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Abstract Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.

ABSTRACT Objective: To evaluate the epidemiological, clinical, and imaging profile of lesions that mimic choroidal melanoma. Methods: Retrospective study of medical records of suspected choroidal melanoma lesions referred to the Ocular Oncology Service from the Universidade Federal de São Paulo, from 2014 to 2020. Demographic data, clinical history, and exams were evaluated. Results: A total of 104 patients (mean age: 65.57 ± 13.18; 49.04% female) were referred to our service with suspected choroidal melanoma. Of these, 32 (30.77%) were classified as pseudomelanoma, while 72 (69.23%) had a confirmed diagnosis of choroidal melanoma. Pseudomelanoma cases manifested in older individuals (p < 0.001), with smaller lesions in height (p < 0.001), anteroposterior diameter (p = 0.008), and lateral diameter (p = 0.003) on ultrasound. Pseudomelanoma cases were associated with higher frequencies of vitreous hemorrhage (p = 0.014) and lower rates of the presence of a mass (p = 0.001) and retinal detachment (p < 0.001). The main diagnoses of pseudomelanoma cases were choroidal nevus (40.63%), subretinal hemorrhage (18.75%) and choroidal neovascular membrane (18.75%). Conclusion: Almost one third of the cases referred with suspected choroidal melanoma were pseudomelanomas, which demonstrates that there is still a considerable path to improve the ability of general ophthalmologists to clinically discriminate melanoma from other conditions that can mimic it.

Abstract Failure to recognize the different possible clinical presentations of ocular toxoplasmosis may delay diagnosis and treatment, compromising visual prognosis. The aim of this paper is to describe an atypical pattern of ocular toxoplasmosis, not yet described. Five Brazilian patients, from 4 different referral centers, presented similar atypical pattern of ocular toxoplasmosis characterized by mild vitritis, foveal cavitation involving predominantly all retinal layers associated with adjacent inner retinal necrosis (a necrotizing retinitis with a persisting inner retinal tissue bridge and loss of subjacent retinal layers). The appearance of the OCT image resembling a “rift”, led the authors to define this pattern as a Recurrent Inner Foveal Toxoplasmic Retinitis (RIFTER), which can be considered as a new description of an atypical pattern of toxoplasma retinochoroiditis, and clinicians should be aware of it and consider testing for toxoplasmosis in patients with similar findings.

Abstract Background Age-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes. Materials and Methods This study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period. Results The best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p

Abstract Background Choroid, ciliary body, and iris melanomas are often grouped as uveal melanoma, the most common intraocular primary malignancy. The purpose of the current study was to analyze the tumor profile of newly diagnosed cases of choroidal melanoma at a reference center in Sao Paulo, Brazil, and to investigate the frequency of eyes treated by enucleation that could have been treated with brachytherapy if available in the service. Methods Medical records of patients referred to our service with initial diagnostic hypothesis of choroidal melanoma from July 2014 to June 2020 were analysed on demographics, diagnosis confirmation, tumor measurement by ultrasonography and established treatment. Data were evaluated on clinical and demographic characteristics as age, sex, affected eye, ultrasound parameters, and treatment management of patients with clinically diagnosed choroidal melanoma. Among the patients submitted to enucleation, we investigated how many could have been selected to receive brachytherapy. Results From the 102 patients referred with the choroidal melanoma diagnosis hypothesis, 70 (68.62%) were confirmed. Mean measurements from the tumors in millimetres were: 9.19 ± 3.69 at height and 12.97 ± 3.09 by 13.30 ± 3.30 at basal. A total of 48 cases (68.57%) were enucleated, 8 (11.43%) were treated by brachytherapy in a different service, and 14 patients (20.00%) returned for enucleation at their original referral center. Out of the 48 patients enucleated, 26 (54.17%) could have been selected to brachytherapy treatment. Conclusions The results indicate a late diagnosis of choroidal melanoma cases referred to our service. Most enucleated cases could have been treated with brachytherapy if it was broadly available at the national public health insurance. Further public health political efforts should focus on early diagnosis and better quality of life post-treatment for oncologic patients.

Abstract Background Tuberculosis (TB) caused by Mycobacterium tuberculosis has a high prevalence in Brazil (Global tuberculosis report 2020. Geneva: World Health Organization; 2020). The ethambutol-induced optic neuropathy damage is partly reversible, making its early diagnosis essential to reduce permanent visual damage. Purpose To observe alterations in the computerized campimetry, Ishihara test and visual acuity secondary to rifampicin, isoniazid, pyrimethamine, ethambutol (RHZE) treatment. Methods Patients undergoing treatment with RHZE at the tuberculosis service of the Federal University of São Paulo were recruited from March 2019 to December 2020. The best-corrected visual acuity (VA) measurements, Ishihara test and visual fields were performed at baseline, monthly, until 2 weeks after treatment. Results Twenty-five patients were included. The VA decreased significantly (P = 0.0129) post-treatment compared to month 1. The mean deviation (MD) did not decrease significantly (P > 0.05); the pattern standard deviation (PSD) decreased post-treatment compared to month 1 (P = 0.0371). Changes in the Ishihara test increased significantly (P

Abstract Background Artificial intelligence and automated technology were first reported more than 70 years ago and nowadays provide unprecedented diagnostic accuracy, screening capacity, risk stratification, and workflow optimization. Diabetic retinopathy is an important cause of preventable blindness worldwide, and artificial intelligence technology provides precocious diagnosis, monitoring, and guide treatment. High-quality exams are fundamental in supervised artificial intelligence algorithms, but the lack of ground truth standards in retinal exams datasets is a problem. Main body In this article, ETDRS, NHS, ICDR, SDGS diabetic retinopathy grading, and manual annotation are described and compared in publicly available datasets. The various DR labeling systems generate a fundamental problem for AI datasets. Possible solutions are standardization of DR classification and direct retinal-finding identifications. Conclusion Reliable labeling methods also need to be considered in datasets with more trustworthy labeling.

