Avaliação oftalmológica de pacientes com coronavírus (SARS-CoV-2) in vivo e post mortem
Data
2024-11-06
Autores
Marinho, Paula Marques 
Orientadores
Belfort Jr, Rubens
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Estudo 1: Avaliar as repercussões oftalmológicas de pacientes com infecção confirmada pelo novo coronavírus de 2019 (SARS-CoV-2), com diferentes níveis de gravidade em Unidades de Terapia Intensiva (UTI) e Enfermaria. Estudo 2: Analisar a presença de alteração de autofluorescência retiniana em pacientes portadores da Doença pelo novo coronavírus 2019 (Covid-19). Estudo 3: Descrever os achados oftalmológicos anormais obtidos por meio de microscopia de luz, microscopia eletrônica de varredura e microscopia eletrônica de transmissão na análise retiniana de pacientes que evoluíram para óbito por Covid-19. Métodos: Estudo 1: Estudo longitudinal, observacional, conduzido entre março e junho de 2020, com realização de retinografia colorida e com filtro red-free após dilatação pupilar. Estudo 2: Estudo observacional, conduzido em São Paulo, em 2020. Foram obtidos dados epidemiológicos e demográficos, bem como informações de eventos concomitantes, medicações em uso, hospitalização e análises laboratoriais. Os pacientes foram submetidos à avaliação oftalmológica ambulatorial e multimodal, incluindo retinografia colorida e red-free, autofluorescência de retina e tomografia de coerência óptica da retina. Estudo 3: Relata os achados de microscopia de luz, microscopia eletrônica de varredura e microscopia eletrônica de transmissão na análise retiniana de cinco pacientes que evoluíram a óbito por Covid-19. Resultados: Estudo 1: 104 pacientes foram avaliados, sendo 60 (58%) vindos da UTI e 44 (42%) da Enfermaria de Covid-19; 21,9% apresentaram achados oftalmológicos, sendo 3% com potencial de comprometimento visual. Estudo 2: Dezoito pacientes, com achados de autofluorescência retiniana (seis mulheres; média de idade de 54 anos, intervalo de 31 a 86 anos; 26 olhos). Hiperautofluorescência presente em seis pacientes, hipoautofluorescência em 14 e seis com achados de padrão misto, combinando hiper e hipoautofluorescência. Estudo 3: Em todos os olhos analisados, foram encontradas manifestações clínicas de hemorragias retinianas e infiltrado inflamatório exacerbado, assim como mitocôndrias edemaciadas e células picnóticas. Conclusões: Estudo 1: Os principais achados foram manchas algodonosas, hemorragias intrarretinianas e exsudatos duros. Nossos resultados demonstraram frequência parecida de lesões intraoculares em pacientes da Enfermaria ou da UTI, independentemente das medicações em uso. Estudo 2: A autofluorescência revelou múltiplos padrões indicativos de lesão aguda e possível disfunção do complexo Epitélio Pigmentar da Retina – coriocapilar, não evidenciados previamente pela retinografia. Estudo 3: Demonstrou-se que a microcirculação retiniana sofre dano severo, provavelmente por complicações tromboembólicas associadas à Covid-19. Dentre os achados, destacam-se: 1) A existência de núcleos picnóticos, indicando processo de morte celular, sinalizando possibilidade de dano tecidual permanente; 2) A presença abundante de polimorfonucleares (PMN), com organização em aspecto de rede, que podem contribuir para microtromboses; 3) PMN sem sinais de remodelamento do retículo endoplasmático e ausência de partículas virais; sugerindo que a proteína S1 e partículas virais tenham vias alternativas de disseminação, como microvesículas e nervos periféricos.
