Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Intraocular Involvement: Clinicopathologic Characteristics and the Treatment Outcome of Intravitreal Injection of Methotrexate

Abstract

Background：Primary intraocular and periocular mucosa-associated lymphoid tissue lymphoma (MALT-lymphoma) was a rare type of non-Hodgkin lymphoma (NHL) with marked differences from other indolent B-cell lymphomas. Transformation to large-cell aggressive lymphomas could occur in a few cases. The initial therapeutic modality has not been fully established for the disease. Methotrexate (MTX), as the most efficient cytotoxic drug for patients with vitreoretinal involvement in primary intraocular lymphoma (PIOL), through intravitreal injection of MTX. Here we reported long-term activity and treatment outcomes of the MALT-lymphoma intraocular and periocular involvement. Patients and Methods: Adult patients with histologically/cytologically confirmed unilateral primary intraocular and periocular B-cell MALT-lymphoma at Beijing Tongren hospital were enrolled. Patients were randomly assigned 1:1 to receive intravitreal injection of MTX (IV-MTX group, 400 µg/0.1 ml) according to a standard Intensive-Consolidation-Maintenance regimen, or Wait-and-See management as a control group. Primary end points were progression-free-survival (PFS), best-corrected visual acuity (BCVA), clinical response to intravitreal chemotherapy, complications during the study period. Results: A total of 10 patients were enrolled (IV-MTX, n=5; Wait-and-See, n=5). Median follow-up was 5.5 years (QIR, 2.0-9.0 years). At the end follow-up, no death and systemic metastasis occurred in all patients. PSF at 5 years was excellent (70% and 80%, respectively) and did not differ between two groups. For the IV-MTX group, the BCVA was not obviously improved and the tumor tissues were unchanged clinically in size after a median 7 times of vitreous injection of MTX in all 5 eyes (P>0.05) and had lower rates of treatment-related complications. For the control group, one of five eyes had worsening BCVA and four remained stable. The volume of tumor tissue increased slowly, and the tumor basal and thickness increased 1.08±1.63 mm and 0.32±0.80 mm on average, respectively. Conclusions: According to our current sample size and the duration of follow-up, it suggests that no clinical benefit of IV-MTX has been found to primary intraocular and periocular MALT-lymphoma. The observing management for these patients with primary intraocular and periocular lymphoma of MALT-type was reasonable, with relatively excellent long-term outcomes. Funding Statement: The National Natural Science Foundation of China (Nr. 81272981), the Beijing Natural Science Foundation (Nr. 7151003), and the priming scientific research foundation for the junior research in Beijing Tongren Hospital Capital Medical University (2017-YJJ-ZZL-009) provided financial support. Declaration of Interests: All authors declare that they have no conflict of interest in this manuscript. Ethics Approval Statement: This study followed the tenets of the Declaration of Helsinki and its ethical standards of 1964. The study was approved by the Medical Ethics Committee of the Beijing Tongren Hospital, and written informed consent was obtained from all participants. All methods were performed in accordance with the relevant guidelines and regulations.