The goal of this project is to develop improved methods for diagnosing and treating human uveitis. To improve our diagnostic acumen, we are analyzing conjunctival and lacrimal gland biopsies from patients with sarcoidosis, vitreous specimens from patients with intraocular lymphoma and Propionibacterium acnes endophthalmitis, and serological tests in patients with Behcet's disease and Lyme disease. The work includes several aspects: (1) Intraocular infection by Propionibacterium acnes is a cause of persistent uveitis following cataract surgery. We have characterized the inflammatory response in these patients, and demonstrated a lack of T suppressor, which may explain the chronic inflammation seen in these patients. (2) We have examined the role of vitrectomy in diagnosing intraocular lymphoma, and showed that repeat vitrectomies were required to make the diagnosis in 30% of cases. (3) Positive Lyme serologies found in 4 of 25 patients with intermediate uveitis appear to represent false-positive tests. Work is also in progress to evaluate the use of serologic tests in predicting the level of activity of Behcet's disease. (4) A masked, randomized crossover study comparing acetazolamide to placebo for the treatment of uveitic cystoid macular edema is in progress. We are also 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 that are felt to be specific for sarcoidosis.