Longitudinal OCT/OCTA Imaging Reveals Early Neurovascular Dysfunction Associated with Ferroptosis-Related Metabolic Stress in Experimental Diabetic Retinopathy

Abstract Diabetic retinopathy (DR) involves early neurovascular and metabolic dysfunction. We evaluated whether longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) can provide in vivo phenotypic readouts of ferroptosis-related retinal injury in streptozotocin-induced diabetic rats. Diabetes caused progressive retinal thinning, reduced capillary plexus vessel area density, and impaired photopic negative responses, accompanied by iron accumulation, lipid peroxidation, reduced antioxidant capacity, and altered ferroptosis-associated protein expression. Liproxstatin-1 partially attenuated these abnormalities. Exploratory analyses further linked OCTA and electrophysiological phenotypes with ferroptosis-related measures. These findings support OCT/OCTA as noninvasive longitudinal readouts of early diabetic retinal injury associated with ferroptosis-related metabolic stress.