Protein profile of purified plasma- and aqueous humor-derived extracellular vesicles from patients with ocular toxoplasmosis

ABSTRACT Purpose: To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis. Methods: Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis. Results: All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion: The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis.

Toxoplasmosis outbreak in São Paulo, Brazil: Epidemiology and visual outcome

ABSTRACT Purpose: To describe a 2019 acute toxoplasmosis outbreak in the city of São Paulo, Brazil, and to evaluate the laboratory serological profile for toxoplasmosis for three consecutive years. The ophthalmological manifestations of the patients involved in the outbreak were also studied. Methods: A cross-sectional descriptive study of a toxoplasmosis outbreak in São Paulo, Brazil, between February and May 2019. Epidemiological data were described, as were the observed ocular manifestations. As part of this study the number of patients with positive IgM toxoplasmosis serology was obtained from a large laboratory network (DASA) for three consecutive years, including the year of the outbreak (2018, 2019, 2020). Results: Eighty-three individuals were identified in the outbreak and two clusters were studied. The clinical picture of at least 77% of the patients, the epidemiological analysis, and the short incubation period (5-8 days) suggested contamination by oocysts. Serological laboratory data analysis revealed an increase of positive toxoplasmosis IgM in 2019 of 73% compared to the previous year. Ophthalmological examination revealed that at least 4.8% of the patients developed toxoplasmic retinochoroiditis, none of whom had been treated during the acute systemic disease. Conclusion: Our findings indicate vegetable contamination as the possible source of this outbreak, a high prevalence of toxoplasmosis in São Paulo during the outbreak period, and a drop in the number of tests during the COVID-19 pandemic. Retinochoroiditis was observed in at least 4.8% of the cases. We confirm the need to implement effective means for the prevention, diagnosis, and treatment of the disease. This may involve raising awareness among the population of the importance of vegetable hygiene, and improved quality control of food and water.

Corneal reshaping: an experiment with a type I collagen-based vitrigel for remodeling porcine corneas / Remodelamento corneano: relato de um experimento com um vitrigel a base de colágeno tipo I para remodelamento de córneas porcinas

ABSTRACT Purpose: This study aimed to report an experiment designed to determine anatomical changes in porcine corneas following placement of a novel polymer implant into the cornea. Methods: An ex vivo porcine eye model was used. A novel type I collagen-based vitrigel implant (6 mm in diameter) was shaped with an excimer laser on the posterior surface to create three planoconcave shapes. Implants were inserted into a manually dissected stromal pocket at a depth of approximately 200 μm. Three treatment groups were defined: group A (n=3), maximal ablation depth 70 μm; Group B (n=3), maximal ablation depth 64 μm; and group C (n=3), maximal ablation depth 104 μm, with a central hole. A control group (D, n=3) was included, in which a stromal pocket was created but biomaterial was not inserted. Eyes were evaluated by optical coherence tomography (OCT) and corneal tomography. Results: Corneal tomography showed a trend for a decreased mean keratometry in all four groups. Optical coherence tomography showed corneas with implants placed within the anterior stroma and visible flattening, whereas the corneas in the control group did not qualitatively change shape. Conclusions: The novel planoconcave biomaterial implant described herein could reshape the cornea in an ex vivo model, resulting in the flattening of the cornea. Further studies are needed using in vivo animal models to confirm such findings.

RESUMO Objetivo: Relatar um experimento projetado para determinar alterações anatômicas em córneas porcinas após a colocação de um novo implante de polímero na córnea. Métodos: Foi utilizado olho de porco ex vivo. Um novo agente modelador biocompatível, de colágeno tipo 1, com 6mm de diâmetro foi moldado com excimer laser em sua face posterior, para criar três formatos planocôncavos. Os implantes foram inseridos dentro de um bolsão, dissecado manualmente, a 200 micrômetros (μm). Foram definidos três grupos de tratamento: grupo A (n=3), teve a profundidade máxima de ablação de 70 μm; o grupo B (n=3), profundidade máxima de ablação de 64 μm; e o grupo C (n=3), profundidade máxima de ablação de 104 μm, com buraco central. O grupo controle, D (n=3), foi incluído, com a criação do bolsão estromal, porém sem inserir o material. A avaliação desses olhos foi realizada por tomografia de coerência óptica (OCT) e por tomografia corneana. Resultados: A tomografia corneana mostrou uma tendência para diminuição da ceratometria média em todos os 4 grupos. A tomografia de coerência óptica mostrou córneas com implantes localizados no estroma anterior e aplanamento visível, enquanto as córneas não mudaram qualitativamente o formato no grupo controle. Conclusões: O novo implante de biomaterial planocôncavo descrito aqui foi capaz de remodelar a córnea em modelo de animal ex vivo, resultando no aplanamento corneano. Novos estudos são necessários usando modelos animais in vivo para confirmar tais achados.

Proposal of a new slit-lamp shield for ophthalmic examination and assessment of its effectiveness using computational simulations / Avaliação da eficácia e proposta de um novo protetor de lâmpada de fenda durante exame oftálmico por meio de simulações computacionais

ABSTRACT Purpose: This study aimed to use computational models for simulating the movement of respiratory droplets when assessing the efficacy of standard slit-lamp shield versus a new shield designed for increased clinician comfort as well as adequate protection. Methods: Simulations were performed using the commercial software Star-CCM+. Respiratory droplets were assumed to be 100% water in volume fraction with particle diameter distribution represented by a geometric mean of 74.4 (±1.5 standard deviation) μm over a 4-min duration. The total mass of respiratory droplets expelled from patients' mouths and droplet accumulation on the manikin were measured under the following three conditions: with no slit-lamp shield, using the standard slit-lamp shield, and using our new proposed shield. Results: The total accumulated water droplet mass (kilogram) and percentage of expelled mass accumulated on the shield under the three aforementioned conditions were as follows: 5.84e-10 kg (28% of the total weight of particle emitted that settled on the manikin), 9.14e-13 kg (0.045%), and 3.19e-13 (0.015%), respectively. The standard shield could shield off 99.83% of the particles that would otherwise be deposited on the manikin, which is comparable to 99.95% for the proposed design. Conclusion: Slit-lamp shields are effective infection control tools against respiratory droplets. The proposed shield showed comparable effectiveness compared with conventional slit-lamp shields, but with potentially enhanced ergonomics for ophthalmologists during slit-lamp examinations.

RESUMO Introdução: Os oftalmologistas têm alto risco de contrair a doença do Coronavírus-19 devido à proximidade com os pacientes durante os exames com lâmpada de fenda. Usamos um modelo de computação para avaliar a eficácia das proteções para lâmpadas de fenda e propusemos uma nova proteção ergonomicamente projetada. Métodos: As simulações foram realizadas no software comercial Star-CCM +. Os aerossóis de gotículas foram considerados 100% de água em fração de volume com distribuição de diâmetro de partícula representada por uma média geométrica de 74,4 ± 1,5 (desvio padrão) μm ao longo de uma duração de quatro minutos. A massa total de gotículas de água acumulada no manequim e a massa expelida pela boca do paciente foram medidas em três condições diferentes: 1) Sem protetor de lâmpada de fenda, 2) com protetor padrão, 3) Com o novo protetor proposto. Resultados: A massa total acumulada das gotas de água (kg) e a porcentagem da massa expelida acumulada no escudo para cada uma das respectivas condições foram; 1) 5,84e-10 kg (28% do peso total da partícula emitida que assentou no manequim), 2) 9,14e-13 kg (0,045%), 3,19e-13 (0,015%). O escudo padrão foi capaz de proteger 99,83% das partículas que, de outra forma, teriam se depositado no manequim, o que é semelhante a 99,95% para o projeto proposto. Conclusão: Protetores com lâmpada de fenda são ferramentas eficazes de controle de infecção contra gotículas respiratórias. O protetor proposto mostrou eficácia comparável em comparação com os protetores de lâmpada de fenda convencionais, mas potencialmente oferece uma melhor ergonomia para oftalmologistas durante o exame de lâmpada de fenda.

Performance of ChatGPT-4 in answering questions from the Brazilian National Examination for Medical Degree Revalidation

SUMMARY OBJECTIVE: The aim of this study was to evaluate the performance of ChatGPT-4.0 in answering the 2022 Brazilian National Examination for Medical Degree Revalidation (Revalida) and as a tool to provide feedback on the quality of the examination. METHODS: A total of two independent physicians entered all examination questions into ChatGPT-4.0. After comparing the outputs with the test solutions, they classified the large language model answers as adequate, inadequate, or indeterminate. In cases of disagreement, they adjudicated and achieved a consensus decision on the ChatGPT accuracy. The performance across medical themes and nullified questions was compared using chi-square statistical analysis. RESULTS: In the Revalida examination, ChatGPT-4.0 answered 71 (87.7%) questions correctly and 10 (12.3%) incorrectly. There was no statistically significant difference in the proportions of correct answers among different medical themes (p=0.4886). The artificial intelligence model had a lower accuracy of 71.4% in nullified questions, with no statistical difference (p=0.241) between non-nullified and nullified groups. CONCLUSION: ChatGPT-4.0 showed satisfactory performance for the 2022 Brazilian National Examination for Medical Degree Revalidation. The large language model exhibited worse performance on subjective questions and public healthcare themes. The results of this study suggested that the overall quality of the Revalida examination questions is satisfactory and corroborates the nullified questions.

Unilateral acute posterior multifocal placoid pigment epitheliopathy in a patient with a strongly positive purified protein derivative test / Epiteliopatia pigmentar placóide multifocal posterior aguda unilateral na presença de reação forte positiva para o teste tuberculínico

ABSTRACT A 27-year-old man presented with a complaint of decreased visual acuity in the right eye. Best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Right eye fundoscopy revealed mild vitritis, multifocal yellowish lesions, and macular serous retinal detachment. Left eye evaluation was normal. Acute posterior multifocal placoid pigment epitheliopathy was diagnosed in the right eye. Complementary exams revealed a strong reaction to the Mycobacterium tuberculosis purified protein derivative test, thus treatment for tuberculosis was initiated. Baseline fluorescein angiography of the right eye revealed early hypofluorescence and late staining of the lesions. Optical coherence tomography of the right eye demonstrated the accumulation of subretinal and intraretinal fluid associated with cystoid macular edema. During follow-up, the retinal fluid and cysts disappeared, which was followed by disorganization of foveal interdigitation and ellipsoid zones. This is the second described case of unilateral acute posterior multifocal placoid pigment epitheliopathy in a patient with a strong positive result to the M. tuberculosis purified protein derivative test.

RESUMO Um homem de 27 anos apresentou uma queixa de diminuição da acuidade visual no olho direito. A acuidade visual melhor corrigida foi 20/60 no olho direito e 20/20 no olho esquerdo. A fundoscopia do olho direito revelou vitreíte leve, lesões amareladas multifocais e descolamento seroso da retina em região macular. A avaliação do olho esquerdo foi normal. Epiteliopatia pigmentar placóide multifocal posterior aguda foi diagnosticada no olho direito. Os exames complementares revelaram forte reação ao teste do derivado proteico purificado Mycobacterium tuberculosis, iniciando terapia antibiótica contra tuberculose. A angiografia fluoresceínica basal do olho direito revelou hipofluorescência precoce e tardia das lesões. A tomografia de coerência óptica do olho direito demonstrou fluído sub- e intrarretiniano associado a edema macular cistóide. Durante o seguimento, os fluídos e cistos retinianos desapareceram, seguido da desorganização das zonas de interdigitação e elipsóide em região foveal. Este é o segundo caso descrito de epiteliopatia pigmentar placóide multifocal posterior aguda unilateral em um paciente com um forte resultado positivo para o teste tuberculínico.

Tacrolimus eye drops as monotherapy for vernal keratoconjunctivitis: a randomized controlled trial / Colírio de Tacrolimus 0, 03% como único agente antialérgico para o tratamento de ceratoconjuntivite primaveril: ensaio clínico randomizado

ABSTRACT Purpose: To assess the efficacy of monotherapy using tacrolimus eye drops versus sodium cromoglycate for the treatment of vernal keratoconjunctivitis (VKC). Methods: Randomized double-masked controlled trial comparing the efficacy of tacrolimus 0.03% eye drops t.i.d. (Group 1) with sodium cromoglycate 4% eye drops t.i.d. (Group 2) for the symptomatic control of VKC at days 0, 15, 30, 45, and 90 of follow-up. Visual acuity, intraocular pressure, and other complications were evaluated to assess safety and side effects. Results: In total, 16 patients were included, with 8 enrolled in each group. Two patients from Group 2 were excluded from the analysis at days 45 and 90 because of corticosteroid use. Most patients were male (81.8%) and presented with limbal VKC (56.3%). There were statistically significant differences in favor of tacrolimus in the following severity scores: itching at day 90 (p=0.001); foreign body sensation at day 15 (p=0.042); photophobia at day 30 (p=0.041); keratitis at day 30 (p=0.048); and limbal activity at days 15 (p=0.011), 30 (p=0.007), and 45 (p=0.015). No relevant adverse effects were reported, except for a burning sensation with tacrolimus, though this did not compromise treatment compliance. Conclusion: Treatment with tacrolimus was superior to sodium cromoglycate when comparing severity scores for symptoms of itching, foreign body sensation, and photophobia, as well as for signs of limbal inflammatory activity and keratitis.

