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. We continue 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. Efalizumab (Raptiva), a humanized anti-CD11a monoclonal antibody shown to reversibly inhibit leukocyte adhesion and trafficking. We evaluated the safety and efficacy of treating macular edema, secondary to non-infectious intermediate and posterior uveitis, with open label efalizumab in a nonrandomized, prospective study. Six patients received weekly subcutaneous treatments. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared to baseline.No serious adverse events were reported by the patients (22-82 years-old). Mean BCVA improvements were 6.76.9 letters (worse eye) and 1.75.2 letters (better eye). Mean CRT reductions were 128105 M (worse eye) and 5768 M (better eye).Efalizumab treatment improved visual function, reduced macular thickness, and potentially may be used in treating other causes of macular edema.We also reported the effective treatment of choroidal neovascularization with rapamycin in a patient with a history of posterior pole inflammatory disease. 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. 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. 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 (this will be reported separately). This study continues with active recruitment.
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| 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 |
| 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 |
| Kurup, Shree K; Levy-Clarke, Grace; Calvo, Katherine R et al. (2007) Primary diffuse large B-cell lymphoma of the spleen with coincident serous retinal detachments responsive to corticosteroids. Clin Experiment Ophthalmol 35:468-72 |
| O'Mahony, Deirdre; Morris, John C; Quinn, Cate et al. (2007) A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin Cancer Res 13:958-64 |
| Nussenblatt, Robert B; Coleman, Hanna; Jirawuthiworavong, Guy et al. (2007) The treatment of multifocal choroiditis associated choroidal neovascularization with sirolimus (rapamycin). Acta Ophthalmol Scand 85:230-1 |
| Levy-Clarke, Grace; Gangaputra, Sapna; Nussenblatt, Robert (2007) Treatment with TNF inhibitors for uveitis associated with juvenile idiopathic arthritis. Nat Clin Pract Rheumatol 3:608-9 |
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