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 its 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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
3U10EY014656-06S1
Application #
8546002
Study Section
Special Emphasis Panel (ZEY1-VSN (11))
Program Officer
Wideroff, Louise
Project Start
2004-07-15
Project End
2017-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
6
Fiscal Year
2012
Total Cost
$28,540
Indirect Cost
$5,889
Name
University of Wisconsin Madison
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Sugar, Elizabeth A; Venugopal, Vidya; Thorne, Jennifer E et al. (2017) Longitudinal Vision-Related Quality of Life for Patients with Noninfectious Uveitis Treated with Fluocinolone Acetonide Implant or Systemic Corticosteroid Therapy. Ophthalmology 124:1662-1669
Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group; Kempen, John H; Altaweel, Michael M et al. (2017) Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis. JAMA 317:1993-2005
Holbrook, Janet T; Sugar, Elizabeth A; Burke, Alyce E et al. (2016) Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Am J Ophthalmol 164:29-36
Altaweel, Michael M; Gangaputra, Sapna S; Thorne, Jennifer E et al. (2016) Morphological assessment of the retina in uveitis. J Ophthalmic Inflamm Infect 6:33
Yu, Tsung; Holbrook, Janet T; Thorne, Jennifer E et al. (2016) Using a patient-centered approach to benefit-harm assessment in treatment decision-making: a case study in uveitis. Pharmacoepidemiol Drug Saf 25:363-71
Sen, H Nida; Abreu, Francis M; Louis, Thomas A et al. (2016) Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology 123:183-90
Kempen, John H; Van Natta, Mark L; Altaweel, Michael M et al. (2015) Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial. Am J Ophthalmol 160:1133-1141.e9
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen, John H; Altaweel, Michael M et al. (2015) Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Ophthalmology 122:1967-75
Multicenter Uveitis Steroid Treatment (MUST) Trial Follow-up Study Research Group (2015) Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatmen Ophthalmology 122:1976-86
Yu, Tsung; Holbrook, Janet T; Thorne, Jennifer E et al. (2015) Outcome Preferences in Patients With Noninfectious Uveitis: Results of a Best-Worst Scaling Study. Invest Ophthalmol Vis Sci 56:6864-72

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