Retinal ischemic cascade: New insights into the pathophysiology and imaging findings

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of is-chemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accom-panying risk factors, the middle and inner retinal vasculature and blood flow, and the vul-nerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resem-bles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible as-sociations between the middle and inner retinal ischemic patterns.(c) 2022 Elsevier Inc. All rights reserved.