Ocular manifestations and treatment of central nervous system lymphomas

Intraocular primary central nervous system lymphoma (PCNSL), also called primary intraocular lymphoma (PIOL), is a subset of PCNSL in which lymphoma cells invade the subretinal pigment epithelial space and vitreous cavity with or without central nervous system involvement at the time of ocular diagnosis. The frequency of this rare condition has increased over the past years in immunosuppressed as well as immunocompetent patients. The authors review the current status of PIOL and elaborate on their group's experience with its diagnosis and treatment. The incidence of PIOL is increasing. There is evidence that chronic antigenic stimulation may result in the development of PIOL. Recent advancements in the diagnosis of PIOL include better handling of vitreous specimens for cytological studies, immunocytological investigation for lymphoid cells, flow cytometry, cytokine evaluation, and molecular analysis. Because PIOL has a nonspecific presentation, the differential diagnosis should include infectious and noninfectious causes presenting with vitreitis and/or subepithelial infiltration as well as paraneoplastic syndromes including CRMP-5 optic neuropathies. Given that therapy is long-term and has significant systemic and ocular complications, tissue diagnosis is important. Treatment of PIOL may include systemic chemotherapy in which high-dose methotrexate-based regimens are used as well as intraocular injections of methotrexate and rituximab (anti-CD20 antibody). Cranial and ocular external-beam radiotherapy is being used less often today. Further studies are needed to prevent the tumor formation in terms of eliminating antigenic load and inhibiting Bcell chemokines as well as to determine the optimal local and systemic chemotherapy and immunotherapy options in the management of PIOL.