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage

PubMed Central

Kiland, Julie A.; Gabelt, B’Ann T.; Tezel, Gülgün; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 ± 6.0%; P ≤ .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm’s canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies. PMID:20126491

Utility of Operative Glaucoma Tube Shunt Viscoelastic Bolus Flush.

PubMed

Groth, Sylvia L; Greider, Kelsi L; Sponsel, William Eric

2015-01-01

To assess the utility of viscoelastic injection to induce bleb expansion and decrease intraocular pressure (IOP) in eyes with encapsulated glaucoma tube shunt blebs. Case series. Forty-three glaucomatous eyes, including 13 eyes with congenital, 13 uveitic, 5 neovascular, 5 open angle, 4 narrow angle and 3 traumatic glaucomas. Methods, interventions or testing: All patients underwent viscoelastic flush procedure. A pre-bent 27 or 30-gauge cannula was passed through a 25-gauge paracentesis, advanced over the iris across the anterior chamber, and insinuated into the tube shunt lumen. Once the cannula was firmly lodged in position, 0.45 to 0.85 ml of viscoelastic was injected to hyperinflate the bleb. Paired t-tests were performed comparing preoperative IOP and number of medications used preoperatively vs levels measured at 1, 6, 12, 18 and 24 months. Intraocular pressure was reduced from a mean preoperative level of 26.0 ± 1.2 (sem) mm Hg to 15.8 ± 1.0 at 1 month, remaining stable thereafter at each 6-month interval with 15.1 ± 1.1 mm Hg at 24 months (p < 0.0001). Medication use did not vary significantly from baseline. Pressure remained < 21 mm Hg after 2 years in 85% of eyes cannulated within 1 year of primary tube shunt implantation (n = 23), and in 62% of eyes cannulated more than 1 year after tube shunt placement (n = 20). Tube shunt expansion with bolus viscoelastic flush successfully restored encapsulated bleb function, providing a substantial (~10 mm Hg) IOP decrease into the mid-normal pressure range. This persisted in the majority of treated eyes for the entire study period. How to cite this article: Groth SL, Greider KL, Sponsel WE. Utility of Operative Glaucoma Tube Shunt Viscoelastic Bolus Flush. J Curr Glaucoma Pract 2015;9(3):73-76.

Are All Retinal Nerve Fiber Layer Defects on Optic Coherence Tomography Glaucomatous?

PubMed Central

Gür Güngör, Sirel; Ahmet, Akman

2017-01-01

Objectives: In this study, we investigated the patients who were referred to our clinic with a prediagnosis of glaucoma based on retinal nerve fiber layer (RNFL) defects on optic coherence tomography (OCT) but were determined to have nonglaucomatous RNLF defects upon detailed examination. Materials and Methods: The ophthalmic examination notes, OCT images, Heidelberg retinal tomography (HRT) II and fundus photographs of 357 patients were retrospectively evaluated. Final diagnoses of these patients were investigated. Results: Of the 357 patients, 216 (60.5%) were diagnosed as open angle glaucoma, 33 (9.2%) as low-tension glaucoma, 39 (10.9%) as pre-perimetric glaucoma. The ophthalmic examinations of 14 patients (3.9%) were normal and there were no RNFL defects in OCT examinations after dilatation. In 39 patients (10.9%), the ophthalmic and optic disc examinations were completely normal and no etiologic factor explaining RNFL defects was found. Twenty-two eyes of 16 patients (4.5%) were included in this study (the mean age was 53.8±11.5 years; 9 men and 7 women). After detailed questioning of the medical history and systemic and neurologic examinations, a diagnosis of ischemic optic neuropathy was made in 11 eyes (10 patients) (2.8%), optic neuritis in 3 eyes (2 patients) (0.6%), optic disc drusen in 4 eyes (2 patients) (0.6%), pseudotumor cerebri in 2 eyes (1 patient) (0.3%), and cerebral palsy in 2 eyes (1 patient) (0.3%). Conclusion: Decrease in RNFL thickness on OCT images alone may be misleading in glaucoma examination. In cases where optic disc cupping is not evident, diagnosis should not be based on OCT RNFL examinations alone, and the patient’s medical history, detailed ophthalmic examination, OCT optic disc parameters, HRT, and visual field tests should all be carefully evaluated together. PMID:29109895

Longitudinal Change Detected by Spectral Domain Optical Coherence Tomography in the Optic Nerve Head and Peripapillary Retina in Experimental Glaucoma

PubMed Central

Strouthidis, Nicholas G.; Fortune, Brad; Yang, Hongli; Sigal, Ian A.

2011-01-01

Purpose. To investigate whether longitudinal changes deep within the optic nerve head (ONH) are detectable by spectral domain optical coherence tomography (SDOCT) in experimental glaucoma (EG) and whether these changes are detectable at the onset of Heidelberg Retina Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany)–defined surface topography depression. Methods. Longitudinal SDOCT imaging (Spectralis; Heidelberg Engineering) was performed in both eyes of nine rhesus macaques every 1 to 3 weeks. One eye of each underwent trabecular laser-induced IOP elevation. Four masked operators delineated internal limiting membrane (ILM), retinal nerve fiber layer (RNFL), Bruch's membrane/retinal pigment epithelium (BM/RPE), neural canal opening (NCO), and anterior lamina cribrosa surface (ALCS) by using custom software. Longitudinal changes were assessed and compared between the EG and control (nonlasered) eyes at the onset of HRT-detected surface depression (follow-up 1; [FU1]) and at the most recent image (follow-up 2; [FU2]). Results. Mean IOP in EG eyes was 7.1 to 24.6 mm Hg at FU1 and 13.5 to 31.9 mm Hg at FU2. In control eyes, the mean IOP was 7.2 to 12.6 mm Hg (FU1) and 8.9 to 16.0 mm Hg (FU2). At FU1, neuroretinal rim decreased and ALCS depth increased significantly (paired t-test, P < 0.01); no change in RNFL thickness was detected. At FU2, however, significant prelaminar tissue thinning, posterior displacement of NCO, and RNFL thinning were observed. Conclusions. Longitudinal SDOCT imaging can detect deep ONH changes in EG eyes, the earliest of which are present at the onset of HRT-detected ONH surface height depression. These parameters represent realistic targets for SDOCT detection of glaucomatous progression in human subjects. PMID:21217108

Subretinal electrical stimulation preserves inner retinal function in RCS rat retina.

PubMed

Ciavatta, Vincent T; Mocko, Julie A; Kim, Moon K; Pardue, Machelle T

2013-01-01

Previously, studies showed that subretinal electrical stimulation (SES) from a microphotodiode array (MPA) preserves electroretinography (ERG) b-wave amplitude and regional retinal structure in the Royal College of Surgeons (RCS) rat and simultaneously upregulates Fgf2 expression. This preservation appears to be associated with the increased current produced when the MPA is exposed to ERG test flashes, as weekly ERG testing produces greater neuroprotection than biweekly or no testing. Using an infrared source to stimulate the MPA while avoiding potential confounding effects from exposing the RCS retina to high luminance white light, this study examined whether neuroprotective effects from SES increased with subretinal current in a dose-dependent manner. RCS rats (n=49) underwent subretinal implantation surgery at P21 with MPA devices in one randomly selected eye, and the other eye served as the control. Naïve RCS rats (n=25) were also studied. To increase SES current levels, implanted eyes were exposed to 15 min per session of flashing infrared light (IR) of defined intensity, frequency, and duty cycle. Rats were divided into four SES groups that received ERG testing only (MPA only), about 450 µA/cm2 once per week (Low 1X), about 450 µA/cm2 three times per week (Low 3X), and about 1350 µA/cm2 once per week (High 1X). One eye of the control animals was randomly chosen for IR exposure. All animals were followed for 4 weeks with weekly binocular ERGs. A subset of the eyes was used to measure retina Fgf2 expression with real-time reverse-transcription PCR. Eyes receiving SES showed significant preservation of b-wave amplitude, a- and b-wave implicit times, oscillatory potential amplitudes, and post-receptoral parameters (Vmax and log σ) compared to untreated eyes. All SES-treated eyes had similar preservation, regardless of increased SES from IR light exposure. SES-treated eyes tended to have greater retinal Fgf2 expression than untreated eyes, but Fgf2 expression did not increase with IR light. The larger post-receptoral responses (Vmax), greater post-receptoral sensitivity (logσ), and larger oscillatory potentials suggest SES-treated eyes maintained better inner retinal function than the opposite, untreated eyes. This suggests that in addition to preserving photoreceptors in RCS rats, SES may also promote more robust signal transmission through the retinal network compared to the control eyes. These studies suggest that the protective effects of SES on RCS retinal function cannot be improved with additional subretinal current induction from the MPA, or the charge injection provided by ERG Ganzfeld flashes was not adequately mimicked by the flashing IR light used in this study.

A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride.

PubMed

Xiong, Cuiju; Chen, Dong; Liu, Jingbo; Liu, Bingqian; Li, Naiyang; Zhou, Yang; Liang, Xuanwei; Ma, Ping; Ye, Chengtian; Ge, Jian; Wang, Zhichong

2008-05-01

To establish a rabbit dry eye model with topical medication of the ocular preparation preservative benzalkonium chloride (BAC). Sixteen white rabbits were used. One eye of each rabbit was chosen randomly for topical administration of 0.1% BAC twice daily for 14 days. The other untreated eyes served as controls. Schirmer test, fluorescein, and rose bengal staining were performed before and after BAC treatment on days 3, 5, 7, and 14. Conjunctiva impression cytology specimens were collected on days 0, 7, and 14. The rabbits were killed after day 14. Immunofluorescence staining was performed to detect mucin-5 subtype AC (MUC5AC) on conjunctival cryosections. Cornea and conjunctiva structures were evaluated by light and electron microscopy. Compared with untreated controls, BAC-treated eyes showed significant decreases in Schirmer scores (P = 0.01) and increases in fluorescein scores (P < 0.001) on days 5, 7, and 14. A significant increase in rose bengal scores was noticed as early as day 3 (P = 0.001). Decreases in goblet cell density occurred on days 7 and 14 (P = 0.001). Decreased MUC5AC and histopathologic and ultrastructural disorders of the cornea and conjunctiva were also observed in the BAC group. These findings demonstrated that an ophthalmic preservative, benzalkonium chloride, induced a dry eye syndrome in rabbits with damage to the cornea and conjunctiva, decreased aqueous tear basal secretion, goblet cell loss, and MUC5AC deficiency. This rabbit model was consistent with human dry eye syndrome in both aqueous tear and mucin deficiency and may be appropriate for studying dry eye syndrome.

Short-Term Moderately Elevated Intraocular Pressure Is Associated With Elevated Scotopic Electroretinogram Responses

PubMed Central

Choh, Vivian; Gurdita, Akshay; Tan, Bingyao; Prasad, Ratna C.; Bizheva, Kostadinka; Joos, Karen M.

2016-01-01

Purpose Moderately elevated intraocular pressure (IOP) is a risk factor for open-angle glaucoma. Some patients suffer glaucoma despite clinically measured normal IOPs. Fluctuations in IOP may have a significant role since IOPs are higher during sleep and inversion activities. Controlled transient elevations of IOPs in rats over time lead to optic nerve structural changes that are similar to the early changes observed in constant chronic models of glaucoma. Because early intervention decreases glaucoma progression, this study was done to determine if early physiological changes to the retina could be detected with noninvasive electrophysiological and optical imaging tests during moderately elevated IOP. Methods Intraocular pressures were raised to moderately high levels (35 mm Hg) in one eye of Sprague-Dawley rats while the other (control) eye was untreated. One group of rats underwent scotopic threshold response (STR) and electroretinogram (ERG) testing, while another 3 groups underwent optical coherence tomography (OCT) imaging, Western blot, or histologic evaluation. Results The amplitudes of the STR and ERG responses in eyes with moderately elevated IOPs were enhanced compared to the values before IOP elevation, and compared to untreated contralateral eyes. Structural changes to the optic nerve also occurred during IOP elevation. Conclusions Although ischemic IOP elevations are well-known to globally reduce components of the scotopic ERG, acute elevation in rats to levels often observed in untreated glaucoma patients caused an increase in these parameters. Further exploration of these phenomena may be helpful in better understanding the mechanisms mediating early retinal changes during fluctuating or chronically elevated IOP. PMID:27100161

Likelihood ratios for glaucoma diagnosis using spectral-domain optical coherence tomography.

PubMed

Lisboa, Renato; Mansouri, Kaweh; Zangwill, Linda M; Weinreb, Robert N; Medeiros, Felipe A

2013-11-01

To present a methodology for calculating likelihood ratios for glaucoma diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography (spectral-domain OCT). Observational cohort study. A total of 262 eyes of 187 patients with glaucoma and 190 eyes of 100 control subjects were included in the study. Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with preperimetric and perimetric glaucomatous damage were included in the glaucoma group. The control group was composed of healthy eyes with normal visual fields from subjects recruited from the general population. All eyes underwent RNFL imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma diagnosis were estimated for specific global RNFL thickness measurements using a methodology based on estimating the tangents to the receiver operating characteristic (ROC) curve. Likelihood ratios could be determined for continuous values of average RNFL thickness. Average RNFL thickness values lower than 86 μm were associated with positive likelihood ratios (ie, likelihood ratios greater than 1), whereas RNFL thickness values higher than 86 μm were associated with negative likelihood ratios (ie, likelihood ratios smaller than 1). A modified Fagan nomogram was provided to assist calculation of posttest probability of disease from the calculated likelihood ratios and pretest probability of disease. The methodology allowed calculation of likelihood ratios for specific RNFL thickness values. By avoiding arbitrary categorization of test results, it potentially allows for an improved integration of test results into diagnostic clinical decision making. Copyright © 2013. Published by Elsevier Inc.

Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation

PubMed Central

Tamimi, Ehab A.; Pyne, Jeffrey D.; Muli, Dominic K.; Axman, Katelyn F.; Howerton, Stephen J.; Davis, Matthew R.; Girkin, Christopher A.; Vande Geest, Jonathan P.

2017-01-01

Purpose The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis. PMID:28846773

Understanding disparities among diagnostic technologies in glaucoma.

PubMed

De Moraes, Carlos Gustavo V; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2012-07-01

To investigate causes of disagreement among 3 glaucoma diagnostic techniques: standard automated achromatic perimetry (SAP), the multifocal visual evoked potential technique (mfVEP), and optical coherence tomography (OCT). In a prospective cross-sectional study, 138 eyes of 69 patients with glaucomatous optic neuropathy were tested using SAP, the mfVEP, and OCT. Eyes with the worse and better mean deviations (MDs) were analyzed separately. If the results of 2 tests were consistent for the presence of an abnormality in the same topographic site, that abnormality was considered a true glaucoma defect. If a third test missed that abnormality (false-negative result), the reasons for disparity were investigated. Eyes with worse MD (mean [SD], -6.8 [8.0] dB) had better agreements among tests than did eyes with better MD (-2.5 [3.5] dB, P<.01). For the 94 of 138 hemifields with abnormalities of the more advanced eyes, the 3 tests were consistent in showing the same hemifield abnormality in 50 hemifields (53%), and at least 2 tests were abnormal in 65 of the 94 hemifields (69%). The potential explanations for the false-negative results fell into 2 general categories: inherent limitations of each technique to detect distinct features of glaucoma and individual variability and the distribution of normative values used to define statistically significant abnormalities. All the cases of disparity could be explained by known limitations of each technique and interindividual variability, suggesting that the agreement among diagnostic tests may be better than summary statistics suggest and that disagreements between tests do not indicate discordance in the structure-function relationship.

Diagnosis of glaucoma and detection of glaucoma progression using spectral domain optical coherence tomography.

PubMed

Grewal, Dilraj S; Tanna, Angelo P

2013-03-01

With the rapid adoption of spectral domain optical coherence tomography (SDOCT) in clinical practice and the recent advances in software technology, there is a need for a review of the literature on glaucoma detection and progression analysis algorithms designed for the commercially available instruments. Peripapillary retinal nerve fiber layer (RNFL) thickness and macular thickness, including segmental macular thickness calculation algorithms, have been demonstrated to be repeatable and reproducible, and have a high degree of diagnostic sensitivity and specificity in discriminating between healthy and glaucomatous eyes across the glaucoma continuum. Newer software capabilities such as glaucoma progression detection algorithms provide an objective analysis of longitudinally obtained structural data that enhances our ability to detect glaucomatous progression. RNFL measurements obtained with SDOCT appear more sensitive than time domain OCT (TDOCT) for glaucoma progression detection; however, agreement with the assessments of visual field progression is poor. Over the last few years, several studies have been performed to assess the diagnostic performance of SDOCT structural imaging and its validity in assessing glaucoma progression. Most evidence suggests that SDOCT performs similarly to TDOCT for glaucoma diagnosis; however, SDOCT may be superior for the detection of early stage disease. With respect to progression detection, SDOCT represents an important technological advance because of its improved resolution and repeatability. Advancements in RNFL thickness quantification, segmental macular thickness calculation and progression detection algorithms, when used correctly, may help to improve our ability to diagnose and manage glaucoma.

A Small Disc Area Is a Risk Factor for Visual Field Loss Progression in Primary Open-Angle Glaucoma: The Glaucoma Stereo Analysis Study.

PubMed

Kitaoka, Yasushi; Tanito, Masaki; Yokoyama, Yu; Nitta, Koji; Katai, Maki; Omodaka, Kazuko; Nakazawa, Toru

2018-01-01

The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (<-0.3 dB/year) and no-progression group (≧-0.3 dB/year). ONH morphological parameters were calculated with prototype analysis software. The correlations between glaucomatous visual field progression and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. The MD slope averages in the progression group and no-progression group were -0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm 2 disc area). A smaller disc area may be associated with more rapid glaucomatous visual field progression.

Mycoplasma and associated bacteria isolated from ovine pink-eye.

PubMed

Langford, E V

1971-01-01

A mycoplasma was recovered from the untreated conjunctival membranes of nine sheep affected by Pink-eye. It was neither isolated from the conjunctiva of treated animals which were affected nor from the conjunctiva of normal animals either in contact or not in contact with affected animals. Bacteria found on normal conjunctival membranes were Neisseria ovis, Escherichia coli, Staphylococcus epidermididis, Streptococcus and Bacillus spp. Bacteria found in clinical cases of Pink-eye were N. ovis, E. coli, a Streptococcus and Pseudomonas spp.

Multifocal blue-on-yellow visual evoked potentials in early glaucoma.

PubMed

Klistorner, Alexander; Graham, Stuart L; Martins, Alessandra; Grigg, John R; Arvind, Hemamalini; Kumar, Rajesh S; James, Andrew C; Billson, Francis A

2007-09-01

To determine the sensitivity and specificity of blue-on-yellow multifocal visual evoked potentials (mfVEPs) in early glaucoma. Cross-sectional study. Fifty patients with a confirmed diagnosis of early glaucoma and 60 normal participants. Black-and-white mfVEPs and blue-on-yellow mfVEPs were recorded using the Accumap version 2.0 (ObjectiVision Pty. Ltd., Sydney, Australia). All patients also underwent achromatic standard automated perimetry (SAP). Multifocal VEP amplitude and latency values in glaucoma patients were analyzed and compared with those of the normal controls. Based on the definition of visual field defect, in the group of glaucomatous eyes with SAP defects, amplitude of blue-on-yellow mfVEP was abnormal in all 64 cases (100% sensitivity), whereas black-and-white mfVEP missed 5 cases (92.2% sensitivity). Generally, larger scotomata were noted on blue-on-yellow mfVEP compared with black-and-white mfVEP for the same eyes. There was high topographic correspondence between SAP and amplitude of blue-on-yellow mfVEP and significant (P<0.0001) correlation between them (correlation coefficient, 0.73). Abnormal amplitude was detected in 3 of 60 eyes of control subjects (95% specificity). There was, however, no correlation between visual field defect and latency delay in glaucoma patients. Although there was a significant difference between averaged latency of control and glaucoma eyes, values considerably overlapped. The blue-on-yellow mfVEP is a sensitive and specific tool for detecting early glaucoma based on amplitude analysis.

A novel method for quantifying the amount of trabecular meshwork pigment in glaucomatous and nonglaucomatous eyes.

PubMed

Kinori, Michael; Hostovsky, Avner; Skaat, Alon; Schwartsman, Jonathan; Melamed, Shlomo

2014-01-01

To assess the use of a computerized program for evaluating the amount of trabecular meshwork (TM) pigmentation in normal (control), primary open-angle glaucoma (POAG), and pseudoexfoliation glaucoma/pigmentary dispersion glaucoma (PXFG/PDG) patients. All included patients were from the Goldschleger Eye Institute glaucoma clinic. After signing an informed consent, each patient's anterior chamber angle was photographed using a single photo-slit under the same conditions. Only one eye per patient was photographed. The superior TM and the inferior TM were documented. Then, the degree of "blackness" (representing melanin pigment) was assessed using the ImageJ program. Of the 43 eyes photographed, 8 were excluded because of low-quality images. Of the remaining 35 patients, 14 were normal, 10 had POAG, and 11 had PXFG/PDG. The amount of pigment was the same in the control and the POAG patients whether the inferior TM (P=0.24), superior TM (P=0.58), or the sum inferior TM+superior TM (P=0.85) was measured. The pigment level was significantly higher in the PXFG/PDG group than in the control group (inferior TM, P<0.01; superior TM, P=0.047; sum, P<0.01). The difference between the inferior and the superior TM pigment levels was found to be statistically insignificant in all the groups (normal, P=0.86; POAG, P=0.10; PXFG/PDG, P=0.22). The use of ImageJ software might play a role in the quantification of pigment evaluation of the TM.

Effect of marihuana on intraocular and blood pressure in glaucoma.

PubMed

Merritt, J C; Crawford, W J; Alexander, P C; Anduze, A L; Gelbart, S S

1980-03-01

Marihuana inhalation was accompanied by increased heart rate and decreased intraocular and blood pressure in 18 subjects with heterogenous glaucomas. The hypotensive effects appeared in 60 to 90 minutes as the decrease in intraocular pressure (IOP) appeared to follow the decrease in blood pressure. In addition to any local effect, the mechanism of lowered to any local effect, the mechanism of lowered IOP may also involve the decreased pressure perfusing the ciliary body vasculature as a result of the peripheral vasodilatory properties of marihuana. Postural hypotension, tachycardia, palpitations, and alterations in mental status occurred with such frequency as to mitigate against the routine used in the general glaucoma population. Our data indicate that further research should be directed to local means of delivering the ocular hypotensive cannabinoid to the glaucomatous eye.

Transient familial hyperbilirubinemia

MedlinePlus

... Babies with this disorder are born with severe jaundice . Causes Transient familial hyperbilirubinemia is an inherited disorder. ... death. Symptoms The newborn may have: Yellow skin (jaundice) Yellow eyes (icterus) Lethargy If untreated, seizures and ...

Changes to upper eyelid orbital fat from use of topical bimatoprost, travoprost, and latanoprost.

PubMed

Park, Juwan; Cho, Hyun Kyung; Moon, Jung-Il

2011-01-01

To confirm the possible mechanism by which topical prostaglandin antiglaucoma drugs cause a deep superior sulcus. Among patients who used bimatoprost (Lumigan), latanoprost (Xalatan), or travoprost (Travatan) and who developed a deep upper lid sulcus, 18 eyes of 11 patients (mean age, 58.2 ± 8.9 years) were studied. Seven patients were binocular users of one of the eye drops and four were monocular users. Preaponeurotic orbital fat was obtained, and the mean adipocyte density compared. In the four monocular users, mean adipocyte density of treated eyes was 1758.21 ± 158.15 cells/mm(2), and that of untreated eyes was 1258.73 ± 127.54 cells/mm(2). This difference was statistically significant (P = 0.04), suggesting that the adipocytes were atrophied in the treated eyes. The mean adipocyte density of the bimatoprost group was 2073.35 ± 184.89 cells/mm(2), that of the travoprost group was 1623.46 ± 218.99 cells/mm(2), and that of the latanoprost group was 1468.20 ± 113.44 cells/mm(2). The densities of the bimatoprost and travoprost groups, but not of the latanoprost group (P = 0.75), were significantly different from that of the untreated group (P < 0.001). Fat atrophy can be considered a mechanism of upper eyelid sulcus deepening in patients using topical prostaglandin analogs. © Japanese Ophthalmological Society 2011.

Evaluating Silent Reading Performance with an Eye Tracking System in Patients with Glaucoma

PubMed Central

Murata, Noriaki; Fukuchi, Takeo

2017-01-01

Objective To investigate the relationship between silent reading performance and visual field defects in patients with glaucoma using an eye tracking system. Methods Fifty glaucoma patients (Group G; mean age, 52.2 years, standard deviation: 11.4 years) and 20 normal controls (Group N; mean age, 46.9 years; standard deviation: 17.2 years) were included in the study. All participants in Group G had early to advanced glaucomatous visual field defects but better than 20/20 visual acuity in both eyes. Participants silently read Japanese articles written horizontally while the eye tracking system monitored and calculated reading duration per 100 characters, number of fixations per 100 characters, and mean fixation duration, which were compared with mean deviation and visual field index values from Humphrey visual field testing (24–2 and 10–2 Swedish interactive threshold algorithm standard) of the right versus left eye and the better versus worse eye. Results There was a statistically significant difference between Groups G and N in mean fixation duration (G, 233.4 msec; N, 215.7 msec; P = 0.010). Within Group G, significant correlations were observed between reading duration and 24–2 right mean deviation (rs = -0.280, P = 0.049), 24–2 right visual field index (rs = -0.306, P = 0.030), 24–2 worse visual field index (rs = -0.304, P = 0.032), and 10–2 worse mean deviation (rs = -0.326, P = 0.025). Significant correlations were observed between mean fixation duration and 10–2 left mean deviation (rs = -0.294, P = 0.045) and 10–2 worse mean deviation (rs = -0.306, P = 0.037), respectively. Conclusions The severity of visual field defects may influence some aspects of reading performance. At least concerning silent reading, the visual field of the worse eye is an essential element of smoothness of reading. PMID:28095478

Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation.

PubMed

Cueva Vargas, Jorge L; Osswald, Ingrid K; Unsain, Nicolas; Aurousseau, Mark R; Barker, Philip A; Bowie, Derek; Di Polo, Adriana

2015-09-02

Loss of vision in glaucoma results from the selective death of retinal ganglion cells (RGCs). Tumor necrosis factor α (TNFα) signaling has been linked to RGC damage, however, the mechanism by which TNFα promotes neuronal death remains poorly defined. Using an in vivo rat glaucoma model, we show that TNFα is upregulated by Müller cells and microglia/macrophages soon after induction of ocular hypertension. Administration of XPro1595, a selective inhibitor of soluble TNFα, effectively protects RGC soma and axons. Using cobalt permeability assays, we further demonstrate that endogenous soluble TNFα triggers the upregulation of Ca(2+)-permeable AMPA receptor (CP-AMPAR) expression in RGCs of glaucomatous eyes. CP-AMPAR activation is not caused by defects in GluA2 subunit mRNA editing, but rather reflects selective downregulation of GluA2 in neurons exposed to elevated eye pressure. Intraocular administration of selective CP-AMPAR blockers promotes robust RGC survival supporting a critical role for non-NMDA glutamate receptors in neuronal death. Our study identifies glia-derived soluble TNFα as a major inducer of RGC death through activation of CP-AMPARs, thereby establishing a novel link between neuroinflammation and cell loss in glaucoma. Tumor necrosis factor α (TNFα) has been implicated in retinal ganglion cell (RGC) death, but how TNFα exerts this effect is poorly understood. We report that ocular hypertension, a major risk factor in glaucoma, upregulates TNFα production by Müller cells and microglia. Inhibition of soluble TNFα using a dominant-negative strategy effectively promotes RGC survival. We find that TNFα stimulates the expression of calcium-permeable AMPA receptors (CP-AMPAR) in RGCs, a response that does not depend on abnormal GluA2 mRNA editing but on selective downregulation of the GluA2 subunit by these neurons. Consistent with this, CP-AMPAR blockers promote robust RGC survival supporting a critical role for non-NMDA glutamate receptors in glaucomatous damage. This study identifies a novel mechanism by which glia-derived soluble TNFα modulates neuronal death in glaucoma. Copyright © 2015 the authors 0270-6474/15/3512088-15$15.00/0.

Perilimbal sclera mechanical properties: Impact on intraocular pressure in porcine eyes

PubMed Central

Man, Xiaofei; Arroyo, Elizabeth; Dunbar, Martha; Reed, David M.; Shah, Neil; Kagemann, Larry; Kim, Wonsuk; Moroi, Sayoko E.

2018-01-01

There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2<0.01 at higher flow rate) nor the viscoelastic properties of any tissue (R2 ≤ 0.08 in all cases). Additionally, the correlation occurred for IOP and not net outflow facility (R2 ≤ 0.12 in all cases). These results provide new evidence that IOP in perfused porcine eyes is strongly influenced by the tangent modulus, sometimes called the tissue stiffness, of the most anterior portion of the sclera, i.e. the limbus. PMID:29718942

Comparison of different methods of inter-eye asymmetry of rim area and disc area analysis

PubMed Central

Fansi, A A K; Boisjoly, H; Chagnon, M; Harasymowycz, P J

2011-01-01

Purpose To describe different methods of inter-eye asymmetry of rim area (RA) to disc area (DA) asymmetry ratio (RADAAR) analysis. Methods This was an observational, descriptive, and cross-sectional study. Both the eyes of all participants underwent confocal scanning laser ophthalmoscopy (Heidelberg retina tomograph (HRT 3)), frequency-doubling technology perimetry (FDT), and complete ophthalmological examination. Based on ophthalmological clinical examination and FDT results of the worse eye, subjects were classified as either normal, possible glaucoma, and probable glaucoma or definitive glaucoma. RADAAR values were calculated based on stereometric HRT 3 values using different mathematical formulae. RADAAR-1 was calculated as a relative difference of rim and DAs between the eyes. RADAAR-2 was calculated by subtracting the value of rim to DA ratio of the smaller disc from the value of rim to DA ratio of the larger disc. RADAAR-3 was calculated by dividing the previous two values. Statistical analyses included ANOVA as well as Student t-tests. Results Data of 334 participants were analysed, 78 of which were classified as definitive glaucoma. RADAAR-1 values were significantly different between the four different groups of diagnosis (F=5.82; P<0.001). The 1st and 99th percentile limits of normality for RADAAR-1, RADAAR-2, and RADAAR-3 in normal group were, respectively, −10.64 and 8.4; −0.32 and 0.22; and 0.58 and 1.32. Conclusions RADAAR-1 seems to best distinguish between the diagnostic groups. Knowledge of RADAAR distribution in various diagnostic groups may aid in clinical diagnosis of asymmetric glaucomatous damage. PMID:21921945

Provider Agreement in the Assessment of Glaucoma Progression within a Team Model.

PubMed

Shah, Saumya; Choo, Clara; Odden, Jamie; Zhao, Bingying; Fang, Chengbo; Schornack, Muriel; Stalboerger, Gina; Bennett, Jeffrey R; Khanna, Cheryl L

2018-06-04

Glaucoma specialists and optometrists who work in a team model at a single institution utilize a common definition of glaucoma progression and treatment algorithm. The purpose of this study was to assess the consistency of agreement in identifying glaucoma progression among glaucoma specialists and optometrists of one team. 399 eyes of 200 patients age 18 or older with glaucoma were enrolled over two years. Clinical data, disc photographs, OCT, and visual fields were independently reviewed by two masked optometrists and two masked fellowship-trained glaucoma specialists. Each eye was judged as progression or no-progression of glaucomatous disease. The following were assessed: (1) agreement among optometrists; (2) agreement among glaucoma specialists; and (3) agreement among optometrists and glaucoma specialists. The frequency of use of testing modality to determine progression was also studied. Kappa statistics were used to evaluate agreements. Optometrists agreed with each other for 74.2% of the eyes assessed (κ=0.42), whereas glaucoma specialists agreed with each other for 78.7% of eyes (κ=0.39). All four providers agreed with each other for 54.4% of the eyes evaluated (κ=0.37). Providers had the highest agreement when the progression decision was based on disc hemorrhage (92%) and the lowest agreement when based on OCT progression analysis (36%). Compared to optometrists, glaucoma specialists used OCT (P= <0.01) more frequently to determine disease progression. Fair to moderate agreement levels were found among providers in their assessment of glaucoma progression, suggesting that a team approach to glaucoma management may be effective. Further work is needed to investigate ways to optimize consistency within the glaucoma team.

Scanning electron microscopy of the trabecular meshwork: understanding the pathogenesis of primary angle closure glaucoma.

PubMed

Sihota, Ramanjit; Goyal, Amita; Kaur, Jasbir; Gupta, Viney; Nag, Tapas C

2012-01-01

To study ultrastructural changes of the trabecular meshwork in acute and chronic primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) eyes by scanning electron microscopy. Twenty-one trabecular meshwork surgical specimens from consecutive glaucomatous eyes after a trabeculectomy and five postmortem corneoscleral specimens were fixed immediately in Karnovsky solution. The tissues were washed in 0.1 M phosphate buffer saline, post-fixed in 1% osmium tetraoxide, dehydrated in acetone series (30-100%), dried and mounted. Normal trabecular tissue showed well-defined, thin, cylindrical uveal trabecular beams with many large spaces, overlying flatter corneoscleral beams and numerous smaller spaces. In acute PACG eyes, the trabecular meshwork showed grossly swollen, irregular trabecular endothelial cells with intercellular and occasional basal separation with few spaces. Numerous activated macrophages, leucocytes and amorphous debris were present. Chronic PACG eyes had a few, thickened posterior uveal trabecular beams visible. A homogenous deposit covered the anterior uveal trabeculae and spaces. Converging, fan-shaped trabecular beam configuration corresponded to gonioscopic areas of peripheral anterior synechiae. In POAG eyes, anterior uveal trabecular beams were thin and strap-like, while those posteriorly were wide, with a homogenous deposit covering and bridging intertrabecular spaces, especially posteriorly. Underlying corneoscleral trabecular layers and spaces were visualized in some areas. In acute PACG a marked edema of the endothelium probably contributes for the acute and marked intraocular pressure (IOP) elevation. Chronically raised IOP in chronic PACG and POAG probably results, at least in part, from decreased aqueous outflow secondary to widening and fusion of adjacent trabecular beams, together with the homogenous deposit enmeshing trabecular beams and spaces.

The Optic Nerve Head in Primary Open-Angle Glaucoma Eyes With High Myopia: Characteristics and Association With Visual Field Defects.

