Pathophysiological Roles of Oxidative Stress and the Translational Potential of Antioxidant Therapy in Retinal Vein Occlusion

Retinal vein occlusion (RVO) is the second most common retinal vascular disorder after diabetic retinopathy and represents a major cause of visual impairment worldwide. In addition to venous congestion, endothelial dysfunction, and inflammation, accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of RVO. The excessive production of reactive oxygen species (ROS) during ischemia-reperfusion injury induces endothelial damage, disruption of the blood-retinal barrier, and upregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF), thereby contributing to macular edema and progressive visual dysfunction. This review summarizes current knowledge from both experimental and clinical studies regarding the mechanisms of oxidative stress generation in RVO and its underlying molecular pathways, highlighting the pathological consequences of impaired antioxidant defense systems. We further review reported alterations in oxidative stress markers and antioxidant factors in serum, aqueous humor, and vitreous fluid, and discuss their potential associations with disease activity and visual prognosis. In addition, the interplay between oxidative stress and current standard treatments, including anti-VEGF therapy and corticosteroids, is discussed, together with the translational potential of antioxidant strategies such as polyphenols, vitamins, and Nrf2 pathway activators. At the same time, we address critical challenges limiting clinical application, including insufficient interventional evidence, the lack of validated biomarkers, and uncertainties regarding optimal timing of antioxidant intervention. By providing a comprehensive overview of oxidative stress in RVO, this review aims to identify emerging therapeutic targets and opportunities for personalized treatment approaches, and to outline future research directions toward improving long-term visual outcomes in patients with RVO.