Quantitative Biomarkers of Diabetic Retinopathy Using Ultra-Widefield Fluorescein Angiography

Introduction: Diabetic retinopathy (DR) is a leading cause of blindness. Retinal imaging is an important tool to monitor the progression of DR. While seven-standard retinal fields are the traditional method for evaluating DR, ultra-widefield (UWF) imaging allows for improved visualization of peripheral areas of nonperfusion (NP) and neovascularization (NV), which could be used as biomarkers to monitor and predict progression of DR. Methods: A retrospective, cross-sectional study was conducted on 651 eyes from 363 patients diagnosed with type 1 or type 2 diabetes who received UWF-FA over 10 years. Fluorescein Angiography (FA) images were segmented, and surface areas of NP and NV were analyzed using multivariate regression to determine if biomarkers of DR and DR severity are associated with increasing areas of NP and NV. Results: Each additional year with a diagnosis of DR was associated with a 10.75 mm 2 increase in the total NP (95% CI, 1.94— 19.56; P = 0.02) and 7.87 mm 2 increase in NP far-periphery (95% CI, 1.62— 14.13; P = 0.01). A one-unit change in severity as defined by the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification was associated with a 25.75 mm 2 increase in total NP (95% CI, 11.16— 40.33; P = 0.001), a 13.15 mm 2 increase in mid-periphery NP (95% CI, 6.93— 19.38; P < 0.0001), and a 12.29 mm 2 increase in far-periphery NP (95% CI, 3.62— 20.97; P = 0.01). Discussion: Biomarkers identified through UWF imaging such as total and regional areas of NP can be used to monitor and predict the progression of DR. This may provide a quantitative method for prognostication in patients with DR.