Association between body mass index and diabetic retinopathy in Asians: the Asian Eye Epidemiology Consortium (AEEC) study.

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/m2, reference), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). 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.

Association between Body Mass Index and Chronic Kidney Disease in Asian Populations: A Participant-level Meta-Analysis.

Obesity and chronic kidney disease (CKD) are major public health problems worldwide. However, the association between body mass index (BMI) and CKD is inconclusive in Asians. In this meta-analysis, eight population-based studies, from China, India, Russia (Asian), Singapore and South Korea, provided individual-level data (n=50037). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. BMI was analyzed both as a continuous variable and in three categories: <25kg/m2, normal; 25-29.9kg/m2, overweight; and ≥30kg/m2, obese. The association between BMI and CKD was evaluated in each study using multivariable logistic regression models and individual estimates were pooled using random-effect meta-analysis to obtain the pooled odds ratio (OR) and 95% confidence interval (CI). Associations were also evaluated in subgroups of age, gender, smoking, diabetes, and hypertension status. Of 50037 adults, 4258 (8.5%) had CKD. 13328 (26.6%) individuals were overweight while 4440 (8.9%) were obese. The prevalence of any CKD ranged from 3.5% to 29.1% across studies. In pooled analysis, both overweight and obesity were associated with increased odds of CKD, with pooled OR (95% CI) of 1.15 (1.03-1.29) and 1.23 (1.06-1.42), respectively. In subgroup analyses, significant associations between BMI and CKD were observed in adult males, non-smokers, and those with diabetes and arterial hypertension (all p<0.05). When evaluated as a continuous variable, BMI was not significantly associated with CKD. If confirmed in longitudinal studies, these results may have clinical implications in risk stratification and preventive measures, given that obesity and CKD are two major chronic diseases with substantial public health burden worldwide.

Novel Serum and Urinary Metabolites Associated with Diabetic Retinopathy in Three Asian Cohorts.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, a metabolic disorder, but understanding of its pathophysiology remains incomplete. Meta-analysis of three population-based cross-sectional studies (2004-11) representing three major Asian ethnic groups (aged 40-80 years: Chinese, 592; Malays, 1052; Indians, 1320) was performed. A panel of 228 serum/plasma metabolites and 54 urinary metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Main outcomes were defined as any DR, moderate/above DR, and vision-threatening DR assessed from retinal photographs. The relationship between metabolites and DR outcomes was assessed using multivariate logistic regression models, and metabolites significant after Bonferroni correction were meta-analyzed. Among serum/plasma metabolites, lower levels of tyrosine and cholesterol esters to total lipids ratio in IDL and higher levels of creatinine were positively associated with all three outcomes of DR (all p < 0.005). Among urinary metabolites, lower levels of citrate, ethanolamine, formate, and hypoxanthine were positively associated with all three DR outcomes (all p < 0.005). Higher levels of serum/plasma 3-hydroxybutyrate and lower levels of urinary 3-hydroxyisobutyrate were associated with VTDR. Comprehensive metabolic profiling in three large Asian cohorts with DR demonstrated alterations in serum/plasma and urinary metabolites mostly related to amino acids, lipoprotein subclasses, kidney function, and glycolysis.

100 most-cited articles on diabetic retinopathy.

Diabetic retinopathy (DR) research has had significant advancements over the past decades. We analysed the impact and characteristics of the top 100 (T100) most-cited articles in DR research. The Scopus database was searched for articles published from 1960 to June 2020 by two independent investigators. The T100 DR articles were published between 1961 and 2017 with median citations of 503 (range: 306-20 100); 84% were published after 1990. More than half (59%) were published in general medical/diabetes journals while 37% in ophthalmology journals. The top six journals contributed to 56% of the T100: Ophthalmology (n=13), Archives of Ophthalmology (n=12), Diabetes (n=9), New England Journal of Medicine (n=8), Journal of the American Medical Association (n=7) and The Lancet (n=7). Although observational studies were most popular (33%), randomised controlled trials (RCTs, 24%) published in journals with higher impact factor (IF) and citations (median IF and citations=7.113, 503 vs 21.437, 696.5, both p-value<0.05). 33 of the T100 were cited by several international DR clinical guidelines. The USA contributed to 63% of T100, but 18% of articles published after 2000 came from Asia. More than 80% of both first and last authors were men. Artificial intelligence (AI) to screen for DR ranked 14th and 99th despite recent publications in 2016 and 2017, respectively. To conclude, our T100 analysis showed that RCTs were most-cited and more articles were published in non-ophthalmology than ophthalmology journals. It highlights the impact the T100 DR has in shaping guidelines used to date in DR management, identifies AI for DR screening as an emerging area and shows a contemporary rise of Asian contribution in DR research.

