Ocular findings in patients with microcephaly can suggest presumed congenital zika virus infection

A 17-year-old boy was referred to our institute for a second opinion. He was born in Argentina and had a previous history of microcephaly (Fig. 1A) and poor visual acuity (VA). At birth, his gestational age was 38 weeks and his weight was 2.800 g. Computerized tomography scans did not evidence cerebral calcifications. He and his mother had negative serology for toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus, syphilis and human immunodeficiency virus (HIV). He had no family history of microcephaly and his mother had no history of alcohol or illicit drug use during pregnancy. He was diagnosed with bilateral chorioretinal scars and left esotropia. At the age of 4, he had strabismus surgery and occlusion therapy without visual improvement. When he came to our centre for the first time, his VA was 20/200 in his right eye and 20/250 in his left eye. Pupils were normally reactive, with no afferent pupillary defect, and Hirschberg testing revealed left esotropia. The patient had normal anterior segment structures. Optic nerve findings consisted of bilateral hypoplasia with the double-ring sign, pallor and increased cup-to-disc ratio. Bilateral foveal reflex loss with macular pigment mottling was observed with two sharply demarcated chorioretinal scars surrounded by hyperpigmented mottling in the superior and inferior temporal arcades in both eyes (Fig. 1B,C). The retinal vessels had normal distribution and appearance. Wide-angle fundus image of both eyes had not changed compared to the previous retinographies taken several years before (Fig. 1D,E). Optical coherence tomography showed bilateral macular atrophy (Fig. 1F,G). Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, CMV and Herpes infections are some of the most common (TORCH) infections associated with these congenital abnormalities. At birth, the patient and his mother had negative serology testings for syphilis, HIV, toxoplasmosis, CMV, herpes simplex virus or rubella. Serology results were still negative at the time of our consultation. Thus, the suspected diagnosis of congenital zika virus (ZIKV) was made 17 years after birth, based on the typical ocular findings and microcephaly of our patient. Zika virus (ZIKV) is a neurotropic flavivirus related to the dengue, yellow fever and West Nile viruses (WHO 2015). It was first reported in humans in 1952, but typical ocular findings and microcephaly were not related to the virus until 2015 (Schuler-Faccini et al. 2016). Maternal-fetal transmission of ZIKV has been detected in the amniotic fluid of two pregnant women with babies with microcephaly, and in the tissue of a newborn with microcephaly that died after birth. Ventura et al. (2016) described the typical ocular findings of 10 infants (mean age 1.9 months) diagnosed with presumed ZIKV infection after the 2015 Brazilian ZIKV infection outbreak. The patients associated microcephaly, macular alterations (gross pigment mottling and/or chorioretinal atrophy in 75% of the eyes) and optic nerve abnormalities (hypoplasia with double-ring sign, pallor and/or increased cup-to-disc ratio in 45% of the cases). Other causes of the chorioretinal and optic nerve abnormalities were also ruled out in those patients to reach the presumed diagnosis of ZIKV. De Paula Freitas et al. (2016) also described the ocular findings in 29 infants born after the outbreak in the state of Bahia in Brazil with microcephaly and presumed diagnosis of congenital ZIKV infection. Bilateral findings were found in seven of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy (65%), followed by optic nerve abnormalities (47%), bilateral iris coloboma (12%) and lens subluxation (6%). The diagnosis of congenital infection due to ZIKV exposure is presumable in all the reported cases with microcephaly and abnormal ocular findings, as the only available method to confirm the diagnosis of ZIKV infection (Balm et al. 2012) is real-time polymerase chain reaction (PCR), which is useful to detect the virus in the acute phase of illness (first 5 days of acute infection). A recent increase in the prevalence of microcephaly in newborn infants and vision-threatening findings in these infants has meant that clinicians should consider ophthalmologic evaluations of newborns from regions in the Americas where ZIKV transmission has spread rapidly to identify lesions associated with this congenital infection and confirm the diagnosis with PCR in the first