Case Report: Longitudinal analysis of local immunoregulatory mediators in a DLBCL vitreoretinal lymphoma receiving local chemotherapy.

Background: Vitreoretinal lymphoma (VRL) is a rare, high-grade B-cell lymphoma that affects immune-privileged sites and is classified as a variant of primary central nervous system lymphoma (PCNSL). The pathogenesis of VRL, including the origin of malignant B-cells, remains poorly understood. Cytokines, chemokines, and growth factors are thought to play critical roles in both the homing and autocrine proliferation of lymphomatous B-cells. In this study, we present the first longitudinal analysis of the dynamic interplay of vitreous immune mediators during intravitreal (IVT) methotrexate and dexamethasone therapy in a patient with VRL. Methods: A patient in their 70s with unilateral VRL underwent nine serial vitreous samplings over 12 weeks of IVT therapy with methotrexate (460 μg/injection) and dexamethasone (0.4 mg/injection). Each 0.2 mL vitreous sample was analyzed using a multiplex panel assessing 58 cytokines, chemokines, and growth factors. Vitreous levels were monitored longitudinally and correlated with clinical responses and optical coherence tomography. Results: During therapy, key cytokines, including IL-10, IL-6, IL-16, IL-1RA, and sIL-2R, decreased progressively, with IL-10 becoming undetectable by day 22. Chemokines CXCL12 and CXCL13, involved in malignant B-cell homing, declined more slowly than IL-10, suggesting persistent microenvironmental support for tumor cells. MCP-1 remained elevated, whereas hepatocyte growth factor (HGF) was consistently high, indicating potentially aggressive behavior. Other immune mediators, including MIP-1α, MIP-1β, Mig (CXCL9), and IP-10 (CXCL10), showed variable kinetics, reflecting a dynamic interplay between the tumor and host immune response. Notably, certain cytokines previously reported in VRL cohorts, such as FGF2, IFN-γ, TNF-α, and IL-17, were not elevated, highlighting patient-specific variability in the immunological profile. Conclusion: This case represents the first longitudinal characterization of vitreous immune mediators during IVT MTX/dexamethasone therapy for VRL. Dynamic changes in soluble mediators mirrored clinical tumor regression and suggested potential biomarkers for disease activity, therapeutic response, and prognosis. Persistent chemokines, such as CXCL12 and CXCL13, may indicate the optimal treatment duration, whereas high HGF levels may identify patients with aggressive disease. These findings propose a novel framework for integrating intraocular immunomonitoring into personalized therapeutic strategies and deepen our understanding of the complex tumor-immune microenvironment in vitreoretinal lymphoma. As derived from a single case, these observations are hypothesis-generating and require confirmation in larger cohorts.