A group of orbital inflammatory diseases, including thyroid eye disease (TED), granulomatosis with polyangiitis (GPA), sarcoidosis, and nonspecific orbital inflammation (NSOI) constitutes an important cause of vision loss, pain, and diplopia. Clinical data with histopathology are sufficient to make a diagnosis for some patients but not for others. Gene expression profiling has proven useful in the diagnosis of several cancers and other inflammatory diseases. Specific hypotheses to be tested include that: (1) tissue from patients with TED does not display nearly as much immune related activity as tissue from patients with GPA, sarcoidosis, or NSOI, even if the TED samples are derived from muscle or from patients with new onset disease; (2) specific inflammatory diseases affecting the lacrimal gland have distinct molecular signatures; (3) an algorithm based on a limited number of transcripts expressed in orbital tissue or peripheral blood can supplement or replace orbital biopsies; (4) a subset of patients with NSOI has a disease that can be distinguished from GPA, sarcoidosis, and TED by molecular profiling. The results from this study are changing the understanding of the pathogenesis of each of these diseases. This improvement in classification/diagnosis and in understanding pathogenesis has the potential to lead to improvement in therapy and outcome.

Public Health Relevance

Inflammation within the eye socket or orbit causes pain, double vision, and loss of vision. Several diseases including sarcoidosis, granulomatosis with polyangiitis, thyroid eye disease, and so called nonspecific orbital inflammatory disease can cause orbital inflammation. We have organized centers from around the world to contribute biopsied tissue so that we can analyze tissue patterns of gene expression from patients with orbital inflammation in order to clarify the cause, predict prognosis, and ultimately improve the therapy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY020249-09
Application #
10016308
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Mckie, George Ann
Project Start
2011-09-30
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
9
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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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