Abstract
Abstract: :
Purpose: An intravitreal sustained release fluocinolone acetonide (FA) device is being used in clinical trials in eyes with chronic posterior uveitis. In this study, we determined the efficacy of two low release–rate (1.0 µg/day and 0.6 µg/day) intravitreal injectable sustained release fluocinolone acetonide devices to inhibit ocular inflammation in a rabbit model of severe uveitis. Methods: An injectable sustained released FA device was delivered into the right vitreous cavity of NZW rabbits through a modified 25 gauge needle, seven days after a subcutaneous injection of tuberculin antigen. Devices with a release rate of either (a) 1.0 µg/day (n=9) or (b) 0.6 µg/day (n=11) were used. Control animals (n=9) received empty devices. Uveitis was induced with an intravitreal tuberculin antigen injection. Masked observers graded anterior chamber (AC) flare, cell and vitreous opacity on days 1–7, 10, and 14 after uveitis induction. Enucleated eyes and recovered devices were used to confirm drug release rates and vitreous drug concentrations Results: The devices inserted into the vitreous cavity without complications. By clinical criteria, treated eyes were less inflamed than untreated eyes. Both injectable sustained–released FA devices significantly reduced vitreous opacity compared to controls (p<0.04). There was a significant difference in anterior chamber flare (p=0.03) and vitreous opacity (p<0.01) among the three groups with inflammation suppressed to a greater degree with the 1.0 µg/day device compared to the 0.6 µg/day device. Vitreous concentration of FA in enucleated eyes was comparable to eyes with standard sized devices. Conclusions: Injectable, low release rate FA devices suppress ocular inflammation in a rabbit model of severe uveitis. The injectable device used in this study could be implanted into eyes in a sterile clinic setting and produced vitreous drug concentrations comparable to standard–sized FA devices.
Keywords: uveitis-clinical/animal model • vitreous • injection