[Topical cyclosporine in ophthalmology: Pharmacology and clinical indications]

Cyclosporine A (CsA) is a cyclic undecapeptide, which is an immunosuppressive drug in the calcineurin inhibitor class. CsA was initially used as a systemic immunosuppressant to minimize rejection of solid organ transplants. In ophthalmology, topically applied CsA was first used to inhibit corneal allograft rejection in the 1980s and later in various inflammatory ocular surface disorders (OSD). Currently, topical ophthalmic CsA is available as a licensed commercial emulsion or is prepared by hospital pharmacies with concentration ranging from 0.05 to 2%. Many of its pharmacological effects on the ocular surface are direct consequences of its ability to inhibit T ciclosporine activation and apoptosis. Topical CsA differs from topical steroids in its favourable local and systemic tolerability at the concentrations used. Most clinical studies have evaluated topical CsA in moderate to severe dry eye disease (DED) and demonstrated its efficacy for improvement of signs and symptoms, thus providing the sole indication for market approval and treatment protocols. For the other indications - corneal graft rejection, blepharitis, allergic or viral keratitis, and ocular surface disease due to graft versus host disease or post-operative DED - evidence-based medicine remains unclear due to the lack of major randomized controlled trials. Despite the lack of standardized protocols or market approval for these conditions, numerous studies suggest clinical efficacy.