Primary Vitreoretinal Lymphoma Treatment

Aims: Bilateral Primary Central Nervous System Lymphoma–Ophthalmic Variant or Primary vitreoretinal B-cell lymphoma (PVRL) is a rare and aggressive malignancy, often considered a subset of primary central nervous system lymphoma (PCNSL) with disease initially localized to the retina or vitreous humor. It comprises less than 1% of all non-Hodgkin lymphoma cases and presents significant diagnostic and therapeutic challenges. This report aims to detail the clinical management and sustained remission of a 63-year-old male with primary bilateral PVRL. The primary objective is to highlight the rationale for employing frontline aggressive consolidation with autologous stem cell transplantation (ASCT) rather than reserving it for salvage therapy, particularly given the high risk—over 50%—of central nervous system (CNS) dissemination or disease relapse.

Methods: A 63-year-old male presented with a two-month history of progressive vision loss and floaters. Diagnostic confirmation was done by vitreous biopsy and flow cytometry. Staging and systemic evaluation included brain MRI, whole-body PET-CT, an autoimmune panel, and cerebrospinal fluid (CSF) analysis. The patient was initiated on the DeAngelis protocol for systemic induction. Concurrently, local ocular therapy was administered via intravitreal injections of Methotrexate and Rituximab. Following induction, clinical response was monitored via repeat PET-CT, CSF analysis, and ophthalmologic evaluations. Upon achieving a complete response, the patient underwent consolidation therapy using Autologous Stem Cell Transplantation (ASCT) with a BCNU (Carmustine) + Thiotepa-based conditioning regimen. We reviewed current literature on PCNSL-O (PVRL) to compare this frontline strategy against traditional salvage-based models.

Results: Flow cytometry of the vitreous specimen revealed a clonal B-cell population (CD19+, CD20+, CD45 moderate+, and kappa-restricted), diagnostic of primary bilateral PVRL. Systemic staging, including PET-CT and brain MRI, showed no evidence of metabolically active systemic disease or parenchymal CNS lymphoma. CSF analysis noted mildly elevated protein without definitive malignant cells. The patient tolerated the DeAngelis induction and local intravitreal therapy without significant toxicity, reaching a complete clinical response. He subsequently underwent ASCT which he tolerated well. At the six-month post-transplantation follow-up, the patient remained in complete clinical and radiological remission. Evidence suggests that while ASCT has traditionally been used as salvage for relapsed PCNSL, utilizing it as a first-line consolidation is associated with improved progression-free and overall survival.

Conclusions: PCNSL-O is a challenging clinical entity with a high propensity for CNS involvement and a poor prognosis when relapse occurs. There is currently a paucity of standardized guidelines, and many institutions reserve aggressive systemic consolidation for relapsed disease. However, the biological similarities between PVRL and PCNSL suggest that aggressive primary management is highly beneficial. This case demonstrates that intensive systemic induction combined with local therapy and frontline ASCT can achieve durable remission. Because more aggressive induction and consolidation are related to decreased relapse and increased overall survival in PCNSL, treating PVRL with primary ASCT should be considered an optimal strategy. Future prospective trials are warranted to establish ASCT as a standard first-line strategy for this rare but aggressive disease