Abstract Recently, it has been recommended that population-based studies report not only frequencies of vision impairment and blindness but also any ocular abnormalities that might lead an individual to seek for eyecare services. The current study aimed to determine prevalence of ocular findings regardless of visual acuity (VA) status in older adults from the Brazilian Amazon Region. Disturbances were grouped into: Eyelids; Anterior Segment; Posterior Segment; Increased intraocular pressure; and Overall Globe. The presence of an ocular finding was considered positive when any abnormality was noted, regardless of VA. Refractive errors were not considered. A total 2384 eligible persons were enumerated and 2041 (85.6%) examined. The prevalence of ocular disturbances in either eye was 87.0% and was associated with male gender, older age, lower education, and rural residence. Overall, main findings were pterygium, cataract, and pinguecula, occurring in 58.8%, 45.4% and 17.4%, respectively. Among individuals with 20/20 VA in both eyes, the most frequent findings were pterygium, pinguecula, and glaucoma cupping, occurring in 47.4%, 31.2% and 6.5%, respectively. The high prevalence of ocular findings observed in this population reinforces that different conditions might not immediately decrease VA but can indicate risk and/or discomfort symptoms and should be considered when planning public health ophthalmic services.

Abstract The main purpose of this study was to investigate the presence of retinal autofluorescence findings in COVID-19 patients. Observational study conducted in São Paulo in 2020. Demographic, medical history, and concomitant events, as well as medications used, hospitalization details, and laboratory test results, were obtained. Patients underwent eye examination and multimodal imaging, including color, red-free, autofluorescence fundus photography and optical coherence tomography. Eighteen patients had autofluorescence findings (6 females; average age 54 years, range 31 to 86 years; 26 eyes). Hyper-autofluorescence findings were present in 6 patients, Hypo-autofluorescence in 14 patients, and 6 patients had mixed pattern lesions. Retinal autofluorescence abnormalities were present in COVID-19 patients and may be secondary to primary or secondary changes caused by the SARS-CoV-2.

Objective: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. Design: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. Participants: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. Methods: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. Main Outcome Measures: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. Results: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5 × 10−5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. Conclusions: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.

Abstract The challenge of COVID-19 has rapidly changed medical management worldwide. The relatively small time from pandemic to vaccines regulatory approval triggered a race toward vaccines development. However, important questions regarding SARS-CoV-2 vaccines remain. A case of complete Vogt-Koyanagi-Harada (VKH) Syndrome that occurred 4 days following SARS-CoV-2 vaccination and another patient that developed VKH 14 days post COVID-19 clinical onset are presented. A causal relationship between COVID-19 and uveitis may exist.

Abstract Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14–22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45–47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82–30.67; p

RESUMO O hemangioma de coroide é um tumor vascular benigno, de coloração vermelho-alaranjada, bem delimitado, caracterizado por uma placa elevada. É um tumor raro, com prevalência de um caso a cada 40 tumores de coroide. O diagnóstico pode ser feito por meio da clínica associada à avaliação biomicroscópica e a exames complementares para diferenciação de outros tumores. O tratamento pode ser expectante nos casos assintomáticos. Para os casos sintomáticos ou com presença de fluido sub-retiniano, existem diversas terapias. O objetivo deste estudo foi relatar um caso de hemangioma circunscrito de coroide submetido a tratamento combinado de terapia fotodinâmica com verteporfina e injeção intravítrea de antiangiogênico (bevacizumabe). A decisão de tratar um hemangioma de coroide deve ser individualizada com base nos sintomas, na perda visual e em qualquer potencial de sua recuperação. O exame oftalmológico completo é necessário, mesmo em casos assintomáticos, para rastreamento precoce de doenças oculares.

Abstract Background Ocular toxoplasmosis is one of the most common causes of intraocular inflammation and posterior uveitis in immunocompetent patients. This paper aims to investigate swept-source optical coherence tomography angiography (SS-OCTA) findings in eyes with active toxoplasmic retinochoroiditis. Methods This case series was conducted from November 2017 through October 2019 in two Brazilian centers. 15 eyes of 15 patients with active toxoplasmic retinochoroiditis were included, and were imaged at baseline and after at least 4 weeks of follow-up. All patients underwent ophthalmic examinations and multimodal imaging including SS-OCT and SS-OCTA before and after treatment of ocular toxoplasmosis. The differential diagnoses included toxoplasmosis, syphilis, and human immunodeficiency virus, which were eliminated through serologic and clinical evaluations. Results All 15 patients presented with positive anti-Toxoplasma gondii immunoglobulin G titers and three also presented with positive anti-T. gondii immunoglobulin M titers. The mean age at examination was 32.4 years ± 12.7 years (range 15–59 years). Sixty percent of the patients were female. In all eyes, the inner retinal layers were abnormally hyperreflective with full-thickness disorganization of the retinal reflective layers at the site of the active toxoplasmic retinochoroiditis. At baseline, 80% of eyes had focal choroidal thickening beneath the retinitis area, and all eyes had a choroidal hyporeflective signal. Before treatment, SS-OCTA showed no OCTA decorrelation signal next to the lesion site in all eyes, and flow signal improvement was noticed after treatment. Three eyes presented with intraretinal vascular abnormalities during follow-up. SS-OCTA showed retinal neovascularization in one patient and a presumed subclinical choroidal neovascular membrane in another patient. Conclusions SS-OCT and SS-OCTA are useful for assessing unexpected structural and vascular retinal and choroidal changes in active and post-treatment toxoplasmic retinochoroiditis and these findings are useful for clinical practice.

