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L. Savar, D. K. Lee, J. Said, R. A. Goldberg, T. J. Smith, R. S. Douglas, C. J. Hwang; Orbital Fat Histology in Active and Chronic Graves' Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3581.
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Graves’ disease is a systemic autoimmune disease which targets the thyroid, orbit, and skin. We have shown orbital fibroblasts are phenotypically unique with an increase in specific immune markers, specifically insulin-like growth factor (IGFR). Graves’ disease patients with thyroid associated orbitopathy (TAO) can present in the active or chronic stages of the disease. Treatment is determined by the patient’s current stage of the disease, active or chronic. We propose that the orbital fat in active Graves’ orbitopathy patients is histologically different than that in patients with chronic Graves’ orbitopathy, with increased expression of immune markers.
After informed consent was obtained, orbital fat was harvested from patients with TAO and patients with no significant past medical history undergoing orbital decompression and blepharoplasty at the Jules Stein Eye Institute. Orbital fat was obtained from 27 patients, 3 with active TAO, 14 with chronic TAO and 10 patients with no significant past medical history. Histological examination was performed on the orbital and brow fat. Specifically, hematoxylin eosin, masson trichrome, alcian blue, insulin-like growth factor receptor 1β (IGFR1β), and thyroid stimulating hormone receptor (TSHR) were stained on each specimen.
Histology between fat obtained from patients with TAO and those without known systemic disease were markedly different. Specimens from patients with active TAO showed increased staining of mucopolysacchrides than specimens from patients with chronic TAO. Specimens from patients with chronic TAO had an increase in fibrosis and fibrous septae seen in masson trichome. In addition specimens from active and chronic TAO had increased expression of IGFR and TSHR versus normal specimens. Fat from normal patients showed normal fat histology, absence of fibrous septae, and no inflammatory infiltrate.
Graves’ disease (GD) is a systemic autoimmune disease which affects patients in a variety of ways. Both active and chronic Graves’ orbitopathy present a therapeutic challenge and increased understanding of the tissues affected will help direct future therapies. In addition, differential expression of TSHR and IGFR1β in Graves’ orbital fat further supports the role of both of these as putative markers in patients with Graves’ disease.
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