Unilateral acute idiopathic maculopathy (UAIM), first described in 1991 by Yannuzzi et al in a series of nine healthy young patients, is a rare inflammatory disease of the outer retina and retinal pigment epithelium.1 It is characterized by acute-onset unilateral severe central vision loss associated with an exudative detachment of the macula and occasional intraretinal hemorrhages, vitritis, and papillitis.1–3 Its exact causative agent is still unknown, but associated systemic findings have included a viral prodrome, hand-foot-mouth disease (HFMD), and positive coxsackievirus titers.1,4,5 The prognosis of UAIM is good, with spontaneous recovery of visual acuity and resolution of the neurosensory retinal detachment, although a bull’seye appearance in the macula usually persists.1–3
We present a case of UAIM associated with HFMD and demonstrate its clinical and morphologic features using spectral-domain optical coherence tomography (SD-OCT), enhanced depth imaging OCT (EDI-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanin green angiography (ICGA).
A 31-year-old healthy man presented with sudden central vision loss in his left eye 4 days after developing signs and symptoms of HFMD: fever, sore throat, mouth ulcers, and a maculopapular rash on the palms of his hands and soles of his feet. His 22-month-old son had also been diagnosed as having HFMD 1 week prior. Best corrected visual acuity (BCVA) was 6/5 in the right eye and 6/24 in the left eye. Intraocular pressure and anterior segment examination findings were normal in both eyes, and there was no relative afferent pupillary defect. Funduscopy in the right eye was unremarkable. Funduscopy in the left eye revealed mild vitritis and an exudative neurosensory macular detachment (Figure 1A). SD-OCT confirmed the above findings (Figure 2A). EDI-OCT measured increased subfoveal choroidal thickness to 478 μm (Figure 2E), and the lesion was hypoautofluorescent on FAF (Figure 3A). FA demonstrated hypofluorescence in the transit phase with subsequent pooling (Figure 4). On ICGA the lesion was hypofluorescent surrounded by a late hyperfluorescent halo (Figure 5).
Color photograph of the left fundus demonstrating exudative neurosensory detachment involving the fovea and superonasal macula associated with small intraretinal hemorrhages and yellowish subretinal exudates at presentation (A) and after 1 week (B). Multi-Color fundus image at 3 months reveal pigmentary changes at the macula with a bull’s-eye appearance (B).
Spectral-domain OCT demonstrates neurosensory retinal detachment, with hyperreflective dots representing the outer segments of the photoreceptors (arrows) and preserved integrity of the external limiting membrane and inner retina at presentation (A). After 1 week: disruption at the level of photoreceptors (asterisk) (B). At 3-month follow-up: residual disturbance superonasally to the fovea (asterisk) (C), being the fovea reconstituted (D). Enhanced depth imaging OCT of the left eye at presentation demonstrated increased subfoveal choroidal thickness (E), which decreased at 3 months in the right (F) and left (G) eyes.
Fundus autofluorescence at presentation. Mainly hypoautofluorescent lesion with a halo of mottled hyperautofluorescence (A) with restoration of normal autofluorescence pattern of the fovea 1 week after and persistent mottling superonasally (B).
Fluorescein angiography frames. Hypofluorescence in the transit phase followed by an early irregular hyperfluorescence of the lesion (A–B) with pooling in the late frames (C–D).
Indocyanin green angiography. Hypofluorescence in all frames related to the neurosensory detachment (A–C) with late hyperfluorescent halo (C).
The patient was diagnosed with UAIM, and no treatment was warranted. One week later, BCVA was 6/18 and the exudative detachment completely resolved (Figure 1B), albeit there was still irregularity and disruption at the level of the photoreceptors on SD-OCT (Figure 2B). FAF showed a mottled autofluorescence involving the superonasal macula in the acute phase, with restoration of the normal autofluorescence pattern of the fovea in the convalescent stage (Figure 3B). At 3 months, BCVA improved to 6/5, funduscopy revealed an eccentric foveal scar (Figure 1C), and SD-OCT showed mild residual disturbance of the ellipsoid superonasally to the fovea (Figure 2C). Complete reconstitution of the foveal photoreceptor layer was noted (Figure 2D), and choroidal thickness measured 450 μm bilaterally (Figure 2F–G). The area of the disturbance was readily detected with infrared imaging, and the FAF presented a similar pattern. Clinical examination in the right eye remained unremarkable during follow-up.
