Comprehensive insights into COVID-19 vaccine-associated multiple evanescent white dot syndrome (MEWDS): A systematic analysis of reported cases

Figures & data

Figure 1. PRISMA flow diagram for study selection.

Table 1. Basic information of 26 patients.

Reference	Gender	Age	Region	Type	Dose	Medical history		Vaccination to symptoms onset
Estefania Ramirez Marquez et al.^Citation9	F	17	USA	BNT162B2 vaccine	2	MEWDS (OS)	3 months (1st); 4 months (2nd, recurrence)
Hannah W. Ng and Rachael L. Niederer^Citation10	F	28	New Zealand	BNT162B2 vaccine	2	Unknown	2d (1st); 1 year (2nd, recurrence)
Kenzo S. Tomishige et al.^Citation11	F	38	Brazil	Inactivated vaccine (Sinovac)	1	None	7d
Rashed Alhabshan and David Scales^Citation12	F	71	USA	Moderna vaccine	3	Myope, retinal tear (OS), hysterectomy, hypercholesterolemia	3d
Abhilasha Baharani and Raja Rami Reddy^Citation13	F	22	India	Adenovirus Vector-Based COVID-19 Vaccine	2	Unknown	1d
Eriko Yasuda et al.^Citation14	F	67	Japan	BNT162B2 vaccine	2	None	1d
Mohamed Ali Gargouri et al.^Citation15 (1/2)	M	40	France	BNT162B2 vaccine	1	None	1 week
Mohamed Ali Gargouri et al.^Citation15 (2/2)	F	23	France	BNT162B2 vaccine	1	SARS-Cov-2 infection	10d
Ebony Smith et al.^Citation16 (1/2)	M	15	Australia	BNT162B2 vaccine	2	None	2 weeks
Ebony Smith et al.^Citation16 (2/2)	F	21	Australia	BNT162B2 vaccine	2	None	3 weeks
Soumaya Bouhout et al.^Citation17 (1/3)	F	28	Canada	Moderna vaccine	2	Oral herpes simplex virus	2 weeks
Soumaya Bouhout et al.^Citation17 (2/3)	M	27	Canada	BNT162B2 vaccine	1	Unknown	22d
Soumaya Bouhout et al.^Citation17 (3/3)	F	26	Canada	BNT162B2 vaccine	2	Unknown	5d
Keng-Sheng Lin and Ming-Hung Hsieh^Citation18	F	36	Taiwan (China)	Medigen Vaccine Biologics Corporation COVID-19 Vaccine	1	None	2d
Sayako Inagawa, MD et al.^Citation19	F	30	Japan	BNT162B2 vaccine	1 (1st); 2 (2nd)	Unknown	7d (1st); 3d (2nd)
Lucas Sejournet et al.^Citation20	F	25	France	BNT162B2 vaccine	2	MEWDS, visual loss	50d
Hyo Jin Seong and Christopher Seungkyu Lee^Citation21	F	33	Korea	BNT162B2 vaccine	2	Unknown	6d
LingUei Wang et al.^Citation2 (1/2)	F	32	Taiwan (China)	Oxford AstraZeneca COVID-19 vaccine	Unknown	Central scotoma	34d
LingUei Wang et al.^Citation2 (2/2)	F	59	Taiwan (China)	Oxford AstraZeneca COVID-19 vaccine	Unknown	Blurred vision	7d
Yao Xu and Wei Shen^Citation22	F	49	China	Inactivated vaccine (Sinovac)	1	MEWDS	2d
Matias Soifer et al.^Citation23	F	31	USA	Moderna vaccine	2 (1st); 4 (2nd)	Lyme disease, myope	2 weeks (1st); Unknown (2nd)
Tamar Rabinovitch et al.^Citation24 (1/2)	M	39	Israel	BNT162B2 vaccine	2	None	5d
Tamar Rabinovitch et al.^Citation24 (2/2)	F	28	Israel	BNT162B2 vaccine	2	None	30d
Elena Bolletta et al.^Citation25 (1/3)	M	53	Italy	BNT162B2 vaccine	2	Unknown	28d
Elena Bolletta et al.^Citation25 (2/3)	F	18	Italy	BNT162B2 vaccine	1	Unknown	4d
Elena Bolletta et al.^Citation25 (3/3)	M	48	Italy	BNT162B2 vaccine	1	Unknown	7d
Zachary C. Wiley et al.^Citation26	F	17	USA	BNT162B2 vaccine	1	Unknown	2d

