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Investigative Ophthalmology & Visual Science, Vol 29, 208-215, Copyright © 1988 by Association for Research in Vision and Ophthalmology


ARTICLES AND REPORTS

Topically applied cyclosporine in azone prolongs corneal allograft survival

C Newton, BM Gebhardt and HE Kaufman
Lions Eye Research Laboratories, LSU Eye Center, New Orleans 70112.

The purpose of this study was to develop and test a topical ocular delivery system for the immunosuppressive drug cyclosporine. To this end, cyclosporine was dissolved in the penetration enhancer, Azone, and applied topically to allografted rabbit eyes. The concentration of cyclosporine in the cornea, the aqueous humor, and blood of the treated rabbits was determined by radioimmunoassay. The effect of the cyclosporine-Azone preparation on the survival of corneal allografts was assessed by clinical evaluation of the grafts and by histopathologic and immunohistologic evaluation of the cellular infiltrate in the grafts. Clinically significant concentrations of cyclosporine were measured in the treated corneas but little or no drug was found in the aqueous humor or blood of the treated animals. Cyclosporine in Azone resulted in suppression in the severity and incidence of graft rejection. The suppression of graft rejection was borne out by the immunohistologic observations. Cyclosporine-treated grafts contained significantly fewer infiltrating T lymphocytes than did the drug/solvent-treated allografts, indicating that the topical application of cyclosporine actively inhibited the entry of T cells into the grafts. This study, for the first time, presents a solvent that is apparently not toxic but is effective in delivering immunologically active concentrations of cyclosporine following topical application to the cornea.





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Copyright © 1988 by the Association for Research in Vision and Ophthalmology