Multicenter uveitis trial using a steroid implant and inflammatory mediators

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Uveitis refers to several ocular disorders characterized by intraocular inflammation, which in the aggregate are a major cause of visual loss and blindness in the United States. Intermediate uveitis, posterior uveitis, and panuveitis are generally the more severe forms of uveitis, with the highest risk of vision loss, often requiring long-term systemic treatment. The fluocinolone acetonide intraocular implant is a surgically implanted reservoir of corticosteroid designed to last approximately 2.5 years in order to provide long-term control of uveitis. The primary objective of the Multicenter Uveitis Steroid Treatment (MUST) Trial, with the NEI being a participating center is to compare the efficacy of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis or panuveitis. Patients with active uveitis have been randomized, with a 1:1 allocation ratio, to treatment with either the fluocinolone acetonide implant or standardized systemic therapy consisting of oral corticosteroids and supplementary immunosuppressive drugs when indicated, according to standardized guidelines. The design outcome variable for the study is visual acuity; other outcomes include other aspects of visual function, success in controlling uveitis, retinal morphologic outcomes, quality of life, cost-effectiveness, and occurrence of potential ocular and systemic complications of uveitis and of therapy. As of November 24, 2008 initial enrollment goal of 250 had been met, and allowed for participants active in the enrollment process who had signed a consent form and had undergone initial evaluations to enroll. This raised the enrollment ceiling to 255 participants. The study will continue until a common study closeout which will be five years from the start of enrollment for patients enrolled prior to January 1, 2007. In addition, we have established a protocol to evaluate the vitreous of patients who undergo the steroid implant here and at other participating centers. The small amount of vitreous that is removed during surgery is usually discarded. We will use microtechnology to look at multiple cytokines and as well will evaluate the small sample for the vitreous proteome as well. In 2008 this study has been opened to all vitreous specimens obtained here at the NIH (as well as control specimens from collaborating outsidfe center-Retina group of Washington under an OHRS clearance and an MTA agreement between NIH and RGW where samples are collected but not yet transferred to NEI), with a large number of vitreous samples and peripheral blood samples collected to date from MUST participating sites. Initial samples have so far been analyzed using multiplex assay and preliminary results have shown the presence of inflammatory cytokines in the vitreous. Proteomic analysis will be one of the major goals this coming year. Dr.Nida Sen has become the PI on the protocol