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BC Gilger, KA Roberge, JH Salmon, LP J Cruysburg, MR Robinson, H Kim, HF Edelhauser, M Papich; In Vivo And In Vitro Studies Of Transscleral Diffusion Of Cyclosporine A Through Equine Sclera . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1852.
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Purpose:Sustained vitreal delivery of cyclosporine A (CsA) has been effective in several animal models of uveitis. The purpose of this study was to determine the transscleral penetration of a large lipid soluble protein, CsA, and to determine the feasibility of this method of drug delivery to the posterior segment of the eye Methods:Normal equine eyes were enucleated immediately after euthanasia and a section of equatorial scleral was placed in diffusion chambers. CsA solution (500 ml of 50 ug/ml) was placed on the episcleral side of the sclera and a sample was collected from the BSS perfusing the uveal side of the sclera every hour for 40 hours. Diffusion experiments were repeated using human sclera. CsA in collected samples were quantitated by HPLC. Devices (PVA matrix / reservoir) delivering an initial 25ug/day burst then a sustained release of 6 ug/day of CsA were placed subconjunctivally in contact with the equatorial sclera, approximately 1 cm dorsolateral to the limbus of one eye. The opposite eye had a non-CsA containing sham device implanted. Horses were euthanized at 7 and 30 days after implantation. CsA levels in the vitreous and equine ocular tissue were quantitated by HPLC. Results:Diffusion of CsA through equine sclera peaked (56.5-62.5 ng/ml) at 4 to 8 hours, while in human sclera, CsA concentrations peaked at 420,000 ng/ml at 24hours. At 7 days postimplantation in vivo, vitreal CsA levels were 20.75 ± 5.3 ng/ml. At 30 days postimplantation, vitreal CsA levels were 42.65 ± 10.3 ng/ml. The eyes with sham devices had no detectable levels of CsA. Conclusion:Although scleral thickness at the equator is comparable, CsA diffusion in vitro was much greater in human vs equine sclera. However, sustained CsA release devices provided low but detectable levels of CsA in the large equine vitreal body by 7 days and sustained these levels through 30 days.
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