A 9-month-old girl presented to the emergency department with significant left periocular edema and erythema 3 days after receiving intra-arterial chemotherapy (IAC) with 0.4 mg/kg of melphalan, 50 mg of carboplatin, and 2 mg of topotecan (with routine intravenous dexamethasone therapy, 0.5 mg/kg) for treatment of unilateral International Classification of Retinoblastoma group C retinoblastoma in the left eye (Figure, A). At the time of IAC, she had an upper respiratory tract infection (coughing, congestion, rhinorrhea, fever [temperature of 38.9 °C]). On postoperative day 1, her temperature reached 39.4 °C, and she was diagnosed as having bilateral acute otitis media and discharged with amoxicillin therapy. On postoperative day 3, she returned to the emergency department with left eye swelling, continued fever, and poor oral intake. On physical examination, her temperature was 40.2 °C, and periorbital swelling and erythema were present without drainage. Dilated fundus examination at the bedside showed the known large retinoblastoma tumor. A large exudative retinal detachment was noted, which was not present prior to treatment. Blood bacterial culture testing showed no growth, respiratory viral testing revealed rhinovirus, and results of comprehensive metabolic testing were unremarkable. Complete blood cell count showed mild leukopenia (2700/μL [to convert to ×109 per liter, multiply by 0.001]) and anemia (hemoglobin, 9.2 g/dL [to convert to grams per liter, multiply by 10]) but were otherwise within reference ranges. Computed tomography scan of the orbits, recommended by the on-call general ophthalmologist, demonstrated preseptal and periorbital soft tissue swelling and edema with subtle retrobulbar stranding, without substantial proptosis, along with retinal detachment (Figure, B). She was admitted for intravenous fluids for her noted dehydration.