PubMed

Chen, Li-Wei; Lan, Yu-Wen; Hsieh, Jui-Wen

2016-06-01

To evaluate the morphologic characteristics of optic neuropathy and its association with visual field (VF) defects in primary open-angle glaucoma (POAG) eyes with high myopia. In this cross-sectional study, we reviewed data from 375 Taiwanese patients (375 eyes) of POAG, ages 20 to 60 years. Optic disc photographs were used for planimetric measurements of morphologic variables. The myopic refraction was divided into high myopia (<-6.0 D) and nonhigh myopia (moderate myopia to hyperopia). The optic disc area was classified as moderate (1.59 to 2.85 mm), large, and small. Differences in characteristics between groups, correlations with the disc area, and factors associated with VF defects were determined. Of the 142 highly myopic eyes, 33 (23%) had a large disc, 26 (18%) had a small disc, and 55 (39%) had a tilted disc. Large discs had a higher cup-to-disc (C/D) area ratio and a higher tilt ratio; small discs had a smaller rim area and a lower tilt ratio (all P<0.05). Characteristics associated with high myopia included a smaller rim area, a higher C/D area ratio, and a lower tilt ratio (all P<0.001). In logistic regression, the refraction, the C/D area ratio, the rim area, and the tilt ratio (all P<0.05) were associated with VF defects. In Taiwanese individuals with POAG, our study found that tilted, large, or small discs were prevalent in highly myopic eyes. Of these characteristics, only the disc tilt and high myopia by itself were associated with the severity of glaucomatous optic neuropathy.

Deep Defects Seen on Visual Fields Spatially Correspond Well to Loss of Retinal Nerve Fiber Layer Seen on Circumpapillary OCT Scans.

PubMed

Mavrommatis, Maria A; Wu, Zhichao; Naegele, Saskia I; Nunez, Jason; De Moraes, Carlos; Ritch, Robert; Hood, Donald C

2018-02-01

To examine the structure-function relationship in glaucoma between deep defects on visual fields (VF) and deep losses in the circumpapillary retinal nerve fiber layer (cpRNFL) on optical coherence tomography (OCT) circle scans. Thirty two glaucomatous eyes with deep VF defects, as defined by at least one test location worse than ≤ -15 dB on the 10-2 and/or 24-2 VF pattern deviation (PD) plots, were included from 87 eyes with "early" glaucoma (i.e., 24-2 mean deviation better than -6 dB). Using the location of the deep VF points and a schematic model, the location of local damage on an OCT circle scan was predicted. The thinnest location of cpRNFL (i.e., deepest loss) was also determined. In 19 of 32 eyes, a region of complete or near complete cpRNFL loss was observed. All 19 of these had deep VF defects on the 24-2 and/or 10-2. All of the 32 eyes with deep VF defects had abnormal cpRNFL regions (red, 1%) and all but 2 had a region of cpRNFL thickness <21 μm. The midpoint of the VF defect and the location of deepest cpRNFL had a 95% limit of agreement within approximately two-thirds of a clock-hour (or 30°) sector (between -22.1° to 25.2°). Individual fovea-to-disc angle (FtoDa) adjustment improved agreement in one eye with an extreme FtoDa. Although studies relating local structural (OCT) and functional (VF) measures typically show poor to moderate correlations, there is good qualitative agreement between the location of deep cpRNFL loss and deep defects on VFs.

Facts about Floaters

MedlinePlus

... is to “conduct and support research, training, health information dissemination, and other programs with respect to blinding eye ... serious condition and should always be considered an emergency . If left untreated, it can lead to permanent ...

Prevalence and characteristics of plateau iris configuration among American Caucasian, American Chinese and mainland Chinese subjects.

PubMed

Li, Yingjie; Wang, Ye Elaine; Huang, Guofu; Wang, Dandan; He, Mingguang; Qiu, Mary; Lin, Shan

2014-04-01

To investigate the prevalence, risk factors and characteristics of plateau iris configuration (PIC) among American Caucasian, American Chinese and mainland Chinese. This multicentre, cross-sectional study of non-glaucomatous subjects (40-80 years) included 111 American Caucasian, 116 American Chinese and 110 mainland Chinese. Prevalence of PIC based on ultrasound biomicroscopy imaging was compared among the different ethnic groups. Risk factors and anterior segment optical coherence tomography-measured iris and angle parameters in eyes with PIC were compared. The prevalence of PIC was 25.2% in American Caucasian, 24.1% in American Chinese and 20.9% in mainland Chinese (p=0.73). The presence of PIC was associated with more positive spherical equivalence (OR=1.31, p=0.002) and shorter axial length (OR=0.75, p=0.04). There were significant differences in angle recess area (ARA) (p=0.04), IT750 (p=0.007) and IT2000 (p<0.001) between Chinese and Caucasians who have PIC. The prevalence of PIC did not differ among American Caucasian, American Chinese and mainland Chinese. PIC was associated with non-myopia and shorter axial length. Chinese eyes with PIC had smaller ARA and thicker irides than Caucasian ones. PIC might be a physiological variation of the iris and ciliary body that exists in normal eyes, both in Chinese and Caucasians.

Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

PubMed Central

Ashtari, Manzar; Zhang, Hui; Cook, Philip A.; Cyckowski, Laura L.; Shindler, Kenneth S.; Marshall, Kathleen A.; Aravand, Puya; Vossough, Arastoo; Gee, James C.; Maguire, Albert M.; Baker, Chris I.; Bennett, Jean

2015-01-01

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber’s congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. PMID:26180100

Simplifying "target" intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma.

PubMed

Sihota, Ramanjit; Angmo, Dewang; Ramaswamy, Deepa; Dada, Tanuj

2018-04-01

Lowering of intraocular pressure is currently the only therapeutic measure for Glaucoma management. Many longterm, randomized trials have shown the efficacy of lowering IOP, either by a percentage of baseline, or to a specified level. This has lead to the concept of 'Target" IOP, a range of IOP on therapy, that would stabilize the Glaucoma/prevent further visual field loss, without significantly affecting a patient's quality of life. A clinical staging of Glaucoma by optic nerve head evaluation and perimetric parameters, allows a patient's eye to be categorized as having - mild, moderate or severe Glaucomatous damage. An initial attempt should be made to achieve the following IOP range for both POAG or PACG after an iridotomy. In mild glaucoma the initial target IOP range could be kept as 15-17 mmHg, for moderate glaucoma 12-15 mmHg and in the severe stage of glaucomatous damage 10-12 mmHg. Factoring in baseline IOP, age, vascular perfusion parameters, and change on perimetry or imaging during follow up, this range may be reassessed over 6 months to a year. "Target" IOP requires further lowering when the patient continues to progress or develops a systemic disease such as a TIA. Conversely, in the event of a very elderly or sick patient with stable nerve and visual field over time, the target IOP could be raised and medications reduced. An appropriate use of medications/laser/surgery to achieve such a "Target" IOP range in POAG or PACG can maintain visual fields and quality of life, preventing Glaucoma blindness.

Rapid pupil-based assessment of glaucomatous damage.

PubMed

Chen, Yanjun; Wyatt, Harry J; Swanson, William H; Dul, Mitchell W

2008-06-01

To investigate the ability of a technique employing pupillometry and functionally-shaped stimuli to assess loss of visual function due to glaucomatous optic neuropathy. Pairs of large stimuli, mirror images about the horizontal meridian, were displayed alternately in the upper and lower visual field. Pupil diameter was recorded and analyzed in terms of the "contrast balance" (relative sensitivity to the upper and lower stimuli), and the pupil constriction amplitude to upper and lower stimuli separately. A group of 40 patients with glaucoma was tested twice in a first session, and twice more in a second session, 1 to 3 weeks later. A group of 40 normal subjects was tested with the same protocol. Results for the normal subjects indicated functional symmetry in upper/lower retina, on average. Contrast balance results for the patients with glaucoma differed from normal: half the normal subjects had contrast balance within 0.06 log unit of equality and 80% had contrast balance within 0.1 log unit. Half the patients had contrast balances more than 0.1 log unit from equality. Patient contrast balances were moderately correlated with predictions from perimetric data (r = 0.37, p < 0.00001). Contrast balances correctly classified visual field damage in 28 patients (70%), and response amplitudes correctly classified 24 patients (60%). When contrast balance and response amplitude were combined, receiver operating characteristic area for discriminating glaucoma from normal was 0.83. Pupillary evaluation of retinal asymmetry provides a rapid method for detecting and classifying visual field defects. In this patient population, classification agreed with perimetry in 70% of eyes.

Rapid Pupil-Based Assessment of Glaucomatous Damage

PubMed Central

Chen, Yanjun; Wyatt, Harry J.; Swanson, William H.; Dul, Mitchell W.

2010-01-01

Purpose To investigate the ability of a technique employing pupillometry and functionally-shaped stimuli to assess loss of visual function due to glaucomatous optic neuropathy. Methods Pairs of large stimuli, mirror images about the horizontal meridian, were displayed alternately in the upper and lower visual field. Pupil diameter was recorded and analyzed in terms of the “contrast balance” (relative sensitivity to the upper and lower stimuli), and the pupil constriction amplitude to upper and lower stimuli separately. A group of 40 patients with glaucoma was tested twice in a first session, and twice more in a second session, 1 to 3 weeks later. A group of 40 normal subjects was tested with the same protocol. Results Results for the normal subjects indicated functional symmetry in upper/lower retina, on average. Contrast balance results for the patients with glaucoma differed from normal: half the normal subjects had contrast balance within 0.06 log unit of equality and 80% had contrast balance within 0.1 log unit. Half the patients had contrast balances more than 0.1 log unit from equality. Patient contrast balances were moderately correlated with predictions from perimetric data (r = 0.37, p < 0.00001). Contrast balances correctly classified visual field damage in 28 patients (70%), and response amplitudes correctly classified 24 patients (60%). When contrast balance and response amplitude were combined, receiver operating characteristic area for discriminating glaucoma from normal was 0.83. Conclusions Pupillary evaluation of retinal asymmetry provides a rapid method for detecting and classifying visual field defects. In this patient population, classification agreed with perimetry in 70% of eyes. PMID:18521026

Reducing Spatial Uncertainty Through Attentional Cueing Improves Contrast Sensitivity in Regions of the Visual Field With Glaucomatous Defects

PubMed Central

Phu, Jack; Kalloniatis, Michael; Khuu, Sieu K.

2018-01-01

Purpose Current clinical perimetric test paradigms present stimuli randomly to various locations across the visual field (VF), inherently introducing spatial uncertainty, which reduces contrast sensitivity. In the present study, we determined the extent to which spatial uncertainty affects contrast sensitivity in glaucoma patients by minimizing spatial uncertainty through attentional cueing. Methods Six patients with open-angle glaucoma and six healthy subjects underwent laboratory-based psychophysical testing to measure contrast sensitivity at preselected locations at two eccentricities (9.5° and 17.5°) with two stimulus sizes (Goldmann sizes III and V) under different cueing conditions: 1, 2, 4, or 8 points verbally cued. Method of Constant Stimuli and a single-interval forced-choice procedure were used to generate frequency of seeing (FOS) curves at locations with and without VF defects. Results At locations with VF defects, cueing minimizes spatial uncertainty and improves sensitivity under all conditions. The effect of cueing was maximal when one point was cued, and rapidly diminished when more points were cued (no change to baseline with 8 points cued). The slope of the FOS curve steepened with reduced spatial uncertainty. Locations with normal sensitivity in glaucomatous eyes had similar performance to that of healthy subjects. There was a systematic increase in uncertainty with the depth of VF loss. Conclusions Sensitivity measurements across the VF are negatively affected by spatial uncertainty, which increases with greater VF loss. Minimizing uncertainty can improve sensitivity at locations of deficit. Translational Relevance Current perimetric techniques introduce spatial uncertainty and may therefore underestimate sensitivity in regions of VF loss. PMID:29600116

Automated detection of Schlemm's canal in spectral-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Tom, Manu; Ramakrishnan, Vignesh; van Oterendorp, Christian; Deserno, Thomas M.

2015-03-01

Recent advances in optical coherence tomography (OCT) technology allow in vivo imaging of the complex network of intra-scleral aqueous veins in the anterior segment of the eye. Pathological changes in this network, draining the aqueous humor from the eye, are considered to play a role in intraocular pressure elevation, which can lead to glaucoma, one of the major causes of blindness in the world. Through acquisition of OCT volume scans of the anterior eye segment, we aim at reconstructing the three dimensional network of aqueous veins in healthy and glaucomatous subjects. A novel algorithm for segmentation of the three-dimensional (3D) vessel system in human Schlemms canal is presented analyzing frames of spectral domain OCT (SD-OCT) of the eyes surface in either horizontal or vertical orientation. Distortions such as vertical stripes are caused by the superficial blood vessels in the conjunctiva and the episclera. They are removed in the discrete Fourier domain (DFT) masking particular frequencies. Feature-based rigid registration of these noise-filtered images is then performed using the scale invariant feature transform (SIFT). Segmentation of the vessels deep in the sclera originating at or in the vicinity of or having indirect connection to the Schlemm's canal is then performed with 3D region growing technique. The segmented vessels are visualized in 3D providing diagnostically relevant information to the physicians. A proof-of-concept study was performed on a healthy volunteer before and after a pharmaceutical narrowing of Schlemm's canal. A relative decreases 17% was measured based on manual ground truth and the image processing method.

Comparison of Heidelberg Retina Tomograph-3 glaucoma probability score and Moorfields regression analysis of optic nerve head in glaucoma patients and healthy individuals.

PubMed

Caglar, Çagatay; Gul, Adem; Batur, Muhammed; Yasar, Tekin

2017-01-01

To compare the sensitivity and specificity of Moorfields regression analysis (MRA) and glaucoma probability score (GPS) between healthy and glaucomatous eyes with Heidelberg Retinal Tomograph 3 (HRT-3). The study included 120 eyes of 75 glaucoma patients and 138 eyes of 73 normal subjects, for a total of 258 eyes of 148 individuals. All measurements were performed with the HRT-3. Diagnostic test criteria (sensitivity, specificity, etc.) were used to evaluate how efficiently GPS and MRA algorithms in the HRT-3 discriminated between the glaucoma and control groups. The GPS showed 88 % sensitivity and 66 % specificity, whereas MRA had 71.5 % sensitivity and 82.5 % specificity. There was 71 % agreement between the final results of MRA and GPS in the glaucoma group. Excluding borderline patients from both analyses resulted in 91.6 % agreement. In the control group the level of agreement between MRA and GPS was 64 % including borderline patients and 84.1 % after excluding borderline patients. The accuracy rate is 92 % for MRA and 91 % for GPS in the glaucoma group excluding borderline patients. The difference was nor statistically different. In both cases, agreement was higher between MRA and GPS in the glaucoma group. We found that both sensitivity and specificity increased with disc size for MRA, while the sensitivity increased and specificity decreased with larger disc sizes for GPS. HRT is able to quantify and clearly reveal structural changes in the ONH and RNFL in glaucoma.

Progressive Decrease of Peripapillary Angioflow Vessel Density During Structural and Visual Field Progression in Early Primary Open-angle Glaucoma.

PubMed

Holló, Gábor

2017-07-01

To present a case of early primary open-angle glaucoma in which retinal nerve fiber layer thickness (RNFLT), ganglion cell complex (GCC), and visual field progression were accompanied with significant progression of peripapillary angioflow vessel density (PAFD) measured with optical coherence tomographic angiography. A 68-year-old female patient who was under topical intraocular pressure (IOP) lowering medication for 20 years for ocular hypertension of the right and preperimetric primary open-angle glaucoma of the left eye (with reproducible inferotemporal and superotemporal neuroretinal rim and RNFL loss) was prospectively imaged with the AngioVue OCT for RNFLT, GCC thickness, and PAFD, and investigated with the Octopus Normal G2 visual field test on the same days at 6-month intervals for 18 months, while the IOP of the left eye escaped from control. IOP of the left eye fluctuated between 14 and 30 mm Hg in the study period. RNFLT, GCC thickness, and peripapillary PAFD all decreased significantly (linear regression analysis, P=0.030, 0.040, and 0.020, respectively), and a significant 2.1 dB/y progression was seen for a superior visual field cluster. The RNFLT, peripapillary PAFD, and visual field of the right eye remained normal and unchanged. In our case IOP elevation, glaucomatous visual field conversion, and structural progression were accompanied with significant progressive decrease of peripapillary PAFD. The simultaneous thinning of RNFLT and GCC and decrease of peripapillary PAFD suggest that PAFD may potentially be an additional indicator of early progression in primary open-angle glaucoma.

The arguments for and against cannabinoids application in glaucomatous retinopathy.

PubMed

Panahi, Yunes; Manayi, Azadeh; Nikan, Marjan; Vazirian, Mahdi

2017-02-01

Glaucoma represents several optic neuropathies leading to irreversible blindness through progressive retinal ganglion cell (RGC) loss. Reduction of intraocular pressure (IOP) is known as the only modifiable factor in the treatment of this disorder. Application of exogenous cannabinoids to lower IOP has attracted attention of scientists as potential agents for the treatment of glaucoma. Accordingly, neuroprotective effect of these agents has been recently described through modulation of endocannabinoid system in the eye. In the present work, pertinent information regarding ocular endocannabinoid system, mechanism of exogenous cannabinoids interaction with the ocular endocannabinoid system to reduce IOP, and neuroprotection property of cannabinoids will be discussed according to current scientific literature. In addition to experimental studies, bioavailability of cannabinoids, clinical surveys, and adverse effects of application of cannabinoids in glaucoma will be reviewed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects of age and refractive error

PubMed Central

Coletta, Nancy J.; Marcos, Susana; Troilo, David

2012-01-01

The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on the wavefront aberrations of the marmoset eye, measured with a clinical Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days. Twenty-one of the subjects were members of studies of emmetropization and accommodation, and two were untreated normal subjects. Eleven of the 21 experimental subjects had worn monocular diffusers or occluders and ten had worn binocular spectacle lenses of equal power. Monocular deprivation or lens rearing began at about 45 days of age and ended at about 108 days of age. All refractions and aberration measures were performed while the eyes were cyclopleged; most aberration measures were made while subjects were awake, but some control measurements were performed under anesthesia. Wavefront error was expressed as a seventh-order Zernike polynomial expansion, using the Optical Society of America’s naming convention. Aberrations in young marmosets decreased up to about 100 days of age, after which the higher-order RMS aberration leveled off to about 0.10 micron over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times greater when the subjects were under general anesthesia than when they were awake. Young marmoset eyes were characterized by negative spherical aberration. Visually deprived eyes of the monocular deprivation animals had greater wavefront aberrations than their fellow untreated eyes, particularly for asymmetric aberrations in the odd-numbered Zernike orders. Both lens-treated and deprived eyes showed similar significant increases in Z3-3 trefoil aberration, suggesting the increase in trefoil may be related to factors that do not involve visual feedback. PMID:20800078

Axonal loss from acute optic neuropathy documented by scanning laser polarimetry

PubMed Central

Meier, F M; Bernasconi, P; Stürmer, J; Caubergh, M-J; Landau, K

2002-01-01

Background/aims: Retinal nerve fibre layer analysis by scanning laser polarimetry has been shown to facilitate diagnosis of glaucoma while its role in glaucoma follow up is still unclear. A major difficulty is the slow reduction of retinal nerve fibre layer thickness in glaucomatous optic neuropathy. Eyes of patients were studied after acute retrobulbar optic nerve lesion in order to evaluate the usefulness of scanning laser polarimetry in documenting retinal nerve fibre layer loss over time. Methods: Five patients who suffered severe retrobulbar optic neuropathy have had repeated measurements of the retinal nerve fibre layer using scanning laser polarimetry at various intervals, the first examination being within 1 week of injury. Results: All eyes showed a marked decrease in peripapillary retinal nerve fibre layer thickness, which followed an exponential curve and occurred predominantly within 8 weeks of injury. Compared to a previous study using red-free photographs, scanning laser polarimetry showed retinal nerve fibre layer loss earlier in the course of descending atrophy. Conclusion: Scanning laser polarimetry is useful for early detection and documentation of retinal nerve fibre layer loss following acute injury to the retrobulbar optic nerve. It seems to be a promising tool for follow up of individual glaucoma patients. PMID:11864884

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients.

PubMed

Mayer, Markus A; Hornegger, Joachim; Mardin, Christian Y; Tornow, Ralf P

2010-11-08

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients

PubMed Central

Mayer, Markus A.; Hornegger, Joachim; Mardin, Christian Y.; Tornow, Ralf P.

2010-01-01

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis. PMID:21258556

Quantitative RNFL attenuation coefficient measurements by RPE-normalized OCT data

NASA Astrophysics Data System (ADS)

Vermeer, K. A.; van der Schoot, J.; Lemij, H. G.; de Boer, J. F.

2012-03-01

We demonstrate significantly different scattering coefficients of the retinal nerve fiber layer (RNFL) between normal and glaucoma subjects. In clinical care, SD-OCT is routinely used to assess the RNFL thickness for glaucoma management. In this way, the full OCT data set is conveniently reduced to an easy to interpret output, matching results from older (non- OCT) instruments. However, OCT provides more data, such as the signal strength itself, which is due to backscattering in the retinal layers. For quantitative analysis, this signal should be normalized to adjust for local differences in the intensity of the beam that reaches the retina. In this paper, we introduce a model that relates the OCT signal to the attenuation coefficient of the tissue. The average RNFL signal (within an A-line) was then normalized based on the observed RPE signal, resulting in normalized RNFL attenuation coefficient maps. These maps showed local defects matching those found in thickness data. The average (normalized) RNFL attenuation coefficient of a fixed band around the optic nerve head was significantly lower in glaucomatous eyes than in normal eyes (3.0mm-1 vs. 4.9mm-1, P<0.01, Mann-Whitney test).

Baseline mean deviation and rates of visual field change in treated glaucoma patients.

PubMed

Forchheimer, I; de Moraes, C G; Teng, C C; Folgar, F; Tello, C; Ritch, R; Liebmann, J M

2011-05-01

To evaluate the relationships between baseline visual field (VF) mean deviation (MD) and subsequent progression in treated glaucoma. Records of patients seen in a glaucoma practice between 1999 and 2009 were reviewed. Patients with glaucomatous optic neuropathy, baseline VF damage, and ≥8 SITA-standard 24-2 VF were included. Patients were divided into tertiles based upon baseline MD. Automated pointwise linear regression determined global and localized rates (decibels (dB) per year) of change. Progression was defined when two or more adjacent test locations in the same hemifield showed a sensitivity decline at a rate of >1.0  dB per year, P<0.01. For mild, moderate, and severe groups, progression was noted in 29.5, 31.2, and 26.0% of eyes (P=0.50) and global rates of VF change of progressing eyes were -1.3±1.2, -1.01±0.7, and -0.9±0.5 dB/year (P=0.09, analysis of variance). Within these groups, intraocular pressure (IOP) in stable vs progressing eyes were 15.5±3.3 vs 17.0±3.1 (P<0.01), 15.4±3.3 vs 15.9±2.5 (P=0.28), and 14.0±2.8 vs 14.8±2.3 mm Hg (P=0.07). More glaucoma filtering surgeries were performed in eyes with worse MD. There was no significant difference between groups regarding their risk of progression in both univariate (P=0.50) and multivariate (P=0.26) analyses adjusting for differences in follow-up IOP. After correcting for differences in IOP in treated glaucoma patients, we did not find a relationship between the rate of VF change (dB per year) and the severity of the baseline VF MD. This finding may have been due to more aggressive IOP lowering in eyes with more severe disease. Eyes with lower IOP progressed less frequently across the spectrum of VF loss.

Effectiveness and safety of combined cataract surgery and microhook ab interno trabeculotomy in Japanese eyes with glaucoma: report of an initial case series.

PubMed

Tanito, Masaki; Ikeda, Yoshifumi; Fujihara, Etsuko

2017-11-01

To report the early postoperative results and safety profile of ab interno microhook trabeculotomy (μLOT) combined with cataract surgery. This retrospective observational case series included 68 consecutive glaucomatous eyes of 23 Japanese men and 25 Japanese women [mean (SD) age, 76.0 ± 8.5 years] who underwent μLOT for intraocular pressure (IOP) and visually relevant cataracts. The LOT site/extent, perioperative complications, and complication treatments were collected from the medical and surgical records. The preoperative and postoperative IOP, numbers of antiglaucoma medications, logarithm of the minimum angle of resolution visual acuity (VA), anterior chamber (AC) flare, and corneal endothelial cell density (CECD) were compared. After small incisional cataract surgery, the trabecular meshwork was incised in the nasal (6 eyes, 3.6 ± 0.5 clock hours), temporal (6 eyes, 3.8 ± 0.8 clock hours), or both nasal and temporal (56 eyes, 6.5 ± 0.6 clock hours) angles. The mean preoperative IOP (16.4 ± 2.9 mmHg) and number of antiglaucoma medications (2.4 ± 1.2) decreased significantly (P < 0.0001 and P = 0.0039, respectively) to 11.8 ± 4.5 and 2.1 ± 1.0 mmHg at 9.5 months postoperatively. Compared with the preoperative conditions, the final VA improved (P = 0.0002), the AC flare increased by 6.3 pc/ms (P = 0.0157), and the CECD decreased by 6% (P = 0.0005). Hyphema with niveau formation (28 eyes, 41%) and hyphema washout (6 eyes, 9%) were the most common postoperative complication and intervention, respectively. At the final visit, 54 eyes (79%) had achieved successful IOP control of 15 mmHg or less and IOP reduction of 15% or greater. Combined μLOT and cataract surgery improves IOP and VA during the early postoperative period in patients with glaucoma and cataract.

Pigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration.

PubMed

Wang, Yujuan; Subramanian, Preeti; Shen, Defen; Tuo, Jingsheng; Becerra, S Patricia; Chan, Chi-Chao

2013-11-26

AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg), followed by a subconjunctival injection of PEDF (3 μg) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

AREDS simplified severity scale as a predictive factor for response to aflibercept therapy for typical neovascular age-related macular degeneration.

PubMed

Sakurada, Yoichi; Kikushima, Wataru; Sugiyama, Atsushi; Yoneyama, Seigo; Tanabe, Naohiko; Matsubara, Mio; Iijima, Hiroyuki

2018-01-01

To investigate whether the severity of the condition in the untreated fellow eye is a predictive factor for the response to intravitreal aflibercept injection (IAI) for exudative age-related macular degeneration (AMD). A retrospective medical chart review was conducted for 88 patients with treatment-naïve neovascular AMD, who were initially treated with three monthly IAIs, followed by monthly monitoring and re-injection as needed for at least 12 months. Subjects were classified into three groups according to the severity of the condition in their untreated eye, based on the severity scale in the Age-Related Eye Disease Study (AREDS): group 0, AREDS severity level 1 (no drusen); group 1, AREDS severity level 2 or 3 (any drusen); group 2, AREDS severity level 4 (advanced AMD). Genotyping was performed in all cases for ARMS2 A69S and CFH I62V. Fellow-eye severity was associated with age and the risk variant of ARMS2 A69S (P = 0.005 and 0.001, respectively). Although best-corrected visual acuity (BCVA) had improved significantly after 12 months in all groups, this improvement was significantly greater in group 0 than in the other groups (P = 0.008). The retreatment-free period was also significantly longer for group 0 than for the other groups (P = 0.016), and the number of additional injections was significantly associated with fellow-eye severity (P = 0.007). Fellow-eye severity was associated with treatment response in terms of visual improvement and retreatment and may be a predictive factor for response to IAI for neovascular AMD.

The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs.

PubMed

Dorbandt, Daniel M; Labelle, Amber L; Mitchell, Mark A; Hamor, Ralph E

2017-03-01

To determine the immediate and chronic effects of topical 0.1% diclofenac and 0.03% flurbiprofen on corneal sensitivity in normal canine eyes. Eighteen normal, nonbrachycephalic dogs. A prospective, randomized, masked, crossover study was performed. To determine the immediate effects associated with treatment, the study drug was instilled into the eye every 5 min for five doses, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment and every 15 min post-treatment for 60 min. To determine the chronic effects, the study drug was instilled every 12 h for 30 days, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment on days 0 and 30. A washout period of at least 30 days occurred between drug crossover. Ambient temperature and humidity were measured throughout the study. After multiple instillations, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.67) or flurbiprofen (P = 0.54), with a median sensitivity of 25 mm (1.8 g/mm 2 ). After chronic dosing, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.82) or flurbiprofen (P = 0.56), with a median sensitivity of 35 mm (1.0 g/mm 2 ). Decreasing ambient humidity was associated with an increase in sensitivity measurements (P = 0.0001). Neither diclofenac nor flurbiprofen had an effect on corneal sensitivity after multiple-drops or twice-daily dosing for 30 days. Ambient humidity may have an effect on corneal sensitivity measurements, with a longer filament length eliciting a blink response at lower humidity. © 2016 American College of Veterinary Ophthalmologists.

Measurement of refractive state and deprivation myopia in two strains of mice.

PubMed

Schaeffel, Frank; Burkhardt, Eva; Howland, Howard C; Williams, Robert W

2004-02-01

The mouse eye has a bright retinal image (f/number <1) but low optical quality (visual acuity about 0.5 cpd) that may render emmetropization unnecessary. However, this species is potentially a powerful model to study eye growth and myopia because its genome can be readily manipulated and has been completely sequenced. We have investigated how precisely eyes of mice can be refracted and tested whether deprivation myopia can be induced by frosted diffusers. An automated eccentric infrared photorefractor was adapted to refract eyes of two mouse strains--C57BL/6 (B6) and DBA/2 (D2)--during Tropicamide cycloplegia without anesthesia. Axial lengths were measured in highly magnified video images of freshly excised eyes. Plastic hemispherical diffusers were applied between postnatal days and 29 and left attached for 7 or 14 days. (1) Trial lenses ranging from +10 to -10 D produced high correlations between the brightness slope in the pupil and applied lens power (r = 0.81 and r = 0.87), demonstrating reliable refraction. Five repeated measures in 12 eyes showed an average standard deviation of 3.0 D, equivalent to an axial length change <10 microm (derived from schematic eye modeling). (2) Deprivation produced a significant shift toward myopia, relative to untreated eyes, but only after 14 days and only in B6 mice (p = 0.02 with or p = 0.00038 without one outlier; N = 9). In contrast, DBA/2J were unaffected by occlusion, perhaps due to mutations that target eye, lens, or anterior segment. (3) Both eyes of untreated animals often had axial lengths that differed markedly. Surprisingly, we detected no significant correlation between refractive error and axial length after treatment. The infrared refraction technique is sufficiently sensitive to resolve equivalent changes in axial length of only +/- 10 microm in alert mice. Prolonged occlusion produces a significant myopic shift in B6 mice, but not in D2 mice. Even among isogenic B6 mice, the response is variable for reasons that presumably trace back to subtle developmental, environmental, and technical factors.

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

PubMed

Ashtari, Manzar; Zhang, Hui; Cook, Philip A; Cyckowski, Laura L; Shindler, Kenneth S; Marshall, Kathleen A; Aravand, Puya; Vossough, Arastoo; Gee, James C; Maguire, Albert M; Baker, Chris I; Bennett, Jean

2015-07-15

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. Copyright © 2015, American Association for the Advancement of Science.

Eye movements during visual search in patients with glaucoma

PubMed Central

2012-01-01

Background Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search. Methods Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: –5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity. Results The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman’s rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman’s rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman’s rho = −0.65; P < 0.001) but this was not apparent in the controls. Conclusions The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease. PMID:22937814

Anti-VEGF and its impact on the outer retina: retinal pigment epithelium tear after an injection of aflibercept in contralateral eye.

PubMed

Campos Polo, R; Rubio Sánchez, C

2016-05-01

A 62-year-old woman with a history of bilateral retinal pigment epithelium detachment (PED), secondary of age-related macular degeneration (AMD), who presented with a retinal pigment epithelium (RPE) tear on her left eye after an aflibercept injection in the contralateral eye one month earlier. A RPE tear is the main complication when the anti-VEGF therapy is used for the management of the PED. Furthermore, it should be noted that systemic absorption of the drug can induce an effect on the untreated eye. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Acquired pit of the optic nerve: a risk factor for progression of glaucoma.

PubMed

Ugurlu, S; Weitzman, M; Nduaguba, C; Caprioli, J

1998-04-01

To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.

Diagnostic Accuracy of Nonmydriatic Fundus Photography for the Detection of Glaucoma in Diabetic Patients.

PubMed

Muñoz-Negrete, Francisco J; Contreras, Inés; Oblanca, Noelia; Pinazo-Durán, M Dolores; Rebolleda, Gema

2015-01-01

To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio ≥ 0.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes ≥ 0.2. This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics.

Physicochemical and pharmacological investigation of water/oil microemulsion of non-selective beta blocker for treatment of glaucoma.

PubMed

Hegde, Rahul Rama; Bhattacharya, Shiv Sankar; Verma, Anurag; Ghosh, Amitava

2014-02-01

Ocular drug delivery system always remained associated with lots of difficulties and faced issues of poor drug absorption and poor bioavailability. Timolol maleate is a nonspecific beta blocker used for reduction of elevated intraocular pressure in glaucoma. Timolol maleate is absorbed systemically and is contraindicated in asthmatic patients. This study is focused to deliver Timolol maleate by a water/oil microemulsion to extend the time of reduced intraocular pressure of glaucomatous rabbit's eye measured by using a Schoetz tonometer. The microemulsion is prepared by mixing the oily components with two nonionic surfactants, drug and water, and evaluated for the physicochemical, in vitro and in vivo parameters. The colloidal system demonstrates monodisperse distribution behavior and exhibits a uniform size distribution of finite width. In vitro drug release from microemulsion was found to follow Higuchi's pattern followed by a zero-order drug release by the emulsion. Ex vivo permeation through goat cornea revealed delayed release of Timolol maleate from microemulsion as compared with its aqueous solution. A reduction in intraocular pressure is seen lasting for 12 h compared to aqueous eye drop that lasted for only 5 h. CONCLUSION. In vivo reduction of intraocular pressure revealed a similar efficacy for once daily dosed 0.3% Timolol maleate in microemulsion formulation compared to 0.5% concentration in both microemulsion as well as aqueous formulation. The possible outcome of dose reduction will reduce the cardiovascular side effects generally reported with Timolol maleate eye drops.

[Pharmacological profiles of latanoprost (Xalatan), a novel anti-glaucoma drug].

PubMed

Nomura, S; Hashimoto, M

2000-05-01

Latanoprost is a novel prostaglandin F2 alpha (PGF2 alpha) derivative. Topically applied latanoprost into the glaucomatous monkey eyes lowered intraocular pressure (IOP). Latanoprost, however, failed to produce the hypotensive effect in either rabbit or cat eyes. This species difference may be attributed to its high selectivity for the FP receptor and differences in prostaglandin receptor subtypes existed in the eye amongst these species. In ligand binding studies with bovine corpus luteum cell membranes, the Kd value for the FP receptor of latanoprost was the same as that for PGF2 alpha, 2.8 nM. Latanoprost augmented uveoscleral outflow (Uv) in monkeys without affecting trabecular outflow or outflow facility like PGF2 alpha. Although the precise mechanism of the increase in Uv is not fully understood, it is suggested that a decrease in extracellular matrix components in ciliary muscle may contribute to the increase in Uv. On the other hand, an increase in blood flow at the optic nerve head and neuroprotective action in addition to the IOP lowering effect may contribute to the efficacy of latanoprost in glaucoma therapy. Only tolerable conjunctival hyperemia was seen in rabbits. A phase III clinical trial revealed latanoprost (0.005%) once daily produced sustained reduction of IOP in ocular hypertension or primary open-angle glaucoma patients to a greater extent than timolol did. Furthermore, the effects of latanoprost on aqueous humor dynamics in normal human volunteers were similar to those in monkeys, indicating that latanoprost lowers IOP by the increase in Uv in humans.

[Clinical observation on the treatment of untreatable childhood glaucoma with microcatheter-assisted trabeculotomy].

PubMed

Wang, H Z; Li, M; Hu, M; Wang, Y W; Shi, Y; Wang, W W; Wang, N L

2017-03-11

Objective: To evaluate the efficacy of microcatheter-assisted trabeculotomy for untreatable childhood glaucoma with traditional surgeries repeatedly. Methods: Clinical charts of fifteen cases (16 eyes) with childhood glaucoma patients from Beijing Tongren Hospital were retrospectively analyzed. All eyes had previously received 2 or more traditional anti-glaucoma surgeries. We performed microcatheter-assisted trabeculotomy for these patients. The intraocular pressure (IOP), numbers of anti-glaucoma medications and post-operative complications were analyzed. The differences between pre-operative and last post-operative IOP and numbers of anti-glaucoma medications were compared using paried t test and wilcoxon signed rank test. Results: Thirteen male and 2 female children aged between 2-10 (median: 4) years old were recruited. 11 cases (12 eyes) were diagnosed as primary congenital glaucoma, 3 eyes of 3 cases were late-onset childhood glaucoma, and 1 eye was secondary glaucoma. The mean pre-operative IOP was (35.69 ± 6.27) mmHg (1 mmHg=0.133 kPa) on a mean of 3(1-4) medications for childhood glaucoma patients. The mean post-operative IOP decreased to (17.88 ± 7.74) mmHg ( t =6.97, P < 0.01) and the median post operative medications decreased to 0(0-3)( Z =-3.15, P <0.01) at last visit. Twelve cases and 14 cases achieved complete and qualified success, respectively. No severe complications were observed for all patients. Conclusion: Microcatheter-assisted trabeculotomy got lower introcular pressure results for 15 childhood glaucoma patients with untreadtable traditional surgeries repeatedly with minimal complications. ( Chin J Ophthalmol , 2017 , 53 :203-206).

Glaucoma-related Changes in the Mechanical Properties and Collagen Micro-architecture of the Human Sclera

PubMed Central

Coudrillier, Baptiste; Pijanka, Jacek K.; Jefferys, Joan L.; Goel, Adhiraj; Quigley, Harry A.; Boote, Craig; Nguyen, Thao D.

2015-01-01

Objective The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. Methods Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix. Results The differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant. Conclusion The observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage. PMID:26161963

Predictors of visual outcomes following Boston type 1 keratoprosthesis implantation.

PubMed

Ahmad, Sumayya; Akpek, Esen K; Gehlbach, Peter L; Dunlap, Karen; Ramulu, Pradeep Y

2015-04-01

To identify predictors of visual outcomes following Boston type 1 Keratoprosthesis (KPro) implantation. Retrospective chart review. Data regarding preoperative clinical and demographic characteristics and postoperative course were collected. Fifty-nine eyes of 59 adult patients who underwent KPro implantation between January 2006 and March 2012 at a single tertiary care center. Preoperative factors associated with all-cause and glaucoma-related loss of visual acuity from the best postoperative visual acuity noted. Fifty-two of 59 eyes (88%) achieved improved vision post implantation, with 7 eyes failing to gain vision as a result of pre-existing glaucoma (n = 4) or retino-choroidal disease (n = 3). Twenty-one eyes (21/52, 40%) maintained their best-ever visual acuity at last visit (mean follow-up period was 37.8 months). The likelihood of maintaining best-ever vision was 71% at 1 year, 59% at 2 years, and 48% at 3 years. Primary KPro implantation was associated with a higher likelihood of losing best-ever vision as compared to KPro implantation as a repeat corneal procedure (hazard ratio [HR] = 3.06; P = 006). The main reasons for postimplantation vision loss was glaucoma (12/31, 39%), and the risk of glaucomatous visual acuity loss was 15% at 2 years and 27% at 3 years. Prior trabeculectomy was associated with a higher rate of vision loss from glaucoma (HR = 3.25, P = .04). Glaucoma is the primary reason for loss of visual acuity after KPro implantation. Conditions necessitating primary KPro surgery are associated with more frequent all-cause vision loss. Prospective trials are necessary to better determine which clinical features best predict KPro success. Copyright © 2015 Elsevier Inc. All rights reserved.

The Association of Glaucomatous Visual Field Loss and Balance

PubMed Central

de Luna, Regina A.; Mihailovic, Aleksandra; Nguyen, Angeline M.; Friedman, David S.; Gitlin, Laura N.; Ramulu, Pradeep Y.

2017-01-01

Purpose To relate balance measures to visual field (VF) damage from glaucoma. Methods The OPAL kinematic system measured balance, as root mean square (RMS) sway, on 236 patients with suspect/diagnosed glaucoma. Balance was measured with feet shoulder width apart while standing on a firm/foam surface with eyes opened/closed (Instrumental Clinical Test of Sensory Integration and Balance [ICTSIB] conditions), and eyes open on a firm surface under feet together, semi-tandem, or tandem positions (standing balance conditions). Integrated VF (IVF) sensitivities were calculated by merging right and left eye 24-2 VF data. Results Mean age was 71 years (range, 57–93) and mean IVF sensitivity was 27.1 dB (normal = 31 dB). Lower IVF sensitivity was associated with greater RMS sway during eyes-open foam-surface testing (β = 0.23 z-score units/5 dB IVF sensitivity decrement, P = 0.001), but not during other ICTSIB conditions. Lower IVF sensitivity also was associated with greater RMS sway during feet together standing balance testing (0.10 z-score units/5 dB IVF sensitivity decrement, P = 0.049), but not during other standing balance conditions. Visual dependence of balance was lower in patients with worse IVF sensitivity (β = −21%/5 dB IVF sensitivity decrement, P < 0.001). Neither superior nor inferior IVF sensitivity consistently predicted balance measures better than measures of overall VF sensitivity. Conclusions Balance was worse in glaucoma patients with greater VF damage under foam surface testing (designed to inhibit proprioceptive contributions to balance) as well as feet-together firm-surface conditions when somatosensory inputs were available. Translational Relevance Good balance is essential to avoid unnecessary falls and patients with VF loss from glaucoma may be at higher risk of falls because of poor balance. PMID:28553562

A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy

PubMed Central

Roberti, Gloria; Tanga, Lucia; Parisi, Vincenzo; Sampalmieri, Massimo; Centofanti, Marco; Manni, Gianluca

2014-01-01

Purpose: To study the neuroprotective effect of topical citicoline. Materials and Methods: Experimental phase to evaluate the ability of citicoline eye drops to reach the vitreous and the retina: The right eyes of 5 mice CD1 were treated with two drops per day for three days of citicoline 1% and 2% (OMK1, Omikron Italia s.r.l.), and then the vitreous was analyzed with the liquid chromatography and spectrometry mass (LC-MS/MS). Clinical phase to determine if topical citicoline is able to delay glaucoma progression, considering perimetric parameters and electro functional tests. Patients were randomized in two groups, OMK1 and OAG. The first group was treated with OMK1 three times per day, plus hypotensive therapy for two months and one month of wash out. The second group was treated only with hypotensive treatment for three months. Results: LC-MS/MS detected the molecule very well, and only OMK1 showed systemic absorption. Thirty-four patients were enrolled, 16 in the OMK1 and 18 in the OAG group. Perimetric parameters showed a positive trend in individual eyes of patients in OMK1 group, but these values were not statistically significant in the whole group. Retinal ganglion cells function improved as shown by reduced P50 latency (P = 0.04) and increased P50-N95 amplitude (P < 0.0001) of pattern electroretinogram, up to 30 days after the washout (P = 0.01; P = 0.002). Visual evoked potential and retino-cortical time improvement regressed after 30 days of washout. In OAG group, there was any change during the follow-up. No adverse reactions were reported in both groups. Conclusions: Topical citicoline seems to have a neuroprotective action. PMID:24881599

Investigating the usefulness of a cluster-based trend analysis to detect visual field progression in patients with open-angle glaucoma.

PubMed

Aoki, Shuichiro; Murata, Hiroshi; Fujino, Yuri; Matsuura, Masato; Miki, Atsuya; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Hirasawa, Kazunori; Shoji, Nobuyuki; Asaoka, Ryo

2017-12-01

To investigate the usefulness of the Octopus (Haag-Streit) EyeSuite's cluster trend analysis in glaucoma. Ten visual fields (VFs) with the Humphrey Field Analyzer (Carl Zeiss Meditec), spanning 7.7 years on average were obtained from 728 eyes of 475 primary open angle glaucoma patients. Mean total deviation (mTD) trend analysis and EyeSuite's cluster trend analysis were performed on various series of VFs (from 1st to 10th: VF1-10 to 6th to 10th: VF6-10). The results of the cluster-based trend analysis, based on different lengths of VF series, were compared against mTD trend analysis. Cluster-based trend analysis and mTD trend analysis results were significantly associated in all clusters and with all lengths of VF series. Between 21.2% and 45.9% (depending on VF series length and location) of clusters were deemed to progress when the mTD trend analysis suggested no progression. On the other hand, 4.8% of eyes were observed to progress using the mTD trend analysis when cluster trend analysis suggested no progression in any two (or more) clusters. Whole field trend analysis can miss local VF progression. Cluster trend analysis appears as robust as mTD trend analysis and useful to assess both sectorial and whole field progression. Cluster-based trend analyses, in particular the definition of two or more progressing cluster, may help clinicians to detect glaucomatous progression in a timelier manner than using a whole field trend analysis, without significantly compromising specificity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expansions of the Neurovascular Scleral Canal and Contained Optic Nerve Occur Early in the Hypertonic Saline Rat Experimental Glaucoma Model

PubMed Central

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K.; Cepurna, W.O.; Johnson, E.C.; Morrison, J.C.; Burgoyne, Claude F.

2015-01-01

Purpose To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONH’s with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p<.0022), and in 7 of 8 EG eyes (p<.005). In at least 5 EG eyes, significant expansions (p<.005) in Bruch’s membrane opening (range 3–10%), the anterior and posterior scleral canal openings (8–21% and 5–21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11–30% and 8–41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R= 0.768, P=.042). Conclusion In the rat ONH, the optic nerve and surrounding Bruch’s membrane opening and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. PMID:26500195

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model.

PubMed

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K; Cepurna, William O; Johnson, Elaine C; Morrison, John C; Burgoyne, Claude F

2016-04-01

To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dry Eye Disease: Prevalence, Assessment, and Management.

PubMed

Rouen, Patricia A; White, Mary L

Dry eye disease is a chronic condition of the corneal surface marked by persistent symptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated. Common risk factors for this syndrome include advancing age, female sex, low humidity environments, systemic medications, and autoimmune disorders. Treatments to relieve symptoms include tear replacement, humidification, improved nutrition, and anti-inflammatory ocular agents. Home healthcare nurses can identify signs and symptoms of dry eye syndrome and initiate strategies that range from warm compresses to physician referrals for more aggressive treatment. Consistent management of this condition improves quality of life and minimizes damage to the ocular surface.

Perimetric measurements with flicker-defined form stimulation in comparison with conventional perimetry and retinal nerve fiber measurements.

PubMed

Horn, Folkert K; Tornow, Ralf P; Jünemann, Anselm G; Laemmer, Robert; Kremers, Jan

2014-04-11

We compared the results of flicker-defined form (FDF) perimetry with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements using spectral domain optical coherence tomography (OCT). A total of 64 healthy subjects, 45 ocular hypertensive patients, and 97 "early" open-angle glaucoma (OAG) patients participated in this study. Definition of glaucoma was based exclusively on glaucomatous optic disc appearance. All subjects underwent FDF perimetry, SAP, and peripapillary measurements of the RNFL thickness. The FDF perimetry and SAP were performed at identical test locations (G1 protocol). Exclusion criteria were subjects younger than 34 years, SAP mean defect (SAP MD) > 5 dB, eye diseases other than glaucoma, or nonreliable FDF measurements. The correlations between the perimetric data on one hand and RNFL thicknesses on the other hand were analyzed statistically. The age-corrected sensitivity values and the local results from the controls were used to determine FDF mean defect (FDF MD). The FDF perimetry and SAP showed high concordance in this cohort of experienced patients (MD values, R = -0.69, P < 0.001). Of a total of 42 OAG patients with abnormal SAP MD, 38 also displayed abnormal FDF MD. However, FDF MD was abnormal in 28 of 55 OAG patients with normal SAP MD. The FDF MD was significantly (R = -0.61, P < 0.001) correlated with RNFL thickness with a (nonsignificantly) larger correlation coefficient than conventional SAP MD (R = -0.48, P < 0.001). The FDF perimetry is able to uncover functional changes concurrent with the changes in RNFL thickness. The FDF perimetry may be an efficient functional test to detect early glaucomatous nerve atrophy. (ClinicalTrials.gov number, NCT00494923.).

Determinants and Heritability of Intraocular Pressure and Cup-to-Disc Ratio in a Defined Older Population

PubMed Central

Chang, Ta C.; Congdon, Nathan G.; Wojciechowski, Robert; Muñoz, Beatriz; Gilbert, Donna; Chen, Ping; Friedman, David S.; West, Sheila K.

2011-01-01

Purpose To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population. Design Family-based cohort study. Participants Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships. Methods Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glacuoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP. Main Outcome Measures Heritability and determinants of IOP and CDR, and impact of siblings’ glaucoma status on IOP and CDR. Results We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12–0.46) for IOP and 0.56 (95% CI, 0.35–0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004). Conclusions In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands. PMID:15939473

Angiopoietin-like 7 Secretion Is Induced by Glaucoma Stimuli and Its Concentration Is Elevated in Glaucomatous Aqueous Humor

PubMed Central

Kuchtey, John; Källberg, Maria E.; Gelatt, Kirk N.; Rinkoski, Tommy; Komàromy, András M.; Kuchtey, Rachel W.

2010-01-01

Purpose To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma. Methods Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor β (TGFβ), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression. Results TGFβ and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs. Conclusions Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target. PMID:18421092

Peripapillary choroidal thickness in healthy controls and patients with focal, diffuse, and sclerotic glaucomatous optic disc damage.

PubMed

Roberts, Kenneth F; Artes, Paul H; O'Leary, Neil; Reis, Alexandre S C; Sharpe, Glen P; Hutchison, Donna M; Chauhan, Balwantray C; Nicolela, Marcelo T

2012-08-01

To examine peripapillary choroidal thickness in healthy controls and in patients with glaucoma who have focal, diffuse, and sclerotic optic disc damage. Healthy controls (n=92) and patients with glaucoma who have focal (n=34), diffuse (n=35), and sclerotic (n=34) optic disc damage were imaged with spectral-domain optical coherence tomography (12° circular scan protocol centered on optic nerve head). Peripapillary choroidal thickness was measured as the distance between the automatically segmented retinal pigment epithelium/Bruch's membrane and the manually outlined interface between the posterior choroid and the anterior border of the sclera in eyes in which the anterior scleral border was visible over more than 85% of the scan circumference. The anterior scleral border was visible in 76 controls (83%) and 89 patients (86%). Peripapillary choroidal thickness in healthy controls decreased linearly with age (-11 μm/decade; P.001; r2=0.16), with a predicted value of 137 μm at age 70 years (95% prediction interval, 62-212 μm). While this value was similar in patients with focal and diffuse optic disc damage (126 and 130 μm, respectively; P=.22 compared with controls), it was approximately 30% lower in patients with sclerotic optic disc damage (96 μm; P.001 compared with controls). The peripapillary choroid of patients with glaucoma who have sclerotic optic disc damage was approximately 25% to 30% thinner compared with that in patients with focal and diffuse optic disc damage and with that in healthy controls. The role of the choroid in the pathophysiology of sclerotic glaucomatous optic disc damage needs further investigation.

Changes in corneal endothelial cell density and the cumulative risk of corneal decompensation after Ahmed glaucoma valve implantation.

PubMed

Kim, Kyoung Nam; Lee, Sung Bok; Lee, Yeon Hee; Lee, Jong Joo; Lim, Hyung Bin; Kim, Chang-Sik

2016-07-01

To evaluate changes in the corneal endothelial cell density (ECD) and corneal decompensation following Ahmed glaucoma valve (AGV) implantation. This study was retrospective and observational case series. Patients with refractory glaucoma who underwent AGV implantation and were followed >5 years were consecutively enrolled. We reviewed the medical records, including the results of central corneal specular microscopy. Of the 127 enrolled patients, the annual change in ECD (%) was determined using linear regression for 72 eyes evaluated at least four times using serial specular microscopic examination and compared with 31 control eyes (fellow glaucomatous eyes under medical treatment). The main outcome measures were cumulative risk of corneal decompensation and differences in the ECD loss rates between subjects and controls. The mean follow-up after AGV implantation was 43.1 months. There were no cases of postoperative tube-corneal touch. The cumulative risk of corneal decompensation was 3.3%, 5 years after AGV implantation. There was a more rapid loss of ECD in the 72 subject eyes compared with the 31 controls (-7.0% and -0.1%/year, respectively; p<0.001). However, the rate of loss decreased over time and statistical significance compared with control eyes disappeared after 2 years postoperatively: -10.7% from baseline to 1 year (p<0.01), -7.0% from 1 year to 2 years (p=0.037), -4.2% from 2 years to 3 years (p=0.230) and -2.7% from 3 years to the final follow-up (p=0.111). In case of uncomplicated AGV implantation, the cumulative risk of corneal decompensation was 3.3%, 5 years after the operation. The ECD loss was statistically greater in eyes with AGV than in control eyes without AGV, but the difference was significant only up to 2 years post surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pupillographic evaluation of the time course of atropine effects in the mouse eye.

PubMed

Schaeffel, Frank; Burkhardt, Eva

2005-03-01

The nonselective muscarinic antagonist atropine is currently the most potent drug against myopia development in both humans and animal models. However, the mechanism by which myopia is suppressed is still unknown, and the time course of its action is not well documented. Therefore, we have studied the duration of mydriasis in the mouse, a new model of myopia, after topical application of a single eye drop with different doses of atropine. The light-induced pupil response of the C57BL/6 (B6) wildtype strain was studied in alert mice that were restrained by grasping their necks. A video image-processing program detected the pupil and measured its diameter at 25 Hz sampling rate. To stimulate, an arrangement of green LEDs, which was attached to the recording video camera, could be flashed for 40 ms by pressing a key on the keyboard. A single drop of atropine solution (1, 0.5, or 0.1%) was instilled in one eye and the recovery of the pupil responses was followed for at least 150 h. Both eyes were measured. 1) Under the defined stimulation conditions, untreated wildtype mice displayed a pupil constriction of 23.7 +/- 2.4%. 2) All doses of atropine caused complete suppression of the pupil responses in the treated eyes within 1 min. 3) The pupil responses of the fellow eyes remained unaffected and were not different from those in untreated animals. 4) The recovery from mydriasis was very slow and did not show clear differences with dose. The extrapolated duration of complete recovery was about 10 d (0.1%: 217 h; 0.5%: 230 h; 1%: 294 h). Atropine caused a longlasting suppression of the pupil responses in the mouse eye. That the duration of recovery was not obviously dose-dependent suggests that all doses used in this study were saturating the receptors in the iris musculature.

Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes

PubMed Central

Miki, Atsuya; Medeiros, Felipe A.; Weinreb, Robert N.; Jain, Sonia; He, Feng; Sharpsten, Lucie; Khachatryan, Naira; Hammel, Na’ama; Liebmann, Jeffrey M.; Girkin, Christopher A.; Sample, Pamela A.; Zangwill, Linda M.

2015-01-01

Purpose To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspect of having glaucoma who developed visual field damage (VFD) to those who did not develop VFD, and to determine whether the rate of RNFL loss can be used to predict who will develop VFD.. Design Prospective observational cohort study Participants Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (Intraocular pressure (IOP)>21 mmHg) without repeatable VFD at baseline from the Diagnostic Innovations in Glaucoma Study, and the African Descent and Glaucoma Evaluation Study. Methods Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT). VFD was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared with eyes not developing VFD using multivariable linear mixed-effects models. A joint longitudinal survival model utilized the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables. Main Outcome Measures The rate of RNFL thinning and the probability of developing VFD. Results Four hundred and fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2–9) with median follow-up time of 2.2 (0.4–4.1) years. Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes developing VFD compared with eyes that did not (−2.02μm/year vs. −0.82μm/year, P<0.001). The joint longitudinal survival model showed that each 1μm/year faster rate of global RNFL loss corresponded to a 2.05 times higher risk of developing VFD (Hazards Ratio (HR)=2.05, 95% Confidence Interval (CI): 1.14–3.71; p=0.017). Conclusions The rate of global RNFL loss was more than twice as fast in eyes developing VFD compared with eyes that did not develop them. Joint longitudinal survival model showed that a 1μm/year faster rate of RNFLT loss corresponded to a 2.05 times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss. PMID:24629619

Relation Between Macular Retinal Ganglion Cell/Inner Plexiform Layer Thickness and Multifocal Electroretinogram Measures in Experimental Glaucoma

PubMed Central

Luo, Xunda; Patel, Nimesh B.; Rajagopalan, Lakshmi P.; Harwerth, Ronald S.; Frishman, Laura J.

2014-01-01

Purpose. We investigated relations between macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) thickness and macular retinal function revealed by multifocal electroretinonography (mfERG) in a nonhuman primate model of experimental glaucoma. Methods. Retinal ganglion cell (RGC) structure and function were followed with spectral-domain optical coherence tomography (SD-OCT) and ERGs in five macaques with unilateral experimental glaucoma. Linear regression was used to study correlations in control (Con) and experimental (Exp) eyes between peripapillary retinal nerve fiber layer (RNFL) thickness, macular RGC+IPL thickness, multifocal photopic negative response (mfPhNR) and high-frequency multifocal oscillatory potentials (mfOP) in slow-sequence mfERG, and low-frequency component (mfLFC) in global-flash mfERG. We used ANOVA and paired t-tests to compare glaucoma-related mfERG changes between superior and inferior hemifields, foveal hexagon, inner three rings, and four quadrants of macula. Results. Average macular RGC+IPL and temporal RNFL thickness were strongly correlated (r2 = 0.90, P < 0.001). In hexagon-by-hexagon analysis, all three mfERG measures were correlated (P < 0.001) with RGC+IPL thickness for Con (r2, 0.33–0.51) and Exp eyes (r2, 0.17–0.35). The RGC structural and functional metrics decreased as eccentricity increased. The reduction in amplitude of mfERG measures in Exp eyes relative to Con eyes was proportionally greater, in general, than the relative thinning of RGC+IPL at the same location for eyes in which structural loss was not evident, or mild to moderate. Although not statistically significant, percent amplitude reduction of mfERG measures was greatest in the inferior temporal quadrant. Conclusions. Macular RGC+IPL thickness and mfERG measures of RGC function can be complementary tools in assessing glaucomatous neuropathy. PMID:24970256

Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

PubMed

Agarwal, Puneet; Agarwal, Renu

2018-06-14

Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure

PubMed Central

Wang, Wan-Heng; McNatt, Loretta G.; Pang, Iok-Hou; Millar, J. Cameron; Hellberg, Peggy E.; Hellberg, Mark H.; Steely, H. Thomas; Rubin, Jeffrey S.; Fingert, John H.; Sheffield, Val C.; Stone, Edwin M.; Clark, Abbot F.

2008-01-01

Elevated intraocular pressure (IOP) is the principal risk factor for glaucoma and results from excessive impedance of the fluid outflow from the eye. This abnormality likely originates from outflow pathway tissues such as the trabecular meshwork (TM), but the associated molecular etiology is poorly understood. We discovered what we believe to be a novel role for secreted frizzled-related protein-1 (sFRP-1), an antagonist of Wnt signaling, in regulating IOP. sFRP1 was overexpressed in human glaucomatous TM cells. Genes involved in the Wnt signaling pathway were expressed in cultured TM cells and human TM tissues. Addition of recombinant sFRP-1 to ex vivo perfusion-cultured human eyes decreased outflow facility, concomitant with reduced levels of β-catenin, the Wnt signaling mediator, in the TM. Intravitreal injection of an adenoviral vector encoding sFRP1 in mice produced a titer-dependent increase in IOP. Five days after vector injection, IOP increased 2 fold, which was significantly reduced by topical ocular administration of an inhibitor of a downstream suppressor of Wnt signaling. Thus, these data indicate that increased expression of sFRP1 in the TM appears to be responsible for elevated IOP in glaucoma and restoring Wnt signaling in the TM may be a novel disease intervention strategy for treating glaucoma. PMID:18274669

Longitudinal and cross-sectional analyses of visual field progression in participants of the Ocular Hypertension Treatment Study.

PubMed

Artes, Paul H; Chauhan, Balwantray C; Keltner, John L; Cello, Kim E; Johnson, Chris A; Anderson, Douglas R; Gordon, Mae O; Kass, Michael A

2010-12-01

To assess agreement between longitudinal and cross-sectional analyses for determining visual field progression in data from the Ocular Hypertension Treatment Study. Visual field data from 3088 eyes of 1570 participants (median follow-up, 7 years) were analyzed. Longitudinal analyses were performed using change probability with total and pattern deviation, and cross-sectional analyses were performed using the glaucoma hemifield test, corrected pattern standard deviation, and mean deviation. The rates of mean deviation and general height change were compared to estimate the degree of diffuse loss in emerging glaucoma. Agreement on progression in longitudinal and cross-sectional analyses ranged from 50% to 61% and remained nearly constant across a wide range of criteria. In contrast, agreement on absence of progression ranged from 97.0% to 99.7%, being highest for the stricter criteria. Analyses of pattern deviation were more conservative than analyses of total deviation, with a 3 to 5 times lesser incidence of progression. Most participants developing field loss had both diffuse and focal changes. Despite considerable overall agreement, 40% to 50% of eyes identified as having progressed with either longitudinal or cross-sectional analyses were identified with only one of the analyses. Because diffuse change is part of early glaucomatous damage, pattern deviation analyses may underestimate progression in patients with ocular hypertension.

Improving our understanding, and detection, of glaucomatous damage: An approach based upon optical coherence tomography (OCT)

PubMed Central

Hood, Donald C.

2017-01-01

Although ophthalmologists are becoming increasingly reliant upon optical coherence tomography (OCT), clinicians who care for glaucoma patients are not taking full advantage of the potential of this powerful technology. First, we ask, how would one describe the nature of glaucomatous damage if only OCT scans were available? In particular, a schematic model of glaucomatous damage is developed in section 2, and the nature of glaucomatous damage seen on OCT scans described in the context of this model in section 3. In particular, we illustrate that local thinning of the circumpapillary retinal nerve fiber layer (cpRNFL) around the optic disc can vary in location, depth, and/or width, as well as homogeneity of damage. Second, we seek to better understand the relationship between the thinning of the cpRNFL and the various patterns of sensitivity loss seen on visual fields obtained with standard automated perimetry. In sections 4 and 5, we illustrate why one should expect a wide range of visual field patterns, and iilustrate why they should not be placed into discrete categories. Finally, section 6 describes how the clinician can take better advantage of the information in OCT scans. The approach is summarized in a single-page report, which can be generated from a single wide-field scan. The superiority of this approach, as opposed to the typical reliance on summary metrics, is described. PMID:28012881

Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Mumcuoglu, Tarkan; Wollstein, Gadi; Wojtkowski, Maciej; Kagemann, Larry; Ishikawa, Hiroshi; Gabriele, Michelle L.; Srinivasan, Vivek; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

Purpose To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. Design Prospective observational case series. Participants Healthy and glaucomatous subjects in various stages of disease. Methods Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. Main Outcome Measures Discrimination of retinal tissue layers and detailed visualization of retinal structures. Results High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. Conclusion High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma. PMID:17884170

The association between compliance with recommended follow-up and glaucomatous disease severity in a county hospital population.

PubMed

Ung, Cindy; Murakami, Yohko; Zhang, Elisa; Alfaro, Tatyana; Zhang, Monica; Seider, Michael I; Singh, Kuldev; Lin, Shan C

2013-08-01

To assess the association between insufficient follow-up and clinical parameters such as disease severity and medication use among glaucoma patients at a metropolitan county hospital. Cross-sectional study. Two-hundred and six patients with established glaucoma were recruited from San Francisco General Hospital. Subjects were classified based on compliance with recommended follow-up examination intervals over the year preceding commencement of the study, as determined by patient medical records. Glaucoma severity was determined based on the American Academy of Ophthalmology Preferred Practice Patterns guidelines. Multivariate logistic regression analysis was used to assess the relationship between adherence with follow-up visits and disease severity. After adjustment for the impact of potential confounding variables, subjects with severe glaucomatous disease were found to have been less adherent to their recommended follow-up than those patients with mild or moderate glaucomatous disease (adjusted OR 1.89, 95% CI 1.21-2.94; P = .01). Subjects who were on glaucoma medications were found to be less adherent to follow-up recommendations (adjusted OR 3.29, 95% CI 1.41-7.65, P = .01). Subjects with poor follow-up adherence were significantly more likely to have severe glaucomatous disease, suggesting that poor follow-up may contribute to disease worsening or, alternatively, those with more severe disease are less inclined to follow up at appropriate intervals. Published by Elsevier Inc.

Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: Implications for pursuit eye tracking

PubMed Central

Lencer, Rebekka; Keedy, Sarah K.; Reilly, James L.; McDonough, Bruce E.; Harris, Margret S. H.; Sprenger, Andreas; Sweeney, John A.

2011-01-01

Visual motion processing and its use for pursuit eye movement control represent a valuable model for studying the use of sensory input for action planning. In psychotic disorders, alterations of visual motion perception have been suggested to cause pursuit eye tracking deficits. We evaluated this system in functional neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic bipolar disorder patients (N=13) and healthy controls (N=20). During a passive visual motion processing task, both patient groups showed reduced activation in the posterior parietal projection fields of motion-sensitive extrastriate area V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual motion information from extrastriate cortex to perceptual systems in parietal association cortex. During active pursuit, activation was enhanced in anterior intraparietal sulcus and insula in both patient groups, and in dorsolateral prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may result from increased demands on sensorimotor systems for pursuit control due to the limited availability of perceptual motion information about target speed and tracking error. Visual motion information transfer deficits to higher -level association cortex may contribute to well-established pursuit tracking abnormalities, and perhaps to a wider array of alterations in perception and action planning in psychotic disorders. PMID:21873035

Myopia progression control lens reverses induced myopia in chicks.

PubMed

Irving, Elizabeth L; Yakobchuk-Stanger, Cristina

2017-09-01

To determine whether lens induced myopia in chicks can be reversed or reduced by wearing myopia progression control lenses of the same nominal (central) power but different peripheral designs. Newly hatched chicks wore -10D Conventional lenses unilaterally for 7 days. The myopic chicks were then randomly divided into three groups: one fitted with Type 1 myopia progression control lenses, the second with Type 2 myopia progression control lenses and the third continued to wear Conventional lenses for seven more days. All lenses had -10D central power, but Type 1 and Type 2 lenses had differing peripheral designs; +2.75D and +1.32D power rise at pupil edge, respectively. Axial length and refractive error were measured on Days 0, 7 and 14. Analyses were performed on the mean differences between treated and untreated eyes. Refractive error and axial length differences between treated and untreated eyes were insignificant on Day 0. On Day 7 treated eyes were longer (T1; 0.44 ± 0.07 mm, T2; 0.27 ± 0.06 mm, C; 0.40 ± 0.06 mm) and more myopic (T1; -9.61 ± 0.52D, T2; -9.57 ± 0.61D, C; -9.50 ± 0.58D) than untreated eyes with no significant differences between treatment groups. On Day 14 myopia was reversed (+2.91 ± 1.08D), reduced (-3.83 ± 0.94D) or insignificantly increased (-11.89 ± 0.79D) in treated eyes of Type 1, Type 2 and Conventional treated chicks respectively. Relative changes in axial lengths (T1; -0.13 ± 0.09 mm, T2; 0.36 ± 0.09 mm, C; 0.56 ± 0.05 mm) were consistent with changes in refraction. Refractive error differences were significant for all group comparisons (p < 0.001). Type 1 length differences were significantly different from Conventional and Type 2 groups (p < 0.001). Myopia progression control lens designs can reverse lens-induced myopia in chicks. The effect is primarily due to axial length changes. Different lens designs produce different effects indicating that lens design is important in modifying refractive error. © 2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

The Advanced Glaucoma Intervention Study (AGIS): 14. Distinguishing progression of glaucoma from visual field fluctuations.

PubMed

Kim, Jonghyeon; Dally, Leonard G; Ederer, Fred; Gaasterland, Douglas E; VanVeldhuisen, Paul C; Blackwell, Beth; Sullivan, E Kenneth; Prum, Bruce; Shafranov, George; Beck, Allen; Spaeth, George L

2004-11-01

To determine the least worsening of a visual field (VF) and the least number of confirming tests needed to identify progression of glaucomatous VF defects. Cohort study of participants in a clinical trial. Seven hundred fifty-two eyes of 565 patients with advanced glaucoma. Visual field tests were quantified with the Advanced Glaucoma Intervention Study (AGIS) VF defect score and the Humphrey Field Analyzer mean deviation (MD). Follow-up was 8 to 13 years. Two measures based on the AGIS VF defect score: (1) sustained decrease of VF (SDVF), a worsening from baseline by 2 (alternatively, 3 or 4) or more units and sustained for 2 (alternatively, 3) consecutive 6-month visits and (2) after the occurrence of SDVF, the average percent of eyes with worsening by 2 (alternatively, 3 or 4) or more units from baseline. Two similar measures based on MD. Based on the original AGIS criteria for SDVF (a worsening of 4 units in the AGIS score sustained during 3 consecutive 6-month visits), 31% of eyes had an SDVF. The percent of eyes with a sustained event increases by approximately 10% when either the minimum number of units of field loss or the minimum number of 6-month visits during which the loss is sustained decreases by 1. During 3 years of follow-up after a sustained event, a worsening of at least 2 units was found in 72% of eyes that had a 2-visit sustained event. The same worsening was found in 84% of eyes that had a 3-visit sustained event. Through the next 10 years after a sustained event, based on worsening of 2, 3, or 4 units at 2 or 3 consecutive tests, the loss reoccurred, on average, in >/=75% of study eyes. Results for MD are similar. In patients with advanced glaucoma, a single confirmatory test 6 months after a VF worsening indicates with at least 72% probability a persistent defect when the worsening is defined by at least 2 units of AGIS score or by at least 2 decibels of MD. When the number of confirmatory tests is increased from 1 to 2, the percentage of eyes that show a persistent defect increases from 72% to 84%.

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma.

PubMed

Fonseca, Begoña; Martínez-Águila, Alejandro; de Lara, María J Pérez; Pintor, Jesús

2017-06-01

Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap 4 A to reduce IOP. The topical application of Ap 4 A when IOP is maximal (9-12 months) reduced IOP 30.6 ± 6.6% in the DBA/2J and 17.9 ± 4.0% in the C57BL/6J mice. Concentration response curves in both animal strains produced similar pD2 values; these being 4.9 ± 0.5 and 5.1 ± 0.4 for the normotensive C57BL/6J and the glaucomatous DBA/2J respectively. Antagonist studies showed differences between the control and the glaucomatous animals. In particular, the main receptor reducing IOP in the control animal was the P2Y 1 receptor and in the glaucomatous model the P2Y 6 , although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap 4 A applied three times a week for 3 months showed a clear stop in the elevation of IOP in the glaucomatous model, thus indicating the possibility of using Ap 4 A as an effective compound for the treatment of glaucoma.

Osteo-Odonto-Keratoprosthesis in Severe Thermal and Chemical Injuries.

PubMed

Vasquez-Perez, Alfonso; Zarei-Ghanavati, Mehran; Avadhanam, Venkata; Liu, Christopher

2018-05-16

To report the results of osteo-odonto-keratoprosthesis (OOKP) surgery in patients who sustained severe chemical and thermal injuries. This is a noncomparative retrospective case series of 14 patients who underwent OOKP surgery between 2001 and 2016 at the Sussex Eye Hospital, Brighton, UK, because of severe chemical and thermal injuries RESULTS:: OOKP surgery was performed in 14 eyes of 14 patients. Eight patients (57%) sustained thermal injuries and 6 patients (43%) chemical injuries. Every eye had previously undergone adnexal or ocular surgery, including 2 cases that underwent synthetic keratoprosthesis implantation. One case had choroidal hemorrhage during stage 2. Laminar retention was observed in 11 cases (85%) at the end of the study. The Kaplan-Meier curve showed a probability of 81% of laminar retention at 5 years and a decrease at 15 years to 61%. Functional visual success was observed in only 7 patients (50%) because of end-stage glaucomatous optic neuropathy in 4 cases and macular scar in 1 case. Two cases developed endophthalmitis. Two cases required removal of laminae, one because of endophthalmitis, bone resorption and aqueous leak and the other because of development of a retroprosthetic membrane. Glaucoma was the most frequent complication (79%) and required surgical intervention with tube shunts in 5 cases. Six cases (43%) required buccal mucosal repair, which included two cases that developed endophthalmitis. Anatomic success was achieved in 11 of 13 cases in this series of OOKP surgery after severe chemical and thermal trauma; 8 of these cases had at least 5 years of follow-up and thus qualified as long-term.

Individual A-Scan Signal Normalization Between Two Spectral Domain Optical Coherence Tomography Devices

PubMed Central

Chen, Chieh-Li; Ishikawa, Hiroshi; Wollstein, Gadi; Ling, Yun; Bilonick, Richard A.; Kagemann, Larry; Sigal, Ian A.; Schuman, Joel S.

2013-01-01

Purpose. We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. Methods. We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured. Results. The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes. Conclusions. The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices. PMID:23611992

[Glaucoma and sleep apnea syndrome].

PubMed

Blumen-Ohana, E; Blumen, M; Aptel, F; Nordmann, J P

2011-06-01

Glaucomatous optic neuropathy is multifactorial, with currently one known and modifiable risk factor, with good results on the prognosis and intraocular pressure. Nevertheless, some patients may experience progression of their neuropathy even though their intraocular pressure seems appropriately controlled. Vascular risk factors are hypothesized and researched. Obstructive sleep apnea syndrome (OSAS) could be considered one of these risk factors. Screening for this cardiovascular risk factor in glaucomatous patients presenting evocative signs, should be proposed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Effect of recording duration on the diagnostic performance of multifocal visual-evoked potentials in high-risk ocular hypertension and early glaucoma.

PubMed

Fortune, Brad; Zhang, Xian; Hood, Donald C; Demirel, Shaban; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L; Cioffi, George A; Johnson, Chris A

2008-01-01

To evaluate the effect on diagnostic performance of reducing multifocal visual-evoked potential (mfVEP) recording duration from 16 to 8 minutes per eye. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were studied. Two 8-minute mfVEP recordings were obtained for each eye in an ABBA order using VERIS. The first recording for each eye was compared against single run (1-Run) mfVEP normative data; the average of both recordings for each eye was compared against 2-Run normative data. Visual fields (VFs) were obtained by standard automated perimetry (SAP) within 22.3+/-27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph images were obtained together, within 24.8+/-50.4 days of the mfVEP and 33.1+/-62.9 days of SAP. Masked experts graded disc photographs as either glaucomatous optic neuropathy or normal. The overall Moorfields Regression Analysis result from the Heidelberg Retina Tomograph was used as a separate diagnostic classification. Thus, 4 diagnostic standards were applied in total, 2 based on optic disc structure alone and 2 others based on disc structure and SAP. Agreement between the 1-Run and 2-Run mfVEP was 90%. Diagnostic performance of the 1-Run mfVEP was similar to that of the 2-Run mfVEP for all 4 diagnostic standards. Sensitivity was slightly higher for the 2-Run mfVEP, whereas specificity was slightly higher for the 1-Run mfVEP. If higher sensitivity is sought, the 2-Run mfVEP will provide better discrimination between groups of eyes with relatively high signal-to-noise ratio (eg, early glaucoma or high-risk suspects). But if higher specificity is a more important goal, the 1-Run mfVEP provides adequate sensitivity and requires only half the test time. Considered alongside prior studies, the present results suggest that the 1-Run mfVEP is an efficient way to confirm (or refute) the extent of VF loss in patients with moderate or advanced glaucoma, particularly in those with unreliable VFs, including malingering or other "functional" forms of VF loss.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

PubMed Central

Sobacı, Güngör; Güngör, Rıza; Özge, Gökhan

2013-01-01

AIM To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). METHODS This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. CONCLUSION Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients. PMID:23638426

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study.

PubMed

Sobacı, Güngör; Güngör, Rıza; Ozge, Gökhan

2013-01-01

To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.

The Marfan Syndrome: A Booklet for Teachers.

ERIC Educational Resources Information Center

Bernhardt, Barbara A.

This booklet explains characteristics of Marfan Syndrome, an inherited disorder of connective tissue which can be life-threatening if untreated. Medical problems affecting various parts of the body such as the heart, the skeleton, the eyes and the skin associated with Marfan Syndrome are discussed. Possible medical emergencies are identified.…

Assessment of Retinal Nerve Fiber Layer Using Optical Coherence Tomography and Scanning Laser Polarimetry in Progressive Glaucomatous Optic Neuropathy

PubMed Central

Sehi, Mitra; Greenfield, David S.

2006-01-01

Purpose To describe a case of progressive glaucomatous optic neuropathy using scanning laser polarimetry with fixed (SLP-FCC) and variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). Design Observational case report. Methods A 21-year-old male with juvenile primary open-angle glaucoma developed progression because of noncompliance with therapy. The patient underwent dilated stereoscopic examination and photography of the optic disk, standard automated perimetry (SAP), OCT, and SLP imaging with FCC and VCC at the baseline examination and after four years of follow-up. Results Optic disk, retinal nerve fiber layer (RNFL) atrophy, and SAP progression was observed. Reduction in mean RNFL thickness (average, superior, inferior) was 18, 18, and 27 microns (OCT); 22, 40, and 17 microns (SLP-FCC); and 6, 12, and 12 microns (SLP-VCC), respectively. Conclusions This case demonstrates that digital imaging of the peripapillary RNFL is capable of documentation and measurement of progressive glaucomatous RNFL atrophy. PMID:17157591

Fatal necrotising enterocolitis due to mydriatic eye drops.

PubMed

Ozgun, Uygur; Demet, Terek; Ozge, Koroglu A; Zafer, Dokumcu; Murat, Sezak; Mehmet, Yalaz; Nilgun, Kultursay

2014-05-01

Retinopathy of prematurity (ROP) is a serious problem of preterm infants which may lead to impairment of vision and even to blindness if untreated. Routine eye examination is necessary for early diagnosis and treatment of ROP in preterm infants. Mydriatic eye drops (cyclopentolate, tropicamide and phenylephrine) are applied before the ophthalmic examination. These agents are rarely absorbed to systemic circulation and in some cases result with serious side effects like skin rash, tachycardia, feeding intolerance, discomfort, apnea, gastric dilatation and ileus, despite different treatment models and dosage reducing strategies. We report here a preterm patient who died because of severe diffuse necrotizing enterocolitis (NEC) after topical application of 0.5% cyclopentolate and 1.25% phenylephrine during ROP screening to emphasise the serious side effects of these agents.

[Is prophylactic YAG iridotomy useful in pigment dispersion syndrome?].

PubMed

Rosentreter, A; Schwenn, O; Funk, J; Dietlein, T

2013-04-01

Despite theoretical considerations concerning the advantage of iridotomy in eyes with pigment dispersion syndrome or early pigment glaucoma, there is a lack of clinical evidence that this procedure has a long-term effect in preventing glaucoma damage under these circumstances. However, several factors may contribute to this lack of evidence, e.g. the statistical problem of a low conversion rate from pigment dispersion syndrome to pigment glaucoma or the inclusion criteria in the studies treating patients older than 40 years or genetic dispositions in pigment glaucoma that are not yet fully clear. On the basis of current data the decision for YAG iridotomy should only be taken in patients younger than 40 years, if the midperipheral iris shows an inverse bowing and the intraocular pressure is normal or slightly increased with no progressive signs of optic nerve damage. In cases of insufficient intraocular pressure and visual defects due to glaucomatous optic nerve damage, incisional glaucoma surgery is usually necessary especially in younger patients with a long life expectancy.

Effect of topical ophthalmic epinastine and olopatadine on tear volume in mice.

PubMed

Villareal, Arturo L; Farley, William; Pflugfelder, Stephen C

2006-12-01

To investigate the effects of topical epinastine and olopatadine on tear volume by using a mouse model. Eighty-five C57BL6 mice (170 eyes) were treated twice daily with topical ophthalmic epinastine 0.05%, olopatadine 0.1%, or atropine 1% or served as untreated controls. A thread-wetting assay was used to measure tear volume at baseline and 15, 45, 90, 120, and 240 minutes after the last instillation of the drug on days 2 and 4 of treatment. After 2 days of treatment, epinastine-treated mice showed greater mean tear volumes than olopatadine-treated mice did at 15, 45, 90, and 240 minutes, with statistical significance at 15 and 45 minutes (P<0.001). Olopatadine significantly reduced tear volume versus untreated controls at 15 and 45 minutes (P<0.001). After 4 days, tear volumes with epinastine treatment exceeded those with olopatadine treatment at all time points, with statistical significance at 45 minutes (P<0.05). Atropine rendered tears undetectable at 15, 45, and 90 minutes; tear volume returned to baseline levels at 240 minutes. Topical epinastine did not inhibit tear secretion, whereas olopatadine caused a significant decrease in tear volume. Because of its neutral impact on the lacrimal functional unit, epinastine may be an especially good choice for the treatment of allergic conjunctivitis in patients with dry eye disease or in those who are at risk for developing dry eye.

A case of herpes zoster ophthalmicus preceded one week by diplopia and ophthalmalgia.

PubMed

Ota, Tomohiro; Yamazaki, Mineo; Toda, Yusuke; Ozawa, Akiko; Kimura, Kazumi

2017-04-28

A 66-year-old man presented with headache and ophthalmalgia. Diplopia developed, and he was hospitalized. The left eye had abducent paralysis and proptosis. We diagnosed him with Tolosa-Hunt syndrome and administered methylprednisolone at 1 g/day for 3 days. However, the patient did not respond to treatment. No abnormality was found on his MRI or cerebrospinal fluid examination. Tests showed his serum immunoglobulin G4 and antineutrophil cytoplasmic antibody titers were within normal limits. He also had untreated diabetes mellitus (HbA1c 9.2). One week after first presenting with symptoms, herpes zoster appeared on the patient's dorsum nasi, followed by keratitis and a corneal ulcer. Herpes zoster ophthalmicus with ophthalmoplegia was diagnosed. We began treatment with acyclovir (15 mg/kg) and prednisolone (1 mg/kg, decreased gradually). Ophthalmalgia and the eruption improved immediately. The eye movement disorder improved gradually over several months. It is rare that diplopia appears prior to cingulate eruption of herpes zoster ophthalmicus. We speculated that onset of the eruption was inhibited by strong steroid therapy and untreated diabetes mellitus.

[Challenge and treatment strategy for ocular surface damage in patients with long term use of antiglaucoma drugs].

PubMed

He, Xiang-Ge

2011-02-01

Long term use of topical anti-glaucoma drugs has been shown to induce chronic conjunctivitis, superficial punctate keratitis (SPK) and dry eye symptom. Under these conditions, a loss of goblet cells in conjunctiva, epithelial squamous metaplasia and apoptosis were morphologically revealed. Benzalkonium Chloride (BKC), a most frequently used preservative in eye drops, has been found to be an important factor causing ocular surface damage. Furthermore, a big challenge for ophthalmologists is that toxic damage of medication to ocular surface tissues is mild, poor specificity, and delayed manifestation in patients, especially when coexisting with other ocular surface diseases. Impairment of ocular surface tissues greatly impacts the life quality of patients and subsequently influences compliance with glaucoma therapy. This paper emphasizes to take measures to prevent ocular surface tissue damage resulted from chronic use of topical anti-glaucoma drugs and further discusses the treatment strategy. Effective and long-lasting action drugs should always be selected for glaucomatous patients in order to decrease the frequency of topical instillation or at a more expensive medication, a fixed combination formula can be considered for glaucoma therapy. An early surgery or laser treatment is also proposed for the patients who require an IOP reduction with an existing ocular surface impairment. Future investigation and development of new medications with long-term efficacy and appropriate BKC are suggested and preservative-free or drugs with new preservative materials recommended.

Non-Invasive Evaluation of Corneal Abnormalities Using Static and Dynamic Light Scattering

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

2002-01-01

A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

Noninvasive evaluation of corneal abnormalities using static and dynamic light scattering

NASA Astrophysics Data System (ADS)

Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

2002-06-01

A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

Changes of Visual Pathway and Brain Connectivity in Glaucoma: A Systematic Review

PubMed Central

Nuzzi, Raffaele; Dallorto, Laura; Rolle, Teresa

2018-01-01

Background: Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration. Objective: In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects. Methods: We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI). Results: Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients. Conclusions: This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations. PMID:29896087

The natural history of polypoidal choroidal vasculopathy: a multi-center series of untreated Asian patients.

PubMed

Cheung, Chui Ming Gemmy; Yang, Elizabeth; Lee, Won Ki; Lee, Gary K Y; Mathur, Ranjana; Cheng, Jacob; Wong, Doric; Wong, Tien Yin; Lai, Timothy Y Y

2015-12-01

We aimed to evaluate the long-term natural history of polypoidal choroidal vasculopathy (PCV) in untreated patients. This is a retrospective observational case series. Patients with symptomatic PCV who did not receive any treatment for at least 12 months were included from the records of three ophthalmic clinics in Asia. The medical records and imaging data were reviewed. Visual outcomes at month 12 and at last follow-up were analyzed. The influence of demographics and presenting features on visual outcome was analyzed. A total of 32 eyes (32 patients) were included in this analysis. The mean follow-up was 59.9 months (range, 18-119 months), the mean age was 65.7 years and 21 (65.6 %) patients were male. The mean presenting logMAR visual acuity was 0.79 (Standard deviation [SD] 0.49). The center of the fovea was involved by the PCV complex in 25 eyes (78.1 %). The mean greatest linear dimension (GLD) of the PCV complex was 2584 μm (SD 880). Twenty-three eyes (71.9 %) had a cluster-of-grapes configuration on indocyanine green angiography. Leakage of fluorescein angiography was present in 29 eyes (90.6 %). The mean logMAR vision deteriorated from 0.79 at baseline to 0.88 at month 12 (p = 0.11), and further to 1.14 (p = 0.003) at the last follow-up. The proportion of eyes that improved, remained unchanged and worsened was 21.9 %, 31.3 % and 46.9 %, respectively, at month 12; and 28.1 %, 9.4 % and 62.5 %, respectively, at last follow-up. The proportion of eyes with logMAR vision worse than 1.0 was 28.1 % at presentation, and increased to 31.3 % at month 12 and further to 53.1 % at last follow-up. Reasons for poor vision were due to retinal, subretinal or vitreous hemorrhage, and retinal pigment epithelium (RPE) atrophy and scarring. None of the presenting features were found to significantly influence visual outcome. Half of eyes presenting with symptomatic PCV had a relatively benign course without treatment and some even had vision improvement. However, in the remaining eyes, vision deteriorated significantly, mainly due to hemorrhage and scarring. There may be subtypes of PCV with divergent natural history.

Evaluation of retinal nerve fiber layer thickness parameters in myopic population using scanning laser polarimetry (GDxVCC).

PubMed

Dada, Tanuj; Aggarwal, A; Bali, S J; Sharma, A; Shah, B M; Angmo, D; Panda, A

2013-01-01

Myopia presents a significant challenge to the ophthalmologist as myopic discs are often large, tilted, with deep cups and have a thinner neuroretinal rim all of which may mimic glaucomatous optic nerve head changes causing an error in diagnosis. To evaluate the retinal fiber layer (RNFL) thickness in low, moderate and high myopia using scanning laser polarimetry with variable corneal compensation (GDxVCC). One hundred eyes of 100 emmetropes, 30 eyes of low myopes (0 to - 4 D spherical equivalent(SE), 45 eyes with moderate myopia (- 4 to - 8D SE), and 30 eyes with high myopia (- 8 to - 15D SE) were subjected to retinal nerve fiber layer assessment using the scanning laser polarimetry (GDxVCC) in all subjects using the standard protocol. Subjects with IOP > 21 mm Hg, optic nerve head or visual field changes suggestive of glaucoma were excluded from the study. The major outcome parameters were temporal-superior-nasal-inferiortemporal (TSNIT) average, the superior and inferior average and the nerve fibre indicator (NFI). The TSNIT average (p = 0.009), superior (p = 0.001) and inferior average (p = 0.008) were significantly lower; the NFI was higher (P less than 0.001) in moderate myopes as compared to that in emmetropes. In high myopia the RNFL showed supranormal values; the TSNIT average, superior and inferior average was significantly higher(p less than 0.001) as compared to that in emmetropes. The RNFL measurements on scanning laser polarimetry are affected by the myopic refractive error. Moderate myopes show a significant thinning of the RNFL. In high myopia due to peripapillary chorioretinal atrophy and contribution of scleral birefringence, the RNFL values are abnormally high. These findings need to be taken into account while assessing and monitoring glaucoma damage in moderate to high myopes on GDxVCC. © NEPjOPH.

Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma.

PubMed

McGrady, Nolan R; Minton, Alena Z; Stankowska, Dorota L; He, Shaoqing; Jefferies, Hayden B; Krishnamoorthy, Raghu R

2017-03-01

Primary open angle glaucoma is a heterogeneous group of optic neuropathies that results in optic nerve degeneration and a loss of retinal ganglion cells (RGCs) ultimately causing blindness if allowed to progress. Elevation of intraocular pressure (IOP) is the most attributable risk factor for developing glaucoma and lowering of IOP is currently the only available therapy. However, despite lowering IOP, neurodegenerative effects persist in some patients. Hence, it would be beneficial to develop approaches to promote neuroprotection of RGCs in addition to IOP lowering therapies. The endothelin system is a key target for intervention against glaucomatous neurodegeneration. The endothelin family of peptides and receptors, particularly endothelin-1 (ET-1) and endothelin B (ET B ) receptor, has been shown to have neurodegenerative roles in glaucoma. The purpose of this study was to examine changes in endothelin A (ET A ) receptor protein expression in the retinas of adult male Brown Norway rats following IOP elevation by the Morrison's model of ocular hypertension and the impact of ET A receptor overexpression on RGC viability in vitro. IOP elevation was carried out in one eye of Brown Norway rats by injection of hypertonic saline through episcleral veins. After 2 weeks of IOP elevation, immunohistochemical analysis of retinal sections from rat eyes showed an increasing trend in immunostaining for ET A receptors in multiple retinal layers including the inner plexiform layer, ganglion cell layer and outer plexiform layer. Following 4 weeks of IOP elevation, a significant increase in immunostaining for ET A receptor expression was found in the retina, primarily in the inner plexiform layer and ganglion cells. A modest increase in staining for ET A receptors was also found in the outer plexiform layer in the retina of rats with IOP elevation. Cell culture studies showed that overexpression of ET A receptors in 661W cells as well as primary RGCs decreases cell viability, compared to empty vector transfected cells. Adeno-associated virus mediated overexpression of the ET A receptor produced an increase in the ET B receptor in primary RGCs. Elevated IOP results in an appreciable change in ET A receptor expression in the retina. Overexpression of the ET A receptor results in an overall decrease in cell viability, accompanied by an increase in ET B receptor levels, suggesting the involvement of both ET A and ET B receptors in mediating cell death. These findings raise possibilities for the development of ET A /ET B dual receptor antagonists as neuroprotective treatments for glaucomatous neuropathy.

Colocalization of outflow segmentation and pores along the inner wall of Schlemm's canal.

PubMed

Braakman, Sietse T; Read, A Thomas; Chan, Darren W-H; Ethier, C Ross; Overby, Darryl R

2015-01-01

All aqueous humor draining through the conventional outflow pathway must cross the endothelium of Schlemm's canal (SC), likely by passing through micron-sized transendothelial pores. SC pores are non-uniformly distributed along the inner wall endothelium, but it is unclear how the distribution of pores relates to the non-uniform or segmental distribution of aqueous humor outflow through the trabecular meshwork. It is hypothesized that regions in the juxtacanalicular tissue (JCT) with higher local outflow should coincide with regions of greater inner wall pore density compared to JCT regions with lower outflow. Three pairs of non-glaucomatous human donor eyes were perfused at 8 mmHg with fluorescent tracer nanospheres to decorate local patterns of outflow segmentation through the JCT. The inner wall was stained for CD31 and/or vimentin and imaged en face using confocal and scanning electron microscopy (SEM). Confocal and SEM images were spatially registered to examine the spatial relationship between inner wall pore density and tracer intensity in the underlying JCT. For each eye, tracer intensity, pore density (n) and pore diameter (D) (for both transcellular "I" and paracellular "B" pores) were measured in 4-7 regions of interest (ROIs; 50 × 150 μm each). Analysis of covariance was used to examine the relationship between tracer intensity and pore density, as well as the relationship between tracer intensity and three pore metrics (nD, nD(2) and nD(3)) that represent the local hydraulic conductivity of the outflow pathway as predicted by various hydrodynamic models. Tracer intensity in the JCT correlated positively with local pore density when considering total pores (p = 0.044) and paracellular B pores on their own (p = 0.016), but not transcellular I-pores on their own (p = 0.54). Local hydraulic conductivity as predicted by the three hydrodynamic models all showed a significant positive correlation with tracer intensity when considering total pores and B-pores (p < 0.0015 and p < 10(-4)) but not I-pores (p > 0.38). These data suggest that aqueous humor passes through micron-sized pores in the inner wall endothelium of SC. Paracellular B-pores appear to have a dominant contribution towards transendothelial filtration across the inner wall relative to transcellular I-pores. Impaired pore formation, as previously described in glaucomatous SC cells, may thereby contribute to greater outflow heterogeneity, outflow obstruction, and IOP elevation in glaucoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Colocalization of Outflow Segmentation and Pores Along the Inner Wall of Schlemm’s Canal

PubMed Central

Braakman, Sietse T.; Read, A. Thomas; Chan, Darren W.-H.; Ethier, C. Ross; Overby, Darryl R.

2014-01-01

All aqueous humor draining through the conventional outflow pathway must cross the endothelium of Schlemm’s canal (SC), likely by passing through micron-sized transendothelial pores. SC pores are non-uniformly distributed along the inner wall endothelium, but it is unclear how the distribution of pores relates to the non-uniform or segmental distribution of aqueous humor outflow through the trabecular meshwork. It is hypothesized that regions in the juxtacanalicular tissue (JCT) with higher local outflow should coincide with regions of greater inner wall pore density compared to JCT regions with lower outflow. Three pairs of non-glaucomatous human donor eyes were perfused at 8 mmHg with fluorescent tracer nanospheres to decorate local patterns of outflow segmentation through the JCT. The inner wall was stained for CD31 and/or vimentin and imaged en face using confocal and scanning electron microscopy (SEM). Confocal and SEM images were spatially registered to examine the spatial relationship between inner wall pore density and tracer intensity in the underlying JCT. For each eye, tracer intensity, pore density (n) and pore diameter (D) (for both transcellular “I” and paracellular “B” pores) were measured in 4-7 regions of interest (ROIs; 50 × 150 μm each). Analysis of covariance was used to examine the relationship between tracer intensity and pore density, as well as the relationship between tracer intensity and three pore metrics (nD, nD2 and nD3) that represent the local hydraulic conductivity of the outflow pathway as predicted by various hydrodynamic models. Tracer intensity in the JCT correlated positively with local pore density when considering total pores (p = 0.044) and paracellular B pores on their own (p = 0.016), but not transcellular I-pores on their own (p = 0.54). Local hydraulic conductivity as predicted by the three hydrodynamic models all showed a significant positive correlation with tracer intensity when considering total pores and B-pores (p < 0.0015 and p < 10−4) but not I-pores (p > 0.38). These data suggest that aqueous humor passes through micron-sized pores in the inner wall endothelium of SC. Paracellular B-pores appear to have a dominant contribution towards transendothelial filtration across the inner wall relative to transcellular I-pores. Impaired pore formation, as previously described in glaucomatous SC cells, may thereby contribute to greater outflow heterogeneity, outflow obstruction, and IOP elevation in glaucoma. PMID:25450060

Patterns of functional vision loss in glaucoma determined with archetypal analysis

PubMed Central

Elze, Tobias; Pasquale, Louis R.; Shen, Lucy Q.; Chen, Teresa C.; Wiggs, Janey L.; Bex, Peter J.

2015-01-01

Glaucoma is an optic neuropathy accompanied by vision loss which can be mapped by visual field (VF) testing revealing characteristic patterns related to the retinal nerve fibre layer anatomy. While detailed knowledge about these patterns is important to understand the anatomic and genetic aspects of glaucoma, current classification schemes are typically predominantly derived qualitatively. Here, we classify glaucomatous vision loss quantitatively by statistically learning prototypical patterns on the convex hull of the data space. In contrast to component-based approaches, this method emphasizes distinct aspects of the data and provides patterns that are easier to interpret for clinicians. Based on 13 231 reliable Humphrey VFs from a large clinical glaucoma practice, we identify an optimal solution with 17 glaucomatous vision loss prototypes which fit well with previously described qualitative patterns from a large clinical study. We illustrate relations of our patterns to retinal structure by a previously developed mathematical model. In contrast to the qualitative clinical approaches, our results can serve as a framework to quantify the various subtypes of glaucomatous visual field loss. PMID:25505132

Improving Glaucoma Detection Using Spatially Correspondent Clusters of Damage and by Combining Standard Automated Perimetry and Optical Coherence Tomography

PubMed Central

Raza, Ali S.; Zhang, Xian; De Moraes, Carlos G. V.; Reisman, Charles A.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2014-01-01

Purpose. To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed. Methods. Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores). Results. The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined structure-function metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014). Conclusions. A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function. PMID:24408977

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study.

PubMed

Goh, Rachel L Z; Kong, Yu Xiang George; McAlinden, Colm; Liu, John; Crowston, Jonathan G; Skalicky, Simon E

2018-01-01

To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups ( P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes ( R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS ( P = 0.044) and greater age ( P = 0.009) were associated with worse stationary test person scores. Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Scleral Biomechanics in the Aging Monkey Eye

PubMed Central

Girard, Michaël J. A.; Suh, J-K. Francis; Bottlang, Michael; Burgoyne, Claude F.; Downs, J. Crawford

2010-01-01

Purpose To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 ± 5.3 years) and young (1.5 ± 0.7 years) rhesus monkeys. Methods The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mmHg while the 3D displacements of the scleral surface were measured using speckle interferometry. Each scleral shell geometry was digitally reconstructed from data generated by a 3D digitizer (topography) and 20 MHz ultrasounds (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera. Results The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (p = 0.038), and tangent modulus and structural stiffness were significantly higher in old monkeys (p < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). We found no difference in the preferred collagen fiber orientation and fiber concentration factor between age groups. Conclusions Posterior sclera from old monkeys is significantly stiffer than that from young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics, and potentially contribute to age-related susceptibility to glaucomatous vision loss. PMID:19494203

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study

PubMed Central

Goh, Rachel L. Z.; McAlinden, Colm; Liu, John; Crowston, Jonathan G.; Skalicky, Simon E.

2018-01-01

Purpose To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Methods Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire – Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Results Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243–0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. Conclusions Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. Translational Relevance The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma. PMID:29372112

In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma.

PubMed

Mastropasqua, Leonardo; Agnifili, Luca; Ciancaglini, Marco; Nubile, Mario; Carpineto, Paolo; Fasanella, Vincenzo; Figus, Michele; Lazzeri, Stefano; Nardi, Marco

2010-12-01

To describe the conjunctival epithelial features seen with in vivo confocal microscopy (IVCM) after gold micro shunt (GMS) implantation in the suprachoroidal space, in patients with uncontrolled glaucoma. This was an observational case series study. Fourteen eyes of 14 consecutive glaucomatous patients with a history of multiple failed incisional surgeries followed by GMS implantation were evaluated with a digital confocal laser-scanning microscope (HRT II Rostock Cornea Module). Patients were divided into two groups: successful implantations (Group 1: eight patients, eight eyes), defined as a one-third reduction in preoperative intraocular pressure (IOP) with or without antiglaucoma medications and failed implantations (Group 2: six patients, six eyes) as a less than one-third reduction in preoperative IOP with maximal tolerated medical therapy. The examination was performed from 3 to 20 months (mean 15.4±5.4) postoperatively. Conjunctival mean microcyst density (MMD: cysts/mm(2)) and mean microcyst area (MMA: μm(2)) were the main outcome measurements. The mean postoperative IOP was statistically different between the two groups (p<0.05), with the values of 14.3±2.77 and 32.3±8.01 mm Hg in Groups 1 and 2, respectively. When comparing successful with failed implantation, the IVCM analysis showed a greater MMD (p<0.01) and MMA (p<0.01). Clinical evidence of filtering bleb was not found in any of the patients. Successful GMS implantation significantly increased conjunctival microcysts density and surface at the site of the device insertion. These findings suggest that the enhancement of the aqueous filtration across the sclera may be one of the possible outflow pathways exploited by the shunt.

Series length used during trend analysis affects sensitivity to changes in progression rate in the ocular hypertension treatment study.

PubMed

Gardiner, Stuart K; Demirel, Shaban; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Cioffi, George A; Ritch, Robert; Gordon, Mae O; Kass, Michael A

2013-02-15

Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability. Series of visual fields (mean 24 per eye) completed at 6-month intervals from participants randomized initially to observation were split into subseries before and after the initiation of treatment (the "split-point"). The mean deviation rate of change (MDR) was derived using these entire subseries, and using only the window length (W) tests nearest the split-point, for different window lengths of W tests. A generalized estimating equation model was used to detect changes in MDR occurring at the split-point. Using shortened subseries with W = 7 tests, the MDR slowed by 0.142 dB/y upon initiation of treatment (P < 0.001), and the proportion of eyes showing "rapid deterioration" (MDR <-0.5 dB/y with P < 5%) decreased from 11.8% to 6.5% (P < 0.001). Using the entire sequence, no significant change in MDR was detected (P = 0.796), and there was no change in the proportion of eyes progressing (P = 0.084). Window lengths 6 ≤ W ≤ 9 produced similar benefits. Event analysis revealed a beneficial treatment effect in this dataset. This effect was not detected by linear trend analysis applied to entire series, but was detected when using shorter subseries of length between six and nine fields. Using linear trend analysis on the entire field sequence may not be optimal for detecting and monitoring progression. Nonlinear analyses may be needed for long series of fields. (ClinicalTrials.gov number, NCT00000125.).

Diagnostic capability of scanning laser polarimetry with variable cornea compensator in Indian patients with early primary open-angle glaucoma.

PubMed

Parikh, Rajul S; Parikh, Shefali R; Kumar, Rajesh S; Prabakaran, S; Babu, J Gansesh; Thomas, Ravi

2008-07-01

To evaluate the diagnostic ability of scanning laser polarimetry (GDx variable corneal compensator [VCC]) for early glaucoma in Asian Indian eyes. Cross-sectional observational study. Two groups of patients (early glaucoma and normal) who satisfied the inclusion and exclusion criteria were included. Early glaucoma was diagnosed in presence of open angles, characteristic glaucomatous optic disc changes correlating with the visual field (VF) on automated perimetry (VF defect fulfilling at least 2 of 3 Anderson and Patella's criteria with mean deviation >or= -6 decibels). Normal subjects had visual acuity >or= 20/30 and intraocular pressure < 22 mmHg, with a normal optic disc and fields and no ocular abnormality. All patients underwent complete ophthalmic evaluation, including VF examination (24-2/30-2 Swedish interactive threshold algorithm standard program) and imaging with GDx VCC. Sensitivity, specificity, positive predictive value and negative predictive value, area under the receiving operating characteristic curve, and likelihood ratios (LRs) were calculated for various GDx VCC parameters. Seventy-four eyes (74 patients) with early glaucoma and 104 eyes (104 normal subjects) were enrolled. TSNIT Std Dev (temporal-superior-nasal-inferior-temporal standard deviation) had the best combination of sensitivity and specificity-61.3 and 95.2, respectively-followed by nerve fiber index score > 50 (sensitivity, 52.7%; specificity, 99%). Nerve fiber index score > 50 had positive and negative predictive values of 74.3% and 97.6%, respectively, for an assumed glaucoma prevalence of 5%. Nerve fiber index score > 50 had a positive LR (+LR) of 54.8 for early glaucoma. GDx VCC has moderate sensitivity, with high specificity, in the diagnosis of early glaucoma. The high +LR for the nerve fiber index score can provide valuable diagnostic information for individual patients.

Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.

PubMed

Kremmer, Stephan; Keienburg, Marcus; Anastassiou, Gerasimos; Schallenberg, Maurice; Steuhl, Klaus-Peter; Selbach, J Michael

2012-01-01

To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.

Circadian rhythm of intraocular pressure in cats.

