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To report the successful medical management of a late-onset Descemet membrane endothelial keratoplasty (DMEK)-related interface infection.A case of DMEK endothelial keratoplasty-related infection treated with intrastromal antifungal injection was identified. The following information was collected: demographic data, surgical indications, donor rim cultures, donor mate outcomes, clinical course, diagnostic tests, and clinical outcome.A DMEK patient developed a single infiltrate approximately 1 month after uncomplicated DMEK. Donor rim culture was positive for Candida glabrata but no prophylactic treatment was initiated. Anterior segment optical coherence tomography confirmed the location of the infiltrate, and the patient was treated with oral fluconazole and an intrastromal injection of amphotericin B with an inadvertent, but negligible, intracameral volume of the same drug. The lesion significantly regressed on examination 2 days later with complete involution and excellent visual acuity to date.Medical therapy, including systemic and intrastromal application, is a viable initial treatment option for late-onset, presumed yeast interface keratitis in patients who have undergone DMEK.