Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Isolated abducens nerve palsy associated with coronavirus disease: an 8-month follow-up / Paresia isolada do nervo abducente associada ao COVID-19: 8 meses de seguimento

ABSTRACT We report the case of a previously healthy 48-year-old man who developed an isolated abducens nerve palsy 18 days after presenting with coronavirus disease (COVID-19) confirmed by reverse transcriptase polymerase chain reaction. His main complaint at arrival was double vision. Ocular examination revealed a sixth cranial nerve palsy in the left eye. The incomitant esotropia at arrival was 30 prism diopters. Abduction was markedly limited, while adduction was normal in the left eye. The patient underwent complete clinical, neurological, and neuroimaging investigations, including cerebrospinal fluid sample analysis to rule out infectious causes. A conservative approach with orthoptic therapy and Fresnel prism was opted. Eight months after the onset of COVID-19, regression of the strabismus was observed, and the patient reported complete recovery of the diplopia. This case suggests that isolated abducens nerve palsy caused by severe acute respiratory syndrome coronavirus 2 infection may improve with a conservative approach.

RESUMO Reportamos o caso de homem previamente hígido, 48 anos, com paralisia isolada do nervo abducente 18 dias após infecção pelo novo coronavírus (COVID-19) confirmada por reação cadeia polimerase de transcriptase reversa. A principal queixa do paciente na admissão era diplopia. O exame ocular revelou paralisia do sexto nervo craniano do olho esquerdo. Esotropia incomitante no exame inicial media 30 dioptrias prismáticas. Abdução estava limitada com adução completa no olho esquerdo. O paciente foi submetido a investigação clínica e neurológica com exame de neuroimagem, incluindo análise de amostra do líquido cefalorraquidiano para descartar causas infecciosas. Optou-se por abordagem conservadora com terapia ortóptica e prisma de Fresnel. Oito meses após a infecção pelo COVID-19, o paciente evoluiu com regressão do estrabismo e informou recuperação completa do quadro. Este relato sugere que paralisia isolada do nervo abducente causada por SARS-CoV-2 pode melhorar com abordagem conservadora.

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects.

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.

Isolated abducens nerve palsy associated with coronavirus disease: an 8-month follow-up.

We report the case of a previously healthy 48-year-old man who developed an isolated abducens nerve palsy 18 days after presenting with coronavirus disease (COVID-19) confirmed by reverse transcriptase polymerase chain reaction. His main complaint at arrival was double vision. Ocular examination revealed a sixth cranial nerve palsy in the left eye. The incomitant esotropia at arrival was 30 prism diopters. Abduction was markedly limited, while adduction was normal in the left eye. The patient underwent complete clinical, neurological, and neuroimaging investigations, including cerebrospinal fluid sample analysis to rule out infectious causes. A conservative approach with orthoptic therapy and Fresnel prism was opted. Eight months after the onset of COVID-19, regression of the strabismus was observed, and the patient reported complete recovery of the diplopia. This case suggests that isolated abducens nerve palsy caused by severe acute respiratory syndrome coronavirus 2 infection may improve with a conservative approach.

Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

Ophthalmological manifestations in congenital Zika syndrome in 469 Brazilian children.

