title: A pilot study on ocular safety of intravitreal infliximab in a rabbit model.
abstract: OBJECTIVE
  To determine whether infliximab may be used safely as an intraocular drug, the ocular safety of intravitreal infliximab in rabbits was studied by clinical examination, electroretinography (ERG), and histology in rabbits.
  
  
  METHODS
  Twelve New Zealand albino rabbits were selected for this study. Different infliximab doses, namely 1.0 mg, 1.7 mg, and 3.3 mg in 0.1 mL, were injected intravitreally into one eye each of three rabbits. As a control, the vehicle solution was injected into the fellow eye of each animal. Eye clinical examination and ERG recordings were made before and 2, 6, and 12 weeks after injection. Eventually, the rabbits were humanely killed, and the retinas were examined by light microscopy. In addition, the elimination half-life of the drug in the vitreous was assessed.
  
  
  RESULTS
  Slit lamp biomicroscopy, indirect funduscopy, and ERG evidenced no significant differences between control and infliximab-injected eyes in this rabbit model, at any of the tested doses. Histologic examination revealed no retinal abnormality in the rabbits injected with 1 mg and 1.7 mg intravitreal infliximab. In two of three eyes injected with 3.3 mg infliximab, significant edema of the nerve fibers was detected compared with the control group. The half-life of the drug was estimated to be 8.5 days.
  
  
  CONCLUSIONS
  These results indicate that infliximab may be a safe intravitreal drug in the rabbit model at a dose of up to 1.7 mg. If proven safe and efficacious in further studies, intravitreal injection of infliximab could be considered an alternative to systemic administration in selected patients.
authors.affiliation: Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, University of Florence, Florence, Italy. fabriziogiansanti@interfree.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giansanti
authors.forename: Matteo
authors.initials: M
authors.lastname: Ramazzotti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Vannozzi
authors.forename: Emilio
authors.initials: E
authors.lastname: Rapizzi
authors.forename: Tito
authors.initials: T
authors.lastname: Fiore
authors.forename: Barbara
authors.initials: B
authors.lastname: Iaccheri
authors.forename: Donatella
authors.initials: D
authors.lastname: Degl' Innocenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Moncini
authors.forename: Ugo
authors.initials: U
authors.lastname: Menchini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects; D006207:Half-Life; D000069285:Infliximab; D007267:Injections; D023421:Models, Animal; D010865:Pilot Projects; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab