Detecting visually significant cataract using retinal photograph-based deep learning.

Age-related cataracts are the leading cause of visual impairment among older adults. Many significant cases remain undiagnosed or neglected in communities, due to limited availability or accessibility to cataract screening. In the present study, we report the development and validation of a retinal photograph-based, deep-learning algorithm for automated detection of visually significant cataracts, using more than 25,000 images from population-based studies. In the internal test set, the area under the receiver operating characteristic curve (AUROC) was 96.6%. External testing performed across three studies showed AUROCs of 91.6-96.5%. In a separate test set of 186 eyes, we further compared the algorithm's performance with 4 ophthalmologists' evaluations. The algorithm performed comparably, if not being slightly more superior (sensitivity of 93.3% versus 51.7-96.6% by ophthalmologists and specificity of 99.0% versus 90.7-97.9% by ophthalmologists). Our findings show the potential of a retinal photograph-based screening tool for visually significant cataracts among older adults, providing more appropriate referrals to tertiary eye centers.

Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Referral for disease-related visual impairment using retinal photograph-based deep learning: a proof-of-concept, model development study.

BACKGROUND: In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We aimed to assess the performance of a newly developed deep learning algorithm for detection of disease-related visual impairment. METHODS: In this proof-of-concept study, using retinal fundus images from 15 175 eyes with complete data related to best-corrected visual acuity or pinhole visual acuity from the Singapore Epidemiology of Eye Diseases Study, we first developed a single-modality deep learning algorithm based on retinal photographs alone for detection of any disease-related visual impairment (defined as eyes from patients with major eye diseases and best-corrected visual acuity of <20/40), and moderate or worse disease-related visual impairment (eyes with disease and best-corrected visual acuity of <20/60). After development of the algorithm, we tested it internally, using a new set of 3803 eyes from the Singapore Epidemiology of Eye Diseases Study. We then tested it externally using three population-based studies (the Beijing Eye study [6239 eyes], Central India Eye and Medical study [6526 eyes], and Blue Mountains Eye Study [2002 eyes]), and two clinical studies (the Chinese University of Hong Kong's Sight Threatening Diabetic Retinopathy study [971 eyes] and the Outram Polyclinic Study [1225 eyes]). The algorithm's performance in each dataset was assessed on the basis of the area under the receiver operating characteristic curve (AUC). FINDINGS: In the internal test dataset, the AUC for detection of any disease-related visual impairment was 94·2% (95% CI 93·0-95·3; sensitivity 90·7% [87·0-93·6]; specificity 86·8% [85·6-87·9]). The AUC for moderate or worse disease-related visual impairment was 93·9% (95% CI 92·2-95·6; sensitivity 94·6% [89·6-97·6]; specificity 81·3% [80·0-82·5]). Across the five external test datasets (16 993 eyes), the algorithm achieved AUCs ranging between 86·6% (83·4-89·7; sensitivity 87·5% [80·7-92·5]; specificity 70·0% [66·7-73·1]) and 93·6% (92·4-94·8; sensitivity 87·8% [84·1-90·9]; specificity 87·1% [86·2-88·0]) for any disease-related visual impairment, and the AUCs for moderate or worse disease-related visual impairment ranged between 85·9% (81·8-90·1; sensitivity 84·7% [73·0-92·8]; specificity 74·4% [71·4-77·2]) and 93·5% (91·7-95·3; sensitivity 90·3% [84·2-94·6]; specificity 84·2% [83·2-85·1]). INTERPRETATION: This proof-of-concept study shows the potential of a single-modality, function-focused tool in identifying visual impairment related to major eye diseases, providing more timely and pinpointed referral of patients with disease-related visual impairment from the community to tertiary eye hospitals. FUNDING: National Medical Research Council, Singapore.

Exploring Factors Underlying Ethnic Difference in Age-related Macular Degeneration Prevalence.