PubMed

Del Sole, María J; Sande, Pablo H; Bernades, José M; Aba, Marcelo A; Rosenstein, Ruth E

2007-01-01

To evaluate the rhythm of intraocular pressure (IOP) in healthy domestic cats with no evidence of ocular disease and to analyze the influence of photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of cat IOP. All animals were Domestic Short-haired cats; 30 were without systemic or ocular diseases, classified as follows: 12 male intact adult cats, five intact adult female, five adult spayed female, and eight male cats; the latter were less than 1 year of age. In addition, five adult cats with uveitis and three adult cats with secondary glaucoma were included. IOP was assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks. Eight animals from the same group were then kept under constant darkness for 48 h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females, and in eight young cats, as well as in five adult cats with uveitis and three glaucomatous cats. Consistent, daily variations in IOP were observed in animals exposed to a light-dark cycle, with maximal values during the night. In cats exposed to constant darkness, maximal values of IOP were observed at subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal-nocturnal variations) persisted in intact females, spayed females, and young animals, as well as in uveitic and glaucomatous eyes. The present results indicate a daily rhythm of cat IOP, which appears to persist in constant darkness, suggesting some level of endogenous circadian control. In addition, daily variations of cat IOP seem to be independent of gender, age, or ocular diseases (particularly uveitis and glaucoma).

Short-term results of microhook ab interno trabeculotomy, a novel minimally invasive glaucoma surgery in Japanese eyes: initial case series.

PubMed

Tanito, Masaki; Sano, Ichiya; Ikeda, Yoshifumi; Fujihara, Etsuko

2017-08-01

To report the first early postoperative results and safety profile after microhook ab interno trabeculotomy (μLOT). This initial retrospective observational case series included 24 consecutive glaucomatous eyes of 17 Japanese patients (7 men, 10 women; mean age ± standard deviation, 66.7 ± 17.9 years) who underwent μLOT. The trabeculotomy extent, surgical time, perioperative complications, interventions for complications and additional glaucoma surgeries during the follow-up for more than 3 months were collected by reviewing the medical and surgical records. The intraocular pressure (IOP), numbers of antiglaucoma medications, logarithm of the minimum angle of resolution visual acuity (VA), anterior chamber (AC) flare and corneal endothelial cell density (CECD) were compared preoperatively and postoperatively. The trabecular meshwork was incised for a mean of 3.6 ± 0.5 clock hours temporally, 3.7 ± 0.5 clock hours nasally and total 7.3 ± 0.6 clock hours during the 6.2 ± 1.6-min surgery. The mean preoperative IOP of 25.9 ± 14.3 mmHg and number of antiglaucoma medication of 3.3 ± 1.0 decreased significantly (p = 0.0002 and p = 0.005, respectively) to 14.7 ± 3.6 mmHg and 2.8 ± 0.8 at the final visit at 188.6 ± 68.8 days postoperatively. Compared with preoperatively, the final VA, AC flare and CECD did not change significantly. Hyphema with niveau formation (nine eyes, 38%) and washout of hyphema (two eyes, 8%) were the most common postoperative complication and intervention, respectively. At the final visit, 19 eyes (79%) achieved successful IOP control of 18 mmHg or less and a 15% reduction or greater. Microhook trabeculotomy normalizes the IOP during the early postoperative period in patients with glaucoma. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Case control study of dry eye and related ocular surface abnormalities in Ibadan, Nigeria.

PubMed

Bekibele, C O; Baiyeroju, A M; Ajaiyeoba, A; Akang, E E U; Ajayi, B G K

2010-02-01

Tear instability is associated with symptoms of ocular discomfort and irritation. Many patients with dry eyes remain untreated due to improper diagnoses. To identify symptoms and surface abnormalities associated with dry eyes. One hundred and fifty-six eyes of 78 subjects attending the Eye Clinic of the University College Hospital Ibadan were screened for dry eyes/tear instability using rose Bengal stain (graded 0-9), tear break-up time (TBUT), Schirmer's 1 tests, tear meniscus height and a standardised symptoms questionnaire. Grades 4-9 rose Bengal staining were considered as positive dry eye and were compared with grades 0-3 staining eyes as negative controls. Mean tear meniscus height, Schirmer's test and TBUT were lower among cases than their corresponding control eyes. The difference between the mean Schirmer's test values of cases and their controls were statistically significant (P = 0.00 for right eyes and P = 0.002 for left eyes). Rose Bengal grades were inversely correlated with the mean Schirmer's values (Pearson correlation -0.429, P = 0.05 for right eyes and -0.335, P = 0.03 for left eyes) and TBUT (Pearson correlation -0.316, P = 0.05 for right eyes and -0.212, P = 0.06 for left eyes). About 95.8% of the cases were symptomatic, as opposed to 70.4% of the controls (P = 0.01, Fisher's exact test) and 95.8% of dry right eyes compared to 61.1% of their controls had ocular surface abnormalities (P = 0.001), while 89.5% of dry left eyes compared to 62.7% of controls had surface abnormalities (P = 0.07). A close relationship exists between ocular irritation symptoms, surface abnormalities and functional evidence of tear instability. Such patients should be treated empirically or screened for dry eyes.

[21st century management of glaucoma].

PubMed

Tsukahara, Shigeo

2003-12-01

According to a recent epidemiological study done in Japan, 2 or 3 million Japanese people are thought to be suffering from glaucoma, and 70-80% of them have not been examined or diagnosed by ophthalmologists. Therefore, the problem is how to find these untreated and undiagnosed people. At present, treatment of glaucoma continues to be directed at lowering intraocular pressure to prevent progression of glaucomatous optic neuropathy. However, theoretically, there are three stages in the prevention of progression of glaucoma. In the first stage, diagnosis of glaucoma can be done by genetic examination, before occurrence of glaucoma. The MYOCILIN/trabecular meshwork-inducible glucocorticoid response gene and the optineurin gene were identified as the genes that cause open angle glaucoma. Although some Japanese patients have sequence changes in the myocilin gene, there are no apparent specific mutations in Japanese glaucoma patients, in the MYOCILIN/TIGR and optineurin genes. Secondary glaucoma such as steroid glaucoma, induced by allergic diseases, and neovascular glaucoma, induced by retinal circulatory insufficiency, are preventable by improving the causal diseases, diabetes and hypertension. The education of doctors and laymen is important to reduce the occurrence of diabetes, and hypertension to prevent diabetic retinopathy, and retinal vessel occlusion. The second stage in preventing progression of glaucoma is to find the disease as early as possible. In Japan, a physical examination system is in place for everybody over 40 years old, in companies and local districts. Therefore, ocular examination, specially non-mydriatic fundus photographs should be taken in these examinations, and the film should be evaluated by an ophthalmologist, to search for retinal and optic disc abnormalities. Primary open angle glaucoma can be detected through this system in early stages. In primary angle closure glaucoma, instruments for estimating anterior chamber rapidly and accurately are necessary for the diagnosis. There is a special machine which can be handled easily, safely, and economically for detecting angle closure glaucoma, has been developed by Yamanashi University. This machine might help to reduce the number of angle closure glaucoma patients in the world. In the near future, a glaucoma network system should be put in place all over Japan. This organization consists of central headquarter and local central office. Most hospitals and private offices will belong to a local central office, and several glaucoma specialists will work in central and local offices. All glaucoma patients will be registered in local glaucoma office. The information on glaucoma patients will be communicated in the system the through light fiber cables or a satellite system. The patients can ask about their own disease through this glaucoma center system. In the third stage of glaucoma prevention, progression of glaucomatous optic neuropathy is retarded by conventional IOP lowering treatment or neuroprotective drugs. This stage compromises rehabilitation of visual function, implant of artificial visual systems, and regeneration of retinal ganglion cells(RGC). The disturbances of axonal flow in guinea pig optic nerve fibers was demonstrated electromicroscopically by quick-freeze, deep-etching method and, the decrease in numbers of motor proteins like "Kinesin" "Dynein" and "MAP-1" was shown in guinea pig eyes with elevated intraocular pressure by immunohistochemistry. Retinal glanglion cells have been isolated and new findings have been reported using this RGC culture system. Therefore, new neuroprotective drugs will be developed through this culture system.

Peripapillary and Macular Vessel Density in Glaucoma Patients with Single-Hemifield Visual Field Defect

PubMed Central

Yarmohammadi, Adeleh; Zangwill, Linda M.; Diniz-Filho, Alberto; Saunders, Luke J.; Suh, Min Hee; Wu, Zhichao; Manalastas, Patricia Isabel C.; Akagi, Tadamichi; Medeiros, Felipe A.; Weinreb, Robert N.

2017-01-01

Purpose To compare hemifield differences in the vessel density of the optic nerve head and macula in open-angle glaucoma (OAG) eyes with visual field (VF) defect confined to one hemifield using optical coherence tomography angiography (OCT-A). Design Cross-sectional study. Participants Fifty-eight eyes of 58 glaucoma patients with VF loss confined to a single hemifield, and 28 healthy eyes. Methods Retinal vasculature information was summarized as circumpapillary vessel density (cpVD) and perifoveal vessel density (pfVD). Circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thickness were also calculated using spectral domain OCT. Paired and unpaired t-tests were utilized to evaluate differences between the perimetrically affected and intact hemiretinae and healthy hemiretinae. Linear regression analyses were performed to evaluate the associations between VF measures with vascular and structural measurements. Main Outcome Measures Total and hemispheric cpVD, pfVD, cpRNFL, mGCC and mean sensitivity (MS). Results Mean cpVD and pfVD in the intact hemiretinae of OAG eyes (59.0% and 51.1%) were higher than the affected hemiretinae (54.7% and 48.3%; p<0.001) but lower than healthy eyes (62.4% and 53.8%; p<0.001). Similar results were noted with cpRNFL and mGCC thickness measurements (p<0.05 for both). The strongest associations between MS in the affected hemifields were found for cpVD (r = 0.707), followed by pfVD (r = 0.615), cpRNFL (r = 0.496) and mGCC (r = 0.482) in the corresponding hemiretinae (p<0.001 for all). Moreover the correlations in the intact hemifields between MS with cpVD and pfVD were found to be higher (r = 0.450 and 0.403) than the correlations between MS and cpRNFL and mGCC thickness measurements (r = 0.340 and 0.290; all p-values <0.05 for all). Conclusions Reduced peripapillary and macular vessel density was detectable in the perimetrically intact hemiretinae of glaucoma eyes with a single-hemifield defect. Moreover vessel density attenuation in both affected and intact hemiretinae was associated with the extent of VF damage in the corresponding hemifields. OCT-A potentially shows promise for identifying glaucomatous damage before focal VF defects are detectable. PMID:28196732

Effect of Recording Duration on the Diagnostic Performance of Multifocal Visual-evoked Potentials in High-risk Ocular Hypertension and Early Glaucoma

PubMed Central

Fortune, Brad; Zhang, Xian; Hood, Donald C.; Demirel, Shaban; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L.; Cioffi, George A.; Johnson, Chris A.

2010-01-01

Purpose To evaluate the effect on diagnostic performance of reducing multifocal visual-evoked potential (mfVEP) recording duration from 16 to 8 minutes per eye. Methods Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were studied. Two 8-minute mfVEP recordings were obtained for each eye in an ABBA order using VERIS. The first recording for each eye was compared against single run (1-Run) mfVEP normative data; the average of both recordings for each eye was compared against 2-Run normative data. Visual fields (VFs) were obtained by standard automated perimetry (SAP) within 22.3±27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph images were obtained together, within 24.8±50.4 days of the mfVEP and 33.1±62.9 days of SAP. Masked experts graded disc photographs as either glaucomatous optic neuropathy or normal. The overall Moorfields Regression Analysis result from the Heidelberg Retina Tomograph was used as a separate diagnostic classification. Thus, 4 diagnostic standards were applied in total, 2 based on optic disc structure alone and 2 others based on disc structure and SAP. Results Agreement between the 1-Run and 2-Run mfVEP was 90%. Diagnostic performance of the 1-Run mfVEP was similar to that of the 2-Run mfVEP for all 4 diagnostic standards. Sensitivity was slightly higher for the 2-Run mfVEP, whereas specificity was slightly higher for the 1-Run mfVEP. Conclusions If higher sensitivity is sought, the 2-Run mfVEP will provide better discrimination between groups of eyes with relatively high signal-to-noise ratio (eg, early glaucoma or high-risk suspects). But if higher specificity is a more important goal, the 1-Run mfVEP provides adequate sensitivity and requires only half the test time. Considered alongside prior studies, the present results suggest that the 1-Run mfVEP is an efficient way to confirm (or refute) the extent of VF loss in patients with moderate or advanced glaucoma, particularly in those with unreliable VFs, including malingering or other “functional” forms of VF loss. PMID:18414101

Bilateral Symmetry of Visual Function Loss in Cone-Rod Dystrophies.

PubMed

Galli-Resta, Lucia; Falsini, Benedetto; Rossi, Giuseppe; Piccardi, Marco; Ziccardi, Lucia; Fadda, Antonello; Minnella, Angelo; Marangoni, Dario; Placidi, Giorgio; Campagna, Francesca; Abed, Edoardo; Bertelli, Matteo; Zuntini, Monia; Resta, Giovanni

2016-07-01

To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control.

Application of adipose-derived stem cells on scleral contact lens carrier in an animal model of severe acute alkaline burn.

PubMed

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2014-07-01

To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits.

Application of Adipose-Derived Stem Cells on Scleral Contact Lens Carrier in an Animal Model of Severe Acute Alkaline Burn

PubMed Central

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2015-01-01

Purpose To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. Materials and Methods After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Results Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Conclusion Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits. PMID:24901976

An update on dry eye disease molecular treatment: advances in drug pipelines.

PubMed

Colligris, Basilio; Crooke, Almudena; Huete-Toral, Fernando; Pintor, Jesus

2014-07-01

Dry eye disease is a common disorder provoking changes in tear film and ocular surface. Untreated dry eye could cause ocular infections, corneal ulcer and blindness. Only a few drugs are authorized so far for the treatment of dry eye disease and the possibilities of evolution in this sector are immense. Consequently, a significant number of new potential solutions are under development or placed in the pharmaceutical pipeline, promising better results and lesser side effects. In this article, the corresponding literature and recent Phase III clinical trial data and the corresponding literature, for dry eye disease treatment are reviewed, revealing the new strategic movements in drug pipelines. From the clinical trial results, the advancement in tear substitutes and secretagogues in addressing specific deficiencies of tear components even though not resolving the underlying conditions of the disease is evident. The vast majority of new compounds under development are anti-inflammatories, steroids, non-steroids and antibiotics; however, there are also some novel lubricating drops and mucin-tear secretagogues. A future aggressive therapy for dry eye, depending on the severity of the symptoms, would include combinations of soft steroids, anti-inflammatories, such as cyclosporine A, with the addition of the new polyvalent mucin and tear secretagogues.

Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in rabbits

PubMed Central

Kawaguchi, Ichiro; Higashide, Tomomi; Takeji, Yasuhiro; Sakurai, Kazushi; Kawaguchi, Chiaki; Sugiyama, Kazuhisa

2017-01-01

Purpose This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops. Methods Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy. Results There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group. Conclusions Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface. PMID:29049370

Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in rabbits.

PubMed

Kawaguchi, Ichiro; Kobayashi, Akira; Higashide, Tomomi; Takeji, Yasuhiro; Sakurai, Kazushi; Kawaguchi, Chiaki; Sugiyama, Kazuhisa

2017-01-01

This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops. Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy. There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group. Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface.

[Subretinal transplantation of human fetal lung fibroblasts expressed ciliary neurotrophic factor gene prevent photoreceptor degeneration in RCS rats].

PubMed

Huang, Qian; Xu, Ping; Xia, Xin; Hu, Hong-hui; Wang, Feng; Li, Hui-ming

2006-02-01

To investigate the efficacy of subretinal transplantation of CNTF gene transfected fibroblasts for preventing photoreceptor degeneration in RCS. The human fetal lung fibroblasts with high level expression of CNTF were established by liposome mediated gene transfer and MTX selection. A 5 microl of cell suspension, containing 1 x 10(5) cells, was injected through pars plana of ciliary body into the subretinal space of the right eye at postnatal 4-5 weeks, the left eye was left without injection or injected with PBS as controls. The both eyes were enucleated for histopathological examinations at 2, 4, 6, 8, 10, 12 and 15 weeks following transplantation. The level of CNTF protein (91,046.15 pg/ml) expressed in the transfected cells was determined by sandwich enzyme-linked immunosorbent assay (ELISA). The four of seven eyes examined by light microscopy and the ten of 14 eyes examined by electro microscopy showed rescue effect. The prolonged photoreceptor survival, reduction of apoptotic cells and debris were observed in transplanted eyes in comparison with untreated or sham-injected eyes. This study provides the first indication that transplanted human fibroblasts with high level expression of CNTF are able to rescue photoreceptor degeneration in RCS dystrophic rat retina.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

PubMed

Ozyazgan, Yilmaz; Ucar, Didar; Hatemi, Gulen; Yazici, Yusuf

2015-12-01

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Eye care for patients receiving neuromuscular blocking agents or propofol during mechanical ventilation.

PubMed

Lenart, S B; Garrity, J A

2000-05-01

The presence of a corneal reflex and the ability to maintain eye closure are instrumental in protecting the cornea. Use of neuromuscular blocking agents or propofol can result in impaired eyelid closure and loss of corneal reflex, leading to corneal exposure. The cornea is then at risk for drying, infection, and scarring, which may lead to permanent visual loss. To determine whether applying artificial tear ointment to the eyes of paralyzed or heavily sedated patients receiving mechanical ventilation decreases the prevalence of exposure keratitis more than does passive closure of the eyelid. A prospective, randomized control trial was done. The sample was 50 patients in the intensive care unit receiving either neuromuscular blocking agents or propofol during mechanical ventilation. In each patient, artificial tear ointment was applied to one eye; passive closure of the eyelid was used for the other eye (control eye). Nine patients had evidence of exposure keratitis in the untreated eye, and 2 had corneal abrasions in both the treated and the control eyes. The remaining 39 patients did not have corneal abrasions in either eye. Use of the artificial tear ointment was more effective in preventing corneal exposure than was passive eyelid closure (P = .004). Eye care with a lubricating ointment on a regular, set schedule can effectively reduce the prevalence of corneal abrasions in patients who are either paralyzed or heavily sedated and thus can help prevent serious complications such as corneal ulceration, infection, and visual loss.

Regression of early diabetic macular oedema is associated with prevention of dark adaptation

PubMed Central

Arden, G B; Jyothi, S; Hogg, C H; Lee, Y F; Sivaprasad, S

2011-01-01

Hypothesis Dark-adapted rods consume oxygen at high rates and light adaptation decreases this oxygen burden and can have therapeutic effects on diabetic macular oedema (DMO). Methods Patients with mild non-proliferative diabetic retinopathy (DR) and early, untreated non-sight-threatening DMO slept for 6 months wearing masks that illuminated the eyelid of one closed eye by 505 nm light. Exclusion criteria were any concomitant eye disease, DR >ETDRS grade 35, and other systemic diseases. Primary outcome: change of OCT retinal thickness in the local region where oedema was present. Results A total of 34 out of 40 patients completed the study. Mean baseline OCT macular cube thickness was equivalent for study and fellow eyes. But study eyes had a greater mean thickness in the central subfield zone 1 (282±53 μm) vs (256±19 μm) the fellow eyes. Twenty-eight study eyes showed intraretinal cysts compared with nine in the fellow eyes. At 6 months, only 19 study eyes had cysts while cysts were seen in 20 fellow eyes. After 6 months, the worst affected ETDRS zone and the central subfield zone 1 reduced in thickness in study eyes only by 12 μm (95% CI 20 to −7, P=0.01). The secondary outcomes of change in visual acuity, achromatic contrast sensitivity, and microperimetric thresholds improved significantly in study eyes and deteriorated in fellow eyes. Conclusions Sleeping in dim light that can keep rods light adapted may reverse the changes of DMO. PMID:22020171

[Clinical evaluation of the optic disc in glaucoma].

PubMed

Greslechner, R; Spiegel, D

2016-10-01

Glaucoma is defined as a progressive neuropathy of the optic nerve, characterized by specific changes of the optic disc, parapapillary region, and retinal nerve fiber layer. Characteristic glaucomatous changes of the optic disc, parapapillary region, and retinal nerve fiber layer are discussed and their ophthalmoscopic examination is described. A literature search in the PubMed database was conducted. A systematic step-by-step approach to a qualitative and quantitative ophthalmoscopic evaluation of the optic disc regarding glaucomatous damage is presented. A systematic, clinical, qualitative, and quantitative assessment of the optic disc can be performed with little effort and forms the basis for diagnosis and treatment of glaucoma.

Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.

PubMed

Xue, Kang; Liu, Ailin; Hui, Ren; Zhang, Jing; Qian, Jiang

2017-10-01

To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma. 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy. When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters. Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma.

PubMed

Honjo, Megumi; Tanihara, Hidenobu

2018-03-01

Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum of fundamental cellular events, including cell adhesion, motility, proliferation, differentiation, and apoptosis. Previous studies, including our own, found that ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the conventional AH outflow pathway, by regulation of contractile properties, fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently, a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma patients. To date, ripasudil, administered together with other glaucoma medications, has proved safe and efficient in lowering IOP as well as additional effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors, all of which help lower IOP by different mechanisms. In addition, we found that long-term treatment with ripasudil exerted an additional IOP-lowering effect, especially in eyes with high IOP, suggesting that late-onset remodeling of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP levels. ROCK inhibitors have also shown several additional effects, including increased retinal blood flow, direct protection of neurons against various types of stress, and regulation of wound healing; these benefits may potentially be useful in glaucoma treatment.

Combined use of Doppler OCT and en face OCT functions for discrimination of an aneurysm in the lamina cribrosa from a disc hemorrhage.

PubMed

Holló, Gábor

2015-12-01

In addition to retinal nerve fiber layer thickness measurements, the recently introduced AngioVue optical coherence tomography (OCT) offers corresponding layer-by-layer Doppler OCT and en face OCT functions, for simultaneous evaluation of perfusion and structure of the optic nerve head. We investigated the clinical usefulness of combined use of Doppler and en face Fourier-domain OCT functions of the AngioVue Fourier-domain OCT for discrimination of a disc hemorrhage and a disc hemorrhage-like atypical vessel structure located deep in the lamina cribrosa. We present our findings with AngioVue OCT on a disc hemorrhage and a spatially related retinal nerve fiber layer bundle defect in a glaucomatous eye (case 1). Both alterations were detected on en face OCT images without any Doppler OCT signal. We also report on an aneurysm suggestive for a disc hemorrhage on clinical examination and disc photography in a treated ocular hypertensive eye (case 2). The aneurysm was within the lamina cribrosa tissue at the border of the cup and the neuroretinal rim. This vascular structure produced strong Doppler signals but no structurally detectable signs on the en face OCT images. Combined evaluation of corresponding Doppler OCT and en face OCT images enables ophthalmologists to easily separate true disc hemorrhages from disc hemorrhage-like deep vascular structures. This is of clinical significance in preventing unnecessary intensification of pressure-lowering treatment in glaucoma.

Glaucoma in high myopia and parapapillary delta zone

PubMed Central

Weber, Pascal; Nagaoka, Natsuko; Ohno-Matsui, Kyoko

2017-01-01

Purpose To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. Methods The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. Results The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13–89 years) and mean axial length of 29.5±2.2 mm (range:23.2–35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of <26.5mm to 28.5% (24.4, 32.5) in eyes with an axial length of ≥26.5mm, to 32.6% (27.9, 37.2) in eyes with an axial length of ≥28mm, to 36.0% (30.5, 41.4) in eyes with an axial length of ≥29mm, and GON prevalence increased to 42.1% (35.5, 48.8) in eyes with an axial length of ≥30mm. In multivariate analysis, higher GON prevalence was associated (Nagelkerke r2: 0.28) with larger parapapillary delta zone diameter (P<0.001; odds ratio (OR):1.86;95%CI:1.33,2.61), longer axial length (P<0.001;OR:1.45;95%CI:1.26,1.67) and older age (P = 0.01;OR:1.03;95%CI:1.01,1.05). If parapapillary delta zone width was replaced by the vertical disc diameter, higher GON prevalence was associated (r2:0.24) with larger vertical optic disc diameter (P = 0.04;OR:1.70;95%CI:1.03,2.81), after adjusting for longer axial length (P<0.001;OR:1.44;95%CI:1.26,1.64) and older age (P<0.001;OR:1.04;95%CI:1.02,1.06). Conclusions Axial elongation associated increase in GON prevalence (mean: 28.1% in a medium to highly myopic study population) was associated with parapapillary delta zone as surrogate for an elongated peripapillary scleral flange and with larger optic disc size. PMID:28380081

24-h Efficacy of Glaucoma Treatment Options.

PubMed

Konstas, Anastasios G P; Quaranta, Luciano; Bozkurt, Banu; Katsanos, Andreas; Garcia-Feijoo, Julian; Rossetti, Luca; Shaarawy, Tarek; Pfeiffer, Norbert; Miglior, Stefano

2016-04-01

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.

Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-γ-Treated Mesenchymal Stromal Cells

PubMed Central

Javorkova, Eliska; Trosan, Peter; Zajicova, Alena; Krulova, Magdalena; Hajkova, Michaela

2014-01-01

The aim of this study was to investigate the effects of systemically administered bone-marrow-derived mesenchymal stromal cells (MSCs) on the early acute phase of inflammation in the alkali-burned eye. Mice with damaged eyes were either untreated or treated 24 h after the injury with an intravenous administration of fluorescent-dye-labeled MSCs that were unstimulated or pretreated with interleukin-1α (IL-1α), transforming growth factor-β (TGF-β), or interferon-γ (IFN-γ). Analysis of cell suspensions prepared from the eyes of treated mice on day 3 after the alkali burn revealed that MSCs specifically migrated to the damaged eye and that the number of labeled MSCs was more than 30-times higher in damaged eyes compared with control eyes. The study of the composition of the leukocyte populations within the damaged eyes showed that all types of tested MSCs slightly decreased the number of infiltrating lymphoid and myeloid cells, but only MSCs pretreated with IFN-γ significantly decreased the percentage of eye-infiltrating cells with a more profound effect on myeloid cells. Determining cytokine and NO production in the damaged eyes confirmed that the most effective immunomodulation was achieved with MSCs pretreated with IFN-γ, which significantly decreased the levels of the proinflammatory molecules IL-1α, IL-6, and NO. Taken together, the results show that systemically administered MSCs specifically migrate to the damaged eye and that IFN-γ-pretreated MSCs are superior in inhibiting the acute phase of inflammation, decreasing leukocyte infiltration, and attenuating the early inflammatory environment. PMID:24849741

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion.

PubMed

Asbell, Penny A

2006-11-01

Dry eye syndrome is a highly prevalent, yet largely under diagnosed, condition that can substantially affect quality of life. Left untreated, dry eye is associated with chronic eye pain and increased risk of ocular surface disease. Current demographic changes and lifestyle factors indicate that the dry eye syndrome patient population will increase significantly, ensuring that general practitioners and ophthalmic clinicians alike will experience more patients presenting with dry eye symptoms. Greater public and practitioner awareness of emerging research, technologies, and therapies is crucial to ensuring appropriate interventions to meet specific patient needs and result in clinically favorable outcomes. In August 2005, a team of ocular surface experts convened for a 1-day roundtable session to discuss the latest information on diagnosing and treating dry eye syndrome and real-world issues in artificial tear therapy, including preservative use. The discussion centered on the mild to moderate dry eye patient and critical features of the ideal artificial tear, which are preservative-free formulation, protection from microbial contamination, cost-effective, non-blurring, and easy to use. Products that match this profile have the advantage of being able to benefit the myriad of patients who comprise the dry eye syndrome population. Ocular surface health should always remain a top priority. Preferred Practice Pattern Dry Eye Syndrome Medical Treatment guidelines should be modified to recommend the use of preservative-free formula artificial tear products for all levels of dry eye conditions in consideration of the medical benefit they offer to dry eye syndrome sufferers. The growing prevalence of dry eye syndrome demands increased attention. Further research, enhanced diagnostic tests, increased use of preservative-free artificial tear formulations as first-line therapy, greater patient-practitioner interaction, and patient education are warranted.

[Uveitic Secondary Glaucoma].

PubMed

Lommatzsch, Claudia; Heinz, Carsten

2018-05-01

An intraocular pressure increase with development of glaucomatous damage is a common complication of uveitis. The prevalence has a wide range depending on various factors such as the underlying uveitis type and the duration of the disease. Pathogenetically, a distinction must be made between a secondary angle closure component and the more frequently occurring open-angle glaucoma. In diagnostics, in addition to the clinical optic nerve head assessment, perimetry and tonometry, the use of imaging examination equipment, such as OCT and HRT, are recommended. In the context of uveitic glaucoma, it must be considered in the evaluation, because the glaucoma-typical changes are generally less pronounced or can be concealed by retinal swelling in comparison with other forms of glaucoma. Therapeutically, drug therapy in the form of eye drops continues to be a first-line recommendation, with the use of topical carbonic anhydrase inhibitors or beta-blockers primarily preferred, depending on the contraindications. An operative therapy follows after unsuccessful or inadequate conservative therapy: the adequate surgical technique depends on the respective finding and includes actually techniques such as filtering procedures and glaucoma drainage devices. Georg Thieme Verlag KG Stuttgart · New York.

Thoughts on treatment of strawberry naevi.

PubMed Central

Illingworth, R S

1976-01-01

Published reports on the treatment of large strawberry naevi have been reviewed. It is suggested that they should normally be left untreated, and that corticosteroids, given for a short period only, should be reserved for massive naevi close to the eye, or interfering with respiration or suckling, or associated with thrombocytopenia. Serial colour photographs of one child illustrate the good result of inactivity. Images p139-a PMID:769700

Effects of lenses with different power profiles on eye shape in chickens.

PubMed

Tepelus, Tudor Cosmin; Vazquez, Daniel; Seidemann, Anne; Uttenweiler, Dietmar; Schaeffel, Frank

2012-02-01

Defocus imposed to the periphery of the visual field can affect the development of foveal/central refractive errors. To make use of this observation, lenses can be designed to reduce myopia progression, but it is important to know which power profiles of the lenses are most effective. We have studied this question in chickens. Sixty male white leghorn chickens were used. From day 7 after hatching, they were treated for 5 days either with full field -7D or +7D lenses, with -7D lenses with a 4mm central hole, with hemi-field lenses of the same power, or with two different types of radial refractive gradient (RRG) lenses with increasing positive power from the center to the periphery, which were designed by Rodenstock GmbH, Munich, Germany. A macro file was written for "ImageJ" to trace and average the outlines of several excised eyes after treatment. Shapes of fellow control eyes and lens-treated eyes were compared in the horizontal and vertical meridians. Refractions were determined at -45°, 0°, and 45° over the horizontal visual field, at the beginning and at the end of experiments, using automated infrared photoretinoscopy. (1) Eye length, as determined by the new automated eye shape tracing technique, was well correlated with A-scan ultrasound data. (2) The effects of previously tested lens designs were reproduced with the new tracing technique. Full field lenses were by far the most effective (-7D: external axial length +0.24mm with an increase in eye volume of about 6%, +7D: -0.08 mm, with a decrease in eye volume of about 2%). Hemi-field lenses and negative lenses with a 4mm central hole induced conspicuous local changes in eye shape. (3) The first type of RRG lenses with a plano zone of about 4mm (equivalent to about ± 12.52° in the visual field for a vertex distance of 5mm) had no apparent effect on central refractions but induced small hyperopic shifts in the periphery, more significant in the temporal retina (+1.70 ± 1.70 D, p<0.001, paired t-test to untreated fellow eyes). The second type of RRG lenses with a small plano zone of 2mm (equivalent to ± 6.34°) induced peripheral hyperopia but also changed the central refraction (temporal retina +1.50 ± 1.17D, p<0.001, central retina +0.77 ± 1.15 D, p<0.01, nasal retina +1.47±1.35D, p<0.001, paired t-test to untreated control eyes). In the afoveate chick, RRG lenses have an effect on central refraction and eye growth only if the central plano zone is small (<4mm). For the second type of RRG lens with a central plano zone of about 2mm, inhibitory effects on eye growth were detected in both the center and periphery even though the optical power of the lenses in the periphery was low. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study.

PubMed

Lass, Jonathan H; Benetz, Beth Ann; Menegay, Harry J; Tsipis, Constantinos P; Cook, Jane Caty; Boyer, David S; Singer, Michael; Erickson, Kristine; Saroj, Namrata; Vitti, Robert; Chu, Karen W; Moini, Hadi; Soo, Yuhwen; Cheng, Yenchieh

2018-05-01

The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration. RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52. No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96). Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.

Protective Effects of Trehalose on the Corneal Epithelial Cells

PubMed Central

Aragona, Pasquale; Colosi, Pietro; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls. PMID:25045743

Protective effects of trehalose on the corneal epithelial cells.

PubMed

Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

The idiopathic intracranial hypertension treatment trial: clinical profile at baseline.

PubMed

Wall, Michael; Kupersmith, Mark J; Kieburtz, Karl D; Corbett, James J; Feldon, Steven E; Friedman, Deborah I; Katz, David M; Keltner, John L; Schron, Eleanor B; McDermott, Michael P

2014-06-01

To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between -2 dB and -7 dB. All but 4 participants were women. Baseline and laboratory characteristics. The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was -3.5 (1.1) dB, (range, -2.0 to -6.4 dB) and in the best eye was -2.3 (1.1) dB (range, -5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire-25 and the Short Form-36 physical and mental health summary scales, were lower compared with population norms. The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection. clinicaltrials.gov Identifier: NCT01003639.

The Rationalization of Unethical Research: Revisionist Accounts of the Tuskegee Syphilis Study and the New Zealand "Unfortunate Experiment".

PubMed

Paul, Charlotte; Brookes, Barbara

2015-10-01

Two studies, widely condemned in the 1970s and 1980s-the Tuskegee study of men with untreated syphilis and the New Zealand study of women with untreated carcinoma in situ of the cervix-received new defenses in the 21st century. We noted remarkable similarities in both the studies and their defenses. Here we evaluate the scientific, political, and moral claims of the defenders. The scientific claims are largely based on incomplete or misinterpreted evidence and exaggeration of the uncertainties of science. The defenders' political arguments mistakenly claim that identity politics clouded the original critiques; in fact such politics opened the eyes of the public to exploitation. The moral defenses demonstrate an overreliance on codes of conduct and have implications for research ethics today.

Protein Disulfide Levels and Lens Elasticity Modulation: Applications for Presbyopia

PubMed Central

Garner, William H.; Garner, Margaret H.

