The goal of this project is to develop improved methods for the diagnosis and treatment of ocular inflammatory diseases in human patients of all ages including uveitis, scleritis, inflammatory diseases of the ocular surface, and intraocular malignancies. Over the past year clinical studies have continued to focus on examining the effectiveness of new therapeutic agents with a milder safety profile than that offered by currently available standard immunosuppressive medications. This year we have initiated our experience with infliximab (Remicade), a chimeric human/murine monoclonal antibody that neutralizes the biologic activity of TNF-alpha for the treatment of Behcet's disease, scleritis, and posterior segment uveitis including retinal vasculitis. Although infliximab seems to be an effective alternate therapy for the treatment of ocular inflammatory disease the potential for ocular complications may limit the usage of the agent. Clinical studies with daclizumab (HAT, Zenapax), a humanized monoclonal anti-IL-2 receptor antibody, are ongoing in patients with non-infectious intermediate and posterior uveitis and are discussed elsewhere. Other clinical studies in development include evaluating the therapeutic efficacy of infliximab for the treatment of active scleritis and anakinra (Kineret), a IL-1 receptor antagonist, for the treatment of anterior uveitis in children and adults. We have completed animal work evaluating the use of the IL-1 inhibitor in animals. In addition to systemic therapy with corticosteroids, ocular inflammatory disease can be treated with corticosteroids given topically or by injection in or around the eye. In the past year we have verified previous work showing that subconjunctival steroids can be effective local therapy for the treatment of non-necrotizing scleritis in patients without a history of increased intraocular pressure or glaucoma. We also demonstrated that mycophenolate mofetil, a selective inhibitor of T and B lymphocytes can be used as an effective steroid sparing agent in patients with active scleritis. We continue to analyze vitreal cytokine levels from primary intraocular lymphoma (PIOL) and uveitic patients and continue to use the cutoff point in disease diagnosis with an IL-10 to IL-6 ratio greater than 1.0 for PIOL. We have used immunopathologic techniques to demonstrate the putative cause of retinal degeneration in patients. In addition, we have begun plans to perform a pilot study using an antiCD11a antibody in the treatment of uveitic macular edema. As well, we are are a site for the MUST (multicenter uveitis steroid treatment study which will evaluate the use of the steroid intraocular implant to standard therapy. We plan to collect vitreous samples from those patients undergoing surgery for implant placement. This samples will be evaluated for the presence of cytokines and for the proteome.
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