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Invited Commentary
December 2016

Use of Retinal Optical Coherence Tomography to Detect Congenital Zika Syndrome

Author Affiliations
  • 1New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
JAMA Ophthalmol. 2016;134(12):1427-1428. doi:10.1001/jamaophthalmol.2016.4299

First identified in rhesus monkeys in Uganda in 1947, the Zika virus (ZIKV), a flavirus spread most commonly by the Aedes aegypti and Aedes albopictus mosquitos,1 was not implicated in human disease until 1953, when it was recognized in Nigeria to produce a mild, febrile illness. The virus, related to the pathogens that cause yellow fever, dengue, and the West Nile virus,1 has emerged recently as a serious health care threat resulting in widespread panic across the globe, particularly in the Pacific and the Americas. The recent outbreak began in Brazil in 2015, with over 1 million people now infected by ZIKV, and has since spread to North and South America, as well as Singapore. Most recently, the Florida Health Department has identified cases in several areas of Miami-Dade country in the United States.2

Recent data show that ZIKV is not only transmitted from mosquito to human but also from mother to fetus during pregnancy, as well as sexually transmitted from affected men to their partners.1 Researchers postulate that ZIKV may be shed in the tears of infected mice, which, if true for humans, could be a significant issue in ophthalmic practice.3

The incubation period is approximately 1 week, and common symptoms include a maculopapular pruritic rash, short-term low-grade fever, arthritis or arthralgias, myalgias, headache, nonpurulent conjunctivitis, retro-orbital pain, edema, and vomiting.1 Zika virus has also been increasingly implicated in neurologic complications such as microcephaly and brain damage in infants of ZIKV-infected mothers, as well as Guillain-Barré syndrome.

Ophthalmic manifestations of ZIKV infection are less well characterized. In January 2016, Ventura et al4 were the first to report ocular findings in infants with microcephaly and presumed ZIKV vertical transmission. They presented risk factors associated with ophthalmoscopic findings in infants with presumed congenital ZIKV infection and noted that 14 of 27 mothers who reported symptoms of rash, fever, headaches, and arthralgias in the first trimester of pregnancy had babies with abnormal ophthalmoscopic findings, including optic nerve hypoplasia, disc pallor, and an enlarged cup-disc ratio, as well as macular abnormalities including loss of the foveal reflex, pigment mottling, and chorioretinal atrophy.

To date, a single case report of real-time polymerase chain reaction–proven ZIKV-associated uveitis by Furtado et al5 describes a middle-aged man with a 2-day history of rash and bilateral ocular hyperemia who developed anterior uveitis in 1 eye 8 days after onset of systemic symptoms, which were successfully treated with an antibiotic-steroid combination drop. Eight days after treatment, the fellow eye had developed similar symptoms of decreased vision, conjunctival hyperemia, nongranulomatous keratic precipitates, and anterior chamber cells and flare. This eye was also successfully treated with topical corticosteroids for 7 days, with a return of visual acuity to baseline and resolution of uveitis.5

Parke et al6 reported on a 64-year-old man who recently traveled to Haiti and who presented with a diffuse upper body rash, arthralgias, and unilateral decreased vision. His anterior chamber was quiet, but there were retinal pigment epithelial changes in the perifoveal area in a bull’s-eye pattern. Optical coherence tomography (OCT) revealed disruption of the outer retina and retinal pigment epithelial layers in the central macula. Fluorescein angiography revealed early blockage and late staining, and the patient received a diagnosis of unilateral acute idiopathic maculopathy until ZIKV serum plaque reduction neutralization technique assay values came back significantly elevated—strongly indicative of ZIKV infection. His visual acuity improved to 20/20 within 6 weeks without treatment, as did the retinal pigment epithelium and outer retina.6

The treatment of ZIKV infection is supportive only. Vaccines are being actively developed but are not yet available. Prevention of ZIKV infection is accomplished by not traveling to endemic areas, with many countries issuing warnings about traveling to these areas, including in the United States, particularly to pregnant women or women who plan to become pregnant in the near future. Warnings are also in effect against unprotected sexual intercourse with potentially affected men.

