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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000356-09
Application #
7968320
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2009
Total Cost
$263,372
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Kim, Jane S; Jaworski, Laurence; Patel-Donnelly, Dipti et al. (2017) WALDENSTRÖM'S MACROGLOBULINEMIA MASQUERADING AS BIRDSHOT CHORIORETINOPATHY. Retin Cases Brief Rep 11:152-155
Knickelbein, Jared E; Sen, H Nida (2016) Multimodal Imaging of the White Dot Syndromes and Related Diseases. J Clin Exp Ophthalmol 7:
Kim, Jane S; Knickelbein, Jared E; Jaworski, Laurence et al. (2016) Enhanced Depth Imaging Optical Coherence Tomography in Uveitis: An Intravisit and Interobserver Reproducibility Study. Am J Ophthalmol 164:49-56
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Liu, Baoying; Dhanda, Ashwin; Hirani, Sima et al. (2015) CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses. J Immunol 194:5150-60
Knickelbein, Jared E; Chan, Chi-Chao; Sen, H Nida et al. (2015) Inflammatory Mechanisms of Age-related Macular Degeneration. Int Ophthalmol Clin 55:63-78
Levin, Marc H; Pistilli, Maxwell; Daniel, Ebenezer et al. (2014) Incidence of visual improvement in uveitis cases with visual impairment caused by macular edema. Ophthalmology 121:588-95.e1
Keane, Pearse A; Karampelas, Michael; Sim, Dawn A et al. (2014) Objective measurement of vitreous inflammation using optical coherence tomography. Ophthalmology 121:1706-14
Lima, Breno R; Mandelcorn, Efrem D; Bakshi, Nupura et al. (2014) Syphilitic outer retinopathy. Ocul Immunol Inflamm 22:4-8

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