Effect of intravitreal triamcinolone acetonide on healing of retinal photocoagulation lesions.

PubMed

Nomoto, Hiroyuki; Lavinsky, Daniel; Paulus, Yannis M; Leung, Loh-Shan; Dalal, Roopa; Blumenkranz, Mark S; Palanker, Daniel

2013-01-01

To evaluate the effect of intravitreal triamcinolone acetonide (TA) on healing of retinal photocoagulation lesions using drug and laser dosing typically employed in clinical practice. Laser burns with a 267-μm retinal beam size at 532-nm wavelength were applied to 40 eyes of Dutch belted rabbits. Barely visible to intense lesions were produced with pulses of 5, 10, 20, and 50 milliseconds and power of 175 mW. Eyes received intravitreal injections of either 2 mg TA/50 μL or balanced salt solution administered either 1 week before or immediately after laser treatment. Lesion grades were assessed acutely ophthalmoscopically and by a masked observer histologically at 1, 3, 7, 30, and 60 days. Both TA groups demonstrated significant reduction in retinal thickness throughout follow-up compared with balanced salt solution groups (P < 0.001). The width of the lesions at 1 day after injection was not significantly different between groups. However, by 7 days, the lesions in balanced salt solution groups contracted much more than in the TA groups, especially the more intense burns, and this difference persisted to 2 months. The healing rate of the barely visible burns was not significantly affected by TA compared with the balanced salt solution control eyes. Triamcinolone acetonide injection previously or concurrently with photocoagulation significantly decreases laser-induced edema but interferes with lesions healing, thereby leaving wider residual scarring, especially persistent in more intense burns.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

PubMed

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Lesion detection in ultra-wide field retinal images for diabetic retinopathy diagnosis

NASA Astrophysics Data System (ADS)

Levenkova, Anastasia; Sowmya, Arcot; Kalloniatis, Michael; Ly, Angelica; Ho, Arthur

2018-02-01

Diabetic retinopathy (DR) leads to irreversible vision loss. Diagnosis and staging of DR is usually based on the presence, number, location and type of retinal lesions. Ultra-wide field (UWF) digital scanning laser technology provides an opportunity for computer-aided DR lesion detection. High-resolution UWF images (3078×2702 pixels) may allow detection of more clinically relevant retinopathy in comparison with conventional retinal images as UWF imaging covers a 200° retinal area, versus 45° by conventional cameras. Current approaches to DR diagnosis that analyze 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) retinal images provide similar results to UWF imaging. However, in 40% of cases, more retinopathy was found outside the 7- field ETDRS fields by UWF and in 10% of cases, retinopathy was reclassified as more severe. The reason is that UWF images examine both the central retina and more peripheral regions. We propose an algorithm for automatic detection and classification of DR lesions such as cotton wool spots, exudates, microaneurysms and haemorrhages in UWF images. The algorithm uses convolutional neural network (CNN) as a feature extractor and classifies the feature vectors extracted from colour-composite UWF images using a support vector machine (SVM). The main contribution includes detection of four types of DR lesions in the peripheral retina for diagnostic purposes. The evaluation dataset contains 146 UWF images. The proposed method for detection of DR lesion subtypes in UWF images using two scenarios for transfer learning achieved AUC ≈ 80%. Data was split at the patient level to validate the proposed algorithm.

Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

PubMed

McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

2014-12-18

To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

PubMed

Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-11-01

To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

Photocoagulation in rabbits: optical coherence tomographic lesion classification, wound healing reaction, and retinal temperatures.

PubMed

Koinzer, Stefan; Hesse, Carola; Caliebe, Amke; Saeger, Mark; Baade, Alexander; Schlott, Kerstin; Brinkmann, Ralf; Roider, Johann

2013-09-01

The rabbit is the most common animal model to study retinal photocoagulation lesions. We present a classification of retinal lesions from rabbits, that is based on optical coherence tomographic (OCT) findings, temperature data, and OCT-follow-up data over 3 months. Four hundred eighty-six photocoagulation lesions (modified Zeiss Visulas® 532 nm CW laser, lesion diameter 133 µm, exposure duration 200  milliseconds or variable, power variable) were analyzed from six eyes of three chinchilla gray rabbits. During the irradiation of each lesion, we used an optoacoustics-based method to measure the retinal temperature profile. Two hours, 1 week, 1 month, and 3 months after the treatment, we obtained fundus color and OCT (Spectralis®) images of each lesion. We classified the lesions according to their OCT morphology and correlated the findings to ophthalmoscopic and OCT lesion diameters, and temperatures. Besides an undetectable lesion class 0, we discerned subthreshold lesions that were invisible on the fundus but detectable in OCT (classes 1 and 2), very mild lesions that were partly visible on the fundus (class 3), and 3 classes of suprathreshold lesions. OCT greatest linear diameters (GLDs) were larger than ophthalmoscopic lesion diameters, both increased for increasing classes, and GLDs decreased over 3 months within each class. Mean peak end temperatures for 200  milliseconds lesions ranged from 61°C in class 2 to 80°C in class 6. The seven step rabbit lesion classifier is distinct from a previously published human lesion classifier. Threshold lesions are generated at comparable temperatures in rabbits and humans, while more intense lesions are created at lower temperatures in rabbits. The OCT lesion classifier could replace routine histology in some studies, and the presented data may be used to estimate lesion end temperatures from OCT images. © 2013 Wiley Periodicals, Inc.

A level-set method for pathology segmentation in fluorescein angiograms and en face retinal images of patients with age-related macular degeneration

NASA Astrophysics Data System (ADS)

Mohammad, Fatimah; Ansari, Rashid; Shahidi, Mahnaz

2013-03-01

The visibility and continuity of the inner segment outer segment (ISOS) junction layer of the photoreceptors on spectral domain optical coherence tomography images is known to be related to visual acuity in patients with age-related macular degeneration (AMD). Automatic detection and segmentation of lesions and pathologies in retinal images is crucial for the screening, diagnosis, and follow-up of patients with retinal diseases. One of the challenges of using the classical level-set algorithms for segmentation involves the placement of the initial contour. Manually defining the contour or randomly placing it in the image may lead to segmentation of erroneous structures. It is important to be able to automatically define the contour by using information provided by image features. We explored a level-set method which is based on the classical Chan-Vese model and which utilizes image feature information for automatic contour placement for the segmentation of pathologies in fluorescein angiograms and en face retinal images of the ISOS layer. This was accomplished by exploiting a priori knowledge of the shape and intensity distribution allowing the use of projection profiles to detect the presence of pathologies that are characterized by intensity differences with surrounding areas in retinal images. We first tested our method by applying it to fluorescein angiograms. We then applied our method to en face retinal images of patients with AMD. The experimental results included demonstrate that the proposed method provided a quick and improved outcome as compared to the classical Chan-Vese method in which the initial contour is randomly placed, thus indicating the potential to provide a more accurate and detailed view of changes in pathologies due to disease progression and treatment.

Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

PubMed

Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

2016-03-01

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. © The Author(s) 2015.

Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study

PubMed Central

Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

2015-01-01

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina. Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry. Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes. These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. PMID:26604209

Measurement of Retinal Sensitivity on Tablet Devices in Age-Related Macular Degeneration.

PubMed

Wu, Zhichao; Guymer, Robyn H; Jung, Chang J; Goh, Jonathan K; Ayton, Lauren N; Luu, Chi D; Lawson, David J; Turpin, Andrew; McKendrick, Allison M

2015-06-01

We compared measurements of central retinal sensitivity on a portable, low-cost tablet device to the established method of microperimetry in age-related macular degeneration (AMD). A customized test designed to measure central retinal sensitivity (within the central 1° radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. The average test duration on PsyPad was 53.9 ± 7.5 seconds, and no significant learning effect was observed over the examinations performed ( P = 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was ±1.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 ± 0.4 dB) and microperimetry (26.1 ± 0.4 dB, P = 0.094), and the 95% limits of agreement between the two measures were between -4.12 and 4.92 dB. The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry. These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented.

The BALB/c mouse: Effect of standard vivarium lighting on retinal pathology during aging

PubMed Central

Bell, Brent A.; Kaul, Charles; Bonilha, Vera L.; Rayborn, Mary E.; Shadrach, Karen; Hollyfield, Joe G.

2015-01-01

BALB/cJ mice housed under normal vivarium lighting conditions can exhibit profound retinal abnormalities, including retinal infoldings, autofluorescent inflammatory cells, and photoreceptor degeneration. To explore the sensitivity of the outer retina to cyclic lighting during aging, a cohort of BALB/cJ mice was evaluated with Scanning Laser Ophthalmoscopy (SLO), Spectral-Domain Optical Coherence Tomography (OCT) and conventional histopathology. Mice were bred and reared in a low-illuminance (extracage/intracage: 13 lx/1 lx) vivarium under cyclic light (14 h light: 10 h dark). Retinal imaging (around postnatal day 70) was performed to screen for any pre-existing abnormalities and to establish a baseline. Mice with normal retinas were separated into groups (A, B, C) and placed on bottom (Groups A & B) or top (Group C) of the cage racks where cage illumination was <10 & 150 lx respectively. Experimental groups B & C were imaged multiple times over a 17 month period. Mice from group A (controls) were imaged only once post-baseline at various times for comparison to groups B & C. Mice were assessed by histology at 8, 15, 20, 36, and 56 weeks and immunohistochemistry at 15 weeks post-baseline. SLO and OCT retinal images were measured and the resulting trends displayed as a function of age and light exposure. Retinal lesions (RL) and autofluorescent foci (AFF) were identified with histology as photoreceptor layer infoldings (IF) and localized microglia/macrophages (MM), respectively. Few RL and AFF were evident at baseline. Retinal infoldings were the earliest changes followed by subjacent punctate autofluorescent MM. The colocalization of IF and MM suggests a causal relationship. The incidence of these pathological features increased in all groups relative to baseline. OCT imaging revealed thinning of the outer nuclear layer (ONL) in all groups at 1 year relative to baseline. ONL thinning followed an exponential rate of change but the decay constant varied depending on

Automatic detection and recognition of multiple macular lesions in retinal optical coherence tomography images with multi-instance multilabel learning

NASA Astrophysics Data System (ADS)

Fang, Leyuan; Yang, Liumao; Li, Shutao; Rabbani, Hossein; Liu, Zhimin; Peng, Qinghua; Chen, Xiangdong

2017-06-01

Detection and recognition of macular lesions in optical coherence tomography (OCT) are very important for retinal diseases diagnosis and treatment. As one kind of retinal disease (e.g., diabetic retinopathy) may contain multiple lesions (e.g., edema, exudates, and microaneurysms) and eye patients may suffer from multiple retinal diseases, multiple lesions often coexist within one retinal image. Therefore, one single-lesion-based detector may not support the diagnosis of clinical eye diseases. To address this issue, we propose a multi-instance multilabel-based lesions recognition (MIML-LR) method for the simultaneous detection and recognition of multiple lesions. The proposed MIML-LR method consists of the following steps: (1) segment the regions of interest (ROIs) for different lesions, (2) compute descriptive instances (features) for each lesion region, (3) construct multilabel detectors, and (4) recognize each ROI with the detectors. The proposed MIML-LR method was tested on 823 clinically labeled OCT images with normal macular and macular with three common lesions: epiretinal membrane, edema, and drusen. For each input OCT image, our MIML-LR method can automatically identify the number of lesions and assign the class labels, achieving the average accuracy of 88.72% for the cases with multiple lesions, which better assists macular disease diagnosis and treatment.

Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

PubMed

Daniel, Ebenezer; Shaffer, James; Ying, Gui-shuang; Grunwald, Juan E; Martin, Daniel F; Jaffe, Glenn J; Maguire, Maureen G

2016-03-01

To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Patients with NVAMD. Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features. Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years. Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P < 0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 μm vs. -161 μm; P < 0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P < 0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025). At both 1 and 2 years

Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration.

PubMed

Papadopoulou, Domniki N; Mendrinos, Efstratios; Mangioris, Georgios; Donati, Guy; Pournaras, Constantin J

2009-09-01

To study the effect of intravitreal (IVT) ranibizumab (Lucentis; Genentech, Inc, San Francisco, CA) on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). Prospective consecutive interventional case series. Eleven eyes of eleven patients with previously untreated neovascular AMD. All eyes had 3 monthly IVT injections of ranibizumab. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyzer (RVA) before the first IVT injection and then 7 and 30 days after the first, second, and third injections. Primary end points were changes in retinal arteriolar diameter and mean arterial pressure (MAP) after IVT ranibizumab. Secondary end points were changes in best-corrected visual acuity (BCVA), central retinal thickness, and intraocular pressure after IVT ranibizumab, and appearance of adverse events during the follow-up period. A significant decrease of the retinal arteriolar diameter was observed after each IVT injection of ranibizumab. Thirty days after the first, second, and third injections, there was a mean decrease of 8.1+/-3.2%, 11.5+/-4.4%, and 17.6+/-7.4%, respectively, of the retinal arteriolar diameter compared with baseline values (P<0.01). There was no significant change in MAP during the period of follow-up (P>0.05). Thirty days after the third IVT injection of ranibizumab, mean BCVA improved by 6.5+/-4.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central retinal thickness decreased by 91+/-122 microm (P = 0.03). These results suggest that IVT ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular AMD after IVT ranibizumab. Further studies evaluating larger sample sizes are needed to confirm these results and potential adverse effects on the retinal circulation in patients with AMD and retinal vascular diseases. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

PubMed

Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

Optical coherence tomography study of retinal changes in normal aging and after ischemia.

PubMed

Shariati, Mohammad Ali; Park, Joyce Ho; Liao, Yaping Joyce

2015-05-01

Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-month-, 1-year-, and 2-year-old mice and after experimental anterior ischemic optic neuropathy (AION). We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after a photochemical thrombosis model of AION. The scans were manually or automatically segmented. In normal aging, there was 1.3-μm thinning of the ganglion cell complex (GCC) between 3 months and 1 year (P < 0.0001) and no further thinning at 2 years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to that of the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three weeks after AION, there was 8.9-μm thinning of the GCC (circular scan; P < 0.0001), 50-μm thinning of the optic disc (posterior pole scan; P < 0.0001), and 17-μm thinning of the retina (posterior pole scan; P < 0.0001) in the 3-month-old group. Changes in the older eyes after AION were similar to those of the 3-month-old group. Optical coherence tomography imaging of a large number of eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. Measurement of the GCC was superior to total retinal thickness in quantifying age-related changes, and both circular and posterior pole scans were useful to track short-term changes after AION.

Plasticity in adult cat visual cortex (area 17) following circumscribed monocular lesions of all retinal layers

PubMed Central

Calford, M B; Wang, C; Taglianetti, V; Waleszczyk, W J; Burke, W; Dreher, B

2000-01-01

In eight adult cats intense, sharply circumscribed, monocular laser lesions were used to remove all cellular layers of the retina. The extents of the retinal lesions were subsequently confirmed with counts of α-ganglion cells in retinal whole mounts; in some cases these revealed radial segmental degeneration of ganglion cells distal to the lesion.Two to 24 weeks later, area 17 (striate cortex; V1) was studied electrophysiologically in a standard anaesthetized, paralysed (artificially respired) preparation. Recording single- or multineurone activity revealed extensive topographical reorganization within the lesion projection zone (LPZ).Thus, with stimulation of the lesioned eye, about 75 % of single neurones in the LPZ had ‘ectopic’ visual discharge fields which were displaced to normal retina in the immediate vicinity of the lesion.The sizes of the ectopic discharge fields were not significantly different from the sizes of the normal discharge fields. Furthermore, binocular cells recorded from the LPZ, when stimulated via their ectopic receptive fields, exhibited orientation tuning and preferred stimulus velocities which were indistinguishable from those found when the cells were stimulated via the normal eye.However, the responses to stimuli presented via ectopic discharge fields were generally weaker (lower peak discharge rates) than those to presentations via normal discharge fields, and were characterized by a lower-than-normal upper velocity limit.Overall, the properties of the ectopic receptive fields indicate that cortical mechanisms rather than a retinal ‘periphery’ effect underlie the topographic reorganization of area 17 following monocular retinal lesions. PMID:10767137

Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

PubMed

Burnat, Kalina; Hu, Tjing-Tjing; Kossut, Małgorzata; Eysel, Ulf T; Arckens, Lutgarde

2017-09-13

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7. SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with

The BALB/c mouse: Effect of standard vivarium lighting on retinal pathology during aging.

PubMed

Bell, Brent A; Kaul, Charles; Bonilha, Vera L; Rayborn, Mary E; Shadrach, Karen; Hollyfield, Joe G

2015-06-01

BALB/cJ mice housed under normal vivarium lighting conditions can exhibit profound retinal abnormalities, including retinal infoldings, autofluorescent inflammatory cells, and photoreceptor degeneration. To explore the sensitivity of the outer retina to cyclic lighting during aging, a cohort of BALB/cJ mice was evaluated with Scanning Laser Ophthalmoscopy (SLO), Spectral-Domain Optical Coherence Tomography (OCT) and conventional histopathology. Mice were bred and reared in a low-illuminance (extracage/intracage: 13 lx/1 lx) vivarium under cyclic light (14 h light: 10 h dark). Retinal imaging (around postnatal day 70) was performed to screen for any pre-existing abnormalities and to establish a baseline. Mice with normal retinas were separated into groups (A, B, C) and placed on bottom (Groups A & B) or top (Group C) of the cage racks where cage illumination was <10 & 150 lx respectively. Experimental groups B & C were imaged multiple times over a 17 month period. Mice from group A (controls) were imaged only once post-baseline at various times for comparison to groups B & C. Mice were assessed by histology at 8, 15, 20, 36, and 56 weeks and immunohistochemistry at 15 weeks post-baseline. SLO and OCT retinal images were measured and the resulting trends displayed as a function of age and light exposure. Retinal lesions (RL) and autofluorescent foci (AFF) were identified with histology as photoreceptor layer infoldings (IF) and localized microglia/macrophages (MM), respectively. Few RL and AFF were evident at baseline. Retinal infoldings were the earliest changes followed by subjacent punctate autofluorescent MM. The colocalization of IF and MM suggests a causal relationship. The incidence of these pathological features increased in all groups relative to baseline. OCT imaging revealed thinning of the outer nuclear layer (ONL) in all groups at 1 year relative to baseline. ONL thinning followed an exponential rate of change but the decay constant varied depending on

X-82 to Treat Age-related Macular Degeneration

ClinicalTrials.gov

2018-05-30

Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

Advancing Bag-of-Visual-Words Representations for Lesion Classification in Retinal Images

PubMed Central

Pires, Ramon; Jelinek, Herbert F.; Wainer, Jacques; Valle, Eduardo; Rocha, Anderson

2014-01-01

Diabetic Retinopathy (DR) is a complication of diabetes that can lead to blindness if not readily discovered. Automated screening algorithms have the potential to improve identification of patients who need further medical attention. However, the identification of lesions must be accurate to be useful for clinical application. The bag-of-visual-words (BoVW) algorithm employs a maximum-margin classifier in a flexible framework that is able to detect the most common DR-related lesions such as microaneurysms, cotton-wool spots and hard exudates. BoVW allows to bypass the need for pre- and post-processing of the retinographic images, as well as the need of specific ad hoc techniques for identification of each type of lesion. An extensive evaluation of the BoVW model, using three large retinograph datasets (DR1, DR2 and Messidor) with different resolution and collected by different healthcare personnel, was performed. The results demonstrate that the BoVW classification approach can identify different lesions within an image without having to utilize different algorithms for each lesion reducing processing time and providing a more flexible diagnostic system. Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up Robust Features (SURF) local descriptor, and mid-level features based on semi-soft coding with max pooling. The best BoVW representation for retinal image classification was an area under the receiver operating characteristic curve (AUC-ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset validation protocol. To assess the accuracy for detecting cases that require referral within one year, the sparse extraction technique associated with semi-soft coding and max pooling obtained an AUC of 94.22.0%, outperforming current methods. Those results indicate that, for retinal image classification tasks in clinical practice, BoVW is equal and, in some instances, surpasses results obtained using dense detection (widely

Monocular focal retinal lesions induce short-term topographic plasticity in adult cat visual cortex.

PubMed Central

Calford, M B; Schmid, L M; Rosa, M G

1999-01-01

Electrophysiological recording in primary visual cortex (VI) was performed both prior to and in the hours immediately following the creation of a discrete retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21-64 mm2) were defined in the visual cortex by mapping the extent of the lesion onto the topographic representation in cortex. There was no effect on neuronal responses to the unlesioned eye or on its topographic representation. However, within hours of producing the retinal lesion, receptive fields obtained from stimulation of the lesioned eye were displaced onto areas surrounding the scotoma and were enlarged compared with the corresponding field obtained through the normal eye. The proportion of such responsive recording sites increased during the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed neurons responsive to the lesioned eye. This is an equivalent proportion to that previously reported with long-term recovery (three weeks to three months). Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ. The reorganization of the lesioned eye representation produced binocular disparities as great as 15 degrees, suggesting interactions between sites in VI up to 5.5 mm apart. PMID:10189714

Outcomes of cytomegalovirus retinitis-related retinal detachment surgery in acquired immunodeficiency syndrome patients in an Asian population.

PubMed

Wong, John X; Wong, Elizabeth P; Teoh, Stephen C

2014-11-27

This study reports the surgical outcomes of acquired immunodeficiency syndrome (AIDS) patients with Cytomegalovirus retinitis (CMVR) -related retinal detachments(RD) in an Asian population. Review of CMVR characteristics, surgical outcomes and complications in 19 eyes with CMVR-related RD that underwent surgery from January 2000 to June 2011. CMVR was inactive in 73.7% of the eyes at time of surgery. Anatomical success was achieved in 14 eyes. Seven eyes (36.8%) had improvement of two or more lines in visual acuity (VA) and 8 eyes (42.1%) maintained VA. Thirteen eyes presented with worse than 6/120 vision, with 30.8% of them achieving ambulatory vision or better. Five eyes had re-detachments. Median durations from CMVR and immune recovery uveitis (IRU) diagnoses to RD were 2.7 and 1.0 months respectively. Surgery for CMVR-related RD is associated with good anatomical outcomes with most eyes maintaining or having improved vision. CMVR lesion size of <50% retinal area is associated with better outcomes. Eyes with CMVR and IRU require close monitoring for RD.

Detection and classification of retinal lesions for grading of diabetic retinopathy.

PubMed

Usman Akram, M; Khalid, Shehzad; Tariq, Anam; Khan, Shoab A; Azam, Farooque

2014-02-01

Diabetic Retinopathy (DR) is an eye abnormality in which the human retina is affected due to an increasing amount of insulin in blood. The early detection and diagnosis of DR is vital to save the vision of diabetes patients. The early signs of DR which appear on the surface of the retina are microaneurysms, haemorrhages, and exudates. In this paper, we propose a system consisting of a novel hybrid classifier for the detection of retinal lesions. The proposed system consists of preprocessing, extraction of candidate lesions, feature set formulation, and classification. In preprocessing, the system eliminates background pixels and extracts the blood vessels and optic disc from the digital retinal image. The candidate lesion detection phase extracts, using filter banks, all regions which may possibly have any type of lesion. A feature set based on different descriptors, such as shape, intensity, and statistics, is formulated for each possible candidate region: this further helps in classifying that region. This paper presents an extension of the m-Mediods based modeling approach, and combines it with a Gaussian Mixture Model in an ensemble to form a hybrid classifier to improve the accuracy of the classification. The proposed system is assessed using standard fundus image databases with the help of performance parameters, such as, sensitivity, specificity, accuracy, and the Receiver Operating Characteristics curves for statistical analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Longitudinal Structural changes in Late-onset Retinal Degeneration

PubMed Central

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A.

2016-01-01

Purpose To characterize longitudinal structural changes in early stages of late-onset retinal degeneration (L-ORD) to investigate pathogenic mechanisms. Methods Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence (FAF) images, near infrared reflectance (NIR-R) fundus images, and spectral domain optical coherence tomography (SD-OCT) scans were acquired during follow-up. Results Both patients, aged 45 and 50 years, had good visual acuities (> 20/20 OU) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on FAF and NIR-R imaging. Baseline SD-OCT imaging revealed subretinal deposits that resemble reticular pseudodrusen (RPD) described in age-related macular degeneration (AMD). During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial (RPE) layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt RPE and outer retinal atrophy. Conclusions Structural changes in early stage L-ORD revealed by multimodal imaging resemble those of RPD observed in AMD and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations. PMID:27388725

Bright Retinal Lesions Detection using Colour Fundus Images Containing Reflective Features

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

Giancardo, Luca; Karnowski, Thomas Paul; Chaum, Edward

2009-01-01

In the last years the research community has developed many techniques to detect and diagnose diabetic retinopathy with retinal fundus images. This is a necessary step for the implementation of a large scale screening effort in rural areas where ophthalmologists are not available. In the United States of America, the incidence of diabetes is worryingly increasing among the young population. Retina fundus images of patients younger than 20 years old present a high amount of reflection due to the Nerve Fibre Layer (NFL), the younger the patient the more these reflections are visible. To our knowledge we are not awaremore » of algorithms able to explicitly deal with this type of reflection artefact. This paper presents a technique to detect bright lesions also in patients with a high degree of reflective NFL. First, the candidate bright lesions are detected using image equalization and relatively simple histogram analysis. Then, a classifier is trained using texture descriptor (Multi-scale Local Binary Patterns) and other features in order to remove the false positives in the lesion detection. Finally, the area of the lesions is used to diagnose diabetic retinopathy. Our database consists of 33 images from a telemedicine network currently developed. When determining moderate to high diabetic retinopathy using the bright lesions detected the algorithm achieves a sensitivity of 100% at a specificity of 100% using hold-one-out testing.« less

Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis

PubMed Central

Omarova, Saida; Charvet, Casey D.; Reem, Rachel E.; Mast, Natalia; Zheng, Wenchao; Huang, Suber; Peachey, Neal S.; Pikuleva, Irina A.

2012-01-01

Several lines of evidence suggest a link between age-related macular degeneration and retinal cholesterol maintenance. Cytochrome P450 27A1 (CYP27A1) is a ubiquitously expressed mitochondrial sterol 27-hydroxylase that plays an important role in the metabolism of cholesterol and cholesterol-related compounds. We conducted a comprehensive ophthalmic evaluation of mice lacking CYP27A1. We found that the loss of CYP27A1 led to dysregulation of retinal cholesterol homeostasis, including unexpected upregulation of retinal cholesterol biosynthesis. Cyp27a1–/– mice developed retinal lesions characterized by cholesterol deposition beneath the retinal pigment epithelium. Further, Cyp27a1-null mice showed pathological neovascularization, which likely arose from both the retina and the choroid, that led to the formation of retinal-choroidal anastomosis. Blood flow alterations and blood vessel leakage were noted in the areas of pathology. The Cyp27a1–/– retina was hypoxic and had activated Müller cells. We suggest a mechanism whereby abolished sterol 27-hydroxylase activity leads to vascular changes and identify Cyp27a1–/– mice as a model for one of the variants of type 3 retinal neovascularization occurring in some patients with age-related macular degeneration. PMID:22820291

Retinal imaging and image analysis.

PubMed

Abràmoff, Michael D; Garvin, Mona K; Sonka, Milan

2010-01-01

Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships.

Retinal Imaging and Image Analysis

PubMed Central

Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

2011-01-01

Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:22275207

Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016.

PubMed

Steptoe, Paul J; Scott, Janet T; Baxter, Julia M; Parkes, Craig K; Dwivedi, Rahul; Czanner, Gabriela; Vandy, Matthew J; Momorie, Fayiah; Fornah, Alimamy D; Komba, Patrick; Richards, Jade; Sahr, Foday; Beare, Nicholas A V; Semple, Malcolm G

2017-07-01

We conducted a case-control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%-85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%-87.9%) of controls. Unilateral white cataracts were present in 7.4% (97.5% CI 2.4%-16.7%) of EVD survivors and no controls. Aqueous humor from 2 EVD survivors with cataract but no anterior chamber inflammation were PCR-negative for Zaire Ebola virus, permitting cataract surgery. A novel retinal lesion following the anatomic distribution of the optic nerve axons occurred in 14.6% (97.5% CI 7.1%-25.6%) of EVD survivors and no controls, suggesting neuronal transmission as a route of ocular entry.

Topographic and age-related changes of the retinal epithelium and Bruch's membrane of rhesus monkeys.

PubMed

Gouras, Peter; Ivert, Lena; Neuringer, Martha; Mattison, Julie A

2010-07-01

To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch's membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age. The retinas of two old (24 and 26 years old) and two young (1 and 6 years old) female monkeys were examined by light fluorescence and electron microscopy at the macula, equator, and ora serrata. All monkeys lacked fluorescence and lipofuscin granules in the RPE at the ora serrata where photoreceptors are absent. The equator and macula showed intense fluorescence and many lipofuscin granules in the RPE of the old but not the young monkeys. At the ora, the RPE contained many dense round melanin granules throughout the cell. At the equator and macula, melanin granules were more apical, less frequent, and often elongated. Mitochondria were clustered at the basal side of the RPE cell near infolds of the plasma membrane. Both mitochondria and infolds tended to increase toward the macula. In all regions, the basal lamina of the RPE did not penetrate the extracellular space adjacent to infolds. The elastin layer of Bruch's membrane was wide at the ora and equator and thinner at the macula. In the old monkeys, drusen were found at all retinal regions between the basal lamina and the internal collagen layer of Bruch's membrane. The drusen were often membrane-bound with a basal lamina and contained material resembling structures in the RPE. Lack of fluorescence and lipofuscin in the RPE at the ora serrata, where photoreceptors are absent, confirms that RPE fluorescence occurs only where outer segments are phagocytized. Mitochondrial clustering indicates that the basal side of the RPE cell uses the most energy and this becomes maximal at the macula. The presence of age-related degenerative changes and drusen at all retinal locations in the older monkeys, even at the ora where RPE lipofuscin was absent, indicates that these processes are not dependent on local lipofuscin accumulation. Therefore lipofuscin

Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation.

PubMed

Litts, Katie M; Messinger, Jeffrey D; Freund, K Bailey; Zhang, Yuhua; Curcio, Christine A

2015-04-01

To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured. Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space. In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.

Hierarchical detection of red lesions in retinal images by multiscale correlation filtering

NASA Astrophysics Data System (ADS)

Zhang, Bob; Wu, Xiangqian; You, Jane; Li, Qin; Karray, Fakhri

2009-02-01

This paper presents an approach to the computer aided diagnosis (CAD) of diabetic retinopathy (DR) -- a common and severe complication of long-term diabetes which damages the retina and cause blindness. Since red lesions are regarded as the first signs of DR, there has been extensive research on effective detection and localization of these abnormalities in retinal images. In contrast to existing algorithms, a new approach based on Multiscale Correlation Filtering (MSCF) and dynamic thresholding is developed. This consists of two levels, Red Lesion Candidate Detection (coarse level) and True Red Lesion Detection (fine level). The approach was evaluated using data from Retinopathy On-line Challenge (ROC) competition website and we conclude our method to be effective and efficient.

Retinal Detachment Associated With Basketball-Related Eye Trauma.

PubMed

Lee, Tsung-Han; Chen, Yi-Hao; Kuo, Hsi-Kung; Chen, Yung-Jen; Chen, Chih-Hsin; Lee, Jong-Jer; Wu, Pei-Chang

2017-08-01

Basketball is a popular sport involving significant body contact, which may frequently result in ocular trauma. The aim of this study was to evaluate the characteristics and visual outcomes of retinal detachment associated with basketball-related injury. Retrospective, interventional case series. We reviewed the course of patients who sustained traumatic retinal detachment from basketball-related ocular trauma between 2003 and 2015. Thirteen patients were evaluated for basketball-related traumatic retinal detachment. Twelve (92%) were male and 1 (8%) female, with an average age of 18.2 years. The majority (9 of 13, 70%) of patients had moderate-to-high myopia, and none were using protective eyewear when they sustained the eye trauma. Rhegmatogenous retinal detachment was observed in all eyes. The preoperative mean visual acuity was 20/625 (range, hand motions to 20/20). Initial surgery using scleral buckling alone was performed in most (8 of 13, 62%) of the patients. Retinal reattachment was achieved in 10 (76%) eyes after the first operation and in 12 (92%) at the end of the intervention. The mean follow-up was 3.9 years (range, 4 months to 12 years). The visual acuity during last follow-up was 20/231 (range, light perception to 20/20). In the multivariable analysis, initial visual acuity was an independent factor affecting the final visual outcome (P = .006). Retinal detachment associated with basketball-related injury may cause severe visual loss. In the current study, all retinal detachments were of rhegmatogenous type and commonly occurred in young individuals with myopia. Initial visual acuity was associated with the prognosis. Risk awareness for early detection and intervention are important in these traumas. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between retinal thickness measured by spectral-domain optical coherence tomography (OCT) and rod-mediated dark adaptation in non-exudative age-related maculopathy.

PubMed

Clark, Mark E; McGwin, Gerald; Neely, David; Feist, Richard; Mason, John O; Thomley, Martin; White, Milton F; Ozaydin, Bunyamin; Girkin, Christopher A; Owsley, Cynthia

2011-10-01

To examine associations between retinal thickness and rod-mediated dark adaptation in older adults with non-exudative age-related maculopathy (ARM) or normal macular health. A cross-sectional study was conducted with 74 adults ≥ 50 years old from the comprehensive ophthalmology and retina services of an academic eye centre. ARM presence and disease severity in the enrolment eye was defined by the masked grading of stereofundus photos using the Clinical Age-Related Maculopathy grading system. High-definition, spectral-domain optical coherence tomography was used to estimate retinal thickness in a grid of regions in the macula. Rod-mediated dark adaptation, recovery of light sensitivity after a photo-bleach, was measured over a 20-min period for a 500 nm target presented at 5° on the inferior vertical meridian. Main outcomes of interest were retinal thickness in the macula (μm) and parameters of rod-mediated dark adaptation (second slope, third slope, average sensitivity, final sensitivity). In non-exudative disease retinal thickness was decreased in greater disease severity; thinner retina was associated with reductions in average and final rod-mediated sensitivity even after adjustment for age and visual acuity. Impairment in rod-mediated dark adaptation in non-exudative ARM is associated with macular thinning.

Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

PubMed

Wavre-Shapton, Silène T; Tolmachova, Tanya; Lopes da Silva, Mafalda; da Silva, Mafalda Lopes; Futter, Clare E; Seabra, Miguel C

2013-01-01

The retinal pigment epithelium (RPE) is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM) is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1). REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox), Tyr-Cre+). Transmission electron microscopy (TEM) was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox), Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD) suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

Outcomes of eyes with lesions composed of >50% blood in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

PubMed

Altaweel, Michael M; Daniel, Ebenezer; Martin, Daniel F; Mittra, Robert A; Grunwald, Juan E; Lai, Michael M; Melamud, Alexander; Morse, Lawrence S; Huang, Jiayan; Ferris, Frederick L; Fine, Stuart L; Maguire, Maureen G

2015-02-01

To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with >50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a multicenter randomized clinical trial. CATT patients with neovascular age-related macular degeneration (AMD). Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA. Morphologic features and VA at 1 and 2 years. The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P < 0.001), total lesion size was greater (4.55 vs 2.31 DA; P <0.001), total retinal thickness was greater (524 vs 455 μm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P < 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years. In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of >50% blood can be

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.

N-acetylcysteine and acute retinal laser lesions in the colubrid snake eye

NASA Astrophysics Data System (ADS)

Elliott, William R., III; Rentmeister-Bryant, Heike K.; Barsalou, Norman; Beer, Jeremy; Zwick, Harry

2004-07-01

This study examined the role of oxidative stress and the effect of a single dose treatment with N-Acetylcysteine (NAC) on the temporal development of acute laser-induced retinal injury. We used the snake eye/Scanning Laser Ophthalmoscope (SLO) model, an in vivo, non-invasive ocular imaging technique, which has the ability to image cellular retinal detail and allows for studying morphological changes of retinal injury over time. For this study 12 corn-snakes (Elaphe g. guttata) received 5 laser exposures per eye, followed by either a single dose of the antioxidant NAC (150mg/kg, IP in sterile saline) or placebo. Laser exposures were made with a Nd: VO4 DPSS, 532nm laser, coaxially aligned to the SLO. Shuttered pulses were 20msec x 50 mW; 1mJ each. Retinal images were taken using a Rodenstock cSLO and were digitally recorded at 1, 6, 24-hrs, and at 3-wks post-exposure. Lesions were assessed by two raters blind to the conditions of the study yielding measures of damaged area and counts of missing or damaged photoreceptors. Treated eyes showed a significant beneficial effect overall, and these results suggest that oxidative stress plays a role in laser-induced retinal injury. The use of NAC or a similar antioxidant shows promise as a therapeutic tool.

Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016

PubMed Central

Scott, Janet T.; Baxter, Julia M.; Parkes, Craig K.; Dwivedi, Rahul; Czanner, Gabriela; Vandy, Matthew J.; Momorie, Fayiah; Fornah, Alimamy D.; Komba, Patrick; Richards, Jade; Sahr, Foday; Beare, Nicholas A.V.; Semple, Malcolm G.

2017-01-01

We conducted a case–control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%–85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%–87.9%) of controls. Unilateral white cataracts were present in 7.4% (97.5% CI 2.4%–16.7%) of EVD survivors and no controls. Aqueous humor from 2 EVD survivors with cataract but no anterior chamber inflammation were PCR-negative for Zaire Ebola virus, permitting cataract surgery. A novel retinal lesion following the anatomic distribution of the optic nerve axons occurred in 14.6% (97.5% CI 7.1%–25.6%) of EVD survivors and no controls, suggesting neuronal transmission as a route of ocular entry. PMID:28628441

Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

PubMed Central

Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin

2015-01-01

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch’s membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. PMID:19698799

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

Ceroid lipofuscinosis in the border collie dog: retinal lesions in an animal model of juvenile Batten disease.

