Long-term outcomes of combined intravitreal methotrexate and systemic high-dose methotrexate therapy in vitreoretinal...

The optimal treatment for vitreoretinal lymphoma (VRL) remains a challenge, as central nervous system (CNS) relapse occurs frequently, leading to the worst impact on survival. We previously proposed combined intravitreal methotrexate and systemic high-dose methotrexate therapy for this disease. This study aimed to report the long-term outcomes of patients with VRL using this combination treatment.

We conducted a retrospective cohort study on patients with VRL at a tertiary referral center between 2003 and 2018.

Thirty-two patients were included, of whom 23 had primary VRL (PVRL) and nine had concurrent intraocular and CNS diseases. The treatment was well tolerated. Twenty-six (81.3%) patients achieved complete response (CR). After a median follow-up time of 103.5 months, the 5-year survival rate was 73.3%, whereas the 5-year progression-free survival (PFS) rate was 29.9%. Twenty-four (75%) patients relapsed, including 12 with isolated intraocular relapses at first relapse and a total of 17 with CNS/systemic relapses. The development of CNS/systemic relapse negatively affected survival, but intraocular relapse did not. The median CNS/systemic PFS was 69.5 months, but the risk of CNS/systemic relapse increased steadily with a cumulative incidence rate at 2, 5, and 10 years being 22.6%, 44.2%, and 65%, respectively. Multivariate analysis identified concurrent CNS disease at diagnosis as the only poor-risk factor for CNS/systemic relapse.

This study confirms good efficacy and acceptable toxicities of the combination approach. However, incorporation of further intensive consolidation strategies into the treatment protocol to effectively prevent subsequent CNS/systemic relapse deserves to be considered.