Unilateral acute idiopathic maculopathy is a rare maculopathy that was first described in 1991;1 however, its exact pathogenesis has remained unclear. It was only in 2004 that it was first associated with the coxsackievirus and HFMD by Beck et al.4 HFMD usually affects children under 10 years of age but can occasionally affect healthy adults. It is typically caused by the coxsackievirus A16 and less commonly by other coxsackie variants and enterovirus 71.4,6 In this case, the HFMD was diagnosed based on clinical criteria and the characteristic physical findings in the patient and his son. The close temporal link between the onset of the HFMD and the maculopathy described in the present report supports the observation that there seems to be a relationship between HFMD and UAIM.4,5
Another debated aspect of UAIM is its physiopathology, which has been related to inflammation of the outer retina and retinal pigment epithelium1,5 but also of the choroid,5 being yet unclear whether this disorder results from a primary involvement of the outer retina or the choriocapillaris. In this case, we performed an EDI-OCT at baseline and at 3 months that showed evidence of increased subfoveal choroidal thickness that decreased in the convalescence phase. This finding suggests that in addition to an inflammatory process at the level of the outer retina, the choroid was also involved. These data may also support the hypothesis that UAIM is a choroidal disease with secondary outer retinal involvement and that it is a bilateral inflammatory phenomenon that has mainly unilateral manifestations.2,3 Similar findings have recently been reported for multiple evanescent white dot syndrome,7 to which UAIM has been compared because of its acute onset, outer retinal inflammation, and good prognosis.2 Further studies are needed to review this finding. The observation that UAIM can be bilateral has been previously reported2 and even led Gass to propose to rename it acute idiopathic maculopathy.8 Also, the finding that UAIM may be associated with the coxsackievirus infection led Beck4 to recently propose naming the condition coxsackie maculopathy, which would leave no doubts about its etiology and would link in this way the disease to the viral infection. Furthermore, our report confirms an indirect choroidal involvement visible only through the increase in choroidal thickness. Recently, Srour et al9 also demonstrated a bilateral increase in choroidal thickness in their patient during the acute phase of the disease. In our case, we are referring to the condition as exudative maculopathy associated with HFMD, a term that is more generic and does not specify whether the macular involvement is unilateral or bilateral. Although reproducible findings are harder to obtain with rare diseases, should further studies prove a more consistent choroidal involvement, it might be appropriate to take this into account when referring to this maculopathy.
In our patient, the ICGA study did not show late staining suggestive of choroidal neovascularization or midphase choroidal hyperpermeability suggestive of central serous chorioretinopathy. Hence both these conditions were excluded in the differential diagnosis. It was also apparent that the normalization of the foveal autofluorescence preceded the restoration of the outer photoreceptor layer. Nevertheless, only when the subfoveal outer retina disruption reverted on SD-OCT did the visual acuity recover.
In conclusion, exudative maculopathy associated with HFMD has a good prognosis, and no treatment is warranted. Multimodality diagnostic imaging during the acute and convalescent phase is useful in the study of this condition. It is critical in differentiating it from other entities such as central serous chorioretinopathy and choroidal neovascularization that may have a worse prognosis. It helps to understand the timing of restoration of visual acuity and supports the evidence that there is an inflammatory process at the level of the outer retina and choroid. Advances in imaging techniques to access the choroid may give further insight regarding the physiopathology of this rare disease.
- Yannuzzi LA, Jampol LM, Rabb MF, Sorenson JA, Beyrer C, Wilcox LM Jr, . Unilateral acute idiopathic maculopathy. Arch Ophthalmol. 1991;109(10):1411–1416. Erratum in: Arch Ophthalmol. 1992;110(4):449. doi:10.1001/archopht.1991.01080100091049 [CrossRef]
- Freund KB, Yannuzzi LA, Barile GR, Spaide RF, Milewski SA, Guyer DR. The expanding clinical spectrum of unilateral acute idiopathic maculopathy. Arch Ophthalmol. 1996;114(5):555–559. doi:10.1001/archopht.1996.01100130547007 [CrossRef]
- Haruta H, Sawa M, Saishin Y, Ohguro N, Tano Y. Clinical findings in unilateral acute idiopathic maculopathy: new findings in acute idiopathic maculopathy. Int Ophthalmol. 2010;30(2):199–202. doi:10.1007/s10792-009-9299-6 [CrossRef]
- Beck AP, Jampol LM, Glaser DA, Pollack JS. Is coxsackievirus the cause of unilateral acute idiopathic maculopathy?Arch Ophthalmol. 2004;122(1):121–123. Erratum in: Arch Ophthalmol. 2005;123(1):63. Glasser, David A [corrected to Glaser, David A]. doi:10.1001/archopht.122.1.121 [CrossRef]
- Jung CS, Payne JF, Bergstrom CS, et al. Multimodality diagnostic imaging in unilateral acute idiopathic maculopathy. Arch Ophthalmol. 2012;130(1):50–56. doi:10.1001/archophthalmol.2011.359 [CrossRef]
- Buchner A. Hand, foot and mouth disease. Oral Surg Oral Med Pathol. 1976;41:333–337. doi:10.1016/0030-4220(76)90147-X [CrossRef]
- Aoyagi R, Hayashi T, Masai A, et al. Subfoveal choroidal thickness in multiple evanescent white dot syndrome. Clin Exp Optom. 2012;95(2):212–217. doi:10.1111/j.1444-0938.2011.00668.x [CrossRef]
- Gass JD. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. 4th ed. St Louis: Mosby; 1997:676.
- Srour M, Querques G, Rostaqui O, Souied EH. Early Spectral-Domain Optical Coherence Tomography Findings in Unilateral Acute Idiopathic Maculopathy. Retina. 2013;33(10):2182–2184. doi:10.1097/IAE.0b013e3182953ccb [CrossRef]