2016-01-01

Purpose The purpose of the experiments described here was to determine the effects of lipoic acid (LA)-dependent disulfide reduction on mouse lens elasticity, to synthesize the choline ester of LA (LACE), and to characterize the effects of topical ocular doses of LACE on mouse lens elasticity. Methods Eight-month-old mouse lenses (C57BL/6J) were incubated for 12 hours in medium supplemented with selected levels (0–500 μM) of LA. Lens elasticity was measured using the coverslip method. After the elasticity measurements, P-SH and PSSP levels were determined in homogenates by differential alkylation before and after alkylation. Choline ester of LA was synthesized and characterized by mass spectrometry and HPLC. Eight-month-old C57BL/6J mice were treated with 2.5 μL of a formulation of 5% LACE three times per day at 8-hour intervals in the right eye (OD) for 5 weeks. After the final treatment, lenses were removed and placed in a cuvette containing buffer. Elasticity was determined with a computer-controlled instrument that provided Z-stage upward movements in 1-μm increments with concomitant force measurements with a Harvard Apparatus F10 isometric force transducer. The elasticity of lenses from 8-week-old C57BL/6J mice was determined for comparison. Results Lipoic acid treatment led to a concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity. The structure and purity of newly synthesized LACE was confirmed. Aqueous humor concentrations of LA were higher in eyes of mice following topical ocular treatment with LACE than in mice following topical ocular treatment with LA. The lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes (i.e., the relative force required for similar Z displacements was higher in the lenses of untreated eyes). In most instances, the lenses of the treated eyes were even more elastic than the lenses of the 8-week-old mice. Conclusions As the elasticity of the human lens decreases with age, humans lose the ability to accommodate. The results, briefly described in this abstract, suggest a topical ocular treatment to increase lens elasticity through reduction of disulfides to restore accommodative amplitude. PMID:27233034

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

PubMed Central

Ban, Norimitsu; Siegfried, Carla J.; Lin, Jonathan B.; Shui, Ying-Bo; Sein, Julia; Pita-Thomas, Wolfgang; Sene, Abdoulaye; Santeford, Andrea; Gordon, Mae; Lamb, Rachel; Dong, Zhenyu; Kelly, Shannon C.; Cavalli, Valeria; Yoshino, Jun

2017-01-01

Glaucoma is the second leading cause of blindness worldwide. Physicians often use surrogate endpoints to monitor the progression of glaucomatous neurodegeneration. These approaches are limited in their ability to quantify disease severity and progression due to inherent subjectivity, unreliability, and limitations of normative databases. Therefore, there is a critical need to identify specific molecular markers that predict or measure glaucomatous neurodegeneration. Here, we demonstrate that growth differentiation factor 15 (GDF15) is associated with retinal ganglion cell death. Gdf15 expression in the retina is specifically increased after acute injury to retinal ganglion cell axons and in a murine chronic glaucoma model. We also demonstrate that the ganglion cell layer may be one of the sources of secreted GDF15 and that GDF15 diffuses to and can be detected in aqueous humor (AH). In validating these findings in human patients with glaucoma, we find not only that GDF15 is increased in AH of patients with primary open angle glaucoma (POAG), but also that elevated GDF15 levels are significantly associated with worse functional outcomes in glaucoma patients, as measured by visual field testing. Thus, GDF15 maybe a reliable metric of glaucomatous neurodegeneration, although further prospective validation studies will be necessary to determine if GDF15 can be used in clinical practice. PMID:28469085

Comparing multifocal VEP and standard automated perimetry in high-risk ocular hypertension and early glaucoma.

PubMed

Fortune, Brad; Demirel, Shaban; Zhang, Xian; Hood, Donald C; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L; Cioffi, George A; Johnson, Chris A

2007-03-01

To compare the diagnostic performance of multifocal visual evoked potential (mfVEP) and standard automated perimetry (SAP), in eyes with high-risk ocular hypertension or early glaucoma. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were evaluated. Subjects ranged in age from 37 to 87 (mean +/- SD: 61 +/- 11 years). Pattern-reversal mfVEPs were obtained by using VERIS (Electro-Diagnostic Imaging, San Mateo, CA) with a four-electrode array and were analyzed with custom software. SAP visual fields (SITA-standard; Carl Zeiss Meditec, Inc., Dublin, CA) were obtained within 22.3 +/- 27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph (HRT) images were obtained during one visit, which was within 24.8 +/- 50.4 days of the mfVEP and 33.1 +/- 62.9 days of the SAP visual field. Abnormalities on the mfVEP were defined by using a variety of cluster criteria: SAP with pattern standard deviation (PSD) P

Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma.

PubMed

Kim, Ko Eun; Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2015-03-01

To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. Prospective, cross-sectional study. A total of 104 healthy eyes of 104 normal participants. All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

PubMed Central

Dang, Yalong; Waxman, Susannah; Wang, Chao; Jensen, Adrianna; Loewen, Ralitsa T.; Bilonick, Richard A.

2017-01-01

Objective The trabecular meshwork (TM) is the primary substrate of outflow resistance in glaucomatous eyes. Repopulating diseased TM with fresh, functional TM cells might be a viable therapeutic approach. Decellularized TM scaffolds have previously been produced by ablating cells with suicide gene therapy or saponin, which risks incomplete cell removal or dissolution of the extracellular matrix, respectively. We hypothesized that improved trabecular meshwork cell ablation would result from freeze-thaw cycles compared to chemical treatment. Materials and Methods We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion within two hours of sacrifice. Intraocular pressure (IOP) was recorded continuously by a pressure transducer system. After 72 h of IOP stabilization, eight eyes were assigned to freeze-thaw (F) ablation (−80 °C × 2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The TM was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture media for 180 h. TM histology was assessed by hematoxylin and eosin staining. TM viability was evaluated by a calcein AM/propidium iodide (PI) assay. The TM extracellular matrix was stained with Picro Sirius Red. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with five degrees of freedom. Results F and S experienced a similar IOP reduction of 30% from baseline (P = 0.64). IOP reduction of about 30% occurred in F within 24 h and in S within 48 h. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis and Picro Sirius staining confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low PI and no calcein staining in F in contrast to many PI-labeled, dead TM cells and calcein-labeled viable TM cells in S. Conclusion We developed a rapid TM ablation method that uses cyclic freezing that is free of biological or chemical agents and able to produce a decellularized TM scaffold with preserved TM extracellular matrix in an organotypic perfusion culture. PMID:28828244

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

PubMed

Shin, Hye-Young; Park, Hae-Young Lopilly; Jung, Kyoung-In; Choi, Jin-A; Park, Chan Kee

2014-01-01

To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. Retrospective, observational study. Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. Comparison of diagnostic ability using AUCs. The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis.

PubMed

Mello-Bosnic, Claudia; Gimenes, Alexandre Dantas; Oliani, Sonia Maria; Gil, Cristiane Damas

2018-05-31

Galectin-1 (Gal-1) is a β-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100 mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3 μg/eye) or sodium cromoglycate (SCG; 40 mg/ml) in both eyes and, after 15 min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3 μg) and SCG. As expected, an increased proportion of degranulated mast cells (62%, P < 0.01) and lower histamine levels were observed after 6 h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3 μg) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population.

PubMed

Micera, Alessandra; Quaranta, Luciano; Esposito, Graziana; Floriani, Irene; Pocobelli, Augusto; Saccà, Sergio Claudio; Riva, Ivano; Manni, Gianluca; Oddone, Francesco

2016-02-01

Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis. TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies. A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes. The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates. This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the "National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation".

[Studies on glial isomerization of lamina cribrosa in rat].

PubMed

Dai, Chao; Li, Da-qing; Li, Ying; Raisman, Geoffrey; Yin, Zheng-qin

2013-08-01

To explore the mechanism of optic nerve damage in glaucoma by study on structure of glial lamina cribrosa(LC) in rats. Experimental study. Albino Swiss(AS) rats were divided into 3 groups. Bilateral eyes of 10 normal rats were employed to be group I (right eye ) and group II (left eye) . Group III was from the left eyes of 13 rats underwent artificially intraocular hypertension in the right eyes. All rats were perfused and fixed with electronic microscopy fixative (2% paraformaldehyde +2% glutaraldehyde). Trimmed optic nerves were embedded with resin. Serial 1.5 µm thick 'semithin' sections were cut, either (2 eyes from group III) longitudinally, through the optic nerve head (ONH) from the retinal end to the commencement of the optic nerve, or (31 eyes) transversely (cross-sections). Ultrathin sections were cut in the middle of glial LC. The morphological observation of glial LC was obtained by light microscopy and transmission electron microscopy. Bonferroni correction was used to counteract the multiple comparison of each group. Fortified astrocytes formed the main supportive structure of glial LC in all rats, including group I, group II and group III. Astrocytes were ranked as a fan-like radial array, firmly attached ventrally to the sheath of the LC by thick basal processes, but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath. These fortified astrocytes form ventral stout basal end feet, radial array, axon free-'preterminal' layer before terminating in a complex layer of fine interdigitating delicate branches at the dorsal. LC astrocytes were highly and uniformly electron dense throughout all the cell processes. An equally striking feature of the astrocytic processes was their massive cytoskeletal 'strengthening' of longitudinal massed filaments and tubules. Especially, massive filaments accumulated as cytoskeletal cores to form 'scaffold' of fortified astrocytes. There was vulnerable area in the dorsal of glial LC. This vulnerable area was isomerisation in bilateral eyes and different rats. There was different space in the vulnerable area. These space could be divided into 3 grades, (-), (+) and (++) . The number of (-), (+) and (++)were 1, 6, 3 eyes in group I, 1, 5, 4 eyes in group II, 1, 7, 3 eyes in group III. The Kruskal-Wallis test was used for statistical evaluations. There was no statistical differences of the ratio of (-), (+) and (++) in group I, group II and group III(χ(2) = 3.35, P = 0.187>0.05;group I vs group II, Z = -1.048, P = 0.294;group I vs group III Z = -1.691, P = 0.091;group II vs group III,Z = -1.343, P = 0.179). The ratio of space (-)was significantly less than space (+) and space (++) in group I, group II and group III(χ(2) = 23.88, P < 0.05; (-) vs (+) , Z = -2.821, P = 0.005; (-) vs (++) , Z = -2.726, P = 0.006). The ratio of space (+)was much more than space (++) in group I, group II and group III(Z = -4.410, P < 0.05). Glial isomerisation in LC may play a key role in glaucomatous optic nerve damage.

Efficacy of the Amsler Grid Test in Evaluating Glaucomatous Central Visual Field Defects.

PubMed

Su, Daniel; Greenberg, Andrew; Simonson, Joseph L; Teng, Christopher C; Liebmann, Jeffrey M; Ritch, Robert; Park, Sung Chul

2016-04-01

To investigate the efficacy of the Amsler grid test in detecting central visual field (VF) defects in glaucoma. Prospective, cross-sectional study. Patients with glaucoma with reliable Humphrey 10-2 Swedish Interactive Threshold Algorithm standard VF on the date of enrollment or within the previous 3 months. Amsler grid tests were performed for each eye and were considered "abnormal" if there was any perceived scotoma with missing or blurry grid lines within the central 10 degrees ("Amsler grid scotoma"). An abnormal 10-2 VF was defined as ≥3 adjacent points at P < 0.01 with at least 1 point at P < 0.005 in the same hemifield on the pattern deviation plot. Sensitivity, specificity, and positive and negative predictive values of the Amsler grid scotoma area were calculated with the 10-2 VF as the clinical reference standard. Among eyes with an abnormal 10-2 VF, regression analyses were performed between the Amsler grid scotoma area and the 10-2 VF parameters (mean deviation [MD], scotoma extent [number of test points with P < 0.01 in total deviation map] and scotoma mean depth [mean sensitivity of test points with P < 0.01 in total deviation map]). Sensitivity, specificity, and positive and negative predictive values of the Amsler grid scotoma area. A total of 106 eyes (53 patients) were included (mean ± standard deviation age, 24-2 MD and 10-2 MD = 66±12 years, -9.61±8.64 decibels [dB] and -9.75±9.00 dB, respectively). Sensitivity, specificity, and positive and negative predictive values of the Amsler grid test were 68%, 92%, 97%, and 46%, respectively. Sensitivity was 40% in eyes with 10-2 MD better than -6 dB, 58% in eyes with 10-2 MD between -12 and -6 dB, and 92% in eyes with 10-2 MD worse than -12 dB. The area under the receiver operating characteristic curve of the Amsler grid scotoma area was 0.810 (95% confidence interval, 0.723-0.880, P < 0.001). The Amsler grid scotoma area had the strongest relationship with 10-2 MD (quadratic R(2)=0.681), followed by 10-2 scotoma extent (quadratic R(2)=0.611) and 10-2 scotoma mean depth (quadratic R(2)=0.299) (all P < 0.001). The Amsler grid can be used to screen for moderate to severe central vision loss from glaucoma. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

PubMed

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

2016-07-01

Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma treatment. For the first time, this study demonstrated that the biodegradable in situ gelling copolymers can incorporate different levels of antioxidant gallic acid to tailor the structure-property-function relationship of the intracameral drug delivery system. The systematic evaluation fully verified the dependence of phase transition, degradation behavior, drug release mechanism, and antiglaucoma efficacy on intrinsic antioxidant capacities of carrier biomaterials. The report highlights the significant role of grafting amount of gallic acid in optimizing performance of antioxidant-functionalized polymer therapeutics as new drug delivery platforms in disease treatment. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Predictors of intraocular pressure change after phacoemulsification in patients with pseudoexfoliation syndrome.

PubMed

Moghimi, Sasan; Johari, Mohammadkarim; Mahmoudi, Alireza; Chen, Rebecca; Mazloumi, Mehdi; He, Mingguang; Lin, Shan C

2017-03-01

To evaluate anterior chamber biometric factors and intraoperative metrics associated with the intraocular pressure (IOP) reduction after phacoemulsification in non-glaucomatous pseudoexfoliative syndrome (PXS) eyes. Thirty-three patients were enrolled in this prospective interventional study. Images were excluded if they had poor quality, poor perpendicularity or inability to locate sclera spurs. Anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness, iris area, iris curvature, lens vault, angle opening distance (AOD500, AOD750) and trabecular iris space area (TISA500, TISA750) were measured in qualified images using the Zhongshan Angle Assessment Program and compared preoperatively and 3 months postoperatively. Cumulative dissipated energy (CDE), aspiration time and infusion fluid usage during cataract surgery were obtained from the phacoemulsification machine's metrics record. Postoperative IOP change was compared with these anatomical and intraoperative metric parameters. Mean IOP was 18.1±3.4 mm Hg preoperatively and decreased by 3.3 mm Hg (18%) to 14.8±3.6 mm Hg at 3 months postoperatively (p<0.001). All angle parameters, ACD and ACA increased significantly postoperatively (p<0.001 for all) and iris curvature decreased (p<0.001). In univariate analysis, preoperative IOP (B=-0.668, p=0.002), infusion fluid usage (B=-0.040, p=0.04) and aspiration time (B=-0.045, p=0.003) were negatively associated with IOP decrease after phacoemulsification. Changes in IOP did not demonstrate significant associations with CDE measurements or anterior segment optical coherence tomography measurements, including preoperative angle, iris or anterior segment parameters. In the final multivariate regression model, preoperative IOP (B=-0.668, p=0.002) and infusion fluid usage (B=-0.041, p=0.04) were significantly associated with IOP drop and together can predict 45.1% (p=0.002) of the variability in IOP change. Non-glaucomatous patients with PXS experience moderate IOP reduction following phacoemulsification, and this effect is correlated with preoperative IOP, aspiration time and infusion fluid used intraoperatively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Glaucomatous Visual Field Loss Associated with Less Travel from Home

PubMed Central

Ramulu, Pradeep Y.; Hochberg, Chad; Maul, Eugenio A.; Chan, Emilie S.; Ferrucci, Luigi; Friedman, David S.

2014-01-01

Purpose To determine the association between glaucoma and travel away from home. Methods Fifty-nine glaucoma suspect controls with normal vision and 80 glaucoma subjects with bilateral visual field (VF) loss wore a cellular tracking device over 1 week of normal activity. Location data was used to evaluate the number of daily excursions away from home as well as daily time spent away from home. Results Control and glaucoma subjects were similar in age, race, gender, employment, driving support, cognitive ability, mood, and comorbid illness (p>0.1 for all). Better-eye VF mean deviation (MD) averaged 0.0 decibels (dB) in controls and –11.1 dB in glaucoma subjects. In multivariable models, glaucoma was associated with fewer daily excursions (β= -0.20; 95% CI=-0.38 to -0.02) and a greater likelihood of not leaving home on a given day (Odds ratio [OR]=1.82; 95% CI=1.05 to 3.06). Each 5 dB decrement in the better-eye VF MD was associated with fewer daily excursions (β= -0.06; 95% CI=-0.11 to -0.01) and a greater chance of not leaving home on a given day (OR=1.24; 95% CI=1.04 to 1.47). Time spent away from home did not significantly differ between the glaucoma subjects and suspects (p=0.18). However, each 5 dB decrement in the better-eye MD was associated with 6% less time away (95% CI=-12 to -1%). Conclusions Individuals with glaucoma, particularly those with greater VF loss, are more home-bound and travel away from home less than individuals with normal vision. Since being confined to the home environment may have detrimental effects on fitness and health, individuals with glaucoma should be considered for interventions such as orientation and mobility training to encourage safe travel away from home. PMID:24374635

Effects of silicone hydrogel contact lenses on ocular surface after Sub-Bowman's Keratomileusis.

PubMed

Gao, Shaohui; Wu, Junshu; Li, Lili; Wang, Yong; Zhong, Xingwu

2013-11-01

To evaluate the efficacy of silicone hydrogel contact lenses on ocular surface after Sub-Bowman Keratomileusis (SBK). Forty-six patients suffered from myopia underwent a bilateral SBK. Post-operatively, one eye of each patient wore a PureVision contact lens for 24 h as a treated eye and the contralateral eye was as a blank control. Afterwards, corneal fluorescein (FL) staining, tear break-up time (TBUT), schirmer I test (SIT), central corneal thickness (CCT), ocular surface disease index (OSDI), corneal hysteresis (CH), corneal resistance factor (CRF) and corneal flap complications were assessed 1 d (except for CH and CRF), 1 week, 1 month and 3 months postoperatively. Following SBK, in contrast to the control, corneal fluorescein staining of treated eyes were significantly reduced and tear break-up time of treated eyes were significantly improved at 1 d and 1 week after SBK. However, Schirmer I test of treated and control eyes were not different after SBK. Central corneal thickness of treated eyes were significantly thinner than that of control at 1 d after SBK, however, there were no differences at other time points. Ocular surface disease index of treated eyes were obviously alleviated more than that of control at 1 d after SBK, but no differences were found at other visits. Moreover, Corneal hysteresis and corneal resistance factor of treated and un-treated eyes were not different after surgery. And also the rate of corneal flap complications were not different between treated and control eyes after SBK. Silicone hydrogel contact lenses played a positive role in accelerating corneal epithelial healing, enhancing tear film stability and reducing discomfort of patients in the early stage after SBK.

Effectiveness and Cost of a Personalized Reminder Intervention to Improve Adherence to Glaucoma Care.

PubMed

Pizzi, Laura T; Tran, Judie; Shafa, Anousheh; Waisbourd, Michael; Hark, Lisa; Murchison, Ann P; Dai, Yang; Mayro, Eileen L; Haller, Julia A

2016-04-01

Glaucoma is the leadi ng cause of irreversible blindness in the USA. Glaucomatous vision loss is preventable with proper eye care, including appointment adherence. Therefore, interventions that improve appointment adherence can reduce the number of patients with more severe glaucoma. The primary study aim was to determine the efficacy and cost-effectiveness of a multifaceted personal reminder intervention, which included a customized letter and personal telephone outreach, in improving appointment adherence of patients with glaucoma. A secondary study aim was to identify patient characteristics that were associated with non-adherence. This prospective, randomized, controlled study included a cost-effectiveness analysis completed using a decision analytic model. The subjects included 256 patients with glaucoma. Study measures included appointment adherence and incremental cost effectiveness ratios. Patients in the intervention group were more likely to adhere to appointments (82.31 vs. 69.05 %; RR 1.23; 95 % CI 1.04-1.37, p < 0.012) than patients in the usual care group. Patients in the intervention group were 23 % more likely to adhere to appointments (RR 1.23; 95 % CI 1.08-1.41, p < 0.0021) than patients in the usual care group, when adjusting for age, secondary insurance, primary open angle glaucoma diagnosis, number of previous visits at Wills Eye Hospital, and follow-up recommendation using Poisson regression. Per-patient cost of the program was US$11.32, and cost per follow-up attended within the adherence window was US$73.56. A low cost reminder intervention consisting of a personalized letter and telephone outreach significantly improved appointment adherence of patients with glaucoma.

Spectral-domain Optical Coherence Tomography in Manifest Glaucoma: Its Additive Role in Structural Diagnosis.

PubMed

Kim, Ko Eun; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2016-11-01

To investigate the additive role of spectral-domain optical coherence tomography (SDOCT) in the structural diagnosis in glaucoma. Reliability and validity analysis. Structural examinations from 109 eyes of 109 healthy individuals and 151 eyes of 151 glaucoma patients with different severities were included. Four structural-diagnostic examination sets were prepared using stereo-optic disc photography (SDP), red-free retinal nerve fiber layer photography (RNFLP), and SDOCT: (1) SDP (S), (2) SDP and SDOCT (SO), (3) SDP and RNFLP (SR), and (4) SDP, RNFLP, and SDOCT (SRO). Five glaucoma specialists were instructed to classify subjects as normal or glaucoma using each of the 4 diagnostic sets in the order S, SO, SR, and SRO, with a 1-month interval. The interobserver agreement was evaluated using kappa (κ) statistics. The additive effect of SDOCT on the diagnostic performance of the specialists was evaluated using the generalized estimating equation. Five glaucoma specialists showed an excellent level of interobserver agreement on the diagnostic assessments based on the 4 sets. In the comparison of the collective diagnostic performance of the specialists, addition of SDOCT to SDP showed an approximately 2-fold significant increase in the diagnostic accuracy. Adding SDOCT to SDP significantly enhanced the specialists' structural-diagnostic ability with respect to the moderate glaucoma, though not mild or advanced glaucoma. SDOCT significantly enhanced the diagnostic accuracy of the glaucoma specialists' performance, showing its additive diagnostic value in judging glaucomatous structural damage, especially in the moderate stage of glaucoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500).

PubMed

Lee, Wonseok; Bae, Hyoung Won; Lee, Si Hyung; Kim, Chan Yun; Seong, Gong Je

2017-03-01

To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R²=0.404). Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors.

Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500)

PubMed Central

Lee, Wonseok; Bae, Hyoung Won; Lee, Si Hyung; Kim, Chan Yun

2017-01-01

Purpose To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. Materials and Methods This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. Results In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R2=0.404). Conclusion Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors. PMID:28120576

Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open-angle glaucoma.

PubMed

Wostyn, Peter; Killer, Hanspeter Esriel; De Deyn, Peter Paul

2017-07-01

The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered 'glymphatic system' in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β-amyloid, from the brain along paravascular channels. Given that β-amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open-angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open-angle glaucoma, present supporting preliminary data from our own post-mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and/or a high trans-lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Combining functional and structural tests improves the diagnostic accuracy of relevance vector machine classifiers

PubMed Central

Racette, Lyne; Chiou, Christine Y.; Hao, Jiucang; Bowd, Christopher; Goldbaum, Michael H.; Zangwill, Linda M.; Lee, Te-Won; Weinreb, Robert N.; Sample, Pamela A.

2009-01-01

Purpose To investigate whether combining optic disc topography and short-wavelength automated perimetry (SWAP) data improves the diagnostic accuracy of relevance vector machine (RVM) classifiers for detecting glaucomatous eyes compared to using each test alone. Methods One eye of 144 glaucoma patients and 68 healthy controls from the Diagnostic Innovations in Glaucoma Study were included. RVM were trained and tested with cross-validation on optimized (backward elimination) SWAP features (thresholds plus age; pattern deviation (PD); total deviation (TD)) and on Heidelberg Retina Tomograph II (HRT) optic disc topography features, independently and in combination. RVM performance was also compared to two HRT linear discriminant functions (LDF) and to SWAP mean deviation (MD) and pattern standard deviation (PSD). Classifier performance was measured by the area under the receiver operating characteristic curves (AUROCs) generated for each feature set and by the sensitivities at set specificities of 75%, 90% and 96%. Results RVM trained on combined HRT and SWAP thresholds plus age had significantly higher AUROC (0.93) than RVM trained on HRT (0.88) and SWAP (0.76) alone. AUROCs for the SWAP global indices (MD: 0.68; PSD: 0.72) offered no advantage over SWAP thresholds plus age, while the LDF AUROCs were significantly lower than RVM trained on the combined SWAP and HRT feature set and on HRT alone feature set. Conclusions Training RVM on combined optimized HRT and SWAP data improved diagnostic accuracy compared to training on SWAP and HRT parameters alone. Future research may identify other combinations of tests and classifiers that can also improve diagnostic accuracy. PMID:19528827

Longitudinal and Cross-Sectional Analyses of Visual Field Progression in Participants of the Ocular Hypertension Treatment Study (OHTS)

PubMed Central

Chauhan, Balwantray C; Keltner, John L; Cello, Kim E; Johnson, Chris A; Anderson, Douglas R; Gordon, Mae O; Kass, Michael A

2014-01-01

Purpose Visual field progression can be determined by evaluating the visual field by serial examinations (longitudinal analysis), or by a change in classification derived from comparison to age-matched normal data in single examinations (cross-sectional analysis). We determined the agreement between these two approaches in data from the Ocular Hypertension Treatment Study (OHTS). Methods Visual field data from 3088 eyes of 1570 OHTS participants (median follow-up 7 yrs, 15 tests with static automated perimetry) were analysed. Longitudinal analyses were performed with change probability with total and pattern deviation, and cross-sectional analysis with Glaucoma Hemifield Test, Corrected Pattern Standard Deviation, and Mean Deviation. The rates of Mean Deviation and General Height change were compared to estimate the degree of diffuse loss in emerging glaucoma. Results The agreement on progression in longitudinal and cross-sectional analyses ranged from 50% to 61% and remained nearly constant across a wide range of criteria. In contrast, the agreement on absence of progression ranged from 97% to 99.7%, being highest for the stricter criteria. Analyses of pattern deviation were more conservative than total deviation, with a 3 to 5 times lesser incidence of progression. Most participants developing field loss had both diffuse and focal change. Conclusions Despite considerable overall agreement, between 40 to 50% of eyes identified as having progressed with either longitudinal or cross-sectional analyses were identified with only one of the analyses. Because diffuse change is part of early glaucomatous damage, pattern deviation analyses may underestimate progression in patients with ocular hypertension. PMID:21149774

Variability of vertical cup to disc ratio measurement and the effects of glaucoma 5-year risk estimation in untreated ocular hypertensive eyes.

PubMed

Chan, Poemen Pui Man; Chiu, Vivian S M; Wong, Mandy O I

2018-06-01

To compare the vertical cup to disc ratio (VCDR) measurements obtained with optical coherence tomography (OCT), Heidelberg retina tomography (HRT) and stereophotography of the optic nerve head (ONH) in patients with ocular hypertension (OHT), and their corresponding estimated 5-year risk for development of glaucoma. ONH images of patients with OHT were taken by fundus camera (stereoscopic images), OCT and HRT. Optic disc stereophotographs were evaluated with a stereo-viewer by two glaucoma specialists (SP1 and SP2) and the VCDR was measured with the ImageJ software. VCDR measurements obtained with stereophotography, OCT and HRT were used to calculate the estimated 5-year risk. One hundred and forty eyes of 75 patients with OHT were included. The VCDR values measured by OCT, HRT, SP1 and SP2 were 0.60±0.14, 0.53±0.23, 0.44±0.13 and 0.49±0.10, respectively. The corresponding 5-year risk for development of glaucoma was 19.54%±16.60%, 18.13%±16.96%, 15.64%±14.35% and 16.70%±14.49%, respectively. Different degrees of proportional biases were observed in VCDR measurements obtained with stereophotography, OCT and HRT. The maximum difference of VCDR measurement was 0.64, while the maximum difference of the corresponding 5-year risk was 24.02%. The disagreement in VCDR measured by OCT, HRT and stereophotography in untreated OHT eyes extends to their 5-year risk estimation of glaucoma development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Rationalization of Unethical Research: Revisionist Accounts of the Tuskegee Syphilis Study and the New Zealand “Unfortunate Experiment”

PubMed Central

Brookes, Barbara

2015-01-01

Two studies, widely condemned in the 1970s and 1980s—the Tuskegee study of men with untreated syphilis and the New Zealand study of women with untreated carcinoma in situ of the cervix—received new defenses in the 21st century. We noted remarkable similarities in both the studies and their defenses. Here we evaluate the scientific, political, and moral claims of the defenders. The scientific claims are largely based on incomplete or misinterpreted evidence and exaggeration of the uncertainties of science. The defenders’ political arguments mistakenly claim that identity politics clouded the original critiques; in fact such politics opened the eyes of the public to exploitation. The moral defenses demonstrate an overreliance on codes of conduct and have implications for research ethics today. PMID:26270295

Ocular manifestations of injection drug use.

PubMed

Kim, Rubin W; Juzych, Mark S; Eliott, Dean

2002-09-01

Injection drug use can result in a variety of severe ocular conditions. Hematogenous dissemination of various fungi and bacteria may produce endophthalmitis with resultant severe visual loss. Retinal arterial occlusive disease may result from talc and other particulate emboli. Most commonly, life-threatening systemic diseases such as endocarditis and HIV infection secondarily affect the eye. Because many of these conditions may result in blindness if untreated, accurate diagnosis and prompt initiation of therapy are essential.

Probing glaucoma visual damage by rarebit perimetry.

PubMed

Brusini, P; Salvetat, M L; Parisi, L; Zeppieri, M

2005-02-01

To compare rarebit perimetry (RBP) with standard achromatic perimetry (SAP) in detecting early glaucomatous functional damage. 43 patients with ocular hypertension (OH), 39 with early primary open angle glaucoma (POAG), and 41 controls were considered. Visual fields were assessed using the Humphrey field analyser (HFA) 30-2 and RBP tests. Differences among the groups were evaluated using Student-Newman-Keuls and chi(2) tests. Correlation between HFA and RBP parameters was assessed using the Pearson's correlation coefficients and regression analysis. Sensitivity and specificity of RBP in detecting early glaucomatous visual damage were calculated with different algorithms. RBP-mean hit rate (MHR) was respectively 88.6% (SD 4.8%) in controls; 79.1% (10.9%) in the OH group; 64.3% (13.8%) in the POAG group (differences statistically significant). Good correlation in the POAG group was found between HFA-mean deviation and RBP-MHR. Largest AROC (0.95) and optimal sensitivity (97.4%) were obtained when an abnormal RBP test was defined as having (at least 1): MHR <80%; >15 areas with a non-hit rate of >10%; > or =2 areas with a non-hit rate of >50%; at least one area with a non-hit rate of > or =70%. The RBP appeared to be a rapid, comfortable, and easily available perimetric test (requiring only a PC device), showing a high sensitivity and specificity in detecting early glaucomatous visual field defects.

In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

NASA Astrophysics Data System (ADS)

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

2017-02-01

To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20-50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.

New Perspectives in Amblyopia Therapy on Adults: A Critical Role for the Excitatory/Inhibitory Balance

PubMed Central

Baroncelli, Laura; Maffei, Lamberto; Sale, Alessandro

2011-01-01

Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1–5% of the total world population. This pathology is caused by early abnormal visual experience with a functional imbalance between the two eyes owing to anisometropia, strabismus, or congenital cataract, resulting in a dramatic loss of visual acuity in an apparently healthy eye and various other perceptual abnormalities, including deficits in contrast sensitivity and in stereopsis. It is currently accepted that, due to a lack of sufficient plasticity within the brain, amblyopia is untreatable in adulthood. However, recent results obtained both in clinical trials and in animal models have challenged this traditional view, unmasking a previously unsuspected potential for promoting recovery after the end of the critical period for visual cortex plasticity. These studies point toward the intracortical inhibitory transmission as a crucial brake for therapeutic rehabilitation and recovery from amblyopia in the adult brain. PMID:22144947

Imaging of the optic nerve and retinal nerve fiber layer: an essential part of glaucoma diagnosis and monitoring.

PubMed

Kotowski, Jacek; Wollstein, Gadi; Ishikawa, Hiroshi; Schuman, Joel S

2014-01-01

Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Citicoline – a neuroprotector with proven effects on glaucomatous disease

PubMed Central

Iulia, Chitu; Ruxandra, Tudosescu; Costin, Leasu-Branet; Liliana-Mary, Voinea

2017-01-01

Citicoline is the generic name of cytidine-5’-diphosphocholine (CDP-choline), an endogenous compound that is able to increase the levels of neurotransmitters in the central nervous system by interacting with the synthesis of cellular membranes phospholipids, especially phosphatidylcholine. Exogenous Citicoline, administered by ingestion or injection, is hydrolyzed and dephosphorylated in order to form cytidine and choline, which resynthesize CDP-choline inside brain cells. It has proven neuroprotective effects in Alzheimer disease, stroke, and Parkinson’s disease, as well as in glaucoma and amblyopia. Citicoline acts as a neuroprotector for those patients with progressive glaucomatous disease in spite of well-controlled intraocular pressure. The purpose of this review was to outline the main features of Citicoline and the evidences of its effect in glaucoma. PMID:29450391

Retinal pigment epithelium changes in Kartagener syndrome.

PubMed

Garcia, Maria D; Ventura, Camila V; Dias, João R; Chang, Ta Chen P; Berrocal, Audina M

2018-06-01

We present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. A 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. We hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

Hypobaric hypoxia: effects on intraocular pressure and corneal thickness.

PubMed

Nebbioso, Marcella; Fazio, Stefano; Di Blasio, Dario; Pescosolido, Nicola

2014-01-01

The purpose of this study focused on understanding the mechanisms underlying ocular hydrodynamics and the changes which occur in the eyes of subjects exposed to hypobaric hypoxia (HH) to permit the achievement of more detailed knowledge in glaucomatous disease. Twenty male subjects, aged 32±5 years, attending the Italian Air Force, were enrolled for this study. The research derived from hypobaric chamber, using helmet and mask supplied to jet pilotes connected to oxygen cylinder and equipped with a preset automatic mixer. The baseline values of intraocular pressure (IOP), recorded at T1, showed a mean of 16±2.23 mmHg, while climbing up to 18,000 feet the mean value was 13.7±4.17 mmHg, recorded at T2. The last assessment was performed returning to sea level (T4) where the mean IOP value was 12.8±2.57 mmHg, with a significant change (P<0.05) compared to T1. Pachymetry values related to corneal thickness in conditions of hypobarism revealed a statistically significant increase (P<0.05). The data collected in this research seem to confirm the increasing outflow of aqueous humor (AH) in the trabecular meshwork (TM) under conditions of HH.

Oxidative stress markers in patients with primary open-angle glaucoma.

PubMed

Ghanem, Asaad A; Arafa, Lamiaa F; El-Baz, Ayman

2010-04-01

To investigate the levels of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPO), superoxide dismutase (SOD), and malondialdehyde (MDA) in human eyes with primary open-angle glaucoma (POAG) and to correlate their concentrations with severity of glaucoma. A prospective cases control study. Thirty patients with primary open-angle glaucoma and twenty-five patients with senile cataracts of matched age and gender were included in the study prospectively. Aqueous humor samples were obtained by paracentesis at the time of elective surgery for glaucomatous and cataractous patients. Aqueous humor were analyzed for CAT, GPO, SOD, and MDA status. GPO, SOD, and MDA enzyme levels revealed a high significant increase in aqueous humor of POAG patients with respect to the comparative group of cataract patients (P < 0.001). No significant difference in the activity of CAT enzyme in aqueous humor of POAG and cataract patient (P = 0.201). Significant correlation was found between the MDA enzyme level and severe visual field loss (P < 0.001) in POAG patients. Increased levels of aqueous humor GPO, SOD, and MDA may be associated with POAG. In addition, they may be useful antioxidant enzyme levels in aqueous humor of POAG patients as a result of glaucoma disease and not a cause.

An Overview on Dry Eye Treatment: Approaches for Cyclosporin A Delivery

PubMed Central

Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2012-01-01

Dry eye syndrome (DES, Keratoconjunctivitis sicca) is a common disorder of the tear film caused by decreased tear production or increased evaporation. Changes in tear composition also promote inflammation on the ocular surface by various mechanisms. Artificial tear drops, tear retention treatment, stimulation of tear secretion, or anti-inflammatory drugs may be used for dry eye treatment according to the severity of the disease. For untreated patients, the risk of ocular infection increases at considerable level and clinical course of the disease may proceed up to infection, corneal ulcer, and blindness. Artificial tears and/or punctual occlusions are used for tear replacement or preservation. New treatment approaches are designed to modify the underlying disease process. For the treatment of severe dry eye disease, cyclosporin A (CsA), the first one of the new generation immunomodulatory drugs, which has an anti-inflammatory effect, is frequently used. CsA has immunosuppressive effects following systemic application. Following local administration of CsA, it is expected to obtain effective drug concentration at the target area and to avoid the various side effects associated with systemic delivery. Microspheres, implants, and liposomes have been developed for administration of CsA subconjunctivally in order to enhance its efficiency. PMID:22619624

The Idiopathic Intracranial Hypertension Treatment Trial

PubMed Central

Wall, Michael; Kupersmith, Mark J.; Kieburtz, Karl D.; Corbett, James J.; Feldon, Steven E.; Friedman, Deborah I.; Katz, David M.; Keltner, John L.; Schron, Eleanor B.; McDermott, Michael P.

2015-01-01

IMPORTANCE To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. OBJECTIVE To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. DESIGN, SETTING, AND PARTICIPANTS We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between −2 dB and −7 dB. All but 4 participants were women. MAIN OUTCOMES AND MEASURES Baseline and laboratory characteristics. RESULTS The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was −3.5 (1.1) dB, (range, −2.0 to −6.4 dB) and in the best eye was −2.3 (1.1) dB (range, −5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire–25 and the Short Form–36 physical and mental health summary scales, were lower compared with population norms. CONCLUSIONS AND RELEVANCE The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01003639 PMID:24756302

Evaluation of a Two-Stage Neural Model of Glaucomatous Defect: An Approach to Reduce Test-Retest Variability

PubMed Central

PAN, FEI; SWANSON, WILLIAM H.; DUL, MITCHELL W.

2006-01-01

Purpose. The purpose of this study is to model perimetric defect and variability and identify stimulus conditions that can reduce variability while retaining good ability to detect glaucomatous defects. Methods. The two-stage neural model of Swanson et al.1 was extended to explore relations among perimetric defect, response variability, and heterogeneous glaucomatous ganglion cell damage. Predictions of the model were evaluated by testing patients with glaucoma using a standard luminance increment 0.43° in diameter and two innovative stimuli designed to tap cortical mechanisms tuned to low spatial frequencies. The innovative stimuli were a luminance-modulated Gabor stimulus (0.5 c/deg) and circular equiluminant red-green chromatic stimuli whose sizes were close to normal Ricco’s areas for the chromatic mechanism. Seventeen patients with glaucoma were each tested twice within a 2-week period. Sensitivities were measured at eight locations at eccentricities from 10° to 21° selected in terms of the retinal nerve fiber bundle patterns. Defect depth and response (test-retest) variability were compared for the innovative stimuli and the standard stimulus. Results. The model predicted that response variability in defective areas would be lower for our innovative stimuli than for the conventional perimetric stimulus with similar defect depths if detection of the chromatic and Gabor stimuli was mediated by spatial mechanisms tuned to low spatial frequencies. Experimental data were consistent with these predictions. Depth of defect was similar for all three stimuli (F = 1.67, p > 0.19). Mean response variability was lower for the chromatic stimulus than for the other stimuli (F = 5.58, p < 0.005) and was lower for the Gabor stimulus than for the standard stimulus in areas with more severe defects (t = 2.68, p < 0.005). Variability increased with defect depth for the standard and Gabor stimuli (p < 0.005) but not for the chromatic stimulus (slope less than zero). Conclusions. Use of large perimetric stimuli detected by cortical mechanisms tuned to low spatial frequencies can make it possible to lower response variability without comprising the ability to detect glaucomatous defect. PMID:16840874

Evaluation of a two-stage neural model of glaucomatous defect: an approach to reduce test-retest variability.

PubMed

Pan, Fei; Swanson, William H; Dul, Mitchell W

2006-07-01

The purpose of this study is to model perimetric defect and variability and identify stimulus conditions that can reduce variability while retaining good ability to detect glaucomatous defects. The two-stage neural model of Swanson et al. was extended to explore relations among perimetric defect, response variability, and heterogeneous glaucomatous ganglion cell damage. Predictions of the model were evaluated by testing patients with glaucoma using a standard luminance increment 0.43 degrees in diameter and two innovative stimuli designed to tap cortical mechanisms tuned to low spatial frequencies. The innovative stimuli were a luminance-modulated Gabor stimulus (0.5 c/deg) and circular equiluminant red-green chromatic stimuli whose sizes were close to normal Ricco's areas for the chromatic mechanism. Seventeen patients with glaucoma were each tested twice within a 2-week period. Sensitivities were measured at eight locations at eccentricities from 10 degrees to 21 degrees selected in terms of the retinal nerve fiber bundle patterns. Defect depth and response (test-retest) variability were compared for the innovative stimuli and the standard stimulus. The model predicted that response variability in defective areas would be lower for our innovative stimuli than for the conventional perimetric stimulus with similar defect depths if detection of the chromatic and Gabor stimuli was mediated by spatial mechanisms tuned to low spatial frequencies. Experimental data were consistent with these predictions. Depth of defect was similar for all three stimuli (F = 1.67, p > 0.19). Mean response variability was lower for the chromatic stimulus than for the other stimuli (F = 5.58, p < 0.005) and was lower for the Gabor stimulus than for the standard stimulus in areas with more severe defects (t = 2.68, p < 0.005). Variability increased with defect depth for the standard and Gabor stimuli (p < 0.005) but not for the chromatic stimulus (slope less than zero). Use of large perimetric stimuli detected by cortical mechanisms tuned to low spatial frequencies can make it possible to lower response variability without comprising the ability to detect glaucomatous defect.

Retinal endoilluminator toxicity of xenon and light-emitting diode (LED) light source: rabbit model.

PubMed

Aydin, Bahri; Dinç, Erdem; Yilmaz, S Necat; Altiparmak, U Emrah; Yülek, Fatma; Ertekin, Sevda; Yilmaz, Mustafa; Yakın, Mehmet

2014-09-01

This study evaluates retinal toxicity due to endoillumination with the light-emitting diode (LED) light source in comparison to endoillumination with xenon light source. Twenty-five eyes of 14 New Zealand pigmented rabbits were used in the study. The LED light (Omesis Medical Systems, Turkey) group was composed of 7 right eyes, while the other 7 right eyes constituted the xenon group (420 nm filter, 357mW/cm(2)) (Bright Star; DORC, Zuidland, Netherlands). Eleven untreated left eyes composed the control group. Twenty gauge pars plana incision 1.5 mm behind the limbus was performed in the right eyes. Twenty gauge bullet type fiberoptic endoilluminator was inserted into the eye from the incision without any pars plana vitrectomy. Fiberoptic endoilluminator was placed in such a way that it was directed toward visual streak of the rabbit retina with a 5 mm distance to retinal surface. Endoillumination was then applied for 20 min with a maximum light intensity for LED and xenon light. In left control eyes, no surgical procedure and no endoillumination were performed. One week after the endoillumination procedure, both eyes of the rabbits were enucleated following electroretinography. Sections stained with hematoxylin and eosin to evaluate morphologic changes. Retina tissues were assessed by active caspase-3 staining. There was no difference in the shape of the waveforms recorded in the eyes endoilluminated with LED light and xenon light sources compared to control eyes both before and after endoillumination application (p > 0.05). Microscopic evaluation of the retinas with hematoxylin and eosin staining demonstrated that all study groups have normal histologic properties similar to control group. No apoptosis positive cells were found within all sections in all groups. When the LED light source is used with maximum power and limited duration for endoillumination in rabbit eyes it does not produce phototoxic effects that may be detectable by electrophysiology and histology similar to xenon light.

Evaluation of the effects of tricaine methanesulfonate on retinal structure and function in koi carp (Cyprinus carpio).

PubMed

Bailey, Kate M; Hempstead, Julie E; Tobias, Jeremy R; Borst, Luke B; Clode, Alison B; Posner, Lysa P

2013-06-01

To determine whether repeated exposure to clinically relevant concentrations of tricaine methanesulfonate (MS-222) would alter retinal function or induce histologically detectable retinal lesions in koi carp (Cyprinus carpio). Prospective, controlled, experimental study. 18 healthy koi carp. 2 fish were euthanized at the start of the study, and eyes were submitted for histologic evaluation as untreated controls. Anesthesia was induced in the remaining fish with 200 mg of MS-222/L and maintained with concentrations of 125 to 150 mg/L for a total exposure time of 20 minutes daily on 1 to 13 consecutive days. On days 1, 7, and 13, electroretinography of both eyes was performed in all fish remaining in the study, and 2 fish were euthanized immediately after each procedure for histologic evaluation of the eyes. Median b-wave amplitudes were compared among study days for right eyes and for left eyes via 1-way repeated-measures ANOVA with a Bonferroni correction for multiple comparisons. Median b-wave amplitudes on days 1, 7, and 13 were 17.7, 20.9, and 17.6 μV, respectively, for right eyes and 15.1, 16.9, and 14.3 μV, respectively, for left eyes. No significant differences in b-wave amplitudes were detected among study days. No histopathologic abnormalities were identified in the retinas of any fish treated with MS-222 or in control fish. Short-term exposure of koi carp to clinically relevant concentrations of MS-222 daily for up to 13 days was not associated with changes in retinal structure or function as measured in this study.

[Possibilities of magnetotherapy in stabilization of visual function in patients with glaucoma].

PubMed

Bisvas Shutanto Kumar; Listopadova, N A

1996-01-01

Courses of magnetotherapy (MT) using ATOS device with 33 mT magnetic field induction were administered to 31 patients (43 eyes) with primary open-angle glaucoma with compensated intraocular pressure. The operation mode was intermittent, with 1.0 to 1.5 Hz field rotation frequency by 6 radii. The procedure is administered to a patient in a sitting posture with magnetic inductor held before the eye. The duration of a session is 10 min, a course consists of 10 sessions. Untreated eyes (n = 15) of the same patients were examined for control. The patients were examined before and 4 to 5 months after MT course. Vision acuity improved by 0.16 diopters, on an average, in 29 eyes (96.7%) out of 30 with vision acuity below 1.0 before treatment. Visocontrastometry was carried out using Visokontrastometer-DT device with spatial frequency range from 0.4 to 19 cycle/degree (12 frequencies) and 125 x 125 monitor. The orientation of lattices was horizontal and vertical. The contrasts ranged from 0.03 to 0.9 (12 levels). MT brought about an improvement of spatial contrast sensitivity by at least 7 values of 12 levels in 22 (84.6%) out of 26 eyes and was unchanged in 4 eyes. Visual field was examined using Humphry automated analyzer. A 120-point threshold test was used. After a course of MT, visual field deficit decreased by at least 10% in 31 (72%) out of 43 eyes, increased in 3, and was unchanged in 9 eyes; on an average, visual field deficit decreased by 22.4% vs. the initial value. After 4 to 5 months the changes in the vision acuity and visual field deficit were negligible. In controls these parameters did not appreciably change over the entire follow-up period.

α5β1-Integrin inhibitor (CLT-28643) effective in rabbit trabeculectomy model.

PubMed

Schultheiss, Maximilian; Schnichels, Sven; Konrad, Eva-Maria; Bartz-Schmidt, Karl U; Zahn, Grit; Caldirola, Patrizia; Fsadni, Mario G; Caram-Lelham, Ninus; Spitzer, Martin S

2017-02-01

Glaucoma filtration surgery (GFS) fails due to fibrosis. The α5β1-integrin plays a pivotal role in fibrosis, angiogenesis and inflammation. This is the first experiment evaluating the prevention of fibrosis after GFS by a specific small molecule α5β1-integrin inhibitor (CLT-28643). Twenty-four rabbits received trabeculectomy on their right eyes. The rabbits were randomized into three groups of eight eyes each. CLT-28643 was given as a single subconjunctival injection intraoperatively to two of the right eye groups followed by postoperative vehicle eye drops (CLT+ group) or CLT-28643 eye drops 4 times daily (CLT++ group). A third group received mitomycin-C (MMC) intraoperatively (sponge application, 0.04%, 2 min) followed by vehicle eye drops postoperatively. The control-surgery group consisted of 12 left eyes having trabeculectomy with no adjunctive therapy. The remaining 12 left eyes formed the untreated group. Clinical assessment included intraocular pressure (IOP) measurement, slit-lamp examination (including bleb survival and morphology) and bleb photography. The rabbits were killed after four weeks for histology. Both CLT-28643-treated groups showed significantly prolonged bleb survival, and better bleb score compared to the control-surgery group. At end of the study, most functioning blebs were found in the MMC group (MMC group 75%; CLT+ group 12.5%, CLT++ group 25%; CLT+ group 12.5%, control-surgery group 0%). CLT-28643 was non-toxic and well tolerated. This rabbit GFS study indicates that inhibition of α5β1-integrin by the novel α5β1-integrin antagonist CLT-28643 significantly improved the outcome. The effect of a single intro-operative application of CLT-28643 seems to be inferior to 0.04% MMC. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

LONG-TERM INTRAOCULAR PRESSURE AFTER UNCOMPLICATED PARS PLANA VITRECTOMY FOR IDIOPATHIC EPIRETINAL MEMBRANE.

PubMed

Tognetto, Daniele; Pastore, Marco R; Cirigliano, Gabriella; DʼAloisio, Rossella; Borelli, Massimo; De Giacinto, Chiara

2017-11-16

To investigate long-term intraocular pressure trends after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane. Three hundred and sixty-eight eyes of 368 consecutive patients were enrolled. Changes in intraocular pressure 1, 3, 6, and 12 months after surgery and during the final follow-up visit were evaluated in vitrectomized eyes and nonvitrectomized fellow eyes. The median follow-up period was 36 months (range 12-92 months). Longitudinal data analysis evidenced a 2.5-mmHg (2.2 mmHg; 2.7 mmHg, 95% confidence interval) statistically significant difference in intraocular pressure 30 days after surgery between treated and fellow untreated eyes, gradually recovering to a not significant 0.2-mmHg (-0.1 mmHg; 0.4 mmHg, 95% confidence interval) difference within 26 months. The incidence of late-onset ocular hypertension was 5.7% (21 over 347, 2%; 12%, 95% confidence interval) without difference between the treated eyes and the group control. No significant difference in the incidence of late-onset ocular hypertension and sex, lens status, or gauge of vitrectomy instruments was detected. Only patient's age was significantly higher (mean difference 4.2 years; 0.1-8.0 years, Monte Carlo, 95% confidence interval) in those who developed late-onset ocular hypertension in the vitrectomized eye. Uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane seems not to increase the risk of late-onset ocular hypertension or open-angle glaucoma development.

Expression of caveolin in trabecular meshwork cells and its possible implication in pathogenesis of primary open angle glaucoma

PubMed Central

Surgucheva, Irina

2011-01-01

Purpose Primary open-angle glaucoma (POAG), which is the most common form of glaucoma, has been associated with a heterogeneous genetic component. A genome-wide association study has identified a common sequence variant at 7q31 (rs4236601 [A]) near the caveolin genes in patients with POAG. Caveolins are a family of integral membrane proteins which participate in many cellular processes, including vesicular transport, cholesterol homeostasis, signal transduction, cell adhesion and migration. The goal of this study was to investigate the expression and regulation of caveolin 1 (CAV-1) and caveolin 2 (CAV-2) in normal and glaucoma trabecular meshwork (TM) cells. Methods CAV-1 and CAV-2 protein expression was quantified by immunoblot analysis using lysates isolated from primary and immortalized TM cells or TM tissue dissected from normal and POAG eyes. The localization of caveolins in TM cells was assessed by immunofluorescent microscopy. CAV-1 and CAV-2 protein expression was also investigated in TM cells at various time points after subjecting the cells to known glaucomatous insults like dexamethasone (DEX) and tumor growth factor beta2 (TGF-β2) treatment. Phosphorylation of CAV-1 at tyrosine 14 in normal and glaucoma TM cell lines was evaluated using a specific monoclonal antibody (Ab). The 5′ upstream region of the CAV-1 gene was amplified and the sequence variant rs4236601 (A/G polymorphic site) and several putative transcription factor-binding sites were modified by in vitro mutagenesis. The effect of nucleotide sequence modifications in the CAV-1 upstream region on gene expression was assayed in a luciferase-based system in TM and non-TM cells. Results CAV-1 and CAV-2 are expressed in TM cells, with localization to the cytoplasm and perinuclear region. DEX increased CAV-1 expression in immortalized glaucoma TM cells by 2.8±0.1 (n=3) fold at 24 h and 2.5±0.1 (n=3) fold at 48 h, compared to 1.3±0.06 (n=3) fold at 24 and 48 h in immortalized normal TM cells. Phosphorylation of CAV-1 at Tyr14 was reduced by 3.2±0.15 (n=3) fold in glaucomatous TM cells when compared to normal TM cells. In POAG and normal TM tissue, CAV-1 expression was found to be uniform. CAV-2, on the other hand, was variable in independent normal and glaucoma TM tissue. Substitution of a G for an A at base pair −2,388 upstream of the start codon of CAV-1, corresponding to the minor allele rs4236601 [A], increased transcriptional activity in TM and non-TM cells when compared to the native sequence. Deletion analysis of putative transcription factor binding sites in the CAV-1 promoter region caused cell-specific effects on gene expression. Conclusions CAV-1 and CAV-2 are expressed in normal and glaucoma tissue and TM cell lines. Phosphorylation of Tyr14 in CAV-1 and transcriptional regulation of CAV-1 expression may have a role in glaucomatous alterations in TM cells. PMID:22128235

Study of long term structural and functional changes in medically controlled glaucoma

PubMed Central

Pandey, Achyut N; Sujata, S

2014-01-01

AIM Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. METHODS Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. RESULTS A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. CONCLUSION Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide. PMID:24634878

Study of long term structural and functional changes in medically controlled glaucoma.

PubMed

Pandey, Achyut N; Sujata, S

2014-01-01

Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide.

Partial Tenon’s capsule resection with adjunctive mitomycin C in Ahmed glaucoma valve implant surgery

PubMed Central

Susanna, R

2003-01-01

Aim: To verify if partial intraoperative Tenon’s capsule resection (PTCR) with adjunctive mitomycin C is effective in developing thin, avascular blebs in eyes undergoing Ahmed glaucoma valve insertion, and to assess the efficacy and safety of this procedure. Methods: A multicentre, prospective, alternating case assignment, investigator unmasked, parallel group, comparative interventional study was conducted in four Latin American countries (Argentina, Brazil, Colombia, and Peru). Ahmed glaucoma valve implant insertion with PTCR (group A) and without PCTR (group B) was performed in neovascular glaucomatous eyes without previous surgery. Adjunctive mitomycin C (MMC) was used in both groups. Patients were examined 1 day, 10 days, 1 month, 2 months, 3 months, 6 months, and 1 year following the surgery. Intraocular pressure (IOP) and the appearance of the bleb were evaluated at each examination. Appearance of the bleb was classified at both the 1 month mark and last examinations into one of three groups: flat and vascularised; elevated avascular; or elevated and not avascular. Results: 92 eyes from 92 patients were included in the study. The preoperative mean IOP was 50.0 (SD 10.5) mm Hg in group A and 48.4 (11.7) in group B (p>0.05). Statistically significant IOP reductions were observed at all periods of follow up. 12 months after surgery, the mean IOP was 17.2 (5.0) mm Hg in group A and 18.3 (8.7) mm Hg in group B (p>0.05). A hypertensive phase occurred in 40.0% in group A and in 46.8% in group B (p>0.05). At the 1 month and the final follow up, the blebs in all eyes were considered elevated and not avascular. The success rate (IOP⩽21 mm Hg) at 1 year after surgery was 70.4% in group A and 77.7% in group B (p>0.05). Overall, 74.2% of the patients achieved an IOP ⩽21 mm Hg and 55.2% an IOP⩽17 mm Hg, with or without additional medication administered to lower IOP. The incidence of complications was similar in both groups. Conclusions: In eyes undergoing Ahmed valve implantation for neovascular glaucoma, PCTR with MMC augmentation showed no additional benefits or complications over MMC augmentation alone; no avascular bleb was obtained with this technique. The incidence of a hypertensive phase was lower than reported in previous studies. PMID:12881343

Driving with Binocular Visual Field Loss? A Study on a Supervised On-Road Parcours with Simultaneous Eye and Head Tracking

PubMed Central

Aehling, Kathrin; Heister, Martin; Rosenstiel, Wolfgang; Schiefer, Ulrich; Papageorgiou, Elena

2014-01-01

Post-chiasmal visual pathway lesions and glaucomatous optic neuropathy cause binocular visual field defects (VFDs) that may critically interfere with quality of life and driving licensure. The aims of this study were (i) to assess the on-road driving performance of patients suffering from binocular visual field loss using a dual-brake vehicle, and (ii) to investigate the related compensatory mechanisms. A driving instructor, blinded to the participants' diagnosis, rated the driving performance (passed/failed) of ten patients with homonymous visual field defects (HP), including four patients with right (HR) and six patients with left homonymous visual field defects (HL), ten glaucoma patients (GP), and twenty age and gender-related ophthalmologically healthy control subjects (C) during a 40-minute driving task on a pre-specified public on-road parcours. In order to investigate the subjects' visual exploration ability, eye movements were recorded by means of a mobile eye tracker. Two additional cameras were used to monitor the driving scene and record head and shoulder movements. Thus this study is novel as a quantitative assessment of eye movements and an additional evaluation of head and shoulder was performed. Six out of ten HP and four out of ten GP were rated as fit to drive by the driving instructor, despite their binocular visual field loss. Three out of 20 control subjects failed the on-road assessment. The extent of the visual field defect was of minor importance with regard to the driving performance. The site of the homonymous visual field defect (HVFD) critically interfered with the driving ability: all failed HP subjects suffered from left homonymous visual field loss (HL) due to right hemispheric lesions. Patients who failed the driving assessment had mainly difficulties with lane keeping and gap judgment ability. Patients who passed the test displayed different exploration patterns than those who failed. Patients who passed focused longer on the central area of the visual field than patients who failed the test. In addition, patients who passed the test performed more glances towards the area of their visual field defect. In conclusion, our findings support the hypothesis that the extent of visual field per se cannot predict driving fitness, because some patients with HVFDs and advanced glaucoma can compensate for their deficit by effective visual scanning. Head movements appeared to be superior to eye and shoulder movements in predicting the outcome of the driving test under the present study scenario. PMID:24523869

Sickle cell retinopathy: A literature review.

PubMed

Ribeiro, Marina Viegas Moura Rezende; Jucá, João Vitor de Omena; Alves, Anna Luyza Correia Dos Santos; Ferreira, Caio Victor Oliveira; Barbosa, Fabiano Timbó; Ribeiro, Êurica Adélia Nogueira

2017-12-01

Hemoglobinopathies are a group of hereditary diseases that cause quantitative or qualitative changes in the shape, function or synthesis of hemoglobin. One of the most common is sickle cell anemia, which, due to sickling of erythrocytes, causes vaso-occlusive phenomena. Among the possible ocular manifestations, the most representative is retinopathy, which can lead to blindness if left untreated. Therefore, periodic ophthalmologic monitoring of these patients is important for early diagnosis and adequate therapeutic management, which can be done localy by treating the lesions in the eyes, or systemically.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

PubMed

Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

2017-05-09

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Combining retinal nerve fiber layer thickness with individual retinal blood vessel locations allows modeling of central vision loss in glaucoma

NASA Astrophysics Data System (ADS)

Wang, Hui; Wang, Mengyu; Baniasadi, Neda; Jin, Qingying; Elze, Tobias

2017-02-01

Purpose: To assess whether modeling of central vision loss (CVL) due to glaucoma by optical coherence tomography (OCT) retinal nerve fiber (RNF) layer thickness (RNFLT) can be improved by including the location of the major inferior temporal retinal artery (ITA), a known correlate of individual RNF geometry. Methods: Pat- tern deviations of the two locations of the Humphrey 24-2 visual field (VF) known to be specifically vulnerable to glaucomatous CVL and OCT RNFLT on the corresponding circumpapillary sector around the optic nerve head within the radius of 1.73mm were retrospectively selected from 428 eyes of 428 patients of a large clinical glaucoma service. ITA was marked on the 1.73mm circle by a trained observer. Linear regression models were fitted with CVL as dependent variable and VF mean deviation (MD) plus either of (1) RNFLT, (2) ITA, and (3) their combination, respectively, as regressors. To assess CVL over all levels of glaucoma severity, the three models were compared to a null model containing only MD. A Baysian model comparison was performed with the Bayes Factor (BF) as measure of strength of evidence (BF<3: no evidence, 3-20: positive evidence, >20: strong evidence over null model). Results: Neither RNFLT (BF=0.9) nor ITA (BF=1.4) alone provided positive evidence over the null model, but their combination resulted in a model with strong evidence (BF=21.4). Conclusion: While the established circumpapillary RNFLT sector, based on population statistics, could not satisfactorily model CVL, the inclusion of a retinal parameter related to individual eye anatomy yielded a strong structure-function model.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

PubMed Central

Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

2017-01-01

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

Glaucoma Diagnostic Capability of Global and Regional Measurements of Isolated Ganglion Cell Layer and Inner Plexiform Layer.

PubMed

Chien, Jason L; Ghassibi, Mark P; Patthanathamrongkasem, Thipnapa; Abumasmah, Ramiz; Rosman, Michael S; Skaat, Alon; Tello, Celso; Liebmann, Jeffrey M; Ritch, Robert; Park, Sung Chul

2017-03-01

To compare glaucoma diagnostic capability of global/regional macular layer parameters in different-sized grids. Serial horizontal spectral-domain optical coherence tomography scans of macula were obtained. Automated macular grids with diameters of 3, 3.45, and 6 mm were used. For each grid, 10 parameters (total volume; average thicknesses in 9 regions) were obtained for 5 layers: macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), ganglion cell-inner plexiform layer (GCIPL; GCL+IPL), and ganglion cell complex (GCC; mRNFL+GCL+IPL). Sixty-nine normal eyes (69 subjects) and 87 glaucomatous eyes (87 patients) were included. For the total volume parameter, the area under the receiver operating characteristic curves (AUCs) in 6-mm grid were larger than the AUCs in 3- and 3.45-mm grids for GCL, GCC, GCIPL, and mRNFL (all P<0.020). For the average thickness parameters, the best AUC in 6-mm grid (T2 region for GCL, IPL, and GCIPL; I2 region for mRNFL and GCC) was greater than the best AUC in 3-mm grid for GCL, GCC, and mRNFL (P<0.045). The AUC of GCL volume (0.920) was similar to those of GCC (0.920) and GCIPL (0.909) volume. The AUC of GCL T2 region thickness (0.942) was similar to those of GCC I2 region (0.942) and GCIPL T2 region (0.934) thickness. Isolated macular GCL appears to be as good as GCC and GCIPL in glaucoma diagnosis, while IPL does not. Larger macular grids may be better at detecting glaucoma. Each layer has a characteristic region with the best glaucoma diagnostic capability.

Comparison of surgically induced astigmatism following different glaucoma operations.

PubMed

Tanito, Masaki; Matsuzaki, Yukari; Ikeda, Yoshifumi; Fujihara, Etsuko

2017-01-01

To compare surgically induced astigmatism (SIA) among glaucomatous eyes treated with trabeculectomy (LEC), EX-PRESS ® shunt (EXP), ab externo trabeculotomy (exLOT), or microhook ab interno trabeculotomy (μLOT). Eighty right eyes of 80 subjects who underwent LEC (n=20), EXP (n=20), exLOT (n=20), or μLOT (n=20) were included. The dataset including the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and keratometry recordings preoperatively and 3 months postoperatively was collected by chart review. The means of the vector magnitude, vector meridian, and arithmetic magnitude of the preoperative and postoperative astigmatism and SIA were calculated. The correlations among the SIA magnitude, postoperative BCVA, and IOP were assessed. The mean astigmatic arithmetic magnitudes did not differ significantly ( P =0.0732) preoperatively among the four groups, but the magnitude was significantly ( P =0.0002) greater in the LEC group than the other groups postoperatively. The mean SIA vectors were calculated to be 1.01 D at 56°, 0.62 D at 74°, 0.23 D at 112°, and 0.12 D at 97° for the LEC, EXP, exLOT, and μLOT groups, respectively. The mean SIA arithmetic magnitudes were significantly ( P <0.0001) greater in the LEC group than the other groups. Three months postoperatively, the SIA magnitude was correlated positively with the logarithm of the minimum angle of resolution (logMAR) BCVA ( r =0.3538) and negatively with the IOP ( r =-0.3265); the logMAR BCVA was correlated negatively with the IOP ( r =-0.3105). EXP, exLOT, and μLOT induce less corneal astigmatism than LEC in the early postoperative period.

Segmented inner plexiform layer thickness as a potential biomarker to evaluate open-angle glaucoma: Dendritic degeneration of retinal ganglion cell.

PubMed

Kim, Eun Kyoung; Park, Hae-Young Lopilly; Park, Chan Kee

2017-01-01

To evaluate the changes of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses and compare structure-function relationships of 4 retinal layers using spectral-domain optical coherence tomography (SD-OCT) in macular region of glaucoma patients. In cross-sectional study, a total of 85 eyes with pre-perimetric to advanced glaucoma and 26 normal controls were enrolled. The glaucomatous eyes were subdivided into three groups according to the severity of visual field defect: a preperimetric glaucoma group, an early glaucoma group, and a moderate to advanced glaucoma group. RNFL, GCL, IPL, and GCIPL thicknesses were measured at the level of the macula by the Spectralis (Heidelberg Engineering, Heidelberg, Germany) SD-OCT with automated segmentation software. For functional evaluation, corresponding mean sensitivity (MS) values were measured using 24-2 standard automated perimetry (SAP). RNFL, GCL, IPL, and GCIPL thicknesses were significantly different among 4 groups (P < .001). Macular structure losses were positively correlated with the MS values of the 24-2 SAP for RNFL, GCL, IPL, and GCIPL (R = 0.553, 0.636, 0.648 and 0.646, respectively, P < .001). In regression analysis, IPL and GCIPL thicknesses showed stronger association with the corresponding MS values of 24-2 SAP compared with RNFL and GCL thicknesses (R2 = 0.420, P < .001 for IPL; R2 = 0.417, P< .001 for GCIPL thickness). Segmented IPL thickness was significantly associated with the degree of glaucoma. Segmental analysis of the inner retinal layer including the IPL in macular region may provide valuable information for evaluating glaucoma.

Retinal Nerve Fiber Layer Thickness Changes in the Pseudoexfoliation Syndrome: A Meta-Analysis of Case-Control Studies.

PubMed

Yu, Ji-Guo; Huang, Qing; Zhou, Xiao-Fang; Ding, Yi; Li, Jing; Xiang, Yi

2018-01-01

To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with the pseudoexfoliation syndrome (PXS) and healthy controls. Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PubMed, and Embase. Results were reviewed to ensure that the included studies met prespecified inclusion/exclusion criteria, and the quality of each study was assessed using the Newcastle-Ottawa Scale. All included studies measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness using optical coherence tomography (OCT). For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence intervals (CIs). Eight case-control studies were included in this meta-analysis involving 225 eyes of PXS patients and 208 eyes of healthy controls in total. Statistical analysis revealed that the average RNFL thickness in PXS patients was significantly reduced compared to healthy controls (WMD = -6.91, 95% CI: -9.99 to -3.82, p < 0.0001). Additionally, differences in RNFL thickness in the superior quadrant (WMD = -10.68, 95% CI: -16.40 to -4.95, p = 0.0003), inferior quadrant (WMD = -8.20, 95% CI: -10.85 to -5.55, p < 0.00001), nasal quadrant (WMD = -3.05, 95% CI: -5.21 to -0.90, p = 0.005), and temporal quadrant (WMD = -6.39, 95% CI: -9.98 to -2.80, p = 0.0005) were all significant between the two groups. These results suggest that it is important to evaluate RNFL thickness and the optic nerve head through OCT in patients with PXS in order to determine early glaucomatous damage and start timely intervention prior to visual field loss. © 2017 S. Karger AG, Basel.

Appositional Closure Identified by Ultrasound Biomicroscopy in Population-Based Primary Angle-Closure Glaucoma Suspects: The Liwan Eye Study

PubMed Central

Kong, Xiangbin; Foster, Paul J.; Huang, Qunxiao; Zheng, Yingfeng; Huang, Wenyong; Cai, Xiaoyu

2011-01-01

Purpose. To describe the characteristics of the iridocorneal angle using ultrasound biomicroscopy (UBM) in Chinese people classified gonioscopically as having suspected primary angle-closure (PACS) glaucoma. Methods. PACS were defined as not having visible posterior (usually pigmented) trabecular meshwork in two or more quadrants examined by static gonioscopy. The PACS and 1 of 10 those who did not meet this criterion were identified from a population-based survey. Iridotrabecular meshwork contact (ITC) was identified and further classified into low and high, according to standard UBM images. Those with high ITC were further classified according the configuration of ITC: B-type, with contiguous ITC from the base of the angle, and S-type, with ITC localized to the region of Schwalbe's line. Results. ITC was identified in 78.6% of the superior, 40.2% of the nasal, 59.8% of the inferior, and 25.6% of the temporal quadrants in the PACS (n = 117). These proportions were 43.9%, 15.8%, 29.8%, and 14.0% in the controls (n = 57), respectively. About two thirds of the eyes with ITC were classified as high. In those with high ITC, the number with B- and S-type ITC was very similar. The proportions of any high ITCs increased substantially from 15.4% in those with Shaffer angle grade 4 and 45.0% in grade 3, to 71.0% in grade 2, 70.2% in grade 1, and 86.4% in grade 0. Conclusions. More ITC is identified on UBM imaging than by gonioscopy. Careful consideration should be given to the assessment modality regarded as the reference standard in defining anatomic risk factors for glaucomatous visual loss and the need for treatment. PMID:21357394

Evaluation of Visual Field Progression in Glaucoma: Quasar Regression Program and Event Analysis.

