title: [A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes].
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ophthalmology Department, Centro de Referência em Oftalmologia, Universidade Federal de Goiás, Goiânia, Brazil. alanrassi@ipvisao.com.br
authors.forename: Alan Ricardo
authors.initials: AR
authors.lastname: Rassi
authors.forename: Moacyr Pezati
authors.initials: MP
authors.lastname: Rigueiro
authors.forename: David Leonardo Cruvinel
authors.initials: DL
authors.lastname: Isaac
authors.forename: Letícia
authors.initials: L
authors.lastname: Dourado
authors.forename: Murilo Batista
authors.initials: MB
authors.lastname: Abud
authors.forename: Ericka Campos
authors.initials: EC
authors.lastname: Freitas
authors.forename: Luciana Barbosa
authors.initials: LB
authors.lastname: Carneiro
authors.forename: Marcos Pereira de
authors.initials: MP
authors.lastname: Avila
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D000069285:Infliximab; D058449:Intravitreal Injections; D009887:Ophthalmoscopy; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab