Different Patterns of Progression in Nonproliferative Diabetic Retinopathy: Findings From a 10-Year Cohort Study

The objective of this study was to characterize 10-year progression patterns of diabetic retinopathy (DR) in type 2 diabetes, focusing on visual, structural, and microvascular changes, using Early Treatment Diabetic Retinopathy Study (ETDRS) grading, optical coherence tomography (OCT), and OCT angiography (OCTA). The PROGRESS 10 study (NCT04650165) followed, annually, 222 participants (mean age 63.1 ± 7.3 years; 68% male) with no DR to mild nonproliferative DR (NPDR) (ETDRS 10, 20, or 35). Longitudinal changes were quantified for retinal thickness, ganglion cell–inner plexiform layer thickness, skeletonized vessel density (SVD), and perfusion density (PD). Linear mixed-effects models accounted for repeated measures. Of the 222 participants, 115 (62%) completed the 10-year visit, and 24 (11%) developed vision-threatening complications: 7.7% developed clinically significant macular edema, and 3.1% developed proliferative DR. Over 10 years, 27% worsened, 50% remained stable, and 21% improved on ETDRS grading. Eyes that worsened showed progressive capillary nonperfusion, with significant SVD decreases (−0.186 ± 0.063 mm−1/year; P = 0.004), while improved eyes showed stable microvascular metrics. At year 10, SVD was lower in worsened eyes compared with stable and improved groups (17.82 ± 2.12 vs. 18.85 ± 2.08 vs. 19.33 ± 2.05; P = 0.020). Eyes with no DR to mild NPDR showed different 10-year progression patterns. Capillary nonperfusion, measured by SVD and PD using noninvasive OCTA, differentiated the eyes that worsened or remained stable from those that improved. Article Highlights Characterization of the 10-year progression of diabetic retinopathy in type 2 diabetes was sought. We evaluated whether noninvasive optical coherence tomography angiography (OCTA) can identify eyes that progress and may develop vision loss. Of 222 participants, 62% completed the study, with 115 reaching the 10-year visit: 27% of eyes worsened, 50% remained stable, and 21% improved, based on Early Treatment Diabetic Retinopathy Study severity grading (2% unclassified); microvascular nonperfusion, measured using noninvasive OCTA, distinguished the eyes that worsened or remained stable from those eyes that improved. Progression of microvascular nonperfusion identified by OCTA enables identification of patients at higher risk for disease progression.