Vascular dysfunctions during radiation retinopathy

Optic tissue toxicity remains a major limitation of radiation therapy for ocular, brain, skull base, and head and neck tumors. Among the most frequent complications, radiation retinopathy (RR) occurs in 6% of patients treated for extraocular tumors and in more than 40% of those with ocular tumors. After an initial asymptomatic stage characterized by vascular remodeling and chronic retinal ischemia, RR may progress to irreversible vision loss and significantly impaired quality of life. Advances in non-invasive, high-resolution imaging have improved our understanding of the molecular and cellular mechanisms underlying RR in both preclinical and clinical models. In particular, multimodal imaging-and especially optical coherence tomography angiography (OCTA)-has enabled earlier detection of RR in humans. Animal studies have highlighted vascular obstruction and rarefaction, together with early neurovascular dysfunction, as central features of the clinical phase. Beyond preventive measures such as dose constraints, biological and imaging biomarkers may help guide targeted interventions. In this review, we summarize current evidence on the sequential endothelial and neuronal alterations that drive RR and discuss molecular and cellular pathways that could inform the development of potential therapeutic strategies.