The goal of this project is to develop improved methods for the diagnosis and treatment of ocular inflammatory diseases in human patients of all ages including uveitis, scleritis, inflammatory diseases of the ocular surface, and intraocular malignancies. Over the past year clinical studies have continued to focus on examining the effectiveness of new therapeutic agents with a milder safety profile than that offered by currently available standard immunosuppressive medications. This year we have initiated our experience with infliximab (Remicade), a chimeric human/murine monoclonal antibody that neutralizes the biologic activity of TNF-alpha for the treatment of Behcet's disease, scleritis, and posterior segment uveitis including retinal vasculitis. Although infliximab seems to be an effective alternate therapy for the treatment of ocular inflammatory disease the potential for ocular complications may limit the usage of the agent. Clinical studies with daclizumab (HAT, Zenapax), a humanized monoclonal anti-IL-2 receptor antibody, are ongoing in patients with non-infectious intermediate and posterior uveitis and are discussed elsewhere. Other clinical studies in development include evaluating the therapeutic efficacy of infliximab for the treatment of active scleritis and anakinra (Kineret), a IL-1 receptor antagonist, for the treatment of anterior uveitis in children and adults. We have completed animal work evaluating the use of the IL-1 inhibitor in animals. In addition to systemic therapy with corticosteroids, ocular inflammatory disease can be treated with corticosteroids given topically or by injection in or around the eye. In the past year we have verified previous work showing that subconjunctival steroids can be effective local therapy for the treatment of non-necrotizing scleritis in patients without a history of increased intraocular pressure or glaucoma. We also demonstrated that mycophenolate mofetil, a selective inhibitor of T and B lymphocytes can be used as an effective steroid sparing agent in patients with active scleritis. We continue to analyze vitreal cytokine levels from primary intraocular lymphoma (PIOL) and uveitic patients and continue to use the cutoff point in disease diagnosis with an IL-10 to IL-6 ratio greater than 1.0 for PIOL. We have used immunopathologic techniques to demonstrate the putative cause of retinal degeneration in patients. In addition, we have begun plans to perform a pilot study using an antiCD11a antibody in the treatment of uveitic macular edema. As well, we are are a site for the MUST (multicenter uveitis steroid treatment study which will evaluate the use of the steroid intraocular implant to standard therapy. We plan to collect vitreous samples from those patients undergoing surgery for implant placement. This samples will be evaluated for the presence of cytokines and for the proteome.

National Institute of Health (NIH)
National Eye Institute (NEI)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
U.S. National Eye Institute
United States
Zip Code
Yeh, Steven; Wong, Wai T; Weichel, Eric D et al. (2010) Fundus Autofluorescence and OCT in the Management of Progressive Outer Retinal Necrosis. Ophthalmic Surg Lasers Imaging :1-4
Cunningham, Matthew A; Austin, Bobbie Ann; Li, Zhuqing et al. (2009) LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells. Invest Ophthalmol Vis Sci 50:249-55
Li, Zhuqing; Liu, Baoying; Maminishkis, Arvydas et al. (2008) Gene expression profiling in autoimmune noninfectious uveitis disease. J Immunol 181:5147-57
Sen, H Nida; Chan, Chi-Chao; Byrnes, Gordon et al. (2008) Intravitreal methotrexate resistance in a patient with primary intraocular lymphoma. Ocul Immunol Inflamm 16:29-33
Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56
Belfort-Neto, Rubens; Nussenblatt, Veronique; Rizzo, Luiz et al. (2007) High prevalence of unusual genotypes of Toxoplasma gondii infection in pork meat samples from Erechim, Southern Brazil. An Acad Bras Cienc 79:111-4
Yin, Philip D; Kurup, Shree K; Fischer, Steven H et al. (2007) Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR. J Clin Virol 38:254-9
Levy-Clarke, Grace; Reed, George; Nussenblatt, Robert (2007) Is anti-tumor necrosis factor therapy effective in reducing uveitis flares in patients with spondyloarthropathies? Nat Clin Pract Rheumatol 3:376-7
Lee, M T; Hooper, L C; Kump, L et al. (2007) Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling. Clin Exp Immunol 147:71-80
Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Liu, Xuebin et al. (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13:711-8

Showing the most recent 10 out of 44 publications