Glaucoma progression detection with frequency doubling technology (FDT) compared to standard automated perimetry (SAP) in the Groningen Longitudinal Glaucoma Study.

PubMed

Wesselink, Christiaan; Jansonius, Nomdo M

2017-09-01

To determine the usefulness of frequency doubling perimetry (FDT) for progression detection in glaucoma, compared to standard automated perimetry (SAP). Data were used from 150 eyes of 150 glaucoma patients from the Groningen Longitudinal Glaucoma Study. After baseline, SAP was performed approximately yearly; FDT every other year. First and last visit had to contain both tests. Using linear regression, progression velocities were calculated for SAP (Humphrey Field Analyzer) mean deviation (MD) and FDT MD and the number of test locations with a total deviation probability below p < 0.01 (TD). Progression velocity tertiles were determined and eyes were classified as slowly, intermediately, or fast progressing for both techniques. Comparison between SAP and FDT classifications were made using a Mantel Haenszel chi-square test. Longitudinal signal-to-noise ratios (LSNRs) were calculated, per patient and per technique, defined as progression velocity divided by the standard deviation of the residuals. Mean (SD) follow-up was 6.4 (1.7) years; median (interquartile range [IQR]) baseline SAP MD -6.6 (-14.2 to -3.6) dB. On average 8.2 and 4.5 tests were performed for SAP and FDT, respectively. Median (IQR) MD slope was -0.16 (-0.46 to +0.02) dB/year for SAP and -0.05 (-0.39 to +0.17) dB/year for FDT. Mantel Haenszel chi-squares of SAP MD vs FDT MD and TD were 12.5 (p < 0.001) and 15.8 (p < 0.001), respectively. LSNRs for SAP MD (median -0.17 yr -1 ) were better than those for FDT MD (-0.04 yr -1 ; p = 0.010). FDT may be a useful technique for monitoring glaucoma progression in patients who cannot perform SAP reliably. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

ARGALI: an automatic cup-to-disc ratio measurement system for glaucoma detection and AnaLysIs framework

NASA Astrophysics Data System (ADS)

Liu, J.; Wong, D. W. K.; Lim, J. H.; Li, H.; Tan, N. M.; Wong, T. Y.

2009-02-01

Glaucoma is an irreversible ocular disease leading to permanent blindness. However, early detection can be effective in slowing or halting the progression of the disease. Physiologically, glaucoma progression is quantified by increased excavation of the optic cup. This progression can be quantified in retinal fundus images via the optic cup to disc ratio (CDR), since in increased glaucomatous neuropathy, the relative size of the optic cup to the optic disc is increased. The ARGALI framework constitutes of various segmentation approaches employing level set, color intensity thresholds and ellipse fitting for the extraction of the optic cup and disc from retinal images as preliminary steps. Following this, different combinations of the obtained results are then utilized to calculate the corresponding CDR values. The individual results are subsequently fused using a neural network. The learning function of the neural network is trained with a set of 100 retinal images For testing, a separate set 40 images is then used to compare the obtained CDR against a clinically graded CDR, and it is shown that the neural network-based result performs better than the individual components, with 96% of the results within intra-observer variability. The results indicate good promise for the further development of ARGALI as a tool for the early detection of glaucoma.

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.

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.

Frequency of Testing to Detect Visual Field Progression Derived Using a Longitudinal Cohort of Glaucoma Patients.

PubMed

Wu, Zhichao; Saunders, Luke J; Daga, Fábio B; Diniz-Filho, Alberto; Medeiros, Felipe A

2017-06-01

To determine the time required to detect statistically significant progression for different rates of visual field loss using standard automated perimetry (SAP) when considering different frequencies of testing using a follow-up scheme that resembles clinical practice. Observational cohort study. One thousand seventy-two eyes of 665 patients with glaucoma followed up over an average of 4.3±0.9 years. Participants with 5 or more visual field tests over a 2- to 5-year period were included to derive the longitudinal measurement variability of SAP mean deviation (MD) using linear regressions. Estimates of variability then were used to reconstruct real-world visual field data by computer simulation to evaluate the time required to detect progression for various rates of visual field loss and different frequencies of testing. The evaluation was performed using a follow-up scheme that resembled clinical practice by requiring a set of 2 baseline tests and a confirmatory test to identify progression. Time (in years) required to detect progression. The time required to detect a statistically significant negative MD slope decreased as the frequency of testing increased, albeit not proportionally. For example, 80% of eyes with an MD loss of -2 dB/year would be detected after 3.3, 2.4, and 2.1 years when testing is performed once, twice, and thrice per year, respectively. For eyes with an MD loss of -0.5 dB/year, progression can be detected with 80% power after 7.3, 5.7, and 5.0 years, respectively. This study provides information on the time required to detect progression using MD trend analysis in glaucoma eyes when different testing frequencies are used. The smaller gains in the time to detect progression when testing is increased from twice to thrice per year suggests that obtaining 2 reliable tests at baseline followed by semiannual testing and confirmation of progression through repeat testing in the initial years of follow-up may provide a good compromise for detecting progression, while minimizing the burden on health care resources in clinical practice. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

[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.

Prediction of functional loss in glaucoma from progressive optic disc damage.

PubMed

Medeiros, Felipe A; Alencar, Luciana M; Zangwill, Linda M; Bowd, Christopher; Sample, Pamela A; Weinreb, Robert N

2009-10-01

To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma.

PubMed

De Moraes, C Gustavo; Liebmann, Jeffrey M; Levin, Leonard A

2017-01-01

Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes. Nonetheless, the effect of these medications on IOP and their associated risks can be consistently and objectively measured. This helps to explain why regulatory approval of new therapies in glaucoma has historically used IOP as the outcome variable. Although all approved treatments for glaucoma involve IOP reduction, patients frequently continue to progress despite treatment. It would therefore be beneficial to develop treatments that preserve visual function through mechanisms other than lowering IOP. The United States Food and Drug Administration (FDA) has stated that they will accept a clinically meaningful definition of visual field progression using Glaucoma Change Probability criteria. Nonetheless, these criteria do not take into account the time (and hence, the speed) needed to reach significant change. In this paper we provide an analysis based on the existing literature to support the hypothesis that decreasing the rate of visual field progression by 30% in a trial lasting 12-18 months is clinically meaningful. We demonstrate that a 30% decrease in rate of visual field progression can be reliably projected to have a significant effect on health-related quality of life, as defined by validated instruments designed to measure that endpoint. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma

PubMed Central

De Moraes, C. Gustavo; Liebmann, Jeffrey M.; Levin, Leonard A.

2016-01-01

Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes. Nonetheless, the effect of these medications on IOP and their associated risks can be consistently and objectively measured. This helps to explain why regulatory approval of new therapies in glaucoma has historically used IOP as the outcome variable. Although all approved treatments for glaucoma involve IOP reduction, patients frequently continue to progress despite treatment. It would therefore be beneficial to develop treatments that preserve visual function through mechanisms other than lowering IOP. The United States Food and Drug Administration (FDA) has stated that they will accept a clinically meaningful definition of visual field progression using Glaucoma Change Probability criteria. Nonetheless, these criteria do not take into account the time (and hence, the speed) needed to reach significant change. In this paper we provide an analysis based on the existing literature to support the hypothesis that decreasing the rate of visual field progression by 30% in a trial lasting 12–18 months is clinically meaningful. We demonstrate that a 30% decrease in rate of visual field progression can be reliably projected to have a significant effect on health-related quality of life, as defined by validated instruments designed to measure that endpoint. PMID:27773767

Detection of Progressive Retinal Nerve Fiber Layer Loss in Glaucoma Using Scanning Laser Polarimetry with Variable Corneal Compensation

PubMed Central

Medeiros, Felipe A.; Alencar, Luciana M.; Zangwill, Linda M.; Bowd, Christopher; Vizzeri, Gianmarco; Sample, Pamela A.; Weinreb, Robert N.

2010-01-01

Purpose To evaluate the ability of scanning laser polarimetry with variable corneal compensation to detect progressive retinal nerve fiber layer (RNFL) loss in glaucoma patients and patients suspected of having the disease. Methods This was an observational cohort study that included 335 eyes of 195 patients. Images were obtained annually with the GDx VCC scanning laser polarimeter, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 3.94 years. Progression was determined using commercial software for SAP and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between RNFL thickness measurements over time and progression as determined by SAP and/or stereophotographs. Results From the 335 eyes, 34 (10%) showed progression over time by stereophotographs and/or SAP. Average GDx VCC measurements decreased significantly over time for both progressors as well as non-progressors. However, the rate of decline was significantly higher in the progressing group (−0.70 μm/year) compared to the non-progressing group (−0.14 μm/year; P = 0.001). Black race and male sex were significantly associated with higher rates of RNFL loss during follow-up. Conclusions The GDx VCC scanning laser polarimeter was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields. These findings suggest that this technology could be useful to detect and monitor progressive disease in patients with established diagnosis of glaucoma or suspected of having the disease. PMID:19029038

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.

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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

Challenges in the management of glaucoma in developing countries.

PubMed

Butt, Nadeem Hafeez; Ayub, Muhammad Hammad; Ali, Muhammad Hassaan

2016-01-01

Glaucoma is the most common optic neuropathy characterized by normal to raised intraocular pressure (IOP), visual field defects, loss of retinal nerve fiber layer, thinning of the neuroretinal rim, and cupping of the optic disc. IOP reduction by medical, laser, or surgical therapies remains the only clinically proven treatment of glaucoma. The challenges in glaucoma management are diverse. They include early detection and diagnosis, setting of appropriate target IOP, choice of treatment, monitoring of quality of life and sight, and compliance with the treatment. Early diagnosis can be made by assessing optic nerve structure using imaging devices and optic nerve function through perimetry. Reducing IOP and controlling its fluctuations are considered to be the most important factors in limiting progression of glaucoma. Selection of the best suitable therapy out of medical, surgical, or laser treatment options is yet another management challenge. Patients suffering from glaucoma experience poor quality of life owing to the diagnosis itself, functional visual loss, inconvenience and cost of treatment, and side effects of treatment. All these factors lead to poor compliance, adherence, and persistence to treatment, and further progression of the disease. It is, therefore, important that ophthalmologists keep all the aforementioned factors in mind when managing patients with glaucoma.

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.

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

The Effectiveness of Teleglaucoma versus In-Patient Examination for Glaucoma Screening: A Systematic Review and Meta-Analysis

PubMed Central

Thomas, Sera-Melisa; Jeyaraman, Maya; Hodge, William G.; Hutnik, Cindy; Costella, John; Malvankar-Mehta, Monali S.

2014-01-01

Background Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness. Methods A systematic search was conducted to help locate published and unpublished studies. Studies which evaluate teleglaucoma as a screening device for glaucoma were included. A meta-analysis was conducted to provide estimates of diagnostic accuracy, diagnostic odds ratio, and the relative percentage of glaucoma cases detected. The improvements to healthcare service quality and cost data were assessed. Results Of 11237 studies reviewed, 45 were included. Our results indicated that, teleglaucoma is more specific and less sensitive than in-person examination. The pooled estimates of sensitivity was 0.832 [95% CI 0.770, 0.881] and specificity was 0.790 [95% CI 0.668, 0.876]. The relative odds of a positive screen test in glaucoma cases are 18.7 times more likely than a negative screen test in a non-glaucoma cases. Additionally, the mean cost for every case of glaucoma detected was $1098.67 US and of teleglaucoma per patient screened was $922.77 US. Conclusion Teleglaucoma can accurately discriminate between screen test results with greater odds for positive cases. It detects more cases of glaucoma than in-person examination. Both patients and the healthcare systems benefit from early detection, reduction in wait and travel times, increased specialist referral rates, and cost savings. Teleglaucoma is an effective screening tool for glaucoma specifically for remote and under-services communities. PMID:25479593

The effectiveness of teleglaucoma versus in-patient examination for glaucoma screening: a systematic review and meta-analysis.

PubMed

Thomas, Sera-Melisa; Jeyaraman, Maya M; Jeyaraman, Maya; Hodge, William G; Hutnik, Cindy; Costella, John; Malvankar-Mehta, Monali S

2014-01-01

Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness. A systematic search was conducted to help locate published and unpublished studies. Studies which evaluate teleglaucoma as a screening device for glaucoma were included. A meta-analysis was conducted to provide estimates of diagnostic accuracy, diagnostic odds ratio, and the relative percentage of glaucoma cases detected. The improvements to healthcare service quality and cost data were assessed. Of 11237 studies reviewed, 45 were included. Our results indicated that, teleglaucoma is more specific and less sensitive than in-person examination. The pooled estimates of sensitivity was 0.832 [95% CI 0.770, 0.881] and specificity was 0.790 [95% CI 0.668, 0.876]. The relative odds of a positive screen test in glaucoma cases are 18.7 times more likely than a negative screen test in a non-glaucoma cases. Additionally, the mean cost for every case of glaucoma detected was $1098.67 US and of teleglaucoma per patient screened was $922.77 US. Teleglaucoma can accurately discriminate between screen test results with greater odds for positive cases. It detects more cases of glaucoma than in-person examination. Both patients and the healthcare systems benefit from early detection, reduction in wait and travel times, increased specialist referral rates, and cost savings. Teleglaucoma is an effective screening tool for glaucoma specifically for remote and under-services communities.

Applications of the water drinking test in glaucoma management.

PubMed

Susanna, Remo; Clement, Colin; Goldberg, Ivan; Hatanaka, Marcelo

2017-08-01

Intraocular pressure (IOP) peaks and means have been considered important factors for glaucoma onset and progression. However, peak IOP detection depends only on appropriated IOP checks at office visits, whereas the mean IOP requires longitudinal IOP data collection and may be affected by the interval between visits. Also, IOP peak assessment is necessary to verify if the peak pressure of a given patient is in target range, to evaluate glaucoma suspect risk, the efficacy of hypotensive drugs and to detect early loss of IOP control. The water-drinking test has gained significant attention in recent years as an important tool to evaluate IOP peaks and instability. The main objective of this review was to present new findings and to discuss the applicability of the water-drinking test in glaucoma management. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Clinical Metabolomics and Glaucoma.

PubMed

Barbosa-Breda, João; Himmelreich, Uwe; Ghesquière, Bart; Rocha-Sousa, Amândio; Stalmans, Ingeborg

2018-01-01

Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options. © 2017 S. Karger AG, Basel.

Automated detection of retinal nerve fiber layer defects on fundus images: false positive reduction based on vessel likelihood

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2016-03-01

Early detection of glaucoma is important to slow down or cease progression of the disease and for preventing total blindness. We have previously proposed an automated scheme for detection of retinal nerve fiber layer defect (NFLD), which is one of the early signs of glaucoma observed on retinal fundus images. In this study, a new multi-step detection scheme was included to improve detection of subtle and narrow NFLDs. In addition, new features were added to distinguish between NFLDs and blood vessels, which are frequent sites of false positives (FPs). The result was evaluated with a new test dataset consisted of 261 cases, including 130 cases with NFLDs. Using the proposed method, the initial detection rate was improved from 82% to 98%. At the sensitivity of 80%, the number of FPs per image was reduced from 4.25 to 1.36. The result indicates the potential usefulness of the proposed method for early detection of glaucoma.

The Effective Dynamic Ranges for Glaucomatous Visual Field Progression With Standard Automated Perimetry and Stimulus Sizes III and V.

PubMed

Wall, Michael; Zamba, Gideon K D; Artes, Paul H

2018-01-01

It has been shown that threshold estimates below approximately 20 dB have little effect on the ability to detect visual field progression in glaucoma. We aimed to compare stimulus size V to stimulus size III, in areas of visual damage, to confirm these findings by using (1) a different dataset, (2) different techniques of progression analysis, and (3) an analysis to evaluate the effect of censoring on mean deviation (MD). In the Iowa Variability in Perimetry Study, 120 glaucoma subjects were tested every 6 months for 4 years with size III SITA Standard and size V Full Threshold. Progression was determined with three complementary techniques: pointwise linear regression (PLR), permutation of PLR, and linear regression of the MD index. All analyses were repeated on "censored'' datasets in which threshold estimates below a given criterion value were set to equal the criterion value. Our analyses confirmed previous observations that threshold estimates below 20 dB contribute much less to visual field progression than estimates above this range. These findings were broadly similar with stimulus sizes III and V. Censoring of threshold values < 20 dB has relatively little impact on the rates of visual field progression in patients with mild to moderate glaucoma. Size V, which has lower retest variability, performs at least as well as size III for longitudinal glaucoma progression analysis and appears to have a larger useful dynamic range owing to the upper sensitivity limit being higher.

Reducing the visual burden of glaucoma in Asia: what we know and what we need to know.

PubMed

Congdon, Nathan

2009-01-01

Despite great progress in elucidating risk factors and effective treatments for eye disease in the last decades, blindness prevalence in the developing and developed world is either static or rising. A research agenda is needed to develop and test specific strategies to reduce the burden of blindness from glaucoma and other common eye diseases. Current knowledge about open and closed-angle glaucoma is reviewed and a strategy to reduce glaucoma blindness in Asia is suggested. A critical component of this strategy is enhanced training in the detection of narrow angles and optic nerve damage by direct examination. Specific research topics that could inform such a strategy are outlined.

Developmental approach towards high resolution optical coherence tomography for glaucoma diagnostics

NASA Astrophysics Data System (ADS)

Kemper, Björn; Ketelhut, Steffi; Heiduschka, Peter; Thorn, Marie; Larsen, Michael; Schnekenburger, Jürgen

2018-02-01

Glaucoma is caused by a pathological rise in the intraocular pressure, which results in a progressive loss of vision by a damage to retinal cells and the optical nerve head. Early detection of pressure-induced damage is thus essential for the reduction of eye pressure and to prevent severe incapacity or blindness. Within the new European Project GALAHAD (Glaucoma Advanced, Label free High Resolution Automated OCT Diagnostics), we will develop a new low-cost and high-resolution OCT system for the early detection of glaucoma. The device is designed to improve diagnosis based on a new system of optical coherence tomography. Although OCT systems are at present available in ophthalmology centres, high-resolution devices are extremely expensive. The novelty of the new Galahad system is its super wideband light source to achieve high image resolution at a reasonable cost. Proof of concept experiments with cell and tissue Glaucoma test standards and animal models are planned for the test of the new optical components and new algorithms performance for the identification of Glaucoma associated cell and tissue structures. The intense training of the software systems with various samples should result in a increased sensitivity and specificity of the OCT software system.

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

Management of Blood Pressure in Patients with Glaucoma.

PubMed

Levine, Russell M; Yang, Alina; Brahma, Venkatesh; Martone, James F

2017-09-19

Ocular perfusion pressure (OPP) is defined as the difference between BP and intraocular pressure (IOP). With low BP comes low OPP and resultant ischemic damage to the optic nerve, leading to glaucoma progression. The purpose of this article is to review the literature on BP as it relates to glaucoma and to create a forum of discussion between ophthalmologists and internal medicine specialists. Both high and low BP has been linked glaucoma. Low BP is particularly associated with glaucoma progression in normal-tension glaucoma (NTG) patients. Patients who have low nighttime BP readings are at highest risk of progression of their glaucoma. Internal medicine specialists and ophthalmologists should consider the relationship between BP and glaucoma when treating patients with concomitant disease. Too-low nighttime BP should be avoided. Ambulatory blood pressure monitoring is a useful tool to identify patients at greatest risk for progression.

Comparison of optical coherence tomography findings and visual field changes in patients with primary open-angle glaucoma and amyotrophic lateral sclerosis.

PubMed

Liu, Ziyuan; Wang, Hongli; Fan, Dongsheng; Wang, Wei

2018-02-01

Recent studies revealing genetic connection of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis (ALS) have received particular attention. Exploring the evidence for common pathogenesis of these two progressive neurological disorders may assist in understanding the mechanism and searching for new treatment. Retinal nerve fiber layer (RNFL) defect and corresponding visual field (VF) impairment are well known neuropathy signs in glaucoma. In our study, thickness of certain retinal layer in ALS patients was analyzed to detect ganglion cell's soma and axon, and for first time visual field was examined for ALS. The correlation of retinal involvement and ALS progression were also investigated. The results were compared with those of POAG. The study may provide new knowledge for these two neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

The Effective Dynamic Ranges for Glaucomatous Visual Field Progression With Standard Automated Perimetry and Stimulus Sizes III and V

PubMed Central

Zamba, Gideon K. D.; Artes, Paul H.

2018-01-01

Purpose It has been shown that threshold estimates below approximately 20 dB have little effect on the ability to detect visual field progression in glaucoma. We aimed to compare stimulus size V to stimulus size III, in areas of visual damage, to confirm these findings by using (1) a different dataset, (2) different techniques of progression analysis, and (3) an analysis to evaluate the effect of censoring on mean deviation (MD). Methods In the Iowa Variability in Perimetry Study, 120 glaucoma subjects were tested every 6 months for 4 years with size III SITA Standard and size V Full Threshold. Progression was determined with three complementary techniques: pointwise linear regression (PLR), permutation of PLR, and linear regression of the MD index. All analyses were repeated on “censored'' datasets in which threshold estimates below a given criterion value were set to equal the criterion value. Results Our analyses confirmed previous observations that threshold estimates below 20 dB contribute much less to visual field progression than estimates above this range. These findings were broadly similar with stimulus sizes III and V. Conclusions Censoring of threshold values < 20 dB has relatively little impact on the rates of visual field progression in patients with mild to moderate glaucoma. Size V, which has lower retest variability, performs at least as well as size III for longitudinal glaucoma progression analysis and appears to have a larger useful dynamic range owing to the upper sensitivity limit being higher. PMID:29356822

Glaucoma Progression and its Relationship with Corrected and Uncorrected Intraocular Pressure in Eyes with History of Refractive Corneal Surgery.

PubMed

Kwon, Junki; Sung, Kyung Rim; Jo, Jaehyuck; Yang, Sung Ho

2018-04-20

To investigate glaucoma progression and its relationship with corrected and uncorrected intraocular pressure (IOP) in patients with a history of refractive corneal surgery (RCS). Totally, 56 eyes of 56 primary open-angle glaucoma patients who had a history of RCS were included. Mean keratometry and central corneal thickness were measured at the time of glaucoma diagnosis. Three IOP measurements, i.e., uncorrected IOP ( UC IOP) and corrected IOP calculated by applying the Kohlhaas ( CK IOP) and Ehlers ( CE IOP) formulas, were used. Participants were categorized into two groups (low-teen [<15 mmHg] and high-teen [≥15 mmHg] groups) according to the mean follow-up IOP, in each of the three IOP measurements. Glaucoma progression was determined based on either structurally or functionally by stereoscopic optic disc/retinal nerve fiber layer photographs or visual field tests. Kaplan-Meier survival curves were compared between the low-teens group and high-teens group for each IOP measurement. Risk factors for glaucoma progression, including uncorrected and corrected IOP measurements, were analyzed using a Cox proportional-hazards model. Among total eyes, glaucoma progression was found in 19 (34%) eyes during 4.3 years of mean follow-up period. Individual values of uncorrected IOP and corrected IOP showed significant differences (p < 0.001). Incidence of glaucoma progression was higher in high-teens group than in low-teens group by corrected IOP values (both Kohlhaas and Ehlers, p = 0.006, 0.003), but not by uncorrected IOP values (p = 0.749). The cumulative probability of glaucoma progression was significantly greater in the high-teens group than in the low-teens group using the Elhers formula determined by Kaplan-Meier analysis (p = 0.030). For glaucoma eyes with history of RCS, high-teen group by corrected mean follow-up IOP showed more glaucoma progression than low-teen group. More intensive IOP-lowering treatment will be required for patient with high-teen follow-up corrected IOP to prevent glaucoma progression.

Ocular hemodynamics and glaucoma: the role of mathematical modeling.

PubMed

Harris, Alon; Guidoboni, Giovanna; Arciero, Julia C; Amireskandari, Annahita; Tobe, Leslie A; Siesky, Brent A

2013-01-01

To discuss the role of mathematical modeling in studying ocular hemodynamics, with a focus on glaucoma. We reviewed recent literature on glaucoma, ocular blood flow, autoregulation, the optic nerve head, and the use of mathematical modeling in ocular circulation. Many studies suggest that alterations in ocular hemodynamics play a significant role in the development, progression, and incidence of glaucoma. Although there is currently a limited number of studies involving mathematical modeling of ocular blood flow, regulation, and diseases (such as glaucoma), preliminary modeling work shows the potential of mathematical models to elucidate the mechanisms that contribute most significantly to glaucoma progression. Mathematical modeling is a useful tool when used synergistically with clinical and laboratory data in the study of ocular blood flow and glaucoma. The development of models to investigate the relationship between ocular hemodynamic alterations and glaucoma progression will provide a unique and useful method for studying the pathophysiology of glaucoma.

[A case of ring melanoma found while treating traumatic glaucoma].

PubMed

Manabe, Kazuyo; Jo, Nobuo; Tateno, Hiroko; Shishidon, Nami; Takahashi, Kanji; Iwashita, Kenshiro; Isei, Taiki; Ohe, Chisato; Sakaida, Noriko; Uemura, Yoshiko

2013-04-01

Ring melanoma, a malignant melanoma which infiltrates over 180 degrees degrees of the ciliary body is very rare in Japan. We report a case of ring melanoma found while treating treatment of traumatic glaucoma with an ultrasound biomicroscope (UBM). A 44-year old woman presented with high intraocular pressure after blunt trauma in her left eye. Best-corrected visual acuity OS was 1.2, and intraocular pressure was 30 mmHg. Gonioscopy showed about 180 degrees of the angle recession. Intraocular pressure was difficult to control in spite of anti-glaucoma drug treatment. Rapid progression of iris elevation and 360 degrees thickening of the ciliary body were detected by UBM. We detected atypical cells with melanine granules in the aqueous fluid and positive findings in PET-CT, leading to a diagnosis of ciliary body malignant melanoma. Consequently we enucleated the left eye. The histopathological diagnosis was ring melanoma. Ring melanoma is an important element in the differential diagnosis for untreatable secondary glaucoma.

A method to detect progression of glaucoma using the multifocal visual evoked potential technique

PubMed Central

Wangsupadilok, Boonchai; Kanadani, Fabio N.; Grippo, Tomas M.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2010-01-01

Purpose To describe a method for monitoring progression of glaucoma using the multifocal visual evoked potential (mfVEP) technique. Methods Eighty-seven patients diagnosed with open-angle glaucoma were divided into two groups. Group I, comprised 43 patients who had a repeat mfVEP test within 50 days (mean 0.9 ± 0.5 months), and group II, 44 patients who had a repeat test after at least 6 months (mean 20.7 ± 9.7 months). Monocular mfVEPs were obtained using a 60-sector pattern reversal dartboard display. Monocular and interocular analyses were performed. Data from the two visits were compared. The total number of abnormal test points with P < 5% within the visual field (total scores) and number of abnormal test points within a cluster (cluster size) were calculated. Data for group I provided a measure of test–retest variability independent of disease progression. Data for group II provided a possible measure of progression. Results The difference in the total scores for group II between visit 1 and visit 2 for the interocular and monocular comparison was significant (P < 0.05) as was the difference in cluster size for the interocular comparison (P < 0.05). Group I did not show a significant change in either total score or cluster size. Conclusion The change in the total score and cluster size over time provides a possible method for assessing progression of glaucoma with the mfVEP technique. PMID:18830654

Detection of retinal nerve fiber layer defects on retinal fundus images for early diagnosis of glaucoma

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Hayashi, Yoshinori; Sawada, Akira; Hatanaka, Yuji; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

2010-01-01

Retinal nerve fiber layer defect (NFLD) is a major sign of glaucoma, which is the second leading cause of blindness in the world. Early detection of NFLDs is critical for improved prognosis of this progressive, blinding disease. We have investigated a computerized scheme for detection of NFLDs on retinal fundus images. In this study, 162 images, including 81 images with 99 NFLDs, were used. After major blood vessels were removed, the images were transformed so that the curved paths of retinal nerves become approximately straight on the basis of ellipses, and the Gabor filters were applied for enhancement of NFLDs. Bandlike regions darker than the surrounding pixels were detected as candidates of NFLDs. For each candidate, image features were determined and the likelihood of a true NFLD was determined by using the linear discriminant analysis and an artificial neural network (ANN). The sensitivity for detecting the NFLDs was 91% at 1.0 false positive per image by using the ANN. The proposed computerized system for the detection of NFLDs can be useful to physicians in the diagnosis of glaucoma in a mass screening.

Scanning laser polarimetry in glaucoma

PubMed Central

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-01-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far. PMID:25494244

Scanning laser polarimetry in glaucoma.

PubMed

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-11-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far.

[Risk factors in the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients].

PubMed

Jass, C M; Böhringer, D; Erb, C; Jordan, J F

2013-11-01

Glaucoma is an ocular disease with typical progressive damage of the optic nerve. In the past it was postulated that glaucoma induces acquired colour vision disorders. Until now all studies about glaucoma and colour vision disorders did not include vascular risk factors. In the present study we determined several vascular risk factors concerning the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. On the basis of an analysis of variance (ANOVA) we determined the influence of several risk factors, such as arteriosclerotic and vasospastic risk factors, on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. 353 glaucoma patients were included in this study. We detected a strong influence of age and mean defect in perimetry and an additional effect of arteriosclerotic and vasospastic risk factors on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. We suspect that arteriosclerotic and vasospastic risk factors independently to glaucoma have an influence on colour vision. In the future attention additionally has to be given to vascular risk factors in the colour vision testing of glaucoma patients. Georg Thieme Verlag KG Stuttgart · New York.

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.).

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

Evaluation of Visual Field and Imaging Outcomes for Glaucoma Clinical Trials (An American Ophthalomological Society Thesis).

PubMed

Garway-Heath, David F; Quartilho, Ana; Prah, Philip; Crabb, David P; Cheng, Qian; Zhu, Haogang

2017-08-01

To evaluate the ability of various visual field (VF) analysis methods to discriminate treatment groups in glaucoma clinical trials and establish the value of time-domain optical coherence tomography (TD OCT) imaging as an additional outcome. VFs and retinal nerve fibre layer thickness (RNFLT) measurements (acquired by TD OCT) from 373 glaucoma patients in the UK Glaucoma Treatment Study (UKGTS) at up to 11 scheduled visits over a 2 year interval formed the cohort to assess the sensitivity of progression analysis methods. Specificity was assessed in 78 glaucoma patients with up to 11 repeated VF and OCT RNFLT measurements over a 3 month interval. Growth curve models assessed the difference in VF and RNFLT rate of change between treatment groups. Incident progression was identified by 3 VF-based methods: Guided Progression Analysis (GPA), 'ANSWERS' and 'PoPLR', and one based on VFs and RNFLT: 'sANSWERS'. Sensitivity, specificity and discrimination between treatment groups were evaluated. The rate of VF change was significantly faster in the placebo, compared to active treatment, group (-0.29 vs +0.03 dB/year, P <.001); the rate of RNFLT change was not different (-1.7 vs -1.1 dB/year, P =.14). After 18 months and at 95% specificity, the sensitivity of ANSWERS and PoPLR was similar (35%); sANSWERS achieved a sensitivity of 70%. GPA, ANSWERS and PoPLR discriminated treatment groups with similar statistical significance; sANSWERS did not discriminate treatment groups. Although the VF progression-detection method including VF and RNFLT measurements is more sensitive, it does not improve discrimination between treatment arms.

Lifestyles guide and glaucoma (II). Diet, supplements, drugs, sleep, pregnancy, and systemic hypertension.

PubMed

Antón-López, A; Moreno-Montañés, J; Duch-Tuesta, S; Corsino Fernández-Vila, P; García-Feijoo, J; Millá-Griñó, E; Muñoz-Negrete, F J; Pablo-Júlvez, L; Rodríguez-Agirretxe, I; Urcelay-Segura, J L; Ussa-Herrera, F; Villegas-Pérez, M P

2018-02-01

To establish evidence based guidelines to advise patients on the relationship between habits, diet, certain circumstances, diseases and glaucoma. Review of all published articles on glaucoma and sports or other activities. The papers were classified according to the level of scientific evidence based on the Oxford Centre for Evidence-based Medicine classification. The evidence on the relationship between diet or supplements and the incidence or progression of glaucoma is insufficient to make a general recommendation for glaucoma patients. Although some studies on normal tension glaucoma suggest that Gingko biloba could reduce glaucoma progression, the results do not allow a general recommendation for all these patients. Similarly, the evidence on the usefulness of vitamin supplements is not conclusive. The studies on smoking do not clearly demonstrate the relationship between this habit and incidence of glaucoma. Marihuana is not a useful treatment for glaucoma. Although the results on the relationship between sleep apnoea and glaucoma are heterogeneous, it is recommended that patients with moderate to intense apnoea are tested for glaucoma. Pregnancy does not influence the course of the disease, but several hypotensive drugs may be harmful for the foetus. Nocturnal systemic hypotension is a risk factor for glaucoma progression. Certain habits, circumstances, or diseases may have an influence on the onset or progression of glaucoma. It is important to have adequate information about the scientific evidence in the publications in order to properly advise patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

[Aiming for zero blindness].

PubMed

Nakazawa, Toru

2015-03-01

Glaucoma is the leading cause of acquired blindness in Japan. One reason that it often leads to blindness is that it can continue to worsen even after effective medical reduction of intraocular pressure (IOP), the only evidence-based treatment. The limitations of current treatments make it critical to identify IOP-independent factors that can cause glaucoma and develop new drugs to target these factors. This is a challenging task, as the pathology of glaucoma is thought to be very complex, with different combinations of factors underlying its development and progression in different patients. Additionally, there is a deficiency in methods to efficiently perform clinical evaluations and reliably probe the state of the disease over relatively short periods. In addition, newly developed drugs need to be evaluated with clinical trials, for which human and financial resources are limited, before they can be widely used for treatment. Taking all these issues into consideration, it is evident that there are two urgent issues to consider: the development of methods to classify glaucoma in detail based on its pathology, and the improvement of clinical evaluation methods. In this review, we discuss some of our efforts to develop new neuroprotective agents for glaucoma, with a focus on the following three areas: 1. Clinical research and development of methods to classify glaucoma in detail based on IOP-independent factors, and the exploration of possibilities for the improvement of clinical evaluation of glaucoma. 2. Pathology-based research and development of new drugs for glaucoma, focusing on comprehensive gene expression analysis and the development of molecule-targeting drugs, using murine optic nerve crush as a disease model. 3. Development of next generation in vivo imaging modalities and the establishment of infrastructure enabling "big-data" analysis. First, we discuss our clinical research and the development of methods to classify glaucoma in detail based on IOP-independent factors, as well as our investigation of ways to improve the clinical evaluation of the disease. Our research was prompted by the multifactorial nature of glaucoma. There is a high degree of variability in the pattern and speed of the progression of visual field defects in individual patients, presenting a major obstacle for successful clinical trials. To overcome this, we classified the eyes of glaucoma patients into 4 types, corresponding to the 4 patterns of glaucomatous optic nerve head morphology described: by Nicolela et al. and then tested the validity of this method by assessing the uniformity of clinical features in each group. We found that in normal tension glaucoma (NTG) eyes, each disc morphology group had a characteristic location in which the loss of circumpapillary retinal nerve fiber layer thickness (cpRNFLT; measured with optical coherence tomography: OCT) was most likely to occur. Furthermore, the incidence of reductions in visual acuity differed between the groups, as did the speed of visual field loss, the distribution of defective visual field test points, and the location of test points that were most susceptible to progressive damage, measured by Humphrey static perimetry. These results indicate that Nicolela's method of classifying eyes with glaucoma was able to overcome the difficulties caused by the diverse nature of the disease, at least to a certain extent. Building on these findings, we then set out to identify sectors of the visual field that correspond to the distribution of retinal nerve fibers, with the aim of detecting glaucoma progression with improved sensitivity. We first mapped the statistical correlation between visual field test points and cpRNFLT in each temporal clock-hour sector (from 6 to 12 o'clock), using OCT data from NTG patients. The resulting series of maps allowed us to identify areas containing visual field test points that were prone to be affected together as a group. We also used a similar method to identify visual field sectors within a 10 x 10 grid displayed by an OCT map of the macula. By analyzing both the visual field and the macular map sectors, we anticipate that a more accurate and sensitive detection of glaucoma progression can become possible. We also used laser speckle flowgraphy (LSFG) to assess optic nerve blood flow. We found that compared to healthy eyes, eyes with early-stage NTG had decreased blood flow, and the peak of the blood flow wave form of each heartbeat was delayed. Finally, we used a method combining swept source OCT (SS-OCT) and newly developed analysis software to reconstruct the entire lamina cribrosa, a structure situated deep in the optic nerve head. This morphological analysis returned preliminary data suggesting that alterations in the morphology of the lamina cribrosa are already present in the early stages of glaucoma. This result indicates that axonal injury, mediated by morphological abnormalities of the lamina cribrosa, is involved in the pathogenesis of glaucoma. The next topic discussed is the pathology-based drug research and development, focusing on the use of comprehensive gene expression analysis and the development of molecule-targeting drugs in a murine model of optic nerve injury. Learning from clinical data on glaucoma and the lamina cribrosa, we carried out basic research to first determine what factors regulate axonal injury, and then develop drugs targeting these factors. Specifically, we performed a comprehensive gene expression analysis, using a next generation sequencer, and pathway analysis of retinal samples obtained from a murine model of axonal injury. This analysis revealed a characteristic upregulation of genes (such as Chop) that belongs to the endoplasmic reticulum stress pathway. An immunohistological analysis revealed that these changes in gene expression took place in the retinal ganglion cells, suggesting that endoplasmic reticulum stress molecules may be suitable therapeutic targets. Among these molecules, we chose CHOP as our primary target for drug development. Currently, we are in the process of screening a library of 1274 drugs, all of which are already used in human subjects, for CHOP inhibitors. The last topic of our discussion is future possibilities for glaucoma management. First, we discuss the development of next generation in vivo imaging modalities that allow detailed description of pathomechanisms of this multifactorial disease, glaucoma. The purpose of this research was to improve the efficacy of glaucoma diagnosis and to visualize its pathology at a cellular/molecular level and develop molecule-specific therapies. Currently available visual field tests are subjective, since they rely on a determination of the threshold of light perception, and are affected by poor reproducibility. The current dependence on visual field tests to ascertain the progression of glaucoma is thus a serious limitation on an important task of ophthalmologists. We, therefore, turned our focus to the establishment of an in vivo imaging method to detect dying retinal ganglion cells, which would highlight the pathologic state of glaucoma with high sensitivity. To this end, we used confocal scanning ophthalmoscopy to assess the usefulness of SYTOX Orange as a cell death probe. Our results showed that this probe could reveal dying retinal ganglion cells clearly, quickly and with high sensitivity. We, therefore, believe that the clinical application of probes that can sensitively detect dying retinal ganglion cells is a highly promising approach. This also applies to the use of molecular tools that can provide information on the molecular pathology of glaucoma. Finally, we would like to introduce our national collaborative work on the analysis of "big-data". The project aims to collect as wide a range of data as possible at an unprecedented scale. The data to be registered ranges from basic glaucoma data, such as IOP and visual field test results, to data from the most sophisticated comprehensive expression analyses or imaging data. This is an important area of research, since it promises to enable the exploration of targets for drug discovery and the identification of new biomarkers to efficiently detect glaucoma progression by applying new analysis strategies to the complex mass data. The project not only depends on the collaborative efforts of various types of clinical settings including private practices, medical centers and university hospitals, but also contributions of the pharmaceutical and the medical device industries. Thus, uniting a wide range of Japanese interests and resources is the key for success. In summary, in order to aim for ZERO BLINDNESS, a drastic improvement in the quality of our patient care, drug development research for unmet medical demands, and a strategic collaboration of various professionals in the ophthalmic industry are essential. With the deep appreciation we fell towards the selfless support extended during the earthquake disaster, we wish to translate our "gratitude" into "power" from Tohoku. In doing so, we as academicians are determined to keep on contributing to the society by making progress in the medicine.

An Automatic Image Processing System for Glaucoma Screening

PubMed Central

Alodhayb, Sami; Lakshminarayanan, Vasudevan

2017-01-01

Horizontal and vertical cup to disc ratios are the most crucial parameters used clinically to detect glaucoma or monitor its progress and are manually evaluated from retinal fundus images of the optic nerve head. Due to the rarity of the glaucoma experts as well as the increasing in glaucoma's population, an automatically calculated horizontal and vertical cup to disc ratios (HCDR and VCDR, resp.) can be useful for glaucoma screening. We report on two algorithms to calculate the HCDR and VCDR. In the algorithms, level set and inpainting techniques were developed for segmenting the disc, while thresholding using Type-II fuzzy approach was developed for segmenting the cup. The results from the algorithms were verified using the manual markings of images from a dataset of glaucomatous images (retinal fundus images for glaucoma analysis (RIGA dataset)) by six ophthalmologists. The algorithm's accuracy for HCDR and VCDR combined was 74.2%. Only the accuracy of manual markings by one ophthalmologist was higher than the algorithm's accuracy. The algorithm's best agreement was with markings by ophthalmologist number 1 in 230 images (41.8%) of the total tested images. PMID:28947898

Neurodegeneration and Neuroprotection in Glaucoma

PubMed Central

Gauthier, Angela C.; Liu, Ji

2016-01-01

Glaucoma is the principal cause of irreversible blindness in the world. The disease leads to progressive optic nerve degeneration with a gradual loss of retinal ganglion cells. Neurodegeneration in glaucoma extends beyond the eye into the lateral geniculate nucleus and visual cortex, and the disease even shares some characteristics with other central nervous system degenerative disorders. Glaucoma destroys neurons through oxidative stress, impairment in axonal transport, neuroinflammation, and excitotoxicity. Autophagy may promote or inhibit disease progression. Currently, lowering intraocular pressure is the only way proven to delay glaucoma advancement. However, many new therapies are being developed, including antioxidants, adenosine receptor antagonists, Rho-pathway inhibitors, stem cell therapy, and neurotrophic factors. These therapies focus on neuroprotection, and they may eventually halt glaucoma progression or reverse the process of the disease itself. PMID:27505018

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.

Perspective: New Recommendations for the Treatment of Systemic Hypertension and their Potential Implications for Glaucoma Management.

PubMed

De Moraes, Carlos Gustavo; Cioffi, George A; Weinreb, Robert N; Liebmann, Jeffrey M

2018-05-10

There is compelling evidence that low systemic blood pressure is associated with glaucoma prevalence and progression. Recently, new guidelines for treatment of systemic hypertension have been implemented and recommend lower target blood pressure. These guidelines may have implications on the rates of glaucoma progression seen in clinical practice and how clinicians should be prepared to identify patients at risk. More importantly, a new paradigm to monitor glaucoma progression is patients treated for systemic hypertension may be warranted in light of these recent changes.

Early detection of glaucoma using fully automated disparity analysis of the optic nerve head (ONH) from stereo fundus images

NASA Astrophysics Data System (ADS)

Sharma, Archie; Corona, Enrique; Mitra, Sunanda; Nutter, Brian S.

2006-03-01

Early detection of structural damage to the optic nerve head (ONH) is critical in diagnosis of glaucoma, because such glaucomatous damage precedes clinically identifiable visual loss. Early detection of glaucoma can prevent progression of the disease and consequent loss of vision. Traditional early detection techniques involve observing changes in the ONH through an ophthalmoscope. Stereo fundus photography is also routinely used to detect subtle changes in the ONH. However, clinical evaluation of stereo fundus photographs suffers from inter- and intra-subject variability. Even the Heidelberg Retina Tomograph (HRT) has not been found to be sufficiently sensitive for early detection. A semi-automated algorithm for quantitative representation of the optic disc and cup contours by computing accumulated disparities in the disc and cup regions from stereo fundus image pairs has already been developed using advanced digital image analysis methodologies. A 3-D visualization of the disc and cup is achieved assuming camera geometry. High correlation among computer-generated and manually segmented cup to disc ratios in a longitudinal study involving 159 stereo fundus image pairs has already been demonstrated. However, clinical usefulness of the proposed technique can only be tested by a fully automated algorithm. In this paper, we present a fully automated algorithm for segmentation of optic cup and disc contours from corresponding stereo disparity information. Because this technique does not involve human intervention, it eliminates subjective variability encountered in currently used clinical methods and provides ophthalmologists with a cost-effective and quantitative method for detection of ONH structural damage for early detection of glaucoma.

Perimetric progression using the Visual Field Index and the Advanced Glaucoma Intervention Study score and its clinical correlations.

PubMed

Gros-Otero, Juan; Castejón, Miguel; Paz-Moreno, Javier; Mikropoulos, Dimitrios; Teus, Miguel

2015-01-01

To evaluate the association between clinical parameters and the diagnosis of progression using VFI (Visual Field Index) and AGIS (Advanced Glaucoma Intervention Study) score in primary open angle glaucoma. Retrospective study of 517 visual fields of 78 eyes with primary open angle glaucoma analyzed with VFI and AGIS score. Clinical data registered included: age, sphere, pachimetry, basal intraocular pressure (IOP), and IOP during the follow up. Only the AGIS score diagnosis of progression was associated with the clinical parameters registered. Among the analyzed data, the mean IOP during follow up (p = 0.0005) and IOP at the third month of follow up (p = 0.004) were statistically associated with progression using the AGIS criteria. The diagnosis of perimetric progression using the AGIS score in the current study was closer to the real functional progression than the diagnosis using the VFI, as the former was associated with known risk factors for progression in glaucoma. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) for adults at risk for glaucoma: study rationale and design.

PubMed

Owsley, Cynthia; Rhodes, Lindsay A; McGwin, Gerald; Mennemeyer, Stephen T; Bregantini, Mary; Patel, Nita; Wiley, Demond M; LaRussa, Frank; Box, Dan; Saaddine, Jinan; Crews, John E; Girkin, Christopher A

2015-11-18

Primary open angle glaucoma is a chronic, progressive eye disease that is the leading cause of blindness among African Americans. Glaucoma progresses more rapidly and appears about 10 years earlier in African Americans as compared to whites. African Americans are also less likely to receive comprehensive eye care when glaucoma could be detected before irreversible blindness. Screening and follow-up protocols for managing glaucoma recommended by eye-care professional organizations are often not followed by primary eye-care providers, both ophthalmologists and optometrists. There is a pressing need to improve both the accessibility and quality of glaucoma care for African Americans. Telemedicine may be an effective solution for improving management and diagnosis of glaucoma because it depends on ocular imaging and tests that can be electronically transmitted to remote reading centers where tertiary care specialists can examine the results. We describe the Eye Care Quality and Accessibility Improvement in the Community project (EQUALITY), set to evaluate a teleglaucoma program deployed in retail-based primary eye care practices serving communities with a large percentage of African Americans. We conducted an observational, 1-year prospective study based in two Walmart Vision Centers in Alabama staffed by primary care optometrists. EQUALITY focuses on new or existing adult patients who are at-risk for glaucoma or already diagnosed with glaucoma. Patients receive dilated comprehensive examinations and diagnostic testing for glaucoma, followed by the optometrist's diagnosis and a preliminary management plan. Results are transmitted to a glaucoma reading center where ophthalmologists who completed fellowship training in glaucoma review results and provide feedback to the optometrist, who manages the care of the patient. Patients also receive eye health education about glaucoma and comprehensive eye care. Research questions include diagnostic and management agreement between providers, the impact of eye health education on patients' knowledge and adherence to follow-up and medication, patient satisfaction, program cost-effectiveness, and EQUALITY's impact on Walmart pharmacy prescription rates. As eye-care delivery systems in the US strive to improve quality while reducing costs, telemedicine programs including teleglaucoma initiatives such as EQUALITY could contribute toward reaching this goal, particularly among underserved populations at-risk for chronic blinding diseases.

Cost and detection rate of glaucoma screening with imaging devices in a primary care center

PubMed Central

Anton, Alfonso; Fallon, Monica; Cots, Francesc; Sebastian, María A; Morilla-Grasa, Antonio; Mojal, Sergi; Castells, Xavier

2017-01-01

Purpose To analyze the cost and detection rate of a screening program for detecting glaucoma with imaging devices. Materials and methods In this cross-sectional study, a glaucoma screening program was applied in a population-based sample randomly selected from a population of 23,527. Screening targeted the population at risk of glaucoma. Examinations included optic disk tomography (Heidelberg retina tomograph [HRT]), nerve fiber analysis, and tonometry. Subjects who met at least 2 of 3 endpoints (HRT outside normal limits, nerve fiber index ≥30, or tonometry ≥21 mmHg) were referred for glaucoma consultation. The currently established (“conventional”) detection method was evaluated by recording data from primary care and ophthalmic consultations in the same population. The direct costs of screening and conventional detection were calculated by adding the unit costs generated during the diagnostic process. The detection rate of new glaucoma cases was assessed. Results The screening program evaluated 414 subjects; 32 cases were referred for glaucoma consultation, 7 had glaucoma, and 10 had probable glaucoma. The current detection method assessed 677 glaucoma suspects in the population, of whom 29 were diagnosed with glaucoma or probable glaucoma. Glaucoma screening and the conventional detection method had detection rates of 4.1% and 3.1%, respectively, and the cost per case detected was 1,410 and 1,435€, respectively. The cost of screening 1 million inhabitants would be 5.1 million euros and would allow the detection of 4,715 new cases. Conclusion The proposed screening method directed at population at risk allows a detection rate of 4.1% and a cost of 1,410 per case detected. PMID:28243057

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.

Structural and Functional Evaluations for the Early Detection of Glaucoma.

PubMed

Lucy, Katie A; Wollstein, Gadi

2016-01-01

The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection.

Structural and Functional Evaluations for the Early Detection of Glaucoma

PubMed Central

Lucy, Katie A.; Wollstein, Gadi

2016-01-01

The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection. PMID:28603546

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.

Determining immune components necessary for progression of pigment dispersing disease to glaucoma in DBA/2J mice

PubMed Central

2014-01-01

Background The molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1 b and Gpnmb R150X ) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP. Results We tested the role of NK cells in disease etiology by genetically modifying the B6.D2-Gpnmb R150X Tyrp1 b strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of Gpnmb R150X Tyrp1 b mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage. Conclusion Our previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression. PMID:24678736

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

Improving Access to Eye Care among Persons at High-Risk of Glaucoma in Philadelphia — Design and Methodology: The Philadelphia Glaucoma Detection and Treatment Project

PubMed Central

Myers, Jonathan S.; Henderer, Jeffrey; Crews, John E.; Saaddine, Jinan B.; Molineaux, Jeanne; Johnson, Deiana; Sembhi, Harjeet; Stratford, Shayla; Suleiman, Ayman; Pizzi, Laura; Spaeth, George L.; Katz, L. Jay

2016-01-01

Purpose The Wills Eye Glaucoma Research Center initiated a 2-year demonstration project to develop and implement a community-based intervention to improve detection and management of glaucoma in Philadelphia. Methods The glaucoma detection examination consisted of: ocular, medical, and family history; visual acuity testing; corneal pachymetry; biomicroscopy of the anterior segment; intraocular pressure (IOP) measurement; gonioscopy; funduscopy; automated visual field testing; and fundus-color photography. Treatment included laser surgery and/or IOP-lowering medication. A cost analysis was conducted to understand resource requirements. Outcome measures included; prevalence of glaucoma-related pathology and other eye diseases among high-risk populations; the impact of educational workshops on level of knowledge about glaucoma (assessed by pre- and post-test evaluation); and patient satisfaction of the glaucoma detection examinations in the community (assessed by satisfaction survey). Treatment outcome measures were change in IOP at 4–6 weeks and 4–6 months following selective laser trabeculoplasty treatment, deepening of the anterior chamber angle following laser-peripheral iridotomy treatment, and rate of adherence to recommended follow-up examinations. Cost outcomes included total program costs, cost per case of glaucoma detected, and cost per case of ocular disease detected. Results This project enrolled 1649 participants (African Americans aged 50+ years, adults 60+ years and individuals with a family history of glaucoma). A total of 1074 individuals attended a glaucoma educational workshop and 1508 scheduled glaucoma detection examination appointments in the community setting. Conclusions The Philadelphia Glaucoma Detection and Treatment Project aimed to improve access and use of eye care and to provide a model for a targeted community-based glaucoma program. PMID:26950056

Improving Access to Eye Care among Persons at High-Risk of Glaucoma in Philadelphia--Design and Methodology: The Philadelphia Glaucoma Detection and Treatment Project.

PubMed

Hark, Lisa; Waisbourd, Michael; Myers, Jonathan S; Henderer, Jeffrey; Crews, John E; Saaddine, Jinan B; Molineaux, Jeanne; Johnson, Deiana; Sembhi, Harjeet; Stratford, Shayla; Suleiman, Ayman; Pizzi, Laura; Spaeth, George L; Katz, L Jay

2016-01-01

The Wills Eye Glaucoma Research Center initiated a 2-year demonstration project to develop and implement a community-based intervention to improve detection and management of glaucoma in Philadelphia. The glaucoma detection examination consisted of: ocular, medical, and family history; visual acuity testing; corneal pachymetry; biomicroscopy of the anterior segment; intraocular pressure (IOP) measurement; gonioscopy; funduscopy; automated visual field testing; and fundus-color photography. Treatment included laser surgery and/or IOP-lowering medication. A cost analysis was conducted to understand resource requirements. Outcome measures included; prevalence of glaucoma-related pathology and other eye diseases among high-risk populations; the impact of educational workshops on level of knowledge about glaucoma (assessed by pre- and post-test evaluation); and patient satisfaction of the glaucoma detection examinations in the community (assessed by satisfaction survey). Treatment outcome measures were change in IOP at 4-6 weeks and 4-6 months following selective laser trabeculoplasty treatment, deepening of the anterior chamber angle following laser-peripheral iridotomy treatment, and rate of adherence to recommended follow-up examinations. Cost outcomes included total program costs, cost per case of glaucoma detected, and cost per case of ocular disease detected. This project enrolled 1649 participants (African Americans aged 50+ years, adults 60+ years and individuals with a family history of glaucoma). A total of 1074 individuals attended a glaucoma educational workshop and 1508 scheduled glaucoma detection examination appointments in the community setting. The Philadelphia Glaucoma Detection and Treatment Project aimed to improve access and use of eye care and to provide a model for a targeted community-based glaucoma program.

[Visual field progression in glaucoma: cluster analysis].

PubMed

Bresson-Dumont, H; Hatton, J; Foucher, J; Fonteneau, M

2012-11-01

Visual field progression analysis is one of the key points in glaucoma monitoring, but distinction between true progression and random fluctuation is sometimes difficult. There are several different algorithms but no real consensus for detecting visual field progression. The trend analysis of global indices (MD, sLV) may miss localized deficits or be affected by media opacities. Conversely, point-by-point analysis makes progression difficult to differentiate from physiological variability, particularly when the sensitivity of a point is already low. The goal of our study was to analyse visual field progression with the EyeSuite™ Octopus Perimetry Clusters algorithm in patients with no significant changes in global indices or worsening of the analysis of pointwise linear regression. We analyzed the visual fields of 162 eyes (100 patients - 58 women, 42 men, average age 66.8 ± 10.91) with ocular hypertension or glaucoma. For inclusion, at least six reliable visual fields per eye were required, and the trend analysis (EyeSuite™ Perimetry) of visual field global indices (MD and SLV), could show no significant progression. The analysis of changes in cluster mode was then performed. In a second step, eyes with statistically significant worsening of at least one of their clusters were analyzed point-by-point with the Octopus Field Analysis (OFA). Fifty four eyes (33.33%) had a significant worsening in some clusters, while their global indices remained stable over time. In this group of patients, more advanced glaucoma was present than in stable group (MD 6.41 dB vs. 2.87); 64.82% (35/54) of those eyes in which the clusters progressed, however, had no statistically significant change in the trend analysis by pointwise linear regression. Most software algorithms for analyzing visual field progression are essentially trend analyses of global indices, or point-by-point linear regression. This study shows the potential role of analysis by clusters trend. However, for best results, it is preferable to compare the analyses of several tests in combination with morphologic exam. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis).

PubMed

Fingert, John H; Robin, Alan L; Scheetz, Todd E; Kwon, Young H; Liebmann, Jeffrey M; Ritch, Robert; Alward, Wallace L M

2016-08-01

To investigate the role of TANK-binding kinase 1 ( TBK1 ) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay. No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.

Automated detection of nerve fiber layer defects on retinal fundus images using fully convolutional network for early diagnosis of glaucoma

NASA Astrophysics Data System (ADS)

Watanabe, Ryusuke; Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2017-03-01

Early detection of glaucoma is important to slow down progression of the disease and to prevent total vision loss. We have been studying an automated scheme for detection of a retinal nerve fiber layer defect (NFLD), which is one of the earliest signs of glaucoma on retinal fundus images. In our previous study, we proposed a multi-step detection scheme which consists of Gabor filtering, clustering and adaptive thresholding. The problems of the previous method were that the number of false positives (FPs) was still large and that the method included too many rules. In attempt to solve these problems, we investigated the end-to-end learning system without pre-specified features. A deep convolutional neural network (DCNN) with deconvolutional layers was trained to detect NFLD regions. In this preliminary investigation, we investigated effective ways of preparing the input images and compared the detection results. The optimal result was then compared with the result obtained by the previous method. DCNN training was carried out using original images of abnormal cases, original images of both normal and abnormal cases, ellipse-based polar transformed images, and transformed half images. The result showed that use of both normal and abnormal cases increased the sensitivity as well as the number of FPs. Although NFLDs are visualized with the highest contrast in green plane, the use of color images provided higher sensitivity than the use of green image only. The free response receiver operating characteristic curve using the transformed color images, which was the best among seven different sets studied, was comparable to that of the previous method. Use of DCNN has a potential to improve the generalizability of automated detection method of NFLDs and may be useful in assisting glaucoma diagnosis on retinal fundus images.

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.

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

Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis)

PubMed Central

Fingert, John H.; Robin, Alan L.; Scheetz, Todd E.; Kwon, Young H.; Liebmann, Jeffrey M.; Ritch, Robert; Alward, Wallace L.M.

2016-01-01

Purpose To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. Methods In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas—juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)—using a quantitative polymerase chain reaction assay. Results No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. Conclusions TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma. PMID:27881886

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.

Long Term Results of Visual Field Progression Analysis in Open Angle Glaucoma Patients Under Treatment.

PubMed

Kocatürk, Tolga; Bekmez, Sinan; Katrancı, Merve; Çakmak, Harun; Dayanır, Volkan

2015-01-01

To evaluate visual field progression with trend and event analysis in open angle glaucoma patients under treatment. Fifteen year follow-up results of 408 eyes of 217 glaucoma patients who were followed at Adnan Menderes University, Department of Ophthalmology between 1998 and 2013 were analyzed retrospectively. Visual field data were collected for Mean Deviation (MD), Visual Field Index (VFI), and event occurrence. There were 146 primary open-angle glaucoma (POAG), 123 pseudoexfoliative glaucoma (XFG) and 139 normal tension glaucoma (NTG) eyes. MD showed significant change in all diagnostic groups (p<0.001). The difference of VFI between first and last examinations were significantly different in POAG (p<0.001), and XFG (p<0.003) but not in NTG. VFI progression rates were -0.3, -0.43, and -0.2 % loss/year in treated POAG, XFG, and NTG, respectively. The number of empty triangles were statistically different between POAG-NTG (p=0.001), and XFG-NTG (p=0.002) groups. The number of half-filled (p=0.002), and full-filled (p=0.010) triangles were significantly different between XFG-NTG groups. Functional long-term follow-up of glaucoma patients can be monitored with visual field indices. We herein report our fifteen year follow-up results in open angle glaucoma.

Heidelberg edge perimeter employment in glaucoma diagnosis--preliminary report.

PubMed

Mulak, Małgorzata; Szumny, Dorota; Sieja-Bujewska, Anna; Kubrak, Magdalena

2012-01-01

In recent years, the authors have seen huge progress in the diagnosis of eye diseases. One of the new diagnostic devices is HEP (Heidelberg Edge Perimeter) - for early diagnosis of glaucoma and its progression. It combines visual field test and HRT (Heidelberg Retina Tomograph), which allows authors to obtain the image of the mutual relation between the structure and the function of the sight organ. It could be also used to assess patients with impaired retina, optic nerve and neurological deficits. The SAP function is more suitable for the detection and monitoring of neurological deficits, moderately advanced and advanced glaucoma as well as other diseases associated with extensive or deep visual field deficits, such as ischemic optic neuropathy. FDF stimulus was designed specifically to detect early glaucoma-related changes in the visual field. For about a year, the Ophthalmology Clinic in Wrocław has owned a new, unique HEP perimeter. The authors present examples of patients diagnosed and treated at the Clinic, with respect to whom the perimeter results obtained using Octopus type perimeter and HEP contour perimeter have been compared. This method has its advantages: it is non-invasive, objective, provides the opportunity to repeat and compare results obtained from subsequent tests. The disadvantages are the difficulty in adapting to a new stimulus, which is not a circular light stimulus, but an outline that is hard to notice for some patients. Although according to the manufacturer the testing time should not exceed 4-5 minutes, it takes 14-15 minutes in many patients. The test is not suitable for patients showing lower manual skills and less attention and those who tire out easily. The HEP perimeter is an innovative method for diagnosing the earliest changes in ganglion cells, that is pre-perimetric glaucoma, or when changes in the visual field are undetectable in a standard test.

Normal-tension glaucoma (Low-tension glaucoma)

PubMed Central

Anderson, Douglas R

2011-01-01

Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP), with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG), defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like), or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wisein mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective. PMID:21150042

The Health Of Patients' Eyes (HOPE) Glaucoma study. The effectiveness of a 'glaucoma personal record' for newly diagnosed glaucoma patients: study protocol for a randomised controlled trial.

PubMed

Forbes, Marina; Fairlamb, Helen; Jonker, Leon

2015-08-07

Glaucoma involves progressive optic nerve fibre loss, subsequently leading to irreversible and disabling visual field defects. In Europe, the prevalence of glaucoma is approximately 2.2 % of all people aged over 40 years; this equates to 12 million people. Glaucoma patients require regular lifelong follow-up, contributing to a large financial and resource burden for the National Health Service (NHS) in the UK. This study aims to determine whether providing newly diagnosed glaucoma patients with a personalised client-held eye health summary ('glaucoma personal record'), improves patients' knowledge of their glaucoma condition. A potential long-term benefit could be improved self-management and henceforth a slower rate of deterioration. HOPE Glaucoma is a 3-year, prospective, parallel-group, pragmatic, single-centred, randomised controlled trial. An anticipated 122 adults, newly diagnosed with glaucoma (including ocular hypertension, suspected glaucoma and/or chronic open-angle glaucoma) will be recruited from a nurse-led ophthalmology outpatient clinic at a medium-sized NHS Trust. Participants will be randomly allocated to receive standard clinical care (control arm) or standard care plus a glaucoma personal record, detailing the current state of their condition (interventional arm). Participant assessments are designed to test whether provision of a glaucoma personal record 1) improves patient knowledge of glaucoma and 2) contributes to improvements in clinical outcomes, i.e. delay of visual field loss. The primary outcome measure is better client knowledge of glaucoma at the 9-12 month follow-up visit. Secondary outcome measures include the rate of visual field loss and patient-reported outcome measures on visual function (National Eye Institute VFQ - 25) measured at baseline, 9-12 months, 24 months and 36 months. Estimating a 20 % drop-out rate, the study will have 90 % power to detect a mean two-point difference in glaucoma knowledge score between groups at 5 % significance - based on two-sided Mann-Whitney U test. If a glaucoma personal record is found to significantly improve glaucoma patients' knowledge of their condition, this intervention could potentially provide a low-cost, straightforward tool to educate and engage glaucoma patients. Subsequently, this could have the potential to increase patient self-management and therefore allow glaucoma patients to prolong their sight functionality for longer. ISRCTN41306818 , registered on 22 August 2013.

