Opposing pathophysiological concepts in multiple evanescent white dot syndrome: The great MEWDS schism

Abstract: Multiple evanescent white dot syndrome (MEWDS) is a benign posterior uveitis involving the outer retina-choriocapillaris complex. The clinical picture, since its first description in 1984, is well-established. Classified at the benign end of the choriocapillaritis spectrum, including, among others, idiopathic multifocal choroiditis, serpiginous choroiditis, and acute posterior multifocal pigment epitheliopathy, a challenge to this classical choriocapillaritis classification of the disease was attempted, attributing the primary lesion process to a photoreceptoritis. The aim of this perspective and review article was to gather a sufficient body of evidence for a credible pathophysiological explanation of MEWDS. We reviewed the literature and integrated the results of some of our own studies on MEWDS. The crucial role of indocyanine green angiography (ICGA) and its correct interpretation is highlighted, giving clear indications that uptake failure of ICG by the retinal pigment epithelial (RPE) cannot explain ICGA hypofluorescence. In contrast to what is often claimed, ICGA hypofluorescence is already present in the early angiographic phases in MEWDS, speaking for a perfusion problem rather than the RPE nonuptake thesis. Hypoxic damage principally affects the photoreceptor cell but only minimally the RPE cell in MEWDS, explaining why primary photoreceptoritis has been privileged by some. The principles of optical coherence tomography angiography, being based on the presence of flow, it cannot detect the presence or absence of flow in low-flow end-capillaries and is, therefore, an inappropriate imaging modality for MEWDS. There is a continuum between MEWDS and other choriocapillaritis entities, which are all based on inflammatory choroidal circulatory dysfunctions of diverse severity, including MEWDS. We found a substantial body of evidence indicating that end-choriocapillaris nonperfusion is at the origin of MEWDS with limited secondary hypoxic damage mainly to the vulnerable photoreceptors and functional preservation of the metabolically more resistant RPE cell. As only small end-choriocapillary vessels are involved in MEWDS, spontaneous resolution of the disease occurs mostly without sequels.