A deep learning algorithm to detect chronic kidney disease from retinal photographs in community-based populations.

BACKGROUND: Screening for chronic kidney disease is a challenge in community and primary care settings, even in high-income countries. We developed an artificial intelligence deep learning algorithm (DLA) to detect chronic kidney disease from retinal images, which could add to existing chronic kidney disease screening strategies. METHODS: We used data from three population-based, multiethnic, cross-sectional studies in Singapore and China. The Singapore Epidemiology of Eye Diseases study (SEED, patients aged ≥40 years) was used to develop (5188 patients) and validate (1297 patients) the DLA. External testing was done on two independent datasets: the Singapore Prospective Study Program (SP2, 3735 patients aged ≥25 years) and the Beijing Eye Study (BES, 1538 patients aged ≥40 years). Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1·73m2. Three models were trained: 1) image DLA; 2) risk factors (RF) including age, sex, ethnicity, diabetes, and hypertension; and 3) hybrid DLA combining image and RF. Model performances were evaluated using the area under the receiver operating characteristic curve (AUC). FINDINGS: In the SEED validation dataset, the AUC was 0·911 for image DLA (95% CI 0·886 -0·936), 0·916 for RF (0·891-0·941), and 0·938 for hybrid DLA (0·917-0·959). Corresponding estimates in the SP2 testing dataset were 0·733 for image DLA (95% CI 0·696-0·770), 0·829 for RF (0·797-0·861), and 0·810 for hybrid DLA (0·776-0·844); and in the BES testing dataset estimates were 0·835 for image DLA (0·767-0·903), 0·887 for RF (0·828-0·946), and 0·858 for hybrid DLA (0·794-0·922). AUC estimates were similar in subgroups of people with diabetes (image DLA 0·889 [95% CI 0·850-0·928], RF 0·899 [0·862-0·936], hybrid 0·925 [0·893-0·957]) and hypertension (image DLA 0·889 [95% CI 0·860-0·918], RF 0·889 [0·860-0·918], hybrid 0·918 [0·893-0·943]). INTERPRETATION: A retinal image DLA shows good performance for estimating chronic kidney disease, underlying the feasibility of using retinal photography as an adjunctive or opportunistic screening tool for chronic kidney disease in community populations. FUNDING: National Medical Research Council, Singapore.

The 100 Most Cited Articles in Ophthalmology in Asia.

PURPOSE: The aim of this study was to review the top 100 most-cited articles in ophthalmology in Asia since 1970. METHODS: The Scopus database was used to identify the top 100 most-cited ophthalmology articles published in ophthalmology (T100-Eye) and nonophthalmology (T100-General) journals. RESULTS: The T100-Eye articles were published between 1982 and 2015, and T100-General from 1982 to 2017. T100-Eye had higher citations [median (range) = 317 (249-1326)] than T100-General [158 (105-2628)], but T100-General were published in journals with higher impact factor (IF) than T100-Eye (median IF= 5.5 vs 4.4) and produced more landmark papers (3 vs 1 articles that were cited >1000 times). Fifty-five % of T100-Eye were published in 3 journals: Ophthalmology (n = 22), Investigative Ophthalmology and Visual Science (n = 17), and American Journal of Ophthalmology (n = 16). T100-Eye had 88 original research articles and 12 reviews, whereas T100-General had 84 original research and 16 reviews. The most-frequent studied disease categories were myopia (n = 16) and age-related macular degeneration (n = 15) in T100-Eye and diabetic retinopathy (n = 24) and glaucoma (n = 16) in T100-General. Japan and Singapore contributed most to T100-Eye (n = 42, n = 17) and T100-General (n = 36, n = 26) articles. More than 80% and 95% of first and last authors were male in both lists. Emerging research topics were optical coherence tomography in T100-Eye and artificial intelligence in T100-General. CONCLUSIONS: Our citation analysis reveals differences in the focus of research topics of top-cited ophthalmology articles published in ophthalmology and nonophthalmology journals in Asia. It highlights that certain eye diseases are studied more in Asia and shows the contribution of specific countries to highly cited publications in ophthalmology research in Asia.

