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Original Investigation
September 21, 2017

Ocular Histopathologic Features of Congenital Zika Syndrome

Author Affiliations
  • 1Florida Lions Ocular Pathology Laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami
  • 2Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • 3Instituto Nacional de Salud, Bogota, Colombia
  • 4Facultad de Ciencias de la Salud, Universidad del Norte, Antigua vía a Puerto Colombia, Barranquilla Colombia
  • 5Department of Perinatology, CEDIUL Diagnostic Images, Barranquilla, Colombia
  • 6Sociedad Colombiana de Oftalmologia, Bogota, Colombia
JAMA Ophthalmol. Published online September 21, 2017. doi:10.1001/jamaophthalmol.2017.3595
Key Points

Question  What are the ocular histopathologic features of fetuses with congenital Zika syndrome?

Findings  In this case series of 4 eyes from 4 fetuses with congenital Zika syndrome, expression of the Zika virus antigen was identified within the iris, neural retina, choroid, and optic nerve. Histopathologic examination revealed a pupillary membrane, an immature anterior chamber angle, lack of differentiation of the nuclear layers of the neural retina, a thin photoreceptor layer, loss of pigment and thinning of the retinal pigment epithelium, a perivascular inflammatory infiltrate within the choroid, and choroidal thinning.

Meaning  Detection of Zika virus antigens within different ocular tissues in the context of congenital Zika syndrome suggests that the histopathologic findings may be associated with Zika virus infection.


Importance  Congenital Zika syndrome (CZS) is known to be associated with severe malformations in newborns. Although microcephaly is the hallmark of this disease, the ocular findings are important given the severe visual impairment that has been observed in these patients. Regardless of the increased number of CZS cases reported, to date, no studies have described the ocular histopathologic findings of this entity.

Objectives  To evaluate the presence of Zika virus (ZIKV) antigens and describe the associated ocular histopathologic features of 4 cases of CZS.

Design, Setting, and Participants  In this observational case series performed from June 19, 2015, through April 30, 2017, ocular tissue samples from 4 deceased fetuses with a diagnosis of CZS from the National Institute of Health in Colombia were sent to the Florida Lions Ocular Pathology Laboratory for evaluation.

Main Outcomes and Measures  The microscopic features of each specimen were described, and immunostaining was performed using a ZIKV NS2B protein antibody.

Results  Ocular tissue samples from the 4 deceased fetuses (2 female, 2 male) ranging from 21.5 to 29 weeks’ gestation with a diagnosis of CZS were studied. The 4 eyes manifested with pupillary membranes, immature anterior chamber angles, loss of pigment and thinning of the retinal pigment epithelium, choroidal thinning, undifferentiated nuclear layers of the retina, and a perivascular inflammatory infiltrate within the choroid. The optic nerve, present in 2 of the eyes, demonstrated atrophy. Expression of ZIKV antigen was present in the iris in cases 1, 3, and 4; the neural retina and choroid in case 1; and in the optic nerve in case 4.

Conclusions and Relevance  Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were consistently present. These findings may be attributed to ZIKV infection and warrant further study.