Beyond Ocular Toxicity: Cerebrovascular Events After Intra-Arterial Chemotherapy for Retinoblastoma

Background: Cerebrovascular accidents (CVAs) are among the most serious complications of intra-arterial chemotherapy (IAC) for retinoblastoma (RB). This study evaluated the incidence and potential risk factors of this rare event. Methods: A retrospective cohort study included RB patients who received IAC at a tertiary cancer center. Diagnosis of CVAs was based on clinical and/or neuroimaging findings. Data included demographics, tumor features, complications, and outcomes. Meta-analysis was not feasible due to heterogeneity. A systematic review following PRISMA guidelines was conducted across major databases up to December 2025, including studies reporting CVA after IAC. Results: The cohort included 33 children who underwent 104 IAC procedures (Melphalan). CVA occurred in three patients (3/33 (9%) of patients, and 3/104 (2.9%) of procedures). Two were confirmed by neuroimaging, while one was a transient ischemic attack. Two patients (67%) were girls, and 2 of 3 (67%) were younger than 1 year. All events occurred during the IAC procedure and were ipsilateral to the treated eye. Two patients had no residual neurological deficits, while one showed improvement with only a minor residual deficit. The systematic review included 14 studies with 932 patients and identified 11 CVA events (1.2%; Range 0-9.1% per patient and 0-2.2% per IAC procedure). All were ischemic with variable presentations. Younger age, repeated catheterization, vasospasm, and embolic events were common risk factors. Outcomes were generally favorable. Conclusions: CVA after IAC, though rare, may be underreported. Events are likely procedure-related and influenced by age, treatment intensity, and vascular toxicity. Careful technique, close monitoring, and standardized reporting are needed to recognize/reduce the real risk.