AIMS: To assess contributions of dietary and genetic factors to ethnic differences in AMD prevalence. DESIGN: Population-based analytical study. METHODS: In the Blue Mountains Eye Study, Australia (European ancestry n = 2826) and Multi-Ethnic Cohort Study, Singapore (Asian ancestry, n = 1900), AMD was assessed from retinal photographs. Patterns of dietary composition and scores of the Alternative Healthy Eating Index were computed using food frequency questionnaire data. Genetic susceptibility to AMD was determined using either single nucleotide polymorphisms (SNPs) of the complement factor H and age-related maculopathy susceptibility 2 genes, or combined odds-weighted genetic risk scores of 24 AMD-associated SNPs. Associations of AMD with ethnicity, diet, and genetics were assessed using logistic regression. Six potential mediators covering genetic, diet and lifestyle factors were assessed for their contributions to AMD risk difference between the two samples using mediation analyses. RESULTS: Age-standardized prevalence of any (early or late) AMD was higher in the European (16%) compared to Asian samples (9%, p < .01). Mean AMD-related genetic risk scores were also higher in European (33.3 ± 4.4) than Asian (Chinese) samples (31.7 ± 3.7, p < .001). In a model simultaneously adjusting for age, ethnicity, genetic susceptibility and Alternative Healthy Eating Index scores, only age and genetic susceptibility were significantly associated with AMD. Genetic risk scores contributed 19% of AMD risk difference between the two samples while intake of polyunsaturated fatty acids contributed 7.2%. CONCLUSION: Genetic susceptibility to AMD was higher in European compared to Chinese samples and explained more of the AMD risk difference between the two samples than the dietary factors investigated.

Association of Cataract Surgery With Risk of Diabetic Retinopathy Among Asian Participants in the Singapore Epidemiology of Eye Diseases Study.

Importance: Cataracts and diabetic retinopathy (DR) are the leading causes of acquired blindness worldwide. Although extraction is the standard treatment option for cataracts, it is also reported to increase the risk of developing DR among individuals with diabetes. Nevertheless, the association between cataract surgery and risk of DR is still not well understood, and there have been no prior population-based reports in this area. Objective: To assess the risk of developing DR after cataract surgery among individuals with type 2 diabetes. Design, Setting, and Participants: A population-based prospective cohort study was conducted among participants recruited from the Singapore Epidemiology of Eye Diseases Study. The baseline visit was conducted between June 1, 2004, and March 31, 2009, and the 6-year follow-up visit was conducted between June 1, 2011, and July 31, 2016. Statistical analysis was performed from October 1 to 31, 2019. Exposures: Cataract surgery performed before a follow-up visit, determined based on slitlamp evaluation of lens status at baseline and follow-up visits. Main Outcomes and Measures: Eyes with incidence of DR were defined as those with the presence of any DR (level ≥15 based on the modified Airlie House classification system, graded from retinal photographs) at 6-year follow-up with no DR at baseline. The association between cataract surgery and incidence of DR was evaluated using a multivariable Poisson regression model with a generalized estimating equation to account for correlation between both eyes. Results: A total of 1734 eyes from 972 participants with diabetes (392 Malay individuals and 580 Indian individuals; 495 men; mean [SD] age, 58.7 [9.1] years) were included in the analysis. A total of 163 study eyes had already undergone cataract surgery at baseline, and a total of 187 eyes (originally phakic at baseline) underwent cataract surgery any time during the follow-up period. Of these 350 eyes, 77 (22.0%) developed DR. Among the 1384 eyes that never underwent cataract surgery, 195 (14.1%) developed DR. After adjustments for age, sex, race/ethnicity, baseline hemoglobin A1c level, duration of diabetes, random blood glucose level, antidiabetic medication use, hypertension, body mass index, and smoking status, multivariable regression analysis showed that any prior cataract surgery was associated with incidence of DR (relative risk, 1.70; 95% CI, 1.26-2.30; P = .001). Subgroup analyses by race/ethnicity showed similar associations in both Malay individuals (relative risk, 1.73; 95% CI, 1.13-2.69; P = .02) and Indian individuals (relative risk, 1.93; 95% CI, 1.33-2.80; P < .001). Conclusions and Relevance: The findings of this population-based cohort study suggest that prior cataract surgery was associated with a higher risk of developing DR among individuals with diabetes. Further validation is warranted to confirm this association.

Incidence, progression and risk factors of age-related cataract in Malays: The Singapore Malay Eye Study.

IMPORTANCE: Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations. BACKGROUND: We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined. METHODS: Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System. MAIN OUTCOMES AND MEASURES: Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalized estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors. RESULTS: Age-adjusted 6-year incidence of cortical, nuclear and PSC cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend <.001 for all types). Diabetes (relative risk [RR], 1.97; 95% confidence intervals [CI], 1.46-2.67) was associated with incident cortical cataract, hypertension was associated with PSC cataract incidence (RR, 2.09; 95% CI, 1.22-3.61), after multivariable adjustment. Progression occurred in 20.4%, 5.9% and 40.6% of baseline cortical, nuclear and PSC cataract cases, respectively. CONCLUSIONS AND RELEVANCE: Similar to other elderly populations, incidence and progression of cataract were common in this Malay population. Diabetes and hypertension were important modifiable risk factors for cataract, highlighting the importance of systemic health on eye disease.

