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Review
. 2022 Jan 21;12(1):3-11.
doi: 10.4103/tjo.tjo_51_21. eCollection 2022 Jan-Mar.

Thyroid eye disease: From pathogenesis to targeted therapies

Jin Sook Yoon  1   2 , Don O Kikkawa  2
Affiliations
Review

Thyroid eye disease: From pathogenesis to targeted therapies

Jin Sook Yoon et al. Taiwan J Ophthalmol. .

Abstract

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of autoimmune Graves' hyperthyroidism. TED is a debilitating and potentially blinding disease with unclear pathogenesis. Autoreactive inflammatory reactions targeting orbital fibroblasts (OFs) lead to the expansion of orbital adipose tissues and extraocular muscle swelling within the fixed bony orbit. There are many recent advances in the understating of molecular pathogenesis of TED. The production of autoantibodies to cross-linked thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) activates OFs to produce significant cytokines and chemokines and hyaluronan production and to induce adipocyte differentiation. In moderately severe active TED patients, multicenter clinical trials showed that inhibition of IGF-1R with teprotumumab was unprecedentedly effective with minimal side effects. The emergence of novel biologics resulted in a paradigm shift in the treatment of TED. We here review the literature on advances of pathogenesis of TED and promising therapeutic targets and drugs.

Keywords: Autoimmune; insulin growth factor-1 receptor; orbital fibroblast; pathogenesis; thyroid eye disease; thyroid-stimulating hormone receptor.

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Conflict of interest statement

The authors declare that there are no conflicts of interest of this paper.

Figures

Figure 1
Figure 1
A schematic presentation of the complex cellular and humoral immune responses against autoantigens, thyroid-stimulating hormone receptor (TSH-R), and insulin-like growth factor-1 receptor (IGF-1R) in orbital fibroblasts and the targeted therapy
See this image and copyright information in PMC

References

    1. Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375:1552–65. - PubMed
    1. Stein JD, Childers D, Gupta S, Talwar N, Nan B, Lee BJ, et al. Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. JAMA Ophthalmol. 2015;133:290–6. - PMC - PubMed
    1. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EH, Perdok R, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341–52. - PubMed
    1. Hwang CJ, Afifiyan N, Sand D, Naik V, Said J, Pollock SJ, et al. Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1. Invest Ophthalmol Vis Sci. 2009;50:2262–8. - PMC - PubMed
    1. Chen B, Tsui S, Smith TJ. IL-1 beta induces IL-6 expression in human orbital fibroblasts: Identification of an anatomic-site specific phenotypic attribute relevant to thyroid-associated ophthalmopathy. J Immunol. 2005;175:1310–9. - PubMed