Misery Perfusion, Diffusive Oxygen Shunting and Interarterial Watershed Infarction Underlie Oxygenation-Based Hypoperfusion Maculopathy

PURPOSE: To describe and explain the entire range of acute ischemic macular damage that follows panretinal hypoperfusion from central retinal artery or vein occlusion. DESIGN: Perspective article. METHODS: To correlate the fundoscopic, fluorescein angiographic, oximetric, and optical coherence tomographic (OCT) features developing within the posterior inner retina following incremental reductions in arteriovenous perfusion pressure across the retinal circulation. RESULTS: The spectrum of acute oxygenation-based hypoperfusion maculopathy (OHM) is consistent with that predictable from a modified Krogh cylinder model of tissue oxygenation. Diffusive oxygen shunting plays a significant role in the artery-dominated generation of ischemic signs during misery perfusion. Three major grades of OHM severity can be discerned according to the predominant oxygenation status of ganglion cells within the superficial inner retina, whether this is normoxic (OHM1), hypoxic (OHM2), or anoxic (OHM3). Densely opaque axoplasmic sentinels are arranged along normoxic/hypoxic interfaces in OHM2. In OHM1 and OHM2, relative hypermetabolism and interarterial watershed infarction of fundal interneurons (WIFI) underpin subtle middle-retinal opacification with periarterial sparing. The fundal signs are optimally displayed en face using autofluorescence imaging whereas cross-sectional OCT reveals Paques' plaque formation. CONCLUSIONS: An exquisite and supremely accessible exhibition of classical oxygen physiopathology unfolds in eyes with panretinal hypoperfusion courtesy of the transparent ocular media and the pattern of macular neuroretinal opacification that evolves as upstream tissues extract oxygen to the detriment of tissues downstream. Recent attempts to overrule the simple conceptual framework embodied in WIFI have no plausible anatomical nor physiological basis. Over-reliance on OCT can result in misdiagnosis. ((C) 2019 Elsevier Inc. All rights reserved.)