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This is a report of an immunocompromised 49-year-old renal transplant patient with Epstein-Barr virus (EBV)-induced necrotizing retinitis (NR). The patient with NR underwent diagnostic vitrectomy. Polymerase chain reaction (PCR) testing of the vitreous fluid was positive for EBV (25,000 IU/mL) and negative for all other organisms. The patient was treated with intravitreous ganciclovir and foscarnet. After only mild clinical improvement in retinitis and an increased quantitative EBV PCR (69,000 IU/mL), intravitreous methotrexate was added to the aforementioned intravitreous antiviral injections. After eight rounds of ganciclovir/foscarnet and three injections of methotrexate, the NR resolved, the quantitative EBV PCR decreased to 29 IU/mL, and the patient’s visual acuity improved. To our knowledge, this is only the second case report to demonstrate efficacy of intravitreous methotrexate in an immunocompromised …