Zika Virus and the eye

Findings from examination of a growing cohort of infants born in Brazil with microcephaly indicate that vision-threatening fundus lesions may be another complication of Zika virus vertical infection. Speaking on behalf of the Zika Virus Study Group at the WOC 2016 in Guadalajara, Mexico, Mauricio Maia MD, PhD said that the first description of a potential association between macular lesions in a microcephalic infant and intrauterine Zika virus infection appeared as a case report published online in The Lancet on 8 January, 2016. 
An article published in the Arquivo Brasileiros de Oftalmologia in February 2016 reported the finding of ocular abnormalities in 17 (85 per cent) of 20 eyes of 10 infants with microcephaly born to mothers with a clinical diagnosis of Zika virus infection. In an online article in JAMA Ophthalmology on 9 February, 2016, the group’s series had grown to 29 infants, of which 10 (34.5 per cent) had ocular lesions and seven had bilateral involvement.
Dr Maia reported at the conference on 141 babies born with microcephaly to mothers thought to have Zika virus infection during pregnancy. In that cohort, about 30 per cent had fundus alterations. 
The lesions, which differed from any previously described in relationship to other congenital infections, could be categorised into four major types: atrophic chorioretinal changes at the macula; atrophic chorioretinal changes outside the macula; atrophic optic nerve changes with increased excavation of the nerve and optic disc hypoplasia without intraocular pressure elevation; and mottling of the macula similar to retinal pigment epithelium defects. 
“Advances in serologic studies for diagnosing Zika virus infection and prospective case-controlled studies of pregnant women with documented Zika infection are necessary to confirm an association between intrauterine exposure to the Zika virus and both congenital microcephaly and fundus abnormalities. However, there is good evidence to support a causal relationship,” said Dr Maia, Assistant Professor of Ophthalmology, Federal University of São Paulo, Brazil. 
“The finding of ocular lesions in these infants is an important issue for public health systems worldwide and the ophthalmology community, considering that Zika virus infection has potential to be a worldwide pandemic. Infants with microcephaly presumed related to maternal Zika virus infection should undergo an ophthalmological examination, and children with fundus lesions should receive early visual stimulation to minimise deleterious consequences and provide the best possible vision in the future,” he added.

HALLMARK SIGNS
Dr Maia added that only 20 per cent to 30 per cent of people infected with the Zika virus are symptomatic with characteristic findings that include cutaneous rash, fever, and arthralgia lasting for about five days. 
“Considering that we have been evaluating newborns of symptomatic mothers, there may be even more children with microcephaly and fundus lesions related to Zika virus infection,” Dr Maia told EuroTimes. 
For all cases, maternal Zika virus infection during pregnancy was established either clinically based on a history of the hallmark signs of infection or by real-time polymerase chain reaction (rt-PCR) performed during the acute phase of infection (which is the only method for diagnosing Zika virus infection available in Brazil). 
“None of the women had evidence of conjunctivitis during their acute infection, and that seems to refute the idea that conjunctivitis with rash, fever, and arthralgia can help differentiate Zika virus infection from dengue fever and Chikungunya virus infection,” Dr Maia noted. 
In all infants, other infectious or non-infectious risk factors for microcephaly were ruled out by serology or history. 

WHAT LIES AHEAD?
Further study is ongoing, including an attempt to correlate the ocular findings in the newborns with gestational age at the time of maternal infection. 
“We believe that the choroidal atrophic changes at the macula are associated with maternal infection during the first trimester of pregnancy. Currently, we are unsure about whether the optic nerve abnormalities are caused by the virus or related instead to the microcephaly,” Dr Maia said. 
In addition, pregnant women with documented Zika virus infection are being followed prospectively, and blood samples are being drawn and frozen from mothers with undocumented infection who give birth to children with microcephaly, anticipating the future availability of a specific serologic test for Zika virus. 
Further research is also necessary to determine whether ophthalmic screening should be performed in infants born without microcephaly, but whose mothers were known or suspected to have had Zika virus infection during pregnancy.
Importantly, efforts are needed to reduce the risk of Zika virus infection. “We wait for the development of a vaccine that can prevent Zika virus infection. In the meantime, eradication of the mosquito vector is of critical importance, and pregnant women should be advised to avoid endemic areas, or use mosquito repellents if that is not possible,” Dr Maia said. 
"The first report in the literature on the possible relationship between congenital Zika virus infection and retinal abnormalities was published for the group in The Lancet journal in January 2016," he added.

In addition to Dr Maia, coordinators of the Zika Virus Study Group include Rubens Belfort Jr MD, PhD; Paul Freitas MD; Liana Ventura MD; and Camila Ventura MD

Mauricio Maia: retina@femanet.com.br