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K. Lalwani, M. Ni, J. Edelman, G. De Vries; Effects of Posurdex in an Experimental Model Panuveitis in Rabbits. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5159.
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Of all the new drug delivery technology, intravitreal steroid implants are the closest to clinical use. Such steroid implants may inhibit inflammation, reduce retinal vessel leakage, or slow down the growth of retinal or subretinal neovascularization. The goal of this study is to investigate the effects of Posurdex, a biodegradable dexamethasone drug delivery system, in reducing ocular autoimmune inflammation using a rabbit experimental model of panuveitis.
Twenty-four (24) Dutch Belted rabbits were immunized subcutaneously twice with 10 mg of Mycobacterium tuberculosis H37Ra antigen on day 0 and day 7. Rabbits were randomized into 3 groups of 8 rabbits each. The right eye of each rabbit was either sham-treated or implanted with Posurdex. Group one received sham intravitreal implant on day 14; group two received Posurdex (700 µg) intravitreal implants on day 14; group three received Posurdex (700 µg) intrascleral implant on day 7. Following the procedures described above, both eyes of each rabbit were challenged with an intravitreal injection of 3 µg Mycobacterium tuberculosis H37Ra antigen formulated in 0.9% saline on day 21. All study eyes were examined with a Slit Lamp and Fundus Camera at day 22, 28 and 35 for any effects that Posurdex may have on intraocular autoimmune inflammation. The severity of the intraocular autoimmune inflammation was evaluated using McDonald-Shadduck (for the anterior segment of the eye) and Nussenblatt Scores (for the posterior segment of the eye). Lastly, rabbits were euthanized on day 28 and 35 for aqueous inflammatory cell count, protein determination, and histological examination.
Eyes with intravitreally-implanted Posurdex exhibited a significantly-reduced intravitreal inflammation compared to the contralateral non-treated eyes or sham-treated eyes. Eyes with intrascleraly-implanted Posurdex exhibited a significantly-reduced intravitreal inflammation compared to the sham-treated eyes. However, there was no difference between right (OD) Posurdex-treated eyes and left (OS) untreated eyes suggesting systemic cross-over.
Our results demonstrate that intravitreal implants of a biodegradable corticosteroid drug-delivery system are highly effective in suppressing intraocular autoimmune disease, thereby offering a potential therapeutic approach for diseases located at the anterior and posterior segment of the eye.
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