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Purpose: To develop and validate a deep learning model for the automatic segmentation of geographic atrophy (GA) using color fundus images (CFIs) and its application to study the growth rate of GA., Design: Prospective, multicenter, natural history study with up to 15 years of follow-up., Participants: Four hundred nine CFIs of 238 eyes with GA from the Rotterdam Study (RS) and Blue Mountain Eye Study (BMES) for model development, and 3589 CFIs of 376 eyes from the Age-Related Eye Disease Study (AREDS) for analysis of GA growth rate., Methods: A deep learning model based on an ensemble of encoder-decoder architectures was implemented and optimized for the segmentation of GA in CFIs. Four experienced graders delineated, in consensus, GA in CFIs from the RS and BMES. These manual delineations were used to evaluate the segmentation model using 5-fold cross-validation. The model was applied further to CFIs from the AREDS to study the growth rate of GA. Linear regression analysis was used to study associations between structural biomarkers at baseline and the GA growth rate. A general estimate of the progression of GA area over time was made by combining growth rates of all eyes with GA from the AREDS set., Main Outcome Measures: Automatically segmented GA and GA growth rate., Results: The model obtained an average Dice coefficient of 0.72±0.26 on the BMES and RS set while comparing the automatically segmented GA area with the graders' manual delineations. An intraclass correlation coefficient of 0.83 was reached between the automatically estimated GA area and the graders' consensus measures. Nine automatically calculated structural biomarkers (area, filled area, convex area, convex solidity, eccentricity, roundness, foveal involvement, perimeter, and circularity) were significantly associated with growth rate. Combining all growth rates indicated that GA area grows quadratically up to an area of approximately 12 mm 2 , after which growth rate stabilizes or decreases., Conclusions: The deep learning model allowed for fully automatic and robust segmentation of GA on CFIs. These segmentations can be used to extract structural characteristics of GA that predict its growth rate., (Copyright © 2020 American Academy of Ophthalmology. All rights reserved.)

Purpose: To report the 6-year incidence of cataract surgery in an Asian population-based cohort of Malay, Indian, and Chinese persons living in Singapore and factors associated with undergoing cataract surgery over the follow-up period., Design: Population-based prospective cohort study., Participants: From 2004 through 2011, 10 033 participants (3280 Malays, 3400 Indians, and 3353 Chinese) 40 years of age or older participated in the Singapore Epidemiology of Eye Diseases Study. Six years later, 6762 participants (78.7% of those eligible, including 1901 Malays [72.1% of eligible], 2200 Indians [75.5% of eligible], and 2661 Chinese [87.7% of eligible]) were re-examined., Methods: Detailed eye examinations including slit-lamp biomicroscopy were conducted at both visits. Logistic regression models were used to assess factors associated with cataract surgery after adjusting for age, gender, socioeconomic status, and other risk factors., Main Outcome Measure: Incident cataract surgery., Results: The age-adjusted 6-year incidence of cataract surgery was 11.0% (9.5%, 12.6%, and 11.1% for Malays, Indians, and Chinese, respectively) and was strongly age related (P < 0.001 for trend). After adjustment, baseline factors associated with incident cataract surgery included older age (odds ratio [OR], 1.13 per 1-year increase; 95% confidence interval [CI], 1.11-1.14), diabetes (OR, 1.90; 95% CI, 1.54-2.33), myopia (OR, 1.78; 95% CI, 1.44-2.20), and baseline presence of any cataract, including nuclear cataract (OR, 3.78; 95% CI, 2.91-4.89), cortical cataract (OR, 3.01; 95% CI, 2.45-3.71), and posterior subcapsular cataract (OR, 5.00; 95% CI, 3.91-6.41). The population attributable risks of cataract surgery related to diabetes and myopia were 17.6% and 19.1%, respectively., Conclusions: One in 10 Malay, Indian, and Chinese Singaporeans 40 years of age or older underwent cataract surgery in at least 1 eye over 6 years. In Asian populations, diabetes and myopia, 2 well-known factors associated with cataract prevalence, are significant and potentially modifiable factors associated with the need for cataract surgery., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study., Design: Population-based, cross-sectional study., Participants: Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore., Methods: Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system., Main Outcome Measures: Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME)., Results: Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P = 0.012); a similar trend was noted for any DME (P = 0.001) and CSME (P = 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups., Conclusions: Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians., Design: Prospective, population cohort study., Participants: The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part., Methods: Fundus photographs were graded using the Wisconsin AMD grading system., Main Outcome Measures: Incidence of early and late AMD., Results: Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%)., Conclusions: This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Genetic association studies to date have not identified any robust risk loci for diabetic retinopathy (DR). We hypothesized that individuals with more diabetes genetic risk alleles have a higher risk of developing DR., Design: Case-control genetic association study., Participants: We evaluated the aggregate effects of multiple type 2 diabetes-associated genetic variants on the risk of DR among 1528 participants with diabetes from the Singapore Epidemiology of Eye Diseases Study, of whom 547 (35.8%) had DR., Methods: Participants underwent a comprehensive ocular examination, including dilated fundus photography. Retinal photographs were graded using the modified Airlie House classification system to assess the presence and severity of DR following a standardized protocol. We identified 76 previously discovered type 2 diabetes-associated single nucleotide polymorphisms (SNPs) and constructed multilocus genetic risk scores (GRSs) for each individual by summing the number of risk alleles for each SNP weighted by the respective effect estimates on DR. Two GRSs were generated: an overall GRS that included all 76 discovered type 2 diabetes-associated SNPs, and an Asian-specific GRS that included a subset of 55 SNPs previously found to be associated with type 2 diabetes in East and/or South Asian ancestry populations. Associations between the GRSs with DR were determined using logistic regression analyses. Discriminating ability of the GRSs was determined by the area under the receiver operating characteristic curve (AUC)., Main Outcome Measures: Odds ratios on DR., Results: Participants in the top tertile of the overall GRS were 2.56-fold more likely to have DR compared with participants in the lowest tertile. Participants in the top tertile of the Asian-specific GRS were 2.00-fold more likely to have DR compared with participants in the bottom tertile. Both GRSs were associated with higher DR severity levels. However, addition of the GRSs to traditional risk factors improved the AUC only modestly by 3% to 4%., Conclusions: Type 2 diabetes-associated genetic loci were significantly associated with higher risks of DR, independent of traditional risk factors. Our findings may provide new insights to further our understanding of the genetic pathogenesis of DR., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the 15-year incidence and progression of age-related macular degeneration (AMD) in an older Australian population., Design: Population-based cohort study., Participants: Blue Mountains Eye Study (BMES) participants (n = 3654) aged 49+ years were examined during 1992-1994. Of these, 2334 (75.8% of survivors) were reexamined after 5 years (1997-1999), 1952 (76.7% of survivors) after 10 years (2002-2004), and 1149 (56.1% of survivors) after 15 years (2007-2010)., Methods: Color retinal photographs were taken, and comprehensive questionnaires were administered at each visit and DNA was genotyped. Retinal photographic grading was performed by the same graders following the Wisconsin AMD grading protocol. Side-by-side comparisons were used to confirm newly developed AMD lesions. Incidence was estimated using Kaplan-Meier estimates. Associations of AMD incidence with age, sex, smoking status, presence of the complement factor H (CFH)-rs1061170 and age-related maculopathy susceptibility 2 (ARMS2)-rs10490924 polymorphisms, and fish consumption were analyzed using discrete logistic regression models. Generalized estimation equation models were used to assess the risk of incident late AMD associated with baseline AMD lesion characteristics., Main Outcome Measures: The 15-year incidence and progression of AMD, and associated factors., Results: The 15-year incidence was 22.7% for early AMD and 6.8% for late AMD. After adjusting for competing risks, early and late AMD incidence were 15.1% and 4.1%, respectively. Age was strongly associated with early and late AMD incidence (both P < 0.0001). After age standardization to the Beaver Dam Eye Study (BDES) population, early and late AMD incidence in the BMES were 13.1% and 3.3%, respectively. Female sex and the presence of both risk alleles of CFH-rs1061170 or ARMS2-rs10490924 were independently associated with early AMD incidence, whereas current smoking and presence of ≥1 risk allele of CFH-rs1061170 or ARMS2-rs10490924 were associated with late AMD incidence. Fish consumption was inversely associated with late but not early AMD incidence. Severity of early AMD lesion characteristics was a strong predictor of progression to late AMD., Conclusions: We documented the 15-year incidence of early and late AMD in an older Australian population that were comparable to BDES observations. Risk of progression to late AMD was strongly associated with severity of early AMD lesions., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population., Design: Population-based, cross-sectional study., Participants: A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study., Methods: Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry., Main Outcome Measures: Age-related cataract., Results: A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays., Conclusions: We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons., Design: Population-based cross-sectional