Six-Year Changes in Myopic Macular Degeneration in Adults of the Singapore Epidemiology of Eye Diseases Study.

Purpose: To examine the 6-year incidence, progression, associated risk factors, and impact of myopic macular degeneration (MMD) in a myopic population in Singapore. Methods: We examined myopic (spherical equivalent ≤-0.5 diopters) adults (N = 2157 persons and 3661 eyes) who were phakic at baseline and participated in both baseline and 6-year follow-up visits of the Singapore Epidemiology of Eye Diseases study. Eye examinations, including visual acuity, subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the META-PM classification. Vision-related quality of life was assessed with Rasch-transformed scores from reading, mobility, and emotional domains of the Impact of Vision Impairment questionnaire. Results: The 6-year eye-specific incidence of MMD among myopic eyes was 1.2% (95% CI, 0.9%-1.6%). Older age, worse spherical equivalent, and longer AL at baseline were associated with MMD incidence (all P < 0.001). The 6-year eye-specific progression of MMD in 288 eyes with baseline MMD was 17.0% (95% CI, 12.6%-21.4%). More severe MMD at baseline, worse spherical equivalent, and longer AL (all P < 0.05) were associated with MMD progression. Patients with Meta-PM categories 3 and 4 had worse best-corrected visual acuity and poorer vision-related quality of life outcomes than those without MMD (all P < 0.05). Conclusions: Over a 6-year period, one in 80 myopic eyes developed MMD and one in six with existing MMD had MMD progression. Myopia severity and AL were strong predictors of MMD development and progression. Eyes with severe MMD were at higher risk of MMD progression than those with less severe MMD, and were associated with poorer visual acuity and vision-related quality of life.

A Deep Learning Model for Segmentation of Geographic Atrophy to Study Its Long-Term Natural History.

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 mm2, 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.

Wholegrain and legume consumption and the 5-year incidence of age-related cataract in the Blue Mountains Eye Study.

The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992-1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997-2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies.

Systemic medications and cortical cataract: the Singapore Epidemiology of Eye Diseases Study.

BACKGROUND/AIMS: To evaluate the association between systemic medications and cortical cataract prevalence in an Asian population. METHODS: The Singapore Epidemiology of Eye Diseases Study recruited 10 033 Chinese, Malay and Indian residents aged 40+ years living in Singapore. Information on medication use was collected at interview using questionnaires. The presence and severity of cortical cataract were assessed from lens photographs using the modified Wisconsin Cataract Grading System. Associations between medications and the presence of cortical cataract were assessed using logistic regression. Associations between medications and greater severity of cortical cataract (none, minimal, early and late) were assessed using ordinal logistic regression. RESULTS: A total of 8965 participants were included, the mean age was 57.6 (SD=9.8) years, and 4555 (50.8%) were women. After adjusting for age, gender, ethnicity, body mass index, smoking status, socioeconomic status, hypertension, hyperlipidaemia, diabetes, duration of diabetes and cardiovascular disease, ACE inhibitors (OR=1.27; 95% CI 1.05 to 1.55), fibrates (OR=1.57; 95% CI 1.05 to 2.35), alpha-glucosidase inhibitors (AGIs) (OR=1.85; 95% CI 1.13 to 3.02) and insulin (OR=1.80; 95% CI 1.11 to 2.93) were significantly associated with the presence of cortical cataract. Further adjusting for concurrent medication use did not alter these associations. Consistently, the four medications were also associated with a greater severity level of cortical cataract. CONCLUSION: ACE inhibitors, fibrates and AGIs were associated with increased prevalence of cortical cataract in this Asian population, independent of the presence of hypertension, hyperlipidaemia and diabetes, respectively. Whether they contribute to the risk of cortical cataract needs confirmation in longitudinal studies.

Association of Genetic Variation With Keratoconus.