Abbreviations: F, female; M, male; MEWDS, Multiple Evanescent White Dot Syndrome; OS, oculus sinister.

Table 2. Summary of clinical manifestation and examination of 26 cases of COVID-19 vaccine-associated MEWDS.

Reference	Eyes involved	BCVA(OD, OS)	Final vision	Symptoms and signs	Ocular examinations	Other examinations
Estefania Ramirez Marquez et al.^Citation9	OD (1st); OD (2nd)	20/20 (1st); 20/20 (2nd)	20/20 (1st); 20/20 (2nd)	Photopsia (1st); Photopsia (2nd)	Multiple white lesions, multiple hyperfluorescent lesions (FAF, FA), numerous hypocyanescent spots (ICGA) (1st); Active MEWDS temporally and recovering MEWDS nasally (2nd)	None (1st); None (2nd)
Hannah W. Ng and Rachael L. Niederer^Citation10	OD (1st); OS (2nd)	20/50 (1st); Unknown (2nd)	20/20 (1st); 20/25 (2nd)	Right central scotoma, photopsia, decreased vision (1st); Similar symptoms (2nd)	Cells in the vitreous, optic disc edema, multiple white lesions, multiple hyperfluorescent lesions (FAF), disruption at the ellipsoid layer (OCT) (1st); Unknown (2nd)	None (1st); None (2nd)
Kenzo S. Tomishige et al.^Citation11	OD	20/400	20/20	Low visual acuity	Anterior chamber inflammatory reaction, cells in the vitreous, RPE atrophy, altered macular reflex, multiple gray-white lesions in the posterior pole of the OD, hyper autofluorescent lesions (FAF), thickening of the retina’s outermost layers (OCT)	None
Rashed Alhabshan and David Scales^Citation12	OS	20/30	Unknown	Pulsating light, blurriness, visual field defects	Outer retinal lesions, posterior vitreous detachments, bilateral myopic degeneration, laser scars (OD), multiple hyperfluorescent lesions (FAF), multiple small subretinal hyper-reflective lesions in the macula, and disruption of the ellipsoid zone (OCT), enlarged blind spot (VF examination), mildly depressed response (full-field electroretinogram)	None
Abhilasha Baharani and Raja Rami Reddy^Citation13	OS	20/32	20/20	Decreased vision, visual field defects, flashing lights	Vitreous haze, multifocal yellowish-white, disruptions in the outer retina (OCT), multiple hyperfluorescent lesions (FAF), a generalized reduction and paracentral islands of sensitivity loss (VF examination)	Elevated ESR
Eriko Yasuda et al.^Citation14	OD	20/100	20/25	Visual loss, photopsia, blurred vision, bright spots, flu-like symptoms	Bilateral mild cataract, moderate vitritis, vitreous haze, multifocal small white lesions, hyperfluorescent lesions (FAF), early punctate hyperfluorescence (FA), multiple hypofluorescent spots (ICGA), punctate hyperreflective lesions of variable sizes in the outer retina and diffuse disruption in the ellipsoid zone (OCT), a central scotoma and paracentral islands of sensitivity loss in OD (goldmann visual field test)	None
