Longitudinal progression of retinal nonperfusion in clinically stable diabetic retinopathy

PURPOSE: To longitudinally assess and quantify changes in retinal nonperfusion (NP) in clinically stable diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWF-FA) and optical coherence tomography angiography (OCTA). METHODS: Fifty-one eyes from thirty-three patients were followed for a mean of 15.9 ± 11.4 months. Retinal NP was quantified on UWF-FA by a central reading centre using the nonperfusion index (NPI) for the posterior pole (NPI_PP), mid-periphery (NPI_MP) and far periphery (NPI_FP). OCTA metrics were analysed using ImageJ (Version 1.53, the National Institutes of Health, Bethesda, MD, USA) and MatLab (Version 2024a, MathWorks, Natick, MA). RESULTS: Best-corrected visual acuity (BCVA) decreased with increasing DR severity (p = 0.0157). Peripheral NPI significantly increased over time (NPI_MP p = 0.007; NPI_FP p = 0.0007), particularly in moderate (NPI_FP p = 0.043) and severe NPDR (NPI_MP p = 0.041; NPI_FP p = 0.004). NPI values were consistently higher in severe NPDR and PDR than in moderate NPDR (all p < 0.0001). OCTA metrics remained stable longitudinally but were larger in advanced DR stages (p < 0.05). CONCLUSIONS: Peripheral NP, as quantified by NPI on UWF-FA, progresses over time despite apparent clinical stability of DR. In contrast, macular OCTA parameters remain unchanged. These findings suggest that peripheral iscahemic changes may occur earlier than detectable macular microvascular alterations and support the potential role of NPI as a quantitative imaging marker of retinal ischemia in DR.