Abstract
PURPOSE: To evaluate the 1-year progression of retinal capillary nonperfusion in eyes with mild to severe nonproliferative diabetic retinopathy (NPDR) using noninvasive retinal imaging. METHODS: The CHART study (Clinicaltrials.gov: NCT04636307) is a multicenter, observational, longitudinal study involving five European research centers and included 202 eyes from 155 participants with type 2 diabetes and mild to severe NPDR. Participants underwent comprehensive ophthalmologic examinations at baseline and 3, 6, and 12 months, including best-corrected visual acuity, color fundus photography (Early Treatment Diabetic Retinopathy Study [ETDRS] severity scale), optical coherence tomography (OCT), and OCT angiography (OCTA). Disease progression was evaluated using mixed-effects models. RESULTS: Of the 202 eyes, 81 eyes were graded as ETDRS level 35, 63 eyes as level 43, 46 eyes as level 47, and 12 eyes as level 53. At baseline, significant differences were observed in OCTA metrics between diabetic retinopathy severity groups. A total of 169 eyes (84%) completed the 1-year follow-up. Over 1 year, eyes with ETDRS levels 35 and 43 showed significant increases in capillary nonperfusion, identified by decreases in skeletonized vessel density in the superficial capillary plexus (rates of progression: β = -0.217 mm-1/y, P = 0.006 and β = -0.310 mm-1/y, P = 0.002, respectively). Eyes with level 47 showed only a borderline statistically significant decrease (P = 0.074), while eyes with level 53 remained stable. Microaneurysm turnover (MAT), formation, and disappearance rates increased in more severe NPDR stages (levels 47 and 53). CONCLUSIONS: Retinal capillary nonperfusion progresses significantly over 1 year in mild to moderate NPDR, identified by changes in rates of progression of vessel and perfusion densities. In more severe stages (levels 47 and 53), capillary nonperfusion stabilizes, and a hyperperfusion response is identified by increases in MAT associated with the development of intraretinal microvascular abnormalities. TRANSLATIONAL RELEVANCE: This study provides quantitative data on 1-year progression of retinal capillary nonperfusion in NPDR using noninvasive imaging, offering the basis for future interventional trials.