Objective: Study 1: To evaluate the ophthalmologic repercussions of patients with confirmed 2019-new coronavirus (SARS-CoV-2), with distinct levels of severity in Intensive Care Units (ICU) and Ward. Study 2: To analyze the presence of fundus autofluorescence alterations in patients with 2019-new coronavirus disease (Covid-19). Study 3: To describe the ocular findings obtained through light, scanning, and transmission electron microscopy in the retinal analysis of patients who died due to Covid-19. Methods: Study 1: Longitudinal, observational study, conducted between March and June 2020, with color fundus picture and red-free filtering after pupil dilation. Study 2: Observational study conducted in São Paulo in 2020. Epidemiological and demographic data were obtained, as well as information on concomitant events, medications in use, hospitalization, and laboratory tests. The patients underwent multimodal and ambulatory ophthalmologic evaluation, including color and red-free retinography, fundus autofluorescence, and optical coherence tomography. Study 3: This publication reports the ocular findings of light, scanning, and transmission electron microscopy in the retinal analysis of five patients deceased due to Covid-19. Results: Study 1: 104 patients were evaluated, 60 (58%) from the ICU and 44 (42%) from the Covid-19 Ward; 21.9% had ophthalmologic findings, and 3% with potential visual impairment. Study 2: Eighteen patients with fundus autofluorescence findings (six women; mean age 54 years, range 31 to 86 years; 26 eyes). Hyperautofluorescence was present in six patients, hypoautofluorescence in 14 and six patients with mixed pattern findings, combining hyper and hypoautofluorescence. Study 3: In all the eyes analyzed, clinical manifestations of retinal hemorrhages and exacerbated inflammatory infiltrate were found, as well as swollen mitochondria and pyknotic cells. Conclusions: Study 1: The main findings were cotton wool spots, intraretinal hemorrhages, and hard exudates. Our results showed a similar frequency of intraocular lesions in Ward and ICU patients, regardless of the medications being used. Study 2: Autofluorescence revealed multiple patterns indicative of acute injury and possible dysfunction of the Retinal Pigment Epithelium – choriocapillaris complex, not previously demonstrated by retinography. Using autofluorescence, multiple lesion patterns were identified in the retinal pigment epithelium (RPE), even in eyes with no obvious alterations on retinography. The presence of a hyperautofluorescence pattern suggests probable acute injury and possible dysfunction of the RPE-choriocapillaris complex that might otherwise go unnoticed. Study 3: Severe damage to the retinal microcirculation was demonstrated, probably due to thromboembolic complications associated with Covid-19. Among the findings, the most notable were: 1) The existence of pyknotic nuclei, indicating a process of cell death, signaling the possibility of permanent tissue damage; 2) The abundant presence of polymorphonuclear neutrophils (PMN), with a networklike organization, which can contribute to microthrombosis; 3) PMN without signs of endoplasmic reticulum remodeling and the absence of viral particles, suggesting that the S1 protein and viral particles have alternative routes of dissemination, such as microvesicles and peripheral nerves.
Objective: Study 1: To evaluate the ophthalmologic repercussions of patients with confirmed 2019-new coronavirus (SARS-CoV-2), with distinct levels of severity in Intensive Care Units (ICU) and Ward. Study 2: To analyze the presence of fundus autofluorescence alterations in patients with 2019-new coronavirus disease (Covid-19). Study 3: To describe the ocular findings obtained through light, scanning, and transmission electron microscopy in the retinal analysis of patients who died due to Covid-19. Methods: Study 1: Longitudinal, observational study, conducted between March and June 2020, with color fundus picture and red-free filtering after pupil dilation. Study 2: Observational study conducted in São Paulo in 2020. Epidemiological and demographic data were obtained, as well as information on concomitant events, medications in use, hospitalization, and laboratory tests. The patients underwent multimodal and ambulatory ophthalmologic evaluation, including color and red-free retinography, fundus autofluorescence, and optical coherence tomography. Study 3: This publication reports the ocular findings of light, scanning, and transmission electron microscopy in the retinal analysis of five patients deceased due to Covid-19. Results: Study 1: 104 patients were evaluated, 60 (58%) from the ICU and 44 (42%) from the Covid-19 Ward; 21.9% had ophthalmologic findings, and 3% with potential visual impairment. Study 2: Eighteen patients with fundus autofluorescence findings (six women; mean age 54 years, range 31 to 86 years; 26 eyes). Hyperautofluorescence was present in six patients, hypoautofluorescence in 14 and six patients with mixed pattern findings, combining hyper and hypoautofluorescence. Study 3: In all the eyes analyzed, clinical manifestations of retinal hemorrhages and exacerbated inflammatory infiltrate were found, as well as swollen mitochondria and pyknotic cells. Conclusions: Study 1: The main findings were cotton wool spots, intraretinal hemorrhages, and hard exudates. Our results showed a similar frequency of intraocular lesions in Ward and ICU patients, regardless of the medications being used. Study 2: Autofluorescence revealed multiple patterns indicative of acute injury and possible dysfunction of the Retinal Pigment Epithelium – choriocapillaris complex, not previously demonstrated by retinography. Using autofluorescence, multiple lesion patterns were identified in the retinal pigment epithelium (RPE), even in eyes with no obvious alterations on retinography. The presence of a hyperautofluorescence pattern suggests probable acute injury and possible dysfunction of the RPE-choriocapillaris complex that might otherwise go unnoticed. Study 3: Severe damage to the retinal microcirculation was demonstrated, probably due to thromboembolic complications associated with Covid-19. Among the findings, the most notable were: 1) The existence of pyknotic nuclei, indicating a process of cell death, signaling the possibility of permanent tissue damage; 2) The abundant presence of polymorphonuclear neutrophils (PMN), with a networklike organization, which can contribute to microthrombosis; 3) PMN without signs of endoplasmic reticulum remodeling and the absence of viral particles, suggesting that the S1 protein and viral particles have alternative routes of dissemination, such as microvesicles and peripheral nerves.
Descrição
Citação
MARINHO, Paula Marques. Avaliação oftalmológica de pacientes com coronavírus (SARS-CoV-2) in vivo e post mortem. 2024. 89 f. Tese (Doutorado em Oftalmologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2024.