Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

The Expanded Clinical Spectrum of Coxsackie Retinopathy

Stephanie J. Weiss, DO; Kyle Kovacs, MD; Luis A. Gonzalez-Gonzalez, MD, MPH; Aristomenis Thanos, MD; David Sarraf, MD; Dean Eliott, MD; Donald J D'Amico, MD; Thanos D. Papakostas, MD

Abstract

The authors present two cases of coxsackie retinopathy that presented with the classic findings of acute outer retinal disruption that evolved to an outer retinal scar. In these two cases, the classic lesions displayed an extramacular distribution. The authors provide detailed multimodal imaging in both cases highlighting the nature of the lesions. It is important to consider coxsackie virus infection in the differential diagnosis of extramacular lesions with outer retinal disruption. The term “unilateral acute idiopathic maculopathy” should be replaced with “coxsackie retinopathy” to better align with the expanded clinical spectrum and the known etiology of this disorder.

[Ophthalmic Surg Lasers Imaging Retina. 2020;51:529–532.]

Abstract

The authors present two cases of coxsackie retinopathy that presented with the classic findings of acute outer retinal disruption that evolved to an outer retinal scar. In these two cases, the classic lesions displayed an extramacular distribution. The authors provide detailed multimodal imaging in both cases highlighting the nature of the lesions. It is important to consider coxsackie virus infection in the differential diagnosis of extramacular lesions with outer retinal disruption. The term “unilateral acute idiopathic maculopathy” should be replaced with “coxsackie retinopathy” to better align with the expanded clinical spectrum and the known etiology of this disorder.

[Ophthalmic Surg Lasers Imaging Retina. 2020;51:529–532.]

Introduction

Hand, foot, and mouth disease caused by coxsackie virus has been associated with a number of systemic and ocular manifestations. Systemically, hand, foot, and mouth disease presents with a maculopapular rash on the palms and soles, oral lesions, and a flu-like viral prodrome.1

Ocular manifestations are rare. Acute idiopathic maculopathy (AIM) is most common and presents with an exudative macular detachment.2–5 Panuveitis, retinal vasculitis, outer retinitis, and chorioretinitis are less common manifestations that have been associated with coxsackie virus and hand, foot, and mouth disease.6–9 Herein, we present a novel presentation of coxsackie virus infection associated with the development of extramacular peripapillary or midperipheral outer retinal lesions in two patients.

Case Reports

Case 1

A 42-year-old man presented with a peripheral scotoma in the left eye for 2 weeks. Three weeks prior to the development of the scotoma, the patient's two daughters developed fevers associated with skin lesions on their legs. Two days later the patient developed fevers and an oral lesion that lasted for 24 hours and then completely resolved. On presentation, visual acuity (VA) was 20/15 in the right eye (OD) and 20/20 in the left eye (OS). Anterior segment examination and intraocular pressures (IOPs) were normal in both eyes (OU). Fundus examination was normal OD. Examination OS was significant for a yellow outer retinal lesion superonasal to the optic disc (Figure 1A). Optical coherence tomography (OCT) of the macula was normal (Figure 1C). OCT through the lesion displayed disruption of the ellipsoid zone and thickening and hyperreflectivity at the level of the RPE (Figure 1D). Fundus autofluorescence (FAF) illustrated hyperautofluorescence in the center of the lesion with surrounding hypoautofluorescence (Figure 1B). Fluorescein angiography (FA) was remarkable for leakage at the site of the outer retinal lesion (Figure 1E), whereas indocyanine green angiography (ICG) was unremarkable (Figure 1F). Coxsackie titers drawn at this time were positive (Coxsackie A4 titer > 1:64, Coxsackie B4 titer 1:80). The remainder of the infectious and inflammatory work-up including poliovirus titers, Lyme disease antibodies, Bartonella henselae antibodies, Zika virus titers, Chikungunya virus titers, angiotensin converting enzyme (ACE), antineutrophil cytoplasmic antibodies (ANCA), QuantiFERON gold, and rapid plasma reagin (RPR), and fluorescent treponemal antibody (FTA) was negative. Observation was recommended. At the last follow-up 6 months later, the patient was asymptomatic, VA remained 20/20 OS, and the lesion was regressed (Figures 1G–1J).

A 42-year-old man with coxsackie retinopathy. (a) Color fundus photography illustrates a hypopigmented outer retinal lesion at the superonasal disc margin in the left eye. Fundus autofluorescence (b) shows hyperautofluorescence. Although optical coherence tomography (OCT) through the macula (c) is unrevealing, OCT superonasal to the optic disc (d) displays an outer retinal lesion with disruption of the ellipsoid zone band and the retinal pigment epithelium (RPE). Fluorescein angiography (e) shows hyperfluorescence and minimal leakage corresponding to the site of the lesion superonasal to the optic disc while indocyanine green angiography (f) is normal. Upon most recent follow-up 6 months after initial presentation, fundus photograph (g), fundus autofluorescence (h), OCT through the macula (i), and OCT through the lesion (j) illustrate partial regression of the lesion.

Figure 1.

A 42-year-old man with coxsackie retinopathy. (a) Color fundus photography illustrates a hypopigmented outer retinal lesion at the superonasal disc margin in the left eye. Fundus autofluorescence (b) shows hyperautofluorescence. Although optical coherence tomography (OCT) through the macula (c) is unrevealing, OCT superonasal to the optic disc (d) displays an outer retinal lesion with disruption of the ellipsoid zone band and the retinal pigment epithelium (RPE). Fluorescein angiography (e) shows hyperfluorescence and minimal leakage corresponding to the site of the lesion superonasal to the optic disc while indocyanine green angiography (f) is normal. Upon most recent follow-up 6 months after initial presentation, fundus photograph (g), fundus autofluorescence (h), OCT through the macula (i), and OCT through the lesion (j) illustrate partial regression of the lesion.

Case 2

A 36-year-old woman presented with photopsia OS for 2 weeks. At the onset of visual symptoms, she developed a flu-like illness associated with fevers for 24 hours and lesions on her palms, which resolved prior to presentation. Just prior to the development of these visual and systemic findings, her 18-month-old daughter was diagnosed with hand, foot, and mouth disease. VA was 20/20 OU. Anterior segment examination and IOPs were normal OU. Funduscopic examination OD was normal. Examination OS was significant for three well-circumscribed hypopigmented outer retinal lesions in the nasal midperiphery (Figure 2A). OCT of the macula was normal (Figure 2E). OCT through the lesions displayed attenuation and disruption of the ellipsoid zone and thickening and disruption of the RPE (Figure 2F). FAF illustrated patchy hyperautofluorescence with surrounding hypoautofluorescence of the lesions (Figure 2B). FA showed window defects in the area of the outer retinal lesions (Figure 2C), whereas ICG was normal (Figure 2D). Coxsackie titers were not performed, but a routine inflammatory and infectious work-up including HLA-B27, lysozyme, ACE, ANCA, QuantiFERON gold, antinuclear antibodies, C-reactive protein, erythrocyte sedimentation rate, RPR, and FTA was unremarkable. Observation was recommended. Upon follow-up 5 weeks later, the lesions appeared partially regressed (Figures 2G–2J).

A 36-year-old woman with coxsackie retinopathy. (a) Color fundus photography illustrates three well-circumscribed hypopigmented outer retinal lesions in the nasal midperiphery of the left eye. Fundus autofluorescence (b) shows patchy hyperautofluorescence resembling a bull's-eye corresponding to the site of the lesions nasal to the optic disc. Fluorescein angiography (c) shows three areas of window defect corresponding to the outer retinal lesions, whereas indocyanine green angiography (d) is unremarkable. Although optical coherence tomography (OCT) through the macula (e) is unrevealing, OCT nasal to the disc (f) displays outer retinal lesions with disruption of the ellipsoid zone band and the retinal pigment epithelium (RPE). Upon follow-up 5 weeks later, fundus photograph (g), fundus autofluorescence (h), OCT through the macula (i), and OCT through the lesions (j) illustrate partial regression of the lesions.

Figure 2.

A 36-year-old woman with coxsackie retinopathy. (a) Color fundus photography illustrates three well-circumscribed hypopigmented outer retinal lesions in the nasal midperiphery of the left eye. Fundus autofluorescence (b) shows patchy hyperautofluorescence resembling a bull's-eye corresponding to the site of the lesions nasal to the optic disc. Fluorescein angiography (c) shows three areas of window defect corresponding to the outer retinal lesions, whereas indocyanine green angiography (d) is unremarkable. Although optical coherence tomography (OCT) through the macula (e) is unrevealing, OCT nasal to the disc (f) displays outer retinal lesions with disruption of the ellipsoid zone band and the retinal pigment epithelium (RPE). Upon follow-up 5 weeks later, fundus photograph (g), fundus autofluorescence (h), OCT through the macula (i), and OCT through the lesions (j) illustrate partial regression of the lesions.

Discussion

Hand, foot, and mouth disease has been associated with a variety of ocular manifestations, most notably AIM.2–5 AIM typically presents as central vision loss with an exudative maculopathy and alteration of the ellipsoid zone band with thickening of the RPE demonstrated by spectral domain OCT.2,4,5,10,11 Cases of exudative maculopathy with vitritis, retinal hemorrhages, exudation, and papillitis have been reported within the AIM spectrum.1,5,11 AIM may present with unilateral (the most common presentation, typically called UAIM) or bilateral involvement.2,11 The most likely cause of AIM is coxsackie virus.3–5 This entity is generally considered to be self-limited with resolution occurring within several weeks.10,11 Upon resolution, a macular scar with RPE alterations may occur, typically in a bull's-eye pattern. The development of a macular hole following AIM has also been described.3,10,11

