Intravitreal infliximab in experimental endotoxin-induced uveitis

Abstract

Purpose: Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of ocular inflammation and the level of TNF-alpha is increased in ocular fluids of patients with uveitis. Intravenous infliximab, a monoclonal antibody against TNF-alpha, has been used for the treatment of uveitis with promising preliminary results. The aim of this study was to evaluate the effect of intravitreal injection of infliximab on experimental uveitis.

Methods: Thirty-three white New Zealand rabbits were divided randomly into three groups. Group 1 (n=5) received intravitreal injection of 1 mg/0.1 cc infliximab plus 0.1 cc normal saline, group 2 (n=14) received intravitreal injection of 2 microg Salmonella typhimurium endotoxin plus 1 mg/0.1 cc infliximab, and group 3 (n=14) animals received intravitreal endotoxin 2 microg/0.1 cc plus normal saline 0.1 cc. Inflammation was evaluated by clinical examinations on days 1, 3, 5, and 7 after the injections; measuring the protein concentration and inflammatory cell content of the aqueous humor; and histopathologic examination.

Results: No inflammation occurred in group 1 animals. There was a statistically significant difference between group 2 and 3 animals with regard to clinical examination on the third, fifth, and seventh postinjection days. The differences between groups 2 and 3 were significant with regard to aqueous cell counts and protein content at day 7 (p=0.02 and p=0.001, respectively). Histopathologic examination results showed less inflammation in group 2 animals compared to group 3 animals (p=0.009).

Conclusions: The results provide evidence that intravitreal injection of infliximab suppresses ocular inflammation in a rabbit model of severe endotoxin-induced uveitis.