0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Bilateral Ophthalmic Artery Occlusions Due to Probable Varicella-Zoster Virus Vasculopathy FREE

Hari Jayaram, MA, MRCSEd, MRCOphth, PhD; Dinu Stanescu-Segal, MD, PhD; Graham E. Holder, PhD; Elizabeth M. Graham, FRCP, FRCOphth
[+] Author Affiliations

Author Affiliations: NIHR Biomedical Research Centre for Ophthalmology, UCL Institute of Ophthalmology and Moorfields Eye Hospital (Dr Jayaram) and Department of Electrophysiology, Moorfields Eye Hospital (Dr Holder), and Medical Eye Unit, St Thomas' Hospital (Dr Graham), London, England; and Academisch Ziekenhuis Maastricht, Maastricht, the Netherlands (Dr Stanescu-Segal).


Arch Ophthalmol. 2012;130(11):1492-1494. doi:10.1001/archophthalmol.2012.544.
Text Size: A A A
Published online

Varicella-zoster virus (VZV) vasculopathies account for almost one-third of arterial ischemic strokes in children.1 Visual complications are rare, with previous reports occurring secondary to unilateral central retinal artery2 or posterior ciliary artery3 occlusion. We describe the first case, to our knowledge, of an immunocompetent child who became blind due to bilateral ophthalmic artery occlusions secondary to probable VZV vasculopathy.

A 6-year-old boy visited his local emergency department with a history of sudden painless bilateral visual loss. He was otherwise in good health apart from a history of chickenpox 8 weeks previously. His father had been treated for culture-negative mediastinal tuberculosis a year earlier. Initial examination in the emergency department showed visual acuity of counting fingers OU, a moderate bilateral panuveitis, and diffuse bilateral retinal edema with sheathing of both retinal arteries and veins. The optic discs were not swollen. Neurological examination findings were otherwise normal. Initial management aimed to treat a possible tuberculosis optic neuropathy and/or vasculopathy, using oral prednisolone, rifampin, pyrazinamide, and isoniazid. Initial investigations showed no abnormality on hematology and biochemistry tests of peripheral blood. Cytomegalovirus and VZV IgG were both detected on testing of serum, but polymerase chain reaction results for the respective DNA were negative. Evidence of tuberculosis infection was not found, with negative results on both enzyme-linked immunosorbent spot and Heaf tests and normal findings on chest radiography. Magnetic resonance imaging demonstrated no abnormal enhancement in the brain or chiasm, with normal optic nerve appearances. During the next week, visual acuity deteriorated to light perception OU. Panuveitis with retinal vascular sheathing (Figure 1A) persisted, with patchy areas of reperfused retina observed peripherally in the left eye on fluorescein angiography (Figure 1B). Doppler ultrasonography showed no detectable flow in central retinal artery or central retinal vein. Polymerase chain reaction results for a vitreous biopsy specimen were negative for both VZV DNA and tuberculosis. Electrophysiology showed a completely undetectable electroretinogram in both eyes, indicative of loss of outer retinal photoreceptor function and thus not in keeping with dysfunction confined to central retinal artery or vein circulation (Figure 2A). Magnetic resonance angiography showed a mostly normal cerebral vasculature but neither ophthalmic artery could be visualized (Figure 2B), in keeping with the electrophysiological data. Subsequently, VZV IgG was detected in cerebrospinal fluid, confirming VZV as the likely cause of the vasculopathy. Despite a course of systemic acyclovir and intravenous methylprednisolone, he maintains visual acuity of light perception OU.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Color fundus photograph and fluorescein angiography. A, Color fundus photograph of the left eye taken 10 days after the initial visit showing diffuse retinal edema and sheathing of the threadlike retinal arteries and veins. B, Fluorescein angiography of the left eye showing patchy areas of reperfused peripheral retina.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Electroretinography and magnetic resonance angiography. A, International Society for Clinical Electrophysiology of Vision standard electroretinography performed with gold foil recording electrodes, mydriasis, and Ganzfeld stimulation of the right and left eyes compared with a normal control. No electroretinogram is detectable in the patient under any recording conditions (note the different scales in the patient's data). Flash visual evoked potentials (VEPs) are not definitely detectable and show only residual background noise. DA indicates dark adapted; LA, light adapted. B, Short T1 inversion recovery magnetic resonance angiography of the cerebral vasculature demonstrating an absence of signal within the ophthalmic arteries (arrows). Asterisks indicate the internal carotid artery.

Vasculopathy caused by VZV can occur after both reactivation (zoster) and primary VZV infection and may involve both large and small cerebral arteries.4 Visual loss, previously reported to affect only the posterior ciliary artery2 and central retinal artery3 unilaterally, is rare but devastating. Branch retinal arterial occlusions in an immunocompetent adult have been reported in association with posterior uveitis and the presence of VZV DNA detected in the vitreous by polymerase chain reaction.5 However, VZV IgG and VZV DNA were absent in the cerebrospinal fluid in that case and subsequent investigations confirmed isolated ocular involvement.

Detection of VZV IgG in the cerebrospinal fluid has been shown to be a more sensitive and specific marker for the diagnosis of VZV vasculopathy compared with detection of VZV DNA by polymerase chain reaction alone,4 where a negative result does not exclude the diagnosis.4 The diagnosis in the present case was challenging owing to the absence of cerebrospinal fluid pleocytosis (present in one-third of cases6) and the presence of normal brain magnetic resonance imaging findings (unusual in VZV vasculopathy3).

Prompt diagnosis of VZV vasculopathy is crucial, with an untreated mortality rate reported at 25%.7 Although ocular complications may be irreversible after several weeks, treatment with systemic acyclovir may prevent further neurological complications and loss of life.3

Correspondence: Dr Jayaram, NIHR Biomedical Research Centre for Ophthalmology, UCL Institute of Ophthalmology and Moorfields Eye Hospital, 11-43 Bath St, London EC1V 9EL, England (h.jayaram@ucl.ac.uk).

Author Contributions: Dr Graham had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest Disclosures: None reported.

Askalan R, Laughlin S, Mayank S,  et al.  Chickenpox and stroke in childhood: a study of frequency and causation.  Stroke. 2001;32(6):1257-1262
PubMed   |  Link to Article
Hall S, Carlin L, Roach ES, McLean WT Jr. Herpes zoster and central retinal artery occlusion.  Ann Neurol. 1983;13(2):217-218
PubMed   |  Link to Article
Gilden DH, Lipton HL, Wolf JS,  et al.  Two patients with unusual forms of varicella-zoster virus vasculopathy.  N Engl J Med. 2002;347(19):1500-1503
PubMed   |  Link to Article
Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment.  Lancet Neurol. 2009;8(8):731-740
PubMed   |  Link to Article
Zamora RL, del Priore LV, Storch GA, Gelb LD, Sharp J. Multiple recurrent branch retinal artery occlusions associated with varicella zoster virus.  Retina. 1996;16(5):399-404
PubMed   |  Link to Article
Nagel MA, Cohrs RJ, Mahalingam R,  et al.  The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.  Neurology. 2008;70(11):853-860
PubMed   |  Link to Article
Hilt DC, Buchholz D, Krumholz A, Weiss H, Wolinsky JS. Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: diagnosis and management approaches.  Ann Neurol. 1983;14(5):543-553
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Color fundus photograph and fluorescein angiography. A, Color fundus photograph of the left eye taken 10 days after the initial visit showing diffuse retinal edema and sheathing of the threadlike retinal arteries and veins. B, Fluorescein angiography of the left eye showing patchy areas of reperfused peripheral retina.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Electroretinography and magnetic resonance angiography. A, International Society for Clinical Electrophysiology of Vision standard electroretinography performed with gold foil recording electrodes, mydriasis, and Ganzfeld stimulation of the right and left eyes compared with a normal control. No electroretinogram is detectable in the patient under any recording conditions (note the different scales in the patient's data). Flash visual evoked potentials (VEPs) are not definitely detectable and show only residual background noise. DA indicates dark adapted; LA, light adapted. B, Short T1 inversion recovery magnetic resonance angiography of the cerebral vasculature demonstrating an absence of signal within the ophthalmic arteries (arrows). Asterisks indicate the internal carotid artery.

Tables

References

Askalan R, Laughlin S, Mayank S,  et al.  Chickenpox and stroke in childhood: a study of frequency and causation.  Stroke. 2001;32(6):1257-1262
PubMed   |  Link to Article
Hall S, Carlin L, Roach ES, McLean WT Jr. Herpes zoster and central retinal artery occlusion.  Ann Neurol. 1983;13(2):217-218
PubMed   |  Link to Article
Gilden DH, Lipton HL, Wolf JS,  et al.  Two patients with unusual forms of varicella-zoster virus vasculopathy.  N Engl J Med. 2002;347(19):1500-1503
PubMed   |  Link to Article
Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment.  Lancet Neurol. 2009;8(8):731-740
PubMed   |  Link to Article
Zamora RL, del Priore LV, Storch GA, Gelb LD, Sharp J. Multiple recurrent branch retinal artery occlusions associated with varicella zoster virus.  Retina. 1996;16(5):399-404
PubMed   |  Link to Article
Nagel MA, Cohrs RJ, Mahalingam R,  et al.  The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.  Neurology. 2008;70(11):853-860
PubMed   |  Link to Article
Hilt DC, Buchholz D, Krumholz A, Weiss H, Wolinsky JS. Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: diagnosis and management approaches.  Ann Neurol. 1983;14(5):543-553
PubMed   |  Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Interpreting Apparently "Positive" Trials