Hypertension, blood pressure control and diabetic retinopathy in a large population-based study.

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.

Association of Diabetic Retinopathy and Diabetic Kidney Disease With All-Cause and Cardiovascular Mortality in a Multiethnic Asian Population.

Importance: The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. Objective: To examine the association of DR and DKD separately and jointly with all-cause and cardiovascular disease (CVD) mortality in a multiethnic Asian population. Design, Setting, and Participants: A population-based cohort study was conducted including 2964 adults between the ages of 40 and 80 years with diabetes who participated in the Singapore Epidemiology of Eye Diseases study (baseline, 2004-2011). Data analysis was performed from January to May 2018. Exposures: Diabetic retinopathy ascertained from retinal photographs and DKD from estimated glomerular filtration rate. Main Outcomes and Measures: All-cause and CVD mortality obtained by linkage with the National Registry of Births and Deaths until May 2017. Results: Of the 2964 adults (mean [SD] age, 61.8 [10.0] years; 1464 [49.4%] female; 592 Chinese, 1052 Malay, and 1320 Indian), 29.9% of the participants had DR, while 20.7% had DKD. Over a median (interquartile range) follow-up of 8.8 (7.2-11.0) years, 610 deaths occurred (20.6%), of which 267 (9.0%) were due to CVD. In separate models, the multivariable hazard ratios for all-cause and CVD mortality were 1.54 (95% CI, 1.24-1.91) and 1.74 (95% CI, 1.27-2.40), respectively, for DR and 2.04 (95% CI, 1.64-2.56) and 2.29 (95% CI, 1.64-3.19), respectively, for DKD. In models including both DR and DKD, the subgroup with DKD alone (27.1% and 12.6%) followed by DR alone (6.5% and 5.2%) contributed substantially to the excess risk of all-cause and CVD mortality. Compared with those with no DR and DKD, the hazard ratios of all-cause and CVD mortality were 1.89 (95% CI, 1.40-2.57) and 2.26 (95% CI, 1.42-3.61), respectively, for DKD alone and 1.38 (95% CI, 1.03-1.86) and 1.64 (95% CI, 1.06-2.56), respectively, for DR alone. Hazard ratios for all-cause and CVD mortality were 2.76 (95% CI, 2.05-3.72) and 3.41 (95% CI, 2.19-5.32), respectively, for those with both DKD and DR. The relative excess risk associated with the interaction was 0.49 (95% CI, -0.29 to 1.27; P = .20) for all-cause mortality and 0.51 (95% CI, -0.83 to 1.85; P = .50) for CVD mortality. Conclusions and Relevance: These results suggest that risks of all-cause and CVD mortality were significantly higher in those with DKD and DR, but DKD was more strongly associated with excess risk. The findings underscore the importance of early identification and close monitoring and management of patients with DR and DKD to reduce the risk of death.

Incidence and progression of diabetic retinopathy: a systematic review.

Diabetic retinopathy is a leading cause of vision impairment and blindness. We systematically reviewed studies published from Jan 1, 1980, to Jan 7, 2018, assessed the methodological quality, and described variations in incidence of diabetic retinopathy by region with a focus on population-based studies that were conducted after 2000 (n=8, including two unpublished studies). Of these eight studies, five were from Asia, and one each from the North America, Caribbean, and sub-Saharan Africa. The annual incidence of diabetic retinopathy ranged from 2·2% to 12·7% and progression from 3·4% to 12·3%. Progression to proliferative diabetic retinopathy was higher in individuals with mild disease compared with those with no disease at baseline. Our Review suggests that more high-quality population-based studies capturing data on the incidence and progression of diabetic retinopathy with stratification by age and sex are needed to consolidate the evidence base. Our data is useful for conceptualisation and development of major public health strategies such as screening programmes for diabetic retinopathy.