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 scleritis, and posterior segment uveitis including retinal vasculitis as well as the humanized form of the antibody Humira. 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. We evaluated the presence of T -regulatory cells in humans and defined their characteristics. We have seen that uveitis patients resistant to steroid therapy have a group of IL-17 producing cells in the CD4+CD25+ subpopulation. An ongoing protocol evaluating oral tolerance in uveitis is mentioned in a separate report. 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. As well, the MUST (multicenter uveitis steroid treatment study results of the study were made available. The SITE study, in which we participated demonstrated that there was no increased mortality due to long term immunosuppressive therapy for uveitis. SITE 2 will start in the near future. The use of anti-IL-12 and Humira in childhood uveitis are planned We have identified elevated levels of IL-17 in patients with Sarcoidosis. As well, the CFH variant associated with AMD we reported to be associated with ocular sarcoidosis at the same incidence as in AMD.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000356-13
Application #
8737622
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2013
Total Cost
$212,753
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Nicholson, Benjamin P; Zhou, Mei; Rostamizadeh, Mahdi et al. (2014) Epidemiology of epiretinal membrane in a large cohort of patients with uveitis. Ophthalmology 121:2393-8
Lima, Breno R; Mandelcorn, Efrem D; Bakshi, Nupura et al. (2014) Syphilitic outer retinopathy. Ocul Immunol Inflamm 22:4-8
Artornsombudh, Pichaporn; Pistilli, Maxwell; Foster, C Stephen et al. (2014) Factors predictive of remission of new-onset anterior uveitis. Ophthalmology 121:778-84
Grange, Landon; Dalal, Monica; Nussenblatt, Robert B et al. (2014) Autoimmune retinopathy. Am J Ophthalmol 157:266-272.e1
Nicholson, Benjamin P; Nigam, Divya; Miller, Darby et al. (2014) Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis. Am J Ophthalmol 157:673-7
Keane, Pearse A; Karampelas, Michael; Sim, Dawn A et al. (2014) Objective measurement of vitreous inflammation using optical coherence tomography. Ophthalmology 121:1706-14
Sen, H Nida; Vitale, Susan; Gangaputra, Sapna S et al. (2014) Periocular corticosteroid injections in uveitis: effects and complications. Ophthalmology 121:2275-86
Jawad, Shayma; Liu, Baoying; Agron, Elvira et al. (2013) Elevated Serum Levels of Interleukin-17A in Uveitis Patients. Ocul Immunol Inflamm :
Thompson, Ian A; Liu, Baoying; Sen, H Nida et al. (2013) Association of complement factor H tyrosine 402 histidine genotype with posterior involvement in sarcoid-related uveitis. Am J Ophthalmol 155:1068-1074.e1
Cunningham, Matthew A; Li, Zhuqing; Liu, Baoying et al. (2013) OX40 ligand expression abrogates the immunosuppressive function of retinal pigment epithelium. J Ophthalmic Inflamm Infect 3:12

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