MUST Competitive Renewal

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Intermediate, posterior, and panuveitis are major causes of vision loss and blindness in the United States. With a peak onset in young adulthood, vision loss due to uveitis will have a greater impact on years of potential vision lost per case than age-related eye diseases. Most of these diseases are chronic and require long-term treatment. Current therapy typically involves the use of oral corticosteroids, supplemented by immunosuppressive drugs in selected situations. The NEI funded MUST trial is comparing the efficacy and morbidity associated with the use of fluocinolone acetonide intraocular implant versus standard therapy with systemic corticosteroids and immunosuppressive medications for such patients. Valuable data being gathered will influence treatment choices. The MUST 2 trial will follow this group for another 6 years, providing objective information regarding the long-term visual and morphologic effects of severe uveitis and further guidance regarding the best management for a chronic disorder. Adalimumab, a TNF inhibitor that downregulates the inflammatory reaction in inflammatory diseases, provides a novel and potentially effective approach to managing uveitis. One protocol will compare the efficacy and morbidity (ocular and systemic) of adalimumab versus corticosteroids and standard immunosuppression for severe uveitis. A common cause of vision loss in uveitis is the development of macular edema. Modalities of treatment found effective for retinal vascular disease have been applied to management of uveitis-related macular edema but do not have sufficient evidence to support their continued use or longterm data regarding safety. Two trials would evaluate the efficacy and safety of intravitreal triamcinolone (Triessence) versus standard subtenons triamcinolone, and intravitreal ranibizumab versus intravitreal triamcinolone for uveitic macular edema. These would be the first randomized trials to properly direct our further management of this common clinical entity. This application supports the creation of a study network that includes a Reading center capable of objectively assessing morphologic ocular changes due to uveitis and it's complications. This resource center will participate in the design, conduct, analysis and reporting of the network studies.