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Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening., (© 2024. The Author(s).)

Background/aims: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR)., Methods: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality., Results: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p ≤8.4×10 -3 ). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p ≤1.4×10 -2 ). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others., Conclusion: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals., (© 2024. The Author(s).)

Background/aims: Obesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes., Methods: Pooled analysis of individual-level cross-sectional data from 10 010 adults with diabetes who participated in 12 population-based studies conducted in China, India, Japan, Russia (Asian), Singapore and South Korea that were part of the Asian Eye Epidemiology Consortium (AEEC). BMI was calculated as weight in kilograms divided by height in square metres and categorised into normal (<25 kg/m 2 , reference), overweight (25-29.9 kg/m 2 ) and obese (≥30 kg/m 2 ). Any-DR (n=1669) and vision-threatening DR (VTDR, n=489) were assessed from digital retinal photographs and graded according to standard protocols. Each study was analysed separately using multivariable logistic regression models adjusted for age, sex, haemoglobin A1c%, systolic blood pressure and diabetes duration, and the estimated odds ratios (ORs) and 95% confidence interval (CIs) from all studies were then combined using random-effects models., Results: In multivariable models, obesity showed a significant inverse association with any-DR (pooled OR (95% CI) =0.74 (0.59 to 0.91)) and VTDR (0.75 (0.60 to 0.93)). Similarly, in continuous analysis, BMI showed a significant inverse association with both any-DR (0.93 (0.87 to 0.99)) and VTDR (0.79 (0.68 to 0.92) per SD increase). Overweight did not show a significant association with any-DR., Conclusions: Among Asian adults with diabetes, both BMI and obesity showed an inverse association with DR. These findings warrant confirmation in further longitudinal studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes., Methods: We included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system., Results: Over the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression., Conclusion: Risk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To use machine learning (ML) to determine the relative contributions of modifiable and non-modifiable clinical, metabolic, genetic, lifestyle and socioeconomic factors on the risk of major eye diseases., Methods: We conducted analyses in a cross-sectional multi-ethnic population-based study (n=10 033 participants) and determined a range of modifiable and non-modifiable risk factors of common eye diseases, including diabetic retinopathy (DR), non-diabetic-related retinopathy (NDR); early and late age-related macular degeneration (AMD); nuclear, cortical and posterior subcapsular (PSC) cataract; and primary open-angle (POAG) and primary angle-closure glaucoma (PACG). Risk factors included individual characteristics, metabolic profiles, genetic background, lifestyle patterns and socioeconomic status (n~100 risk factors). We used gradient boosting machine to estimate the relative influence (RI) of each risk factor., Results: Among the range of risk factors studied, the highest contributions were duration of diabetes for DR (RI=22.1%), and alcohol consumption for NDR (RI=6.4%). For early and late AMD, genetic background (RI~20%) and age (RI~15%) contributed the most. Axial length was the main risk factor of PSC (RI=30.8%). For PACG, socioeconomic factor (mainly educational level) had the highest influence (20%). POAG was the disease with the highest contribution of modifiable risk factors (cumulative RI~35%), followed by PACG (cumulative RI ~30%), retinopathy (cumulative RI between 20% and 30%) and late AMD (cumulative RI ~20%)., Conclusion: This study illustrates the utility of ML in identifying factors with the highest contributions. Risk factors possibly amenable to interventions were intraocular pressure (IOP) and Body Mass Index (BMI) for glaucoma, alcohol consumption for NDR and levels of HbA1c for DR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Topic: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045., Clinical Relevance: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population., Methods: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019., Results: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians., Discussion: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined the longitudinal association of baseline alcohol intake and frequency with the 6-year incidence and progression of diabetic retinopathy (DR) in a population-based cohort of Singaporean Indians., Methods: We included 656 participants with diabetes mellitus, gradable retinal photographs from baseline (2007-2009) and follow-up (2013-2015) examinations, information on alcohol intake and other relevant data from the Singapore Indian Eye Study were included. Incident DR was defined using the Modified Airlie House Classification as no DR at baseline and at least minimal non-proliferative DR at follow-up; and DR progression as at least a one-step worsening in DR at follow-up from minimal or worse status at baseline, excluding those with proliferative DR., Results: The mean age (SD) of our participants (n=656) was 58.8 (9.2) years, and 54.4% were male. At follow-up, 82 of 510 (16%) participants developed DR, and 45 of 146 (30.8%) had DR progression. 