Efficacy and Safety of Response-Adapted Intravitreal Methotrexate Therapy for Vitreoretinal Lymphoma: A Two-Center Retrospective Cohort Study

Objectives: Longitudinal visual and imaging outcomes after intravitreal methotrexate (MTX) for vitreoretinal lymphoma (VRL), and baseline factors associated with remission, remain poorly defined. We evaluated the 12-month efficacy and safety of a reduced-intensity induction regimen followed by response-guided continuation therapy. Methods: Seventeen consecutive patients with VRL confirmed by vitreous cytology and flow cytometry received intravitreal MTX (400 μg/0.1 mL) at two centers in Bucharest, Romania, between 2018 and 2023. Visual acuity (VA), vitritis and optical coherence tomography (OCT) findings were assessed at baseline and at 1, 3, 6 and 12 months (Friedman and Cochran’s Q tests). Results: Mean VA improved from 1.22 ± 0.70 to 0.74 ± 0.63 logMAR (χ2 = 30.82, p < 0.001; Kendall’s W = 0.45), with statistically significant improvement from month 6. At the scheduled 12-month assessment, vitritis and retinal infiltrates had resolved (both unadjusted p < 0.001). Sub-RPE lesions and outer retinal hyperreflectivity decreased (both unadjusted p = 0.031), but these comparisons did not meet the Bonferroni-adjusted significance threshold. Outer retinal disorganization and foveal involvement did not change significantly. Fourteen patients (82.4%) achieved complete ocular remission (median, 6 months); three (17.6%) relapsed and regained disease control after retreatment. Keratopathy was the most frequent adverse event (41.2%); no severe complications occurred. Conclusions: This regimen was associated with a high ocular remission rate, progressive visual improvement and a manageable safety profile. Because all 10 patients with central nervous system lymphoma also received systemic therapy and/or radiotherapy, ocular outcomes cannot be attributed solely to intravitreal MTX.