Risk Factors Associated With the Ophthalmoscopic Findings Identified in Infants With Presumed Zika Virus Congenital Infection

Abstract

IMPORTANCE The Zika virus (ZIKV) might cause microcephaly and ophthalmoscopic findings in infants of mothers infected during pregnancy. OBJECTIVE To assess and identify possible risk factors for ophthalmoscopic findings in infants born with microcephaly and a presumed clinical diagnosis of ZIKV intrauterine infection. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional study at the Altino Ventura Foundation in Recife, Brazil, that included 40 infants with microcephaly born in Pernambuco state, Brazil, between May and December 2015. Toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus were ruled out in all of them. Testing of cerebrospinal fluid for ZIKV using IgM antibody-capture enzyme-linked immunosorbent assay was performed in 24 of 40 infants (60.0%). The infants and mothers underwent ocular examinations. The infants were divided into 2 groups, those with and without ophthalmoscopic alterations, for comparison. MAIN OUTCOMES AND MEASURES Identification of risk factors for ophthalmoscopic findings in infants born with microcephaly and ZIKV intrauterine infection. RESULTS Among the 40 infants, the mean (SD) age was 2.2 (1.2) months (range, 0.1-7.3 months). Of the 24 infants tested, 100% had positive results for ZIKV infection: 14 of 22 infants (63.6%) from the group with ophthalmoscopic findings and 10 of 18 infants (55.6%) from the group without ophthalmoscopic findings. The major symptoms reported in both groups were rash by 26 mothers (65.0%), fever by 9 mothers (22.5%), headache by 9 mothers (22.5%), and arthralgia by 8 mothers (20.0%). No mothers reported conjunctivitis or other ocular symptoms during pregnancy or presented signs of uveitis at the time of examination. Thirty-seven eyes (46.3%) of 22 infants (55.0%) had ophthalmoscopic alterations. Ten mothers (71.4%) of infants with ocular findings reported symptoms during the first trimester (frequency, 0.48; 95% CI, 0.02-0.67; P = .04). A difference was also observed between the groups of infants with and without ocular findings regarding the cephalic perimeter: mean (SD) of 28.8 (1.7) and 30.3 (1.5), respectively (frequency, −1.50; 95% CI, −2.56 to −0.51; P = .004). CONCLUSIONS AND RELEVANCE Ocular involvement in infants with presumed ZIKV congenital infection were more often seen in infants with smaller cephalic diameter at birth and in infants whose mothers reported symptoms during the first trimester.

Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes

“…Consequently, there has been significant interest in understanding the pathogenesis of ZIKV in nonneurological diseases. Because clinical studies have linked ZIKV to ocular abnormalities, primarily in the retina of infants (8,12) and adults (45,46) and uveitis in adults (45), it is important to study ZIKV pathogenesis in the eye to identify potential targets for intervention. We have shown that direct inoculation of ZIKV in the adult mouse eye results in retinal lesions with a clinical presentation (chorioretinal atrophy and RPE mottling) resembling some of the features of ZIKV-associated ocular pathology described in humans.…”

“…In view of limited data, microcephaly may represent only one possible adverse outcome among a spectrum of conditions of congenital Zika syndrome (4). Indeed, several clinical studies have reported ocular abnormalities, specifically in the retina and choroid, of infants with congenital ZIKV infection (8)(9)(10)(11)(12)(13). Although currently undetermined, if a causal link between ZIKV infection and ocular disorders is established conclusively, it will have significant long-term economic, psychological, and health implications.…”

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know

“…In another Brazilian case series, which included 29 infants with microcephaly and presumed CZS, more than one-third of the children had ocular abnormalities. 21 In a report of 40 infants with microcephaly and presumed CZS from Pernambuco, Brazil, Ventura et al 22 described ophthalmoscopic alterations in 55% (n ¼ 22) of the infants.…”

“…[21][22][23][24][25] Musculoskeletal, Genitourinary, and Pulmonary Abnormalities Musculoskeletal abnormalities are frequently described in published reports of CZS, but their actual prevalence among infants of women infected during pregnancy remains unknown. Schwartz 9 analyzed 9 reported autopsies of fetuses and infants with intrauterine ZIKV infection and congenital microcephaly; of which 6 had variable findings of craniofacial malformations, craniosynostosis, and limb abnormalities, which included contractures of multiple joints or arthrogryposis.…”

Zika Virus: Current Status, Protective Vaccine Trials, and Antiviral Treatment Alternatives

“…Bu nedenle araştırmacılar Zika virus ile enfekte hastaların yalnızca %10-15'inde konjunktivit geliştiğini ve bu nedenle konjunktivitin ayırıcı tanıda önemi olmadığı sonucuna varmışlardır (31) . Konjenital Zika virus enfeksiyonlarında bildirilen oküler anormallikler; fokal pigment birikimleri, koryoretinal atrofi, optik sinir anormallikleri, iris kolobomu, lens subluksasyonu, maküler pigment birikimi, foveal refleks kaybı, makula atrofisi, bilateral hipersensitif iridosiklit, üveit ve mikroftalmidir (9,28,29,32,44,45) .…”