Childhood glaucoma surgery in the 21st Century

PubMed Central

Papadopoulos, M; Edmunds, B; Fenerty, C; Khaw, P T

2014-01-01

Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma. PMID:24924446

Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

PubMed

Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

2013-06-01

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Central corneal thickness and progression of the visual field and optic disc in glaucoma

PubMed Central

Chauhan, B C; Hutchison, D M; LeBlanc, R P; Artes, P H; Nicolela, M T

2005-01-01

Aims: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. Methods: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. Results: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression. PMID:16024855

Log-gamma linear-mixed effects models for multiple outcomes with application to a longitudinal glaucoma study

PubMed Central

Zhang, Peng; Luo, Dandan; Li, Pengfei; Sharpsten, Lucie; Medeiros, Felipe A.

2015-01-01

Glaucoma is a progressive disease due to damage in the optic nerve with associated functional losses. Although the relationship between structural and functional progression in glaucoma is well established, there is disagreement on how this association evolves over time. In addressing this issue, we propose a new class of non-Gaussian linear-mixed models to estimate the correlations among subject-specific effects in multivariate longitudinal studies with a skewed distribution of random effects, to be used in a study of glaucoma. This class provides an efficient estimation of subject-specific effects by modeling the skewed random effects through the log-gamma distribution. It also provides more reliable estimates of the correlations between the random effects. To validate the log-gamma assumption against the usual normality assumption of the random effects, we propose a lack-of-fit test using the profile likelihood function of the shape parameter. We apply this method to data from a prospective observation study, the Diagnostic Innovations in Glaucoma Study, to present a statistically significant association between structural and functional change rates that leads to a better understanding of the progression of glaucoma over time. PMID:26075565

Short-wavelength automated perimetry and frequency-doubling technology perimetry in glaucoma.

PubMed

Fogagnolo, Paolo; Rossetti, Luca; Ranno, Stefano; Ferreras, Antonio; Orzalesi, Nicola

2008-01-01

Standard automated perimetry (SAP) is today still the clinical standard for the management of glaucoma and its progression, though it has been shown that it may detect the disease only after the death of a high number of retinal ganglion cells (RGCs). A number of "unconventional" perimetries have recently been evaluated by several clinical studies which showed their ability to identify the earliest glaucoma changes; the most promising of these techniques are short-wavelength automated perimetry (SWAP) and frequency-doubling technology perimetry (FDT). The applicability of these techniques is still limited by a number of factors: the limited economic resources allocated to perimetry; the paucity of well-conducted, prospective longitudinal studies showing the superiority of SWAP and FDT over SAP; and the lack of a consensus on the criteria to define test abnormality with these techniques. The aim of this article is to review the rationale, the limits, and the potentiality of SWAP and FDT for glaucoma management and to summarize the tasks required to improve the clinical usefulness of these two instruments in the future.

Costs of a community-based glaucoma detection programme: analysis of the Philadelphia Glaucoma Detection and Treatment Project.

PubMed

Pizzi, Laura T; Waisbourd, Michael; Hark, Lisa; Sembhi, Harjeet; Lee, Paul; Crews, John E; Saaddine, Jinan B; Steele, Deon; Katz, L Jay

2018-02-01

Glaucoma is the foremost cause of irreversible blindness, and more than 50% of cases remain undiagnosed. Our objective was to report the costs of a glaucoma detection programme operationalised through Philadelphia community centres. The analysis was performed using a healthcare system perspective in 2013 US dollars. Costs of examination and educational workshops were captured. Measures were total programme costs, cost/case of glaucoma detected and cost/case of any ocular disease detected (including glaucoma). Diagnoses are reported at the individual level (therefore representing a diagnosis made in one or both eyes). Staff time was captured during site visits to 15 of 43 sites and included time to deliver examinations and workshops, supervision, training and travel. Staff time was converted to costs by applying wage and fringe benefit costs from the US Bureau of Labor Statistics. Non-staff costs (equipment and mileage) were collected using study logs. Participants with previously diagnosed glaucoma were excluded. 1649 participants were examined. Mean total per-participant examination time was 56 min (SD 4). Mean total examination cost/participant was $139. The cost/case of glaucoma newly identified (open-angle glaucoma, angle-closure glaucoma, glaucoma suspect, or primary angle closure) was $420 and cost/case for any ocular disease identified was $273. Glaucoma examinations delivered through this programme provided significant health benefit to hard-to-reach communities. On a per-person basis, examinations were fairly low cost, though opportunities exist to improve efficiency. Findings serve as an important benchmark for planning future community-based glaucoma examination programmes. © 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.

Does the Location of Bruch's Membrane Opening Change Over Time? Longitudinal Analysis Using San Diego Automated Layer Segmentation Algorithm (SALSA).

PubMed

Belghith, Akram; Bowd, Christopher; Medeiros, Felipe A; Hammel, Naama; Yang, Zhiyong; Weinreb, Robert N; Zangwill, Linda M

2016-02-01

We determined if the Bruch's membrane opening (BMO) location changes over time in healthy eyes and eyes with progressing glaucoma, and validated an automated segmentation algorithm for identifying the BMO in Cirrus high-definition coherence tomography (HD-OCT) images. We followed 95 eyes (35 progressing glaucoma and 60 healthy) for an average of 3.7 ± 1.1 years. A stable group of 50 eyes had repeated tests over a short period. In each B-scan of the stable group, the BMO points were delineated manually and automatically to assess the reproducibility of both segmentation methods. Moreover, the BMO location variation over time was assessed longitudinally on the aligned images in 3D space point by point in x, y, and z directions. Mean visual field mean deviation at baseline of the progressing glaucoma group was -7.7 dB. Mixed-effects models revealed small nonsignificant changes in BMO location over time for all directions in healthy eyes (the smallest P value was 0.39) and in the progressing glaucoma eyes (the smallest P value was 0.30). In the stable group, the overall intervisit-intraclass correlation coefficient (ICC) and coefficient of variation (CV) were 98.4% and 2.1%, respectively, for the manual segmentation and 98.1% and 1.9%, respectively, for the automated algorithm. Bruch's membrane opening location was stable in normal and progressing glaucoma eyes with follow-up between 3 and 4 years indicating that it can be used as reference point in monitoring glaucoma progression. The BMO location estimation with Cirrus HD-OCT using manual and automated segmentation showed excellent reproducibility.

The Philadelphia Glaucoma Detection and Treatment Project

PubMed Central

Waisbourd, Michael; Pruzan, Noelle L.; Johnson, Deiana; Ugorets, Angela; Crews, John E.; Saaddine, Jinan B.; Henderer, Jeffery D.; Hark, Lisa A.; Katz, L. Jay

2016-01-01

Purpose To evaluate the detection rates of glaucoma-related diagnoses and the initial treatments received in the Philadelphia Glaucoma Detection and Treatment Project, a community-based initiative aimed at improving the detection, treatment, and follow-up care of individuals at risk for glaucoma. Design Retrospective analysis. Participants A total of 1649 individuals at risk for glaucoma who were examined and treated in 43 community centers located in underserved communities of Philadelphia. Methods Individuals were enrolled if they were African American aged ≥50 years, were any other adult aged ≥60 years, or had a family history of glaucoma. After attending an informational glaucoma workshop, participants underwent a targeted glaucoma examination including an ocular, medical, and family history; visual acuity testing, intraocular pressure (IOP) measurement, and corneal pachymetry; slit-lamp and optic nerve examination; automated visual field testing; and fundus color photography. If indicated, treatments included selective laser trabeculoplasty (SLT), laser peripheral iridotomy (LPI), or IOP-lowering medications. Follow-up examinations were scheduled at the community sites after 4 to 6 weeks or 4 to 6 months, depending on the clinical scenario. Main Outcome Measures Detection rates of glaucoma-related diagnoses and types of treatments administered. Results Of the 1649 individuals enrolled, 645 (39.1%) received a glaucoma-related diagnosis; 20.0% (n = 330) were identified as open-angle glaucoma (OAG) suspects, 9.2% (n = 151) were identified as having narrow angles (or as a primary angle closure/suspect), and 10.0% (n = 164) were diagnosed with glaucoma, including 9.0% (n = 148) with OAG and 1.0% (n = 16) with angle-closure glaucoma. Overall, 39.0% (n = 64 of 164) of those diagnosed with glaucoma were unaware of their diagnosis. A total of 196 patients (11.9%) received glaucoma-related treatment, including 84 (5.1%) who underwent LPI, 13 (0.8%) who underwent SLT, and 103 (6.2%) who were prescribed IOP-lowering medication. Conclusions Targeting individuals at risk for glaucoma in underserved communities in Philadelphia yielded a high detection rate (39.1%) of glaucoma-related diagnoses. Providing examinations and offering treatment, including first-line laser procedures, at community-based sites providing services to older adults are effective to improve access to eye care by underserved populations. PMID:27221736

Effect of Age and Glaucoma on the Detection of Darks and Lights

PubMed Central

Zhao, Linxi; Sendek, Caroline; Davoodnia, Vandad; Lashgari, Reza; Dul, Mitchell W.; Zaidi, Qasim; Alonso, Jose-Manuel

2015-01-01

Purpose We have shown previously that normal observers detect dark targets faster and more accurately than light targets, when presented in noisy backgrounds. We investigated how these differences in detection time and accuracy are affected by age and ganglion cell pathology associated with glaucoma. Methods We asked 21 glaucoma patients, 21 age-similar controls, and 5 young control observers to report as fast as possible the number of 1 to 3 light or dark targets. The targets were positioned at random in a binary noise background, within the central 30° of the visual field. Results We replicate previous findings that darks are detected faster and more accurately than lights. We extend these findings by demonstrating that differences in detection of darks and lights are found reliably across different ages and in observers with glaucoma. We show that differences in detection time increase at a rate of approximately 55 msec/dB at early stages of glaucoma and then remain constant at later stages at approximately 800 msec. In normal subjects, differences in detection time increase with age at a rate of approximately 8 msec/y. We also demonstrate that the accuracy to detect lights and darks is significantly correlated with the severity of glaucoma and that the mean detection time is significantly longer for subjects with glaucoma than age-similar controls. Conclusions We conclude that differences in detection of darks and lights can be demonstrated over a wide range of ages, and asymmetries in dark/light detection increase with age and early stages of glaucoma. PMID:26513506

Effect of Age and Glaucoma on the Detection of Darks and Lights.

PubMed

Zhao, Linxi; Sendek, Caroline; Davoodnia, Vandad; Lashgari, Reza; Dul, Mitchell W; Zaidi, Qasim; Alonso, Jose-Manuel

2015-10-01

We have shown previously that normal observers detect dark targets faster and more accurately than light targets, when presented in noisy backgrounds. We investigated how these differences in detection time and accuracy are affected by age and ganglion cell pathology associated with glaucoma. We asked 21 glaucoma patients, 21 age-similar controls, and 5 young control observers to report as fast as possible the number of 1 to 3 light or dark targets. The targets were positioned at random in a binary noise background, within the central 30° of the visual field. We replicate previous findings that darks are detected faster and more accurately than lights. We extend these findings by demonstrating that differences in detection of darks and lights are found reliably across different ages and in observers with glaucoma. We show that differences in detection time increase at a rate of approximately 55 msec/dB at early stages of glaucoma and then remain constant at later stages at approximately 800 msec. In normal subjects, differences in detection time increase with age at a rate of approximately 8 msec/y. We also demonstrate that the accuracy to detect lights and darks is significantly correlated with the severity of glaucoma and that the mean detection time is significantly longer for subjects with glaucoma than age-similar controls. We conclude that differences in detection of darks and lights can be demonstrated over a wide range of ages, and asymmetries in dark/light detection increase with age and early stages of glaucoma.

Glaucoma risk index: automated glaucoma detection from color fundus images.

PubMed

Bock, Rüdiger; Meier, Jörg; Nyúl, László G; Hornegger, Joachim; Michelson, Georg

2010-06-01

Glaucoma as a neurodegeneration of the optic nerve is one of the most common causes of blindness. Because revitalization of the degenerated nerve fibers of the optic nerve is impossible early detection of the disease is essential. This can be supported by a robust and automated mass-screening. We propose a novel automated glaucoma detection system that operates on inexpensive to acquire and widely used digital color fundus images. After a glaucoma specific preprocessing, different generic feature types are compressed by an appearance-based dimension reduction technique. Subsequently, a probabilistic two-stage classification scheme combines these features types to extract the novel Glaucoma Risk Index (GRI) that shows a reasonable glaucoma detection performance. On a sample set of 575 fundus images a classification accuracy of 80% has been achieved in a 5-fold cross-validation setup. The GRI gains a competitive area under ROC (AUC) of 88% compared to the established topography-based glaucoma probability score of scanning laser tomography with AUC of 87%. The proposed color fundus image-based GRI achieves a competitive and reliable detection performance on a low-priced modality by the statistical analysis of entire images of the optic nerve head. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Epidemiology of Glaucoma in Sub-Saharan Africa: Prevalence, Incidence and Risk Factors

PubMed Central

Kyari, Fatima; Abdull, Mohammed M.; Bastawrous, Andrew; Gilbert, Clare E.; Faal, Hannah

2013-01-01

Purpose: The purpose of this study is to review the epidemiology of different types of glaucoma relevant to Sub-Saharan Africa (SSA) and to discuss the evidence regarding the risk factors for onset and progression of glaucoma, including risk factors for glaucoma blindness. Methods: Electronic databases (PubMed, MedLine, African Journals Online- AJOL) were searched using the full text, Medical Subject Headings (MeSH) terms, author(s) and title to identify publications since 1982 in the following areas: population-based glaucoma prevalence and incidence studies in SSA and in African-derived black populations outside Africa; population-based prevalence and incidence of blindness and visual impairment studies in SSA including rapid assessment methods, which elucidate the glaucoma-specific blindness prevalence; studies of risk factors for glaucoma; and publications that discussed public health approaches for the control of glaucoma in Africa. Results: Studies highlighted that glaucoma in SSA is a public health problem and predominantly open-angle glaucoma. It is the second-leading cause of blindness, has a high prevalence, an early onset and progresses more rapidly than in Caucasians. These factors are further compounded by poor awareness and low knowledge about glaucoma even by persons affected by the condition. Conclusion: Glaucoma care needs to be given high priority in Vision 2020 programs in Africa. Many questions remain unanswered and there is a need for further research in glaucoma in SSA in all aspects especially epidemiology and clinical care and outcomes involving randomized controlled trials. Genetic and genome-wide association studies may aid identification of high-risk groups. Social sciences and qualitative studies, health economics and health systems research will also enhance public health approaches for the prevention of blindness due to glaucoma. PMID:23741130

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.

Baseline 24-2 Central Visual Field Damage Is Predictive of Global Progressive Field Loss.

PubMed

Garg, Aakriti; De Moraes, C Gustavo; Cioffi, George A; Girkin, Christopher A; Medeiros, Felipe A; Weinreb, Robert N; Zangwill, Linda M; Liebmann, Jeffrey M

2018-03-01

Central visual field (VF) damage in glaucoma patients can significantly hinder daily activities. The present study investigates whether the presence of localized baseline damage to the central 10 degrees of the VF is predictive of faster global mean deviation (MD) progression. Prospective cohort study. Eyes from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES) with established glaucoma and VF loss and a minimum of 5 24-2 VFs were eligible. Baseline central 24-2 damage was defined as any of the 12 central-most points with total deviation (TD) values at P < 0.5% on 2 consecutive examinations. Progression was determined using trend-based and event-based criteria: (1) rates of MD change significantly faster than zero and (2) >-5 dB MD loss over the entire follow-up. A total of 827 eyes of 584 patients were studied. Mean rate of MD change of the entire sample was -0.15 dB/year (95% CI: -0.19 to -0.12, P < .001). Eyes with baseline central damage progressed faster than those without (difference: β central  = -0.07 dB/year, 95% CI: -0.11 to -0.01, P = .011) and were more likely to experience MD loss greater than 5 dB (hazard ratio = 3.0 [95% CI: 2.1-4.1, P < .001]). These differences remained significant after adjusting for confounders. The presence of central VF damage at baseline is significantly associated with more rapid global progression. Detection of central VF damage aids in stratification of high-risk patients who may need intensive surveillance and aggressive treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of Glaucoma Progression in Large-Scale Clinical Data: The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG).

PubMed

Fujino, Yuri; Asaoka, Ryo; Murata, Hiroshi; Miki, Atsuya; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Shoji, Nobuyuki

2016-04-01

To develop a large-scale real clinical database of glaucoma (Japanese Archive of Multicentral Databases in Glaucoma: JAMDIG) and to investigate the effect of treatment. The study included a total of 1348 eyes of 805 primary open-angle glaucoma patients with 10 visual fields (VFs) measured with 24-2 or 30-2 Humphrey Field Analyzer (HFA) and intraocular pressure (IOP) records in 10 institutes in Japan. Those with 10 reliable VFs were further identified (638 eyes of 417 patients). Mean total deviation (mTD) of the 52 test points in the 24-2 HFA VF was calculated, and the relationship between mTD progression rate and seven variables (age, mTD of baseline VF, average IOP, standard deviation (SD) of IOP, previous argon/selective laser trabeculoplasties (ALT/SLT), previous trabeculectomy, and previous trabeculotomy) was analyzed. The mTD in the initial VF was -6.9 ± 6.2 dB and the mTD progression rate was -0.26 ± 0.46 dB/year. Mean IOP during the follow-up period was 13.5 ± 2.2 mm Hg. Age and SD of IOP were related to mTD progression rate. However, in eyes with average IOP below 15 and also 13 mm Hg, only age and baseline VF mTD were related to mTD progression rate. Age and the degree of VF damage were related to future progression. Average IOP was not related to the progression rate; however, fluctuation of IOP was associated with faster progression, although this was not the case when average IOP was below 15 mm Hg.

Equine Glaucoma.

PubMed

Michau, Tammy Miller

2017-12-01

Glaucoma is a multifactorial neurodegenerative ocular disease leading to progressive loss of retinal ganglion cells and their axons that form the optic nerve, causing blindness. Knowledge of the pathogenesis and development of equine glaucoma is in its infancy compared with human glaucoma. Glaucoma occurs most commonly secondary to uveitis and may be underdiagnosed or misdiagnosed in horses suffering from uveitis. Recognition and clinical diagnosis of glaucoma in the horse is improved with clinician awareness and the availability of handheld tonometers. Therapy for glaucoma is aimed at decreasing aqueous humor production through medical and surgical means. Even with therapy, long-term prognosis for vision is poor. Copyright © 2017 Elsevier Inc. All rights reserved.

Challenges In Early Glaucoma Detection.

PubMed

Dervisevic, Edita; Pavljasevic, Suzana; Dervisevic, Almir; Kasumovic, Sanja Sefic

2016-06-01

Glaucoma is the most common optic neuropathy which is characterized by progressive loss of retinal ganglion cells, the excavation of the optic nerve head, associated with defects in the visual field. It is not a disease, but the final result of united and yet completely unidentified cellular and subcellular processes and effects of many factors responsible for changes in retinal ganglion cells leading to their accelerated apoptosis. This is a prospective-retrospective, comparative, randomized clinical trial that included 150 patients, 97 were female and 53 male. The age of patients ranged from 18 to 80 years. The highest degree of myopia in category of tilted optic discs had patients with large disc (4.05 + -0.65). Values of the degree of myopia have linearly declined in relation to the size of the oblique disc. The analysis of the results revealed that the subjects who had a higher degree of myopia associated with glaucoma had frequent parapapillar atrophy of alpha and beta zones. The highest percentage of subjects with parapapillar changes were in the group of patients who had other than glaucoma and myopia (62%), then in the group of patients with glaucoma only (56%). Previous studies on the relationship between myopia and open-angle glaucoma are based on the results of observational studies. However, according to recent findings, based on the available studies, the systematic approach to estimate the association between myopia and glaucoma does not exist. Disc Damage Likelihood Scale (DDLS) is a new system for assessing glaucomatous damage of the optic disc which strongly correlates with the degree of visual field loss.

Hierarchical cluster analysis of progression patterns in open-angle glaucoma patients with medical treatment.

PubMed

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

2014-04-29

To classify medically treated open-angle glaucoma (OAG) by the pattern of progression using hierarchical cluster analysis, and to determine OAG progression characteristics by comparing clusters. Ninety-five eyes of 95 OAG patients who received medical treatment, and who had undergone visual field (VF) testing at least once per year for 5 or more years. OAG was classified into subgroups using hierarchical cluster analysis based on the following five variables: baseline mean deviation (MD), baseline visual field index (VFI), MD slope, VFI slope, and Glaucoma Progression Analysis (GPA) printout. After that, other parameters were compared between clusters. Two clusters were made after a hierarchical cluster analysis. Cluster 1 showed -4.06 ± 2.43 dB baseline MD, 92.58% ± 6.27% baseline VFI, -0.28 ± 0.38 dB per year MD slope, -0.52% ± 0.81% per year VFI slope, and all "no progression" cases in GPA printout, whereas cluster 2 showed -8.68 ± 3.81 baseline MD, 77.54 ± 12.98 baseline VFI, -0.72 ± 0.55 MD slope, -2.22 ± 1.89 VFI slope, and seven "possible" and four "likely" progression cases in GPA printout. There were no significant differences in age, sex, mean IOP, central corneal thickness, and axial length between clusters. However, cluster 2 included more high-tension glaucoma patients and used a greater number of antiglaucoma eye drops significantly compared with cluster 1. Hierarchical cluster analysis of progression patterns divided OAG into slow and fast progression groups, evidenced by assessing the parameters of glaucomatous progression in VF testing. In the fast progression group, the prevalence of high-tension glaucoma was greater and the number of antiglaucoma medications administered was increased versus the slow progression group. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Modifiable factors in the management of glaucoma: a systematic review of current evidence.

PubMed

Hecht, Idan; Achiron, Asaf; Man, Vitaly; Burgansky-Eliash, Zvia

2017-04-01

Primary open angle glaucoma is a chronic optic neuropathy affecting millions of people worldwide and represents a major public health issue. Environmental factors, behaviors, and diet are intimately related to patient health and may play a role in the pathogenesis and progression of glaucoma. This study aims to review the literature, focusing on the last three years, regarding modifiable lifestyle interventions in the management of primary open angle glaucoma. Electronic databases were searched for studies published between January 2013 and July 2016 on the topic of lifestyle interventions in primary open angle glaucoma. Sleeping with the head elevated and avoiding the worst eye-dependent side during sleep may slightly lower intraocular pressure and reduce visual field loss. Some food supplements and moderate aerobic exercise may also reduce intraocular pressure up to 2.0 and 3.0 mmHg, respectively. Frequency of coffee intake may be associated with disease progression. Potential negative effects are associated with weight-lifting and yoga exercises. Certain lifestyle habits could influence glaucoma progression, yet no specific interventions are currently supported by robust evidence. Awareness of the possible influences of certain habits should help guide clinical advice and is important to help patients avoid adverse outcomes and take an active role in the management of their disease.

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.

Copy Number Variations of TBK1 in Australian Patients With Primary Open-Angle Glaucoma

PubMed Central

AWADALLA, MONA S.; FINGERT, JOHN H.; ROOS, BENJAMIN E.; CHEN, SIMON; HOLMES, RICHARD; GRAHAM, STUART L.; CHEHADE, MARK; GALANOPOLOUS, ANNA; RIDGE, BRONWYN; SOUZEAU, EMMANUELLE; ZHOU, TIGER; SIGGS, OWEN M.; HEWITT, ALEX W.; MACKEY, DAVID A.; BURDON, KATHRYN P.; CRAIG, JAMIE E.

2015-01-01

PURPOSE To investigate the presence of TBK1 copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases. DESIGN A retrospective cohort study. METHODS DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for TBK1 copy number variations using real-time quantitative polymerase chain reaction. Samples with additional copies of the TBK1 gene were further tested using custom comparative genomic hybridization arrays. RESULTS Four out of 334 normal-tension glaucoma cases (1.2%) were found to carry TBK1 copy number variations using quantitative polymerase chain reaction. One extra dose of the TBK1 gene (duplication) was detected in 3 normal-tension glaucoma patients, while 2 extra doses of the gene (triplication) were detected in a fourth normal-tension glaucoma patient. The results were further confirmed by custom comparative genomic hybridization arrays. Further, the TBK1 copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance. No TBK1 copy number variations were detected in 1045 Australian patients with high-tension glaucoma or in 254 unaffected controls. CONCLUSION We report the presence of TBK1 copy number variations in our Australian normal-tension glaucoma cohort, including the first example of more than 1 extra copy of this gene in glaucoma patients (gene triplication). These results confirm TBK1 to be an important cause of normal-tension glaucoma, but do not suggest common involvement in high-tension glaucoma. PMID:25284765

Current perspective of neuroprotection and glaucoma

PubMed Central

Tian, Kailin; Shibata-Germanos, Shannon; Pahlitzsch, Milena; Cordeiro, M Francesca

2015-01-01

Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs). The main concomitant factor is the elevated intraocular pressure (IOP). Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment. PMID:26635467

Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

PubMed

Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2017-12-06

Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optical coherence tomography angiography in glaucoma care.

PubMed

Chansangpetch, Sunee; Lin, Shan C

2018-05-14

Rapid improvements in optical coherence tomography (OCT) technology have allowed for enhancement of both image resolution and scanning speed, and the development of vascular assessment modality. Optical coherence tomography angiography (OCTA) is the non-invasive in vivo imaging of the vasculature located within the retina and optic nerve head area. The principle of OCTA is to use the variations in OCT signals caused by moving particles as the contrast mechanism for imaging of flow. Several algorithms which aim to maximize the contrast signal and minimize the noise have been developed including the phase-based techniques, intensity-based techniques (e.g., split-spectrum amplitude decorrelation angiography (SSADA)), and complex-based techniques (e.g., optical microangiography (OMAG)). With its reliable technique, high image resolution, and current availability, OCTA has been widely used in the assessment of posterior segment diseases including glaucoma in which ocular perfusion dysfunction has been proposed as a pathophysiological mechanism. This review will provide the reader with information on the principle techniques of OCTA; the current literature on OCTA reproducibility; its applications to glaucoma detection and monitoring of progression; and the role of OCTA in the assessment of the vascular component in glaucoma pathogenesis.

Optical Coherence Tomography Angiography of Optic Disc Perfusion in Glaucoma

PubMed Central

Jia, Yali; Wei, Eric; Wang, Xiaogang; Zhang, Xinbo; Morrison, John C.; Parikh, Mansi; Lombardi, Lori H.; Gattey, Devin M.; Armour, Rebecca L.; Edmunds, Beth; Kraus, Martin F.; Fujimoto, James G.; Huang, David

2014-01-01

Purpose To compare optic disc perfusion between normal and glaucoma subjects using optical coherence tomography (OCT) angiography and detect optic disc perfusion changes in glaucoma. Design Observational, cross-sectional study. Participants Twenty-four normal subjects and 11 glaucoma patients were included. Methods One eye of each subject was scanned by a high-speed 1050 nm wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography algorithm (SSADA) was used to compute three-dimensional optic disc angiography. A disc flow index was computed from four registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc ratios. Wide field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. Main Outcome Measurements Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations between disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. Results In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in glaucoma subjects. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV respectively. The disc flow index was reduced by 25% in the glaucoma group (p = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R2 = 0.752, p = 0.001). These correlations were significant even after accounting for age, cup/disc area ratio, NFL, and rim area. Conclusions OCT angiography, generated by the new SSADA algorithm, repeatably measures optic disc perfusion. OCT angiography could be useful in the evaluation of glaucoma and glaucoma progression. PMID:24629312

Automatic optic disc segmentation based on image brightness and contrast

NASA Astrophysics Data System (ADS)

Lu, Shijian; Liu, Jiang; Lim, Joo Hwee; Zhang, Zhuo; Tan, Ngan Meng; Wong, Wing Kee; Li, Huiqi; Wong, Tien Yin

2010-03-01

Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness. As glaucoma often produces additional pathological cupping of the optic disc (OD), cupdisc- ratio is one measure that is widely used for glaucoma diagnosis. This paper presents an OD localization method that automatically segments the OD and so can be applied for the cup-disc-ratio based glaucoma diagnosis. The proposed OD segmentation method is based on the observations that the OD is normally much brighter and at the same time have a smoother texture characteristics compared with other regions within retinal images. Given a retinal image we first capture the ODs smooth texture characteristic by a contrast image that is constructed based on the local maximum and minimum pixel lightness within a small neighborhood window. The centre of the OD can then be determined according to the density of the candidate OD pixels that are detected by retinal image pixels of the lowest contrast. After that, an OD region is approximately determined by a pair of morphological operations and the OD boundary is finally determined by an ellipse that is fitted by the convex hull of the detected OD region. Experiments over 71 retinal images of different qualities show that the OD region overlapping reaches up to 90.37% according to the OD boundary ellipses determined by our proposed method and the one manually plotted by an ophthalmologist.

Detection and characterization of glaucoma-like canine retinal tissues using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Karl; Hamouche, Nicholas; Kecova, Helga; Lazic, Tatjana; Hernandez-Merino, Elena; Yu, Chenxu

2013-06-01

Early detection of pathological changes and progression in glaucoma and other neuroretinal diseases remains a great challenge and is critical to reduce permanent structural and functional retina and optic nerve damage. Raman spectroscopy is a sensitive technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, spectroscopic analysis was conducted on the retinal tissues of seven beagles with acute elevation of intraocular pressure (AEIOP), six beagles with compressive optic neuropathy (CON), and five healthy beagles. Spectroscopic markers were identified associated with the different neuropathic conditions. Furthermore, the Raman spectra were subjected to multivariate discriminate analysis to classify independent tissue samples into diseased/healthy categories. The multivariate discriminant model yielded an average optimal classification accuracy of 72.6% for AEIOP and 63.4% for CON with 20 principal components being used that accounted for 87% of the total variance in the data set. A strong correlation (R2>0.92) was observed between pattern electroretinography characteristics of AEIOP dogs and Raman separation distance that measures the separation of spectra of diseased tissues from normal tissues; however, the underlining mechanism of this correlation remains to be understood. Since AEIOP mimics the pathological symptoms of acute/early-stage glaucoma, it was demonstrated that Raman spectroscopic screening has the potential to become a powerful tool for the detection and characterization of early-stage disease.

Teleglaucoma: ready to go?

PubMed Central

Strouthidis, N G; Chandrasekharan, G; Diamond, J P; Murdoch, I E

2014-01-01

Telemedicine technologies and services allow today's ophthalmic clinicians to remotely diagnose, manage and monitor several ophthalmic conditions from a distance. But is this the case for glaucomas? There has been a proliferation of telemedicine friendly devices in recent years that improves the capabilities of the clinician in managing glaucomas. The existing instruments still need to align themselves with accepted industry standards. There are successful programmes running in several areas of the world. The safety and efficacy of these programmes needs further exploration. The inability of a single device or test to diagnose glaucomas satisfactorily has also hampered progress in remotely diagnosing these conditions. There is, however, significant potential for telemedicine-friendly devices to remotely monitor the progress of glaucoma and, thereby, reduce some of the workload on an overstretched health service. PMID:24723617

Baseline Fourier-Domain Optical Coherence Tomography Structural Risk Factors for Visual Field Progression in the Advanced Imaging for Glaucoma Study.

PubMed

Zhang, Xinbo; Dastiridou, Anna; Francis, Brian A; Tan, Ou; Varma, Rohit; Greenfield, David S; Schuman, Joel S; Sehi, Mitra; Chopra, Vikas; Huang, David

2016-12-01

To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. Multicenter cohort study. Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model. Copyright © 2016 Elsevier Inc. All rights reserved.

Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population.

PubMed

Gomez Goyeneche, Hector Fernando; Hernandez-Mendieta, Diana Patricia; Rodriguez, Diego Andres; Sepulveda, Ana Irene; Toledo, Jose Daniel

2015-01-01

To determine the progression of pigment dispersion syndrome (PDS) into pigmentary glaucoma (PG) in a population at the Central Military Hospital in Bogotá, Colombia. A retrospective study was conducted, based on a review of medical records of patients with PDS evaluated in the Glaucoma Clinic. Data were collected in a database in excel and subsequently analyzed with the software Statistical Package for the Social Sciences (SPSS), performing Chi-square test analysis and Spearman's rho test. Forty-eight eyes of 24 patients were included. Forty-two percent were women and 58% were men. Pigmentation of the trabecular meshwork was the most frequent clinical sign (100%), followed by Krukenberg's spindle (91.7%), the least frequent were the iris concavity and iris heterochromia (4.2%), the average of the spherical equivalent was of - 1.33 (SD 2.07). The rate of conversion of PDS to PG was 37.5%, after an average follow-up of 50.7 months. Having an intraocular pressure (IOP) greater than 21 mm Hg was statistically the only significant risk factor for conversion. We found several differences in frequency and clinical signs in these patients in contrast to previous data, probably due to different racial characteristics. The rate of progression is similar to previous reports despite of heterogeneity of these. Having IOP > 21 mm Hg was the only risk factor associated with progression in this sample. How to cite this article: Gomez Goyeneche HF, Hernandez-Mendieta DP, Rodriguez DA, Sepulveda AI, Toledo JD. Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population. J Curr Glaucoma Pract 2015;9(3):69-72.

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

PubMed Central

Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

2017-01-01

The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

Pigment dispersion syndrome and pigmentary glaucoma--a major review.

PubMed

Niyadurupola, Nuwan; Broadway, David C

2008-12-01

Pigment dispersion syndrome (PDS) is an interesting condition that can lead to secondary open angle glaucoma. Pigmentary glaucoma is primarily a disease of young people, myopes and men. PDS is characterized by the presence of Krukenberg spindles, iris trans-illumination defects, trabecular meshwork pigmentation and backward bowing of the iris. Posterior bowing of the iris causes rubbing of the pigmented iris epithelium against lens structures, liberation of pigment and trabecular meshwork changes that result in reduced aqueous outflow with the risk of glaucoma. Peripheral laser iridotomy can reverse backward bowing of the iris and may prevent progression of pigmentary glaucoma.

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.

Clinical Utility of Optical Coherence Tomography in Glaucoma

PubMed Central

Dong, Zachary M.; Wollstein, Gadi; Schuman, Joel S.

2016-01-01

Optical coherence tomography (OCT) has established itself as the dominant imaging modality in the management of glaucoma and retinal diseases, providing high-resolution visualization of ocular microstructures and objective quantification of tissue thickness and change. This article reviews the history of OCT imaging with a specific focus on glaucoma. We examine the clinical utility of OCT with respect to diagnosis and progression monitoring, with additional emphasis on advances in OCT technology that continue to facilitate glaucoma research and inform clinical management strategies. PMID:27537415

Comparing the Rates of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Loss in Healthy Eyes and in Glaucoma Eyes.

PubMed

Hammel, Naama; Belghith, Akram; Weinreb, Robert N; Medeiros, Felipe A; Mendoza, Nadia; Zangwill, Linda M

2017-06-01

To compare the rates of circumpapillary retinal nerve fiber layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) change over time in healthy and glaucoma eyes. Cohort study. The rates of circumpapillary RNFL and macular GCIPL loss in 28 healthy subjects and 97 glaucoma subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared using mixed-effects models. The median follow-up time and number of visits were 1.7 years and 6 visits and 3.2 years and 7 visits for healthy and glaucoma eyes, respectively. Significant rates of loss of both global circumpapillary RNFL and average macular GCIPL thickness were detectable in early and moderate glaucoma eyes; in severe glaucoma eyes, rates of average macular GCIPL loss were significant, but rates of global circumpapillary RNFL loss were not. In glaucoma eyes, mean rates of global circumpapillary RNFL thickness change (-0.98 μm/year [95% confidence interval (CI), -1.20 to -0.76]) and normalized global circumpapillary RNFL change (-1.7%/year [95% CI, -2.1 to -1.3]) were significantly faster than average macular GCIPL change (-0.57 μm/year [(95% CI, -0.73 to -0.41]) and normalized macular GCIPL change (-1.3%/year [95% CI, -1.7 to -0.9]). The rates of global and inferior RNFL change were weakly correlated with global and inferior macular GCIPL change (r ranges from 0.16 to 0.23, all P < .05). In this cohort, the rate of circumpapillary RNFL thickness change was faster than macular GCIPL change for glaucoma eyes. Global circumpapillary RNFL thickness loss was detectable in early and moderate glaucoma, and average macular GCIPL thickness loss was detectable in early, moderate, and severe glaucoma, suggesting that structural changes can be detected in severe glaucoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

PubMed

Hudson, C J W; Kim, L S; Hancock, S A; Cunliffe, I A; Wild, J M

2007-05-01

To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

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.

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.

Innovative approaches to glaucoma management of Boston keratoprosthesis type 1.

PubMed

Vajaranant, Thasarat S; Liu, Jessica; Wilensky, Jacob; Cortina, M Soledad; Aref, Ahmad A

2016-09-01

Glaucoma remains a prevalent disorder and visual limiting factor after Boston keratoprosthesis type 1 implantation. Patients with glaucoma have worse initial and late visual acuity outcomes after otherwise successful keratoprosthesis implantation. Management of glaucoma in the setting of a keratoprosthesis is challenging because of relatively rapid progression and an inability to accurately measure intraocular pressure (IOP). In addition, there are no standard guidelines for glaucoma surveillance and monitoring after keratoprosthesis surgery. This report provides a review of the current literature and offers innovative strategies that will overcome the challenges in managing glaucoma in the setting of a Boston keratoprosthesis type 1 implant. The topics that will be discussed in this section include alternative methods for IOP measurement, rationales and surgical techniques for a pars plana tube placement for glaucoma drainage device, effective medical and laser treatment, the risk for IOP elevations after YAG laser, and practical guides to glaucoma surveillance and monitoring.

Update on pigment dispersion syndrome and pigmentary glaucoma.

PubMed

Okafor, Kingsley; Vinod, Kateki; Gedde, Steven J

2017-03-01

The present article reviews the clinical features and pathogenesis of pigment dispersion syndrome and pigmentary glaucoma and provides an update regarding their diagnosis and management. Newer imaging modalities including ultrasound biomicroscopy and anterior segment optical coherence tomography facilitate visualization of the iris concavity characteristic of eyes with pigment dispersion syndrome and pigmentary glaucoma. Patients with pigmentary glaucoma may be distinguished from those with other glaucoma types by the presence of typical symptoms, personality type, and patterns of diurnal intraocular pressure fluctuation. Although laser iridotomy has been shown to alter iris anatomy in pigmentary glaucoma, it is not proven to slow visual field progression. Multiple trials have validated the safety and efficacy of filtering surgery in treating pigmentary glaucoma, with fewer studies published on the role of micro-invasive glaucoma surgery. Literature from the review period has further defined the unique clinical characteristics of pigment dispersion syndrome and pigmentary glaucoma. Laser surgery has a limited role in the management of these entities, whereas trabeculectomy remains an acceptable first-line surgical treatment. Further studies are needed to define the potential application of the newer micro-invasive glaucoma procedures in pigmentary glaucoma.

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.

Automatic CDR Estimation for Early Glaucoma Diagnosis

PubMed Central

Sarmiento, A.; Sanchez-Morillo, D.; Jiménez, S.; Alemany, P.

2017-01-01

Glaucoma is a degenerative disease that constitutes the second cause of blindness in developed countries. Although it cannot be cured, its progression can be prevented through early diagnosis. In this paper, we propose a new algorithm for automatic glaucoma diagnosis based on retinal colour images. We focus on capturing the inherent colour changes of optic disc (OD) and cup borders by computing several colour derivatives in CIE L∗a∗b∗ colour space with CIE94 colour distance. In addition, we consider spatial information retaining these colour derivatives and the original CIE L∗a∗b∗ values of the pixel and adding other characteristics such as its distance to the OD centre. The proposed strategy is robust due to a simple structure that does not need neither initial segmentation nor removal of the vascular tree or detection of vessel bends. The method has been extensively validated with two datasets (one public and one private), each one comprising 60 images of high variability of appearances. Achieved class-wise-averaged accuracy of 95.02% and 81.19% demonstrates that this automated approach could support physicians in the diagnosis of glaucoma in its early stage, and therefore, it could be seen as an opportunity for developing low-cost solutions for mass screening programs. PMID:29279773

Nanotechnology Applications for Glaucoma.

PubMed

Cetinel, Sibel; Montemagno, Carlo

2016-01-01

Glaucoma is the second leading cause of blindness worldwide, and the antiglaucoma treatments currently available suffer from various complications. Nanotechnology-based treatments show a great deal of promise in overcoming these complications and form the basis for next-generation glaucoma treatment strategies, with the help of applications such as controlled release, targeted delivery, increased bioavailability, diffusion limitations, and biocompatibility. Significant progress has been made in nanomedicine in the efficiency of antiglaucoma medications, nanofabrication systems such as microelectromechanical systems that remove the limitations of nanodevices, and tissue regeneration vesicles for developing glaucoma treatments not based on intraocular pressure. With the use of these advanced technologies, the prevention of glaucoma-induced blindness will be possible in the near future. Herein, we reviewed the recent advances in nanotechnology-based treatment strategies for glaucoma.

Incidence and rates of visual field progression after longitudinally measured optic disc change in glaucoma.

PubMed

Chauhan, Balwantray C; Nicolela, Marcelo T; Artes, Paul H

2009-11-01

To determine whether glaucoma patients with progressive optic disc change have subsequent visual field progression earlier and at a faster rate compared with those without disc change. Prospective, longitudinal, cohort study. Eighty-one patients with open-angle glaucoma. Patients underwent confocal scanning laser tomography and standard automated perimetry every 6 months. The complete follow-up was divided into initial and subsequent periods. Two initial periods-first 3 years (Protocol A) and first half of the total follow-up (Protocol B)-were used, with the respective remainder being the subsequent follow-up. Disc change during the initial follow-up was determined with liberal, moderate, or conservative criteria of the Topographic Change Analysis. Subsequent field progression was determined with significant pattern deviation change in >or=3 locations (criterion used in the Early Manifest Glaucoma Trial). As a control analysis, field change during the initial follow-up was determined with significant pattern deviation change in >or=1, >or=2, or >or=3 locations. Survival time to subsequent field progression, rates of mean deviation (MD) change, and positive and negative likelihood ratios. The median (interquartile range) total follow-up was 11.0 (8.0-12.0) years with 22 (18-24) examinations. More patients had disc changes during the initial follow-up compared with field changes. The mean time to field progression was consistently shorter (protocol A, 0.8-1.7 years; protocol B, 0.3-0.7 years) in patients with prior disc change. In the control analysis, patients with prior field change had statistically earlier subsequent field progression (protocol A, 2.9-3.0 years; protocol B, 0.7-0.9). Similarly, patients with either prior disc or field change always had worse mean rates of subsequent MD change, although the distributions overlapped widely. Patients with subsequent field progression were up to 3 times more likely to have prior disc change compared with those without, and up to 5 times more likely to have prior field change compared with those without. Longitudinally measured optic disc change is predictive of subsequent visual field progression and may be an efficacious end point for functional outcomes in clinical studies and trials in glaucoma.

Rate of progression of total, upper, and lower visual field defects in patients with open-angle glaucoma and high myopia.

PubMed

Yoshino, Takaiko; Fukuchi, Takeo; Togano, Tetsuya; Sakaue, Yuta; Seki, Masaaki; Tanaka, Takayuki; Ueda, Jun

2016-03-01

We evaluated the rate of progression of total, upper, and lower visual field defects in patients with treated primary open-angle glaucoma (POAG) with high myopia (HM). Seventy eyes of 70 POAG patients with HM [≤-8 diopters (D)] were examined. The mean deviation (MD) slope and the upper and lower total deviation (upper TD, lower TD) slopes of the Humphrey Field Analyzer were calculated in patients with high-tension glaucoma (HTG) (>21 mmHg) versus normal-tension glaucoma (NTG) (≤21 mmHg). The mean age of all the patients (29 eyes with HTG and 41 eyes with NTG) was 48.5 ± 9.6 years. The MD slope, and upper and lower TD slopes of the HM group were compared to those of the non-HM group (NHM) (>-8 D) selected from 544 eyes in 325 age-matched POAG patients. In all, 70 eyes with HM and NHM were examined. The mean MD slope was -0.33 ± 0.33 dB/year in the HM, and -0.38 ± 0.49 dB/year in the NHM. There were no statistical differences between the HM and NHM (p = 0.9565). In the comparison of HTG versus NTG patients in both groups, the MD slope, and upper and lower TD slopes were similar. The rate of progression of total, upper, and lower visual field defects was similar among patients with HM and NHM. Although HM is a risk factor for the onset of glaucoma, HM may not be a risk factor for progression of visual field defects as assessed by the progression rate under treatment.

Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population

PubMed Central

Hernandez-Mendieta, Diana Patricia; Rodriguez, Diego Andres; Sepulveda, Ana Irene; Toledo, Jose Daniel

2015-01-01

ABSTRACT Objective: To determine the progression of pigment dispersion syndrome (PDS) into pigmentary glaucoma (PG) in a population at the Central Military Hospital in Bogotá, Colombia. Materials and methods: A retrospective study was conducted, based on a review of medical records of patients with PDS evaluated in the Glaucoma Clinic. Data were collected in a database in excel and subsequently analyzed with the software Statistical Package for the Social Sciences (SPSS), performing Chi-square test analysis and Spearman’s rho test. Results: Forty-eight eyes of 24 patients were included. Forty-two percent were women and 58% were men. Pigmentation of the trabecular meshwork was the most frequent clinical sign (100%), followed by Krukenberg’s spindle (91.7%), the least frequent were the iris concavity and iris heterochromia (4.2%), the average of the spherical equivalent was of - 1.33 (SD 2.07). The rate of conversion of PDS to PG was 37.5%, after an average follow-up of 50.7 months. Having an intraocular pressure (IOP) greater than 21 mm Hg was statistically the only significant risk factor for conversion. Conclusion: We found several differences in frequency and clinical signs in these patients in contrast to previous data, probably due to different racial characteristics. The rate of progression is similar to previous reports despite of heterogeneity of these. Having IOP > 21 mm Hg was the only risk factor associated with progression in this sample. How to cite this article: Gomez Goyeneche HF, Hernandez-Mendieta DP, Rodriguez DA, Sepulveda AI, Toledo JD. Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population. J Curr Glaucoma Pract 2015;9(3):69-72. PMID:26997839

Experiences with developing and implementing a virtual clinic for glaucoma care in an NHS setting.

PubMed

Kotecha, Aachal; Baldwin, Alex; Brookes, John; Foster, Paul J

2015-01-01

This article describes the development of a virtual glaucoma clinic, whereby technicians collect information for remote review by a consultant specialist. This was a hospital-based service evaluation study. Patients suitable for the stable monitoring service (SMS) were low-risk patients with "suspect", "early"-to-"moderate" glaucoma who were deemed stable by their consultant care team. Three technicians and one health care assistant ran the service. Patients underwent tests in a streamlined manner in a dedicated clinical facility, with virtual review of data by a consultant specialist through an electronic patient record. Feasibility of developing a novel service within a UK National Health Service setting and improvement of patient journey time within the service were studied. Challenges to implementation of virtual clinic include staffing issues and use of information technology. Patient journey time within the SMS averaged 51 minutes, compared with 92 minutes in the glaucoma outpatient department. Patient satisfaction with the new service was high. Implementing innovation into existing services of the National Health Service is challenging. However, the virtual clinic showed an improved patient journey time compared with that experienced within the general glaucoma outpatient department. There exists a discrepancy between patient management decisions of reviewers, suggesting that some may be more risk averse than others when managing patients seen within this model. Future work will assess the ability to detect progression of disease in this model compared with the general outpatient model of care.

A Closer Look at Schlemm's Canal Cell Physiology: Implications for Biomimetics.

PubMed

Dautriche, Cula N; Tian, Yangzi; Xie, Yubing; Sharfstein, Susan T

2015-09-21

Among ocular pathologies, glaucoma is the second leading cause of progressive vision loss, expected to affect 80 million people worldwide by 2020. A primary cause of glaucoma appears to be damage to the conventional outflow tract. Conventional outflow tissues, a composite of the trabecular meshwork and the Schlemm's canal, regulate and maintain homeostatic responses to intraocular pressure. In glaucoma, filtration of aqueous humor into the Schlemm's canal is hindered, leading to an increase in intraocular pressure and subsequent damage to the optic nerve, with progressive vision loss. The Schlemm's canal encompasses a unique endothelium. Recent advances in culturing and manipulating Schlemm's canal cells have elucidated several aspects of their physiology, including ultrastructure, cell-specific marker expression, and biomechanical properties. This review highlights these advances and discusses implications for engineering a 3D, biomimetic, in vitro model of the Schlemm's canal endothelium to further advance glaucoma research, including drug testing and gene therapy screening.

Low-Cost Rapid Prototyping of Liquid Crystal Polymer Based Magnetic Microactuators for Glaucoma Drainage Devices

PubMed Central

Park, Hyunsu; John, Simon; Lee, Hyowon

2017-01-01

Glaucoma is one of the leading causes of blindness in the world. Although there is no cure for glaucoma, pharmaceutical or surgical interventions are known to delay the progression of this debilitating disease. In recent years, implantation of glaucoma drainage devices (GDD) have increased due to their ability to manage IOP better than other therapeutic approaches. However, only 50% of the implanted devices remain functional after 5 years often due to biofouling. Here, we report our latest progress towards developing self-clearing GDDs using integrated magnetic microactuators. Our hypothesis is that these magnetic microdevices can provide local mechanical perturbations to prophylactically remove biological accumulation. To reduce the cost and increase the throughput of fabrication, we utilize a maskless photolithography setup and commercially available liquid crystal polymer foils to create prototype devices. The mechanical response of the devices is reported and compared with the theoretical values. PMID:28269212

Low-cost rapid prototyping of liquid crystal polymer based magnetic microactuators for glaucoma drainage devices.

PubMed

Hyunsu Park; John, Simon; Hyowon Lee

2016-08-01

Glaucoma is one of the leading causes of blindness in the world. Although there is no cure for glaucoma, pharmaceutical or surgical interventions are known to delay the progression of this debilitating disease. In recent years, implantation of glaucoma drainage devices (GDD) have increased due to their ability to manage IOP better than other therapeutic approaches. However, only 50% of the implanted devices remain functional after 5 years often due to biofouling. Here, we report our latest progress towards developing self-clearing GDDs using integrated magnetic microactuators. Our hypothesis is that these magnetic microdevices can provide local mechanical perturbations to prophylactically remove biological accumulation. To reduce the cost and increase the throughput of fabrication, we utilize a maskless photolithography setup and commercially available liquid crystal polymer foils to create prototype devices. The mechanical response of the devices is reported and compared with the theoretical values.

Teleglaucoma: ready to go?

PubMed

Strouthidis, N G; Chandrasekharan, G; Diamond, J P; Murdoch, I E

2014-12-01

Telemedicine technologies and services allow today's ophthalmic clinicians to remotely diagnose, manage and monitor several ophthalmic conditions from a distance. But is this the case for glaucomas? There has been a proliferation of telemedicine friendly devices in recent years that improves the capabilities of the clinician in managing glaucomas. The existing instruments still need to align themselves with accepted industry standards. There are successful programmes running in several areas of the world. The safety and efficacy of these programmes needs further exploration. The inability of a single device or test to diagnose glaucomas satisfactorily has also hampered progress in remotely diagnosing these conditions. There is, however, significant potential for telemedicine-friendly devices to remotely monitor the progress of glaucoma and, thereby, reduce some of the workload on an overstretched health service. 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.

Angle closure glaucoma in congenital ectropion uvea.

PubMed

Wang, Grace M; Thuente, Daniel; Bohnsack, Brenda L

2018-06-01

Congenital ectropion uvea is a rare anomaly, which is associated with open, but dysplastic iridocorneal angles that cause childhood glaucoma. Herein, we present 3 cases of angle-closure glaucoma in children with congenital ectropion uvea. Three children were initially diagnosed with unilateral glaucoma secondary to congenital ectropion uvea at 7, 8 and 13 years of age. The three cases showed 360° of ectropion uvea and iris stromal atrophy in the affected eye. In one case, we have photographic documentation of progression to complete angle closure, which necessitated placement of a glaucoma drainage device 3 years after combined trabeculotomy and trabeculectomy. The 2 other cases, which presented as complete angle closure, also underwent glaucoma drainage device implantation. All three cases had early glaucoma drainage device encapsulation (within 4 months) and required additional surgery (cycloablation or trabeculectomy). Congenital ectropion uvea can be associated with angle-closure glaucoma, and placement of glaucoma drainage devices in all 3 of our cases showed early failure due to plate encapsulation. Glaucoma in congenital ectropion uvea requires attention to angle configuration and often requires multiple surgeries to obtain intraocular pressure control.

The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma

PubMed Central

Fingeret, Murray; Dickerson, Jaime E.

2018-01-01

SIGNIFICANCE Noncompliance is a problem affecting glaucoma patients. Approaches to improve adherence include the use of drug-delivery systems and safer forms of surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications, particularly in combination with cataract surgery, and with its good intraocular pressure (IOP) reduction may reduce or eliminate glaucoma medications. Glaucoma is a progressive disease and a leading cause of irreversible blindness. Elevated IOP is the most important risk factor, but effective medical management is dependent on patient adherence. This review summarizes the adherence problem in glaucoma and the efforts, including MIGS, to provide effective IOP control that is not dependent on patient compliance. The current understanding of patient adherence to pharmacological treatment of glaucoma is discussed including the challenges facing glaucoma patients. Historical approaches to providing IOP control in a sustained and reliable way are presented culminating in a review of the burgeoning use of MIGS devices. It is estimated that, in the United States, 27% of prescriptions written, across all medications, are not filled or are filled but not taken. For ocular hypotensive medications, even when filled, a large percentage (which varies widely by study) are not instilled as prescribed. To address this problem, methods for sustained drug delivery have been and continue to be developed, as well as surgical and laser approaches. Most recently, MIGS devices have gained popularity because of the ease of implantation during cataract surgery, favorable safety profile, and the possibility for effective and long-lasting IOP lowering, as well as the reduction or elimination of need for IOP-lowering medication. Poor adherence to treatment is relatively common among glaucoma patients and is associated with progression of disease. Recommending MIGS implantation during cataract surgery may offer optometrists a valuable treatment option in managing glaucoma patients, particularly where good adherence is in doubt. PMID:29370021

Longitudinal changes in the visual field and optic disc in glaucoma.

PubMed

Artes, Paul H; Chauhan, Balwantray C

2005-05-01

The nature and mode of functional and structural progression in open-angle glaucoma is a subject of considerable debate in the literature. While there is a traditionally held viewpoint that optic disc and/or nerve fibre layer changes precede visual field changes, there is surprisingly little published evidence from well-controlled prospective studies in this area, specifically with modern perimetric and imaging techniques. In this paper, we report on clinical data from both glaucoma patients and normal controls collected prospectively over several years, to address the relationship between visual field and optic disc changes in glaucoma using standard automated perimetry (SAP), high-pass resolution perimetry (HRP) and confocal scanning laser tomography (CSLT). We use several methods of analysis of longitudinal data and describe a new technique called "evidence of change" analysis which facilitates comparison between different tests. We demonstrate that current clinical indicators of visual function (SAP and HRP) and measures of optic disc structure (CSLT) provide largely independent measures of progression. We discuss the reasons for these findings as well as several methodological issues that pose challenges to elucidating the true structure-function relationship in glaucoma.

Visual field progression in glaucoma: what is the specificity of the Guided Progression Analysis?

PubMed

Artes, Paul H; O'Leary, Neil; Nicolela, Marcelo T; Chauhan, Balwantray C; Crabb, David P

2014-10-01

To estimate the specificity of the Guided Progression Analysis (GPA) (Carl Zeiss Meditec, Dublin, CA) in individual patients with glaucoma. Observational cohort study. Thirty patients with open-angle glaucoma. In 30 patients with open-angle glaucoma, 1 eye (median mean deviation [MD], -2.5 decibels [dB]; interquartile range, -4.4 to -1.3 dB) was tested 12 times over 3 months (Humphrey Field Analyzer, Carl Zeiss Meditec; SITA Standard, 24-2). "Possible progression" and "likely progression" were determined with the GPA. These analyses were repeated after the order of the tests had been randomly rearranged (1000 unique permutations). Rate of false-positive alerts of "possible progression" and "likely progression" with the GPA. On average, the specificity of the GPA "likely progression" alert was high-for the entire sample, the mean rate of false-positive alerts after 10 follow-up tests was 2.6%. With "possible progression," the specificity was considerably lower (false-positive rate, 18.5%). Most important, the cumulative rate of false-positive alerts varied substantially among patients, from <1% to 80% with "possible progression" and from <0.1% to 20% with "likely progression." Factors associated with false-positive alerts were visual field variability (standard deviation of MD, Spearman's rho = 0.41, P<0.001) and the reliability indices (proportion of false-positive and false-negative responses, fixation losses, rho>0.31, P≤0.10). On average, progression criteria currently used in the GPA have high specificity, but some patients are more likely to show false-positive alerts than others. This is a natural consequence of population-based change criteria and may not matter in clinical trials and studies in which large groups of patients are compared. However, it must be considered when the GPA is used in clinical practice where specificity needs to be controlled for individual patients. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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.

Glaucoma detection based on local binary patterns in fundus photographs

NASA Astrophysics Data System (ADS)

Alsheh Ali, Maya; Hurtut, Thomas; Faucon, Timothée.; Cheriet, Farida

2014-03-01

Glaucoma, a group of diseases that lead to optic neuropathy, is one of the most common reasons for blindness worldwide. Glaucoma rarely causes symptoms until the later stages of the disease. Early detection of glaucoma is very important to prevent visual loss since optic nerve damages cannot be reversed. To detect glaucoma, purely data-driven techniques have advantages, especially when the disease characteristics are complex and when precise image-based measurements are difficult to obtain. In this paper, we present our preliminary study for glaucoma detection using an automatic method based on local texture features extracted from fundus photographs. It implements the completed modeling of Local Binary Patterns to capture representative texture features from the whole image. A local region is represented by three operators: its central pixel (LBPC) and its local differences as two complementary components, the sign (which is the classical LBP) and the magnitude (LBPM). An image texture is finally described by both the distribution of LBP and the joint-distribution of LBPM and LBPC. Our images are then classified using a nearest-neighbor method with a leave-one-out validation strategy. On a sample set of 41 fundus images (13 glaucomatous, 28 non-glaucomatous), our method achieves 95:1% success rate with a specificity of 92:3% and a sensitivity of 96:4%. This study proposes a reproducible glaucoma detection process that could be used in a low-priced medical screening, thus avoiding the inter-experts variability issue.

Ibopamine challenge testing differentiates glaucoma suspect, stable glaucoma and progressive glaucoma cases.

PubMed

Landers, John; Ullrich, Katja; Craig, Jamie E

2015-12-01

An ibopamine challenge is a novel technique for assessing glaucoma using ibopamine, a topical drug which temporarily increases aqueous production. We aimed to determine whether change in intraocular pressure (IOP) and/or optic cup volume (OCV) during the test differentiated between glaucoma patients at different stages of disease; namely, glaucoma suspects (GS), glaucoma patients who are stable (SG) and glaucoma patients who have demonstrated rapid progression (PG). Non-randomized clinical trial evaluating a diagnostic test. Sixty-one patients were recruited through glaucoma clinics at the Flinders Medical Centre (24 GS, 24 SG and 13 PG). Patients underwent IOP measurement and OCV assessment using optical coherence tomography. Two drops of ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP and OCV were reassessed. Changes from baseline were compared between groups. Change in IOP and OCV after ibopamine challenge. Following the ibopamine challenge, IOP increased by 1.8 mmHg for GS patients, 4.5 mmHg for SG patients (P = 0.003) and 8.1 mmHg for PG patients (P < 0.0001). OCV increased by 0.2% for GS patients, 0.6% for SG patients and 5.5% for PG patients. This was not significantly different between GS patients and SG patients; however, it was significantly different between GS patients and PG patients (P < 0.0001), and between SG and PG patients (P = 0.001). GS patients may be differentiated from those with SG or PG by their IOP response, and SG may be differentiated from PG patients by their change in OCV following an ibopamine challenge. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Visual disability and quality of life in glaucoma patients.

PubMed

Cesareo, Massimo; Ciuffoletti, Elena; Ricci, Federico; Missiroli, Filippo; Giuliano, Mario Alberto; Mancino, Raffaele; Nucci, Carlo

2015-01-01

Glaucoma is an optic neuropathy that can result in progressive and irreversible vision loss, thereby affecting quality of life (QoL) of patients. Several studies have shown a strong correlation between visual field damage and visual disability in patients with glaucoma, even in the early stages of the disease. Visual impairment due to glaucoma affects normal daily activities required for independent living, such as driving, walking, and reading. There is no generally accepted instrument for assessing quality of life in glaucoma patients; different factors involved in visual disability from the disease are difficult to quantify and not easily standardized. This chapter summarizes recent works from clinical and epidemiological studies, which describe how glaucoma affects the performance of important vision-related activities and QoL. © 2015 Elsevier B.V. All rights reserved.

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

Evaluation of the effectiveness of ophthalmic assistants as screeners for glaucoma in North India

PubMed Central

Sinha, S K; Astbury, N

2011-01-01

Aim To assess whether ophthalmic assistants are effective in screening people for glaucoma in India. Methodology The study subjects were examined by both trained ophthalmic assistants and an ophthalmologist in both hospital and community settings. Specific tests for the diagnosis of glaucoma suspects included visual field examination using frequency doubling technology perimetry, intraocular pressure measurement (Tonopen), A-scan central anterior chamber depth measurement and dilated optic disc examination. The findings recorded by the ophthalmic assistants were masked to the ophthalmologist to avoid measurement bias. Results In the hospital setting, there was a substantial level of agreement between the ophthalmic assistants and the ophthalmologist in the diagnosis of glaucoma suspects (89.29%, k=0.7, 95% confidence interval (CI)=0.54–0.86). The diagnostic accuracy of the ophthalmic assistants in detecting glaucoma suspects was high for sensitivity (95.2%, 95% CI=91.4–97.7%) but lower for specificity at 71.4% (95% CI=60.0–78.7%). In the community setting, there was a moderate level of agreement between the ophthalmic assistants and the ophthalmologist in the diagnosis of glaucoma suspects (78.23%, k=0.50, 95% CI=0.37–0.64). The diagnostic accuracy of the ophthalmic assistants in detecting glaucoma suspects was moderate for sensitivity (82.9, 95% CI=69.7–91.5%) but lower for specificity at 76.8% (95% CI=72.7–79.5%). Conclusion Ophthalmic assistants can be used for opportunistic case detection of glaucoma suspects in the community. Structured training of the ophthalmic assistants together with enhanced clinical experience would improve their performance in detecting glaucoma suspects in the community. PMID:21720416

Alternative therapy in glaucoma management: is there any role?

