Nonspecific orbital inflammation (NSOI) is an inflammatory disease which causes pain, diplopia, and loss of vision. The pathogenesis of NSOI is largely unknown and virtually unstudied. Microarray analysis of gene expression has enjoyed marked success in providing novel insights into disease pathogenesis. In addition, microarray profiling has been used to identify distinct subsets of disease that in many instances are indistinguishable by histopathology. We propose to utilize microarray gene expression profiling from formalin- fixed, paraffin-embedded (FFPE) orbital biopsies to gain insight into the pathogenesis of NSOI. Gene expression patterns from orbital tissue of patients with NSOI will be compared with gene expression patterns from orbital biopsies from patients with thyroid orbitopathy, sarcoidosis, or Wegener's granulomatosis as well as patterns from normal orbital fat, normal lacrimal gland, or extraocular muscle. We hypothesize that patients with NSOI will have distinct patterns of gene expression that will provide insights into the pathogenesis of the disease. Furthermore, we hypothesize that NSOI is a heterogeneous collection of diseases and that this heterogeneity can be definitively demonstrated by gene expression profiling. Finally we hypothesize that gene expression profiling will help in prognostic and therapeutic decision making for patients with this highly morbid diagnosis.

Public Health Relevance

Inflammation within the eye socket or orbit causes pain, double vision, and loss of vision. Several diseases including sarcoidosis, Wegener's granulomatous, Graves'disease (hyperthyroidism) and so called nonspecific orbital inflammatory disease can cause orbital inflammation. We have organized 14 centers from around the world to contribute previously biopsied tissue to analyze tissue patterns of gene expression from patients with orbital inflammation in order to clarify the cause, predict prognosis, and ultimately improve the therapy.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Special Emphasis Panel (ZRG1-ETTN-E (92))
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Mckie, George Ann
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Oregon Health and Science University
Schools of Medicine
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Rosenbaum, James T; Choi, Dongseok; Harrington, Christina A et al. (2017) Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland. JAMA Ophthalmol 135:1156-1162
Yang, Sung J; Salek, Sherveen; Rosenbaum, James T (2017) Ocular sarcoidosis: new diagnostic modalities and treatment. Curr Opin Pulm Med 23:458-467
Rosenbaum, James T; Sibley, Cailin H; Choi, Dongseok et al. (2016) Molecular diagnosis: Implications for ophthalmology. Prog Retin Eye Res 50:25-33
Rosenbaum, James T; Choi, Dongseok; Wilson, David J et al. (2015) Fibrosis, gene expression and orbital inflammatory disease. Br J Ophthalmol 99:1424-9
Rosenbaum, James T; Choi, Dongseok; Wilson, David J et al. (2015) Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling. Exp Mol Pathol 99:271-8
Rosenbaum, James T; Choi, Dongseok; Wilson, David J et al. (2015) Molecular diagnosis of orbital inflammatory disease. Exp Mol Pathol 98:225-9
Rivera-Grana, Erick; Lin, Phoebe; Suhler, Eric B et al. (2015) Methotrexate as a Corticosteroid-Sparing Agent for Thyroid Eye Disease. J Clin Exp Ophthalmol 6:
Rosenbaum, James T; Choi, Dongseok; Wong, Amanda et al. (2015) The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment. PLoS One 10:e0137654
Rosenbaum, James T; Choi, Dongseok; Wilson, David J et al. (2015) Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood. JAMA Ophthalmol 133:770-7
Pasadhika, Sirichai; Rosenbaum, James T (2015) Ocular Sarcoidosis. Clin Chest Med 36:669-83

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