Clinicopathologic Reports, Case Reports, and Small Case Series
December 2001

Multiple Evanescent White Dot Syndrome Following Hepatitis A Vaccination

Author Affiliations

Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001

Arch Ophthalmol. 2001;119(12):1856-1858. doi:

The multiple evanescent white dot syndrome (MEWDS) is an inflammatory retinal disorder, typically observed in young patients, that is characterized by unilateral visual loss and the presence of small, punctate, yellow-white lesions that involve the outer retina. In addition to reduced central visual acuity, patients usually experience photopsias and scotomas in the affected eye. A characteristic granular appearance may be observed in the macula as well.1 Patients usually recover good visual acuity with disappearance of the outer retinal lesions within 4 to 8 weeks of initial examination, although subjective difficulties with vision may persist. Bilateral involvement, recurrence, and delayed choroidal neovascularization can occur, but are infrequent.2,3 Although the cause of MEWDS is unknown, the presence of elevated serum immunoglobulin levels4 and the description of MEWDS following a booster vaccination for hepatitis B virus5 suggest an immune basis for this disorder.

Immunization with inactivated hepatitis A virus vaccine (HAVV) is an effective means of preventing infection with hepatitis A, a virus typically transmitted by contaminated water or food, particularly shellfish. Currently, HAVV is recommended for travelers to developing countries, children in endemic areas, people with chronic liver disease, homosexual males, and injection drug users. Nearly 6 million vaccine doses have been given in the United States during the past 2 years, and a recent safety review showed few vaccine-associated adverse events, the most serious of which were hematologic or immunologic in nature, including vasculitis, thrombocytopenia, and autoimmune hemolytic anemia.6 Our case represents the first reported ophthalmic complication following HAVV.

Report of a Case

A previously healthy, 30-year-old, white man complained of 36 hours of worsening vision in his left eye, which he described as a steadily enlarging, shimmering gray cloud over his central vision. Medical history was notable for a hepatitis A booster vaccination administered 13 days before initial examination.

On examination, best-corrected visual acuity was 20/20 in the right eye and 20/25-2 in the left eye. A relative afferent pupillary defect and decreased color vision were present in the left eye. Examination of the left posterior segment disclosed mild optic disc edema, a shallow serous macular detachment, and multiple, faint, yellow-white lesions that affected the outer retina temporal to the fovea (Figure 1, A-B). The results of examination of the right posterior segment were unremarkable. A Humphrey 30-2 visual field test showed marked enlargement of the blind spot (Figure 1C) and decreased foveal sensitivity. A fluorescein angiogram showed late leakage from the disc and faint late hyperfluorescence of the outer retinal lesions.

Image not available

A, Color fundus photograph of the left eye at initial examination showing multiple, faint, yellow-white lesions that affected the outer retina (arrows). B, A higher-power color photograph of the left fundus showed a shallow serous macular detachment that produced retinal striae. C, Humphrey visual field testing showed an enlarged blind spot and decreased foveal sensitivity.

Three days after the onset of symptoms, vision decreased to 20/40 in the affected eye, and the discrete, yellow-white outer retinal spots were more numerous and pronounced. At 10 days, the visual acuity remained 20/40, the left afferent pupillary defect had disappeared, the blind spot had decreased in size, and a second posterior segment examination disclosed persistent, although milder, optic disc edema, with partial resolution of the macular serous detachment and disappearance of the outer retinal spots. Six weeks after initial examination, the patient's vision had returned to 20/20 and the optic disc edema and serous detachment had completely resolved. Subsequent Humphrey visual field examination results were normal. One year after initial examination, vision remained 20/20 for each eye and retinal examination results were normal, although subjective nyctalopia persisted in the affected eye.


We present the first case, to our knowledge, of MEWDS following a booster HAVV. Our patient sought care 13 days after the vaccine because of unilateral loss of vision, photopsias, an enlarged blind spot, optic disc edema, and multiple yellow-white dots at the level of the outer retina, all findings that are consistent with the diagnosis of MEWDS. Symptoms, visual acuity, visual field changes, and fundus abnormalities all returned to normal within 6 weeks.

The cause of MEWDS is unknown, although both infectious and immune-mediated origins have been proposed. Jampol et al,1 in the original description of this syndrome, reported an antecedent flulike illness in 50% of patients. Others, in contrast, have cited the presence of increased levels of circulating immunoglobulins in the acute phase of MEWDS4 and the occurrence of MEWDS following hepatitis B vaccination5 in support of an immune basis for this disorder. Although it is possible that the occurrence of visual symptoms following HAVV was coincidental, this association observed in our patient would seem to support the role of an immune mechanism in the pathogenesis of MEWDS, particularly since hepatitis A vaccination utilizes inactivated virus. An immune mechanism has also been implicated in the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy,7 which, like MEWDS,5 has been observed following inactivated hepatitis B vaccination.8

This work was supported in part by a Career Development Award from Research to Prevent Blindness Inc, New York, NY (Dr Cunningham).

Corresponding author: Emmett T. Cunningham, Jr, MD, PhD, MPH, The Pearl and Samuel J. Kimura Ocular Immunology Laboratory, The Francis I. Proctor Foundation, UCSF Medical Center, San Francisco, CA 94143-0944 (e-mail:

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