Mohamed Ali Gargouri et al.^Citation15 (1/2)	OS	20/25	Not acquired	Photopsia, decrease of vision, flu-like illness	Multiple granular white lesions (funduscopic examination), foveal granularity, subtle deep retinal white lesions in the posterior pole (color fundus), bilateral granular hyperfluorescence (FAF), hyperreflective spots in ellipsoid zone (OCT), early bilateral granular hyperfluorescence (FA), hypofluorescent spots (ICGA)	None
Mohamed Ali Gargouri et al.^Citation15 (2/2)	OS	20/20	20/20	Blurred vision	Altered macular reflex, foveal granularity, subtle deep retinal white lesions in the posterior pole (color fundus), bilateral granular hyperfluorescence, numerous hyperautofluorescent lesions (FAF), a disruption of the outer retina (OCT), early bilateral granular hyperfluorescence that correlates with the granularity seen on dilated fundus examination (FA), numerous hypofluorescent spots during the late phase (ICGA)	None
Ebony Smith et al.^Citation16 (1/2)	OD	20/100	20/20	Blurred vision, seeing black floaters and lights, mild myalgia and headache	Vitritis, papillitis, several small discrete white lesions at the posterior pole, ellipsoid disruption (OCT), multiple hyperautofluorescent lesions (FAF)	None
Ebony Smith et al.^Citation16 (2/2)	OD	20/60	20/20	Blurred vision, mild headaches, mild myalgia	Cells in the vitreous, multiple subretinal white lesions at the posterior pole, subtle disc edema, disruption in the ellipsoid zone (OCT), hyperautofluorescent lesions (FAF), both early and late hyperfluorescence of the lesions (FA)	None
Soumaya Bouhout et al.^Citation17 (1/3)	OD	20/60	20/25	Photopsia decreased VA	Multiple small deep gray-white lesions in the posterior pole, early hyperfluorescent lesions (FA), hyperautofluorescent lesions (FAF), disruption of the outer retina with hyperreflective projections extending to the outer nuclear layer (OCT)	None
Soumaya Bouhout et al.^Citation17 (2/3)	OD	20/20	20/20	Photopsia	Altered macular reflex, multiple deep grayish posterior-pole lesions, FAF, FA, and macular OCT were suggestive of MEWDS	None
Soumaya Bouhout et al.^Citation17 (3/3)	OS	20/20	20/20	Scotoma, photopsia	Pigmentary punctiform changes in the posterior pole, early hyperfluorescent lesions (FA), and OCT were normal	None
Keng-Sheng Lin and Ming-Hung Hsieh^Citation18	OD	20/25	20/20	Photopsia, mild fatigue	Multiple whitish round spots in the posterior pole (color fundus imaging)	None
Sayako Inagawa, MD et al.^Citation19	OU (1st); OU (2nd)	20/20 (1st); 30/20 (2nd)	20/20 (1st); 30/20 (2nd)	Soreness (1st); Fever (2nd)	Multiple yellowish-white lesions in the perifovea area (fundus examination) (1st); An increase in the flash value in both eyes (slit-lamp examination), Cells in the vitreous, hyperfluorescent lesions (FFA), early hyperfluorescent spots (FA), disruption of the ellipsoid zone superior to the fovea (OCT) (2nd)	None