Both cases described in this series were associated with symptomatic hand, foot, and mouth disease, and one of the patients was positive for coxsackie serum virus titers. The cases were unilateral with well circumscribed lesions occurring at the level of the ellipsoid zone and RPE, typical of UAIM. Subretinal fluid was not observed in our cases; however, small midperipheral lesions may be less likely to develop exudative detachment compared to the large macular lesions associated with typical AIM. Haamann et al. and Freund et al. reported cases similar to our Case 1, in which a well-circumscribed area of outer retinitis was described.9,11 However, Haamann et al. did not include OCT or FA during the acute phase, which is essential to fully characterize the location and activity of these lesions, and the case by Freund et al. reported negative coxsackie virus titers. Kadrmas et al. reported a case of multiple paracentral and mid-peripheral creamy chorioretinal lesions in a patient with Coxsackie virus B4 infection,8 and these lesions resembled the solitary lesion in Case 1. The Kadrmas study was performed in the pre-OCT era, therefore one cannot be sure of the exact nature of these lesions. Balaratnasingam et al. reported two cases of multifocal outer retinal satellite lesions associated with a central neurosensory detachment.2 It is reasonable to conclude that there is a spectrum of coxsackie retinopathy ranging from an exudative maculopathy versus multifocal disease complicated by peripapillary or peripheral retinal lesions.

It is important to consider coxsackie virus infection in the differential diagnosis of extramacular lesions with outer retinal disruption. The term “uni-lateral acute idiopathic maculopathy” should be replaced with “coxsackie retinopathy” to better align with the expanded clinical spectrum and the known etiology of this disorder.

References

  1. Tandon M, Gupta A, Singh P, Subathra GN. Unilateral hemorrhagic maculopathy: an uncommon manifestation of hand, foot, and mouth disease. Indian J Ophthalmol. 2016;64(10):772–774. doi:10.4103/0301-4738.195014 [CrossRef] PMID:27905343
  2. Balaratnasingam C, Lally DR, Tawse KL, et al. A unique posterior segment phenotypic manifestation of coxsackie virus infection. Retin Cases Brief Rep. 2016;10(3):278–282. doi:10.1097/ICB.0000000000000250 [CrossRef] PMID:26584330
  3. Ghazi NG, Daccache A, Conway BP. Acute idiopathic maculopathy: report of a bilateral case manifesting a macular hole. Ophthalmology. 2007;114(5):e1–e6. doi:10.1016/j.ophtha.2006.08.055 [CrossRef] PMID:17258809
  4. Meyerle CB, Yannuzzi LA. Acute positive titers of antibody to coxsackievirus in acute idiopathic maculopathy. Retin Cases Brief Rep. 2008;2(1):34–35. doi:10.1097/01.iae.0000243065.91330.e0 [CrossRef] PMID:25389612
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  6. Mine I, Taguchi M, Sakurai Y, Takeuchi M. Bilateral idiopathic retinal vasculitis following coxsackievirus A4 infection: a case report. BMC Ophthalmol. 2017;17(1):128. doi:10.1186/s12886-017-0523-2 [CrossRef] PMID:28724375
  7. Förster W, Bialasiewicz AA, Busse H. Coxsackievirus B3-associated panuveitis. Br J Ophthalmol. 1993;77(3):182–183. doi:10.1136/bjo.77.3.182 [CrossRef] PMID:8384474
  8. Kadrmas EF, Buzney SM. Coxsackievirus B4 as a cause of adult chorioretinitis. Am J Ophthalmol. 1999;127(3):347–349. doi:10.1016/S0002-9394(98)00322-5 [CrossRef] PMID:10088751
  9. Haamann P, Kessel L, Larsen M. Monofocal outer retinitis associated with hand, foot, and mouth disease caused by coxsackievirus. Am J Ophthalmol. 2000;129(4):552–553. doi:10.1016/S0002-9394(99)00440-7 [CrossRef] PMID:10764878
  10. Yannuzzi LA, Jampol LM, Rabb MF, Sorenson JA, Beyrer C, Wilcox LM. Unilateral acute idiopathic maculopathy. Arch Ophthalmol. 1991;109(10):1411–1416. doi:10.1001/archopht.1991.01080100091049 [CrossRef] PMID: 1929931
  11. 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] PMID: 8619764
Authors

From Retina Service, Department of Ophthalmology, Weill Cornell Medical College, New York, New York (SJW, KK, LG, DJD, TDP); Retina Service, Devers Eye Institute, Portland, Oregon (AT); Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, UCLA, Los Angeles, California (DS); and Retina Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts (DE).

Presented at the Atlantic Coast Retina Club in January 2019 in Boston, Massachusetts.

The authors report no relevant financial disclosures.

Address correspondence to Thanos D. Papakostas, MD, Retina Service, Department of Ophthalmology, Weill Cornell Medical College, New York, NY; email: thp9034@med.cornell.edu.

Received: May 05, 2020
Accepted: July 09, 2020

10.3928/23258160-20200831-08

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