PubMed

Parikh, Rajul S; Parikh, Shefali R

2011-01-01

Glaucoma is one of the leading causes of blindness worldwide. Various randomized controlled clinical trials have shown that lowering intraocular pressure (IOP) does reduce progression of primary open-angle glaucoma. However, there is lots of interest in nonpharmacological options that includes lifestyle adjustment and alternative and complementary therapy (ACT). At least 5% glaucoma population uses ACT. Various lifestyle activities like exercise and alcohol can reduce IOP by 1 to 2 mm Hg but would have small effect on glaucoma. The psychological stress can increase IOP. Hypothetically and few studies do show neuroprotective effect (or effect on ocular blood flow) of alcohol, Gingko biloba, bilberry, but the current evidence is weak for its routine use. We must also remember the side effects of 'medications' (e.g., marijuana, alcohol) before promoting as remedy for glaucoma. In current armamentarium of glaucoma management, ACT cannot substitute the conventional treatment available to lower IOP.

Vertical cup-to-disc ratio measurement for diagnosis of glaucoma on fundus images

NASA Astrophysics Data System (ADS)

Hatanaka, Yuji; Noudo, Atsushi; Muramatsu, Chisako; Sawada, Akira; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

2010-03-01

Glaucoma is a leading cause of permanent blindness. Retinal fundus image examination is useful for early detection of glaucoma. In order to evaluate the presence of glaucoma, the ophthalmologists determine the cup and disc areas and they diagnose glaucoma using a vertical cup-to-disc ratio. However, determination of the cup area is very difficult, thus we propose a method to measure the cup-to-disc ratio using a vertical profile on the optic disc. First, the blood vessels were erased from the image and then the edge of optic disc was then detected by use of a canny edge detection filter. Twenty profiles were then obtained around the center of the optic disc in the vertical direction on blue channel of the color image, and the profile was smoothed by averaging these profiles. After that, the edge of the cup area on the vertical profile was determined by thresholding technique. Lastly, the vertical cup-to-disc ratio was calculated. Using seventy nine images, including twenty five glaucoma images, the sensitivity of 80% and a specificity of 85% were achieved with this method. These results indicated that this method can be useful for the analysis of the optic disc in glaucoma examinations.

Macular ganglion cell imaging study: glaucoma diagnostic accuracy of spectral-domain optical coherence tomography.

PubMed

Jeoung, Jin Wook; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung

2013-07-01

We evaluated the diagnostic accuracy of macular ganglion cell-inner plexiform layer (GCIPL) measurements using a high-definition optical coherence tomography (Cirrus HD-OCT) ganglion cell analysis algorithm for detecting early and moderate-to-severe glaucoma. Totals of 119 normal subjects and 306 glaucoma patients (164 patients with early glaucoma and 142 with moderate-to-severe glaucoma) were enrolled from the Macular Ganglion Cell Imaging Study. Macular GCIPL, peripapillary retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured in each subject. Areas under the receiver operating characteristic curves (AUROCs) were calculated and compared. Based on the internal normative database, the sensitivity and specificity for detecting early and moderate-to-severe glaucoma were calculated. There was no statistically significant difference between the AUROCs for the best OCT parameters. For detecting early glaucoma, the sensitivity of the Cirrus GCIPL parameters ranged from 26.8% to 73.2% and that of the Cirrus RNFL parameters ranged from 6.1% to 61.6%. For the early glaucoma group, the best parameter from the GCIPL generally had a higher sensitivity than those of the RNFL and ONH parameters with comparable specificity (P < 0.05, McNemar's test). There were no significant differences between the AUROCs for Cirrus GCIPL, RNFL, and ONH parameters, indicating that these maps have similar diagnostic potentials for glaucoma. The minimum GCIPL showed better glaucoma diagnostic performance than the other parameters at comparable specificities. However, other GCIPL parameters showed performances comparable to those of the RNFL parameters.

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.

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

Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt.

PubMed

Harake, Ryan S; Ding, Yuzhe; Brown, J David; Pan, Tingrui

2015-10-01

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

Lifestyles guide and glaucoma (i). Sports and activities.

PubMed

Moreno-Montañés, J; Antón-López, A; Duch-Tuesta, S; Corsino Fernández-Vila, P; García-Feijoó, J; Millá-Griñó, E; Muñoz-Negrete, F J; Pablo-Júlvez, L; Rodríguez-Agirretxe, I; Urcelay-Segura, J L; Ussa-Herrera, F; Villegas-Pérez, M P

2018-02-01

The increase in quality and life expectancy, often leads to many patients asking the glaucoma specialist whether some sports, activities or hobbies would affect their illness. The aim of this article is to establish guidelines for patients, based on the scientific evidence of published papers. Review of all published articles on glaucoma and sports or other activities. The papers were classified according to the level of scientific evidence based on the Oxford Centre for Evidence-Based Medicine classification. Aerobic sports are beneficial for the patient. Yoga indoor sports or relaxation techniques should be avoided if Valsalva manoeuvres are performed or the head is placed very low. Also, the patients must avoid sudden changes in height. Intense heat does not seem to lead to progression of glaucoma, but intense cold can affect patients with vascular dysregulation. Activities using the near vision slightly reduce the intraocular pressure. The use of wind instruments may raise intraocular pressure, depending on the technique used. Certain sports and activities may have an influence on the onset or progression of glaucoma. Glaucoma specialists should have adequate information about the scientific evidence in the publications, in order to properly advise the patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rational Basis For Nutraceuticals In The Treatment Of Glaucoma.

PubMed

Morrone, Luigi Antonio; Rombola, Laura; Adornetto, Annagrazia; Corasaniti, Maria Tiziana; Russo, Rossella

2017-11-09

Glaucoma, the second leading cause of blindness worldwide, is a chronic optic neuropathy characterized by progressive retinal ganglion cell (RGC) axons degeneration and death. The pathogenesis of primary open-angle glaucoma (OAG), the most common type, is still largely unknown and it is often associated with increased intraocular pressure (IOP) although IOP-independent mechanisms play also a role. Neurodegenerative process, including oxidative stress, excitotoxicity and neuroinflammation, and an impaired ocular blood flow are examples of mechanisms supposed to contribute to the IOP independent deterioration in OAG. For these reasons glaucoma progress it is not always under the control of currently available drugs. Interestingly, recent studies have suggested a link between dietary factors and glaucoma risk. Particularly, some nutrients have proven capable of lower IOP, increase circulation to the optic nerve, modulate excitotoxicity and promote RGC survival, but the lack of clinical trials limit their current therapeutic use. The finding of appropriate use of nutraceuticals that may be able to modify the risk of glaucoma may provide insight into glaucoma pathogenesis and decrease the need for, and therefore the side effects from, conventional therapies. For these reasons the effects of nutrients with anti-oxidant and neuroprotective properties are of great interest and nutraceuticals may offer some therapeutic potential. Although a further rigorous evaluation of nutraceuticals in the treatment of glaucoma is needed to determine their safety and efficacy, in this review we summarize the potential of nutritional supplements for limiting retinal damage and improving RGC survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Philadelphia Telemedicine Glaucoma Detection and Follow-Up Study

ClinicalTrials.gov

2017-05-02

Glaucoma; Glaucoma Suspect; Diabetic Retinopathy; Ocular Hypertension; Cataract; Branch Retinal Vein Occlusion; Branch Retinal Arterial Occlusion; Central Retinal Vein Occlusion; Central Retinal Artery Occlusion; Epi-retinal Membrane; Macular Degeneration; Drusen; Loss of Vision

[Study of free radicals in aqueous humor in glaucoma and cataracts: differences in presence or absence of diabetes mellitus and neovascular glaucoma].

PubMed

Oshida, Eiki; Arai, Kiyomi; Sakai, Miki; Chikuda, Makoto

2014-09-01

This study was conducted for the purpose of comparing differences in the types of free radicals in the aqueous humor of glaucoma and cataract patients. Free radicals in the aqueous humor of 44 glaucoma eyes and 15 cataract eyes were measured by electron spin resonance (ESR), followed by comparing the detection rates. In addition, subgroup analyses were also conducted for the presence or absence of complications of diabetes mellitus (DM) and neovascular glaucoma (NVG) in the patients. Three types of free radicals were measured, ascorbate-free radical (AFR), AFR containing a trace amount of superoxide (SO) (AFR +), and SO containing a trace amount of AFR (SO +). Significant differences were observed in the detection rates of each type between the glaucoma group (maximum SO +) and the cataract group (maximum AFR), between the DM group (maximum SO +) and the non-DM group (maximum AFR) in the glaucoma, and between the DM group (maximum AFR +) and the non-DM group (maximum AFR) in the cataract. SO + was detected in all cases of NVG regardless of whether they were DM or non-DM. Glaucoma cases are more susceptible to the generation of SO in the aqueous humor than cataracts, and they are more liable to occur in DM than in non-DM in both glaucoma and cataract cases. This study suggest an evidence for a strong correlation with SO and vascularization in NVG.

Progression to Legal Blindness in Patients With Normal Tension Glaucoma: Hospital-Based Study.

PubMed

Sawada, Akira; Rivera, Jonathan A; Takagi, Daisuke; Nishida, Takashi; Yamamoto, Tetsuya

2015-06-01

To determine the probability of an eye with normal tension glaucoma (NTG) progressing to legal blindness under standard ophthalmic care. Patients diagnosed with NTG (n = 382) between 1985 and 2007 at Gifu University Hospital were followed for at least 5 years under standard ophthalmic care. The collected data included the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and visual field status. Blindness was defined as a BCVA of <20/400 or a constriction of the central visual field to <10° according to the World Health Organization criteria. Kaplan-Meier life table analysis was used to estimate the probability of progressing to blindness in one or both eyes. The mean follow-up period after diagnosis was 13.3 ± 5.4 years with a range of 5.0 to 29.1 years. At diagnosis, 18 patients (4.7%) had unilateral blindness due to glaucoma. At final examination, 34 patients had progressed to unilateral blindness and 5 to bilateral blindness. The Kaplan-Meier life table analysis estimate for unilateral blindness was 5.8 ± 1.3% at 10 years and 9.9 ± 1.9% at 20 years. Similarly, that for bilateral blindness was 0.3 ± 0.3% at 10 years and 1.4 ± 0.8% at 20 years. A Cox proportional hazard model analysis showed that a lower initial BCVA (P < 0.001), a worse initial AGIS (Advanced Glaucoma Intervention Study) score (P = 0.002), and the frequency of changing glaucoma medications during the follow-up periods (P < 0.001) were significantly correlated with the development of blindness in at least one eye. The probability of blindness in eyes with NTG is much lower than previously reported in patients with high-tension glaucoma. Nevertheless, special care should be taken to follow NTG patients, and especially those with worse BCVA and more advanced visual field loss at diagnosis.

Barriers to glaucoma case finding as perceived by optometrists in Ireland.

PubMed

Barrett, Catriona; O'Brien, Colm; Butler, John S; Loughman, James

2018-01-01

This research was designed to provide an in-depth exploration of the perceptions of optometrists relating to the challenges of glaucoma case finding in the Irish health-care system. A survey was developed, piloted and distributed for anonymous completion by optometrists registered to practise in Ireland. The survey included 10 five-level Likert items exploring potential barriers to glaucoma detection and a free-text box for participants to comment more broadly. One hundred and ninety-nine optometrists (27 per cent of registrants) responded to the survey. Among the barriers identified, there was notable agreement (71 per cent) with the need for extra training on glaucoma detection. Logistic regression showed that optometrists without postgraduate qualifications were more likely to agree with the need for extra training (OR 3.2, 95 per cent CI 1.3-8.1). Respondents largely agreed (61 per cent) that patient unwillingness to pay additional fees for supplementary glaucoma-specific tests was also a barrier. Appointment times of less than 30 minutes were significantly associated with six of the 10 proposed barriers to glaucoma detection. A logistic regression analysis (n = 179) confirmed that the time allotted per appointment was a significant predictor of the agreement time of optometrists as a barrier (χ 2 [1] = 13.52, p < 0.001). Multiple linear regression showed that optometrists with less experience, charging lower fees, and working in large multiples or franchised practices have the shortest appointment times. The strong link found between postgraduate education and the confidence of optometrists in detecting glaucoma indicates that optometrists wishing to increase their scope of practice in the new legislative environment in Ireland may more actively seek training in areas of interest. The responses also indicate a lack of funding for the level of diagnostic testing required for accurate glaucoma diagnosis. Recent increases in the state's eye examination fees look likely to address the identified time and financial barriers to glaucoma detection in Ireland. Future work should look to analyse the effects of increased funding on optometric case finding for glaucoma. © 2017 Optometry Australia.

High rate of incidental glaucoma detection in New Zealand.

PubMed

LaHood, Benjamin R; Erceg, Joshua; Bevin, Tui H; Sanderson, Gordon

2016-12-02

To investigate how glaucoma is initially detected in New Zealanders and what factors aroused disease suspicion. A postal survey of 500 randomly selected members of the Glaucoma New Zealand database was undertaken in 2012 to analyse factors relating to their initial presentation and diagnosis of glaucoma. Online surveys and telephone interviews were used to increase the response rate. The overall response rate was 80% (376/468) of eligible participants. The sample had an average age of 76 years. Prior to diagnosis, 80% (290/361) of participants who responded to this question reported no suspicion of glaucoma. A positive family history for glaucoma was the most common reason (71%) for presenting to a health care professional with a suspicion of glaucoma (13% of total sample). After diagnosis, 95% (357/376) of respondents reported that they had informed family members of their diagnosis. This study confirmed that the majority of glaucoma was discovered through incidental findings. A positive family history was the most common risk factor prompting examination, knowledge about which appeared to increase dramatically post-diagnosis. These findings indicated that there was potential to educate the public about glaucoma in order to raise awareness and diagnose the disease earlier.

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.

Brain: The Potential Diagnostic and Therapeutic Target for Glaucoma.

PubMed

Faiq, Muneeb A; Dada, Rima; Kumar, Ashutosh; Saluja, Daman; Dada, Tanuj

2016-01-01

Glaucoma is a form of multifactorial ocular neurodegeneration with immensely complex etiology, pathogenesis and pathology. Though the mainstream therapeutic management of glaucoma is lowering of intraocular pressure, there is, as of now, no cure for the disease. New evidences ardently suggest brain involvement in all aspects of this malady. This consequently advocates the opinion that brain should be the spotlight of glaucoma research and may form the impending and promising target for glaucoma diagnosis and treatment. The present analysis endeavors at understanding glaucoma vis-à-vis brain structural and/or functional derangement and central nervous system (CNS) degeneration. Commencing with the premise of developing some understanding about the brain-nature of ocular structures; we discuss the nature of the cellular and molecular moieties involved in glaucoma and Alzheimer's disease. Substantial deal of literature implies that glaucoma may well be a disease of the brain, nevertheless, manifesting as progressive loss of vision. If that is the case, then targeting brain will be far more imperative in glaucoma therapeutics than any other remedial regimen currently being endorsed.

Oral Microbiome Link to Neurodegeneration in Glaucoma

PubMed Central

Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen; Dong, Cecilia Q.; Igboin, Christina; Hyman, Leslie; Griffen, Ann; Mittag, Thomas; Danias, John

2014-01-01

Background Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma. Methods Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined. Findings Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage. Conclusions The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders. PMID:25180891

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

Risk factors for predicting visual field progression in Chinese patients with primary open-angle glaucoma: A retrospective study.

PubMed

Hung, Kuo-Hsuan; Cheng, Ching-Yu; Liu, Catherine Jui-Ling

2015-07-01

Glaucoma is a leading cause of irreversible blindness worldwide. It is characterized by progressive deterioration of the visual field (VF) that results in a complete loss of vision. This study aimed to determine the risk factors associated with VF progression in Chinese patients with primary open-angle glaucoma (POAG). We reviewed the charts of POAG patients who visited our clinic between July 2009 and June 2010. We included patients with five or more reliable VF tests using the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA, USA) during a period of at least 2 years. The scoring system of the Collaborative Initial Glaucoma Treatment Study (CIGTS) was used to code the VF. Progression was defined as an increasing score ≥3, compared to the averaged baseline data. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of VF progression. There were 92 patients (representing 92 eyes) with an average of 8.9 reliable VFs over a mean follow up of 5.4 years. Multivariate logistic regression showed that eyes with more VF tests [odds ratio (OR) = 1.500, p < 0.010] and either increased peak intraocular pressure (IOP) (OR = 1.235, p = 0.044) or a wide IOP range (OR = 1.165, p = 0.041) favored VF progression. High myopia (less than -6.0 D) was not a risk factor (OR = 1.289, p = 0.698) for VF progression in this study. In addition to a greater number of VF tests, Chinese patients with treated POAG who experienced a high peak IOP or a wide range of IOP during follow up were more likely to have VF deterioration. Copyright © 2015. Published by Elsevier Taiwan.

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

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

The Advanced Glaucoma Intervention Study (AGIS): 9. Comparison of glaucoma outcomes in black and white patients within treatment groups.

PubMed

2001-09-01

To compare in eyes of black and white patients the progression of glaucoma after failure of medical therapy and upon start of surgical intervention. Cohort study analysis of data from a randomized clinical trial. This multicenter study included open-angle glaucoma patients who had failed medical therapy: 451 eyes of 332 black patients, 325 eyes of 249 white patients. Eyes were randomly assigned to an argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) sequence or a trabeculectomy-ALT-trabeculectomy (TAT) sequence; they had been followed for 7 to 11 years at database closure. Main outcome measures were decrease of visual field (DVF), sustained decrease of visual field (SDVF), decrease of visual acuity (DVA), sustained decrease of visual acuity (SDVA), and failure of first surgical glaucoma intervention. Statistical methods included logistic regression to obtain average adjusted black-white odds ratios for binary outcomes, and Cox regression to estimate adjusted black-white risk ratios for time-to-event outcomes. In the ATT sequence blacks were at lower risk than whites of failure of first intervention (ALT, RR = 0.68, P = 0.040). In the TAT sequence blacks were at higher risk than whites of failure of the first intervention (trabeculectomy, RR = 1.79, P = 0.033), of intraocular pressure > or =18 mm Hg (average OR = 1.41, P = 0.026), and of DVF (average OR = 1.78, P = 0.007). In both treatment sequences, the average number of prescribed medications was greater for blacks than whites (P < or = 0.002). The results support the hypothesis that after failure of medical therapy and upon initiation of surgical intervention, an initial intervention with trabeculectomy retards the progression of glaucoma more effectively in white than in black patients. The data provide a weak suggestion that an initial surgical intervention with ALT retards the progression of glaucoma more effectively in black than in white patients.

Progress in anterior chamber angle imaging for glaucoma risk prediction - A review on clinical equipment, practice and research.

PubMed

V K, Shinoj; Hong, Xun Jie Jeesmond; V M, Murukeshan; M, Baskaran; Tin, Aung

2016-12-01

The visualization capabilities of various ocular imaging instruments can generally be categorized into photographic (e.g. gonioscopy, Pentacam, RetCam) and optical tomographic (e.g. optical coherence tomography (OCT), photoacoustic (PA) imaging, ultrasound biomicriscopy (UBM)) methods. These imaging instruments allow vision researchers and clinicians to visualize the iridocorneal angle, and are essential in the diagnosis and management of glaucoma. Each of these imaging modalities has particular benefits and associated drawbacks in obtaining repeatable and reliable measurement in the evaluation of the angle. This review article in this context summarized recent progresses in anterior chamber imaging techniques in glaucoma diagnosis and follow-up procedures. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Cytidine 5′-Diphosphocholine (Citicoline) in Glaucoma: Rationale of Its Use, Current Evidence and Future Perspectives

PubMed Central

Roberti, Gloria; Tanga, Lucia; Michelessi, Manuele; Quaranta, Luciano; Parisi, Vincenzo; Manni, Gianluca; Oddone, Francesco

2015-01-01

Cytidine 5′-diphosphocholine or citicoline is an endogenous compound that acts in the biosynthetic pathway of phospholipids of cell membranes, particularly phosphatidylcholine, and it is able to increase neurotrasmitters levels in the central nervous system. Citicoline has shown positive effects in Parkinson’s disease and Alzheimer’s disease, as well as in amblyopia. Glaucoma is a neurodegenerative disease currently considered a disease involving ocular and visual brain structures. Neuroprotection has been proposed as a valid therapeutic option for those patients progressing despite a well-controlled intraocular pressure, the main risk factor for the progression of the disease. The aim of this review is to critically summarize the current evidence about the effect of citicoline in glaucoma. PMID:26633368

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

Experiences with developing and implementing a virtual clinic for glaucoma care in an NHS setting

PubMed Central

Kotecha, Aachal; Baldwin, Alex; Brookes, John; Foster, Paul J

2015-01-01

Background This article describes the development of a virtual glaucoma clinic, whereby technicians collect information for remote review by a consultant specialist. Design and Methods This was a hospital-based service evaluation study. Patients suitable for the stable monitoring service (SMS) were low-risk patients with “suspect”, “early”-to-“moderate” glaucoma who were deemed stable by their consultant care team. Three technicians and one health care assistant ran the service. Patients underwent tests in a streamlined manner in a dedicated clinical facility, with virtual review of data by a consultant specialist through an electronic patient record. Main outcome measure Feasibility of developing a novel service within a UK National Health Service setting and improvement of patient journey time within the service were studied. Results Challenges to implementation of virtual clinic include staffing issues and use of information technology. Patient journey time within the SMS averaged 51 minutes, compared with 92 minutes in the glaucoma outpatient department. Patient satisfaction with the new service was high. Conclusion Implementing innovation into existing services of the National Health Service is challenging. However, the virtual clinic showed an improved patient journey time compared with that experienced within the general glaucoma outpatient department. There exists a discrepancy between patient management decisions of reviewers, suggesting that some may be more risk averse than others when managing patients seen within this model. Future work will assess the ability to detect progression of disease in this model compared with the general outpatient model of care. PMID:26508830

Risk Factors Associated with Progression to Blindness from Primary Open-Angle Glaucoma in an African-American Population.

PubMed

Pleet, Alexander; Sulewski, Melanie; Salowe, Rebecca J; Fertig, Raymond; Salinas, Julia; Rhodes, Allison; Merritt Iii, William; Natesh, Vikas; Huang, Jiayan; Gudiseva, Harini V; Collins, David W; Chavali, Venkata Ramana Murthy; Tapino, Paul; Lehman, Amanda; Regina-Gigiliotti, Meredith; Miller-Ellis, Eydie; Sankar, Prithvi; Ying, Gui-Shuang; O'Brien, Joan M

2016-08-01

To determine the risk factors associated with progression to blindness from primary open-angle glaucoma (POAG) in an African-American population. This study examined 2119 patients enrolled in the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study. A total of 59 eyes were identified as legally blind as a result of POAG (cases) and were age-and sex-matched to 59 non-blind eyes with glaucoma (controls). Chart reviews were performed to record known and suspected risk factors. Cases were diagnosed with POAG at an earlier age than controls (p = 0.005). Of the 59 eyes of cases, 16 eyes (27.1%) presented with blindness at diagnosis. Cases had worse visual acuity (VA) at diagnosis (p < 0.0001), with VA worse than 20/40 conferring a 27 times higher risk of progression to blindness (p = 0.0005). Blind eyes also demonstrated more visual field defects (p = 0.01), higher pre-treatment intraocular pressure (IOP; p < 0.0001), and higher cup-to-disc ratio (p = 0.006) at diagnosis. IOP was less controlled in cases, and those with IOP ≥21 mmHg at more than 20% of follow-up visits were 73 times more likely to become blind (p < 0.0001). Cases missed a greater number of appointments per year (p = 0.003) and had non-adherence issues noted in their charts more often than controls (p = 0.03). However, other compliance data did not significantly differ between groups. Access to care, initial VA worse than 20/40, and poor control of IOP were the major risk factors associated with blindness from POAG. Future studies should examine earlier, more effective approaches to glaucoma screening as well as the role of genetics in these significantly younger patients who progress to blindness.

A new approach to measure visual field progression in glaucoma patients using variational bayes linear regression.

PubMed

Murata, Hiroshi; Araie, Makoto; Asaoka, Ryo

2014-11-20

We generated a variational Bayes model to predict visual field (VF) progression in glaucoma patients. This retrospective study included VF series from 911 eyes of 547 glaucoma patients as test data, and VF series from 5049 eyes of 2858 glaucoma patients as training data. Using training data, variational Bayes linear regression (VBLR) was created to predict VF progression. The performance of VBLR was compared against ordinary least-squares linear regression (OLSLR) by predicting VFs in the test dataset. The total deviation (TD) values of test patients' 11th VFs were predicted using TD values from their second to 10th VFs (VF2-10), the root mean squared error (RMSE) associated with each approach then was calculated. Similarly, mean TD (mTD) of test patients' 11th VFs was predicted using VBLR and OLSLR, and the absolute prediction errors compared. The RMSE resulting from VBLR averaged 3.9 ± 2.1 (SD) and 4.9 ± 2.6 dB for prediction based on the second to 10th VFs (VF2-10) and the second to fourth VFs (VF2-4), respectively. The RMSE resulting from OLSLR was 4.1 ± 2.0 (VF2-10) and 19.9 ± 12.0 (VF2-4) dB. The absolute prediction error (SD) for mTD using VBLR was 1.2 ± 1.3 (VF2-10) and 1.9 ± 2.0 (VF2-4) dB, while the prediction error resulting from OLSLR was 1.2 ± 1.3 (VF2-10) and 6.2 ± 6.6 (VF2-4) dB. The VBLR more accurately predicts future VF progression in glaucoma patients compared to conventional OLSLR, especially in short VF series. © ARVO.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma.

PubMed

Murphy, Matthew C; Conner, Ian P; Teng, Cindy Y; Lawrence, Jesse D; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C

2016-08-11

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

PubMed Central

Murphy, Matthew C.; Conner, Ian P.; Teng, Cindy Y.; Lawrence, Jesse D.; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A.; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

2016-01-01

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease. PMID:27510406

Glaucoma history and risk factors.

PubMed

McMonnies, Charles W

Apart from the risk of developing glaucoma there is also the risk that it is not detected and irreversible loss of vision ensues. Some studies of methods of glaucoma diagnosis have examined the results of instrument-based examinations with great if not complete reliance on objective findings in arriving at a diagnosis. The very valuable advances in glaucoma detection instrument technologies, and apparent increasing dependence on them, may have led to reduced consideration of information available from a patient history in those studies. Dependence on objective evidence of glaucomatous pathology may reduce the possibility of detecting glaucoma suspects or patients at risk for becoming glaucoma suspects. A valid positive family history of glaucoma is very valuable information. However, negative family histories can often be unreliable due to large numbers of glaucoma cases being undiagnosed. No evidence of family history is appropriate rather than no family history. In addition the unreliability of a negative family history is increased when patients with glaucoma fail to inform their family members. A finding of no family history can only be stated as no known family history. In examining the potential diagnostic contribution from a patient history, this review considers, age, frailty, race, type and degree of refractive error, systemic hyper- and hypotension, vasospasm, migraine, pigmentary dispersion syndrome, pseudoexfoliation syndrome, obstructive sleep apnea syndrome, diabetes, medication interactions and side effects, the degree of exposure to intraocular and intracranial pressure elevations and fluctuations, smoking, and symptoms in addition to genetics and family history of the disease. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

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

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography.

PubMed

Larrosa, José Manuel; Moreno-Montañés, Javier; Martinez-de-la-Casa, José María; Polo, Vicente; Velázquez-Villoria, Álvaro; Berrozpe, Clara; García-Granero, Marta

2015-10-01

The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911-0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Mutation analysis of seven known glaucoma-associated genes in Chinese patients with glaucoma.

PubMed

Huang, Xiaobo; Li, Miaoling; Guo, Xiangming; Li, Shiqiang; Xiao, Xueshan; Jia, Xiaoyun; Liu, Xing; Zhang, Qingjiong

2014-05-13

To evaluate mutations in the MYOC, WDR36, OPTN, OPA1, NTF4, CYP1B1, and LTBP2 genes in a cohort of Chinese patients with primary glaucoma. Genomic DNA was prepared from 683 unrelated patients, including 50 with primary congenital glaucoma, 104 with juvenile open-angle glaucoma (JOAG), 186 with primary open-angle glaucoma (POAG), and 343 with primary angle-closure glaucoma (PACG). Mutations in the seven genes in 257 patients (36 with JOAG, 89 with POAG, and 132 with PACG) were initially analyzed by exome sequencing and then confirmed by Sanger sequencing. In addition, Sanger sequencing was used to detect MYOC mutations in the remaining 426 patients. Exome sequencing identified 19 mutations (6 in MYOC, 9 in WDR36, 3 in OPA1, and 1 in OPTN) in 20 of 257 patients, including 4 patients with JOAG, 8 patients with POAG, and 8 patients with PACG. No mutation was detected in the other three genes. In addition, Sanger sequencing detected additional MYOC mutations in 5 of the remaining 426 patients, including 3 patients with JOAG and 2 patients with POAG. Twenty-two mutations in MYOC, WDR36, OPA1, and OPTN were detected in 25 of the 683 patients with primary glaucoma, including nine MYOC mutations in 11 patients, nine WDR36 mutations in 11 patients, three OPA1 mutations in 3 patients, and one OPTN mutation in a patient who also carried a MYOC mutation. Eight mutations in MYOC, WDR36, and OPA1 in 8 of the 343 PACG patients are of uncertain significance and need to be analyzed further. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression.

PubMed

Mwanza, Jean-Claude; Budenz, Donald L

2016-03-01

Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed Central

Sun, Xiaoshen; Xu, Chaoying S.; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-01-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed. PMID:26339209

Marijuana for Glaucoma: A Recipe for Disaster or Treatment?

PubMed

Sun, Xiaoshen; Xu, Chaoying S; Chadha, Nisha; Chen, Allshine; Liu, Ji

2015-09-01

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients. Under extremely rare circumstances, a few categories of glaucoma patients may be potential candidates for treatment with medical marijuana. Further studies on alternate routes and more focused means of cannabinoid molecule delivery to the eye for glaucoma treatment are needed.

Filtering data from the collaborative initial glaucoma treatment study for improved identification of glaucoma progression.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Stein, Joshua D; Musch, David C

2013-12-21

Open-angle glaucoma (OAG) is a prevalent, degenerate ocular disease which can lead to blindness without proper clinical management. The tests used to assess disease progression are susceptible to process and measurement noise. The aim of this study was to develop a methodology which accounts for the inherent noise in the data and improve significant disease progression identification. Longitudinal observations from the Collaborative Initial Glaucoma Treatment Study (CIGTS) were used to parameterize and validate a Kalman filter model and logistic regression function. The Kalman filter estimates the true value of biomarkers associated with OAG and forecasts future values of these variables. We develop two logistic regression models via generalized estimating equations (GEE) for calculating the probability of experiencing significant OAG progression: one model based on the raw measurements from CIGTS and another model based on the Kalman filter estimates of the CIGTS data. Receiver operating characteristic (ROC) curves and associated area under the ROC curve (AUC) estimates are calculated using cross-fold validation. The logistic regression model developed using Kalman filter estimates as data input achieves higher sensitivity and specificity than the model developed using raw measurements. The mean AUC for the Kalman filter-based model is 0.961 while the mean AUC for the raw measurements model is 0.889. Hence, using the probability function generated via Kalman filter estimates and GEE for logistic regression, we are able to more accurately classify patients and instances as experiencing significant OAG progression. A Kalman filter approach for estimating the true value of OAG biomarkers resulted in data input which improved the accuracy of a logistic regression classification model compared to a model using raw measurements as input. This methodology accounts for process and measurement noise to enable improved discrimination between progression and nonprogression in chronic diseases.

A Comparison of Functional and Structural Measures for Identifying Progression of Glaucoma

PubMed Central

Xin, Daiyan; Greenstein, Vivienne C.; Ritch, Robert; Liebmann, Jeffrey M.; De Moraes, Carlos Gustavo

2011-01-01

Purpose. To compare glaucoma progression by functional and structural tests. Methods. The authors prospectively studied 33 glaucoma patients (55 eyes); 20 eyes (15 patients) had disc hemorrhage, and 35 eyes (18 patients) had exfoliation glaucoma. The following tests were performed at two baseline and three follow-up examinations: frequency doubling perimetry (FDT), 24-2 Humphrey visual fields (HVF), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT). To identify progression, the baseline measurements were averaged and compared to those obtained at the final examination. Stereophotographs of the optic disc were obtained at baseline and compared with those at the final examination. Results. Patients were followed up for 21.1 ± 1.8 months. For HVF there were significant changes in mean deviation (MD) in eight (14.5%) eyes but in pattern standard deviation (P/SD) in only two (3.6%) eyes. For FDT, there were significant changes in MD in 13 (23.6%) eyes. Five eyes showed changes in MD for HVF and FDT. For mfVEP, there was an increase in abnormal points in nine (16.4%) eyes. Six of these eyes did not show significant HVF or FDT changes. For OCT, RNFL average thickness values were significantly decreased in nine (16.4%) eyes. Nine (16.4%) eyes showed progression on stereophotography; four of these eyes did not show significant changes on OCT and functional tests. Conclusions. Each test showed evidence of progression in some eyes. However, agreement among tests and stereophotography regarding which eyes showed progression was poor, illustrating the importance of following up patients with a combination of functional and structural tests. PMID:20847115

Effect of glaucoma on eye movement patterns and laboratory-based hazard detection ability

PubMed Central

Black, Alex A.; Wood, Joanne M.

2017-01-01

Purpose The mechanisms underlying the elevated crash rates of older drivers with glaucoma are poorly understood. A key driving skill is timely detection of hazards; however, the hazard detection ability of drivers with glaucoma has been largely unexplored. This study assessed the eye movement patterns and visual predictors of performance on a laboratory-based hazard detection task in older drivers with glaucoma. Methods Participants included 30 older drivers with glaucoma (71±7 years; average better-eye mean deviation (MD) = −3.1±3.2 dB; average worse-eye MD = −11.9±6.2 dB) and 25 age-matched controls (72±7 years). Visual acuity, contrast sensitivity, visual fields, useful field of view (UFoV; processing speeds), and motion sensitivity were assessed. Participants completed a computerised Hazard Perception Test (HPT) while their eye movements were recorded using a desk-mounted Tobii TX300 eye-tracking system. The HPT comprises a series of real-world traffic videos recorded from the driver’s perspective; participants responded to road hazards appearing in the videos, and hazard response times were determined. Results Participants with glaucoma exhibited an average of 0.42 seconds delay in hazard response time (p = 0.001), smaller saccades (p = 0.010), and delayed first fixation on hazards (p<0.001) compared to controls. Importantly, larger saccades were associated with faster hazard responses in the glaucoma group (p = 0.004), but not in the control group (p = 0.19). Across both groups, significant visual predictors of hazard response times included motion sensitivity, UFoV, and worse-eye MD (p<0.05). Conclusions Older drivers with glaucoma had delayed hazard response times compared to controls, with associated changes in eye movement patterns. The association between larger saccades and faster hazard response time in the glaucoma group may represent a compensatory behaviour to facilitate improved performance. PMID:28570621

[Sensitivity and specificity of flicker perimetry with Pulsar. Comparison with achromatic (white-on-white) perimetry in glaucoma patients].

PubMed

Göbel, K; Erb, C

2013-02-01

The early detection of functional glaucoma damage plays an increasingly more central role in the diagnosis and treatment of glaucoma disease. Using selective perimetry detection of early glaucomatous defects is more likely and one of these methods is flicker perimetry with Pulsar. Flicker perimetry is used to analyze the temporal visual function in combination with spatial resolution and contrast sensitivity as opposed to standard automated perimetry which measures the differential light sensitivity with a non-specific stimulus. This study showed a higher sensitivity and specificity of Pulsar perimetry in comparison to achromatic perimetry in glaucoma patients.

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

PubMed

Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

2015-01-01

To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

Relationship between visual field progression and baseline refraction in primary open-angle glaucoma.

PubMed

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

2016-01-01

To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma. In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction. A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran-Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03-1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94-0.99) had a significant association with MD slope deterioration. In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Proposing new indicators for glaucoma healthcare service.

PubMed

Liang, Yuan Bo; Zhang, Ye; Musch, David C; Congdon, Nathan

2017-01-01

Glaucoma is the first leading cause of irreversible blindness worldwide with increasing importance in public health. Indicators of glaucoma care quality as well as efficiency would benefit public health assessments, but are lacking. We propose three such indicators. First, the glaucoma coverage rate (GCR), which is the number of people known to have glaucoma divided by the total number of people with glaucoma as estimated from population-based studies multiplied by 100%. Second, the glaucoma detection rate (GDR), which is number of newly diagnosed glaucoma patients in one year divided by the population in a defined area in millions. Third, the glaucoma follow-up adherence rate (GFAR), calculated as the number of patients with glaucoma who visit eye care provider(s) at least once a year over the total number of patients with glaucoma in given eye care provider(s) in a specific period. Regularly tracking and reporting these three indicators may help to improve the healthcare system performance at national or regional levels.

Glaucoma and clinical characteristics in Vietnamese Americans.

PubMed

Peng, Pai-Huei; Manivanh, Richard; Nguyen, Ngoc; Weinreb, Robert N; Lin, Shan C

2011-08-01

To assess the proportions of glaucoma types and clinical characteristics in Vietnamese Americans in a single-center, retrospective study. Medical charts of Vietnamese-American patients who visited a single private practice in Northern California from 1998-2007 were reviewed. The main outcome measures included the distribution and characteristics of glaucoma types, and clinical parameters associated with the presence of various glaucomas. Data from 2247 patients aged 18-98 years were reviewed. Glaucoma was determined for 305 patients (13.6%). Among this group, 54.8% had primary open-angle glaucoma (POAG), 26.9% had primary angle-closure glaucoma (PACG), 13.4% had mixed mechanism glaucoma (MMG), and 4.9% had secondary glaucoma. In the MMG group (41 patients), 27 patients who initially had open angles developed narrow angles and underwent laser peripheral iridotomy (LPI) with a mean follow up of 6.4 years from the time of iridotomy. The other 13 patients had glaucoma progression with open angles after LPI. One POAG patient had neovascular glaucoma due to retinal vein occlusion several years later. Compared to the PACG group, the MMG group had significantly lower baseline intraocular pressure (25.0 vs. 20.2 mmHg, p = 0.007) but with no difference in biometry. POAG is the major type of glaucoma in this clinic-based Vietnamese population. However, Vietnamese appear to have a relatively higher proportion of PACG than Caucasians and those of African descent. It is recommended that gonioscopy be part of the regular eye check-up for adult Vietnamese patients.

Anterior chamber angle imaging with swept-source optical coherence tomography: measuring peripheral anterior synechia in glaucoma.

PubMed

Lai, Isabel; Mak, Heather; Lai, Gilda; Yu, Marco; Lam, Dennis S C; Leung, Christopher K S

2013-06-01

To investigate the use of swept-source optical coherence tomography (OCT) for measuring the area and degree of peripheral anterior synechia (PAS) involvement in patients with angle-closure glaucoma. Cross-sectional study. Twenty-three eyes with PAS (detected by indentation gonioscopy) from 20 patients with angle-closure glaucoma (20 eyes had primary angle-closure glaucoma and 3 eyes had angle-closure glaucoma secondary to chronic anterior uveitis [n = 2] and Axenfeld-Rieger syndrome [n = 1]). The anterior chamber angles were evaluated with indentation gonioscopy and imaged by swept-source OCT (Casia OCT, Tomey, Nagoya, Japan) in room light and in the dark using the "angle analysis" protocol, which was composed of 128 radial B-scans each with 512 A-scans (16-mm scan length). The area and degree of PAS involvement were measured in each eye after manual detection of the scleral spur and the anterior irido-angle adhesion by 2 masked observers. The interobserver variability of the PAS measurements was calculated. The agreement of PAS assessment by gonioscopy and OCT, the area and the degree of PAS involvement, and the intraclass correlation coefficient (ICC) of interobserver PAS measurements. The area of PAS (mean ± standard deviation) was 20.8 ± 16.9 mm(2) (range, 3.9-74.9 mm(2)), and the degree of PAS involvement was 186.5 ± 79.9 degrees (range, 42-314 degrees). There was no difference in the area of PAS (P = 0.90) and the degree of PAS involvement (P = 0.95) between images obtained in room light and in the dark. The interobserver ICCs were 0.99 (95% confidence interval [CI], 0.98-1.00) for the area of PAS and 0.99 (95% CI, 0.97-1.00) for the degree of PAS involvement. There was good agreement of PAS assessment between gonioscopy and OCT images (kappa = 0.79; 95% CI, 0.67-0.91). Swept-source OCT allows visualization and reproducible measurements of the area and degree of PAS involvement, providing a new paradigm for evaluation of PAS progression and risk assessment for development of angle-closure glaucoma. 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.

Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma.

PubMed

Williams, Pete A; Harder, Jeffrey M; John, Simon W M

2017-12-01

Mitochondrial dysfunction may be an important, if not essential, component of human glaucoma. Using transcriptomics followed by molecular and neurobiological techniques, we have recently demonstrated that mitochondrial dysfunction within retinal ganglion cells is an early feature in the DBA/2J mouse model of inherited glaucoma. Guided by these findings, we discovered that the retinal level of nicotinamide adenine dinucleotide (NAD, a key molecule for mitochondrial health) declines in an age-dependent manner. We hypothesized that this decline in NAD renders retinal ganglion cells susceptible to damage during periods of elevated intraocular pressure. To replete NAD levels in this glaucoma, we administered nicotinamide (the amide of vitamin B3). At the lowest dose tested, nicotinamide robustly protected from glaucoma (~70% of eyes had no detectable glaucomatous neurodegeneration). At this dose, nicotinamide had no influence on intraocular pressure and so its effect was neuroprotective. At the highest dose tested, 93% of eyes had no detectable glaucoma. This represents a ~10-fold decrease in the risk of developing glaucoma. At this dose, intraocular pressure still became elevated but there was a reduction in the degree of elevation showing an additional benefit. Thus, nicotinamide is unexpectedly potent at preventing this glaucoma and is an attractive option for glaucoma therapeutics. Our findings demonstrate the promise for both preventing and treating glaucoma by interventions that bolster metabolism during increasing age and during periods of elevated intraocular pressure. Nicotinamide prevents age-related declines in NAD (a decline that occurs in different genetic contexts and species). NAD precursors are reported to protect from a variety of neurodegenerative conditions. Thus, nicotinamide may provide a much needed neuroprotective treatment against human glaucoma. This manuscript summarizes human data implicating mitochondria in glaucoma, and argues for studies to further assess the safety and efficacy of nicotinamide in human glaucoma care.

Glaucoma in atomic bomb survivors.

PubMed

Kiuchi, Yoshiaki; Yokoyama, Tomoko; Takamatsu, Michiya; Tsuiki, Eiko; Uematsu, Masafumi; Kinoshita, Hirofumi; Kumagami, Takeshi; Kitaoka, Takashi; Minamoto, Atsushi; Neriishi, Kazuo; Nakashima, Eiji; Khattree, Ravindra; Hida, Ayumi; Fujiwara, Saeko; Akahoshi, Masazumi

2013-10-01

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11-1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.

Ensemble Pruning for Glaucoma Detection in an Unbalanced Data Set.

PubMed

Adler, Werner; Gefeller, Olaf; Gul, Asma; Horn, Folkert K; Khan, Zardad; Lausen, Berthold

2016-12-07

Random forests are successful classifier ensemble methods consisting of typically 100 to 1000 classification trees. Ensemble pruning techniques reduce the computational cost, especially the memory demand, of random forests by reducing the number of trees without relevant loss of performance or even with increased performance of the sub-ensemble. The application to the problem of an early detection of glaucoma, a severe eye disease with low prevalence, based on topographical measurements of the eye background faces specific challenges. We examine the performance of ensemble pruning strategies for glaucoma detection in an unbalanced data situation. The data set consists of 102 topographical features of the eye background of 254 healthy controls and 55 glaucoma patients. We compare the area under the receiver operating characteristic curve (AUC), and the Brier score on the total data set, in the majority class, and in the minority class of pruned random forest ensembles obtained with strategies based on the prediction accuracy of greedily grown sub-ensembles, the uncertainty weighted accuracy, and the similarity between single trees. To validate the findings and to examine the influence of the prevalence of glaucoma in the data set, we additionally perform a simulation study with lower prevalences of glaucoma. In glaucoma classification all three pruning strategies lead to improved AUC and smaller Brier scores on the total data set with sub-ensembles as small as 30 to 80 trees compared to the classification results obtained with the full ensemble consisting of 1000 trees. In the simulation study, we were able to show that the prevalence of glaucoma is a critical factor and lower prevalence decreases the performance of our pruning strategies. The memory demand for glaucoma classification in an unbalanced data situation based on random forests could effectively be reduced by the application of pruning strategies without loss of performance in a population with increased risk of glaucoma.

Correlation between CHA2DS2-VASc Score and Glaucoma Treatment and Prognosis.

PubMed

Pikkel, Yoav Y; Krebs, Daniel; Igal, Vadim; Sharabi-Nov, Adi; Epstein, Irena; Pikkel, Joseph

2018-01-01

To find if CHA 2 DS 2 -VASc scale can accurately predict the treatment, prognosis, and outcome for primary open-angle glaucoma (POAG). A survey of 250,000 patient years was taken, using the records of the Ophthalmology Department at Ziv Medical Center. Data was collected regarding the retinal nerve fiber layer (RNFL), visual field (VF), line of treatment (LOT) of glaucoma, and all the data needed to accurately calculate CHA 2 DS 2 -VASc score for each patient. Sixty-seven patients were included in the statistical analysis. The mean age was 72.5 years. The mean CHA 2 DS 2 -VASc score was 3.27 + -1.7. Positive Pearson's correlation coefficients were found for LOT and CHA 2 DS 2 -VASc score, 0.35, and for RNFL grade and CHA2DS2-VASc score, 0.37. The correlation was negative for RNFL width and CHA2DS2-VASc score, -0.35. CHA 2 DS 2 -VASc score was shown to be correlated with glaucoma. This correlation was manifested positively by the LOT needed to stop glaucoma progression, with higher CHA 2 DS 2 -VASc scores correlated with more aggressive treatment. Since glaucoma is a disease with a progressing nature, it is important to treat patients aggressively on one hand, while offering the most benign treatment as possible on the other hand. Modification of the CHA 2 DS 2 -VASc score could achieve an even higher correlation.

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

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.

Investigational and experimental drugs for intraocular pressure reduction in ocular hypertension and glaucoma.

PubMed

Lusthaus, Jed Asher; Goldberg, Ivan

2016-10-01

Intraocular pressure (IOP) is the most significant modifiable risk factor to prevent onset or progression of glaucoma. Glaucoma prevalence continues to increase, emphasizing the need for improved ocular hypotensive treatment options. To try to improve on both tolerance and IOP control of currently available therapies, different receptors or mechanisms are being explored to reduce IOP more effectively and to improve tolerance. We review synthetic topical and oral drugs in early development for the management of ocular hypertension and glaucoma. New therapeutic agents for IOP control have been discovered; some appear to be reasonably tolerated. IOP reduction may be limited with some agents, but other benefits although unproven may compensate for this, such as less ocular surface disease, enhanced neuro-protection or increased ocular blood flow. Further product development promises improved treatment options for ocular hypertensives and glaucoma sufferers.

[Application value of corneal hysteresis in diagnosis and treatment of glaucoma].

PubMed

He, L Y; Liang, L; Zhu, M N

2017-02-11

Glaucoma is the first leading cause of irreversible blindness world widely, but the pathogenesis was still unclear. The collagen fibers from cornea and sclera connect to each other and both of them have similar extracellular matrix components. The biomechanical characteristics of optic nerve lamina cribrosa may associated with the biomechanical properties of the cornea. Therefore, the study of corneal physiological can indirectly reflex the compression and damage in optic nerve lamina cribrosa. The technical developments in corneal hysteresis examination had been updated these years constantly. Many researches implicated that low corneal hysteresis involved in pathogenesis and progression of glaucoma which refresh our recognition of the relationship between cornea and glaucoma. This review summarized the characteristics of corneal hysteresis, the examination and the connection with glaucoma to provide the reference for clinical work. (Chin J Ophthalmol, 2017, 53: 140-143) .

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection

PubMed Central

Mwanza, Jean-Claude; Warren, Joshua L.; Hochberg, Jessica T.; Budenz, Donald L.; Chang, Robert T.; Ramulu, Pradeep Y.

2014-01-01

Purpose To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. Methods One hundred and ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike’s information criterion (AIC), and prediction confidence interval lengths (PIL). Results For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDX-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT * NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAPFDT, and interaction GDx-TSNIT*NAP-FDT consistently provided better discriminating abilities for detecting early, moderate and severe glaucoma than the best single variable models. Conclusions The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDX-TSNIT * NAP-FDT provides the best glaucoma prediction compared to all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared to using GDx or FDT alone. PMID:24777046

Developing an Item Bank to Measure Quality of Life in Individuals With Glaucoma, and the Results of the Interview With Patients: The Effect of Visual Function, Visual Field Progression Rate, Medical, and Surgical Treatments on Quality of Life.

PubMed

Matsuura, Masato; Hirasawa, Kazunori; Hirasawa, Hiroyo; Yanagisawa, Mieko; Murata, Hiroshi; Mayama, Chihiro; Asaoka, Ryo

2017-02-01

To construct a new item bank to measure quality of life (QOL) in glaucoma patients and to evaluate glaucoma patients' QOL using the item bank. An item bank of questions was generated through a literature review of QOL instruments useful for glaucoma patients. Using this item bank, a cognitive survey was performed on 203 patients with glaucoma (112 males and 91 females, 61.9±11.9 y old; mean±SD). The results were then analyzed using the Rasch analysis, and the Rasch-derived disability scores were predicted using linear modelling and the following clinical parameters: age, mean total deviation (mTD) in superior and inferior visual field (mTDsup/mTDinf), mTD progression rate, better visual acuity, worse visual acuity, number of eye drops administered per day, number of trabeculectomy procedures experienced in both eyes. A total of 23 questionnaires of QOL in glaucoma patients were identified resulting in an item bank of 187 questions related to the following tasks: reading/writing, walking, going out, eating and driving (direct disability) as well as questions concerned with worry/anxiety, social participation, and physical symptoms (indirect disability). In the optimal model for direct disability, age and mTDinf were identified as significant predictors, whereas number of eye drops administered per day and number of trabeculectomy experienced were included in the optimal model for indirect disability. A new item bank to measure QOL in glaucoma patients was developed and evaluated. Age and mTDinf were found to be related to direct disability while medical and surgical treatments were related to indirect disability.

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

PubMed

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

2012-04-01

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.

Cost-effectiveness of treating normal tension glaucoma.

PubMed

Li, Emmy Y; Tham, Clement C; Chi, Stanley C; Lam, Dennis S

2013-05-13

To assess the long-term cost-effectiveness of treating normal tension glaucoma (NTG). A Markov decision-analytic health model was developed to determine the cost-effectiveness of treating NTG with IOP lowering therapy to prevent progressive visual field loss. Transitional probabilities were derived from the Collaborative Normal Tension Glaucoma Study and cost data obtained from the literature and the Medicare fee schedule. Incremental cost-effectiveness ratios (ICER) of treating all patients with NTG and treating selected individuals with risk factors for disease progression were determined using Monte Carlo simulation. Sensitivity analyses were performed by varying the cost of consultations, medications, laser/surgery, and adjusting utility loss from progressed states. The ICER of treating all patients with NTG over a 10-year period was United States (US) $34,225 per quality-adjusted life year (QALY). The ICER would be reduced when treatment was offered selectively to those with risk factors for disease progression. The ICER for treating NTG patients with disc hemorrhage, migraine, and those who were female were US $24,350, US $25,533, and US $27,000 per QALY, respectively. The cost-effectiveness of treating all NTG patients in this model was sensitive to cost fluctuation of medications, choice of utility score associated with disease progression, and insensitive to cost of consultations and laser/surgery. It is cost-effective, in the long-term, to offer IOP lowering therapy, aiming for a 30% reduction from the baseline, to all NTG patients. The incremental cost-effectiveness ratio of treating all patients with normal tension glaucoma over a 10-year period was $34,225 per quality-adjusted life year and should be offered to individuals in need.

Asymmetry of Peak Thicknesses between the Superior and Inferior Retinal Nerve Fiber Layers for Early Glaucoma Detection: A Simple Screening Method.

PubMed

Bae, Hyoung Won; Lee, Sang Yeop; Kim, Sangah; Park, Chan Keum; Lee, Kwanghyun; Kim, Chan Yun; Seong, Gong Je

2018-01-01

To assess whether the asymmetry in the peripapillary retinal nerve fiber layer (pRNFL) thickness between superior and inferior hemispheres on optical coherence tomography (OCT) is useful for early detection of glaucoma. The patient population consisted of Training set (a total of 60 subjects with early glaucoma and 59 normal subjects) and Validation set (30 subjects with early glaucoma and 30 normal subjects). Two kinds of ratios were employed to measure the asymmetry between the superior and inferior pRNFL thickness using OCT. One was the ratio of the superior to inferior peak thicknesses (peak pRNFL thickness ratio; PTR), and the other was the ratio of the superior to inferior average thickness (average pRNFL thickness ratio; ATR). The diagnostic abilities of the PTR and ATR were compared to the color code classification in OCT. Using the optimal cut-off values of the PTR and ATR obtained from the Training set, the two ratios were independently validated for diagnostic capability. For the Training set, the sensitivities/specificities of the PTR, ATR, quadrants color code classification, and clock-hour color code classification were 81.7%/93.2%, 71.7%/74.6%, 75.0%/93.2%, and 75.0%/79.7%, respectively. The PTR showed a better diagnostic performance for early glaucoma detection than the ATR and the clock-hour color code classification in terms of areas under the receiver operating characteristic curves (AUCs) (0.898, 0.765, and 0.773, respectively). For the Validation set, the PTR also showed the best sensitivity and AUC. The PTR is a simple method with considerable diagnostic ability for early glaucoma detection. It can, therefore, be widely used as a new screening method for early glaucoma. © Copyright: Yonsei University College of Medicine 2018

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.

Detection of Glaucoma and Its Association With Diabetic Retinopathy in a Diabetic Retinopathy Screening Program.

PubMed

Gangwani, Rita A; McGhee, Sarah M; Lai, Jimmy S M; Chan, Christina K W; Wong, David

2016-01-01

To determine the type of glaucoma in subjects with diabetes mellitus detected during a diabetic retinopathy screening program and to determine any association between diabetic retinopathy (DR) and glaucoma. This is a population-based prospective cross-sectional study, in which subjects with diabetes mellitus underwent screening for DR in a primary care outpatient clinic. Digital fundus photographs were taken and graded for presence/absence and severity of DR. During this grading, those fundus photographs showing increased cup-to-disc ratio (CDR) (≥0.6) were identified and these patients were referred to the specialist ophthalmology clinic for detailed examination. The presence of glaucoma was established based on CDR and abnormal visual field (VF) defects according to Hodapp-Parrish-Anderson's criteria. An elevation of intraocular pressure was not required for the diagnosis of glaucoma. The patients said to have definite glaucoma were those with vertical CDR>/=0.6, glaucomatous defects on VF examination, or retinal nerve fiber thinning if VF was unreliable. Of the 2182 subjects who underwent screening, 81 subjects (3.7%) had increased CDR and 40 subjects (1.8%) had confirmed glaucoma. Normal-tension variant of primary open-angle glaucoma was the most prevalent type (1.2%) We did not find any evidence that DR is a risk factor for glaucoma [odds ratio for DR vs. no DR=1.22 (95% confidence interval, 0.59-2.51)]. The overall prevalence of glaucoma in this diabetic population, based on finding increased cupping of optic disc in a teleretinal screening program was 1.8% (95% confidence interval, 1.0-3.0).

In Glaucoma the Upregulated Truncated TrkC.T1 Receptor Isoform in Glia Causes Increased TNF-α Production, Leading to Retinal Ganglion Cell Death

PubMed Central

Bai, Yujing; Shi, ZhiHua; Zhuo, Yehong; Liu, Jing; Malakhov, Andrey; Ko, Eunhwa; Burgess, Kevin; Schaefer, Henry; Esteban, Pedro F.; Tessarollo, Lino; Saragovi, H. Uri

2010-01-01

Purpose. Glaucoma is a distinct neuropathy characterized by the chronic and progressive death of retinal ganglion cells (RGCs). The etiology of RGC death remains unknown. Risk factors for glaucomatous RGC death are elevated intraocular pressure and glial production of tumor necrosis factor-alpha (TNF-α). Previously, the authors showed that glaucoma causes a rapid upregulation of a neurotrophin receptor truncated isoform lacking the kinase domain, TrkC.T1, in retina. Here they examined the biological role of TrkC.T1 during glaucoma progression. Methods. Rat and mouse models of chronic ocular hypertension were used. Immunofluorescence Western blot analysis and in situ mRNA hybridization were used to identify cells upregulating TrkC.T1. A genetic model of engineered mice lacking TrkC.T1 (TrkC.T1−/−) was used to validate a role for this receptor in glaucoma. Pharmacologic studies were conducted to evaluate intravitreal delivery of agonists or antagonists of TrkC.T1, compared with controls, during glaucoma. Surviving RGCs were quantified by retrograde-labeling techniques. Production of neurotoxic TNF-α and α2 macroglobulin were quantified. Results. TrkC.T1 was upregulated in retinal glia, with a pattern similar to that of TNF-α. TrkC.T1−/− mice had normal retinas. However, during experimental glaucoma, TrkC.T1−/− mice had lower rates of RGC death and produced less TNF-α than wild-type littermates. In rats with glaucoma, the pharmacologic use of TrkC antagonists delayed RGC death and reduced the production of retinal TNF-α. Conclusions. TrkC.T1 is implicated in glaucomatous RGC death through the control of glial TNF-α production. Overall, the data point to a paracrine mechanism whereby elevated intraocular pressure upregulated glial TrkC.T1 expression in glia; TrkC.T1 controlled glial TNF-α production, and TNF-α caused RGC death. PMID:20574020

Risk Factors Associated with Progression to Blindness from Primary Open-Angle Glaucoma in an African-American Population

PubMed Central

Pleet, Alexander; Sulewski, Melanie; Salowe, Rebecca J.; Fertig, Raymond; Salinas, Julia; Rhodes, Allison; Merritt, William; Natesh, Vikas; Huang, Jiayan; Gudiseva, Harini V.; Collins, David W.; Chavali, Venkata Ramana Murthy; Tapino, Paul; Lehman, Amanda; Regina-Gigiliotti, Meredith; Miller-Ellis, Eydie; Sankar, Prithvi; Ying, Gui-Shuang; O’Brien, Joan M.

2016-01-01

Purpose To determine the risk factors associated with progression to blindness from primary open-angle glaucoma (POAG) in an African-American population. Methods This study examined 2119 patients enrolled in the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study. A total of 59 eyes were identified as legally blind as a result of POAG (cases) and were age-and sex-matched to 59 non-blind eyes with glaucoma (controls). Chart reviews were performed to record known and suspected risk factors. Results Cases were diagnosed with POAG at an earlier age than controls (p = 0.005). Of the 59 eyes of cases, 16 eyes (27.1%) presented with blindness at diagnosis. Cases had worse visual acuity (VA) at diagnosis (p < 0.0001), with VA worse than 20/40 conferring a 27 times higher risk of progression to blindness (p = 0.0005). Blind eyes also demonstrated more visual field defects (p = 0.01), higher pretreatment intraocular pressure (IOP; p < 0.0001), and higher cup-to-disc ratio (p = 0.006) at diagnosis. IOP was less controlled in cases, and those with IOP ≥21 mmHg at more than 20% of follow-up visits were 73 times more likely to become blind (p < 0.0001). Cases missed a greater number of appointments per year (p = 0.003) and had non-adherence issues noted in their charts more often than controls (p = 0.03). However, other compliance data did not significantly differ between groups. Conclusion Access to care, initial VA worse than 20/40, and poor control of IOP were the major risk factors associated with blindness from POAG. Future studies should examine earlier, more effective approaches to glaucoma screening as well as the role of genetics in these significantly younger patients who progress to blindness. PMID:27348239

Relationship between progression of visual field defect and intraocular pressure in primary open-angle glaucoma.

PubMed

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

2015-01-01

To analyze the relationship between intraocular pressure (IOP) and the progression of visual field defects in Japanese primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) patients. The subjects of the study were patients undergoing treatment for POAG or NTG who had performed visual field tests at least ten times with a Humphrey field analyzer (Swedish interactive thresholding algorithm standard, C30-2 program). The progression of visual field defects was defined by a significantly negative value of the mean deviation slope at the final visual field test during the follow-up period. The relationships between the progression of visual field defects and IOP, as well as other clinical factors, were retrospectively analyzed. A total of 156 eyes of 156 patients were included in the analysis. Significant progression of visual field defects was observed in 70 eyes of 70 patients (44.9%), while no significant progression was evident in 86 eyes of 86 patients (55.1%). The eyes with visual field defect progression had significantly lower baseline IOP (P<0.05), as well as significantly lower IOP reduction rate (P<0.01). The standard deviation of IOP values during follow-up was significantly greater in the eyes with visual field defect progression than in eyes without (P<0.05). Reducing IOP is thought to be useful for Japanese POAG or NTG patients to suppress the progression of visual field defects. In NTG, IOP management should take into account not only achieving the target IOP, but also minimizing the fluctuation of IOP during follow-up period.

Opportunistic detection of glaucomatous optic discs within a diabetic retinopathy screening service.

PubMed

Treacy, Maxwell P; O'Neill, Evelyn C; Murphy, Melissa; O'Toole, Louise; Delaney, Yvonne; O'Brien, Colm; Connell, Paul P

2016-06-10

To determine the prevalence of glaucoma among patients referred to a glaucoma service with suspicious disc photographs from the diabetic retinopathy (DR) screening program. A clinical audit of all patients attending a single-center DR screening program in the Mater Misericordiae University Hospital, Dublin, between July 2010 and October 2011 was conducted with a minimum follow-up of 30 months. The DR screening service uses trained technician graders to assess 2-field color retinal photographs for the features of DR. Recently, the service was enhanced so that optic discs are also assessed for signs of glaucoma. In the 16-month study period, 3,697 diabetic patients were photographed. Following photograph grading, 91 (2.46%) were judged to require referral for assessment at the glaucoma clinic. Of these, 63 (69.23%) presented for assessment. Thirteen patients (20.63%) were diagnosed with glaucoma, comprising 7 cases of low-tension glaucoma and 6 cases of primary open-angle glaucoma. Thirty-six patients (57.14%) were classified as glaucoma suspects and 14 patients (22.22%) were discharged back to the DR screening program following normal ocular examination. Only 6 (9.52%) of the 63 patients examined had an intraocular pressure greater than 21 mm Hg. The assessment of DR screening photographs for signs of glaucomatous optic nerve damage should be considered as part of a strategy to improve glaucoma case detection and to reduce the burden of this disease on society.

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.

Peripapillary schisis in open-angle glaucoma.