PubMed

Taylor, R M; Farrow, B R

1992-02-15

Ceroid lipofuscinosis, an inherited disorder of lipopigment accumulation, was identified in a group of Border Collie dogs. The dogs developed mental, motor, and visual signs between age 15 and 22 months and progressed rapidly to severe neurological disease. The principal signs were blindness and gait and behavioural abnormalities with progressive dementia. Lipopigment accumulation was severe in neurones and glial cells of the central nervous system and was present in some visceral cells. Inclusions with variable ultrastructure were common in all cells of the retina, but the pigment accumulation did not damage the retinal architecture. The cytoplasmic inclusions were granular, sudanophilic, eosinophilic, and autofluorescent. Ultrastructural morphology varied, but fingerprint and curvilinear patterns predominated. The retinal lesions in the Border Collies were similar to those in English Setters with ceroid lipofuscinosis, but were much less severe than in juvenile human ceroid lipofuscinosis. This disorder bears a close resemblance to ceroid lipofuscinosis in English Setters and is another useful model for Batten's disease.

Optical coherence tomography angiography in age-related macular degeneration: The game changer.

PubMed

Lupidi, Marco; Cerquaglia, Alessio; Chhablani, Jay; Fiore, Tito; Singh, Sumit Randhir; Cardillo Piccolino, Felice; Corbucci, Roberta; Coscas, Florence; Coscas, Gabriel; Cagini, Carlo

2018-04-01

Optical coherence tomography angiography is one of the biggest advances in ophthalmic imaging. It enables a depth-resolved assessment of the retinal and choroidal blood flow, far exceeding the levels of detail commonly obtained with dye angiographies. One of the first applications of optical coherence tomography angiography was in detecting the presence of choroidal neovascularization in age-related macular degeneration and establishing its position in relation to the retinal pigmented epithelium and Bruch's membrane, and thereby classifying the CNV as type 1, type 2, type 3, or mixed lesions. Optical coherence tomography angiograms, due to the longer wavelength used by optical coherence tomography, showed a more distinct choroidal neovascularization vascular pattern than fluorescein angiography, since there is less suffering from light scattering or is less obscured by overlying subretinal hemorrhages or exudation. Qualitative and quantitative assessments of optical coherence tomography angiography findings in exudative and nonexudative age-related macular degeneration have been largely investigated within the past 3 years both in clinical and experimental settings. This review constitutes an up-to-date of all the potential applications of optical coherence tomography angiography in age-related macular degeneration in order to better understand how to translate its theoretical usefulness into the current clinical practice.

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

PubMed

Lee, S C; Lee, E T; Kingsley, R M; Wang, Y; Russell, D; Klein, R; Warn, A

2001-04-01

To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Diagnostic Exercise: Retinal Lesions in a Mouse

DTIC Science & Technology

1989-12-07

retinal degeneration is reported as an autosomal recessive trait, particularly prevalent in Swiss-derived strains; and the allele responsible is...should be used for breeding purposes. Affected mice can be identified by indirect ophthalmoscopy at 3 weeks of age. 10 This precaution alone will not...should be carefully screened prior to initiation of the study. REFERENCES 1. Bellhom R W, Laboratory Animal Ophthalmology . In Gelatt K N ed

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

DOE PAGES

Sridharan, Deepa M.; Enerio, Shiena; Stampfer, Martha M.; ...

2017-02-28

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations andmore » changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.« less

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

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

Sridharan, Deepa M.; Enerio, Shiena; Stampfer, Martha M.

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations andmore » changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.« less

A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.

PubMed

Kashiwagi, Kenji; Ito, Sadahiro; Maeda, Shuichiro; Kato, Goro

2017-12-01

Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole retinas was significantly lower than that in young SD/SD mice in the absence of inflammation and elevated intraocular pressure, resembling the pathogenesis of progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice exhibited no age-related RGC loss. The age-related retinal RGC number reduction was greater in the peripheral rather than the mid-peripheral region of the retina in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of ageing SD/SD mice was significantly higher than that in young SD/SD mice. These results suggest that Src regulates RGC survival during ageing in a manner that depends on Ser75 phosphorylation.

Retinal microvasculature and white matter microstructure: The Rotterdam Study.

PubMed

Mutlu, Unal; Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Klaver, Caroline C W; Ikram, M Arfan; Vernooij, Meike W; Ikram, M Kamran

2016-09-06

To investigate whether retinal microvascular damage is related to normal-appearing white matter microstructure on diffusion tensor MRI. We included 2,436 participants (age ≥45 years) from the population-based Rotterdam Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. White matter microstructure was assessed using diffusion tensor MRI. We used linear regression models to investigate the associations of retinal vascular calibers with markers of normal-appearing white matter microstructure, adjusting for age, sex, the fellow vascular caliber, and additionally for structural MRI markers and cardiovascular risk factors. Narrower arterioles and wider venules were associated with poor white matter microstructure: adjusted difference in fractional anisotropy per SD decrease in arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and increase in venular caliber 0.047 (0.008-0.085). The associations for venules were more prominent in women. Retinal vascular calibers are related to normal-appearing white matter microstructure. This suggests that microvascular damage in the white matter is more widespread than visually detectable as white matter lesions. © 2016 American Academy of Neurology.

Reticular pseudodrusen in age-related macular degeneration.

PubMed

Hogg, Ruth Esther

2014-08-01

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

Cytomegalovirus Retinitis in Three Pediatric Cases with Acute Lymphoblastic Leukemia: Case Series and Review of the Literature.

PubMed

Demir, Sevliya Öcal; Çeliker, Hande; Karaaslan, Ayşe; Kadayifci, Eda Kepenekli; Akkoç, Gülşen; Atıcı, Serkan; Yakut, Nurhayat; Şenay, Emel; Kazokoğlu, Haluk; Koç, Ahmet; Bakır, Mustafa; Soysal, Ahmet

2016-11-22

Cytomegalovirus (CMV) retinitis is typically diagnosed in patient with AIDS and those who underwent allogeneic hematopoietic cell transplant. However, it may develop in patients with acute lymphoblastic leukemia (ALL) who have not undergone hematopoietic cell transplantation. To increase awareness of CMV retinitis in this group, we describe 3 patients ages 3, 9, and 12, with ALL who developed CMV retinitis. The diagnosis of CMV retinitis was made on the basis of ophthalmological findings suggesting typical retinal lesions. In 2 cases, CMV DNAemia was present, while in 1 patient CMV DNA was detected only in vitreous fluid using the PCR technique. All cases were treated with intravenous ganciclovir for 2 or 3 weeks as induction therapy, followed by oral valganciclovir prophylaxis. Initially, active retinitis lesions resolved in all cases; however, in 1 patient CMV retinitis relapsed 3 times during follow-up. In this case, by using foscarnet therapy, satisfactory responses were achieved and the progression of CMV retinitis lesions stopped and eventually regressed.

Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions.

PubMed

Kern, Kyle C; Wright, Clinton B; Bergfield, Kaitlin L; Fitzhugh, Megan C; Chen, Kewei; Moeller, James R; Nabizadeh, Nooshin; Elkind, Mitchell S V; Sacco, Ralph L; Stern, Yaakov; DeCarli, Charles S; Alexander, Gene E

2017-01-01

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

AGGRESSIVE RETINAL ASTROCYTOMAS IN FOUR PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX

PubMed Central

Shields, Jerry A; Eagle, Ralph C; Shields, Carol L; Marr, Brian P

2004-01-01

ABSTRACT Objective To report the clinical and histopathologic findings of retinal astrocytic tumors that showed progressive growth in four patients with tuberous sclerosis complex (TSC). Methods Four young children each developed an enlarging retinal neoplasm that eventually necessitated enucleation of the affected eye. The systemic findings, clinical course, and histopathologic findings were reviewed. Results Each patient had a progressively enlarging retinal mass associated with a total exudative retinal detachment and neovascular glaucoma. Enucleation was necessary in each case because the affected eye became blind and painful. The mean patient age at enucleation was 7 years, and the median age was 3 years. At the time of enucleation the tumors ranged from 10 to 20 mm in basal diameter and from 10 to 25 mm in thickness. Histopathologic studies of each eye revealed a giant cell astrocytoma that had produced a total exudative retinal detachment. The tumor cells showed positive immunoreactivity to neuron-specific enolase and glial fibrillary acidic protein. The retinal neoplasms in these cases were identical histopathologically to the subependymal giant cell astrocytoma that typifies TSC in the brain. One tumor filled the entire eye and perforated the globe. Although the lesions simulated retinoblastoma clinically, each patient had ocular and systemic findings of TSC, supporting the diagnosis of astrocytic hamartoma. Conclusions Although retinal astrocytic lesions of TSC generally are stationary, they can sometimes grow relentlessly and cause severe ocular complications. Patients with retinal astrocytic hamartomas should have serial ophthalmic evaluations because of this possibility. PMID:15747752

Treatment of cytomegalovirus (CMV) retinitis with intravitreous ganciclovir in HIV-infected children.

PubMed

Surachatkumtonekul, Thammanoon; Chokephaibulkit, Kulkanya; Vanprapar, Nirun; Pamonvaechavan, Pittaya

2008-03-01

To evaluate the efficacy, visual outcomes, and complications of intravitreous ganciclovir treatment in cytomegalovirus (CMV) retinitis in HIV-infected children. The medical records of HIV-infected children who were screened for CMV retinitis from February 2002 to February 2005 were reviewed. The children with CD4+ < 15%, or with clinical category C would have complete ophthalmic examination every 3 months. Ganciclovir (4 mg/0.04 ml) was administered intravitreously to the eye with CMV retinitis every 2 weeks under general anaesthesia. After injection, fundi were examined immediately, 1 day, 14 days and every 2 weeks until the lesions were stable. Six (9 eyes) out of 45 children (13%) aged 2-12 years were found to have CMV retinitis. All CMV retinitis lesions were "cheese and ketchup like" (retinal hemorrhage and exudate) lesions and presented in the posterior pole. Bilateral CMV retinitis were found in 3 children. Intravitreous ganciclovir was injected in 4 children (5 eyes). The average number of intravitreous injections for each patient was 5.6 (3-7) times. All of the children received antiretroviral therapy and 3 children also received intravenous ganciclovir CMV retinitis lesions were improved in every eye. The visual acuity (VA) remained stable in 4 eyes, but endophthalmitis developed in one eye a few days after injection. The average duration of follow-up was 13.5 months (3-23 months). CMV retinitis was not uncommon. The authors found that intravitreous ganciclovir was effective but may cause complications. This treatment should be considered in a resource-limited setting.

Quantitative susceptibility mapping of multiple sclerosis lesions at various ages.

PubMed

Chen, Weiwei; Gauthier, Susan A; Gupta, Ajay; Comunale, Joseph; Liu, Tian; Wang, Shuai; Pei, Mengchao; Pitt, David; Wang, Yi

2014-04-01

To assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging. Retrospectively selected were 32 clinically confirmed MS patients (nine men and 23 women; 39.3 years ± 10.9) who underwent two MR examinations (interval, 0.43 years ± 0.16) with three-dimensional gradient-echo sequence from August 2011 to August 2012. To estimate the ages of MS lesions, MR examinations performed 0.3-10.6 years before study examinations were studied. Hyperintensity on T2-weighted images was used to define MS lesions. QSM images were reconstructed from gradient-echo data. Susceptibility of MS lesions and temporal rates of change were obtained from QSM images. Lesion susceptibilities were analyzed by t test with intracluster correlation adjustment and Bonferroni correction in multiple comparisons. MR imaging of 32 patients depicted 598 MS lesions, of which 162 lesions (27.1%) in 23 patients were age measurable and six (1.0%) were only visible at QSM. The susceptibilities relative to normal-appearing white matter (NAWM) were 0.53 ppb ± 3.34 for acute enhanced lesions, 38.43 ppb ± 13.0 (positive; P < .01) for early to intermediately aged nonenhanced lesions, and 4.67 ppb ± 3.18 for chronic nonenhanced lesions. Temporal rates of susceptibility changes relative to cerebrospinal fluid were 12.49 ppb/month ± 3.15 for acute enhanced lesions, 1.27 ppb/month ± 2.31 for early to intermediately aged nonenhanced lesions, and -0.004 ppb/month ± 0 for chronic nonenhanced lesions. Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions. Online supplemental material is available for this

In Vivo Confocal Intrinsic Optical Signal Identification of Localized Retinal Dysfunction

PubMed Central

Zhang, Qiu-Xiang; Lu, Rong-Wen; Curcio, Christine A.; Yao, Xin-Cheng

2012-01-01

Purpose. The purposes of this study were to investigate the physiological mechanism of stimulus-evoked fast intrinsic optical signals (IOSs) recorded in dynamic confocal imaging of the retina, and to demonstrate the feasibility of in vivo confocal IOS mapping of localized retinal dysfunctions. Methods. A rapid line-scan confocal ophthalmoscope was constructed to achieve in vivo confocal IOS imaging of frog (Rana pipiens) retinas at cellular resolution. In order to investigate the physiological mechanism of confocal IOS, comparative IOS and electroretinography (ERG) measurements were made using normal frog eyes activated by variable-intensity stimuli. A dynamic spatiotemporal filtering algorithm was developed to reject the contamination of hemodynamic changes on fast IOS recording. Laser-injured frog eyes were employed to test the potential of confocal IOS mapping of localized retinal dysfunctions. Results. Comparative IOS and ERG experiments revealed a close correlation between the confocal IOS and retinal ERG, particularly the ERG a-wave, which has been widely used to evaluate photoreceptor function. IOS imaging of laser-injured frog eyes indicated that the confocal IOS could unambiguously detect localized (30 μm) functional lesions in the retina before a morphological abnormality is detectable. Conclusions. The confocal IOS predominantly results from retinal photoreceptors, and can be used to map localized photoreceptor lesion in laser-injured frog eyes. We anticipate that confocal IOS imaging can provide applications in early detection of age-related macular degeneration, retinitis pigmentosa, and other retinal diseases that can cause pathological changes in the photoreceptors. PMID:23150616

Ageing of the vitreous: From acute onset floaters and flashes to retinal detachment.

PubMed

Lumi, Xhevat; Hawlina, Marko; Glavač, Damjan; Facskó, Andrea; Moe, Morten C; Kaarniranta, Kai; Petrovski, Goran

2015-05-01

Floaters and flashes are most commonly symptoms of age-related degenerative changes in the vitreous body and posterior vitreous detachment. The etiology and pathogenesis of floaters' formation is still not well understood. Patients with acute-onset floaters, flashes and defects in their visual field, represent a medical emergency with the need for same day referral to an ophthalmologist. Indirect ophthalmoscopy with scleral indentation is needed in order to find possible retinal break(s), on-time treatment and prevention of retinal detachment. The molecular and genetic pathogenesis, as well as the epidemiology of the ageing changes of the vitreous is summarized here, with view on the several treatment modalities in relation to their success rate and side-effects. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Retinal Morphology on Contrast Sensitivity and Reading Ability in Neovascular Age-Related Macular Degeneration

PubMed Central

Keane, Pearse A.; Patel, Praveen J.; Ouyang, Yanling; Chen, Fred K.; Ikeji, Felicia; Walsh, Alexander C.; Tufail, Adnan

2010-01-01

Purpose. To investigate the effect of changes in retinal morphology on contrast sensitivity and reading ability in patients with neovascular age-related macular degeneration (AMD) in the Avastin (bevacizumab; Genentech, South San Francisco, CA) for choroidal neovascularization (ABC) Trial. Methods. Contrast sensitivity obtained with Pelli-Robson charts, reading ability assessed with Minnesota Reading charts, and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) obtained by protocol refraction, were recorded. Raw Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA) images were analyzed with the publicly available software OCTOR, which allows precise delineation of any retinal compartment of interest. Thickness and volume were calculated for neurosensory retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelium detachment, and the resulting measurements were correlated with each visual function parameter. Results. One hundred twenty-two patients with newly diagnosed neovascular AMD and enrolled in the ABC Trial, were evaluated. Increased subretinal tissue volume correlated with decreased contrast sensitivity (Pearson's correlation coefficient, r = −0.4944, P = 0.001). A modest correlation was detected between SRF volume and contrast sensitivity (r = −0.2562, P = 0.004). Increased retinal thickness at the foveal center also correlated with decreased visual function (ETDRS VA: r = −0.4530, P < 0.001). Conclusions. The strongest correlation detected between the functional parameters assessed and any of the OCT-derived morphologic parameters was that between decreased contrast sensitivity and increased subretinal tissue. In the future, assessment of contrast sensitivity and reading ability, in combination with quantitative subanalysis of retinal compartments, may lead to the identification of parameters relevant to functional improvement and ultimate prognosis in patients with newly diagnosed

Retinal Diseases

MedlinePlus

... You are here Home Listen Retinal Diseases Macular Degeneration Age-related macular degeneration (AMD) is a retinal degenerative disease that causes ... is the most common form of inherited juvenile macular degeneration. The progressive vision loss associated with Stargardt disease ...

Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases.

PubMed

Nishimura, Yuhei; Hara, Hideaki

2016-01-01

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases.

Activated Retinal Pigment Epithelium, an Optical Coherence Tomography Biomarker for Progression in Age-Related Macular Degeneration

PubMed Central

Curcio, Christine A.; Zanzottera, Emma C.; Ach, Thomas; Balaratnasingam, Chandrakumar; Freund, K. Bailey

2017-01-01

Purpose To summarize and contextualize recent histology and clinical imaging publications on retinal pigment epithelium (RPE) fate in advanced age-related macular degeneration (AMD); to support RPE activation and migration as important precursors to atrophy, manifest as intraretinal hyperreflective foci in spectral-domain optical coherence tomography (SDOCT). Methods The Project MACULA online resource for AMD histopathology was surveyed systematically to form a catalog of 15 phenotypes of RPE and RPE-derived cells and layer thicknesses in advanced disease. Phenotypes were also sought in correlations with clinical longitudinal eye-tracked SDOCT and with ex vivo imaging–histopathology correlations in geographic atrophy (GA) and pigment epithelium detachments (PED). Results The morphology catalog suggested two main pathways of RPE fate: basolateral shedding of intracellular organelles (apparent apoptosis in situ) and activation with anterior migration. Acquired vitelliform lesions may represent a third pathway. Migrated cells are packed with RPE organelles and confirmed as hyperreflective on SDOCT. RPE layer thickening due to cellular dysmorphia and thick basal laminar deposit is observed near the border of GA. Drusenoid PED show a life cycle of slow growth and rapid collapse preceded by RPE layer disruption and anterior migration. Conclusions RPE activation and migration comprise an important precursor to atrophy that can be observed at the cellular level in vivo via validated SDOCT. Collapse of large drusen and drusenoid PED appears to occur when RPE death and migration prevent continued production of druse components. Data implicate excessive diffusion distance from choriocapillaris in RPE death as well as support a potential benefit in targeting drusen in GA. PMID:28785769

Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

PubMed

Rastogi, Neelesh; Smith, R Theodore

2016-01-01

Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Ocular Risk Factors for Age-related Macular Degeneration: The Los Angeles Latino Eye Study (LALES)

PubMed Central

Fraser-Bell, Samantha; Choudhury, Farzana; Klein, Ronald; Azen, Stanley; Varma, Rohit

2010-01-01

Purpose To assess the association of ocular factors and age-related macular degeneration (AMD) in Latinos. Design Population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older. Methods Ophthalmic examination included subjective refraction, measurement of axial length, evaluation of iris color, Lens Opacities Classification System II (LOCS II) grading of cataracts, and stereoscopic macular photographs for AMD lesions. Generalized estimating equation analysis incorporated data from both eyes to estimate odds ratios adjusted for covariates. Results After controlling for confounders (age, gender and smoking), prior cataract surgery was associated with advanced AMD (OR: 2.8, 95% CI 1.0, 7.8), increased retinal pigment (OR: 1.6, 95% CI 1.0, 1.5) and retinal pigment epithelial depigmentation (OR: 2.2, 95% CI 1.1, 4.4). The presence of any lens opacity was associated with soft drusen (OR: 1.2; 95% CI 1.0, 1.5). Longer axial length (per mm) was associated with a decreased odds of soft drusen, increased retinal pigment, and geographic atrophy (GA) (ORs: 0.8 [95% CI 0.7, 0.9], 0.8 [95% CI 0.7, 0.9], 0.7 [95% CI 0.5, 0.9], respectively. Myopia was inversely associated with soft drusen (OR: 0.8; 95% CI 0.7, 1.0). Lighter colored irises were associated with GA (OR: 5.0; 95% CI 1.0, 25.3). Conclusions Cross-sectional associations of ocular factors such as cataract, cataract surgery, and refractive errors with early AMD lesions found in Latinos were consistent with those in whites. Additionally, prior cataract surgery was associated with advanced AMD. PMID:20138605

Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

PubMed

Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

2016-08-10

We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

RETINAL VASCULAR PATHOLOGY RISK DEVELOPMENT IN THE IRRADIATED AT DIFFERENT AGES AS A RESULT OF CHERNOBYL NPP ACCIDENT.

PubMed

Fedirko, P A; Babenko, T F; Dorichevska, R Yu; Garkava, N A

2015-12-01

To assess the relationship between the age at which a person undergoes radiation exposure and risk of developing eye lesions (case study of the retinal angiopathy prevalence). The object of the study was the state of the retinal vessels in 2,531 persons (1,948 evacuated from the city of Pripyat under the age of 20 and 583 exposed to radiation in utero as a result of the Chernobyl NPP disaster. The results of standardized ophthalmic examination conducted from 1993 to 2000 within the framework of Clinical and epidemiological registry are used for the analysis. The evacuees were subdivided into different age groups of the exposed to radiation. The cohort of control group formed corresponding age groups of the unirradiated control. Statistical analysis of the survey results was carried out using the free trial version of «Open Epi 2.2.1» software package. The results obtained revealed a significant prevalence of retinal vessels pathology in all groups. The difference in angiopathy prevalence in exposed in utero persons was significant compared to age-control. The prevalence of retinal vascular pathology was also significantly higher in all groups of evacuees. Angiopathy prevalence was higher in the group exposed in utero and at the age of 8-12 years, and in the group of people who were exposed at the age of 4-7 years, the risk of angiopathy was lower. It is proved that the occurrence of distant radiation effects mainly depends on the age at which a person has undergone irradiation. It should be noted that all the other conditions were approximately the same. If working conditions of the persons who were exposed in utero or were aged 8 to 20 years when the Chernobyl disaster happened are connected with occupational radiation exposure it is necessary to take additional preventive measures. P. А. Fedirko, T. F. Babenko, R. Yu. Dorichevska, N. А. Garkava.

Lack of P4H-TM in mice results in age-related retinal and renal alterations.

PubMed

Leinonen, Henri; Rossi, Maarit; Salo, Antti M; Tiainen, Päivi; Hyvärinen, Jaana; Pitkänen, Marja; Sormunen, Raija; Miinalainen, Ilkka; Zhang, Chi; Soininen, Raija; Kivirikko, Kari I; Koskelainen, Ari; Tanila, Heikki; Myllyharju, Johanna; Koivunen, Peppi

2016-09-01

Age-related macular degeneration (AMD), affecting the retinal pigment epithelium (RPE), is the leading cause of blindness in middle-aged and older people in developed countries. Genetic and environmental risk factors have been identified, but no effective cure exists. Using a mouse model we show that a transmembrane prolyl 4-hydroxylase (P4H-TM), which participates in the oxygen-dependent regulation of the hypoxia-inducible factor (HIF), is a potential novel candidate gene for AMD. We show that P4h-tm had its highest expression levels in the mouse RPE and brain, heart, lung, skeletal muscle and kidney. P4h-tm -/- mice were fertile and had a normal life span. Lack of P4h-tm stabilized HIF-1α in cortical neurons under normoxia, while in hypoxia it increased the expression of certain HIF target genes in tissues with high endogenous P4h-tm expression levels more than in wild-type mice. Renal erythropoietin levels increased in P4h-tm -/- mice with aging, but the resulting ∼2-fold increase in erythropoietin serum levels did not lead to erythrocytosis. Instead, accumulation of lipid-containing lamellar bodies in renal tubuli was detected in P4h-tm -/- mice with aging, resulting in inflammation and fibrosis, and later glomerular sclerosis and albuminuria. Lack of P4h-tm was associated with retinal thinning, rosette-like infoldings and drusen-like structure accumulation in RPE with aging, as is characteristic of AMD. Photoreceptor recycling was compromised, and electroretinograms revealed functional impairment of the cone pathway in adult P4h-tm -/- mice and cone and rod deficiency in middle-aged mice. P4H-TM is therefore imperative for normal vision, and potentially a novel candidate for age-induced diseases, such as AMD. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases

PubMed Central

Hara, Hideaki

2016-01-01

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases. PMID:28053689

Loosely coupled level sets for retinal layers and drusen segmentation in subjects with dry age-related macular degeneration

NASA Astrophysics Data System (ADS)

Novosel, Jelena; Wang, Ziyuan; de Jong, Henk; Vermeer, Koenraad A.; van Vliet, Lucas J.

2016-03-01

Optical coherence tomography (OCT) is used to produce high-resolution three-dimensional images of the retina, which permit the investigation of retinal irregularities. In dry age-related macular degeneration (AMD), a chronic eye disease that causes central vision loss, disruptions such as drusen and changes in retinal layer thicknesses occur which could be used as biomarkers for disease monitoring and diagnosis. Due to the topology disrupting pathology, existing segmentation methods often fail. Here, we present a solution for the segmentation of retinal layers in dry AMD subjects by extending our previously presented loosely coupled level sets framework which operates on attenuation coefficients. In eyes affected by AMD, Bruch's membrane becomes visible only below the drusen and our segmentation framework is adapted to delineate such a partially discernible interface. Furthermore, the initialization stage, which tentatively segments five interfaces, is modified to accommodate the appearance of drusen. This stage is based on Dijkstra's algorithm and combines prior knowledge on the shape of the interface, gradient and attenuation coefficient in the newly proposed cost function. This prior knowledge is incorporated by varying the weights for horizontal, diagonal and vertical edges. Finally, quantitative evaluation of the accuracy shows a good agreement between manual and automated segmentation.

Automatic temperature controlled retinal photocoagulation

NASA Astrophysics Data System (ADS)

Schlott, Kerstin; Koinzer, Stefan; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf

2012-06-01

Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns/523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE=273 J mol-1 and A=3.1044 s-1. Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162+/-34 μm and 189+/-34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis.

PubMed

Chen, Mei; Rajapakse, Dinusha; Fraczek, Monika; Luo, Chang; Forrester, John V; Xu, Heping

2016-06-01

Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Objective visual assessment of antiangiogenic treatment for wet age-related macular degeneration.

PubMed

Baseler, Heidi A; Gouws, André; Crossland, Michael D; Leung, Carmen; Tufail, Adnan; Rubin, Gary S; Morland, Antony B

2011-10-01

To assess cortical responses in patients undergoing antiangiogenic treatment for wet age-related macular degeneration (AMD) using functional magnetic resonance imaging (fMRI) as an objective, fixation-independent measure of topographic visual function. A patient with bilateral neovascular AMD was scanned using fMRI before and at regular intervals while undergoing treatment with intravitreal antiangiogenic injections (ranibizumab). Blood oxygenation level-dependent signals were measured in the brain while the patient viewed a stimulus consisting of a full-field flickering (6 Hz) white light alternating with a uniform gray background (18 s on and 18 s off). Topographic distribution and magnitude of activation in visual cortex were compared longitudinally throughout the treatment period (<1 year) and with control patients not currently undergoing treatment. Clinical behavioral tests were also administered, including visual acuity, microperimetry, and reading skills. The area of visual cortex activated increased significantly after the first treatment to include more posterior cortex that normally receives inputs from lesioned parts of the retina. Subsequent treatments yielded no significant further increase in activation area. Behavioral measures all generally showed an improvement with treatment but did not always parallel one another. The untreated control patient showed a consistent lack of significant response in the cortex representing retinal lesions. Retinal treatments may not only improve vision but also result in a concomitant improvement in fixation stability. Current clinical behavioral measures (e.g., acuity and perimetry) are largely dependent on fixation stability and therefore cannot separate improvements of visual function from fixation improvements. fMRI, which provides an objective and sensitive measure of visual function independent of fixation, reveals a significant increase in visual cortical responses in patients with wet AMD after treatment with

HUMAN HtrA1 IN THE ARCHIVED EYES WITH AGE-RELATED MACULAR DEGENERATION

PubMed Central

Chan, Chi-Chao; Shen, Defen; Zhou, Min; Ross, Robert J.; Ding, Xiaoyan; Zhang, Kang; Green, W. Richard; Tuo, Jingsheng

2007-01-01

Purpose HtrA1 belongs to the high temperature requirement factor A family of serine proteases, which are involved in protein quality control and cell fate. A single-nucleotide polymorphism (SNP), rs11200638, in the promoter of HtrA1 at chromosome 10q26 is reported as a likely causal variant for age-related macular degeneration (AMD). The SNP is located in the regulatory region and increases production of HtrA1 protein. This study investigates HtrA1 expression and SNP genotypes in archived ocular slides with AMD. Methods Macular, nonretinal, and peripheral retinal cells were microdissected from archived slides from 57 eyes with AMD and 16 age-matched, non-AMD controls. HtrA1 rs11200638 SNP genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. HtrA1 transcripts were measured using real-time reverse transcriptase–PCR. HtrA1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. Results HtrA1 (G/A) SNP was successfully genotyped in 52 AMD cases and 13 non-AMD subjects. The frequencies of the risk allele (A) were 55 of 104 (52.9%) and 8 of 26 (30.8%) in AMD and control groups, respectively. HtrA1 mRNA was detected in normal peripheral and macular retinas, higher in the periphery than maculae. HtrA1 mRNA was much higher in the macula and a lot lower in the periphery of the AMD eyes as compared to control eyes. HtrA1 protein was expressed in normal retinal vascular endothelia and retinal pigment epithelia. Intense immunoreaction against HtrA1 was found in AMD lesions, slightly more in wet than dry AMD lesions. Conclusion This study successfully analyzes HtrA1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Up-regulation of HtrA1 is detected in the macular lesions of AMD eyes. The data further suggest that rs11200638 in HtrA1 promoter is associated with AMD development. PMID:18427598

Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

PubMed Central

Ausayakhun, Somsanguan; Keenan, Jeremy D; Ausayakhun, Sakarin; Jirawison, Choeng; Khouri, Claire M; Skalet, Alison H; Heiden, David; Holland, Gary N; Margolis, Todd P

2011-01-01

Purpose To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. Design Prospective, observational cross-sectional study. Methods We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. Results Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze was often present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (OR 1.24 [1.01 – 1.51]), and marked or severe border opacity (OR 1.36 [1.11 – 1.67]). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. Conclusions Patients presenting to a tertiary medical center in northern Thailand have advanced CMV retinitis, possibly due to delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and prevent visual impairment in this population. PMID:22265148

Association of Retinopathy and Retinal Microvascular Abnormalities with Stroke and Cerebrovascular Disease

PubMed Central

Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

2016-01-01

Background and purpose Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and 1) strokes and subclinical cerebral infarcts and 2) cerebral white matter lesions in a UK-based tri-ethnic population-based cohort. Methods 1185 participants (age 68.8±6.1y; 77% male) underwent retinal imaging and cerebral MRI. Cerebral infarcts and white matter hyperintensities (WMH) were identified on MRI, retinopathy was graded and retinal vessels were measured. Results Higher retinopathy grade (odds ratio (OR) = 1.40 (1.16, 1.70)), narrower arteriolar diameter (OR = 0.98 (0.97, 0.99)), fewer symmetrical arteriolar bifurcations (OR = 0.84 (0.75, 0.95)), higher arteriolar optimality deviation (OR = 1.16 (1.00, 1.34)) and more tortuous venules (OR = 1.20(1.09, 1.32)) were associated with strokes/infarcts and WMH. Associations with quantitative retinal microvascular measures were independent of retinopathy. Conclusions Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts and white matter lesions. PMID:27729577

Retinal flavoprotein autofluorescence as a measure of retinal health.

PubMed

Elner, Susan G; Elner, Victor M; Field, Matthew G; Park, Seung; Heckenlively, John R; Petty, Howard R

2008-01-01

To establish that increased autofluorescence of mitochondrial flavoproteins, an indicator of mitochondrial oxidative stress, correlates with retinal cell dysfunction. Retinal flavoprotein autofluorescence (FA) was imaged in humans with a fundus camera modified with 467DF8-nm excitation and 535-nm emission filters and a back-illuminated, electron-multiplying, charge-coupled device camera interfaced with a computer equipped with customized image capture software. Multiple digital images, centered on the fovea, were obtained from each eye. Histograms of pixel intensities in grayscale units were analyzed for average intensity and average curve width. Adults with diabetes mellitus, age-related macular degeneration (ARMD), central serous retinopathy, and retinal dystrophies, as well as healthy control volunteers, were imaged. Monolayers of cultured human retinal pigment epithelial (HRPE) cells, HRPE cells exposed to sublethal doses of H2O2, and HRPE cells exposed to H2O2 in the presence of antioxidants were imaged for FA using fluorescent photomicroscopy. Control patients demonstrated low levels of retinal FA, which increased progressively with age. Diabetics without visible retinopathy demonstrated increased FA levels compared to control volunteers (P < .001). Diabetics with retinopathy demonstrated significantly higher FA values than those without retinopathy (P < .04). Patients with ARMD, central serous retinopathy, or retinal dystrophies also demonstrated significantly increased FA. Compared to control RPE cells, cells oxidatively stressed with H2O2 had significantly elevated FA (P < .05), which was prevented by antioxidants (P < .05). Retinal FA is significantly increased with age and diseases known to be mediated by oxidative stress. Retinal FA imaging may provide a novel, noninvasive method of assessing retinal health and retinal dysfunction prior to retinal cell death.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

PubMed

Aleman, Tomas S; Brodie, Frank; Garvin, Christopher; Gewaily, Dina Y; Ficicioglu, Can H; Mills, Monte D; Forbes, Brian J; Maguire, Albert M; Davidson, Stefanie L

2015-01-01

To describe the retinal structure in a patient with cobalamin C (cblC) disease. A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

Spectrally optimal illuminations for diabetic retinopathy detection in retinal imaging

NASA Astrophysics Data System (ADS)

Bartczak, Piotr; Fält, Pauli; Penttinen, Niko; Ylitepsa, Pasi; Laaksonen, Lauri; Lensu, Lasse; Hauta-Kasari, Markku; Uusitalo, Hannu

2017-04-01

Retinal photography is a standard method for recording retinal diseases for subsequent analysis and diagnosis. However, the currently used white light or red-free retinal imaging does not necessarily provide the best possible visibility of different types of retinal lesions, important when developing diagnostic tools for handheld devices, such as smartphones. Using specifically designed illumination, the visibility and contrast of retinal lesions could be improved. In this study, spectrally optimal illuminations for diabetic retinopathy lesion visualization are implemented using a spectrally tunable light source based on digital micromirror device. The applicability of this method was tested in vivo by taking retinal monochrome images from the eyes of five diabetic volunteers and two non-diabetic control subjects. For comparison to existing methods, we evaluated the contrast of retinal images taken with our method and red-free illumination. The preliminary results show that the use of optimal illuminations improved the contrast of diabetic lesions in retinal images by 30-70%, compared to the traditional red-free illumination imaging.

Mitochondrial Dysfunction in Retinal Diseases

PubMed Central

Barot, Megha; Gokulgandhi, Mitan R.; Mitra, Ashim K.

2015-01-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases. PMID:21978133

Mitochondrial dysfunction in retinal diseases.

PubMed

Barot, Megha; Gokulgandhi, Mitan R; Mitra, Ashim K

2011-12-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.

Risk of cataract in persons with cytomegalovirus retinitis and the acquired immune deficiency syndrome.

PubMed

Kempen, John H; Sugar, Elizabeth A; Lyon, Alice T; Lewis, Richard Alan; Jabs, Douglas A; Heinemann, Murk-Hein; Dunn, James P

2012-11-01

To evaluate cataract risk in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis and to identify risk factors. Prospective cohort study. Patients with AIDS and CMV retinitis. Patients 13 years of age and older were enrolled between 1998 and 2008. Demographic and clinical characteristics, slit-lamp biomicroscopy findings, and dilated ophthalmoscopy results were documented at quarterly visits. Cataract status was determined at the initial visit (prevalence) and at follow-up visits (incidence). For cataract, a high grade of lens opacity by biomicroscopy to which best-corrected visual acuity worse than 20/40 was attributed. Eyes that had undergone cataract surgery before enrollment or between visits also were counted as having cataract. Seven hundred twenty-nine eyes of 489 patients diagnosed with CMV retinitis were evaluated. Higher prevalence was observed for patients with bilateral versus unilateral CMV retinitis (adjusted odds ratio [aOR], 2.74; 95% confidence interval [CI], 1.76-4.26) and, among unilateral CMV retinitis cases, for eyes with retinitis versus without retinitis (15% vs. 1.4%; P<0.0001). The age-adjusted prevalence of cataract among CMV retinitis cases was higher than that in a population-based sample (P<0.0001). Cataract prevalence increased with age (aOR, 11.77; 95% CI, 2.28-60.65 for age ≥ 60 years vs. younger than 40 years) and longer duration of retinitis (aOR, 1.36; 95% CI, 1.20-1.54 per year). Among eyes with CMV retinitis initially free of cataract, the cataract incidence was 8.1%/eye-year (95% CI, 6.7%-10.0%). Prior retinal detachment was associated with higher cataract risk (if repaired with silicone oil: adjusted hazard ratio [aHR], 10.37; 95% CI, 6.51-16.52; otherwise: aHR, 2.90; 95% CI, 1.73-4.87). Large CMV retinitis lesions also were associated with higher risk of cataract (for involvement of 25-49% retinal area: aHR, 2.30; 95% CI, 1.51-3.50; for ≥ 50% involvement: aHR, 3.63; 95% CI, 2.18-6.04), each with respect to �

Risk of Cataract in Persons with Cytomegalovirus Retinitis and the Acquired Immune Deficiency Syndrome

PubMed Central

Kempen, John H.; Sugar, Elizabeth A.; Lyon, Alice T.; Lewis, Richard Alan; Jabs, Douglas A.; Heinemann, Murk-Hein; Dunn, James P.