study., Participants: A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore., Methods: We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models., Main Outcome Measures: Early and late AMD., Results: Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88)., Conclusions: Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the 15-year incidence and progression of reticular drusen and associations of this lesion with age-related macular degeneration (AMD) risk factors., Design: Population-based cohort., Participants: Blue Mountains Eye Study participants (n = 3654) 49 years of age and older attended baseline examinations; of these, 75.8%, 76.7%, and 56.1% of survivors attended 5-year, 10-year, and 15-year follow-up examinations, respectively., Methods: Color retinal photographs were obtained and comprehensive questionnaires were administered at each visit, and DNA samples were genotyped. Fundus autofluorescence images were not available. Reticular drusen identified from photographs were confirmed with side-by-side grading using the Wisconsin AMD grading protocol. Incidence was assessed using Kaplan-Meier product limit survival methods, controlling for competing risk of death. Associations between smoking, fish consumption, serum lipids, systemic and dietary factors, the CFH single nucleotide polymorphism (SNP) rs1061170 and ARMS2 SNP rs10490924, and the 15-year incidence of reticular drusen were analyzed in discrete logistic regression models. Generalized estimating equation models were used to analyze eye-specific relationships between these risk factors and 5-year progression from reticular drusen to late AMD., Main Outcome Measures: Incidence and progression of reticular drusen., Results: The 15-year cumulative incidence of reticular drusen was 4.0% (n = 95). Increasing age (per decade increase; odds ratio [OR], 3.4; 95% confidence interval [CI], 2.6-4.4), female sex (OR, 2.0; 95% CI, 1.3-3.2), and presence of risk alleles of CFH-rs1061170 (OR, 1.8; 95% CI, 1.3-2.4) or ARMS2-rs10490924 (OR, 3.0; 95% CI, 2.1-4.4) were associated with higher reticular drusen incidence. Current smoking at baseline predicted higher reticular drusen incidence (OR 2.1, 95% CI 1.0-4.5) after adjusting for age, sex, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Of 118 eyes with reticular drusen, 40 (33.9%) developed late AMD over 5 years. A higher proportion of eyes with reticular drusen located outside versus within the macular area progressed to late AMD (50.0% vs. 37.8%). Dietary lutein-zeaxanthin intake was associated with decreased likelihood of progression from reticular drusen to late AMD (adjusted OR, 0.5; 95% CI, 0.3-1.0)., Conclusions: Known AMD risk factors were associated with greater long-term risk of reticular drusen. Neither total area nor central location of reticular drusen predicted 5-year progression to late AMD. Increased consumption of lutein-zeaxanthin predicted a lower risk of progression., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk., Design: Pooled data analysis of population-based cohorts., Participants: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS)., Methods: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses., Main Outcome Measures: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale., Results: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status., Conclusions: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies., Design: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC)., Participants: People (n = 10,106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline., Methods: Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to construct a risk score, and risk of incident late AMD was calculated using Cox proportional hazard analysis. Cumulative incident risks were estimated using Kaplan-Meier product-limit analysis., Main Outcome Measures: Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits., Results: Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95% confidence interval [CI], 0.01-0.04) to develop late AMD, and individuals with high-risk scores had an HR of 22.0 (95% CI, 15.2-31.8). Cumulative risk of incident late AMD ranged from virtually 0 to more than 65% for those with the highest risk scores., Conclusions: Our prediction model is robust and distinguishes well between those who will develop late AMD and those who will not. Estimated risks were lower in these population-based studies than in previous case-control studies., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To describe the change in visual acuity (VA) and incidence of visual impairment (VI) in an older population over a 15-year period., Design: Population-based cohort., Participants: Of the 3654 participants of the Blue Mountains Eye Study (BMES) baseline examination from 1992 through 1994, 1149 were re-examined during the 15-year follow-up between 2007 and 2010., Methods: Best-corrected VA by means of subjective refraction was measured with a logarithm of the minimum angle of resolution chart using Early Treatment Diabetic Retinopathy Study methods at each examination., Main Outcome Measures: Unilateral VI was defined as VA worse than 20/40 and blindness was defined as VA worse than 20/200 in the worse eye. Incident bilateral VI and blindness were determined according to VA in the better eye at the 15-year visit. Doubling of the visual angle was defined as a loss of 15 letters or more from baseline to the 15-year visit. Halving of the visual angle was defined as a VA improvement of 15 letters or more over the same period. Causes of VI were determined at examination, by photographic grading, and from medical records., Results: Cumulative 15-year incidence of unilateral and bilateral VI was 12.3% (95% confidence interval [CI], 11.0-13.6) and 5.2% (95% CI, 4.3-6.1), respectively, and for unilateral and bilateral blindness, the cumulative incidence was 3.7% (95% CI, 3.0-4.4) and 0.9% (95% CI, 0.5-1.3), respectively. These incidence rates increased significantly with increasing age (P<0.01 for trend). Doubling and halving of the visual angle occurred in 6.9% (95% CI, 5.9-7.9) and 1.6% (95% CI, 1.0-2.2) of participants, respectively. Cataract accounted for 48.5% of unilateral and bilateral incident VI, followed by age-related macular degeneration (26.9%). Age-related macular degeneration accounted for 56.9% of unilateral and bilateral incident blindness cases, followed by cataract (20.7%)., Conclusions: These data provide population-based estimates of long-term incidence of visual impairment among older persons. Our estimate for cumulative incidence of blindness, accounting for competing risk of death, was similar to that of the Beaver Dam Eye Study (BDES) after age standardization. However, our estimate for cumulative incidence of VI was lower compared with that observed in the BDES population. This difference may be explained in part by a higher mortality rate among our population., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine early age-related macular degeneration (AMD) lesion characteristics and risk factors associated with the long-term development and progression of geographic atrophy (GA)., Design: Population-based cohort., Participants: Of 3654 participants aged ≥49 years in the Blue Mountains Eye Study, 75.8%, 76.7%, and 56.1% of survivors attended the 5-, 10-, and 15-year follow-up examinations, respectively., Methods: Retinal photographs were taken at each visit. Incident GA was confirmed using a side-by-side grading method. Computer planimetry was used to measure the area involved by GA. Fast and slow/normal progression rates were defined as GA area enlargement by ≥2 and <2 mm(2)/year, respectively. Incident GA was estimated using the Kaplan-Meier product-limit method. Early AMD lesion characteristics were assessed for association with GA incidence using eye-specific data and generalized estimating equation models adjusting for age, current smoking, and presence of risk alleles of the complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS2) genes, genotyped or imputed using genome-wide scan data., Main Outcome Measures: Incidence and progression of GA., Results: By excluding 41 subjects with GA at baseline, of 2503 participants at risk of GA, incident pure GA (without coexisting neovascular AMD lesions) was confirmed in 57 participants, with a 15-year incidence of 3.6%. Baseline early AMD lesion characteristics associated with GA incidence included drusen type (soft indistinct: odds ratio [OR], 59.0; 95% confidence interval [CI], 20.4-171.0; reticular drusen: OR, 13.9; 95% CI, 4.0-47.6); drusen location within a 500-μm radius of the fovea (OR, 15.1; 95% CI, 7.4-30.8); drusen area greater than 375 μm in diameter (OR, 10.1; 95% CI, 4.0-25.6); presence of retinal pigment epithelial depigmentation (OR, 9.0; 95% CI, 4.1-19.8); or hyperpigmentation (OR, 12.0; 95% CI, 6.1-23.5), referenced to subjects with no or hard drusen only. Fast progression was more frequent among current smokers at baseline, subjects with the CFH or ARMS2 risk genotypes, and pseudophakic eyes., Conclusions: Early AMD lesion characteristics (type, location, area involved) were strongly associated with higher long-term risk of developing GA independent of age, smoking, and AMD genetic susceptibility from the CFH or ARMS2 genes. Known AMD risk factors also were more frequently present among quickly progressing GA cases., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: We assessed whether correction of visual impairment (VI) by cataract surgery was associated with improved long-term survival in an older Australian population., Design: Population-based cohort study., Participants: In the Blue Mountains Eye Study, 354 participants, aged ≥ 49 years, had both cataract and VI or had undergone cataract surgery before baseline examinations. They were subsequently examined after 5- and 10-year follow-ups., Methods: Associations between the mortality risk and the surgical correction of VI (visual acuity [VA] <20/40, attributable to cataract) were assessed in Cox proportional hazard regression models, after multivariate adjustment, using time-dependent variables for the study factor., Main Outcome Measures: All-cause mortality., Results: The 15-year crude mortality of participants who had undergone cataract surgery at baseline with no subsequent VI (71.8%) was relatively similar to that in participants with cataract-related VI who had not yet undergone surgery (79.4%). However, after adjusting for age and sex, participants who underwent cataract surgery before baseline or during follow-up and no longer had VI had significantly lower long-term mortality risk (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.77) than