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

Woo-Kyung Park,Rae-Young Kim,Mirinae Kim,Young Gun Park,Young-Hoon Park

doi:10.1038/s41598-020-73111-2

Woo-Kyung Park, Rae-Young Kim + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-73111-2

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Abstract

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.

Highlights

Primary vitreoretinal lymphoma (PVRL) is a very rare disease with only approximately 380 cases diagnosed every year in the United States, but its incidence has been gradually increasing in the recent years[1,2]
We evaluated the serial changes in the cytokine profile of CD4-positive T-helper clones (Th1/Th2), including IL-6, IL-10, interferon-gamma (IFN-γ), IL-2, IL-12, IL-17, and tumor necrosis factor-alpha (TNF-α), in the aqueous humor of patients with PVRL treated with intravitreal MTX injections and we analyzed the relation of these changes with the patients’ clinical course and the recurrence of PVRL
PVRL is difficult to diagnose because it often masquerades as inflammatory or infective posterior uveitis, which can lead to delays in the correct diagnosis of a disease that is life-threatening

Summary

Introduction

Primary vitreoretinal lymphoma (PVRL) is a very rare disease with only approximately 380 cases diagnosed every year in the United States, but its incidence has been gradually increasing in the recent years[1,2]. The gold standard for PVRL diagnosis is cytological analysis, usually made by examination of the vitreous after diagnostic vitrectomy or by retinal biopsy This method poses difficulties due to problems with specimen preservation and fragility of the lymphoma cells. Multiple studies have shown that an IL-10/IL-6 ratio greater than one or increased IL-10 level of more than 150 pg/mL supports the diagnosis of lymphoma[7,8] Systemic chemotherapy, such as that with intravenous methotrexate (MTX), is the first-line treatment; systemic administration is associated with severe side. We evaluated the serial changes in the cytokine profile of CD4-positive T-helper clones (Th1/Th2), including IL-6, IL-10, interferon-gamma (IFN-γ), IL-2, IL-12, IL-17, and tumor necrosis factor-alpha (TNF-α), in the aqueous humor of patients with PVRL treated with intravitreal MTX injections and we analyzed the relation of these changes with the patients’ clinical course and the recurrence of PVRL

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