Importance: Keratoconus is a condition in which the cornea progressively thins and protrudes in a conical shape, severely affecting refraction and vision. It is a major indication for corneal transplant. To discover new genetic loci associated with keratoconus and better understand the causative mechanism of this disease, we performed a genome-wide association study on patients with keratoconus. Objective: To identify genetic susceptibility regions for keratoconus in the human genome. Design, Setting, and Participants: This study was conducted with data from eye clinics in Australia, the United States, and Northern Ireland. The discovery cohort of individuals with keratoconus and control participants from Australia was genotyped using the Illumina HumanCoreExome single-nucleotide polymorphism array. After quality control and data cleaning, genotypes were imputed against the 1000 Genomes Project reference panel (phase III; version 5), and association analyses were completed using PLINK version 1.90. Single-nucleotide polymorphisms with P < 1.00 × 10-6 were assessed for replication in 3 additional cohorts. Control participants were drawn from the cohorts of the Blue Mountains Eye Study and a previous study of glaucoma. Replication cohorts were from a previous keratoconus genome-wide association study data set from the United States, a cohort of affected and control participants from Australia and Northern Ireland, and a case-control cohort from Victoria, Australia. Data were collected from January 2006 to March 2019. Main Outcomes and Measures: Associations between keratoconus and 6 252 612 genetic variants were estimated using logistic regression after adjusting for ancestry using the first 3 principal components. Results: The discovery cohort included 522 affected individuals and 655 control participants, while the replication cohorts included 818 affected individuals (222 from the United States, 331 from Australia and Northern Ireland, and 265 from Victoria, Australia) and 3858 control participants (2927 from the United States, 229 from Australia and Northern Ireland, and 702 from Victoria, Australia). Two novel loci reached genome-wide significance (defined as P < 5.00 × 10-8), with a P value of 7.46 × 10-9 at rs61876744 in patatin-like phospholipase domain-containing 2 gene (PNPLA2) on chromosome 11 and a P value of 6.35 × 10-12 at rs138380, 2.2 kb upstream of casein kinase I isoform epsilon gene (CSNK1E) on chromosome 22. One additional locus was identified with a P value less than 1.00 × 10-6 in mastermind-like transcriptional coactivator 2 (MAML2) on chromosome 11 (P = 3.91 × 10-7). The novel locus in PNPLA2 reached genome-wide significance in an analysis of all 4 cohorts (P = 2.45 × 10-8). Conclusions and Relevance: In this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11.

Correction: Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

[This corrects the article DOI: 10.1371/journal.pone.0220143.].

Evaluating the associations between obesity and age-related cataract: a Mendelian randomization study.

BACKGROUND: The obesity-cataract association has been inconsistently reported. The fat mass and obesity-related (FTO) single-nucleotide polymorphism (SNP) rs9939609 is a major SNP associated with obesity and has been used as an instrumental variable for obesity in a Mendelian randomization (MR) approach. An interaction between the FTO SNP and macronutrient intake for obesity was suggested previously. OBJECTIVE: The aim of this study was to assess the associations between obesity and cataract, using FTO SNP rs9939609 as an instrumental variable in an MR approach, and explore interactions of this SNP with macronutrient intake in relation to risk of cataract in a population-based cohort. METHODS: The Blue Mountains Eye Study (BMES) is a longitudinal population-based study of common eye disease. Of 3654 baseline participants of the BMES (1992-1994), 2334 (75.8% of survivors) and 1952 (76.7% of survivors) were followed 5 and 10 y later. During the 5-y follow-up, 1174 new participants were examined. Cumulative cataract was defined as the presence of cortical, nuclear, or posterior subcapsular (PSC) cataract at any visit, following the Wisconsin Cataract Grading System. Imputed dosage of the FTO SNP rs9939609 was used. Quintiles of macronutrient intake (carbohydrates, protein, fats) were derived from an FFQ. ORs and 95% CIs were estimated using multivariable-adjusted logistic regression models. RESULTS: After multivariable adjustment, there were no associations between BMI and any cataract types in MR models using rs9939609 as an instrumental variable. However, an interaction between rs9939609 and protein intake for PSC cataract risk was suggested (P = 0.03). In analyses stratified by quintiles of protein intake, each minor allele of rs9939609 was associated with increased odds of PSC (OR: 2.14; 95% CI: 1.27, 3.60) in the lowest quintile subgroup only. CONCLUSIONS: Obesity was not causally associated with age-related cataract. However, among persons in the lowest quintile of protein intake, obesity may be associated with PSC cataract.

