The Efficacy of Posurdex® (Dexamethasone in a Slow Release Biodegradable Device), in the Treatment of Experimental Anterior Uveitis

Abstract

Purpose:: Uveitis describes a group of ocular inflammatory diseases that can result in permanent vision loss if left untreated. Corticosteroids remain the mainstay of uveitis therapy, but many patients are resistant or intolerant of corticosteroid treatment. An intravitreal sustained-release drug delivery system with a potent corticosteroid may improve both the efficacy and safety of steroid therapy. This study evaluated the efficacy of intravitreal Posurdex®, a system that slowly releases the corticosteroid dexamethasone, on suppressing experimental anterior uveitis in rabbits.

Methods:: Anterior uveitis was induced by an intracameral injection of 20ug Mycobacterium Tuberculosis (Mbt) in one eye of 19 rabbits pre-immunized 20 days previously with 2 subcutaneous doses of 10mg Mbt. Animals were divided into 2 groups and dosed intravitreally with either Posurdex® 700 ug or a 22-gauge sham injection 4 days after disease induction. Follow-up consisted of anterior chamber cell scoring (0-4+) with a slit-lamp using a standard grading scale and gross ocular observations. These measures were made prior to and following uveitis induction and drug dosing. Eyes were enucleated at 4 and 13 days for histological evaluation, including morphometric analysis of the ciliary body.

Results:: At baseline, inflammatory cell scores were similar between the two groups: 89 ± 11% of sham eyes had AC cells of ≥3 compared with 90 ± 10% of Posurdex® eyes; at the time of drug dosing. Three days after dosing, 100 ± 0% (n=9) in the sham group had AC cells of ≥ 3 or not evaluable due to massive inflammation and corneal edema (CE) vs 40 ± 16% of eyes in the Posurdex® group (n=10); p = 0.0029. Thirteen days after dosing, 100 ± 0% (n=4) in the sham group had AC cells of ≥ 3 or CE vs 20 ± 20% (n =5) in the Posurdex® group; p = 0.0096. Histological assessment show that this model induces inflammatory infiltrates (lymphocytes, macrophages) and/or edema at the level of the iris, ciliary body, anterior chamber and cornea, but not the vitreous or retina. At the 13 day time-point, ciliary body cross-sectional area for Posurdex® (n=5) was 0.73 ± 0.06 mm² vs 2.47 ± 0.73 mm² for sham (n=4), p = 0.03. There was also a marked decrease of inflammatory cells in eyes treated with Posurdex® compared to the sham-treated eyes.

Conclusions:: Intravitreal dosing with an intravitreal dexamethasone sustained-release drug delivery system (Posurdex®) significantly reduced intraocular inflammation in experimental anterior uveitis.

Keywords: uveitis-clinical/animal model • corticosteroids • inflammation