Effects of Intravitreal Methotrexate Injection on Choroidal Structure in Intraocular Malignant Lymphoma and Identification of Prognostic Factors for Central Nervous System Lymphoma Development

<b>Background</b>: Vitreoretinal lymphoma (VRL) often presents with features resembling uveitis and is commonly associated with central nervous system lymphoma (CNSL). Intravitreal methotrexate (IVMTX) is widely used as local therapy; however, objective markers for treatment response and prognosis remain limited. This study investigated choroidal structural changes after IVMTX via enhanced depth imaging optical coherence tomography (EDI-OCT) and explored prognostic indicators for subsequent CNSL development. <b>Methods</b>: This retrospective study included 18 patients (27 eyes) with VRL treated with IVMTX at Tokushima University Hospital between 2006 and 2021. EDI-OCT was conducted at baseline and at 1 and 3 months after IVMTX. Choroidal thickness and luminal and stromal areas were quantified through image binarization. The stromal/choroidal area (S/C) ratio and its association with CNSL onset were statistically analyzed. <b>Results</b>: The mean number of IVMTX injections administered over 3 months was 5.9 ± 1.3. Foveal retinal thickness did not significantly change, whereas foveal choroidal thickness significantly decreased from 275.8 ± 15.8 µm at baseline to 257.5 ± 14.7 µm at 1 month (<i>p</i> < 0.01). Total choroidal and stromal areas, particularly in the outer choroidal layer, were significantly decreased after IVMTX (<i>p</i> < 0.0001), whereas the luminal area in the inner layer modestly reduced (<i>p</i> < 0.05). The S/C ratio significantly declined at 1 month post-treatment (<i>p</i> < 0.001). Patients who developed CNSL within 2 years of VRL onset demonstrated higher baseline S/C ratios (<i>p</i> < 0.05). <b>Conclusions</b>: IVMTX induces measurable reductions in choroidal areas and stromal proportion, indicating decreased inflammatory infiltration. The baseline S/C ratio observed on EDI-OCT is a potential noninvasive biomarker of VRL activity and a prognostic indicator for early CNSL development.