An Overview of Multiple Evanescent White Dot Syndrome

Durray Nayab Ali

Introduction

Multiple evanescent white dot syndrome, or MEWDs, was first described by Jampol and colleagues in 1984 (1). It is categorised as a white dot syndrome (WDS), a group of inflammatory chorioretinopathies which clinically present as numerous, discrete white lesions affecting multiple layers of the retina including the retinal pigment epithelium (RPE), choroid and choriocapillaris (2,3). Other white dot syndromes include acute retinal pigment epitheliopathy (ARPE), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multifocal choroiditis and panuveitis (MCP) acute zonal occult outer retinopathy (AZOOR), punctate inner choroidopathy (PIC), serpiginous choroidopathy and birdshot chorioretinopathy (2). MEWDs is a unilateral condition which typically presents in women aged 20-50 years with a viral prodrome and has a benign and self-limiting course (3). The white dot syndromes are a rare entity with one multi-centre study calculating the incidence of WDS as 0.45 cases per 100,000, whilst other studies have reported the incidence of MEWDs as 0.22 per 100,000 population annually (4,5).  We will provide an overview of this rare condition characterising its clinical presentation, clinical course and findings on ophthalmic imaging.

Clinical Presentation

MEWDs is a posterior uveitis which has a female preponderance and characteristically occurs in myopic individuals with sudden onset photopsia, reduced visual acuity and temporal visual field defects following an episode of flu-like symptoms (6). A relative afferent pupillary defect may also be detected, as well as optic nerve hyperaemia and vitreous cells in the anterior segment (3).  Colour fundus photograph shows multi-focal 100-200  grey-white spots in the macula, posterior pole and optic disc (5). These discrete white spots are usually at the level of the retinal pigment epithelium or outer retina (3). Foveal granularity is also characteristic of MEWDS (5). Whilst MEWDS is typically a unilateral condition, reports of bilateral cases have been made (3). Most of the white dot syndromes follow a benign and self-limiting course (2).

Diagnosis

The use of multi-modal imaging has proved instrumental in the diagnosis of white dot syndromes. Optical Coherence Tomography (OCT), indocyanine green angiography (ICGA) and fundus autofluorescence (FAF) are common modes of imaging used in diagnosis. OCT demonstrates disruption of the outer retina with a focus on the ellipsoid zone in MEWDs (7). Imaging modalities such as ICGA demonstrate scattered hypofluorescence indicative of choriocapillaris hypo or non-perfusion (6). Fundus autofluorescence (FAF) demonstrates hyperautofluorescence around the optic disc and macula (8). Distribution of MEWDs lesions is usually most confluent around the optic disc (9). The use of multi-modal imaging provides a comprehensive assessment of MEWDS during presentation and follow-up with spontaneous resolution of fundus findings and associated recovery of the vision within several weeks (6).

Aetiology

The aetiology of white dot syndromes is unclear. It is presumed an unknown trigger precipitates an inflammatory response in the posterior eye (2). Multiple reports of SARS-Cov-2 vaccinations resulting in a MEWDs type inflammatory response have been made in recent years (10). There have been suggestions of a possible genetic predisposition of certain individuals towards MEWDs and other white dot syndromes with common susceptibilities leading to the overlapping occurrence of one or more disease (5). The use of multimodal imaging such as en face OCT has advanced our understanding of MEWDs and allowed further hypothesis to be made about the underlying pathology (11). One study suggested muller cell activation triggered by inflammation produces changes in the central reflectivity of central Muller cells as well as structural and functional changes resulting in the transient inflammatory changes visualised on imaging (11). Lesions in MEWDs are considered to disrupt the photoreceptor outer segments, with a change in photoreceptor structure being linked to visual function (12,13). Choroidal involvement with areas of inflammatory infiltrates reaching the RPE from the choroid, resulting in the accumulation of lipofuscin granules visualised as hyperautofluorescent lesions on fundus autofluorescence has also been reported (14). Whilst the exact cause of MEWDs still remains uncertain, it is clear advances in ophthalmic imaging has allowed us to study the condition and gain a greater understanding of its possible aetiology.

Prognosis

The white dot syndromes are characteristically self-resolving with little need for treatment (2). However, some literature has demonstrated clinical manifestation of retinal disease prior to and following the acute stages of MEWDs (8). Choroidal neovascularisation is a rare complication of primary MEWDs (8). Focal choroidal excavation is also a phenomenon that can rarely occur secondary to the white dot syndromes (8). Despite these rare complications, the overall prognosis for white dot syndromes such as MEWDS is good with a return to near baseline visual function within several weeks without intervention (2). However, even after inflammation has subsided a residual pathognomonic granular appearance of the fovea may remain (3).

References

  1. Jampol LM. Multiple evanescent white dot syndrome. Arch Ophthalmol. 1984;102(5):671.
  2. Mount GR, Kaufman EJ. White Dot Syndromes. [Updated 2023 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557854/
  3. Crawford CM, Igboeli O. A review of the inflammatory chorioretinopathies: the white dot syndromes. ISRN Inflamm. 2013 Oct 31;2013:783190.
  4. Abu-Yaghi NE, Hartono SP, Hodge DO, Pulido JS, Bakri SJ. White dot syndromes: a 20-year study of incidence, clinical features, and outcomes. Ocul Immunol Inflamm. 2011 Dec;19(6):426-30.
  5. Chen CL, Cheng YZ, Zhang ZH, Wang G, Peng XY. Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events: a narrative review. Int J Ophthalmol. 2024 Mar 18;17(3):583-595.
  6. Papasavvas I, Mantovani A, Tugal-Tutkun I, Herbort CP Jr. Multiple evanescent white dot syndrome (MEWDS): update on practical appraisal, diagnosis and clinicopathology; a review and an alternative comprehensive perspective. J Ophthalmic Inflamm Infect. 2021 Dec 18;11(1):45.
  7. Pereira F, Lima LH, de Azevedo AGB, Zett C, Farah ME, Belfort R Jr. Swept-source OCT in patients with multiple evanescent white dot syndrome. J Ophthalmic Inflamm Infect. 2018 Oct 13;8(1):16.
  8. Chen C, Cheng Y, Zhang Z, Zhang Y, Hou S, Wang G, Peng X. The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study. BMC Ophthalmol. 2024
  9. Ong AY, Birtel J, Agorogiannis E, Sharma SM, Charbel Issa P. Topographic patterns of retinal lesions in multiple evanescent white dot syndrome. Graefes Arch Clin Exp Ophthalmol. 2023 Aug;261(8):2257-2264.
  10. Kashyap H, Manoharan A, Mahendradas P, Agarwal A, Majumder PD. A COVID-19 perspective of multiple evanescent white dot syndrome (MEWDS). Indian J Ophthalmol. 2024 May 1;72(5):620-625.
  11. Cicinelli MV, Menean M, Apuzzo A, Scandale P, Marchese A, Introini U, Battaglia Parodi M, Bandello F, Miserocchi E. Presumed Müller Cell Activation in Multiple Evanescent White Dot Syndrome. Invest Ophthalmol Vis Sci. 2023 Oct 3;64(13):20.
  12. Akiyama H, Itakura H, Li D, Kashima T, Nitta K, Shimoda Y, Mukai R, Kishi S. Retinal ganglion cell analysis in multiple evanescent white dot syndrome. BMC Ophthalmol. 2014 Nov 19;14:132.
  13. Cicinelli MV, Montesano G, Berni A, Scandale P, Ometto G, Introini U, Battaglia Parodi M, Bandello F, Miserocchi E, Marchese A. Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations. Invest Ophthalmol Vis Sci. 2024 Apr 1;65(4):28.
  14. Penha FM, Navajas EV, Bom Aggio F, Rodrigues EB, Farah ME. Fundus autofluorescence in multiple evanescent white dot syndrome. Case Rep Ophthalmol Med. 2011;2011:807565.

Leave a Reply