PubMed

Dhingra, N; Manoharan, R; Gill, S; Nagar, M

2017-03-01

PurposeTo report clinical features, topographic findings and outcome of 10 eyes with peripapillary schisis in open-angle glaucoma.Patients and methodsA retrospective review of patients with open-angle glaucoma who were noted to have peripapillary schisis on optical coherence tomography (OCT) were included. Serial peripapillary and macula infrared and OCT images, visual acuity, visual fields, and schisis appearance were reviewed.ResultsTen eyes of nine patients with open-angle glaucoma were detected to have the presence of peripapillary schisis. Nerve fibre layer schisis was detected in all eyes and one eye had an associated macular schisis. None of the eyes had an acquired pit of the optic nerve or pathological myopia. The mean intraocular pressures at detection was 18.3±4.3 mm Hg and the schisis resolved in four eyes after a mean follow-up of 21.2±8.8 months. Visual field worsening was noted in 4 of the 10 eyes and the resolution of schisis resulted in significant reduction in the retinal nerve fibre layer (RNFL) thickness.ConclusionsPeripapillary schisis detected during the normal course of open-angle glaucoma can resolve spontaneously and rarely involves the macula. Its resolution leads to reduction in RNFL thickness; therefore, caution is advised while interpreting serial scans.

The Effect of Simulated Altitude on the Visual Fields of Glaucoma Patients and the Elderly

DTIC Science & Technology

1991-01-01

certification policy does not appear to put pilots or passengers with glaucoma at risk for disease progression. Under short-term exposure to mild hypoxia, we...9. Kobrick JL, Crohn E, Shukitt B, Houston CS, Sutton JR, Cymerman A. Operation Everest II: lack of an effect of extreme altitude on visual contrast

Management of exfoliative glaucoma: challenges and solutions.

PubMed

Holló, Gábor; Katsanos, Andreas; Konstas, Anastasios Gp

2015-01-01

Exfoliative glaucoma is the most common type of secondary open-angle glaucoma worldwide. It is characterized by high intraocular pressure (IOP) and worse 24-hour IOP characteristics. In order to minimize progression, treatment of exfoliative glaucoma has to provide a low long-term mean IOP and good 24-hour IOP control. To achieve these goals, fixed-dose combination eye drops, argon and selective laser trabeculoplasty, and various forms of surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, ab interno trabeculotomy, trabecular aspiration, and cataract surgery) all need to be considered during the long-term management of the disease. Since exfoliative glaucoma is a disease of the elderly, and is frequently associated with systemic vascular disease, interdisciplinary consultations are of great clinical importance. These management aspects and the current medical, laser, and surgical results are covered in this review, with a special focus on the needs of the general ophthalmologist.

Management of exfoliative glaucoma: challenges and solutions

PubMed Central

Holló, Gábor; Katsanos, Andreas; Konstas, Anastasios GP

2015-01-01

Exfoliative glaucoma is the most common type of secondary open-angle glaucoma worldwide. It is characterized by high intraocular pressure (IOP) and worse 24-hour IOP characteristics. In order to minimize progression, treatment of exfoliative glaucoma has to provide a low long-term mean IOP and good 24-hour IOP control. To achieve these goals, fixed-dose combination eye drops, argon and selective laser trabeculoplasty, and various forms of surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, ab interno trabeculotomy, trabecular aspiration, and cataract surgery) all need to be considered during the long-term management of the disease. Since exfoliative glaucoma is a disease of the elderly, and is frequently associated with systemic vascular disease, interdisciplinary consultations are of great clinical importance. These management aspects and the current medical, laser, and surgical results are covered in this review, with a special focus on the needs of the general ophthalmologist. PMID:26045655

Adherence to Follow-up Recommendations Among Individuals in the Philadelphia Glaucoma Detection and Treatment Project.

PubMed

Hark, Lisa A; Leiby, Benjamin E; Waisbourd, Michael; Myers, Jonathan S; Fudemberg, Scott J; Mantravadi, Anand V; Dai, Yang; Gilligan, John P; Resende, Arthur F; Katz, L Jay

2017-08-01

To evaluate rates of adherence to free follow-up eye exam appointments among participants in the Philadelphia Glaucoma Detection and Treatment Project. Ophthalmologists and testing equipment were brought directly to participants at risk for glaucoma at 43 community sites in Philadelphia. Those diagnosed with glaucoma-related pathology were recommended to return for follow-up to be reexamined on site. Rates of adherence and clinical and demographic risk factors for adherence were evaluated. Five hundred thirty-one participants were diagnosed with glaucoma-related conditions and recommended to attend community-based follow-up exams. Follow-up adherence rate was 61.2% (n=325/531). Significant factors associated with greater eye exam appointment adherence, based on our univariable analysis, included final diagnosis of glaucoma (risk ratio [RR]=1.33; 95% confidence interval [CI], 1.13-1.57), male sex (RR=1.19; 95% CI, 1.04-1.36), white race (RR=1.26; 95% CI, 1.08-1.48), age (RR=1.17; 95% CI, 1.00-1.37) recommendation for glaucoma medication (RR=1.52; 95% CI, 1.35-1.71), recommendation for laser peripheral iridotomy (RR=1.18; 95% CI, 1.02-1.35), diagnosis of age-related macular degeneration (RR=1.42; 95% CI, 1.13-1.77) and an increased intraocular pressure (>22 mm Hg in the worse eye) (RR=1.23; 95% CI, 1.06-1.42). On the basis of our multivariable model, diagnosis, sex, and recommended glaucoma medications were significantly associated with follow-up adherence. This study demonstrates that individuals living in underserved urban communities would take advantage of free eye exams in community sites and return for follow-up eye exams in these same settings. Future studies could investigate interventions to improve eye exam appointment adherence in community-based settings to detect glaucoma-eye conditions.

Incidence of and risk factors for glaucoma in lost-to-follow-up normal-tension glaucoma suspect patients.

PubMed

Lim, Jong Hoon; Park, Jun Sang; Lee, So Yeon; Hong, Young Jae

2016-05-25

To investigate the incidence and risk factors of glaucoma in normal-tension glaucoma (NTG) suspect patients who had been lost-to-follow-up for at least 24 months. Seventy-two eyes of 72 NTG suspect patients who returned to the hospital after at least 24 months of follow-up loss were enrolled in this study between January 2009 and June 2013. The data were collected retrospectively. The incidence of glaucoma was investigated using a comprehensive glaucoma evaluation in lost-to-follow-up NTG suspect patients. The patients were classified into the glaucoma group, who developed glaucoma during the study period, and the glaucoma suspect group, who did not, to analyse the risk factors for glaucoma. The number of patients who developed glaucoma was 7 (9.7 %) out of the 72 NTG suspect patients who had been mean lost-to-follow-up for 44 months. The rate of progression from suspected to glaucoma was 2.6 %/year. In the glaucoma group, the baseline intraocular pressure (IOP) was 18.43 ± 2.44 mmHg, and the average retinal nerve fiber layer (RNFL) thickness was 78.14 ± 7.60 μm; in the glaucoma suspect group, the baseline IOP was 14.95 ± 2.47 mmHg, and the average RNFL thickness was 92.55 ± 7.65 μm. The study results showed that the glaucoma group had higher baseline IOP and a thinner average RNFL (p = 0.003; p < 0.001). The results of the multivariable logistic regression analysis showed that the risk factors for glaucoma were high baseline IOP (OR = 1.63; p = 0.037) and a thin average RNFL (OR = 0.841; p = 0.004). The incidence of glaucoma in the lost-to-follow-up NTG suspect patients was 9.7 % for approximately 44 months, at a rate of 2.6 %/year. The risk factors for glaucoma in these patients were high baseline IOP and a thin average RNFL.

[Music and Glaucoma].

PubMed

Plange, N

2017-02-01

Music may have multiple influences on the human organism. A possible therapeutic effect for patients with glaucoma has been postulated, aside from the known impact of music on the cardiovascular system, psychogenic effects and a short-term improvement in mental performance (Mozart effect). The higher level of mental stress in patients with glaucoma and type-A personality behaviour may be related to higher intraocular pressure in patients with glaucoma. Relaxing music may have a positive impact in these patients, related to a reduction in intraocular pressure or its fluctuations. However, only limited data exist on the effects of music on intraocular pressure. No clinical studies have yet been performed to investigate the effect of music or music therapy on glaucoma progression. The music of Mozart may influence visual field examinations, possibly due to a positive short term effect on mental performance. This factor needs to be addressed in studies dealing with the effect of music in glaucoma. The relevance of intraocular pressure increases in professional wind instrument players is controversial. An increased level of care might be advisable in patients with advanced glaucoma. The influences of music on humans, altered personality profiles in patients with glaucoma and the studies showing some effect of stress on intraocular pressure stress the relevance of psychological support for glaucoma patients, who are confronted with a disease with a high longterm risk of blindness. Georg Thieme Verlag KG Stuttgart · New York.

Glaucoma management in patients with osteo-odonto-keratoprosthesis (OOKP): the Singapore OOKP Study.

PubMed

Kumar, Rajesh S; Tan, Donald T H; Por, Yong-Ming; Oen, Francis T; Hoh, Sek-Tien; Parthasarathy, Anand; Aung, Tin

2009-01-01

To report diagnostic modalities and treatment options for glaucoma in eyes with osteo-odonto keratoprosthesis (OOKP). Eyes that underwent OOKP were evaluated for glaucoma at the time of the first postoperative visit, then at 1 and 3 months after the procedure, and thereafter every 6 months. All eyes underwent stereo-biomicroscopic optic nerve head (ONH) assessment, kinetic (Goldmann perimetry) and automated static visual field testing, ONH photography, Heidelberg retina tomograph, scanning laser polarimetery (GDx), and optical coherence tomography. Treatment of glaucoma was also reviewed. Average follow-up period was 19.1 (range: 5 to 31) months. Of the 15 eyes that underwent OOKP, 5 eyes had preexisting glaucoma. None of the other 10 eyes developed glaucoma after OOKP. ONH photography and visual field testing were the most reliable methods to assess status of the disease, whereas Heidelberg retina tomograph and optical coherence tomography could be performed with reasonable reproducibility and quality; GDx imaging was poor. All patients with glaucoma were treated with oral acetazolamide 500 mg twice a day. Transscleral cyclophotocoagulation was performed in 3 eyes at stage 2 of OOKP surgery. Progression of glaucoma was noted in 2 eyes on the basis of optic disc photographs and automated perimetry. Visual field testing and optic disc assessment with optic disc photographs seem to be effective methods to monitor eyes with OOKP for glaucoma. Treatment strategies include oral medications to lower intraocular pressure and cyclophotocoagulation.

Change in Visual Field Progression Following Treatment Escalation in Primary Open-angle Glaucoma.

PubMed

Aptel, Florent; Bron, Alain M; Lachkar, Yves; Schweitzer, Cédric

2017-10-01

To evaluate the effect of treatment escalation on the rate of visual field progression in patients with primary open-angle glaucoma (POAG). Multicenter database study. We reviewed the electronic records of 171 patients with POAG under medical hypotensive treatment who underwent 5 consecutive visits 6 months apart before and after medical treatment escalation or additive laser trabeculoplasty. We calculated the rate of visual field progression (mean deviation change per year) before and after treatment escalation. The mean duration of follow-up was 5.1±0.5 years and the mean number of visual field examinations was 10.2±0.2. In 139 eyes with medical treatment escalation, the rate of progression was significantly reduced [from -0.57 to -0.29 dB/y; P=0.022; intraocular pressure (IOP) reduction 11.1%]. In detail, the rate of progression was significantly reduced after escalation from mono to dual therapy, dual to triple therapy, and from mono to triple therapy (-0.35 to -0.24 dB/y, P=0.018; -1.01 to -0.48 dB/y, P=0.038; -1.04 to -0.35 dB/y, P=0.020, respectively). In 32 eyes with additive laser trabeculoplasty, the rate of progression was significantly reduced (-0.60 to -0.24 dB/y; P=0.014; IOP reduction 9.4%). Medical treatment escalation or additive laser trabeculoplasty significantly reduced the rate of visual field progression in POAG. Larger IOP reduction has a greater probability of reducing glaucoma progression.

Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

PubMed

Toris, Carol B; Gelfman, Claire; Whitlock, Andy; Sponsel, William E; Rowe-Rendleman, Cheryl L

2017-09-01

Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems. Here, we present the case for the development of such maps and consensus statements, which are critical for faster development of the most efficacious glaucoma therapy. We underscore that interrogating the preclinical path of both successful and unsuccessful clinical programs is essential to defining future research. One aspect of this is evaluation of available preclinical research tools. To begin this process, we highlight the utility of currently available animal models for glaucoma and emphasize that there is a particular need for models of glaucoma with normal intraocular pressure. In addition, we outline a series of discoveries from cell-based, animal, and translational research that begin to reveal a map of glaucoma from cell biology to physiology to disease pathology. Completion of these maps requires input and consensus from the global glaucoma research community. This article sets the stage by outlining various approaches to such a consensus. Together, these efforts will help accelerate basic science research, leading to discoveries with significant clinical impact for people with glaucoma.

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

The Role of Epigenetics in the Fibrotic Processes Associated with Glaucoma

PubMed Central

O'Brien, Colm

2014-01-01

Glaucoma is an optic neuropathy that affects 60 million people worldwide. The main risk factor for glaucoma is increased intraocular pressure (IOP), this is currently the only target for treatment of glaucoma. However, some patients show disease progression despite well-controlled IOP. Another possible therapeutic target is the extracellular matrix (ECM) changes in glaucoma. There is an accumulation of ECM in the lamina cribrosa (LC) and trabecular meshwork (TM) and upregulation of profibrotic factors such as transforming growth factor β (TGFβ), collagen1α1 (COL1A1), and α-smooth muscle actin (αSMA). One method of regulating fibrosis is through epigenetics; the study of heritable changes in gene function caused by mechanisms other than changes in the underlying DNA sequence. Epigenetic mechanisms have been shown to drive renal and pulmonary fibrosis by upregulating profibrotic factors. Hypoxia alters epigenetic mechanisms through regulating the cell's response and there is a hypoxic environment in the LC and TM in glaucoma. This review looks at the role that hypoxia plays in inducing aberrant epigenetic mechanisms and the role these mechanisms play in inducing fibrosis. Evidence suggests that a hypoxic environment in glaucoma may induce aberrant epigenetic mechanisms that contribute to disease fibrosis. These may prove to be relevant therapeutic targets in glaucoma. PMID:24800062

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

The Ahmed Glaucoma Valve in Refractory Glaucoma: Experiences in Southwest Ethiopia.

PubMed

Gessesse, Girum W

2015-07-01

The management of refractory glaucoma is a challenging task for any glaucoma surgeon. This study is aimed to evaluate the efficacy of Ahmed Glaucoma Valve implantation in refractory glaucomas in South-West Ethiopia. A retrospective review was conducted on the charts of consecutive patients treated with Ahmed glaucoma valve implantation at Jimma University Specialized Hospital between August 2012 and August 2014. Success was defined as Intraocular Pressure (IOP) less than 22 mm Hg and greater than 5mm Hg at 6 months, with at least 30% reduction from baseline, without medical therapy (complete success) or either with or without medication (qualified successes). A total of 12 eyes of 11 patients were included. The mean age of patients was 40.7 (SD= 19.0) years; 63.6% of them were males. The main types of glaucoma were pseudoexfoliative (3 eyes), uveitic (2 eyes), chronic angle closure (2 eyes) and Juvenile Open Angle (JOAG) (2 eyes). The mean IOP was reduced from preoperative level (32.75±7.14 mmHg) to (15.75 ±4.35 mmHg) at six postoperative months, (P<0.001); 66.7% eyes had complete successes while 83.3% had qualified success. Intra-operative complications were encountered in 2(16.7%) eyes, while 5/12 (41.7%) eyes had post-operative complications-hypotony (one with choroidal effusion) and progression of cataract in 2 eyes each. Hypertensive phase was diagnosed in 2(16.7%) eyes. The Ahmed glaucoma valve implant appears to be effective and relatively safe for treating complicated glaucomas with success rate comparable with those reported from other studies. Ahmed glaucoma valve, refractory glaucoma, complications, Ethiopia.

Benzalkonium Chloride and Glaucoma

PubMed Central

Kaufman, Paul L.; Kiland, Julie A.

2014-01-01

Abstract Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative in glaucoma medications. BAK has been detected in the trabecular meshwork (TM), corneal endothelium, lens, and retina after topical drop installation and may accumulate in those tissues. There is evidence that BAK causes corneal and conjunctival toxicity, including cell loss, disruption of tight junctions, apoptosis and preapoptosis, cytoskeleton changes, and immunoinflammatory reactions. These same effects have been reported in cultured human TM cells exposed to concentrations of BAK found in common glaucoma drugs and in the TM of primary open-angle glaucoma donor eyes. It is possible that a relationship exists between chronic exposure to BAK and glaucoma. The hypothesis that BAK causes/worsens glaucoma is being tested experimentally in an animal model that closely reflects human physiology. PMID:24205938

Ultrahigh-Resolution Optical Coherence Tomography in Glaucoma

PubMed Central

Wollstein, Gadi; Paunescu, Leila A.; Ko, Tony H.; Fujimoto, James G.; Kowalevicz, Andrew; Hartl, Ingmar; Beaton, Siobahn; Ishikawa, Hiroshi; Mattox, Cynthia; Singh, Omah; Duker, Jay; Drexler, Wolfgang; Schuman, Joel S.

2007-01-01

Objective Optical coherence tomography (OCT) has been shown to be a valuable tool in glaucoma assessment. We investigated a new ultrahigh-resolution OCT (UHR-OCT) imaging system in glaucoma patients and compared the findings with those obtained by conventional-resolution OCT. Design Retrospective comparative case series. Participants A normal subject and 4 glaucoma patients representing various stages of glaucomatous damage. Testing All participants were scanned with StratusOCT (axial resolution of ~10 μm) and UHR-OCT (axial resolution of ~3 μm) at the same visit. Main Outcome Measure Comparison of OCT findings detected with StratusOCT and UHR-OCT. Results Ultrahigh-resolution OCT provides a detailed cross-sectional view of the scanned retinal area that allows differentiation between retinal layers. These UHR images were markedly better than those obtained by the conventional-resolution OCT. Conclusions Ultrahigh-resolution OCT provides high-resolution images of the ocular posterior segment, which improves the ability to detect retinal abnormalities due to glaucoma. PMID:15691556

An introduction to DARC technology.

PubMed

Ahmad, Syed Shoeb

2017-01-01

Glaucoma is a multi-factorial neurodegenerative disorder. The common denominator in all types of glaucomas is retinal ganglion cell death through apoptosis. However, this cellular demise in glaucoma is detected late by structural or functional analyses. There can be a 10-year delay prior to the appearance of visual field defects and pre-perimetric glaucoma is an issue still being addressed. However, a new cutting-edge technology called detection of apoptosing retinal cells (DARC) is being developed. This technique is capable of non-invasive, real-time visualization of apoptotic changes at the cellular level. It can detect glaucomatous cell damage at a very early stage, at the moment apoptosis starts, and thus management can be initiated even prior to development of visual field changes. In future, this technique will also be able to provide conclusive evidence of the effectiveness of treatment protocol and the need for any modifications which may be required. This article aims to provide a concise review of DARC technology.

Image processing based automatic diagnosis of glaucoma using wavelet features of segmented optic disc from fundus image.

PubMed

Singh, Anushikha; Dutta, Malay Kishore; ParthaSarathi, M; Uher, Vaclav; Burget, Radim

2016-02-01

Glaucoma is a disease of the retina which is one of the most common causes of permanent blindness worldwide. This paper presents an automatic image processing based method for glaucoma diagnosis from the digital fundus image. In this paper wavelet feature extraction has been followed by optimized genetic feature selection combined with several learning algorithms and various parameter settings. Unlike the existing research works where the features are considered from the complete fundus or a sub image of the fundus, this work is based on feature extraction from the segmented and blood vessel removed optic disc to improve the accuracy of identification. The experimental results presented in this paper indicate that the wavelet features of the segmented optic disc image are clinically more significant in comparison to features of the whole or sub fundus image in the detection of glaucoma from fundus image. Accuracy of glaucoma identification achieved in this work is 94.7% and a comparison with existing methods of glaucoma detection from fundus image indicates that the proposed approach has improved accuracy of classification. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Progression: things we need to remember but often forget to think about.

PubMed

Artes, Paul H

2008-06-01

Detecting progression, and estimating the rate of change, are among the most important challenges in the care of patients with glaucoma. With rapidly developing technology, there is a need to rethink what we mean to measure, why we measure it, and how we think about these measurements and how they relate to the disease. This article outlines, informally, a small number of issues that may be important to clinicians and researchers alike but are not often discussed in the literature. It is intended to be useful as a highly selective minireview of recent work and a stimulus for future research. It is organized under three main headings that sum up the main message of each section.

Measurement of Optic Disc Cup Surface Depth Using Cirrus HD-OCT.

PubMed

Kim, Young Kook; Ha, Ahnul; Lee, Won June; Jeoung, Jin Wook; Park, Ki Ho

2017-12-01

To introduce the measurement method of optic disc cup surface depth using spectral-domain optical coherence tomography (SD-OCT) and then evaluate the rates of cup surface depression at 3 different stages of glaucoma. We retrospectively identified 52 eyes with preperimetric glaucoma, 56 with mild-or-moderate glaucoma and 50 with severe glaucoma and followed them for at least 48 months. Eyes were imaged using SD-OCT (Cirrus HD-OCT) at 12-month intervals. The mean cup surface depth was calculated using the following formula: Cup volume/(disc area×average cup-to-disc ratio)-200 μm. The rates of mean cup surface depression (μm/y) were significantly greater in mild-or-moderate glaucoma (-7.96±1.03) than in preperimetric (-3.11±0.61) and severe glaucoma (-0.70±0.12; all P<0.001). The percentile rates of mean cup surface depression (%/y) were significantly greater than those of average of retinal nerve fiber layer (RNFL) thinning (%/y) in preperimetric glaucoma (-1.64±0.12 vs. -1.11±0.07; P<0.001) and mild-or-moderate glaucoma (-4.20±0.33 vs. -3.14±0.19; P<0.001); and conversely, in severe glaucoma, mean cup surface depth changed slower than did average RNFL thickness (-0.64±0.06 vs. -0.75±0.08%/y; P<0.001). In early-to-moderate glaucoma, the cup surface depth changed faster than did the RNFL thickness. These results signify the possibility that SD-OCT-based estimation of cup surface depth might be useful for monitoring of glaucoma development and progression.

Molecular genetics of the glaucomas: Mapping of the first five {open_quotes}GLC{close_quotes} loci

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, V.

1997-02-01

Glaucoma encompasses a complex of ocular-disease entities characterized by an optic neuropathy in which degeneration of retinal ganglion cells leads to a characteristic excavation of the head of the optic nerve. Such damage causes progressive narrowing of the visual fields and, when uncontrolled, blindness. Affected people often have ocular hypertension defined as intraocular pressures consistently >21 mm Hg in both eyes. Although ocular hypertension is no longer an obligatory diagnostic criterion for glaucoma, it is still recognized as one of the most important risk factors. A diagnosis of glaucoma is made after observation of the characteristic atrophy of the opticmore » nerve, which is associated with typical visual field defects. In 1992, the World Health Organization estimated that, in the global population, 5.2 million people were blind as a result of glaucoma, making it the third leading cause of blindness worldwide. The most common form is adult-onset primary open-angle glaucoma, which represents {ge}50% of all cases of glaucoma. Among Caucasians, this form of the disorder affects {approximately}2% of the population >45 years old. In African Americans, prevalence of adult-onset open-angle glaucoma is three to four times higher than that observed in White Americans. More than 15 million North Americans may have some form of glaucoma, but at least half of them may not be aware of it. 43 refs., 1 tab.« less

Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment

PubMed Central

Gemenetzi, M; Yang, Y; Lotery, A J

2012-01-01

Glaucoma is a common, complex, heterogenous disease and it constitutes the major cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is the most common type of glaucoma in all populations. Most of the molecular mechanisms leading to POAG development are still unknown. Gene mutations in various populations have been identified by genetic studies and a genetic basis for glaucoma pathogenesis has been established. Linkage analysis and association studies are genetic approaches in the investigation of the genetic basis of POAG. Genome-wide association studies (GWAS) are more powerful compared with linkage analysis in discovering genes of small effect that might contribute to the development of the disease. POAG links to at least 20 genetic loci, but only 2 genes identified in these loci, myocilin and optineurin, are considered as well-established glaucoma-causing genes, whereas the role of other loci, genes, and variants implicated in the development of POAG remains controversial. Gene mutations associated with POAG result in retinal ganglion cell death, which is the common outcome of pathogenetic mechanisms in glaucoma. In future, if the sensitivity and specificity of genotyping increases, it may be possible to screen individuals routinely for disease susceptibility. This review is an update on the latest progress of genetic studies associated with POAG. It emphasizes the correlation of recent achievements in genetics with glaucoma pathophysiology, glaucoma treatment perspectives, and the possibility of future prevention of irreversible visual loss caused by the disease. PMID:22173078

Evaluation of a glaucoma patient

PubMed Central

Thomas, Ravi; Loibl, Klaus; Parikh, Rajul

2011-01-01

The diagnosis of glaucoma is usually made clinically and requires a comprehensive eye examination, including slit lamp, applanation tonometry, gonioscopy and dilated stereoscopic evaluation of the optic disc and retina. Automated perimetry is obtained if glaucoma is suspected. This establishes the presence of functional damage and provides a baseline for follow-up. Imaging techniques are not essential for the diagnosis but may have a role to play in the follow-up. We recommend a comprehensive eye examination for every clinic patient with the objective of detecting all potentially sight-threatening diseases, including glaucoma. PMID:21150033

Obstacle Avoidance, Visual Detection Performance, and Eye-Scanning Behavior of Glaucoma Patients in a Driving Simulator: A Preliminary Study

PubMed Central

Prado Vega, Rocío; van Leeuwen, Peter M.; Rendón Vélez, Elizabeth; Lemij, Hans G.; de Winter, Joost C. F.

2013-01-01

The objective of this study was to evaluate differences in driving performance, visual detection performance, and eye-scanning behavior between glaucoma patients and control participants without glaucoma. Glaucoma patients (n = 23) and control participants (n = 12) completed four 5-min driving sessions in a simulator. The participants were instructed to maintain the car in the right lane of a two-lane highway while their speed was automatically maintained at 100 km/h. Additional tasks per session were: Session 1: none, Session 2: verbalization of projected letters, Session 3: avoidance of static obstacles, and Session 4: combined letter verbalization and avoidance of static obstacles. Eye-scanning behavior was recorded with an eye-tracker. Results showed no statistically significant differences between patients and control participants for lane keeping, obstacle avoidance, and eye-scanning behavior. Steering activity, number of missed letters, and letter reaction time were significantly higher for glaucoma patients than for control participants. In conclusion, glaucoma patients were able to avoid objects and maintain a nominal lane keeping performance, but applied more steering input than control participants, and were more likely than control participants to miss peripherally projected stimuli. The eye-tracking results suggest that glaucoma patients did not use extra visual search to compensate for their visual field loss. Limitations of the study, such as small sample size, are discussed. PMID:24146975

Research progress on human genes involved in the pathogenesis of glaucoma (Review).

PubMed

Wang, Hong-Wei; Sun, Peng; Chen, Yao; Jiang, Li-Ping; Wu, Hui-Ping; Zhang, Wen; Gao, Feng

2018-05-23

Glaucoma is the leading cause of irreversible blindness globally. It is known that the incidence of glaucoma is closely associated with inheritance. A large number of studies have suggested that genetic factors are involved in the occurrence and development of glaucoma, and even affect the drug sensitivity and prognosis of glaucoma. In the present review, 22 loci of glaucoma are presented, including the relevant genes (myocilin, interleukin 20 receptor subunit B, optineurin, ankyrin repeat‑ and SOCS box‑containing protein 10, WD repeat‑containing protein 36, EGF‑containing fibulin‑like extracellular matrix protein 1, neurotrophin 4, TANK‑binding kinase 1, cytochrome P450 subfamily I polypeptide 1, latent transforming growth factor β binding protein 2 and TEK tyrosine kinase endothelial) and 74 other genes (including toll‑like receptor 4, sine oculis homeobox Drosophila homolog of 1, doublecortin‑like kinase 1, RE repeats‑encoding gene, retinitis pigmentosa GTPase regulator‑interacting protein, lysyl oxidase‑like protein 1, heat‑shock 70‑kDa protein 1A, baculoviral IAP repeat‑containing protein 6, 5,10‑methylenetetrahydrofolate reductase and nitric oxide synthase 3 and nanophthalmos 1) that are more closely associated with glaucoma. The pathogenesis of these glaucoma‑associated genes, glaucomatous genetics and genetic approaches, as well as glaucomatous risk factors, including increasing age, glaucoma family history, high myopia, diabetes, ocular trauma, smoking, intraocular pressure increase and/or fluctuation were also discussed.

Compliance with eye care in glaucoma patients with comorbid depression.

PubMed

Weiss, Guy A; Goldich, Yakov; Bartov, Elisha; Burgansky-Eliash, Zvia

2011-12-01

Comorbid depression may play an important role in non-compliance with medical treatment among patients with chronic illnesses. Glaucoma is a potentially blinding chronic disease requiring life-long commitment to medical therapy. Failure to adhere to anti-glaucoma treatment may lead to disease progression and visual loss. To assess the prevalence of depressive symptoms in glaucoma patients and the association between these symptoms and non-compliance with anti-glaucoma therapy. In this cross-sectional observational study, compliance with pharmacotherapy was assessed with the Morisky Medication Adherence questionnaire (eight items). Screening for depression was performed by means of the CES-D (Center for Epidemiologic Studies Depression scale). The association between depression and compliance rates was analyzed. The study group comprised 76 glaucoma patients; 19.7% of the subjects were classified as non-compliant (Morisky cutoff 10) and 21.1% suffered from depression (CES-D cutoff > or = 16). We found a similar level of non-compliance when comparing depressed with non-depressed glaucoma patients. However, a correlation was observed between the level of depression and the level of non-compliance (P = 0.04). Our study revealed a similar rate of depression in glaucoma patients and the general israeli population. The presence of depression was not associated with the presence of non-compliance, yet the level of depression was associated with the level of non-compliance.

[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.

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

Medical Management of Glaucoma in the 21st Century from a Canadian Perspective

PubMed Central

Birt, Catherine; Gooi, Patrick; Heckler, Lisa; Hutnik, Cindy; Jinapriya, Delan; Shuba, Lesya; Yan, David; Day, Radmila

2016-01-01

Glaucoma is a medical term describing a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and retinal nerve fibre layer and resulting in changes in the optic nerve head. Glaucoma is a leading cause of irreversible vision loss worldwide. With the aging population it is expected that the prevalence of glaucoma will continue to increase. Despite recent advances in imaging and visual field testing techniques that allow establishment of earlier diagnosis and treatment initiation, significant numbers of glaucoma patients are undiagnosed and present late in the course of their disease. This can lead to irreversible vision loss, reduced quality of life, and a higher socioeconomic burden. Selection of therapeutic approaches for glaucoma should be based on careful ocular examination, patient medical history, presence of comorbidities, and awareness of concomitant systemic therapies. Therapy should also be individualized to patients' needs and preferences. Recent developments in this therapeutic field require revisiting treatment algorithms and integration of traditional and novel approaches in order to ensure optimal visual outcomes. This article provides an overview of recent developments and practice trends in the medical management of glaucoma in Canada. A discussion of the surgical management is beyond the scope of this paper. PMID:27895937

The use of Bruch's membrane opening-based optical coherence tomography of the optic nerve head for glaucoma detection in microdiscs.

PubMed

Enders, Philip; Schaub, Friederike; Adler, Werner; Nikoluk, Roman; Hermann, Manuel M; Heindl, Ludwig M

2017-04-01

To assess the performance of Bruch's membrane opening (BMO)-based spectral domain optical coherence tomography (SD-OCT) of the optic nerve head for glaucoma detection in microdiscs in comparison with confocal scanning laser tomography (CSLT). Retrospective cohort study. 82 eyes of 82 patients with disc size <1.63 mm 2 underwent SD-OCT and CSLT measurements, visual field testing and clinical examination. BMO-based minimal rim width (BMO-MRW), retinal nerve fibre layer thickness (RNFLT) in SD-OCT and rim area measured in CSLT were compared and correlated with visual field defects. 51 patients with glaucoma, 11 patients with ocular hypertension (OHT) and 20 healthy controls had a mean disc area of 1.36±0.19 mm 2 in CSLT, and BMO area was 1.45±0.22 mm 2 (r=0.17; p=0.12). In patients with glaucoma, visual field mean defect was -7.5±6.7 dB. Global BMO-MRW correlated better with visual field function (Spearman's r=0.65; p<0.001) than RNFLT (r=0.58; p≤0.001) and CSLT rim area (r=0.47; p=0.004). BMO-MRW significantly deteriorated with progressive visual field loss (p<0.001). In receiver operating characteristic analysis, sensitivity of BMO-MRW was 68.6% at 95% specificity (area under curve (AUC)=0.87), similar to sensitivity of RNFLT (66.4%; AUC=0.81). Performance of CSLT rim area was significantly worse (AUC=0.70, p=0.008). In healthy controls, mean BMO-MRW was 344.3±64.1 µm, mean RNFLT 78.0±11.3 µm and CSLT mean rim area 1.07±0.18 mm 2 . In small optic discs, BMO-MRW and peripapillary RNFLT (OCT) have similar sensitivity to discriminate patients with glaucoma from normal controls; both exceed CSLT rim area in diagnostic power. In glaucomatous patients, BMO-MRW correlates strongest with visual field function. 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/.

[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.

Improving services for glaucoma care in Nigeria: implications for policy and programmes to achieve universal health coverage.

PubMed

Kyari, Fatima; Gilbert, Clare; Blanchet, Karl; Wormald, Richard

2017-05-01

Glaucoma in Africa is sometimes referred to as the silent thief of sight. In Nigeria, glaucoma is common, it is serious, ophthalmologists face many constraints in managing it, people do not even know they have it until it is advanced, patients do not understand or comply with treatment after they are diagnosed and the poor are more likely to be glaucoma blind. Available evidence indicates that the health system in Nigeria is failing to meet the needs of patients with glaucoma. Based on evidence, we propose future directions for improving services for glaucoma care in Nigeria, and the implications for policy and programmes to control glaucoma blindness, using a health system-oriented approach. Three complementary strategies are required: (i) strengthening clinical services for glaucoma-by developing models of glaucoma care, improving clinical treatment options, making medicines and equipment available, financing glaucoma care and training eye care workers; (ii) introducing initiatives for earlier detection of glaucoma in the clinic and approaches in the community and (iii) strengthening health system governance. Glaucoma is a complex disease to manage and addressing it as a public health problem is challenging. However, we need to change the paradigm to recognise that glaucoma is a potentially avoidable cause of blindness in Africa. 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/.

Enhancement of optic cup detection through an improved vessel kink detection framework

NASA Astrophysics Data System (ADS)

Wong, Damon W. K.; Liu, Jiang; Tan, Ngan Meng; Zhang, Zhuo; Lu, Shijian; Lim, Joo Hwee; Li, Huiqi; Wong, Tien Yin

2010-03-01

Glaucoma is a leading cause of blindness. The presence and extent of progression of glaucoma can be determined if the optic cup can be accurately segmented from retinal images. In this paper, we present a framework which improves the detection of the optic cup. First, a region of interest is obtained from the retinal fundus image, and a pallor-based preliminary cup contour estimate is determined. Patches are then extracted from the ROI along this contour. To improve the usability of the patches, adaptive methods are introduced to ensure the patches are within the optic disc and to minimize redundant information. The patches are then analyzed for vessels by an edge transform which generates pixel segments of likely vessel candidates. Wavelet, color and gradient information are used as input features for a SVM model to classify the candidates as vessel or non-vessel. Subsequently, a rigourous non-parametric method is adopted in which a bi-stage multi-resolution approach is used to probe and localize the location of kinks along the vessels. Finally, contenxtual information is used to fuse pallor and kink information to obtain an enhanced optic cup segmentation. Using a batch of 21 images obtained from the Singapore Eye Research Institute, the new method results in a 12.64% reduction in the average overlap error against a pallor only cup, indicating viable improvements in the segmentation and supporting the use of kinks for optic cup detection.

Multifocal visual evoked potentials for early glaucoma detection.

PubMed

Weizer, Jennifer S; Musch, David C; Niziol, Leslie M; Khan, Naheed W

2012-07-01

To compare multifocal visual evoked potentials (mfVEP) with other detection methods in early open-angle glaucoma. Ten patients with suspected glaucoma and 5 with early open-angle glaucoma underwent mfVEP, standard automated perimetry (SAP), short-wave automated perimetry, frequency-doubling technology perimetry, and nerve fiber layer optical coherence tomography. Nineteen healthy control subjects underwent mfVEP and SAP for comparison. Comparisons between groups involving continuous variables were made using independent t tests; for categorical variables, Fisher's exact test was used. Monocular mfVEP cluster defects were associated with an increased SAP pattern standard deviation (P = .0195). Visual fields that showed interocular mfVEP cluster defects were more likely to also show superior quadrant nerve fiber layer thinning by OCT (P = .0152). Multifocal visual evoked potential cluster defects are associated with a functional and an anatomic measure that both relate to glaucomatous optic neuropathy. Copyright 2012, SLACK Incorporated.

A young Botswana patient with congenital iris ectropion uvea.

PubMed

Shifa, Jemal Zeberga; Nkomazana, Othokawa; Bekele, Negussie Alula; Kassa, Mamo Woldu

2016-01-01

Congenital iris ectropion is a rare condition; non-progressive anomaly characterised by the presence of iris pigment epithelium on the anterior surface of the iris stroma and is frequently associated with anterior iris insertion, dysgenesis of the drainage angle and glaucoma. This paper describes unusual case of bilateral case of congenital iris ectropion in adult patient with pupillary abnormality, normal anterior chamber angle structure and with no evidence of glaucoma.

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

The Role of Magnesium in the Pathogenesis and Treatment of Glaucoma

PubMed Central

Korkmaz, Şafak; Sül, Sabahattin; Tufan, Hasan Ali; Aydın, Bahri; Dileköz, Ergin

2014-01-01

Glaucoma is characterized by chronic optic neuropathy resulting in progressive vision loss. Not only is glaucoma considered as a condition of elevated intraocular pressure (IOP), but also other risk factors may play a role in the pathogenesis of glaucomatous optic nerve damage. Vascular dysregulation in ocular blood flow and oxidative stress are currently suggested as important risk factors for glaucomatous retinal ganglion cell loss. New treatment modalities that improve ocular blood flow and reduce oxidative stress have been investigated in many studies. Magnesium (Mg) is thought to be one of the molecules that has a treatment potential in glaucoma. Mg has been shown to improve blood flow by modifying endothelial function via endothelin-1 (ET-1) and endothelial nitric oxide (NO) pathways. Mg also exhibits neuroprotective role by blocking N-methyl-D-aspartate (NMDA) receptor-related calcium influx and by inhibiting the release of glutamate, and hence protects the cell against oxidative stress and apoptosis. Both improvement in ocular blood flow and prevention of ganglion cell loss would make magnesium a good candidate for glaucoma management. Further studies on the effect of Mg may open a new therapeutic era in glaucoma. PMID:27433524

Stage of visual field loss and age at diagnosis in 1988 patients with different glaucomas: implications for glaucoma screening and driving ability.

PubMed

Gramer, Gwendolyn; Gramer, Eugen

2018-04-01

To compare stage of visual field loss (VFL) and age at diagnosis between patients with different types of glaucoma with regard to glaucoma screening and driving ability. In a cross-sectional study of 1988 consecutive patients with different types of glaucoma VFL at diagnosis and age at diagnosis were assessed. Patients with binocular advanced or severe VFL were classified unable, patients with no VFL in one eye and VFL I-V (Aulhorn classification) in the other eye able, all other constellations questionably able to drive. There were significant differences in age at diagnosis between different glaucomas and between patients with different stages of VFL at diagnosis. Age-related assessment of VFL at diagnosis in normal tension glaucoma (NTG) compared to primary open-angle glaucoma (POAG) showed that NTG is not a disease of the elderly but a disease with late diagnosis at severe VFL. In POAG a solely age-related glaucoma screening, e.g. from the age of 50 years, does not sufficiently lead to diagnosis at an early stage of the disease. In POAG solely based on binocular VFL 11.5% of patients were judged unable, 29.2% questionably able to drive, in NTG 19.6%/43.1%, pigmentary glaucoma 16%/22%, pseudoexfoliation glaucoma 9.1%/16.7%, and in primary angle-closure glaucoma 14.6%/30%. Depending on type of glaucoma more than 50% of patients require counselling regarding safe driving as part of clinical care. A disease-specific, age-related perimetric examination considering additional risk factors like family history of glaucoma is essential for early detection of glaucoma and road safety.

Risk Factors for Primary Open Angle Glaucoma (POAG) Progression: A Study Ruled in Torino

PubMed Central

Actis, A.G.; Versino, E.; Brogliatti, B.; Rolle, T.

2016-01-01

Purpose: Aim of this retrospective, observational study is to describe features of a population sample, affected by primary open angle glaucoma (POAG) in order to evaluate damage progression on the basis of the emerged individual risk factors. Methods: We included 190 caucasian patients (377 eyes), evaluating relationship between individual risk factors (explicative variables) and MD (Mean Deviation) of standard automated perimetry. We also considered the dependent variable NFI (Neural Fiber Index) of GDx scanning laser polarimetry. Progression has been evaluated through a statistic General Linear Model on four follow up steps (mean follow up 79 months). Results: Factors reaching statistical significance, determining a worsening of the MD variable, are: age (P<0.0001), intraocular pressure (IOP) at follow up (P < 0.0001), female gender (P<0.0001), hypertension (P< 0.0001) and familiarity (P = 0.0006). Factors reaching statistical significance, determining a worsening of the NFI variable, are only IOP at follow up (P = 0.0159) and depression (P = 0.0104). Conclusion: Results of this study confirm and enforce data coming from most recent studies: IOP remains the main risk factor for glaucoma assess and progression; age and familiarity are great risk factors as underlined in the last decades; female sex can be an important risk factors as emerged only in the last years; arterial hypertension should always be evaluated in timing of our clinic follow up. PMID:27347249

Imaging of single retinal ganglion cell with differential interference contrast microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Oh, Juyeong; Kim, Yu Jeong; Kim, Chul-Ki; Lee, Taik Jin; Seo, Mina; Lee, Seok; Woo, Deok Ha; Jun, Seong Chan; Park, Ki-Ho; Kim, Seok Hwan; Kim, Jae Hun

2017-02-01

Glaucoma is a progressive optic neuropathy, characterized by the selective loss of retinal ganglion cells (RGCs). Therefore, monitoring the change of number or morphology of RGC is essential for the early detection as well as investigation of pathophysiology of glaucoma. Since RGC layer is transparent and hyporeflective, the direct optical visualization of RGCs has not been successful so far. Therefore, glaucoma evaluation mostly depends on indirect diagnostic methods such as the evaluation of optic disc morphology or retinal nerve fiber layer thickness measurement by optical coherence tomography. We have previously demonstrated single photoreceptor cell imaging with differential interference contrast (DIC) microscopy. Herein, we successfully visualized single RGC using DIC microscopy. Since RGC layer is much less reflective than photoreceptor layer, various techniques including the control of light wavelength and bandwidth using a tunable band pass filter were adopted to reduce the chromatic aberration in z-axis for higher and clearer resolution. To verify that the imaged cells were the RGCs, the flat-mounted retina of Sprague-Dawley rat, in which the RGCs were retrogradely labeled with fluorescence, was observed by both fluorescence and DIC microscopies for direct comparison. We have confirmed that the cell images obtained by fluorescence microscopy were perfectly matched with cell images by DIC microscopy. As conclusion, we have visualized single RGC with DIC microscopy, and confirmed with fluorescence microscopy.

Ultra-high resolution profiles of macular intra-retinal layer thicknesses and associations with visual field defects in primary open angle glaucoma

NASA Astrophysics Data System (ADS)

Chen, Qi; Huang, Shenghai; Ma, Qingkai; Lin, Huiling; Pan, Mengmeng; Liu, Xinting; Lu, Fan; Shen, Meixiao

2017-02-01

The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma.

Optic disc boundary segmentation from diffeomorphic demons registration of monocular fundus image sequences versus 3D visualization of stereo fundus image pairs for automated early stage glaucoma assessment

NASA Astrophysics Data System (ADS)

Gatti, Vijay; Hill, Jason; Mitra, Sunanda; Nutter, Brian

2014-03-01

Despite the current availability in resource-rich regions of advanced technologies in scanning and 3-D imaging in current ophthalmology practice, world-wide screening tests for early detection and progression of glaucoma still consist of a variety of simple tools, including fundus image-based parameters such as CDR (cup to disc diameter ratio) and CAR (cup to disc area ratio), especially in resource -poor regions. Reliable automated computation of the relevant parameters from fundus image sequences requires robust non-rigid registration and segmentation techniques. Recent research work demonstrated that proper non-rigid registration of multi-view monocular fundus image sequences could result in acceptable segmentation of cup boundaries for automated computation of CAR and CDR. This research work introduces a composite diffeomorphic demons registration algorithm for segmentation of cup boundaries from a sequence of monocular images and compares the resulting CAR and CDR values with those computed manually by experts and from 3-D visualization of stereo pairs. Our preliminary results show that the automated computation of CDR and CAR from composite diffeomorphic segmentation of monocular image sequences yield values comparable with those from the other two techniques and thus may provide global healthcare with a cost-effective yet accurate tool for management of glaucoma in its early stage.

A New Glaucoma Severity Score Combining Structural and Functional Defects.

PubMed

Wachtl, J; Töteberg-Harms, M; Frimmel, S; Kniestedt, C

2017-04-01

Background In order to assess glaucoma severity and to compare the success of surgical and medical therapy and study outcomes, an objective and independent staging tool is necessary. A combination of information from both structural and functional testing is probably the best approach to stage glaucomatous damage. There has been no universally accepted standard for glaucoma staging. The aim of this study was to develop a Glaucoma Severity Score (GSS) for objective assessment of a patient's glaucoma severity, combining both functional and structural information. Materials and methods The Glaucoma Severity Score includes the following 3 criteria: superior and inferior Retinal Nerve Fibre Layer (RNFL) thickness, perimetric mean defect (MD), and agreement of anatomical and perimetric defects, as assessed by two glaucoma specialists. The specialists defined a staging tool for each of the 3 criteria in a consensus process, assigning specific characteristics to a scale value between 0 and 2 or 0 and 3, respectively. The GSS ranges between 0 and 10 points. In a prospective observational study, the data of 112 glaucoma patients were assessed independently by the two specialists according to this staging tool. Results The GSS was applied to 112 eyes and patients (59.8 % female) with a mean age of 66.3 ± 13.1 years. Mean GSS was 4.73 points. Cohen's kappa coefficient was determined to measure inter-rater agreement between glaucoma specialists for the third criterion. With κ = 0.83, the agreement was very good. Thus, all 3 criteria of the GSS may be regarded as objective. Conclusions The Glaucoma Severity Score is an objective tool, combining both structural and functional characteristics, and permitting comparison of different patients, populations and studies. The Glaucoma Severity Score has proven effective in the objective assessment of 112 glaucoma patients and is relatively user-friendly in clinical practice. A comparative study of the GSS with the results of the FORUM® Glaucoma Workplace (Carl Zeiss Meditec AG, Jena, Germany) will be the next step. If outcomes match, the Glaucoma Severity Score can be accepted as a promising tool to stage glaucoma and monitor changes objectively in patients when comparing glaucoma progression in study analyses. Georg Thieme Verlag KG Stuttgart · New York.

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.

Normal tension glaucoma management: a survey of contemporary practice.

PubMed

Symes, Richard J; Mikelberg, Frederick S

2017-08-01

The aim of this study was to investigate contemporary practice patterns with respect to normal tension glaucoma (NTG) management and to determine whether the 2 largest NTG trials have influenced ophthalmologists' clinical practice. A survey questionnaire was sent to ophthalmologists via the American Glaucoma Society, the Canadian Glaucoma Society, and the Canadian Ophthalmological Society. The questionnaire was designed to investigate ophthalmologists' usual practice with respect to NTG and the extent to which practice has been influenced by the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Low pressure Glaucoma Treatment Study (LoGTS). In total, 419 ophthalmologists completed the survey. Of these, 264 respondents were glaucoma subspecialists. The survey showed that 95% and 64% of ophthalmologists were familiar with the CNTGS and the LoGTS, respectively. Of the respondents, 70% indicated that they would initiate treatment in mild-to-moderate NTG without waiting for documented disease progression. Of the respondents, 61% of the total surveyed and 50% of the glaucoma subspecialists felt that the LoGTS results had no impact on their usual clinical practice. The first-choice topical drug for NTG was a prostaglandin analogue (88% of respondents) or brimonidine (10% of respondents). Most ophthalmologists treat NTG more aggressively than recommended by the CTNGS protocol. Most ophthalmologists felt that the LoGTS results had no impact on their normal clinical practice. The prostaglandin analogues are, by far, the most popular choice of drug for contemporary management of NTG. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Ocular complications of diabetes mellitus

PubMed Central

Sayin, Nihat; Kara, Necip; Pekel, Gökhan

2015-01-01

Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

[Self-relaxation techniques for glaucoma patients. Significance of autogenic training, hypnosis and music therapy].

PubMed

Bertelmann, T; Strempel, I

2016-02-01

Glaucoma is currently the second most common cause of severe visual impairment and blindness worldwide. Standard pharmaceutical and surgical interventions often fail to prevent progression of glaucomatous optic neuropathy. To evaluate whether adjuvantly applied self-relaxation techniques can significantly impact intraocular pressure, ocular perfusion and the overall mental state of affected patients. A search of the literature was carried out and a comprehensive overview of currently available data is presented. Autogenic training, hypnosis and music therapy can significantly impact intraocular pressure, ocular perfusion and overall mental state of patients suffering from glaucoma. As all of these adjuvant therapeutic options are cost-effective, available almost everywhere and at anytime as well as without any known side effects, they can be useful additional techniques in the overall concept for treating glaucoma patients. Regular ocular examinations by an ophthalmologist are, however, mandatory.

Are we ready for genetic testing for primary open-angle glaucoma?

PubMed

Khawaja, Anthony P; Viswanathan, Ananth C

2018-05-01

Following a dramatic reduction in the cost of genotyping technology in recent years, there have been significant advances in the understanding of the genetic basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient activity in the UK hospital eye service and are a huge burden for the National Health Service. A potential benefit of genetic testing is personalised glaucoma management, allowing direction of our limited healthcare resources to the glaucoma patients who most need it. Our review aims to summarise recent discoveries in the field of glaucoma genetics and to discuss their potential clinical utility. While genome-wide association studies have now identified over ten genes associated with primary open-angle glaucoma (POAG), individually, variants in these genes are not predictive of POAG in populations. There are data suggesting some of these POAG variants are associated with conversion from ocular hypertension to POAG and visual field progression among POAG patients. However, these studies have not been replicated yet and such genetic testing is not currently justified in clinical care. In contrast, genetic testing for inherited early-onset disease in relatives of POAG patients with a known genetic mutation is of clear benefit; this can support either regular review to commence early treatment when the disease develops, or discharge from ophthalmology services of relatives who do not carry the mutation. Genetic testing for POAG at a population level is not currently justified.

Methods to Induce Chronic Ocular Hypertension

PubMed Central

Dey, Ashim; Manthey, Abby L.; Chiu, Kin; Do, Chi-Wai

2018-01-01

Glaucoma, a form of progressive optic neuropathy, is the second leading cause of blindness worldwide. Being a prominent disease affecting vision, substantial efforts are being made to better understand glaucoma pathogenesis and to develop novel treatment options including neuroprotective and neuroregenerative approaches. Cell transplantation has the potential to play a neuroprotective and/or neuroregenerative role for various ocular cell types (e.g., retinal cells, trabecular meshwork). Notably, glaucoma is often associated with elevated intraocular pressure, and over the past 2 decades, several rodent models of chronic ocular hypertension (COH) have been developed that reflect these changes in pressure. However, the underlying pathophysiology of glaucoma in these models and how they compare to the human condition remains unclear. This limitation is the primary barrier for using rodent models to develop novel therapies to manage glaucoma and glaucoma-related blindness. Here, we review the current techniques used to induce COH-related glaucoma in various rodent models, focusing on the strengths and weaknesses of the each, in order to provide a more complete understanding of how these models can be best utilized. To so do, we have separated them based on the target tissue (pre-trabecular, trabecular, and post-trabecular) in order to provide the reader with an encompassing reference describing the most appropriate rodent COH models for their research. We begin with an initial overview of the current use of these models in the evaluation of cell transplantation therapies. PMID:29637819

Early detection of glaucoma by means of a novel 3D computer‐automated visual field test

PubMed Central

Nazemi, Paul P; Fink, Wolfgang; Sadun, Alfredo A; Francis, Brian; Minckler, Donald

2007-01-01

Purpose A recently devised 3D computer‐automated threshold Amsler grid test was used to identify early and distinctive defects in people with suspected glaucoma. Further, the location, shape and depth of these field defects were characterised. Finally, the visual fields were compared with those obtained by standard automated perimetry. Patients and methods Glaucoma suspects were defined as those having elevated intraocular pressure (>21 mm Hg) or cup‐to‐disc ratio of >0.5. 33 patients and 66 eyes with risk factors for glaucoma were examined. 15 patients and 23 eyes with no risk factors were tested as controls. The recently developed 3D computer‐automated threshold Amsler grid test was used. The test exhibits a grid on a computer screen at a preselected greyscale and angular resolution, and allows patients to trace those areas on the grid that are missing in their visual field using a touch screen. The 5‐minute test required that the patients repeatedly outline scotomas on a touch screen with varied displays of contrast while maintaining their gaze on a central fixation marker. A 3D depiction of the visual field defects was then obtained that was further characterised by the location, shape and depth of the scotomas. The exam was repeated three times per eye. The results were compared to Humphrey visual field tests (ie, achromatic standard or SITA standard 30‐2 or 24‐2). Results In this pilot study 79% of the eyes tested in the glaucoma‐suspect group repeatedly demonstrated visual field loss with the 3D perimetry. The 3D depictions of visual field loss associated with these risk factors were all characteristic of or compatible with glaucoma. 71% of the eyes demonstrated arcuate defects or a nasal step. Constricted visual fields were shown in 29% of the eyes. No visual field changes were detected in the control group. Conclusions The 3D computer‐automated threshold Amsler grid test may demonstrate visual field abnormalities characteristic of glaucoma in glaucoma suspects with normal achromatic Humphrey visual field testing. This test may be used as a screening tool for the early detection of glaucoma. PMID:17504855

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.

Slow Reading in Glaucoma: Is it due to the Shrinking Visual Span in Central Vision?

PubMed Central

Liu, Rong; Patel, Bhavika N.; Girkin, Christopher

2017-01-01

Purpose Glaucoma is a leading cause of blindness worldwide, characterized by progressive loss of retinal ganglion cells. Patients with bilateral glaucoma read slower than normal cohorts. Here we examined the factors that may underlie slow reading in glaucoma and determined the best predictor of reading speed in glaucoma. Methods A total of 38 subjects participated in this study: 17 patients with primary open-angle glaucoma (mean age = 64.71 years) and 21 age-similar normal controls (58.24 years). For each subject, we measured binocular visual acuity (BVA); binocular contrast sensitivity (BCS); stereoacuity; visual field mean deviation (MD); and the visual span (i.e., the number of letters recognizable at one glance) known to limit reading speed. The visual span was measured with a trigram letter-recognition task in which subjects identify trigrams flashed at varying letter positions left and right of the fixation. Oral reading speed was measured with short blocks of text. Results Even after controlling for age, glaucoma patients showed significantly slower reading speed (by 19%, P < 0.05) and smaller visual span (by 11 bits, P < 0.001) compared to normal controls. While their BVA was relatively normal (20/20 Snellen equivalent), their BCS (P < 0.001); stereoacuity (P < 0.001); and visual field MD (P < 0.001) showed pronounced deficits. Multiple regression analysis further revealed that reading speed in glaucoma was best predicted by the visual span. Conclusions Our results showed that slower reading speed in glaucoma was closely related to the shrinkage of the visual span. Our findings further support the view that the visual span plays a limiting role in reading speed. PMID:29131903

Slow Reading in Glaucoma: Is it due to the Shrinking Visual Span in Central Vision?

PubMed

Kwon, MiYoung; Liu, Rong; Patel, Bhavika N; Girkin, Christopher

2017-11-01

Glaucoma is a leading cause of blindness worldwide, characterized by progressive loss of retinal ganglion cells. Patients with bilateral glaucoma read slower than normal cohorts. Here we examined the factors that may underlie slow reading in glaucoma and determined the best predictor of reading speed in glaucoma. A total of 38 subjects participated in this study: 17 patients with primary open-angle glaucoma (mean age = 64.71 years) and 21 age-similar normal controls (58.24 years). For each subject, we measured binocular visual acuity (BVA); binocular contrast sensitivity (BCS); stereoacuity; visual field mean deviation (MD); and the visual span (i.e., the number of letters recognizable at one glance) known to limit reading speed. The visual span was measured with a trigram letter-recognition task in which subjects identify trigrams flashed at varying letter positions left and right of the fixation. Oral reading speed was measured with short blocks of text. Even after controlling for age, glaucoma patients showed significantly slower reading speed (by 19%, P < 0.05) and smaller visual span (by 11 bits, P < 0.001) compared to normal controls. While their BVA was relatively normal (20/20 Snellen equivalent), their BCS (P < 0.001); stereoacuity (P < 0.001); and visual field MD (P < 0.001) showed pronounced deficits. Multiple regression analysis further revealed that reading speed in glaucoma was best predicted by the visual span. Our results showed that slower reading speed in glaucoma was closely related to the shrinkage of the visual span. Our findings further support the view that the visual span plays a limiting role in reading speed.

LOXL1 deficiency in the lamina cribrosa as candidate susceptibility factor for a pseudoexfoliation-specific risk of glaucoma.

PubMed

Schlötzer-Schrehardt, Ursula; Hammer, Christian M; Krysta, Anita W; Hofmann-Rummelt, Carmen; Pasutto, Francesca; Sasaki, Takako; Kruse, Friedrich E; Zenkel, Matthias

2012-09-01

To test the hypothesis that a primary disturbance in lysyl oxidase-like 1 (LOXL1) and elastin metabolism in the lamina cribrosa of eyes with pseudoexfoliation syndrome constitutes an independent risk factor for glaucoma development and progression. Observational, consecutive case series. Posterior segment tissues obtained from 37 donors with early and late stages of pseudoexfoliation syndrome without glaucoma, 37 normal age-matched control subjects, 5 eyes with pseudoexfoliation-associated open-angle glaucoma, and 5 eyes with primary open-angle glaucoma (POAG). Protein and mRNA expression of major elastic fiber components (elastin, fibrillin-1, fibulin-4), collagens (types I, III, and IV), and lysyl oxidase crosslinking enzymes (LOX, LOXL1, LOXL2) were assessed in situ by quantitative real-time polymerase chain reaction, (immuno)histochemistry, and light and electron microscopy. Lysyl oxidase-dependent elastin fiber assembly was assessed by primary optic nerve head astrocytes in vitro. Expression levels of elastic proteins, collagens, and lysyl oxidases in the lamina cribrosa. Lysyl oxidase-like 1 proved to be the major lysyl oxidase isoform in the normal lamina cribrosa in association with a complex elastic fiber network. Compared with normal and POAG specimens, lamina cribrosa tissues obtained from early and late stages of pseudoexfoliation syndrome without and with glaucoma consistently revealed a significant coordinated downregulation of LOXL1 and elastic fiber constituents on mRNA and protein level. In contrast, expression levels of collagens and other lysyl oxidase isoforms were not affected. Dysregulated expression of LOXL1 and elastic proteins was associated with pronounced (ultra)structural alterations of the elastic fiber network in the laminar beams of pseudoexfoliation syndrome eyes. Inhibition of LOXL1 interfered with elastic fiber assembly by optic nerve head astrocytes in vitro. The findings provide evidence for a pseudoexfoliation-specific elastinopathy of the lamina cribrosa resulting from a primary disturbance in LOXL1 regulation and elastic fiber homeostasis, possibly rendering pseudoexfoliation syndrome eyes more vulnerable to pressure-induced optic nerve damage and glaucoma development and progression. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Predicting progression of glaucoma from rates of frequency doubling technology perimetry change.

PubMed

Meira-Freitas, Daniel; Tatham, Andrew J; Lisboa, Renato; Kuang, Tung-Mei; Zangwill, Linda M; Weinreb, Robert N; Girkin, Christopher A; Liebmann, Jeffrey M; Medeiros, Felipe A

2014-02-01

To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. Prospective, observational cohort study. The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7 ± 1.9 FDT tests during a mean follow-up time of 73.1 ± 28.0 months. Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). The R(2) index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04-1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24), respectively. Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Flicker-defined form perimetry in glaucoma patients.

PubMed

Horn, Folkert K; Kremers, Jan; Mardin, Christian Y; Jünemann, Anselm G; Adler, Werner; Tornow, Ralf P

2015-03-01

To assess the potential of flicker-defined form (FDF) perimetry to detect functional loss in patient groups with beginning glaucoma, and to evaluate the dynamic range of the FDF stimulus in individual patients and at individual test positions. FDF perimetry and standard automated perimetry (SAP) were performed at identical test locations (adapted G1 protocol) in 60 healthy subjects and 111 glaucoma patients. All patients showed glaucomatous optic disc appearance. Grouping within the glaucoma cohort was based on SAP-performance: 33 "preperimetric" open-angle glaucoma (OAG) patients, 28 "borderline" OAG (focal defects and SAP-mean defect (MD) <2 dB), 33 "early" OAG (SAP-MD < 5 dB), 17 "advanced" OAG. All participants were experienced in psychophysical and perimetric tests. Defect values and the areas under receiver operating characteristic curves (ROC) in patient groups were statistically compared. The values of FDF-MD in the preperimetric, borderline, and early OAG group were 2.7 ± 3.4 dB, 5.5 ± 2.6 dB, and 8.5 ± 3.4 dB respectively (all significantly above normal). The percentage of patients exceeding normal FDF-MD was 27.3 %, 60.7 %, and 87.9 % respectively. The age-adjusted FDF-mean defect (MD) of the G1X-protocol was not significantly correlated with refractive error, lens opacity, pupil size, or gender. Occurrence of ceiling effects (inability to detect targets at highest contrast) showed a high correlation with visual field losses (R = 0.72, p < 0.001). Local analysis indicates that SAP losses exceeding 5 dB could not be distinguished with the FDF technique. The FDF stimulus was able to detect beginning glaucoma damage. Patients with SAP-MD values exceeding 5 dB should be monitored with conventional perimetry because of its larger dynamic range.

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.

Presence and Risk Factors for Glaucoma in Patients with Diabetes

PubMed Central

Song, Brian J.; Aiello, Lloyd Paul; Pasquale, Louis R.

2017-01-01

Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure – the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better-defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients. PMID:27766584

The molecular basis of retinal ganglion cell death in glaucoma.

