The retinal pigment epithelium (RPE) constitutes a monolayer of cuboidal cells on the exterior of the neurosensory retina and has multiple functions [1],[2]. One of the most important functions of the RPE is the phagocytosis of photoreceptor outer segments (POS) that are being shed [1],[2]. When the phagocytosis of the POS is impaired, it leads to an accumulation of debris separating the photoreceptors (PR) from the RPE resulting in PR degeneration as seen in MERTK-mutated rodent models [3]. The subretinal debris of accumulated POS can be seen as hyperreflective material on optical coherence tomography (OCT) [3]. Other subretinal materials, deposits, and tissue components are also hyperreflective on OCT [4]. The term subretinal hyperreflective material is therefore used as catch-all term to describe all the hyperreflective material located external to the neurosensory retina and internal to the RPE on OCT [3],[4],[5]. It is a nonspecific finding present in various retinal disorders [4]. We report an unusual thick and extensive transient unilateral accumulation of subretinal hyperreflective material in a 77-year-old female with multiple evanescent white dot syndrome (MEWDS). MEWDS is a rare white dot syndrome that typically occurs in young to middle-aged healthy women presenting with a sudden, unilateral change in vision and is characterized by transient multifocal yellowwhite fundus lesions [6]. The pathogenesis is unknown but might be infectious as viral prodrome is associated in up to 50% of the cases [6].

A 77-year-old female with a past medical history of Crohn’s disease and Graves’ disease presented with a history of photopsia and a decreased eyesight in the right eye for the past two weeks. The visual acuity at presentation was 6/24 in the right eye and 6/6 in the left eye. Slit lamp examination was normal. There was no anterior chamber or vitreous inflammation present. Fundus examination revealed a yellow placoid macular lesion and multiple yellow subretinal deposits in the midperiphery in the right eye (Figure 1). Fundus autofluorescence showed a low intensity mottled hyperautofluorescence of the lesions (Figure 1). Fluorescein angiography showed a maculate hypo-and hyperautofluorescence of the macular lesion (Figure 1). Indocyanine green angiography was also performed and showed a late hypofluorescence of the lesions temporally in the late phase (Figure 1). Optical coherence tomography imaging revealed a subretinal hyperreflective deposition (Figure 2). Multimodal imaging of left eye was normal. Infectious serology was negative for bacterial infections (Bartonella henselae, Mycobacterium tuberculosis, Borrelia burgdorferi, Coxiella, Treponema pallidum, Brucella abortus, and Brucella melitensis), viral infections [Hepatitis B and C, cytomegalovirus (CMV), human immunodeficiency viruses (HIV), Epstein–Barr virus (EBV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella zoster virus (VZV)], and parasitic infections (Toxoplasma gondii, Toxocara canis, Toxocara cati, and Strongyloides stercoralis). Autoimmune serology (rheumatoid factor, antinuclear antibodies, antineutrophil cytoplasmic antibodies, and human leukocyte antigen B27) was also negative. Hematologic workout revealed a monoclonal gammopathy of unknown significance. Follow-up showed spontaneous resolution of the retinal deposits and the hyperreflective subretinal deposition on OCT (Figure 2) with recovery of the visual acuity to 6/6 without any systemic treatment over a period of four weeks. The subretinal hyperreflective material did not recur during a one-year follow-up period.

The pathological separation of the neurosensory retina and the RPE results in a subretinal space containing materials, deposits, and tissue components that are, with the exception of serous fluid, to some degree hyperreflective on OCT and which is referred to as subretinal hyperreflective material [4]. It may be present in age-related macular degeneration (AMD), myopia, central serous chorioretinopathy (CSC), adult-onset vitelliform macular dystrophy (AVMD), and other less frequent diseases, such as pseudoxanthoma elasticum (PXE) and acute exudative polymorphous vitelliform maculopathy (AEPVM). The subretinal hyperreflective material may consist of neovascular tissue, fibrosis, exudate, hemorrhage, vitelliform material, and reticular pseudodrusen [4],[5],[6]. Other imaging modalities, i.e., autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography, may help resolve the differential diagnosis [4].

Subretinal hyperreflective material is frequently observed in AMD and is assumed to consist of fibrin, blood, and choroidal neovascularization with the composition changing over time [4],[5]. Presence of subretinal hyperreflective material in neovascular AMD is associated with a poorer visual outcome, in particular if persistent despite intravitreal antivascular endothelial growth factor therapy [5]. The pathogenesis of AMD is complex and remains poorly understood, but one of the underlying mechanisms seems to be a dysfunctional autophagy of the RPE [7].

CSC is characterized by a serous retinal detachment and/or an RPE detachment in the macular region and is associated with leakage of fluid trough the RPE in the subretinal space due to a hyperpermeability of the choroid [8],[9]. Dysfunction of the RPE plays an important role in the pathogenesis of CSC: the loss of the RPE barrier and pumping function results in chronic subretinal fluid [9]. Optical coherence tomography imaging typically shows a neurosensory detachment, sometimes in combination with an elongation of the POS which can be seen as subretinal hyperreflective material [8],[9],[10]. The elongation of the POS represents a transient accumulation of waste products in the POS in the absence of phagocytosis by the RPE [8],[9].

Adult-onset vitelliform macular dystrophy is characterized by a solitary, yellow round to oval macular lesion [11],[12]. Optical coherence tomography imaging of those lesions shows a highly reflective fusiform thickening of the retinal pigment epithelium ultimately resulting in an atrophic outer retinal lesion [12]. Histopathological studies demonstrated massive accumulation of lipofuscin pigments in the macular retinal pigment epithelial cells with infiltration of pigment containing macrophages in the photoreceptor layer in those lesions [11],[12],[13]. Excess POS production and/or impaired POS phagocytosis by the RPE are likely the underlying pathophysiologic mechanisms in AVMD [11].

In our case, an elderly patient presenting with photopsia and a decreased eyesight in the right eye had a transient and diffuse subretinal hyperreflective deposition. A complete work-up revealed no systemic disorders except for a monoclonal gammopathy of unknown significance. A paraproteinemic maculopathy was not considered likely as the presentation was unilateral with spontaneous resolution of the fundus abnormalities and the subretinal hyperreflective deposition.

A wide spectrum of MEWDS has been described in the literature, with atypical features reported, such as a presentation in elderly patients, bilateral involvement, chronicity, and lack of white dots [14],[15],[16]. The typical lesions in MEWDS are a disrupted ellipsoid zone on OCT with accumulations of hyperreflective material variable in size and shape [6]. We describe in this case report a transient extensive and thick subretinal hyperreflective layer as yet another OCT manifestation in MEWDS.

An unusual and transient accumulation of subretinal hyperreflective material in MEWDS is described and considered to reflect a temporary and completely reversible dysfunction of the RPE in MEWDS. An accumulation of subretinal hyperreflective material may be identified in various other retinal conditions, often resulting in scarring of the outer retina.