Oxidative stress in diabetic retinopathy

Diabetic retinopathy (DR) remains a leading cause of blindness, with oxidative stress as a central pathogenic driver. However, the translation of this mechanistic knowledge into clinical diagnostics and targeted therapies has been hampered by inconsistent biomarkers and a simplistic view of redox balance. This critical review moves beyond cataloging oxidative markers to evaluate their biological specificity, analytical robustness, and compartmentalization between systemic circulation and the ocular microenvironment. We dissect the technical challenges of direct reactive species measurement and appraise established markers of macromolecular damage, lipid peroxidation adducts, protein carbonyls, and oxidized nucleic acids, emphasizing that analytical rigor is paramount for interpretability. Furthermore, we explore integrative pathways linking glycoxidation, inflammation, and VEGF in a feed-forward loop. A key translational hurdle is the poor correlation between systemic biomarkers and intraretinal oxidative events. We propose a future roadmap featuring a tiered "DR oxidative stress profile" that combines scalable systemic screening with pathway-specific panels and advanced ocular imaging. This refined approach aims to enable precision phenotyping, enriching clinical trials for mechanism-targeted therapies and ultimately paving the way for personalized antioxidant strategies tailored to the dominant oxidative axis in individual patients.