When first described in 1984, MEWDS was characterized electrophysiologically by an acute decline in the amplitude of both the early receptor potential (ERP) and electroretinogram (ERG) a-wave with a prolonged ERP regeneration time . Thus, even from this very first report, MEWDS had been prominently linked to photoreceptors as the first known disease involving profound electrophysiologic impairment of the photoreceptor outer segments with full recovery to normal. The specific deficit in photoreceptors was hypothesized to involve either a decrease in the quantity of photoreceptor pigment or misalignment of photoreceptors as implied by the observed ERP , either of which may account for the foveal granularity most specific to the disease. The electrophysiology findings, though clearly implying dysfunction of the photoreceptor layer, were initially deemed secondary consequences of (primary) RPE dysfunction. It is likely that the FA pattern in MEWDS contributed to this interpretation as the characteristic hyperfluorescent lesions were seen as window defects thus localizing MEWDS principally to the RPE.
With the widespread clinical use indocyanine green angiography (ICGA) in the 1990s, MEWDS came to be seen as a choroidopathy. Specifically, the observation that early-phase ICGA showed no abnormalities discredited the FA-based conception of RPE window defects (which would have predicted early ICGA hyperfluorescent lesions corresponding to those seen on FA) [3, 4]. The additional observation of late-phase hypofluorescent lesions on ICGA which outnumbered those seen on FA gave rise to the notion that MEWDS involved either choroidal ischemia or exudative choroidal lesions into which indocyanine green (ICG) could not enter [3, 5]. It was further suggested that only a subset of these choroidal lesions perturbed the RPE and outer retina function sufficiently to account for the characteristic white dots of the RPE and hyperfluorescent lesions observed on FA [3, 5]. Our case suggests a component of choroidal ischemia or inflammation (the distinction of which is not presently feasible) in demonstrating hypofluorescent lesions which correspond to a subset of hyperflourescent FA lesions (Fig. 3, inferior arterial arcade). The choroid, however, is unlikely the primary site of pathology as the numerous lesions seen on FA (i.e., Fig. 2, proximal superior arterial arcade) lack a correlate on ICG (Fig. 3).
With advances in imaging, MEWDS is now understood to be an outer retinal disease. The advent of ultrahigh-resolution optical coherence tomography capable of 3 μm axial resolution has clearly identified pathologic disruptions of the IS/OS junction in cases of MEWDS without evidence of either RPE disturbances (which would be predicted by acute choroidal ischemia) or photoreceptor cell body loss [4, 6]. Localization of pathology to the photoreceptor layer is further supported by electrophysiology analysis noting multifocal ERG and full-field ERG amplitudes corresponding with IS/OS line integrity in the acute and recovery phase of MEWDS . Quantitative measurements of photoreceptor length have even measured photoreceptor outer segment shortening during the acute phase of the disease with gradual relengthening paralleling visual recovery [4, 7]. It has also been noted that the preservation of other retinal layers, most notably the outer nuclear layer, perhaps accounts for the potential for full visual recovery after photoreceptor outer segment disruption unique to MEWDS . We here present a case of MEWDS both classic in appearance on posterior segment photography and angiography with SD-OCT studies clearly demonstrating disruption of the IS–OS junction with preservation of other outer retinal layers.