Divergent nasal-temporal changes in superficial vascular density as early biomarkers of diabetic retinopathy

This study utilized ultra-widefield optical coherence tomography angiography (UWF-OCTA) to explore quadrant-specific alterations in retinal vascular density (VD) in the progression of diabetic retinopathy (DR). In this observational cross-sectional study, 193 eyes from 107 participants were enrolled: 54 eyes of 30 healthy controls (NC), 77 eyes of 40 diabetic patients without DR (DM group), and 62 eyes of 37 patients with DR (DR group). All participants underwent 24 × 20 mm UWF-OCTA imaging. The superficial and deep vascular complex (SVC and DVC) VD were analyzed across four quadrants (superior, inferior, nasal, temporal) and multiple concentric regions (up to 21 mm from the macula). Two distinct patterns of opposing vascular changes were identified. First, in the SVC of the DM group, VD was significantly increased in the temporal quadrant (T6, T11) but decreased in the nasal quadrant (N11, N16, N21) compared to NC. This nasal-temporal divergence strongly correlated with subsequent DR progression. Second, an opposing change was observed between vascular layers: while SVC VD decreased globally in DR, DVC VD within the central macula showed an initial decrease in the DM group followed by a significant increase in the DR group. ROC analysis confirmed that SVC changes, particularly in the temporal 16–21 mm region, held high diagnostic value for predicting DR (AUC > 0.8). UWF-OCTA uncovers novel, quadrant-specific vascular changes in early diabetes. The opposing nasal-temporal SVC changes, driven by anatomical and hemodynamic factors, suggest a compensatory mechanism in the temporal region and heightened vulnerability in the nasal region. The temporal periphery (16–21 mm) emerges as a critical area for early DR detection. These findings provide new insights into the pathogenesis of DR and highlight the potential of UWF-OCTA in improving early screening strategies.