2012-01-01

Objective To evaluate cataract risk in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis and to identify risk factors. Design Prospective cohort study. Participants Patients with AIDS and CMV retinitis. Methods Patients 13 years of age and older were enrolled between 1998 and 2008. Demographic and clinical characteristics, slit-lamp biomicroscopy findings, and dilated ophthalmoscopy results were documented at quarterly visits. Cataract status was determined at the initial visit (prevalence) and at follow-up visits (incidence). Main Outcome Measures For cataract, a high grade of lens opacity by biomicroscopy to which best-corrected visual acuity worse than 20/40 was attributed. Eyes that had undergone cataract surgery before enrollment or between visits also were counted as having cataract. Results Seven hundred twenty-nine eyes of 489 patients diagnosed with CMV retinitis were evaluated. Higher prevalence was observed for patients with bilateral versus unilateral CMV retinitis (adjusted odds ratio [aOR], 2.74; 95% confidence interval [CI], 1.76–4.26) and, among unilateral CMV retinitis cases, for eyes with retinitis versus without retinitis (15% vs. 1.4%; P<0.0001). The age-adjusted prevalence of cataract among CMV retinitis cases was higher than that in a population-based sample (P<0.0001). Cataract prevalence increased with age (aOR, 11.77; 95% CI, 2.28–60.65 for age ≥60 years vs. younger than 40 years) and longer duration of retinitis (aOR, 1.36; 95% CI, 1.20–1.54 per year). Among eyes with CMV retinitis initially free of cataract, the cataract incidence was 8.1%/eye-year (95% CI, 6.7%–10.0%). Prior retinal detachment was associated with higher cataract risk (if repaired with silicone oil: adjusted hazard ratio [aHR], 10.37; 95% CI, 6.51–16.52; otherwise: aHR, 2.90; 95% CI, 1.73–4.87). Large CMV retinitis lesions also were associated with higher risk of cataract (for involvement of 25–49% retinal area: aHR, 2.30; 95% CI, 1.51–3

Multifocal retinitis in New Zealand sheep dogs.

PubMed

Hughes, P L; Dubielzig, R R; Kazacos, K R

1987-01-01

Thirty-nine percent of 1,448 working sheep dogs were affected with varying degrees of multifocal retinal disease on ophthalmoscopic examination. Lesions consisted of localized areas of hyperreflexia in the tapetal fundus, often associated with hyperpigmentation. Severely affected animals had widespread hyperreflexia with retinal vascular attenuation. Only 6% of 125 New Zealand dogs raised in urban environment were similarly affected. Both eyes of 70 dogs from New Zealand were examined histologically. Forty-seven of 70 dogs had ocular inflammatory disease. Ten other dogs had noninflammatory eye disease, and 13 dogs had normal eyes. Histologically, eyes with inflammatory disease were divided into three categories: Dogs 3 years of age or less with active inflammatory disease of the retina, uvea, and vitreous. Four dogs in this group had migrating nematode larvae identified morphologically as genus Toxocara. Diffuse retinitis and retinal atrophy in conjunction with localized retinal necrosis and choroidal fibrosis. Dogs in this category were severely, clinically affected. Chronic, low-grade retinitis with variable retinal atrophy. Most dogs in this category were over 3 years of age, and many were visually functional. The existence of a definable spectrum of morphological changes associated with inflammation, suggests that Toxocara sp. ocular larva migrans may be the cause of a highly prevalent, potentially blinding syndrome of working sheep dogs in New Zealand.

Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD.

PubMed

Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

2016-03-01

To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. 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/

Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

PubMed Central

Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

2015-01-01

Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

Combination of Neuroprotective and Regenerative Agents for AGE-Induced Retinal Degeneration: In Vitro Study

PubMed Central

Yamamoto, Shuichi

2017-01-01

To determine the most effective combination of neuroprotective and regenerative agents for cultured retinal neurons from advanced glycation end products- (AGEs-) induced degeneration, retinal explants of 7 adult Sprague-Dawley rats were three-dimensionally cultured in collagen gel and incubated in serum-free media and in 7 media; namely, AGEs, AGEs + 100 μM citicoline, AGEs + 10 ng/mL NT-4, AGEs + 100 μM TUDCA, AGEs + 100 μM citicoline + TUDCA (doublet), and AGEs + 100 μM citicoline + TUDCA + 10 ng/mL NT-4 (triplet) were examined. The number of regenerating neurites was counted after 7 days of culture, followed by performing TUNEL and DAPI staining. The ratio of TUNEL-positive cells to the number of DAPI-stained nuclei was calculated. Immunohistochemical examinations for the active form of caspase-9 and JNK were performed. All of the neuroprotectants increased the number of neurites and decreased the number of TUNEL-positive cells. However, the number of neurites was significantly higher, and the number of TUNEL-positive cells and caspase-9- and JNK-immunopositive cells was fewer in the retinas incubated with the combined three agents. Combination solutions containing citicoline, TUDCA, and NT-4 should be considered for neuroprotective and regenerative therapy for AGE-related retinal degeneration. PMID:28573143

Predicting the Significance of Injuries Potentially Caused by Non-Lethal Weapons: Tympanic Membrane Rupture (TMR), Permanent Threshold Shift (PTS), and Photothermal Retinal Lesions

DTIC Science & Technology

2016-06-21

during cooking . Retinal Lesions: medical care 29 of 37 • Suprathreshold lesions can lead to complications like hemorrhage, macular holes and...Effects Review Board (HERB). Members of the multi-service HERB include health care professionals and safety officers. The purpose of IDA’s analyses

Development of an integrated automated retinal surgical laser system.

PubMed

Barrett, S F; Wright, C H; Oberg, E D; Rockwell, B A; Cain, C; Rylander, H G; Welch, A J

1996-01-01

Researchers at the University of Texas and the USAF Academy have worked toward the development of a retinal robotic laser system. The overall goal of this ongoing project is to precisely place and control the depth of laser lesions for the treatment of various retinal diseases such as diabetic retinopathy and retinal tears. Separate low speed prototype subsystems have been developed to control lesion depth using lesion reflectance feedback parameters and lesion placement using retinal vessels as tracking landmarks. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Preliminary testing on rhesus primate subjects have been accomplished with the CW argon laser and also the ultrashort pulse laser. Recent efforts have concentrated on combining the two subsystems into a single prototype capable of simultaneously controlling both lesion depth and placement. We have designated this combined system CALOSOS for Computer Aided Laser Optics System for Ophthalmic Surgery. Several interesting areas of study have developed in integrating the two subsystems: 1) "doughnut" shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, 2) the optimal retinal field of view (FOV) to achieve both tracking and lesion parameter control, and 3) development of a hybrid analog/digital tracker using confocal reflectometry to achieve retinal tracking speeds of up to 100 dgs. This presentation will discuss these design issues of this clinically significant prototype system. Details of the hybrid prototype system are provided in "Hybrid Eye Tracking for Computer-Aided Retinal Surgery" at this conference. The paper will close with remaining technical hurdles to clear prior to testing the full-up clinical prototype system.

Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000).

PubMed

Holland, Gary N; Vaudaux, Jean D; Shiramizu, Kevin M; Yu, Fei; Goldenberg, David T; Gupta, Anurag; Carlson, Margrit; Read, Russell W; Novack, Roger D; Kuppermann, Baruch D

2008-01-01

To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings. Retrospective, observational case series. We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California. The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054). Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

Accidental human laser retinal injuries from military laser systems

NASA Astrophysics Data System (ADS)

Stuck, Bruce E.; Zwick, Harry; Molchany, Jerome W.; Lund, David J.; Gagliano, Donald A.

1996-04-01

The time course of the ophthalmoscopic and functional consequences of eight human laser accident cases from military laser systems is described. All patients reported subjective vision loss with ophthalmoscopic evidence of retinal alteration ranging from vitreous hemorrhage to retinal burn. Five of the cases involved single or multiple exposures to Q-switched neodymium radiation at close range whereas the other three incidents occur over large ranges. Most exposures were within 5 degrees of the foveola, yet none directly in the foveola. High contrast visual activity improved with time except in the cases with progressive retinal fibrosis between lesion sites or retinal hole formation encroaching the fovea. In one patient the visual acuity recovered from 20/60 at one week to 20/25 in four months with minimal central visual field loss. Most cases showed suppression of high and low spatial frequency contrast sensitivity. Visual field measurements were enlarged relative to ophthalmoscopic lesion size observations. Deep retinal scar formation and retinal traction were evident in two of the three cases with vitreous hemorrhage. In one patient, nerve fiber layer damage to the papillo-macular bundle was clearly evident. Visual performance measured with a pursuit tracking task revealed significant performance loss relative to normal tracking observers even in cases where acuity returned to near normal levels. These functional and performance deficits may reflect secondary effects of parafoveal laser injury.

Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease.

PubMed

Hughes, Alun D; Falaschetti, Emanuela; Witt, Nicholas; Wijetunge, Sumangali; Thom, Simon A McG; Tillin, Therese; Aldington, Steve J; Chaturvedi, Nish

2016-11-01

Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions. © 2016 American Heart Association, Inc.

Neuroprotective Treatment of Laser-Induced Retinal Injuries.

DTIC Science & Technology

1999-10-01

evaluate the neuroprotective effect of dextromethorphan , which is FDA approved and clinically used drug, in our rat model of laser-induced retinal...lesions. Methods: Argon laser retinal lesions were inflicted in the eyes of 36 pigmented rats. The treated group received dextromethorphan 50 mg/kg...size and the magnitude of photoreceptor nuclei loss within the lesions. Conclusions: Dextromethorphan treatment is not effective in ameliorating the

Neuroprotective therapy for argon-laser-induced retinal injury

NASA Astrophysics Data System (ADS)

Belkin, Michael; Rosner, Mordechai; Solberg, Yoram; Turetz, Yosef

1999-06-01

Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcim-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were sacrificed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent nomral retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invations of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated wtih argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser expsoure, the rats were sacrificed and their lesions were

Clinicopathologic correlation of submacular membranectomy with retention of good vision in a patient with age-related macular degeneration.

PubMed

Rosa, R H; Thomas, M A; Green, W R

1996-04-01

We present the clinicopathologic features of the eye of a patient with age-related macular degeneration who underwent submacular membranectomy and had retention of good visual acuity for almost 4 years despite recurrent choroidal neovascularization treated with krypton laser photocoagulation and mild expansion of the laser lesion with time. Histopathologic study of the surgically removed membrane from the right eye disclosed a thin fibrovascular membrane lined by retinal pigment epithelium on one surface. Microscopic examination of the right eye obtained post mortem disclosed a 2.75-mm (horizontal) x 2.1-mm (vertical) retinal pigment epithelium defect with overlying photoreceptor cell atrophy centered on the temporal parafoveal area, and a 0.6 x 0.1-mm subretinal pigment epithelium fibrovascular membrane with an area of retinal pigment epithelial hyperplasia and vascularization from the retina 0.4 mm temporal to the fovea. Basal laminar deposit was present in the region of the fovea and nasal parafoveal area.

Treatment of laser-induced retinal injuries by neuroprotection

NASA Astrophysics Data System (ADS)

Solberg, Yoram; Rosner, Mordechai; Belkin, Michael

1997-05-01

Retinal laser photocoagulation treatments are often complicated with immediate side-effect of visual impairment. To determine whether glutamate-receptor blockers can serve as adjuvant neuroprotective therapy, we examined the effect of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Argon laser retinal lesions were created in the retina of 36 DA rats. Treatment with intraperitoneal injections of MK-801 or saline was started immediately after the laser photocoagulation. The animals were sacrificed after 3, 20 or 60 days and the retinal lesions were evaluated histologically and morphometrically. Photoreceptor-cell loss was significantly smaller in MK-801-treated rats than controls. The proliferative membrane composed of retinal pigment epithelial cells which was seen at the base of the lesion in control retinas, was smaller in the MK-801-treated retinas. MK-801 exhibited neuroprotective and anti-proliferative properties in the retina. Glutamate-receptor blockers should be further investigated for serving as adjuvant therapy to retinal photocoagulation treatments.

The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

PubMed Central

Kim, Junghyun; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Chan-Sik; Kim, Jin Sook

2016-01-01

Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID:27657123

Age-Related Macular Degeneration.

PubMed

Mehta, Sonia

2015-09-01

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related changes in the diagnostic assessment of women with severe cervical lesions.

PubMed

Giannella, L; Fodero, C; Boselli, F; Mfuta, K; Rubino, T; Prandi, S

2015-01-01

To evaluate the effect of age on the diagnostic assessment of women with severe cervical intraepithelial neoplasia (CIN). This retrospective observational study included 338 consecutive women with a diagnosis of CIN3 on cone specimen. Patients were divided into three groups according to age: < 35 years (Group A), 35-49 years (Group B), and ≥ 50 years (Group C). Clinical and colposcopic variables were compared, and human papillomavirus (HPV) genotype distribution was measured. The most common HPV genotype was HPV-16 (63.65%), followed by HPV-33 (7%), HPV-18 (6.2%), and HPV-31 (5.4%). The rate of the following high-grade lesion predictors was lower in Group C than in Groups A and B: HPV-16 infections (55.9% vs. 75% vs. 70.9%, respectively, p = 0.022); high-grade colposcopic impression (29.4% vs. 51.8% vs. 51.7%, respectively, p < 0.0001); and high-grade cytological changes (30.9% vs. 56.2% vs. 45.4%, respectively, p = 0.025). An endocervical lesion location was more frequent in Group C than in Groups A and B (55.6% vs. 6.8% vs. 11.8%, respectively, p < 0.0001). Women aged 50 years and older with CIN3 showed a significant reduction of high-grade lesion predictors along with physiological confounding cervical changes (transformation zone type 3 and endocervical lesion location). The diagnostic work-up of cervical lesions in older women should provide their potential consideration as a special population.

Neuroprotective Treatment of Laser-Induced Retinal Injuries

DTIC Science & Technology

2000-10-01

to evaluate the neuroprotective effect of memantine in our rat model of laser-induced retinal-lesions. Methods: Argon laser retinal lesions were...inflicted in the eyes of 36 pigmented rats. The treated group received memantine 10 mg/kg dissolved in saline, immediately after exposure to laser and then

Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

PubMed

Geng, Shuang; Ye, Jun-jie; Zhao, Jia-liang; Li, Tai-sheng; Han, Yang

2011-04-01

Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS. It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4(+) T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 µg) were performed in 4 eyes (2 patients). Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque. Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4(+) T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6 ± 25.3) × 10(6)/L (range, (0 - 85) × 10(6)/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed. CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Retinal iron homeostasis in health and disease

PubMed Central

Song, Delu; Dunaief, Joshua L.

2013-01-01

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD. PMID:23825457

[Cytomegalovirus retinitis in immunocompetent patients].

PubMed

Yoshinaga, Wakako; Mizushima, Yuka; Abematsu, Noriko; Nakao, Kumiko; Sakamoto, Taiji

2008-08-01

Cytomegalovirus (CMV) retinitis usually affects severely immunosuppressed individuals. We report two immunocompetent patients who developed CMV retinitis. Case 1 was a 65-year-old man who was referred to us with blurred vision and floaters of 2 weeks duration in his left eye. Slit-lamp biomicroscopy showed keratic precipitates, aqueous cells, and vitreous opacity in his left eye. Funduscopic examination revealed yellow-white retinal lesions with arterial sheathing in the superotemporal midperiphery. Case 2 was a 63-year-old man who presented with a 2-week history of blurred vision in his left eye. Ophthalmologic examination of the left eye showed keratic precipitates, aqueous cells, vitreous opacity, and yellow-white lesions in the superotemporal peripheral retina. In both cases, CMV DNA was detected in the aqueous humor and therefore the diagnosis was CMV retinitis. CMV retinitis in both cases was indolent and was resolved in one month without treatment with antiviral drugs. Although both patients had diabetes mellitus, the results of their laboratory examinations were unremarkable and they were immunocompetent. Unlike CMV retinitis in immunocompromised patients, CMV retinitis in immunocompetent patients had significant anterior and vitreous inflammation but did not require antiviral treatment. A possible association between CMV retinitis and diabetes mellitus was suggested.

Outcome of cytomegalovirus retinitis in immunocompromised patients without Human Immunodeficiency Virus treated with intravitreal ganciclovir injection.

PubMed

Agarwal, Aniruddha; Kumari, Neha; Trehan, Amita; Khadwal, Alka; Dogra, Mangat R; Gupta, Vishali; Sharma, Aman; Gupta, Amod; Singh, Ramandeep

2014-09-01

To study the outcomes of treatment with intravitreal ganciclovir injection for cytomegalovirus (CMV) retinitis in patients without Human Immunodeficiency Virus (HIV) infection. In this retrospective cohort study, demographic and clinical characteristics of patients with CMV retinitis without HIV were noted. Patients received intravitreal ganciclovir injection (2 mg/0.1 ml) alone until quiescence. The outcome measures were time taken for the lesions to heal, number of injections, change in best-corrected visual acuity (BCVA), recurrence of retinitis, occurrence of immune recovery uveitis (IRU) or injection-related complications and retinal detachment (RD). 18 eyes of ten patients (six males) with mean age of 33.7 years from June 2004 to March 2013 were included. Thirteen eyes with active lesions (mean BCVA of 0.51 ± 0.41) received 5.54 ± 3.36 intravitreal ganciclovir injections with complete healing within 1.81 ± 1.25 months. The final BCVA was 0.43 ± 0.52. IRU was observed in six eyes (33.33%) and RD developed in one eye. One eye had recurrence 1 month after stopping ganciclovir injections. The rest of the patients had recurrence-free follow-up at 9.46 ± 12.42 months. Non-HIV patients with CMV retinitis can be successfully treated with intravitreal ganciclovir injection alone, avoiding the systemic side effects of systemic anti-CMV therapy.

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

PubMed

Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

2018-02-07

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

PubMed

Saad, Leonide; Washington, Ilyas

2016-01-01

We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration.

PubMed

Cloutier, Frank; Lawrence, Matthew; Goody, Robin; Lamoureux, Stéphanie; Al-Mahmood, Salman; Colin, Sylvie; Ferry, Antoine; Conduzorgues, Jean-Pascal; Hadri, Amel; Cursiefen, Claus; Udaondo, Patricia; Viaud, Eric; Thorin, Eric; Chemtob, Sylvain

2012-03-09

Aganirsen, an antisense oligonucleotide inhibiting insulin receptor substrate (IRS)-1 expression, has been shown to promote the regression of pathologic corneal neovascularization in patients. In this study, the authors aimed to demonstrate the antiangiogenic activity of aganirsen in animal models of retinal neovascularization. Eyedrops of aganirsen were applied daily in nonhuman primates after laser-induced choroidal neovascularization (CNV; model of wet age-related macular degeneration [AMD]) and in newborn rats after oxygen-induced retinopathy (OIR; model of ischemic retinopathy). Retinal aganirsen concentrations were assessed in rabbits and monkeys after topical delivery (21.5, 43, or 86 μg). Clinical significance was further evaluated by determination of IRS-1 expression in monkey and human retinal biopsy specimens. Topical corneal application of aganirsen attenuated neovascular lesion development dose dependently in African green monkeys. The incidence of high-grade CNV lesions (grade IV) decreased from 20.5% in vehicle-treated animals to 1.7% (P < 0.05) at the 86-μg dose. Topical aganirsen inhibited retinal neovascularization after OIR in rats (P < 0.05); furthermore, a single intravitreal injection of aganirsen reduced OIR as effectively as ranibizumab, and their effects were additive. Significantly, topical applications of aganirsen did not interfere with physiological retinal vessel development in newborn rats. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD. Topical application of aganirsen offers a safe and effective therapy for both choroidal and retinal neovascularization without preventing its normal vascularization. Together, these findings support the clinical testing of aganirsen for human retinal neovascular diseases.

Treatment of dry age-related macular degeneration with dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

2012-01-01

The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration.

PubMed

Ying, Gui-shuang; Huang, Jiayan; Maguire, Maureen G; Jaffe, Glenn J; Grunwald, Juan E; Toth, Cynthia; Daniel, Ebenezer; Klein, Michael; Pieramici, Dante; Wells, John; Martin, Daniel F

2013-01-01

To determine the baseline predictors of visual acuity (VA) outcomes 1 year after treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). Cohort study within the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). A total of 1105 participants with neovascular AMD, baseline VA 20/25 to 20/320, and VA measured at 1 year. Participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as-needed schedule. Masked readers evaluated fundus morphology and features on optical coherence tomography (OCT). Visual acuity was measured using electronic VA testing. Independent predictors were identified using regression techniques. The VA score, VA score change from baseline, and ≥3-line gain at 1 year. At 1 year, the mean VA score was 68 letters, mean improvement from baseline was 7 letters, and 28% of participants gained ≥3 lines. Older age, larger area of choroidal neovascularization (CNV), and elevation of retinal pigment epithelium (RPE) were associated with worse VA (all P<0.005), less gain in VA (all P<0.02), and a lower proportion gaining ≥3 lines (all P<0.04). Better baseline VA was associated with better VA at 1 year, less gain in VA, and a lower proportion gaining ≥3 lines (all P<0.0001). Predominantly or minimally classic lesions were associated with worse VA than occult lesions (66 vs. 69 letters; P=0.0003). Retinal angiomatous proliferans (RAP) lesions were associated with more gain in VA (10 vs. 7 letters; P=0.03) and a higher proportion gaining ≥3 lines (odds ratio, 1.9; 95% confidence interval, 1.2-3.1). Geographic atrophy (GA) was associated with worse VA (64 vs. 68 letters; P=0.02). Eyes with total foveal thickness in the second quartile (325-425 μm) had the best VA (P=0.01) and were most likely to gain ≥3 lines (P=0.004). Predictors did not vary by treatment group. For all treatment groups, older age, better baseline VA, larger CNV area, predominantly or minimally

Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin

PubMed Central

Yu, Chia-Chia; Nandrot, Emeline F.; Dun, Ying; Finnemann, Silvia C.

2011-01-01

In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5−/− RPE but not neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants grapes or marigold extract containing macular pigments lutein/zeaxanthin was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in β5−/− mice. Acute generation of HNE-adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet. PMID:22178979

Transcorneal Electrical Stimulation Therapy for Retinal Disease

ClinicalTrials.gov

2012-05-03

Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

Optical Coherence Tomography Angiography of Retinal Cavernous Hemangioma.

PubMed

Pierro, Luisa; Marchese, Alessandro; Gagliardi, Marco; Bandello, Francesco

2017-08-01

Retinal cavernous hemangioma is a rare, benign, retinal tumor characterized by angiomatous proliferation of vessels within the inner retina or the optic disc.1 Here we report a case of retinal cavernous hemangioma on the margin of the optic disc in the right eye of a 61-year-old asymptomatic female. The lesion was studied with multimodal imaging which included structural optical coherence tomography, fluorescein angiography, blue fundus auto-fluorescence, optical coherence tomography angiography (OCTA) (DRI OCT Triton; Topcon, Tokyo, Japan) and visual field examination. Blood circulation inside retinal cavernous hemangioma lesion is typically low-stagnant.2 However, OCTA demonstrated blood flow inside the lesion, illustrating its vascular circulation.3 Visual field was within the normal limits, except from a slight enlargement of the blind spot. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:684-685.]. Copyright 2017, SLACK Incorporated.

Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration.

PubMed

Cymerman, Rachel M; Skolnick, Adam H; Cole, William J; Nabati, Camellia; Curcio, Christine A; Smith, R Theodore

2016-11-01

Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45-80 years, documented either with or without CAD, to determine if CAD is associated with RMD. A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Presence or absence of RMD/SDD and soft drusen. RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08-3.95, P = 0.03). There was no association of CAD with soft drusen. A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

Multimodal imaging in a case of bilateral outer retinitis associated with mumps infection.

PubMed

Kahloun, Rim; Ben Amor, Hager; Ksiaa, Imen; Zina, Sourour; Jelliti, Bechir; Ben Yahia, Salim; Khairallah, Moncef

2018-02-01

To report the results of multimodal imaging of acute outer retinitis associated to mumps infection. A patient with mumps-associated outer retinitis evaluated by color fundus photography, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography, fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA). We report a case of a 12-year-old boy who developed bilateral outer retinitis related to mumps. Ophthalmoscopy showed confluent areas of outer retinitis involving the posterior pole and the periphery with a centrifugal gyrate pattern. SD-OCT revealed a marked disorganization of the outer retinal layers with multiple highly reflective spicules. FA shows diffuse late hyperfluorescence with optic disk staining. ICGA shows macular and peripheral hyperfluorescent lesions with a geographical pattern in the late phases. The patient was treated with acyclovir and oral prednisone. Four weeks after presentation visual acuity remained unchanged, and retinal changes seen at the acute phase had resolved leading to extensive retinal atrophy and optic disk pallor. SD-OCT showed atrophy of the retinal pigment epithelial and outer retinal layers. FAF revealed scattered hyperautofluorescent lesions. Electrophysiology showed generalized retinal dysfunction. Mumps infection should be considered in the differential diagnosis of bilateral necrotizing outer retinitis in children and young adults. A multimodal imaging approach may help distinguish mumps-associated retinitis from other causes of viral retinitis and facilitate appropriate management.

Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy.

PubMed

Ometto, Giovanni; Assheton, Phil; Calivá, Francesco; Chudzik, Piotr; Al-Diri, Bashir; Hunter, Andrew; Bek, Toke

2017-12-01

Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy.

Cancer-associated retinopathy with unusual retinal whitening.

PubMed

Lee, Joan J; Vrabec, Tamara R; Baldassano, Vincent F

2015-01-01

To describe the clinical characteristics and results of ocular and systemic testing in an atypical case of cancer-associated retinopathy. This study is a retrospective case report of a female patient. Rapidly progressive visual loss, vitritis, white, ring- and coin-shaped retinal lesions, and panretinal optical coherence tomography thinning preceded the diagnosis of poorly differentiated cervical carcinoma with neuroendocrine features consistent with small-cell carcinoma. Cancer-associated retinopathy can present with ring- and coin-shaped retinal lesions, vitritis, and panretinal thinning. The presence of intraocular inflammation and retinal and choroidal vasculopathy may herald more rapid visual demise.

PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PubMed

Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

2016-11-01

To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

Paracentral acute middle maculopathy in nonischemic central retinal vein occlusion.

PubMed

Rahimy, Ehsan; Sarraf, David; Dollin, Michael L; Pitcher, John D; Ho, Allen C

2014-08-01

To better characterize a novel spectral-domain optical coherence tomography (OCT) presentation, termed paracentral acute middle maculopathy, to describe this finding in patients with nonischemic central retinal vein occlusion (CRVO), and to support a proposed pathogenesis of intermediate and deep retinal capillary ischemia. Retrospective observational case series. Clinical histories, high-resolution digital color imaging, red-free photography, fluorescein angiography, near-infrared reflectance, and spectral-domain OCT images of 484 patients with acute CRVO from 2 centers were evaluated for the presence of coexisting paracentral acute middle maculopathy. Of 484 patients diagnosed with CRVO, 25 (5.2%) demonstrated evidence of concurrent paracentral acute middle maculopathy. Patients averaged 51 years of age and presented with complaints of paracentral scotomas. All patients demonstrated hyper-reflective plaquelike lesions at the level of the inner nuclear layer by spectral-domain OCT and showed corresponding dark-gray lesions on near-infrared reflectance and perivenular deep retinal whitening on color fundus photography. There was no fluorescein angiographic correlate to these lesions. On follow-up spectral-domain OCT imaging, the lesions had resolved into areas of inner nuclear layer atrophy with persistence of scotomas. Paracentral acute middle maculopathy refers to characteristic hyper-reflective spectral-domain OCT lesions involving the middle layers of the retina at the level of the inner nuclear layer that may develop in response to ischemia of the intermediate and deep capillary plexuses. This series is the largest to describe this spectral-domain OCT finding to date, and it is the first to associate it with nonischemic CRVO. Copyright © 2014 Elsevier Inc. All rights reserved.

The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy.

PubMed

Moran, C; Tapp, R J; Hughes, A D; Magnussen, C G; Blizzard, L; Phan, T G; Beare, R; Witt, N; Venn, A; Münch, G; Amaratunge, B C; Srikanth, V

2016-01-01

It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy.

Idiopathic preretinal glia in aging and age-related macular degeneration

PubMed Central

Edwards, Malia M.; McLeod, D. Scott; Bhutto, Imran A.; Villalonga, Mercedes B.; Seddon, Johanna M.; Lutty, Gerard A.

2015-01-01

During analysis of glia in wholemount aged human retinas, frequent projections onto the vitreal surface of the inner limiting membrane (ILM) were noted. The present study characterized these preretinal glial structures. The amount of glial cells on the vitreal side of the ILM was compared between eyes with age-related macular degeneration (AMD) and age-matched control eyes. Retinal wholemounts were stained for markers of retinal astrocytes and activated Müller cells (glial fibrillary acidic protein, GFAP), Müller cells (vimentin, glutamine synthetase) and microglia/hyalocytes (IBA-1). Retinal vessels were labeled with UEA lectin. Images were collected using a Zeiss 710 confocal microscope. Retinas were then cryopreserved. Laminin labeling of cryosections determined the location of glial structures in relation to the ILM. All retinas investigated herein had varied amounts of preretinal glial. These glial structures were classified into three groups based on size: sprouts, blooms, and membranes. The simplest of the glial structures observed were focal sprouts of singular GFAP-positive cells or processes on the vitreal surface of the ILM. The intermediate structures observed, glial blooms, were created by multiple cells/processes exiting from a single point and extending along the vitreoretinal surface. The most extensive structures, glial membranes, consisted of compact networks of cells and processes. Preretinal glia were observed in all areas of the retina but they were most prominent over large vessels. While all glial blooms and membranes contained vimentin and GFAP-positive cells, these proteins did not always co-localize. Many areas had no preretinal GFAP but had numerous vimentin only glial sprouts. In double labelled glial sprouts, vimentin staining extended beyond that of GFAP. Hyalocytes and microglia were detected along with glial sprouts, blooms, and membranes. They did not, however, concentrate in the retina below these structures. Cross sectional

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PubMed

Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

2015-08-01

To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Variation of cone photoreceptor packing density with retinal eccentricity and age.

PubMed

Song, Hongxin; Chui, Toco Yuen Ping; Zhong, Zhangyi; Elsner, Ann E; Burns, Stephen A

2011-09-01

To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages. High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22-35 years) and 10 older subjects (age range, 50-65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity. As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6-12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average. Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions.

Pilot evaluation of short-term changes in macular pigment and retinal sensitivity in different phenotypes of early age-related macular degeneration after carotenoid supplementation.

PubMed

Corvi, Federico; Souied, Eric H; Falfoul, Yousra; Georges, Anouk; Jung, Camille; Querques, Lea; Querques, Giuseppe

2017-06-01

To investigate the response of carotenoid supplementation in different phenotypes of early age-related macular degeneration (AMD) by measuring macular pigment optical density (MPOD) and retinal sensitivity. Consecutive patients with only medium/large drusen and only reticular pseudodrusen (RPD) and age-matched and sex-matched controls were enrolled. At baseline, participants underwent a complete ophthalmological examination including measurement of best-corrected visual acuity (BCVA), MPOD and retinal sensitivity. Patients were put on vitamin supplementation (lutein 10 mg/day, zeaxanthin 2 mg/day) and 3 months later underwent a repeated ophthalmological examination. Twenty patients with medium/large drusen, 19 with RPD and 15 control subjects were included. At baseline, in controls, mean MPOD and BCVA were significantly higher compared with RPD (p=0.001 and p=0.01) but similar to medium/large drusen (p=0.9 and p=0.4). Mean retinal sensitivity was significantly higher in controls compared with RPD and medium/large drusen (for all p<0.0001). After 3 months of carotenoid supplementation the mean MPOD significantly increased in RPD (p=0.002), thus showing no more difference compared with controls (p=0.3); no significant changes were found in mean retinal sensitivity and BCVA (p=0.3 and p=0.7). Medium/large drusen did not show significant changes on MPOD, retinal sensitivity and BCVA (p=0.5, p=0.7 and p=0.7, respectively). Patients with early AMD, especially RPD phenotype, show lower macular sensitivity and MPOD than controls. After supplementation, MPOD significantly increased in RPD. These results suggest different pathophysiology for RPD as compared with medium/large drusen and may open new ways to identifying further therapeutic targets in this phenotype of early AMD. 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/.

Automated detection of dark and bright lesions in retinal images for early detection of diabetic retinopathy.

PubMed

Akram, Usman M; Khan, Shoab A

2012-10-01

There is an ever-increasing interest in the development of automatic medical diagnosis systems due to the advancement in computing technology and also to improve the service by medical community. The knowledge about health and disease is required for reliable and accurate medical diagnosis. Diabetic Retinopathy (DR) is one of the most common causes of blindness and it can be prevented if detected and treated early. DR has different signs and the most distinctive are microaneurysm and haemorrhage which are dark lesions and hard exudates and cotton wool spots which are bright lesions. Location and structure of blood vessels and optic disk play important role in accurate detection and classification of dark and bright lesions for early detection of DR. In this article, we propose a computer aided system for the early detection of DR. The article presents algorithms for retinal image preprocessing, blood vessel enhancement and segmentation and optic disk localization and detection which eventually lead to detection of different DR lesions using proposed hybrid fuzzy classifier. The developed methods are tested on four different publicly available databases. The presented methods are compared with recently published methods and the results show that presented methods outperform all others.

Digital Tracking and Control of Retinal Images

DTIC Science & Technology

1993-01-01

induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal tears or breaks. Both the location and...one second and typical treatment for a disease such as diabetic retinopathy requires as many as 2000 lesions per eye. This type of tedious task is...Oxygenation and Laser Treatment in Patients with Diabetic Retinopathy ", American Journal of Ophthalmology, Volume 113, January 1992, pp 36 - 38. [21

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CYTOMEGALOVIRUS RETINITIS: A Longitudinal Study.

PubMed

Invernizzi, Alessandro; Agarwal, Aniruddha; Ravera, Vittoria; Oldani, Marta; Staurenghi, Giovanni; Viola, Francesco

2018-01-01

To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

ZIKA virus infection causes persistent chorioretinal lesions.

PubMed

Manangeeswaran, Mohanraj; Kielczewski, Jennifer L; Sen, H Nida; Xu, Biying C; Ireland, Derek D C; McWilliams, Ian L; Chan, Chi-Chao; Caspi, Rachel R; Verthelyi, Daniela

2018-05-25

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.

Automated multi-lesion detection for referable diabetic retinopathy in indigenous health care.

PubMed

Pires, Ramon; Carvalho, Tiago; Spurling, Geoffrey; Goldenstein, Siome; Wainer, Jacques; Luckie, Alan; Jelinek, Herbert F; Rocha, Anderson

2015-01-01

Diabetic Retinopathy (DR) is a complication of diabetes mellitus that affects more than one-quarter of the population with diabetes, and can lead to blindness if not discovered in time. An automated screening enables the identification of patients who need further medical attention. This study aimed to classify retinal images of Aboriginal and Torres Strait Islander peoples utilizing an automated computer-based multi-lesion eye screening program for diabetic retinopathy. The multi-lesion classifier was trained on 1,014 images from the São Paulo Eye Hospital and tested on retinal images containing no DR-related lesion, single lesions, or multiple types of lesions from the Inala Aboriginal and Torres Strait Islander health care centre. The automated multi-lesion classifier has the potential to enhance the efficiency of clinical practice delivering diabetic retinopathy screening. Our program does not necessitate image samples for training from any specific ethnic group or population being assessed and is independent of image pre- or post-processing to identify retinal lesions. In this Aboriginal and Torres Strait Islander population, the program achieved 100% sensitivity and 88.9% specificity in identifying bright lesions, while detection of red lesions achieved a sensitivity of 67% and specificity of 95%. When both bright and red lesions were present, 100% sensitivity with 88.9% specificity was obtained. All results obtained with this automated screening program meet WHO standards for diabetic retinopathy screening.

Analysis of Retinal Thinning Using Spectral-domain Optical Coherence Tomography Imaging of Sickle Cell Retinopathy Eyes Compared to Age- and Race-Matched Control Eyes.

PubMed

Lim, Jennifer I; Cao, Dingcai

2018-03-17

To determine whether the retina is thinner in sickle cell patients than in race- and age-matched controls, and, if it is thinner, whether there is any association with systemic diseases. Sickle cell and control (age- and race-matched) patients were prospectively enrolled from a university retina clinic into this observational study. Participants underwent visual acuity testing, slit-lamp biomicroscopy, dilated ophthalmoscopy, and spectral-domain optical coherence tomography imaging. Sickle cell retinal lesions, degree of vascular tortuosity, caliber of arteriovenous anastomosis, and stage of retinopathy were noted. Early Treatment Diabetic Retinopathy Study (ETDRS) subfield measurements were compared between sickle cell and control subjects and also among sickle cell hemoglobin subtypes. Associations between ETDRS subfield measurements and hemoglobin subtype, retinopathy stage, and systemic diseases were assessed. A total of 513 sickle cell eyes (260 patients) and 75 control eyes (39 patients) had median visual acuities of 20/20. ETDRS central (P = .002), inner (nasal P = .009, superior P = .021, temporal P < .001, inferior P = .017), and temporal outer (P = .012) subfield measurements were thinner in sickle cell eyes compared to control eyes. Hemoglobin SS eyes had significantly thinner inner ETDRS subfield measurements compared to SC and SThal eyes. Retinal thinning in all subfields was associated with age (P = .017) for sickle cell and control eyes. No association was found between retinal thinning and hydroxyurea use or arteriovenous anastomosis caliber. The macula is thinner in sickle cell eyes compared to control eyes; retinal thickness decreases with increasing age and sickle cell retinopathy stage and is most severe in hemoglobin SS subtypes. Copyright © 2018 Elsevier Inc. All rights reserved.

Variation of Cone Photoreceptor Packing Density with Retinal Eccentricity and Age

PubMed Central

Song, Hongxin; Chui, Toco Yuen Ping; Zhong, Zhangyi; Elsner, Ann E.

2011-01-01

Purpose. To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages. Methods. High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22–35 years) and 10 older subjects (age range, 50–65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity. Results. As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6–12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average. Conclusions. Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions. PMID:21724911

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

PubMed Central

Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

2015-01-01

The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

PubMed

Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J; Foster, Russell G; Peirson, Stuart N; Nolan, Patrick M

2015-01-01

The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence of age-related macular degeneration in rural southern China: the Yangxi Eye Study.

PubMed

Jin, Guangming; Ding, Xiaohu; Xiao, Wei; Xu, Xiao; Wang, Lanhua; Han, Xiaotong; Xiao, Ou; Liu, Ran; Wang, Wei; Yan, William; An, Lei; Zhao, Jialiang; He, Mingguang

2018-05-01

To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China. Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations. Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%). AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women. © 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.

