Possible triggering of psychotic symptoms after repeated intravitreal bevacizumab exposure in a polymedicated geriatric patient: a case report

Intravitreal bevacizumab is widely used for retinal diseases. It may lead to greater systemic exposure than some other anti-VEGF agents, but psychiatric adverse effects after intravitreal administration have not been established. We report new-onset psychotic symptoms temporally associated with repeated intravitreal bevacizumab exposure, while recognising the difficulty of causal attribution in an elderly patient with vascular comorbidities. A 75-year-old woman with age-related macular degeneration and central vision loss, without prior psychiatric history or known cognitive decline, received intravitreal bevacizumab 1.25 mg/0.05 mL. After two previous injections without psychiatric symptoms, the third injection, administered to the right eye, was defined as Day 0. Persecutory delusions, auditory hallucinations, suicidal ideation, insomnia, and behavioural change emerged on Day +1, before the left-eye injection was administered on Day +2. No peri-injection or topical corticosteroid exposure was documented. She had hypertension, type 2 diabetes mellitus, and atrial fibrillation, but medication reconciliation revealed no recent medication changes, toxicity, or withdrawal. Urine toxicology was negative, and no major psychosocial stressors or family history of psychiatric illness were reported. On examination, orientation and memory were intact, with paranoid ideation and impaired insight. The Mini-Mental State Examination score was 27/30, and the Confusion Assessment Method was negative. Brain MRI showed mild age-related atrophy and chronic small-vessel ischaemic changes, without acute lesions or diffusion restriction. Laboratory findings were unremarkable. The presentation was atypical for primary psychotic, mood, or neurocognitive disorders. A possible medication-related adverse effect was considered, although multifactorial neuropsychiatric decompensation could not be excluded. Aripiprazole was initiated at 2.5 mg/day and titrated to 7.5 mg/day. Psychotic symptoms resolved during treatment. On Day +33, she was discharged in a clinically stable condition on aripiprazole 7.5 mg/day. No recurrence occurred during six-month follow-up, including bevacizumab re-exposure while she remained on aripiprazole. This case highlights a possible temporal association between repeated intravitreal bevacizumab exposure and new-onset psychotic symptoms in an elderly patient with vascular comorbidities. The absence of recurrence during re-exposure while receiving aripiprazole limits causal inference. Further research is needed to determine whether this association is causal or coincidental. Not applicable.