Case report: Orelabrutinib-rituximab with intravitreal methotrexate shows response in primary vitreoretinal lymphoma

Primary vitreoretinal lymphoma (PVRL) is a rare intraocular malignancy for which the optimal therapeutic strategy remains controversial, largely due to the disease’s rarity and considerable heterogeneity in treatment approaches across medical centers. While some studies suggest that combined systemic chemotherapy may prevent central nervous system progression in PVRL, others have failed to confirm such benefits, particularly given the severe treatment-related toxicities associated with intensive regimens. Although agents such as lenalidomide and Bruton’s tyrosine kinase(BTK) inhibitors have demonstrated efficacy in relapsed/refractory (R/R)PVRL, their role in treatment-naïve patients remains unclear. Herein, we retrospectively report the efficacy and safety of Orelabrutinib and rituximab combined with intravitreal methotrexate(MTX) in a patient with PVRL. The patient received this regimen as first-line treatment, which led to rapid improvement in visual acuity and intraocular tumor control in all affected eyes. Interleukin-10, a well-established biomarker for vitreoretinal lymphoma, decreased to normal levels after five months of therapy. The treatment was well-tolerated, with no reported adverse events. In conclusion, the combination of Orelabrutinib, rituximab, and intravitreal MTX is a feasible therapeutic strategy for PVRL. Our findings may contribute to a potential paradigm shift in the management of this rare disease.