65 (12.7%) and 28 (19.1%) participants consumed alcohol in incident DR and progression categories, respectively. In multivariable analyses, those who consumed alcohol had nearly two-thirds reduced odds of incident DR (OR (95% CI): 0.36 (0.13 to 0.98)) compared with those who did not. Participants with infrequent consumption of alcohol also had a reduction in odds of incident DR (0.17 (0.04 to 0.69)), compared with non-drinkers. No association was found between alcohol consumption and DR progression., Conclusions and Relevance: In our longitudinal population of Singapore Indians, baseline alcohol intake, particularly infrequent consumption, was associated with lower risk of developing DR, compared with non-drinkers, in line with previous cross-sectional findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To investigate the longitudinal associations between person-level and area-level socioeconomic status (PLSES and ALSES, respectively) with diabetic retinopathy (DR) and visual impairment (VI) in Asians with diabetes mellitus (DM)., Methods: In this population-based cohort study, we included 468 (39.4%) Malays and 721 (60.6%) Indians with DM, with a mean age (SD) of 58.9 (9.1) years; 50.6% were female and the mean follow-up duration was 6.2 (0.9) years. Individual PLSES parameters (education, monthly income and housing type) were quantified using questionnaires. ALSES was assessed using the Socioeconomic Disadvantage Index derived from Singapore's 2010 areal census (higher scores indicate greater disadvantage). Incident DR and VI were defined as absent at baseline but present at follow-up, while DR and VI progression were defined as a ≥1 step increase in severity category at follow-up. Modified Poisson regression analysis was used to determine the associations of PLSES and ALSES with incidence and progression of DR and VI, adjusting for relevant confounders., Results: In multivariable models, per SD increase in ALSES score was associated with greater DR incidence (risk ratio (95% CI) 1.27 (1.13 to 1.44)), DR progression (1.10 (1.00 to 1.20)) and VI incidence (1.10 (1.04 to 1.16)), while lower PLSES variables were associated with increased DR (low income: 1.68 (1.21 to 2.34)) and VI (low income: 1.44 (1.13 to 1.83); ≤4 room housing: 2.00 (1.57 to 2.54)) incidence., Conclusions: We found that both PLSES and ALSES variables were independently associated with DR incidence, progression and associated vision loss in Asians. Novel intervention strategies targeted at low socioeconomic status communities to decrease rates of DR and VI are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We aimed to estimate the supply of ophthalmologists in relation to the global and regional burden of vision-threatening diabetic retinopathy (VTDR). Diabetes mellitus (DM) population data from seven world regions were obtained from the International Diabetes Federation Atlas 2017. A systematic review was performed to include population-, community-based studies that reported country-specific VTDR prevalence. Random effect meta-analysis was then performed to estimate global and regional VTDR prevalence. VTDR prevalence estimates coupled with DM population data were then used to estimate the number of VTDR cases. Global and regional number of ophthalmologists were derived from the International Council of Ophthalmology Report 2015. Fifty studies (17 from Western Pacific [WP], nine North America and Caribbean [NAC], nine Middle East and North Africa [MENA], five Europe, eight South East Asia [SEA], one South and Central America [SACA] and one from Africa) were included. Global VTDR prevalence was 7.26% (95% CI, 6.18-8.32%). Regional VTDR prevalence was 14.35% in Africa, 11.21% in MENA, 10.00% in NAC, 6.32% in Europe, 6.22% in WP, 5.83% in SACA and 2.97% in SEA. Globally, there were 7.16 ophthalmologists per 1000 VTDR patients. Europe had the highest ophthalmologist per 1000 VTDR patient ratio at 18.03 followed by SACA (17.41), while NAC, MENA and Africa had the lowest at 4.90, 4.81 and 0.91 respectively. Across regions, the ophthalmologist densities ranged from 0.91 to 18.03 per 1000 VTDR patients, with NAC, MENA and Africa having less than 5 ophthalmologists per 1000 patients. These findings will aid global and regional policy planning and healthcare resource allocation for VTDR management.