PubMed

Almasieh, Mohammadali; Wilson, Ariel M; Morquette, Barbara; Cueva Vargas, Jorge Luis; Di Polo, Adriana

2012-03-01

Glaucoma is a group of diseases characterized by progressive optic nerve degeneration that results in visual field loss and irreversible blindness. A crucial element in the pathophysiology of all forms of glaucoma is the death of retinal ganglion cells (RGCs), a population of CNS neurons with their soma in the inner retina and axons in the optic nerve. Strategies that delay or halt RGC loss have been recognized as potentially beneficial to preserve vision in glaucoma; however, the success of these approaches depends on an in-depth understanding of the mechanisms that lead to RGC dysfunction and death. In recent years, there has been an exponential increase in valuable information regarding the molecular basis of RGC death stemming from animal models of acute and chronic optic nerve injury as well as experimental glaucoma. The emerging landscape is complex and points at a variety of molecular signals - acting alone or in cooperation - to promote RGC death. These include: axonal transport failure, neurotrophic factor deprivation, toxic pro-neurotrophins, activation of intrinsic and extrinsic apoptotic signals, mitochondrial dysfunction, excitotoxic damage, oxidative stress, misbehaving reactive glia and loss of synaptic connectivity. Collectively, this body of work has considerably updated and expanded our view of how RGCs might die in glaucoma and has revealed novel, potential targets for neuroprotection. Copyright © 2011. Published by Elsevier Ltd.

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.

A cloud-based system for automatic glaucoma screening.

PubMed

Fengshou Yin; Damon Wing Kee Wong; Ying Quan; Ai Ping Yow; Ngan Meng Tan; Gopalakrishnan, Kavitha; Beng Hai Lee; Yanwu Xu; Zhuo Zhang; Jun Cheng; Jiang Liu

2015-08-01

In recent years, there has been increasing interest in the use of automatic computer-based systems for the detection of eye diseases including glaucoma. However, these systems are usually standalone software with basic functions only, limiting their usage in a large scale. In this paper, we introduce an online cloud-based system for automatic glaucoma screening through the use of medical image-based pattern classification technologies. It is designed in a hybrid cloud pattern to offer both accessibility and enhanced security. Raw data including patient's medical condition and fundus image, and resultant medical reports are collected and distributed through the public cloud tier. In the private cloud tier, automatic analysis and assessment of colour retinal fundus images are performed. The ubiquitous anywhere access nature of the system through the cloud platform facilitates a more efficient and cost-effective means of glaucoma screening, allowing the disease to be detected earlier and enabling early intervention for more efficient intervention and disease management.

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

Five-Year Incidence of Primary Open-Angle Glaucoma and Rate of Progression in Health Center-Based Korean Population: The Gangnam Eye Study

PubMed Central

Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung

2014-01-01

Objective To investigate the 5-year incidence and progression rate of primary open-angle glaucoma (POAG) in a health-center-based Korean population. Methods The study population comprised 5,021 subjects who participated in standardized health screening (including non-contact tonometry and fundus photography) at the Gangnam Healthcare Center during the period from January 2005 to December 2006 and again from January 2010 to December 2011. Among these subjects, 948 (18.9%) with findings suggestive of glaucoma were subjected to a comprehensive glaucoma evaluation, which included applanation tonometry and standard automated perimetry. Based on the results, the subjects were diagnosed as POAG suspect or definite POAG. Results The 5-year incidences of POAG suspect and definite POAG were 0.84% (42 subjects) and 0.72% (36 subjects), respectively. The rate of progression from POAG suspect to definite POAG was 4.75% per year. In subjects with a baseline intraocular pressure (IOP) >21 mmHg, the incidence of POAG suspect or definite POAG was significantly higher than in those with a baseline IOP≤21 mmHg (32% vs. 1.05%; P<0.001). A multivariate analysis showed that the progression from POAG suspect to definite POAG was significantly associated with older age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03–1.10), higher baseline IOP (OR, 1.10; 95% CI, 1.01–1.24), higher body mass index (BMI) (OR, 1.15; 95% CI, 1.03–1.31), higher education level (OR, 1.57; 95% CI, 1.05–2.17), and higher hematocrit level (OR, 1.22; 95% CI, 1.08–1.43). Conclusions In the health-center-based Korean population, the 5-year incidence of POAG was 0.72%, and the rate of progression from POAG suspect to definite POAG was 4.75% per year. This study identified old age, high baseline IOP, high BMI, high level of education, and high hematocrit level as significant risk factors for incident POAG. PMID:25474589

Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma.

PubMed

González-Iglesias, Héctor; Álvarez, Lydia; García, Montserrat; Escribano, Julio; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega, Luis; Coca-Prados, Miguel

2014-02-26

Alterations in the sera proteins between patients with Primary Open-Angle Glaucoma (POAG), Pseudoexfoliation Glaucoma (PEXG), and healthy controls were identified through a proven approach utilizing equalization of high-abundance serum proteins with ProteoMiner™, two-dimensional fluorescent difference gel electrophoresis (2D-DIGE), MALDI-TOF/TOF, and nanoLC-MS-MS. Quantitative immunoassays of the 17 most-differentially-altered proteins identified in this analysis confirmed that they were also over expressed in the intact serum of newly recruited glaucoma patients. Overall, this report identifies a panel of candidates for glaucoma biomarkers and supports their further validation in large population studies. Additionally, functional pathway analysis of these candidate proteins suggested that they are part of a network linked to regulating immune and inflammatory-related processes. The data have been deposited to the ProteomeXchange with identifier PXD000198. POAG and PEXG are major causes of age-related blindness in the world; however, treatment can be very effective if they are identified early on in the progression. Genetic linkage studies can only explain a limited number of cases, suggesting that these forms of glaucoma are multigenic in nature. Other important factors, such as modifier genes, epigenetic influences, environmental and dietary agents, and inflammatory and oxidative effects are also believed to affect the development of these diseases. The characterization of metabolic and/or proteins changes, for example in bodily fluids, before the clinical manifestation of glaucoma is of considerable relevance for its early diagnosis. In the present work, identification of over-expressed proteins in serum of glaucoma patients (POAG and PEXG) linked to immune and inflammatory processes supports the finding that changes in these pathways also manifest systemically in patients with these pathologies. This study provides a new basis to validate the identified proteins as biomarkers of glaucoma in a large-scale-multiplexed screening in sera. Copyright © 2013 Elsevier B.V. All rights reserved.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

Neuroprotection in glaucoma

PubMed Central

Vasudevan, Sushil K; Gupta, Viney; Crowston, Jonathan G

2011-01-01

Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications. PMID:21150020

Twenty-four hour intraocular pressure monitoring with the SENSIMED Triggerfish contact lens: effect of body posture during sleep.

PubMed

Beltran-Agulló, Laura; Buys, Yvonne M; Jahan, Farzana; Shapiro, Colin M; Flanagan, John G; Cheng, Jason; Trope, Graham E

2017-10-01

To determine the difference in relative intraocular pressure (IOP) measured by the SENSIMED Triggerfish (TF) contact lens in flat compared with 30° head-up sleeping positions in patients with progressive primary open-angle glaucoma or normotensive glaucoma, based on recent or recurrent disc haemorrhage. Prospective, randomised, cross-over, open-label comparative study. IOP was monitored for 24 hours using TF on two separate sessions. Patients were randomly assigned to sleep flat one night and 30° head-up the other. Outputs in arbitrary units were obtained. Sleep and wake periods were defined as 22:00-6:00 and 8:00-22:00, respectively. Mean TF values during sleep and wake periods and wake-sleep and sleep-wake slopes were calculated for each session. TF output signals were compared between positions. Twelve subjects completed the study. Significant mean positive slopes were noted during the sleep period for both positions (p<0.01). No significant differences in the TF mean values were observed between positions (p=0.51). Six (54%) subjects had mean TF values significantly higher during the flat supine session, while four (36%) subjects had higher values during the head-up session. A significant increase in Goldmann IOP (p=0.001) and TF (p=0.02) measurements were observed after 24 hours of TF wear ('drift phenomenon'). Sleep position affects IOP as measured by TF in some patients with progressive glaucoma. The upward drift in TF output detected in >50% of the subjects requires further investigation to establish whether the increased output values over time are an artefact induced by the TF or a real change in IOP. NCT01351779. 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/.

Ethnic differences in primary angle-closure glaucoma.

PubMed

Yip, Jennifer L Y; Foster, Paul J

2006-04-01

Observational studies from different countries have shown that populations of East Asian origin have a higher frequency of primary angle-closure glaucoma compared with those of European or African descent. As half of all cases of glaucoma reside in Asia, and with primary angle-closure glaucoma carrying a higher rate of visual morbidity, primary angle-closure glaucoma poses an important public health problem; however, the inconsistent use of techniques and definitions to detect and diagnose primary angle-closure glaucoma has resulted in difficulties in interpreting the accuracy and comparability of such data. Therefore it is important to review these studies in the light of a consistent classification system. There are increasing reports that support previous findings on the incidence and prevalence of primary angle-closure glaucoma in different ethnic groups. There have also been further investigations into the mechanism and natural history of primary angle-closure glaucoma in Asian populations. International investigations into primary angle-closure glaucoma have demonstrated reproducible evidence that ethnic variations do exist. Cross-sectional studies in this area have also suggested that differences in anterior chamber depth, together with its association with peripheral anterior synechiae, may be part of the underlying mechanism behind these differences. The ideas generated need to be further explored with longitudinal data of changes in anterior chamber depth and peripheral anterior synechiae in different populations. The detailed mechanisms behind the development of angle-closure and primary angle-closure glaucoma should also be investigated.

Development of visual field defect after first-detected optic disc hemorrhage in preperimetric open-angle glaucoma.

PubMed

Kim, Hae Jin; Song, Yong Ju; Kim, Young Kook; Jeoung, Jin Wook; Park, Ki Ho

2017-07-01

To evaluate functional progression in preperimetric glaucoma (PPG) with disc hemorrhage (DH) and to determine the time interval between the first-detected DH and development of glaucomatous visual field (VF) defect. A total of 87 patients who had been first diagnosed with PPG were enrolled. The medical records of PPG patients without DH (Group 1) and with DH (Group 2) were reviewed. When glaucomatous VF defect appeared, the time interval from the diagnosis of PPG to the development of VF defect was calculated and compared between the two groups. In group 2, the time intervals from the first-detected DH to VF defect of the single- and recurrent-DH were compared. Of the enrolled patients, 45 had DH in the preperimetric stage. The median time interval from the diagnosis of PPG to the development of VF defect was 73.3 months in Group 1, versus 45.4 months in Group 2 (P = 0.042). The cumulative probability of development of VF defect after diagnosis of PPG was significantly greater in Group 2 than in Group 1. The median time interval from first-detected DH to the development of VF defect was 37.8 months. The median time interval from DH to VF defect and cumulative probability of VF defect after DH did not show a statistical difference between single and recurrent-DH patients. The median time interval between the diagnosis of PPG and the development of VF defect was significantly shorter in PPG with DH. The VF defect appeared 37.8 months after the first-detected DH in PPG.

Unilateral glaucoma in Sotos syndrome (cerebral gigantism).

PubMed

Yen, M T; Gedde, S J; Flynn, J T

2000-12-01

To report a patient with unilateral glaucoma associated with Sotos syndrome. Sotos syndrome (cerebral gigantism) is a disorder of growth and development with characteristic facial changes and normal endocrine function. Ocular manifestations may also include megalocornea, iris hypoplasia, cataracts, megalophthalmos, strabismus, nystagmus, and retinal dystrophy. Case report. A 50 year-old man with the clinical features of Sotos syndrome presented with complaints of decreased vision in the left eye. Ophthalmologic examination revealed bilateral megalocornea, megalophthalmos, iris hypoplasia and transillumination defects, cataracts, and unilateral glaucoma. Intraocular pressure was lowered, and visual field loss was stabilized with topical medications. Sotos syndrome patients should be examined routinely to allow for early detection and treatment of potential ocular problems, including glaucoma.

The spectrum of glaucoma presentation at Menelik II Hospital, Addis Ababa.

PubMed

Giorgis, Abeba T; Mulugeta, Abiye; Aga, Assegid; Deyassa, Neggusie

2012-07-01

Glaucoma is a major cause of blindness in Africa. However, many do not know if they have the disease until late. The aim of this study was to describe the type and severity of glaucoma at presentation A hospital based prospective review of 602 glaucoma patients was conducted over 18 month period ending in 2009. A special registry captured Socio demographic and clinical data at the glaucoma clinic of Menelik II Hospital in Addis Ababa. The vertical cup disc ratio (CDR) of the optic nerve head provided the bases to stage, the severity of glaucoma. Large portion of the total reviewed patients were men, 401 (66.6%) or above the age of 40 years, 484 (80.4%). The mean intraocular pressure was 28.5 and 30.6 in the right and left eye in mmHg. The leading subtypes of glaucoma, accounting 64.3% (n = 387), were Primary Open Angle Glaucoma, 227 (37.7%) and Pseudo exfoliation glaucoma, 160 (26.6%). At presentation, 260 (44%) and 109 (18%)) were unilaterally and bilaterally blind (vision < 3/60) respectively. Bilateral glaucoma was found in 464 (77%) and 366 (61%) presented with advanced stage (CDR > or = 9.0). Cases with advanced stage were likely to present with blindness [Odds Ratio (OR) -6.2 95% CI (3-8-10.1) and 6.9 95% CI (4.2-11.3)] or high Intraocular pressure >30mmHg [OR=3.4, 95% CI (2.2 -5.2) and 2.8, 95% CI (1.4-3.4)] in the respective right and left eyes. The stage, had no statistically significant association with age, sex, residence or type of glaucoma (Chi2 test, p > 0.05). A large proportion of patients still arrive at glaucoma clinic with a very late stage of open angle glaucoma. Intervention strategies are requiredfor early detection and treatment of glaucoma in Ethiopia.

Automated Detection of Glaucoma From Topographic Features of the Optic Nerve Head in Color Fundus Photographs.

PubMed

Chakrabarty, Lipi; Joshi, Gopal Datt; Chakravarty, Arunava; Raman, Ganesh V; Krishnadas, S R; Sivaswamy, Jayanthi

2016-07-01

To describe and evaluate the performance of an automated CAD system for detection of glaucoma from color fundus photographs. Color fundus photographs of 2252 eyes from 1126 subjects were collected from 2 centers: Aravind Eye Hospital, Madurai and Coimbatore, India. The images of 1926 eyes (963 subjects) were used to train an automated image analysis-based system, which was developed to provide a decision on a given fundus image. A total of 163 subjects were clinically examined by 2 ophthalmologists independently and their diagnostic decisions were recorded. The consensus decision was defined to be the clinical reference (gold standard). Fundus images of eyes with disagreement in diagnosis were excluded from the study. The fundus images of the remaining 314 eyes (157 subjects) were presented to 4 graders and their diagnostic decisions on the same were collected. The performance of the system was evaluated on the 314 images, using the reference standard. The sensitivity and specificity of the system and 4 independent graders were determined against the clinical reference standard. The system achieved an area under receiver operating characteristic curve of 0.792 with a sensitivity of 0.716 and specificity of 0.717 at a selected threshold for the detection of glaucoma. The agreement with the clinical reference standard as determined by Cohen κ is 0.45 for the proposed system. This is comparable to that of the image-based decisions of 4 ophthalmologists. An automated system was presented for glaucoma detection from color fundus photographs. The overall evaluation results indicated that the presented system was comparable in performance to glaucoma classification by a manual grader solely based on fundus image examination.

[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.

Personalized Prediction of Glaucoma Progression Under Different Target Intraocular Pressure Levels Using Filtered Forecasting Methods.

PubMed

Kazemian, Pooyan; Lavieri, Mariel S; Van Oyen, Mark P; Andrews, Chris; Stein, Joshua D

2018-04-01

To generate personalized forecasts of how patients with open-angle glaucoma (OAG) experience disease progression at different intraocular pressure (IOP) levels to aid clinicians with setting personalized target IOPs. Secondary analyses using longitudinal data from 2 randomized controlled trials. Participants with moderate or advanced OAG from the Collaborative Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention Study (AGIS). By using perimetric and tonometric data from trial participants, we developed and validated Kalman Filter (KF) models for fast-, slow-, and nonprogressing patients with OAG. The KF can generate personalized and dynamically updated forecasts of OAG progression under different target IOP levels. For each participant, we determined how mean deviation (MD) would change if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or 24 mmHg) over the next 5 years. We also model and predict changes to MD over the same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the level attained in the trials. Personalized estimates of the change in MD under different target IOP levels. A total of 571 participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same target IOPs and time frame. When using our tool to quantify the OAG progression dynamics for all 571 patients, we found no statistically significant differences over 5 years between progression for black versus white, male versus female, and CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all). To our knowledge, this is the first clinical decision-making tool that generates personalized forecasts of the trajectory of OAG progression at different target IOP levels. This approach can help clinicians determine appropriate, personalized target IOPs for patients with OAG. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Iridotomy to slow progression of angle-closure glaucoma

PubMed Central

Le, Jimmy T; Rouse, Benjamin; Gazzard, Gus

2016-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective is to assess the role of iridotomy-compared with observation-in the prevention of visual field loss for individuals who have primary angle closure or primary angle-closure glaucoma in at least one eye. We will also examine the role of iridotomy in the prevention of elevated intraocular pressure (IOP) in individuals with narrow angles (primary angle-closure suspect) in at least one eye. PMID:27551238

Cataracts and Glaucoma in the Infant and Preschool Child: Detection, Systemic Aspects, and Treatment.

ERIC Educational Resources Information Center

Raab, Edward L.

1980-01-01

The author discusses how cataracts and glaucoma differ when they occur in children and why they may be more difficult to treat. While these conditions occur infrequently in children, they are more damaging and difficult to treat than when they occur in adults. (PHR)

Optic cup segmentation from fundus images for glaucoma diagnosis.

PubMed

Hu, Man; Zhu, Chenghao; Li, Xiaoxing; Xu, Yongli

2017-01-02

Glaucoma is a serious disease that can cause complete, permanent blindness, and its early diagnosis is very difficult. In recent years, computer-aided screening and diagnosis of glaucoma has made considerable progress. The optic cup segmentation from fundus images is an extremely important part for the computer-aided screening and diagnosis of glaucoma. This paper presented an automatic optic cup segmentation method that used both color difference information and vessel bends information from fundus images to determine the optic cup boundary. During the implementation of this algorithm, not only were the locations of the 2 types of information points used, but also the confidences of the information points were evaluated. In this way, the information points with higher confidence levels contributed more to the determination of the final cup boundary. The proposed method was evaluated using a public database for fundus images. The experimental results demonstrated that the cup boundaries obtained by the proposed method were more consistent than existing methods with the results obtained by ophthalmologists.

The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice

PubMed Central

Harder, Jeffrey M.; Fernandes, Kimberly A.; Libby, Richard T.

2012-01-01

Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-apoptotic Bcl-2 family member BIM is known to induce BAX activation. BIM expression increased in RGCs after axonal injury and its induction was dependent on JUN. Partial and complete Bim deficiency delayed RGC death after mechanical optic nerve injury. However, in a mouse model of glaucoma, DBA/2J mice, Bim deficiency did not prevent RGC death in eyes with severe optic nerve degeneration. In a subset of DBA/2J mice, Bim deficiency altered disease progression resulting in less severe nerve damage. Bim deficient mice exhibited altered optic nerve head morphology and significantly lessened intraocular pressure elevation. Thus, a decrease in axonal degeneration in Bim deficient DBA/2J mice may not be caused by a direct role of Bim in RGCs. These data suggest that BIM has multiple roles in glaucoma pathophysiology, potentially affecting susceptibility to glaucoma through several mechanisms. PMID:22833783

Optic cup segmentation from fundus images for glaucoma diagnosis

PubMed Central

Hu, Man; Zhu, Chenghao; Li, Xiaoxing; Xu, Yongli

2017-01-01

ABSTRACT Glaucoma is a serious disease that can cause complete, permanent blindness, and its early diagnosis is very difficult. In recent years, computer-aided screening and diagnosis of glaucoma has made considerable progress. The optic cup segmentation from fundus images is an extremely important part for the computer-aided screening and diagnosis of glaucoma. This paper presented an automatic optic cup segmentation method that used both color difference information and vessel bends information from fundus images to determine the optic cup boundary. During the implementation of this algorithm, not only were the locations of the 2 types of information points used, but also the confidences of the information points were evaluated. In this way, the information points with higher confidence levels contributed more to the determination of the final cup boundary. The proposed method was evaluated using a public database for fundus images. The experimental results demonstrated that the cup boundaries obtained by the proposed method were more consistent than existing methods with the results obtained by ophthalmologists. PMID:27764542

In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma.

PubMed

Katiyar, Shefali; Pandit, Jayamanti; Mondal, Rabi S; Mishra, Anil K; Chuttani, Krishna; Aqil, Mohd; Ali, Asgar; Sultana, Yasmin

2014-02-15

The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164 nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5 min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops. Copyright © 2013 Elsevier Ltd. All rights reserved.

Who's lost first? Susceptibility of retinal ganglion cell types in experimental glaucoma.

PubMed

Della Santina, Luca; Ou, Yvonne

2017-05-01

The purpose of this article is to summarize our current knowledge about the susceptibility of specific retinal ganglion cell (RGC) types in experimental glaucoma, and to delineate the initial morphological and functional alterations that occur in response to intraocular pressure (IOP) elevation. There has been debate in the field as to whether RGCs with large somata and axons are more vulnerable, with definitive conclusions still in progress because of the wide diversity of RGC types. Indeed, it is now estimated that there are greater than 30 different RGC types, and while we do not yet understand the complete details, we discuss a growing body of work that supports the selective vulnerability hypothesis of specific RGC types in experimental glaucoma. Specifically, structural and functional degeneration of various RGC types have been examined across different rodent models of experimental glaucoma (acute vs. chronic) and different strains, and an emerging consensus is that OFF RGCs appear to be more vulnerable to IOP elevation compared to ON RGCs. Understanding the mechanisms by which this selective vulnerability manifests across different RGC types should lead to novel and improved strategies for neuroprotection and neuroregeneration in glaucoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnosis and Management of Iridocorneal Endothelial Syndrome

PubMed Central

Sacchetti, Marta; Mantelli, Flavio; Macchi, Ilaria; Ambrosio, Oriella; Rama, Paolo

2015-01-01

The iridocorneal endothelial (ICE) syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of “ICE-cells” on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty. PMID:26451377

Therapeutic endorsement enhances compliance with national glaucoma guidelines in Australian and New Zealand optometrists.

PubMed

Zangerl, Barbara; Hayen, Andrew; Mitchell, Paul; Jamous, Khalid F; Stapleton, Fiona; Kalloniatis, Michael

2015-03-01

Previous studies confirmed that optometrists have access to and confidence in applying clinical tests recommended for glaucoma assessment. Less is known about factors best predicting compliance with national clinical guidelines and thus by inference, the provision of suitable care by primary care ophthalmic practitioners. We utilised the unique two-tiered profession (therapeutic and non-therapeutic scope of practice) in Australia and New Zealand to assess the prospective adherence to glaucoma guidelines dependent on the clinician's background. Australian and New Zealand optometrists were surveyed on ophthalmic techniques for glaucoma assessment, criteria for the evaluation of the optic nerve head, glaucoma risk categories and review times while also recording background, training, and experience. Parameters identifying progression/conversion and patients' risk levels were analysed comparatively to ophthalmologists' opinions. Linear regression analysis identified variables significantly improving the likelihood of concordance with guidelines. Reported application of techniques complied well with glaucoma guidelines although gonioscopy and pachymetry, pupil dilation for optic nerve head examination, and acquisition of permanent records were less frequently employed. The main predictors for entry-level diagnostic standards were therapeutic endorsement together with the associated knowledge of relevant guidance and procedural confidence. Other findings suggested a potential underestimation in the value of optic disc size and intraocular pressure for the prediction of glaucoma risk, while optometrists more frequently relied on the outcomes of non-standardised automated perimetry and auxiliary imaging. Optometrists in Australia and New Zealand may not always exercise optimal clinical acumen regarding techniques/criteria for glaucoma diagnosis. Therapeutic endorsement was gradually adopted in different jurisdictions in various forms since 1999 and is mandatory for registration since late 2014. The result of the two-tiered optometric cohorts suggest that inclusion of therapeutic training as part of the core training is likely a key factor to enhanced compliance with glaucoma guidelines. Improved adherence to the current clinical standards should positively impact on the facilitation of appropriate glaucoma diagnosis and management. Obligatory knowledge and possibly accreditation of available guidelines might ensure a uniform standard in glaucoma testing protocols in concordance with compulsory entry-level skills. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection.

PubMed

Schulze, Andreas; Lamparter, Julia; Pfeiffer, Norbert; Berisha, Fatmire; Schmidtmann, Irene; Hoffmann, Esther M

2015-08-01

To compare the diagnostic accuracy and to evaluate the correlation of optic nerve head and retinal nerve fiber layer thickness values between Fourier-Domain optical coherence tomography (FD-OCT), confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) for early glaucoma detection. Ninety-three patients with early open-angle glaucoma, 58 patients with ocular hypertension, and 60 healthy control subjects were included in this observational, cross-sectional study. All study participants underwent FD-OCT (RTVue-100), CSLO (HRT3), and SLP (GDx VCC) imaging of the optic nerve head and the retinal nerve fiber layer. Area under the receiver operating characteristic curves (AUROC) and Bland-Altman analysis were performed. The parameters with the highest diagnostic accuracy were found for FD-OCT cup-to-disc ratio (AUROC=0.841), for SLP NFI (AUROC=0.835), and for CSLO cup-to-disc ratio (AUROC=0.789). Diagnostic accuracy of the best CSLO and SLP parameter was similar (P=0.259). There was a small statistically significant difference between the best CSLO and FD-OCT parameters for differentiating between glaucoma and healthy eyes (P=0.047). FD-OCT and SLP have a similarly good diagnostic ability to distinguish between early glaucoma and healthy subjects. The diagnostic accuracy of CSLO was comparable with SLP and marginally lower compared with FD-OCT.

Split-Ring Resonator-Based Strain Sensor on Flexible Substrates for Glaucoma Detection

NASA Astrophysics Data System (ADS)

Ekinci, Gizem; Deniz Yalcinkaya, Arda; Dundar, Gunhan; Torun, Hamdi

2016-10-01

This paper presents split-ring resonator-based strain sensors designed and characterized for glaucoma detection application. The geometry of the sensor is optimized such that it can be embedded in a contact lens. Silver conductive paint is to form the sensors realized on flexible substrates made of cellulose acetate and latex rubber. The devices are excited and interrogated using a pair of monopole antennas and the characteristics of devices with different curvature profiles are obtained. The sensitivity of the device, i.e. the change in resonant frequency for a unit change in radius of curvature, on acetate film is calculated as -4.73 MHz/mm and the sensitivity of the device on latex is 33.2 MHz/mm. The results indicate that the demonstrated device is suitable for glaucoma diagnosis.

Translamina Cribrosa Pressure Difference as Potential Element in the Pathogenesis of Glaucomatous Optic Neuropathy.

PubMed

Jonas, Jost B; Wang, Ningli; Yang, Diya

2016-01-01

The main proven risk factor for glaucomatous optic neuropathy (GON) is an intraocular pressure (IOP) higher than the pressure sensibility of the optic nerve head allows. Fulfilling Koch postulates, numerous studies have shown that the presence of high IOP leads to GON, that lowering IOP stops the progression of GON, and that a re-increase in IOP again causes the progression of GON. There are, however, many patients with glaucoma who have statistically normal or low IOP, and despite low IOP values, they develop progressing GON. These observations led to findings that IOP is only 1 of 2 determinants of the translamina cribrosa pressure difference (TLCPD), which is the main pressure-related parameter for the physiology and pathophysiology of the optic nerve head. The second parameter influencing TLCPD is orbital cerebrospinal fluid pressure (CSFP) as the counter pressure against IOP across the lamina cribrosa. Recent experimental and clinical studies have suggested that a low CSFP could be associated with GON in normal-pressure glaucoma. These investigations included studies with an experimental long-term reduction in CSFP in monkeys, population-based studies, and clinical retrospective and prospective investigations on patients with normal-pressure glaucoma. Besides TLCPD, other ocular parameters influenced by CSFP may be choroidal thickness, retinal vein pressure and diameter, occurrence of retinal vein occlusions, and occurrence and severity of diabetic retinopathy.

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): study protocol for a randomized controlled trial.

PubMed

Azuara-Blanco, Augusto; Burr, Jennifer M; Cochran, Claire; Ramsay, Craig; Vale, Luke; Foster, Paul; Friedman, David; Quayyum, Zahidul; Lai, Jimmy; Nolan, Winnie; Aung, Tin; Chew, Paul; McPherson, Gladys; McDonald, Alison; Norrie, John

2011-05-23

Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care. EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate. ISRCTN44464607.

Additive diagnostic role of imaging in glaucoma: optical coherence tomography and retinal nerve fiber layer photography.

PubMed

Kim, Ko Eun; Kim, Seok Hwan; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung

2014-11-20

To investigate the additive diagnostic role of spectral-domain optical coherence tomography (SD-OCT) and red-free retinal nerve fiber layer photography (RNFLP) in making clinical glaucoma diagnosis. Four diagnostic combination sets, including the most recent image from each measurement of 196 glaucoma eyes (including the 44 preperimetric glaucoma eyes) and 101 healthy eyes, were prepared: (1) stereo disc photography and Humphrey visual field (SH), (2) SH and SD-OCT (SHO), (3) SH and RNFLP (SHR), and (4) SHR and SD-OCT (SHRO). Each randomly sorted set was serially presented at 1-month intervals to five glaucoma specialists who were asked to evaluate them in a subjective and independent manner. The specialists' glaucoma-diagnostic performances based on the sets were then compared. For each specialist, adding SD-OCT to SH or SHR increased the glaucoma-diagnostic sensitivity but not to a level of statistical significance. For one specialist, adding RNFLP to SH significantly increased the sensitivity. Each specialist showed a high level of specificity regardless of the diagnostic set. The overall sensitivity of all specialists' assessments was significantly increased by adding RNFLP or the combination of SD-OCT and RNFLP to SH (P < 0.001); however, adding SD-OCT to SH or SHR did not significantly increase the sensitivity. A similar relationship was noted also for the preperimetric glaucoma subgroup. In contrast to RNFLP, SD-OCT did not significantly enhance the diagnostic accuracy of detecting glaucoma or even of preperimetric glaucoma. Our results suggest that, at least for glaucoma specialists, the additive diagnostic role of OCT is limited. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population.

PubMed

Wahl, Jochen; Barleon, Lorenz; Morfeld, Peter; Lichtmeß, Andrea; Haas-Brähler, Sibylle; Pfeiffer, Norbert

2016-01-01

To develop an expert system for glaucoma screening in a working population based on a human expert procedure using images of optic nerve head (ONH), visual field (frequency doubling technology, FDT) and intraocular pressure (IOP). 4167 of 13037 (32%) employees between 40 and 65 years of Evonik Industries were screened. An experienced glaucoma expert (JW) assessed papilla parameters and evaluated all individual screening results. His classification into "no glaucoma", "possible glaucoma" and "probable glaucoma" was defined as "gold standard". A screening model was developed which was tested versus the gold-standard. This model took into account the assessment of the ONH. Values and relationships of CDR and IOP and the FDT were considered additionally and a glaucoma score was generated. The structure of the screening model was specified a priori whereas values of the parameters were chosen post-hoc to optimize sensitivity and specificity of the algorithm. Simple screening models based on IOP and / or FDT were investigated for comparison. 111 persons (2.66%) were classified as glaucoma suspects, thereof 13 (0.31%) as probable and 98 (2.35%) as possible glaucoma suspects by the expert. Re-evaluation by the screening model revealed a sensitivity of 83.8% and a specificity of 99.6% for all glaucoma suspects. The positive predictive value of the model was 80.2%, the negative predictive value 99.6%. Simple screening models showed insufficient diagnostic accuracy. Adjustment of ONH and symmetry parameters with respect to excavation and IOP in an expert system produced sufficiently satisfying diagnostic accuracy. This screening model seems to be applicable in such a working population with relatively low age and low glaucoma prevalence. Different experts should validate the model in different populations.

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.

Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome?

PubMed

Taha, Doris; Barbar, Maha; Kanaan, Hassan; Williamson Balfe, John

2003-10-15

We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. Mutation analysis for several candidate genes is warranted. Copyright 2003 Wiley-Liss, Inc.

Vision Loss in Older Adults.

PubMed

Pelletier, Allen L; Rojas-Roldan, Ledy; Coffin, Janis

2016-08-01

Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

A Portable Platform for Evaluation of Visual Performance in Glaucoma Patients

PubMed Central

Rosen, Peter N.; Boer, Erwin R.; Gracitelli, Carolina P. B.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Marvasti, Amir H.; Medeiros, Felipe A.

2015-01-01

Purpose To propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes. Design Cross-sectional study. Methods The study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively. Results When adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls. Conclusion A portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls. PMID:26445501

Clinical model assisting with the collaborative care of glaucoma patients and suspects.

PubMed

Jamous, Khalid F; Kalloniatis, Michael; Hennessy, Michael P; Agar, Ashish; Hayen, Andrew; Zangerl, Barbara

2015-01-01

Optimizing patient management will reduce unnecessary vision loss in glaucoma through early detection. One method is the introduction of collaborative care schemes between optometrists and ophthalmologists. We conducted a retrospective study to evaluate the impact of the Centre for Eye Health (CFEH) on glaucoma patient outcomes and management in primary optometric care. Patients referred to CFEH by optometrists for a glaucoma assessment were eligible for this study if written consent was provided (500 participants were randomly chosen). Clinical data were classified according to disease risk and implemented patient care and analysed against the original diagnosis and patient parameters, followed by statistical analysis. Two main parameters were evaluated; suitable referral of patients for glaucoma condition assessment and appropriate implementation of follow-up care. The majority of patients referred for glaucoma assessment (86.2%) were classified as glaucoma suspects or likely to have glaucoma, indicating suitable referral of patients for a CFEH evaluation. Further, the involvement of CFEH resulted in a false positive rate of 7.8% for those patients who proceeded to ophthalmological care. However, long-term optometric patient care was not maintained for up to a third of primarily lower risk patients. The investigated collaborative eye health-care model led to a substantial improvement in appropriate referrals of glaucoma patients to ophthalmologists and could be suitable for optimizing patient care and utilization of resources. Improvement in follow-up of patients by optometrists is required to minimize inappropriately discontinued patient care. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Impact of patient access to Internet health records on glaucoma medication: randomized controlled trial.

PubMed

Kashiwagi, Kenji; Tsukahara, Shigeo

2014-01-15

Glaucoma is one of the leading causes of blindness. Reduction of intraocular pressure is the only proven way to prevent progression of glaucomatous optic neuropathy. The majority of glaucoma patients need to use antiglaucoma ophthalmic solutions over the course of their life. Thus, good adherence and persistency of glaucoma treatment are important factors for better glaucoma care. The purpose of this study was to investigate the impact of an Internet-based glaucoma care support system on glaucoma medication use. Patients were randomly divided into two groups. The non-Internet access (NIA) group consisted of patients who had access to the Internet-based glaucoma care support system during the 4-year period only when they were examined by ophthalmologists. The Internet access (IA) group consisted of patients who had the same Internet-based glaucoma care support system access as the NIA group for the first 2 years following enrollment but who were also given free access to the glaucoma care support system for the remaining 2 years. Changes in glaucoma medication use were investigated. In total, 81 patients in the IA group and 90 patients in the NIA group satisfied the study protocol. The number of antiglaucoma ophthalmic solutions used during the study period significantly increased in the NIA group (P<.03) but not in the IA group. The percentages of patients with unchanged, increased, and decreased antiglaucoma ophthalmic solution use during the study period were 61.1% (55/90), 17.8% (16/90), and 3.3% (3/90), respectively, in the NIA group, and 56.8% (46/81), 8.6% (7/81), and 13.6% (11/81), respectively, in the IA group (P<.001). Internet access significantly shifted from an increasing intraocular pressure trend to a decreasing trend in the IA group (P=.002) among the patients who did not have any medication changes. Allowing patients to browse their medical data may reduce the use and improve the effectiveness of glaucoma medication. UMIN-CTR Clinical Trial Number: UMIN000006982; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000008238&language=E (Archived by WebCite at http://www.webcitation.org/6MRPQeEAv).

Iterative variational mode decomposition based automated detection of glaucoma using fundus images.

PubMed

Maheshwari, Shishir; Pachori, Ram Bilas; Kanhangad, Vivek; Bhandary, Sulatha V; Acharya, U Rajendra

2017-09-01

Glaucoma is one of the leading causes of permanent vision loss. It is an ocular disorder caused by increased fluid pressure within the eye. The clinical methods available for the diagnosis of glaucoma require skilled supervision. They are manual, time consuming, and out of reach of common people. Hence, there is a need for an automated glaucoma diagnosis system for mass screening. In this paper, we present a novel method for an automated diagnosis of glaucoma using digital fundus images. Variational mode decomposition (VMD) method is used in an iterative manner for image decomposition. Various features namely, Kapoor entropy, Renyi entropy, Yager entropy, and fractal dimensions are extracted from VMD components. ReliefF algorithm is used to select the discriminatory features and these features are then fed to the least squares support vector machine (LS-SVM) for classification. Our proposed method achieved classification accuracies of 95.19% and 94.79% using three-fold and ten-fold cross-validation strategies, respectively. This system can aid the ophthalmologists in confirming their manual reading of classes (glaucoma or normal) using fundus images. Copyright © 2017 Elsevier Ltd. All rights reserved.

Auditory processing deficits in individuals with primary open-angle glaucoma.

PubMed

Rance, Gary; O'Hare, Fleur; O'Leary, Stephen; Starr, Arnold; Ly, Anna; Cheng, Belinda; Tomlin, Dani; Graydon, Kelley; Chisari, Donella; Trounce, Ian; Crowston, Jonathan

2012-01-01

The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.

The diagnostic use of choroidal thickness analysis and its correlation with visual field indices in glaucoma using spectral domain optical coherence tomography.

PubMed

Lin, Zhongjing; Huang, Shouyue; Huang, Ping; Guo, Lei; Shen, Xi; Zhong, Yisheng

2017-01-01

To evaluate the quantitative characteristics of choroidal thickness in primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and in normal eyes using spectral-domain optical coherence tomography (SD-OCT). To evaluate the diagnostic ability of choroidal thickness in glaucoma and to determine the correlation between choroidal thickness and visual field parameters in glaucoma. A total of 116 subjects including 40 POAG, 30 NTG and 46 healthy subjects were enrolled in this study. Choroidal thickness measurements were acquired in the macular and peripapillary regions using SD-OCT. All subjects underwent white-on-white (W/W) and blue-on-yellow (B/Y) visual field tests using Humphrey Field Analyzer. The receiver operating characteristic (ROC) curve and the area under curve (AUC) were generated to assess the discriminating power of choroidal thickness for glaucoma. Pearson's correlation coefficients were calculated to assess the structure function correlation for glaucoma patients. No significant differences were observed for macular choroidal thickness among the different groups (all P > 0.05). Regarding the peripapillary choroidal thickness (PPCT), significant differences were observed among the three groups (all P < 0.05). Post hoc tests for multiple comparisons revealed a significant difference in the NTG-normal comparison group (all P < 0.01). The inferior and temporal PPCT in POAG patients were significantly thinner than those in normal subjects (P = 0.007, P = 0.002, respectively). Different parameters of PPCT showed significantly low diagnostic values to detect POAG from normal subjects (AUC: 0.555 to 0.652) and to discriminate NTG from POAG (AUC: 0.462 to 0.702), but moderate diagnostic power to detect NTG from normal subjects (AUC: 0.708 to 0.771). Regarding the diagnosis of early glaucoma, different parameters of PPCT showed relatively low diagnostic power (AUC: 0.606 to 0.698). In all the glaucoma subjects, PPCT was not significantly correlated with W/W mean deviation (MD) (all P > 0.05), but showed significant correlations with B/Y MD (all P < 0.05). In the early glaucomatous eyes, PPCT showed significant correlations with W/W MD and B/Y MD (all P < 0.05). In our study, peripapillary choroidal thickness measured on OCT showed a low to moderate but statistically significant diagnostic power and a significant correlation with blue-on-yellow visual field indices in glaucoma. This may indicate a potential adjunct for peripapillary choroidal thickness in glaucoma diagnosis.

Automated retinal nerve fiber layer defect detection using fundus imaging in glaucoma.

PubMed

Panda, Rashmi; Puhan, N B; Rao, Aparna; Padhy, Debananda; Panda, Ganapati

2018-06-01

Retinal nerve fiber layer defect (RNFLD) provides an early objective evidence of structural changes in glaucoma. RNFLD detection is currently carried out using imaging modalities like OCT and GDx which are expensive for routine practice. In this regard, we propose a novel automatic method for RNFLD detection and angular width quantification using cost effective redfree fundus images to be practically useful for computer-assisted glaucoma risk assessment. After blood vessel inpainting and CLAHE based contrast enhancement, the initial boundary pixels are identified by local minima analysis of the 1-D intensity profiles on concentric circles. The true boundary pixels are classified using random forest trained by newly proposed cumulative zero count local binary pattern (CZC-LBP) and directional differential energy (DDE) along with Shannon, Tsallis entropy and intensity features. Finally, the RNFLD angular width is obtained by random sample consensus (RANSAC) line fitting on the detected set of boundary pixels. The proposed method is found to achieve high RNFLD detection performance on a newly created dataset with sensitivity (SN) of 0.7821 at 0.2727 false positives per image (FPI) and the area under curve (AUC) value is obtained as 0.8733. Copyright © 2018 Elsevier Ltd. All rights reserved.

Morphological Features and Important Parameters of Large Optic Discs for Diagnosing Glaucoma

PubMed Central

Okimoto, Satoshi; Yamashita, Keiko; Shibata, Tetsuo; Kiuchi, Yoshiaki

2015-01-01

Purpose To compare the optic disc parameters of glaucomatous eyes to those of non-glaucomatous eyes with large discs. Methods We studied 225 consecutive eyes with large optic discs (>2.82 mm2): 91 eyes with glaucoma and 134 eyes without glaucoma. An eye was diagnosed with glaucoma when visual field defects were detected by the Humphrey Field Analyzer. All of the Heidelberg Retina Tomograph II (HRT II) parameters were compared between the non-glaucomatous and glaucomatous eyes. A logistic regression analysis of the HRT II parameters was used to establish a new formula for diagnosing glaucoma, and the sensitivity and specificity of the Moorfields Regression Analysis (MRA) was compared to the findings made by our analyses. Results The mean disc area was 3.44±0.50 mm2 in the non-glaucomatous group and 3.40±0.52 mm2 in the glaucoma group. The cup area, cup volume, cup-to-disc area ratio, linear cup/disc ratio, mean cup depth, and the maximum cup depth were significantly larger in glaucomatous eyes than in the non-glaucomatous eyes. The rim area, rim volume, cup shape measurement, mean retinal nerve fiber layer (RNFL) thickness, and RFNL cross-sectional area were significantly smaller in glaucomatous eyes than in non-glaucomatous eyes. The cup-to-disc area ratio, the height variation contour (HVC), and the RNFL cross-sectional area were important parameters for diagnosing the early stage glaucoma, and the cup-to-disc area ratio and cup volume were useful for diagnosing advanced stage glaucoma in eyes with a large optic disc. The new formula had higher sensitivity and specificity for diagnosing glaucoma than MRA. Conclusions The cup-to-disc area ratio, HVC, RNFL cross-sectional area, and cup volume were important parameters for diagnosing glaucoma in eyes with a large optic disc. The important disc parameters to diagnose glaucoma depend on the stage of glaucoma in patients with large discs. PMID:25798580

Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population

PubMed Central

Millá, Elena; Mañé, Begoña; Duch, Susana; Hernan, Imma; Borràs, Emma; Planas, Ester; Dias, Miguel de Sousa; Carballo, Miguel

2013-01-01

Purpose To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Methods Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. Results We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). Conclusions The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1. PMID:23922489

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss.

PubMed

Chen, Chieh-Li; Bojikian, Karine D; Wen, Joanne C; Zhang, Qinqin; Xin, Chen; Mudumbai, Raghu C; Johnstone, Murray A; Chen, Philip P; Wang, Ruikang K

2017-05-01

Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] μm; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] μm; 95% CI, -6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman ρ = 0.44; P = .045) and RNFL thickness (Spearman ρ = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

Association between rates of binocular visual field loss and vision-related quality of life in patients with glaucoma.

PubMed

Lisboa, Renato; Chun, Yeoun Sook; Zangwill, Linda M; Weinreb, Robert N; Rosen, Peter N; Liebmann, Jeffrey M; Girkin, Christopher A; Medeiros, Felipe A

2013-04-01

It is reasonable to hypothesize that for 2 patients with similar degrees of integrated binocular visual field (BVF) loss, the patient with a history of faster disease progression will report worse vision-related quality of life (VRQOL) than the patient with slowly progressing damage. However, to our knowledge, this hypothesis has not been investigated in the literature. To evaluate the association between binocular rates of visual field change and VRQOL in patients with glaucoma. DESIGN Observational cohort study. Patients were recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. The study included 796 eyes of 398 patients with diagnosed or suspected glaucoma followed up from October 1, 1998, until January 31, 2012, for a mean (SD) of 7.3 (2.0) years. The VRQOL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at the last follow-up visit. The NEI VFQ-25 was completed for all patients during the period extending from December 1, 2009, through January 31, 2012. Integrated BVFs were calculated from the monocular fields of each patient. Linear regression of mean deviation values was used to evaluate rates of BVF change during the follow-up period. Logistic regression models were used to investigate the association between abnormal VRQOL and rates of BVF change, while adjusting for potentially confounding socioeconomic and demographic variables. Thirty-two patients (8.0%) had abnormal VRQOL as determined by the results of the NEI VFQ-25. Patients with abnormal VRQOL had significantly faster rates of BVF change than those with normal VRQOL (-0.18 vs -0.06 dB/y; P < .001). Rates of BVF change were significantly associated with abnormality in VRQOL (odds ratio = 1.31 per 0.1 dB/y faster; P = .04), after adjustment for confounding variables. Patients with faster rates of BVF change were at higher risk of reporting abnormal VRQOL. Assessment of rates of BVF change may provide useful information in determining risk of functional impairment in glaucoma.

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".

Economic impact of primary open-angle glaucoma in Australia.

PubMed

Dirani, Mohamed; Crowston, Jonathan G; Taylor, Penny S; Moore, Peter T; Rogers, Sophie; Pezzullo, M Lynne; Keeffe, Jill E; Taylor, Hugh R

2011-01-01

Glaucoma is the World's leading cause of irreversible blindness, and poses serious public health and economic concerns.   Review. Published randomized trials and population-based studies since 1985. We report the economic impact of primary open-angle glaucoma and model the effect of changes in detection rates and management strategies. The cost-effectiveness of different interventions to prevent vision loss from primary open-angle glaucoma was measured in terms of financial cost (Australian dollars) and disability-adjusted life years. The prevalence of glaucoma in Australia is expected to increase from 208 000 in 2005 to 379 000 in 2025 because of the aging population. Health system costs over the same time period are estimated to increase from $AU355 million to $AU784 million. Total costs (health system costs, indirect costs and costs of loss of well-being) will increase from $AU1.9 billion to $AU4.3 billion in Australia. Primary open-angle glaucoma poses a significant economic burden, which will increase substantially by 2025. This dynamic model provides a valuable tool for ongoing policy formulation and determining the economic impact of interventions to better prevent visual impairment and blindness from glaucoma. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Toward comprehensive detection of sight threatening retinal disease using a multiscale AM-FM methodology

NASA Astrophysics Data System (ADS)

Agurto, C.; Barriga, S.; Murray, V.; Murillo, S.; Zamora, G.; Bauman, W.; Pattichis, M.; Soliz, P.

2011-03-01

In the United States and most of the western world, the leading causes of vision impairment and blindness are age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. In the last decade, research in automatic detection of retinal lesions associated with eye diseases has produced several automatic systems for detection and screening of AMD, DR, and glaucoma. However. advanced, sight-threatening stages of DR and AMD can present with lesions not commonly addressed by current approaches to automatic screening. In this paper we present an automatic eye screening system based on multiscale Amplitude Modulation-Frequency Modulation (AM-FM) decompositions that addresses not only the early stages, but also advanced stages of retinal and optic nerve disease. Ten different experiments were performed in which abnormal features such as neovascularization, drusen, exudates, pigmentation abnormalities, geographic atrophy (GA), and glaucoma were classified. The algorithm achieved an accuracy detection range of [0.77 to 0.98] area under the ROC curve for a set of 810 images. When set to a specificity value of 0.60, the sensitivity of the algorithm to the detection of abnormal features ranged between 0.88 and 1.00. Our system demonstrates that, given an appropriate training set, it is possible to use a unique algorithm to detect a broad range of eye diseases.

The usefulness of CorvisST Tonometry and the Ocular Response Analyzer to assess the progression of glaucoma

NASA Astrophysics Data System (ADS)

Matsuura, Masato; Hirasawa, Kazunori; Murata, Hiroshi; Nakakura, Shunsuke; Kiuchi, Yoshiaki; Asaoka, Ryo

2017-01-01

Corneal Visualization Scheimpflug Technology (CST) and Ocular Response Analyzer (ORA) measurements were carried out in 105 eyes of 69 patients with primary open-angle glaucoma. All patients had axial length (AL), central corneal thickness (CCT), intraocular pressure (IOP) with Goldmann applanation tonometry (GAT) and eight visual fields (VF)s with the Humphrey Field Analyzer. VF progression was summarized using a time trend analysis of mean total deviation (mTD) and the association between mTD progression rate and a number of ocular parameters (including CST and ORA measurements) was assessed using mixed linear regression analysis. The optimal model of VF progression selected based on the corrected Akaike Information Criteria (AICc) included ORA’s corneal hysteresis (CH) parameter as well as a number of CST measurements: mTD progression rate = 1.2-0.070 * mean GAT + 0.090 * CH-1.5 * highest concavity deformation amplitude with CST + 9.4 * A1 deformation amplitude with CST-0.05 * A2 length with CST (AICc = 125.8). Eyes with corneas that experience deep indentation at the maximum deformation, shallow indentation at the first applanation and wide indentation at the second applanation in the CST measurement are more likely to experience faster rates of VF progression.

Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

PubMed Central

Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

2016-01-01

Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

Glaucoma and its association with obstructive sleep apnea: A narrative review

PubMed Central

Chaitanya, Aditya; Pai, Vijaya H.; Mohapatra, Aswini Kumar; Ve, Ramesh S.

2016-01-01

Obstructive sleep apnea (OSA) is one of the systemic risk factors for glaucoma which causes irreversible visual field (VF) damage. We reviewed the published data of all types of studies on the association between these two conditions and papers regarding functional and structural changes related to glaucomatous damage using Scopus, web of science, and PubMed databases. There is evidence that the prevalence of glaucoma is higher in OSA patients, which independent of intraocular pressure (IOP). Studies have reported thinning of retinal nerve fiber layer (RNFL), alteration of optic nerve head, choroidal and macular thickness, and reduced VF sensitivity in patients of OSA with no history glaucoma. A negative correlation of apnea-hypopnea index with RNFL and VF indices has been described in some studies. Raised IOP was noted which is possibly related to obesity, supine position during sleep, and raised intracranial pressure. Diurnal fluctuations of IOP show more variations in OSA patients before and after continuous positive airway pressure (CPAP) therapy when compared with the normal cases. The vascular factors behind the pathogenesis include recurrent hypoxia with increased vascular resistance, oxidative stress damage to the optic nerve. In conclusion, comprehensive glaucoma evaluation should be recommended in patients with OSA and should also periodically monitor IOP during CPAP treatment which may trigger the progression of glaucomatous damage. PMID:27843225

Uveitis-glaucoma-hyphema syndrome associated with recurrent vitreous hemorrhage.

PubMed

Alfaro-Juárez, A; Vital-Berral, C; Sánchez-Vicente, J L; Alfaro-Juárez, A; Muñoz-Morales, A

2015-08-01

A 61-year-old pseudophakic male with recurrent blurred vision episodes associated with uveitis, hyphema, glaucoma and vitreous hemorrhage. Iris transillumination defects and apposition of the optic and iris were found. The patient was diagnosed with Uveitis-Glaucoma-Hyphema (UGH) Syndrome. Mechanical irritation of the iris is a consequence of intraocular lens malposition and causes UGH Syndrome. Occasionally it is associated with vitreous hemorrhage. Lens malposition is detected by optical coherence tomography and/or ultrasound biomicroscopy. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Diagnostic Abilities of Variable and Enhanced Corneal Compensation Algorithms of GDx in Different Severities of Glaucoma.

PubMed

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

2016-02-01

To compare the abilities of retinal nerve fiber layer (RNFL) parameters of variable corneal compensation (VCC) and enhanced corneal compensation (ECC) algorithms of scanning laser polarimetry (GDx) in detecting various severities of glaucoma. Two hundred and eighty-five eyes of 194 subjects from the Longitudinal Glaucoma Evaluation Study who underwent GDx VCC and ECC imaging were evaluated. Abilities of RNFL parameters of GDx VCC and ECC to diagnose glaucoma were compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities, and likelihood ratios. After excluding 5 eyes that failed to satisfy manufacturer-recommended quality parameters with ECC and 68 with VCC, 56 eyes of 41 normal subjects and 161 eyes of 121 glaucoma patients [36 eyes with preperimetric glaucoma, 52 eyes with early (MD>-6 dB), 34 with moderate (MD between -6 and -12 dB), and 39 with severe glaucoma (MD<-12 dB)] were included for the analysis. Inferior RNFL, average RNFL, and nerve fiber indicator parameters showed the best AUCs and sensitivities both with GDx VCC and ECC in diagnosing all severities of glaucoma. AUCs and sensitivities of all RNFL parameters were comparable between the VCC and ECC algorithms (P>0.20 for all comparisons). Likelihood ratios associated with the diagnostic categorization of RNFL parameters were comparable between the VCC and ECC algorithms. In scans satisfying the manufacturer-recommended quality parameters, which were significantly greater with ECC than VCC algorithm, diagnostic abilities of GDx ECC and VCC in glaucoma were similar.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

PubMed Central

Seet, Li-Fong; Lee, Wing Sum; Su, Roseline; Finger, Sharon N; Crowston, Jonathan G; Wong, Tina T

2011-01-01

Glaucoma is a progressive optic neuropathy, which, if left untreated, leads to blindness. The most common and most modifiable risk factor in glaucoma is elevated intraocular pressure (IOP), which can be managed surgically by filtration surgery. The postoperative subconjunctival scarring response, however, remains the major obstacle to achieving long-term surgical success. Antiproliferatives such as mitomycin C are commonly used to prevent postoperative scarring. Efficacy of these agents has been tested extensively on monkey and rabbit models of glaucoma filtration surgery. As these models have inherent limitations, we have developed a model of glaucoma filtration surgery in the mouse. We show, for the first time, that the mouse model typically scarred within 14 d, but when augmented with mitomycin C, more animals maintained lower intraocular pressures for a longer period of time concomitant with prolonged bleb survival to beyond 28 d. The morphology of the blebs following mitomycin C treatment also resembled well-documented clinical observations, thus confirming the validity and clinical relevance of this model. We demonstrate that the antiscarring response to mitomycin C is likely to be due to its effects on conjunctival fibroblast proliferation, apoptosis and collagen deposition and the suppression of inflammation. Indeed, we verified some of these properties on mouse conjunctival fibroblasts cultured in vitro. These data support the suitability of this mouse model for studying the wound healing response in glaucoma filtration surgery, and as a potentially useful tool for the in vivo evaluation of antifibrotic therapeutics in the eye. PMID:21229189

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.

An adherence based cost-consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%.

PubMed

Wong, William B; Patel, Vaishali D; Kowalski, Jonathan W; Schwartz, Gail

2013-09-01

Estimate the long-term direct medical costs and clinical consequences of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the treatment of glaucoma. A cost-consequence model was constructed from the perspective of a US healthcare payer. The model structure included three adherence levels (high, moderate, low) and four mean deviation (MD) defined health states (mild, moderate, severe glaucoma, blindness) for each adherence level. Clinical efficacy in terms of IOP reduction was obtained from the randomized controlled trial comparing bimatoprost 0.01% with bimatoprost 0.03%. Medication adherence was based on observed 12 month rates from an analysis of a nationally representative pharmacy claims database. Patients with high, moderate and low adherence were assumed to receive 100%, 50% and 0% of the IOP reduction observed in the clinical trial, respectively. Each 1 mmHg reduction in IOP was assumed to result in a 10% reduction in the risk of glaucoma progression. Worse glaucoma severity health states were associated with higher medical resource costs. Outcome measures were total costs, proportion of patients who progress and who become blind, and years of blindness. Deterministic sensitivity analyses were performed on uncertain model parameters. The percentage of patients progressing, becoming blind, and the time spent blind slightly favored bimatoprost 0.01%. Improved adherence with bimatoprost 0.01% led to higher costs in the first 2 years; however, starting in year 3 bimatoprost 0.01% became less costly compared to bimatoprost 0.03% with a total reduction in costs reaching US$3433 over a lifetime time horizon. Deterministic sensitivity analyses demonstrated that results were robust, with the majority of analyses favoring bimatoprost 0.01%. Application of 1 year adherence and efficacy over the long term are limitations. Modeling the effect of greater medication adherence with bimatoprost 0.01% compared with bimatoprost 0.03% suggests that differences may result in improved economic and patient outcomes.

[Predicting the probability of development and progression of primary open angle glaucoma by regression modeling].

PubMed

Likhvantseva, V G; Sokolov, V A; Levanova, O N; Kovelenova, I V

2018-01-01

Prediction of the clinical course of primary open-angle glaucoma (POAG) is one of the main directions in solving the problem of vision loss prevention and stabilization of the pathological process. Simple statistical methods of correlation analysis show the extent of each risk factor's impact, but do not indicate the total impact of these factors in personalized combinations. The relationships between the risk factors is subject to correlation and regression analysis. The regression equation represents the dependence of the mathematical expectation of the resulting sign on the combination of factor signs. To develop a technique for predicting the probability of development and progression of primary open-angle glaucoma based on a personalized combination of risk factors by linear multivariate regression analysis. The study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed primary open-angle glaucoma. The control group consisted of 14 patients (8 male and 6 female). Standard ophthalmic examination was supplemented with biochemical study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP-9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked immunosorbent assay (ELISA) method. The study resulted in the development of regression equations and step-by-step multivariate logistic models that can help calculate the risk of development and progression of POAG. Those models are based on expert evaluation of clinical and instrumental indicators of hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular fluid secretion - F, fluctuation of intraocular pressure), as well as personalized morphometric parameters of the retina (central retinal thickness in the macular area) and concentration of MMP-2 and MMP-9 in the tear film. The newly developed regression equations are highly informative and can be a reliable tool for studying of the influence vector and assessment of pathogenic potential of the independent risk factors in specific personalized combinations.

The effect of mitomycin C trabeculectomy on the progression of visual field defect in normal-tension glaucoma.

PubMed

Hagiwara, Y; Yamamoto, T; Kitazawa, Y

2000-03-01

We investigated in a prospective fashion the visual prognosis and complications in normal-tension glaucoma following unilateral trabeculectomy with adjunctive mitomycin C. Trabeculectomy with adjunctive mitomycin C was carried out unilaterally in 21 cases of normal-tension glaucoma. Intraocular pressure (IOP), visual prognosis, and complications were compared between the operated eyes and the non-operated fellow eyes. The follow-up period ranged from 2 to 7 years. The IOP dropped significantly from 14.8+/-1.8 mmHg (mean +/- SD) to 9.6+/-3.9 mmHg in the operated eyes (P=0.0002, Wilcoxon signed-rank test), but did not drop in the non-operated eyes. The mean deviation (MD) was -12.69+/-6.41 dB preoperatively and -14.70+/-5.49 dB at the last clinic visit in the operated eyes, whereas in non-operated eyes it was -7.85+/-5.65 dB and -11.15+/-5.62 dB, respectively. The MD deteriorated significantly in both operated and non-operated eyes (operated eyes P=0.0239, non-operated eyes: P=0.0002; Wilcoxon signed-rank test). The MD slope was -0.37+/-0.60 dB/year and -0.71+/-0.89 dB/year for the operated and non-operated eyes, respectively (P=0.5243, Mann-Whitney U-test). Visual field deterioration was more frequently observed in the non-operated eyes by a pointwise definition of the progression (P<0.05, McNemar test). Visual acuity deteriorated in 6 of the operated eyes and in 5 of the non-operated eyes. Cataract developed in 6 (29%) of the 21 operated eyes, while among the non-operated eyes 4 (19%) developed cataract. Mitomycin C trabeculectomy is effective in delaying progression of visual field defect in normal-tension glaucoma, but complications may arise and cause some visual disturbance.

Role of laser peripheral iridotomy in pigmentary glaucoma and pigment dispersion syndrome: A review of the literature.

PubMed

Buffault, J; Leray, B; Bouillot, A; Baudouin, C; Labbé, A

2017-11-01

Pigment dispersion syndrome (PDS) is characterized by a structural abnormality of the posterior surface of the iris causing contact with the zonular fibers. It can lead to an open-angle glaucoma secondary to pigment dispersion into the trabecular meshwork. Laser peripheral iridotomy (PI) has been proposed as a treatment for pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) by reducing the dispersion of pigment. The goal of this review was to assess the effects of PI for PDS and PG. We included six randomized controlled trials and two cohort studies (286 eyes of 218 participants). Four trials included participants with PG, and 4 trials enrolled participants with PDS with or without elevated intraocular pressure (IOP). Among patients with PG, at an average of 9 months of follow-up, the mean difference in IOP between groups was 2.69mm Hg less in the PI group (95% CI: -6.05 to 0.67; 14 eyes). In patients with PDS, the average IOP was statistically lower after PI as compared to baseline (Student test t=11.49, P<0.01, 38 eyes). With regard to visual field progression in participants with PG, after an average follow-up of 28 months, the risk of progression was not influenced by PI (RR 1.00 95% CI: 0.16 to 6.25; 32 eyes). No trials that enrolled patients with PDS showed a diminution of the risk of glaucoma conversion at mid- and long-terms. PI decreases the biomechanical factor causing contact between the iris and zonular fibers and may lower IOP over the long-term. Nevertheless, the effects of PI on visual field changes or progression have not been established in PG and PDS. There is no scientific evidence as of yet to advocate PI as a treatment for PDS or PG. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Role of laser peripheral iridotomy in pigmentary glaucoma and pigment dispersion syndrome: A review of the literature [French version

PubMed

Buffault, J; Leray, B; Bouillot, A; Baudouin, C; Labbé, A

2017-12-01

Pigment dispersion syndrome (PSD) is characterized by a structural abnormality of the posterior surface of the iris causing contact with the zonular fibers. It can lead to an open-angle glaucoma secondary to pigment dispersion into the trabecular meshwork. Laser peripheral iridotomy (PI) has been proposed as a treatment for pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) by reducing the dispersion of pigment. The goal of this review was to assess the effects of PI for PSD and PG. We included six randomized controlled trials and two cohort studies (286 eyes of 218 participants). Four trials included participants with PG, and 4 trials enrolled participants with PSD with or without elevated intraocular pressure (IOP). Among patients with PG, at an average of 9 months of follow-up, the mean difference in IOP between groups was 2.69mmHg less in the PI group (95 % CI: -6.05 to 0.67; 14 eyes). In patients with PDS, the average IOP was statistically lower after PI as compared to baseline (Student test, t=11.49, P<0.01). With regard to visual field progression in participants with GP, after an average follow-up of 28 months, the risk of progression was not influenced by PI (RR 1.00 95 %: CI 0.16 to 6.25; 32 eyes). No trials that enrolled patients with PSD showed a diminution of the risk of glaucoma conversion at mid- and long-term. PI decreases the biomechanical factor causing contact between the iris and zonular fibers and may lower IOP over the long-term. Nevertheless, the effects of PI on visual field changes or progression have not been established in PG and PDS. There is no scientific evidence as of yet to advocate PI as a treatment for PDS or PG. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Early aggressive intraocular pressure lowering, target intraocular pressure, and a novel concept for glaucoma care.

