Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemDiabetic Retinopathy in 2011: Further Insights From New Epidemiological Studies and Clinical Trials(AMER DIABETES ASSOC, 2011-04)
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ItemImpact of Visual Impairment and Eye diseases on Mortality: the Singapore Malay Eye Study (SiMES)(NATURE PORTFOLIO, 2015-11-09)We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40-80 years between 2004-2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25-1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24-2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25-2.36) and CVD mortality (HR 1.57; 95% CI, 1.05-2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26-7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.
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ItemSerum Cystatin C, Markers of Chronic Kidney Disease, and Retinopathy in Persons with Diabetes(HINDAWI LTD, 2015)PURPOSE: We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR). METHODS: We examined 1,119 Indian adults with diabetes, aged 40-80 years, who participated in the Singapore Indian Eye Study (2007-2009), a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c. RESULTS: The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1%) compared to CKD defined separately by creatinine (26.6%), cystatin C (20.9%), and albuminuria (23.4%). People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI) = 13.63 (6.08-30.54)) compared to those without CKD by any marker. Nearly half (48.7%) of participants with cystatin C ≥ 1.12 mg/L have moderate DR. CONCLUSIONS: CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes.
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ItemIncreased Burden of Vision Impairment and Eye Diseases in Persons with Chronic Kidney Disease - A Population-Based Study(ELSEVIER, 2016-03)BACKGROUND: Chronic kidney disease (CKD) has been shown to be associated with diabetic retinopathy (DR) and age-related macular degeneration (AMD), leading causes of blindness in elderly adults in previous studies. However, the association of CKD with visual impairment (VI) is not clear. We aimed to examine the association of CKD with VI and other age-related ocular diseases in a population-based sample of Asian adults. METHODS: We analyzed data from 10,033 adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases (SEED, 2004-11) Study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2) from serum creatinine. VI was defined as best-corrected visual acuity < 20/40 in the better eye. Cataract, retinopathy, DR, glaucoma and AMD were assessed using standardized ocular examination, retinal photography and visual field assessments. The associations of CKD with VI and ocular conditions were examined using logistic regression models adjusted for age, sex, race, smoking, alcohol intake, education status, body mass index, systolic blood pressure, diabetes mellitus, cholesterol levels and cardiovascular disease. FINDINGS: The prevalence of VI and ocular disease were significantly higher in participants with CKD (36.1% and 84.7%) than in those without (12.9% and 54.3%, both p < 0.001). In multivariable models, CKD was significantly associated with VI (odds ratio [95% confidence interval] = 1.34 [1.14-1.58]), any ocular disease (1.28 [1.03-1.61]), cataract (1.24 [1.01-1.52]), any retinopathy (1.77 [1.45-2.15]), and DR (1.94 [1.47-2.54]). INTERPRETATION: The burden of VI and eye diseases is high among persons with CKD. Our findings suggest that it may be useful to screen for ocular disease and VI in persons with CKD.
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ItemThe Impact of Macronutrients on Retinal Microvasculature among Singapore Pregnant Women during the Mid-Late Gestation(PUBLIC LIBRARY SCIENCE, 2016-08-10)BACKGROUND: Imbalanced macronutrient intakes can induce impairment of endothelial and vascular function, and further lead to metabolic and cardiovascular disease. However, little is known about the influence of such diets on endothelial and vascular dysfunction in pregnant women, even though high-fat diet is a known risk for pregnancy complications such as gestational diabetes and pre-eclampsia. OBJECTIVE: We aimed to assess the association between maternal macronutrient intakes (protein, fat and carbohydrates), dietary quality and retinal microvascular changes in a multi-ethnic Asian mother-offspring cohort. METHODS: Pregnant women (n = 614) with singleton pregnancies were recruited during their first trimester from June 2009 to Sep 2010. Maternal diet quality and macronutrient intakes, expressed as a percentage of total energy during pregnancy, were ascertained using 24 hr recalls and 3 d food diaries at 26-28 weeks gestation. Retinal examination was completed at the same clinic visit. Dietary quality was assessed and scored using the Health Eating Index in Asian Pregnant women (HEI-AP), while macronutrients intakes ware expressed as percentages of total energy and further log transformed for analysis. Associations were examined cross-sectionally by substitution models with the use of multiple linear regression. RESULTS: In adjusted model, each 20 points decrease in HEI-AP score was associated with a significant increase of 1.70 μm (p<0.05) in retinal venular calibre. Each 0.1 log increase in percentage of total fat intake was associated with a significant increment of 1.84 μm (p<0.05) in retinal venular caliber. Additionally, each 0.1 log increase in percentage of mono-unsaturated fat intake was associated with an increment of 1.84 μm (p<0.01) in retinal venular caliber. CONCLUSIONS: In this cross-sectional study, we found that women with higher fat and lower protein intakes, and lower diet quality tended to have wider retinal venular caliber, which is suggestive of suboptimal microvasculature.