Lucas Sejournet et al.^Citation20	OD	18/20	20/20	Visual loss, photopsia, flu-like symptoms	Multifocal white lesions in the posterior pole retina, optic disc edema (fundus examination), multiple disruptions of the ellipsoid zone (OCT), multiple hyperautofluorescent lesions (FAF)	None
Hyo Jin Seong and Christopher Seungkyu Lee^Citation21	OD	20/40	20/50	Dark spot, metamorphopsia	Multiple gray-white lesions at the posterior pole and nasal and temporal periphery (fundus examination), a dome-shaped macula, subretinal fluid, interruption of the ellipsoid zone (OCT)	None
LingUei Wang et al.^Citation2 (1/2)	OD	10/20	20/20	Scotoma	Multiple gray-white lesions in the peripapillary area and posterior deep retina (fundus examination), hyperautofluorescence (FAF), interrupted ellipsoid zones and intraretinal hyperreflective lesions above the ellipsoid zones line (OCT), enlarged blind spot (VF examination)	None
LingUei Wang et al.^Citation2 (2/2)	OS	20/25	Unknown	Blurred vision	Unknown	Unknown
Yao Xu and Wei Shen^Citation22	OS	20/100	20/20	Blurred vision	Irregularities of outer retinal and RPE (OCT), enlarged blind spot (VF examination), multiple ill-defined spots of markedly increased autofluorescence in the posterior pole (FAF), multiple round lesions in the posterior pole with early hyper-fluorescence and late staining (FA)	Hypertension
Matias Soifer et al.^Citation23	OS	Unknown (1st); 20/50 (2nd)	Unknown (1st); 20/25 (2nd)	Scotoma, photopsia	Unknown (1st); Enlarged blind spot, cells in the vitreous, scattered faint hypopigmented round lesions, multifocal areas of ellipsoid zone loss with associated areas of outer retinal hyperreflectivity (OCT), scattered hyperautofluorescent lesions (FAF), hyperfluorescent staining of the corresponding areas (FA), diffuse hypocyanescent spots (ICGA) (2nd)	None
Tamar Rabinovitch et al.^Citation24 (1/2)	OS	20/32	20/20	Blurred vision, scotoma, photopsia	Unknown	None
Tamar Rabinovitch et al.^Citation24 (2/2)	OS	20/32	20/20	Blurred vision, scotoma, photopsia	Unknown	None
Elena Bolletta et al.^Citation25 (1/3)	OS	20/25	20/20	Decreased VA, visual field defect, fever	Unknown	None
Elena Bolletta et al.^Citation25 (2/3)	OD	20/66	20/20	Blurred vision, visual field defect, pain	Unknown	None
Elena Bolletta et al.^Citation25 (3/3)	OD	20/400	20/20	Decreased VA	Unknown	None
Zachary C. Wiley et al.^Citation26	OU	20/20	20/20	Visual loss, fever, headache	Bilateral optic disc edema, a peripapillary hemorrhage, white lesions (ophthalmoscopy), bilateral optic disc leakage, choroidal hyperfluorescence of the posterior pole (FA), optic nerve edema OU (OCT)	Elevated ESR, elevated cerebrospinal fluid pressure and elevated white blood cells

