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 NE! 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.

Public Health Relevance

Uveitis is a major cause of visual impairment, requiring chronic treatment with systemic and/or ocular therapy that may induce significant morbidity. Newer treatments designed to improve outcome while limiting adverse effects include the fluocinilone implant, intravitreal steroids, intravitreal ranibizumab, and Adalimumab. Evidence supporting such treatments is limited. Randomized trials will elucidate appropriate management.

National Institute of Health (NIH)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZEY1)
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Wideroff, Louise
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University of Wisconsin Madison
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United States
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Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Sugar, Elizabeth A; Holbrook, Janet T et al. (2014) Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for noninfectious intermediate, posterior, and panuveitis. Ophthalmology 121:1855-62
Hsieh, Jane; Honda, Andrea F; Suarez-Farinas, Mayte et al. (2013) Fundus image diagnostic agreement in uveitis utilizing free and open source software. Can J Ophthalmol 48:227-34
Friedman, David S; Holbrook, Janet T; Ansari, Husam et al. (2013) Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial. Ophthalmology 120:1571-9
Kempen, John H; Sugar, Elizabeth A; Jaffe, Glenn J et al. (2013) Fluorescein angiography versus optical coherence tomography for diagnosis of uveitic macular edema. Ophthalmology 120:1852-9
Frick, Kevin D; Drye, Lea T; Kempen, John H et al. (2012) Associations among visual acuity and vision- and health-related quality of life among patients in the multicenter uveitis steroid treatment trial. Invest Ophthalmol Vis Sci 53:1169-76
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Taylor, Simon R J; Lightman, Susan L; Sugar, Elizabeth A et al. (2012) The impact of macular edema on visual function in intermediate, posterior, and panuveitis. Ocul Immunol Inflamm 20:171-81
Madow, Brian; Galor, Anat; Feuer, William J et al. (2011) Validation of a photographic vitreous haze grading technique for clinical trials in uveitis. Am J Ophthalmol 152:170-176.e1
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen, John H; Altaweel, Michael M et al. (2011) Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology 118:1916-26
Holbrook, Janet T; Kempen, John H; Prusakowski, Nancy A et al. (2011) Challenges in the design and implementation of the Multicenter Uveitis Steroid Treatment (MUST) Trial--lessons for comparative effectiveness trials. Clin Trials 8:736-43

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