Role of systemic high‐dose methotrexate and combined approaches in the management of vitreoretinal lymphoma: A single center experience 1990‐2018

Abstract

Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990‐2018. Three nondiffuse large B‐cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively. Among primary and concurrent VRL, median failure free survival (FFS), CNS relapse‐free survival (CNS‐RFS) and overall survival (OS) were: 1.8, 4.9, and 4.1 years, respectively; among PVRL, median FFS, CNS‐RFS, and OS were: 2.6 year, Not Reached and 9.3 year, respectively. No CNS relapse occurred beyond 4 years in PVRL. Median OS for patients diagnosed between 1990 and 1999 vs between 2000 and 2018 was 1.5 vs 9.4 years, respectively (P = .0002). OS was significantly higher in PVRL, as compared with concurrent VRL (P = .04). Previous immunosuppression and poor performance status were predictive of worse outcome. In PVRL, a combined systemic and intraocular therapy showed higher FFS (P = .002) and CNS‐RFS (P = .003), but no differences in OS. Among 18 secondary VRL, at a median follow‐up of 1.1 year after vitreoretinal relapse, median FFS and OS were 0.3 and 1.3 years. An improvement in survival of VRL has been observed over the decades. PVRL should undergo combined systemic and intraocular chemotherapy to prevent CNS progression.

Intraocular chemotherapy for vitreoretinal lymphoma: A review

“…Subsequent to the original clinical case series, medical centres in North America, Europe, the Middle East and Asia also have reported their experience in treating groups totalling at least 177 eyes of 114 patients with VRL, as well as multiple individual patients, using intravitreal methotrexate injections. Additional reports have described groups of patients suffering from VRL, who received a range of treatments that included methotrexate and/or rituximab intravitreal injections (see below) . Outcomes reported for the 114 patients were consistent with those previously reported by the OHSU and Hadassah University investigators .…”

“…Case reports and small series have detailed consistent experiences with intraocular rituximab therapy at ophthalmology centres in other countries, including Puerto Rico, Spain and Italy . In addition, a number of North American eye clinics have published outcomes of VRL patient cohorts cumulatively totalling almost 200 individuals, including some patients treated with intravitreal rituximab and/or methotrexate therapy; while these studies indicate treatment remissions, the impact of the local therapy specifically is not readily dissected since multiple approaches to treatment are included …”

“…Additional drugs have also been used in intraocular chemotherapy protocols for VRL, albeit less often, including thiotepa, melphalan and corticosteroid . Here we describe the technique of intravitreal injection, ahead of summarizing clinical studies of the different chemotherapeutic drugs delivered into the eye (Table ), and considering the role of intraocular chemotherapy in the management of PVRL.…”

“…In addition to the treatments listed, intraocular chemotherapy with thiotepa has been reported in 1 patient, and in one study listed under “drug not specified and/or outcome not reported separately from outcomes of other treatments”, corticosteroid was included in the intraocular chemotherapy …”

“…Another potential choice is direct intraocular treatment with dexamethasone or a long acting steroid preparation.” Corticosteroids have lymphocytotoxic effects, which is why VRL masquerading as uveitis may show partial response to treatment with different corticosteroid preparations that are prescribed before the diagnosis of lymphoma is recognized . While most ophthalmologists combine methotrexate and rituximab as multi‐agent chemotherapy for VRL, some groups include intravitreal corticosteroid in their management of VRL …”