PubMed

Singh, Kuldev; Shrivastava, Anurag

2008-11-01

Early diagnosis of glaucomatous optic nerve damage offers the potential for early treatment which may prevent vision loss from this neurodegenerative disease. Even in patients who do not begin early treatment, early diagnosis allows for better monitoring of disease at a stage where the stakes are lower relative to later stages of the disease. For these reasons, early diagnosis of glaucomatous optic nerve disease is desirable and opens the door for appropriately aggressive therapy. The target intraocular pressure (IOP) concept is widely employed by glaucoma practitioners. Although there have been no randomized clinical trials or other high-quality studies showing the benefits of setting a target IOP versus not using this approach, there is ample evidence that lowering IOP slows glaucoma progression and, in general, lower is better, regardless of disease stage and baseline IOP level. We propose an alternative approach to managing glaucoma without the use of the target IOP concept and suggest that this market IOP concept should be compared with the target IOP approach in an appropriately powered comparative clinical trial.

Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

PubMed Central

Vitart, Veronique; Nag, Abhishek; Hewitt, Alex W; Höhn, René; Venturini, Cristina; Mirshahi, Alireza; Ramdas, Wishal D.; Thorleifsson, Gudmar; Vithana, Eranga; Khor, Chiea-Chuen; Stefansson, Arni B; Liao, Jiemin; Haines, Jonathan L; Amin, Najaf; Wang, Ya Xing; Wild, Philipp S; Ozel, Ayse B; Li, Jun Z; Fleck, Brian W; Zeller, Tanja; Staffieri, Sandra E; Teo, Yik-Ying; Cuellar-Partida, Gabriel; Luo, Xiaoyan; Allingham, R Rand; Richards, Julia E; Senft, Andrea; Karssen, Lennart C; Zheng, Yingfeng; Bellenguez, Céline; Xu, Liang; Iglesias, Adriana I; Wilson, James F; Kang, Jae H; van Leeuwen, Elisabeth M; Jonsson, Vesteinn; Thorsteinsdottir, Unnur; Despriet, Dominiek D.G.; Ennis, Sarah; Moroi, Sayoko E; Martin, Nicholas G; Jansonius, Nomdo M; Yazar, Seyhan; Tai, E-Shyong; Amouyel, Philippe; Kirwan, James; van Koolwijk, Leonieke M.E.; Hauser, Michael A; Jonasson, Fridbert; Leo, Paul; Loomis, Stephanie J; Fogarty, Rhys; Rivadeneira, Fernando; Kearns, Lisa; Lackner, Karl J; de Jong, Paulus T.V.M.; Simpson, Claire L; Pennell, Craig E; Oostra, Ben A; Uitterlinden, André G; Saw, Seang-Mei; Lotery, Andrew J; Bailey-Wilson, Joan E; Hofman, Albert; Vingerling, Johannes R; Maubaret, Cécilia; Pfeiffer, Norbert; Wolfs, Roger C.W.; Lemij, Hans G; Young, Terri L; Pasquale, Louis R; Delcourt, Cécile; Spector, Timothy D; Klaver, Caroline C.W.; Small, Kerrin S; Burdon, Kathryn P; Stefansson, Kari; Wong, Tien-Yin; Viswanathan, Ananth; Mackey, David A; Craig, Jamie E; Wiggs, Janey L; van Duijn, Cornelia M; Hammond, Christopher J; Aung, Tin

2014-01-01

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and IOP variability may herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multiethnic participants for IOP. We confirm genetic association of known loci for IOP and primary open angle glaucoma (POAG) and identify four new IOP loci located on chromosome 3q25.31 within the FNDC3B gene (p=4.19×10−08 for rs6445055), two on chromosome 9 (p=2.80×10−11 for rs2472493 near ABCA1 and p=6.39×10−11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best p=1.04×10−11 for rs747782). Separate meta-analyses of four independent POAG cohorts, totaling 4,284 cases and 95,560 controls, show that three of these IOP loci are also associated with POAG. PMID:25173106

Intermediate and Long-term Outcomes of Mitomycin C-enhanced Trabeculectomy as a First Glaucoma Procedure in Uveitic Glaucoma.

PubMed

Almobarak, Faisal A; Alharbi, Ali H; Morales, Jose; Aljadaan, Ibrahim

2017-05-01

To evaluate the intermediate and long-term outcomes of mitomycin C-enhanced trabeculectomy as a first glaucoma procedure in uveitic glaucoma. Retrospective cohort study included 70 eyes of 50 patients with uveitic glaucoma who underwent mitomycin C-enhanced trabeculectomy as a first glaucoma procedure at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between 1996 and 2014. The main outcome measures were: the intraocular pressure (IOP), the number of antiglaucoma medications, the presence of visually threatening complications, and the need for further surgeries to control the IOP. Surgical outcome of each eye was classified as an absolute success, qualified success, or failure, based on the main outcome measures. The mean follow-up period was 77.0 months (±40.9). The IOP and number of antiglaucoma medications decreased significantly from a mean of 39.5 mm Hg (±8.9) and 3.7 (±0.8) to 14.4 mm Hg (±6.9) and 1 (±1.3) at the last follow-up, respectively (P<0.001 for both). The cumulative probabilities of success were 60% and 35.7% at 36 and 60 months postoperatively, respectively. The most common complications were cataract development and progression (45.3%), hypotony (IOP ≤5 mm Hg) (30%) and IOP spike≥30 mm Hg (10%). Eighteen eyes (25.7%) needed a second procedure to control the IOP. Although mitomycin C-enhanced trabeculectomy offers reasonable intermediate and long-term IOP control and safety in uveitic glaucoma, a significant number of patients needed further procedures to control the pressure. Thus, continuous monitoring of the pressure and inflammation are crucial.

Virtual clinics in glaucoma care: face-to-face versus remote decision-making.

PubMed

Clarke, Jonathan; Puertas, Renata; Kotecha, Aachal; Foster, Paul J; Barton, Keith

2017-07-01

To examine the agreement in clinical decisions of glaucoma status made in a virtual glaucoma clinic with those made during a face-to-face consultation. A trained nurse and technicians entered data prospectively for 204 patients into a proforma. A subsequent face-to-face clinical assessment was completed by either a glaucoma consultant or fellow. Proformas were reviewed remotely by one of two additional glaucoma consultants, and 12 months later, by the clinicians who had undertaken the original clinical examination. The interobserver and intraobserver decision-making agreements of virtual assessment versus standard care were calculated. We identified adverse disagreement between face-to-face and virtual review in 7/204 (3.4%, 95% CI 0.9% to 5.9%) patients, where virtual review failed to predict a need to accelerated follow-up identified in face-to-face review. Misclassification events were rare, occurring in 1.9% (95% CI 0.3% to 3.8%) of assessments. Interobserver κ (95% CI) showed only fair agreement (0.24 (0.04 to 0.43)); this improved to moderate agreement when only consultant decisions were compared against each other (κ=0.41 (0.16 to 0.65)). The intraobserver agreement κ (95% CI) for the consultant was 0.274 (0.073 to 0.476), and that for the fellow was 0.264 (0.031 to 0.497). The low rate of adverse misclassification, combined with the slowly progressive nature of most glaucoma, and the fact that patients will all be regularly reassessed, suggests that virtual clinics offer a safe, logistically viable option for selected patients with glaucoma. 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/.

Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study.

PubMed

Schweitzer, Cedric; Korobelnik, Jean-Francois; Le Goff, Melanie; Rahimian, Olivier; Malet, Florence; Rougier, Marie-Benedicte; Delyfer, Marie-Noelle; Dartigues, Jean-Francois; Delcourt, Cecile

2016-11-01

To assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population. The antioxidants, essential lipids, nutrition and ocular maladies study (ALIENOR: "Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires") is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR). A total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05). Parameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care. EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care. Methods/Design EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible. The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events. A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate. Trial Registration: ISRCTN44464607. PMID:21605352

Neuroretinal Rim Area Change in Glaucoma Patients With Visual Field Progression Endpoints and Intraocular Pressure Reduction. The Canadian Glaucoma Study: 4.

PubMed

Malik, Rizwan; O'Leary, Neil; Mikelberg, Frederick S; Balazsi, A Gordon; LeBlanc, Raymond P; Lesk, Mark R; Nicolela, Marcelo T; Trope, Graham E; Chauhan, Balwantray C

2016-03-01

To compare rim area rates in patients with and without the visual field (VF) progression endpoint in the Canadian Glaucoma Study and determine whether intraocular pressure (IOP) reduction following the endpoint altered rim area rate. Prospective multicenter cohort study. setting: University hospitals. Two hundred and six patients with open-angle glaucoma were examined at 4-month intervals with standard automated perimetry and confocal scanning laser tomography. After the endpoint, IOP was reduced by ≥20%. Univariate analysis for change in rim area rate and multivariable analysis to adjust for independent covariates (eg, age, sex, and IOP). Patients with an endpoint (n = 59) had a worse rim area rate prior to the endpoint compared to those without (n = 147; median [interquartile range]: -14 [-32, 11] × 10(-3) mm(2)/y and -5 [-14, 5] × 10(-3) mm(2)/y, respectively, P = .02). In univariate analysis, there was no difference in rim area rate before and after the endpoint (median difference [95% CI], 8 (-10, 24) × 10(-3) mm(2)/y), but the muItivariate analysis showed that IOP reduction >2 mm Hg after the endpoint was strongly linked to a reduction in rim area rate decline (8 × 10(-3) mm(2)/y for each additional 1 mm Hg reduction). Patients with a VF endpoint had a median rim area rate that was nearly 3 times worse than those without an endpoint. Lower mean follow-up IOP was independently associated with a slower decline in rim area. Copyright © 2016 Elsevier Inc. All rights reserved.

Open angle glaucoma effects on preattentive visual search efficiency for flicker, motion displacement and orientation pop-out tasks.

PubMed

Loughman, James; Davison, Peter; Flitcroft, Ian

2007-11-01

Preattentive visual search (PAVS) describes rapid and efficient retinal and neural processing capable of immediate target detection in the visual field. Damage to the nerve fibre layer or visual pathway might reduce the efficiency with which the visual system performs such analysis. The purpose of this study was to test the hypothesis that patients with glaucoma are impaired on parallel search tasks, and that this would serve to distinguish glaucoma in early cases. Three groups of observers (glaucoma patients, suspect and normal individuals) were examined, using computer-generated flicker, orientation, and vertical motion displacement targets to assess PAVS efficiency. The task required rapid and accurate localisation of a singularity embedded in a field of 119 homogeneous distractors on either the left or right-hand side of a computer monitor. All subjects also completed a choice reaction time (CRT) task. Independent sample T tests revealed PAVS efficiency to be significantly impaired in the glaucoma group compared with both normal and suspect individuals. Performance was impaired in all types of glaucoma tested. Analysis between normal and suspect individuals revealed a significant difference only for motion displacement response times. Similar analysis using a PAVS/CRT index confirmed the glaucoma findings but also showed statistically significant differences between suspect and normal individuals across all target types. A test of PAVS efficiency appears capable of differentiating early glaucoma from both normal and suspect cases. Analysis incorporating a PAVS/CRT index enhances the diagnostic capacity to differentiate normal from suspect cases.

[Basic and clinical studies of pressure-independent damaging factors of open angle glaucoma].

PubMed

Araie, Makoto

2011-03-01

Pathogenesis of open-angle glaucoma involves both pressure-dependent damaging factors and pressure-independent damaging factors. The high prevalence of open-angle glaucoma with normal pressure (normal-tension glaucoma) in Japan implies that treatment of pressure-independent damaging factors in Japanese open-angle glaucoma patients is of importance. In an attempt to investigate the roles of pressure-independent damaging factors in open-angle glaucoma, we carried out basic and clinical studies and obtained the following results. 1. The rate of deterioration of visual field after trabeculectomy in normal tension glaucoma patients with post-operative intraocular pressure (IOP) of 10 mmHg was found to be -0.25 dB/year of mean deviation (MD), suggesting that contribution of pressure-independent damaging factors to the deterioration of MD in open-angle glaucoma is around -0.25 dB/year of mean deviation (MD). 2. Experiments using isolated purified cultured retinal ganglion cells (RGCs) indicated that calcium-channel blockers and some of antiglaucoma drugs showed neuroprotective effects on RGCs at concentrations of 0.01 microM or higher. 3. In mice, damage to RGCs resulted in secondary degeneration of neurons and activation of glial cells in the lateral geniculate nucleous (LGN) and superior colliculus, and these secondary changes in the central nervous system (CNS) due to RGC damage was partly ameliorated by systemic administration of memantine. 4. Mice experimental high IOP glaucoma models could be established using laser irradiation of the limbal area, and the usefulness of Tonolab in IOP measurements of mice eye was confirmed. 5. Monkey experimental high IOP glaucoma models revealed that in the glaucomatous optic nerve head vaso-constrictive reactions to an alpha-1 agonist was abolished, while vasodilative reaction to a prostaglandin FP receptor agonist was retained. 6. In monkeys with experimental high IOP glaucoma, secondary damage to neurons in the LGN and the glial reaction to it were also found, similar to the mice experiments. In living monkeys the glial reaction in the LGN could be observed by means of positron emission tomography. 7. In the LGN of monkeys with experimental high IOP glaucoma, the M-cell system was preferentially damaged in the early stage, while in the later stages both the M- and P-cell systems were damaged. 8. In a single-instituted prospective double-blinded clinical trial, oral administration of nilvadipine at 4 mg/day, a DHP calcium-channel blocker, was found to significantly retard the visual field progression in normal tension glaucoma patients over 3 years, while significantly increasing the choroidal and optic nerve blood flow by about 35%. 9. A multi-instituted prospective double-blinded clinical trial in normal tension glaucoma patients revealed that the rate of MD deterioration under monotherapy with either topical nipradilol or timolol was around -0.05 dB/year, thought to be considerably slower than -0.25 dB/year, the commonly estimated rate of MD deterioration by pressure-independent damaging factors. The current results indicate the possibility of treatment of pressure-independent damaging factors of open-angle glaucoma in Japanese open-angle glaucoma patients with oral nilvadipine and topical anti-glaucoma agents.

[Results of the ocular hypertension treatment study and the confocal scanning laser ophthalmoscopy ancillary study and evaluation of the heidelberg retina tomograph].

PubMed

Klatt, K; Schmidt, E; Scheuerle, A F

2008-04-01

The Ocular Hypertension Treatment Study (OHTS) has shown that analyzing changes of the optic disc configuration is superior to evaluating visual field findings for the early detection of primary open angle glaucoma. The Confocal Scanning Laser Ophthalmoscopy Ancillary Study (CSLO) is the first study to reveal that certain topographic baseline measurements of the optic disc are significantly associated with the development of primary open angle glaucoma in patients with ocular hypertension. An abnormally increased "mean height contour" value proved to be the individual parameter connected with the highest risk. The reliability of the Moorfields Regression Analysis of certain individual sectors during early detection of a primary angle glaucoma is higher than that of the global measurement. The temporal superior and inferior as well as the nasal inferior sectors have the highest positive predictive values and the largest risks in both univariate and multivariate analysis.

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.

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.

Diagnostic power of optic disc morphology, peripapillary retinal nerve fiber layer thickness, and macular inner retinal layer thickness in glaucoma diagnosis with fourier-domain optical coherence tomography.

PubMed

Huang, Jehn-Yu; Pekmezci, Melike; Mesiwala, Nisreen; Kao, Andrew; Lin, Shan

2011-02-01

To evaluate the capability of the optic disc, peripapillary retinal nerve fiber layer (P-RNFL), macular inner retinal layer (M-IRL) parameters, and their combination obtained by Fourier-domain optical coherent tomography (OCT) in differentiating a glaucoma suspect from perimetric glaucoma. Two hundred and twenty eyes from 220 patients were enrolled in this study. The optic disc morphology, P-RNFL, and M-IRL were assessed by the Fourier-domain OCT (RTVue OCT, Model RT100, Optovue, Fremont, CA). A linear discriminant function was generated by stepwise linear discriminant analysis on the basis of OCT parameters and demographic factors. The diagnostic power of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis. The diagnostic power in the clinically relevant range (specificity ≥ 80%) was presented as the partial area under the ROC curve (partial AROC). The individual OCT parameter with the largest AROC and partial AROC in the high specificity (≥ 80%) range were cup/disc vertical ratio (AROC = 0.854 and partial AROC = 0.142) for the optic disc parameters, average thickness (AROC = 0.919 and partial AROC = 0.147) for P-RNFL parameters, inferior hemisphere thickness (AROC = 0.871 and partial AROC = 0.138) for M-IRL parameters, respectively. The linear discriminant function further enhanced the ability in detecting perimetric glaucoma (AROC = 0.970 and partial AROC = 0.172). Average P-RNFL thickness is the optimal individual OCT parameter to detect perimetric glaucoma. Simultaneous evaluation on disc morphology, P-RNFL, and M-IRL thickness can improve the diagnostic accuracy in diagnosing glaucoma.

Interocular asymmetry of the visual field defects in newly diagnosed normal-tension glaucoma, primary open-angle glaucoma, and chronic angle-closure glaucoma.

PubMed

Huang, Ping; Shi, Yan; Wang, Xin; Liu, Mugen; Zhang, Chun

2014-09-01

To compare the interocular asymmetry of visual field loss in newly diagnosed normal-tension glaucoma (NTG), primary open-angle glaucoma (POAG), and chronic angle-closure glaucoma (CACG) patients. Visual field results of 117 newly diagnosed, treatment-naive glaucoma patients (42 NTG, 38 POAG, and 37 CACG) were studied retrospectively. The following 3 visual field defect parameters were used to evaluate the interocular asymmetry: (1) global indices; (2) local mean deviations (MDs) of 6 predefined visual field areas; and (3) stage designated by glaucoma staging system 2. The differences of the above parameters between the trial eye (the eye with greater MDs) and the fellow eye in each subject were defined as interocular asymmetry scores. Interocular asymmetry of visual field loss was presented in all the 3 groups (all P<0.05). CACG group had greater total MD interocular asymmetry score compared with the NTG and POAG groups (among groups, P=0.008; NTG vs. CACG, P=0.005; POAG vs. CACG, P=0.009). CACG also presented with significantly higher local MD interocular asymmetry scores at central, inferior, and temporal areas compared with those of the POAG group and at inferior area compared with that of NTG group. No significant difference in either total or local MDs was detected between NTG and POAG (all P>0.05). Interocular asymmetry scores of glaucoma staging system 2 had no significant difference among the 3 groups (P=0.068). All CACG, POAG, and NTG groups presented with interocular asymmetric visual field loss at the time of diagnosis. CACG had greater interocular asymmetry compared with NTG and POAG. No significant interocular asymmetry difference was observed between NTG and POAG.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images.

PubMed

Pachiyappan, Arulmozhivarman; Das, Undurti N; Murthy, Tatavarti Vsp; Tatavarti, Rao

2012-06-13

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images

PubMed Central

2012-01-01

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized. PMID:22695250

Automated Detection of Optic Disc in Fundus Images

NASA Astrophysics Data System (ADS)

Burman, R.; Almazroa, A.; Raahemifar, K.; Lakshminarayanan, V.

Optic disc (OD) localization is an important preprocessing step in the automated image detection of fundus image infected with glaucoma. An Interval Type-II fuzzy entropy based thresholding scheme along with Differential Evolution (DE) is applied to determine the location of the OD in the right of left eye retinal fundus image. The algorithm, when applied to 460 fundus images from the MESSIDOR dataset, shows a success rate of 99.07 % for 217 normal images and 95.47 % for 243 pathological images. The mean computational time is 1.709 s for normal images and 1.753 s for pathological images. These results are important for automated detection of glaucoma and for telemedicine purposes.

Is high myopia a risk factor for visual field progression or disk hemorrhage in primary open-angle glaucoma?

PubMed

Nitta, Koji; Sugiyama, Kazuhisa; Wajima, Ryotaro; Tachibana, Gaku

2017-01-01

The purpose of this study was to clarify differences between highly myopic and non-myopic primary open-angle glaucoma (POAG) patients, including normal-tension glaucoma patients. A total of 269 POAG patients were divided into two groups: patients with ≥26.5 mm of axial length (highly myopic group) and patients with <24.0 mm of axial length (non-myopic group). We analyzed 53 highly myopic and 93 non-myopic POAG patients. Age at first visit of the highly myopic group was significantly less than that of the non-myopic group ( P <0.0001). Baseline intraocular pressures (IOPs) showed no significant differences. Follow-up IOPs of the non-myopic group were significantly lower than those of the highly myopic group ( P =0.0009). According to the mean deviation definition of progression, the cumulative probability of non-progression of visual field (VF) loss was significantly greater in the highly myopic group (10-year survival rate, 73.7%±6.8%) than in the non-myopic group (10-year survival rate, 46.3%±5.8%; log-rank test, P =0.0142). The occurrence of disk hemorrhage (DH) in the non-myopic group (1.60±3.04) was significantly greater than that in the highly myopic group (0.93±2.13, P =0.0311). The cumulative probability of DH was significantly lower in the highly myopic group (10-year survival rate, 26.4%±5.4%) than in the non-myopic group (10-year survival rate, 47.2%±6.6%, P =0.0413). Highly myopic POAG is considered as a combination of myopic optic neuropathy and glaucomatous optic neuropathy (GON). If GON is predominant, it has frequent DH and more progressive VF loss. However, when the myopic optic neuropathy is predominant, it has less DH and less progressive VF loss.

Perspectives on biomechanical growth and remodeling mechanisms in glaucoma⋆

PubMed Central

Grytz, Rafael; Girkin, Christopher A.; Libertiaux, Vincent; Downs, J. Crawford

2012-01-01

Glaucoma is a blinding diseases in which damage to the axons results in loss of retinal ganglion cells. Experimental evidence indicates that chronic intraocular pressure elevation initiates axonal insult at the level of the lamina cribrosa. The lamina cribrosa is a porous collagen structure through which the axons pass on their path from the retina to the brain. Recent experimental studies revealed the extensive structural changes of the lamina cribrosa and its surrounding tissues during the development and progression of glaucoma. In this perspective paper we review the experimental evidence for growth and remodeling mechanisms in glaucoma including adaptation of tissue anisotropy, tissue thickening/thinning, tissue elongation/shortening and tissue migration. We discuss the existing predictive computational approaches that try to elucidate the potential biomechanical basis of theses growth and remodeling mechanisms and highlight open questions, challenges, and avenues for further development. PMID:23109748

Is Estrogen a Therapeutic Target for Glaucoma?

PubMed Central

Dewundara, Samantha; Wiggs, Janey; Sullivan, David A.; Pasquale, Louis R.

2016-01-01

Objective To provide an overview of the association between estrogen and glaucoma. Methods A literature synthesis of articles published in peer review journals screened through May 05, 2015 using the PubMed database. Key words used were “estrogen and glaucoma,” “reproductive factors and glaucoma,” “estrogen, nitric oxide and eye.” Forty three journal articles were included. Results Markers for lifetime estrogen exposure have been measured by several studies and show that the age of menarche onset, oral contraceptive (OC) use, bilateral oophorectomy, age of menopause onset and duration between menarche to menopause are associated with primary open angle (POAG) risk. The Blue Mountain Eye Study found a significantly increased POAG risk with later (>13 years) compared with earlier (≤12 years) age of menarche. Nurses’ Health Study (NHS) investigators found that OC use of greater than 5 years was associated with a 25% increased risk of POAG. The Mayo Clinic Cohort Study of Oophorectomy and Aging found that women who underwent bilateral oophorectomy before age 43 had an increased risk of glaucoma. The Rotterdam Study found that women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma (2.6-fold increased risk) while the NHS showed a reduced risk of POAG among women older than 65 who entered menopause after age ≥ 54 years. Increased estrogen states may confer a reduced risk of glaucoma or glaucoma related traits such as reduced intraocular pressure (IOP). Pregnancy, a hyperestrogenemic state, is associated with decreased IOP during the third trimester. Though the role of post-menopausal hormone (PMH) use in the reduction of IOP is not fully conclusive, PMH use may reduce the risk of POAG. From a genetic epidemiologic perspective, estrogen metabolic pathway single nucleotide polymorphisms (SNPs) were associated with POAG in women and polymorphisms in endothelial nitric oxide synthase, a gene receptive to estrogen regulation, are associated with glaucoma. Conclusions Increasing evidence suggests that lifetime exposure to estrogen may alter the pathogenesis of glaucoma. Estrogen exposure may have a neuroprotective effect on the progression of POAG but further studies need to confirm this finding. The role of sex-specific preventive and therapeutic treatment may be on the horizon. PMID:26959139

Vection in patients with glaucoma.

PubMed

Tarita-Nistor, Luminita; Hadavi, Shahriar; Steinbach, Martin J; Markowitz, Samuel N; González, Esther G

2014-05-01

Large moving scenes can induce a sensation of self-motion in stationary observers. This illusion is called "vection." Glaucoma progressively affects the functioning of peripheral vision, which plays an important role in inducing vection. It is still not known whether vection can be induced in these patients and, if it can, whether the interaction between visual and vestibular inputs is solved appropriately. The aim of this study was to investigate vection responses in patients with mild to moderate open-angle glaucoma. Fifteen patients with mild to moderate glaucoma and 15 age-matched controls were exposed to a random-dot pattern at a short viewing distance and in a dark room. The pattern was projected on a large screen and rotated clockwise with an angular speed of 45 degrees per second to induce a sensation of self-rotation. Vection latency, vection duration, and objective and subjective measures of tilt were obtained in three viewing conditions (binocular, and monocular with each eye). Each condition lasted 2 minutes. Patients with glaucoma had longer vection latencies (p = 0.005) than, but the same vection duration as, age-matched controls. Viewing condition did not affect vection responses for either group. The control group estimated the tilt angle as being significantly larger than the actual maximum tilt angle measured with the tilt sensor (p = 0.038). There was no relationship between vection measures and visual field sensitivity for the glaucoma group. These findings suggest that, despite an altered visual input that delays vection, the neural responses involved in canceling the illusion of self-motion remain intact in patients with mild peripheral visual field loss.

Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities.

PubMed

Teotia, Pooja; Van Hook, Matthew J; Wichman, Christopher S; Allingham, R Rand; Hauser, Michael A; Ahmad, Iqbal

2017-11-01

Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252. © 2017 AlphaMed Press.

Exclusion of chromosome 1q21-q31 from linkage to three pedigrees affected by the pigment-dispersion syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paglinauan, C.; Haines, J.L.; Del Bono, E.A.

1995-05-01

The pigment-dispersion syndrome is a form of open-angle glaucoma that usually affects individuals in the first 3 decades of life. In addition to the typical optic-nerve degeneration seen in all types of glaucoma, the pigment-dispersion syndrome is characterized by distinctive clinical features including the deposition of pigment granules from the iris epithelium on a variety of ocular structures including the trabecular meshwork. Frequently this disorder affects young myopic individuals. In the early stages of the disease, affected individuals may have clinical evidence of dispersed pigment without an associated elevation of intraocular pressure and optic-nerve degeneration. However, as the disease processmore » progresses, many affected individuals ({approximately}50%) will develop elevated intraocular pressure and degeneration of the optic nerve, causing a permanent loss of sight. The pigment-dispersion syndrome shares several clinical features with the form of autosomal dominant juvenile open-angle glaucoma that recently has been mapped to the 1q21-q31 region of chromosome 1. Our results indicate that the pigment-dispersion syndrome, a form of glaucoma that may also affect the juvenile population, is genetically unrelated to the autosomal dominant form of juvenile glaucoma caused by a defect in a gene located in the 1q21-q31 region of chromosome 1. 15 refs., 2 figs., 1 tab.« less

Biomechanical aspects of axonal damage in glaucoma: a brief review1

PubMed Central

Stowell, Cheri; Burgoyne, Claude; Tamm, Ernst R.; Ethier, C. Ross

2017-01-01

The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor. PMID:28223180

Demographic features of subjects with congenital glaucoma

PubMed Central

Tamçelik, Nevbahar; Atalay, Eray; Bolukbasi, Selim; Çapar, Olgu; Ozkok, Ahmet

2014-01-01

Context: Congenital glaucoma is a potentially blinding ocular disease of the childhood. Identification of the possible associated risk factors and may be helpful for prevention or early detection of this public health problem. Aims: To demonstrate the demographic features of congenital glaucoma subjects. Setting and Design: The charts of congenital glaucoma patients referred to Tamcelik Glaucoma Center were retrospectively reviewed through the dates of 2000 and 2013. Materials and Methods: Analyzed data included diagnosis, age at first presentation, symptoms at first presentation, laterality of the disease, sex, presence of consanguinity, family history of congenital glaucoma, maturity of the fetus at delivery, and maternal age at conception. Statistical Analysis Used: Statistical Package for Social Sciences (SPSS) version 19.0 by IBM (SPSS Inc, Chicago, Illinois, USA) was used to compare the mean of continuous variables with Student's t-test and analysis of variance (ANOVA) and χ2 test was used to test differences in proportions of categorical variables. Results: The data of 600 eyes of 311 patients were analyzed. The distribution of primary and secondary congenital glaucoma among the patients were 63.3% (n = 197) and 36.7% (n = 114), respectively. Of the 311 patients, 57.2% (n = 178) were male and 42.8% (n = 133) were female. The overall frequency of bilateral disease was 92.3% (n = 287). Overall rate of consanguinity and positive family history was 45.3% (n = 141) and 21.2% (n = 66), respectively. Conclusions: Bilateral disease in this study was more common than previously reported studies. Positive family history was more frequent in primary congenital glaucoma although not statistically significant. PMID:24881602

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.

Comparison between visual field defect in pigmentary glaucoma and primary open-angle glaucoma.

PubMed

Nilforushan, Naveed; Yadgari, Maryam; Jazayeri, Anisalsadat

2016-10-01

To compare visual field defect patterns between pigmentary glaucoma and primary open-angle glaucoma. Retrospective, comparative study. Patients with diagnosis of primary open-angle glaucoma (POAG) and pigmentary glaucoma (PG) in mild to moderate stages were enrolled in this study. Each of the 52 point locations in total and pattern deviation plot (excluding 2 points adjacent to blind spot) of 24-2 Humphrey visual field as well as six predetermined sectors were compared using SPSS software version 20. Comparisons between 2 groups were performed with the Student t test for continuous variables and the Chi-square test for categorical variables. Thirty-eight eyes of 24 patients with a mean age of 66.26 ± 11 years (range 48-81 years) in the POAG group and 36 eyes of 22 patients with a mean age of 50.52 ± 11 years (range 36-69 years) in the PG group were studied. (P = 0.00). More deviation was detected in points 1, 3, 4, and 32 in total deviation (P = 0.03, P = 0.015, P = 0.018, P = 0.023) and in points 3, 4, and 32 in pattern deviation (P = 0.015, P = 0.049, P = 0.030) in the POAG group, which are the temporal parts of the field. It seems that the temporal area of the visual field in primary open-angle glaucoma is more susceptible to damage in comparison with pigmentary glaucoma.

The Muranga Teleophthalmology Study: Comparison of Virtual (Teleglaucoma) with in-Person Clinical Assessment to Diagnose Glaucoma.

PubMed

Kiage, Dan; Kherani, Irfan N; Gichuhi, Stephen; Damji, Karim F; Nyenze, Muindi

2013-01-01

While the effectiveness of teleophthalmology is generally accepted, its ability to diagnose glaucomatous eye disease remains relatively unknown. This study aimed to compare a web-based teleophthalmology assessment with clinical slit lamp examination to screen for glaucoma among diabetics in a rural African district. Three hundred and nine diabetic patients underwent both the clinical slit lamp examination by a comprehensive ophthalmologist and teleglaucoma (TG) assessment by a glaucoma subspecialist. Both assessments were compared for any focal glaucoma damage; for TG, the quality of photographs was assessed, and vertical cup-to-disk ratio (VCDR) was calculated in a semi-automated manner. In patients with VCDR > 0.7, the diagnostic precision of the Frequency Doubling Technology (FDT) C-20 screening program was assessed. Of 309 TG assessment photos, 74 (24%) were deemed unreadable due to media opacities, patient cooperation, and unsatisfactory photographic technique. While the identification of individual optic nerve factors showed either fair or moderate agreement, the ability to diagnose glaucoma based on the overall assessment showed moderate agreement (Kappa [κ] statistic 0.55% and 95% confidence interval [CI]: 0.48-0.62). The use of FDT to detect glaucoma in the presence of disc damage (VCDR > 0.7) showed substantial agreement (κ statistic of 0.84 and 95% CI 0.79-0.90). A positive TG diagnosis of glaucoma carried a 77.5% positive predictive value, and a negative TG diagnosis carried an 82.2% negative predicative value relative to the clinical slit lamp examination. There was moderate agreement between the ability to diagnose glaucoma using TG relative to clinical slit lamp examination. Poor quality photographs can severely limit the ability of TG assessment to diagnose optic nerve damage and glaucoma. Although further work and validation is needed, the TG approach provides a novel, and promising method to diagnose glaucoma, a major cause of ocular morbidity throughout the world.

The Muranga Teleophthalmology Study: Comparison of Virtual (Teleglaucoma) with in-Person Clinical Assessment to Diagnose Glaucoma

PubMed Central

Kiage, Dan; Kherani, Irfan N.; Gichuhi, Stephen; Damji, Karim F.; Nyenze, Muindi

2013-01-01

Purpose: While the effectiveness of teleophthalmology is generally accepted, its ability to diagnose glaucomatous eye disease remains relatively unknown. This study aimed to compare a web-based teleophthalmology assessment with clinical slit lamp examination to screen for glaucoma among diabetics in a rural African district. Materials and Methods: Three hundred and nine diabetic patients underwent both the clinical slit lamp examination by a comprehensive ophthalmologist and teleglaucoma (TG) assessment by a glaucoma subspecialist. Both assessments were compared for any focal glaucoma damage; for TG, the quality of photographs was assessed, and vertical cup-to-disk ratio (VCDR) was calculated in a semi-automated manner. In patients with VCDR > 0.7, the diagnostic precision of the Frequency Doubling Technology (FDT) C-20 screening program was assessed. Results: Of 309 TG assessment photos, 74 (24%) were deemed unreadable due to media opacities, patient cooperation, and unsatisfactory photographic technique. While the identification of individual optic nerve factors showed either fair or moderate agreement, the ability to diagnose glaucoma based on the overall assessment showed moderate agreement (Kappa [κ] statistic 0.55% and 95% confidence interval [CI]: 0.48-0.62). The use of FDT to detect glaucoma in the presence of disc damage (VCDR > 0.7) showed substantial agreement (κ statistic of 0.84 and 95% CI 0.79-0.90). A positive TG diagnosis of glaucoma carried a 77.5% positive predictive value, and a negative TG diagnosis carried an 82.2% negative predicative value relative to the clinical slit lamp examination. Conclusion: There was moderate agreement between the ability to diagnose glaucoma using TG relative to clinical slit lamp examination. Poor quality photographs can severely limit the ability of TG assessment to diagnose optic nerve damage and glaucoma. Although further work and validation is needed, the TG approach provides a novel, and promising method to diagnose glaucoma, a major cause of ocular morbidity throughout the world. PMID:23741134

Detection of Functional Change Using Cluster Trend Analysis in Glaucoma.

PubMed

Gardiner, Stuart K; Mansberger, Steven L; Demirel, Shaban

2017-05-01

Global analyses using mean deviation (MD) assess visual field progression, but can miss localized changes. Pointwise analyses are more sensitive to localized progression, but more variable so require confirmation. This study assessed whether cluster trend analysis, averaging information across subsets of locations, could improve progression detection. A total of 133 test-retest eyes were tested 7 to 10 times. Rates of change and P values were calculated for possible re-orderings of these series to generate global analysis ("MD worsening faster than x dB/y with P < y"), pointwise and cluster analyses ("n locations [or clusters] worsening faster than x dB/y with P < y") with specificity exactly 95%. These criteria were applied to 505 eyes tested over a mean of 10.5 years, to find how soon each detected "deterioration," and compared using survival models. This was repeated including two subsequent visual fields to determine whether "deterioration" was confirmed. The best global criterion detected deterioration in 25% of eyes in 5.0 years (95% confidence interval [CI], 4.7-5.3 years), compared with 4.8 years (95% CI, 4.2-5.1) for the best cluster analysis criterion, and 4.1 years (95% CI, 4.0-4.5) for the best pointwise criterion. However, for pointwise analysis, only 38% of these changes were confirmed, compared with 61% for clusters and 76% for MD. The time until 25% of eyes showed subsequently confirmed deterioration was 6.3 years (95% CI, 6.0-7.2) for global, 6.3 years (95% CI, 6.0-7.0) for pointwise, and 6.0 years (95% CI, 5.3-6.6) for cluster analyses. Although the specificity is still suboptimal, cluster trend analysis detects subsequently confirmed deterioration sooner than either global or pointwise analyses.

A case report of progressive obstruction of Ex-PRESS miniature glaucoma shunt after transient flat anterior chamber and treatment using Nd:YAG laser.

PubMed

Tanito, Masaki; Sano, Ichiya; Ohira, Akihiro

2015-01-08

We report a case of Ex-PRESS miniature glaucoma shunt obstruction resulting from progressive iris synechial formation after transient anterior chamber shallowing. A 68-year-old woman with pseudoexfoliation glaucoma in her right eye underwent filtration surgery with implantation of the Ex-PPESS shunt (model P-50, Alcon Japan, Tokyo, Japan) in combination with intra-surgical 0.04% mitomycin C use. After the anterior chamber injection of viscoelastic material and 100% sulfur hexafluoride gas for treatment of early postoperative over filtration, the intraocular pressure (IOP) was controlled between 9 and 12 mmHg. On postoperative day 121, gonioscopy showed that synechial formation around the shunt obstructed the axial port leaving the relief port opened. On postoperative day 274, the intraocular pressure increased to 40 mmHg and synechiae obstructed both the axial and relief ports. Dispersion of iris tissue by neodymium:yttrium-aluminium-garnet (Nd:YAG) laser (2 mJ, one shot to each port) opened both ports and immediately lowered the IOP, leaving peripheral anterior synechiae around the shunt. Up to postoperative day 400, the IOP was controlled between 13 and 15 mmHg, and the cystic bleb was maintained. The synechiae formed gradually extends around the shunt's shaft and can result in later external obstruction of the relief port. The current case requires further follow-up since synechiae remaining around the shaft can cause future obstruction. We emphasize the fact that, if the iris synechiae to the shunt once formed, it can progress and obstruct the shunt ports later.

Ametropia, retinal anatomy, and OCT abnormality patterns in glaucoma. 2. Impacts of optic nerve head parameters

NASA Astrophysics Data System (ADS)

Baniasadi, Neda; Wang, Mengyu; Wang, Hui; Jin, Qingying; Elze, Tobias

2017-12-01

Clinicians use retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) as an adjunct to glaucoma diagnosis. Ametropia is accompanied by changes to the optic nerve head (ONH), which may affect how OCT machines mark RNFLT measurements as abnormal. These changes in abnormality patterns may bias glaucoma diagnosis. Here, we investigate the relationship between OCT abnormality patterns and the following ONH-related and ametropia-associated parameters on 421 eyes of glaucoma patients: optic disc tilt and torsion, central retinal vessel trunk location (CRVTL), and nasal and temporal retinal curvature adjacent to ONH, quantified as nasal/temporal slopes of the inner limiting membrane. We applied multivariate logistic regression with abnormality marks as regressands to 40,401 locations of the peripapillary region and generated spatial maps of locations of false positive/negative abnormality marks independent of glaucoma severity. Effects of torsion and temporal slope were negligible. The effect of tilt could be explained by covariation with ametropia. For CRVTL/nasal slope, abnormality pattern shifts at 7.2%/23.5% of the peripapillary region were detected, respectively, independent of glaucoma severity and ametropia. Therefore, CRVTL and nasal curvature should be included in OCT RNFLT norms. Our spatial location maps may aid clinicians to improve diagnostic accuracy.

Comparative evaluation of RetCam vs. gonioscopy images in congenital glaucoma.

PubMed

Azad, Raj V; Chandra, Parijat; Chandra, Anuradha; Gupta, Aparna; Gupta, Viney; Sihota, Ramanjit

2014-02-01

To compare clarity, exposure and quality of anterior chamber angle visualization in congenital glaucoma patients, using RetCam and indirect gonioscopy images. Cross-sectional study Participants. Congenital glaucoma patients over age of 5 years. A prospective consecutive pilot study was done in congenital glaucoma patients who were older than 5 years. Methods used are indirect gonioscopy and RetCam imaging. Clarity of the image, extent of angle visible and details of angle structures seen were graded for both methods, on digitally recorded images, in each eye, by two masked observers. Image clarity, interobserver agreement. 40 eyes of 25 congenital glaucoma patients were studied. RetCam image had excellent clarity in 77.5% of patients versus 47.5% by gonioscopy. The extent of angle seen was similar by both methods. Agreement between RetCam and gonioscopy images regarding details of angle structures was 72.50% by observer 1 and 65.00% by observer 2. There was good agreement between RetCam and indirect gonioscopy images in detecting angle structures of congenital glaucoma patients. However, RetCam provided greater clarity, with better quality, and higher magnification images. RetCam can be a useful alternative to gonioscopy in infants and small children without the need for general anesthesia.

Comparative evaluation of RetCam vs. gonioscopy images in congenital glaucoma

PubMed Central

Azad, Raj V; Chandra, Parijat; Chandra, Anuradha; Gupta, Aparna; Gupta, Viney; Sihota, Ramanjit

2014-01-01

Purpose: To compare clarity, exposure and quality of anterior chamber angle visualization in congenital glaucoma patients, using RetCam and indirect gonioscopy images. Design: Cross-sectional study Participants. Congenital glaucoma patients over age of 5 years. Materials and Methods: A prospective consecutive pilot study was done in congenital glaucoma patients who were older than 5 years. Methods used are indirect gonioscopy and RetCam imaging. Clarity of the image, extent of angle visible and details of angle structures seen were graded for both methods, on digitally recorded images, in each eye, by two masked observers. Outcome Measures: Image clarity, interobserver agreement. Results: 40 eyes of 25 congenital glaucoma patients were studied. RetCam image had excellent clarity in 77.5% of patients versus 47.5% by gonioscopy. The extent of angle seen was similar by both methods. Agreement between RetCam and gonioscopy images regarding details of angle structures was 72.50% by observer 1 and 65.00% by observer 2. Conclusions: There was good agreement between RetCam and indirect gonioscopy images in detecting angle structures of congenital glaucoma patients. However, RetCam provided greater clarity, with better quality, and higher magnification images. RetCam can be a useful alternative to gonioscopy in infants and small children without the need for general anesthesia. PMID:24008788

Collagen and collagen-chondroitin sulfate scaffolds with uniaxially aligned pores for the biomimetic, three dimensional culture of trabecular meshwork cells.

PubMed

Osmond, Matthew; Bernier, Sarah M; Pantcheva, Mina B; Krebs, Melissa D

2017-04-01

Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated with glaucoma is due to increased aqueous humor outflow resistance, primarily through the trabecular meshwork (TM) of the eye. Current in vitro models of the trabecular meshwork are oversimplified and do not capture the organized and complex three-dimensional nature of this tissue that consists primarily of collagen and glycoasaminoglycans. In this work, collagen and collagen-chondroitin sulfate (CS) scaffolds were fabricated via unidirectional freezing and lyophilization to induce the formation of aligned pores. Scaffolds were characterized by scanning electron microscopy, dynamic mechanical analysis, and a chondroitin sulfate quantification assay. Scaffold characterization confirmed the formation of aligned pores, and also that the CS was leaching out of the scaffolds over time. Primary porcine trabecular meshwork (TM) cells were seeded onto the surface of scaffolds and their gene expression, proliferation, viability, migration into the scaffolds, and morphology were examined. The TM cells were viable and proliferated 2 weeks after seeding. The cells migrated down into the internal scaffold structure and their morphology reflected the topography and alignment of the scaffold structure. This work is a promising step toward the development of a three dimensional in vitro model of the TM that can be used for testing of glaucoma pharmacological agents in future experimentation and to better our understanding of the trabecular meshwork and its complex physiology. Biotechnol. Bioeng. 2017;114: 915-923. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Glaucoma: Biological Trabecular and Neuroretinal Pathology with Perspectives of Therapy Innovation and Preventive Diagnosis

PubMed Central

Nuzzi, Raffaele; Tridico, Federico

2017-01-01

Glaucoma is a common degenerative disease affecting retinal ganglion cells (RGC) and optic nerve axons, with progressive and chronic course. It is one of the most important reasons of social blindness in industrialized countries. Glaucoma can lead to the development of irreversible visual field loss, if not treated. Diagnosis may be difficult due to lack of symptoms in early stages of disease. In many cases, when patients arrive at clinical evaluation, a severe neuronal damage may have already occurred. In recent years, newer perspective in glaucoma treatment have emerged. The current research is focusing on finding newer drugs and associations or better delivery systems in order to improve the pharmacological treatment and patient compliance. Moreover, the application of various stem cell types with restorative and neuroprotective intent may be found appealing (intravitreal autologous cellular therapy). Advances are made also in terms of parasurgical treatment, characterized by various laser types and techniques. Moreover, recent research has led to the development of central and peripheral retinal rehabilitation (featuring residing cells reactivation and replacement of defective elements), as well as innovations in diagnosis through more specific and refined methods and inexpensive tests. PMID:28928631

Preserve the (intraocular) environment: the importance of maintaining normal oxygen gradients in the eye.

PubMed

Beebe, David C; Shui, Ying-Bo; Siegfried, Carla J; Holekamp, Nancy M; Bai, Fang

2014-05-01

Oxygen levels in the eye are generally low and tightly regulated. Oxygen enters the eye largely by diffusion from retinal arterioles and through the cornea. In intact eyes, oxygen from the retinal arterioles diffuses into the vitreous body. There is a decreasing oxygen gradient from the retina to the lens, established by oxygen consumption by ascorbate in the vitreous fluid and lens metabolism. Age-related degeneration of the vitreous body or removal during vitrectomy exposes the posterior of the lens to increased oxygen, causing nuclear sclerotic cataracts. Lowering oxygen in the vitreous, as occurs in patients with ischemic diabetic retinopathy, protects against cataracts after vitrectomy. Vitrectomy and cataract surgery increase oxygen levels at the trabecular meshwork and with it the risk of open angle glaucoma. Two additional risk factors for glaucoma, African heritage and having a thinner cornea, are also associated with increased oxygen in the anterior chamber angle. Preservation of the vitreous body and the lens, two important oxygen consumers, would protect against nuclear sclerotic cataracts and open angle glaucoma. Delaying removal of the lens for as long as possible after vitrectomy would be an important step in delaying ocular hypertension and glaucoma progression.

Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency.

PubMed

Kulkarni, Sadhana V; Damji, Karim F; Buys, Yvonne M

2008-02-02

Primary open angle glaucoma is a chronic optic neuropathy often requiring lifelong treatment. Patient compliance, adherence and persistence with therapy play a vital role in improved outcomes by reducing morbidity and the economic consequences that are associated with disease progression. A literature review including searches of The Cochrane Library, MEDLINE, PubMed, conference proceedings, and bibliographies of identified articles reveals the enormous public health burden in various populations due to the impact of glaucoma associated visual impairment on the overall quality of life eg, fear of blindness, inability to work in certain occupations, driving restrictions, motor vehicle accidents, falls, and general health status. Providing specific definitions for the frequently misunderstood terms "compliance, persistence and adherence" with reference to medication use is central not only for monitoring patients' drug dosing histories and clinical outcomes but also for subsequent research. In this review article, a summary of the advantages/disadvantages including cost-effectiveness of various medical approaches to glaucoma treatment, techniques employed for measuring patient compliance and actual patient preferences for therapy are outlined. We conclude by identifying the key barriers to ongoing treatment and suggest some best practices to enhance compliance and persistence.

Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency

PubMed Central

Kulkarni, Sadhana V; Damji, Karim F; Buys, Yvonne M

2008-01-01

Primary open angle glaucoma is a chronic optic neuropathy often requiring lifelong treatment. Patient compliance, adherence and persistence with therapy play a vital role in improved outcomes by reducing morbidity and the economic consequences that are associated with disease progression. A literature review including searches of The Cochrane Library, MEDLINE, PubMed, conference proceedings, and bibliographies of identified articles reveals the enormous public health burden in various populations due to the impact of glaucoma associated visual impairment on the overall quality of life eg, fear of blindness, inability to work in certain occupations, driving restrictions, motor vehicle accidents, falls, and general health status. Providing specific definitions for the frequently misunderstood terms “compliance, persistence and adherence” with reference to medication use is central not only for monitoring patients’ drug dosing histories and clinical outcomes but also for subsequent research. In this review article, a summary of the advantages/disadvantages including cost-effectiveness of various medical approaches to glaucoma treatment, techniques employed for measuring patient compliance and actual patient preferences for therapy are outlined. We conclude by identifying the key barriers to ongoing treatment and suggest some best practices to enhance compliance and persistence. PMID:19920977

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

Assessment of contrast sensitivity by Spaeth Richman Contrast Sensitivity Test and Pelli Robson Chart Test in patients with varying severity of glaucoma.

PubMed

Thakur, Sahil; Ichhpujani, Parul; Kumar, Suresh; Kaur, Ravneet; Sood, Sunandan

2018-05-14

This study was designed to assess the efficacy, reliability and repeatability of SPARCS (Spaeth Richman Contrast Sensitivity Test) as compared to the conventional Pelli Robson Chart Test for the assessment of contrast sensitivity in patients with glaucoma. We evaluated 135 eyes of 135 patients who were age and sex matched into three groups (controls, disc suspects and glaucoma) of 45 patients each. The glaucoma subgroup was further divided into subgroups of mild, moderate and severe based on the visual field damage. There was a strong positive correlation between Pelli Robson scores and SPARCS scores (S = 0.807, P < 0.001). Intraclass correlation coefficient (ICC) for Pelli Robson Test was 0.952 and 0.988 for SPARCS. The coefficient of repeatability (COR) for mean SPARCS was 5.65%, while COR of Pelli Robson Test was 12.44%. SPARCS was found to have better repeatability than Pelli Robson Test based on COR values. Pelli Robson score had a sensitivity of 80% and a specificity of 65.6% for detecting glaucoma patients as compared to 84.4% and 70%, respectively, for SPARCS scores. SPARCS is a better alternative to conventional Pelli Robson Chart Test for assessment of contrast sensitivity in patients with glaucoma. Being independent of the effects of literacy and educational status, it offers a universal way to measure contrast sensitivity. It can also be reliably used in patients with varying severity of glaucoma.

Structural characteristics of the acquired optic disc pit and the rate of progressive retinal nerve fiber layer thinning in primary open-angle glaucoma.

PubMed

Lee, Seung Hyen; Lee, Eun Ji; Kim, Tae-Woo

2015-10-01

The optic disc pit (ODP) has been considered a region of localized susceptibility to the damage of glaucoma. To determine whether the rate of retinal nerve fiber layer (RNFL) thinning differs according to the presence and structural characteristics of an ODP in primary open-angle glaucoma. We performed a prospective case-control study that included 163 eyes with primary open-angle glaucoma (83 with an ODP and 80 without an ODP) from Glaucoma Clinic of Seoul National University Bundang Hospital. Participants were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2012, through May 31, 2014. Mean (SD) follow-up was 3.32 (0.49) years (through May 31, 2014). Optic nerve heads underwent swept-source optical coherence tomography (OCT) to determine the presence of focal lamina cribrosa alteration and its structural characteristics. Eyes with and without photographic ODPs and corresponding microscopic laminar alterations were assigned to the ODP and non-ODP groups, respectively. The rates of progressive thinning of global and 6 sectoral spectral-domain OCT RNFL thicknesses were determined by linear regression and compared between the 2 groups. We used a general linear model to determine the factors associated with the rate of RNFL thinning; data obtained from September 21, 2009, through May 31, 2014, were used to calculate the rate of RNFL thinning. The relationship between the presence and structural characteristics of ODPs and the rate of progressive OCT RNFL thinning. Thinning of the RNFL was faster in the ODP group than in the non-ODP group in the global (mean [SD], -1.44 [1.31] vs -0.93 [1.10] [95% CI, -0.97 to -0.19] μm/y; P = .008), temporoinferior (mean [SD], -4.17 [4.15] vs -1.97 [3.26] [95% CI, -3.36 to -1.04] μm/y; P < .001), and temporal (mean [SD], -1.92 [2.62] vs -0.89 [1.62] [95% CI, -1.70 to -0.35] μm/y; P = .003) sectors. The rate of RNFL thinning was maximum in the temporoinferior sector (mean [SD], -4.17 [4.15] μm/y) and corresponded to the frequency distribution of ODPs. Regression analysis revealed that faster global RNFL thinning was related to a higher untreated intraocular pressure (β = -0.07; 95% CI, -0.11 to -0.03; P = .001), episodes of disc hemorrhage (β = -0.74; 95% CI, -1.79 to 0.31; P = .003), the presence of β-zone parapapillary atrophy (β = -0.47; 95% CI, -1.13 to 0.20; P = .02), and the presence of ODPs (β = -0.41; 95% CI, -1.14 to 0.32; P = .02). The maximum rate of RNFL thinning was associated with higher untreated intraocular pressure (β = -0.24; 95% CI, -0.35 to -0.13; P < .001), disc hemorrhage (β = -1.54; 95% CI, -2.88 to -0.19; P < .001), and the presence (β = -1.04; 95% CI, -2.14 to 0.07; P = .004), far-peripheral location (β = -1.75; 95% CI, -3.05 to -0.46; P = .008), and partial-thickness depth (β = -1.45; 95% CI, -2.75 to -0.16; P = .03) of an ODP. The presence and structural characteristics of ODPs were associated with global and focal progression as assessed by the rate of OCT RNFL thinning. The assessment of ODP structure using swept-source OCT may help to predict the location of future progression.

Comprehensive eye evaluation algorithm

NASA Astrophysics Data System (ADS)

Agurto, C.; Nemeth, S.; Zamora, G.; Vahtel, M.; Soliz, P.; Barriga, S.

2016-03-01

In recent years, several research groups have developed automatic algorithms to detect diabetic retinopathy (DR) in individuals with diabetes (DM), using digital retinal images. Studies have indicated that diabetics have 1.5 times the annual risk of developing primary open angle glaucoma (POAG) as do people without DM. Moreover, DM patients have 1.8 times the risk for age-related macular degeneration (AMD). Although numerous investigators are developing automatic DR detection algorithms, there have been few successful efforts to create an automatic algorithm that can detect other ocular diseases, such as POAG and AMD. Consequently, our aim in the current study was to develop a comprehensive eye evaluation algorithm that not only detects DR in retinal images, but also automatically identifies glaucoma suspects and AMD by integrating other personal medical information with the retinal features. The proposed system is fully automatic and provides the likelihood of each of the three eye disease. The system was evaluated in two datasets of 104 and 88 diabetic cases. For each eye, we used two non-mydriatic digital color fundus photographs (macula and optic disc centered) and, when available, information about age, duration of diabetes, cataracts, hypertension, gender, and laboratory data. Our results show that the combination of multimodal features can increase the AUC by up to 5%, 7%, and 8% in the detection of AMD, DR, and glaucoma respectively. Marked improvement was achieved when laboratory results were combined with retinal image features.

Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension.

PubMed

Gugleta, Konstantin

2010-06-01

Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension. An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review. A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years. For the first time one study could demonstrate that an improvement in ocular blood flow in the long run results in preservation of visual field in glaucoma patients. Dorzolamide, combined with the beta-blocker timolol, seems to be superior in this regard to brinzolamide plus timolol.

New Normative Database of Inner Macular Layer Thickness Measured by Spectralis OCT Used as Reference Standard for Glaucoma Detection.

PubMed

Nieves-Moreno, María; Martínez-de-la-Casa, José M; Bambo, María P; Morales-Fernández, Laura; Van Keer, Karel; Vandewalle, Evelien; Stalmans, Ingeborg; García-Feijoó, Julián

2018-02-01

This study examines the capacity to detect glaucoma of inner macular layer thickness measured by spectral-domain optical coherence tomography (SD-OCT) using a new normative database as the reference standard. Participants ( N = 148) were recruited from Leuven (Belgium) and Zaragoza (Spain): 74 patients with early/moderate glaucoma and 74 age-matched healthy controls. One eye was randomly selected for a macular scan using the Spectralis SD-OCT. The variables measured with the instrument's segmentation software were: macular nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) volume and thickness along with circumpapillary RNFL thickness (cpRNFL). The new normative database of macular variables was used to define the cutoff of normality as the fifth percentile by age group. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of each macular measurement and of cpRNFL were used to distinguish between patients and controls. Overall sensitivity and specificity to detect early-moderate glaucoma were 42.2% and 88.9% for mRNFL, 42.4% and 95.6% for GCL, 42.2% and 94.5% for IPL, and 53% and 94.6% for RNFL, respectively. The best macular variable to discriminate between the two groups of subjects was outer temporal GCL thickness as indicated by an AUROC of 0.903. This variable performed similarly to mean cpRNFL thickness (AUROC = 0.845; P = 0.29). Using our normative database as reference, the diagnostic power of inner macular layer thickness proved comparable to that of peripapillary RNFL thickness. Spectralis SD-OCT, cpRNFL thickness, and individual macular inner layer thicknesses show comparable diagnostic capacity for glaucoma and RNFL, GCL, and IPL thickness may be useful as an alternative diagnostic test when the measure of cpRNFL shows artifacts.

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.

The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population

PubMed Central

Wahl, Jochen; Barleon, Lorenz; Morfeld, Peter; Lichtmeß, Andrea; Haas-Brähler, Sibylle; Pfeiffer, Norbert

2016-01-01

Purpose To develop an expert system for glaucoma screening in a working population based on a human expert procedure using images of optic nerve head (ONH), visual field (frequency doubling technology, FDT) and intraocular pressure (IOP). Methods 4167 of 13037 (32%) employees between 40 and 65 years of Evonik Industries were screened. An experienced glaucoma expert (JW) assessed papilla parameters and evaluated all individual screening results. His classification into “no glaucoma”, “possible glaucoma” and “probable glaucoma” was defined as “gold standard”. A screening model was developed which was tested versus the gold-standard. This model took into account the assessment of the ONH. Values and relationships of CDR and IOP and the FDT were considered additionally and a glaucoma score was generated. The structure of the screening model was specified a priori whereas values of the parameters were chosen post-hoc to optimize sensitivity and specificity of the algorithm. Simple screening models based on IOP and / or FDT were investigated for comparison. Results 111 persons (2.66%) were classified as glaucoma suspects, thereof 13 (0.31%) as probable and 98 (2.35%) as possible glaucoma suspects by the expert. Re-evaluation by the screening model revealed a sensitivity of 83.8% and a specificity of 99.6% for all glaucoma suspects. The positive predictive value of the model was 80.2%, the negative predictive value 99.6%. Simple screening models showed insufficient diagnostic accuracy. Conclusion Adjustment of ONH and symmetry parameters with respect to excavation and IOP in an expert system produced sufficiently satisfying diagnostic accuracy. This screening model seems to be applicable in such a working population with relatively low age and low glaucoma prevalence. Different experts should validate the model in different populations. PMID:27479301

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.

On-road Driving Performance of Patients with Bilateral Moderate and Advanced Glaucoma

PubMed Central

Bhorade, Anjali M.; Yom, Victoria H.; Barco, Peggy; Wilson, Bradley; Gordon, Mae; Carr, David

2017-01-01

Purpose To compare on-road driving performance of patients with moderate or advanced glaucoma to controls and evaluate factors associated with unsafe driving. Design Case-control pilot study. Methods A consecutive sample of 21 patients with bilateral moderate or advanced glaucoma from Washington University, St. Louis, MO and 38 community-dwelling controls were enrolled. Participants, ages 55–90 years, underwent a comprehensive clinical evaluation by a trained occupational therapist and an on-road driving evaluation by a masked driver rehabilitation specialist. Overall driving performance of pass vs. marginal/fail and number of wheel and/or brake interventions were recorded. Results Fifty-two percent of glaucoma participants scored a marginal/fail compared to 21% of controls (odds ratio [OR], 4.1; 95% CI, 1.30–13.14;p=.02). Glaucoma participants had a higher risk of wheel interventions than controls (OR, 4.67; 95% CI, 1.03–21.17;p=.046). There were no differences detected between glaucoma participants who scored a pass vs. marginal/fail for visual field mean deviation of the better (p=.62) or worse (p=.88) eye, binocular distance (p=.15) or near (p=.23) visual acuity, contrast sensitivity (p=.28) or glare (p=.88). However, glaucoma participants with a marginal/fail score performed worse on Trail Making Tests A (p=.03) and B (p=.05), right-sided Jamar grip strength (p=.02), Rapid Pace Walk (p=.03), Braking Response Time (p=.03), and identifying traffic signs (p=.05). Conclusions and Relevance Patients with bilateral moderate or advanced glaucoma are at risk for unsafe driving – particularly those with impairments on psychometric and mobility tests. A comprehensive clinical assessment and on-road driving evaluation is recommended to effectively evaluate driving safety of these patients. PMID:26949136

Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

2011-01-01

Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

Genetic Factors of Ophthalmic Importance.

ERIC Educational Resources Information Center

Pollard, Zane F.

Reviewed are chromosomal anomalies affecting one's eyes. Brief descriptions are given of the genetic etiology of bilateral retinoblastoma (malignant tumors), aniridia (absence of the iris), cataracts, congenital glaucoma, Reginitis Pigmentosa (progressive deterioration of the visual cells), Choroidermia (degeneration of the vascular coat of the…

Circumferential Trabeculotomy Versus Conventional Angle Surgery: Comparing Long-term Surgical Success and Clinical Outcomes in Children With Primary Congenital Glaucoma.