participants with VI due to cataract who had not undergone cataract surgery. This lower mortality risk in the group with surgically corrected VI (HR, 0.54; 95% CI, 0.41-0.73) persisted after further adjustment for smoking, body mass index, home ownership, qualifications, poor self-rated health, the presence of poor mobility, hypertension, diabetes, self-reported history of angina, myocardial infarction, stroke, cancer, asthma, and arthritis. This finding remained significant (HR, 0.55; 95% CI, 0.41-0.73) after additional adjustment for the number of medications taken (continuous variable) and the number (≥ 5 vs. <5) of comorbid conditions (poor mobility, hypertension, diabetes, angina, myocardial infarction, stroke, cancer, asthma, or arthritis) as indicators of frailty., Conclusions: Surgical correction of VI due to cataract was associated with significantly better long-term survival of older persons after accounting for known cataract and mortality risk factors, and indicators of general health. Whether some uncontrolled factors (frailty or general health) could have influenced decisions not to perform cataract surgery in some participants is unknown. However, this finding strongly supports many previous reports linking VI with poor survival., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract, and primary open-angle glaucoma (POAG)., Design: Population-based, cross-sectional study., Participants: A total of 3400 Indians (75.6% response rate) aged 40 to 84 years in Singapore., Methods: Refractive error was determined by subjective refraction, and AL was determined by noncontact partial coherence laser interferometry. Age-related macular degeneration and DR were defined from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. Age-related cataract was diagnosed clinically using the Lens Opacity Classification System (LOCS) III system. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria., Main Outcome Measures: Age-related macular degeneration, DR, age-related cataract, and POAG., Results: Myopic eyes (spherical equivalent [SE] <-0.5 diopter [D]) were less likely to have AMD (early plus late AMD) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.79) or DR (OR, 0.68; 95% CI, 0.46-0.98) compared with emmetropic eyes; each millimeter increase in AL was associated with a lower prevalence of AMD (OR, 0.76; 95% CI, 0.65-0.89) and DR (OR, 0.73; 95% CI, 0.63-0.86). Myopic eyes were more likely to have nuclear (OR, 1.57; 95% CI, 1.13-2.20) and posterior subcapsular (OR, 1.73; 95% CI, 1.10-2.72) cataract, but not cortical cataract (P = 0.64); each millimeter increase in AL was associated with a higher prevalence of posterior subcapsular cataract (PSC) (OR, 1.29; 95% CI, 1.07-1.55), but not nuclear (P = 0.77) or cortical (P = 0.39) cataract. Eyes with high myopia (SE <-6.0 D) were more likely to have POAG (OR, 5.90; 95% CI, 2.68-12.97); each millimeter increase in AL was associated with a higher prevalence of POAG (OR, 1.43; 95% CI, 1.13-1.80)., Conclusions: Myopic eyes are less likely to have AMD and DR but more likely to have nuclear cataract, PSC, and POAG. The associations of myopia with AMD, DR, and POAG are mostly explained by longer AL. However, the association between myopia and nuclear cataract is explained by lens refraction rather than AL., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Myopia is a common complex condition influenced by genetic and environmental factors. Two recent genome-wide association studies have identified loci on chromosomes 15q25 and 15q14 associated with refractive error in Caucasian populations. Our study aimed to assess the association of these 2 loci with refractive error and ocular biometric measures in an independent ethnically matched Caucasian cohort., Design: Genetic association study using unrelated individuals., Participants: Blue Mountains Eye Study (BMES) cohort. A total of 1571 individuals were included in this study., Methods: Single nucleotide polymorphism (SNP) genotype data were collected from the BMES cohort as part of the Wellcome Trust Case Control Consortium 2. Imputation was performed using MACH version 1.1.16, and statistical analysis was conducted using PLINK. Association tests were performed at both loci using refractive error (spherical equivalent), axial length, corneal curvature, and anterior chamber depth as the phenotypes., Main Outcome Measures: Refractive error, axial length, corneal curvature, and anterior chamber depth., Results: A total of 1571 individuals were available from the BMES for analysis. A statistically significant association for refractive error was evident for SNPs at the 15q14 locus, with P values ranging from 1.5 × 10(-2) at rs685352 to 6.4 × 10(-4) at rs560764, whereas association could not be confirmed for SNPs at the 15q25 locus, with P values ranging from 8.0 × 10(-1) to 6.4 × 10(-1). Ocular biometric analysis revealed that axial length was the most likely trait underlying the refractive error association at the 15q14 locus for SNPs rs560766 (P=0.0054), rs634990 (P=0.0086), and rs8032019 (P=0.0081)., Conclusions: Our results confirm the association with refractive error at the 15q14 locus but do not support the association observed at the 15q25 locus. Axial length seemed to be a major parameter at the 15q14 locus, underscoring the importance of this locus in myopia and future clinical treatment., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine associations between quantitatively measured retinal vessel caliber and the 10-year incidence of primary open-angle glaucoma (OAG)., Design: Population-based cohort study., Participants: The Blue Mountains Eye Study examined 3654 persons at baseline and 2461 persons at either 5 years, 10 years, or both times. After excluding 44 subjects with OAG at baseline, 2417 participants at risk of OAG at the 5- or 10-year examinations were included., Methods: Retinal vessel calibers of baseline retinal photographs were measured using a computer-based program and summarized as central retinal artery and vein equivalents (CRAE, CRVE). Incident OAG was defined as the development of typical glaucomatous visual field loss combined with matching optic disc rim thinning and an enlarged cup-to-disc (C:D) ratio of >0.7 or C:D asymmetry between the 2 eyes (≥0.3) at either the 5- or 10-year examination. Generalized estimating equation models were used to account for correlation between eyes while adjusting for glaucoma risk characteristics including intraocular pressure (IOP) or ocular perfusion pressure (OPP)., Main Outcome Measures: We assessed the 10-year incidence of OAG., Results: There were 82 persons (104 eyes) who developed incident OAG over the 10-year follow-up. After adjusting for age, sex, family history of glaucoma, smoking, diabetes, hypertension, hypercholesterolemia, body mass index, spherical equivalent refraction, and C:D ratio, narrower CRAE was associated with higher risk of incident OAG (adjusted odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12-2.79, per standard deviation decrease in CRAE). This association persisted after further adjustment for IOP (adjusted OR, 1.87; 95% CI, 1.14-3.05) or OPP (adjusted OR, 1.76; 95% CI, 1.11-2.78), and remained significant when analyses were confined to eyes with IOP<20 mmHg and C:D ratio<0.6 at baseline. There were no independent associations between CRVE and incident OAG., Conclusions: Retinal arteriolar narrowing, quantitatively measured from retinal photographs, was associated with long-term risk of OAG. These data support the concept that early vascular changes are involved in the pathogenesis of OAG and suggest that computer-based measurements of retinal vessel caliber may be useful to identify people with an increased risk of developing the clinical stage of glaucoma., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD)., Design: Clinic-based cohort., Participants: We followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included., Methods: We performed annual examinations with retinal photography. We assessed AMD using side-by-side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated <12 months previously) were made using generalized estimating equation models., Main Outcome Measures: Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD., Results: Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23-2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74-1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07-2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79-1.60)., Conclusions: Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of and risk factors for diabetic retinopathy (DR) in Indian persons living in a newly urbanized society in Asia., Design: Population-based study., Participants: Ethnic Indians aged ≥40 years living in Singapore., Methods: The Singapore Indian Eye Study was conducted between 2007 and 2009. All participants underwent an extensive ophthalmic examination, including retinal photographs obtained after pupil dilation. These images were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetes was defined as hemoglobin A1c level of ≥6.5%, use of diabetic medication, or a physician diagnosis of diabetes. Risk factors were measured using questionnaires, clinical assessments, or laboratory tests., Main Outcome Measures: Any DR, diabetic macular edema (DME), or vision-threatening DR (VTDR)., Results: Among the 3400 participants, the age-standardized prevalence was 33.6% (95% confidence interval [CI], 31.4-35.8) for diabetes and 10.5% (95% CI, 9.3-11.8) for DR. Among those with diabetes only, the age-standardized prevalence was 30.4% (95% CI, 26.5-34.8) for any DR, 7.2% (95% CI, 5.3-9.7) for DME, and 7.1% (95% CI, 5.4-9.5) for VTDR. In multivariate analysis, independent risk factors for any DR were younger age (odds ratio [OR], 0.98; 95% CI, 0.96-1.00, per year increase), longer diabetes duration (OR, 1.09; 95% CI, 1.07-1.11 per year increase), higher hemoglobin A1c (OR, 1.23; 95% CI, 1.13-1.34 per percent increase), higher systolic blood pressure (OR, 1.01; 95% CI, 1.00-1.02 per 1-mmHg increase), lower diastolic blood pressure (OR, 0.97; 95% CI, 0.96-0.99 per 1-mmHg increase), history of previous stroke (OR, 2.16; 95% CI, 1.12-4.16), and insulin treatment (OR, 2.99; 95% CI, 1.84-4.87). Similar independent risk factors, except for blood pressure, were found for VTDR. Additionally, persons with lower income and living in smaller houses were associated with VTDR., Conclusions: One in 3 migrant Indians living in newly urbanized Asian societies have diabetes and 1 in 10 has DR. This is similar to rates reported in Western populations and significantly higher than those reported in India., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the