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

PubMed Central

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

RETINAL DEEP CAPILLARY ISCHEMIA ASSOCIATED WITH AN OCCLUDED CONGENITAL RETINAL MACROVESSEL.

PubMed

Hasegawa, Taiji; Ogata, Nahoko

2017-01-01

To report the case of a patient with an occluded congenital retinal macrovessel accompanied by retinal deep capillary ischemia. A 38-year-old woman presented with a 2-day history of a paracentral scotoma of her right eye. Fundus photograph showed a dilated congenital retinal macrovessel with arteriovenous anastomosis, an intravascular white region indicating the thrombus at arteriovenous anastomotic region, and an area of retinal whitening temporal to the fovea. The spectral domain optical coherence tomography images through the area of retinal whitening showed a thickening and highly reflectivity at the level of the inner nuclear layer, which is likely due to the deep capillary ischemia. After 6 weeks, spectral domain optical coherence tomography images through the same area demonstrated a thinning and atrophy of only the inner nuclear layer, and the patient's paracentral scotoma persisted. Acute capillary hemodynamic changes caused deep capillary ischemia. The spectral domain optical coherence tomography showed a highly reflective lesion at the level of the inner nuclear layer in the acute phase.

Steroidal and nonsteroidal antiinflammatory medications can improve photoreceptor survival after laser retinal photocoagulation.

PubMed

Brown, Jeremiah; Hacker, Henry; Schuschereba, Steven T; Zwick, Harry; Lund, David J; Stuck, Bruce E

2007-10-01

To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model. Experimental study. Twenty rhesus monkeys. Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months. The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group. Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

PubMed Central

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-01-01

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Ocular Lesions in Red-Tailed Hawks ( Buteo jamaicensis) With Naturally Acquired West Nile Disease.

PubMed

Wünschmann, A; Armién, A G; Khatri, M; Martinez, L C; Willette, M; Glaser, A; Alvarez, J; Redig, P

2017-03-01

Ocular lesions are common in red-tailed hawks with West Nile (WN) disease. These lesions consist of pectenitis, choroidal or retinal inflammation, or retinal necrosis, but detailed investigation of the ocular lesions is lacking. Postmortem examination of the eyes of 16 red-tailed hawks with naturally acquired WN disease and 3 red-tailed hawks without WN disease was performed using histopathology, immunohistochemistry for West Nile virus (WNV) antigen, glial fibrillary acid protein, cleaved caspase-3, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method. Retinal lesions were classified as type I or type II lesions. Type I lesions were characterized by lymphoplasmacytic infiltrates in the subjacent choroid with degeneration limited to the outer retina (type Ia lesion) or with degeneration and necrosis of the outer retina or outer and inner retina (type Ib lesion) while retinal collapse, atrophy, and scarring were hallmarks of type II lesions. Type II retinal lesions were associated with a more pronounced choroiditis. Although not statistically significant, WNV antigen tended to be present in larger quantity in type Ib lesions. Type I lesions are considered acute while type II lesions are chronic. The development of retinal lesions was associated with the presence of an inflammatory infiltrate in the choroid. A breakdown of the blood-retina barrier is suspected to be the main route of infection of the retina. Within the retina, virus appeared to spread via both neuronal and Müller cell processes.

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

PubMed

Arcinue, Cheryl A; Bartsch, Dirk-Uwe; El-Emam, Sharif Y; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R

2015-01-01

To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

Spontaneous Resolution of Intravitreal Steroid-Induced Bilateral Cytomegalovirus Retinitis

PubMed Central

Cho, Won Bin; Kim, Hyung Chan

2012-01-01

A 73-year-old woman underwent vitrectomy and intravitreal triamcinolone acetonide (IVTA) of the right eye and cataract surgery with IVTA of the left eye, for bilateral diabetic macular edema. The patient presented with visual loss in both eyes three-months postoperatively. The fundoscopic examination revealed white-yellow, necrotic peripheral lesions in the superotemporal quadrant of both eyes. Although bilateral acute retinal necrosis was suspected, azotemia resulting from diabetic nephropathy limited the use of acyclovir. Antiviral treatment was not started. A sample of the aqueous humor for polymerase chain reaction (PCR) analysis was obtained. One week later, the PCR results indicated the presence of cytomegalovirus (CMV). Since the retinal lesions did not progress and did not threaten the macula, the patient was followed without treatment for CMV. The retinal lesions progressively regressed and completely resolved in both eyes by six months of follow-up. Patients with IVTA-induced CMV retinitis may not require systemic treatment with ganciclovir. PMID:22511845

Kinetics of Lipofuscin Formation in Aging Retinal Pigment Epithelium Cells

NASA Astrophysics Data System (ADS)

Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

2010-03-01

Lipofuscin is a deposit that is formed over time by aggregation and clustering of incompletely degraded membrane material in various types of cells. Lipofuscin is made of free-radical-damaged protein and fat and is known to be present in age- related macular dgeneration (AMD), Alzheimer disease, and Parkinson disease. AMD is the leading cause of blindness in adults. The degradation of retinal pigment epithelium cells (RPE) through accumulation of lipsofuscin is considered a significant pathogenic factor in the development of AMD. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results with the number of lipofuscin granules in eyes with early age-related degeneration.

Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.

PubMed

Kaarniranta, Kai; Tokarz, Paulina; Koskela, Ali; Paterno, Jussi; Blasiak, Janusz

2017-04-01

Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells. Autophagy, a cellular clearing system, plays an important role in AMD pathogenesis, and this role is closely associated with the activation of the NLRP3 inflammasome, a central event for advanced AMD. Autophagy can play a role in apoptosis, pyroptosis, and necroptosis, but its contribution to AMD-specific cell death is not completely clear. Autophagy can be involved in the regulation of proteins important for cellular antioxidative defense, including Nrf2, which can interact with p62/SQSTM, a protein essential for autophagy. As oxidative stress is implicated in AMD pathogenesis, autophagy can contribute to this disease by deregulation of cellular defense against the stress. However, these and other interactions do not explain the mechanisms of RPE cell death in AMD. In this review, we present basic mechanisms of autophagy and its involvement in AMD pathogenesis and try to show a regulatory role of autophagy in RPE cell death. This can result in considering the genes and proteins of autophagy as molecular targets in AMD prevention and therapy.

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.

PubMed

Katschke, Kenneth J; Xi, Hongkang; Cox, Christian; Truong, Tom; Malato, Yann; Lee, Wyne P; McKenzie, Brent; Arceo, Rommel; Tao, Jianhua; Rangell, Linda; Reichelt, Mike; Diehl, Lauri; Elstrott, Justin; Weimer, Robby M; Campagne, Menno van Lookeren

2018-05-09

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.

Body fat distribution, metabolic and inflammatory markers and retinal microvasculature in school-age children. The Generation R Study.

PubMed

Gishti, O; Jaddoe, V W V; Hofman, A; Wong, T Y; Ikram, M K; Gaillard, R

2015-10-01

To examine the associations of body fatness, metabolic and inflammatory markers with retinal vessel calibers among children. We performed a population-based cohort study among 4145 school-age children. At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured body mass index, total and abdominal fat mass, metabolic and inflammatory markers (blood levels of lipids, insulin and C-peptide and C-reactive protein) and retinal vascular calibers from retinal photographs. We observed that compared with normal weight children, obese children had narrower retinal arteriolar caliber (difference -0.21 s.d. score (SDS; 95% confidence interval (CI) -0.35, -0.06)), but not venular caliber. Continuous analyses showed that higher body mass index and total body fat mass, but not android/gynoid fat mass ratio and pre-peritoneal fat mass, were associated with narrower retinal arteriolar caliber (P<0.05 for body mass index and total body fat mass), but not with retinal venular caliber. Lipid and insulin levels were not associated with retinal vessel calibers. Higher C-reactive protein was associated with only wider retinal venular caliber (difference 0.10 SDS (95% CI 0.06, 0.14) per SDS increase in C-reactive protein). This latter association was not influenced by body mass index. Higher body fatness is associated with narrower retinal arteriolar caliber, whereas increased C-reactive protein levels are associated with wider retinal venular caliber. Increased fat mass and inflammation correlate with microvascular development from school-age onwards.

Relation of retinal blood flow and retinal oxygen extraction during stimulation with diffuse luminance flicker

PubMed Central

Palkovits, Stefan; Lasta, Michael; Told, Reinhard; Schmidl, Doreen; Werkmeister, René; Cherecheanu, Alina Popa; Garhöfer, Gerhard; Schmetterer, Leopold

2015-01-01

Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker–induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown. PMID:26672758

Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial Adenomatous Polyposis - the First FAP registry in Iran

PubMed

Mirinezhad, Seyed Kazem; Mousavi, Farideh; Baghri, Masood; Sepehri, Bita; Ghavidel, Ali; Ghojazadeh, Morteza; Somi, Mohammad Hossein

2018-01-27

Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited disorder is characterized by the presence of multiple adenomatous colorectal polyps, which can develop into cancer during early adulthood. Therefore, early diagnosis is essential. Most FAP patients have several extracolonic manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE). Whereas genetic markers may provide the main route to detection of ‘‘at risk’’ subjects , at present this approach is clearly limited and searches for a noninvasive phenotypic marker continue to be high priority.The aim of this study was to describe the pattern of distribution of CHRPE lesions and evaluate their diagnostic value in FAP patients and their family members in a local population. Methods: A total of 23 FAP patients and 26 relatives belonging to 12 families at high risk of developing FAP were subjected to colonoscopic and ophthalmological examination. Result: Retinal examinations demonstrated prevalences of CHRPE in FAP patents and their siblings of 78% and 38%, respectively. We were able to illustrate a significant correlation between FAP disease and the presence of retinal lesions. Sensitivity and specificity of CHRPE as a screening test to detect the presence of FAP are 78.3% and 61.5%, respectively, with a positive predictive value of 64.3% and a negative predictive value of 76.2 %. A “lesion form” significant difference was found between FAP and normal participants.Spearman nonparametric analysis revealed no correlation between age and number or size of lesions. Conclusion: Multiple CHRPE lesions are a diagnostic feature of FAP patients They are specific and sensitive clinical markers of this disease (specificity 60% and sensitivity 77%). Creative Commons Attribution License

Effects of methylprednisolone on laser-induced retinal injuries

NASA Astrophysics Data System (ADS)

Rosner, Mordechai; Tchirkov, Marina; Dubinski, Galina; Solberg, Yoram; Belkin, Michael

1997-05-01

Methylprednisolone have been demonstrated to ameliorate retinal photic injury. In the current study we examined its effect on laser induced retinal injury. Retinal lesions were inflicted by argon laser in 36 pigmented DA rats. The treated groups received intra-peritoneally methylprednisolone in saline, injected 3 times a day for 2 days, starting immediately after exposure. The controls received the vehicle on the same schedule. The rats were sacrificed 3, 20 or 60 days after laser exposure and the lesions were evaluated by light microscopy and morphometric measurements. Laser injuries were associated with disruption of the outer retinal layers. Three and 20 days after exposure, the loss of the photoreceptor-cell nuclei was significantly milder in the treated groups as compared with controls. There was no difference 60 days after exposure. In conclusion, methylprednisolone reduced temporarily the photoreceptor cell loss in argon laser induced retinal injury, when treatment was started immediately after laser exposure. There was no long term effect.

Selective retinal therapy with a continuous line scanning laser

NASA Astrophysics Data System (ADS)

Paulus, Yannis M.; Jain, ATul; Gariano, Ray F.; Nomoto, Hiroyuki; Schuele, Georg; Sramek, Christopher; Charalel, Resmi; Palanker, Daniel

2010-02-01

This study evaluates the effects of exposure duration, beam diameter, and power on the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser. A 532 nm laser (PASCALTM) with retinal beam diameters of 40 and 66 μm was applied to 60 eyes of 30 Dutch-Belted rabbits. Retinal exposure duration varied from 15 to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography (FA). RPE flatmounts were evaluated with live-dead fluorescent assay (LD). Histological analysis was performed at 1 hour, 1 and 3 days, 1 and 2 weeks, and 1 and 2 months following laser treatment. Ophthalmoscopic visibility (OV) of the lesions corresponded to photoreceptor damage on histological analysis at 1 hour. In subvisible lesions, FA and LD yielded similar thresholds of RPE damage. The ratios of the threshold of rupture and of OV to FA visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Above the threshold of OV, histology showed focal RPE damage and photoreceptor loss at one day without inner retinal effects. By one week, continuity of photoreceptor and RPE layers was restored. By 1 month, photoreceptors appeared normal while hypertrophy and hyperpigmentation of the RPE persisted. Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors. The damage zone in the photoreceptor layer is quickly filled-in, likely due to photoreceptor migration from adjacent zones. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

Automated Multi-Lesion Detection for Referable Diabetic Retinopathy in Indigenous Health Care

PubMed Central

Pires, Ramon; Carvalho, Tiago; Spurling, Geoffrey; Goldenstein, Siome; Wainer, Jacques; Luckie, Alan; Jelinek, Herbert F.; Rocha, Anderson

2015-01-01

Diabetic Retinopathy (DR) is a complication of diabetes mellitus that affects more than one-quarter of the population with diabetes, and can lead to blindness if not discovered in time. An automated screening enables the identification of patients who need further medical attention. This study aimed to classify retinal images of Aboriginal and Torres Strait Islander peoples utilizing an automated computer-based multi-lesion eye screening program for diabetic retinopathy. The multi-lesion classifier was trained on 1,014 images from the São Paulo Eye Hospital and tested on retinal images containing no DR-related lesion, single lesions, or multiple types of lesions from the Inala Aboriginal and Torres Strait Islander health care centre. The automated multi-lesion classifier has the potential to enhance the efficiency of clinical practice delivering diabetic retinopathy screening. Our program does not necessitate image samples for training from any specific ethnic group or population being assessed and is independent of image pre- or post-processing to identify retinal lesions. In this Aboriginal and Torres Strait Islander population, the program achieved 100% sensitivity and 88.9% specificity in identifying bright lesions, while detection of red lesions achieved a sensitivity of 67% and specificity of 95%. When both bright and red lesions were present, 100% sensitivity with 88.9% specificity was obtained. All results obtained with this automated screening program meet WHO standards for diabetic retinopathy screening. PMID:26035836

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

PubMed

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

Impacts of age and sex on retinal layer thicknesses measured by spectral domain optical coherence tomography with Spectralis.

PubMed

Nieves-Moreno, María; Martínez-de-la-Casa, José M; Morales-Fernández, Laura; Sánchez-Jean, Rubén; Sáenz-Francés, Federico; García-Feijoó, Julián

2018-01-01

To examine differences in individual retinal layer thicknesses measured by spectral domain optical coherence tomography (SD-OCT) (Spectralis®) produced with age and according to sex. Cross-sectional, observational study. The study was conducted in 297 eyes of 297 healthy subjects aged 18 to 87 years. In one randomly selected eye of each participant the volume and mean thicknesses of the different macular layers were measured by SD-OCT using the instrument's macular segmentation software. Volume and mean thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigmentary epithelium (RPE) and photoreceptor layer (PR). Retinal thickness was reduced by 0.24 μm for every one year of age. Age adjusted linear regression analysis revealed mean GCL, IPL, ONL and PR thickness reductions and a mean OPL thickness increase with age. Women had significantly lower mean GCL, IPL, INL, ONL and PR thicknesses and volumes and a significantly greater mRNFL volume than men. The thickness of most retinal layers varies both with age and according to sex. Longitudinal studies are needed to determine the rate of layer thinning produced with age.

Generation of Transplantable Retinal Pigmented Epithelial (RPE) Cells for Treatment of Age-Related Macular Degeneration (AMD).

PubMed

Surendran, Harshini; Rathod, Reena J; Pal, Rajarshi

2018-06-13

Age-related macular degeneration (AMD) is the foremost cause of blindness in people over the age of 60 worldwide. Clinically, this disease starts with distortion in central vision eventually leading to legal blindness. Vision loss has a significant impact on quality of life and incurs a substantial cost to the economy. Furthermore, AMD is a complex and progressive neurodegenerative disorder that triggers visual impairment due to the loss of retinal pigmented epithelium (RPE) and the light-sensitive photoreceptors that they support, protect and provide nutrition. Currently, there is no curative treatment for the most common form of this disease, i.e., dry AMD. A novel approach to treat AMD involves the transplantation of RPE cells derived from human induced pluripotent stem cells (iPSCs) in the outer retina. These iPSC-derived RPE cells not only show characteristics similar to native RPE but also could replace as well as regenerate damaged pathologic RPE and produce supportive growth factors and cytokines. Several clinical trials are being conducted taking advantage of a variety of cell- and tissue engineering-based approaches. Here, we present a simple, cost effective, and scalable cell-culture model for generation of purified RPE thus providing the foundation for developing an allogeneic cell therapy for AMD.

The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

PubMed Central

Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Smith, R. Theodore; Freund, K. Bailey; Curcio, Christine A.

2015-01-01

Purpose. To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. Methods. Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral-domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at predefined locations. Retinal pigment epithelial cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. Results. In 13 GA eyes (449 locations), ‘Shedding,’ ‘Sloughed,’ and ‘Dissociated’ morphologies were abundant; 22.2% of atrophic locations had ‘Dissociated’ RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had ‘Entombed’ RPE; ‘Sloughed,’ ‘Dissociated,’ and ‘Bilaminar’ morphologies were abundant. Of abnormal RPE, CNV and GA both had ∼35% ‘Sloughed’/‘Intraretinal,’ with more Intraretinal in CNV (9.5% vs. 1.8%). ‘Shedding’ cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. Conclusions. Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are ‘Dissociated’ and ‘Sloughed’ cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping

Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens

PubMed Central

2012-01-01

Background The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. Methods Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer. Results The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only. The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions. Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p = 0.02). Conclusions Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

PubMed

Schneider, Eric W; Elner, Susan G; van Kuijk, Frederik J; Goldberg, Naomi; Lieberman, Ronni M; Eliott, Dean; Johnson, Mark W

2013-10-01

To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

Lack of differences in the regional variation of oxygen saturation in larger retinal vessels in diabetic maculopathy and proliferative diabetic retinopathy.

PubMed

Jørgensen, Christina Mørup; Bek, Toke

2017-06-01

Diabetic retinopathy is characterised by morphological lesions in the ocular fundus related to disturbances in retinal blood flow. The two vision threatening forms of retinopathy show specific patterns of distribution of retinal lesions with proliferative diabetic retinopathy (PDR) developing secondary to ischaemia and hypoxia in the retinal periphery and diabetic maculopathy (DM) developing secondary to hyperperfusion and increased vascular permeability in the macular area. These differences in the distribution of retinal lesions might be reflected in regional differences in oxygen saturation in the larger retinal vessels. Dual-wavelength retinal oximetry was performed in 30 normal persons, 30 patients with DM and 30 patients with PDR, and the oxygen saturation was measured in peripapillary vessels supplying the four retinal quadrants and in branches from the upper temporal arcades supplying, respectively, the macular area and the retinal periphery. The overall oxygen saturation was significantly higher in diabetic patients than in normal persons and the arteriovenous (AV) saturation difference significantly lower in the patients with DM. The regional variation in oxygen saturation was similar in the three studied groups with a decreasing saturation from the upper nasal through the lower nasal, lower temporal and the upper temporal peripapillary vessels, and with a significantly higher oxygen saturation in venules draining the macular area than in venules draining the retinal periphery. The regional differences in retinal lesions in vision threatening diabetic retinopathy are not reflected in regional differences in the oxygen saturation of larger retinal vessels. The development of vision threatening diabetic retinopathy depends on other factors, such as, for example, regional differences in the retinal microcirculation. 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/.

MACULAR HOLES, VITELLIFORM LESIONS, AND MIDPERIPHERAL RETINOSCHISIS IN ALPORT SYNDROME.

PubMed

Thomas, Akshay S; Baynham, Justin T; Flaxel, Christina J

2016-01-01

To describe the retinal findings in two cases of Alport syndrome. Observational case series. The clinical findings of the two patients were documented with color fundus photography and high resolution spectral domain optical coherence tomography. Patient 1 was found to have fleck retinopathy in both eyes, inner retinal thinning in the right eye and a full-thickness macular hole in the left eye. Patient 2 was found to have a full-thickness macular hole in the right eye as well as retinoschisis in the temporal macula in the right eye. The left eye revealed inner retinal thinning involving the fovea, a vitelliform lesion of the temporal macula and midperipheral retinoschisis involving multiple retinal layers. Retinal abnormalities including fleck retinopathy, retinal thinning, macular holes, retinoschisis, and vitelliform lesions are variably present in Alport syndrome. This is only the second report of a vitelliform lesion in a patient with Alport syndrome and the first report of midperipheral retinoschisis. The array of retinal findings is believed to reflect a dysfunctional Type IV collagen present in the internal limiting membrane and Bruch membrane.

Imaging polarimetry in patients with neovascular age-related macular degeneration

PubMed Central

Elsner, Ann E.; Weber, Anke; Cheney, Michael C.; VanNasdale, Dean A.; Miura, Masahiro

2007-01-01

Imaging polarimetry was used to examine different components of neovascular membranes in age-related macular degeneration. Retinal images were acquired with a scanning laser polarimeter. An innovative pseudo-color scale, based on cardinal directions of color, displayed two types of image information: relative phases and magnitudes of birefringence. Membranes had relative phase changes that did not correspond to anatomical structures in reflectance images. Further, membrane borders in depolarized light images had significantly higher contrasts than those in reflectance images. The retinal birefringence in neovascular membranes indicates optical activity consistent with molecular changes rather than merely geometrical changes. PMID:17429494

Copolymer-1 vaccination regimens for neuroprotection in laser-induced retinal injuries

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Epstein, Yoram; Rosner, Mordechai

2005-04-01

The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1, Copaxone) in adjuvant against laser-induced retinal damage was previously reported. The present study quantitatively compares various regimens of this vaccination for reducing the spread of laser-induced retinal damage and investigates the cellular mechanism of Cop-1 activity. Standard argon laser lesions were created in 78 DA pigmented rats divided into five groups: three Cop-1 single treatment groups (treated 7 days before, immediately after, or 24 hours after the injury), one group treated twice (7 days before and 20 days after injury), and a control group treated with adjuvant 7 days before the injury. The retinal lesions were evaluated 3, 20, and 60 days after the injury. Immunostaining of the retinas of the pretreated and control group animals 3 days after the laser injury was performed for T-cell detection. Cop-1 pre-immunization reduced photoreceptor loss at all time points as measured over the central zone of the lesion and 3 and 20 days after lasing as measured over the whole damaged area. Lesion diameter was reduced only 60 days after laser injury in pre-treated animals. Cop-1 given immediately after injury reduced cell loss as measured 20 and 60 days later in the whole lesion and 20 days after the laser irradiation, when measured in the center of lesion. It had no effect on lesion diameter. Late treatment reduced only the lesion diameter at all time points. Repeated treatment enhanced the neuroprotective effect, decreasing the cell loss in the center of lesion and reducing the diameter of lesion. T-cells were detected in the retinal lesions of pre-immunized animals and not in non-treated group, demonstrating the cellular immune mechanism of Cop-1. Immunization with Cop-1 is neuroprotective against laser-induced retinal injuries, and repeating the treatment enhances this effect. Cellular immune action of Cop-1 of was detected.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

2017-07-01

To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

Retinal Thickness Analysis by Race, Gender, and Age Using Stratus OCT™

PubMed Central

Kashani, Amir H.; Zimmer-Galler, Ingrid E.; Shah, Syed Mahmood; Dustin, Laurie; Do, Diana V.; Eliott, Dean; Haller, Julia A.; Nguyen, Quan Dong

2010-01-01

PURPOSE To detect differences in retinal thickness among patients of different race, gender and age using Stratus OCT™. DESIGN Cross-sectional study. METHODS In a multicenter, university-based study, 126 patients with no history of ocular disease were enrolled (78 diabetics without retinopathy and 48 nondiabetics). Optical coherence tomography measurements were performed using Stratus OCT™. Statistical comparisons of centerpoint foveal thickness and mean foveal thickness were made using generalized estimating equations adjusting for diabetic status, race, age, and gender. RESULTS The study population consisted of 36% males, 39% Caucasians, 33% African Americans, and 28% Hispanics. Mean foveal thickness was 191.6±2.7µm and 194.5±2.7µm for diabetics and nondiabetics, respectively (P=0.49). Mean foveal thickness in males was significantly larger than in females (201.8±2.7µm and 186.9±2.6µm, respectively; P<0.001). Mean foveal thickness was 200.2±2.7µm for Caucasians, 181.0±3.7µm for African Americans, and 194.7±3.9µm for Hispanics. Mean foveal thickness was significantly less for African Americans than Caucasians (P <0.0001) or Hispanics (P=0.005). Centerpoint foveal thickness and mean foveal thickness showed a significant increase with age. CONCLUSIONS There are statistically significant differences in retinal thickness between subjects of different race, gender, and age. When compared to Caucasians and Hispanics, African-American race is a predictor of decreased mean foveal thickness; and male sex (regardless of race) is a significant predictor of increased mean foveal thickness. Mean foveal thickness is similar among diabetics and nondiabetics when data are controlled for age, race, and sex. These results suggest that studies comparing OCT measurements should carefully control for age, race, and gender-based variations in retinal thickness. PMID:20042179

Intake of dietary salt and drinking water: Implications for the development of age-related macular degeneration

PubMed Central

Hollborn, Margrit; Kohen, Leon; Wiedemann, Peter

2016-01-01

Purpose Systemic hypertension is a risk factor of age-related retinal diseases such as diabetic retinopathy and age-related macular degeneration. High intake of dietary salt and low intake of water increase extracellular osmolality resulting in hypertension, in particular in salt-sensitive individuals. This review summarizes the present knowledge regarding the impact of salt and water intake on the regulation of blood pressure, retinal function, and the development of age-related retinal diseases. Methods A literature search of the Medline database and a summary of recent studies that used human RPE cells. Results The salt sensitivity of the blood pressure and plasma osmolality increase with age, and body water deficits are common in older individuals. High plasma osmolality has adverse effects in the retina. In RPE cells, high osmolality induces expression and secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF), placental growth factor, and basic fibroblast growth factor, and expression of aquaporin-5, a water channel implicated in transepithelial water transport. The transcriptional activities of hypoxia-inducible factor-1 (HIF-1) and nuclear factor of activated T cell 5 (NFAT5) are critical for the production of VEGF in response to salt-induced osmotic stress. Salt-induced osmotic stress also induces priming of the NLRP3 inflammasome and activates inflammatory enzymes in RPE cells. Conclusions Raised plasma osmolality may aggravate age-related retinal diseases by stimulation of local inflammation and angiogenic factor production in the RPE. Alterations in salt and water consumption, and of minerals that stimulate renal salt excretion, may offer nutritional approaches to prevent age-related retinal disorders, in particular in salt-sensitive individuals and individuals who show signs of body dehydration. PMID:28031693

Intake of dietary salt and drinking water: Implications for the development of age-related macular degeneration.

PubMed

Bringmann, Andreas; Hollborn, Margrit; Kohen, Leon; Wiedemann, Peter

2016-01-01

Systemic hypertension is a risk factor of age-related retinal diseases such as diabetic retinopathy and age-related macular degeneration. High intake of dietary salt and low intake of water increase extracellular osmolality resulting in hypertension, in particular in salt-sensitive individuals. This review summarizes the present knowledge regarding the impact of salt and water intake on the regulation of blood pressure, retinal function, and the development of age-related retinal diseases. A literature search of the Medline database and a summary of recent studies that used human RPE cells. The salt sensitivity of the blood pressure and plasma osmolality increase with age, and body water deficits are common in older individuals. High plasma osmolality has adverse effects in the retina. In RPE cells, high osmolality induces expression and secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF), placental growth factor, and basic fibroblast growth factor, and expression of aquaporin-5, a water channel implicated in transepithelial water transport. The transcriptional activities of hypoxia-inducible factor-1 (HIF-1) and nuclear factor of activated T cell 5 (NFAT5) are critical for the production of VEGF in response to salt-induced osmotic stress. Salt-induced osmotic stress also induces priming of the NLRP3 inflammasome and activates inflammatory enzymes in RPE cells. Raised plasma osmolality may aggravate age-related retinal diseases by stimulation of local inflammation and angiogenic factor production in the RPE. Alterations in salt and water consumption, and of minerals that stimulate renal salt excretion, may offer nutritional approaches to prevent age-related retinal disorders, in particular in salt-sensitive individuals and individuals who show signs of body dehydration.

Bilateral chorioretinal coloboma discovered with ultra-wide field retinal imaging

PubMed Central

Barnard, Simon; Shneor, Einat; Brauner, Joel; Millodot, Michel; Gordon-Shaag, Ariela

2012-01-01

Uveal coloboma results from incomplete closure of the optic cup fissure. While conducting an evaluation of a new ultra-wide field retinal imaging camera (Optomap), which provides a view of the fundus up to 200° at one time without mydriasis, we discovered a case of bilateral chorioretinal coloboma in a 21-year-old student. The lesion was located in the midperiphery of each eye less than 2 disc diameters (DD) below the optic disc in the inferonasal quadrants. The size of the coloboma in the right eye was 1.8 DD in height and 1.3 DD in width, while the left lesion was 2.4 DD in height and 2.6 DD in width. The subject was totally asymptomatic and without any complication such as retinal detachment or choroidal neovascularization, which often accompany this type of lesion. The visual field of each eye displayed an absolute scotoma corresponding to the size and location of the coloboma. No management was necessary but the subject was advised to report for visual examination at regular intervals because complications can occur at any age.

The Role of Retinal Vascular Density as a Screening Tool for Ageing and Stroke.

PubMed

Sprödhuber, Andrea; Wolz, Johannes; Budai, Attila; Laumeier, Inga; Audebert, Heinrich J; Michelson, Georg

2018-06-06

To measure the density of retinal vessels from digitized fundus photographs in patients with recent stroke and age-matched controls. To investigate whether the parameter retinal vascular density (RVD) served as a quantitative marker for cerebrovascular events. Digitized fundus photographs of n = 158 subjects with stroke or transient ischemic attack within 1 year at the time of examination and n = 1,250 age-matched controls without any remarkable medical history were examined. Sex, hypertension, and diabetes were considered to be cofactors. Measurement of RVD was performed with a computer-aided image-analyzing program by segmenting automatically all visible retinal vessels and measuring areas of vessels in distinct circles around the optic disk. In controls RVD dwindles with increasing distance from the optic disk. RVD decreased significantly with age (p = 0.000). Stroke patients showed significantly lower values of RVD of -15% in comparison to age-matched controls. In old subjects, stroke in combination with hypertension is associated with a significant decreased RVD, and in middle-aged subjects diabetes and stroke are associated with a significant decreased RVD (p = 0.01). Age and stroke are significant risk factors for decreased RVD. Diabetes and arterial hypertension are additional significant risk factors in patients with stroke with respect to RVD. © 2018 S. Karger AG, Basel.

Prevalence of retinal diseases and their pattern in Tehran: the Tehran eye study.

PubMed

Hatef, Elham; Fotouhi, Akbar; Hashemi, Hassan; Mohammad, Kazem; Jalali, Kamran Hodjat

2008-05-01

To determine the prevalence of retinal diseases and their pattern in Tehran through a population-based study. In 2002, through a stratified random cluster sampling, 6497 citizens representing a cross-section of the population of Tehran were selected from 160 clusters. Eligible people were recruited through a door-to-door household survey in selected clusters and transferred to a clinic for an extensive eye examination and interview. The prevalence of retinal diseases was 8.56 per 100 (95% CI, 7.74-9.39). Acquired retinopathies (3.33 per 100) and peripheral retinal lesions (3.29 per 100) were the most common retinal diseases in our population. Cataract (12.47 per 100) was the major ocular comorbidity; high blood pressure (21.14 per 100) and diabetes mellitus (15.99 per 100) were the main systemic comorbidities among 415 patients with retinal diseases. The prevalence of low vision on the basis of best-corrected and presenting visual acuity was 0.63 and 2.87 per 100 in 415 patients with retinal disease. Two patients (0.48 per 100) were blind with corrected and presenting visual acuity. The prevalence of diabetic retinopathy in the studied population was 0.61 per 100 (95% CI, 0.39-0.82) and age-related macular degeneration was detected in 1.95 per 100 (95% CI, 1.55-2.34) of the population. These findings reveal a considerable prevalence of retinal diseases in the population. The prevalence might be underestimated due to the lack of fundus photography. The findings could be considered for case finding and planning treatment programs for specific retinal diseases.

[Retinal vasculopathy with cerebral leukoencephalopathy carrying TREX1 mutation diagnosed by the intracranial calcification: a case report].

PubMed

Komaki, Ryouhei; Ueda, Takehiro; Tsuji, Yukio; Miyawaki, Toko; Kusuhara, Sentaro; Hara, Shigeo; Toda, Tatsushi

2018-02-28

A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.

Automated segmentation of lesions including subretinal hyperreflective material in neovascular age-related macular degeneration.

PubMed

Lee, Hyungwoo; Kang, Kyung Eun; Chung, Hyewon; Kim, Hyung Chan

2018-04-12

To evaluate an automated segmentation algorithm with a convolutional neural network (CNN) to quantify and detect intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM) through analyses of spectral domain optical coherence tomography (SD-OCT) images from patients with neovascular age-related macular degeneration (nAMD). Reliability and validity analysis of a diagnostic tool. We constructed a dataset including 930 B-scans from 93 eyes of 93 patients with nAMD. A CNN-based deep neural network was trained using 11550 augmented images derived from 550 B-scans. The performance of the trained network was evaluated using a validation set including 140 B-scans and a test set of 240 B-scans. The Dice coefficient, positive predictive value (PPV), sensitivity, relative area difference (RAD), and intraclass correlation coefficient (ICC) were used to evaluate segmentation and detection performance. Good agreement was observed for both segmentation and detection of lesions between the trained network and clinicians. The Dice coefficients for segmentation of IRF, SRF, SHRM, and PED were 0.78, 0.82, 0.75, and 0.80, respectively; the PPVs were 0.79, 0.80, 0.75, and 0.80, respectively; and the sensitivities were 0.77, 0.84, 0.73, and 0.81, respectively. The RADs were -4.32%, -10.29%, 4.13%, and 0.34%, respectively, and the ICCs were 0.98, 0.98, 0.97, and 0.98, respectively. All lesions were detected with high PPVs (range 0.94-0.99) and sensitivities (range 0.97-0.99). A CNN-based network provides clinicians with quantitative data regarding nAMD through automatic segmentation and detection of pathological lesions, including IRF, SRF, PED, and SHRM. Copyright © 2018 Elsevier Inc. All rights reserved.

Towards a Completely Implantable, Light-Sensitive Intraocular Retinal Prosthesis

DTIC Science & Technology

2001-10-25

electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable...34Preservation of the inner retina in retinitis pigmentosa . A morphometric analysis," Arch Ophthalmol, vol. 115, no. 4, pp. 511-515, Apr.1997...Towards a completely implantable, light-sensitive intraocular retinal prosthesis. M.S. Humayun, J.D. Weiland, B. Justus1, C. Merrit1, J. Whalen, D

Identification of Age-Related Macular Degeneration Using OCT Images

NASA Astrophysics Data System (ADS)

Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

2018-02-01

Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

Visual Acuity is Related to Parafoveal Retinal Thickness in Patients with Retinitis Pigmentosa and Macular Cysts

PubMed Central

Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.

2008-01-01

Purpose To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. Methods In 316 patients with typical forms of retinitis pigmentosa, we measured visual acuities with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, detected macular cysts with optical coherence tomography (OCT), and quantified retinal thicknesses by OCT. We used the FREQ, LOGISTIC, and GENMOD procedures of SAS to evaluate possible risk factors for cyst prevalence and the MIXED procedure to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. Results We found macular cysts in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (p = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (p = 0.038) and within a ring spanning an eccentricity of 5° to 10° from the foveal center (p = 0.004). Conclusions Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly-inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. PMID:18552390

Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.

PubMed

Vessey, Kirstan A; Gu, Ben J; Jobling, Andrew I; Phipps, Joanna A; Greferath, Ursula; Tran, Mai X; Dixon, Michael A; Baird, Paul N; Guymer, Robyn H; Wiley, James S; Fletcher, Erica L

2017-08-01

Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

PubMed Central

Rossi, Ethan A.; Rangel-Fonseca, Piero; Parkins, Keith; Fischer, William; Latchney, Lisa R.; Folwell, Margaret A.; Williams, David R.; Dubra, Alfredo; Chung, Mina M.

2013-01-01

Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan’s method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm2, which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health. PMID:24298413

Development and recovery of laser-induced retinal injury in rats

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Epstein, Yoram; Rosner, Mordechai

2005-04-01

Retinal photocoagulation lesions undergo primary and secondary degeneration followed by partial healing. This study follows the sequential changes in laser-induced retinal lesion over a time span of 60 days. Argon laser lesions were created in 36 pigmented rats. Sections of the retinal lesions were evaluated by light microscopy 1, 24, 48, 72 hours, and 20, and 60 days after the injury (six animals at each time point). The diameter of the lesion was equal to that of the laser spot 1h after irradiation and increased by 24h. It decreased later, slightly during the following 48h and significantly by 20 days. The destruction of photoreceptors was most severe after 24-48h. The nuclei in the outer-nuclear layer were pyknotic at the lesion site at 1h and disappeared later. Healing processes began 72h after the irradiation and was completed by 60 days. Filling-in by sliding of near nuclei was observed by the 60th day. Reversible changes were seen also in the retinal pigment epithelium (with formation of a plaque at 72h and its degradation later on) and in the choroid (disorganization of capillaries by 48h with later reorganization). Conclusions: The development of a laser-induced injury is gradual. The photoreceptors are damaged first and than the damage spreads to other layers of retina and to areas adjacent the primary injury site. The extension of the damage is later stopped and the adjacent tissues tend to fill the lesion and remodel the retina.

Bioelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Weiland, James D.

2016-05-01

Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

Color Doppler imaging of retinal diseases.

PubMed

Dimitrova, Galina; Kato, Satoshi

2010-01-01

Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting.

Preferred retinal locus in macular disease: characteristics and clinical implications.

