MEWDS is a true primary choriocapillaritis and basic mechanisms do not seem to differ from other choriocapillaritis entities

In choroiditis, fundoscopic examination is very limited. Only the choroidal foci of sufficient importance causing yellow-white discoloration can be visible through the retinal pigment epithelium (RPE). This is the reason why several inflammatory choroidal entities, with different pathophysiologic mechanisms, were grouped under the general term “white dot syndromes”.1 With the advent of indocyanine green angiography (ICGA), we gained access to the choroidal compartment which allowed the differentiation between the two main mechanisms at the origin of choroidal inflammatory pathology: choriocapillaris diseases (inflammatory choriocapillaropathies/choriocapillaritis) and stromal diseases (stromal choroiditis). Primary inflammatory choriocapillaropathies include multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), idiopathic multifocal choroiditis (MFC), serpiginous choroiditis as well as acute macular neuroretinopathy such as acute zonal occult outer retinopathy (AZOOR).2, 3 In these conditions, ICGA shows patchy or geographic hypofluorescent areas of variable sizes more clearly visible on the late frames. These areas correspond to areas of hypo or non-perfusion of the choriocapillaris. Recently, optical coherence tomography angiography (OCT-A), a new imaging technique which allows visualization of the retinal and choroidal vasculature, was developed. It has the advantage of being fast and easy to acquire, non-invasive, and depth-selective.4 OCT-A of active lesions of APMPPE and serpiginous choroiditis revealed areas of non-perfused choriocapillaris which corresponded topographically to hypofluorescent areas in ICGA,5, 6 supporting the theory of choriocapillaris hypo and/or non-perfusion as the origin of these diseases. However, a recent study by Pichi et al.7 has created doubt about choriocapillaritis being the origin of the morphological and functional alterations in MEWDS,7 as OCT-A seems not to show any alterations in choriocapillaris circulation. We present in detail the reasons why choriocapillaritis should not be discarded as the origin of the pathological lesions in MEWDS.
Arguments in favor of MEWDS being a primary choriocapillaritis
Choriocapillaritis entities belong to the same nosological group
Numerous reports indicate that primary choriocapillaritis entities (i.e., MEWDS, APMPPE, MFC, serpiginous choroiditis, and intermediary forms) belong to the same nosological group.8, 9, 10, 11 These are young patients who present with uniform symptoms described as blurred vision, photopsias, and visual field disturbances12, 13, 14 probably caused by ischemic damage to photoreceptor outer segments due to inflammatory non-perfusion of the choriocapillaris. In more than 50% of primary choriocapillaritis patients, a viral flu-like episode precedes the onset of the disease.8, 11 MEWDS patients conform perfectly to all points of this nosological ensemble. For more than two decades, this group has also been united by ICG angiographic findings showing diverse patterns of hypofluorescence depending on the level and importance of choriocapillaris involvement. Most reports for nearly three decades have interpreted these ICGA signs as choriocapillaris non-perfusion. Therefore, it is very unlikely that these ICGA findings are suddenly attributed to a new, questionable mechanism solely for MEWDS and not other choriocapillaritis entities.
Different choriocapillaritis entities can occur in the same patient In addition to similar nosological characteristics, indicating a similar physiopathological process and the involvement of a similar structure, namely the choriocapillaris, numerous reports have shown that more than one type of choriocapillaritis can occur in the same patient,15, 16, 17, 18, 19, 20 underlining the unitarian character of this group of disorders. MEWDS patients that have evolved to MFC have been described, supporting the hypothesis of a common mechanism. Fig. 1 shows an overlapping case of MEWDS with MFC.