Abstract Background To objectively evaluate YAG laser vitreolysis for symptomatic vitreous floaters using color photo imaging. Methods In this interventional and prospective study, 32 eyes of 32 patients with symptomatic vitreous floaters secondary to posterior vitreous detachment (PVD) were treated with a single session of yttrium aluminum garnet (YAG) laser. Primary outcomes were objective and subjective changes measured by masked grading of color fundus photographs and National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25), respectively. Secondary outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA) and adverse events. Wilcoxon signed-rank test was used to analyze the results of the objective and subjective assessments at each time point. P

ABSTRACT: Background: Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. Methods: A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. Results: Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. Conclusion: To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

Importance: Large language models being approved in medical boarding examinations highlights problems and challenges for healthcare education, improving tests, and deployment of chatbots. Objective: The objective of this study was to evaluate the performance of ChatGPT-3.5 in answering the Brazilian Council of Ophthalmology Board Examination. Material and Methods: Two independent ophthalmologists inputted all questions to ChatGPT-3.5 and evaluated the responses for correctness, adjudicating in disagreements. We compared the performance of the ChatGPT across tests, ophthalmological themes, and mathematical questions. The included test was the 2022 Brazilian Council of Ophthalmology Board Examination which consists of theoretical test I, II, and theoretical–practical. Results: ChatGPT-3.5 answered 68 (41.46%) questions correctly, 88 (53.66%) wrongly, and 8 (4.88%) undetermined. In questions involving mathematical concepts, artificial intelligence correctly answered 23.8% of questions. In theoretical examinations I and II, correctly answered 43.18% and 40.83%, respectively. There was no statistical difference (odds ratio 1.101, 95% confidence interval 0.548–2.215, P = 0.787) comparing correct answers between tests and comparing within the test themes (P = 0.646) for correct answers. Conclusion and Relevance: Our study shows that ChatGPT would not succeed in the Brazilian ophthalmological board examination, a specialist-level test, and struggle with mathematical questions. Poor performance of ChatGPT can be explained by a lack of adequate clinical data in training and problems in question formulation, with caution recommended in deploying chatbots for ophthalmology.

Purpose: The purpose of this study was to describe a new corneal drug delivery technique using a tattoo machine. Materials and Methods: Five human eye bank corneas and four rabbits were included in the study. All interventions were performed with a tattoo machine with the following: 60-Hz needling speed, 200-μ needling depth, and liner cartridges with seven solid microneedles. Our study was conducted in two stages: an experimental model with ink injection in eye bank corneas and a drug delivery in the corneas of live rabbis. Each cornea received from the eye bank was injected with black and brown inks. Each rabbit received an intrastromal application of biguanide 0.2 mg/mL, triamcinolone 40 mg/mL, or bevacizumab 25 mg/mL. Dry needling was performed in the fourth rabbit. The rabbits were followed clinically for 30 days and were euthanized on day 30. All corneas were photographed before and after the procedure and then processed, stained with H and E, and underwent microscope analysis. Results: In the human corneas, pigment was delivered into the corneas with the tattoo machine and the ink remained in the stroma at the desired and stipulated depth. In the rabbits, the treated corneas showed no vascularization, inflammatory cells, or corneal perforation after 30 days of the procedure. Conclusions: Corneal drug delivery performed with the tattoo machine was achieved without side effects. Further studies are needed to determine the safety and effectiveness of the intervention in ocular pathologies.

Abstract Background With increasing incidence of yellow fever, mass campaign vaccinations are underway and little ophthalmological alterations have been reported in literature, specially regarding non-combined vaccines. Case presentation We report the case of a patient with no previous ocular or systemic diseases whom received a single dose of yellow fever vaccination and developed haematological, hepatic and renal alterations progressing with a later onset bilateral asymmetric diffuse uveitis. Ophthalmological findings included fine keratic precipitates scattered throughout the cornea and mild vitritis. Multimodal evaluation showed subtle puntiform choriocapillaris changes with decreased vascular density associated. The patient had a good visual outcome after mild oral prednisone dose, but the image findings have not presented remission. Conclusions Clinicians should be aware of clinical and subclinical ocular manifestations such as subtle puntiform choriocapillaris changes as possible vaccine-related adverse events with potential to impact vision.

Abstract Background The World Health Organization (WHO) estimates that the number of individuals who lose their vision due to retinal degeneration is expected to reach 6 million annually in 2020. The retinal degenerative diseases affect the macula, which is responsible for central and detailed vision. Most macular degeneration, i.e., age-related macular degeneration (AMD) develops in the elderly; however, certain hereditary diseases, such as the Stargardt disease, also affect young people. This degeneration begins with loss of retinal pigmented epithelium (RPE) due to formation of drusen (atrophic) or abnormal vessels (exudative). In wet AMD, numerous drugs are available to successful treat the disease; however, no proven therapy currently is available to treat dry AMD or Stargardt. Since its discovery, human embryonic stem cells (hESCs) have been considered a valuable therapeutic tool. Some evidence has shown that transplantation of RPEs differentiated from hESCs cells can result in recovery of both RPE and photoreceptors and prevent visual loss. Methods The human embryonic WA-09 stem cell lineage was cultured under current Good Manufacturing Practices (cGMP) conditions using serum-free media and supplements. The colonies were isolated manually and allowed to spontaneously differentiate into RPE cells. Results This simple and effective protocol required minimal manipulation and yielded more than 10e8 RPE cells by the end of the differentiation and enrichment processes, with cells exhibiting a cobblestone morphology and displaying cellular markers and a gene expression profile typical of mature RPE cells. Moreover, the differentiated cells displayed phagocytic activity and only a small percentage of the total cells remained positive for the Octamer-binding transcriptions factor 4 (OCT-4) pluripotency cell marker. Conclusions These results showed that functional RPE cells can be produced efficiently and suggested the possibility of scaling-up to aim at therapeutic protocols for retinal diseases associated with RPE degeneration.

Abstract Background To evaluate the benefits of lutein in preventing retinal phototoxicity generated by xenon light sources during vitreoretinal surgery. Methods A prospective cross-sectional study in pigmented rabbit eyes exposed to different vitreoretinal surgery lighting simulations. Twenty Dutch-belted rabbits were divided into two groups exposed to two different xenon wavelength light sources filters (420 nm and 435 nm). In addition, two subgroups were administered with daily supplemental of 10 mg of Lutein systemically. Electroretinography (ERG), optical coherence tomography (OCT) and fluorescein angiography (FA) were performed before and after surgery to quantify the retinal damage. Results All animals submitted to the experiment presented some degree of phototoxicity independent of wavelength light filter used. Retinal damage was evident as the FA presented areas of hyperfluorescence, and the OCT depicted increased reflective areas of the inner and outer retinal layers, and RPE. ERG showed a diffuse reduction of the a and b waves amplitudes in all animals. Conclusion Use of systemic administration of lutein showed no benefit to avoiding retinal phototoxicity generate to xenon light source using filters of 435 nm and 420 nm when comparing to the control group.

BackgroundThe prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.Methodology/principal findingsWe performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1-24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3-26.9), with a PAF of 59.5%.ConclusionsA significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

Purpose: The photopic negative response (PhNR) is an electrophysiological method that provides retinal ganglion cell function assessment using full-field stimulation that does not require clear optics or refractive correction. The purpose of this study was to assess ganglion cell function by PhNR in affected and asymptomatic carriers from Brazilian families with LHON.Methods: Individuals either under suspicion or previously diagnosed with LHON and their family members were invited to participate in this cross-sectional study. Screening for the most frequent LHON mtDNA mutations was performed. Visual acuity, color discrimination, visual fields, pattern-reversal visual evoked potentials (PRVEP), full-field electroretinography and PhNR were tested. A control group of healthy subjects was included. Full-field ERG PhNR were recorded using red (640 nm) flashes at 1 cd.s/m2, on blue (470 nm) rod saturating background. PhNR amplitude (μV) was measured using baseline-to-trough (BT). Optical coherence tomography scans of both the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were measured. PhNR amplitudes among affected, carriers and controls were compared by Kruskal-Wallis test followed by post-hoc Dunn test. The associations between PhNR amplitude and OCT parameters were analyzed by Spearman rank correlation.Results: Participants were 24 LHON affected patients (23 males, mean age=30.5 ± 11.4 yrs) from 19 families with the following genotype: m.11778G>A [N = 15 (62%), 14 males]; m.14484T>C [N = 5 (21%), all males] and m.3460G>A [N = 4 (17%), all males] and 14 carriers [13 females, mean age: 43.2 ± 13.3 yrs; m.11778G>A (N = 11); m.3460G>A (N = 2) and m.14484T>C (N = 1)]. Controls were eight females and seven males (mean age: 32.6 ± 11.5 yrs). PhNR amplitudes were significantly reduced (p = 0.0001) in LHON affected (−5.96 ± 3.37 μV) compared to carriers (−16.53 ± 3.40 μV) and controls (−23.91 ± 4.83; p < 0.0001) and in carriers compared to controls (p = 0.01). A significant negative correlation was found between PhNR amplitude and total macular ganglion cell thickness (r = −0.62, p < 0.05). Severe abnormalities in color discrimination, visual fields and PRVEPs were found in affected and subclinical abnormalities in carriers.Conclusions: In this cohort of Brazilian families with LHON the photopic negative response was severely reduced in affected patients and mildly reduced in asymptomatic carriers suggesting possible subclinical abnormalities in the latter. These findings were similar among pathogenic mutations.

ObjectiveTo describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age.MethodWe followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively.ResultsOf the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (β = 0.29; CI 95% = 0.02-0.57) and motor raw scores (β = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (β = 1.27; CI 95% = 0.01-2.53) and motor raw scores (β = 2.03; CI 95% = 0.25-3.81).ConclusionChildren with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.

Introduction: Pterygium represents a significant cause of visual impairment and blindness in the Amazon and surgery is the only definitive treatment available. The cost of surgery and the need for prolonged postoperative follow-up have proved to be an obstacle to its management. The aim of this prospective study carried out in the southern region of the Amazon was to evaluate telemedicine in the pterygium surgery follow-up to help make pterygium surgery postoperative care feasible in places without ophthalmologic assistance. Materials and Methods: Postoperative follow-up care was done through teleconsultation. It involved capturing photographs from the corneal and conjunctiva by trained technicians and sending them to a reading center for an ophthalmologist's assessment based on an asynchronous (store-and-forward) model. Patients and ophthalmologists were inquired about their satisfaction regarding the postoperative follow-up. Results: All pictures were classified as adequate, allowing proper assessments of results and complications. It was possible to manage the postoperative and conclude there were no postoperative surgical complications during the 6-month follow-up. All patients reported satisfaction with the remote performed evaluation and considered that all their doubts and expectations were met. Conclusion: Teleophthalmology allows remote access and can significantly improve eye care quality, access, and affordability. It may represent an alternative to providing pterygium surgery postoperative monitoring in areas without the availability of an ophthalmologist, making it possible to combat one of the leading causes of reversible blindness in the equatorial region.

Abstract Background Swept-source optical coherence tomography (SS-OCT) has a higher scanning rate and longer wavelength in comparison with spectral-domain OCT (SD-OCT), allowing an improved imaging of retinal vascular plexuses and choriocapillaris. The present two patients diagnosed with multiple evanescent white dot syndrome (MEWDS) underwent fundus autofluorescence (FAF), en-face SS-OCT, and SS-OCT angiography (OCTA) imaging, and its features were described and correlated. Results The clinical and imaging findings of both cases were consistent with the diagnosis of MEWDS. Color fundus photograph revealed subtle deep retinal white spots in the posterior pole and around the optic disk. FAF showed several hyperautofluorescent lesions corresponding topographically to the subtle deep retinal white lesions observed on color fundus photographs. Cross-sectional SS-OCT showed disruption of the ellipsoid zone (EZ) within the macular area in all study patients. En-face SS-OCT at the level of the outer retina showed lower reflectivity correspondent to the diffuse attenuation due to the EZ disruption on cross-sectional OCT. SS-OCTA demonstrated flow preservation within the retinal vasculature and choriocapillaris. Conclusions SS-OCT imaging allows a better visualization of the choriocapillaris, and its normal appearance in MEWDS may suggest that the outer retina and photoreceptors represent the primary site of inflammation.

Abstract Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-β superfamily (TGF-β1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.

Abstract Purpose To evaluate the concentration of vascular endothelial growth factor (VEGF) in aqueous humor after a single intravitreal injection of bevacizumab (IVB) in eyes with neovascular age-related macular degeneration (AMD). Methods In this prospective interventional case series study, 24 eyes of 24 patients with types 1 and 2 choroidal neovascularization secondary to neovascular AMD were treated with a single intravitreal injection of bevacizumab. Aqueous humor samples were obtained before the intravitreal injection and at one week, one month, and three months follow-up periods. Best-corrected visual acuity (BCVA) and three spectral-domain optical coherence tomography parameters (central retinal thickness, macular volume and macular area) were also analyzed and correlated with VEGF expression at the baseline and each follow-up period. Results All of the ninety-six aqueous humor study taps were well tolerated by the study patients without adverse events. Increased VEGF levels (mean ± SD = 179.7 ± 88.3 pg/mL) were observed in the aqueous humor of all study patients before the intravitreal injection of bevacizumab. At all follow-up periods, compared to baseline, levels of VEGF significantly reduced (P 0.005), CRT, MV and MA also reduced in comparison to baseline. Conclusions Single intravitreal bevacizumab injection in eyes with neovascular AMD resulted in a substantial decrease of aqueous VEGF levels 1 week after treatment with the greatest improvement of clinical outcomes occurring at 1 month follow-up.

We found significantly higher incidence of Toxoplasma gondii DNA in eye bank specimens from Joinville in southern Brazil (13/15, 87%) than in São Paulo (3/42, 7%; p = 2.1 × 10E–8). PCR DNA sequence analysis was more sensitive at locus NTS2 than at locus B1; a high frequency of mixed co-infections was detected.

Purpose: Zika virus infection is associated with vision-threatening ocular complications including uveitis and outer retinopathy. The aim of this report is to describe a case of an adult patient with serologically confirmed Zika infection who presented with retinal vascular abnormalities that coincided with systemic post-viral neurological manifestations of the disease. Observations: A 34-year-old white female presented with symptoms of peripheral neuropathy following serologically confirmed Zika virus infection that was acquired in Puerto Rico four months prior to presentation. Ocular evaluation revealed perifoveal microaneurysms which were not associated with visual symptoms. Conclusions and importance: These data potentially expand the phenotypic spectrum of Zika virus retinopathy. In addition to outer retinal abnormalities which are well-described in infants and adults, inner retinal vascular abnormalities may also occur and may be temporally associated with post-viral neurological sequelae of Zika virus infection. Clinicians should be aware of potential retinal involvement in affected patients who present with neurological symptoms after recovery from acute Zika virus infection. Keywords: Zika virus, Retina, Vision, Vasculopathy, Angiography, Multimodal imaging

Context: Extracellular vesicles (EVs) are related to the dissemination of the pathogen and to the regulation of the host immune system in infectious diseases. However, the role of EVs in Ocular toxoplasmosis remains unclear. Aims: The goal of this study was to identify and characterize the concentration and size of EVs in the aqueous humor (AH) and plasma of patients with ocular toxoplasmosis (OT) compared to other types of uveitis (OTU) and cataract. Settings and Design: AH and plasma were collected from six patients with active OT, six patients with OTU, and six patients with cataract. All patients were also assessed clinically. Subjects and Methods: EVs were isolated using the membrane affinity column method. Nanoparticle Tracking Analysis (NTA) was performed to determine the size and concentration of EVs. Statistical Analysis Used: The ANOVA test was used to determine statistical difference. P < 0.05 was considered statistically significant. Results: EV was present in the AH of different types of uveitis as well as in patients with cataract. The concentration of EV in AH was significantly lower in OT and OTU compared to cataract (P = 0.03). However, in the plasma, all groups presented a similar concentration of EV. The size of EV was the same in the AH and plasma among the three groups. Conclusion: This initial study successfully identified and characterized EVs in the AH and plasma from patients with OT as well as OTU and cataract. Further studies are necessary to better understand the role of EVs in different ocular pathologies.

OBJECTIVES: To identify Chlamydia trachomatis via polymerase chain reaction and a direct fluorescent antibodyassay in patients with vernal keratoconjunctivitis while comparing the efficacies of both tests for detectingChlamydia trachomatis in these conditions. METHODS: Conjunctival scraping samples were obtained from 177 patients who were divided into two groups: avernal keratoconjunctivitis group (group A) and a control group (group B). The polymerase chain reaction and adirect fluorescent antibody assay were performed. Sensitivity, specificity, receiver operating characteristic curves,and areas under the curve were calculated for both tests in groups A and B. Receiver operating characteristic curveswere plotted using a categorical variable with only two possible outcomes (positive and negative). RESULTS: Statistical analysis revealed a significant association between vernal keratoconjunctivitis and Chlamydia trachomatis infection detected by a direct fluorescent antibody assay with high sensitivity and specificity. Allpatients in group A with positive polymerase chain reactions also presented with positive direct fluorescentantibody assays. CONCLUSION: The association between vernal keratoconjunctivitis and Chlamydia trachomatis infection wasconfirmed by positive direct fluorescent antibody assays in 49.4% of vernal keratoconjunctivitis patients and bypositive polymerase chain reactions in 20% of these patients. The direct fluorescent antibody assay detectedChlamydia trachomatis in a higher number of patients than did the polymerase chain reaction. Although thediagnosis of trachoma is essentially clinical, the disease may not be detected in vernal keratoconjunctivitis patients.Due to the high frequency of chlamydial infection detected in patients with vernal keratoconjunctivitis, we suggestconsidering routine laboratory tests to detect Chlamydia trachomatis in patients with severe and refractory allergicdisease.

Toxoplasmosis, a disease described worldwide, which is caused by the protozoan Toxoplasma gondii, commonly involves the retina. The disease has a higher impact in immunocompromised individuals and in congenital infection because of the severity of central nervous system involvement. Although simple prophylactic measures could reduce transmission, T. gondii seroprevalence is still high, especially in South America. Educational campaigns and the development of new drugs to prevent primary infection could potentially reduce the burden of the disease.

ABSTRACT Experimental autoimmune uveitis is an organ-specific T-cell mediated autoimmune disease characterized by inflammation and consequent destruction of the neural retina and adjacent tissues. Inflammation in experimental autoimmune uveitis may be induced in rodents by immunization with retinal antigens, such as interphotoreceptor retinoid-binding protein. We present a review of experimental studies that correlate primary immunobiological functions with this chronic disease and the possible use of molecules for the treatment of autoimmune uveitis.

OBJETIVO: A proposta deste estudo é avaliar a eficácia e eficiência em uma série de casos do protótipo de um equipamento nacional de magnificação para leitura. MÉTODOS: Participaram deste estudo 30 pacientes na faixa etária entre 9 e 80 anos (17 do sexo masculino). Foi desenvolvido um aparelho portátil, patenteado pela UNIFESP (PI#020050145260), com um sistema de captura de imagens acoplado a um monitor de 5,6 polegadas proporcionando um aumento de 15 X. Foram analisadas a eficácia da acuidade visual e a eficiência de leitura após a utilização do protótipo proposto. RESULTADOS: Seis pacientes (20%) apresentaram AV 8M, 12 pacientes (40%) apresentaram AV 6M, 7 pacientes (23,3%) apresentaram 5 M, 5 pacientes (16,7%) apresentaram 4M. A média de acuidade visual antes da utilização do SLP medida pela tabela LHNV-1 logMAR foi de 5,75M e após a utilização 100% dos pacientes atingiram a eficácia de AV J1. CONCLUSÃO: O protótipo do SLP mostrou-se um recurso alternativo no processo de inclusão social das pessoas com baixa visão com diferentes níveis de resíduo visual. Também pode proporcionar incentivo psicológico, permitir conforto, mobilidade e independência àqueles que necessitam de uma leitura mais prolongada e maior distância de trabalho.PURPOSE: The proposal of this study is to test and to validate as the effectiveness and efficiency in a series of cases the prototype of a national equipment of magnification to reading. METHODS: A recently developed of equipment of magnification (patent pending Brazilian Institutte of Industrial Property # 020050145260) was tested in a group of 30 patients (age range 9 to 80 years, 17 males). A portable apparatus was developed with a system of capture of images coupled with a 5,6 inch monitor, providing an increase of 15 X. The effectiveness of the visual acuity and the reading efficiency were analyzed after the use of the proposed prototype. RESULTS: Six patients (20%) presented AV 8M, 12 patients (40%) presented AV 6,0M, 7 patients (23.3%) presented AV 5M, 5 patients (16.7%) presented 4M. The average of visual acuity before the utilization of SPR measured by LHNV-1 logMAR chart was 5,75M. After the use of LHNV-1 logMAR chart, 100% (one hundred percent) of the patients reached the efficacy of AV J1. CONCLUSION: The prototype of SPR is an alternative resource in the social inclusion process of low vision patients with different levels of visual residue. It demonstrates psychological incentive, allows comfort, mobility and independence to those who need a more extended lecture and more distance of work.

Our purpose is to provide a summary overview of blindness and visual impairment on the context of recent Brazilian ocular epidemiologic studies. Synthesis of data from two cross-sectional population-based studies - the São Paulo Eye Study and the Refractive Error in School Children Study is presented. 3678 older adults and 2441 school children were examined between July 2004 and December 2005. Prevalence of blindness in older adults using presenting visual acuity was 1.51% decreasing to 1. 07% with refractive correction. The most common causes of blindness in older adults were retinal disorders, followed by cataract and glaucoma. In school children, the prevalence of uncorrected visual impairment was 4.82% decreasing to 0.41% with refractive correction. The most common cause of visual impairment in school children was uncorrected refractive error. Visual impairment and blindness in Brazil is an important public health problem. It is a significant problem in older Brazilians, reinforcing the need to implement prevention of blindness programs for elderly people with emphasis on those without schooling. In school-children cost-effective strategies are needed to address a readily treatable cause of vision impairment - prescription and provision of glasses.Nosso objetivo é fazer uma revisão de cegueira e deficiência visual no contexto de recentes estudos epidemiológicos oculares brasileiros. É apresentada a síntese dos dados de dois estudos populacionais transversais - o Estudo Ocular de São Paulo e o Estudo de Erros Refrativos em Escolares. Entre julho de 2004 e dezembro de 2005 foram examinados 3678 adultos e 2441 escolares. A prevalência de cegueira em adultos mais velhos considerando a acuidade visual apresentada foi de 1, 51% diminuindo para 1, 07% com a correção refrativa. As causas mais comuns de cegueira em adultos mais velhos foram os distúrbios de retina, seguidos de catarata e glaucoma. Em escolares a prevalência de deficiência visual não corrigida foi de 4,82% diminuindo para 0,41% com a correção refrativa. Em escolares a causa mais comum de deficiência visual foram erros refrativos não corrigidos. A deficiência visual e a cegueira são um importante problema de saúde pública no Brasil. É um problema significante em brasileiros mais velhos reforçando a necessidade de implementação de programas de prevenção de cegueira para pessoas idosas com ênfase nos indivíduos sem escolaridade. Em escolares são necessárias estratégias de custo-eficácia para atingir uma causa de deficiência visual facilmente tratável - a prescrição e a provisão de óculos.

Ocular toxoplasmosis is the most common cause of posterior uveitis worldwide. The infection can be acquired congenitally or postnatally and ocular lesions may present during or years after the acute infection occur. Current treatment controls ocular infection and inflammation, but does not prevent recurrences. We present a review and update on ocular toxoplasmosis and address misconceptions still found in the current medical literature.

Mauro Campos, Mariana Ávila, Anelise Wallau, Cristina Muccioli, Ana Luisa Höfling-Lima, Rubens Belfort JrDepartment of Ophthalmology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilPurpose: To compare the efficacy and tolerability of a fixed-dose combination of 0.5% moxifloxacin and 0.1% dexamethasone formulation (MFLX/DEX) vs conventional dosing with both agents dosed separately for prophylaxis after laser-assisted in situ keratomileusis (LASIK).Methods: A prospective, randomized, double-masked, parallel-group study of 64 patients undergoing bilateral LASIK. Patients received either combined MFLX/DEX and placebo or moxifloxacin and dexamethasone dosed separately in both eyes. Baseline and postoperative assessments were made on surgery days –2, 1, 3, 8, and 15 and consisted of uncorrected visual acuity (UCVA), intraocular pressure (IOP), severity of inflammation, endothelial cell loss, ocular pain, burning, and itching sensation. The posterior segment was evaluated at the screening and exit visits.Results: Of the 64 patients treated, 7 eyes did not meet the inclusion criteria and were excluded from the analysis. No ocular infection or persistent inflammation developed. Postoperatively there were no statistical differences between treatments for most parameters measured. More eyes in the combined MFLX/DEX group reported pruritus and burning post operatively; however, differences were also observed at baseline.Conclusion: Topical prophylaxis with MFLX/DEX eye drops was well tolerated and is therapeutically equivalent to conventional dosing with moxifloxacin and dexamethasone from individual bottles.Keywords: moxifloxacin, dexamethasone, LASIK, prophylaxis

The purpose of this study was to evaluate the effects of the use of the subconjunctival injection of bevacizumab (Avastin®) on angiogenesis in the rat cornea. Corneas of 20 Wistar male rats were cauterized with silver nitrate crystal. Animals were divided in four groups: control group (GC) that received subconjunctivally 0.02 ml of 0.9% saline solution on the day of the lesion; group GO that received subconjunctivally 0.02 ml of bevacizumab just after the lesion; group G3 that received bevacizumab on day 3 and group G5 that received bevacizumab on day 5 after lesion. Animals were euthanized on day 7. The newly formed vessels were quantified after China Ink perfusion and photographs were obtained and analyzed in a computerized system (Image Pro-Plus®). In the control group, neovascularization covered 53.56% ± 15.11 (mean ± SD) of the corneal surface, compared with 35.57% ± 18.80 (mean ± SD) in the G0 group, 30.60%±11.82 (mean±SD) in the G3 and 35.86%±0.07 (mean±SD) in the G5. The results showed an inhibition of angiogenesis when the control group was compared with all treated groups. These results suggest that subconjunctival injection of bevacizumab is able to inhibit corneal angiogenesis independently of the day of treatment.O objetivo deste estudo foi avaliar os efeitos da aplicação subconjuntival de bevacizumab (Avastin®) na angiogênese corneal em ratos. Vinte ratos Wistar, machos, foram submetidos a cauterização química com cristal de nitrato de prata. Os animais foram divididos em 4 grupos: O grupo controle (GC), recebeu injeção de 0,02 ml de solução fisiológica pela via subconjuntival no momento da lesão. O grupo G0 recebeu 0,02 ml de bevacizumab (Avastin®) imediatamente depois da lesão. O grupo G3 recebeu 0,02 ml de bevacizumab no terceiro dia após a lesão.O grupo G5 recebeu 0,02 ml de bevacizumab no quinto dia após a lesão. Os animais foram eutanasiados 7 dias após a cauterização. Os vasos neoformados foram quantificados após preenchimento do leito vascular com Tinta da China e imagens foram obtidas e analisadas em sistema computadorizado (Image Pro-Plus®). No grupo controle a neovascularização ocupou 53,56% ± 15,11 (média ± DP) da superfície corneal comparando a 35,57% ± 18,80 no grupo G0, 30,60% ± 11,82 (média ± DP) no G3 e 35,86% ± 0,07 (média ± DP) no G5. Os resultados mostram uma inibição da angiogênese quando se compara GC com os grupos tratados. Os resultados sugerem que a injeção subconjuntival de Bevacizumab é capaz de inibir a angiogênese corneal independentemente do dia de aplicação.

Toxoplasmosis is the most common cause of infectious uveitis in Brazil, with a higher frequency in the South of the country. We have collected samples from porcine tongue and diaphragm obtained in both large and small abattoirs and used molecular biological technique to determine the prevalence of infection and RFLP analysis to type the parasites. Seventeen out of 50 (34%) samples from the diaphragm and 33 out of 50 (66%) samples from the tongue demonstrated a positive PCR reaction for T. gondii and restriction analysis of four of the positive samples revealed that all had a type I genotype at SAG2. However, when other unlinked loci were analyzed, these strains had a type III genotype at markers BTUB, SAG3, and GRA6. One of the strains (8T) had a type II allele at SAG3, indicating it has a combination of alleles normally seen in the clonal lineages. Our sampling indicates a high prevalence of infection and suggests that unusual genotypes of T. gondii are found in Brazil even among domesticated pigs.Toxoplasmose é a causa mais comum de uveíte infecciosa no Brasil, com maior freqüência no sul do país. Coletamos amostras de diafragma e língua de porcos em pequenos e grandes abatedouros e utilizamos biologia molecular para determinar a taxa de infecção e ''DNA genotyping'' para tipar os parasitas. Dezessete das 50 amostras de diafragma (34%) e 33 das 50 amostras de língua (66%) foram positivas na reação de PCR para T. gondii. A análise restritiva e o sequenciamento do DNA em quatro amostras revelaram que todas apresentam genótipo tipo I no SAG2. No entanto, quando outros loci não ligados foram analisados, estas mesmas amostras se mostraram como tipo III nos marcadores BTUB, SAG3 e GRA6. Uma das amostras (8T) mostrava-se como tipo II no SAG3, indicando um perfil misto. Estas amostras demonstraram não só uma alta taxa de infecção, mas também genótipos incomuns que não foram observados com freqüência em estudos prévios. Nosso trabalho sugere que genótipos incomuns de T. gondii podem ser encontrados no Brasil, até mesmo em porcos domesticados.