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.

Background: Clinical trials have shown beneficial effects of blood pressure (BP) control in reducing the risk of diabetic retinopathy (DR). However, association between BP control and DR in population-based studies is not clear. We aimed to examine the association of hypertension and BP control with DR., Methods: We analysed data from a population-based cross-sectional study of Chinese, Malay and Indians adults with diabetes and hypertension (2004-2011, n = 2189, aged 40-80 years) in Singapore. DR severity was assessed from retinal photographs and graded for any- and vision-threatening DR (VTDR) using the modified Airlie House classification. Hypertension status was classified into (1) good control: on treatment (SBP < 130 and DBP < 80 mm Hg), (2) moderate control: on treatment, with BP levels other than group 1 and 3, (3) poor control: on treatment (SBP ≥140 and DBP ≥ 90 mm Hg), (4) untreated hypertension, any BP level. SBP, DBP and pulse pressure (PP) were analyzed as categories and as continuous variables. The association between BP and DR was assessed using multivariable logistic regression models., Results: The prevalence of any-DR and VTDR in the study population was 33.8% and 9.0% respectively. Both poorly controlled and untreated hypertension were significantly associated with any-DR with odds ratio (OR) (95% confidence interval [CI]) of 1.97 (1.39-2.83), and 2.01 [1.34-3.05]. Among BP components, SBP and PP were associated with both any-DR and VTDR with OR (95% CI) of 1.45 (1.28-1.65) and 1.61 (1.41-1.84) for any-DR, and 1.44 (1.19-1.76) and 1.67 (1.37-2.06) for VTDR., Conclusion: In a population-based sample of Asian adults with diabetes and hypertension, treated but poorly controlled as well as untreated hypertension were significantly associated with any-DR. Among the BP components, higher SBP and PP levels were associated with both any-DR and VTDR. Further longitudinal studies are necessary to confirm our findings., Competing Interests: The authors have declared that no competing interests exist.

Background: To evaluate retinal thickness profiles in eyes with and without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT) among individuals with diabetes., Methods: Participants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians aged 40 years or older residing in Singapore. All participants underwent standardised systemic and ophthalmic examinations. Average thickness of the macula, ganglion cell-inner plexiform layer and outer retina layer (from the outer plexiform layer to the retinal pigment epithelium layer) were measured using SD-OCT. DR status and severity were graded based on fundus photographs using the modified Airlie House classification system. Participants with macular oedema were excluded., Results: 2240 eyes from 1280 participants were included. Of these, 1764 (78.7%) eyes had no DR, 351 (15.7%) eyes had minimal or mild DR and 125 (5.6%) eyes had moderate or worse DR. After adjusting for age, gender, ethnicity, axial length, hypertension, glycated haemoglobin, body mass index, total cholesterol and diabetes duration, eyes with DR had thicker macula (245.44 µm vs 243.04 µm, P=0.03) and outer retina (124.26 µm vs 123.08 µm, P=0.01) than eyes without DR. When stratified by DR severity, thicker macula (250.24 µm vs 242.88 µm, P=0.011) and outer retina (126.4 µm vs 123.0 μm, P=0.006) were observed in eyes with moderate or worse, but not minimal or mild DR, compared with eyes without DR., Conclusions: Even in the absence of macular oedema, eyes with DR, particularly those with more severe DR, had thicker macular and outer retinal layers than eyes without DR., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR)., Methods: In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 ± 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011-15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6≤ h <8), and long (≥8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders., Results: Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03-2.89) and 2.17 (1.28-3.66) respectively. Long sleep duration (2.37 [1.16-4.89]), high risk of OSA (2.24 [1.09-4.75]), and excessive daytime sleepiness (3.27 [1.02-10.30]) were separately associated with VTDR., Conclusion: Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR., Competing Interests: The authors have declared that no competing interests exist.

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.)

Background/aims: To determine the association between aspirin use and diabetic retinopathy (DR) among persons with diabetes, in a population-based, cross-sectional study., Methods: Subjects with diabetes aged >40 years from the Singapore Epidemiology of Eye Diseases Study were enrolled in this study. Retinal photographs were graded for DR according to the modified Airlie House classification system. Vision threatening diabetic retinopathy (VTDR) was defined as the presence of severe non-proliferative DR, or proliferative DR, or clinically significant macular oedema. The association between aspirin use and the presence of DR or VTDR was assessed using multivariable logistic regression models including age, gender, ethnicity, socioeconomic status, HbA1c, systolic blood pressure, anti-hypertension medicine, total cholesterol, anti-cholesterol medicine, BMI, current smoking status, diabetes duration, history of cardiovascular disease (CVD) and chronic kidney disease (CKD.)., Results: A total of 2,061 participants with diabetes and complete record of relevant systemic and DR data were included. Of these, 711 (34.5%) had any stage of DR, and among these 177 (8.6%) had VTDR. After adjusting for co-variables listed, the association between aspirin use and VTDR was significant (OR = 1.69, P = 0.019), while the association between aspirin use and any DR was borderline (OR = 1.31, P = 0.063). Aspirin use was not associated with either DR or VTDR after additional adjustment of CVD and CKD. Further stratification by history of CVD or CKD showed no association between aspirin use and DR/VTDR in either subgroup., Conclusion: Aspirin use was not significantly associated with DR but might be an indicator of diabetic complications (CVD, CKD) that were co-present with more severe DR type. Future longitudinal studies are warranted to confirm our findings.

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.)