Zika Virus Infection and the Eye.

Human and insect travel between continents has resulted in the dissemination of previously remote infections to more populated parts of the world. West Nile virus apparently moved from Israel to New York, where it decimated bird populations, and subsequently moved across the United States, producing human neurologic disease and retinal lesions. Now, a related virus—Zika virus—has been implicated as the cause of an epidemic of microcephaly, first in Brazil and now spreading into other parts of the western hemisphere. Zika virus was identified by reverse transcription– polymerase chain reaction in the amniotic fluid of 2 women in Brazil whose fetuses had been found to have microcephaly by prenatal ultrasonography,1 and the Centers for Disease Control and Prevention have confirmed that a microcephalic baby born in Hawaii to a mother from Brazil had been infected with the virus.2 Ongoing registry studies are under way to confirm the causative association between the viral infection and microcephaly. Millions of people in Brazil are believed to have been infected with the virus, which has rapidly spread throughout the Americas. It is transmitted primarily by the Aedes aegypti mosquito, although sexual transmission has been very rarely noted. The infection itself is rarely life threatening, manifesting typically as short-lived fever, nonspecific rash, and joint pain, or it may be completely asymptomatic. The mild nature of the infection makes ascertainment of a relationship between maternal infection and subsequent fetal anomalies difficult, as the illness is often unnoticed or unreported. Ophthalmologic manifestations of congenital Zika virus infection are not yet well described. A report earlier this year described 3 babies from Brazil with microcephaly and presumed Zika virus intrauterine infection who had macular pigment mottling and loss of foveal reflex, with 1 manifesting well-defined macular atrophy.3 The report by de Paula Freitas et al4 in this issue of JAMA Ophthalmology implicates this infection as the cause of chorioretinal scarring and possibly other ocular abnormalities in infants with microcephaly recently born in Brazil. Microcephaly can be genetic, metabolic, drug related, or due to perinatal insults such as hypoxia, malnutrition, or infection. The present 20-fold reported increase of microcephaly in parts of Brazil is temporally associated with the outbreak of Zika virus. However, this association is still presumptive because definitive serologic testing for Zika virus was not available in Brazil at the time of the outbreak and confusion may occur with other causes of microcephaly.5 Similarly, the currently described eye lesions are presumptively associated with the virus. Zika virus is a flavivirus transmitted by Aedes mosquitoes and is related to yellow fever virus, dengue virus, and West Nile virus. Zika virus was first identified in Uganda in 1947 in macaques and then in humans as early as 1968.6 It has also been identified in French Polynesia, where an epidemic was associated with perinatal transmission and fetal abnormalities. The virus presently in Brazil appears to have originated from Polynesia. The clinical findings of primary infection mimic both dengue virus and chikungunya virus, also present in Brazil and carried by the same mosquito. Testing for Zika virus is not readily available, making the diagnosis challenging; however, the Centers for Disease Control and Prevention in Atlanta, Georgia, can perform serologic testing (IgM and plaque-reduction neutralization), and polymerase chain reaction testing is available. The infection causing microcephaly and retinal lesions typically occurs during the first or second trimester of pregnancy. In the series described by de Paula Freitas and colleagues, almost 80% of mothers reported symptoms consistent with Zika virus infection, most in the first trimester.4 Ocular abnormalities were present in 10 of the 29 infants examined (35%) and were bilateral in 7 of the 10. The characteristic lesions included posterior pole pigmentary clumping and areas of sharply circumscribed chorioretinal atrophy. In addition, 1 baby showed iris colobomas and lens subluxation (although it is not clear whether this was related to Zika virus). It is likely with further experience that the spectrum of ocular lesions will increase. At the present time it has been suggested that women in the areas of the epidemic consider not getting pregnant and it is recommended that pregnant women, especially during their first 2 trimesters, not travel to areas where the disease is epidemic. As West Nile virus spread across the United States and then became endemic, uveitis and chorioretinitis were seen. Interestingly, West Nile virus was reported to have transplacental transmission, producing lesions somewhat similar to the current cases.7 The differential diagnosis of chorioretinal lesions such as those reported in this series includes many other Related article page 529 Ocular Findings in Infants With Presumed Zika Virus Infection Original Investigation Research