# Real world outcomes of intravitreal and systemic therapy in primary and secondary vitreoretinal lymphoma

## TL;DR

This study examines the effectiveness of different treatments for a rare eye cancer called vitreoretinal lymphoma, finding that combined therapies may improve patient outcomes.

## Contribution

The study provides real-world outcomes of intravitreal and systemic therapies for vitreoretinal lymphoma in a large cohort.

## Key findings

- Patients receiving combined Rituximab and methotrexate intravitreal therapy had no relapses during follow-up.
- Systemic therapy added to intravitreal treatment was associated with longer relapse-free survival.
- Methotrexate intravitreal therapy showed a trend toward better ocular relapse-free survival than Rituximab alone.

## Abstract

Vitreoretinal large B-cell lymphoma (VR-LBCL) is a rare hematologic malignancy. It is classified as primary (PVR-LBCL) or secondary (SVR-LBCL) based on the initial site of manifestation. Owing to limited prospective data and absent standardized guidelines, treatment remains challenging. This dual-center retrospective study aimed to evaluate outcomes of methotrexate (MTX) intravitreal (itv.), Rituximab itv., or combinatorial itv. therapy (R-MTX) and assess the impact of additional systemic immunochemotherapy. Among 65 patients (median age 72 years) included, 55.4% (n = 36) had PVR-LBCL. The median time to diagnosis was 31 days (1–2805). Over a median follow-up of 23.2 months, 35 patients relapsed. MTX itv. showed a trend toward better ocular relapse-free-survival than Rituximab itv. (P = 0.07). Intriguingly, patients receiving R-MTX itv. experienced no relapses throughout follow-up. In general, addition of systemic therapy was associated with significantly longer relapse-free-survival compared to itv. monotherapy (P = 0.05). Keratopathy and elevated intraocular pressure were common side effects with MTX itv. and Rituximab itv., respectively. Despite compelling findings and being one of the largest cohorts published to date, the heterogeneity of the patient population and small subgroups limit direct clinical translation. Nonetheless, this study provides a strong foundation for the design of future clinical trials.

The online version contains supplementary material available at 10.1038/s41598-026-37804-4.