Is Coxsackievirus the Cause of Unilateral Acute Idiopathic Maculopathy?

Unilateral acute idiopathic maculopathy (UAIM) is an inflammatory processinvolving the outer retina and retinal pigment epithelium (RPE) of the macula.It is typically associated with a serous neurosensory detachment and is sometimesassociated with papillitis, subretinal exudation, intraretinal hemorrhages,and/or vitreous cells.^1,2 Patientsreport a loss of central vision followed by a remarkable spontaneous recoveryover a period of several weeks. This entity frequently affects young, healthyindividuals and is often associated with a prodromal flulike illness. We describe2 patients who developed ocular findings consistent with UAIM shortly afterdeveloping classic signs and symptoms of hand-foot-and-mouth disease. We believethat coxsackievirus, which causes hand-foot-and-mouth disease, may also causeUAIM.

A 30-year-old woman had a 5-day history of decreased vision in her lefteye. Hand-foot-and-mouth disease had spread through her child's daycare centerthat same week. The patient had a sore throat and small erythematous papuleson the palms of her hands and the soles of her feet.

Visual acuity was 20/20 OD and 20/200 OS. Findings from an anteriorsegment examination were unremarkable in both eyes; intraocular pressure wasnormal in both eyes. Results of a fundus examination were unremarkable inthe right eye. Ophthalmoscopic examination of the left eye revealed a yellowlesion bisecting the fovea at the level of the outer retina, RPE, and choroid.There was no evidence of vitreous cells, subretinal fluid, or papillitis.Some mottling of the RPE was present (Figure1A). Fluorescein angiography of the left eye revealed early irregularhyperfluorescence and late staining (Figure1B).

The patient was observed without intervention and 3 weeks later hervisual acuity improved to 20/20 OS. The RPE and choroid had lost their yellowappearance with the development of a bull's-eye flat pigmented scar (Figure 2). Coxsackievirus titers drawn 3weeks after the onset of symptoms showed that the level of coxsackievirusA16 antibody was elevated at 1:8 (reference range, <1:8), which may beindicative of a past or recent infection. The level of coxsackievirus B6 antibodytiter was also elevated at 1:16 (reference range, <1:8).

A 38-year-old white man developed signs and symptoms characteristicof hand-foot-and-mouth disease including a fever, sore throat, and erythematouspapules on the palms of his hands and on the soles of his feet approximately4 days after 2 of his children were diagnosed as having hand-foot-and-mouthdisease. One to 2 days later he noted decreased central vision in his lefteye. Visual acuity was 20/20 OD and 20/200 OS. Intraocular pressure was normalin both eyes. Findings from an anterior segment examination were unremarkablein both eyes. Results of a fundus examination were unremarkable in the righteye. Ophthalmoscopic examination of the left eye revealed a white lesion atthe level of the RPE and choroid, involving the fovea and superotemporal macula(Figure 3A). There were 2 smallintraretinal hemorrhages but no evidence of vitreous cells, subretinal fluid,or papillitis. There was also a small hypopigmented lesion inferotemporalto this lesion (Figure 3A and Figure 3B). Fluorescein angiography revealedblockage of underlying fluorescence during early transit. In midtransit therewas irregular hyperfluorescence within the center of the lesions and latetransit revealed leakage and staining at the level of the RPE (Figure 3C). One week later there was less intense whitening andthe RPE developed mild pigment mottling. Although the patient reported subjectiveimprovement in vision, his visual acuity was unchanged at 20/200 OS. Visualacuity improved to 20/40 OS 3 weeks after the initial examination and 20/20OS 6 weeks after the initial examination, although the patient still notedmild haziness localized to the inferonasal portion of his central visual field.Fundus examination revealed a bull's-eye configuration to the scar presentjust eccentric to the center of the fovea (Figure 4).

We report 2 cases of suspected UAIM closely following the onset of hand-foot-and-mouthdisease. Both patients developed relatively rapid loss of central vision withsigns of acute lesions in the outer retina and RPE. The changes healed withreturn of vision and the appearance of a bull's-eye type of scar. These ocularfindings and the associated viral prodrome are typical of UAIM.² Thelack of subretinal fluid, however, is somewhat atypical of UAIM. In the firstcase it is possible that the fluid had resolved by the time the patient wasexamined 5 days after the onset of symptoms since pigment mottling was alreadybeginning to develop. In the second case the patient was seen within a fewdays after the onset of symptoms, so this scenario is less likely. However,we do know that UAIM represents a spectrum of ocular findings that is notconsistently present in all patients. Therefore, the absence of subretinalfluid may represent another presentation of the spectrum of macular changeswe call UAIM. The reduced visual acuity in UAIM is secondary to an exudativemaculopathy.^1,2

A possible association of UAIM and coxsackievirus has been alluded toin a previous report of a woman with the disease who had (along with her daughter)systemic symptoms characteristic of coxsackievirus infection preceding hervisual symptoms.² However, the acute andconvalescent coxsackievirus antibody titers that were obtained in the womanwere not abnormal. There have been several reports of coxsackievirus infectionassociated with chorioretinitis, and the lesions described bear some resemblanceto UAIM.^3-5

Coxsackievirus A16 and less commonly coxsackie variants A2, A5, A7,A9, A10, B1, B2, B3, B4, B6, and enterovirus 71 are generally responsiblefor hand-foot-and-mouth disease.⁶ Clinicalinterpretation of complement fixation test results for coxsackievirus ideallyrequires comparison of a short-term serum sample with a convalescent serumsample. In our first patient, although only convalescent serum samples wereobtained, the level of coxsackievirus A16 and B6 antibodies was elevated.The second case of hand-foot-and-mouth disease was diagnosed clinically basedon the presence of the classic physical findings that defined the diseasein the patient and his 2 children. The temporal relationship between the onsetof hand-foot-and-mouth disease and the development of retinal findings consistentwith UAIM suggests that they may be related. Heightened awareness of thispossible relationship should prompt retinal specialists to obtain acute andconvalescent coxsackievirus antibody titers so that we can determine whetherUAIM should be renamed "coxsackievirus maculopathy."

The authors have no relevant financial interest in this article.

This study was supported in part by an unrestricted grant from Researchto Prevent Blindness Inc, New York, NY, to Northwestern University, Chicago.

Corresponding author and reprints: Lee M. Jampol, MD, Departmentof Ophthalmology, Feinberg School of Medicine, Northwestern University, 645N Michigan Ave, Suite 440, Chicago, IL 60611 (e-mail: L-jampol@northwestern.edu).