A case of intravascular lymphoma diagnosed with a primary vitreoretinal lymphoma-like fundus lesion

Purpose We report a case of intravascular lymphoma with primary vitreoretinal lymphoma-like fundus findings. Case A 61-year-old man with a one-week history of temporal visual field defect in the left eye was referred by a local ophthalmologist to our department. A yellowish-white raised patchy lesion was found in the nasal fundus of the left eye. Vitreoretinal lymphoma was suspected, and vitrectomy was performed in the left eye for diagnostic purpose. However, vitreous interleukin-10 concentration was low and no significant result was obtained. He had fever of around 38 °C, and respiratory failure that started 2 weeks before ophthalmological examination, worsened. Intravascular lymphoma was diagnosed from the results of histopathological examinations of transbronchial lung biopsy, bone marrow biopsy and random skin biopsy. With the start of systemic chemotherapy, the subretinal lesions shrank gradually and systemic condition was stable. However, 5 months after the start of chemotherapy, spread to the central nervous system was observed, and chimeric antigen receptor T cell (CAR-T) therapy was started in another hospital. After the start of CAR-T therapy, the subretinal lesions shrank further. Conclusions Intravascular lymphoma may be accompanied by primary vitreoretinal lymphoma-like intraocular lesions. If intraocular lesions are accompanied by systemic symptoms such as fever of unknown origin, the possibility of intravascular lymphoma should be suspected and systemic work-up should be performed.

Clinical outcomes following intravitreal methotrexate for primary vitreoretinal lymphoma

Purpose To describe the visual acuity and anatomic outcomes of intravitreal methotrexate (MTX) for the treatment of primary vitreoretinal lymphoma (PVRL). Methods Single-center retrospective case series of patients with a diagnosis of PVRL treated with intravitreal MTX. Patient records were reviewed for demographic information, ocular exam findings, and treatment regimens including number of MTX injections. Clinical outcomes recorded included visual acuity (VA), time to partial (PR) or complete response (CR), disease-free survival, time to relapse, and any CNS progression. Results Ten eyes of 7 patients (4 male, 6 female) were reviewed. The mean age ± standard deviation (SD) was 70 ± 12 years. Five patients had prior or concomitant diagnosis of primary CNS lymphoma with a history of systemic chemotherapy including MTX. Three eyes (30%) exhibited isolated vitreous involvement, four (40%) had subretinal lesions, and three (30%) presented with both vitreous and subretinal disease. Mean initial logMAR VA was 0.38 ± 0.52 (Snellen visual equivalent 20/50), while mean final logMAR VA ± SD was 0.34 ± 0.27 (Snellen visual equivalent 20/40) with a mean follow-up time of 26 months (Range, 3–49 months). Patients received an average of 6 intravitreal MTX injections (Range 1–10) over the course of treatment. Two patients received concomitant systemic chemotherapy. Mean time to either PR or CR was 57 days, and 6 eyes (60%) exhibited regression with no relapse after local treatment. For the 4 eyes that eventually relapsed, the mean time ± SD to first relapse was 193 days ± 155 days, and one eye experienced a second relapse. Two of 3 patients with subretinal disease showed complete regression with extended follow-up of 1 and 4 years following treatment with less than 3 doses of intravitreal MTX. One patient with PVRL developed CNS lymphoma during the study period. VA remained stable overall between the initial treatment visit, 3, 6, and 12-months (P > 0.05 for paired comparisons of VA over time). Conclusions Intravitreal methotrexate was well-tolerated and led to local disease response in the majority of patients at approximately 2 months after initiation of treatment of intraocular lymphoma. Further studies on the efficacy of intravitreal treatment alone versus combined systemic and intravitreal treatment are warranted.

Lenalidomide and Rituximab Regimen Combined With Intravitreal Methotrexate Followed by Lenalidomide Maintenance for Primary Vitreoretinal Lymphoma: A Prospective Phase II Study

Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system (CNS) lymphoma, for which currently there are no optimal treatment options. This prospective single-center study enrolled immunocompetent patients with newly diagnosed PVRL between August 2018 and January 2020. Patients received local and systemic therapies: intravitreal methotrexate (MTX, 400 μg, 0.1 mL) injections for 1 year (total 16 injections) and six cycles of the rituximab (375 mg/m2 on day 1) and lenalidomide (25 mg on day 1–21; R2) regimen. Lenalidomide was maintained for 2 years in patients who had achieved a response. We enrolled 11 patients with a mean age of 58 (range, 48–70) years, of which 10 achieved complete remission at the first evaluation. The median follow-up period was 18.3 (range, 10.6–27.8) months, and the median progression-free survival was 12.7 months. Moreover, a total of eight patients relapsed. The most common adverse event (AE) was neutropenia, which occurred in seven patients (63.6%), followed by grade 3 ocular toxicities, including cataract formation, in six patients (54%). These findings suggest that the R2 regimen combined with intravitreal MTX, followed by lenalidomide maintenance, is a safe option for PVRL with moderate efficacy. This trial is registered with ClinicalTrials.gov (number NCT 03746223).

Primary vitreoretinal lymphoma: A diagnostic and management challenge.

Primary vitreoretinal lymphoma (PVRL) is a rare form of primary central nervous system lymphoma (PCNSL) arising in the intraocular compartment without brain involvement. Despite its apparent indolent clinical course, PVRL can cause permanent vision loss and CNS relapse, the major cause of death in PVRL patients. The pathophysiology of PVRL is unknown. As in PCNSL, the transformation of the tumor cells likely originates outside the CNS, before the cells migrate to the eye and proliferate within an immune-permissive microenvironment. PVRL exhibits a biased immunoglobulin repertoire, suggesting underlying antigen selection. The diagnosis remains challenging, requiring close coordination between ophthalmologists and cytologists. Because of their rarity and fragility in the vitreous, lymphoma cells cannot always be identified. Interleukin levels, molecular biology and imaging are used in combination with clinical ophthalmological examination to support the diagnosis of PVRL. Multi-institutional prospective studies are urgently needed to validate the equivocal conclusions regarding treatments drawn from heterogeneous retrospective or small cohort studies. Intravitreal injections of methotrexate or rituximab or local radiotherapy are effective at clearing tumor cells within the eyes but do not prevent CNS relapse. Systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce this risk. At relapse, intensive consolidation chemotherapy followed by stem cell transplantation can be considered. Single-agent ibrutinib, lenalidomide and temozolomide treatments are effective in patients with relapsed PVRL and should be tested as first-line treatments. Therapeutic response assessment based on a clinical examination is improved by measuring cytokine levels but still needs to be refined.

Primary Vitreoretinal Lymphoma Therapy Monitoring: Significant Vitreous Haze Reduction After Intravitreal Rituximab

BACKGROUND/AIMS: Intravitreal rituximab is an off-label treatment option for primary vitreoretinal lymphoma (PVRL). The objective of this study was to monitor the therapeutic response and safety profile of intravitreal rituximab in a cohort of PVRL patients. METHODS: In this retrospective, uncontrolled, open label, multicentre study, 20 eyes from 15 consecutive patients diagnosed with PRVL received at least one intravitreal injection of 1mg in 0.1ml rituximab. Biodata of the PVRL patients was recorded as well as visual acuity and vitreous haze score immediately before rituximab intravitreal injection and at follow-up examinations. Intravitreal rituximab safety data was also recorded. Additional rituximab injections were made during control visits on a pro re nata (PRN) regime using increased vitreous haze to indicate recurrence. RESULTS: There was significant vitreous haze reduction (p=0.0002) followed by significant improvement of visual acuity (mean best visual acuity before therapy 0.57 logMAR, after therapy 0.20 logMAR (p=0.0228) during the follow-up time up to 4 years. Only mild ocular side effects were reported. Median follow-up time was 565 days (range, 7-1253 days). CONCLUSION: Intravitreal rituximab therapy shows promising PVRL regression without any severe side effects. Although our clinical data support rituximab as intravitreal therapy in PVRL disease, further study is warranted.