PubMed

Neustein, Rebecca F; Beck, Allen D

2017-11-01

This study compares the long-term efficacy of circumferential trabeculotomy to that of conventional angle surgeries in primary congenital glaucoma (PCG), as judged by glaucoma and visual outcomes. Retrospective observational case series. Setting: Emory Eye Center, Atlanta, Georgia. This was a single-institution retrospective study involving children with PCG who underwent circumferential trabeculotomy, standard trabeculotomy, or goniotomy with ≥2-year follow-up. Postoperative success (intraocular pressure [IOP] < 22 mm Hg ± glaucoma medications, without glaucoma progression/additional IOP-lowering surgery), Snellen-equivalent visual acuity (VA), and IOP at last follow-up. Kaplan-Meier method estimated the probability of glaucoma control vs time postoperatively, and values were compared between angle surgery cohorts using Wilcoxon signed rank tests, Mann-Whitney U tests, and Fisher exact tests. Included were 58 eyes (33 children) after circumferential trabeculotomy and 42 eyes (27 children) after standard trabeculotomy/goniotomy, with mean follow-up of 7.2 ± 4.0 and 8.2 ± 4.5 years, respectively. Postoperative success at last follow-up in the circumferential vs conventional cohorts was 81% (47 of 58 eyes) vs 31% (13 of 42 eyes) (P < .0001). At last follow-up, the circumferential cohort had better median VA than the conventional cohort (20/30 (interquartile range [IQR] 20/25 to 20/70) vs 20/70 (IQR 20/40 to 20/200), P = .009), required fewer glaucoma medications (0.55 ± 1.2 vs 1.61 ± 1.51, P < .0001), had lower IOP in first operated eye (15.2 ± 3.6 vs 18.2 ± 7.0, P = .048), and had comparable incidence of devastating complications (P = .065). In this retrospective study, circumferential trabeculotomy afforded better long-term success and visual outcomes than conventional angle surgery for children with PCG. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the Ahmed and Baerveldt glaucoma shunts with combined cataract extraction.

PubMed

Rai, Amrit S; Shoham-Hazon, Nir; Christakis, Panos G; Rai, Amandeep S; Ahmed, Iqbal Ike K

2018-04-01

To compare the surgical outcomes of combined phacoemulsification with either Ahmed glaucoma valve (AGV) or Baerveldt glaucoma implant (BGI). Retrospective cohort study. A total of 104 eyes that underwent combined phacoemulsification with either AGV (PhacoAGV; n = 57) or BGI (PhacoBGI; n = 47) implantation. Failure was defined as uncontrolled intraocular pressure (IOP; <5 mm Hg, ≥18 mm Hg, or <20% reduction), additional glaucoma surgery, vision-threatening complications, or progression to no-light-perception vision. The PhacoAGV group was older (p = 0.03), had poorer baseline visual acuity (VA; p = 0.001), and had fewer previous glaucoma surgeries (p = 0.04). Both groups had similar baseline IOP (PhacoAGV: 26.4 ± 8.3 mm Hg; PhacoBGI: 25.7 ± 7.3; p = 0.66) and glaucoma medications (PhacoAGV: 3.8 ± 1.0; PhacoBGI: 3.6 ± 1.5; p = 0.54). At 2 years, failure rates were 44% in the PhacoAGV group and 23% in the PhacoBGI group (p = 0.02). Both groups had similar mean IOP reduction (PhacoAGV: 45%; PhacoBGI: 47%, p = 0.67) and medication use reduction (PhacoAGV: 47%; PhacoBGI: 58%, p = 0.38). The PhacoBGI group had higher IOP and medication use up to 1 month (p < 0.05). Both groups improved in VA from baseline (p < 0.05) and had similar overall complication rates (p = 0.31). The PhacoBGI group required more overall interventions (p < 0.0005). This comparative study found no difference in IOP, glaucoma medications, or complication rates between PhacoAGV and PhacoBGI at 2 years, despite BGIs being implanted in patients at higher risk for failure. The PhacoAGV group had higher failure rates at 2 years. Both groups had significant improvements in VA due to removal of their cataracts. The PhacoBGI group required more interventions, but most of these were minor slit-lamp procedures. Copyright © 2018. Published by Elsevier Inc.

Assessing the True Intraocular Pressure in the Non-human Primate.

PubMed

McAllister, Faith; Harwerth, Ronald; Patel, Nimesh

2018-02-01

For glaucoma patients, high intraocular pressure (IOP) is a risk factor for progressive neuropathy. Similarly, animal models used to study the disease are based on an experimental elevation of IOP. Thus, accurate IOP measurements are important in characterizing experimental models and resulting effects. The purpose of the present study was to investigate IOP measurements in a non-human primate model of experimental glaucoma by comparing clinical tonometry (Tono-Pen and TonoVet) to the true IOP from intracameral manometry. A total of 17 rhesus macaque eyes from 12 animals were used for this study. Eleven eyes had no previous experimental intervention, whereas six eyes were at varying stages of laser-induced experimental glaucoma. IOPs were adjusted by inserting a needle in the anterior chamber that was attached to a pressure transducer and syringe pump system. The anterior chamber IOP was adjusted to values between 10 and 50 mmHg and corresponding measures with Tono-Pen and TonoVet were taken. The IOPs by TonoVet and Tono-Pen were linearly related over the range of pressures tested (slope = 0.68 normal/healthy and 0.72 experimental glaucoma). For the most, TonoVet measures overestimated IOP at all anterior chamber pressure settings (mean difference of 3.17 mmHg, 95% CI 12.53 to -4.74 normal and 3.90 mmHg, 95% CI 12.90 to -6.53 experimental glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and underestimated at higher IOP (slope = -0.26 normal and -0.21 experimental glaucoma). The TonoVet and Tono-Pen tonometers that are often used to assess IOP in both clinical and experimental settings generally reflect the status of IOP, but the results from this study suggest that the instruments need calibration with true anterior chamber pressure for accurate measures in experimental models of glaucoma.

Pathophysiology of primary open-angle glaucoma from a neuroinflammatory and neurotoxicity perspective: a review of the literature.

PubMed

Evangelho, Karine; Mogilevskaya, Maria; Losada-Barragan, Monica; Vargas-Sanchez, Jeinny Karina

2017-12-30

Glaucoma is the leading cause of blindness in humans, affecting 2% of the population. This disorder can be classified into various types including primary, secondary, glaucoma with angle closure and with open angle. The prevalence of distinct types of glaucoma differs for each particular region of the world. One of the most common types of this disease is primary open-angle glaucoma (POAG), which is a complex inherited disorder characterized by progressive retinal ganglion cell death, optic nerve head excavation and visual field loss. Nowadays, POAG is considered an optic neuropathy, while intraocular pressure is proposed to play a fundamental role in its pathophysiology and especially in optic disk damage. However, the exact mechanism of optic nerve head damage remains a topic of debate. This literature review aims to bring together the information on the pathophysiology of primary open-angle glaucoma, particularly focusing on neuroinflammatory mechanisms leading to the death of the retinal ganglion cell. A literature search was done on PubMed using key words including primary open-angle glaucoma, retinal ganglion cells, Müller cells, glutamate, glial cells, ischemia, hypoxia, exitotoxicity, neuroinflammation, axotomy and neurotrophic factors. The literature was reviewed to collect the information published about the pathophysiologic mechanisms of RGC death in the POAG, from a neuroinflammatory and neurotoxicity perspective. Proposed mechanisms for glaucomatous damage are a result of pressure in RGC followed by ischemia, hypoxia of the ONH, and consequently death due to glutamate-induced excitotoxicity, deprivation of energy and oxygen, increase in levels of inflammatory mediators and alteration of trophic factors flow. These events lead to blockage of anterograde and retrograde axonal transport with ensuing axotomy and eventually blindness. The damage to ganglion cells and eventually glaucomatous injury can occur via various mechanisms including baric trauma, ischemia and impact of metabolic toxins, which triggers an inflammatory process and secondary degeneration in the ONH.

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

PubMed Central

Gracitelli, Carolina P. B.; Tatham, Andrew J.; Zangwill, Linda M.; Weinreb, Robert N.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Paranhos, Augusto; Baig, Saif; Medeiros, Felipe A.

2016-01-01

Purpose We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. Methods A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. Results There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R2 = 0.350, P < 0.001) and SAP MD (R2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. Conclusions Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma. PMID:27064394

A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice

PubMed Central

Cueva Vargas, Jorge L.; Di Polo, Adriana

2016-01-01

The use of rodent models of glaucoma has been essential to understand the molecular mechanisms that underlie the pathophysiology of this multifactorial neurodegenerative disease. With the advent of numerous transgenic mouse lines, there is increasing interest in inducible murine models of ocular hypertension. Here, we present an occlusion model of glaucoma based on the injection of magnetic microbeads into the anterior chamber of the eye using a modified microneedle with a facetted bevel. The magnetic microbeads are attracted to the iridocorneal angle using a handheld magnet to block the drainage of aqueous humour from the anterior chamber. This disruption in aqueous dynamics results in a steady elevation of intraocular pressure, which subsequently leads to the loss of retinal ganglion cells, as observed in human glaucoma patients. The microbead occlusion model presented in this manuscript is simple compared to other inducible models of glaucoma and also highly effective and reproducible. Importantly, the modifications presented here minimize common issues that often arise in occlusion models. First, the use of a bevelled glass microneedle prevents backflow of microbeads and ensures that minimal damage occurs to the cornea during the injection, thus reducing injury-related effects. Second, the use of magnetic microbeads ensures the ability to attract most beads to the iridocorneal angle, effectively reducing the number of beads floating in the anterior chamber avoiding contact with other structures (e.g., iris, lens). Lastly, the use of a handheld magnet allows flexibility when handling the small mouse eye to efficiently direct the magnetic microbeads and ensure that there is little reflux of the microbeads from the eye when the microneedle is withdrawn. In summary, the microbead occlusion mouse model presented here is a powerful investigative tool to study neurodegenerative changes that occur during the onset and progression of glaucoma. PMID:27077732

Long-Term Trends in Glaucoma-Related Blindness in Olmsted County, Minnesota

PubMed Central

Malihi, Mehrdad; Moura Filho, Edney R.; Hodge, David O.; Sit, Arthur J.

2013-01-01

Objective To determine the longitudinal trends in the probability of blindness due to open-angle glaucoma (OAG) in Olmsted County, Minnesota from 1965 to 2009. Design Retrospective, population-based cohort study. Participants All residents of Olmsted County, Minnesota (40 years of age and over) who were diagnosed with OAG between January 1, 1965 to December 31, 2000. Methods All available medical records of every incident case of OAG were reviewed until December 31, 2009 to identify progression to blindness, defined as visual acuity of 20/200 or worse, and/or visual field constriction to 20° or less. Kaplan–Meier analysis was used to estimate the cumulative probability of glaucoma-related blindness. Population incidence of blindness within 10 years of diagnosis was calculated using United States Census data. Rates for subjects diagnosed in the period 1965–1980 were compared with rates for subjects diagnosed in the period 1981–2000 using logrank tests and Poisson regression models. Main Outcome Measures Cumulative probability of OAG-related blindness, and population incidence of blindness within 10 years of diagnosis. Results Probability of glaucoma-related blindness in at least one eye at 20 years decreased from 25.8 % (95% Confidence interval [CI]: 18.5–32.5) for subjects diagnosed in 1965–1980, to 13.5% (95% CI: 8.8–17.9) for subjects diagnosed in 1981–2000 (P=0.01). The population incidence of blindness within 10 years of the diagnosis decreased from 8.7 per 100,000 (95% CI: 5.9–11.5) for subjects diagnosed in 1965–1980, to 5.5 per 100,000 (95% CI: 3.9–7.2) for subjects diagnosed in 1981–2000 (P=0.02). Higher age at diagnosis was associated with increased risk of progression to blindness (P< 0.001). Conclusions The 20-year probability and the population incidence of blindness due to OAG in at least one eye have decreased over a 45 year period from 1965 to 2009. However, a significant proportion of patients still progress to blindness despite recent diagnostic and therapeutic advancements. PMID:24823760

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

PubMed Central

Ramirez, Ana I.; de Hoz, Rosa; Salobrar-Garcia, Elena; Salazar, Juan J.; Rojas, Blanca; Ajoy, Daniel; López-Cuenca, Inés; Rojas, Pilar; Triviño, Alberto; Ramírez, José M.

2017-01-01

Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic loss in the cerebral cortex, resulting in cognitive deficit and dementia. The extracellular deposits of beta-amyloid (Aβ) and intraneuronal accumulations of hyperphosphorylated tau protein (pTau) are the hallmarks of this disease. These deposits are also found in the retina and optic nerve. PD is a neurodegenerative locomotor disorder with the progressive loss of dopaminergic neurons in the substantia nigra. This is accompanied by Lewy body inclusion composed of α-synuclein (α-syn) aggregates. PD also involves retinal dopaminergic cell degeneration. Glaucoma is a multifactorial neurodegenerative disease of the optic nerve, characterized by retinal ganglion cell loss. In this pathology, deposition of Aβ, synuclein, and pTau has also been detected in retina. These neurodegenerative diseases share a common pathogenic mechanism, the neuroinflammation, in which microglia play an important role. Microglial activation has been reported in AD, PD, and glaucoma in relation to protein aggregates and degenerated neurons. The activated microglia can release pro-inflammatory cytokines which can aggravate and propagate neuroinflammation, thereby degenerating neurons and impairing brain as well as retinal function. The aim of the present review is to describe the contribution in retina to microglial-mediated neuroinflammation in AD, PD, and glaucomatous neurodegeneration. PMID:28729832

Glaucoma-induced optic disc morphometric changes and glaucoma diagnostic ability of Heidelberg Retina Tomograph II in highly myopic eyes.

PubMed

Mayama, Chihiro; Tsutsumi, Tae; Saito, Hitomi; Asaoka, Ryo; Tomidokoro, Atsuo; Iwase, Aiko; Otani, Shinichiro; Miyata, Kazunori; Araie, Makoto

2014-01-01

This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes. Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (-1.0 to +1.0 diopters) and highly myopic eyes (-12.0 to -5.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes. Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes. In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients.

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

PubMed

Ellis, J D; Evans, J M; Ruta, D A; Baines, P S; Leese, G; MacDonald, T M; Morris, A D

2000-11-01

To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma.

PubMed

Chan, Hiu-Chi; Chang, Raymond Chuen-Chung; Koon-Ching Ip, Angel; Chiu, Kin; Yuen, Wai-Hung; Zee, Sze-Yong; So, Kwok-Fai

2007-01-01

Glaucoma is one of the major neurological disorders in eye leading to irreversible blindness in elderly. Increase in intraocular pressure (IOP) has been considered to be the major risk factor for the progressive loss of retinal ganglion cells (RGCs) in retina. While attenuation of IOP has been a major pharmaceutical target, reduction of IOP cannot prevent progressive loss of RGCs. In this regard, urgent need for alternative treatment has to be investigated. Anti-aging medicinal herb Lycium barbarum L. has been used for centuries in Eastern World to protect the eyes and maintain good health. Using an ocular hypertension (OH) model in rat by laser photocoagulation of episcleral and limbal veins, we attempted to investigate whether L. barbarum can promote RGCs survival against elevated IOP. Oral administration of L. barbarum in Sprague-Dawley rats (250-280 g) significantly reduced the loss of RGCs, although elevated IOP was not significantly altered. Rats fed with the 1 mg/kg extract could nearly totally escape from pressure-induced loss of RGCs. In conclusion, this is the first in vivo report showing the therapeutic function of L. barbarum against neurodegeneration in the retina of rat OH model. The results demonstrate that this extract may be a potential candidate for the development of neuroprotective drug against the loss of RGCs in glaucoma.

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.

The development of a micro‐shunt made from poly(styrene‐block‐isobutylene‐block‐styrene) to treat glaucoma

PubMed Central

Riss, Isabelle; Batlle, Juan F.; Kato, Yasushi P.; Martin, John B.; Arrieta, Esdras; Palmberg, Paul; Parrish, Richard K.; Weber, Bruce A.; Kwon, Yongmoon; Parel, Jean‐Marie

2015-01-01

Abstract Glaucoma is the second leading cause of blindness with ∼70 million people worldwide who are blind from this disease. The currently practiced trabeculectomy surgery, the gold standard treatment used to stop the progression of vision loss, is rather draconian, traumatic to the patient and requires much surgical skill to perform. This article summarizes the more than 10‐year development path of a novel device called the InnFocus MicroShunt®, which is a minimally invasive glaucoma drainage micro‐tube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's Capsule. The safety and clinical performance of this device approaches that of trabeculectomy. The impetus to develop this device stemmed from the invention of a new biomaterial called poly(styrene‐block‐isobutylene‐block‐styrene), or “SIBS.” SIBS is ultra‐stable with virtually no foreign body reaction in the body, which manifests in the eye as clinically insignificant inflammation and capsule formation. The quest for an easier, safer, and more effective method of treating glaucoma led to the marriage of SIBS with this glaucoma drainage micro‐tube. This article summarizes the development of SIBS and the subsequent three iterations of design and four clinical trials that drove the one‐year qualified success rate of the device from 43% to 100%. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 211–221, 2017. PMID:26380916

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.

Retinal fundus images for glaucoma analysis: the RIGA dataset

NASA Astrophysics Data System (ADS)

Almazroa, Ahmed; Alodhayb, Sami; Osman, Essameldin; Ramadan, Eslam; Hummadi, Mohammed; Dlaim, Mohammed; Alkatee, Muhannad; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

2018-03-01

Glaucoma neuropathy is a major cause of irreversible blindness worldwide. Current models of chronic care will not be able to close the gap of growing prevalence of glaucoma and challenges for access to healthcare services. Teleophthalmology is being developed to close this gap. In order to develop automated techniques for glaucoma detection which can be used in tele-ophthalmology we have developed a large retinal fundus dataset. A de-identified dataset of retinal fundus images for glaucoma analysis (RIGA) was derived from three sources for a total of 750 images. The optic cup and disc boundaries for each image was marked and annotated manually by six experienced ophthalmologists and included the cup to disc (CDR) estimates. Six parameters were extracted and assessed (the disc area and centroid, cup area and centroid, horizontal and vertical cup to disc ratios) among the ophthalmologists. The inter-observer annotations were compared by calculating the standard deviation (SD) for every image between the six ophthalmologists in order to determine if the outliers amongst the six and was used to filter the corresponding images. The data set will be made available to the research community in order to crowd source other analysis from other research groups in order to develop, validate and implement analysis algorithms appropriate for tele-glaucoma assessment. The RIGA dataset can be freely accessed online through University of Michigan, Deep Blue website (doi:10.7302/Z23R0R29).

Brightness discrimination test is not useful in screening for open angle glaucoma.

PubMed

Peter, E; Thomas, R; Muliyil, J

1996-06-01

Brightness discrimination test (BDT) is routinely employed to assess asymmetrical optic nerve dysfunction and has been suggested as a screening test for primary open angle glaucoma (POAG). We tested the reliability and validity of BDT in the diagnosis of POAG. The study groups included 34 patients with established primary open angle glaucoma, 20 glaucoma suspects, and 33 age-sex matched controls. Cataract was not an exclusion criterion in these groups. The normal brightness score was determined to be 88% (mean score, 94%-2 SD) in a pilot study. Brightness discrimination test was performed in all subjects by two observers independently. BDT showed an excellent interobserver agreement (weighted Kappa 0.84). The presence of a cataract alone increased the risk of brightness impairment twofold, glaucoma alone increased the risk eightfold, and the presence of both conditions by 17 times compared to those with neither condition. BDT was not a useful test in the diagnosis of POAG (sensitivity 67% and specificity 93%); the ability to detect a significant field defect was also poor (sensitivity 53% and specificity 76%). There was poor association between decreased brightness scores and asymmetrical field defects as determined by the Humphrey's field analyzer (HFA).

Missing Optomotor Head-Turning Reflex in the DBA/2J Mouse

PubMed Central

Huang, Wei; Chen, Hui; Koehler, Christopher L.; Howell, Gareth; John, Simon W. M.; Tian, Ning; Rentería, René C.; Križaj, David

2011-01-01

Purpose. The optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb+ (D2-Gpnmb+), and C57BL/6J (B6) mouse strains was assayed, and the retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision was compared between the D2 and B6 mouse lines. Methods. Intraocular pressure (IOP) measurements, real-time PCR, and immunohistochemical analysis were used to assess the time course of glaucomatous changes in D2 retinas. Behavioral analyses of optomotor head-turning reflex, visible platform Morris water maze and Rotarod measurements were conducted to test vision and vestibulomotor function. Electroretinogram (ERG) measurements were used to assay outer retinal function. The multielectrode array (MEA) technique was used to characterize RGC spiking and direction selectivity in D2 and B6 retinas. Results. Progressive increase in IOP and loss of Brn3a signals in D2 animals were consistent with glaucoma progression starting after 6 months of age. D2 mice showed no response to visual stimulation that evoked robust optomotor responses in B6 mice at any age after eye opening. Spatial frequency threshold was also not measurable in the D2-Gpnmb+ strain control. ERG a- and b-waves, central vision, vestibulomotor function, the spiking properties of ON, OFF, ON-OFF, and direction-selective RGCs were normal in young D2 mice. Conclusions. The D2 strain is characterized by a lack of optomotor reflex before IOP elevation and RGC degeneration are observed. This behavioral deficit is D2 strain–specific, but is independent of retinal function and glaucoma. Caution is advised when using the optomotor reflex to follow glaucoma progression in D2 mice. PMID:21757588

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.

Cellular proliferation after experimental glaucoma filtration surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jampel, H.D.; McGuigan, L.J.; Dunkelberger, G.R.

1988-01-01

We used light microscopic autoradiography to determine the time course of cellular incorporation of tritiated thymidine (a correlate of cell division) following glaucoma filtration surgery in seven eyes of four cynomolgus monkeys with experimental glaucoma. Incorporation of tritiated thymidine was detected as early as 24 hours postoperatively. Peak incorporation occurred five days postoperatively and had returned to baseline levels by day 11. Cells incorporating tritiated thymidine included keratocytes, episcleral cells, corneal and capillary endothelial cells, and conjunctival and corneal epithelial cells. Transmission electron microscopy was correlated with the autoradiographic results to demonstrate that fibroblasts were dividing on the corneoscleral margin.more » These findings have potential clinical implications for the use of antiproliferative agents after filtration surgery.« less

Composite fibrous glaucoma drainage implant

NASA Astrophysics Data System (ADS)

Klapstova, A.; Horakova, J.; Shynkarenko, A.; Lukas, D.

2017-10-01

Glaucoma is a frequent reason of loss vision. It is usually caused by increased intraocular pressure leading to damage of optic nerve head. This work deals with the development of fibrous structure suitable for glaucoma drainage implants (GDI). Commercially produced metallic glaucoma implants are very effective in lowering intraocular pressure. However, these implants may cause adverse events such as damage to adjacent tissue, fibrosis, hypotony or many others [1]. The aim of this study is to reduce undesirable properties of currently produced drains and improve their properties by creating of the composite fibrous drain for achieve a normal intraocular pressure. Two types of electrospinning technologies were used for the production of very small tubular implants. First type was focused for production of outer part of tubular drain and the second type of electrospinning method made the inner part of shape follows the connections of both parts. Complete implant had a special properties suitable for drainage of fluid. Morphological parameters, liquid transport tests and in-vitro cell adhesion tests were detected.

Optic Disc and Optic Cup Segmentation Methodologies for Glaucoma Image Detection: A Survey

PubMed Central

Almazroa, Ahmed; Burman, Ritambhar; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

2015-01-01

Glaucoma is the second leading cause of loss of vision in the world. Examining the head of optic nerve (cup-to-disc ratio) is very important for diagnosing glaucoma and for patient monitoring after diagnosis. Images of optic disc and optic cup are acquired by fundus camera as well as Optical Coherence Tomography. The optic disc and optic cup segmentation techniques are used to isolate the relevant parts of the retinal image and to calculate the cup-to-disc ratio. The main objective of this paper is to review segmentation methodologies and techniques for the disc and cup boundaries which are utilized to calculate the disc and cup geometrical parameters automatically and accurately to help the professionals in the glaucoma to have a wide view and more details about the optic nerve head structure using retinal fundus images. We provide a brief description of each technique, highlighting its classification and performance metrics. The current and future research directions are summarized and discussed. PMID:26688751

Progression of pectinate ligament dysplasia over time in two populations of Flat-Coated Retrievers.

PubMed

Pearl, Rose; Gould, David; Spiess, Bernhard

2015-01-01

Two of the authors (DG, BS) independently observed that a number of Flat-Coated Retrievers (FCRs) previously unaffected by pectinate ligament dysplasia (PLD) appeared to develop the condition later in life. This study was instigated to investigate progression of PLD within individual dogs over time. Flat-Coated Retrievers that had previously undergone gonioscopy under the UK/ECVO hereditary eye schemes were included in the study. A second gonioscopic examination was performed 1.92-12.58 years later (mean 6, median 5.75 years) and the results compared. 39 FCR (17 males, 22 females) in the UK and 57 FCR (27 males, 30 females) in Switzerland were included. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and gonioscopy were performed in all dogs. Gonioscopy allowed classification as either unaffected or affected; percentage of the iridocorneal drainage angle (ICA) affected by PLD was determined, before calculating progression observed as mild, moderate, or severe. 39 of 96 (40.6%) dogs demonstrated progression of PLD (P < 0.0001). Of these, 13 of 96 (13.5%) were classified as mild progression (from either unaffected to 10-20% or 10-20% to 20-90% ICA affected). Progression was more extensive in 26 of 96 (27.1%) dogs (P < 0.0001), of which 12 of 96 (12.5%) went from unaffected to severe PLD of >90% ICA affected, consistent with a high risk of glaucoma. To the authors' knowledge, this is the first report describing progression of PLD in individual dogs over time, in a breed affected by primary, angle closure glaucoma. © 2013 American College of Veterinary Ophthalmologists.

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

Real-time imaging of single neuronal cell apoptosis in patients with glaucoma

PubMed Central

Normando, Eduardo M.; Cardoso, M. Jorge; Miodragovic, Serge; Jeylani, Seham; Davis, Benjamin M.; Guo, Li; Ourselin, Sebastien; A’Hern, Roger; Bloom, Philip A.

2017-01-01

Abstract See Herms and Schön (doi:10.1093/brain/awx100) for a scientific commentary on this article. Retinal cell apoptosis occurs in many ocular neurodegenerative conditions including glaucoma—the major cause of irreversible blindness worldwide. Using a new imaging technique that we have called DARC (detection of apoptosing retinal cells), which until now has only been demonstrated in animal models, we assessed if annexin 5 labelled with fluorescent dye DY-776 (ANX776) could be used safely in humans to identify retinal cell apoptosis. Eight patients with glaucomatous neurodegeneration and evidence of progressive disease, and eight healthy subjects were randomly assigned to intravenous ANX776 doses of 0.1, 0.2, 0.4 and 0.5 mg in an open-label, phase 1 clinical trial. In addition to assessing the safety, tolerability and pharmacokinetics of ANX776, the study aimed to explore whether DARC could successfully visualize individual retinal cell apoptosis in vivo in humans, with the DARC count defined as the total number of unique ANX776-labelled spots. DARC enabled retinal cell apoptosis to be identified in the human retina using ANX776. Single ANX776-labelled cells were visualized in a dose-dependent pattern (P < 0.001) up to 6 h after injection. The DARC count was significantly higher (2.37-fold, 95% confidence interval: 1.4–4.03, P = 0.003) in glaucoma patients compared to healthy controls, and was significantly (P = 0.045) greater in patients who later showed increasing rates of disease progression, based on either optic disc, retinal nerve fibre layer or visual field parameters. Additionally, the DARC count significantly correlated with decreased central corneal thickness (Spearman’s R = −0.68, P = 0.006) and increased cup-disc ratios (Spearman’s R = 0.47, P = 0.038) in glaucoma patients and with increased age (Spearman’s R = 0.77, P = 0.001) in healthy controls. Finally, ANX776 was found to be safe and well-tolerated with no serious adverse events, and a short half-life (10–36 min). This proof-of-concept study demonstrates that retinal cell apoptosis can be identified in the human retina with increased levels of activity in glaucomatous neurodegenerative disease. To our knowledge, this is the first time individual neuronal apoptosis has been visualized in vivo in humans and is the first demonstration of detection of individual apoptotic cells in a neurodegenerative disease. Furthermore, our results suggest the level of apoptosis (‘DARC count’) is predictive of disease activity, indicating the potential of DARC as a surrogate marker. Although further trials are clearly needed, this study validates experimental findings supporting the use of DARC as a method of detection and monitoring of patients with glaucomatous neurodegeneration, where retinal ganglion cell apoptosis is an established process and where there is a real need for tools to non-invasively assess treatment efficacy. PMID:28449038

National and subnational prevalence and burden of glaucoma in China: A systematic analysis.

PubMed

Song, Peige; Wang, Jiawen; Bucan, Kajo; Theodoratou, Evropi; Rudan, Igor; Chan, Kit Yee

2017-12-01

Glaucoma, the second leading cause of blindness, affects approximately 64.3 million individuals worldwide. In China, demographic ageing is in rapid progress. Yet detailed and up-to-date estimates of the scale of glaucoma are rare. We aimed to quantify and understand the prevalence and burden of glaucoma in China from 1990 to 2015, with projections until 2050. For this systematic review and meta-analysis, we searched China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline using comprehensive search strategies to identify all relevant articles that have reported the prevalence of glaucoma in the general Chinese population. We used a multilevel mixed-effect meta-regression to estimate the prevalence rates of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and a random-effects meta-analysis to pool the overall prevalence of secondary glaucoma. United Nations population data were used to estimate and project the number of people with glaucoma from 1990 to 2050. Univariable and multivariable meta-regressions were conducted to assess the association between the prevalence of POAG and PACG and relevant demographic and geographic factors. The national burden of POAG and PACG in the years 2000 and 2010 were distributed to six geographic regions accordingly. From 1990 to 2015, the prevalence of all glaucoma ranged from 2.59% (95% CI = 1.96-3.49) to 2.58% (95% CI = 1.94-3.47). For different subtypes of glaucoma, the overall prevalence of POAG ranged from 1.03% (95% CI = 0.67-1.58) in 1990 to 1.02% (95% CI = 0.67-1.57) in 2015, PACG from 1.41% (95% CI = 1.18-1.68) to 1.40% (95% CI = 1.17-1.68). The overall prevalence of secondary glaucoma was 0.15% (95% CI = 0.10-0.23) during this period. The number of people with all glaucoma in China was 5.92 million (95% CI = 4.47-7.97) in 1990, and 13.12 million (95% CI = 9.88-17.68) in 2015. This increasing trend was also witnessed in different subtypes of glaucoma. The number of people affected by POAG increased from 2.35 million (95% CI = 1.54-3.60) in 1990 to 5.22 million (95% CI = 3.40-7.98) in 2015, PACG from 3.22 million (95% CI = 2.70-3.84) to 7.14 million (95% CI = 5.97-8.53), and secondary glaucoma from 0.34 million (95% CI = 0.23-0.53) to 0.76 million (95% CI = 0.51-1.17). In 2015, more than half (54.42%) of the glaucoma cases were PACG, followed by POAG (39.79%) and secondary glaucoma (5.79%). By 2050, the number of all glaucoma cases in China will be 25.16 million (95% CI = 18.96-33.86). In the multivariable meta-regressions, the odds ratio (OR) for each decade's increase in age was 1.43 (95% CI = 1.33-1.55) for POAG, and 1.65 (95% CI = 1.51-1.80) for PACG; males were more likely to have POAG (OR 1.36, 95% CI = 1.17-1.59), but less likely to have PACG (OR 0.53, 95% CI = 0.46-0.60) compared with females. After adjustment of age and gender, people living in urban areas were more likely to have POAG compared with those in rural areas (OR 1.54, 95% CI = 1.02-2.35). People in Northeast China were at a higher risk (OR 1.77, 95% CI = 1.07-2.94) of having PACG than people in East China. Among the six regions, East China owed the most POAG and PACG cases, whereas Northwest China owed the least. This systematic review and meta-analysis suggests a substantial burden of glaucoma in China, with great variances among the different age groups, genders, settings and geographic regions. With the dramatic ageing trend in the next three decades, the prevalence and burden of glaucoma will continue to increase. More elaborate epidemiological studies are needed to optimise public health strategies for mitigating this important health problem.

Evaluation of a New Software Version of the RTVue Optical Coherence Tomograph for Image Segmentation and Detection of Glaucoma in High Myopia.

PubMed

Holló, Gábor; Shu-Wei, Hsu; Naghizadeh, Farzaneh

2016-06-01

To compare the current (6.3) and a novel software version (6.12) of the RTVue-100 optical coherence tomograph (RTVue-OCT) for ganglion cell complex (GCC) and retinal nerve fiber layer thickness (RNFLT) image segmentation and detection of glaucoma in high myopia. RNFLT and GCC scans were acquired with software version 6.3 of the RTVue-OCT on 51 highly myopic eyes (spherical refractive error ≤-6.0 D) of 51 patients, and were analyzed with both the software versions. Twenty-two eyes were nonglaucomatous, 13 were ocular hypertensive and 16 eyes had glaucoma. No difference was seen for any RNFLT, and average GCC parameter between the software versions (paired t test, P≥0.084). Global loss volume was significantly lower (more normal) with version 6.12 than with version 6.3 (Wilcoxon signed-rank test, P<0.001). The percentage agreement (κ) between the clinical (normal and ocular hypertensive vs. glaucoma) and the software-provided classifications (normal and borderline vs. outside normal limits) were 0.3219 and 0.4442 for average RNFLT, and 0.2926 and 0.4977 for average GCC with versions 1 and 2, respectively (McNemar symmetry test, P≥0.289). No difference in average RNFLT and GCC classification (McNemar symmetry test, P≥0.727) and the number of eyes with at least 1 segmentation error (P≥0.109) was found between the software versions, respectively. Although GCC segmentation was improved with software version 6.12 compared with the current version in highly myopic eyes, this did not result in a significant change of the average RNFLT and GCC values, and did not significantly improve the software-provided classification for glaucoma.

Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma

PubMed Central

Taylor, Sarah; Calder, Claudia J.; Albon, Julie; Erichsen, Jonathan T.; Boulton, Micheal E.; Morgan, James E.

2013-01-01

The interaction of the myeloid restricted molecule CD200R with its widely expressed ligand CD200 is involved in the down-regulation of microglia activation. In the present study, we examined the involvement of CD200R in microglia activation in experimental ocular hypertension to determine the role of microglia activation in retinal ganglion cell (RGC) death, the key pathological event in glaucoma. Experimental glaucoma was induced in adult Brown Norway rats by sclerosis of the episcleral veins with the injection of hypertonic saline. Immunohistochemical methods were used to determine the involvement of microglia using GFAP, CD45, OX42 and OX41 and the involvement of CD200 and CD200R in the optic nerve head. Our data demonstrate the increased presence of microglia within the optic nerve head during ocular hypertension, identified by positive staining with OX42 and OX41. The peak of microglia correlates with peak in RGC death at days 20–27 (T3) post OHT induction. In addition, CD200 and CD200R positive cells were increased in ocular hypertensive eyes. Increased expression of CD200 was detected in the early phase (days 1–7; T1) of OHT and decreased over time, whilst the expression of CD200R was detected in the middle phase (days 20–27; T3) of OHT, correlating with the increase in microglia markers. Changes in the expression of CD200R/CD200 occur early in experimental glaucoma and precede the peak in microglia infiltration and RGC death, suggesting that CD200R-positive microglia play an important role in the initiation of RGC death during OHT, indicating a potential area for therapeutic intervention in treating glaucoma. PMID:21296076

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.

Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

PubMed Central

Barua, Nabanita; Sitaraman, Chitra; Goel, Sonu; Chakraborti, Chandana; Mukherjee, Sonai; Parashar, Hemandra

2016-01-01

Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL) in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD) optical coherence tomography (OCT) among primary open angle glaucoma (POAG) and ocular hypertension (OHT) versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group). After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC) parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson's coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P < 0.001). Inferior GCC had highest area under curve (AUC) for detecting glaucoma (0.827) in POAG from normal population. However, the difference was not statistically significant (P > 0.5) when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715). Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable. PMID:27221682

Nondiabetic retinal pathology - prevalence in diabetic retinopathy screening.

PubMed

Nielsen, Nathan; Jackson, Claire; Spurling, Geoffrey; Cranstoun, Peter

2011-07-01

To determine the prevalence of photographic signs of nondiabetic retinal pathology in Australian general practice patients with diabetes. Three hundred and seven patients with diabetes underwent retinal photography at two general practices, one of which was an indigenous health centre. The images were assessed for signs of pathology by an ophthalmologist. Signs of nondiabetic retinal pathology were detected in 31% of subjects with adequate photographs. Features suspicious of glaucoma were detected in 7.7% of subjects. Other abnormalities detected included signs of age related macular degeneration (1.9%), epiretinal membranes (2.4%), vascular pathology (9.6%), chorioretinal lesions (2.9%), and congenital disc anomalies (2.9%). Indigenous Australian patients were more likely to have signs of retinal pathology and glaucoma. Signs of nondiabetic retinal pathology were frequently encountered. In high risk groups, general practice based diabetic retinopathy screening may reduce the incidence of preventable visual impairment, beyond the benefits of detection of diabetic retinopathy alone.

Comparison of Ocular Pulse Amplitude Lowering Effects of Preservative-Free Tafluprost and Preservative-Free Dorzolamide-Timolol Fixed Combination Eyedrops.

PubMed

Seo, Du Ri; Ha, Seung Joo

2015-01-01

To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry. In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment. After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01). Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP.

Novel drug delivery systems for glaucoma

PubMed Central

Lavik, E; Kuehn, M H; Kwon, Y H

2011-01-01

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Automated detection of kinks from blood vessels for optic cup segmentation in retinal images

NASA Astrophysics Data System (ADS)

Wong, D. W. K.; Liu, J.; Lim, J. H.; Li, H.; Wong, T. Y.

2009-02-01

The accurate localization of the optic cup in retinal images is important to assess the cup to disc ratio (CDR) for glaucoma screening and management. Glaucoma is physiologically assessed by the increased excavation of the optic cup within the optic nerve head, also known as the optic disc. The CDR is thus an important indicator of risk and severity of glaucoma. In this paper, we propose a method of determining the cup boundary using non-stereographic retinal images by the automatic detection of a morphological feature within the optic disc known as kinks. Kinks are defined as the bendings of small vessels as they traverse from the disc to the cup, providing physiological validation for the cup boundary. To detect kinks, localized patches are first generated from a preliminary cup boundary obtained via level set. Features obtained using edge detection and wavelet transform are combined using a statistical approach rule to identify likely vessel edges. The kinks are then obtained automatically by analyzing the detected vessel edges for angular changes, and these kinks are subsequently used to obtain the cup boundary. A set of retinal images from the Singapore Eye Research Institute was obtained to assess the performance of the method, with each image being clinically graded for the CDR. From experiments, when kinks were used, the error on the CDR was reduced to less than 0.1 CDR units relative to the clinical CDR, which is within the intra-observer variability of 0.2 CDR units.

Glaucoma

MedlinePlus

Open-angle glaucoma; Chronic glaucoma; Chronic open-angle glaucoma; Primary open-angle glaucoma; Closed-angle glaucoma; Narrow-angle glaucoma; Angle-closure glaucoma; Acute glaucoma; Secondary glaucoma; Congenital glaucoma; Vision ...

Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms

PubMed Central

2018-01-01

We explore the ideas and advances surrounding the genetic basis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). As PG is the leading cause of nontraumatic blindness in young adults and current tailored interventions have proven ineffective, a better understanding of the underlying causes of PDS, PG, and their relationship is essential. Despite PDS being a subclinical disease, a large proportion of patients progress to PG with associated vision loss. Decades of research have supported a genetic component both for PDS and conversion to PG. We review the body of evidence supporting a genetic basis in humans and animal models and reevaluate classical mechanisms of PDS/PG considering this new evidence. PMID:29780638

Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms.

PubMed

Lahola-Chomiak, Adrian A; Walter, Michael A

2018-01-01

We explore the ideas and advances surrounding the genetic basis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). As PG is the leading cause of nontraumatic blindness in young adults and current tailored interventions have proven ineffective, a better understanding of the underlying causes of PDS, PG, and their relationship is essential. Despite PDS being a subclinical disease, a large proportion of patients progress to PG with associated vision loss. Decades of research have supported a genetic component both for PDS and conversion to PG. We review the body of evidence supporting a genetic basis in humans and animal models and reevaluate classical mechanisms of PDS/PG considering this new evidence.

Longitudinal Detection of Optic Nerve Head Changes by Spectral Domain Optical Coherence Tomography in Early Experimental Glaucoma

PubMed Central

He, Lin; Yang, Hongli; Gardiner, Stuart K.; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Fortune, Brad; Burgoyne, Claude F.

2014-01-01

Purpose. We determined if the detection of spectral-domain optical coherence tomography (SDOCT) optic nerve head (ONH) change precedes the detection of confocal scanning laser tomography (CSLT) ONH surface, SDOCT retinal nerve fiber layer (RNFL), scanning laser perimetry (SLP), and multifocal electroretinography (mfERG) change in eight experimental glaucoma (EG) eyes. Methods. Both eyes from eight monkeys were tested at least three times at baseline, and then every 2 weeks following laser-induced chronic unilateral IOP elevation. Event and trend-based definitions of onset in the control and EG eyes for 11 SDOCT neural and connective tissue, CSLT surface, SDOCT RNFL, SLP, and mfERG parameters were explored. The frequency and timing of onset for each parameter were compared using a logrank test. Results. Maximum post-laser IOP was 18 to 42 mm Hg in the EG eyes and 12 to 20 mm Hg in the control eyes. For event- and trend-based analyses, onsets were achieved earliest and most frequently within the ONH neural and connective tissues using SDOCT, and at the ONH surface using CSLT. SDOCT ONH neural and connective tissue parameter change preceded or coincided with CSLT ONH surface change in most EG eyes. The SDOCT and SLP measures of RNFL thickness, and mfERG measures of visual function demonstrated similar onset rates, but occurred later than SDOCT ONH and CSLT surface change, and in fewer eyes. Conclusions. SDOCT ONH change detection commonly precedes or coincides with CSLT ONH surface change detection, and consistently precedes RNFLT, SLP, and mfERG change detection in monkey experimental glaucoma. PMID:24255047

A survey on computer aided diagnosis for ocular diseases

PubMed Central

2014-01-01

Background Computer Aided Diagnosis (CAD), which can automate the detection process for ocular diseases, has attracted extensive attention from clinicians and researchers alike. It not only alleviates the burden on the clinicians by providing objective opinion with valuable insights, but also offers early detection and easy access for patients. Method We review ocular CAD methodologies for various data types. For each data type, we investigate the databases and the algorithms to detect different ocular diseases. Their advantages and shortcomings are analyzed and discussed. Result We have studied three types of data (i.e., clinical, genetic and imaging) that have been commonly used in existing methods for CAD. The recent developments in methods used in CAD of ocular diseases (such as Diabetic Retinopathy, Glaucoma, Age-related Macular Degeneration and Pathological Myopia) are investigated and summarized comprehensively. Conclusion While CAD for ocular diseases has shown considerable progress over the past years, the clinical importance of fully automatic CAD systems which are able to embed clinical knowledge and integrate heterogeneous data sources still show great potential for future breakthrough. PMID:25175552

Novel Bruch's Membrane Opening Minimum Rim Area Equalizes Disc Size Dependency and Offers High Diagnostic Power for Glaucoma.

PubMed

Enders, Philip; Adler, Werner; Schaub, Friederike; Hermann, Manuel M; Dietlein, Thomas; Cursiefen, Claus; Heindl, Ludwig M

2016-12-01

The purpose of this study was to assess the diagnostic power of the novel two-dimensional parameter Bruch's membrane opening minimal rim area (BMO-MRA) in spectral-domain optical coherence tomography (SD-OCT) for detection of glaucoma compared to minimal rim width (BMO-MRW) and retinal nerve fiber layer (RNFL) thickness in large and small optic discs. In this case-control, cross-sectional study, 207 eyes of 207 participants, including 89 controls and 97 patients with glaucoma and 21 with ocular hypertension (OHT), with a disc size <1.63 mm2 or >2.43 mm2 underwent SD-OCT, confocal laser scanning tomography (CSLT), visual field testing, and clinical examination. Bruch's membrane opening-MRA BMO-MRW, RNFL thickness of SD-OCT and disc margin rim area (DM-RA) of CSLT were evaluated and analyzed for diagnostic power to detect glaucoma. In healthy eyes with macrodiscs, mean BMO-MRW of 243.14 ± 43.12 μm was significantly smaller than BMO-MRW in microdiscs (338.97 ± 69.39; P < 0.001). Bruch's membrane opening-MRA was comparable between disc size groups with 1.22 ± 0.25 mm2 for macrodiscs and 1.26 ± 0.27 mm2 for microdiscs (P = 0.51), as was RNFL thickness (82.69 ± 15.76 μm versus 78.53 ± 11.01 μm, respectively; P = 0.28). Perimetric mean deviation was -8.7 ± 6.3 dB in glaucoma and -0.6 ± 1.60 dB in OHT patients. Correlation of BMO-MRA and visual field function was rho (ρ) = 0.70 (P < 0.001). Diagnostic power to differentiate glaucoma patients was highest for BMO-MRA. Partial area under the curve (pAUC) for BMO-MRA was 0.14 for specificity between 0.8 and 1.0, exceeding pAUCs of BMO-MRW (P < 0.001), RNFL thickness (P = 0.03), and DM-RA (P = 0.01). Bruch's membrane opening-based minimum rim area measurements offer advantages compared to one-dimensional parameters assessing neuroretinal rim by SD-OCT. In nonglaucomatous eyes, BMO-MRA values seem comparable for the full range of disc sizes. Bruch's membrane opening-MRA surpasses other parameters in diagnostic power for glaucoma.

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.

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.

[Preservative-free glaucoma treatment : Selection of the correct treatment in 1 min].

PubMed

Pfennigsdorf, S; Eschstruth, P

2016-05-01

The presence of preservatives in topical glaucoma treatments may impact ocular surface function and structure. For treatment to be effective, side effects need to be minimized, in order to promote compliance and allow continuation of therapy. Therefore, in daily clinical practice, it needs to be decided on an individual basis whether a preservative-free treatment is required. This study aimed to develop a questionnaire which helps to quickly and easily identify patients who require preservative-free treatment. A questionnaire was prepared to collect relevant clinical findings needed to make a therapeutic decision (preservative-free required? Yes/No). Moreover, a rating scheme was developed to enable efficient final assessment of the collected data. To check their practicability in daily clinical practice, both instruments were tested in 11 ophthalmological centers in Germany. The questionnaire and rating scheme were easy to use, integrated efficiently into everyday routine, and performed in about 1 min. Data of 1150 glaucoma patients were collected and preservative-free eyedrops recommended for 586 (51 %). Parameters most frequently associated with such a recommendation were a reduced tear film break-up time of < 10 s (87.5 %) or marked corneal staining (65.5 %). The presented approach helps to decide within 1 min, in daily clinical practice, whether preservative-free glaucoma threatment should be recommended. Individualized therapy decisions can thus be made, allowing goal-oriented use of preservative-free antiglaucomatosa. This might help to promote compliance and lead to reduced progression of glaucoma.

The development of a micro-shunt made from poly(styrene-block-isobutylene-block-styrene) to treat glaucoma.

PubMed

Pinchuk, Leonard; Riss, Isabelle; Batlle, Juan F; Kato, Yasushi P; Martin, John B; Arrieta, Esdras; Palmberg, Paul; Parrish, Richard K; Weber, Bruce A; Kwon, Yongmoon; Parel, Jean-Marie

2017-01-01

Glaucoma is the second leading cause of blindness with ∼70 million people worldwide who are blind from this disease. The currently practiced trabeculectomy surgery, the gold standard treatment used to stop the progression of vision loss, is rather draconian, traumatic to the patient and requires much surgical skill to perform. This article summarizes the more than 10-year development path of a novel device called the InnFocus MicroShunt®, which is a minimally invasive glaucoma drainage micro-tube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's Capsule. The safety and clinical performance of this device approaches that of trabeculectomy. The impetus to develop this device stemmed from the invention of a new biomaterial called poly(styrene-block-isobutylene-block-styrene), or "SIBS." SIBS is ultra-stable with virtually no foreign body reaction in the body, which manifests in the eye as clinically insignificant inflammation and capsule formation. The quest for an easier, safer, and more effective method of treating glaucoma led to the marriage of SIBS with this glaucoma drainage micro-tube. This article summarizes the development of SIBS and the subsequent three iterations of design and four clinical trials that drove the one-year qualified success rate of the device from 43% to 100%. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 211-221, 2017. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

[Angle-closure glaucoma secondary to nonspecific orbital inflammatory: case report].

PubMed

Násser, Luciano Sólia; Liendo da Costa, Vera Lucia; Taniguchi, Marcel Papa; Bolanho, Anamaria; Petrilli, Ana Maria Noriega

2007-01-01

The nonspecific orbital inflammatory presents several clinical forms. When it evolves the posterior segment of the eye, usually by contiguity, it can lead to serious damage to vision functions. Posterior scleritis causes permanent damage to the vision and rarely progresses to acute glaucoma. E.N., a 24-year-old black man, complained of pain in the left eye (OS) for ten days, with low visual acuity, malaise, nauseas and vomiting. On ophthalmologic examination, he presented proptosis, restricted eye movements and edema on the upper left eyelid. Best-corrected visual acuity was 20/20 in OD and counting fingers at 1.5m in OS. The intraocular pressure was 14 mmHg in OD and 34 mmHg in OS. The biomicroscopy presented in OS conjunctival hyperemia cornea with keratic precipitates, shallow anterior chamber with cells and flare 2+. Gonioscopy in OS showed angle-closure of 360 masculine. The ophthalmoscopic examination revealed increased vascular tortuosity and posterior pole edema. Treatment for acute glaucoma was initiated and complementary tests were ordered. Ocular ultrasonography and orbit computerized tomography showed a diffuse thickening of the ocular wall and extrinsic muscles. Other tests were normal. The presumptive diagnosis was acute nonspecific orbital inflammation affecting the ocular bulb posterior segment together with acute glaucoma. He initiated on prednisone 60 mg/day PO. After two weeks of systemic corticotherapy, the patient was asymptomatic, with evident regression of proptosis and scleritis and normal intraocular pressure (11 mmHg in AU). Although not very frequent, acute glaucoma may be present in orbital inflammatory process and should be treated with systemic corticotherapy and topical medication.

Fixed-combination treatments for intraocular hypertension in Chinese patients – focus on bimatoprost-timolol

PubMed Central

Fang, Yuan; Ling, Zhihong; Sun, Xinghuai

2015-01-01

Glaucoma is a common eye disease that can lead to irreversible vision loss if left untreated. The early diagnosis and treatment of primary open-angle glaucoma is challenging, and visual impairment in Chinese glaucoma patients is a serious concern. Most of these patients need more than one topical antiglaucoma agent to control their intraocular pressures (IOPs). In the People’s Republic of China, the daily cost of different glaucoma medication varies greatly, and the treatment habits differ throughout the country. Prostaglandin analogs (PGAs) are recommended as first-line monotherapy, because of their efficacy and low risk of systemic side effects. Fixed-combination drops, particularly PGA-based fixed combinations, have recently been developed and used in patients with progression or who have failed to achieve their target IOPs. Here, we reviewed the current literature on the use of bimatoprost-timolol fixed combination (BTFC) in the People’s Republic of China. BTFC has achieved good efficacy and tolerability in Chinese clinical trials. In addition, BTFC is more cost effective compared with other fixed combinations available in the People’s Republic of China. Fixed-combination drops may offer benefits, such as keeping the ocular surface healthy, convenience of administration, and improvement in long-term adherence and quality of life. Therefore, BTFC has great potential for the treatment of Chinese glaucoma patients. However, the long-term efficacy of BTFC, comparisons of BTFC with other fixed-combination drugs, and treatment adherence and persistence with treatment in Chinese patients are unknown and will require further study. PMID:25999695

Peripheral iridotomy for pigmentary glaucoma

PubMed Central

Michelessi, Manuele; Lindsley, Kristina

2016-01-01

Background Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome. Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. Objectives The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. Search methods We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. Selection criteria We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. Data collection and analysis We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest. Main results We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting. Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression. One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI −6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI −0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes. Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low. Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy. Authors' conclusions We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma). PMID:26871761

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.

Evaluating Glaucomatous Retinal Nerve Fiber Damage by GDx VCC Polarimetry in Taiwan Chinese Population

PubMed Central

Chen, Hsin-Yi; Huang, Mei-Ling; Huang, Wei-Cheng

2010-01-01

Purpose To study the capability of scanning laser polarimetry with variable corneal compensation (GDx VCC) to detect differences in retinal nerve fiber layer thickness between normal and glaucomatous eyes in a Taiwan Chinese population. Methods This study included 44 normal eyes and 107 glaucomatous eyes. The glaucomatous eyes were divided into three subgroups on the basis of its visual field defects (early, moderate, severe). Each subject underwent a GDx-VCC exam and visual field testing. The area under the receiver-operating characteristic curve (AROC) of each relevant parameter was used to differentiate normal from each glaucoma subgroup, respectively. The correlation between visual field index and each parameter was evaluated for the eyes in the glaucoma group. Results For normal vs. early glaucoma, the parameter with the best AROC was Nerve fiber indicator (NFI) (0.942). For normal vs. moderate glaucoma, the parameter showing the best AROC was NFI (0.985). For normal vs. severe glaucoma, the parameter that had the best AROC was NFI (1.000). For early vs. moderate glaucoma, the parameter with the best AROC was NFI (0.732). For moderate vs. severe, the parameter showing the best AROC was temporal-superior-nasal-inferior-temporal average (0.652). For early vs. severe, the parameter with the best AROC was NFI (0.852). Conclusions GDx-VCC-measured parameters may serve as a useful tool to distinguish normal from glaucomatous eyes; in particular, NFI turned out to be the best discriminating parameter.

Identifying key genes in glaucoma based on a benchmarked dataset and the gene regulatory network.

PubMed

Chen, Xi; Wang, Qiao-Ling; Zhang, Meng-Hui

2017-10-01

The current study aimed to identify key genes in glaucoma based on a benchmarked dataset and gene regulatory network (GRN). Local and global noise was added to the gene expression dataset to produce a benchmarked dataset. Differentially-expressed genes (DEGs) between patients with glaucoma and normal controls were identified utilizing the Linear Models for Microarray Data (Limma) package based on benchmarked dataset. A total of 5 GRN inference methods, including Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT) and GEne Network Inference with Ensemble of Trees (Genie3) were evaluated using receiver operating characteristic (ROC) and precision and recall (PR) curves. The interference method with the best performance was selected to construct the GRN. Subsequently, topological centrality (degree, closeness and betweenness) was conducted to identify key genes in the GRN of glaucoma. Finally, the key genes were validated by performing reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 176 DEGs were detected from the benchmarked dataset. The ROC and PR curves of the 5 methods were analyzed and it was determined that Genie3 had a clear advantage over the other methods; thus, Genie3 was used to construct the GRN. Following topological centrality analysis, 14 key genes for glaucoma were identified, including IL6 , EPHA2 and GSTT1 and 5 of these 14 key genes were validated by RT-qPCR. Therefore, the current study identified 14 key genes in glaucoma, which may be potential biomarkers to use in the diagnosis of glaucoma and aid in identifying the molecular mechanism of this disease.

Overcoming Barriers to Eye Care: Patient Response to a Medical Social Worker in a Glaucoma Service.

PubMed

Fudemberg, Scott J; Amarasekera, Dilru C; Silverstein, Marlee H; Linder, Kathryn M; Heffner, Paul; Hark, Lisa A; Waisbourd, Michael

2016-08-01

This paper investigates the patient response to a medical social worker in a glaucoma clinic. The literature suggests that medical social workers are effective in a variety of health care settings, yet the efficacy of a medical social worker in an adult ophthalmic setting has not been studied. We present the results of a retrospective chart review of 50 patients with glaucoma referred to a medical social worker between January 5, 2015 and June 31, 2015 in an outpatient clinic of an urban eye hospital. Clinical and demographic data, as well as the data from a quality of care questionnaire, were collected for each patient. Patients rated their interaction with the medical social worker as highly positive (mean = 4.75, 5-point Likert scale), and nearly 90 % of patients expressed interest in future contact with the social worker. Additionally, most patients reported that the social worker resolved the issues they were facing (61.1 %), supported them in seeing their ophthalmologist (70.6 %), and helped them to manage their glaucoma (69.7 %). Reported barriers to glaucoma care were emotional distress; cost of office visits and medications; lack of medical insurance; transportation; poor medication adherence; impairment of daily activities; follow-up adherence; and language. As vision loss from glaucoma is irreversible, it is important to detect and treat patients at early stages of the disease. Therefore, it is imperative for patients to regularly visit their eye care providers and adhere to treatment and follow-up recommendations. This study suggests that a medical social worker could play a pivotal role in helping patients with glaucoma overcome barriers to treatment and facilitate disease management.

Conjunctival inclusion cyst following repair of tube erosion in a child with aphakic glaucoma, leading to endophthalmitis.

PubMed

Roy, Avik Kumar; Senthil, Sirisha

2015-01-01

Glaucoma in aphakia is a major long term complication following congenital cataract surgery. Implantation of glaucoma drainage device provides an effective approach to manage refractory paediatric glaucoma. However implant surgery in young individuals is not free of complications. The prompt detection and management of tube erosion is of utmost importance to prevent devastating sequel of endophthalmitis. Implantation cyst following repair of tube erosion has not been reported so far. This case illustrates the rare occurrence of inclusion cyst following repair of tube erosion, the possible causes and its consequences. A 2-year-old child with aphakia developed intractable glaucoma. Following a failed glaucoma filtering surgery he underwent sequential Ahmed Glaucoma Valve implantation in both the eyes. Six weeks following right eye surgery, the child presented with conjunctival erosion overlying the tube, which was treated with scleral patch graft and conjunctival advancement. One month after the repair of tube erosion, the child presented with implantation cyst under the scleral patch graft, which was treated by drainage with a 29G needle. The child presented with endophthalmitis of his right eye following an episode of bilateral conjunctivitis. This was managed by an emergency pars plana vitrectomy, intraocular antibiotics and tube excision. At the last follow up visit, the IOP was 20 mmHg with 2 topical antiglaucoma medications in the right eye following a trans scleral photocoagulation. Lifelong careful follow-up of paediatric eyes with implant surgery is mandatory to look for complication such as tube erosion. It is important to place additional sutures to secure the patch graft during implantation of glaucoma drainage devices in children to prevent graft displacement and consequent tube erosion. During repair of tube erosion, it is crucial to remove all the conjunctival epithelium around the tube, thus not to incorporate epithelial tissue within the surgical wound.

The Cost-Effectiveness Analysis of Teleglaucoma Screening Device

PubMed Central

Thomas, Sera

2015-01-01

Glaucoma is the leading cause of irreversible vision loss and costs the American economy $2.9 billion. Teleglaucoma remotely detects glaucoma improving access to ophthalmic care in rural areas. It helps manage glaucoma more efficiently to preserve vision and reduce healthcare costs. A cost-effectiveness analysis was conducted using healthcare provider or third-party payer perspective within rural Canada. The study population were patients at-risk of glaucoma which includes those with diabetes and/or hypertension, family history of glaucoma, adults older than 50 years, and concurrent ocular conditions in rural Alberta. Markov modelling was used to model glaucoma health states. Effectiveness was measured in Quality-Adjusted Life Years (QALYs) and costs were used in Canadian dollars. Using TreeAge Pro 2009, incremental cost-effectiveness ratios (ICER) were developed in dollars per QALYs. Deterministic and probabilistic sensitivity analyses were performed to assess the factors affecting cost-effectiveness. Teleglaucoma had a 20% increase in ophthalmologist-referral rate; it reduced patient travel times by 61 hours and physician wait times by 30% in comparison to in-person examination (standard of care). Teleglaucoma costs $872 per patient screened which was 80% less than in-person examination. Teleglaucoma had a greater incremental effectiveness providing an additional 0.12 QALY per patient examination. It was more sensitive (86.5%) and less specific (78.6%) than in-person examination. Teleglaucoma was more cost-effective than in-person examination with an ICER of-$27,460/QALY. This indicated that teleglaucoma will save $27, 460 for each additional QALY gained. Long term benefits showed teleglaucoma prevents 24% cases of glaucoma blindness after 30 years. Teleglaucoma demonstrated improved health outcomes, as well as, cost benefits. It increases access to ophthalmic care and improves healthcare service efficiency, specifically in rural areas. Teleglaucoma is more cost-effective than current in-person examination and can improve the quality of life in glaucoma patients. PMID:26382956

The Cost-Effectiveness Analysis of Teleglaucoma Screening Device.

PubMed

Thomas, Sera; Hodge, William; Malvankar-Mehta, Monali

2015-01-01

Glaucoma is the leading cause of irreversible vision loss and costs the American economy $2.9 billion. Teleglaucoma remotely detects glaucoma improving access to ophthalmic care in rural areas. It helps manage glaucoma more efficiently to preserve vision and reduce healthcare costs. A cost-effectiveness analysis was conducted using healthcare provider or third-party payer perspective within rural Canada. The study population were patients at-risk of glaucoma which includes those with diabetes and/or hypertension, family history of glaucoma, adults older than 50 years, and concurrent ocular conditions in rural Alberta. Markov modelling was used to model glaucoma health states. Effectiveness was measured in Quality-Adjusted Life Years (QALYs) and costs were used in Canadian dollars. Using TreeAge Pro 2009, incremental cost-effectiveness ratios (ICER) were developed in dollars per QALYs. Deterministic and probabilistic sensitivity analyses were performed to assess the factors affecting cost-effectiveness. Teleglaucoma had a 20% increase in ophthalmologist-referral rate; it reduced patient travel times by 61 hours and physician wait times by 30% in comparison to in-person examination (standard of care). Teleglaucoma costs $872 per patient screened which was 80% less than in-person examination. Teleglaucoma had a greater incremental effectiveness providing an additional 0.12 QALY per patient examination. It was more sensitive (86.5%) and less specific (78.6%) than in-person examination. Teleglaucoma was more cost-effective than in-person examination with an ICER of-$27,460/QALY. This indicated that teleglaucoma will save $27, 460 for each additional QALY gained. Long term benefits showed teleglaucoma prevents 24% cases of glaucoma blindness after 30 years. Teleglaucoma demonstrated improved health outcomes, as well as, cost benefits. It increases access to ophthalmic care and improves healthcare service efficiency, specifically in rural areas. Teleglaucoma is more cost-effective than current in-person examination and can improve the quality of life in glaucoma patients.

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

Evaluation of retinal ganglion cell function after intraocular pressure reduction measured by pattern electroretinogram in patients with primary open-angle glaucoma.

PubMed

Karaśkiewicz, Joanna; Penkala, Krzysztof; Mularczyk, Maciej; Lubiński, Wojciech

2017-04-01

To evaluate retinal ganglion cell (RGC) function after intraocular pressure (IOP) reduction measured by pattern electroretinogram (PERG) in patients with newly diagnosed, non-treated preperimetric and early stages of primary open-angle glaucoma (POAG). Twenty-four eyes from 24 patients with POAG: 11 eyes with preperimetric glaucoma and 13 eyes with early glaucoma received Ganfort ® (bimatoprost + timolol) once a day for a period of 1 month. Before and after the treatment, following measurements were analyzed: IOP, mean ocular perfusion pressure (MOPP), peak time of P50 and amplitude of P50 and N95 waves in PERG (ISCEV standard 2012). Correlations between PERG P50 and N95 waves, IOP and MOPP were calculated. After therapy, IOP significantly decreased in all eyes, on average 31%. Significant increase in MOPP in all eyes on average 14% was detected. PERG amplitude of P50 and N95 waves increased in 75 and 79% eyes, respectively, on average P50 by 28% and N95 by 38%. There were no significant interactions between the change of PERG parameters in time and stage of glaucoma. Significant IOP-lowering therapy can improve RGC function measured by PERG, in patients with preperimetric and early stages of POAG.

