To evaluate cone- and rod-specific nonperfusion indices (CPI, RPI) on ultrawide field fluorescein angiography (UWF-FA) and their correlation with diabetic retinopathy (DR) severity and center-involving diabetic macular edema (ciDME).

Sixty-nine eyes of 43 patients with diabetes underwent UWF color photography (UWF-CP), UWF-FA, and macular optical coherence tomography (OCT). DR severity was graded by a masked reader on UWF-CP. UWFFA images were segmented into posterior pole (≤10 mm from fovea), mid-periphery (10–15 mm) and far periphery (>15 mm), and into the macula, within ETDRS fields and extended peripheral fields. Ischemic areas were quantified using ImageJ to calculate nonperfusion index (NPI), CPI, and RPI. ciDME was determined on OCT. Correlations were analyzed using Pearson coefficients (r).

DR severity correlated significantly with global NPI (r = 0.56, p < 0.0001) and across all retinal zones (r = 0.35– 0.57). Both CPI (global: r = 0.56, p < 0.0001; zones: r = 0.42–0.59) and RPI (global: r = 0.55, p < 0.0001; zones: r = 0.40–0.59) showed similar associations. ciDME presence was also correlated with NPI (global: r = 0.40, p = 0.0014; zones: r = 0.42–0.54), CPI (global: r = 0.47, p = 0.0001; zones: r = 0.32–0.55), and RPI (global: r = 0.46, p = 0.0002; zones: r = 0.33–0.54).

Cone- and rod-related retinal nonperfusion strongly correlate with DR severity and ciDME. UWF-FA may help identify high-risk eyes and guide surveillance of ischemia-related progression. Further studies are needed to define ischemic thresholds predictive of vision-threatening complications.