Deep nasal capillary plexus density is associated with preclinical diabetic retinopathy

Abstract Early identification of diabetic retinopathy (DR) is crucial for vision-loss prevention. This cross-sectional study identified quantitative imaging biomarkers in patients with preclinical or early non-proliferative DR (NPDR) using optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT). We included 62 eyes in patients with diabetes without DR (NDR), 62 eyes with NPDR, and 58 eyes from healthy controls without diabetes. OCTA and OCT examinations were performed to measure superficial/deep retinal vessel density and ganglion cell-inner plexiform layer (GCIPL) thickness. Compared with controls, the NDR group demonstrated significantly reduced nasal deep capillary plexus density, which was an independent factor associated with preclinical DR (OR = 0.730, P = 0.003). ROC curve analysis indicated good diagnostic performance (AUC = 0.744, P < 0.001). In NPDR, superficial and deep vascular densities were reduced in all regions except the temporal superficial region; nasal GCIPL thinning was observed. Vascular density parameters outperformed GCIPL thickness in distinguishing NPDR from NDR. Additionally, microaneurysms and hard exudates were associated with lower vessel densities and larger foveal avascular zone areas, while cotton wool spots were associated with thinner nasal GCIPL. These cross-sectional findings suggest that reduced nasal deep retinal vascular density is associated with early DR and that progressive vascular impairment correlates with neurodegenerative changes, supporting its potential role as an early imaging biomarker for risk stratification. However, temporality and causality cannot be established, which necessitates prospective longitudinal studies to validate these associations.