Camila V. Ventura
Federal University of São Paulo
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The Lancet | 2016
Camila V. Ventura; Mauricio Maia; Vasco Bravo-Filho; Adriana L. Gois; Rubens Belfort
228 www.thelancet.com Vol 387 January 16, 2016 reflex loss. A well defined macular neuroretinal atrophy was detected in one child (fi gure). To our knowledge, this is the fi rst report of ocular fi ndings in infants with microcephaly born after the ZIKV outbreak. All three children had fundoscopic alterations in the macular region. Although ZIKV infection was not tested by real-time PCR, cases fulfi l criteria for ZIKV vertical infection. Further studies are being conducted in a larger group of infants to assess the ocular manifestations of ZIKV vertical infection.
Arquivos Brasileiros De Oftalmologia | 2016
Camila V. Ventura; Mauricio Maia; Bruna Vieira Ventura; Vanessa van der Linden; Eveline B. Araújo; Regina Coeli Ferreira Ramos; Maria Angela Wanderley Rocha; M. Carvalho; Rubens Belfort; Liana O. Ventura
PURPOSE In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. METHODS We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. RESULTS Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to-disk ratio) in nine eyes (45.0%). CONCLUSIONS Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations.
JAMA Pediatrics | 2017
Cynthia A. Moore; J. Erin Staples; William B. Dobyns; André Pessoa; Camila V. Ventura; Eduardo Borges da Fonseca; Erlane Marques Ribeiro; Liana O. Ventura; Norberto Nogueira Neto; J. Fernando P. Arena; Sonja A. Rasmussen
Importance Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE for Zika from inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (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. Conclusions and Relevance Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype—the congenital Zika syndrome—has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care.
BMJ | 2016
Vanessa van der Linden; Epitácio Leite Rolim Filho; Otávio Gomes Lins; Ana van der Linden; Maria de Fátima Viana Vasco Aragão; Alessandra Mertens Brainer-Lima; Danielle Di Cavalcanti Sousa Cruz; Maria Angela Wanderley Rocha; Paula Fabiana Sobral da Silva; M. Carvalho; Fernando José do Amaral; Joelma Arruda Gomes; Igor Colaço Ribeiro de Medeiros; Camila V. Ventura; Regina Coeli Ferreira Ramos
Objective To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Design Retrospective case series study. Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil. Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. Results The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Conclusions Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders.
JAMA Ophthalmology | 2016
Camila V. Ventura; Mauricio Maia; Simone Travassos; Thayze T. Martins; Felipe Patriota; Marcos Eugênio Nunes; Cristiana Agra; Virginia L. Torres; Vanessa van der Linden; Regina Coeli Ferreira Ramos; Maria Ângela Wanderley Rocha; Paula Fabiana Sobral da Silva; Liana O. Ventura; Rubens Belfort
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.
The Lancet | 2016
Camila V. Ventura; Mauricio Maia; Natalia C. Dias; Liana O. Ventura; Rubens Belfort
The emergence of Zika virus (ZIKV) in Brazil coincided with increased reports of newborn babies with microcephaly, congenital malformations, and neurological syndromes. 1 In February, 2016, WHO declared ZIKV and microcephaly a Public Health Emergency of International Concern because of the rapid spread of ZIKV infection. In January, 2016, we reported ocular fi ndings in infants with microcephaly and presumed congenital Zika virus infection in Pernambuco, Brazil. Similar ocular findings have been reported in infants assessed in Bahia, Brazil. These reports followed establishment of microcephaly (head circumference two SDs below the mean for age and sex) as an inclusion criterion for the screening of babies for congenital Zika virus infection. Therefore, the presence or absence of microcephaly was used as a cutoff for screening, and only cases that fulfi lled this criterion were classifi ed as presumed cases of congenital Zika virus infection and further investigated. To the best of our knowledge, no reports exist on infants with diagnosis of congenital Zika virus infection, who did not have microcephaly, but did have ocular fi ndings. Here we report the ophthalmic findings of an infant (age at exam: 57 days; head circumference: 33 cm; weight at birth: 3500 g; gestational age at birth: 38 weeks) who was referred for ophthalmic examination by a neurologist for suspected congenital Zika virus infection. The mother reported that she did not have ZIKV-related symptoms, use illicit drugs, drink alcohol, or smoke during pregnancy. The infant presented lower limb and upper limb spasms at birth. CT scans detected cerebral calcifi cations in the basal ganglia, ventriculomegaly, and lissencephaly. Ocular examination included anterior segment biomicroscopy and fundus evaluation. A chorioretinal scar was detected on the macular region of the left eye (fi gure), similar to scars previously reported in congenital Zika virus infection. Toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV, and dengue fever virus were ruled out in both mother and infant. IgM antibody capture (MAC)-ELISA for ZIKV was done in the cerebral spinal fl uid of the infant, which was positive, confirming our hypothesis of congenital Zika virus infection. This case highlights that microcephaly should not be a required criterion for congenital Zika virus infection diagnosis, since infants without microcephaly could still have been infected by ZIKV during gestation. We emphasise the need for public health authorities to provide fundus screening to infants with suspected congenital Zika virus infection, because ocular findings might be underdiagnosed if microcephaly continues to be an inclusion criterion in the screening of this group of infants. We declare no competing interests.
