Serial changes in the aqueous IL-10 level after intravitreal methotrexate injection as an indicator of primary vitreoretinal lymphoma recurrence

Primary vitreoretinal lymphoma (PVRL) often masquerades as other uveitic diseases. We investigated the aqueous cytokine level changes and the effects of intraocular methotrexate (MTX) in patients with PVRL. In this retrospective consecutive case-series study, we reviewed the records of 14 consecutive patients with PVRL treated between 2018 and 2020. The concentrations of interleukin (IL)-2, IL-6, IL-10, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were determined at baseline and several time points after intravitreal MTX injections during follow-up. Markedly elevated IL-10 levels and a higher IL-10/IL-6 ratio were found in patients with PVRL. The aqueous levels of IL-10, IL-12, and TNF-α, and the IL-10/IL-6 ratio significantly decreased at 1 month after intravitreal MTX therapy onset compared with the baseline values (P = 0.001, 0.002, 0.001, and 0.001, respectively). The mean duration to normalized IL-10 levels was 1.17 ± 0.4 months. Where serially recorded IL-10 levels were available, regular intravitreal MTX treatment was associated with rapid reduction in IL-10 levels, while elevated IL-10 level was associated with disease recurrence. Elevated IL-10 levels and high IL-10/IL-6 ratio may aid in the diagnosis of PVRL. Aqueous IL-10 level monitoring can help assess the therapeutic response and indicate disease recurrence.