PubMed

Greenstein, Vivienne C; Santos, Rodrigo A V; Tsang, Stephen H; Smith, R Theodore; Barile, Gaetano R; Seiple, William

2008-10-01

To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity. Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull's eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter. Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli. Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function.

Repeatability of Retinal Sensitivity Measurements Using a Medmont Dark-Adapted Chromatic Perimeter in Healthy and Age-Related Macular Degeneration Cases.

PubMed

Tan, Rose S; Guymer, Robyn H; Luu, Chi D

2018-05-01

To determine the intrasession and intersession test-retest repeatability of retinal sensitivity measurements using a dark-adapted chromatic perimeter (DACP). For intrasession testing, retinal sensitivity within the central 24° for the 505-nm stimulus was measured after 20, 30, and 40 minutes of dark adaptation (DA) and for the 625-nm stimulus was measured after the first and second 505-nm tests. For intersession testing, retinal sensitivity for both stimuli was measured after 30 minutes of DA at baseline and 1 month. The point-wise sensitivity (PWS) difference and coefficient of repeatability (CoR) of each stimulus and group were determined. For intrasession testing, 10 age-related macular degeneration (AMD) and eight control subjects were recruited. The overall CoR for the 505-nm stimulus was 8.4 dB for control subjects and 9.1 dB for AMD cases, and for the 625-nm stimulus was 6.7 dB for control subjects and 9.5 dB for AMD cases. For intersession testing, seven AMD cases and 13 control subjects returned an overall CoR for the 505-nm stimulus of 8.2 dB for the control and 11.7 dB for the AMD group. For the 625-nm stimulus the CoR was 6.2 dB for the control group and 8.4 dB for the AMD group. Approximately 80% of all test points had a PWS difference of ±5 dB between the two intrasession or intersession measurements for both stimuli. The CoR for the DACP is larger than that reported for scotopic perimeters; however, the majority of test points had a PWS difference of ±5 dB between tests. The DACP offers an opportunity to measure static and dynamic rod function at multiple locations with an acceptable reproducibility level.

Automatic discrimination of color retinal images using the bag of words approach

NASA Astrophysics Data System (ADS)

Sadek, I.; Sidibé, D.; Meriaudeau, F.

2015-03-01

Diabetic retinopathy (DR) and age related macular degeneration (ARMD) are among the major causes of visual impairment all over the world. DR is mainly characterized by small red spots, namely microaneurysms and bright lesions, specifically exudates. However, ARMD is mainly identified by tiny yellow or white deposits called drusen. Since exudates might be the only visible signs of the early diabetic retinopathy, there is an increase demand for automatic diagnosis of retinopathy. Exudates and drusen may share similar appearances; as a result discriminating between them plays a key role in improving screening performance. In this research, we investigative the role of bag of words approach in the automatic diagnosis of retinopathy diabetes. Initially, the color retinal images are preprocessed in order to reduce the intra and inter patient variability. Subsequently, SURF (Speeded up Robust Features), HOG (Histogram of Oriented Gradients), and LBP (Local Binary Patterns) descriptors are extracted. We proposed to use single-based and multiple-based methods to construct the visual dictionary by combining the histogram of word occurrences from each dictionary and building a single histogram. Finally, this histogram representation is fed into a support vector machine with linear kernel for classification. The introduced approach is evaluated for automatic diagnosis of normal and abnormal color retinal images with bright lesions such as drusen and exudates. This approach has been implemented on 430 color retinal images, including six publicly available datasets, in addition to one local dataset. The mean accuracies achieved are 97.2% and 99.77% for single-based and multiple-based dictionaries respectively.

Age-related adaptive responses of mitochondria of the retinal pigment epithelium to the everyday blue LED lighting.

PubMed

Serezhnikova, N B; Pogodina, L S; Lipina, T V; Trofimova, N N; Gurieva, T S; Zak, P P

2017-07-01

The effect of everyday blue light (λ = 440-460 nm) on mitochondria of the retinal pigment epithelium of different age groups of Japanese quail was studied using electron microscopy, morphometric methods, and biochemical analysis. We have found a significant increase in the number of mitochondria, including those modified, mainly in young birds. In addition, cell metabolic activity increased in response to blue lighting. These changes are assumed to reflect an adaptive response of mitochondria aimed at neutralizing the phototoxic effect of blue light caused by accumulation of lipofuscin granules.

Age, Sex, and Ethnic Variations in Inner and Outer Retinal and Choroidal Thickness on Spectral-Domain Optical Coherence Tomography.

PubMed

Bafiq, Rinoza; Mathew, Raeba; Pearce, Elizabeth; Abdel-Hey, Ahmed; Richardson, Matthew; Bailey, Thomas; Sivaprasad, Sobha

2015-11-01

To evaluate age, sex, and ethnic variations in inner and outer retinal and choroidal thickness and foveal pit, using spectral-domain optical coherence tomography (SD OCT). Single-center observational cross-sectional study. Ninety randomly selected, healthy individuals of white, black, and South Asian origin underwent SD OCT raster and enhanced depth imaging scan. Manual measurements of inner and outer retinal thickness and choroidal thickness up to 3 mm nasal and temporal to the fovea were performed. The age, sex, and ethnic differences in these parameters were analyzed. The mean inner retinal thickness was lower by approximately 12 μm in black subjects across the central retina compared to white subjects (P < .05). The central foveal thickness below the foveal pit was lower in eyes of blacks compared to South Asians (12 μm, P = .035) and white subjects (18 μm, P < .0001). The fovea was also significantly wider in eyes of black and South Asian subjects compared to white individuals. The inner retinal thickness decreased by 0.5 μm per year of age of subjects and was thinner by 6.1 μm (P < .02) in female compared to male subjects. The subfoveal choroidal thickness did not vary between ethnic groups but the temporal choroid was significantly thinner in black subjects (P < .05). The choroid showed an age-related decline in thickness of 2 μm per year of age of the subjects. Interethnic differences include wider fovea, lower central foveal thickness, and thinner inner retina in eyes of black subjects compared to their white and South Asian counterparts. Copyright © 2015 Elsevier Inc. All rights reserved.

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

PubMed Central

Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

2016-01-01

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209

Retinal diseases in a tertiary hospital: the need for establishment of a vitreo-retinal care unit.

PubMed

Onakpoya, Oluwatoyin Helen; Olateju, Samuel Oluremi; Ajayi, Iyiade Adeseye

2008-11-01

To evaluate the need for vitreo-retinal care for suburban and rural communities of southwestern Nigeria. A retrospective review of patients with posterior segment diseases attending the general ophthalmology clinics of Obafemi Awolowo University Teaching Hospital's complex, Ile Ife, southwestern Nigeria, between January 2001 and December 2006 was conducted. The age, sex and diagnosis were analyzed and needs assessment conducted. Three-thousand, one-hundred-thirty-one new cases were reviewed of which 407(13%) patients presented with retinal diseases. Their mean age was 46.3 +/- 21.4 years, mode 60 years and male:female ratio 1.3:1 (P=0.05). Macula diseases (35.6%), hypertensive retinopathy (12%), retinochoroiditis (11.5%) and diabetic retinopathy (9.6%) were the predominant retinal diseases. Age-related macular degeneration was the most frequent of the macular diseases (38.6%), with a female preponderance (p=0.06). It is estimated that fundus photography +/- fluorescein will be beneficial in 89.4%, laser photocoagulation in 36.4% and vitreo-retinal surgical procedure in 16.4%. Posterior segment diseases are not uncommon in rural communities of southwestern Nigeria. Facilities for fundus angiography, laser photocoagulation and a vitreoretinal surgical unit in trained hands will improve the capacity for specific diagnosis and appropriate management of vitreo-retinal diseases in these communities.

The short-term effect of flavonoid-rich dark chocolate on retinal vessel diameter in glaucoma patients and age-matched controls.

PubMed

Terai, Naim; Gedenk, Alexandra; Spoerl, Eberhard; Pillunat, Lutz E; Stodtmeister, Richard

2014-08-01

To investigate the effect of flavonoid-rich dark chocolate and non-flavonoid-rich white chocolate on retinal vessel diameter in glaucoma patients and age-matched controls. Thirty glaucoma patients and 30 age-matched subjects were assigned to dark or white chocolate by randomization with forced equal distribution. The number in each of the four groups was 15. Measured parameters included systemic blood pressure (BP), blood glucose levels, static retinal vessel analysis, as measured by central retinal artery equivalent (CRAE) (which relates to the diameter of the central retinal artery), central retinal vein equivalent (CRVE) (which relates to the diameter of central retinal vein) and the arterio-venous ratio (AVR), which represents the CRAE/CRVE ratio, dynamic retinal vessel analysis as measured by the change in vessel diameter in response to flicker light stimulation. Three recording cycles from each were averaged. Blood pressure parameters (systolic BP, diastolic BP and pulse), IOP and blood glucose levels did not differ significantly between both groups before and after consumption of white or dark chocolate. Static vessel analysis did not show any significant changes in CRAE, CRVE or AVR before and after dark or white chocolate in both groups (p > 0.05). Mean dilatation of the venules in the control group was 3.2 ± 0.9 % before dark chocolate and 4.2 ± 1.4 % after dark chocolate intake, which was statistically significantly different (p = 0.01). Mean dilatation of the arterioles in the control group was 2.8 ± 1.8 % before dark chocolate and 3.5 ± 1.8 % after dark chocolate intake with a trend to statistical significance (p = 0.14), but not reaching the significance level. Mean diameter changes in the glaucoma group did not show any significant differences after dark chocolate consumption. The present study showed a significant improvement of venous vasodilatation 2 hr after dark chocolate intake in the control group, but not in the glaucoma group. This

Complement factor h is critical in the maintenance of retinal perfusion.

PubMed

Lundh von Leithner, Peter; Kam, Jaimie Hoh; Bainbridge, James; Catchpole, Ian; Gough, Gerald; Coffey, Peter; Jeffery, Glen

2009-07-01

Vascular pathologies are known to be associated with age-related macular degeneration. Recently, age-related macular degeneration was associated with a single-nucleotide substitution of the complement factor H (CFH) gene, part of the alternative pathway of the complement system, a critical element in the innate immune response. Such polymorphisms are found in more than 50% of cases of age-related macular degeneration. Here we show that the absence of CFH causes an autoimmune response that targets the vascular endothelium of both the inner and outer retinal vascular networks. In CFH-knockout (cfh(-/-)) mice, C3 and C3b, key components of the complement system, are progressively deposited on retinal vessels, which subsequently become restricted and wither, resulting in a reduction of retinal blood supply. This result leads to increased oxygen stress. While such effects are not systemic, these structural changes are mirrored in functional changes with a substantial decline in retinal blood flow dynamics. When the system is challenged functionally by laser-induced choroidal neovascularization, fluorescein leakage was significantly smaller in cfh(-/-) mice compared with controls, likely due to reduced retinal perfusion. These data reveal that in both the presence and absence of exogenous challenge to the innate immune system, CFH is required to maintain normal levels of retinal perfusion. It is likely that C3 and C3b accumulation in the aged CFH-deficient retina is associated with complement-mediated retinal endothelium destruction.

Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

PubMed Central

Luhmann, Ulrich F. O.; Lange, Clemens A.; Robbie, Scott; Munro, Peter M. G.; Cowing, Jill A.; Armer, Hannah E. J.; Luong, Vy; Carvalho, Livia S.; MacLaren, Robert E.; Fitzke, Frederick W.; Bainbridge, James W. B.; Ali, Robin R.

2012-01-01

Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2−/−/Crb1Rd8/RD8, Cx3cr1−/−/Crb1Rd8/RD8 and CCl2−/−/Cx3cr1−/−/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings

Retinal Vascular Fractal Dimension, Childhood IQ, and Cognitive Ability in Old Age: The Lothian Birth Cohort Study 1936

PubMed Central

Taylor, Adele M.; MacGillivray, Thomas J.; Henderson, Ross D.; Ilzina, Lasma; Dhillon, Baljean; Starr, John M.; Deary, Ian J.

2015-01-01

Purpose Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (D f) as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability. Methods Participants from the Lothian Birth Cohort 1936 Study (LBC1936) had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648). IQ scores were available from childhood. Retinal vascular D f was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular D f and general cognitive ability (g), processing speed, and memory. Results Only three out of 24 comparisons (two eyes × four D f parameters × three cognitive measures) were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye. Conclusions The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing. PMID:25816017

Congenital hypertrophy of retinal pigment epithelium (CHRPE) in patients with familial adenomatous polyposis (FAP); a polyposis registry experience.

PubMed

Nusliha, Anwer; Dalpatadu, Ushantha; Amarasinghe, Binara; Chandrasinghe, Pramodh Chitral; Deen, Kemal Ismail

2014-10-18

Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition giving rise to multiple adenomatous polyps in the colon which invariably become malignant by the fourth decade. Congenital hypertrophy of retinal pigment epithelium (CHRPE) is one of its extra intestinal manifestations early in childhood seen, present in 90% of FAP population and is easy to detect. Patients diagnosed with FAP and at risk first degree family members were screened for CHRPE using a slit lamp and indirect ophthalmoscopy. The retina of 17 diagnosed FAP patients and 13 individuals at risk were examined. The site and size of CHRPE lesions were documented. Thirteen (76%) of 17 FAP patients (male-10, female - 7, median age - 30 years; range 15-55 years) had CHRPE lesions; seven (54%) had bilateral CHRPE lesions and six (46%) had unilateral lesions. A single lesion was detected in 6 (46%) while 7 (54%) patients had multiple lesions. Of 13 at risk individuals (7- male, female-6 ; median age 34; range 16-52 years), one was positive for CHRPE and 12 were free of retinal lesions. The sensitivity of the presence of a CHRPE lesion in association with colonic polyps in FAP was 76%, specificity 92%, positive predictive value 93%, and negative predictive value 75%. This study found a high sensitivity and specificity for a CHRPE lesion to be associated with colonic polyps of FAP and hence a useful screening method in a burdened health-care system. The method is minimally invasive and simple and would be of particular value in screening children at risk for FAP.

Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.

PubMed

Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

2012-08-01

Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration.

PubMed

MacLaren, Robert E; Uppal, Gurmit S; Balaggan, Kamaljit S; Tufail, Adnan; Munro, Peter M G; Milliken, Andrew B; Ali, Robin R; Rubin, Gary S; Aylward, G William; da Cruz, Lyndon

2007-03-01

To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Prospective interventional cohort study. Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could

Mitochondrial ferritin affects mitochondria by stabilizing HIF-1α in retinal pigment epithelium: implications for the pathophysiology of age-related macular degeneration.

PubMed

Wang, Xiying; Yang, Hongkuan; Yanagisawa, Daijiro; Bellier, Jean-Pierre; Morino, Katsutaro; Zhao, Shiguang; Liu, Ping; Vigers, Piers; Tooyama, Ikuo

2016-11-01

Mitochondrial ferritin (FtMt) is believed to play an antioxidant role via iron regulation, and FtMt gene mutation has been reported in age-related macular degeneration (AMD). However, little is known about FtMt's functions in the retina and any links to AMD. In this study, we observed age-related increase in FtMt and hypoxia-inducible factor-1α (HIF-1α) in murine retinal pigment epithelium (RPE). FtMt overexpression in ARPE-19 cells stabilized HIF-1α, and increased the secretion of vascular endothelial growth factor. Conversely, HIF-1α stabilization reduced the protein level of the mature, functional form of FtMt. FtMt-overexpressing ARPE-19 cells exhibited less oxidative phosphorylation but unchanged production of adenosine triphosphate, enhanced mitochondrial fission, and triggered mitophagy in a HIF-1α-dependent manner. These findings suggest that increased FtMt in RPE may be protective via triggering mitophagy but cause wet AMD by inducing neovascularization due to increased vascular endothelial growth factor secretion. However, reduced level of functional FtMt in RPE under hypoxia may allow dry AMD through susceptibility to age-related stress. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

DETECTION OF NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Palejwala, Neal V; Jia, Yali; Gao, Simon S; Liu, Liang; Flaxel, Christina J; Hwang, Thomas S; Lauer, Andreas K; Wilson, David J; Huang, David; Bailey, Steven T

2015-11-01

To evaluate eyes with age-related macular degeneration and high-risk characteristics for choroidal neovascularization (CNV) with optical coherence tomographic (OCT) angiography to determine whether earlier detection of CNV is possible. Eyes with drusen, pigmentary changes, and with CNV in the fellow eye were scanned with a 70-kHz spectral domain OCT system (Optovue RTVue-XR Avanti). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. Two masked graders reviewed scans for CNV, defined as flow in the outer retinal/sub-RPE slab. Choroidal neovascularization flow area repeatability and between-grader reproducibility were calculated. Of 32 eyes, 2 (6%) were found to have Type 1 CNV with OCT angiography. The lesions were not associated with leakage on fluorescein angiography or fluid on OCT. One case was followed for 8 months without treatment, and the CNV flow area enlarged slightly without fluid buildup on OCT or vision loss. Between-grader reproducibility of the CNV flow area was 9.4% (coefficient of variation) and within-visit repeatability was 5.2% (pooled coefficient of variation). Optical coherence tomographic angiography can detect the presence of nonexudative CNV, lesions difficult to identify with fluorescein angiography and OCT. Further study is needed to understand the significance and natural history of these lesions.

Age-Related Susceptibility to Apoptosis in Human Retinal Pigment Epithelial Cells Is Triggered by Disruption of p53–Mdm2 Association

PubMed Central

Bhattacharya, Sujoy; Chaum, Edward; Johnson, Dianna A.; Johnson, Leonard R.

2012-01-01

Purpose. Relatively little is known about the contribution of p53/Mdm2 pathway in apoptosis of retinal pigment epithelial (RPE) cells or its possible link to dysfunction of aging RPE or to related blinding disorders such as age-related macular degeneration (AMD). Methods. Age-associated changes in p53 activation were evaluated in primary RPE cultures from human donor eyes of various ages. Apoptosis was evaluated by activation of caspases and DNA fragmentation. Gene-specific small interfering RNA was used to knock down expression of p53. Results. We observed that the basal rate of p53-dependent apoptosis increased in an age-dependent manner in human RPE. The age-dependent increase in apoptosis was linked to alterations in several aspects of the p53 pathway. p53 phosphorylation Ser15 was increased through the stimulation of ATM-Ser1981. p53 acetylation Lys379 was increased through the inhibition of SIRT1/2. These two posttranslational modifications of p53 blocked the sequestration of p53 by Mdm2, thus resulting in an increase in free p53 and of p53 stimulation of apoptosis through increased expression of PUMA (p53 upregulated modulator of apoptosis) and activation of caspase-3. Aged RPE also had reduced expression of antiapoptotic Bcl-2, which contributed to the increase in apoptosis. Of particular interest in these studies was that pharmacologic treatments to block p53 phosphorylation, acetylation, or expression were able to protect RPE cells from apoptosis. Conclusions. Our studies suggest that aging in the RPE leads to alterations of specific checkpoints in the apoptotic pathway, which may represent important molecular targets for the treatment of RPE-related aging disorders such as AMD. PMID:23139272

[Retinal detachment in HIV-infected patients with cytomegalovirus retinitis].

PubMed

Onishchenko, A L; Kolbasko, A V; Tatarnikova, G N; Grebenchuk, O S

2014-01-01

The authors present their own clinical experience in three HIV-infected patients with cytomegalovirus retinitis aged from 8 to 36 years. Detailed analysis of the results of physical and laboratory examinations is provided. Given short life expectancy for these patients, the authors pose a deontological question as to whether or not active treatment of retinal detachment in patients with AIDS and CMV retinitis is reasonable.

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

PubMed Central

Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

2016-01-01

This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812

[Effect of Bushen Huoxue Compound on Retinal Müller Cells in High Glucose or AGEs Conditions].

PubMed

Xie, Xue-jun; Song, Ming-xia; Zhang, Mei; Qin, Wei; Wan, Li; Fang, Yang

2015-06-01

To explore the effect of Bushen Huoxue Compound (BHC) on lactate dehydrogenase (LDH) leakage, expressions of vascular endothelial growth factor (VEGF) and VEGF mRNA in retinal Muller cells under high glucose condition or advanced glycosylation end products (AGEs) condition by using serum pharmacological method. The retinal Müller cells of 5-7 days post-natal Sprague Dawley (SD) rats were cultured with modified enzyme-digestion method. Purified retinal Muller cells were cultured in normal conditions, high glucose condition (50 mmol/L) or AGEs (50 mg/L and 100 mg/L) conditions, and BHC-containing serum was added to culture medium. The LDH leakage and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the relative expression of VEGF mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR). Compared with the normal control group, expressions of VEGF and VEGF mRNA were significantly increased in the high glucose group, the low dose AGEs group and the high dose AGEs group (all P < 0.01). The LDH leakage was obviously increased in the high dose AGEs group, when compared with the normal control group and the high glucose group (P < 0.01). The LDH leakage, expressions of VEGF and VEGF mRNA were obviously decreased by BHC-containing serum both in high glucose and AGEs conditions (P < 0.05, P < 0.01). BHC-containing serum had no significant effect on the LDH leakage and expressions of VEGF and VEGF mRNA in normal conditions (P > 0.05). AGEs intervention could obviously lower the stability of Müller cell membrane. Up-regulated expressions of VEGF and VEGF mRNA in cultured Müller cells could be induced by AGEs or high glucose. BHC-containing serum could stabilize the stability of Müller cell membrane, inhibit the transcription of VEGF mRNA and decrease the protein expression of VEGF, which might be one of important mechanisms for preventing and treating diabetic retinopathy.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Fisher, Diana E; Klein, Barbara E K; Wong, Tien Y; Rotter, Jerome I; Li, Xiaohui; Shrager, Sandi; Burke, Gregory L; Klein, Ronald; Cotch, Mary Frances

2016-06-01

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with

Retinal findings in a patient of French ancestry with CABP4-related retinal disease.

PubMed

Smirnov, Vasily Mikhaïlovitch; Zeitz, Christina; Soumittra, Nagasamy; Audo, Isabelle; Defoort-Dhellemmes, Sabine

2018-04-01

CABP4-related retinal dysfunction is a cone-rod synaptic transmission disorder with electronegative electroretinogram (ERG) waveform. It is a rare retinal dysfunction that can be classified into the incomplete form of congenital stationary night blindness. Absent foveal reflex and overall foveal thinning were previously reported, but in most cases the fundus appearance was described as nearly normal. We report here peculiar macular changes in a patient of French ancestry harbouring CABP4 mutations. Complete ocular examination and full-field ERG were performed at the initial presentation and follow-up. Multimodal fundus imagining, including spectral-domain optical coherence tomography, colour, infrared reflectance and short-wavelength autofluorescence photographs, was performed during follow-up visits. A 7-month-old infant was addressed to our department for visual unresponsiveness and nystagmus. ERG had an electronegative waveform, even for light-adapted stimuli, thus supporting the diagnosis of photoreceptor-bipolar cell transmission disorder. Genetic investigations discovered a compound heterozygous mutation in CABP4: c.646C > T, p.Arg216*/c.673C > T, p.Arg225*. Multimodal fundus imaging, performed at follow-up visits, showed fine radial folds at the vitreomacular interface and dark foveal dots in both eyes. Optic coherence tomography revealed a focal foveal ellipsoid zone gap. Initial presentation was misleading with Leber congenital amaurosis. The electronegative ERG waveform reoriented the genetic investigations and thus establishing a correct diagnosis. To the best of our knowledge, the peculiar fundus changes observed in our patient were never reported before. We hypothesized that a foveal ellipsoid zone interruption discovered in our patient could reflect mostly a cone dysfunction. It was unclear whether the fine radial folds in both maculae were linked with high hyperopia or were an intrinsic feature of the retinal disease. CABP4-related retinal

Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond to Histology

PubMed Central

Schaal, Karen B.; Freund, K. Bailey; Litts, Katie M.; Zhang, Yuhua; Messinger, Jeffrey D.; Curcio, Christine A.

2014-01-01

Purpose To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration (AMD) in patients and in post-mortem specimens, with particular attention to the basis of the hyper-reflective border of ORT. Method A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced AMD were compared to high-resolution histological sections through the fovea and superior perifovea of donor eyes (13 atrophic AMD and 40 neovascular AMD) preserved ≤4 hours after death. Results ORT seen on OCT corresponded to histologic findings of tubular structures comprised largely of cones lacking outer segments (OS) and lacking inner segments (IS). Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end-stage (IS and OS; IS only; no IS; no photoreceptors and only Müller cells forming external limiting membrane, ELM, respectively). Mitochondria, which are normally long and bundled within IS ellipsoids, were small and scattered within shrunken IS and cell bodies of surviving cones. A lumenal border was delimited by an ELM. ORT observed in closed and open configurations were distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyper-reflective lumenal material seen on OCT represents trapped retinal pigment epithelium (RPE) and non-RPE cells. Conclusions The defining OCT features of ORT are location in the outer nuclear layer (ONL), a hyper-reflective band differentiating it from cysts, and RPE that is either dysmorphic or absent. ORT histologic and OCT findings corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an OS or an IS/OS junction, indicating an

Telemedicine screening for cytomegalovirus retinitis at the point of care for human immunodeficiency virus infection.

PubMed

Jirawison, Choeng; Yen, Michael; Leenasirimakul, Prattana; Chen, Jenny; Guadanant, Siripim; Kunavisarut, Paradee; Patikulsila, Direk; Watanachai, Nawat; Ausayakhun, Somsanguan; Heiden, David; Holland, Gary N; Margolis, Todd P; Keenan, Jeremy D

2015-02-01

Cytomegalovirus (CMV) retinitis is a leading cause of blindness in many developing countries, likely the result of inadequate screening. Telemedicine screening for CMV retinitis instituted at the point of care for human immunodeficiency virus (HIV) infection may allow for earlier detection. To determine the diagnostic accuracy of retinal photography in detecting CMV retinitis at the point of HIV care and to characterize the clinical manifestations of CMV retinitis detected through the screening program. We enrolled 103 participants from a population of 258 patients with HIV and a CD4 level of less than 100/μL treated at an HIV clinic in Thailand from June 2010 through June 2012. We captured mosaic fundus photographs through a dilated pupil using a digital fundus camera. An experienced on-site ophthalmologist masked to the results of the fundus images subsequently examined each eye with indirect ophthalmoscopy and recorded the clinical findings on a standardized form. Three remote graders evaluated each image for CMV retinitis. Fundus photography and indirect ophthalmoscopy. Sensitivity and specificity of telemedicine relative to indirect ophthalmoscopy for diagnosis of CMV retinitis and clinical features of CMV retinitis lesions. Sixteen patients (15.5%) were diagnosed as having CMV retinitis, of whom 5 (31%) had bilateral disease. Of the 21 eyes (10.2%) with CMV retinitis, 7 (33%) had visual symptoms. Retinitis lesions occupied less than 10% of the total retinal surface area in 13 of 21 eyes (62%) and did not involve the posterior pole (ie, zone 1) in 15 of 21 eyes (71%). Mean logMAR visual acuity in affected eyes was 0.41 (95% CI, 0.11-0.71; Snellen equivalent, 20/50 [95% CI, 20/25-20/100]). The mean sensitivity for the 3 remote graders in detecting CMV retinitis on fundus photography was 30.2% (95% CI, 10.5%-52.4%), and mean specificity was 99.1% (95% CI, 97.8%-100.0%). The CMV retinitis lesions missed by the remote graders (false-negative findings) were more

Metabolic physiology in age related macular degeneration.

PubMed

Stefánsson, Einar; Geirsdóttir, Asbjörg; Sigurdsson, Haraldur

2011-01-01

Ischemia and hypoxia have been implicated in the pathophysiology of age related macular degeneration (AMD). This has mostly been based on studies on choroidal perfusion, which is not the only contributor to retinal hypoxia found in AMD eyes. Other features of AMD may also interfere with retinal oxygen metabolism including confluent drusen, serous or hemorrhagic retinal detachment, retinal edema and vitreoretinal adhesion. Each of these features contributes to retinal hypoxia: the drusen and retinal elevation by increasing the distance between the choriocapillaris and retina; vitreoretinal adhesion by reducing diffusion and convection of oxygen towards and vascular endothelial growth factor (VEGF) away from hypoxic retinal areas. Hypoxia-inducible-factor is known to exist in subretinal neovascularization and hypoxia is the main stimulus for the production of VEGF. Each feature may not by itself create enough hypoxia and VEGF accumulation to stimulate wet AMD, but they may combine to do so. Choroidal ischemia in AMD has been demonstrated by many researchers, using different technologies. Choroidal ischemia obviously decreases oxygen delivery to the outer retina. Confluent drusen, thickening of Bruch's membrane and any detachment of retina or retinal pigment epithelium, increases the distance between the choriocapillaris and the retina and thereby reduces the oxygen flux from the choroid to the outer retina according to Fick's law of diffusion. Retinal elevation and choroidal ischemia may combine forces to reduce choroidal oxygen delivery to the outer retina, produce retinal hypoxia. Hypoxia leads to production of VEGF leading to neovascularization and tissue edema. A vicious cycle may develop, where VEGF production increases effusion, retinal detachment and edema, further increasing hypoxia and VEGF production. Adhesion of the viscous posterior vitreous cortex to the retina maintains a barrier to diffusion and convection currents in the vitreous cavity according to

Laser-induced retinal damage thresholds for annular retinal beam profiles

NASA Astrophysics Data System (ADS)

Kennedy, Paul K.; Zuclich, Joseph A.; Lund, David J.; Edsall, Peter R.; Till, Stephen; Stuck, Bruce E.; Hollins, Richard C.

2004-07-01

The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.

Measurement of retinal wall-to-lumen ratio by adaptive optics retinal camera: a clinical research.

PubMed

Meixner, Eva; Michelson, Georg

2015-11-01

To measure the wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera. Forty-seven human subjects were examined and their medical history was explored. WLR and WCSA were measured on the basis of retinal arteriolar wall thickness (VW), lumen diameter (LD) and vessel diameter (VD) assessed by rtx1 Adaptive Optics retinal camera. WLR was calculated by the formula [Formula: see text]. Arterio-venous ratio (AVR) and microvascular abnormalities were attained by quantitative and qualitative assessment of fundus photographs. Influence of age, arterial hypertension, body mass index (BMI) and retinal microvascular abnormalities on the WLR was examined. An age-adjusted WLR was created to test influences on WLR independently of age. Considering WLR and WCSA, a distinction between eutrophic and hypertrophic retinal remodeling processes was possible. The intra-observer variability (IOV) was 6 % ± 0.9 for arteriolar wall thickness and 2 % ± 0.2 for arteriolar wall thickness plus vessel lumen. WLR depended significantly on the wall thickness (r = 0.715; p < 0.01) of retinal arterioles, but was independent of the total vessel diameter (r = 0.052; p = 0.728). WLR correlated significantly with age (r = 0.769; p < 0.01). Arterial hypertension and a higher BMI were significantly associated with an increased age-adjusted WLR. WLR correlated significantly with the stage of microvascular abnormalities. 55 % of the hypertensive subjects and 11 % of the normotensive subjects showed eutrophic remodeling, while hypertrophic remodeling was not detectable. WLR correlated inversely with AVR. AVR was independent of the arteriolar wall thickness, age and arterial hypertension. The technique of AO retinal imaging allows a direct measurement of the retinal vessel wall and lumen diameter with good intra-observer variability. Age, arterial hypertension and an elevated BMI level

Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD).

PubMed

Amoroso, Francesca; Miere, Alexandra; Semoun, Oudy; Jung, Camille; Capuano, Vittorio; Souied, Eric H

2018-06-01

To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Prospective non-interventional study. Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm 2 for the first measurement and 0.75+/-0.76 mm 2 for the second measurement; difference between the first and the second measurement was 0.03 mm 2 . Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both 'vessel area' and 'select area' features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for 'select area' and 'vessel area' features. Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD. © 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.

Type 3 Neovascularization Associated with Retinitis Pigmentosa.

PubMed

Sayadi, Jihene; Miere, Alexandra; Souied, Eric H; Cohen, Salomon Y

2017-01-01

To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP) complicated by macular edema. A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Type 3 neovascularization may be considered a possible complication of RP.

Age, ocular magnification, and circumpapillary retinal nerve fiber layer thickness

NASA Astrophysics Data System (ADS)

Wang, Mengyu; Elze, Tobias; Li, Dian; Baniasadi, Neda; Wirkner, Kerstin; Kirsten, Toralf; Thiery, Joachim; Loeffler, Markus; Engel, Christoph; Rauscher, Franziska G.

2017-12-01

Optical coherence tomography (OCT) manufacturers graphically present circumpapillary retinal nerve fiber layer thickness (cpRNFLT) together with normative limits to support clinicians in diagnosing ophthalmic diseases. The impact of age on cpRNFLT is typically implemented by linear models. cpRNFLT is strongly location-specific, whereas previously published norms are typically restricted to coarse sectors and based on small populations. Furthermore, OCT devices neglect impacts of lens or eye size on the diameter of the cpRNFLT scan circle so that the diameter substantially varies over different eyes. We investigate the impact of age and scan diameter reported by Spectralis spectral-domain OCT on cpRNFLT in 5646 subjects with healthy eyes. We provide cpRNFLT by age and diameter at 768 angular locations. Age/diameter were significantly related to cpRNFLT on 89%/92% of the circle, respectively (pointwise linear regression), and to shifts in cpRNFLT peak locations. For subjects from age 42.1 onward but not below, increasing age significantly decreased scan diameter (r=-0.28, p<0.001), which suggests that pathological cpRNFLT thinning over time may be underestimated in elderly compared to younger subjects, as scan diameter decrease correlated with cpRNFLT increase. Our detailed numerical results may help to generate various correction models to improve diagnosing and monitoring optic neuropathies.

Macular pigment optical density is related to serum lutein in retinitis pigmentosa

USDA-ARS?s Scientific Manuscript database

Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

Management of giant retinal tear and retinal detachment in a patient with active toxoplasmosis retinochoroiditis.

PubMed

Scott, Nathan L; Sridhar, Jayanth; Flynn, Harry W

2018-06-01

To describe the management of a giant retinal tear with retinal detachment in a patient with active toxoplasmosis retinochoroiditis. While receiving systemic medications for toxoplasmosis, the patient underwent scleral buckling, pars plana vitrectomy, and C3F8 gas tamponade without removal of the lens. At last follow-up, best corrected visual acuity was 20/20 with an attached retina and the toxoplasmosis lesion was inactive. and Importance: Using modern surgical techniques, anatomic and clinical success is possible during active retinochoroiditis.

Effect of ranibizumab on high-speed indocyanine green angiography and minimum intensity projection optical coherence tomography findings in neovascular age-related macular degeneration.

PubMed

Nicholson, Benjamin P; Nigam, Divya; Toy, Brian; Stetson, Paul F; Agrón, Elvira; Jacobs-El, Naima; Cunningham, Denise; Cukras, Catherine; Wong, Wai; Wiley, Henry; Chew, Emily; Ferris, Frederick; Meyerle, Catherine B

2015-01-01

The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

So-called massive retinal gliosis: A critical review and reappraisal.

PubMed

Jakobiec, Frederick A; Thanos, Aristomenis; Stagner, Anna M; Grossniklaus, Hans E; Proia, Alan D

2016-01-01

Massive retinal gliosis, a nonneoplastic retinal glial proliferation, was first described in detail over 25 years ago, before the era of immunohistochemistry, in a series of 38 cases-to which can be added 30 case reports or small series (no more than 3 cases) subsequently. We analyze a new series of 3 nontumoral intraretinal glioses and 15 cases of tumoral retinal gliosis, not all of which, strictly speaking, were massive. The data from this series are compared with the findings in previously published cases. Included are 2 cases of massive retinal gliosis diagnosed from evisceration specimens. In reviewing all published and current cases, we were able to establish 3 subgroups of retinal tumoral glioses rather than a single "massive" category: focal nodular gliosis, submassive gliosis, and massive gliosis. Among 43 reported cases, including the present series, but excluding the previous large series of 38 cases in which substantial clinical data were omitted, there were 19 men and 24 women. Their mean and median ages were 36.2 years and 36 years, respectively, with a range of 2 to 79 years. All lesions were composed of mitotically quiet, compact spindled fibrous astrocytes devoid of an Alcian blue-positive myxoid matrix. The most common associated ocular conditions were phthisis bulbi and congenital diseases or malformations. Histopathologically, all 3 tumoral categories were accompanied by progressively more extensive fibrous and osseous metaplasia of the pigment epithelium, the latter forming a clinically and diagnostically useful, almost continuous, outer rim of eggshell calcification in the submassive and massive categories that should be detectable with appropriate imaging studies. In decreasing order of frequency, microcysts and macrocysts, vascular sclerosis, exudates, calcospherites, and Rosenthal fibers were observed among the proliferating fibrous astrocytes. Immunohistochemistry was positive for glial fibrillary acidic protein in all cases and nestin in

Estrogen signalling in the pathogenesis of age-related macular degeneration.

PubMed

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Relationship between arsenic skin lesions and the age of natural menopause.

PubMed

Yunus, Fakir Md; Rahman, Musarrat Jabeen; Alam, Md Zahidul; Hore, Samar Kumar; Rahman, Mahfuzar

2014-05-02

Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases

PubMed Central

2016-01-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway. PMID:27818722

Association of Age Related Macular Degeneration and Age Related Hearing Impairment

PubMed Central

Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

2016-01-01

Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

Characteristics of dynamic processing in the visual field of patients with age-related maculopathy

PubMed Central

Eisenbarth, Werner; MacKeben, Manfred; Poggel, Dorothe A.

2007-01-01

Purpose To investigate the characteristics of dynamic processing in the visual field of patients with age-related maculopathy (ARM) by measuring motion sensitivity, double-pulse resolution (DPR), and critical flicker fusion. Methods Fourteen subjects with ARM (18 eyes), 14 age-matched controls (19 eyes), and 7 young controls (8 eyes) served as subjects. Motion contrast thresholds were determined by a four-alternative forced-choice (4 afc) staircase procedure with a modification by Kernbach for presenting a plaid (size = 3.8°) moving within a stationary spatial and temporal Gaussian envelope in one of four directions. Measurements were performed on the horizontal meridian at 10°, 20°, 30°, 40°, and 60° eccentricity. DPR was defined as the minimal temporal gap detectable by the subject using a 9-fold interleaved adaptive procedure, with stimuli positioned on concentric rings at 5°, 10°, and 20° eccentricity on the principal and oblique meridians. Critical flicker fusion thresholds (CFF) and the Lanthony D-15 color vision test were applied foveally, and the subjects were free to use their fovea or whatever retinal area they needed to use instead, due to their retinal lesions caused by ARM. All measurements were performed under photopic conditions. Results Motion contrast sensitivity in subjects with ARM was pronouncedly reduced (0.23–0.66 log units, p < 0.01), not only in the macula but in a region up to 20° eccentricity. In the two control groups, motion contrast sensitivity systematically declined with retinal eccentricity (0.009–0.032 log units/degree) and with age (0.01 log units/year). Double-pulse thresholds in healthy subjects were approximately constant in the central visual field and increased outside a radius of 10° (1.73 ms/degree). DPR thresholds were elevated in subjects with ARM (by 23–32 ms, p < 0.01) up to 20° eccentricity, and their foveal CFFs were increased by 5.5 Hz or 14% (p < 0.01) as compared with age

Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation Surgery: Clinical OCT and Experimental Study

PubMed Central

Soleimani, A.; Rasta, S.H.; Banaei, T.; Asgharsharghi Bonab, A.

2017-01-01

Introduction: The aim of the present study was to determine burn intensity in retinal laser photocoagulation based on laser parameters; wavelength, power, beam size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera, physical eye model and computer simulation in a clinical study. Materials and Methods: Participants were 10 adult patients between 50-80 years with proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm green and 672 nm red for retina photocoagulation in diabetic retinopathy was used to investigate the participants. Lesion size was measured for spot sizes 50 and 100 μm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by OCT. Artificial eye and Zemax-optical design software were used with the same laser parameters. Results: Appearance of OCT and fundus images showed direct relationship between retina burn size and lesion intensity with exposure time and power and also reverse relationship with laser spot size. Compared to red wavelength, burn size and lesion intensity increased in green wavelength. On the other hand, results from physical eye model were the same as clinical examination shown. Laser spot size in retina with Zemax simulation demonstrated that red wavelength was greater than green one. Conclusion: This study showed shorter pulses provide decrease in duration of laser surgery with significantly reduced pain. Results and calculations described in this article can help clinicians adjusting the required total coagulated area, the number of lesions and pattern density. PMID:29445713

Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation Surgery: Clinical OCT and Experimental Study.

PubMed

Soleimani, A; Rasta, S H; Banaei, T; Asgharsharghi Bonab, A

2017-12-01

The aim of the present study was to determine burn intensity in retinal laser photocoagulation based on laser parameters; wavelength, power, beam size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera, physical eye model and computer simulation in a clinical study. Participants were 10 adult patients between 50-80 years with proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm green and 672 nm red for retina photocoagulation in diabetic retinopathy was used to investigate the participants. Lesion size was measured for spot sizes 50 and 100 μm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by OCT. Artificial eye and Zemax-optical design software were used with the same laser parameters. Appearance of OCT and fundus images showed direct relationship between retina burn size and lesion intensity with exposure time and power and also reverse relationship with laser spot size. Compared to red wavelength, burn size and lesion intensity increased in green wavelength. On the other hand, results from physical eye model were the same as clinical examination shown. Laser spot size in retina with Zemax simulation demonstrated that red wavelength was greater than green one. This study showed shorter pulses provide decrease in duration of laser surgery with significantly reduced pain. Results and calculations described in this article can help clinicians adjusting the required total coagulated area, the number of lesions and pattern density.

N-Terminal Pro-B-Type Natriuretic Peptide Is Related to Retinal Microvascular Damage: The Rotterdam Study.

PubMed

Mutlu, Unal; Ikram, M Arfan; Hofman, Albert; de Jong, Paulus T V M; Klaver, Caroline C W; Ikram, M Kamran

2016-08-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage. From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio [95% confidence interval] per SD increase in natural log-transformed NT-proBNP: 1.14 [1.03-1.27]). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP: -0.89 µm [-1.54 to -0.24]). This association remained unchanged after excluding participants with retinopathy signs. In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease. © 2016 American Heart Association, Inc.

Relationship between arsenic skin lesions and the age of natural menopause

PubMed Central

2014-01-01

Background Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women’s reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. Methods We compared menopausal age in two groups of women – with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies— participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Results Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups’ age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. Conclusions The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure. PMID:24886424

Regulatory and Economic Considerations of Retinal Drugs.

PubMed

Shah, Ankoor R; Williams, George A

2016-01-01

The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs. © 2016 S. Karger AG, Basel.

Genetic factors of age-related macular degeneration

PubMed Central

Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

2007-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies. PMID:15094132

Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration

PubMed Central

Haeri, Mohammad; Knox, Barry E

2012-01-01

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) and their aggregation impair normal cellular function and can be toxic, leading to cell death. Prolonged expression of misfolded proteins triggers ER stress, which initiates a cascade of reactions called the unfolded protein response (UPR). Protein misfolding is the basis for a variety of disorders known as ER storage or conformational diseases. There are an increasing number of eye disorders associated with misfolded proteins and pathologic ER responses, including retinitis pigmentosa (RP). Herein we review the basic cellular and molecular biology of UPR with focus on pathways that could be potential targets for treating retinal degenerative diseases. PMID:22737387

The application of optical coherence tomography angiography in retinal diseases.

PubMed

Sambhav, Kumar; Grover, Sandeep; Chalam, Kakarla V

Optical coherence tomography angiography (OCTA) is a new, noninvasive imaging technique that generates real-time volumetric data on chorioretinal vasculature and its flow pattern. With the advent of high-speed optical coherence tomography, established enface chorioretinal segmentation, and efficient algorithms, OCTA generates images that resemble an angiogram. The principle of OCTA involves determining the change in backscattering between consecutive B-scans and then attributing the differences to the flow of erythrocytes through retinal blood vessels. OCTA has shown promise in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions. It quantifies vascular compromise reflecting the severity of diabetic retinopathy. OCTA detects the presence of choroidal neovascularization in exudative age-related macular degeneration and maps loss of choriocapillaris in nonexudative age-related macular degeneration. We describe principles of OCTA and findings in common and some uncommon retinal pathologies. Finally, we summarize its potential future applications. Its current limitations include a relatively small field of view, inability to show leakage, and a tendency for image artifacts. Further larger studies will define OCTAs utility in clinical settings and establish if the technology may offer its utility in decreasing morbidity through early detection and guide therapeutic interventions in retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Pathogenesis of rhegmatogenous retinal detachment: predisposing anatomy and cell biology.

PubMed

Mitry, Danny; Fleck, Brian W; Wright, Alan F; Campbell, Harry; Charteris, David G

2010-01-01

The pathogenesis of rhegmatogenous retinal detachment is complex, and our knowledge of the exact mechanism of vitreoretinal attachment and detachment remains incomplete. We performed a Medline, Ovid, and EMBASE search using search words rhegmatogenous, retinal detachment, vitreous, and retinal adhesion. All appropriate articles were reviewed, and the evidence was compiled. Cortical vitreous contains fibrillar collagens type II, V/XI, and IX. The inner limiting membrane of the retina contains collagens type I, IV, VI, and XVIII as well as numerous other glycoproteins and potential adhesion molecules. The distribution and age-related changes in the structure of these molecules play an important role in the formation of a retinal break, which may compromise and disrupt the normal mechanisms of neurosensory retinal adhesion. Rhegmatogenous retinal detachment development is intimately related to changes in the fibrillar structure of the aging vitreous culminating in posterior vitreous detachment with regions of persistent and tangential vitreoretinal traction predisposing to retinal tear formation. A complex interplay of factors such as weakening of vitreoretinal adhesion, posterior migration of the vitreous base, and molecular changes at the vitreoretinal interface are important in predisposing to focal areas of vitreoretinal traction precipitating rhegmatogenous retinal detachment. Once formed, the passage of liquefied vitreous through a retinal break may overwhelm normal neurosensory-retinal pigment epithelium adhesion perpetuating and extending detachment and causing visual loss. To understand the molecular events underlying rhegmatogenous retinal detachment so that new therapies can be developed, it is important to appreciate the structural organization of the vitreous, the biology underlying vitreous liquefaction and posterior vitreous detachment, and the mechanisms of vitreoretinal attachment and detachment.

Iron homeostasis and toxicity in retinal degeneration.

PubMed

He, Xining; Hahn, Paul; Iacovelli, Jared; Wong, Robert; King, Chih; Bhisitkul, Robert; Massaro-Giordano, Mina; Dunaief, Joshua L

2007-11-01

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including

Iron homeostasis and toxicity in retinal degeneration

PubMed Central

He, Xining; Hahn, Paul; Iacovelli, Jared; Wong, Robert; King, Chih; Bhisitkul, Robert; Massaro-Giordano, Mina; Dunaief, Joshua L.

2007-01-01

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels build up with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich’s Ataxia, and panthothenate kinase associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age- matched controls. Over the past ten years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter 1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including

Patients with diffuse uveitis and inactive toxoplasmic retinitis lesions test PCR positive for Toxoplasma gondii in their vitreous and blood.

PubMed

Novais, Eduardo A; Commodaro, Alessandra G; Santos, Fábio; Muccioli, Cristina; Maia, André; Nascimento, Heloisa; Moeller, Cecilia T A; Rizzo, Luiz V; Grigg, Michael E; Belfort, Rubens

2014-07-01

To determine if patients with inactive chorioretinitis lesions who experience chronic toxoplasmic uveitis test PCR positive for Toxoplasma in their ocular fluids. Two patients undergoing long-term anti-toxoplasmic treatment developed chronic uveitis and vitritis. They underwent therapeutic and diagnostic pars plana vitrectomy. Patient specimens were tested for toxoplasmosis by real-time PCR and nested PCR. Patient specimens were also tested for the presence of Toxoplasma antibodies that recognise allelic peptide motifs to determine parasite serotype. Patients tested positive for Toxoplasma by real-time PCR at the B1 gene in the vitreous and aqueous humours of patient 1, but only the vitreous of patient 2. Patients were not parasitemic by real-time PCR in plasma and blood. During surgery, only old hyperpigmented toxoplasmic scars were observed; there was no sign of active retinitis. Multilocus PCR-DNA sequence genotyping at B1, NTS2 and SAG1 loci established that two different non-archetypal Toxoplasma strains had infected patients 1 and 2. A peptide-based serotyping ELISA confirmed the molecular findings. No active lesions were observed, but both patients possessed sufficient parasite DNA in their vitreous to permit genotyping. Several hypotheses to explain the persistence of the vitritis and anterior uveitis in the absence of active retinitis are discussed. 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.

Cerebellar Growth Impairment Characterizes School-Aged Children Born Preterm without Perinatal Brain Lesions.

PubMed

Pieterman, K; White, T J; van den Bosch, G E; Niessen, W J; Reiss, I K M; Tibboel, D; Hoebeek, F E; Dudink, J

2018-05-01

Infants born preterm are commonly diagnosed with structural brain lesions known to affect long-term neurodevelopment negatively. Yet, the effects of preterm birth on brain development in the absence of intracranial lesions remain to be studied in detail. In this study, we aim to quantify long term consequences of preterm birth on brain development in this specific group. Neonatal cranial sonography and follow-up T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic characteristics of the cerebrum and cerebellum in a cohort of school-aged children (6-12 years of age) were related to gestational age at birth in children free of brain lesions in the perinatal period. In the cohort consisting of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1-weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar white matter volume (β = 0.387, P < .001), altered fractional anisotropy of cerebellar white matter (β = -0.236, P = .02), and a reduction of cerebellar gray and white matter surface area (β = 0.337, P < .001; β = 0.375, P < .001, respectively) in relation to birth age. Such relations were not observed for the cerebral cortex or white matter volume, surface area, or diffusion quantities. The results of our study show that perinatal influences that are not primarily neurologic are still able to disturb long-term neurodevelopment, particularly of the developing cerebellum. Including the cerebellum in future neuroprotective strategies seems therefore essential. © 2018 by American Journal of Neuroradiology.

Protective effect of basic fibroblast growth factor on retinal injury induced by argon laser photocoagulation

NASA Astrophysics Data System (ADS)

Chen, P.; Zhang, C. P.; San, Q.; Wang, C. Z.; Yang, Z. F.; Kang, H. X.; Qian, H. W.

2010-12-01

Laser photocoagulation treatment is often complicated by a side effect of visual impairment, which is caused by the unavoidable laser-induced retinal destruction. At present no specific is found to cure this retinopathy. The aim of this study was to observe the neuroprotective effect of bFGF on laser-induced retinal injury. Chinchilla rabbits were divided into three groups and argon laser lesions were created in the retinas. Then bFGF or dexamethasone, a widely used ophthalmic preparation, or saline was given severally by retrobulbar injection. The retinal lesions were evaluated histologically and morphometrically, and visual function was examined by ERG. The results showed that bFGF administration better preserved morphology of retinal photoreceptors and significantly diminished the area of the lesions. Furthermore, bFGF promoted the restoration of the ERG b-wave amplitude. In rabbits treated with dexamethasone, however, the lesions showed almost no ameliorative changes. This is the first study to investigate the potential role of bFGF as a remedial agent in laser photocoagulation treatment. These findings suggest that bFGF has significant neuroprotective properties in the retina and this type of neuroprotection may be of clinical significance in reducing iatrogenic laser-induced retinal injuries in humans.

Coping strategies, vision-related quality of life, and emotional health in managing retinitis pigmentosa: a survey study.

PubMed

Anil, Krithika; Garip, Gulcan

2018-01-30

Retinitis pigmentosa is a group of genetic progressive retinal dystrophies that may adversely affect daily life. Those with RP should develop adaptive coping strategies to manage their condition. This study investigates the relationship between engaging (ECS) and disengaging coping strategies (DCS), vision-related quality of life (VRQoL), and emotional health, in adults living at home with retinitis pigmentosa. One hundred and five participants (70 female; mean age of 46.98, SD age  = 13.77) completed a cross-sectional survey. The questionnaire booklet consisted of the Coping Strategies Inventory - Short Form (32 items), the National Eye Institute Visual Functioning Questionnaire 25 (25 items), Marylands Trait Depression Scale (18 items), the Warwick-Edinburgh Mental Well-being Scale (14 items), and the Subjective Happiness Scale (4 items). Data was analysed with a two-block hierarchical multiple regression, with the first block controlling for the demographic data (age, sex, years since retinitis pigmentosa diagnosis, number of comorbidities, participant-perceived retinitis pigmentosa severity, and knowing RP type) and the second block consisting of primary measures (type of coping strategy, VRQoL, and Emotional Health). Type of coping strategy was found to impact psychosocial variables of VRQoL, not overall VRQoL. These psychosocial VRQoL variables had a positive association with ECS and a negative association with DCS. Emotional Health increased with ECS and decreased with DCS. There was a larger impact of DCS on VRQoL and Emotional Health compared to ECS, that is, VRQoL and Emotional Health decreased more with increasing DCS than VRQoL, and Emotional Health increased with increasing ECS. In concordance with previous research, ECS increased with increasing VRQoL and DCS decreased with increasing VRQoL. However, the findings also indicated that DCS had a greater impact than ECS on VRQoL and Emotional Health. This suggests that diminishing DCS should be

Retinal Spectral Domain Optical Coherence Tomography in Early Atrophic Age-Related Macular Degeneration (AMD) and a New Metric for Objective Evaluation of the Efficacy of Ocular Nutrition

PubMed Central

Richer, Stuart; Cho, Jane; Stiles, William; Levin, Marc; Wrobel, James S.; Sinai, Michael; Thomas, Carla

2012-01-01

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the

Stem cells in retinal regeneration: past, present and future.

PubMed

Ramsden, Conor M; Powner, Michael B; Carr, Amanda-Jayne F; Smart, Matthew J K; da Cruz, Lyndon; Coffey, Peter J

2013-06-01

Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

High-dose methylprednisolone treatment of laser-induced retinal injury exacerbates acute inflammation and long-term scarring

NASA Astrophysics Data System (ADS)

Schuschereba, Steven T.; Cross, Michael E.; Scales, David K.; Pizarro, Jose M.; Edsall, Peter R.; Stuck, Bruce E.; Marshall, John

1999-06-01

Purpose. To evaluate therapeutics for attenuating retinal laser injury. Methods. New Zealand Red rabbits (n=76) were pretreated (IV) with either a single dose of hydroxyethyl starch conjugated deferoxamine (HES-DFO, n=29) (6.1 ml/kg, 16.4 mg/ml) or methylprednisolone sodium succinate (MP, n=22) (30 mg/kg, followed by taper of 30, 20, 20, and 10 mg/kg/day for a total of 5d). Controls were untreated (n=25). Fifteen min later, animals were irradiated with a multiline cw argon laser (285 mW, 10 msec pulse durations, 16 lesions/eye). Funduscopy, fluorescein angiography, histology, and morphometry were performed at 10 min, 1h, 3h, 24h, 1 mo, and 6 mo after irradiation. Leukocytes were counted at lesion centers for retinal and choroidal compartments at 1, 3, and 24h. Results. At 3h, percent area incrase for the lesions was highest for MP (44%) and lowest for HES-DFO (16%)(p<0.05). In hemorrhagic lesions, MP treatment resulted in the highest increase of retinal neotrophils by 24h (p<0.05), and by 1 and 6 mo extensive chorio-retinal scarring occurred in nonhemorrhagic and hemorrhagic lesions. Also, no benefit was demonstrated on sparing of photoreceptors with MP treatment. Conclusions. Treatment of laser-induced retinal injury with methylprednisolone (MP) exacerbates acute inflammation and long-term chorio-retinal scarring; however, hydroxyethyl starch conjugated deferoxamine therapy ameliorates these aspects of injury. Data suggest caution in the use of MP therapy for laser injuries.

Automated detection of red lesions from digital colour fundus photographs.

PubMed

Jaafar, Hussain F; Nandi, Asoke K; Al-Nuaimy, Waleed

2011-01-01

Earliest signs of diabetic retinopathy, the major cause of vision loss, are damage to the blood vessels and the formation of lesions in the retina. Early detection of diabetic retinopathy is essential for the prevention of blindness. In this paper we present a computer-aided system to automatically identify red lesions from retinal fundus photographs. After pre-processing, a morphological technique was used to segment red lesion candidates from the background and other retinal structures. Then a rule-based classifier was used to discriminate actual red lesions from artifacts. A novel method for blood vessel detection is also proposed to refine the detection of red lesions. For a standarised test set of 219 images, the proposed method can detect red lesions with a sensitivity of 89.7% and a specificity of 98.6% (at lesion level). The performance of the proposed method shows considerable promise for detection of red lesions as well as other types of lesions.

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

PubMed

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

2013-11-26

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

Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with retinitis pigmentosa and usher syndrome.

PubMed

Genead, Mohamed A; Fishman, Gerald A

2010-09-01

To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with retinitis pigmentosa and Usher syndrome. In a retrospective case series at a university hospital, 64 eyes of 32 patients with retinitis pigmentosa or Usher syndrome receiving treatment with the topical dorzolamide formulation for 6 to 58 months were enrolled. Changes in visual acuity on the Early Treatment Diabetic Retinopathy Study chart and central foveal zone thickness on optical coherence tomography were measured during follow-up for the duration of treatment. Among the study cohort, 20 of 32 patients (63%) showed a positive response to treatment in at least 1 eye and 13 patients (41%) showed a positive response in both eyes. Four patients (20%) showed an initial response and a subsequent rebound of macular cysts. In 8 patients (25%), there was no response to treatment and the macular cysts worsened when compared with the pretreatment level. Ten patients (31%) had improvement in visual acuity by 7 or more letters in at least 1 eye at the most recent follow-up visit. Sixteen patients (67%) showed a reduction of more than 11% in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. Patients with either retinitis pigmentosa or Usher syndrome who received treatment of cystoid macular edema with topical dorzolamide followed by an optical coherence tomography-guided strategy showed a decrease in central foveal zone thickness in most cases. Visual acuity improved in almost one-third of the cases, suggesting a potential corresponding visual benefit.

Rickettsial retinitis: Direct bacterial infection or an immune-mediated response?

PubMed

Chawla, Rohan; Pundlik, Gadkar Amit; Chaudhry, Rama; Thakur, Chandan

2017-10-01

Infectious retinitis postfebrile illness is known to be caused by chikungunya, dengue, West Nile virus, Bartonella, Lyme's disease, Rift Valley fever, rickettsia, Herpes viruses etc. Rickettsia is Gram-negative bacteria transmitted by arthropods vectors. Ocular involvement is common including conjunctivitis, keratitis, anterior uveitis, panuveitis, retinitis, retinal vascular changes, and optic nerve involvement. Retinitis lesions in rickettsia can occur because of an immunological response to the bacteria or because of direct invasion and proliferation of bacteria in the inner retina. We report such a case of bilateral rickettsial retinitis proven by serology which worsened on systemic steroids and responded dramatically to therapy with oral doxycycline and steroid taper. We thus believe that direct bacterial invasion plays a major role in the pathogenesis of rickettsial retinitis.

Rickettsial retinitis: Direct bacterial infection or an immune-mediated response?

PubMed Central

Chawla, Rohan; Pundlik, Gadkar Amit; Chaudhry, Rama; Thakur, Chandan

2017-01-01

Infectious retinitis postfebrile illness is known to be caused by chikungunya, dengue, West Nile virus, Bartonella, Lyme's disease, Rift Valley fever, rickettsia, Herpes viruses etc. Rickettsia is Gram-negative bacteria transmitted by arthropods vectors. Ocular involvement is common including conjunctivitis, keratitis, anterior uveitis, panuveitis, retinitis, retinal vascular changes, and optic nerve involvement. Retinitis lesions in rickettsia can occur because of an immunological response to the bacteria or because of direct invasion and proliferation of bacteria in the inner retina. We report such a case of bilateral rickettsial retinitis proven by serology which worsened on systemic steroids and responded dramatically to therapy with oral doxycycline and steroid taper. We thus believe that direct bacterial invasion plays a major role in the pathogenesis of rickettsial retinitis. PMID:29044082

Retinoids and Retinal Diseases

PubMed Central

Kiser, Philip D.; Palczewski, Krzysztof

2016-01-01

Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions. PMID:27917399

Characteristics of exudative age-related macular degeneration determined in vivo with confocal and indirect infrared imaging.

PubMed

Hartnett, M E; Elsner, A E

1996-01-01

To evaluate the current and future interventions in age-related macular degeneration (AMD), it is essential to delineate the early clinical features associated with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch membrane region in ten patients with advance exudative AMD using current angiographic techniques and a noninvasive method: infrared (IR) imaging with the scanning laser ophthalmoscope. Ten patients with exudative AMD, evidence by choroidal neovascularization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous subretinal fluid,were examined using IR imaging, fluorescein angiography, indocyanine green angiography, and stereoscopic viewing of fundus slides. The authors determined the number and size of drusen and subretinal deposits and the topographic character of the RPE/Bruch membrane area and of CNV. In all patients, IR imaging yielded the greatest number of drusen and subretinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen, were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal neovascularization appeared as a complex with a dark central core, an enveloping reflective structure which created a halo-like appearance in the plane of focus, and outer retinal/subretinal striae. Infrared imaging provides a noninvasive, in vivo method to image early changes in the RPE/Bruch membrane. It offers advantages over current imaging techniques by minimizing light scatter through cloudy media and enhancing the ability to image through small pupils, retinal hyperpigmentation, blood, heavy exudation, or subretinal fluid. It provides additional information regarding early CNV, and the character of drusen and subretinal deposits.

Neuroprotective Treatment of Laser-Induced Retinal Injuries

DTIC Science & Technology

2001-10-01

to evaluate the neuroprotective effect of dextromethorphan, memantine and brimonidine in our rat model of laser- induced retinal-lesions Methods: Argon...dextromethorphan, memantine or brimonidine. The control groups (18 rats for each compound) received the solvent at the same volume and schedule as...size and the magnitude of photoreceptor nuclei loss within the lesions. Conclusions: Systemic treatments with dextromethorphan, memantine or brimonidine

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

PubMed

Meshi, Amit; Lin, Tiezhu; Dans, Kunny; Chen, Kevin C; Amador, Manuel; Hasenstab, Kyle; Muftuoglu, Ilkay Kilic; Nudleman, Eric; Chao, Daniel; Bartsch, Dirk-Uwe; Freeman, William R

2018-03-16

To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

PubMed

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics.

PubMed

Rosenbaum, David; Mattina, Alessandro; Koch, Edouard; Rossant, Florence; Gallo, Antonio; Kachenoura, Nadjia; Paques, Michel; Redheuil, Alban; Girerd, Xavier

2016-06-01

In humans, adaptive optics camera enables precise large-scale noninvasive retinal microcirculation evaluation to assess ageing, blood pressure and antihypertensive treatments respective roles on retinal arterioles anatomy. We used adaptive optics camera rtx1 (Imagine-Eyes, Orsay, France) to measure wall thickness, internal diameter and to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. This assessment was repeated within a short period in two subgroups of hypertensive individuals without or with a drug-induced blood pressure drop. In 1000 individuals, mean wall thickness, lumen diameter and WLR were 23.2 ± 3.9, 78.0 ± 10.9 and 0.300 ± 0.054 μm, respectively. Blood pressure and age both independently increased WLR by thickening arterial wall. In opposite, hypertension narrowed lumen in younger as compared to older individuals (73.2 ± 9.0 vs. 81.7 ± 10.2 μm; P < 0.001), whereas age exerted no influence on lumen diameter. Short-term blood pressure drop (-29.3 ± 17.3/-14.4 ± 10.0 mmHg) induced a WLR decrease (-6.0 ± 8.0%) because of lumen dilatation (+4.4 ± 5.9%) without wall thickness changes. By contrast, no modifications were observed in individuals with stable blood pressure. In treated and controlled hypertensives under monotherapy WLR normalization was observed because of combined wall decrease and lumen dilatation independently of antihypertensive pharmacological classes. In multivariate analysis, hypertension drug regimen was not an independent predictor of any retinal anatomical indices. Retinal arteriolar remodeling comprised blood pressure and age-driven wall thickening as well as blood pressure-triggered lumen narrowing in younger individuals. Remodeling reversal observed in controlled hypertensives seems to include short-term functional and long-term structural changes.

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.

Iron, zinc, and copper in retinal physiology and disease.

PubMed

Ugarte, Marta; Osborne, Neville N; Brown, Laurence A; Bishop, Paul N

2013-01-01

The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of "free" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Outcomes and Predictive Factors After Cataract Surgery in Patients With Neovascular Age-related Macular Degeneration. The Fight Retinal Blindness! Project.

PubMed

Daien, Vincent; Nguyen, Vuong; Morlet, Nigel; Arnold, Jennifer J; Essex, Rohan W; Young, Stephanie; Hunyor, Alex; Gillies, Mark C; Barthelmes, Daniel

2018-06-01

To evaluate outcomes and predictive factors of visual acuity (VA) change after cataract surgery in patients being treated for neovascular age-related macular degeneration (nAMD). Retrospective, matched case-control study. We studied eyes undergoing cataract surgery that had been tracked since they first started treatment for nAMD. These eyes were compared with a cohort of unoperated phakic eyes being treated for nAMD (3 per case) matched for treatment duration before cataract surgery, baseline VA, age, and length of follow-up. We included 124 patients that had cataract surgery and 372 matched controls. The mean (95% confidence interval) VA gained was 10.6 letters (7.8, 13.2; P < .001) 12 months after surgery; 26.0% had gained ≥3 lines and 1.6% had lost ≥3 lines of VA. Visual acuity (mean [standard deviation]) 12 months after surgery was higher in eyes that had cataract extraction compared with controls (65.8 [17.1] vs 61.3 [20.8] letters, respectively, P = .018). The proportion of visits where the choroidal neovascular (CNV) lesion was graded active and the mean number of injections were similar before and after surgery (P = .506 and P = .316, respectively), whereas both decreased in the control group, suggesting that surgery modestly increased the level of activity of the CNV lesion. Mean [SD] VA prior to surgery was lower in eyes that gained ≥15 letters compared with eyes that gained 0-14 letters (40.2 [21.4] vs 62.1 [15.1], P < .001). Patients undergoing cataract surgery within the first 6 months of anti-VEGF therapy were more likely to lose rather than gain vision (20.8% lost vision vs 12.8% and 4.4% gaining ≥15 or 0-14 letters respectively, P = .023). Age, receiving an injection at least 2 weeks before surgery, and the CNV lesion type had no discernible association with VA outcomes. We found evidence of a modest effect of cataract surgery on CNV lesion activity in eyes being treated for nAMD. Despite this, visual outcomes were reassuringly

Intracellular Signalling in Retinal Ischemia

DTIC Science & Technology

1990-07-01

36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

NASA Astrophysics Data System (ADS)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

Clinical applications of fundus autofluorescence in retinal disease.

PubMed

Yung, Madeline; Klufas, Michael A; Sarraf, David

2016-01-01

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

RETINAL DISEASES IN A TERTIARY HOSPITAL IN SOUTHERN NIGERIA.

PubMed

Uhumwangho, O M; Itina, E I

2015-01-01

Retinal diseases are an important and common cause of ophthalmic consultation. To determine the pattern of retinal diseases in the ophthalmic department of a tertiary hospital in Southern Nigeria. A retrospective review of the case folders of patients with retinal pathologies seen between 2012 and 2013 was performed. Relevant demographic and clinical data was recorded. Analysis was performed for frequencies, proportions and percentages with the GraphPad Instat Software, Inc. version V2.05a program, San Diego, CA. There were 185 patients made of 94 (50.8%) males and 91 (49.2%) females with a peak age group of 61-70 years, (range 1-85 years) who made consultations for retinal diseases. Age related macular degeneration, 37(15.0%), and macula hole, 10(4.0%), were the common macula pathologies while retinal detachment, 11(4.5%), was the most common condition that required emergency vitreo-retinal surgical intervention. Diabetic retinopathy/maculopathy, 31(12.6%), hypertensive retinopathy 22(8.9%), and retinal vascular occlusion 12(4.8%), were the common retinal vascular diseases found. Bilateral visual impairment (low vision and blindness) from retinal diseases was present in 28(14.4%) persons. The common vitreo-retinal treatment options were use of intravitreal antivascular endothelial growth factors 32(13.0%), laser 16(6.5%), and vitreoretinal surgery in 22(8.9%) eyes. Retinal diseases remain an important cause of ophthalmic consultation and visual loss. Provision of facilities to manage these conditions will improve service delivery and quality of lives of affected patients.

Neuroprotective vaccination with copolymer-1 decreases laser-induced retinal damage

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Rosner, Mordechai

2003-06-01

The retinal damage induced by laser photocoagulation increases manifold by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1) in adjuvant was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions. The present study tested the neuroprotective ability of Cop-1 to reduce the spread of laser-induced retinal damage. Standard argon laser lesions were created in 72 DA pigmented rats divided into four groups: two Cop-1 treated groups (animals treated seven days before or immediately after the laser session) and two control groups treated respectively by saline or the effective but toxic neuroprotective compound MK-801. The histological and morphological evaluations of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss of the retinas of the pre-immunized animals. Cop-1 given after the laser injury did not prevent cell loss significantly, while the neuroprotective effect of MK-801 was observed only on the third day after the laser injury. The results show that pre-immunization with Cop-1 is neuroprotective in unmyelinated (gray matter) neural tissue such as the retina. This approach may be of clinical significance in ameliorating laser-induced retinal injuries in humans.

Adaptive Optics Technology for High-Resolution Retinal Imaging

PubMed Central

Lombardo, Marco; Serrao, Sebastiano; Devaney, Nicholas; Parravano, Mariacristina; Lombardo, Giuseppe

2013-01-01

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging. PMID:23271600

Retinal response of Macaca mulatta to picosecond laser pulses of varying energy and spot size.

PubMed

Roach, William P; Cain, Clarence P; Narayan, Drew G; Noojin, Gary D; Boppart, Stephen A; Birngruber, Reginald; Fujimoto, James G; Toth, Cynthia A

2004-01-01

We investigate the relationship between the laser beam at the retina (spot size) and the extent of retinal injury from single ultrashort laser pulses. From previous studies it is believed that the retinal effect of single 3-ps laser pulses should vary in extent and location, depending on the occurrence of laser-induced breakdown (LIB) at the site of laser delivery. Single 3-ps pulses of 580-nm laser energy are delivered over a range of spot sizes to the retina of Macaca mulatta. The retinal response is captured sequentially with optical coherence tomography (OCT). The in vivo OCT images and the extent of pathology on final microscopic sections of the laser site are compared. With delivery of a laser pulse with peak irradiance greater than that required for LIB, OCT and light micrographs demonstrate inner retinal injury with many intraretinal and/or vitreous hemorrhages. In contrast, broad outer retinal injury with minimal to no choriocapillaris effect is seen after delivery of laser pulses to a larger retinal area (60 to 300 microm diam) when peak irradiance is less than that required for LIB. The broader lesions extend into the inner retina when higher energy delivery produces intraretinal injury. Microscopic examination of stained fixed tissues provide better resolution of retinal morphology than OCT. OCT provides less resolution but could be guided over an in vivo, visible retinal lesion for repeated sampling over time during the evolution of the lesion formation. For 3-ps visible wavelength laser pulses, varying the spot size and laser energy directly affects the extent of retinal injury. This again is believed to be partly due to the onset of LIB, as seen in previous studies. Spot-size dependence should be considered when comparing studies of retinal effects or when pursuing a specific retinal effect from ultrashort laser pulses. Copyright 2004 Society of Photo-Optical Instrumentation Engineers.

Retinal oximetry in patients with ischaemic retinal diseases.

PubMed

Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

2017-03-01

The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO 2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO 2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO 2 was reduced, but raSatO 2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO 2 and might also be related to increased raSatO 2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO 2 but unrelated to raSatO 2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retinitis Pigmentosa Associated with Vasoproliferative Tumors and Coats-like Fundus

PubMed Central

Ghassemi, Fariba; Akbari-Kamrani, Marjan

2013-01-01

Purpose To report two cases of retinitis pigmentosa (RP) associated with vasoproliferative tumors (VPTs) and Coats-like fundus. Case Reports Two patients with RP presented with recent loss of vision due to combined VPTs and Coats-like retinal vascular alterations. One patient had two VPTs with adjacent capillary nonperfusion, telangiectasia and aneurysmal vascular changes in one eye. The other patient had prominent VPT with Coats-like retinal vascular alterations in both eyes. These lesions received treatment resulting in improved vision in both patients. Conclusion Although rare, VPTs and Coats-like retinal vascular alterations including retinal exudation associated with telangiectatic vessels, aneurysmal changes and capillary nonperfusion may occur in patients with RP. PMID:24349671

Introduction to the issue regarding research regarding age related macular degeneration

USDA-ARS?s Scientific Manuscript database

Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

Automated detection of retinal whitening in malarial retinopathy

NASA Astrophysics Data System (ADS)

Joshi, V.; Agurto, C.; Barriga, S.; Nemeth, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Lewallen, S.; Harding, S.

2016-03-01

Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.

Dynamics of retinal photocoagulation and rupture

NASA Astrophysics Data System (ADS)

Sramek, Christopher; Paulus, Yannis; Nomoto, Hiroyuki; Huie, Phil; Brown, Jefferson; Palanker, Daniel

2009-05-01

In laser retinal photocoagulation, short (<20 ms) pulses have been found to reduce thermal damage to the inner retina, decrease treatment time, and minimize pain. However, the safe therapeutic window (defined as the ratio of power for producing a rupture to that of mild coagulation) decreases with shorter exposures. To quantify the extent of retinal heating and maximize the therapeutic window, a computational model of millisecond retinal photocoagulation and rupture was developed. Optical attenuation of 532-nm laser light in ocular tissues was measured, including retinal pigment epithelial (RPE) pigmentation and cell-size variability. Threshold powers for vaporization and RPE damage were measured with pulse durations ranging from 1 to 200 ms. A finite element model of retinal heating inferred that vaporization (rupture) takes place at 180-190°C. RPE damage was accurately described by the Arrhenius model with activation energy of 340 kJ/mol. Computed photocoagulation lesion width increased logarithmically with pulse duration, in agreement with histological findings. The model will allow for the optimization of beam parameters to increase the width of the therapeutic window for short exposures.

Visual Space and Object Space in the Cerebral Cortex of Retinal Disease Patients

PubMed Central

Spileers, Werner; Wagemans, Johan; Op de Beeck, Hans P.

2014-01-01

The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings). This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration), and a patient where input to the peripheral retina is lost (retinitis pigmentosa). From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline) rather than relative activation (comparing different stimulus conditions). Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (de)activation is consistent with the retinal loss. PMID:24505449

Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy.

PubMed

Srinivasan, Sangeetha; Pritchard, Nicola; Vagenas, Dimitrios; Edwards, Katie; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2016-10-01

To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA 1c levels. In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA 1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04). DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.

Detection of retinal lesions in diabetic retinopathy: comparative evaluation of 7-field digital color photography versus red-free photography.

PubMed

Venkatesh, Pradeep; Sharma, Reetika; Vashist, Nagender; Vohra, Rajpal; Garg, Satpal

2015-10-01

Red-free light allows better detection of vascular lesions as this wavelength is absorbed by hemoglobin; however, the current gold standard for the detection and grading of diabetic retinopathy remains 7-field color fundus photography. The goal of this study was to compare the ability of 7-field fundus photography using red-free light to detect retinopathy lesions with corresponding images captured using standard 7-field color photography. Non-stereoscopic standard 7-field 30° digital color fundus photography and 7-field 30° digital red-free fundus photography were performed in 200 eyes of 103 patients with various grades of diabetic retinopathy ranging from mild to moderate non-proliferative diabetic retinopathy to proliferative diabetic retinopathy. The color images (n = 1,400) were studied with corresponding red-free images (n = 1,400) by one retina consultant (PV) and two senior residents training in retina. The various retinal lesions [microaneurysms, hemorrhages, hard exudates, soft exudates, intra-retinal microvascular anomalies (IRMA), neovascularization of the retina elsewhere (NVE), and neovascularization of the disc (NVD)] detected by all three observers in each of the photographs were noted followed by determination of agreement scores using κ values (range 0-1). Kappa coefficient was categorized as poor (≤0), slight (0.01-0.20), fair (0.2 -0.40), moderate (0.41-0.60), substantial (0.61-0.80), and almost perfect (0.81-1). The number of lesions detected by red-free images alone was higher for all observers and all abnormalities except hard exudates. Detection of IRMA was especially higher for all observers with red-free images. Between image pairs, there was substantial agreement for detection of hard exudates (average κ = 0.62, range 0.60-0.65) and moderate agreement for detection of hemorrhages (average κ = 0.52, range 0.45-0.58), soft exudates (average κ = 0.51, range 0.42-0.61), NVE (average κ = 0.47, range 0.39-0.53), and NVD

Implantable multilayer microstrip antenna for retinal prosthesis: antenna testing.

PubMed

Permana, Hans; Fang, Qiang; Rowe, Wayne S T

2012-01-01

Retinal prosthesis has come to a more mature stage and become a very strategic answer to Retinitis Pigmentosa (RP) and Age-related Macular Degeneration (AMD) diseases. In a retinal prosthesis system, wireless link holds a great importance for the continuity of the system. In this paper, an implantable multilayer microstrip antenna was proposed for the retinal prosthesis system. Simulations were performed in High Frequency Structure Simulator (HFSS) with the surrounding material of air and Vitreous Humor fluid. The fabricated antenna was measured for characteristic validation in free space. The results showed that the real antenna possessed similar return loss and radiation pattern, while there was discrepancy with the gain values.

HYPERSPECTRAL AUTOFLUORESCENCE IMAGING OF DRUSEN AND RETINAL PIGMENT EPITHELIUM IN DONOR EYES WITH AGE-RELATED MACULAR DEGENERATION.

PubMed

Tong, Yuehong; Ben Ami, Tal; Hong, Sungmin; Heintzmann, Rainer; Gerig, Guido; Ablonczy, Zsolt; Curcio, Christine A; Ach, Thomas; Smith, R Theodore

2016-12-01

To elucidate the molecular pathogenesis of age-related macular degeneration (AMD) and interpretation of fundus autofluorescence imaging, the authors identified spectral autofluorescence characteristics of drusen and retinal pigment epithelium (RPE) in donor eyes with AMD. Macular RPE/Bruch membrane flat mounts were prepared from 5 donor eyes with AMD. In 12 locations (1-3 per eye), hyperspectral autofluorescence images in 10-nm-wavelength steps were acquired at 2 excitation wavelengths (λex 436, 480 nm). A nonnegative tensor factorization algorithm was used to recover 5 abundant emission spectra and their corresponding spatial localizations. At λex 436 nm, the authors consistently localized a novel spectrum (SDr) with a peak emission near 510 nm in drusen and sub-RPE deposits. Abundant emission spectra seen previously (S0 in Bruch membrane and S1, S2, and S3 in RPE lipofuscin/melanolipofuscin, respectively) also appeared in AMD eyes, with the same shapes and peak wavelengths as in normal tissue. Lipofuscin/melanolipofuscin spectra localizations in AMD eyes varied widely in their overlap with drusen, ranging from none to complete. An emission spectrum peaking at ∼510 nm (λex 436 nm) appears to be sensitive and specific for drusen and sub-RPE deposits. One or more abundant spectra from RPE organelles exhibit characteristic relationships with drusen.

Detection of retinal changes from illumination normalized fundus images using convolutional neural networks

NASA Astrophysics Data System (ADS)

Adal, Kedir M.; van Etten, Peter G.; Martinez, Jose P.; Rouwen, Kenneth; Vermeer, Koenraad A.; van Vliet, Lucas J.

2017-03-01

Automated detection and quantification of spatio-temporal retinal changes is an important step to objectively assess disease progression and treatment effects for dynamic retinal diseases such as diabetic retinopathy (DR). However, detecting retinal changes caused by early DR lesions such as microaneurysms and dot hemorrhages from longitudinal pairs of fundus images is challenging due to intra and inter-image illumination variation between fundus images. This paper explores a method for automated detection of retinal changes from illumination normalized fundus images using a deep convolutional neural network (CNN), and compares its performance with two other CNNs trained separately on color and green channel fundus images. Illumination variation was addressed by correcting for the variability in the luminosity and contrast estimated from a large scale retinal regions. The CNN models were trained and evaluated on image patches extracted from a registered fundus image set collected from 51 diabetic eyes that were screened at two different time-points. The results show that using normalized images yield better performance than color and green channel images, suggesting that illumination normalization greatly facilitates CNNs to quickly and correctly learn distinctive local image features of DR related retinal changes.

Combined branch retinal vein and artery occlusion in toxoplasmosis.

PubMed

Aggio, Fabio Bom; Novelli, Fernando José de; Rosa, Evandro Luis; Nobrega, Mário Junqueira

2016-01-01

A 22-year-old man complained of low visual acuity and pain in his left eye for five days. His ophthalmological examination revealed 2+ anterior chamber reaction and a white, poorly defined retinal lesion at the proximal portion of the inferotemporal vascular arcade. There were retinal hemorrhages in the inferotemporal region extending to the retinal periphery. In addition, venous dilation, increased tortuosity, and ischemic retinal whitening along the inferotemporal vascular arcade were also observed. A proper systemic work-up was performed, and the patient was diagnosed with ocular toxoplasmosis. He was treated with an anti-toxoplasma medication, and his condition slowly improved. Inferior macular inner and middle retinal atrophy could be observed on optical coherence tomography as a sequela of ischemic injury. To our knowledge, this is the first report of combined retinal branch vein and artery occlusion in toxoplasmosis resulting in a striking and unusual macular appearance.

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area.

PubMed

Stanislovaitiene, Daiva; Zaliuniene, Dalia; Krisciukaitis, Algimantas; Petrolis, Robertas; Smalinskiene, Alina; Lesauskaite, Vita; Tamosiunas, Abdonas; Lesauskaite, Vaiva

2017-01-01

Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380-0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00-39.06) vs. 3.09 (0.02-19.30) and 0.27 (0.00-34.57) vs. 0.75 (0.00-39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49-39.06) mm 2 vs. 5.02 (0.03-37.06) mm 2 , p = 0.006). SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease-an area of macular lesion.

Recent developments in the management of dry age-related macular degeneration

PubMed Central

Buschini, Elisa; Fea, Antonio M; Lavia, Carlo A; Nassisi, Marco; Pignata, Giulia; Zola, Marta; Grignolo, Federico M

2015-01-01

Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy. PMID:25878491

Optical Coherence Tomography Angiography in Retinal Diseases.

PubMed

Chalam, K V; Sambhav, Kumar

2016-01-01

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases.

Optical Coherence Tomography Angiography in Retinal Diseases

PubMed Central

Chalam, K. V.; Sambhav, Kumar

2016-01-01

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

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

Comprehensive analysis of mouse retinal mononuclear phagocytes.

PubMed

Lückoff, Anika; Scholz, Rebecca; Sennlaub, Florian; Xu, Heping; Langmann, Thomas

2017-06-01

The innate immune system is activated in a number of degenerative and inflammatory retinal disorders such as age-related macular degeneration (AMD). Retinal microglia, choroidal macrophages, and recruited monocytes, collectively termed 'retinal mononuclear phagocytes', are critical determinants of ocular disease outcome. Many publications have described the presence of these cells in mouse models for retinal disease; however, only limited aspects of their behavior have been uncovered, and these have only been uncovered using a single detection method. The workflow presented here describes a comprehensive analysis strategy that allows characterization of retinal mononuclear phagocytes in vivo and in situ. We present standardized working steps for scanning laser ophthalmoscopy of microglia from MacGreen reporter mice (mice expressing the macrophage colony-stimulating factor receptor GFP transgene throughout the mononuclear phagocyte system), quantitative analysis of Iba1-stained retinal sections and flat mounts, CD11b-based retinal flow cytometry, and qRT-PCR analysis of key microglia markers. The protocol can be completed within 3 d, and we present data from retinas treated with laser-induced choroidal neovascularization (CNV), bright white-light exposure, and Fam161a-associated inherited retinal degeneration. The assays can be applied to any of the existing mouse models for retinal disorders and may be valuable for documenting immune responses in studies for immunomodulatory therapies.

Retinal damage from a Q-switched YAG laser.

PubMed

Jampol, L M; Goldberg, M F; Jednock, N

1983-09-01

A 42-year-old woman with sickle cell anemia and proliferative retinopathy underwent neodymium-YAG laser therapy for a taut posterior hyaloid membrane causing peripapillary and peripheral traction detachment of the retina. Vitrectomy was not done because the patient required anticoagulation. A Q-switched YAG laser was capable of cutting holes in the taut membrane, but treatment 2 to 3 mm from the retina resulted in microperforation of a retinal vein and focal areas of damage to the retinal pigment epithelium. The damage to the retinal pigment epithelium was not immediately apparent, and ophthalmoscopically visible lesions were seen only when the patient was reexamined 48 hours later.

Heat shock protein expression as guidance for the therapeutic window of retinal laser therapy

NASA Astrophysics Data System (ADS)

Wang, Jenny; Huie, Philip; Dalal, Roopa; Lee, Seungjun; Tan, Gavin; Lee, Daeyoung; Lavinksy, Daniel; Palanker, Daniel

2016-03-01

Unlike conventional photocoagulation, non-damaging retinal laser therapy (NRT) limits laser-induced heating to stay below the retinal damage threshold and therefore requires careful dosimetry. Without the adverse effects associated with photocoagulation, NRT can be applied to critical areas of the retina and repeatedly to manage chronic disorders. Although the clinical benefits of NRT have been demonstrated, the mechanism of therapeutic effect and width of the therapeutic window below damage threshold are not well understood. Here, we measure activation of heat shock response via laser-induced hyperthermia as one indication of cellular response. A 577 nm laser is used with the Endpoint Management (EpM) user interface, a titration algorithm, to set experimental pulse energies relative to a barely visible titration lesion. Live/dead staining and histology show that the retinal damage threshold in rabbits is at 40% of titration energy on EpM scale. Heat shock protein 70 (HSP70) expression in the retinal pigment epithelium (RPE) was detected by whole-mount immunohistochemistry after different levels of laser treatment. We show HSP70 expression in the RPE beginning at 25% of titration energy indicating that there is a window for NRT between 25% and 40% with activation of the heat shock protein expression in response to hyperthermia. HSP70 expression is also seen at the perimeter of damaging lesions, as expected based on a computational model of laser heating. Expression area for each pulse energy setting varied between laser spots due to pigmentation changes, indicating the relatively narrow window of non-damaging activation and highlighting the importance of proper titration.

LASER RESENSITIZATION OF MEDICALLY UNRESPONSIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Efficacy and Implications.

PubMed

Luttrull, Jeffrey K; Chang, David B; Margolis, Benjamin W L; Dorin, Giorgio; Luttrull, David K

2015-06-01

Drug tolerance is the most common cause of treatment failure in neovascular age-related macular degeneration. "Low-intensity/high-density" subthreshold diode micropulse laser (SDM) has been reported effective for a number of retinal disorders without adverse effects. It has been proposed that SDM normalizes retinal pigment epithelial function. On this basis, it has been postulated that SDM treatment might restore responsiveness to anti-vascular endothelial growth factor drugs in drug-tolerant eyes. Subthreshold diode micropulse laser treatment was performed in consecutive eyes unresponsive to all anti-vascular endothelial growth factor drugs, including at least three consecutive ineffective aflibercept injections. Monthly aflibercept was resumed 1 month after SDM treatment. Thirteen eyes of 12 patients, aged 73 to 97 years (average, 84 years), receiving 16 to 67 (average, 34) anti-vascular endothelial growth factor injections before SDM treatment were included and followed for 3 months to 7 months (average, 5 months) after SDM treatment. After SDM treatment and resumption of aflibercept, 92% (12 of 13) of eyes improved, with complete resolution of macular exudation in 69% (9 of 13). Visual acuity remained unchanged. Central and maximum macular thicknesses significantly improved. Subthreshold diode micropulse laser treatment restored drug response in drug-tolerant eyes with neovascular age-related macular degeneration. Based on these findings, a theory of SDM action is proposed, suggesting a wider role for SDM as retinal reparative/protective therapy.

Occlusive retinal vasculitis in a patient with West Nile virus.

PubMed

Teitelbaum, Bruce A; Newman, Tricia L; Tresley, David J

2007-11-01

West Nile virus (WNV) was first identified in the United States in 1999. In addition to a spectrum of systemic manifestations, several ocular conditions secondary to the virus have been reported, including chorioretinitis, uveitis and optic neuritis. Age and diabetes mellitus (DM) have been reported to be associated risk factors for the more severe forms of the systemic disease. Only seven cases of occlusive retinal vasculitis have been reported in patients with WNV infection. A 60-year-old Asian male presented with complaints of decreased vision in his left eye. He had been hospitalised approximately seven weeks earlier with meningo-encephalitis secondary to presumed WNV infection, at which time he was also diagnosed with DM. The visual loss coincided with the manifestation of systemic WNV infection. Old peripheral chorioretinal lesions without active inflammation in both eyes were consistent with WNV infection. In addition, retinal haemorrhage and cotton wool spots were noted in the posterior pole of both eyes with severe macular ischaemia in the left eye. Occlusive retinal vasculitis is an uncommon ocular manifestation of WNV, which should be suspected in patients with meningitis or encephalitis who reside in endemic areas with ocular findings of the disease.

Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons

PubMed Central

Banday, Abdul Rouf; Baumgartner, Marybeth; Al Seesi, Sahar; Karunakaran, Devi Krishna Priya; Venkatesh, Aditya; Congdon, Sean; Lemoine, Christopher; Kilcollins, Ashley M; Mandoiu, Ion; Punzo, Claudio; Kanadia, Rahul N

2014-01-01

In the mammalian genome, each histone family contains multiple replication-dependent paralogs, which are found in clusters where their transcription is thought to be coupled to the cell cycle. Here, we wanted to interrogate the transcriptional regulation of these paralogs during retinal development and aging. We employed deep sequencing, quantitative PCR, in situ hybridization (ISH), and microarray analysis, which revealed that replication-dependent histone genes were not only transcribed in progenitor cells but also in differentiating neurons. Specifically, by ISH analysis we found that different histone genes were actively transcribed in a subset of neurons between postnatal day 7 and 14. Interestingly, within a histone family, not all paralogs were transcribed at the same level during retinal development. For example, expression of Hist1h1b was higher embryonically, while that of Hist1h1c was higher postnatally. Finally, expression of replication-dependent histone genes was also observed in the aging retina. Moreover, transcription of replication-dependent histones was independent of rapamycin-mediated mTOR pathway inactivation. Overall, our data suggest the existence of variant nucleosomes produced by the differential expression of the replication-dependent histone genes across retinal development. Also, the expression of a subset of replication-dependent histone isotypes in senescent neurons warrants re-examining these genes as “replication-dependent.” Thus, our findings underscore the importance of understanding the transcriptional regulation of replication-dependent histone genes in the maintenance and functioning of neurons. PMID:25486194

Automatic Detection of Optic Disc in Retinal Image by Using Keypoint Detection, Texture Analysis, and Visual Dictionary Techniques

PubMed Central

Bayır, Şafak

2016-01-01

With the advances in the computer field, methods and techniques in automatic image processing and analysis provide the opportunity to detect automatically the change and degeneration in retinal images. Localization of the optic disc is extremely important for determining the hard exudate lesions or neovascularization, which is the later phase of diabetic retinopathy, in computer aided eye disease diagnosis systems. Whereas optic disc detection is fairly an easy process in normal retinal images, detecting this region in the retinal image which is diabetic retinopathy disease may be difficult. Sometimes information related to optic disc and hard exudate information may be the same in terms of machine learning. We presented a novel approach for efficient and accurate localization of optic disc in retinal images having noise and other lesions. This approach is comprised of five main steps which are image processing, keypoint extraction, texture analysis, visual dictionary, and classifier techniques. We tested our proposed technique on 3 public datasets and obtained quantitative results. Experimental results show that an average optic disc detection accuracy of 94.38%, 95.00%, and 90.00% is achieved, respectively, on the following public datasets: DIARETDB1, DRIVE, and ROC. PMID:27110272

Spectral domain optical coherence tomography in the evaluation and management of infectious retinitis.

PubMed

Kurup, Sudhi P; Khan, Samira; Gill, Manjot K

2014-11-01

To describe spectral domain optical coherence tomography (SD-OCT) findings of infectious retinitis, including affected layer of retinal involvement, changes at the vitreoretinal interface, and response to therapy. Observational case series. A retrospective review of five patients with infectious retinitis: one with toxoplasmosis, three with herpetic retinitis secondary to cytomegalovirus, and one with herpetic retinitis secondary to varicella zoster virus. Each patient underwent a complete ophthalmologic examination, fundus photography, and SD-OCT imaging (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany) of the affected retina at the initial visit with serial fundus photography and SD-OCT imaging at follow-up visits. Approval was obtained from the Institutional Review Board of Northwestern University. Spectral domain ocular coherence tomography of retinitis associated with Toxoplasma, cytomegalovirus, or varicella zoster virus demonstrates full-thickness disruption of the retinal architecture and overall thickening. This was in contrast to clinically imitating lesions such as cotton-wool spots, which only showed focal swelling of the inner retina. There was a clear demarcation between the area of active retinitis and unaffected retina. Inactivity was apparent when the previously affected thickened area became atrophic. The SD-OCT also demonstrated changes at the vitreoretinal interface where there was frequently a detachment of the posterior hyaloid (four of five cases) associated with overlying vitreous debris and formation of tractional changes. In the case of varicella zoster virus retinitis, this traction subsequently led to a total retinal detachment. In the assessment of infectious retinitides, SD-OCT is a helpful adjunct to clinical examination and fundus photography. It provides high-resolution detail regarding the border of infectious activity, the vitreoretinal interface, and the differentiation of lesions that can clinically mimic

[Change of therapy from ranibizumab to aflibercept for recurrent or persistent exudative age-related macular degeneration].

PubMed

Ziegler, M; Heimes, B; Book, B; Dietzel, M; Zeimer, M; Spital, G; Gutfleisch, M; Pauleikhoff, D; Lommatzsch, A

2015-05-01

Even during consistent anti-vascular endothelial growth factor (VEGF) therapy a reactivation of exudative age-related macular degeneration (AMD) lesions can be observed in many patients. The present case series examined whether a switch from ranibizumab to aflibercept is safe and whether differences in potency can be observed. In 56 consecutive patients with recurrent activity of AMD according to the morphological criteria of the spectral domain optical coherence tomography (SD-OCT) examination, a change to aflibercept was made after 6-41 (mean 18.9, SD 6.3) injections with ranibizumab. In all controls and before each injection logMAR visual acuity was measured and a SD-OCT (volume scan) was performed in addition to the clinical examination. The mean visual acuity was stable under both therapies. The analysis of the morphological parameters showed a greater reduction of the retinal thickness after the change in therapy (mean retinal thickness within 1000 μm and central foveal thickness) compared to the initial treatment. The changes in the subretinal fluid as well as the height of an associated pigment epithelial detachment (PED) did not show any significant differences. The analysis of the morphological parameters at the level of the photoreceptors showed a decrease in discontinuity in the ellipsoid layer and also in the external limiting membrane (ELM). In patients with recurrent or high SD-OCT-based activity of exudative AMD lesions, a switch of the treatment strategy from ranibizumab to aflibercept can achieve a new functional stability in spite of multiple pretreatment. We found morphological indications of a regression of intraretinal edema and improvement in the photoreceptor area. In the context of a well-defined treatment strategy, a switch from anti-VEGF therapy to a similar active substance is safe. Before a definitive evaluation can be made, prospective controlled conditions are required to verify the clinical benefits of the switch.

Dark and white lesions observed in central serous chorioretinopathy on optical coherence tomography angiography.

PubMed

De Bats, Flore; Cornut, Pierre-Loïc; Wolff, Benjamin; Kodjikian, Laurent; Mauget-Faÿsse, Martine

2018-03-01

To describe abnormal dark (hyposignal) and white (hypersignal) lesions observed on optical coherence tomography angiography in central serous chorioretinopathy. Prospective, multicenter, and descriptive study including patients with active or quiescent central serous chorioretinopathy. All patients had undergone a complete ophthalmic examination. Abnormal dark lesions were detected as "dark spots" and "dark areas" on optical coherence tomography angiography. A "dark spot" could correspond to six different abnormalities: pigment epithelium detachment, subretinal deposit, "Lucency" within surrounding subretinal fibrin, choroidal cavitation, choroidal excavation, and choroidal fluid. A "dark area" could be related to a serous retinal detachment or choriocapillary compression. Abnormal white lesions were also detected: A "white spot" could correspond with the leaking point on fluorescein angiography or with hyper-reflective dots; A "white filamentous pattern" at the Brüch's membrane level corresponded to abnormal choroidal neovascular vessels. A semiology is described using optical coherence tomography angiography in central serous chorioretinopathy as abnormal dark and white lesions. Multimodal imaging is mandatory in addition to optical coherence tomography angiography to diagnose non-neovascular retinal and choroidal central serous chorioretinopathy lesions. However, optical coherence tomography angiography alone is helpful in detecting choroidal neovascular membrane in central serous chorioretinopathy.

Vessel Segmentation in Retinal Images Using Multi-scale Line Operator and K-Means Clustering.

PubMed

Saffarzadeh, Vahid Mohammadi; Osareh, Alireza; Shadgar, Bita

2014-04-01

Detecting blood vessels is a vital task in retinal image analysis. The task is more challenging with the presence of bright and dark lesions in retinal images. Here, a method is proposed to detect vessels in both normal and abnormal retinal fundus images based on their linear features. First, the negative impact of bright lesions is reduced by using K-means segmentation in a perceptive space. Then, a multi-scale line operator is utilized to detect vessels while ignoring some of the dark lesions, which have intensity structures different from the line-shaped vessels in the retina. The proposed algorithm is tested on two publicly available STARE and DRIVE databases. The performance of the method is measured by calculating the area under the receiver operating characteristic curve and the segmentation accuracy. The proposed method achieves 0.9483 and 0.9387 localization accuracy against STARE and DRIVE respectively.

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel Assessment Software Across the Human Age Range.

PubMed

Huang, Qi-Fang; Wei, Fang-Fei; Zhang, Zhen-Yu; Raaijmakers, Anke; Asayama, Kei; Thijs, Lutgarde; Yang, Wen-Yi; Mujaj, Blerim; Allegaert, Karel; Verhamme, Peter; Struijker-Boudier, Harry A J; Li, Yan; Staessen, Jan A

2018-03-10

Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measures of arteriolar and venular geometry. Few studies addressed the reproducibility of SIVA measurements across a wide age range. In the current study, 2 blinded graders read images obtained by nonmydriatic retinal photography twice in 20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60 adults (age range, 18.9-86.1 years). Former preterm compared with term children had lower microvessel diameter and disorganized vessel geometry with no differences in intraobserver and interobserver variability. Among adults, microvessel caliber decreased with age and blood pressure and arteriolar geometry was inversely correlated with female sex and age. Intraobserver differences estimated by the Bland-Altman method did not reach significance for any measurement. Across measurements, median reproducibility (RM) expressed as percent of the average trait value was 8.8% in children (median intraclass correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise, interobserver differences did not reach significance with RM (ICC) of 10.6% (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96), worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for arteriolar geometry (10.9%/14.9%; 0.95/0.86). SIVA produces repeatable measures of the retinal microvasculature in former preterm and term children and in adults, thereby proving its usability from childhood to old age.

Retinal tear: an unusual complication of ocular toxoplasmosis.

PubMed

Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, Ugur Emrah; Cosar, Cemile Banu; Ozkiris, Abdullah

2015-01-01

It is aimed to report on a 16-year-old patient with acquired ocular toxoplasmosis complicated by a retinal tear. Retrospective medical chart review. A 16-year-old Caucasian female presented with vision loss in her right eye. In addition to a white active lesion between the fovea and the optic nerve head, marked vitreous opacification was noted. She was diagnosed with ocular toxoplasmosis. The patient was treated with oral azithromycin, clindamycin, and trimethoprimsulfamethoxazole. One month later, retinochoroiditis resolved and vitreous cleared. Three months after onset, patient presented with floaters in the right eye and a retinal tear was located at the temporal region of the retina. Prophylactic argon laser treatment that encircled the retinal tear was performed. No other abnormalities were noted during 6 months of follow-up. Retinal tear associated with ocular toxoplasmosis is rare; however, a retinal tear can occur due to vitreoretinal traction following post-inflammatory structural alteration of the vitreous. Retinal tears may be seen during the healing phase, when the inflammation turns into tightening of vitreous substance. Careful retinal examination in cases of ocular toxoplasmosis is warranted, especially in patients with severe vitreous inflammation.

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

PubMed

Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T

2014-11-01

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published

Panoramic autofluorescence: highlighting retinal pathology.

PubMed

Slotnick, Samantha; Sherman, Jerome

2012-05-01

Recent technological advances in fundus autofluorescence (FAF) are providing new opportunities for insight into retinal physiology and pathophysiology. FAF provides distinctly different imaging information than standard photography or color separation. A review of the basis for this imaging technology is included to help the clinician understand how to interpret FAF images. Cases are presented to illustrate image interpretation. Optos, which manufactures equipment for simultaneous panoramic imaging, has recently outfitted several units with AF capabilities. Six cases are presented in which panoramic autofluorescent (PAF) images highlight retinal pathology, using Optos' Ultra-Widefield technology. Supportive imaging technologies, such as Optomap® images and spectral domain optical coherence tomography (SD-OCT), are used to assist in the clinical interpretation of retinal pathology detected on PAF. Hypofluorescent regions on FAF are identified to occur along with a disruption in the photoreceptors and/or retinal pigment epithelium, as borne out on SD-OCT. Hyperfluorescent regions on FAF occur at the advancing zones of retinal degeneration, indicating impending damage. PAF enables such inferences to be made in retinal areas which lie beyond the reach of SD-OCT imaging. PAF also enhances clinical pattern recognition over a large area and in comparison with the fellow eye. Symmetric retinal degenerations often occur with genetic conditions, such as retinitis pigmentosa, and may impel the clinician to recommend genetic testing. Autofluorescent ophthalmoscopy is a non-invasive procedure that can detect changes in metabolic activity at the retinal pigment epithelium before clinical ophthalmoscopy. Already, AF is being used as an adjunct technology to fluorescein angiography in cases of age-related macular degeneration. Both hyper- and hypoautofluorescent changes are indicative of pathology. Peripheral retinal abnormalities may precede central retinal impacts, potentially

Differentiation between Malignant and Benign Solitary Lesions in the Liver with 18FDG PET/CT: Accuracy of Age-related Diagnostic Standard

PubMed Central

Xia, Qian; Feng, Yuanbo; Wu, Cheng; Huang, Gang; Liu, Jianjun; Chen, Tao; Sun, Xiaoguang; Song, Shaoli; Tong, Linjun; Ni, Yicheng

2015-01-01

Objective: This study was to determine the reliability of age-stratified diagnostic index in differential diagnosis of malignant and benign solitary lesions in the liver using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT). Methods: The enrolled 272 patients with solitary lesions in the liver were divided into three age groups, younger group (under 50 years), middle-aged group (50-69 years), and elderly group (70 years and above). Patients' ages were compared, and the optimal cut-offs of the standard uptake value (SUV) ratio (tumor-to-non-tumor ratio of the SUV), as well as areas under the curves (AUC), were evaluated in terms of malignant and benign lesions in each age group by using receiver operating characteristic (ROC) analysis. Based on optimal cut-offs, the sensitivity, specificity, accuracy were calculated, and the diagnostic accordance rate was compared between each age group and all patients, supported by 18FDG PET/CT imaging data. Results: There was a significant age difference between the malignant and benign groups (t=3.905 p=0.0001). ROC analysis showed that the optimal cut-off value in all patients, younger group, middle-aged group and elderly group was 1.25, 1.17, 1.45 and 1.25 for SUVratio, and 0.856, 0.962, 0.650, 0.973 for AUC. The chi-square test proved that diagnostic accordance rate of 18FDG PET/CT in younger group and elderly group were superior to that in all patients (χ2=13.352, P=0.0003) and (χ2=8.494, P=0.0036). Conversely, overall diagnostic accordance rate in all patient group was higher than that in middle-aged group (χ2=9.057, P=0.0026). Representative 18FDG PET/CT imaging findings are demonstrated. Conclusion: This study indicates that diagnostic optimal cut-offs of SUVratio of liver solitary lesions of 18FDG PET/CT were different in each age group. In addition, the diagnostic performance of SUVratio was better in younger and elderly groups than that in all patients, and was poorer

Retinal complications of gout: a case report and review of the literature.

PubMed

Jiang, Ying; Brenner, Jason E; Foster, William J

2018-01-19

There have been few reported findings of posterior segment complications of gout. While exudative lesions, an increased risk of macular degeneration, and vascular occlusions have been previously reported, to our knowledge, refractile macular lesions have not been reported in a patient with chronic uncontrolled gout. Highly refractile, crystal-like lesions were found in the macula of a 62 year old male patient with chronically uncontrolled gout. The lesions appeared at the termination of retinal arterioles and were located at the level of the retinal pigment epithelium. The lesions did not stain with fluorescein and were associated with larger areas geographic atrophy. Review of the patient's blood tests revealed well-controlled vasculopathic risk factors. Fundus appearance and best-corrected visual acuity remained stable over 12 months of follow-up during which the uric acid levels were well controlled. Retinopathy may be associated with chronically uncontrolled gout and patients with visual complaints should undergo a dilated examination in addition to the typical anterior segment slit-lamp exam.

Microsystems Technology for Retinal Implants

NASA Astrophysics Data System (ADS)

Weiland, James

2005-03-01

The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

PubMed

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

Punctate retinal hemorrhage and its relation to ocular and systemic disease in dogs: 83 cases.

PubMed

Violette, Nathaniel P; Ledbetter, Eric C

2018-05-01

To describe clinical aspects of dogs with punctate retinal hemorrhage (PRH). 83 dogs (119 eyes) with PRH. Medical records of dogs evaluated by the Cornell University ophthalmology service with a clinical diagnosis of PRH between 2006 and 2015 were reviewed. For this study, PRH was defined as retinal hemorrhages ≤ 1 optic disk diameter in size and dogs with other posterior segment ocular diseases were excluded. Signalment and clinical features of the dogs were recorded, including concurrent ocular and systemic diseases. Punctate retinal hemorrhage was identified in 119 eyes of 83 dogs. The mean (±standard deviation) age of dogs was 10.0 (±3.8) years. Mixed-breed dogs, Golden Retrievers, Jack Russell Terriers, and English Springer Spaniels were statistically overrepresented relative to the ophthalmology service canine referral population during the same period. Hemorrhages were found in all retinal locations and varied in number. Concurrent ocular disease was present in 78 eyes (66%) including keratoconjunctivitis sicca, uveitis, and cataracts. Fifty dogs (60%) suffered from concurrent systemic disease and diabetes mellitus, multiple myeloma, and systemic hypertension were statistically overrepresented in the PRH population. Less frequently, other serious systemic diseases were present in dogs with PRH including immune-mediated thrombocytopenia, leptospirosis, metastatic neoplasia, and thromboembolic disease. The risk of PRH in dogs may be increased by certain ocular and systemic diseases. As the presence of PRH can be associated with underlying systemic disease in dogs, it may prompt further clinical investigation and diagnostics. © 2017 American College of Veterinary Ophthalmologists.

A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

PubMed

Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

2004-06-01

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

A new understanding of multiple-pulsed laser-induced retinal injury thresholds.

PubMed

Lund, David J; Sliney, David H

2014-04-01

Laser safety standards committees have struggled for years to formulate adequately a sound method for treating repetitive-pulse laser exposures. Safety standards for lamps and LEDs have ignored this issue because averaged irradiance appeared to treat the issue adequately for large retinal image sizes and skin exposures. Several authors have recently questioned the current approach of three test conditions (i.e., limiting single-pulse exposure, average irradiance, and a single-pulse-reduction factor) as still insufficient to treat pulses of unequal energies or certain pulse groupings. Schulmeister et al. employed thermal modeling to show that a total-on-time pulse (TOTP) rule was conservative. Lund further developed the approach of probability summation proposed by Menendez et al. to explain pulse-additivity, whereby additivity is the result of an increasing probability of detecting injury with multiple pulse exposures. This latter argument relates the increase in detection probability to the slope of the probit curve for the threshold studies. Since the uncertainty in the threshold for producing an ophthalmoscopically detectable minimal visible lesion (MVL) is large for retinal exposure to a collimated laser beam, safety committees traditionally applied large risk reduction factors ("safety factors") of one order of magnitude when deriving intrabeam, "point-source" exposure limits. This reduction factor took into account the probability of visually detecting the low-contrast lesion among other factors. The reduction factor is smaller for large spot sizes where these difficulties are quite reduced. Thus the N⁻⁰·²⁵ reduction factor may result from the difficulties in detecting the lesion. Recent studies on repetitive pulse exposures in both animal and in vitro (retinal explant) models support this interpretation of the available data.

Aging decreases CO2 reactivity in the retinal artery, but not in the ocular choroidal vessels; a cross-sectional study.

PubMed

Miyaji, Akane; Ikemura, Tsukasa; Hayashi, Naoyuki

2018-04-14

The CO2 reactivity is often used to assess vascular function, but it is still unclear whether this reactivity is affected by aging. To investigate the effects of aging on the CO2 reactivity in ocular and cerebral vessels, both of which are highly sensitive to hypercapnia, we compared the CO2 reactivity in the retinal artery (RA), retinal and choroidal vessels (RCV), optic nerve head (ONH), and middle cerebral artery (MCA) between young and middle-aged subjects. We measured the CO2 reactivity in 14 young and 11 middle-aged males using laser-speckle flowgraphy during a 3-min inhalation of CO2-rich air. The CO2 reactivity in the RA and ONH were lower in the middle-aged group than in the young group, but no significant effect of age was observed in the RCV or MCA. The CO2 reactivity in the RA and ONH were correlated significantly with age, whereas those in the RCV or MCA were not. These findings suggest that there are regional differences in the effect of age on the CO2 reactivity among not only ocular and cerebral vessels, but also the retinal and choroidal vessels, even though these vessels are in neighboring areas.

Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials.

PubMed

Jaffe, Glenn J; Martin, Daniel F; Toth, Cynthia A; Daniel, Ebenezer; Maguire, Maureen G; Ying, Gui-Shuang; Grunwald, Juan E; Huang, Jiayan

2013-09-01

To describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD). Prospective cohort study within a randomized clinical trial. Participants in the Comparison of Age-related Macular Degeneration Treatments Trials. Participants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes. Fluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA. Intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features. Anti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA

Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration.

PubMed

Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

2015-01-09

Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas "plasma" that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV.

Prevalence and pattern of vitreo-retinal diseases in Nepal: the Bhaktapur glaucoma study.

PubMed

Thapa, Suman S; Thapa, Raba; Paudyal, Indira; Khanal, Shankar; Aujla, Jaskirat; Paudyal, Govinda; Rens, Ger van

2013-03-28

Vitreo-retinal diseases are among the leading causes of visual impairment and blindness worldwide. This study reports the prevalence and pattern of vitreo-retinal diseases in the Bhaktapur Glaucoma Study (BGS), a population based study conducted in Nepal. BGS was a population based cross-sectional study involving 4800 subjects aged 40 years and over from Bhaktapur district. Subjects were selected using a cluster sampling methodology and a door-to-door enumeration. All subjects underwent a detailed ocular examination at the base hospital which included log MAR visual acuity, refraction, applanation tonometry and a dilated fundus examination. Fundus photography, optical coherence tomography and fundus fluorescein angiography were performed where indicated. Complete data was available for 3966 (82.62%) out of the total of 4800 enumerated subjects. The mean age was 55.08 years (SD 11.51). The overall prevalence of vitreo-retinal disorders was 5.35% (95% CI, 4.67 - 6.09). Increasing age was associated with a higher prevalence of vitreo-retinal disorders (P < 0.001). The prevalence of diabetes mellitus was 7.69% (95% CI, 6.88 - 8.56). Age-related macular degeneration (AMD) was the most common vitreo-retinal disorder with a prevalence of 1.50% (95% CI, 1.15 - 1.94), increasing significantly with age. The prevalence of diabetic retinopathy among the study population was 0.78% (95% CI, 0.53 - 1.11) and among the diabetic population 10.16% (95% CI, 7.01 - 14.12). The population prevalence of other retinal disorders were hypertensive retinopathy 0.88%, macular scar 0.37%, retinal vein occlusion 0.50%, macular hole 0.20%, retinitis pigmentosa 0.12%. and retinal detachment 0.10%.The prevalence of low vision and blindness due to vitreo-retinal disorders was 1.53% (95% CI, 1.18 - 1.97) and 0.65% (95% CI, 0.43 - 0.96), respectively. The prevalence of low vision and blindness was 28.77% (95% CI, 22.78-35.37) and 12.26% (95% CI, 8.17-17.45), respectively among cases with vitreo-retinal

Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging.

PubMed

Han, Meng; Giese, Guenter; Schmitz-Valckenberg, Steffen; Bindewald-Wittich, Almut; Holz, Frank G; Yu, Jiayi; Bille, Josef F; Niemz, Markolf H

2007-01-01

The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

Minireview: Fibronectin in retinal disease.

PubMed

Miller, Charles G; Budoff, Greg; Prenner, Jonathan L; Schwarzbauer, Jean E

2017-01-01

Retinal fibrosis, characterized by dysregulation of extracellular matrix (ECM) protein deposition by retinal endothelial cells, pigment epithelial cells, and other resident cell-types, is a unifying feature of several common retinal diseases. Fibronectin is an early constituent of newly deposited ECM and serves as a template for assembly of other ECM proteins, including collagens. Under physiologic conditions, fibronectin is found in all layers of Bruch's membrane. Proliferative vitreoretinopathy (PVR), a complication of retinal surgery, is characterized by ECM accumulation. Among the earliest histologic manifestations of diabetic retinopathy (DR) is capillary basement membrane thickening, which occurs due to perturbations in ECM homeostasis. Neovascularization, the hallmark of late stage DR as well as exudative age-related macular degeneration (AMD), involves ECM assembly as a scaffold for the aberrant new vessel architecture. Rodent models of retinal injury demonstrate a key role for fibronectin in complications characteristic of PVR, including retinal detachment. In mouse models of DR, reducing fibronectin gene expression has been shown to arrest the accumulation of ECM in the capillary basement membrane. Alterations in matrix metalloproteinase activity thought to be important in the pathogenesis of AMD impact the turnover of fibronectin matrix as well as collagens. Growth factors involved in PVR, AMD, and DR, such as PDGF and TGFβ, are known to stimulate fibronectin matrix assembly. A deeper understanding of how pathologic ECM deposition contributes to disease progression may help to identify novel targets for therapeutic intervention. © 2016 by the Society for Experimental Biology and Medicine.

Real-time optical coherence tomography observation of retinal tissue damage during laser photocoagulation therapy on ex-vivo porcine samples

NASA Astrophysics Data System (ADS)

Steiner, P.; Považay, B.; Stoller, M.; Morgenthaler, P.; Inniger, D.; Arnold, P.; Sznitman, R.; Meier, Ch.

2015-07-01

Retinal laser photocoagulation represents a widely used treatment for retinal pathologies such as diabetic chorioretinopathy or diabetic edema. For effective treatment, an appropriate choice of the treatment energy dose is crucial to prevent excessive tissue damage caused by over-irradiation of the retina. In this manuscript we investigate simultaneous and time-resolved optical coherence tomography for its applicability to provide feedback to the ophthalmologist about the introduced retinal damage during laser photocoagulation. Time-resolved and volumetric optical coherence tomography data of 96 lesions on ex-vivo porcine samples, set with a 577 nm laser prototype and irradiance of between 300 and 8800 W=cm2 were analyzed. Time-resolved scans were compared to volumetric scans of the lesion and correlated with ophthalmoscopic visibility. Lastly, image parameters extracted from optical coherence tomography Mscans, suitable for lesion classification were identified. Results presented in this work support the hypothesis that simultaneous optical coherence tomography provides valuable information about the extent of retinal tissue damage and may be used to guide retinal laser photocoagulation in the future.

Characteristics of eyes with inner retinal cleavage.

PubMed

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

2015-02-01

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

Cytomegalovirus retinitis in a patient with proliferative diabetes retinopathy.

PubMed

Takayama, Kei; Ogawa, Manabu; Mochizuki, Manabu; Takeuchi, Masaru

2013-06-01

To report a case of cytomegalovirus (CMV) retinitis in an immunocompetent patient with proliferative diabetic retinopathy (PDR). Case report. A 69-year-old man presented with a 44-year history of diabetes mellitus and 4 years of PDR. Fundus of left eye could not be visualized because of vitreous hemorrhage. Laboratory tests indicated normal immunological status. Yellowish white retinal exudative lesion and whitening inside vascular arcades were observed during vitrectomy. Multiplex PCR using vitreous sample detected CMV DNA at 4.37 × 10(4) copies/mL. CMV retinitis was diagnosed. If atypical findings of PDR are observed, a multiplex PCR test should be performed for further investigation.

Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration.

PubMed

Ding, Jin-Dong; Johnson, Lincoln V; Herrmann, Rolf; Farsiu, Sina; Smith, Stephanie G; Groelle, Marybeth; Mace, Brian E; Sullivan, Patrick; Jamison, Jeffrey A; Kelly, Una; Harrabi, Ons; Bollini, Sangeetha Subbarao; Dilley, Jeanette; Kobayashi, Dione; Kuang, Bing; Li, Wenlin; Pons, Jaume; Lin, John C; Bowes Rickman, Catherine

2011-07-12

Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human apolipoprotein E 4 targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function. Strikingly, these electroretinographic deficits are abrogated in a dose-dependent manner by systemic administration of an antibody targeting the C termini of Aβ40 and Aβ42. Concomitant reduction in the levels of Aβ and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-Aβ40/42 antibody immunotherapy and visual protection. These observations are consistent with the reduction in amyloid plaques and improvement of cognitive function in mouse models of Alzheimer's disease treated with anti-Aβ antibodies. They also implicate Aβ in the pathogenesis of AMD and identify Aβ as a viable therapeutic target for its treatment.

Cellular and 3D Optical Coherence Tomography Assessment During the Initiation and Progression of Retinal Degeneration in the Ccl2/Cx3cr1-deficient Mouse

PubMed Central

Zhou, Yongdong; Sheets, Kristopher G.; Knott, Eric J.; Regan, Cornelius E.; Tuo, Jingsheng; Chan, Chi-Chao; Gordon, William C.; Bazan, Nicolas G.

2011-01-01

Retinal pathologies common to human eye diseases, including abnormal retinal pigment epithelial (RPE) cells, drusen-like accumulation, photoreceptor atrophy, and choroidal neovascularization, have been reported in the Ccl2/Cx3cr1-deficient mouse. The Ccl2 gene encodes the pro-inflammatory chemokine CCL2 (MCP-1), which is responsible for chemotactic recruitment of monocyte-derived macrophages to sites of inflammation. The Cx3cr1 gene encodes the fractalkine receptor, CX3CR1, and is required for accumulation of monocytes and microglia recruited via CCL2. Chemokine-mediated inflammation is implicated in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and uveoretinitis, and proper chemokine signaling from the RPE, Müller glia, and astrocytes is necessary to regulate leukocyte trafficking. Therefore, this mouse, possessing aberrant chemokine signaling coupled with retinal degenerative pathologies, presents an ideal opportunity to investigate the effect of altered signaling on retinal homeostasis and photoreceptor degeneration. Since this mouse is a recent development, more data covering the onset, location, and progression rate of pathologies is needed. In the present study we establish these parameters and show two photoreceptor cell death processes. Our observations of decreased glutamine synthetase and increased glial fibrillary acidic protein suggest that Müller cells respond very early within regions where lesions are forming. Finally, we demonstrate that retinal angiomatous proliferation contributes to pathological angiogenesis in this Ccl2/Cx3cr1-deficient mouse. PMID:21854772

SPOTTED FEVER GROUP RICKETTSIA RETINITIS IN A TRAVELER TO AFRICA.

PubMed

Duval, Renaud; Merrill, Pauline T

2016-01-01

To describe a case of rickettsial retinitis in a traveler returning from Africa. Case description. A 67-year-old woman returning from an excursion in the jungles of Africa presented with a 2-day history of floaters and decreased vision in the right eye. In the two preceding weeks, she had experienced fever, malaise, a black eschar on the right elbow, and a rash on her extremities. Examination revealed panuveitis with a solitary, white retinal lesion adjacent to a retinal vessel in the posterior pole of each eye. Extensive diagnostic workup revealed a positive serology for rickettsial antibodies. Her treatment consisted of a course of oral doxycycline. Rickettsial retinitis is an emerging ocular infection in several endemic areas. This case description constitutes the first report of spotted fever group rickettsial retinitis in a traveler to Africa.

The Modification of Fluorescein Angiography and Its Applications in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

PubMed

Peng, Qing; Chen, Yutong; Hua, Rui

2018-06-07

To establish a novel retinal angiography method, red-free angiography (RFA), to investigate retinal changes in age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Following the venous phase of fundus fluorescein angiography (FFA), the detection mode was switched to red-free reflectance to acquire RFA images using the same parameters. RFA showed subretinal fluid, polyps, and outer retinal tubulation, with a higher definition than the FFA and red-free reflectance results. The absorption coefficients in RFA provided more detailed images for AMD and PCV diagnosis. RFA is therefore a promising approach to supplement FFA. © 2018 S. Karger AG, Basel.

Measurement of the relative afferent pupillary defect in retinal detachment.

PubMed

Bovino, J A; Burton, T C

1980-07-01

A swinging flashlight test and calibrated neutral density filters were used to quantitate the depth of relative afferent pupillary defects in ten patients with retinal detachment. Postoperatively, the pupillary responses returned to normal in seven of nine patients with anatomically successful surgery.

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

PubMed Central

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Primary amines protect against retinal degeneration in mouse models of retinopathies

PubMed Central

Maeda, Akiko; Golczak, Marcin; Chen, Yu; Okano, Kiichiro; Kohno, Hideo; Shiose, Satomi; Ishikawa, Kaede; Harte, William; Palczewska, Grazyna; Maeda, Tadao; Palczewski, Krzysztof

2011-01-01

Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore, 11-cis-retinal, and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomered product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing FDA-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by mass spectrometry. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that displays features of Stargardt’s and age-related retinal degeneration. PMID:22198730

Color vision impairment in multiple sclerosis points to retinal ganglion cell damage.

PubMed

Lampert, E J; Andorra, M; Torres-Torres, R; Ortiz-Pérez, S; Llufriu, S; Sepúlveda, M; Sola, N; Saiz, A; Sánchez-Dalmau, B; Villoslada, P; Martínez-Lapiscina, Elena H

2015-11-01

Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy-Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS.

a Review of Retinal Prosthesis Approaches

NASA Astrophysics Data System (ADS)

Kien, Tran Trung; Maul, Tomas; Bargiela, Andrzej

Age-related macular degeneration and retinitis pigmentosa are two of the most common diseases that cause degeneration in the outer retina, which can lead to several visual impairments up to blindness. Vision restoration is an important goal for which several different research approaches are currently being pursued. We are concerned with restoration via retinal prosthetic devices. Prostheses can be implemented intraocularly and extraocularly, which leads to different categories of devices. Cortical Prostheses and Optic Nerve Prostheses are examples of extraocular solutions while Epiretinal Prostheses and Subretinal Prostheses are examples of intraocular solutions. Some of the prostheses that are successfully implanted and tested in animals as well as humans can restore basic visual functions but still have limitations. This paper will give an overview of the current state of art of Retinal Prostheses and compare the advantages and limitations of each type. The purpose of this review is thus to summarize the current technologies and approaches used in developing Retinal Prostheses and therefore to lay a foundation for future designs and research directions.

Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases.

PubMed

Zhang, Xun; Tohari, Ali Mohammad; Marcheggiani, Fabio; Zhou, Xinzhi; Reilly, James; Tiano, Luca; Shu, Xinhua

2017-01-01

Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration. The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed. CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions. A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Retinal Laminar Architecture in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Herrera, Waldo; White, D. Alan; Kaushal, Shalesh; Naidu, Anjani; Roman, Alejandro J.; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

Purpose. To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. Methods. Patients with RHO-ADRP (n = 17, ages 6–73 years), representing class A (R135W and P347L) and class B (P23H, T58R, and G106R) functional phenotypes, were studied with optical coherence tomography (OCT), and colocalized visual thresholds were determined by dark- and light-adapted chromatic perimetry. Autofluorescence imaging was performed with near-infrared light. Retinal histology in hT17M-rhodopsin mice was compared with the human results. Results. Class A patients had only cone-mediated vision. The outer nuclear layer (ONL) thinned with eccentricity and was not detectable within 3 to 4 mm of the fovea. Scotomatous extracentral retina showed loss of ONL, thickening of the inner retina, and demelanization of RPE. Class B patients had superior–inferior asymmetry in function and structure. The superior retina could have normal rod and cone vision, normal lamination (including ONL) and autofluorescence of the RPE melanin; laminopathy was found in the scotomas. With Fourier-domain-OCT, there was apparent inner nuclear layer (INL) thickening in regions with ONL thinning. Retinal regions without ONL had a thick hyporeflective layer that was continuous with the INL from neighboring regions with normal lamination. Transgenic mice had many of the laminar abnormalities found in patients. Conclusions. Retinal laminar abnormalities were present in both classes of RHO-ADRP and were related to the severity of colocalized vision loss. The results in human class B and the transgenic mice support the following disease sequence: ONL diminution with INL thickening; amalgamation of residual ONL with the thickened INL; and progressive retinal remodeling with eventual thinning. PMID:18385078

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

PubMed Central

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-01-01

Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study.

PubMed

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-07-26

The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (µm) and group B with RTA equal to or more than 250 µm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity.

Association of Anticholinergic Drug Use With Risk for Late Age-Related Macular Degeneration.

PubMed

Aldebert, Gauthier; Faillie, Jean-Luc; Hillaire-Buys, Dominique; Mura, Thibault; Carrière, Isabelle; Delcourt, Cécile; Creuzot-Garcher, Catherine; Villain, Max; Daien, Vincent

2018-05-24

Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Association between exposure to ACDs and late AMD. Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection

PubMed Central

IKEGAMI, HISASHI; TAKEDA, MAKIO; DOI, KUNIO

1997-01-01

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 × 104 plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system. PMID:9203984

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

PubMed

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-07-28

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases

PubMed Central

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-01-01

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action. PMID:28788088

A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration.

PubMed

George, Akash K; Singh, Mahavir; Homme, Rubens Petit; Majumder, Avisek; Sandhu, Harpal S; Tyagi, Suresh C

2018-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways. ROS becomes a source of functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells and retinal ganglion cells. Reports demonstrated that hydrogen sulfide (H 2 S) acts as a signaling molecule and that it may treat ailments. Therefore, we propose a novel hypothesis that H 2 S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation. Since H 2 S has been shown to be a powerful antioxidant because of its free-radicals' inhibition properties in addition to its beneficial effects in age-related conditions, therefore, patients may benefit from H 2 S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

A CMOS active pixel sensor for retinal stimulation

NASA Astrophysics Data System (ADS)

Prydderch, Mark L.; French, Marcus J.; Mathieson, Keith; Adams, Christopher; Gunning, Deborah; Laudanski, Jonathan; Morrison, James D.; Moodie, Alan R.; Sinclair, James

2006-02-01

Degenerative photoreceptor diseases, such as age-related macular degeneration and retinitis pigmentosa, are the most common causes of blindness in the western world. A potential cure is to use a microelectronic retinal prosthesis to provide electrical stimulation to the remaining healthy retinal cells. We describe a prototype CMOS Active Pixel Sensor capable of detecting a visual scene and translating it into a train of electrical pulses for stimulation of the retina. The sensor consists of a 10 x 10 array of 100 micron square pixels fabricated on a 0.35 micron CMOS process. Light incident upon each pixel is converted into output current pulse trains with a frequency related to the light intensity. These outputs are connected to a biocompatible microelectrode array for contact to the retinal cells. The flexible design allows experimentation with signal amplitudes and frequencies in order to determine the most appropriate stimulus for the retina. Neural processing in the retina can be studied by using the sensor in conjunction with a Field Programmable Gate Array (FPGA) programmed to behave as a neural network. The sensor has been integrated into a test system designed for studying retinal response. We present the most recent results obtained from this sensor.

Retinal pigment epithelium changes in Kartagener syndrome.

PubMed

Garcia, Maria D; Ventura, Camila V; Dias, João R; Chang, Ta Chen P; Berrocal, Audina M

2018-06-01

We present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. A 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. We hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

Small Animal Retinal Imaging

NASA Astrophysics Data System (ADS)

Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

Stem Cell Therapies in Retinal Disorders.

PubMed

Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H

2017-02-02

Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients' diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

Molecular pharmacodynamics of emixustat in protection against retinal degeneration

PubMed Central

Zhang, Jianye; Kiser, Philip D.; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

2015-01-01

Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

Transplanting Retinal Cells using Bucky Paper for Support

NASA Technical Reports Server (NTRS)

Loftus, David J.; Cinke, Martin; Meyyappan, Meyya; Fishman, Harvey; Leng, Ted; Huie, Philip; Bilbao, Kalayaan

2004-01-01

A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.

The use of microperimetry in assessing visual function in age-related macular degeneration.

PubMed

Cassels, Nicola K; Wild, John M; Margrain, Tom H; Chong, Victor; Acton, Jennifer H

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated retinal layer segmentation and characterization

NASA Astrophysics Data System (ADS)

Luisi, Jonathan; Briley, David; Boretsky, Adam; Motamedi, Massoud

2014-05-01

Spectral Domain Optical Coherence Tomography (SD-OCT) is a valuable diagnostic tool in both clinical and research settings. The depth-resolved intensity profiles generated by light backscattered from discrete layers of the retina provide a non-invasive method of investigating progressive diseases and injury within the eye. This study demonstrates the application of steerable convolution filters capable of automatically separating gradient orientations to identify edges and delineate tissue boundaries. The edge maps were recombined to measure thickness of individual retinal layers. This technique was successfully applied to longitudinally monitor changes in retinal morphology in a mouse model of laser-induced choroidal neovascularization (CNV) and human data from age-related macular degeneration patients. The steerable filters allow for direct segmentation of noisy images, while novel recombination of weaker segmentations allow for denoising post-segmentation. The segmentation before denoising strategy allows the rapid detection of thin retinal layers even under suboptimal imaging conditions.

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration.

PubMed

Wolf-Schnurrbusch, Ute E K; Brinkmann, Christian K; Berger, Lisa; Wolf, Sebastian

2011-09-01

This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 μm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

Retinal Remodeling in Human Retinitis Pigmentosa

PubMed Central

Jones, B.W.; Pfeiffer, R.L.; Ferrell, W. D.; Watt, C.B.; Marmor, M.; Marc, R.E.

2016-01-01

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies. PMID:27020758

RNCR3: A regulator of diabetes mellitus-related retinal microvascular dysfunction

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

Shan, Kun; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing

Retinal microvascular abnormality is an important pathological feature of diabetic retinopathy. Herein, we report the role of lncRNA-RNCR3 in diabetes mellitus-induced retinal microvascular abnormalities. We show that RNCR3 is significantly up-regulated upon high glucose stress in vivo and in vitro. RNCR3 knockdown alleviates retinal vascular dysfunction in vivo, as shown by decreased acellular capillaries, decreased vascular leakage, and reduced inflammatory response. RNCR3 knockdown decreases retinal endothelial cell proliferation, and reduces cell migration and tube formation in vitro. RNCR3 regulates endothelial cell function through RNCR3/KLF2/miR-185-5p regulatory network. RNCR3 inhibition may be a treatment option for the prevention of diabetes mellitus-induced retinal microvascular abnormalities. - Highlights:more » • RNCR3 expression is significantly up-regulated upon high glucose stress. • RNCR3 knockdown alleviates retinal vascular dysfunction in vivo. • RNCR3 regulates retinal endothelial cell function in vitro. • RNCR3 regulates retinal endothelial cell function via RNCR3/KLF2/miR-185-5p pathway.« less

A Novel Role for the Immunoproteasome in Retinal Function

PubMed Central

Hussong, Stacy A.; Roehrich, Heidi; Kapphahn, Rebecca J.; Maldonado, Marcela; Pardue, Machelle T.

2011-01-01

Purpose. The immunoproteasome is a proteasome subtype with a well-characterized role in the immune system. The presence of high immunoproteasome concentrations in the photoreceptors and synaptic regions of the immune-privileged retina implies a role in visual transmission. In this study, immunoproteasome knockout (KO) mice lacking either one (lmp7−/−, L7) or two (lmp7−/−/mecl-1−/−, L7M1) catalytic subunits of the immunoproteasome were used to test the hypothesis that it is essential for the maintenance of normal retinal function. Methods. Wild-type (WT) and immunoproteasome KO mice lacking either one (L7) or two (L7M1) catalytic subunits of the immunoproteasome were studied to determine the importance of the immunoproteasome in maintaining normal retinal function and morphology. Changes in retinal morphology were assessed in mice 2 to 24 months of age. Retinal function was measured with electroretinography (ERG), and relative content of select retinal proteins was assessed by immunoblot analysis. Results. Retinal morphometry showed no major abnormalities in age-matched WT or KO mice. No significant difference was observed in the levels of proteins involved in vision transmission. ERGs from KO mice exhibited an approximate 25% decrease in amplitude of the dark- and light-adapted b-waves and faster dark-adapted b-wave implicit times. Conclusions. Immunoproteasome deficiency causes defects in bipolar cell response. These results support a previously unrecognized role for the immunoproteasome in vision transmission. PMID:20881299

Temperature controlled retinal photocoagulation

NASA Astrophysics Data System (ADS)

Schlott, Kerstin; Koinzer, Stefan; Baade, Alexander; Birngruber, Reginald; Roider, Johann; Brinkmann, Ralf

2013-06-01

Retinal photocoagulation lacks objective dosage in clinical use, thus the commonly applied lesions are too deep and strong, associated with pain reception and the risk of visual field defects and induction of choroidal neovascularisations. Optoacoustics allows real-time non-invasive temperature measurement in the fundus during photocoagulation by applying short probe laser pulses additionally to the treatment radiation, which excite the emission of ultrasonic waves. Due to the temperature dependence of the Grüneisen parameter, the amplitudes of the ultrasonic waves can be used to derive the temperature of the absorbing tissue. By measuring the temperatures in real-time and automatically controlling the irradiation by feedback to the treatment laser, the strength of the lesions can be defined. Different characteristic functions for the time and temperature dependent lesion sizes were used as rating curves for the treatment laser, stopping the irradiation automatically after a desired lesion size is achieved. The automatically produced lesion sizes are widely independent of the adjusted treatment laser power and individual absorption. This study was performed on anaesthetized rabbits and is a step towards a clinical trial with automatically controlled photocoagulation.

Evaluation of white matter hyperintensities and retinal fiber layer, ganglion cell layer, inner-plexiform layer, and choroidal layer in migraine patients.

PubMed

Tak, Ali Zeynel Abidin; Sengul, Yıldızhan; Bilak, Şemsettin

2018-03-01

The aim of our study is to assess retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), inner-plexiform layer (IPL), and choroidal layer in migraine patients with white matter lesion (WML) or without WML, using spectral domain optical coherence tomography (OCT). To our study, 77 migraine patients who are diagnosed with migraine in accordance to the International Classification of Headache Disorders (ICHD)-3 beta and 43 healthy control are included. In accordance to cranial MRI, migraine patients are divided into two groups as those who have white matter lesions (39 patients), and those who do not have a lesion (38 patients). OCT was performed for participants. The average age of participants was comparable. The RNFL average thickness parameter in the migraine group was significantly lower than in the control group (p < 0.01). However, no significant difference was detected among those migraine patients who have WML, and those who do not have. No significant difference is detected among all groups in terms of IPL, GCL, and choroidal layer measuring scales. The proofs showing that affected retinal nerve fiber layer are increased in migraine patients. However, it is not known whether this may affect other layers of retina, or whether there is a correlation between affected retinal structures and white matter lesions. In our study, we found thinner RNFL in migraine patients when we compared with controls but IPL, GCL, and choroid layer values were similar between each patient groups and controls. Also, all parameters were similar between patients with WML and without WML. Studies in this regard are required.

Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products.

PubMed

Lin, Wen-Jian; Ma, Xue-Fei; Hao, Ming; Zhou, Huan-Ran; Yu, Xin-Yang; Shao, Ning; Gao, Xin-Yuan; Kuang, Hong-Yu

2018-07-01

Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability. AGEs also significantly enhanced phosphatidylinositol 3-kinase (PI3K)/Akt activation, and changed the expressions of migration-related proteins, including phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase (MMP)-2 and vinculin. PI3K inhibition significantly attenuated the AGEs-induced migration of retinal pericytes and reversed the overexpression of MMP-2. Glucagon-like peptide-1 receptor (Glp1r) was expressed in retinal pericytes, and liraglutide, a GLP-1 analog, significantly attenuated the migration of pericytes by Glp1r and reversed the changes in p-Akt/Akt, p-FAK/FAK, vinculin and MMP-2 levels induced by AGEs, indicating that the protective effect of liraglutide was associated with the PI3K/Akt pathway. These results provided new insights into the mechanism underlying retinal pericyte migration. The early use of liraglutide exerts a potential bebefical effect on regulating pericyte migration, which might contribute to mechanisms that maintain the integrity of vascular barrier and delay the development of DR. Copyright © 2018 Elsevier Inc. All rights reserved.

Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa.

PubMed

Sevgi, D Damla; Davoudi, Samaneh; Comander, Jason; Sobrin, Lucia

2017-09-01

To present retinal pigmentary changes mimicking retinitis pigmentosa (RP) as a finding of advanced uveitis. We retrospectively reviewed charts of patients without a family history of inherited retinal degenerations who presented with retinal pigment changes and signs of past or present intraocular inflammation. Comprehensive eye examination including best-corrected visual acuity, slit-lamp examination and dilated fundus examination was performed on all patients in addition to color fundus photography, optical coherence tomography, fluorescein angiography (FA), and full-field electroretinogram testing. We identified five patients with ages ranging from 33 to 66 years, who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. The changes were bilateral in three cases and unilateral in two cases. Four of five cases presented with active inflammation, and the remaining case showed evidence of active intraocular inflammation during follow-up. This study highlights the overlapping features of advanced uveitis and RP including the extensive pigmentary changes. Careful review of possible past uveitis history, detailed examination of signs of past or present inflammation and ancillary testing, with FA often being most helpful, are required for the correct diagnosis. This is important, because intervention can prevent further damage if the cause of the pigmentary changes is destructive inflammation.

Retinitis pigmentosa.

PubMed

Hamel, Christian

2006-10-11

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).

Retinitis pigmentosa

PubMed Central

Hamel, Christian

2006-01-01

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466

ROLE OF TYROSINE-SULFATED PROTEINS IN RETINAL STRUCTURE AND FUNCTION

PubMed Central

Kanan, Y.; Al-Ubaidi, M.R.

2014-01-01

The extracellular matrix (ECM) plays a significant role in cellular and retinal health. The study of retinal tyrosine-sulfated proteins is an important first step toward understanding the role of ECM in retinal health and diseases. These secreted proteins are members of the retinal ECM. Tyrosine sulfation was shown to be necessary for the development of proper retinal structure and function. The importance of tyrosine sulfation is further demonstrated by the evolutionary presence of tyrosylprotein sulfotransferases, enzymes that catalyze proteins’ tyrosine sulfation, and the compensatory abilities of these enzymes. Research has identified four tyrosine-sulfated retinal proteins: fibulin 2, vitronectin, complement factor H (CFH), and opticin. Vitronectin and CFH regulate the activation of the complement system and are involved in the etiology of some cases of age-related macular degeneration. Analysis of the role of tyrosine sulfation in fibulin function showed that sulfation influences the protein's ability to regulate growth and migration. Although opticin was recently shown to exhibit anti-angiogenic properties, it is not yet determined what role sulfation plays in that function. Future studies focusing on identifying all of the tyrosine-sulfated retinal proteins would be instrumental in determining the impact of sulfation on retinal protein function in retinal homeostasis and diseases. PMID:25819460

Oral mucosal lesions in older people: relation to salivary secretion, systemic diseases and medications.

PubMed

Lynge Pedersen, A M; Nauntofte, B; Smidt, D; Torpet, L A

2015-09-01

To determine the prevalence of oral mucosal lesions in a sample of older Danish people and to investigate their associations with age, gender, systemic diseases, medications, xerostomia and salivary secretion. A total of 668 community-dwelling individuals aged 65-95 years underwent a clinical examination, measurements of unstimulated and stimulated whole and labial salivary flow rates and an interview regarding xerostomia, general health, medication, tobacco and alcohol habits. Seventy-five per cent of all participants and 70% of the non-medicated ones had one or more oral mucosal lesions. The most prevalent lesions were lingual varicosities (28.3%), denture stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional keratosis (8.4%). Lesions were generally associated with smoking and xerostomia. Varicosities were more common in participants with systemic diseases and medication intake, particularly with cardiovascular diseases and agents. Fissured tongue and atrophic tongue were associated with female gender, xerostomia and low unstimulated whole and labial salivary secretion. Oral candidiasis was associated with older age; being male; current smoker; having >3 diseases, intake of medications and low salivary flow rates; and identified in relation to denture stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis. Oral mucosal lesions are prevalent in older Danish people and generally associated with changes in both local and systemic factors. Tongue lesions in particular appeared as indicators that may identify patients with specific need of oral intervention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.

PubMed

Molins, Blanca; Romero-Vázquez, Sara; Fuentes-Prior, Pablo; Adan, Alfredo; Dick, Andrew D

2018-01-01

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro . In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

PubMed

Lin, Tai-Chi; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Liu, Jorn-Hon; Woung, Lin-Chung; Tsai, Ching-Yao; Chen, Shih-Jen; Chen, Yan-Ting; Hsu, Chih-Chien

2015-11-01

Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration. Copyright © 2015. Published by Elsevier Taiwan.

Post-fever retinitis: a single center experience from south India.

PubMed

Vishwanath, Srilatha; Badami, Kalpana; Sriprakash, K S; Sujatha, B L; Shashidhar, S D; Shilpa, Y D

2014-08-01

Various retinal manifestations can occur following a febrile illness due to viral, bacterial or protozoal etiology. As there are limited data in the literature, we undertook this study to analyse the clinical presentation of post-fever retinitis due to various etiologies, as well as its course and management. This was a retrospective study of 14 consecutive cases who presented to the Vitreo Retina Department of our hospital over a 1-year period between January 2010 and December 2010. All patients underwent detailed ophthalmic examination and relevant investigations including fundus fluorescein angiography and optical coherence tomography (OCT). Basic and specific investigations were performed as necessary. All patients were given systemic steroids which were tapered based on clinical response. Twenty-one eyes of 14 patients (7 bilateral, 7 unilateral) were studied. Onset of ocular symptoms was approximately 3 weeks after fever. Four patients had specific etiology-one each of chikungunya, enteric fever, malaria and abdominal abscess with pneumococcal pneumonia. The presenting visual acuity of the affected eyes averaged 2/60. Six eyes had relative afferent pupillary defect. All patients had solitary or multiple patches of retinitis at the posterior pole and exudation at the macula. OCT through the lesions revealed inner retinal hyperreflectivity and thickening with after-shadowing. All patients showed improvement in vision with unilateral cases improving to an average of 6/12 and bilateral cases improving to an average of 6/24. Patients also showed resolution of retinitis, macular edema and serous detachment. Post-fever retinitis as a condition manifested approximately 3 weeks after onset of fever. Irrespective of the cause of the fever, clinical presentation of cases was similar with inner retinitis at the posterior pole and a favourable response to steroids, suggesting a possible immunological basis for this condition.

Screening retinal transplants with Fourier-domain OCT

NASA Astrophysics Data System (ADS)

Rao, Bin

2009-02-01

Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

Retinal detachment

PubMed Central

2009-01-01

Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids; cryotherapy; daunorubicin; fluorouracil plus low-molecular-weight heparin; laser photocoagulation; pneumatic retinopexy; scleral buckling; short-acting or long-acting gas tamponade; silicone oil tamponade; and vitrectomy. PMID:19450333

Retinal detachment

PubMed Central

2010-01-01

Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, cryotherapy, daunorubicin, fluorouracil plus low molecular weight heparin, laser photocoagulation, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy. PMID:21406128

Treatment of caries in relation to lesion severity: implications for minimum intervention dentistry.

PubMed

Brennan, D S; Balasubramanian, M; Spencer, A J

2015-01-01

To date there is little evidence of minimum intervention in relation to treatment patterns, particularly for initial carious lesions. The objective of this study was to investigate treatment provided to patients with a main diagnosis of coronal caries in relation to the severity of the caries lesion. A random sample of Australian dentists was surveyed by mailed questionnaires in 2009-2010 (response rate 67%). Data on services, patient characteristics and main diagnosis were collected from a service log. Models of service rates adjusted for age, sex, insurance status and reason for visit showed that compared to the reference category of gross caries lesions, there were higher rates [rate ratio, 95% CI] of restorative services for initial [1.63, 1.31-2.03] and cavitated [1.69, 1.39-2.05] lesions, higher rates of prophylaxis for initial [3.77, 2.09-6.79] and cavitated [3.88, 2.29-6.58] lesions, lower rates of endodontic services for initial [0.07, 0.02-0.30] and cavitated [0.11, 0.04-0.30] lesions, and lower rates of extraction for initial [0.15, 0.06-0.34] and cavitated [0.15, 0.07-0.31] lesions. Treatment of coronal caries was characterized by high rates of restorative services, but gross lesions had lower restorative rates and higher rates of endodontic and extraction services. There was little differentiation in treatment of coronal caries between initial and cavitated lesions, suggesting scope for increased management of initial carious lesions by the adoption of more minimum intervention approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.

Automated detection of diabetic retinopathy in retinal images.

PubMed

Valverde, Carmen; Garcia, Maria; Hornero, Roberto; Lopez-Galvez, Maria I

2016-01-01

Diabetic retinopathy (DR) is a disease with an increasing prevalence and the main cause of blindness among working-age population. The risk of severe vision loss can be significantly reduced by timely diagnosis and treatment. Systematic screening for DR has been identified as a cost-effective way to save health services resources. Automatic retinal image analysis is emerging as an important screening tool for early DR detection, which can reduce the workload associated to manual grading as well as save diagnosis costs and time. Many research efforts in the last years have been devoted to developing automatic tools to help in the detection and evaluation of DR lesions. However, there is a large variability in the databases and evaluation criteria used in the literature, which hampers a direct comparison of the different studies. This work is aimed at summarizing the results of the available algorithms for the detection and classification of DR pathology. A detailed literature search was conducted using PubMed. Selected relevant studies in the last 10 years were scrutinized and included in the review. Furthermore, we will try to give an overview of the available commercial software for automatic retinal image analysis.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

PubMed

Charbel Issa, Peter; Reuter, Peggy; Kühlewein, Laura; Birtel, Johannes; Gliem, Martin; Tropitzsch, Anke; Whitcroft, Katherine L; Bolz, Hanno J; Ishihara, Kenji; MacLaren, Robert E; Downes, Susan M; Oishi, Akio; Zrenner, Eberhart; Kohl, Susanne; Hummel, Thomas

2018-05-24

Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Genetics Home Reference: retinitis pigmentosa

MedlinePlus

... Email Facebook Twitter Home Health Conditions Retinitis pigmentosa Retinitis pigmentosa Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Retinitis pigmentosa is a group of related eye disorders that ...

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture.

PubMed

Cunha-Vaz, José

2017-01-01

Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal

Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.

PubMed

Sparrow, Janet R; Duncker, Tobias; Woods, Russell; Delori, François C

2016-01-01

Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina.

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Adaptive Optics Microperimetry and OCT Images Show Preserved Function and Recovery of Cone Visibility in Macular Telangiectasia Type 2 Retinal Lesions

PubMed Central

Wang, Qinyun; Tuten, William S.; Lujan, Brandon J.; Holland, Jennifer; Bernstein, Paul S.; Schwartz, Steven D.; Duncan, Jacque L.; Roorda, Austin

2015-01-01

Purpose. To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2. Methods. Adaptive optics scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss. Results. Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased with increasing eccentricity (slope = 0.054 au/degree, r2 = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT. Conclusions. Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.) PMID:25587056

Improvement of retinal blood vessel detection using morphological component analysis.

PubMed

Imani, Elaheh; Javidi, Malihe; Pourreza, Hamid-Reza

2015-03-01

Detection and quantitative measurement of variations in the retinal blood vessels can help diagnose several diseases including diabetic retinopathy. Intrinsic characteristics of abnormal retinal images make blood vessel detection difficult. The major problem with traditional vessel segmentation algorithms is producing false positive vessels in the presence of diabetic retinopathy lesions. To overcome this problem, a novel scheme for extracting retinal blood vessels based on morphological component analysis (MCA) algorithm is presented in this paper. MCA was developed based on sparse representation of signals. This algorithm assumes that each signal is a linear combination of several morphologically distinct components. In the proposed method, the MCA algorithm with appropriate transforms is adopted to separate vessels and lesions from each other. Afterwards, the Morlet Wavelet Transform is applied to enhance the retinal vessels. The final vessel map is obtained by adaptive thresholding. The performance of the proposed method is measured on the publicly available DRIVE and STARE datasets and compared with several state-of-the-art methods. An accuracy of 0.9523 and 0.9590 has been respectively achieved on the DRIVE and STARE datasets, which are not only greater than most methods, but are also superior to the second human observer's performance. The results show that the proposed method can achieve improved detection in abnormal retinal images and decrease false positive vessels in pathological regions compared to other methods. Also, the robustness of the method in the presence of noise is shown via experimental result. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Monte Carlo investigation on quantifying the retinal pigment epithelium melanin concentration by photoacoustic ophthalmoscopy.

PubMed

Shu, Xiao; Liu, Wenzhong; Zhang, Hao F

2015-10-01

The retinal pigment epithelium (RPE) melanin plays an important role in maintaining normal visual functions. A decrease in the RPE melanin concentration with aging is believed to be associated with several blinding diseases, including age-related macular degeneration. Quantifying the RPE melanin noninvasively is therefore important in evaluating the retinal health and aging conditions. Photoacoustic ophthalmoscopy (PAOM), as an optical absorption-based imaging technology, can potentially be applied to measure variations in the RPE melanin if the relationship between the detected photoacoustic (PA) signal amplitudes and the RPE melanin concentrations can be established. In this work, we tested the feasibility of using PA signals from retinal blood vessels as references to measure RPE melanin variation using Monte Carlo (MC) simulation. The influences from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness were examined. We proposed a calibration scheme by relating detected PA signals to the RPE melanin concentrations, and we found that the scheme is robust to these tested parameters. This study suggests that PAOM has the capability of quantitatively measuring the RPE melanin in vivo.

Monte Carlo investigation on quantifying the retinal pigment epithelium melanin concentration by photoacoustic ophthalmoscopy

NASA Astrophysics Data System (ADS)

Shu, Xiao; Liu, Wenzhong; Zhang, Hao F.

2015-10-01

The retinal pigment epithelium (RPE) melanin plays an important role in maintaining normal visual functions. A decrease in the RPE melanin concentration with aging is believed to be associated with several blinding diseases, including age-related macular degeneration. Quantifying the RPE melanin noninvasively is therefore important in evaluating the retinal health and aging conditions. Photoacoustic ophthalmoscopy (PAOM), as an optical absorption-based imaging technology, can potentially be applied to measure variations in the RPE melanin if the relationship between the detected photoacoustic (PA) signal amplitudes and the RPE melanin concentrations can be established. In this work, we tested the feasibility of using PA signals from retinal blood vessels as references to measure RPE melanin variation using Monte Carlo (MC) simulation. The influences from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness were examined. We proposed a calibration scheme by relating detected PA signals to the RPE melanin concentrations, and we found that the scheme is robust to these tested parameters. This study suggests that PAOM has the capability of quantitatively measuring the RPE melanin in vivo.

Retinal microvascular network geometry and cognitive abilities in community-dwelling older people: The Lothian Birth Cohort 1936 study

PubMed Central

McGrory, Sarah; Taylor, Adele M; Kirin, Mirna; Corley, Janie; Pattie, Alison; Cox, Simon R; Dhillon, Baljean; Wardlaw, Joanna M; Doubal, Fergus N; Starr, John M; Trucco, Emanuele; MacGillivray, Thomas J; Deary, Ian J