A comparative approach to topical cyclosporine therapy

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Abstract
Topical cyclosporine has been used by veterinary ophthalmologists since 1989 for the treatment of ocular surface inflammatory disease and keratoconjunctivitis sicca (KCS). As well as ameliorating clinical signs of ocular surface lymphocyte-driven inflammation in the dog, cat and horse, topical cyclosporine significantly raises tear production in both normal and KCS-affected animals. A licensed ointment preparation of 0.2% cyclosporine, Optimmune (Schering-Plough), is now available for administration to dogs. In this paper we examine the mechanisms by which cyclosporine exerts both its immunomodulatory and its lacrimogenic actions. The pharmacokinetics of topical cyclosporine are examined to determine whether these effects are truly local or are influenced by generalised immunosuppression caused by systemic absorption of topically applied drug. The paper reviews the few side effects of cyclosporine preparations in the experience of veterinary ophthalmologists and the experimental evidence which appears to implicate the vehicle rather than the active agent cyclosporine as causing many of these effects. Given that topical cyclosporine has been so widely accepted as a valuable ophthalmic preparation in the veterinary world and licensed as such, it is surprising that human ophthalmologists have not employed the drug to the same extent for conditions from vernal keratoconjunctivitis to Sjögren's syndrome.