PURPOSE: To analyze the spectrum of ophthalmologic manifestations in a large sample of children with congenital Zika syndrome (CZS) in Brazil. METHODS: The medical records of infants born in the states of Pernambuco, Bahia, and Rio de Janeiro, Brazil, between December 2015 and December 2016 with clinical manifestations of CZS and positive reverse transcription polymerase-chain-reaction (RT-PCR) and/or serology for the Zika virus were reviewed retrospectively. Data were collected from the record of the first ophthalmological assessment, performed on admission. Children with other congenital infectious diseases, genetic conditions, and incomplete medical records were excluded. RESULTS: A total of 469 infants (242 female [51.6%]) were included. Mean age at examination was 5.0 ± 7.1 months (range, 0.0-36.0 months). Of the 469 infants, 197 (42.0%) were from Rio de Janeiro, 144 (30.7%) from Pernambuco, and 128 (27.3%) from Bahia States. Microcephaly at birth was detected in 214 (45.6%) children; 62 cases (29.0%) were severe. Pernambuco had significantly more children born with microcephaly compared with Bahia and Rio de Janeiro (P < 0.001). Ocular manifestations were found in 269 of 938 eyes (28.7%; 148/469 children [31.6%]). The main ocular alterations were optic nerve pallor in 122 of 938 eyes (13.0%), focal pigment mottling in 112 eyes (11.9%), and chorioretinal scars in 101 eyes (10.8%). A higher prevalence of ocular manifestations was seen in Pernambuco (P < 0.001). No microcephaly was observed in 252 of 466 children (54.1%); of these, 19 children (7.5%) had funduscopic findings. CONCLUSIONS: One-third of children with CZS had ocular manifestations. Children from Pernambuco were more affected. Ocular abnormalities were found in 7.5% of children without microcephaly.

Pattern-Reversal Visual Evoked Potential in Children With Congenital Zika Syndrome.

PURPOSE: To objectively evaluate the visual function in children with congenital Zika syndrome using pattern-reversal visual evoked potential (PR-VEP). METHODS: This was a cross-sectional study composed of two patient groups: children aged between 18 and 24 months who were positive for the Zika virus (congenital Zika syndrome group) and age-matched healthy children (control group). All patients underwent a comprehensive ophthalmologic examination and PR-VEP was performed binocularly in a room with constant dim illumination. The P100 peak time in the 60' arc stimuli was used, and the results were correlated with visual acuity, cephalic perimeter at birth, and funduscopic findings. RESULTS: Thirty-seven children were included in the congenital Zika syndrome group and 15 in the control group. The mean age was 18.5 ± 0.9 months (range: 17 to 20 months) in the congenital Zika syndrome group and 24.3 ± 1.6 months (range: 21 to 28 months) in the control group. The P100 response was normal in 7 patients (18.9%) with congenital Zika syndrome, borderline in 2 (5.4%), abnormal with prolonged latency in 18 (48.6%), and abnormal with no response in 10 (27.0%). A significant correlation between the visual acuity and P100 peak time was observed (P < .001). The P100 values were not correlated significantly with the cephalic perimeter at birth (P = .412) or the funduscopic findings (P = .510). PR-VEP in children with congenital Zika syndrome and no funduscopic findings was significantly worse than in the control group (P = .001). CONCLUSIONS: Children with congenital Zika syndrome have characteristically abnormal PR-VEPs regardless of the funduscopic findings and severe microcephaly. The PR-VEP findings supported the diagnosis of cortical visual impairment in these children. [J Pediatr Ophthalmol Strabismus. 2021;58(2):78-83.].

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

Color Fundus Imaging Using a High-Magnification Lens for Detecting Subtle Macular Changes in Infants With Congenital Zika Syndrome.

Purpose: We describe subtle macular changes that were detected by high-magnification color fundus imaging in infants with congenital Zika syndrome. Methods: This series included 4 infants (age: 1.4 ± 0.1 years [range, 1.3-1.5 years]) who were serologically confirmed with congenital Zika syndrome, examined under anesthesia, and underwent fundus examination and color fundus documentation. The fundus images were captured using 130° and 80° field lenses. Fluorescein angiography confirmed macular lesions. Results: Wide-angle color fundus images detected unilateral retinal findings in all 4 infants. Chorioretinal atrophy was identified in 2 eyes (25%) of 2 infants (50%) and pigment mottling in 3 eyes (37.5%) of 2 infants (50%). High-magnification imaging revealed subtle macular changes in the contralateral eyes of the 4 infants that were confirmed by fluorescein angiography imaging. Conclusions: High-magnification fundus imaging can be effective and reliable in revealing and documenting subtle structural changes in the macula of infants with congenital Zika syndrome.

Another piece of the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

BACKGROUND: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. RESULTS: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. CONCLUSION: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.

Developmental Outcomes Among Young Children With Congenital Zika Syndrome in Brazil.

