Carol Yim-Lui Cheung1,2, Charumathi Sabanayagam1,3, Antony Kwan-Pui Law2, Neelam Kumari1, Daniel Shu-Wei Ting1, Gavin Tan1, Paul Mitchell4, Ching Yu Cheng1,3,5, Tien Yin Wong6,7,8. 1. Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, 168751, Singapore, Republic of Singapore. 2. Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China. 3. Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Republic of Singapore. 4. Centre for Vision Research, University of Sydney, Sydney, NSW, Australia. 5. Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-NUS Medical School, National University of Singapore, Singapore, Republic of Singapore. 6. Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, 168751, Singapore, Republic of Singapore. wong.tien.yin@snec.com.sg. 7. Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Republic of Singapore. wong.tien.yin@snec.com.sg. 8. Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-NUS Medical School, National University of Singapore, Singapore, Republic of Singapore. wong.tien.yin@snec.com.sg.
Abstract
AIMS/HYPOTHESIS: We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy. METHODS: We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Diabetic retinopathy was graded from baseline and follow-up photographs using the modified Airlie House classification system. Incidence of diabetic retinopathy was defined as a severity of ≥15 at follow-up among those without diabetic retinopathy at baseline. Incidence of referable diabetic retinopathy was defined as moderate or severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or diabetic macular oedema at follow-up in participants who had had no or mild non-proliferative diabetic retinopathy at baseline. Progression of diabetic retinopathy was defined as an increase in severity of ≥2 steps at follow-up. Log-binomial models with an expectation-maximisation algorithm were used to estimate RR adjusting for age, sex, diabetes duration, HbA1c level, BP, BMI, estimated GFR and total and HDL-cholesterol at baseline. RESULTS: A total of 427 individuals with diabetes participated in the baseline and 6 year follow-up examinations. Of these, 19.2%, 7.57% and 19.2% developed incidence of diabetic retinopathy, incidence of referable diabetic retinopathy and diabetic retinopathy progression, respectively. After multivariate adjustment, greater arteriolar simple tortuosity (mean RR [95% CI], 1.34 [1.04, 1.74]), larger venular branching angle (RR 1.26 [1.00, 1.59]) and larger venular branching coefficient (RR 1.26 [1.03, 1.56]) were associated with incidence of diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.82 [1.32, 2.52]), larger venular branching coefficient (RR 1.46 [1.03, 2.07]), higher arteriolar fractal dimension (RR 1.59 [1.08, 2.36]) and larger arteriolar calibre (RR 1.83 [1.15, 2.90]) were associated with incidence of referable diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.34 [1.12, 1.61]) was associated with diabetic retinopathy progression. Addition of retinal vascular variables improved discrimination (C-statistic 0.796 vs 0.733, p = 0.031) and overall reclassification (net reclassification improvement 18.8%, p = 0.025) of any diabetic retinopathy risk beyond established risk factors. CONCLUSIONS/ INTERPRETATION: Retinal vascular geometry measured from fundus photographs predicted the incidence and progression of diabetic retinopathy in adults with diabetes, beyond established risk factors.
AIMS/HYPOTHESIS: We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy. METHODS: We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Diabetic retinopathy was graded from baseline and follow-up photographs using the modified Airlie House classification system. Incidence of diabetic retinopathy was defined as a severity of ≥15 at follow-up among those without diabetic retinopathy at baseline. Incidence of referable diabetic retinopathy was defined as moderate or severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or diabetic macular oedema at follow-up in participants who had had no or mild non-proliferative diabetic retinopathy at baseline. Progression of diabetic retinopathy was defined as an increase in severity of ≥2 steps at follow-up. Log-binomial models with an expectation-maximisation algorithm were used to estimate RR adjusting for age, sex, diabetes duration, HbA1c level, BP, BMI, estimated GFR and total and HDL-cholesterol at baseline. RESULTS: A total of 427 individuals with diabetes participated in the baseline and 6 year follow-up examinations. Of these, 19.2%, 7.57% and 19.2% developed incidence of diabetic retinopathy, incidence of referable diabetic retinopathy and diabetic retinopathy progression, respectively. After multivariate adjustment, greater arteriolar simple tortuosity (mean RR [95% CI], 1.34 [1.04, 1.74]), larger venular branching angle (RR 1.26 [1.00, 1.59]) and larger venular branching coefficient (RR 1.26 [1.03, 1.56]) were associated with incidence of diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.82 [1.32, 2.52]), larger venular branching coefficient (RR 1.46 [1.03, 2.07]), higher arteriolar fractal dimension (RR 1.59 [1.08, 2.36]) and larger arteriolar calibre (RR 1.83 [1.15, 2.90]) were associated with incidence of referable diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.34 [1.12, 1.61]) was associated with diabetic retinopathy progression. Addition of retinal vascular variables improved discrimination (C-statistic 0.796 vs 0.733, p = 0.031) and overall reclassification (net reclassification improvement 18.8%, p = 0.025) of any diabetic retinopathy risk beyond established risk factors. CONCLUSIONS/ INTERPRETATION: Retinal vascular geometry measured from fundus photographs predicted the incidence and progression of diabetic retinopathy in adults with diabetes, beyond established risk factors.
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