A large number of randomized clinical trials have identified intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy as a first-line treatment for visual impairment in DME.[4,5] Although anti-VEGF injections have a positive effect on vision and retinal thickening, DME can persist in some eyes.[6] Methotrexate is an anti-tumor and anti-inflammatory drug that has been used to treat various malignant tumors and rheumatic diseases. This evidence concerns the gene VEGFA and neoplasm.