[Evaluation of the efficacy of diode laser endocyclophotocoagulation combined with cataract surgery in glaucoma].

PubMed

Ezzouhairi, S M

2015-11-01

Surgical techniques, which reduce the secretion of aqueous humor are underutilized in the surgical management of glaucoma; the diode laser coupled to an endoscope, endocyclophotocoagulation (ECP), is an emerging technology in the treatment of glaucoma. Indeed, thanks to its direct, focal and controllable approach to diode laser treatment of the ciliary processes, ECP renders this a safer technique compared to transscleral diode laser. We present preliminary results and an evaluation of the efficacy of ECP combined with cataract surgery performed at the Al Bassar clinic in Mohammedia, Morocco. We conducted a retrospective study on a series of 82 patients who underwent combined surgery: diode laser endocyclophotocoagulation and cataract for treatment of glaucoma during the period from December 2012 to July 2013. For this study, we recorded: age and gender of the patients, number and power of diode laser spots, pre- and postoperative intraocular pressure (IOP), and the number of anti-glaucoma treatments prescribed pre- and postoperatively (3 months minimum). Technically, a 20-gauge endo-ocular probe is inserted through the corneal incision used for phacoemulsification. The probe is equipped with a light source, a camera and a pulsed 810 nm laser beam; it is connected to an Endo-optiks type generator, which allows for direct visualization of the ciliary processes and their precise treatment. The surgical procedure is both simple and quick. Postoperative follow-up is unchanged from the management of cataract extraction by phacoemulsification. The average age in our series was 69.5 years (range 33-81 years), mean follow-up was 5.7 months. The reduction in intraocular pressure was 28.5%. In 40% of patients, a significant reduction in medications was noted, and in 20%, a total suspension of anti-glaucoma medications. No serious complications were noted in our series. This technique can perfectly fit into the medical, natural and/or surgical armamentarium medical, physical, surgical to halt progression of glaucomatous disease. The IOP lowering obtained by this combined surgery is significantly greater than that obtained after phacoemulsification alone in open-angle glaucoma. It can accommodate many situations for which conventional surgery has limitations. In addition, this technique has the advantage of preserving the bulbar conjunctiva for any subsequent glaucoma surgeries. Our preliminary results are very satisfactory. This combined technique is simple, safe and effective. This allows broadening of its indications to include moderate glaucoma, stabilized or not, in addition to refractory glaucoma. Also, from an economic point of view, the gain for the patient is significant. Of course, longer-term follow-up is required to confirm these results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

Can Automated Imaging for Optic Disc and Retinal Nerve Fiber Layer Analysis Aid Glaucoma Detection?

PubMed

Banister, Katie; Boachie, Charles; Bourne, Rupert; Cook, Jonathan; Burr, Jennifer M; Ramsay, Craig; Garway-Heath, David; Gray, Joanne; McMeekin, Peter; Hernández, Rodolfo; Azuara-Blanco, Augusto

2016-05-01

To compare the diagnostic performance of automated imaging for glaucoma. Prospective, direct comparison study. Adults with suspected glaucoma or ocular hypertension referred to hospital eye services in the United Kingdom. We evaluated 4 automated imaging test algorithms: the Heidelberg Retinal Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) glaucoma probability score (GPS), the HRT Moorfields regression analysis (MRA), scanning laser polarimetry (GDx enhanced corneal compensation; Glaucoma Diagnostics (GDx), Carl Zeiss Meditec, Dublin, CA) nerve fiber indicator (NFI), and Spectralis optical coherence tomography (OCT; Heidelberg Engineering) retinal nerve fiber layer (RNFL) classification. We defined abnormal tests as an automated classification of outside normal limits for HRT and OCT or NFI ≥ 56 (GDx). We conducted a sensitivity analysis, using borderline abnormal image classifications. The reference standard was clinical diagnosis by a masked glaucoma expert including standardized clinical assessment and automated perimetry. We analyzed 1 eye per patient (the one with more advanced disease). We also evaluated the performance according to severity and using a combination of 2 technologies. Sensitivity and specificity, likelihood ratios, diagnostic, odds ratio, and proportion of indeterminate tests. We recruited 955 participants, and 943 were included in the analysis. The average age was 60.5 years (standard deviation, 13.8 years); 51.1% were women. Glaucoma was diagnosed in at least 1 eye in 16.8%; 32% of participants had no glaucoma-related findings. The HRT MRA had the highest sensitivity (87.0%; 95% confidence interval [CI], 80.2%-92.1%), but lowest specificity (63.9%; 95% CI, 60.2%-67.4%); GDx had the lowest sensitivity (35.1%; 95% CI, 27.0%-43.8%), but the highest specificity (97.2%; 95% CI, 95.6%-98.3%). The HRT GPS sensitivity was 81.5% (95% CI, 73.9%-87.6%), and specificity was 67.7% (95% CI, 64.2%-71.2%); OCT sensitivity was 76.9% (95% CI, 69.2%-83.4%), and specificity was 78.5% (95% CI, 75.4%-81.4%). Including only eyes with severe glaucoma, sensitivity increased: HRT MRA, HRT GPS, and OCT would miss 5% of eyes, and GDx would miss 21% of eyes. A combination of 2 different tests did not improve the accuracy substantially. Automated imaging technologies can aid clinicians in diagnosing glaucoma, but may not replace current strategies because they can miss some cases of severe glaucoma. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

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.

Managing high risk glaucoma with the Ahmed valve implant: 20 years of experience

PubMed Central

Rotsos, Tryfon; Tsioga, Anastasia; Andreanos, Konstantinos; Diagourtas, Andreas; Petrou, Petros; Georgalas, Ilias; Papaconstantinou, Dimitrios

2018-01-01

AIM To estimate the efficacy and safety of the Ahmed implant in patients with high risk for failure after glaucoma surgery. METHODS In 342 eyes of 342 patients with refractory glaucoma, even with application of medical treatment, the Ahmed valve was introduced for intraocular pressure (IOP) control, in the period of the last 20y. The nature of glaucoma was neovascular in 162 eyes, pseudophakic or aphakic in 49 eyes, inflammatory in 29 eyes and non working previous antiglaucomatic surgical interventions in 102 eyes. RESULTS Follow-up ranged from 18 to 120mo with a mean follow-up of 63.2mo. IOP before the operation decreased from 31.6±10.4 mm Hg to 18.3±5.4 mm Hg (no systemic treatment) at the end of follow up period. When we compared the IOP values before the operation using ANOVA showed statistically significant difference (P<0.001). The success rate was 85.2% during the first semester, 76.8% at 12mo and 50.3% at the end of follow up period (18 to 120mo after implantation). Success rate was 25.7% in neovascular glaucoma, 63.2% in aphakic glaucoma and 73.8% in non working previous antiglaucomatic surgical interventions. Complications due to the implant were: serous choroidal detachment in 14.8%, blockage of the tube in 2.8%, malposition of the tube in 4.9%, suprachoroidal hemorrhage in 2.1%, cataract progression in 39.6% (phakic eyes), shallow anterior chamber in 9.2%, hyphaema in 28.9%, exposure of valve in 2.6%, exposure of tube in 9.3%, hypotony in 4.9% and conjunctival fibrosis in 41.5%. CONCLUSION Despite the fact that Ahmed valve implant had suchlike results as other implants concerning the IOP control, complications rate due to hypotony or over filtration in the first days after the intervention are not that frequent as with other valve implants. PMID:29487813

Managing high risk glaucoma with the Ahmed valve implant: 20 years of experience.

PubMed

Rotsos, Tryfon; Tsioga, Anastasia; Andreanos, Konstantinos; Diagourtas, Andreas; Petrou, Petros; Georgalas, Ilias; Papaconstantinou, Dimitrios

2018-01-01

To estimate the efficacy and safety of the Ahmed implant in patients with high risk for failure after glaucoma surgery. In 342 eyes of 342 patients with refractory glaucoma, even with application of medical treatment, the Ahmed valve was introduced for intraocular pressure (IOP) control, in the period of the last 20y. The nature of glaucoma was neovascular in 162 eyes, pseudophakic or aphakic in 49 eyes, inflammatory in 29 eyes and non working previous antiglaucomatic surgical interventions in 102 eyes. Follow-up ranged from 18 to 120mo with a mean follow-up of 63.2mo. IOP before the operation decreased from 31.6±10.4 mm Hg to 18.3±5.4 mm Hg (no systemic treatment) at the end of follow up period. When we compared the IOP values before the operation using ANOVA showed statistically significant difference ( P <0.001). The success rate was 85.2% during the first semester, 76.8% at 12mo and 50.3% at the end of follow up period (18 to 120mo after implantation). Success rate was 25.7% in neovascular glaucoma, 63.2% in aphakic glaucoma and 73.8% in non working previous antiglaucomatic surgical interventions. Complications due to the implant were: serous choroidal detachment in 14.8%, blockage of the tube in 2.8%, malposition of the tube in 4.9%, suprachoroidal hemorrhage in 2.1%, cataract progression in 39.6% (phakic eyes), shallow anterior chamber in 9.2%, hyphaema in 28.9%, exposure of valve in 2.6%, exposure of tube in 9.3%, hypotony in 4.9% and conjunctival fibrosis in 41.5%. Despite the fact that Ahmed valve implant had suchlike results as other implants concerning the IOP control, complications rate due to hypotony or over filtration in the first days after the intervention are not that frequent as with other valve implants.

An automated and robust image processing algorithm for glaucoma diagnosis from fundus images using novel blood vessel tracking and bend point detection.

PubMed

M, Soorya; Issac, Ashish; Dutta, Malay Kishore

2018-02-01

Glaucoma is an ocular disease which can cause irreversible blindness. The disease is currently identified using specialized equipment operated by optometrists manually. The proposed work aims to provide an efficient imaging solution which can help in automating the process of Glaucoma diagnosis using computer vision techniques from digital fundus images. The proposed method segments the optic disc using a geometrical feature based strategic framework which improves the detection accuracy and makes the algorithm invariant to illumination and noise. Corner thresholding and point contour joining based novel methods are proposed to construct smooth contours of Optic Disc. Based on a clinical approach as used by ophthalmologist, the proposed algorithm tracks blood vessels inside the disc region and identifies the points at which first vessel bend from the optic disc boundary and connects them to obtain the contours of Optic Cup. The proposed method has been compared with the ground truth marked by the medical experts and the similarity parameters, used to determine the performance of the proposed method, have yield a high similarity of segmentation. The proposed method has achieved a macro-averaged f-score of 0.9485 and accuracy of 97.01% in correctly classifying fundus images. The proposed method is clinically significant and can be used for Glaucoma screening over a large population which will work in a real time. Copyright © 2017 Elsevier B.V. All rights reserved.

[Comparing the ranges of defect measured with standard white on white and Pulsar perimetries].

PubMed

González de la Rosa, M; González-Hernández, M; García-Feijoo, J; Sánchez Méndez, M; García-Sánchez, J

2011-04-01

Normal thresholds on Pulsar perimetry fall faster than those of standard perimetry in the peripheral visual field. Two related studies were performed. Firstly, the frequency distributions of glaucoma defects on standard automated perimetry (SAP) and the relationship of the centre and periphery (Study A) were studied first, followed by an attempt to establish the limits of pulsar perimetry (Study B). A: frequency of defects was calculated in 78.663 SAP perimetries (G1-TOP, Octopus 1-2-3, Haag-Streit). Study B: 204 eyes with mean defect (MD-SAP) lower than 9 dB were examined 8.92 ± 4.19 times with SAP (TOP-32, Octopus 311) and temporal modulation perimetry (T30W, Pulsar Perimeter, Haag-Streit). Study A: 50.7% of the SAP examinations showed MD values lower than 9 dB and 32.7% bellow 6 dB. The MD correlation of the central 20° with the MD of the most peripheral points was r=0.933. Study B: in cases with MD-TOP-32 lower than 6 dB, SAP had the maximum possibility of detecting defect in 0.02% of points and Pulsar in 0.29%. In subjects with MD-TOP-32 between 6 and 9 dB frequencies were 0.38% in SAP and 3.5% in Pulsar (5.1% for eccentricities higher than 20°). Pulsar allows detecting defects, without range limitations, in the initial half of SAP frequencies expected on glaucoma patients. In order to study the progression of deeper defects the examination should focus on the central points, where the dynamic range of both systems is more equivalent. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

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%.

National and subnational prevalence and burden of glaucoma in China: A systematic analysis

PubMed Central

Song, Peige; Wang, Jiawen; Bucan, Kajo; Theodoratou, Evropi; Rudan, Igor; Chan, Kit Yee

2017-01-01

Background Glaucoma, the second leading cause of blindness, affects approximately 64.3 million individuals worldwide. In China, demographic ageing is in rapid progress. Yet detailed and up–to–date estimates of the scale of glaucoma are rare. We aimed to quantify and understand the prevalence and burden of glaucoma in China from 1990 to 2015, with projections until 2050. Methods For this systematic review and meta–analysis, we searched China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM–SinoMed), PubMed, Embase and Medline using comprehensive search strategies to identify all relevant articles that have reported the prevalence of glaucoma in the general Chinese population. We used a multilevel mixed–effect meta–regression to estimate the prevalence rates of primary open–angle glaucoma (POAG) and primary angle–closure glaucoma (PACG), and a random–effects meta–analysis to pool the overall prevalence of secondary glaucoma. United Nations population data were used to estimate and project the number of people with glaucoma from 1990 to 2050. Univariable and multivariable meta–regressions were conducted to assess the association between the prevalence of POAG and PACG and relevant demographic and geographic factors. The national burden of POAG and PACG in the years 2000 and 2010 were distributed to six geographic regions accordingly. Results From 1990 to 2015, the prevalence of all glaucoma ranged from 2.59% (95% CI = 1.96–3.49) to 2.58% (95% CI = 1.94–3.47). For different subtypes of glaucoma, the overall prevalence of POAG ranged from 1.03% (95% CI = 0.67–1.58) in 1990 to 1.02% (95% CI = 0.67–1.57) in 2015, PACG from 1.41% (95% CI = 1.18–1.68) to 1.40% (95% CI = 1.17–1.68). The overall prevalence of secondary glaucoma was 0.15% (95% CI = 0.10–0.23) during this period. The number of people with all glaucoma in China was 5.92 million (95% CI = 4.47–7.97) in 1990, and 13.12 million (95% CI = 9.88–17.68) in 2015. This increasing trend was also witnessed in different subtypes of glaucoma. The number of people affected by POAG increased from 2.35 million (95% CI = 1.54–3.60) in 1990 to 5.22 million (95% CI = 3.40–7.98) in 2015, PACG from 3.22 million (95% CI = 2.70–3.84) to 7.14 million (95% CI = 5.97–8.53), and secondary glaucoma from 0.34 million (95% CI = 0.23–0.53) to 0.76 million (95% CI = 0.51–1.17). In 2015, more than half (54.42%) of the glaucoma cases were PACG, followed by POAG (39.79%) and secondary glaucoma (5.79%). By 2050, the number of all glaucoma cases in China will be 25.16 million (95% CI = 18.96–33.86). In the multivariable meta–regressions, the odds ratio (OR) for each decade’s increase in age was 1.43 (95% CI = 1.33–1.55) for POAG, and 1.65 (95% CI = 1.51–1.80) for PACG; males were more likely to have POAG (OR 1.36, 95% CI = 1.17–1.59), but less likely to have PACG (OR 0.53, 95% CI = 0.46–0.60) compared with females. After adjustment of age and gender, people living in urban areas were more likely to have POAG compared with those in rural areas (OR 1.54, 95% CI = 1.02–2.35). People in Northeast China were at a higher risk (OR 1.77, 95% CI = 1.07–2.94) of having PACG than people in East China. Among the six regions, East China owed the most POAG and PACG cases, whereas Northwest China owed the least. Conclusions This systematic review and meta–analysis suggests a substantial burden of glaucoma in China, with great variances among the different age groups, genders, settings and geographic regions. With the dramatic ageing trend in the next three decades, the prevalence and burden of glaucoma will continue to increase. More elaborate epidemiological studies are needed to optimise public health strategies for mitigating this important health problem. PMID:29302324

Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.

PubMed

Nafissi, Nafiseh; Foldvari, Marianna

2015-01-01

Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect. It has been suggested that the long-term expression of neurotrophic factors is the ultimate approach to prevent and/or treat neurodegenerative disorders such as glaucoma in patients who do not respond to available treatments or are at the progressive stage of the disease. Recent preclinical research suggests that novel neuroprotective gene and cell therapeutics could be promising approaches for both non-invasive neuroprotection and regenerative functions in the eye. Several progenitor and retinal cell types have been investigated as potential candidates for glaucoma neurotrophin therapy either as targets for gene therapy, options for cell replacement therapy, or as vehicles for gene delivery. Therefore, in parallel with deeper understanding of the specific protective effects of different neurotrophic factors and the potential therapeutic cell candidates for glaucoma neuroprotection, the development of non-invasive and highly specific gene delivery methods with safe and effective technologies to modify cell candidates for life-long neuroprotection in the eye is essential before investing in this field.

Edaravone suppresses retinal ganglion cell death in a mouse model of normal tension glaucoma

PubMed Central

Akaiwa, Kei; Namekata, Kazuhiko; Azuchi, Yuriko; Guo, Xiaoli; Kimura, Atsuko; Harada, Chikako; Mitamura, Yoshinori; Harada, Takayuki

2017-01-01

Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP) and exhibits glaucomatous pathology including glutamate neurotoxicity and oxidative stress. In the present study, we found that edaravone, a free radical scavenger that is used for treatment of acute brain infarction and amyotrophic lateral sclerosis (ALS), reduces oxidative stress and prevents RGC death and thinning of the inner retinal layer in EAAC1-deficient (KO) mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment in EAAC1 KO mice was ameliorated with edaravone treatment, clearly establishing that edaravone beneficially affects both histological and functional aspects of the glaucomatous retina. Our findings raise intriguing possibilities for the management of glaucoma by utilizing a widely prescribed drug for the treatment of acute brain infarction and ALS, edaravone, in combination with conventional treatments to lower IOP. PMID:28703795

Upcoming Methods and Specifications of Continuous Intraocular Pressure Monitoring Systems for Glaucoma

PubMed Central

Molaei, Amir; Karamzadeh, Vahid; Safi, Sare; Esfandiari, Hamed; Dargahi, Javad; Khosravi, Mohammad Azam

2018-01-01

Glaucoma is the leading cause of irreversible blindness and vision loss in the world. Although intraocular pressure (IOP) is no longer considered the only risk factor for glaucoma, it is still the most important one. In most cases, high IOP is secondary to trabecular meshwork dysfunction. High IOP leads to compaction of the lamina cribrosa and subsequent damage to retinal ganglion cell axons. Damage to the optic nerve head is evident on funduscopy as posterior bowing of the lamina cribrosa and increased cupping. Currently, the only documented method to slow or halt the progression of this disease is to decrease the IOP; hence, accurate IOP measurement is crucial not only for diagnosis, but also for the management. Due to the dynamic nature and fluctuation of the IOP, a single clinical measurement is not a reliable indicator of diurnal IOP; it requires 24-hour monitoring methods. Technological advances in microelectromechanical systems and microfluidics provide a promising solution for the effective measurement of IOP. This paper provides a broad overview of the upcoming technologies to be used for continuous IOP monitoring. PMID:29403593

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

Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension.

PubMed

Aptel, Florent; Choudhry, Reena; Stalmans, Ingeborg

2016-08-01

This study compared the efficacy, safety, and pharmacokinetics of a preservative-free latanoprost formulation to an established, benzalkonium chloride (BAK) containing formulation for the treatment of open-angle glaucoma or ocular hypertension. This was a phase II, randomized, cross-over, investigator-masked, multi-center, pilot study (NCT01494753). A total of 30 untreated adult patients (aged ≥18 years) with primary open angle glaucoma, pseudo-exfoliative glaucoma, pigmentary glaucoma, or ocular hypertension received either preservative-free or preserved latanoprost once daily in both eyes for 6 weeks, before crossing over to receive the other treatment. Efficacy (intraocular pressure [IOP] at 8 am, midday, 4 pm and 8 pm, and global efficacy assessment by investigator), safety (adverse events, ocular symptoms and global tolerance, slit lamp examination, funduscopy, visual field examination, visual acuity, and heart rate), and pharmacokinetics were assessed at Days 0, 42, and 84. Both treatments resulted in a reduction in IOP that was similar for the preservative-free and the preserved formulation at all time points. Similarly, the overall diurnal reduction was similar in both groups (6.3 mmHg [27.9% reduction] and 6.4 mmHg [28.1% reduction] for preserved and preservative-free latanoprost, respectively). There were no differences in global efficacy assessment or in the safety and tolerance of each treatment. Systemic concentrations of latanoprost were very low; AUC0-30 and Cmax were lower and tmax was longer for preservative-free latanoprost. Preservative-free latanoprost showed similar efficacy at all time points compared to BAK preservative containing formulation, with no difference in tolerance, allowing progression to phase III clinical development.

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics.

PubMed

Rossetti, Luca; Digiuni, Maurizio; Montesano, Giovanni; Giovanni, Montesano; Centofanti, Marco; Fea, Antonio M; Iester, Michele; Frezzotti, Paolo; Figus, Michele; Ferreras, Antonio; Oddone, Francesco; Tanga, Lucia; Rolle, Teresa; Battaglino, Valentina; Posarelli, Chiara; Motolese, Ilaria; Mittica, Pietro; Bagaglia, Simone Alex; Menicacci, Cristina; De Cilla', Stefano; Autelitano, Alessandro; Fogagnolo, Paolo

2015-01-01

To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder ('controls'). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Evaluation of retinal nerve fiber layer thickness and choroidal thickness in pseudoexfoliative glaucoma and pseudoexfoliative syndrome.

PubMed

Ozge, Gokhan; Koylu, Mehmet Talay; Mumcuoglu, Tarkan; Gundogan, Fatih Cakir; Ozgonul, Cem; Ayyildiz, Onder; Kucukevcilioglu, Murat

2016-05-01

To compare retinal nerve fiber layer thickness (RNFLT) and choroidal thickness (ChT) measurements in eyes with pseudoexfoliative (PEX) glaucoma, PEX syndrome and healthy control eyes. Eighteen patients with PEX glaucoma in one eye and PEX syndrome in the fellow eye were included. The right eyes of thirty-nine age- and sex-matched healthy subjects were included as control group. All participants underwent a detailed biomicroscopic and funduscopic examination. RNFLT and ChT measurements were performed with a commercially available spectral-domain optical coherence tomography (SD-OCT). ChT measurements were performed by using enhanced depth imaging (EDI) mode. Patients with PEX underwent diurnal IOP measurements with 4-hour intervals before inclusion in the study. RNFLT results included the average measurement and 6 quadrants (temporal, inferotemporal, inferonasal, nasal, superonasal and supero-temporal). ChT measurements were performed in the subfoveal region and around the fovea (500µm and 1500 µm nasal and temporal to the fovea), as well as around the optic disc (average peripapillary and eight quadrants in the peripapillary region (temporal, inferotemporal, inferior, inferonasal, nasal, superonasal, superior, supero-temporal)). RNFLT in all quadrants and average thickness were significantly lower in PEX glaucoma eyes compared to PEX syndrome eyes and healthy control eyes (p<0.001 for both). RNFLT comparisons between PEX syndrome and healthy control eyes did not show a significant difference (p>0.05) except the inferotemporal quadrant. ChT measurements were similar between groups (p>0.05). Thinning of the RNFL in association with unchanged ChT may mean that the presence of PEX material is a much more significant risk factor than choroidal changes in the progression of PEX syndrome to PEX glaucoma.

Wireless miniature implantable devices and ASICs for monitoring, treatment, and study of glaucoma and cardiac disease

NASA Astrophysics Data System (ADS)

Chow, Eric Y.

Glaucoma affects about 65 million people and is the second leading cause of blindness in the world. Although the condition is irreversible and incurable, early detection is vital to slowing and even stopping the progression of the disease. Our work focuses on the design, fabrication, and assembly of a continuous active glaucoma intraocular pressure (IOP) monitor that provides clinicians with the necessary data to more accurately diagnose and treat patients. Major benefits of an active monitoring device include the potential to develop a closed-loop treatment system and to operate independently for extended periods of time. The fully wireless operation uses gigahertzfrequency electromagnetic wave propagation, which allows for an orientation independent transfer of power and data over reasonable distances. Our system is comprised of a MEMS capacitive sensor, capacitive power storage array, ASIC, and monopole antenna assembled into a biocompatible liquid crystal polymer (LCP) package. We have performed in vivo trials on rabbits, both chronic and acute, to validate system functionality, fully wireless feasibility, and biocompatibility. Heart failure (HF) affects approximately 2% of the adult population in developed countries and 6-10% of people over the age of 65. Continuous monitoring of blood pressure, flow, and chemistry from a minimally invasive device can serve as a diagnostic and early-warning system for cardiac health. We developed a miniaturized system attached to the outer surface of an FDA approved stent, used as both the antenna for wireless telemetry/powering and structural support. The system comprises of a MEMS pressure sensor, ASIC for the sensor interface and wireless capabilities, LCP substrate, and FDA approved stent. In vivo studies on pigs validated functionality and fully wireless operation and demonstrate the feasibility of a stent-based wireless implant for continuous monitoring of blood pressure as well as other parameters including oxygen, flow and turbulence, chemistry, and glucose.

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.

[Thinking about the present primary open angle glaucoma early diagnosis concepts and methods].

PubMed

Ren, Zeqin

2014-05-01

Early diagnosis of primary open-angle glaucoma has not been clear and consistent in concepts and methods. At present, according to the pathophysiology process of optic nerve damage and its detection technology, early diagnosis on the concept still belongs to the early clinical diagnosis instead of preclinical diagnosis, and on the method depends on the fundus as morphological index combined with the visual field as functional index. The direction of early clinical diagnosis mainly lies in exploring more effective diagnosis index, rather than blindly adopt new diagnostic technology.

Measurement precision in a series of visual fields acquired by the standard and fast versions of the Swedish interactive thresholding algorithm: analysis of large-scale data from clinics.

PubMed

Saunders, Luke J; Russell, Richard A; Crabb, David P

2015-01-01

Swedish Interactive Thresholding Algorithm (SITA) testing strategies for the Humphrey Field Analyzer have become a clinical standard. Measurements from SITA Fast are thought to be more variable than SITA Standard, yet some clinics routinely use SITA Fast because it is quicker. To examine the measurement precision of the 2 SITA strategies across a range of sensitivities using a large number of visual field (VF) series from 4 glaucoma clinics in England. Retrospective cohort study at Moorfields Eye Hospital in London, England; Gloucestershire Eye Unit at Cheltenham General Hospital; Queen Alexandra Hospital in Portsmouth, England; and the Calderdale and Huddersfield National Health Service Foundation Trust that included 66,974 Humphrey 24-2 SITA Standard VFs (10,124 eyes) and 19,819 Humphrey 24-2 SITA Fast VFs (3654 eyes) recorded between May 20, 1997, and September 20, 2012. Pointwise ordinary least squares linear regression of measured sensitivity over time was conducted using VF series of 1 random eye from each patient. Residuals from the regression were pooled according to fitted sensitivities. For each sensitivity (decibel) level, the standard deviation of the residuals was used to estimate measurement precision and were compared for SITA Standard and SITA Fast. Simulations of progression from different VF baselines were used to evaluate how different levels of precision would affect time to detect VF progression. Median years required to detect progression. Median (interquartile range) patient age, follow-up, and series lengths for SITA Standard were 64 (53-72) years, 6.0 (4.0-8.5) years, and 6 (4-8) VFs, respectively; for SITA Fast, medians (interquartile range) were 70 (61-78) years, 5.1 (3.2-7.3) years, and 5 (4-6) VFs. Measurement precision worsened as sensitivity decreased for both test strategies. In the 20 to 5 dB range, SITA Fast was less precise than SITA Standard; this difference was largest between 15 to 10 dB, where variability in both methods peaked. Translated to median time to detection, differences in measurement precision were negligible, suggesting minimal effects on time to detect progression. Although SITA Standard is a more precise testing algorithm than SITA Fast at lower VF sensitivities, it is unlikely to make a sizeable difference to improving the time to detect VF progression.

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

Protecting the retinal neurons from glaucoma: lowering ocular pressure is not enough.

PubMed

Pascale, Alessia; Drago, Filippo; Govoni, Stefano

2012-07-01

The retina is theater of a number of biochemical reactions allowing, within its layers, the conversion of light impulses into electrical signals. The axons of the last neuronal elements, the ganglion cells, form the optic nerve and transfer the signals to the brain. Therefore, an appropriate cellular communication, not only within the different retinal cells, but also between the retina itself and the other brain structures, is fundamental. One of the most diffuse pathologies affecting retinal function and communication, which thus reverberates in the whole visual system, is glaucoma. This insidious disease is characterized by a progressive optic nerve degeneration and sight loss which may finally lead to irreversible blindness. Nevertheless, the progressive nature of this pathology offers an opportunity for therapeutic intervention. To better understand the cellular processes implicated in the development of glaucoma useful to envision a targeted pharmacological strategy, this manuscript first examines the complex cellular and functional organization of the retina and subsequently identifies the targets sensitive to neurodegeneration. Within this context, high ocular pressure represents a key risk factor. However, recent literature findings highlight the concept that lowering ocular pressure is not enough to prevent/slow down glaucomatous damage, suggesting the importance of combining the hypotensive treatment with other pharmacological approaches, such as the use of neuroprotectants. Therefore, this important and more novel aspect is extensively considered in this review, also emphasizing the idea that the neuroprotective strategy should be extended to the entire visual system and not restricted to the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care.

PubMed

Rhodes, Lindsay A; Huisingh, Carrie E; McGwin, Gerald; Mennemeyer, Stephen T; Bregantini, Mary; Patel, Nita; Saaddine, Jinan; Crews, John E; Girkin, Christopher A; Owsley, Cynthia

2016-01-01

To assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients' knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY. New or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: African Americans ≥40 years of age, Whites ≥50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients' CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2-4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar's test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized. At follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline (P≤0.01 for all questions). Those who were unemployed (odds ratio =0.63, 95% confidence interval =0.42-0.95, P=0.026) or had lower education (odds ratio =0.55, 95% confidence interval =0.29-1.02, P=0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level characteristics. Ninety-eight percent (n=501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n=326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%). Improved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness.

Do non-communicable diseases such as hypertension and diabetes associate with primary open-angle glaucoma? Insights from a case-control study in Nepal.

PubMed

Shakya-Vaidya, Suraj; Aryal, Umesh Raj; Upadhyay, Madan; Krettek, Alexandra

2013-11-04

Non-communicable diseases (NCDs) such as hypertension and diabetes are rapidly emerging public health problems worldwide, and they associate with primary open-angle glaucoma (POAG). POAG is the most common cause of irreversible blindness. The most effective ways to prevent glaucoma blindness involve identifying high-risk populations and conducting routine screening for early case detection. This study investigated whether POAG associates with hypertension and diabetes in a Nepalese population. To explore the history of systemic illness, our hospital-based case-control study used non-random consecutive sampling in the general eye clinics in three hospitals across Nepal to enroll patients newly diagnosed with POAG and controls without POAG. The study protocol included history taking, ocular examination, and interviews with 173 POAG cases and 510 controls. Data analysis comprised descriptive and inferential statistics. Descriptive statistics computed the percentage, mean, and standard deviation (SD); inferential statistics used McNemar's test to measure associations between diseases. POAG affected males more frequently than females. The odds of members of the Gurung ethnic group having POAG were 2.05 times higher than for other ethnic groups. Hypertension and diabetes were strongly associated with POAG. The overall odds of POAG increased 2.72-fold among hypertensive and 3.50-fold among diabetic patients. POAG associates significantly with hypertension and diabetes in Nepal. Thus, periodic glaucoma screening for hypertension and diabetes patients in addition to opportunistic screening at eye clinics may aid in detecting more POAG cases at an early stage and hence in reducing avoidable blindness.

Reproducibility of intraocular pressure peak and fluctuation of the water-drinking test.

PubMed

Hatanaka, Marcelo; Alencar, Luciana M; De Moraes, Carlos G; Susanna, Remo

2013-01-01

The water-drinking test has been used as a stress test to evaluate the drainage system of the eye. However, in order to be clinically applicable,a test must provide reproducible results with consistent measurements. This study was performed to verify the reproducibility of intraocular pressure peaks and fluctuation detected during the water-drinking test in patients with ocular hypertension and open-angle glaucoma. A prospective analysis of patients in a tertiary care unit for glaucoma treatment. Twenty-four ocular hypertension and 64 open-angle glaucoma patients not under treatment. The water-drinking test was performed in 2 consecutive days by the same examiners in patients not under treatment. Reproducibility was assessed using the intraclass correlation coefficient. Peak and fluctuation of intraocular pressure obtained with the water-drinking test were analysed for reproducibility. Eighty-eight eyes from 24 ocular hypertension and 64 open-angle glaucoma patients not under treatment were evaluated. Test and retest intraocular pressure peak values were 28.38 ± 4.64 and 28.38 ± 4.56 mmHg, respectively (P = 1.00). Test and retest intraocular pressure fluctuation values were 5.75 ± 3.9 and 4.99 ± 2.7 mmHg, respectively (P = 0.06). Based on intraclass coefficient, reproducibility was excellent for peak intraocular pressure (intraclass correlation coefficient = 0.79) and fair for intraocular pressure fluctuation (intraclass correlation coefficient = 0.37). Intraocular pressure peaks detected during the water-drinking test presented excellent reproducibility, whereas the reproducibility of fluctuation was considered fair. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

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

Diagnostic Capability of Peripapillary Retinal Thickness in Glaucoma Using 3D Volume Scans

PubMed Central

Simavli, Huseyin; Que, Christian John; Akduman, Mustafa; Rizzo, Jennifer L.; Tsikata, Edem; de Boer, Johannes F.; Chen, Teresa C.

2015-01-01

Purpose To determine the diagnostic capability of spectral domain optical coherence tomography (SD-OCT) peripapillary retinal thickness (RT) measurements from 3-dimensional (3D) volume scans for primary open angle glaucoma (POAG). Design Cross-sectional study. Methods Setting Institutional Study population 156 patients (89 POAG and 67 normal subjects) Observation procedures One eye of each subject was included. SD-OCT peripapillary RT values from 3D volume scans were calculated for four quadrants of three different sized annuli. Peripapillary retinal nerve fiber layer (RNFL) thickness values were also determined. Main outcome measures Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Results The top five RT AUROCs for all glaucoma patients and for a subset of early glaucoma patients were for the inferior quadrant of outer circumpapillary annulus of circular grid (OCA) 1 (0.959, 0.939), inferior quadrant of OCA2 (0.945, 0.921), superior quadrant of OCA1 (0.890, 0.811), inferior quadrant of OCA3 (0.887, 0.854), and superior quadrant of OCA2 (0.879, 0.807). Smaller RT annuli OCA1 and OCA2 consistently showed better diagnostic performance than the larger RT annulus OCA3. For both RNFL and RT measurements, best AUROC values were found for inferior RT OCA1 and OCA2, followed by inferior and overall RNFL thickness. Conclusion Peripapillary RT measurements from 3D volume scans showed excellent diagnostic performance for detecting both glaucoma and early glaucoma patients. Peripapillary RT values have the same or better diagnostic capability compared to peripapillary RNFL thickness measurements, while also having fewer algorithm errors. PMID:25498354

Meta-analysis of the efficacy and safety of combined surgery in the management of eyes with coexisting cataract and open angle glaucoma.

PubMed

Jiang, Nan; Zhao, Gui-Qiu; Lin, Jing; Hu, Li-Ting; Che, Cheng-Ye; Wang, Qian; Xu, Qiang; Li, Cui; Zhang, Jie

2018-01-01

To conduct a systematic review and quantitative Meta-analysis of the efficacy and safety of combined surgery for the eyes with coexisting cataract and open angle glaucoma. We performed a systematic search of the related literature in the Cochrane Library, PubMed, EMBASE, Web of Science databases, CNKI, CBM and Wan Fang databases, with no limitations on language or publication date. The primary efficacy estimate was identified by weighted mean difference of the percentage of intraocular pressure reduction (IOPR%) from baseline to end-point, the percentage of number of glaucoma medications reduction from pre- to post-operation, and the secondary efficacy evaluations were performed by odds ratio (OR) and 95% confidence interval (CI) for complete and qualified success rate. Besides, ORs were applied to assess the tolerability of adverse incidents. Meta-analyses of fixed or random effect models were performed using RevMan software 5.2 to gather the consequences. Heterogeneity was evaluated by Chi 2 test and the I 2 measure. Ten studies enrolling 3108 patients were included. The combined consequences indicated that both glaucoma and combined cataract and glaucoma surgery significantly decreased IOP. For deep sclerectomy vs deep sclerectomy plus phacoemulsification and canaloplasty vs phaco-canaloplasty, the differences in IOPR% were not all statistically significant while trabeculotomy was detected to gain a quantitatively greater IOPR% compared with trabeculotomy plus phacoemulsification. Furthermore, there was no statistical significance in the complete and qualified success rate, and the rates of adverse incidents for trabeculotomy vs trabeculotomy plus phacoemulsification. Compared with trabeculotomy plus phacoemulsification, trabeculectomy alone is more effective in lowering IOP and the number of glaucoma medications, while the two surgeries can not demonstrate statistical differences in the complete success rate, qualified success rate, or incidence of adverse incidents.

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

PubMed

Harrison, R J; Wild, J M; Hobley, A J

1988-11-05

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective.

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

PubMed Central

Harrison, R. J.; Wild, J. M.; Hobley, A. J.

1988-01-01

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective. PMID:3144331

Sensitivity and Specificity of Swedish Interactive Threshold Algorithm and Standard Full Threshold Perimetry in Primary Open-angle Glaucoma.

PubMed

Bamdad, Shahram; Beigi, Vahid; Sedaghat, Mohammad Reza

2017-01-01

Perimetry is one of the mainstays in glaucoma diagnosis and treatment. Various strategies offer different accuracies in glaucoma testing. Our aim was to determine and compare the diagnostic sensitivity and specificity of Swedish Interactive Threshold Algorithm (SITA) Fast and Standard Full Threshold (SFT) strategies of the Humphrey Field Analyzer (HFA) in identifying patients with visual field defect in glaucoma disease. This prospective observational case series study was conducted in a university-based eye hospital. A total of 37 eyes of 20 patients with glaucoma were evaluated using the central 30-2 program and both the SITA Fast and SFT strategies. Both strategies were performed for each strategy in each session and for four times in a 2-week period. Data were analyzed using the Student's t-test, analysis of variance, and chi-square test. The SITA Fast and SFT strategies had similar sensitivity of 93.3%. The specificity of SITA Fast and SFT strategies was 57.4% and 71.4% respectively. The mean duration of SFT tests was 14.6 minutes, and that of SITA Fast tests was 5.45 minutes (a statistically significant 62.5% reduction). In gray scale plots, visual field defect was less deep in SITA Fast than in SFT; however, more points had significant defect (p < 0.5% and p < 1%) in pattern deviation plots in SITA Fast than in SFT; these differences were not clinically significant. In conclusion, the SITA Fast strategy showed higher sensitivity for detection of glaucoma compared to the SFT strategy, yet with reduced specificity; however, the shorter test duration makes it a more acceptable choice in many clinical situations, especially for children, elderly, and those with musculoskeletal diseases.

Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain Optical Coherence Tomography for Glaucoma Diagnosis.

PubMed

Jeong, Jae Hoon; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

2016-01-01

To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection. A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements. Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness. Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size.

Automatic counting of microglial cell activation and its applications

PubMed Central

Gallego, Beatriz I.; de Gracia, Pablo

2016-01-01

Glaucoma is a multifactorial optic neuropathy characterized by the damage and death of the retinal ganglion cells. This disease results in vision loss and blindness. Any vision loss resulting from the disease cannot be restored and nowadays there is no available cure for glaucoma; however an early detection and treatment, could offer neuronal protection and avoid later serious damages to the visual function. A full understanding of the etiology of the disease will still require the contribution of many scientific efforts. Glial activation has been observed in glaucoma, being microglial proliferation a hallmark in this neurodegenerative disease. A typical project studying these cellular changes involved in glaucoma often needs thousands of images - from several animals - covering different layers and regions of the retina. The gold standard to evaluate them is the manual count. This method requires a large amount of time from specialized personnel. It is a tedious process and prone to human error. We present here a new method to count microglial cells by using a computer algorithm. It counts in one hour the same number of images that a researcher counts in four weeks, with no loss of reliability. PMID:27651757

Diagnostic ability of macular ganglion cell inner plexiform layer measurements in glaucoma using swept source and spectral domain optical coherence tomography.

PubMed

Yang, Zhiyong; Tatham, Andrew J; Weinreb, Robert N; Medeiros, Felipe A; Liu, Ting; Zangwill, Linda M

2015-01-01

To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection.

Diagnostic Ability of Macular Ganglion Cell Inner Plexiform Layer Measurements in Glaucoma Using Swept Source and Spectral Domain Optical Coherence Tomography

PubMed Central

Yang, Zhiyong; Tatham, Andrew J.; Weinreb, Robert N.; Medeiros, Felipe A.; Liu, Ting; Zangwill, Linda M.

2015-01-01

Purpose To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Results Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Conclusion Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection. PMID:25978420

Assessing the changes in the spatial stiffness of the posterior sclera as a function of IOP with air-pulse OCE

NASA Astrophysics Data System (ADS)

Singh, Manmohan; Nair, Achuth; Aglyamov, Salavat R.; Wu, Chen; Han, Zhaolong; Lafon, Ericka; Larin, Kirill V.

2017-02-01

The mechanophysiology of tissues in the posterior eye have been implicated for diseases such as myopia and glaucoma. For example, the eye-globe shape, and consequently optical axial length, can be affected by scleral stiffness. In glaucoma, an elevated intraocular pressure is the primary risk factor for glaucoma, which is the 2nd most prevalent known cause of blindness. Recent work has shown that biomechanical properties of the optic nerve are critical for the onset and progression of glaucoma because weak tissues cause large displacements in the optic nerve, causing tissue damage. In this work, we utilize air-pulse optical coherence elastography (OCE) to quantify the spatial distribution of biomechanical properties of the optic nerve, its surrounding tissues, and the posterior sclera. Air-pulse measurements were made in a grid on in situ porcine eyes in the whole eye-globe configuration as various IOPs. The OCE-measured displacement process was linked to tissue stiffness by a simple kinematic equation. The results show that the optic nerve and peripapillary sclera are much stiffer than the surrounding sclera, and the stiffness of the optic nerve and peripapillary sclera increased as a function of IOP. However, the stiffness of the surrounding sclera did not dramatically increase. Our results show that understanding the dynamics of the biomechanical properties of the eye are critical to understand the aforementioned diseases and may provide additional information for assessing visual health and integrity.

Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

PubMed Central

Kecova, Helga; Harper, Matthew M.; Nilaweera, Wijitha; Kuehn, Markus H.; Kardon, Randy H.

2010-01-01

Purpose. To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Methods. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). Results. A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Conclusions. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss. PMID:19661222

Treatment of glaucoma with high intensity focused ultrasound.

PubMed

Aptel, Florent; Lafon, Cyril

2015-05-01

Glaucoma is a common disease mainly due to an increase in pressure inside the eye, leading to a progressive destruction of the optic nerve, potentially to blindness. Intraocular pressure (IOP) is the result of a balance between production of liquid that fills the eye--aqueous humour--and its resorption. All treatments for glaucoma aim to reduce IOP and can therefore have two mechanisms of action: reducing aqueous humour production by the partial destruction or medical inhibition of the ciliary body--the anatomical structure responsible for production of aqueous humour--or facilitating the evacuation of aqueous humour from the eye. Several physical methods can be used to destroy the ciliary body, e.g. laser, cryotherapy, microwave. All these methods have two major drawbacks: they are non-selective for the organ to be treated and they have an unpredictable dose–effect relationship. High intensity focused ultrasound (HIFU) can be used to coagulate the ciliary body and avoid these drawbacks. A commercially available device was marketed in the 1980s, but later abandoned, essentially for technical reasons. A smaller circular device using miniaturised transducers was recently developed and proposed for clinical practice. Experimental studies have shown selective coagulation necrosis of the treated ciliary body. The first three clinical trials in humans have shown that this device was well tolerated and allowed a significant, predictable and sustained reduction of IOP. The aim of this contribution is to present a summary of the work concerning the use of HIFU to treat glaucoma.

Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies.

PubMed

Oddone, Francesco; Lucenteforte, Ersilia; Michelessi, Manuele; Rizzo, Stanislao; Donati, Simone; Parravano, Mariacristina; Virgili, Gianni

2016-05-01

Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular parameters, specifically the ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL), with the accuracy of RNFL parameters for detecting manifest glaucoma is important to guide clinical practice and future research. Studies using spectral domain optical coherence tomography (SD OCT) and reporting macular parameters were included if they allowed the extraction of accuracy data for diagnosing manifest glaucoma, as confirmed with automated perimetry or a clinician's optic nerve head (ONH) assessment. Cross-sectional cohort studies and case-control studies were included. The QUADAS 2 tool was used to assess methodological quality. Only direct comparisons of macular versus RNFL parameters (i.e., in the same study) were conducted. Summary sensitivity and specificity of each macular or RNFL parameter were reported, and the relative diagnostic odds ratio (DOR) was calculated in hierarchical summary receiver operating characteristic (HSROC) models to compare them. Thirty-four studies investigated macular parameters using RTVue OCT (Optovue Inc., Fremont, CA) (19 studies, 3094 subjects), Cirrus OCT (Carl Zeiss Meditec Inc., Dublin, CA) (14 studies, 2164 subjects), or 3D Topcon OCT (Topcon, Inc., Tokyo, Japan) (4 studies, 522 subjects). Thirty-two of these studies allowed comparisons between macular and RNFL parameters. Studies generally reported sensitivities at fixed specificities, more commonly 0.90 or 0.95, with sensitivities of most best-performing parameters between 0.65 and 0.75. For all OCT devices, compared with RNFL parameters, macular parameters were similarly or slightly less accurate for detecting glaucoma at the highest reported specificity, which was confirmed in analyses at the lowest specificity. Included studies suffered from limitations, especially the case-control study design, which is known to overestimate accuracy. However, this flaw is less relevant as a source of bias in direct comparisons conducted within studies. With the use of OCT, RNFL parameters are still preferable to macular parameters for diagnosing manifest glaucoma, but the differences are small. Because of high heterogeneity, direct comparative or randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma.

PubMed

Della Santina, Luca; Inman, Denise M; Lupien, Caroline B; Horner, Philip J; Wong, Rachel O L

2013-10-30

Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using a microbead injection technique to chronically raise IOP for 15 or 30 d in mice, we identified the early changes in visual response properties of different types of retinal ganglion cells (RGCs) and correlated these changes with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well as cell death. In such eyes, multielectrode array recordings revealed that four RGC types show diverse alterations in their light responses upon IOP elevation. OFF-transient RGCs exhibited a more rapid decline in both structural and functional organizations compared with other RGCs. In contrast, although the light-evoked responses of OFF-sustained RGCs were perturbed, the dendritic arbor of this cell type remained intact. ON-transient and ON-sustained RGCs had normal functional receptive field sizes but their spontaneous and light-evoked firing rates were reduced. ON- and OFF-sustained RGCs lost excitatory synapses across an otherwise structurally normal dendritic arbor. Together, our observations indicate that there are changes in spontaneous activity and light-evoked responses in RGCs before detectable dendritic loss. However, when dendrites retract, we found corresponding changes in receptive field center size. Importantly, the effects of IOP elevation are not uniformly manifested in the structure and function of diverse RGC populations, nor are distinct RGC types perturbed within the same time-frame by such a challenge.

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.

Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

PubMed

Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

2013-10-01

To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

Clinical evaluation of a novel population-based regression analysis for detecting glaucomatous visual field progression.

PubMed

Kovalska, M P; Bürki, E; Schoetzau, A; Orguel, S F; Orguel, S; Grieshaber, M C

2011-04-01

The distinction of real progression from test variability in visual field (VF) series may be based on clinical judgment, on trend analysis based on follow-up of test parameters over time, or on identification of a significant change related to the mean of baseline exams (event analysis). The aim of this study was to compare a new population-based method (Octopus field analysis, OFA) with classic regression analyses and clinical judgment for detecting glaucomatous VF changes. 240 VF series of 240 patients with at least 9 consecutive examinations available were included into this study. They were independently classified by two experienced investigators. The results of such a classification served as a reference for comparison for the following statistical tests: (a) t-test global, (b) r-test global, (c) regression analysis of 10 VF clusters and (d) point-wise linear regression analysis. 32.5 % of the VF series were classified as progressive by the investigators. The sensitivity and specificity were 89.7 % and 92.0 % for r-test, and 73.1 % and 93.8 % for the t-test, respectively. In the point-wise linear regression analysis, the specificity was comparable (89.5 % versus 92 %), but the sensitivity was clearly lower than in the r-test (22.4 % versus 89.7 %) at a significance level of p = 0.01. A regression analysis for the 10 VF clusters showed a markedly higher sensitivity for the r-test (37.7 %) than the t-test (14.1 %) at a similar specificity (88.3 % versus 93.8 %) for a significant trend (p = 0.005). In regard to the cluster distribution, the paracentral clusters and the superior nasal hemifield progressed most frequently. The population-based regression analysis seems to be superior to the trend analysis in detecting VF progression in glaucoma, and may eliminate the drawbacks of the event analysis. Further, it may assist the clinician in the evaluation of VF series and may allow better visualization of the correlation between function and structure owing to VF clusters. © Georg Thieme Verlag KG Stuttgart · New York.

[The questionnaire survey on glaucoma diagnosis and treatment in China (2016)].

PubMed

Zhang, Q; Cao, K; Kang, M T; Sun, Y X; Gan, J H; Tian, J X; Ran, A R; Zhang, X; Su, Y D; Li, S N

2017-02-11

Objective: To investigate the present situation of diagnosis and treatment for primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and awareness of the relevant progress among Chinese ophthalmologists. Methods: This study was a cross-sectional, non-randomized sampling survey. Participants were ophthalmologists who attended the 11st Chinese Glaucoma Society Congress during November 11 to 12, 2016. They were invited to fill out a questionnaire. The questionnaire included participants' basic information and their knowledge about glaucoma diagnosis and treatment. The data collected through questionnaire were analyzed with SAS9.4. Results: A total of 450 questionnaires were distributed and 372 valid questionnaires were retrieved, with a response rate of 82. 7%(372/450). ISGEO classification system was adopted by 58.9% (219/372) of the participants as the diagnostic criteria for PACG. Of the respondents, 48.1% (179/372) of the participants believed that "anterior chamber angle closure mechanism-based PACG classification system" was more instructive for treatment, the percentage was higher than ISGEO classification system (42.2%, 157/372). Most (72.3%, 269/372) of the participants knew the 3-minute dark room prone test, but only 27.7%(103/372) of them applied it in clinical practice. A total of 83.4%(310/372) of the participants believed that low cerebrospinal fluid pressure is a risk factor for POAG. In all, 71.8% (267/372) of the participants reported that their institutes had applied compound trabeculectomy with adjustable suture, with 76.9%(286/372) of the participants agreeing that the adjustable suture reduced the rate of complications after trabeculectomy. Conclusions: Currently, both ISGEO classification system and anterior chamber angle closure mechanism-based PACG classification system were adopted in the diagnosis and treatment of glaucoma. Low cerebrospinal fluid pressure as new risk factors for POAG has been widely acknowledged and given attentions by Chinese ophthalmologists. The 3-minute darkroom prone test and compound trabeculectomy with adjustable suture still need to be promoted. (Chin J Ophthalmol, 2017, 53: 115-120) .

Level of adherence to ocular hypotensive agents and its determinant factors among glaucoma patients in Menelik II Referral Hospital, Ethiopia.

PubMed

Mehari, Tesfay; Giorgis, Abeba T; Shibeshi, Workineh

2016-08-02

Good adherence to ocular hypotensive agents is important to control intraocular pressure and hence to prevent progressive glaucomatous optic nerve head damage. Periodic investigation of adherence is crucial in glaucoma treatment. The purpose of this study was to assess level of adherence to ocular hypotensive agents and to identify factors affecting adherence among glaucoma patients at a tertiary public eye care center. The study was a hospital-based cross-sectional study that was conducted in Menelik II Referral Hospital from June 1, 2015 to July 31, 2015. A systematic random sampling technique was used to select 359 study participants from the source population. The study patients were interviewed and their medical charts were reviewed using a pretested structured questionnaire. Adherence was assessed using Morisky Medication Adherence Scale - 8 and adherence determinant factors were identified using multivariate binary logistic regression analysis. The association was declared statistically significant at p < 0.05. Among the 359 study glaucoma patients, 42.6 % were adherent to their prescribed hypotensive agents. Higher educational level (AOR = 4.60, 95 % CI: 1.01-21.03, p < 0.049), being self - employed (AOR = 6.14, 95 % CI: 1.37-27.50, p < 0.018) and taking lesser frequency of drops (AOR = 2.89, 95 % CI: 1.25-6.66, p < 0.013) were significantly associated with adherence, whereas being a farmer (AOR = 0.07, 95 % CI: 0.01-0.75, p < 0.028), having very low monthly family income (AOR = 0.22, 95 % CI: 0.06-0.77, p < 0.019) and self - purchasing of medications (AOR = 0.30, 95 % CI: 0.10-0.93, p < 0.036) were significantly associated with non-adherence. The study has identified the adherence level to the prescribed ocular hypotensive agents to be sub-optimal and is influenced by different factors among glaucoma patients of the public tertiary center. We recommend glaucoma care providers to pay due attention on the importance of adherence.

Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

NASA Astrophysics Data System (ADS)

Tornow, Ralf P.; Kolář, Radim; Odstrčilík, Jan

2015-07-01

The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

In Vivo Detection of Laminar and Peripapillary Scleral Hypercompliance in Early Monkey Experimental Glaucoma

PubMed Central

Ivers, Kevin M.; Yang, Hongli; Gardiner, Stuart K.; Qin, Lirong; Reyes, Luke; Fortune, Brad; Burgoyne, Claude F.

2016-01-01

Purpose To compare optical coherence tomography (OCT) detected, optic nerve head (ONH) compliance within control and experimental glaucoma (EG) eyes of 15 monkeys at EG onset. Methods Intraocular pressure (IOP) was chronically elevated in one eye of each animal using a laser. Experimental glaucoma onset was identified using confocal scanning laser tomography (CSLT). Optical coherence tomography ONH imaging (40 radial B-scans) was performed at 10 mm Hg before and after laser. At EG onset, OCT scans were obtained at IOP 10 and 30 mm Hg. Optical coherence tomography landmarks within the IOP 10/30 images were delineated to quantify IOP 10/30 differences (compliance) for anterior lamina cribrosa surface depth (ALCSD) relative to Bruch's membrane opening (BMO) (ALCSD-BMO), ALCSD relative to peripheral BM (ALCSD-BM), and BMO depth relative to peripheral BM (BMOD-BM). A linear mixed effects model assessed for acute IOP elevation effects, control versus EG eye effects, and their interaction Results Effects of IOP elevation were greater in EG versus control eyes for ALCSD-BMO (−46 ± 45 vs. −8 ± 13 μm, P = 0.0042) and ALCSD-BM (−92 ± 64 vs. −42 ± 22 μm, P = 0.0075). Experimental glaucoma eye-specific ALCSD-BMO and ALCSD-BM compliance exceeded the range of control eye compliance in 9 and 8 of the 15 EG eyes, respectively. Post-laser peak IOP (R2 = 0.798, P < 0.0001) and post-laser mean IOP (R2 = 0.634, P < 0.0004) most strongly correlated to EG versus control eye differences in ALCSD-BMO compliance. Conclusions Laminar (ALCSD-BMO) and peripapillary scleral (ALCSD-BM) hypercompliance are present in most monkey eyes at the onset of EG. PMID:27409498

Development of ocular viscosity characterization method.

PubMed

Shu-Hao Lu; Guo-Zhen Chen; Leung, Stanley Y Y; Lam, David C C

2016-08-01

Glaucoma is the second leading cause for blindness. Irreversible and progressive optic nerve damage results when the intraocular pressure (IOP) exceeds 21 mmHg. The elevated IOP is attributed to blocked fluid drainage from the eye. Methods to measure the IOP are widely available, but methods to measure the viscous response to blocked drainage has yet been developed. An indentation method to characterize the ocular flow is developed in this study. Analysis of the load-relaxation data from indentation tests on drainage-controlled porcine eyes showed that the blocked drainage is correlated with increases in ocular viscosity. Successful correlation of the ocular viscosity with drainage suggests that ocular viscosity maybe further developed as a new diagnostic parameter for assessment of normal tension glaucoma where nerve damage occurs without noticeable IOP elevation; and as a diagnostic parameter complimentary to conventional IOP in conventional diagnosis.

Rapid learning curve assessment in an ex vivo training system for microincisional glaucoma surgery.

PubMed

Dang, Yalong; Waxman, Susannah; Wang, Chao; Parikh, Hardik A; Bussel, Igor I; Loewen, Ralitsa T; Xia, Xiaobo; Lathrop, Kira L; Bilonick, Richard A; Loewen, Nils A

2017-05-09

Increasing prevalence and cost of glaucoma have increased the demand for surgeons well trained in newer, microincisional surgery. These procedures occur in a highly confined space, making them difficult to learn by observation or assistance alone as is currently done. We hypothesized that our ex vivo outflow model is sensitive enough to allow computing individual learning curves to quantify progress and refine techniques. Seven trainees performed nine trabectome-mediated ab interno trabeculectomies in pig eyes (n = 63). An expert surgeon rated the procedure using an Operating Room Score (ORS). The extent of outflow beds accessed was measured with canalograms. Data was fitted using mixed effect models. ORS reached a half-maximum on an asymptote after only 2.5 eyes. Surgical time decreased by 1.4 minutes per eye in a linear fashion. The ablation arc followed an asymptotic function with a half-maximum inflection point after 5.3 eyes. Canalograms revealed that this progress did not correlate well with improvement in outflow, suggesting instead that about 30 eyes are needed for true mastery. This inexpensive pig eye model provides a safe and effective microsurgical training model and allows objective quantification of outcomes for the first time.

Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care

PubMed Central

Rhodes, Lindsay A; Huisingh, Carrie E; McGwin, Gerald; Mennemeyer, Stephen T; Bregantini, Mary; Patel, Nita; Saaddine, Jinan; Crews, John E; Girkin, Christopher A; Owsley, Cynthia

2016-01-01

Purpose To assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients’ knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY. Patients and methods New or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: African Americans ≥40 years of age, Whites ≥50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients’ CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2–4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar’s test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized. Results At follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline (P≤0.01 for all questions). Those who were unemployed (odds ratio =0.63, 95% confidence interval =0.42–0.95, P=0.026) or had lower education (odds ratio =0.55, 95% confidence interval =0.29–1.02, P=0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level characteristics. Ninety-eight percent (n=501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n=326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%). Conclusion Improved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness. PMID:27274329

Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not involved in pigment dispersion syndrome and pigmentary glaucoma.

PubMed

Rao, Kollu Nageswara; Ritch, Robert; Dorairaj, Syril K; Kaur, Inderjeet; Liebmann, Jeffrey M; Thomas, Ravi; Chakrabarti, Subhabrata

2008-07-09

Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). We have shown that these SNPs are not associated with the primary glaucomas such as primary open-angle (POAG) glaucoma and primary angle-closure glaucoma (PACG). To further establish the specificity of LOXL1 SNPs for XFS and XFG, we determined whether these SNPs were involved in pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). Three SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were screened in a cohort of 78 unrelated and clinically well characterized glaucoma cases comprising of PG (n=44) and PDS (n=34) patients as well as 108 ethnically matched normal controls of Caucasian origin. The criteria for diagnosis of PDS/PG were Krukenberg spindle, hyperpigmentation of the trabecular meshwork, and wide open angle. Transillumination defects were detected by infrared pupillography, and the presence of a Zentmayer ring was considered as a confirmatory sign. All three SNPs were genotyped in cases and controls by resequencing the genomic region of LOXL1 harboring these variants and were further confirmed by polymerase chain reaction (PCR)-based restriction digestions. Haplotypes were generated from the genotype data, and the linkage disequilibrium (LD) and haplotype analysis were done with Haploview software that uses the expectation maximization (EM) algorithm. The LOXL1 SNPs showed no significant association with PDS or PG. There was no significant difference in the frequencies of the risk alleles of rs1048661 ('G' allele; p=0.309), rs3825942 ('G' allele' p=0.461), and rs2165241 ('T' allele; p=0.432) between PG/PDS cases and controls. Similarly, there was no involvement of the XFS/XFG-associated haplotypes, 'G-G' (p=0.643; [OR=1.08, 95%CI, 0.59-1.97]) and 'T-G' (p=0.266; [OR=1.35, 95%CI, 0.70-2.60]), with the PDS/PG phenotypes. The risk haplotype 'G-G' was observed in ~55% of the normal controls. There was no involvement of the LOXL1 SNPs in patients with PDS and PG. The results further indicate that the associations of these SNPs are specific to XFS/XFG.

Graft failure: III. Glaucoma escalation after penetrating keratoplasty.

PubMed

Greenlee, Emily C; Kwon, Young H

2008-06-01

Glaucoma after penetrating keratoplasty is a frequently observed post-operative complication and is a risk factor for graft failure. Penetrating keratoplasty performed for aphakic and pseudophakic bullous keratopathy and inflammatory conditions are more likely to cause postoperative glaucoma compared with keratoconus and Fuchs' endothelial dystrophy. The intraocular pressure elevation may occur immediately after surgery or in the early to late postoperative period. Early postoperative causes of glaucoma include pre-existing glaucoma, retained viscoelastic, hyphema, inflammation, pupillary block, aqueous misdirection, or suprachoroidal hemorrhage. Late causes include pre-existing glaucoma, angle-closure glaucoma, ghost cell glaucoma, suprachoroidal hemorrhage, and steroid-induced glaucoma. Determining the cause of IOP elevation can help guide therapeutic intervention. Treatments for refractory glaucoma include topical anti-glaucoma medications such as beta-adrenergic blockers. Topical carbonic anhydrase inhibitors, miotic agents, adrenergic agonists, and prostaglandin analogs should be used with caution in the post-keratoplasty patient, because of the possibility of corneal decompensation, cystoid macular edema, or persistent inflammation. Various glaucoma surgical treatments have reported success in post-keratoplasty glaucoma. Trabeculectomy with mitomycin C can be successful in controlling IOP without the corneal toxicity noted with 5-fluorouracil. Glaucoma drainage devices have successfully controlled intraocular pressure in postkeratoplasty glaucoma; this is, however, associated with increased risk of graft failure. Placement of the tube through the pars plana may improve graft success compared with implantation within the anterior chamber. In addition, cyclophotocoagulation remains a useful procedure for eyes that have refractory glaucoma despite multiple surgical interventions.