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ItemDeep learning in estimating prevalence and systemic risk factors for diabetic retinopathy: a multi-ethnic study(NATURE PORTFOLIO, 2019-04-10)In any community, the key to understanding the burden of a specific condition is to conduct an epidemiological study. The deep learning system (DLS) recently showed promising diagnostic performance for diabetic retinopathy (DR). This study aims to use DLS as the grading tool, instead of human assessors, to determine the prevalence and the systemic cardiovascular risk factors for DR on fundus photographs, in patients with diabetes. This is a multi-ethnic (5 races), multi-site (8 datasets from Singapore, USA, Hong Kong, China and Australia), cross-sectional study involving 18,912 patients (n = 93,293 images). We compared these results and the time taken for DR assessment by DLS versus 17 human assessors - 10 retinal specialists/ophthalmologists and 7 professional graders). The estimation of DR prevalence between DLS and human assessors is comparable for any DR, referable DR and vision-threatening DR (VTDR) (Human assessors: 15.9, 6.5% and 4.1%; DLS: 16.1%, 6.4%, 3.7%). Both assessment methods identified similar risk factors (with comparable AUCs), including younger age, longer diabetes duration, increased HbA1c and systolic blood pressure, for any DR, referable DR and VTDR (p > 0.05). The total time taken for DLS to evaluate DR from 93,293 fundus photographs was ~1 month compared to 2 years for human assessors. In conclusion, the prevalence and systemic risk factors for DR in multi-ethnic population could be determined accurately using a DLS, in significantly less time than human assessors. This study highlights the potential use of AI for future epidemiology or clinical trials for DR grading in the global communities.
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ItemThe relationship of dietary fish intake to diabetic retinopathy and retinal vascular caliber in patients with type 2 diabetes(NATURE PORTFOLIO, 2018-01-15)In this cross-sectional study, we evaluated the association of dietary fish intake with varying severity of diabetic retinopathy (DR) and retinal vascular caliber in Asians with type 2 diabetes mellitus. 357 Asians (median age: 58 years; 31% women; 78% Chinese) were recruited from a tertiary eye care institution in Singapore. Fish consumption was evaluated using a validated food frequency questionnaire. Digital retinal photographs assessed for DR severity and retinal vascular caliber. Ordered logistic and linear regression models were used to investigate the association of fish intake with DR severity and vascular caliber. Increasing frequency of fish consumption was significantly associated with lower odds of having severe DR (odds ratio [OR] = 0.91, 95% CI: 0.84-0.99 per 1-unit increase of fish intake; P = 0.038). Among those with no retinopathy, persons in quartile 4 fish intake had a wider retinal vascular caliber for arteriolar (β = 22.27 µm, 95% CI: 12.64-31.90; P-trend < 0.001) and venular (β = 32.00 µm, 95% CI: 17.56-46.43; P-trend < 0.001), than those in quartile 1 fish intake. Persons with higher fish intake had a decreased likelihood of having severe DR. In diabetics without retinopathy, higher fish intake was associated with wider retinal vascular caliber. Future research is needed to reinforce the direction of the casualty.
