The ocular manifestations of the differentiation syndrome (DS) are rarely reported in the literature with only six cases published until now. Patients with acute promyelocytic leukemia (APL) who undergo treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are especially susceptible to developing DS. This is a serious diagnosis with a life-threatening impact on some patients, however, amenable to prophylaxis and treatment by systemic corticosteroids. An exudative retinal detachment (ERD) may either complicate or herald the development of DS. In this article, we present a case of APL who developed ERD in advance of DS symptoms, its multimodal imaging characteristics, and review the published articles concerning this rare disease manifestation.