PubMed

Díaz-Alemán, Valentín T; González-Hernández, Marta; Perera-Sanz, Daniel; Armas-Domínguez, Karintia

2016-01-01

To determine the sensitivity, specificity and agreement between the Quasar program, glaucoma progression analysis (GPA II) event analysis and expert opinion in the detection of glaucomatous progression. The Quasar program is based on linear regression analysis of both mean defect (MD) and pattern standard deviation (PSD). Each series of visual fields was evaluated by three methods; Quasar, GPA II and four experts. The sensitivity, specificity and agreement (kappa) for each method was calculated, using expert opinion as the reference standard. The study included 439 SITA Standard visual fields of 56 eyes of 42 patients, with a mean of 7.8 ± 0.8 visual fields per eye. When suspected cases of progression were considered stable, sensitivity and specificity of Quasar, GPA II and the experts were 86.6% and 70.7%, 26.6% and 95.1%, and 86.6% and 92.6% respectively. When suspected cases of progression were considered as progressing, sensitivity and specificity of Quasar, GPA II and the experts were 79.1% and 81.2%, 45.8% and 90.6%, and 85.4% and 90.6% respectively. The agreement between Quasar and GPA II when suspected cases were considered stable or progressing was 0.03 and 0.28 respectively. The degree of agreement between Quasar and the experts when suspected cases were considered stable or progressing was 0.472 and 0.507. The degree of agreement between GPA II and the experts when suspected cases were considered stable or progressing was 0.262 and 0.342. The combination of MD and PSD regression analysis in the Quasar program showed better agreement with the experts and higher sensitivity than GPA II.

Comparison of surgically induced astigmatism following different glaucoma operations

PubMed Central

Tanito, Masaki; Matsuzaki, Yukari; Ikeda, Yoshifumi; Fujihara, Etsuko

2017-01-01

Aim To compare surgically induced astigmatism (SIA) among glaucomatous eyes treated with trabeculectomy (LEC), EX-PRESS® shunt (EXP), ab externo trabeculotomy (exLOT), or microhook ab interno trabeculotomy (μLOT). Subjects and methods Eighty right eyes of 80 subjects who underwent LEC (n=20), EXP (n=20), exLOT (n=20), or μLOT (n=20) were included. The dataset including the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and keratometry recordings preoperatively and 3 months postoperatively was collected by chart review. The means of the vector magnitude, vector meridian, and arithmetic magnitude of the preoperative and postoperative astigmatism and SIA were calculated. The correlations among the SIA magnitude, postoperative BCVA, and IOP were assessed. Results The mean astigmatic arithmetic magnitudes did not differ significantly (P=0.0732) preoperatively among the four groups, but the magnitude was significantly (P=0.0002) greater in the LEC group than the other groups postoperatively. The mean SIA vectors were calculated to be 1.01 D at 56°, 0.62 D at 74°, 0.23 D at 112°, and 0.12 D at 97° for the LEC, EXP, exLOT, and μLOT groups, respectively. The mean SIA arithmetic magnitudes were significantly (P<0.0001) greater in the LEC group than the other groups. Three months postoperatively, the SIA magnitude was correlated positively with the logarithm of the minimum angle of resolution (logMAR) BCVA (r=0.3538) and negatively with the IOP (r=−0.3265); the logMAR BCVA was correlated negatively with the IOP (r=−0.3105). Conclusion EXP, exLOT, and μLOT induce less corneal astigmatism than LEC in the early postoperative period. PMID:29238159

The relationship between 3D morphology of optic disc and spatial patterns of visual field loss in glaucoma

NASA Astrophysics Data System (ADS)

Wang, Mengyu; Wang, Hui; Baniasadi, Neda; Elze, Tobias

2017-02-01

Purpose: Optic disc tilt defined over 3D optic disc morphology has been shown to be associated with the location of initial glaucomatous damages. In this work, we study the impact of optic cup depth (OCD) on spatial patterns of visual field loss in glaucoma. Methods: Pairs of reliable Cirrus OCT scans around optic disc and Humphrey visual fields of glaucoma patients without visually significant cataract and age-related macular degeneration were selected. The most recent visit of a randomly selected eye of each patient was chosen. The OCD was automatically calculated on the superior-inferior cross sectional image passing through the optic disc center. The correlations between the mean pattern deviation (PD) of each sector in glaucoma hemifield test (GHT) and Garway-Heath scheme and OCD were evaluated for all severities glaucoma and mild glaucoma (mean deviation >= -5 dB), respectively. Results: 424 eyes of 424 patients passed the data reliability criteria with 346 mild glaucoma patients. For all severities glaucoma, there was no significant correlation between the mean sector PD and OCD. For mild glaucoma, OCD was uniquely correlated to the mean PD of the inferior pericentral sector (r=-0.18, p=0.01) in GHT, which was independent of mean deviation and retinal nerve fiber layer thickness (p<0.001 for both). Conclusion: OCD was uniquely correlated to the vision loss of the inferior pericentral sector in GHT and Garway- Health scheme for mild glaucoma. Future advancement of OCT imaging techniques may provide better clinical diagnosis for early glaucoma by focusing on 3D morphological variation of the optic disc.

Changes in ocular flora in eyes exposed to ophthalmic antibiotics.

PubMed

Dave, Sarita B; Toma, Hassanain S; Kim, Stephen J

2013-05-01

To determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics. Prospective, controlled, longitudinal study with 1-year follow-up. Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization. Patients received 4 consecutive monthly unilateral intravitreal injections and were then treated as needed. Each patient was randomized to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic for 4 days after each injection. Conjunctival cultures of the treated eye and untreated fellow eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Changes in bacteria composition of the conjunctiva over time. In azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (P<0.01) and 4.5% (P<0.01), respectively, after azithromycin exposure. In fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S epidermidis and S aureus, respectively, but these percentages increased to 63.4% (P<0.03) and 13% (P = 0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of gram-negative species decreased from 8.7% at baseline to 1.6% (P<0.05) in fluoroquinolone-treated eyes. The percentage of S epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (P<0.01) or fluoroquinolone-treated eyes (P<0.01). The percentage of S epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and to a lesser degree fluoroquinolone antibiotics at the expense of other commensal flora. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

PubMed

Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

2001-01-01

An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. Without definitions or examples of optic disc rim notching, the glaucoma subspecialists had relatively high intraobserver agreement but were likely to disagree with each other in characterizing the degree of disc rim notching. We recommend development of a standard photographic classification of disc rim notching. The classification should be tested for inter- and intra-observer agreement.

The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

PubMed Central

Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

2001-01-01

PURPOSE: An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. METHODS: Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. RESULTS: In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. CONCLUSION: Without definitions or examples of optic disc rim notching, the glaucoma subspecialists had relatively high intraobserver agreement but were likely to disagree with each other in characterizing the degree of disc rim notching. We recommend development of a standard photographic classification of disc rim notching. The classification should be tested for inter- and intra-observer agreement. PMID:11797305

Wavefront-guided correction of ocular aberrations: Are phase plate and refractive surgery solutions equal?

NASA Astrophysics Data System (ADS)

Marchese, Linda E.; Munger, Rejean; Priest, David

2005-08-01

Wavefront-guided laser eye surgery has been recently introduced and holds the promise of correcting not only defocus and astigmatism in patients but also higher-order aberrations. Research is just beginning on the implementation of wavefront-guided methods in optical solutions, such as phase-plate-based spectacles, as alternatives to surgery. We investigate the theoretical differences between the implementation of wavefront-guided surgical and phase plate corrections. The residual aberrations of 43 model eyes are calculated after simulated refractive surgery and also after a phase plate is placed in front of the untreated eye. In each case, the current wavefront-guided paradigm that applies a direct map of the ocular aberrations to the correction zone is used. The simulation results demonstrate that an ablation map that is a Zernike fit of a direct transform of the ocular wavefront phase error is not as efficient in correcting refractive errors of sphere, cylinder, spherical aberration, and coma as when the same Zernike coefficients are applied to a phase plate, with statistically significant improvements from 2% to 6%.

Supercritical fluid-mediated liposomes containing cyclosporin A for the treatment of dry eye syndrome in a rabbit model: comparative study with the conventional cyclosporin A emulsion

PubMed Central

Karn, Pankaj Ranjan; Kim, Hyun Do; Kang, Han; Sun, Bo Kyung; Jin, Su-Eon; Hwang, Sung-Joo

2014-01-01

Background The objective of this study was to compare the efficacy of cyclosporin (CsA)-encapsulated liposomes with the commercially available CsA emulsion (Restasis®) for the treatment of dry eye syndrome in rabbits. Methods Liposomes containing CsA were prepared by the supercritical fluid (SCF) method consisted of phosphatidylcholine from soybean (SCF-S100) and egg lecithins (SCF-EPCS). An in vitro permeation study was carried out using artificial cellulose membrane in Franz diffusion cells. Dry eye syndrome was induced in male albino rabbits and further subdivided into untreated, Restasis®-treated, EPCS, and S100-treated groups. Tear formation in the dry-eye-induced rabbits was evaluated using the Schirmer tear test. All formulations were also evaluated by ocular irritation tests using the Draize eye and winking methods with the determination of CsA concentration in rabbit tears. Results After the treatment, the Schirmer tear test value significantly improved in EPCS-treated (P=0.005) and S100-treated (P=0.018) groups compared to the Restasis®-treated group. The AUC0–24 h for rabbit’s tear film after the administration of SCF-S100 was 32.75±9.21 μg·h/mg which was significantly higher than that of 24.59±8.69 μg·h/mg reported with Restasis®. Liposomal CsA formulations used in this study showed lower irritation in rabbit eyes compared with Restasis®. Conclusion These results demonstrate that the novel SCF-mediated liposomal CsA promises a significant improvement in overcoming the challenges associated with the treatment of dry eyes. PMID:25143728

Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

PubMed

Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

2014-12-18

To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Supercritical fluid-mediated liposomes containing cyclosporin A for the treatment of dry eye syndrome in a rabbit model: comparative study with the conventional cyclosporin A emulsion.

PubMed

Karn, Pankaj Ranjan; Kim, Hyun Do; Kang, Han; Sun, Bo Kyung; Jin, Su-Eon; Hwang, Sung-Joo

2014-01-01

The objective of this study was to compare the efficacy of cyclosporin (CsA)-encapsulated liposomes with the commercially available CsA emulsion (Restasis) for the treatment of dry eye syndrome in rabbits. Liposomes containing CsA were prepared by the supercritical fluid (SCF) method consisted of phosphatidylcholine from soybean (SCF-S100) and egg lecithins (SCF-EPCS). An in vitro permeation study was carried out using artificial cellulose membrane in Franz diffusion cells. Dry eye syndrome was induced in male albino rabbits and further subdivided into untreated, Restasis-treated, EPCS, and S100-treated groups. Tear formation in the dry-eye-induced rabbits was evaluated using the Schirmer tear test. All formulations were also evaluated by ocular irritation tests using the Draize eye and winking methods with the determination of CsA concentration in rabbit tears. After the treatment, the Schirmer tear test value significantly improved in EPCS-treated (P=0.005) and S100-treated (P=0.018) groups compared to the Restasis-treated group. The AUC₀₋₂₄ h for rabbit's tear film after the administration of SCF-S100 was 32.75±9.21 μg·h/mg which was significantly higher than that of 24.59±8.69 μg·h/mg reported with Restasis. Liposomal CsA formulations used in this study showed lower irritation in rabbit eyes compared with Restasis. These results demonstrate that the novel SCF-mediated liposomal CsA promises a significant improvement in overcoming the challenges associated with the treatment of dry eyes.

Fatigue characteristics of SAE52100 steel via ultrasonic nanocrystal surface modification technology.

PubMed

Pyun, Young Sik; Suh, Chang Min; Yamaguchi, Tokutaro; Im, Jong Soon; Kim, Jun Hyong; Amanov, Auezhan; Park, Jeong Hyeon

2012-07-01

Ultrasonic nanocrystal surface modification (UNSM) technology is a novel surface modification technology that can improve the mechanical and tribological properties of interacting surfaces in relative motion. UNSM treatment was utilized to improve the wear resistance fatigue strength of slim bearing rings made of SAE52100 bearing steel without damaging the raceway surfaces. In this study, wear and fatigue results that were subjected to different impact loads of the UNSM treatment were investigated and compared with those of the untreated specimen. The microhardness of the UNSM-treated specimens increased by about 20%, higher than that of the untreated specimens. The X-ray diffraction analysis showed that a compressive residual stress of more than 1,000 MPa was induced after the UNSM treatment. Also, electron backscatter diffraction analysis was used to study the surface structure and nanograin refinement. The results showed that the rolling contact fatigue life and the rotary bending fatigue strength of the UNSM-treated specimens increased by about 80% and 31%, respectively, compared to those of the untreated specimen. These results might be attributed to the increased microhardness, the induced compressive residual stress, and the nanocrystal structure modification after the UNSM treatment. In addition, the fracture surface analysis showed that the fish eye crack initiation phenomenon was observed after the UNSM treatment.

Accommodation and the Visual Regulation of Refractive State in Marmosets

PubMed Central

Troilo, David; Totonelly, Kristen; Harb, Elise

2009-01-01

Purpose To determine the effects of imposed anisometropic retinal defocus on accommodation, ocular growth, and refractive state changes in marmosets. Methods Marmosets were raised with extended-wear soft contact lenses for an average duration of 10 wks beginning at an average age of 76 d. Experimental animals wore either a positive or negative contact lens over one eye and a plano lens or no lens over the other. Another group wore binocular lenses of equal magnitude but opposite sign. Untreated marmosets served as controls and three wore plano lenses monocularly. Cycloplegic refractive state, corneal curvature, and vitreous chamber depth were measured before, during, and after the period of lens wear. To investigate the accommodative response, the effective refractive state was measured through each anisometropic condition at varying accommodative stimuli positions using an infrared refractometer. Results Eye growth and refractive state are significantly correlated with the sign and power of the contact lens worn. The eyes of marmosets reared with monocular negative power lenses had longer vitreous chambers and were myopic relative to contralateral control eyes (p<0.01). Monocular positive power lenses produced a significant reduction in vitreous chamber depth and hyperopia relative to the contralateral control eyes (p<0.05). In marmosets reared binocularly with lenses of opposite sign, we found larger interocular differences in vitreous chamber depths and refractive state (p<0.001). Accommodation influences the defocus experienced through the lenses, however, the mean effective refractive state was still hyperopia in the negative-lens-treated eyes and myopia in the positive-lens-treated eyes. Conclusions Imposed anisometropia effectively alters marmoset eye growth and refractive state to compensate for the imposed defocus. The response to imposed hyperopia is larger and faster than the response to imposed myopia. The pattern of accommodation under imposed anisometropia produces effective refractive states that are consistent with the changes in eye growth and refractive state observed. PMID:19104464

The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma.

PubMed

Hayes, Sally; Kamma-Lorger, Christina S; Boote, Craig; Young, Robert D; Quantock, Andrew J; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M

2013-01-01

To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm(2)) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm(2)). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion. It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen.

The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma

PubMed Central

Hayes, Sally; Kamma-Lorger, Christina S.; Boote, Craig; Young, Robert D.; Quantock, Andrew J.; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M.

2013-01-01

Purpose To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. Methods One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm2) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm2). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Results Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion. Conclusions It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen. PMID:23349690

Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.

PubMed

Chen, Wensheng; Zhang, Zhenhao; Hu, Jiaoyue; Xie, Hui; Pan, Juxin; Dong, Nuo; Liu, Zuguo

2013-12-01

To investigate the effect of benzalkonium chloride (BAK) on corneal nerves. Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9. The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes. The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.

Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.

PubMed

Wong, Wai T; Dresner, Samuel; Forooghian, Farzin; Glaser, Tanya; Doss, Lauren; Zhou, Mei; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y

2013-04-26

To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

[Treatment of keratitis superficialis chronica of the dog with strontium 90].

PubMed

Höcht, Stefan; Grüning, Georg; Allgoewer, Ingrid; Nausner, Martin; Brunnberg, Leo; Hinkelbein, Wolfgang

2002-02-01

Corneal pannus is a disease which, if untreated, nearly always is progressive and may lead to blindness of the affected dog. A therapeutic standard is yet to be defined. Beta-ray irradiation with Sr-90 is often recommended on a casuistic basis, but systematic studies are sparse. The aim of the present study was to evaluate efficacy and to document side effects of radiotherapy with Sr-90. 17 animals were treated. 13 of them received treatment of 15 Gy surface dose twice within 2 days with additional medical therapy with ciclosporin and prednisolon. Only the more affected eye was treated with radiation which was applied with an eye-applicator, the other eye served as control. Four animals with already advanced impairment of vision received keratectomy, afterwards radiation was applied on both sides. Medical treatment alone led to deterioration in vascularization and spread of pigmentation in eleven of 13 (85%) of the control-eyes, density of pigmentation increased in eight of 13 (62%). After radiation therapy, almost all animals showed a marked initial improvement. Even if progressive disease occurred later on, further worsening as it happened in the control-eyes could be stopped in nine resp. ten of 13 eyes (69% and 77%). All animals with keratectomy and radiotherapy regained and preserved adequate vision. Besides short-term blepharospasm, no side effects were recorded. Corneal pannus is responsive to radiation therapy with Sr-90 and long-term benefit can be achieved. Side effects are minimal. Optimal sequencing of therapy and dosage still have to be examined.

Customizing Perimetric Locations Based on En Face Images of Retinal Nerve Fiber Bundles With Glaucomatous Damage

PubMed Central

Alluwimi, Muhammed S.; Swanson, William H.; Malinovsky, Victor E.; King, Brett J.

2018-01-01

Purpose Prior studies suggested the use of customized perimetric locations in glaucoma; these studies were limited by imaging only the superficial depths of the retinal nerve fiber layer (RNFL) and by prolonged perimetric testing. We aimed to develop a rapid perimetric test guided by high-resolution images of RNFL bundles. Methods We recruited 10 patients with glaucoma, ages 56 to 80 years, median 68 years, and 10 controls, ages 55 to 77 years, median 68 years. The patients were selected based on discrepancies between locations of glaucomatous damage for perimetric and structural measures. Montaging was used to produce optical coherence tomography en face images of the RNFL covering much of the 24-2 grid locations. In experiment 1, we presented the Goldmann size III stimulus at preselected retinal locations of glaucomatous damage, using just two contrasts. In experiment 2, we developed an elongated sinusoidal stimulus, aligned within the defect, to measure contrast sensitivities; abnormalities were defined based on lower 95% reference limits derived from the controls. Results The percentage of predicted locations where size III was not seen at 28 dB ranged from 16% to 80%, with a median of 48%. Contrast sensitivity for the sinusoidal stimulus was below the 95% reference range for 37 of 44 stimuli aligned within the defects. Conclusions We developed methods for rapid perimetric testing guided by en face images of the RNFL bundles in patients with glaucoma. Results indicated ganglion cell damage under all of the visible RNFL defects. Translational Relevance Customized perimetric locations have potential to improve clinical assessment of glaucoma. PMID:29576929

Validation of the UNC OCT Index for the Diagnosis of Early Glaucoma

PubMed Central

Lee, Gary; Budenz, Donald L.; Warren, Joshua L.; Wall, Michael; Artes, Paul H.; Callan, Thomas M.; Flanagan, John G.

2018-01-01

Purpose To independently validate the performance of the University of North Carolina Optical Coherence Tomography (UNC OCT) Index in diagnosing and predicting early glaucoma. Methods Data of 118 normal subjects (118 eyes) and 96 subjects (96 eyes) with early glaucoma defined as visual field mean deviation (MD) greater than −4 decibels (dB), aged 40 to 80 years, and who were enrolled in the Full-Threshold Testing Size III, V, VI comparison study were used in this study. CIRRUS OCT average and quadrants' retinal nerve fiber layer (RNFL); optic disc vertical cup-to-disc ratio (VCDR), cup-to-disc area ratio, and rim area; and average, minimum, and six sectoral ganglion cell-inner plexiform layer (GCIPL) measurements were run through the UNC OCT Index algorithm. Area under the receiver operating characteristic curve (AUC) and sensitivities at 95% and 99% specificity were calculated and compared between single parameters and the UNC OCT Index. Results Mean age was 60.1 ± 11.0 years for normal subjects and 66.5 ± 8.1 years for glaucoma patients (P < 0.001). MD was 0.29 ± 1.04 dB and −1.30 ± 1.35 dB in normal and glaucomatous eyes (P < 0.001), respectively. The AUC of the UNC OCT Index was 0.96. The best single metrics when compared to the UNC OCT Index were VCDR (0.93, P = 0.054), average RNFL (0.92, P = 0.014), and minimum GCIPL (0.91, P = 0.009). The sensitivities at 95% and 99% specificity were 85.4% and 76.0% (UNC OCT Index), 71.9% and 62.5% (VCDR, all P < 0.001), 64.6% and 53.1% (average RNFL, all P < 0.001), and 66.7% and 58.3% (minimum GCIPL, all P < 0.001), respectively. Conclusions The findings confirm that the UNC OCT Index may provide improved diagnostic perforce over that of single OCT parameters and may be a good tool for detection of early glaucoma. Translational Relevance The UNC OCT Index algorithm may be incorporated easily into routine clinical practice and be useful for detecting early glaucoma. PMID:29629238

Validation of the UNC OCT Index for the Diagnosis of Early Glaucoma.

PubMed

Mwanza, Jean-Claude; Lee, Gary; Budenz, Donald L; Warren, Joshua L; Wall, Michael; Artes, Paul H; Callan, Thomas M; Flanagan, John G

2018-04-01

To independently validate the performance of the University of North Carolina Optical Coherence Tomography (UNC OCT) Index in diagnosing and predicting early glaucoma. Data of 118 normal subjects (118 eyes) and 96 subjects (96 eyes) with early glaucoma defined as visual field mean deviation (MD) greater than -4 decibels (dB), aged 40 to 80 years, and who were enrolled in the Full-Threshold Testing Size III, V, VI comparison study were used in this study. CIRRUS OCT average and quadrants' retinal nerve fiber layer (RNFL); optic disc vertical cup-to-disc ratio (VCDR), cup-to-disc area ratio, and rim area; and average, minimum, and six sectoral ganglion cell-inner plexiform layer (GCIPL) measurements were run through the UNC OCT Index algorithm. Area under the receiver operating characteristic curve (AUC) and sensitivities at 95% and 99% specificity were calculated and compared between single parameters and the UNC OCT Index. Mean age was 60.1 ± 11.0 years for normal subjects and 66.5 ± 8.1 years for glaucoma patients ( P < 0.001). MD was 0.29 ± 1.04 dB and -1.30 ± 1.35 dB in normal and glaucomatous eyes ( P < 0.001), respectively. The AUC of the UNC OCT Index was 0.96. The best single metrics when compared to the UNC OCT Index were VCDR (0.93, P = 0.054), average RNFL (0.92, P = 0.014), and minimum GCIPL (0.91, P = 0.009). The sensitivities at 95% and 99% specificity were 85.4% and 76.0% (UNC OCT Index), 71.9% and 62.5% (VCDR, all P < 0.001), 64.6% and 53.1% (average RNFL, all P < 0.001), and 66.7% and 58.3% (minimum GCIPL, all P < 0.001), respectively. The findings confirm that the UNC OCT Index may provide improved diagnostic perforce over that of single OCT parameters and may be a good tool for detection of early glaucoma. The UNC OCT Index algorithm may be incorporated easily into routine clinical practice and be useful for detecting early glaucoma.

Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

PubMed

Cowley, D S; Roy-Byrne, P P; Radant, A; Ritchie, J C; Greenblatt, D J; Nemeroff, C B; Hommer, D W

1995-04-01

The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

Effects of unilateral topical atropine on binocular pupil responses and eye growth in mice.

PubMed

Barathi, V A; Beuerman, Roger W; Schaeffel, Frank

2009-02-01

Studies on drugs selected to target myopia development often use the vehicle-treated fellow eye as a control. However, it is not clear how much of the drug reaches the fellow eye, rendering it a potentially invalid control. Therefore, in this study, pupil responses were used to probe the effects of atropine in both eyes in mice, after unilateral topical application. In a second experiment, interocular differences in refractive development and axial eye growth were studied while atropine was applied daily to one eye. In 20 C57BL/6 (B6) wildtype mice, a single drop of 1% atropine solution was instilled into one eye. Mice were gently restrained by holding their necks while video image processing software detected the pupil and measured its diameter at a sampling rate of 30 Hz. A bright green LED, attached to the photoretinoscope of the video camera, was flashed. Pupil responses were quantified daily over a period of 2 weeks. In another group of 24 mice, one drop of 1% atropine was applied daily for 28 days. Axial length was measured pre- and post-treatment, using low coherence interferometry (the Zeiss AC-Master). Refractive development was measured by infrared photorefraction. Similar to previous findings with the same device, untreated eyes displayed a pupil constriction of 24.84+/-1.73% upon stimulation with the green LED. A single drop of 1% atropine caused complete suppression with no significant recovery over the whole observation period of two weeks. The responses in the fellow eye were temporarily reduced to about 75% and then recovered towards baseline. After daily atropine application, there was significant reduction in axial length of the eyes, relative to the saline-treated fellow eyes (3.234+/-0.186 versus 3.378+/-0.176 mm, n=24, p<0.01, paired t-test) and the refractions became more hyperopic/less myopic (+13.46+/-2.15 D versus +10.06+/-2.02 D, n=24, p<0.01). In line with previous findings, one drop of atropine solution caused a long lasting suppression of pupil responses in the mouse eye. New data show that the transfer to the fellow eye was limited, making interocular comparisons feasible. It is also new that topical atropine reduced axial eye growth even when mice had largely normal vision.

Environmental Enrichment Promotes Plasticity and Visual Acuity Recovery in Adult Monocular Amblyopic Rats

PubMed Central

Bonaccorsi, Joyce; Cenni, Maria Cristina; Sale, Alessandro; Maffei, Lamberto

2012-01-01

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people. PMID:22509358

Automated analysis of connected speech reveals early biomarkers of Parkinson's disease in patients with rapid eye movement sleep behaviour disorder.

PubMed

Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan

2017-02-02

For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.

Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia.

PubMed

Spiegel, Daniel P; Byblow, Winston D; Hess, Robert F; Thompson, Benjamin

2013-10-01

Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Effects of the holmium laser on the human cornea: a preliminary study

NASA Astrophysics Data System (ADS)

Mueller, Linda J.; Tassignon, Marie J.; Trau, Rene; Pels, Liesbeth; Vrensen, Gijs F.

1996-12-01

Treatment of peripheral post-mortem human corneas with the Holmium laser in a ring pattern resulted in opaque spots. One pair of treated eyes was immediately processed for light and electron microscopy and three other treated eyes were preserved for 4 days in medium in order to compare direct and short-term effects of the Holmium laser. Cross as well as frontal light microscopical sections of all eyes revealed interconnecting bands between the spots. At the ultrastructural level the anterior corneal tissue within these spots was characterized by coagulation of cells and collagen and shoed either a dramatic distorting effect on the epithelium in the eyes processed immediately or a single layer of flattened multi-nucleolated epithelial cells having more than one nucleolus per nucleus in the eyes stored in medium. Furthermore, the spots showed disturbed Bowman's layer, destroyed keratocytes and collagen fibrils which were either coagulated or organized chaotically. The interconnecting bands contained alternating normal and coagulated collagen fibers. The rest of the cornea outside the spots had a normal appearance. In corneas stored in medium, both keratocytes and epithelial cells over the entire cornea exhibited accumulations of cytoplasmic fibrils and glycogen particles. These phenomena were not observed in non-preserved corneas, suggesting that the differences are due to preservation and not due to the laser treatment. It is concluded that morphological changes occur mainly in the treated peripheral cornea whereas the central untreated cornea remains unaffected,indicating that the Holmium laser is a reliable instrument to treat hypermetropic patients.

Hypobaric Hypoxia: Effects on Intraocular Pressure and Corneal Thickness

PubMed Central

Di Blasio, Dario; Pescosolido, Nicola

2014-01-01

Objective. The purpose of this study focused on understanding the mechanisms underlying ocular hydrodynamics and the changes which occur in the eyes of subjects exposed to hypobaric hypoxia (HH) to permit the achievement of more detailed knowledge in glaucomatous disease. Methods. Twenty male subjects, aged 32 ± 5 years, attending the Italian Air Force, were enrolled for this study. The research derived from hypobaric chamber, using helmet and mask supplied to jet pilotes connected to oxygen cylinder and equipped with a preset automatic mixer. Results. The baseline values of intraocular pressure (IOP), recorded at T1, showed a mean of 16 ± 2.23 mmHg, while climbing up to 18,000 feet the mean value was 13.7 ± 4.17 mmHg, recorded at T2. The last assessment was performed returning to sea level (T4) where the mean IOP value was 12.8 ± 2.57 mmHg, with a significant change (P < 0.05) compared to T1. Pachymetry values related to corneal thickness in conditions of hypobarism revealed a statistically significant increase (P < 0.05). Conclusions. The data collected in this research seem to confirm the increasing outflow of aqueous humor (AH) in the trabecular meshwork (TM) under conditions of HH. PMID:24550712

Biomarkers in primary open angle glaucoma.

PubMed

Kokotas, Haris; Kroupis, Christos; Chiras, Dimitrios; Grigoriadou, Maria; Lamnissou, Klea; Petersen, Michael B; Kitsos, George

2012-12-01

Glaucoma, a leading cause of blindness worldwide, is currently defined as a disturbance of the structural or functional integrity of the optic nerve that causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. This disturbance usually can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Glaucoma can be divided roughly into two main categories, ‘ open angle ’ and ‘ closed angle ’ glaucoma.Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice loss of vision until the disease has progressed significantly. Primary open angle glaucoma(POAG) is described distinctly as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and IOP that is too high for the healthy eye. It manifests by cupping and atrophy of the optic disc, in the absence of other known causes of glaucomatous disease. Several biological markers have been implicated with the disease. The purpose of this study was to summarize the current knowledge regarding the non-genetic molecular markers which have been predicted to have an association with POAG but have not yet been validated.

Ginkgo biloba: An adjuvant therapy for progressive normal and high tension glaucoma

PubMed Central

Cybulska-Heinrich, A.K.; Mozaffarieh, M.

2012-01-01

Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma. Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress. PMID:22355250

Appropriate Objective Functions for Quantifying Iris Mechanical Properties Using Inverse Finite Element Modeling.

PubMed

Pant, Anup D; Dorairaj, Syril K; Amini, Rouzbeh

2018-07-01

Quantifying the mechanical properties of the iris is important, as it provides insight into the pathophysiology of glaucoma. Recent ex vivo studies have shown that the mechanical properties of the iris are different in glaucomatous eyes as compared to normal ones. Notwithstanding the importance of the ex vivo studies, such measurements are severely limited for diagnosis and preclude development of treatment strategies. With the advent of detailed imaging modalities, it is possible to determine the in vivo mechanical properties using inverse finite element (FE) modeling. An inverse modeling approach requires an appropriate objective function for reliable estimation of parameters. In the case of the iris, numerous measurements such as iris chord length (CL) and iris concavity (CV) are made routinely in clinical practice. In this study, we have evaluated five different objective functions chosen based on the iris biometrics (in the presence and absence of clinical measurement errors) to determine the appropriate criterion for inverse modeling. Our results showed that in the absence of experimental measurement error, a combination of iris CL and CV can be used as the objective function. However, with the addition of measurement errors, the objective functions that employ a large number of local displacement values provide more reliable outcomes.

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population.

PubMed

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

Innovative Vision Products, Inc. (IVP)'s scientists developed the lubricant eye drops (Can-C) designed as 1% N-acetylcarnosine (NAC) prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C eye drops. In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients' glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C eye drops since December 2001. Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients' compliance rate to self-administer NAC eye-drops. The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies. The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision.

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

PubMed Central

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

Background: Innovative Vision Products, Inc. (IVP)’s scientists developed the lubricant eye drops (Can-C™) designed as 1% N-acetylcarnosine (NAC) prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural l-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops. Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. Patients or other participants: The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C™ eye drops since December 2001. Intervention: Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients’ compliance rate to self-administer NAC eye-drops. Main outcome measure and results: The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies. Conclusion: The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision. PMID:19503764

[An in vivo study of basic fibroblast growth factor on activation and proliferation of retinal progenitor cell in RCS rats].

PubMed

Xia, Xiaoping; Song, Guoxiang; Liu, Xiangfu; Tang, Xiangchen; Ye, Hui

2010-11-01

To investigate the effect of intravitreal basic fibroblast growth factor(bFGF) on activation and proliferation of endogenous retinal progenitor cells in the Royal College of Surgeons(RCS) rats. Twenty-four rats were studied after the 30th postnatal day(≥30). Eighteen affected rats were randomly divided into 3 groups: bFGF-treated, vehicle-treated and untreated group, and 6 unaffected rats were used as normal controls. Six μl of bFGF (5μg/10 μl) or vehicle was injected into the vitreous on days 31, 33 and 35 after birth (P31, P33, P35) in the bFGF group and vehicle group, and no injection was administered in the untreated and control groups. All the rats were euthanized, and their eyes were enucleated, hemisected and fixed at 50 d after birth for immunohistochemistry and measurement of outer nuclear layer thickness. Nestin and Chx10 were positively expressed in all retinal layers, intravitreous injection of bFGF in retina-dystrophic RCS(RCS-p+/Lav) rats induced intense labeling for the retinal progenitor cell markers Chx10 and Nestin, which were highly colocalized. Fluorescence intensity for both labels was slightly less in the control rats, and much less in the vehicle-injected rats as well as in the untreated RCS rats. The outer nuclear layer (ONL) was significantly thicker in bFGF group than that of vehicle-treated or untreated group(p<0.01), but thinner than that of the control group(p<0.01). No significant difference was observed in the ONL thicknesses between the vehicle group and untreated group(P>0.05). bFGF may contribute to the activation of retinal progenitor cells in RCS rats, thus counteract degeneration by promoting the proliferation of the progenitor cells.