association of ocular biometric parameters and refractive error with diabetic retinopathy (DR) and diabetic macular edema (DME) in persons with diabetes., Design: Cross-sectional, clinic-based study., Participants: Patients with diabetes aged 18 years or more from the Royal Victorian Eye and Ear Hospital, Victoria, Australia., Methods: Spherical equivalent (SE) refraction was assessed using objective autorefraction. Axial length (AL), corneal curvature (CC), and anterior chamber depth (ACD) were measured using the IOLMaster (Carl Zeiss Meditech AG, Jena, Germany). Diabetic retinopathy was graded from 2-field retinal photographs using the modified Airlie House classification system. Diabetic macular edema was defined as absent or present from fundus photographs and confirmed by optical coherence tomography (Stratus, Carl Zeiss Meditech AG)., Main Outcome Measures: Severity of DR was grouped as no DR, mild DR (Early Treatment of Diabetic Retinopathy Study [ETDRS] = 20), moderate DR (ETDRS = 31-43), and severe DR (ETDRS >43). Diabetic macular edema severity was classified as mild, moderate, or severe., Results: A total of 208 of 630 eyes (33.0%) had DR. In multivariate models, eyes with longer AL were less likely to have mild (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.41-0.83; P = 0.006 per mm increase), moderate (OR, 0.73; 95% CI, 0.60-0.88; P = 0.002), and severe DR (OR, 0.67; 95% CI, 0.53-0.85; P=0.01), and had a lesser risk of mild (OR, 0.70; 95% CI, 0.56-0.86; P < 0.001) and moderate DME (OR, 0.72; 95% CI, 0.56-0.93; P=0.002) but not severe DME. No association was found for SE, ACD, and CC with DR., Conclusions: In persons with diabetes, eyes with longer ALs are less likely to have DR and DME., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence and causes of visual impairment and blindness in an urban Indian population., Design: Population-based study., Participants: Ethnic Indians aged more than 40 years living in Singapore., Methods: Participants underwent standardized ophthalmic assessments for visual impairment and blindness, defined using best-corrected visual acuity (BCVA) and presenting visual acuity (PVA), according to US and modified World Health Organization (WHO) definitions., Main Outcome Measures: Unilateral visual impairment or blindness was defined on the basis of the worse eye, and bilateral visual impairment or blindness was defined on the basis of the better eye. Primary causes of visual impairment were determined., Results: A total of 3400 eligible individuals (75.6% response rate) participated. On the basis of US definitions, the age-standardized prevalence was 0.4% for bilateral blindness (≤20/200, better eye) and 3.4% for bilateral visual impairment (<20/40 to >20/200, better eye). Another 0.3% of bilateral blindness and 13.4% of bilateral visual impairment were correctable with refraction. Cataract was the principal cause of best-corrected bilateral blindness (60.0%) and bilateral visual impairment (65.7%). Other major causes of blindness and visual impairment included diabetic retinopathy, age-related macular degeneration, glaucoma, corneal opacity, and myopic maculopathy., Conclusions: The prevalence of bilateral blindness and visual impairment in Indians living in Singapore is lower than estimates from populations living in India, but similar to estimates obtained from Singapore Malay and Chinese populations. Cataract is the leading cause of blindness and visual impairment. One in 20 cases of bilateral blindness and 1 in 10 cases of bilateral visual impairment are attributable to diabetic retinopathy. These data may have relevance to many ethnic Indian persons living outside India., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: There are limited data on the natural history and longitudinal changes of retinal microvascular lesions. We examined 10-year changes in retinal microvascular lesions, focusing on those related to hypertension and shown to predict development of cardiovascular disease., Design: Prospective cohort., Participants: We included 1120 middle-aged participants without diabetes of the Atherosclerosis Risk in Communities (ARIC) Study in 1993 to 1995 and again 10 years later in 2003 to 2005., Methods: Retinal microvascular lesions were graded from retinal photographs using the same protocol at both examinations, with changes (incidence or disappearance) adjudicated by a side-by-side comparison of photographs. The study sample was stratified by carotid intima media thickness (IMT) and ARIC field center; thus, all analyses were weighted by these factors. Persons with diabetes were excluded because the frequency and pathophysiology of diabetic retinal lesions is different., Main Outcome Measures: Incidence and disappearance rates of lesions., Results: The 10-year incidence of focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy in persons without diabetes was 3.4% (95% confidence interval [CI], 2.3-4.9), 2.5% (95% CI, 1.6-3.9), and 2.2% (95% CI, 1.3-3.5) respectively. Over the 10-year period, of 32, 219, and 24 eyes with focal arteriolar narrowing, AV nicking and retinopathy at baseline, 50.3% (95% CI, 28.6-71.9), 40.7% (95% CI, 32.7-49.4), and 65.9% (95% CI, 42.4-83.5), respectively, disappeared. Higher baseline plasma fibrinogen and white cell counts were associated with incident focal arteriolar narrowing; antihypertensive medication use was associated with incident AV nicking, and higher diastolic blood pressure, carotid IMT, and white cell counts were associated with incident retinopathy. Higher fasting serum glucose was not significantly associated with incident retinopathy, although this may be related to the small number of lesions (odds ratio, 5.88; 95% CI, 0.74-46.64 per standard deviation difference)., Conclusions: In this sample of middle-aged adults, new retinal microvascular lesions appeared at a rate between 2% and 4% over 10 years. A high percentage of lesions (≥40%) disappeared over the same period, suggesting considerable remodeling in the retinal microvasculature., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the prevalence and associations of visual impairment (VI) in preschool children., Design: Cross-sectional, population-based study., Participants: A total of 2461 children (73.8% participation rate), aged 6 to 72 months, were examined in the Sydney Paediatric Eye Disease Study during 2007-2009; of whom 1188, aged 30 to 72 months, with complete visual acuity (VA) data in both eyes, were included in this report., Methods: Measurement of VA was attempted on all children using the Electronic Visual Acuity (EVA) system or a logarithm of the minimum angle of resolution (logMAR) chart. Visual impairment was defined as presenting VA <20/40 in children aged ≥48 months and <20/50 in those aged <48 months. Post-cycloplegic refraction was measured, and myopia was defined as spherical equivalent (SE) ≤-0.50 diopters (D), hyperopia was defined as SE ≥2.00 D, astigmatism was defined as cylinder ≥1.00 D, and anisometropia was defined as SE difference ≥1.00 D between 2 eyes. Ethnicity, birth parameters, and sociodemographic information were collected in questionnaires completed by parents., Main Outcome Measures: Visual impairment prevalence and its associations with child demographic factors and birth parameters., Results: Visual impairment was found in 6.4% of the worse eye and 2.7% of the better eye in our sample. Refractive errors (69.7%) and amblyopia (26.3%) were the principal causes of VI in the worse eye. Astigmatism (51.3%) and hyperopia (28.9%) were the main refractive errors causing VI. In regression analysis controlling for other factors, VI was independently associated with low birthweight of <2500 g (odds ratio 2.4, 95% confidence interval, 1.1-5.3), but not with age, gender, ethnicity, or measures of socioeconomic status (P > 0.05)., Conclusions: Visual impairment in at least 1 eye was found in 6.4% of Australian preschool children, with bilateral VI found in 2.7%. Uncorrected refractive errors and amblyopia were the principal ocular conditions associated with VI. Low birthweight was a significant risk factor independent of age, gender, and ethnicity., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of age-related degeneration (AMD) in a rural Chinese population and to assess its associations with age, gender, and smoking., Design: Population-based cross-sectional., Participants: Persons aged 30+ years, recruited between October 2006 and October 2007, from Yongnian County, Handan, Hebei Province, China., Methods: All participants underwent a standardized interview and comprehensive eye examinations, including digital retinal photography of both eyes. Trained graders assessed the presence and severity of AMD lesions following the modified Wisconsin Age-related Maculopathy Grading System (WARMGS) used in the Blue Mountains Eye Study (BMES). Direct age standardization to the world population (year 2000) was performed to compare the prevalence across different populations., Main Outcome Measures: AMD and WARMGS., Results: Of 6830 participates, fundus photographs were gradable for 6581 persons (96.4%), including 4049 aged 50+ years. Early and late AMD prevalence rates were 3.0% and 0.1%, respectively, among participants. The age-standardized prevalence rates among participants aged 50+ years were 4.7% and 0.2%, respectively. After controlling for age, men had a higher prevalence of early (3.9% vs. 2.3%, odds ratio [OR] 1.7; 95% confidence interval [CI], 1.3-2.2) and late AMD (0.1% vs. 0.03%; OR 3.5; CI, 0.4-33.4) compared with women. Older age (sex-adjusted OR 1.7; CI, 1.3-2.2 per decade of age) and current smoking (age-sex-adjusted OR 1.4; CI, 1.0-2.1) were significantly associated with early AMD prevalence. The proportion of current smokers was substantially higher in men (58.7%) than in women (0.3%). The attributable risk of early AMD from smoking among Chinese men was 24.2%. After controlling for current smoking, the excess prevalence of early AMD in men compared with women reduced by 50% (OR 1.4; 95% CI, 0.9-2.0)., Conclusions: The prevalence of early AMD in this rural Chinese sample was similar to white persons in the BMES and Asian Malays in the Singapore Malay Eye Study. Late AMD prevalence, however, was lower. Higher prevalence rates for early and late AMD in men compared with women were largely attributed to substantially higher proportions of smokers in rural Chinese men than in women., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the association between serum total bilirubin levels and diabetic retinopathy prevalence in participants of the Hisayama Study who had diabetes and impaired glucose metabolism., Design: Population-based, cross-sectional study., Participants: Of 3119 participants of the Hisayama Study Eye Examinations in 2007, Japan, 1672 aged ≥40 years with either diabetes or impaired glucose metabolism (defined by a 75-g oral glucose tolerance test) were enrolled in the present study., Methods: Diabetic retinopathy was assessed via ophthalmic examination after pupil dilatation. The presence and the severity of diabetic retinopathy were determined by grading of color fundus photographs using the modified Airlie House classification system. Association of diabetic retinopathy with serum bilirubin quartiles was assessed using logistic regression model adjusting for age and known risk factors for diabetic retinopathy., Main Outcome Measures: Prevalent diabetic retinopathy., Results: Diabetic retinopathy was present in 70 of 1672 (4.2%) participants. The prevalence of diabetic retinopathy in persons with the highest bilirubin quartile (≥0.9 mg/dL) was 2.7%, compared with the prevalence of 3.4%, 5.1%, and 5.1% in those with the first (<0.6 mg/dL), second (0.6-0.69 mg/dL), and third quartiles (0.7-0.89 mg/dL). After adjusting for factors known to be associated with diabetic retinopathy, the prevalence was significantly lower among persons with the highest bilirubin quartile compared with those with the lowest quartile (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.09-0.72) or compared with those in the 3 lower quartiles (OR, 0.25; 95% CI, 0.11-0.58)., Conclusions: Elevated serum bilirubin levels may be protective against diabetic retinopathy among persons with either diabetes or impaired glucose metabolism, independent of known risk factors for diabetic retinopathy., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the relationship of retinal vascular tortuosity to age, blood pressure, and other cardiovascular risk factors., Design: Population-based, cross-sectional study., Participants: A total of 3280 participants aged 40 to 80 years from the Singapore Malay Eye Study (78.7% response rate)., Methods: Retinal arteriolar and venular (vascular) tortuosity were quantitatively measured from fundus images using a computer-assisted program. Retinal vascular tortuosity was defined as the integral of the curvature square along the path of the vessel, normalized by the total path length. Data on blood pressure and major cardiovascular disease (CVD) risk factors were collected from all participants., Mean Outcome Measures: Retinal arteriolar and venular tortuosity., Results: A total of 2915 participants contributed data to this study. The mean (standard deviation) and median were 2.99 (1.40) and 2.73 for retinal arteriolar tortuosity (×10(4)), and 4.64 (2.39) and 4.19 for retinal venular tortuosity (×10(4)), respectively. Retinal venules were significantly more tortuous than retinal arterioles (P<0.001). In multivariable-adjusted linear regression models, less arteriolar tortuosity was independently associated with older age, higher blood pressure, higher body mass index (BMI), and narrower retinal arteriolar caliber (all P<0.05); greater venular tortuosity was independently associated with younger age, higher blood pressure, lower high-density lipoprotein (HDL) cholesterol level, and wider retinal venular caliber (all P<0.05)., Conclusions: Retinal arteriolar tortuosity was associated with older age and higher levels of blood pressure and BMI, whereas venular tortuosity was also associated with lower HDL level. The quantitative assessment of retinal vascular tortuosity from retinal images may provide further information regarding effects of cardiovascular risk factors on the retinal vasculature., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of and risk factors for epiretinal membrane (ERM) in a multi-ethnic population and to evaluate possible racial or ethnic differences., Design: Cross-sectional study., Participants: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), examined at the second visit of the MESA when retinal photography was performed., Methods: Data on 5960 participants aged 45 to 84 years from MESA, including white, black, Hispanic, and Chinese persons from 6 United States communities, were analyzed. Epiretinal membrane was assessed from digital nonstereoscopic fundus photographs and was defined as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations., Main Outcome Measures: Epiretinal membrane prevalence by ethnic or racial group and risk factors associated with ERM., Results: The prevalence of any ERM was 28.9%, of which 25.1% were CMR cases and 3.8% were PMF cases. The prevalence of ERM was significantly higher in Chinese persons (39.0%), compared with Hispanic (29.3%), white (27.5%), or black (26.2%; P<0.001) persons. In multivariate models, increasing age (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.34, per year increase in age), diabetes (OR, 1.92; 95% CI, 1.39-2.65), and hypercholesterolemia (OR, 1.33; 95% CI, 1.04-1.69) were significantly associated with CMR., Conclusions: This study showed that ERM was significantly more common in Chinese persons compared with whites, blacks, and Hispanics. Risk factors for ERM were increasing age, presence of diabetes, and hypercholesterolemia., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the prevalence of retinopathy and associations with cardiovascular risk factors in persons without diabetes in 4 racial/ethnic groups (white, black, Hispanic, and Chinese)., Design: Population-based, cross-sectional study., Participants: We included 6176 subjects aged 45-84 years without diabetes, selected from 6 United States communities., Methods: Fundus images were taken using 45° digital camera through dark-adapted pupils and were graded for retinopathy as defined by the Early Treatment Diabetic Retinopathy Study severity scale: microaneurysms, hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading, and new vessels., Main Outcome Measures: Retinopathy and the association with cardiovascular risk factors., Results: Prevalence rates of retinopathy in persons without diabetes were 12.5% overall, varying from 11.9% (white), 13.9% (black), 12.6% (Hispanic), to 17.2% (Chinese). Hypertension was strongly associated with retinopathy (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.23-1.75). After adjusting for age, gender, race, and other parameters, smoking (OR, 1.50; 95% CI, 1.09-2.06) and increased internal carotid intima media thickness (OR, 1.22; 95% CI, 1.05-1.41) were associated with retinopathy. A range of serum inflammatory factors were examined, but none were found to be significant., Conclusions: Retinopathy in persons without diabetes is common, varies with race/ethnicity, and associated with cardiovascular risk factors, including hypertension, smoking, and carotid artery intima media thickness., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of and factors associated with amblyopia in a rural Chinese population., Design: Population-based, cross-sectional study., Participants: Six thousand eight hundred thirty Han Chinese aged 30 years or more, recruited from Yongnian County, Handan, Hebei Province, China., Methods: Thirteen villages in the Yongnian County of Handan were selected randomly, and residents of these selected villages 30 years of age or older were invited to participate in the Handan Eye Study. Participants underwent a comprehensive eye examination, including standardized visual acuity (VA) tests using logarithm of the minimum angle of resolution charts. Prevalence rates were age- and gender-standardized to the 2000 China census., Main Outcome Measures: The proportion of rural Chinese population aged 30 years or older with amblyopia. Unilateral amblyopia was diagnosed if best-corrected VA (BCVA) was 20/32 or worse in the amblyopic eye and was not attributable directly to any underlying structural abnormality of the eye or visual pathway. Bilateral amblyopia was diagnosed if BCVA was 20/32 or less in both eyes and if there was a history of form deprivation during the sensitive period of visual development, such as media opacities or high, uncorrected ametropia., Results: Amblyopia was diagnosed in 205 participants, with an age- and gender-adjusted prevalence of 2.8%. Of these, 1.7% were unilateral cases and 1.1% were bilateral cases. Underlying causes included anisometropia (67.3%), strabismus (5.4%), mixed strabismus and anisometropia (4.4%), visual deprivation (9.8%), astigmatism association (9.8%), and other (3.4%). Of the amblyopia cases, 47.6% were hypermetropic., Conclusions: In this rural Chinese population, 2.8% of adults 30 to 80 years of age had amblyopia, a prevalence rate broadly consistent with that of most other studies. One third of the cases were bilateral, and anisometropia was the most common cause of this condition., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe macular thickness measured by optical coherence tomography (OCT) in healthy eyes of adult Chinese persons., Design: Population-based cross-sectional study., Participants: Chinese adults aged 30+ years who were residents of Handan, North China., Methods: The Handan Eye Study is a population-based study of eye disease in Chinese persons. Eligible residents underwent a comprehensive ophthalmic examination including OCT (Stratus OCT, Carl Zeiss Meditec Inc., Jena, Germany). Fast macular thickness scans were performed over maculae within 6 mm in diameter, divided into 3 regions (central, inner, and outer, with a diameter of 1, 3, and 6 mm, respectively) and 9 quadrants (1 in the central region and 4 each in the inner and outer regions). Retinal thickness (means and standard deviations) was calculated by OCT mapping software, presented for foveal minimum, central macula (within 1 mm diameter), and inner and outer regions divided by 8 quadrants., Main Outcome Measures: Macular thickness measured by OCT., Results: Of the 6830 participants (90.4% response rate) examined, 2230 eyes of healthy subjects with high-quality OCT scans were selected (32.7% of participants; mean age, 46.4+/-9.9 years, 58.4% were women). The mean foveal minimum, central, inner, and outer macular thicknesses were 150.3 (18.1) microm, 176.4 (17.5) microm, 255.3 (14.9) microm, and 237.7 (12.4) microm, respectively (overall differences, P<0.001). The mean foveal volume was 0.139 (0.014) mm(3), and the mean total macular volume was 6.761 (0.516) mm(3). In the inner region, the nasal quadrant was thinner than the superior and inferior quadrants, and in the outer region, the nasal quadrant was the thickest (P<0.001). Age was positively correlated with foveal (beta coefficient = 3.582) and central macular (beta coefficient = 2.422) thicknesses. The foveal minimum, central, inner, and outer