Objective: To determine the efficacy of 0.5-mg and 0.1-mg sustained-release fluocinolone acetonide intravitreal implants to inhibit ocular inflammation in a rabbit model of severe uveitis.
Methods: The in vitro pharmacokinetic profile of both the 0.5-mg and 0.1-mg sustained-release fluocinolone intravitreal implants was determined during a 10-day period. A sustained-release fluocinolone acetonide intravitreal implant with a release rate of either 0.5 microg/d (n = 16) or 0.1 microg/d (n = 16) was implanted into the vitreous cavity of the right eye in albino rabbits after a subcutaneous injection of tuberculin antigen. Control animals (n = 14) received empty devices. Uveitis was induced with an intravitreal tuberculin antigen injection. A masked observer graded anterior chamber flare, anterior chamber cells, vitreous opacity, and inflammation on histologic sections.
Results: In vitro, the drug was released from both devices in a linear manner. In vivo, treated eyes were significantly less inflamed than untreated eyes (P< or =.02). Inflammation was suppressed to a greater degree with the 0.5-microg/d implant compared with the 0.1-microg/d implant.
Conclusion: Sustained-release fluocinolone intravitreal implants suppress ocular inflammation in a rabbit model of severe uveitis.
Clinical relevance: The efficacy demonstrated with the 0.1-microg/d implant provides the rationale for future human studies with lower-release-rate implants than are currently used in noninfectious uveitis clinical trials.