Combined systemic and intraocular methotrexate (MTX)-based treatments may lead to improved outcomes for patients with vitreoretinal lymphoma (VRL), according to a study published in the American Journal of Hematology.

Researchers retrospectively identified 69 patients who had been diagnosed with VRL with diffuse large B cell lymphoma at the Mayo Clinic in Rochester, Minnesota, between January 1990 and January 2018. The cohort included 33 patients with primary VRL, 18 patients with concurrent intraocular and systemic or central nervous system (CNS) disease, and 18 patients with secondary VRL.

Patients received intraocular chemotherapy (9 patients), consisting of rituximab, MTX, steroids, or local radiotherapy; systemic therapy (34 patients), consisting of high-dose MTX-based regimens and cyclophosphamide, doxorubicin, vincristine, and prednisone; radiotherapy only (10 patients); combined intraocular and systemic therapy; or no therapy.

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Median failure-free survival (FFS) for the whole cohort was 1.8 years and overall survival (OS) was 4.1 years after a median follow-up of 2.8 years. OS was found to be higher for patients diagnosed between 2000 and 2018 compared with patients diagnosed between 1990 and 1999 (9.4 years vs 1.5 years; P =.0002), as well as for patients who received an autologous stem cell transplant (P =.009).

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Median intraocular and CNS relapse-free survival were 3.8 years (95% CI, 1.8-8.5) and 4.9 years (95% CI, 2.5-not reached), respectively, with 45.1% of patients experiencing intraocular relapse and 37% of patients experiencing CNS relapse. No patients experienced CNS relapse more than 4 years after being diagnosed.

In patients with primary VRL, median FFS and OS were 2.6 years and 9.3 years, respectively. Patients who received combined treatment had similar OS but higher FFS (P =.002) and higher CNS relapse-free survival (P =.003) compared with patients receiving systemic or intraocular therapy alone.

Toxicities experienced by patients receiving intraocular therapy included cataract (32.4%), vitreous detachment (8.8%), ocular hypertension or glaucoma (14.7%), retinal vessel occlusion (8.85), and keratitis (5.9%). Patients receiving systemic treatment experienced acute kidney failure (11.6%), infections (11.6%), hemorrhage (4.3%), and pancytopenia (1.4%).

The researchers concluded that although no differences in OS were reported, combined MTX-based treatment may reduce risk for relapse and should therefore be considered for patients with VRL.


1. Castellino A, Pulido JS, Johnston PB, et al. Role of systemic high-dose methotrexate and combined approaches in the management of vitreoretinal lymphoma: A single center experience 1990-2018 [published online December 5, 2018]. Am J Hematol. doi: 10.1002/ajh.25350