Background: This systematic review and meta-analysis investigated different treatment modalities' effect on the risk of central nervous system lymphoma progression, ocular disease relapse, systemic lymphoma development and overall survival in primary vitreoretinal lymphoma patients. Methods: PubMed, EMBASE, Scopus and the Cochrane Library of clinical trials were searched from inception to April 21, 2024. Cohort, cross-sectional and case series studies were included. Methodological quality was assessed using the NIH quality assessment tools. Heterogeneity between studies was assessed using Chi square test andI2statistic. Outcomes were pooled as odds ratios(OR) using fixed-effects models. Risk of publication bias was assessed using a funnel plot. Results: Included were 28 studies with 476 participants. Ocular treatments included intravitreal methotrexate and/or rituximab injections and ocular radio-therapy. Systemic treatments included intravenous and/or intrathecal chemotherapy, whole-brain radiotherapy and autologous stem cell transplantation. Oculartreatment alone, as compared to systemic or combined treatment, resulted in sig-nificantly lower risk of central nervous system lymphoma development(OR=0.54,p=0.02) and in no significant difference in the risk for progression to systemic disease (OR=0.38,p=0.30) or in overall survival. Significantly lower risk of ocular relapse was found in patients receiving ocular or combined therapy as compared to systemic therapy alone (OR=0.26,p=0.001). A subgroup analysis, comparing ocular treatment alone and combined treatment, found no significant difference regarding the risk of central nervous system or systemic lymphoma progression, ocular disease relapse and overall survival. Conclusions: No benefit was observed for the addition of systemic therapy to ocular treatment in patients with primary vitreoretinal lymphoma.