Abbreviations: BCVA, best corrected visual acuity; MEWDS, multiple evanescent white dot syndrome; OD, oculus dextrus; OS, oculus sinister; OU, oculus unati; FA, fluorescein angiography; FAF, fundus autofluorescence; ICGA, indocyanine green angiography; OCT, optical coherence tomography; RPE, retinal pigment epithelium; VF, visual field; ESR, equivalent series resistance.

Table 3. Treatment and recovery of 26 patients.

Reference	Treatment	Course of disease	Outcome
Estefania Ramirez Marquez et al.^Citation9	None (1st);	Unknown (1st);	Recovery (1st);
	None (2nd)	6 months (2nd)	Recovery (2nd)
Hannah W. Ng and Rachael L. Niederer^Citation10	None (1st);	3 months (1st);	Recovery (1st);
	None (2nd)	9 months (2nd)	Recovery (2nd)
Kenzo S. Tomishige et al.^Citation11	Tapered oral prednisolone, starting with 80 mg	4 weeks	Recovery
Rashed Alhabshan and David Scales^Citation12	None	6 weeks	Recovery
Abhilasha Baharani and Raja Rami Reddy^Citation13	None	2 weeks	Recovery
Eriko Yasuda et al.^Citation14	None	2 weeks	Recovery
Mohamed Ali Gargouri et al.^Citation15 (1/2)	None	6 weeks	Recovery
Mohamed Ali Gargouri et al.^Citation15 (2/2)	None	6 weeks	Recovery
Ebony Smith et al.^Citation16 (1/2)	40 mg of oral prednisolone	2 weeks	Recovery
Ebony Smith et al.^Citation16 (2/2)	40 mg of oral prednisolone	2 weeks	Recovery
Soumaya Bouhout et al.^Citation17 (1/3)	None	1 month	Recovery
Soumaya Bouhout et al.^Citation17 (2/3)	None	3 months	Recovery
Soumaya Bouhout et al.^Citation17 (3/3)	None	4 months	Recovery
Keng-Sheng Lin and Ming-Hung Hsieh^Citation18	None	4 weeks	Recovery
Sayako Inagawa, MD et al.^Citation19	Topical fluorometholone (1st); Topical corticosteroids (2nd)	21d (1st); 2 months (2nd)	Visibility of yellowish-white spots decreased (1st); Recovery (2nd)
Lucas Sejournet et al.^Citation20	None	1 month	Recovery
Hyo Jin Seong and Christopher Seungkyu Lee^Citation21	Tapered oral prednisolone, starting with 15 mg, intravitreal bevacizumab	10 weeks	Symptoms improved
LingUei Wang et al.^Citation2 (1/2)	Oral steroids 10 mg prednisolone per day	7 weeks	Recovery
LingUei Wang et al.^Citation2 (2/2)	Topical steroids	Unknown	Unknown
Yao Xu and Wei Shen^Citation22	Prednisone 20 mg per day, then tapered gradually, antiviral agent (acyclovir) combined with Vitamin B2 and C	8 weeks	Recovery
Reference	Treatment	Course of disease	Outcome
Matias Soifer et al.^Citation23	None (1st); Tapered oral prednisolone, starting with 60 mg (2nd)	3 months (1st); 4 weeks (2nd)	Recovery (1st); Improvement in symptoms (2nd)
Tamar Rabinovitch et al.^Citation24 (1/2)	None	Unknown	Significant improvement
Tamar Rabinovitch et al.^Citation24 (2/2)	None	Unknown	Significant improvement
Elena Bolletta et al.^Citation25 (1/3)	None	Unknown	Recovery
Elena Bolletta et al.^Citation25 (2/3)	None	Unknown	Recovery
Elena Bolletta et al.^Citation25 (3/3)	None	Unknown	Recovery
Zachary C. Wiley et al.^Citation26	Valacyclovir 1000 mg and acetazolamide 750 mg twice per day	Unknown	Recovery

Figure 2. The potential mechanisms of COVID-19 vaccine-associated MEWDS. Including (1) molecular mimicry,³⁶ (2) hypersensitivity reactions,³⁷ (3) adjuvant-induced autoimmunity,³⁸ and (4) direct infection with attenuated, live vaccines.¹³

Table 4. Summary of MEDWS caused by different vaccines.

Reference	Gender	Age	Region	Type
Estefania Ramirez Marquez et al.^Citation9	F	17	USA	Human papillomavirus combined with meningococcal vaccines.
Laura Fine, MD et al.^Citation6	M	33	USA	Hepatitis A vaccine
Edoardo Baglivo et al.^Citation42	F	23	Switzerland	Hepatitis B vaccine
Ken Ogino et al.^Citation43	F	16	Japan	Human papillomavirus vaccine
Steven M and Cohen, MD^Citation7	F	17	USA	Human papillomavirus combined with meningococcal vaccines
Caleb C. Ng et al.^Citation44	M	34	USA	Influenza vaccination
Abdullah Abou-Samra and Ahmad B. Tarabishy^Citation45	F	27	USA	Influenza vaccination
Jia-song Yang et al.^Citation46	F	33	China	Rabies vaccination
Sunali Goyal et al.^Citation8	M	53	USA	Influenza vaccine
Alexandros Stangos et al.^Citation47	F	50	Switzerland	Hepatitis-A virus (HAV) combined with yellow fever (YF) vaccination

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Data availability statement

All data generated in this article are included in the paper and supplementary materials.