Outer Retinal Volume on Macular OCT Predicts Two-Year Diabetic Retinopathy Progression

Purpose: To evaluate whether baseline retinal volume from macular optical coherence tomography (OCT) is associated with diabetic retinopathy (DR) progression over two years. Methods: In this longitudinal observational study, 190 eyes from 121 patients, across the DR severity spectrum without diabetic macular edema, completed two-year follow-up and were included in the analysis. Baseline 3 × 3-mm macular OCT scans, with manual correction of segmentation, were analyzed to derive inner and outer retinal volumes in the central subfield, 1-3 mm parafoveal area, and whole 3 × 3-mm scan. Disease progression was defined as having one or more of the following events: DR worsening on fluorescein angiography or vision loss ≥ 10 letters at the two-year timepoint, or development of vitreous hemorrhage or initiation of pan-retinal photocoagulation or anti-VEGF therapy at any point during follow-up. Generalized Estimating Equations were used for analysis. Results: Of the 190 eyes (121 patients), 48 eyes (25.3%; 39 patients) demonstrated progression. Higher outer retinal volume (parafoveal and whole) at baseline was significantly associated with disease progression (P < 0.001), whereas inner retinal volume showed no significant association. After adjusting for baseline DR severity, hypertension, age, lens and Bonferroni correction, outer retinal volume remained independently associated with higher odds of progression (P < 0.001). Conclusions: Increased outer retinal volume (parafoveal and entire 3 × 3-mm macular scan) predicts DR progression over two years. These findings highlight the prognostic value of OCT-derived outer retinal volume and support its potential role as a clinically accessible biomarker for identifying eyes at higher risk for DR complications.