ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

PURPOSE: To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS: Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS: Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION: A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

CLINICAL CHARACTERISTICS OF EYES WITH DIFFERENT GRADES OF MYOPIC TRACTION MACULOPATHY: Based on the New Classification System.

PURPOSE: To analyze clinical characteristics in eyes with myopic traction maculopathy (MTM). METHODS: Nine hundred and ninety-one patients (1,334 eyes) with MTM, who visited Zhongshan Ophthalmic Center from January 2014 to December 2019, were involved. Myopic traction maculopathy was classified into six grades according to the new classification system: no macular schisis (T0), inner or outer foveoschisis (FS) (T1); inner and outer FS (T2), foveal detachment (T3), full-thickness macular hole (T4), and macular hole retinal detachment (T5). RESULTS: Seven hundred and seventy-eight (58.32%) eyes were in T0, 157 (11.77%) in T1, 177 (13.27%) in T2, 129 (9.67%) in T3, 45 (3.37%) in T4, and 48 (3.67%) in T5. With the severity of MTM, age increased and the best-corrected visual acuity became worse (P < 0.001). However, no significant differences were found on spherical equivalent refraction or axial length among different grades of MTM (P > 0.05). Moreover, significant differences on best-corrected visual acuity, spherical equivalent refraction, axial length, and staphyloma rate existed between eyes with inner FS and eyes with outer FS (P < 0.01), but not between eyes with outer FS and eyes with both inner FS and outer FS (P > 0.05). Besides, significant differences were found on spherical equivalent refraction, axial length, and staphyloma rate between full-thickness macular hole with and without macular schisis (P < 0.001). CONCLUSION: Spherical equivalent refraction and axial length were not correlated with the severity of MTM in this cohort. It might be preferable to categorize eyes with outer FS and eyes with both inner FS and outer FS as a same grade. Potential difference in the pathogenesis between full-thickness macular hole with and without macular schisis might exist.

Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 4.

PURPOSE: To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. DESIGN: Consensus meeting. PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. MAIN OUTCOME MEASURES: Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. RESULTS: OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. CONCLUSIONS: An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated.

IDENTIFICATION AND CLASSIFICATION OF MACULAR MORPHOLOGIC BIOMARKERS RELATED TO VISUAL ACUITY IN RADIATION MACULOPATHY: A Multimodal Imaging Study.

PURPOSE: To identify and classify, by a multimodal imaging approach, the most relevant macular morphologic biomarkers related to visual acuity in patients affected by radiation maculopathy secondary to brachytherapy. METHODS: Fifty-one consecutive patients previously treated with Iodine-125 brachytherapy because of uveal melanoma were enrolled. Each patient underwent full ophthalmologic examination including best-corrected visual acuity and multimodal macular imaging analysis. Macular morphological parameters were processed by a stepwise selection analysis. RESULTS: Three macular parameters were identified as the most relevant macular morphologic biomarkers of poor visual acuity: the vertical thickness of the thickest macular cyst (P = 0.0001), the presence of foveal inner segment/outer segment (IS/OS) layer disruption (P = 0.0054), and the presence of foveal retinal pigment epithelium atrophy (0.0884). The intergrader agreement for these morphologic biomarkers was 0.98, 0.92, and 0.92, respectively (interclass correlation coefficient). CONCLUSION: The vertical thickness of the thickest macular cyst, the presence of foveal retinal pigment epithelium atrophy, and IS/OS layer disruption can be used to clinically characterize radiation maculopathy. These parameters allow for separation of the edematous component of radiation maculopathy, which is potentially treatable in early disease stages, from late onset atrophic components, which are theoretically irreversible.