The central nervous system and tropic nature of ZIKV is obvious from the reported clinical presentation, but how and why neural cells bear the brunt of the damage is not yet clear. In the cross-sectional, consecutive case series published in this issue of JAMA Ophthalmology, a small piece of this puzzle is clarified by Ventura et al,7 who are the first to report the retinal and choroidal structural OCT findings in children with posterior segment effects of congenital Zika syndrome. Eight of 9 children had microcephaly, and 8 of 9 had confirmed ZIKV infection based on a positive enzyme-linked immunosorbent assay of cerebrospinal fluid samples showing IgM for ZIKV. Optical coherence tomography was performed prior to 5 months of age in all cases. Eleven eyes of the 8 infants had retinal alterations detected by ophthalmoscopy, and OCT was performed on 9 of these 11 affected eyes. The most common OCT findings, found in all scanned eyes, were loss of the outer retina and retinal pigment epithelium, not dissimilar to the case report by Parke et al.6 One important finding is that the retinal effects of intrauterine ZIKV infection are not necessarily bilaterally symmetric. The most severe reported OCT findings consist of complete loss of the inner and outer retina and choriocapillaris. Clinically, this is seen as a “coloboma-like” excavation of the macular area. It was detected in about half of affected eyes.

Ventura et al7 are to be commended for publishing this timely and important case series showing the structural changes produced by intraocular congenital ZIKV infection. Microstructural evaluation of the pathology of organs affected by ZIKV will assist us in understanding the pathogenesis of the disease and may also be helpful in determining whether milder, subclinical forms of the disease exist. The limitations of the study are that the clinical and OCT findings are nonspecific and, therefore, cannot necessarily delineate ZIKV infections from other congenital diseases that can result in similar clinical findings. In addition, because these OCT findings were largely “end stage,” they may not prove to be useful biomarkers should a treatment be developed for manifestations of ZIKV in the central nervous system.

Zika virus has emerged as an important pathogen in many parts of the world. This case series7 adds to our understanding of where in the eye the virus causes its damage, but more work is needed before the use of OCT for ZIKV-infected individuals becomes standard clinical practice.

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Article Information

Corresponding Author: Jay S. Duker, MD, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, 800 Washington St, PO Box 450, Boston, MA 02111 (jduker@tuftsmedicalcenter.org).

Published Online: November 10, 2016. doi:10.1001/jamaophthalmol.2016.4299

Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and Dr Duker reports that he receives research support and is a consultant for Zeiss, Optovue, and Topcon. No other disclosures are reported.

References
1.
Sikka  V, Chattu  VK, Popli  RK,  et al.  The emergence of Zika virus as a global health security threat: a review and a consensus statement of the INDUSEM Joint Working Group (JWG). J Glob Infect Dis. 2016;8(1):3-15.PubMedArticle
2.
Zika virus. Centers for Disease Control and Prevention website. https://www.cdc.gov/zika. Accessed September 14, 2016.
3.
Miner  JJ, Sene  A, Richner  JM,  et al.  Zika virus infection in mice causes panuveitis with shedding of virus in tears. Cell Rep. 2016;16(12):3208-3218. PubMedArticle
4.
Ventura  CV, Maia  M, Ventura  BV,  et al.  Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol. 2016;79(1):1-3.PubMedArticle
5.
Furtado  JM, Espósito  DL, Klein  TM, Teixeira-Pinto  T, da Fonseca  BA.  Uveitis associated with Zika virus infection. N Engl J Med. 2016;375(4):394-396.PubMedArticle
6.
Parke  DW  3rd, Almeida  DR, Albini  TA, Ventura  CV, Berrocal  AM, Mittra  RA.  Serologically confirmed Zika-related unilateral acute maculopathy in an adult  [published July 27, 2016]. Ophthalmology. doi:10.1016/j.ophtha.2016.06.039
7.
Ventura  CV, Ventura  LO, Bravo-Filho  V,  et al.  Optical coherence tomography of retinal lesions in infants with congenital Zika syndrome  [published online November 10, 2016]. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2016.4283
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