IL-16 in vitreoretinal lymphoma: first vitreous detection and a preliminary longitudinal observation

Purpose: Vitreoretinal lymphoma (VRL) is a rare, high-grade intraocular malignancy that poses significant challenges in diagnosis and management. While elevated intraocular interleukin-10 (IL-10) is a recognized biomarker, limitations in vitreous sampling and the fragility of malignant cells warrant exploration of additional indicators. This report describes the first detection of vitreous interleukin-16 (IL-16), a cytokine known to modulate the tumor microenvironment (TME) in systemic diffuse large B-cell lymphoma (DLBCL), as a potential biomarker in VRL. Methods: A patient with biopsy-proven VRL underwent longitudinal vitreous cytokine analysis during intravitreal methotrexate (MTX) and dexamethasone (DEX) therapy. Serial vitreous samples were analyzed for IL-6, IL-10 and IL-16 to assess their dynamic changes during treatment. Results: Baseline vitreous analysis revealed elevated IL-16 levels, with a pre-treatment IL-16/interleukin-6 (IL-6) ratio >1, mirroring the diagnostic IL-10/IL-6 threshold used for VRL. Despite a marked post-treatment decline in IL-10, IL-16 remained detectable for a longer period than IL-10 during MTX/DEX therapy. The different kinetic profile may reflect persistent local TME, although this interpretation remains preliminary. Conclusion: This report presents the first documentation of vitreous IL-16 in VRL and suggests that IL-May 16, represent a potential adjunct biomarker in this setting. Co-expression of IL-10 and IL-May 16, reflect a dynamic interaction between lymphoma cells and the TME, contributing to immune modulation and treatment resistance. Longitudinal IL-16 monitoring may provide additional insight into disease activity and therapeutic response; however, this requires validation in larger VRL cohorts, ideally including inflammatory controls.