Ophthalmological manifestations in congenital Zika syndrome in 469 Brazilian children

Ventura, Camila V.; Zin, Andréa; Freitas, Bruno de Paula; Ventura, Liana O.; Rocha, Camilla Silva da; Costa, Federico; Nery, Nívison; Senna, T.; Moreira, Maria Elisabeth Lopes; Maia, Maurício; Belfort, Rubens

doi:10.1016/j.jaapos.2021.01.009

Cited by 17 publications

(8 citation statements)

References 16 publications

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“…Optic nerve abnormalities included hypoplastic disc, nerve pallor, and an increased cup-to-disc ratio [79]. These findings were consistently documented in studies thereafter [89][90][91]. De Paula Freitas observed additional findings, including lens subluxation and iris coloboma.…”

Section: Anterior Segment Neuro-ophthalmic Posterior Segmentmentioning

confidence: 64%

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Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Labib

Chigbu

2022

TropicalMed

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Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.

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Section: Anterior Segment Neuro-ophthalmic Posterior Segmentmentioning

confidence: 64%

“…This is presumably due to the CNS involvement associated with CZS. Decreased visual acuity was confirmed in a later study but improvement was observed by prescribing full visual correction in these cases [90].…”

Section: Anterior Segment Neuro-ophthalmic Posterior Segmentmentioning

confidence: 76%

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Labib

Chigbu

2022

TropicalMed

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“…To our knowledge, we present the largest (330 children) cross-sectional multicentric study of fundus screening of an entire population exposed to ZIKV. The series of Ventura et al, which includes 469 infants with CZS, is a multicentric Brazilian study. The 3 Brazilian series with the highest number of patients had 112, 119, and 173 children.…”

Section: Discussionmentioning

confidence: 99%

Fundus Changes in the Offspring of Mothers With Confirmed Zika Virus Infection During Pregnancy in French Guiana, Guadeloupe, and Martinique, French West Indies

et al. 2022

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ImportanceMost ocular lesions have been described for children with congenital Zika syndrome. The frequency of finding ocular abnormalities is unknown among children exposed to Zika virus (ZIKV) during pregnancy. This study was conducted on newborns whose mothers were positive for ZIKV, confirmed with reverse-transcription polymerase chain reaction (RT-PCR) testing.ObjectiveTo report ocular fundus manifestations in newborns with congenital ZIKV exposure in French Guiana, Martinique, and Guadeloupe, French West Indies, to assess its prevalence. Risk factors, such as the presence of extraocular fetopathies and the gestational term at infection, were sought.Design, Setting, and ParticipantsThis was a cross-sectional multicentric study, conducted from August 1, 2016, to April 30, 2019, for which data were collected prospectively. The study inception was at the beginning of 2016 from the onset of the ZIKV epidemic in the French West Indies. Newborns whose mothers tested positive (by RT-PCR) for ZIKV during pregnancy were included.InterventionsFundus examination was performed using widefield retinal imaging after pupil dilation. Infection date, delivery mode, and newborn measurements were collected.Main Outcomes and MeasuresAnomalies of the vitreous, choroid, retina, and optic disc.ResultsA total of 330 children (mean [SD] age, 68 [IQR, 22-440] days; 170 girls [51.5%]) were included. Eleven children (3.3%) had perivascular retinal hemorrhages, and 3 (0.9%) had lesions compatible with congenital ZIKV infection: 1 child had torpedo maculopathy, 1 child had a chorioretinal scar with iris and lens coloboma, and 1 child had a chorioretinal scar. Retinal hemorrhages were found at childbirth during early screening. Lesions compatible with congenital ZIKV infection were not associated with the presence of extraocular fetopathy. Microcephaly was not associated with lesions compatible with congenital ZIKV infection (odds ratio [OR], 9.1; 95% CI, 0.8-105.3; P = .08), but severe microcephaly was associated with an OR of 81 (95% CI, 5.1-1297.8; P = .002).Conclusions and RelevanceResults of this cross-sectional study suggest that the ocular anomalies found may be associated with ZIKV in 0.9% of the exposed population. Ocular lesions were rare, affected mostly the choroid and retina, and seemed to be associated with choroiditis-related scarring that developed during fetal growth.

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“…Most (62%) children in our Registry had ocular anomalies, which is higher than reported in other studies 10 , including a Brazilian multicentre study of 469 children with laboratoryconfirmed CZS where 32% had ocular manifestations (although this varied geographically), most commonly optic nerve findings (20% of eyes) and retinal anomalies (20% of eyes). 24 Current understanding of the range of ophthalmic anomalies in ZIKV-exposed and infected children remains incomplete. The predominance of fundus abnormalities among children with ophthalmic manifestations here is consistent with the literature, with structural defects such as microphthalmia or iris coloboma much less commonly reported in children with CZS, as was the case here.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%