Topical Calcineurin Inhibitors: Expanding Indications for Corneal and Ocular Surface Inflammation

The immune system protects the host against environmental and pathogenic insults while maintaining tolerance to self-antigens and commensal microbial flora. Inflammation and hyperactivity of the immune system play a central role in the pathophysiology of many ocular diseases such as vernal keratoconjunctivitis (VKC), dry eye disease, stromal keratitis, etc. Inflammation is the key target in the treatment of most cornea and ocular surface diseases. Despite many advances in the last several decades, corticosteroids still remain the mainstay of therapy for anterior segment inflammation and are the most widely used topical anti-inflammatory drugs. However, unwanted ocular side effects such as glaucoma and cataract often preclude their use on a chronic basis. Calcineurin inhibitors such as cyclosporine A and tacrolimus are now commonly used as “steroid sparing” topical agents to prevent and treat diseases with T-cell-mediated pathophysiology. They specifically inhibit calcineurin which plays a central role in T-cell activation. Successful treatment of multiple refractory anterior segment inflammatory diseases has been reported with these agents. These conditions include prophylaxis and treatment of corneal graft rejection, chronic allergic keratoconjunctivitis, and ocular graft-versus-host disease.