Exploring the role of oxidative stress in retinal vein occlusion: an updated and comprehensive review on the pathophysiology and treatment perspectives.

Introduction: Retinal vein occlusion (RVO) represents a prevalent cause of vision impairment within retinal vascular diseases. Although hypoperfusion and inflammation are recognized pathogenic contributors, emerging evidence highlights oxidative stress as a pivotal mediator operating through ischemia-hypoxia-inflammation cascades.

Methods: We conducted a systematic review of preclinical models and clinical studies examining reactive oxygen species (ROS) mechanisms in RVO pathogenesis. We searched PubMed/MEDLINE^™ database for studies published through May 2025, focusing on oxidative stress biomarkers, therapeutic interventions, and neurovascular outcomes.

Results: In ischemic retina, ROS accumulation stabilizes hypoxia-inducible factor-1α (HIF-1α) and induces vascular endothelial growth factor (VEGF) expression, promoting vascular hyperpermeability and proinflammatory cytokine release. Bidirectional interactions between ROS signaling and systemic vascular mediators, including hypertension and the renin-angiotensin-aldosterone system (RAAS), disrupt redox homeostasis, increase retinal venous pressure, and impair microvascular perfusion. Oxidative stress-mediated activation of resident microglia and infiltrating macrophages promotes tight-junction protein degradation, resulting in blood-retinal barrier (BRB) breakdown and subsequent neurovascular injury. Patients with elevated systemic oxidative burden frequently present with bilateral, subclinical retinal microvascular impairment. Targeted antioxidant interventions, including nanoparticle-based delivery systems and bioactive phytochemicals, demonstrated efficacy in preclinical models by restoring redox balance, preserving BRB integrity, and reducing neurovascular damage.

Conclusion: Oxidative stress represents a critical factor in RVO progression through interconnected vascular, inflammatory, and immune pathways. We propose a comprehensive management framework incorporating multimodal imaging for oxidative biomarker detection, artificial intelligence implementation for risk stratification, and personalized antioxidant therapy guided by validated biomarkers. Future investigations must establish causal relationships and identify specific, noninvasive biomarkers to advance precision prevention and treatment strategies for RVO.