BackgroundPrimary congenital glaucoma (PCG), occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. The present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601) and Brazil (n=300).MethodsGenotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. The demographic (gender, and history of consanguinity) and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H) and Brazil (4340delG). All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software (version 2.14.1).ResultsThe overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024) and compound heterozygous mutations in the later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. The adjusted ORs for the binary (demographic) and continuous (clinical) variables did not indicate any susceptibility to the observed mutations (p>0.05).ConclusionsThe present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the susceptibility of these mutations to the long-term progression of these traits are yet to be deciphered.

Age-related macular degeneration (AMD) is a disease that causes reduced visual acuity and blindness. The new treatment options for AMD are not provided by the Brazilian public health system.To conduct a budget impact analysis of three scenarios for the introduction of AMD treatments: all the medications (verteporfin, ranibizumab, and bevacizumab-the reference scenario), ranibizumab alone, and bevacizumab alone.The basic assumption was that the Brazilian public health system would treat the entire target population with AMD aged > 70 years between 2008 and 2011. The size of the population of interest was estimated from official population projections and the prevalence of the disease was obtained from a systematic review. Medication prices were estimated by weighting their market values with correction factors to take account of the public procurement policy. The possibility of aliquoting bevacizumab was also considered. A panel of experts was consulted to estimate the market share of the different medications for the reference scenario. The incremental costs of the ranibizumab-alone and bevacizumab-alone scenarios compared to the reference scenario were calculated. Univariate sensitivity analyses were run to check the robustness of the model.In four years, the Brazilian public health system would have treated 1,136,349 individuals with AMD. The annual costs of treating one patient would have been US$476.65 for bevacizumab, US$11,469.39 for ranibizumab, and US$4,376.28 for verteporfin. The incremental cost of the ranibizumab-alone scenario would have been US$1,878,318,056.00 in four years, while the incremental cost for the bevacizumab-alone scenario would have been a reduction of US$4,978,326,359.00 (i.e., a cost saving) in the same period. The bevacizumab-alone option was found to represent a cost saving across sensitivity analyses.The introduction of bevacizumab for the treatment of AMD is recommended for the Brazilian Public Health System.

Purpose. To report a case of bilateral punctate inner choroidopathy (PIC). Case Report. A 26-year-old Caucasian woman presented with bilateral blurred vision with one year of evolution. There was no relevant systemic disease or family history. Best-corrected visual acuity in the right eye was 20/30 and in the left eye was 20/20; there was no clinically significant refractive error. Fundoscopy evidenced multiple, small, round, yellow-white lesions limited to the posterior pole of both eyes, with greater macular involvement in the RE. There were no signs of inflammation in the anterior chamber or vitreous cavity. Fluorescein angiography revealed the presence of multiple hyperfluorescent lesions more evident in the later stages of the angiogram in both eyes. On indocyanine green angiography, these lesions appeared hypofluorescent in both early and late phases. Optical coherence tomography showed the presence of focal elevations of the retinal pigment epithelium with underlying hyporeflective space, bilaterally. Laboratory and imaging evaluation for evidence of autoimmune and infectious diseases were negative. Conclusion. The PIC is a relatively uncommon condition. In this report, an attempt has been made to describe a classic clinic presentation of this disease in a young and female patient.

Previous studies have shown a high prevalence of toxoplasmosis and the frequent occurrence of ocular disease in Brazil. To identify the genotypes of parasite strains associated with ocular disease, we compared 25 clinical and animal isolates of Toxoplasma gondii from Brazil to previously characterized clonal lineages from North America and Europe. Multilocus nested polymerase chain reaction analysis was combined with direct sequencing of a polymorphic intron to classify strains by phylogenetic methods. The genotypes of T. gondii strains isolated from Brazil were highly divergent when compared to the previously described clonal lineages. Several new predominant genotypes were identified from different regions of Brazil, including 2 small outbreaks attributable to foodborne or waterborne infection. These findings show that the genetic makeup of T. gondii is more complex than previously recognized and suggest that unique or divergent genotypes may contribute to different clinical outcomes of toxoplasmosis in different localities.

The city of Erechim, Brazil, has a 17% prevalence of ocular toxoplasmosis, and type 1 Toxoplasma gondii predominates. To examine risk factors for acute T. gondii infection in this area, we administered a questionnaire to recently infected persons (n = 131) and seronegative controls (n = 110). Eating undercooked meat; having a garden; working in the garden or yard more than once per week; eating rare meat; eating cured, dried, or smoked meat; eating frozen lamb; and being male increased risk for T. gondii infection in univariate analysis. Risk factors independently associated with acute T. gondii infection in multivariate analysis were working in the garden (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.27–4.33) and eating frozen lamb (OR 2.06, 95% CI 1.15–3.67). Among women (n = 86), having had children markedly increased the risk for T. gondii infection (OR 14.94, 95% CI 3.68–60.73).

Experimental autoimmune uveitis (EAU) is a well established model for immune-mediated organ-specific disease. Our group has recently shown that the M. leprae Hsp65 aggravated the uveitis in mice; in the present study, we evaluated the action of M. leprae K409A mutant protein and the synthetic peptides Leader pep and K409A pep (covering amino acids residues 352–371 of WT and K409A proteins of M. leprae Hsp65, resp.) on the pathogenesis of EAU. Mice received the 161–180 IRBP peptide and B. pertussis toxin followed by the intraperitoneal inoculation of K409A protein or the Leader pep or K409A pep. The Leader pep aggravated the disease, but mice receiving the K409A pep did not develop the disease and presented an increase in IL-10 levels by spleen cells and a decrease in the percentage of CD4+ IFN-γ+ T cells. Moreover, animals receiving the Leader pep presented the highest scores of the disease associated with increase percentage of CD4+ IFN-γ+ T cells. These results would contribute to understanding of the pathogenesis of EAU and support the concept that immune responses to Hsp are of potential importance in exacerbating, perpetuating, or even controlling organ-restricted autoimmune diseases, and it is discussed the irreversibility of autoimmune syndromes.

The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+)IL-17(+), CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+)IFN-gamma(+) and CD4(+)IL-17(+) T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.