Thinking inside the box: Current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease

Abstract

Thyroid eye disease (TED) is an autoimmune disorder that manifests in the orbit. In TED, the connective tissue behind the eye becomes inflamed and remodels with increased fat accumulation and/or increased muscle and scar tissue. As orbital tissue expands, patients develop edema, exophthalmos, diplopia, and optic neuropathy. In severe cases vision loss may occur secondary to corneal scarring from exposure or optic nerve compression. Currently there is no cure for TED, and treatments are limited. A major breakthrough in TED therapy occurred with the FDA approval of teprotumumab, a monoclonal insulin-like growth factor 1 receptor (IGF1R) blocking antibody. Yet, teprotumumab therapy has limitations, including cost, infusion method of drug delivery, variable response, and relapse. We describe approaches to target orbital fibroblasts and the complex pathophysiology that underlies tissue remodeling and inflammation driving TED. Further advances in the elucidation of the mechanisms of TED may lead to prophylaxis based upon early biomarkers as well as lead to more convenient, less expensive therapies.

Keywords: Graves’ orbitopathy; Thyroid eye disease; fibroblast; insulin-like growth factor 1 receptor; microRNA; orbital fibroblast; teprotumumab; therapeutics, targeted therapy.