Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1590/S0004-27492011000500009 http://repositorio.unifesp.br/handle/11600/6657 |
Resumo: | PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid. |
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Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhosA safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyesTumor necrosis factor-alphaInjections, intravenousRetinaRetinal diseasesChoroid diseasesMacular degenerationAntibodies, mono-clonalElectroretinographyAnimalsRabbitsFator de necrose tumoral alfaInjeções intravenosasRetinaDoenças retinianasDoenças da coróideDegeneração macularAnticorpos monoclonaisEletrorretinografiaAnimaisCoelhosPURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.OBJETIVO: Determinar os níveis de toxicidade de duas e três aplicações intravítreas de infliximabe na retina de coelhos albinos, por meio de exames clínicos oftalmológicos, eletrorretinográficos e histológicos. MÉTODOS: Foram utilizados doze coelhos albinos divididos em dois grupos. No primeiro grupo de 10 coelhos, cada olho recebeu duas (n=10 olhos) ou três injeções (n=10 olhos) intravítreas de 2 mg de infliximabe dissolvidos em 0,06 ml de solução salina, em intervalos mensais. Um segundo grupo de dois coelhos, que serviu como grupo controle (n=4 olhos), foram submetidos a duas e três aplicações intravítreas de BSS. Noventa dias após, os coelhos foram novamente submetidos a exame oftalmológico (biomicroscopia, oftalmoscopia e tonometria), eletrorretinográfico e, após enucleados, a exame histológico. RESULTADOS: O exame biomicroscópico e oftalmoscópico não revelou anormalidades retinianas nos olhos injetados com infliximabe e no grupo controle. Alteração histológica notada foi a presença de raros linfócitos e eosinófilos no vítreo posterior em quatro e em seis olhos submetidos a duas e três aplicações de infliximabe sem significado clínico. A única alteração clinicamente significante foi uma reação inflamatória severa com presença de exsudatos vítreos na interface vítreo retiniana e discreto edema de células ganglionares nos dois olhos de um único coelho, sem alterações no vítreo posterior. Os exames eletrorretinográficos mostraram amplitudes em média 12-13% menores daquelas obtidas antes do tratamento, contudo não houve nenhuma diferença estatisticamente significante quando comparamos as amplitudes e a latencia entre os achados electrorretinográficos pré e pós-tratamento. CONCLUSÃO: Duas e três aplicações intravítreas de infliximabe em olhos de coelhos em intervalos mensais, na dosagem de 2 mg, não provocam alterações significantes após um seguimento de noventa dias, quer no exame histológico, na eletrorretinografia e na avaliação clínica oftalmológica. Conclui-se que doses seriadas de infliximabe por via intravítrea é um procedimento seguro. Estudos clínicos em humanos devem ser realizados para melhor avaliação da segurança do seu uso no tratamento de determinadas doenças que acometem a retina e a coroide.Universidade Federal de Goiás Centro de Referência em Oftalmologia Ophthalmology DepartmentUniversidade Federal de São Paulo (UNIFESP) Pathology DepartmentUniversidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Retina e VítreoUniversidade Federal de Goiás Centro de Referência em Oftalmologia Setor de EletrofisiologiaUNIFESP, Pathology DepartmentSciELOConselho Brasileiro de OftalmologiaUniversidade Federal de Goiás Centro de Referência em Oftalmologia Ophthalmology DepartmentUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Retina e VítreoUniversidade Federal de Goiás Centro de Referência em Oftalmologia Setor de EletrofisiologiaRassi, Alan RicardoRigueiro, Moacyr Pezati [UNIFESP]Isaac, David Leonardo CruvinelDourado, Letícia [UNIFESP]Abud, Murilo BatistaFreitas, Éricka CamposCarneiro, Luciana BarbosaÁvila, Marcos Pereira de2015-06-14T13:43:18Z2015-06-14T13:43:18Z2011-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion352-356application/pdfhttp://dx.doi.org/10.1590/S0004-27492011000500009Arquivos Brasileiros de Oftalmologia. Conselho Brasileiro de Oftalmologia, v. 74, n. 5, p. 352-356, 2011.10.1590/S0004-27492011000500009S0004-27492011000500009.pdf0004-2749S0004-27492011000500009http://repositorio.unifesp.br/handle/11600/6657WOS:000298348100010porArquivos Brasileiros de Oftalmologiainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-28T23:14:31Zoai:repositorio.unifesp.br/:11600/6657Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-28T23:14:31Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes |
title |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
spellingShingle |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos Rassi, Alan Ricardo Tumor necrosis factor-alpha Injections, intravenous Retina Retinal diseases Choroid diseases Macular degeneration Antibodies, mono-clonal Electroretinography Animals Rabbits Fator de necrose tumoral alfa Injeções intravenosas Retina Doenças retinianas Doenças da coróide Degeneração macular Anticorpos monoclonais Eletrorretinografia Animais Coelhos |
title_short |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
title_full |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
title_fullStr |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
title_full_unstemmed |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
title_sort |
Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos |
author |
Rassi, Alan Ricardo |
author_facet |
Rassi, Alan Ricardo Rigueiro, Moacyr Pezati [UNIFESP] Isaac, David Leonardo Cruvinel Dourado, Letícia [UNIFESP] Abud, Murilo Batista Freitas, Éricka Campos Carneiro, Luciana Barbosa Ávila, Marcos Pereira de |
author_role |
author |
author2 |
Rigueiro, Moacyr Pezati [UNIFESP] Isaac, David Leonardo Cruvinel Dourado, Letícia [UNIFESP] Abud, Murilo Batista Freitas, Éricka Campos Carneiro, Luciana Barbosa Ávila, Marcos Pereira de |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Goiás Centro de Referência em Oftalmologia Ophthalmology Department Universidade Federal de São Paulo (UNIFESP) Universidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Retina e Vítreo Universidade Federal de Goiás Centro de Referência em Oftalmologia Setor de Eletrofisiologia |
dc.contributor.author.fl_str_mv |
Rassi, Alan Ricardo Rigueiro, Moacyr Pezati [UNIFESP] Isaac, David Leonardo Cruvinel Dourado, Letícia [UNIFESP] Abud, Murilo Batista Freitas, Éricka Campos Carneiro, Luciana Barbosa Ávila, Marcos Pereira de |
dc.subject.por.fl_str_mv |
Tumor necrosis factor-alpha Injections, intravenous Retina Retinal diseases Choroid diseases Macular degeneration Antibodies, mono-clonal Electroretinography Animals Rabbits Fator de necrose tumoral alfa Injeções intravenosas Retina Doenças retinianas Doenças da coróide Degeneração macular Anticorpos monoclonais Eletrorretinografia Animais Coelhos |
topic |
Tumor necrosis factor-alpha Injections, intravenous Retina Retinal diseases Choroid diseases Macular degeneration Antibodies, mono-clonal Electroretinography Animals Rabbits Fator de necrose tumoral alfa Injeções intravenosas Retina Doenças retinianas Doenças da coróide Degeneração macular Anticorpos monoclonais Eletrorretinografia Animais Coelhos |
description |
PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-10-01 2015-06-14T13:43:18Z 2015-06-14T13:43:18Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/S0004-27492011000500009 Arquivos Brasileiros de Oftalmologia. Conselho Brasileiro de Oftalmologia, v. 74, n. 5, p. 352-356, 2011. 10.1590/S0004-27492011000500009 S0004-27492011000500009.pdf 0004-2749 S0004-27492011000500009 http://repositorio.unifesp.br/handle/11600/6657 WOS:000298348100010 |
url |
http://dx.doi.org/10.1590/S0004-27492011000500009 http://repositorio.unifesp.br/handle/11600/6657 |
identifier_str_mv |
Arquivos Brasileiros de Oftalmologia. Conselho Brasileiro de Oftalmologia, v. 74, n. 5, p. 352-356, 2011. 10.1590/S0004-27492011000500009 S0004-27492011000500009.pdf 0004-2749 S0004-27492011000500009 WOS:000298348100010 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
Arquivos Brasileiros de Oftalmologia |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
352-356 application/pdf |
dc.publisher.none.fl_str_mv |
Conselho Brasileiro de Oftalmologia |
publisher.none.fl_str_mv |
Conselho Brasileiro de Oftalmologia |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268282911326208 |