Importance: Although birth defects in children with congenital Zika syndrome (CZS) are expected to result in significant intellectual disabilities, the extent of delay and profiles of development have yet to be fully described. Objectives: To describe the neurodevelopmental profiles of children with CZS and to test whether prenatal and postpartum characteristics were associated with the severity of developmental delays. Design, Setting, and Participants: This is a case series of the trajectories of developmental, behavioral, and medical needs of 121 young children with CZS who were assessed at a specialized rehabilitation center in Recife, Brazil, beginning in January 2018 as part of 5-year longitudinal study. Children were included if they had serologic confirmation of Zika virus and met clinical criteria accompanied by parental report of suspected exposure to Zika virus during pregnancy. Exposures: Prenatal Zika virus exposure. Main Outcomes and Measures: The Brazilian version of the Bayley Scales of Infant and Toddler Development, Third Edition, was administered by trained assessors as part of an initial comprehensive assessment battery. Caregiver interviews and medical record reviews were conducted to gather basic demographic information and medical comorbidities. Linear regression was used to identify potential factors for development. Results: The sample included 121 young children (mean [SD] age, 31.2 [1.9] months; 61 [50.4%] girls). At age approximately 2.5 years, nearly all children in this sample demonstrated profound developmental delays across all domains of functioning, with a mean (SD) developmental age equivalent to approximately 2 to 4 months (eg, cognitive domain, 2.24 [3.09] months; fine motor subscale, 2.15 [2.93] months; expressive language subscale, 2.30 [2.52] months). A relative strength was found in receptive language, with scores on this scale significantly higher than most other domains (eg, cognition: t = 3.73; P < .001; fine motor: t = 6.99; P < .001). Head circumference at birth was the single strongest factor associated with outcomes across all developmental domains (eg, cognitive: ß = 1.41; SE, 0.67; P = .04; fine motor: ß = 1.36; SE, 0.49; P = .007). Conclusions and Relevance: The findings of this study provide important information regarding the severity of disability that these children and their families will experience. The findings also establish an initial point from which to monitor developmental trajectories, medical comorbidities (eg, seizures), effectiveness of interventions, and cumulative consequences on families.

Congenital Zika Syndrome: Surgical and Visual Outcomes After Surgery for Infantile Strabismus.

PURPOSE: To evaluate the surgical and functional outcomes in children with congenital Zika syndrome who underwent strabismus surgery. METHODS: This prospective case series included children with congenital Zika syndrome who presented with horizontal infantile strabismus and underwent strabismus surgery. Ocular motility and visual fields were assessed preoperatively and postoperatively. Visual fields were considered normal if they exceeded 70 degrees in the temporal meridian. Postoperatively, parents and caregivers answered a questionnaire that assessed their child's behavioral improvements. A final ocular alignment within ±10 prism diopters (PD) and expansion of the visual fields were considered satisfactory motor surgical results at 6 months postoperatively. RESULTS: Five children (3 girls [60%]) with congenital Zika syndrome (age: 36.4 ± 0.9 months) were included in this study. All children (100%) presented with moderate to severe visual impairment and 4 (80%) presented with funduscopic abnormalities. Preoperatively, 4 children (80%) had infantile esotropia (mean preoperative angle of deviation: 41.3 ± 6.3 PD) and 1 (20%) had infantile exotropia measuring 65 PD. The postoperative outcomes demonstrated ocular alignment in 4 children (80%) at the 6-month follow-up visit. Expansion of the temporal visual field was observed in 7 eyes (70%) of 4 children (80%). Four caregivers (80%) reported behavioral improvement in daily activities, and all caregivers (100%) reported improved peripheral target detection and socialization skills. CONCLUSIONS: Strabismus surgery can be an effective procedure for treating horizontal strabismus in children with congenital Zika syndrome because it can improve ocular alignment, expand the visual field, and improve the child's social, functional, and behavioral skills. [J Pediatr Ophthalmol Strabismus. 2020;57(3):169-175.].

