THE DIAGNOSIS AND TREATMENT OF HUMAN UVEITIS

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The goal of this project is to develop improved methods for diagnosing and treating human uveitis. In the area of diagnosis, biopsy and pathology specimens are examined from patients with uveitis and AIDS to develop improved diagnostic tests for better understanding the pathophysiology of inflammatory eye disease. This laboratory has shown that repeat vitrectomies are required to make the diagnosis of intraocular lymphoma in 30% of cases, and lymphoma can often be diagnosed by examination of the cerebrospinal fluid. To improve methods for diagnosing ocular sarcoidosis, we are testing lacrimal gland and conjunctival biopsies for the presence of interferon-gamma; Kveim antigen; interleukins 2, 3, 4, 6, and 8; and T-cell receptors possibly specific for this disease. Indocyanine green angiography is used to study choroidal blood flow in patients with uveitis. Corticotropin-releasing hormone tests are performed on patients with uveitis to determine whether a defective hypothalamic-pituitary- adrenal axis is associated with increased risk for autoimmune ocular inflammatory disease. We are the first to demonstrate coinfection of the retina and choroid with Pneumocystis carinii and Mycobacteria avium-intracellulare in a patient with AIDS. Our studies of animals with endotoxin-induced uveitis have shown that animal strains with increased numbers of mast cells in the anterior uveal tract have more severe disease. We have documented the role of various cytokines in this disease. In the area of treatment, several studies are in progress: (1) A masked, randomized crossover study comparing acetazolamide to placebo for the treatment of uveitic cystoid macular edema is in progress, and 26 patients have been recruited. (2) Topically applied FK506 is being tested as a treatment for acute anterior uveitis using animals with endotoxin-induced uveitis in the rat. (3) Behet's disease may cause profound ocular inflammation and blindness. We retrospectively reviewed 19 patients with severe Behet's uveitis treated with cyclosporine. Followup (mean, 50.9 months) of patients on cyclosporine (initial doses, 2.7-10.9 mg/kg) showed 11 of 19 patients (58%) had stabilization or improvement of visual acuity in each eye. Cyclosporine was discontinued because of side effects in three patients due to renal toxicity, hypertension, and neurologic symptoms. Cyclosporine is an effective treatment for many patients with Behet's uveitis.