RESUMO Objetivo: Demonstrar a eficácia do colírio de tacrolimus 0,03% como único agente antialérgico versus o colírio de cromoglicato de sódio 4% no tratamento de ceratoconjuntivite primaveril (CCP). Métodos: Ensaio clínico randomizado duplo-mascarado comparando a eficácia do colírio de tacrolimus 0,03% 3 vezes ao dia, versus o colírio de cromoglicato 4% 3 vezes ao dia, no controle dos sintomas e sinais de pacientes com o diagnóstico de ceratoconjuntivite primaveril, durante o período de 3 meses, com avaliações nos dias 0, 15, 30, 45 e 90. Acuidade visual, pressão intraocular e outras possíveis complicações foram avaliadas para determinar segurança e efeitos adversos. Resultados: Dezesseis pacientes foram incluídos no estudo, sendo que oito fizeram uso de colírio de tacrolimus 0,03% (Grupo 1) e oito fizeram uso de colírio de cromoglicato de sódio 4% (Grupo 2). Dois pacientes do Grupo 2 foram excluídos da análise dos dias 45 e 90, devido à necessidade de utilização de corticosteroide tópico. A maioria dos pacientes era do sexo masculino (81,8%) e 56,3% apresentavam a doença em sua forma limbar. Houve diferença estatisticamente significativa entre os Grupos 1 e 2 em relação à graduação de severidade para os sintomas de prurido no dia 90 (p=0,001), sensação de corpo estranho no dia 15 (p=0,042), fotofobia no dia 30 (p=0,041) e para os sinais de atividade inflamatória limbar nos dias 15 (p=0,011), 30 (p=0,007) e 45 (p=0,015), e ceratite no dia 30 (p=0,048). Nenhum efeito adverso relevante foi notado, exceto queixa de queimação ocular quando da instilação de tacrolimus, o que não comprometeu à adesão ao tratamento. Conclusão: O colírio de tacrolimus 0,03% foi superior ao colírio de cromoglicato de sódio 4% comparando a graduação de severidade para os sintomas de prurido, sensação de corpo estranho e fotofobia, assim como para os sinais de atividade inflamatória limbar e ceratite, em determinados períodos de tempo durante o seguimento.

Vision status, ophthalmic assessment, and quality of life in the very old / Visão, avaliação oftalmológica e qualidade de vida em longevos

ABSTRACT Purpose: To determine the vision status, ophthalmic findings, and quality of life among the very elderly. Methods: This was a cross-sectional observational study of individuals aged 80 years and above. A comprehensive ophthalmic exam was performed with mea surement of both the presenting (PVA) and best-corrected visual acuity. The Quality of Life Short Form-36 (SF-36) and the Visual Function Questionnaire (VFQ-25) were also administered. Results: A total of 150 non-institutionalized participants were assigned to three age groups: 80-89 years (n=70), 90-99 years (n=50), and 100 years and older (n=30). PVA and best-corrected visual acuity were normal (≥20/30) in 20 (13.3%) and 37 participants (24.7%), respectively. Regarding PVA, mild visual impairment (<20/30 to ≥20/60) was found in in 53 (35.4%), moderate visual impairment (<20/60 to ≥20/200) in 50 (33.3%), severe visual impairment (<20/200 to ≥20/400) in 8 (5.3%), and blindness (<20/400) in 19 (12.7%) participants. Regarding best-corrected visual acuity, mild, moderate, and severe visual impairments were present in 55 (36.7%), 38 (25.3%), and 5 (3.3%) participants, respectively, and blindness was present in 15 (10%). The main causes of visual impairment/blindness were cataract (43.8%), refractive errors (21.5%), age-related macular degeneration (17.7%), and myopic degeneration (3.8%). SF-36 scores were worse in those with low visual acuity, while VFQ-25 domain scores were poorer in those with vision impairment/blindness. Conclusion: Vision impairment and blindness was present in three-quarters of this sample, but it was notable that adequate correction with spectacles improved visual acuity. This reinforces the need for regular ophthalmic care in elderly patients to improve their quality of life by optimizing vision.

RESUMO Objetivos: Determinar a visão, achados oftalmológicos e qualidade de vida em longevos. Métodos: Estudo observacional transversal em indivíduos com idade entre 80 anos ou mais. Realizado exame oftalmológico com medida da acuidade visual apresentada e da acuidade visual melhor corrigida. Foram administrados os questionários: Qualidade de Vida Forma Curta - 36 (SF-36) e Qualidade de Função Visual (VFQ-25). Resultados: Total de 150 indivíduos não-institucionalizados foram estudados, divididos em três faixas etárias: 80 a 89 anos (n=70); 90 a 99 anos (n=50) e 100 anos ou mais (n=30). Acuidade visual apresentada normal (≥20/30) foi encontrada em 20 (13,3%) participantes; deficiência visual leve (<20/30 a ≥20/60), em 53 (35,4%); deficiência visual moderada (< 20/60 a ≥20/200) em 50 (33,3%); deficiência visual grave (<20/200 para ≥20/400) em 8 (5,3%) e cegueira (<20/400) em 19 (12,7%). A acuidade visual com a melhor correção aumentou para 37 (24,7%) indivíduos normais; deficiência leve aumentou para 55 (36,7%); deficiência visual moderada diminuiu para 38 (25,3%); deficiência visual grave foi reduzida para 5 (3,3%) e cegueira foi reduzida para 15 (10%). As principais causas de deficiência visual/cegueira foram: catarata (43,8%) erro refrativo (21,5%), degeneração macular relacionada à idade (17,7%), e degeneração miópica (3,8%). A pontuação no Questionário de Qualidade de Vida foi pior naqueles com baixa visão para perto. No questionário VFQ -25 os domínios com menor pontuação ocorreram nos indivíduos com baixa visão/cegueira. Conclusão: Deficiência visual/cegueira mostrou-se presente em três quartos desta amostra de longevos. A prescrição de óculos adequados proporcionou melhora da acuidade visual, reforçando a necessidade de atendimento oftalmológico regular desses pacientes para assegurar a qualidade de vida e de visão.

Large colloid drusen analyzed with structural en face optical coherence tomography / Análise de drusas grandes coloidais através de OCT en face estrutural

ABSTRACT Drusen are extracellular deposits between the basal lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. Large colloid drusen (LCD) are located below the RPE and are characterized by multiple, large, dome-shaped RPE detachments, with marked attenuation of the ellipsoid zone overlaying the drusen. This report presents the structural en face optical coherence tomography (OCT) findings of LCD and relates them to findings from fluorescein and indocyanine green angiography. We describe the case of a 55-year-old woman who presented with the chief complaint of a 5-year history of progressively worsening vision. Her best-corrected visual acuities were 20/40 and 20/400 in the right eye and the left eye, respectively. Fundus examination showed large bilateral, symmetrical, sub-retinal, yellowish lesions compatible with LCD. We describe the structural en face OCT characteristics and angiographic findings from this patient.

RESUMO Drusas são depósitos extracelulares localizados entre a lâmina basal do epitélio pig mentado da retina (RPE) e a camada colágena interna da membrana de Bruch. Drusas grandes coloidais (LCD) estão localizadas abaixo do EPR, e são caracterizadas por múltiplos descolamentos cupuliformes do EPR com atenuação da zona elipsoide sobrejacente às drusas. O objetivo deste relato é apresentar os achados de tomografia de coerência óptica (OCT en face estrutural em uma paciente com LCD, bem como correlacioná-los com angiografia fluoresceínica e angiografia com indocianina verde. Descrevemos o caso de uma paciente do sexo feminino, 55 anos, que referiu baixa acuidade visual em ambos os olhos há 5 anos. Sua acuidade visual corrigida era de 20/40 no olho direito e 20/400 no olho esquerdo. Ao exame fundoscópico a paciente apresentava lesões compatíveis com drusas grandes coloidais. As características tomográficas e angiográficas também são descritas neste relato de caso.