macular thicknesses were significantly greater in men than in women. Fasting plasma glucose was negatively correlated with central macular thickness (2.416 mm reduction per millimole/liter increase in glucose), and axial length was positively correlated with central macular thickness (2.138 mm increase per millimeter increase in axial length)., Conclusions: Normal macular thickness measurements using OCT in a large population-based sample of adult Chinese persons aged 30 to 85 years were generally thinner in the foveal and central macular areas than measurements reported in other populations. Age and axial length were positively correlated with macular thickness., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature., Clinical Relevance: Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse., Methods: English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators., Results: Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels., Conclusions: Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature., Clinical Relevance: Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear., Methods: Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO; an untreated control arm was included., Results: Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare., Conclusions: Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of age-related macular degeneration (AMD) in Asian populations and to compare this with prevalence in white populations., Design: A clear understanding of AMD prevalence in Asians is essential to meet future demands for eye health care., Methods: We searched published literature reporting AMD prevalence in Asian populations. We limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the international classification proposed by the International ARM Epidemiological Study Group). We used metaanalytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. We also calculated pooled estimates of age-standardized prevalence. A metaregression model was used to examine gender differences and differences between Asian and white populations., Results: We identified 9 studies reporting AMD prevalence from 4 Asian populations. Pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 years were 6.8% (95% confidence interval [CI], 4.6%-8.9%) and 0.56% (95% CI, 0.30%-0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8%-13.8%) and 0.59% (95% CI, 0.35%-0.84%), respectively. Reliable prevalence estimates of AMD in Asian persons aged > or =80 years were not available owing to small subject numbers in this age category., Conclusions: Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to describe norms for the distribution of axial length (AL) and other ocular biometric parameters in an older Caucasian population, measured using partial coherence laser interferometry (Zeiss IOL Master; Carl Zeiss AG, Oberkochen, Germany), a technique now routinely used in measuring AL before cataract surgery. We also aimed to assess age and gender relationships with these parameters and their correlations with spherical equivalent refraction (SER)., Design: Cross-sectional analysis of the Blue Mountains Eye Study (BMES) cohort at the examinations (10-year follow-up examination)., Participants: From 2002 to 2004, 1952 persons (76% of surviving baseline BMES participants) aged 59 years or older had ocular biometry measured at the 10-year examinations., Methods: Spherical equivalent refraction was calculated as the sum of sphere +0.5 cylinder power, after protocol refraction. Measurements of AL, corneal curvature (K1), anterior chamber depth (ACD), and corneal diameter (WTW) were performed using the IOL Master. Only right phakic eyes (n = 1335) with biometry data were included., Main Outcome Measures: Axial length distribution., Results: Mean AL was 23.44 mm (95% confidence interval [CI], 23.38-23.50) and was greater in men, 23.76 mm (CI, 23.68-23.84), than in women, 23.19 mm (CI, 23.11-23.27). The mean K1, ACD, and WTW were 43.42 diopters (D), 3.10 mm, and 12.06 mm, respectively. The AL and ACD distributions were both positively skewed and peaked, whereas the WTW and K1 distributions were near normal. From age 59 years or older, a mean reduction in AL with age was observed (P for trend = 0.005), 0.12 mm per decade (P = 0.0176) in women but only 0.02 mm per decade (P = 0.6319) in men. Mean SER was 0.58 D, and the distribution was peaked with a negative skew. The SER was negatively correlated with both AL (beta coefficient -0.688) and ACD (beta coefficient -0.222), but not with K1 or WTW., Conclusions: These data provide normative values in the older general population for AL measured using the IOL Master. Axial length distribution was peaked and skewed, suggesting an active modulation process., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence and associations of retinopathy in a population-based nondiabetic sample of rural Chinese., Design: Population-based cross-sectional study., Participants: We included 6830 Han Chinese aged > or =30 years from 13 villages of Yongnian County, Handan City, Hebei Province, China., Methods: All participants underwent a standardized interview and extensive examinations including retinal photography, measurement of blood pressure (BP) and fasting plasma glucose (FPG). Diabetes mellitus was defined as either FPG > or = 7.0 mmol/l, use of diabetic medication or a physician diagnosis of diabetes. Photographic grading of retinopathy followed the modified Early Treatment Diabetic Retinopathy Study classification system. Logistic regression models were used to assess associations of retinopathy., Main Outcome Measures: Any retinopathy., Results: The prevalence of retinopathy among participants without diabetes was 13.6% (95% confidence interval [CI], 12.6-14.6%). The age and gender standardized prevalence of retinopathy in the Chinese adult population (aged 30+ years) without diabetes was estimated to be 12.1% (95% CI 11.1-12.9%). Independent risk factors associated with retinopathy were age (odds ratio [OR], 1.02 ; 95% CI 1.01-1.03 per year increase), male gender (male vs. female, OR 1.27; 95% CI 1.08-1.49), higher FPG (OR 1.30; 95% CI 1.11-1.53 per mmol/l increase), higher systolic BP (OR 1.15; 95% CI 1.05-1.27 per 10 mmHg increase) and higher diastolic BP (OR 1.16; 95% CI 1.09-1.22 per 10 mmHg increase)., Conclusions: Retinopathy was common among rural Chinese adults without diabetes. Its association with FPG and BP suggests that early microvascular damage is occurring at "high normal" levels of blood glucose and BP., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To summarize the prevalence of retinal vein occlusion (RVO) from studies in the United States, Europe, Asia, and Australia., Design: Pooled analysis using individual population-based data., Participants: Individual participant data from population-based studies around the world that had ascertained RVO from fundus photographs., Methods: Each study provided data on branch RVO and central RVO by age, sex, and ethnicity. Prevalence rates were directly age and sex standardized to the 2008 world population aged 30 years and older. Estimates were calculated by study and, after pooling, by ethnicity. Summary estimates included studies in which RVO was assessed from fundus photographs on >or=2 fields of both eyes., Main Outcome Measures: Any RVO, CRVO, or BRVO., Results: The combined pooled data contained 68,751 individuals from 15 studies, with participants' ages ranging from 30 to 101 years. In analyses of 11 studies that assessed >or=2 fundus fields of both eyes (n=49,869), the age- and sex-standardized prevalence was 5.20 per 1000 (confidence interval [CI], 4.40-5.99) for any RVO, 4.42 per 1000 (CI, 3.65-5.19) for BRVO, and 0.80 per 1000 (CI, 0.61-0.99) for CRVO. Prevalence varied by race/ethnicity and increased with age, but did not differ by gender. The age- and sex-standardized prevalence of any RVO was 3.7 per 1000 (CI, 2.8-4.6) in whites (5 studies), 3.9 per 1000 (CI, 1.8-6.0) in blacks (1 study), 5.7 per 1000 (CI, 4.5-6.8) in Asians (6 studies), and 6.9 per 1000 (CI, 5.7-8.3) in Hispanics (3 studies). Prevalence for CRVO was lower than BRVO in all ethnic populations. On the basis of these data, an estimated 16.4 million (CI, 13.9-18.9) adults are affected by RVO, with 2.5 million (CI, 1.9-3.1) affected by CRVO and 13.9 million (CI, 11.5-16.4) affected by BRVO. Study limitations include non-uniform sampling frames in identifying study participants and in acquisition and grading of RVO data., Conclusions: Our study provides summary data on the prevalence of RVO and suggests that approximately 16 million people may have this condition. Research on preventive and treatment strategies for this sight-threatening eye disease is needed., (Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of and risk factors for myopia and other refractive errors in a rural, adult, Chinese population., Design: Population-based, cross-sectional study., Participants: A clustered, random sampling procedure was used to select 7557 Chinese people aged >or=30 years from Handan, China., Methods: All eligible subjects were invited to undergo a comprehensive eye examination, including standardized refraction. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of more than -0.5 diopter (D), less than -5.0 D, and 0.5 D or more, respectively. Astigmatism was less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of >1.0 D between the 2 eyes. Only phakic eyes were analyzed., Main Outcome Measures: Myopia and other refractive errors., Results: We included 6491 (85.9% participation rate) eligible subjects in this study. Adjusted to the 2000 China population census, the prevalence rate of myopia was 26.7% (95% confidence interval [CI], 25.6-27.8), hyperopia 15.9 % (95% CI, 15.0-16.8), astigmatism 24.5% (95% CI, 23.5-25.5), and anisometropia 7.7% (95% CI, 7.0-8.4). The prevalence of high myopia was 1.8% (95% CI, 1.5-2.1). Using a multivariate regression model, current smoking (odds ratio [OR], 0.7, 95% CI, 0.5-0.9), hours of reading (OR, 1.2; 95% CI, 1.1-1.4), diabetes (OR, 8.4; 95% CI, 2.2-32.5), and number of family members with myopia (OR, 1.3; 95% CI, 1.1-1.7, for each family member) were associated with myopia in younger persons (30-49 years). High school or higher education (OR, 1.8; 95% CI, 1.1-3.1), diabetes (OR, 1.6; 95% CI, 1.2-2.7), nuclear opacity (OR, 1.7; 95% CI, 1.2-2.3), and number of family members with myopia (OR, 1.5; 95% CI, 1.2-1.9) were risk factors in persons >or=50 years of age., Conclusions: Myopia affects more than one quarter of rural Chinese persons >or=30 years of age. Myopia is more common in younger people and is associated with different risk factors than in older people.

Objective: To assess whether phacoemulsification cataract surgery exacerbates the development and progression of diabetic retinopathy (DR) in a cataract surgical cohort., Design: Clinic-based cohort study., Participants: Patients aged 65+ years undergoing cataract surgery at an eye clinic in Sydney, Australia, between 2004 and 2006., Methods: Digital retinal photography was performed after pupil dilation preoperatively and at 1-, 6-, and 12-month postoperative visits. DR was assessed using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Preoperative and 1-month postoperative (baseline) photographs were compared side-by-side with 12-month postoperative photographs. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for DR progression in operated (pseudophakic) compared with nonoperated (phakic) eyes, adjusted for age, sex, diabetes duration, and preoperative glycosylated hemoglobin level., Main Outcome Measures: Incident DR was defined in eyes without DR at baseline in which DR was detected at 12-month postoperative visits. DR progression was defined as an increase of 1 or more ETDRS steps during the same period, including incident cases., Results: Of 1994 surgical patients recruited, 190 (9.53%) with diabetes and complete data and thus were included. There were 56 patients with unilateral surgery performed before baseline (mean postoperative duration 3.3+/-3.3 years). The prevalence of DR at baseline was higher in these 56 pseudophakic eyes than in 324 phakic eyes (71.4% vs. 48.2%, respectively, adjusted OR 2.16; 95% CI, 1.16-4.03). Of the 190 patients, 169 were followed for 12+ months postoperatively; 278 eyes were pseudophakic, and 60 eyes remained phakic at 12 months. During the 12-month postoperative period, incident DR developed in 28.2% of pseudophakic eyes and 13.8% of phakic eyes (adjusted OR 2.65; 95% CI, 1.06-6.61). In a paired-eye comparison of 45 patients who remained unilaterally pseudophakic at 12 months and were at risk of DR progression, 35.6% of pseudophakic eyes exhibited DR progression compared with 20.0% of the fellow phakic eyes (adjusted OR 2.21; 95% CI, 0.85-5.71)., Conclusions: Diabetic patients undergoing phacoemulsification cataract surgery appear to have a doubling of DR progression rates 12 months after surgery. This outcome, however, represents less progression than was previously documented with intracapsular and extracapsular cataract surgical techniques.

Objective: Longitudinal associations between inhaled and oral corticosteroid use and 10-year incident cataract were examined., Design: Population-based cohort study., Participants: The Blue Mountains Eye Study examined 3654 Australians aged 49 years or older (1992-1994); 2335 were re-examined after 5 years and 1952 were re-examined after 10 years (75.1%, 75.6% of survivors, respectively)., Methods: Questionnaires were used to assess inhaled and oral corticosteroid use at baseline. Past users were participants who had used these medications for at least 1 month in the past but were not using them at baseline. Current users were those who were using these medications at baseline and had been doing so for at least 1 month. Ever users combined past and current users., Main Outcome Measures: Lens photographs were obtained at each examination and graded for nuclear, cortical, and posterior subcapsular (PSC) cataracts following the Wisconsin Cataract Grading System. Participants without a specific subtype of cataract in either eye at baseline were considered to be at risk of that type of cataract developing over the 10-year follow-up. Incidence of each cataract subtype in this report refers to person-specific, first-eye incidence., Results: At baseline, 103 participants were current and 120 past users of inhaled corticosteroids, and 31 were current and 147 were past users of oral corticosteroids. Current users had a greater risk of developing PSC cataract after adjustment for age and gender (inhaled: odds ratio [OR] 2.50, 95% confidence interval [CI] 1.33-4.69; oral: OR 4.11; 95% CI 1.67-10.08) and nuclear cataract (inhaled: OR 2.04, 95% CI 1.21-3.43; oral: OR 3.45, 95% CI 1.26-9.43) but not cortical cataract. Interaction between inhaled and oral corticosteroid use was significant for PSC (P = 0.01) and nuclear (P = 0.02) cataract incidence. In subgroup analyses, only individuals who used both inhaled and oral steroids were at increased risk of PSC cataract (after adjusting for age, sex, smoking, hypertension, diabetes, and education levels; OR 4.76, 95% CI 2.59-8.74), comparing ever users of both with users of neither., Conclusions: High long-term risks of PSC and nuclear cataract development were found for users of combined inhaled and oral corticosteroids.

Purpose: To describe the age- and gender-specific prevalence, characteristics, and severity of diabetic retinopathy (DR) in a rural population in northern China., Design: A population-based cross-sectional study., Participants: A total of 6830 Han Chinese aged 30 years and older from 13 villages of Yongnian County, Handan City, Hebei Province, China., Methods: All participants underwent a standardized interview, a comprehensive eye examination, and fasting blood glucose testing according to the American Diabetes Association diagnostic criteria (fasting plasma glucose >or=7.0 mmol/l). Retinal photographs obtained after pupil dilation were graded for the presence and severity of DR according to the modified Early Treatment Diabetic Retinopathy Study classification system., Main Outcome Measures: Any DR, retinopathy grades, macular edema, or vision-threatening retinopathy., Results: Of the 6830 eligible individuals participating in the study, 5597 (81.9%) had fasting blood glucose results available. Of these, 387 participants (6.9%) were diagnosed with diabetes mellitus, including 247 subjects with new diabetes mellitus (NDM) and 140 subjects with known diabetes mellitus (KDM). For these, gradable photographs were available for 368 subjects (95.1%). The overall prevalence of DR was 43.1% (95% confidence interval, 38.1-48.4) and was higher in persons with KDM (65.2%) than NDM (33.5%). The prevalence of proliferative DR, macular edema, and vision-threatening retinopathy was 1.6%, 5.2%, and 6.3%, respectively, with 12.1% with KDM having untreated vision-threatening DR. No age- or gender-related differences were present. The prevalence of DR was strongly related to duration of disease., Conclusions: Our study reports a high prevalence of DR among adults 30 years and older with diabetes in rural China. On the basis of estimates obtained from our study, we projected that in rural China, 21.1 million persons aged 30+ years have diabetes and 9.2 million have DR, including 1.3 million with vision-threatening DR. There is a pressing need for appropriate screening and management of diabetes and its complications in rural China.

Objective: To assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol., Design: Clinic-based and population-based case control study., Participants: A total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank., Methods: DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed., Main Outcome Measures: AMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined., Results: Strong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD., Conclusions: Findings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA1 was combined with either CFH risk alleles or history of smoking.

Objective: Fractals represent a type of derived geometric pattern that permits the characterization of the branching pattern of retinal vessels. We examined a new semiautomated method to measure retinal vessel fractals., Design: Methodology study., Participants: Three hundred randomly selected participants from the population-based Blue Mountains Eye Study., Methods: We developed a semiautomated computer program to measure the fractal dimension (D(f)) of the retinal vessels from digitized images of disk-centered retinal photographs. Two trained graders masked to participant characteristics measured D(f) of right eye images of participants. Reliability was determined by repeat grading of the images from 60 participants, and association with systolic and diastolic blood pressure was examined in all 300 participants., Main Outcome Measure: D(f) of the retinal vessels., Results: Mean D(f) was 1.437 with a standard deviation of 0.025. Intragrader and intergrader reliability estimates were high with intraclass correlation ranging from 0.93 to 0.95. D(f) was inversely correlated with age (r = -0.42, P = 0.001) and systolic blood pressure (r = -0.29, P<0.0001). After adjustment for age and sex, mean D(f) was significantly lower in participants with than without hypertension (D(f) difference 0.01, P = 0.02)., Conclusions: The D(f) of the retinal vessels can be reliably measured from photographs and shows a strong inverse correlation with blood pressure. These data suggest that the D(f) may be a measure of early microvascular alterations from elevated blood pressure. Further studies to examine the systemic and ocular correlates of the D(f) of the retinal vessels are needed.

Objective: To validate the VF-11, a vision-specific function scale and determine the relationship among vision impairment, ocular conditions, and vision-specific functioning in an Asian Malay population., Design: Population-based cross-sectional study., Participants: Persons aged 40 to 80 years of Malay ethnicity in Singapore., Methods: Of the 3280 participants, 3267 answered the VF-11 scale. Participants underwent an extensive and standardized examination procedure, which included visual acuity testing. Sociodemographic and medical data were recorded using a standardized questionnaire. Rasch analysis was initially used to validate the VF-11 and determine its measurement characteristics. Analyses were performed to explore the relationship between the overall functioning score and the presenting unilateral and bilateral vision and ocular conditions using linear regression models., Main Outcome Measure: Vision-specific functioning score., Results: The mean presenting visual acuity values in the better and worse eyes were 0.21 (+/-0.23) and 0.36 (+/-0.27) logarithm of the minimum angle of resolution, respectively. Some 46.4% of participants had some form of visual impairment in either eye, and 1.8% of participants had severe visual impairment in both eyes. By using Rasch analysis, it was shown that a modified VF-11 is a unidimensional, reliable, and valid scale to assess vision-specific functioning in this population. Participants with unilateral or bilateral visual impairment had significantly lower vision functioning scores. The independent association between severe vision loss in one or both eyes and functioning was considered to be clinically meaningful. Eye conditions were not independently associated with overall visual function with bilateral visual impairment in the model with the exception of glaucoma (P<0.05 and beta = -1.08). Compared with people with normal vision, people with mild/moderate visual impairment were 1.6 (95% confidence intervals [CI], 1.2-2.2; P = 0.01) and 2.2 (95% CI, 1.6-3.0; P = 0.007) times more likely to have moderate and poor vision function, respectively. Similarly, participants with severe visual impairment were 3.5 (95% CI, 1.1-12.7; P<0.001) and 13.6 (CI, 4.0-45.4; P<0.001) times more likely to have moderate and poor vision function, respectively., Conclusions: Presenting unilateral and bilateral vision impairment is significantly associated with poor vision-specific functioning across the spectrum of mild to severe vision impairment in this Asian Malay population.

Purpose: To describe the prevalence and risk factors of diabetic retinopathy in Asian Malays., Design: Population-based cross-sectional study., Participants: Persons with diabetes of Malay ethnicity aged 40 to 80 years in Singapore., Methods: Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Retinal photographs taken from both eyes were graded for diabetic retinopathy using the modified Airlie House classification system., Main Outcome Measures: Any diabetic retinopathy, retinopathy grades, macular edema, or vision-threatening retinopathy., Results: Of the 3261 persons who participated in this study, 757 (23.1%) had diabetes and gradable retinal photographs. In persons with diabetes, the overall prevalence of any retinopathy was 35.0% (95% confidence interval [CI], 28.2-43.4), the overall prevalence of macular edema was 5.7% (95% CI, 3.2-9.9), and the overall prevalence of vision-threatening retinopathy was 9.0% (95% CI, 5.8-13.8). Compared with men, women had significantly higher proportions with more severe diabetic retinopathy, moderate (12% vs. 4%) and severe (3% vs. 0.2%) nonproliferative retinopathy, proliferative retinopathy (7% vs. 2%), and vision-threatening retinopathy (13% vs. 3%). In multiple logistic regression, independent risk factors for any retinopathy were longer diabetes duration (odds ratio [OR], 1.07; 95% CI, 1.04-1.09, per year increase), higher hemoglobin A1(c) (OR, 1.21; 95% CI, 1.10-1.33, per % increase), hypertension (OR, 1.85; 95% CI, 1.04-3.30), and higher pulse pressure (OR, 1.34, 95% CI, 1.19-1.51, per 10-mmHg increase); older age (OR, 0.73; 95% CI, 0.57-0.93, per decade increase) and higher total cholesterol levels (OR, 0.75; 95% CI, 0.63-0.89, per 1-mmol/l increase) were protective of any retinopathy. Vision-threatening retinopathy additionally was associated with previous stroke (OR, 3.74; 95% CI, 1.24-11.26), cardiovascular disease (OR, 2.23; 95% CI, 1.08-4.62), and chronic kidney disease (OR, 4.45; 95% CI, 2.18-9.07). Female gender was not an independent risk factor for diabetic retinopathy after adjusting for metabolic and socioeconomic risk factors., Conclusions: One in 10 Malay adults with diabetes in Singapore has vision-threatening diabetic retinopathy. Risk factors for retinopathy in this population are largely similar to white populations elsewhere, suggesting that control of these risk factors may reduce both the prevalence and impact of retinopathy.

Purpose: To describe the prevalence and causes of low vision and blindness in a rural population in Northern China., Design: Population-based, cross-sectional study., Participants: A study of 6830 Han Chinese aged 30 years and older was conducted between October 2006 and October 2007 in rural Yongnian County in Handan, Northern China., Methods: Clustered samples of adults aged 30 years or more residing in 13 residential villages were selected randomly and were invited to participate the Handan Eye Study. Participants underwent a comprehensive eye examination, including standardized visual acuity (VA) tests using logarithm of the minimum angle resolution charts. Prevalence was age- and gender-standardized to the 2000 China Census., Main Outcome Measures: Low vision was defined as VA <20/60 but >/=20/400, and blindness was defined as VA <20/400 following the Modified World Health Organization (WHO) definitions. Primary causes of low vision and blindness were determined by study ophthalmologists according to WHO definitions., Results: Six thousand eight hundred thirty (90.4%) of 7577 eligible individuals participated in the study, and 6799 (89.7%) had VA data available. Population-weighted prevalence of presenting bilateral blindness was 0.6% and bilateral low vision was 4.7% for persons 30 years of age and older. Based on best-corrected visual acuity (BCVA), the corresponding prevalence of blindness was 0.5% and that of low vision was 1.0%. Blindness and low vision were strongly age related (P<0.05). Cataract was the predominant cause of presenting bilateral blindness (36.6%), whereas undercorrected refractive error was the predominant cause of presenting low vision (78.4%). After refractive correction, cataract became the first leading cause of blindness (41.9%), and low vision (48.2%), myopic retinopathy (16.1%), glaucoma (9.7%), and corneal opacity (9.7%) were other common causes of blindness defined using BCVA., Conclusions: A higher prevalence of blindness and low vision was seen in this rural Chinese sample than has been reported from urban Chinese populations. The estimated numbers with BCVA-defined low vision and blindness in 2020, based on best-corrected vision in rural Chinese adults aged 30 years or more, is expected to be 12.4 million and 2.9 million, respectively. Predominant causes of low vision and blindness in China are treatable.

Objective: To describe the prevalence of age-related macular degeneration (AMD) in an Asian Malay population., Design: Population-based cross-sectional study., Participants: An age-stratified random sample of Malay persons aged 40 to 80 years living in Singapore., Methods: Participants were invited to a central clinic for a comprehensive examination., Main Outcome Measures: Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system., Results: Of 3280 participants who participated (78.7% response rate), 3265 had photographs of sufficient quality for grading of AMD signs. Early and late AMD were present in 160 (4.9%) and 23 (0.70%) participants, respectively. After age standardization, the prevalence of early AMD in Malay persons aged 40 to 80 years was estimated to be 3.5% (95% confidence interval [CI], 2.9%-4.1%) and that of late AMD was 0.34% (95% CI, 0.20%-0.49%). Early AMD was more prevalent in men than in women (6.1% vs. 3.8%); this was significant despite adjusting for age and smoking (odds ratio [OR], 1.56; 95% CI, 1.11-2.20). Late AMD also was more prevalent in men than in women (1.0% vs. 0.4%), although this was not statistically significant after adjusting for age and smoking (OR, 1.39; 95% CI, 0.52-3.68). The prevalence of early and late AMD was similar to that reported in the Blue Mountains Eye Study among white persons., Conclusions: The prevalence of AMD in Asian Malay people is similar to that in white persons from the Blue Mountains Eye Study. Early AMD signs were more frequent in men compared with women, an association that was not fully explained by the higher smoking rates in men.

Objective: To determine whether local nutritional or ischemic factors are involved in cataract pathogenesis, we aimed to assess whether narrowed retinal vessel caliber predicted the long-term incidence of age-related cataract, as shown in 1 previous report., Design: Population-based cohort study., Participants: The Blue Mountains Eye Study examined 3654 baseline participants (1992-1994), 2335 (75.1% of survivors) after 5 years, and 1952 (75.6% of survivors) after 10 years., Methods: Retinal vessel caliber was measured from baseline retinal photographs using computer-assisted techniques. Mean arteriolar and venular diameters of each eye were summarized as central retinal arterial (CRAE) and venular (CRVE) equivalents. Cataract was assessed from lens photographs of both eyes using the Wisconsin grading system., Main Outcome Measures: Nuclear cataract was defined as opacity > Wisconsin standard photograph 3, cortical cataract defined as opacity >or=5% of the lens area, and posterior subcapsular (PSC) cataract as any present. Eye-specific data were analyzed using generalized estimating equations. Odds ratios (OR) and 95% confidence intervals (CI) are reported., Results: After adjusting for age, gender, smoking, hypertension, diabetes, body mass index, and inhaled steroid use, reduced incidence of nuclear cataract was associated with the narrowest compared with the widest quintile of CRAE and CRVE (for CRAE: OR, 0.62; 95% CI 0.42-0.92; for CRVE: OR, 0.70; 95% CI, 0.47-1.05) but a higher incidence of PSC cataract (for CRAE: OR, 2.40; 95% CI, 1.34-4.29; for CRVE: OR, 3.17; 95% CI, 1.62-6.20) and cataract surgery (for CRAE: OR, 1.52; 95% CI, 1.06-2.17; for CRVE: OR, 1.58; 95% CI, 1.08-2.32). These associations were not maintained when both CRAE and CRVE were included simultaneously in the same models. Path analysis suggested that age was the most important contributor to nuclear cataract incidence, and CRAE and CRVE, as markers of a latent age-related variable, were only indirectly associated with its incidence (for CRAE: OR, 0.61; 95% CI, 0.41-0.91; for CRVE: OR, 0.62; 95% CI, 0.41-0.94)., Conclusions: Retinal vessel narrowing predicted greater risk of long-term incidence of PSC cataract and cataract surgery, and was indirectly linked to a lower incidence of nuclear cataract. Retinal vessel narrowing could be a marker of age-related factors associated with risk of PSC and nuclear cataract.