title: Intravitreal administration of the anti-TNF monoclonal antibody infliximab in the rabbit.
abstract: BACKGROUND
  Tumor necrosis factor (TNF) is known to play an important role in various immune-mediated ocular diseases; intravenous administration of the anti-TNF monoclonal antibody infliximab has proved beneficial in such cases. Since intravitreal injection (when available) is a substitute for systemic administration of various drugs targeting the eye, we aimed to evaluate the safety of intravitreal injection of infliximab in the rabbit eye.
  
  
  METHODS
  Seven groups of New Zealand white rabbits (four animals in each group) received a single unilateral intravitreal injection (0.1 ml) of increasing doses of infliximab (namely 1, 2, 5, 8, 10 or 20 mg infliximab [Remicade]) or a sham injection respectively. Slit-lamp biomicroscopy, fundoscopy and electrophysiology recordings, i.e. scotopic, photopic and flicker responses, were performed at baseline and after 1, 5, 10, 15, 30 and 45 days. Infliximab-injected eyes were compared with sham-injected and with uninjected fellow eyes (n = 28). Animals were euthanized on day 45 for histopathological examination of the retinas.
  
  
  RESULTS
  Clinical examination and electrophysiological testing were consistently unremarkable after either sham or 1 mg or 2 mg infliximab injections. In contrast, electrophysiological recordings were significantly reduced in a dose-dependent manner from day 1 through day 45, after 5, 8, 10 and 20 mg infliximab injections. Flicker responses were the most sensitive in detecting the lower toxic dose of 5 mg. Histopathological findings were similar in uninjected and sham-injected eyes, as well as after 1 mg or 2 mg infliximab injections. Consistent with the functional abnormalities, retinal deformities and diffuse edema were observed after injection of 5 mg or higher doses of infliximab.
  
  
  CONCLUSIONS
  Intravitreal infliximab may be safely administered up to a dose of 2 mg in the rabbit eye. Such doses can be used in the design of future clinical trials assessing the effects of infliximab for selected patients with immune-mediated ocular conditions.
authors.affiliation: 2nd Department of Ophthalmology, Attikon University Hospital, University of Athens, Athens, Greece. patheo@med.uoa.gr
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Theodossiadis
authors.forename: Vasilios S
authors.initials: VS
authors.lastname: Liarakos
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
authors.forename: Alexander
authors.initials: A
authors.lastname: Charonis
authors.forename: Georgios
authors.initials: G
authors.lastname: Agrogiannis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Vergados
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000633:toxicity; D055253:Color Vision / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005128:Eye Diseases / Q000188:drug therapy; D005425:Flicker Fusion / Q000187:drug effects; D000069285:Infliximab; D007267:Injections; D008297:Male; D023421:Models, Animal; D055254:Night Vision / Q000187:drug effects; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014822:Vitreous Body
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab