A Pilot Study on Ocular Safety of Intravitreal Infliximab in a Rabbit Model

• Published in: Investigative ophthalmology & visual science 2008-03, Vol.49 (3), p.1151-1156
• Main Authors: Giansanti, Fabrizio, Ramazzotti, Matteo, Vannozzi, Lorenzo, Rapizzi, Emilio, Fiore, Tito, Iaccheri, Barbara, Degl' Innocenti, Donatella, Moncini, Daniela, Menchini, Ugo
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - toxicity; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - toxicity; Biological and medical sciences; Electroretinography - drug effects; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Half-Life; Infliximab; Injections; Medical sciences; Models, Animal; Ophthalmology; Pilot Projects; Rabbits; Retina - drug effects; Retina - pathology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Vertebrates: nervous system and sense organs; Vitreous Body - metabolism
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-0932

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. 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. 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. 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.