Perspective

Risk factors associated with ocular findings in infants with presumed Zika infection

Two main risk factors associated with ocular findings encountered in infants with congenital Zika syndrome were identified in a Brazilian study, according to lead study author Camila V. Ventura, MD.

The first was symptoms referred by mothers in the first trimester of pregnancy, and the second was smaller cephalic diameter at birth.

“In other words, pregnant women that report symptoms during the first 3 months of gestation have a greater risk of having a baby with ocular findings, as well as babies born with very small head circumference have more chance of having retinal and optic nerve findings,” Ventura said.

Ventura said recent studies were able to explain in mice models how the virus causes microcephaly. The study results have reported that the virus crosses the placenta and attacks the cortical progenitor cells in the brain, causing cell death by apoptosis and autophagy, and stopping the brain’s growth and normal development. Furthermore, Ventura explained that early exposure to Zika virus during early development of the brain is directly related to severe microcephaly because the brain’s growth is affected in early stages of development.

“In fact, these two risk factors are intrinsically related to each other since exposure to the virus during the first trimester is related to severe microcephaly, exposure to the virus during the first trimester is related to the ocular findings, and the ocular findings are related to severe microcephaly,” she said.

This information is important because early identification of retinal and optic nerve lesions indicates early visual rehabilitation for the affected infants, she said.

Another milestone of this study was “to prove that the ocular findings seen in the babies are part of the [congenital Zika syndrome],” according to Ventura.

Researchers tested the cerebrospinal fluid of 24 of the 40 infants with microcephaly in the cross-sectional study and all 24 were found to have positive results for Zika virus infection. Fourteen of 22 infants with ophthalmoscopic findings and 10 of 18 infants without ophthalmoscopic findings were positive for the virus.

Ten mothers of infants with ocular findings reported experiencing Zika virus symptoms such as rash (65%), fever (22.5%), headache (22.5%) and arthralgia (20%) during the first trimester of pregnancy. No mothers reported conjunctivitis or other ocular symptoms during pregnancy, and none presented signs of uveitis during their examinations. – by Robert Linnehan

Disclosure: Ventura reports no relevant financial disclosures.

Two main risk factors associated with ocular findings encountered in infants with congenital Zika syndrome were identified in a Brazilian study, according to lead study author Camila V. Ventura, MD.

The first was symptoms referred by mothers in the first trimester of pregnancy, and the second was smaller cephalic diameter at birth.

“In other words, pregnant women that report symptoms during the first 3 months of gestation have a greater risk of having a baby with ocular findings, as well as babies born with very small head circumference have more chance of having retinal and optic nerve findings,” Ventura said.

Ventura said recent studies were able to explain in mice models how the virus causes microcephaly. The study results have reported that the virus crosses the placenta and attacks the cortical progenitor cells in the brain, causing cell death by apoptosis and autophagy, and stopping the brain’s growth and normal development. Furthermore, Ventura explained that early exposure to Zika virus during early development of the brain is directly related to severe microcephaly because the brain’s growth is affected in early stages of development.

“In fact, these two risk factors are intrinsically related to each other since exposure to the virus during the first trimester is related to severe microcephaly, exposure to the virus during the first trimester is related to the ocular findings, and the ocular findings are related to severe microcephaly,” she said.

This information is important because early identification of retinal and optic nerve lesions indicates early visual rehabilitation for the affected infants, she said.

Another milestone of this study was “to prove that the ocular findings seen in the babies are part of the [congenital Zika syndrome],” according to Ventura.

Researchers tested the cerebrospinal fluid of 24 of the 40 infants with microcephaly in the cross-sectional study and all 24 were found to have positive results for Zika virus infection. Fourteen of 22 infants with ophthalmoscopic findings and 10 of 18 infants without ophthalmoscopic findings were positive for the virus.

Ten mothers of infants with ocular findings reported experiencing Zika virus symptoms such as rash (65%), fever (22.5%), headache (22.5%) and arthralgia (20%) during the first trimester of pregnancy. No mothers reported conjunctivitis or other ocular symptoms during pregnancy, and none presented signs of uveitis during their examinations. – by Robert Linnehan

Disclosure: Ventura reports no relevant financial disclosures.

    Perspective

    In their recent publication, “Risk factors associated with the ophthalmoscopic findings identified in infants with presumed Zika virus congenital infection,” Ventura and colleagues have outlined the key findings associated with ocular Zika infection, namely children with microcephaly born to mothers with rash, fever, headaches and arthralgias in an endemic region of Brazil.

    The senior author, Rubens Belfort Jr., was the first to describe ocular Zika with its characteristic chorioretinal atrophy, the first to describe a large series of infants with microcephaly and ocular findings including localized pigmentary retinopathy, optic nerve hypoplasia and colobomas, iris colobomas, and chorioretinal atrophy, and also the first to describe congenital Zika infection with chorioretinal atrophy in the absence of microcephaly. This latter finding is of great import when considering screening of infants because microcephaly is an easily identified morphologic abnormality and is independently associated with all of the previously described ocular Zika findings, and he and his group are to be congratulated for staying on top of this developing outbreak. To date, only the findings of chorioretinal atrophy and pigmentary mottling have been found to occur with congenital Zika infection in the absence of microcephaly. However, we are likely to see more cases as formalized screening programs take shape.

    Presently, the most conservative recommendation with respect to identifying ocular disease would be that all infants born to mothers with symptoms suggestive of Zika infection during pregnancy and living in or having traveled to an endemic region be screened by an ophthalmologist shortly after birth in order to maximize therapeutic options to prevent visual loss. This applies doubly so for any infant with microcephaly.

    • Darius M. Moshfeghi, MD
    • Byers Eye Institute, Stanford University School of Medicine Palo Alto, Calif.

    Disclosures: Moshfeghi reports receiving travel support from Clarity, and he is the founder and director of Versyl, is a consultant for and on the advisory board of Visunex Medical Systems, and receives equity from Versyl and Visunex Medical Systems.