Primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) is an ocular subset of PCNSL predominantly involving subretinal pigment epithelium (RPE) space, retina, and vitreous. The ophthalmic manifestations can precede, occur simultaneously, or follow other compartments of the CNS. Clinical trials have resulted in a significantly improved outcome in PCNSL patients over the past 2 decades, with a higher proportion of patients receiving frontline high dose methotrexate-based polychemotherapy regimens with curative intent; however, the current management of PCNSL-O remains controversial due to lack of prospective data. The goals of PCNSL-O treatment are both to achieve local (ocular) control and to prevent tumor-specific mortality from further CNS involvement. Despite achieving high rates of ocular control with intravitreal agents like methotrexate and rituximab, the overall survival is poor, as 65-85% of patients eventually succumb to CNS disease. Few studies define the role of systemic chemotherapy with/without local treatment as a first line induction treatment for PCNSL-O considering limiting factors such as ocular penetration of systemically administered drugs and treatment related neurotoxicity. Also, the role of adjuvant treatment for PCNSL-O to prevent CNS progression and to improve overall survival is unknown. In this systematic review of the literature, we analyze treatment outcomes of various regimens (local, systemic, and combination) in terms of local control, CNS progression, and overall survival.