JAMA Ophthalmology | 2016
Camila V. Ventura; Liana O. Ventura; Vasco Bravo-Filho; Thayze T. Martins; Audina M. Berrocal; Adriana L. Gois; Joao Rafael Dias; Leandro Araújo; Paulo Escarião; Vanessa van der Linden; Rubens Belfort; Mauricio Maia
Importance Zika virus (ZIKV) can cause severe changes in the retina and choroid that may result in marked visual impairment in infants with congenital Zika syndrome (CZS), the term created for a variety of anomalies associated with intrauterine ZIKV infection. Objective To evaluate the affected retinal layers in infants with CZS and associated retinal abnormalities using optical coherence tomography (OCT). Design, Setting, and Participants This cross-sectional, consecutive case series included 8 infants (age range, 3.0-5.1 months) with CZS. Optical coherence tomographic images were obtained in the affected eyes of 7 infants with CZS who had undergone previous ophthalmologic examinations on March 17, 2016, and in 1 infant on January 1, 2016. An IgM antibody-capture enzyme-linked immunosorbent assay for ZIKV was performed on the cerebrospinal fluid samples of 7 of the 8 infants (88%), and other congenital infections were ruled out. Main Outcomes and Measures Observation of retinal and choroidal findings in the OCT images. Results Among the 8 infants included in the study (3 male; 5 female; mean [SD] age at examination, 4.1 [0.7] months), 7 who underwent cerebrospinal fluid analysis for ZIKV had positive findings for IgM antibodies. Eleven of the 16 eyes (69%) of the 8 infants had retinal alterations and OCT imaging was performed in 9 (82%) of them. Optical coherence tomography was also performed in 1 unaffected eye. The main OCT findings in the affected eyes included discontinuation of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium in 9 eyes (100%), retinal thinning in 8 eyes (89%), choroidal thinning in 7 eyes (78%), and colobomatouslike excavation involving the neurosensory retina, retinal pigment epithelium, and choroid in 4 eyes (44%). Conclusions and Relevance Zika virus can cause severe damage to the retina, including the internal and external layers, and the choroid. The colobomatouslike finding seen in the OCT images relate to the excavated chorioretinal scar observed clinically.
Retina-the Journal of Retinal and Vitreous Diseases | 2012
Rohini Rao; Nina J. Jonsson; Camila V. Ventura; Rony Gelman; Martin A. Lindquist; Daniel S. Casper; Michael F. Chiang
Purpose: To examine the impact of retinal field of view and magnification on interexpert reliability of plus disease diagnosis in retinopathy of prematurity. Methods: Fifteen wide-angle images from infants with retinopathy of prematurity were cropped and adjusted in magnification to create 2 additional image categories: medium angle (40°–50°) and narrow angle (20°–30°). These 45 images were uploaded to a Web-based system and interpreted independently by 13 experts of retinopathy of prematurity using a 3-level (plus, preplus, neither) and 2-level (plus, not plus) classification. Absolute agreement and kappa statistics were calculated to compare interexpert reliability. Results: In the 3-level classification, ≥70% experts agreed on the same diagnosis in 8 of the 15 wide-angle images (53%), but only in 3 of the 15 medium-angle (20%) and 3 of the 15 narrow-angle (20%) images. In the 2-level classification, ≥80% experts agreed on the same diagnosis in 11 of the 15 wide-angle images (73%), but only in 9 of the 15 medium-angle (60%) and 3 of the 15 narrow-angle (20%) images. Mean kappa of each expert compared with all other experts was 0.40 to 0.59 in 8 of 13 experts (62%) using wide-angle images, was 0 to 0.19 in 7 of 13 experts (54%) using medium-angle images, and was 0.20 to 0.39 in 9 of 13 experts (69%) using narrow-angle images. Conclusion: Interexpert agreement in plus disease diagnosis in wide-angle images is higher than from medium-angle and narrow-angle images. Plus disease is defined using a narrow-angle standard published photograph, yet this study suggests that peripheral findings also contribute to diagnosis.
Retinal Cases & Brief Reports | 2017
João Rafael de Oliveira Dias; Camila V. Ventura; Paula Borba; Bruno de Paula Freitas; Ligia Camera Pierroti; Ana Patricia do Nascimento; Nilva Moraes; Mauricio Maia; Rubens Belfort
Background/Purpose: To describe the ocular findings of two infants with congenital Zika syndrome born in São Paulo state, Brazil, outside the primary outbreak region. Methods: Two female infants with congenital Zika syndrome were submitted to a complete screening for infectious diseases, as well as ocular examination, fundus photography, and optical coherence tomography of the retina. One of the infants was submitted to ocular ultrasound. Results: Both children showed positive serology for Zika virus, and other infectious diseases were ruled out. On fundus examination, one newborn had extensive bilateral macular chorioretinal atrophy with hyperpigmented borders associated with gross pigment mottling, as well as atrophic well-limited roundish peripheral lesions in the right eye. Spectral domain optical coherence tomography of the right eye showed complete chorioretinal atrophy in the temporal quadrant. The other infant presented bilateral gross pigment mottling in a paramacular location and a normal optical coherence tomography. Discussion: In this report, the ophthalmologic findings of two infants with Zika syndrome and ocular findings born in São Paulo state, Brazil, are described. Optical coherence tomography findings demonstrate the broad range of retinal damage caused by congenital Zika virus infection. Conclusion: The autochthonous cases of infants with congenital Zika syndrome and ocular findings described in this report demonstrate that Zika virus infection is not limited to northeast Brazil, with the potential for even greater spread.
JAMA Ophthalmology | 2017
Tomas S. Aleman; Camila V. Ventura; Milena M. Cavalcanti; Leona W. Serrano; Anastasia Traband; Akosua A. Nti; Adriana L. Gois; Vasco Bravo-Filho; Thayze T. Martins; Charles W. Nichols; Mauricio Maia; Rubens Belfort
Importance A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). Objective To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. Design, Setting, and Participants This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. Main Outcomes and Measures The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Results Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency. Conclusions and Relevance Congenital Zika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the first, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.