CHARACTERISTICS AND CLASSIFICATION OF TYPE 3 NEOVASCULARIZATION WITH B-SCAN FLOW OVERLAY AND EN FACE FLOW IMAGES OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study B-scan flow overlay and en face flow optical coherence tomography angiography (OCT-A) images of Type 3 neovascularization (NV) and to characterize a staging system for Type 3 NV based on the OCT-A findings. METHODS: We retrospectively collected data on consecutive treatment-naive eyes with Type 3 NV. All eyes underwent fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCT-A (AngioPlex). Localization and extension of abnormal flows detected by B-scan flow overlay and en face OCT-A images were assessed. RESULTS: Of 24 eyes of 22 patients with Type 3 NV, B-scan flow overlay images showed that 4.2% had telangiectatic flow in the deep retinal layer without outer plexiform layer disruption (Stage 1), 8.3% had downward intraretinal flow and subretinal flow without retinal pigment epithelium disruption (Stage 2), and 87.5% had downward flow and retinal pigment epithelium disruption (Stage 3). Of the Stage 3 eyes, 95.2% showed flow signal penetrating at the site of the retinal pigment epithelium disruption on the B-scan flow overlay images. CONCLUSION: We showed the characteristics of Type 3 NV using B-scan flow overlay and en face OCT-A images. B-scan flow overlay OCT-A images seem useful to improve the detection and accurate diagnosis of Type 3 NV.

DISEASE CLASSIFICATION OF MACULAR OPTICAL COHERENCE TOMOGRAPHY SCANS USING DEEP LEARNING SOFTWARE: Validation on Independent, Multicenter Data.

PURPOSE: To evaluate Pegasus optical coherence tomography (OCT), a clinical decision support software for the identification of features of retinal disease from macula OCT scans, across heterogenous populations involving varying patient demographics, device manufacturers, acquisition sites, and operators. METHODS: Five thousand five hundred and eighty-eight normal and anomalous macular OCT volumes (162,721 B-scans), acquired at independent centers in five countries, were processed using the software. Results were evaluated against ground truth provided by the data set owners. RESULTS: Pegasus-OCT performed with areas under the curve of the receiver operating characteristic of at least 98% for all data sets in the detection of general macular anomalies. For scans of sufficient quality, the areas under the curve of the receiver operating characteristic for general age-related macular degeneration and diabetic macular edema detection were found to be at least 99% and 98%, respectively. CONCLUSION: The ability of a clinical decision support system to cater for different populations is key to its adoption. Pegasus-OCT was shown to be able to detect age-related macular degeneration, diabetic macular edema, and general anomalies in OCT volumes acquired across multiple independent sites with high performance. Its use thus offers substantial promise, with the potential to alleviate the burden of growing demand in eye care services caused by retinal disease.

Age-related macular degeneration.

Age-related macular degeneration is a leading cause of visual impairment and severe vision loss. Clinically, it is classified as early-stage (medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic). Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids). Progression from early-stage to late-stage disease can be slowed with high-dose zinc and antioxidant vitamin supplements. Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab, aflibercept, or bevacizumab) is highly effective at treating neovascular age-related macular degeneration, and has markedly decreased the prevalence of visual impairment in populations worldwide. Currently, no proven therapies for atrophic disease are available, but several agents are being investigated in clinical trials. Future progress is likely to be from improved efforts in prevention and risk-factor modification, personalised medicine targeting specific pathways, newer anti-vascular endothelial growth factor agents or other agents, and regenerative therapies.

Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3.

PURPOSE: To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). DESIGN: Consensus meeting. PARTICIPANTS: Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. METHODS: As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. MAIN OUTCOME MEASURES: A consensus classification system for atrophy and OCT-based criteria to identify atrophy. RESULTS: OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 µm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 µm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. CONCLUSIONS: A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

IMPROVING THE AGE-RELATED MACULAR DEGENERATION CONSTRUCT: A New Classification System.

Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

[Exudative AMD in OCT Angiography]. / Exsudative AMD in der OCT-Angiografie.

OCT angiography provides a combination of vascular and structural information. In contrast to conventional fluorescein angiography, there is no need for dye injection to give an image of choroidal neovascularisation. Although there is currently no classification of OCT angiography, different neovascular patterns can be observed, with criteria for activity. In the future, OCT angiography may help us to understand pathophysiological mechanisms and to develop therapeutic strategies.

Validating the AREDS Simplified Severity Scale of Age-Related Macular Degeneration with 5- and 10-Year Incident Data in a Population-Based Sample.

PURPOSE: Most classification systems for age-related macular degeneration (AMD) were developed from patients in clinical trials. We aimed to validate the Age-Related Eye Diseases Study (AREDS) simplified severity scale of AMD classification using 5- and 10-year incident late AMD data from the population-based Blue Mountains Eye Study (BMES) cohort. DESIGN: Comparative study of population-based cohort and clinical trial. PARTICIPANTS: Blue Mountains Eye Study participants 40 to 97 years of age at baseline (n = 2134) and AREDS participants 55 to 80 years of age (n = 3640). METHODS: In the BMES, AMD lesions were graded from stereoscopic color photographs and were classified according to the AREDS simplified severity scale. The AREDS simplified scale calculates a risk score based on the number of early AMD risk factors (large drusen and pigment abnormalities) in both eyes that can range from 0 to 4. MAIN OUTCOME MEASURES: Five- and 10-year incident late AMD (presence of geographic atrophy or choroidal neovascularization). RESULTS: The AREDS simplified scale performed similarly when applied to both the BMES population-based participants and the AREDS clinical trial-based participants in predicting 5- and 10-year incidence of late AMD. For scores 0 to 4, the 5-year incidence rates for the BMES compared with the AREDS were 0.2% versus 0.4%, 3.1% versus 3.1%, 12.1% versus 11.8%, 13.5% versus 25.9%, and 47.1% versus 47.3%, respectively. The corresponding 10-year incidence rates for the BMES compared with the AREDS were 0.7% versus 1.5%, 7.3% versus 8.4%, 36.6% versus 27.6%, 20.0% versus 52.7%, and 75.0% versus 71.4%, respectively. CONCLUSIONS: The AREDS simplified severity scale classified late AMD risk levels similarly when applied to population-based and clinical trial samples. These results support the robustness of the AREDS simplified severity scale.

Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration.

PURPOSE: To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later. DESIGN: Prospective cohort. PARTICIPANTS: Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators. METHODS: Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD. MAIN OUTCOME MEASURES: Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline. RESULTS: Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline. CONCLUSIONS: Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, 2 tissues with prominent age- and AMD-related pathology.

HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. RESULTS: Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. CONCLUSION: Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

Genetic factors associated with the development of age-related macular degeneration.

Age-related macular degeneration (AMD) affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people aged more than 60 years. This disease affects 2.5 million individuals in Europe. AMD is caused by both environmental and genetic factors. Numerous risk factors have been reported, but the pathogenesis of AMD is complex and fairly understood. Age, female gender, obesity, race, education status, family history, hyperopia, iris color, cigarette smoking, previous cataract surgery, history of cardiovascular and cerebrovascular disease, diabetes, sunlight exposure and many other factors have been shown to be associated with AMD development. Scientific evidence shows that genes may play a role in the development of nearly 3 out of 4 cases of this devastating eye disease. The genes that have been shown to be associated with AMD are genes encoding complement system components such as CFH, C2, C3, CFB, and other.

A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration-Like Lesions at the Peripheral Retina.

