Liana O. Ventura

Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection

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.

Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians

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.

AUTISM AND MÖBIUS SEQUENCE An exploratory study of children in northeastern Brazil

The psychiatric examination was performed with diagnostic instruments for autism (DSM-IV and Childhood Autism Rating Scale-CARS) in 23 children with Möbius sequence. From the 23 patients studied with Möbius sequence, five (26.1%) met the diagnostic criteria for infantile autism according DSM-IV and two (8.6%), under two years old, showed autistic-like behavior. The scores for six children were compatible to severe autism symptoms according CARS and one child met the criteria for moderate autism symptoms. Among five children with autism, three (60%) had positive history of misoprostol exposure during the first trimester of pregnancy and from two cases autistic-like, one (50%) had positive history of misoprostol exposure during pregnancy. According to our data, this is the first report of Möbius sequence with autism and positive history of misoprostol use during pregnancy.

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

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: neurological and ocular findings in infant without microcephaly

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.

Optical Coherence Tomography of Retinal Lesions in Infants With Congenital Zika Syndrome

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.

Barreiras para o acesso ao tratamento da catarata senil na Fundação Altino Ventura

PURPOSE: To identify the barriers in the access to treatment of senile cataract and to evaluate the patients costs in this process. METHODS: A survey of 101 patients who would undergo cataract surgery at Altino Ventura Foundation was performed using a questionnaire. The economical and social aspects of the whole process of treatment were evaluated. RESULTS: The principal barriers of cataract treatment were: fear of surgery, patients low income, the need for preoperative examinations and the number of times the patient had to return to the service (3.2±1.5), as well as the waiting time between the first examination and the surgery (3.2±2.6 months - Mean ±SEM). The examination costs varied from 5 to 170 reais (16.6±2.7 - Mean ±SEM). DISCUSSION: The main reasons for not seeking for cataract treatment, as the fear to undergo surgery and the lack of financial resources had been similar to other Brazilian institutions. The number of times that the patient had to return to the service increased the expenses of the patient and the difficulties faced by him. Altino Ventura Foundation mainly takes care of the poorest population of the State, therefore, the expenses of the patients with transportation and examinations become obstacles to the treatment of cataract. CONCLUSIONS: The fear of surgery and the patients low income and the social level of the institutions users were the principal barriers in the access to cataract treatment in this study. The need for preoperative examinations, sometimes unnecessary, contributes to a lower efficiency of the medical services offered to individuals of low income and social conditions. The surgery carried out at the same day of the cataract diagnosis makes the solution of the illness quickly possible, diminishing the number of times necessary for the patients return to health service from three or more, to only one.

Outcomes of congenital cataract surgery: Intraoperative intracameral triamcinolone injection versus postoperative oral prednisolone

Purpose To compare the outcomes of congenital cataract surgery using intraoperative intracameral triamcinolone versus postoperative oral prednisolone to modulate ocular inflammation. Setting Department of Congenital Cataract, Altino Ventura Foundation, Recife, Brazil. Design Randomized clinical trial. Methods Children younger than 2 years were randomly divided into 2 groups. The study group received an intraoperative intracameral injection of 1.2 mg/0.03 mL of triamcinolone acetonide. The control group (29 eyes) received 1 mg/kg per day of prednisolone syrup for 15 days postoperatively, which was then tapered over the following 2 weeks. Intraocular pressure (IOP), central corneal thickness (CCT), cell deposits on the intraocular lens (IOL), posterior synechiae, visual axis obscuration, additional surgical procedures, and IOL centration were assessed 12 months postoperatively. Results The mean patient age at surgery was 10.45 months ± 6.22 (SD) in the study group (31 eyes) and 10.0 ± 6.15 months in the control group (29 eyes) (P = .779). In both groups, the mean IOP and CCT did not change significantly postoperatively (study group P = .922 and P = .149, respectively; control group P = .483 and P = .416, respectively). The groups had similar incidences of cell deposits (P = .517) and posterior synechiae (P = .247). No eye developed visual axis obscuration or had additional surgical procedures. All eyes had a clinically centered IOL. Conclusion One year postoperatively, the outcomes were similar with intraoperative intracameral triamcinolone injection and postoperative oral prednisolone for modulating inflammation after congenital cataract surgery. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Resposta humoral ao vírus dengue em mães/filhos: relação com a sequência de Möbius

PURPOSE To investigate the humoral immune response to dengue virus in patients with Möbius sequence and their mothers, assessing the relation between this infection during pregnancy and Möbius sequence. METHODS The medical records were reviewed, and a questionnaire was answered by each mother. IgG ELISA was performed in 35 patients and their mothers. A plaque reduction neutralization test was further done in the mothers who reported a viral infection during pregnancy and in their children for determining which dengue serotype virus had caused the infection. RESULTS Fever, headache and/or retrobulbar pain during pregnancy was referred by eighteen (51.4%) mothers. Three (8.6%) reported dengue during the first or second quarteers of pregnancy. When cross analyzing the mothers and their respective children serological results, 57.1% of them matched. Of the three mothers with clinical diagnosis of viral infection during pregnancy, one and its respective children had a positive plaque reduction neutralization test for dengue serotype three (DENV-3), this serotype reached Pernambuco in 2002, which excludes the possibility of a vertical transmission to the children. CONCLUSION The serology of the cases that had clinical diagnosis of dengue during pregnancy proved to be incompatible with the hypothesis of the disease vertical transmission. Therefore, in the present serie, the dengue virus infection can not be considered as a factor involved in the genesis of Möbius sequence.

Retinoblastoma bilateral de aparecimento tardio: relato de caso

A case of retinoblastoma with uncommon features is reported, aiming at improving follow-up. In 1993, SJMMF, 9-month-old white boy, presented a squint in the left eye. A retinal tumor was detected. The patient had a family history of retinoblastoma. Enucleation was performed and retinoblastoma was proved. The patient underwent examination for staging, all were normal. The fellow eye remained normal for 10 years. During routine examination the retina map revealed three retinoblastoma white lesions in the nasal retina. The patient underwent transpupillary thermotherapy with diode laser. After 30 days, the lesions became atrophic. After 60 days there was tumor recurrence on the border of the lesion. Sclera cryotherapy was performed. There was tumor regression for six months. During follow-up, condensations next to the atrophic tumor lesions were discovered, which were vitreous seeds. Brachitherapy with 125 iodine was done. The lesions disappeared after 30 days. New vitreous seeds appeared 3 months later, set on the retina surface. They were blocked with sclera cryotherapy and transpupillary thermotherapy. The patient presented with new vitreous seeds after six months, which adhered to the retina. They were blocked with transpupillary thermotherapy. Follow-up was for 38 months since the appearance of the bilateral tumor. The patient presents normal visual acuity and clinical examination. This case is important considering the low frequency of the disease at this age. It is essential to maintain alertness when cases of retinoblastoma are seen as cured.