Though rare, acute macular neuroretinopathy is a well-described clinical entity. We report for the first time a detailed analysis of macular hyalocyte count and morphology during the acute phase of acute macular neuroretinopathy. We present a case of a 19-year-old man with bilateral acute onset paracentral scotomas in the setting of an antecedent viral infection. Multimodal imaging demonstrated classic features of acute macular neuroretinopathy. Further analysis revealed increased macular hyalocyte count and an activated hyalocyte morphology during the acute phase of the disease course. Multimodal imaging not only allows for greater confidence in a diagnosis and prognosis but also helps to shed light on underlying pathophysiology. The new clinical capability of monitoring cellular behavior, such as hyalocyte count and morphology, in physiological and pathological conditions may prove useful as biomarkers of early disease activity or response to therapy.