Retinal Vascular Geometry and 6 year Incidence and Progression of Diabetic Retinopathy

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, HbA 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.