Fluorescein Angiography Findings in Children With Congenital Zika Syndrome.

BACKGROUND AND OBJECTIVE: To evaluate the retinal and vasculature changes in infants with congenital Zika syndrome (CZS) using fluorescein angiography (FA). PATIENTS AND METHODS: This consecutive case series included six infants with CZS. FA and color fundus imaging were performed under general anesthesia in both eyes of all infants using a contact widefield digital imaging system. All color fundus images were obtained using a 130° field of view lens, and the FA images were captured using either a 130° or 80° field of view lens. The immunoglobulin M antibody capture enzyme-linked immunosorbent assay was positive for Zika virus in the cerebrospinal fluid samples of all infants. Other congenital infections were ruled out. RESULTS: The mean ± standard deviation age of the infants at the time of examination was 1.4 years ± 0.1 years (range: 1.3 years to 1.5 years). Contact fundus photographs showed macular abnormalities in seven eyes (58%) and retinal vasculature changes in two eyes (17%). FA detected macular abnormalities in all 12 eyes (100%) and retinal vasculature changes in five eyes (42%). The main retinal vasculature changes were peripheral avascularity in five eyes (42%) and microvasculature abnormalities in three eyes (25%). CONCLUSION: FA may be an important tool for detecting subtle macular and retinal vasculature changes in CZS. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:702-708.].

Ocular Manifestations and Visual Outcome in Children With Congenital Zika Syndrome.

The recent Zika virus (ZIKV) outbreak and the link to birth defects in newborns exposed in utero, caught international attention. Due to its rapid spread throughout the Americas, authorities declared ZIKV a Public Health Emergency of International Concern that lasted from February to November 2016."Congenital Zika Syndrome" (CZS) is a new entity that reflects a broad spectrum of symptoms and signs observed in newborns infected by the ZIKV in utero. A recent review concluded that CZS differs from other congenital infections for its five distinct features: "(1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement."Diagnosing and managing CZS has become a challenge for health professionals including ophthalmologists. The ocular manifestations of CZS are unique and have important consequences on vision. This article reviews the ocular manifestations of the CZS, addresses the visual outcomes of affected infants, and elucidates the early intervention protocols for visual improvement.

Glaucoma Workup in Congenital Zika Syndrome.

PURPOSE: The main aim of this study was to perform a glaucoma workup in infants with congenital Zika syndrome (CZS). PATIENT AND METHODS: This cross-sectional study included 188 eyes of 107 children (1.1±0.3 y; range, 0.3 to 1.8 y) with CZS. The confirmation of the syndrome was possible in 77 of 107 (72.0%) of the enrolled infants based on positive immunoglobulin M antibody capture enzyme-linked immunosorbent assay for Zika virus in the cerebrospinal fluid. All infants underwent a complete ophthalmic examination and bilateral fundus imaging was captured using a wide-angle digital fundus camera (RetCam). RESULTS: Five eyes (2.6%) presented 2 criteria for glaucoma diagnosis: 1 eye (0.5%) presented increased intraocular pressure and increased vertical cup-to-disc ratio (CDR); 3 eyes (1.6%) presented increased horizontal corneal diameter and increased vertical, and 1 eye (0.5%) presented myopia related to increased axial length and increased vertical CDR. When excluding the CDR criterion, there was no case of glaucoma in this sample. A significant correlation was observed between high vertical CDR and small cephalic perimeter at birth (P=0.002) and the presence of clinical macular lesions (P=0.031). CONCLUSION AND RELEVANCE: Although childhood glaucoma was not detected in this sample, increased vertical CDR is present in children with CZS, associated with microcephaly and clinical macular lesions at birth. This finding may lead to a misdiagnosis of glaucoma.

Skills attained by infants with congenital Zika syndrome: Pilot data from Brazil.

The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13-22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6-8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.

Zika and the Eye: Pieces of a Puzzle.

Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that analyzed ocular findings in mothers and infants with CZS, with or without microcephaly, was conducted and a theoretical pathophysiologic explanation for ZIKV-ocular abnormalities was formulated.