Vitreoretinal Lymphoma: A Comprehensive Clinical Review and Current Standards in Management

To summarize current evidence on clinical features, multimodal imaging findings, diagnostic techniques, and management strategies for vitreoretinal lymphoma.

A literature review was performed to provide updated information on available treatment options for vitreoretinal lymphoma.

Diagnosis of vitreoretinal lymphoma requires vitreous biopsy, with or without retinal/subretinal tissue, for cytology and immunohistochemistry, along with ancillary tests such as flow cytometry, cytokine profiling (interleukin-10/interleukin-6 ratio >1), immunoglobulin heavy chain gene rearrangement analysis, and detection of the MYD88 L265P mutation. Optical coherence tomography and other multimodal imaging techniques have become increasingly useful in raising suspicion, guiding biopsy, and monitoring treatment response. No standardized treatment protocol exists for isolated vitreoretinal lymphoma. Management options include intravitreal chemotherapy (methotrexate and/or rituximab), radiation therapy, and systemic chemotherapy, often showing a good initial response, but relapse and subsequent central nervous system (CNS) involvement are common, resulting in poor overall prognosis and survival. For vitreoretinal lymphoma with CNS disease, current strategies favor high-dose methotrexate-based systemic chemotherapy, with or without intrathecal chemotherapy; whole-brain radiation is generally reserved as rescue therapy. Emerging directions for earlier diagnosis include metagenomic deep sequencing, and chimeric antigen receptor T-cell (CAR-T) therapy has shown promise for treatment of selected relapsed/refractory cases of primary CNS lymphoma with a potential to prolong survival.

Treatment of vitreoretinal lymphoma requires a multidisciplinary, individualized approach that integrates multimodal imaging, cytologic and molecular diagnostics, CNS evaluation, and tailored local or systemic therapy. Prospective multicenter studies are needed to refine diagnostic algorithms and standardize management.