Normalized Blood Flow Index in Optical Coherence Tomography Angiography Provides a Sensitive Biomarker of Early Diabetic Retinopathy

Purpose: To evaluate the sensitivity of normalized blood flow index (NBFI) for detecting early diabetic retinopathy (DR).Methods: Optical coherence tomography angiography (OCTA) images of healthy controls, diabetic patients without DR (NoDR), and patients with mild nonproliferative DR (NPDR) were analyzed in this study. The OCTA images were centered on the fovea and covered a 6 mm x 6 mm area. Enface projections of the superficial vascular plexus (SVP) and the deep capillary plexus (DCP) were obtained for the quantitative OCTA feature analysis. Three quantitative OCTA features were examined: blood vessel density (BVD), blood flow flux (BFF), and NBFI. Each feature was calculated from both the SVP and DCP and their sensitivities to distinguish the three cohorts of the study were evaluated.Results: The only quantitative feature capable of distinguishing all three cohorts was NBFI in the DCP image. Comparative study revealed that both BVD and BFF were able to distinguish the controls and NoDR from mild NPDR. However, neither BVD nor BFF was sensitive enough to separate NoDR from the healthy controls.Conclusions: The NBFI has been demonstrated as a sensitive biomarker of early DR, revealing retinal blood flow abnormality better than traditional BVD and BFF. The NBFI in the DCP was verified as the most sensitive biomarker, supporting that diabetes affects the DCP earlier than SVP in DR.Translational Relevance: NBFI provides a robust biomarker for quantitative analysis of DR-caused blood flow abnormalities, promising early detection and objective classifica-tion of DR.