A man in his mid-20s with cystic fibrosis (CF) underwent bilateral lung transplant. Four weeks after the transplant, the patient developed acute vision loss of the left eye. Visual acuity was 20/20 OD and hand motion OS. Anterior segment was remarkable for 1+ hyperemia and 4+ anterior chamber (AC) cell in the left eye. Posterior segment was notable for retinal whitening and occlusive vasculitis in the right eye and more extensive retinal whitening associated with an exudative retinal detachment in the left eye. Microbial and broad-range polymerase chain reaction (PCR) analysis and culture results of the AC and vitreous were negative as well as numerous blood cultures and serum fungitell. Despite broad-spectrum intravenous (ie, vancomycin and piperacillin/tazobactam) and intravitreal antibiotics (vancomycin and ceftazidime), antifungals (amphotericin B and voriconazole), and antivirals (foscarnet), the patient’s visual acuity and intraocular inflammation worsened in both eyes to light perception. Over a week, the areas of retinal whitening became elevated owing to enlarging subretinal infiltrates (Figure, A) that were nearly kissing in the right eye (Figure, B). Owing to the diagnostic dilemma, a pars plana vitrectomy with subretinal biopsy was performed in the left eye, and again, microbiological analysis including culture and PCR analysis was inconclusive. Pain worsened, intraocular pressure elevated into the mid-40s mm Hg, visual acuity waned to no light perception, and intraocular inflammation and subretinal infiltrates continued to worsen, producing nearly closed funnel retinal detachments in both eyes, including developing orbital cellulitis in the right eye despite broad-spectrum antimicrobials. During this period, the patient remained afebrile; however, the patient’s white blood cell count was uptrending, raising concern for systemic spread of the infection.