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.