PURPOSE: Our understanding of the relevance of peripheral retinal abnormalities to disease in general and in age-related macular degeneration (AMD) in particular is limited by the lack of detailed peripheral imaging studies. The purpose of this study was to develop image grading protocols suited to ultra-widefield imaging (UWFI) in an aged population. DESIGN: A cross-sectional study of a random population sample in which UWFI was introduced at the 12-year review of the Reykjavik Eye Study in Iceland. PARTICIPANTS: Five hundred seventy-six subjects 62 years of age or older. METHODS: Ultra-widefield (up to 200°) color and autofluorescence images were obtained using the Optos P200CAF laser scanning ophthalmoscope (Optos plc, Dunfermline, Scotland). The images were graded at Moorfields Eye Hospital Reading Centre primarily based on the International Classification for AMD. Macular and peripheral changes were graded using a standardized grid developed for this imaging method. MAIN OUTCOME MEASURES: Presence or absence of hard, crystalline, and soft drusen; retinal pigment epithelial changes; choroidal neovascularization (CNV); atrophy; and hypoautofluorescence and hyperautofluorescence were graded in the peripheral retina. RESULTS: Of the eyes examined, 81.1% had AMD-like changes in the macula alone (13.6%), periphery alone (10.1%), and both periphery and macula (57.4%). There was no AMD-like CNV or pigment epithelial detachment in the periphery except in those cases in which these clearly originated from the macula. Seven patients had AMD-like atrophy in the periphery without end-stage disease in the macula. One patient with end-stage disease in the macula had normal periphery results on the color images. While analyzing the eyes, we detected pathologic appearances that were very reliably identified by graders. CONCLUSIONS: Phenotyping the retinal periphery using the categories defined by the International Classification confirmed the presence of wide-ranging AMD-like pathologic changes even in those without central sight-threatening macular disease. Based on our observations, we propose here new, reliably identifiable grading categories that may be more suited for population-based UWFI.

Changes in lens opacities on the age-related eye disease study grading scale predict progression to cataract surgery and vision loss: age-related eye disease study report no. 34.

PURPOSE: To investigate whether the 2-year change in lens opacity severity on the Age-Related Eye Disease Study (AREDS) lens grading scale predicts progression to cataract surgery or loss of visual acuity by 5 years. DESIGN: Prospective cohort study within a randomized clinical trial of oral supplements. PARTICIPANTS: The AREDS participants whose eyes were phakic at baseline and free of late age-related macular degeneration throughout the study. METHODS: Baseline and annual lens photographs of AREDS participants (n = 3466/4757; 73%) were graded for severity of cataracts using the AREDS system for classifying cataracts from photographs. Clinical examinations conducted semiannually collected data on cataract surgery and visual acuity. Association of the change in lens opacities at 2 years with these outcomes at 5 years was analyzed with adjusted Cox proportional hazard models. MAIN OUTCOME MEASUREMENTS: Progression of lens opacities on stereoscopic lens photographs at 2 years, cataract surgery, and visual acuity loss of 2 lines or more at 5 years. RESULTS: The adjusted hazard ratios (HRs) for association of progression to cataract surgery at 5 years were: nuclear cataract increase of 1.0 unit or more compared with less than 1.0-unit change at 2 years, 2.77 (95% confidence interval [CI], 2.07-3.70; P < 0.001); cortical cataract increase of 5% or more in lens opacity in the central 5 mm of the lens compared with less than 5% increase at 2 years, 1.91 (95% CI, 1.27-2.87; P = 0.002); and posterior subcapsular cataract increase of 5% or more versus less than 5% in the central 5 mm of the lens, 8.25 (95% CI, 5.55-12.29; P < 0.001). Similarly, HRs of vision loss of 2 lines or more at 5 years for this degree of lens changes at 2 years were the following: nuclear, 1.83 (95% CI, 1.49-2.25; P < 0.001); cortical, 1.13 (95% CI, 0.78-1.65; P = 0.519); and posterior subcapsular cataract, 3.05 (95% CI, 1.79-5.19; P < 0.001). CONCLUSIONS: Two-year changes in severity of lens opacities on the AREDS lens grading scale are predictive of long-term clinically relevant outcomes, making them potential surrogate end points in follow-up studies.

Is aspirin use associated with age-related macular degeneration? A meta-analysis.

WHAT IS KNOWN AND OBJECTIVES: Aspirin is one of the most widely used medications in the world. The evidence on its effect on the risk of age-related macular degeneration (AMD) appears inconsistent across different types of studies. The aim of this meta-analysis was to evaluate the association between aspirin use and the risk of AMD. METHODS: Relevant studies were searched using databases including PubMed, EMBASE, Cochrane Library and MEDLINE up to March 2014. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects or fixed-effect models. The heterogeneity was assessed by the inconsistency index (I(2) ). The publication bias was evaluated by Begg's funnel plot and Egger's weighted regression. Sensitivity analysis was also performed in different ways. RESULTS: Ten eligible studies including 180 834 individuals based on the inclusion criteria were analysed in this meta-analysis. The pooled RR for the aspirin use on the risk of AMD was 1·137 (95% CI, 1·003-1·289; I(2) , 68·4%). The pooled RR for the aspirin use on the risk of early and late AMD was 1·19 (95% CI, 0·92-1·53; I(2) , 82·6%) and 1·22 (95% CI, 0·87-1·72; I(2) , 55·7%), respectively. In different types of late AMD, the pooled RR was 1·95 (95% CI, 1·40-2·72; I(2) , 27%) for neovascularization and 0·84 (95% CI, 0·62-1·15; I(2) , 0%) for geographic atrophy. The pooled RR in studies with standardized AMD classification was 1·307 (95% CI, 1·006-1·698; I(2) , 79·2%). WHAT IS NEW AND CONCLUSION: This meta-analysis updates similar reviews that included studies with various types of biases. A rigorous analysis shows a weak but statistically significant association between aspirin use and the risk of AMD; a result which is different to that previously reported.

Quantitative classification of eyes with and without intermediate age-related macular degeneration using optical coherence tomography.

OBJECTIVE: To define quantitative indicators for the presence of intermediate age-related macular degeneration (AMD) via spectral-domain optical coherence tomography (SD-OCT) imaging of older adults. DESIGN: Evaluation of diagnostic test and technology. PARTICIPANTS AND CONTROLS: One eye from 115 elderly subjects without AMD and 269 subjects with intermediate AMD from the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. METHODS: We semiautomatically delineated the retinal pigment epithelium (RPE) and RPE drusen complex (RPEDC, the axial distance from the apex of the drusen and RPE layer to Bruch's membrane) and total retina (TR, the axial distance between the inner limiting and Bruch's membranes) boundaries. We registered and averaged the thickness maps from control subjects to generate a map of "normal" non-AMD thickness. We considered RPEDC thicknesses larger or smaller than 3 standard deviations from the mean as abnormal, indicating drusen or geographic atrophy (GA), respectively. We measured TR volumes, RPEDC volumes, and abnormal RPEDC thickening and thinning volumes for each subject. By using different combinations of these 4 disease indicators, we designed 5 automated classifiers for the presence of AMD on the basis of the generalized linear model regression framework. We trained and evaluated the performance of these classifiers using the leave-one-out method. MAIN OUTCOME MEASURES: The range and topographic distribution of the RPEDC and TR thicknesses in a 5-mm diameter cylinder centered at the fovea. RESULTS: The most efficient method for separating AMD and control eyes required all 4 disease indicators. The area under the curve (AUC) of the receiver operating characteristic (ROC) for this classifier was >0.99. Overall neurosensory retinal thickening in eyes with AMD versus control eyes in our study contrasts with previous smaller studies. CONCLUSIONS: We identified and validated efficient biometrics to distinguish AMD from normal eyes by analyzing the topographic distribution of normal and abnormal RPEDC thicknesses across a large atlas of eyes. We created an online atlas to share the 38 400 SD-OCT images in this study, their corresponding segmentations, and quantitative measurements.

Visual acuity after cataract surgery in patients with age-related macular degeneration: age-related eye disease study 2 report number 5.

OBJECTIVE: To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. METHODS: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. RESULTS: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). CONCLUSIONS: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity.