Cyclosporine: A Historical Perspective on Its Role in the Treatment of Noninfectious Uveitis

The history of cyclosporine and uveitis is intertwined with the development of experimental autoimmune uveitis (EAU) animal models and the understanding that T lymphocytes play a major role in the pathogenesis of uveitis. The early studies of CsA in uveitis also demonstrated the power of collaborative efforts in translational research. Dr. Robert Nussenblatt and his colleagues were the first to show that CsA can inhibit EAU. Over many years after the initial CsA experiments, Dr. Nussenblatt's group as well as others continued to study CsA under experimental conditions as well as in clinical trials with human patients. The data and observations from these studies significantly advanced our knowledge of uveitis pathophysiology and demonstrated the value of well-designed masked, controlled treatment trials in uveitis. Dr. Nussenblatt and his collaborators delved into the most significant adverse effect of CsA, renal toxicity, and helped elucidate the pathophysiology of renal injury. They explored adjunctive treatments to improve the efficacy and decrease the toxicity of CsA and also studied other members of the cyclosporine family. Among the immunosuppressives used to treat ocular inflammation, CsA was the first, and remains the only medication comprehensively studied under both experimental and clinical conditions.