DIAGNOSIS AND TREATMENT OF OCULAR INFLAMMATORY DISEASE

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The goal of this project is to develop improved methods for diagnosing and treating ocular inflammatory disease and encompasses both laboratory and clinical studies of uveitis, ocular malignancy, and ocular allergy. The development of ocular inflammation depends on the production of specific inflammatory cytokines and the expression of cell adhesion molecules that lead to the homing and migration of leukocytes into the eye. Using a murine model of ocular allergy developed in our lab, we demonstrated an exacerbation of allergic conjunctivitis in gamma-interferon knock out mice and resistance to ocular allergy in interleukin-4 knockout mice suggesting the important immunoregulatory function of these two cytokines. Over the past year we also showed that allergic conjunctivitis could be inhibited by blocking two cell adhesion molecules, a monoclonal antibody against (ICAM-1) or its ligand, lymphocyte function-associated molecule-1 (LFA-1), inhibited the development of allergic conjunctivitis. We have previously shown that blocking cell adhesion molecules inhibits other forms of ocular inflammation such as uveitis. Clinical trials for treating ocular inflammation by blocking cell adhesion molecules are planned. Clinical studies have focused on the diagnosis and treatment of uveitis and intraocular lymphoma. The diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebral spinal fluid (CSF), or vitreous; however, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. We showed that the occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to IL-6 and that measurement of these cytokines can be useful for the diagnosis of this malignancy. Ongoing clinical trials are studying the natural history of vision and visual functioning in patients with uveitis. The NEI has also been investigating the safety and efficacy of oral administration of antigens as a treatment for uveitis. Type II collagen is a possible autoimmune antigen in patients with various forms of rheumatoid arthritis. We are conducting a Phase I/II, open label trial of type II collagen for patients with juvenile rheumatoid arthritis with both joint and eye disease.