Isolated Ocular Relapse Following Prolonged Remission in Primary Central Nervous System Lymphoma: A Case Report.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma most commonly involving the brain and leptomeninges. While high-dose methotrexate (HD-MTX)-based therapy has improved outcomes, relapse remains common and typically occurs within the CNS. Isolated ocular relapse after prolonged CNS remission is uncommon and diagnostically challenging. We report the case of a 78-year-old woman diagnosed in 2020 with PCSNL presenting with subacute constitutional and neurologic symptoms found to have a right frontal periventricular mass. She achieved complete radiographic remission following induction with HD-MTX and rituximab and remained free of CNS disease for nearly five years on serial surveillance imaging. Beginning in 2023, she developed progressive unilateral visual decline that was initially attributed to age-related macular degeneration, with repeatedly negative MRI studies of the brain and orbits. In 2025, further ophthalmologic evaluation with an ocular oncologist revealed vitreous and retinal involvement confirming isolated ocular relapse in the absence of systemic recurrence. She was retreated with HD-MTX and rituximab, resulting in clinical and fundoscopic improvement. This case highlights a rare pattern of delayed isolated ocular relapse following long-term remission in PCNSL. It underscores the limitations of neuroimaging in detecting ocular disease and emphasizes the importance of continued ophthalmologic surveillance with those specifically trained in ocular oncology in patients with persistent visual symptoms. Guideline-consistent systemic retreatment may provide effective disease control even in late relapse, particularly in patients with prior methotrexate sensitivity.