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ItemFalls and Recurrent Falls among Adults in A Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study(NATURE PORTFOLIO, 2018-05-15)We evaluated the rate and risk factors associated with falls and recurrent falls in a multi-ethnic Asian population. 10,009 participants aged ≥40 years (mean[SD] age = 58.9[10.4] years) underwent clinical examinations and completed interviewer-administered questionnaires. Participants who self-reported at least one fall or ≥2 falls in past 12 months were defined as fallers and recurrent fallers, respectively. Age-standardized rates for falls and recurrent falls were 13.8% (95%CI, 13.1-14.6%) and 4.6% (95%CI, 4.2-5.1%), respectively. Multivariable analyses showed older age (OR = 1.20; 95%CI, 1.11-1.30), female gender (OR = 1.79; 95%CI, 1.54-2.07), diabetes (OR = 1.22; 95%CI, 1.07-1.40), cardiovascular disease (CVD, OR = 1.37; 95%CI, 1.14-1.65), ≥3 systemic comorbidities (OR = 1.35; 95%CI, 1.09-1.67), lower European Quality of Life-5 Dimensions (EQ-5D) score (OR = 1.36; 95%CI, 1.29-1.44), alcohol consumption (OR = 1.41, 95%CI, 1.11-1.78) and presenting visual impairment (VI, OR = 1.23; 95%CI, 1.02-1.47) were associated with falls. For recurrent falls, female gender (OR = 2.27; 95%CI, 1.75-2.94), diabetes (OR = 1.28; 95%CI, 1.03-1.61), CVD (OR = 2.00; 95%CI, 1.53-2.62), ≥3 systemic comorbidities (OR = 1.69; 95%CI, 1.19-2.39), lower EQ-5D score (OR = 1.47; 95%CI, 1.35-1.59), living in 1-2 room public flat (OR = 1.57; 95%CI, 1.05-2.33), monthly income <2000 Singapore Dollar (OR = 1.62; 95%CI, 1.13-2.31), alcohol consumption (OR = 1.81, 95%CI, 1.23-2.66) and presenting VI (OR = 1.34; 95%CI, 1.01-1.79) were significant risk factors. These findings will be useful for the formulation of fall prevention programs.
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ItemU-Shaped Relationship between Serum Leptin Concentration and Cognitive Performance in Older Asian Adults(MDPI, 2019-03-19)The role of leptin (a hormone related to fat mass) in cognition remains equivocal. Our objective was to investigate the relationship between circulating leptin concentration and cognition in older adults, accounting for potential confounders. We categorized 1061 community-dwelling older participants ≥60 years (mean ± SD, 70.6 ± 6.4 years; 41.6% female) from the Singapore Kidney Eye Study according to quintiles of leptin concentration (≤2.64; 2.64⁻5.1; 5.2⁻8.6; 8.7⁻17.96; ≥18 ng/mL). Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Age, gender, body mass index, mean arterial pressure, smoking, alcohol, education, memory complaint, anxiodepressive disorders, circulating concentrations of 25-hydroxyvitamin D, glycosylated hemoglobin, low-density lipoprotein cholesterol, and estimated glomerular filtration rate were used as potential confounders. Participants within the lowest (Q1) and highest (Q5) leptin quintiles exhibited lower (i.e., worse) mean total AMT scores compared to those within the intermediate quintiles (Q2, Q3, and Q4). Compared to Q3 as the reference, Q1 and Q5 were associated with decreased total AMT score (respectively, β = -0.53 p = 0.018; β = -0.60 p = 0.036). Compared to Q3, Q5 was also associated with decreased subscores on anterograde (β = -0.19 p = 0.020) and retrograde episodic memories (β = -0.18 p = 0.039). We found a non-linear U-shaped relationship between circulating leptin and cognition, with both lower and higher concentrations of leptin being associated with more severe cognitive impairment in community-dwelling older Asians.
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ItemGenetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium(PUBLIC LIBRARY SCIENCE, 2019-08-15)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.