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

PURPOSE: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

The Combination of Healthy Diet and Healthy Body Weight Is Associated with Lower Risk of Nuclear Cataract in the Blue Mountains Eye Study.

BACKGROUND: Greater adherence to dietary guidelines has previously been found to be associated with decreased risk of visual impairment. However, whether or not this association extends to age-related cataract, 1 of the leading causes of visual impairment, is unknown. OBJECTIVES: The aim of this study was to assess the association between adherence to dietary guidelines, using total diet score, and incidence of age-related cataract. METHODS: Of 3654 baseline participants of the population-based Blue Mountains Eye Study cohort (1992-1994), 2334 (75.8% survivors) and 1952 (76.7% survivors) were examined after 5 and 10 y, respectively. Cataract was assessed from lens photographs using the Wisconsin Cataract Grading System. Baseline total diet score was calculated from FFQ data following a modified version of the Healthy Eating Index for Australians. OR with 95% CI were estimated using discrete logistic regression analyses, adjusting for age, sex, and other confounders. To test interaction, a cross-product term of 2 factors was included in regression models. RESULTS: Of 2173 participants (84.7% of those returned for 1 or both follow-ups) with total diet score estimated, 57% were women, mean baseline age was 63.9 ± 8.4y, and mean baseline BMI was 26.3 ± 4.3 kg/m2. After multivariable adjustment, baseline total diet score was not associated with incidence of any cataract. A multiplicative interaction was observed between total diet score and BMI for incident nuclear cataract (P-interaction = 0.04): increasing baseline total diet score was associated with decreased risk of nuclear cataract among participants with BMI <25 (per unit increased total diet score, OR: 0.90; 95% CI: 0.81, 0.99; P = 0.02), but not among participants with BMI ≥25 (OR: 1.00; 95% CI: 0.92, 1.10; P = 0.95). CONCLUSIONS: Adherence to dietary guidelines had no appreciable influence on cataract development overall in this older Australian population. However, adherence to dietary guidelines combined with healthy BMI is associated with decreased risk of nuclear cataract, an aging marker.

Six-year incidence and progression of diabetic retinopathy in Indian adults: the Singapore Indian Eye study.

AIMS: Diabetes is a major public health problem in migrants and ethnic minorities worldwide. We determined the incidence and risk factors of diabetic retinopathy (DR) in migrant Indians living in Singapore. METHODS: We included data from 759 Indian adults with diabetes, who participated in the baseline (aged 40-80 years, 2007-2009) and 6-year follow-up 2012-2015 of the Singapore Indian Eye Study. Retinal photographs were graded for the presence and severity of DR using modified Airlie House Classification. Incidence was assessed in participants who were free of DR at baseline visit (n=501), while progression in those with DR but free of proliferative DR at baseline visit (n=189). Risk factors included demographic, lifestyle, socioeconomic, family history, genes, duration of diabetes, glycaemic control, insulin use, ocular and clinical factors. RESULTS: The 6-year age-standardised DR incidence and progression were 21.89% and 33.45%, respectively. HbA1c (risk ratio (RR) 1.41, 95% CI 1.28 to 1.55 per unit increase), current smoking (RR 1.63, 95% CI 1.02 to 2.62) and insulin use (RR 2.63, 95% CI 1.44 to 4.82) were associated with higher incidence, whereas estimated cerebrospinal fluid pressure (RR 0.90, 95% CI 0.82 to 0.98) and body mass index (BMI) (RR 0.74, 95% CI 0.60 to 0.93) were associated with lower incidence of DR. Higher HbA1c (RR 1.26, 95% CI 1.13 to 1.42), BMI (RR 1.26, 95% CI 1.02 to 1.56) and estimated cerebrospinal fluid pressure (RR 1.11, 95% CI 1.02 to 1.21) were associated with DR progression. The population attributable risk of HbA1c >8% was 41.29% and 49.63% for DR incidence and progression. CONCLUSION: DR incidence and progression in migrant Indians living in Singapore was more than double that reported in Indians living in urban India. Consistent with past studies, poor glycaemic control was an important predictor for incidence and progression of DR.

Beyond vision loss: the independent impact of diabetic retinopathy on vision-related quality of life in a Chinese Singaporean population.

BACKGROUND/AIMS: To assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population. METHODS: The Singapore Chinese Eye Study (n=3353; 2009-2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the 'Reading', 'Mobility' and 'Emotional' domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models. RESULTS: Of the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR. CONCLUSIONS: We documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR.