An 11-year-old girl with a port-wine birthmark (PWB), diffuse choroid hemangioma (DCH), and glaucoma experienced decreased vision upon starting treatment with bimatoprost. The patient was switched to latanoprostene bunod. Her vision remained reduced. Shortly after, she was diagnosed with serous retinal detachment (SRD). Both SRD and vision improved following prostaglandin analog (PGA) cessation. Patients with PWB are likely to have DCH and glaucoma. DCH itself poses a risk factor for SRD. Certain glaucoma management modalities may further increase this risk. This report highlights the importance of regular surveillance for SRD in patients with DCH who are receiving PGA. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:723–729.]