Fibrocyte Participation in Thyroid-Associated Ophthalmopathy Suggests New Approaches to Therapy

Abstract

Purpose: Review the historical context of research and changing therapeutic landscape of thyroid-associated ophthalmopathy (TAO) by focusing on the relationship between TAO, CD34+ fibrocytes, thyrotropin receptor (TSHR), and insulin-like growth factor-I receptor (IGF-IR). Methods: A literature review using search terms, including fibrocytes, IGF-IR, TSHR, TAO, and thyroid eye disease. Results: The mechanisms involved in TAO have been partially identified. Substantial progress has been made over several decades, including 1) recognizing the interplay between the professional immune system and orbital tissues; 2) TSHR and IGF-IR act interdependently in mediating the pathogenesis of TAO; 3) Multiple cytokines and specific immune cells are involved in activating and remodeling orbital tissue; 4) Recognition of these mechanisms is allowing the development of target therapies such as teprotumumab, a monoclonal antibody IGF-IR inhibitor approved by the US Food and drug administration for treatment of TAO; and 5) It appears that teprotumumab acts on the systemic immune system peripheral to the orbit. Conclusion: Additional molecules targeting IGF-IR and other plausible disease mechanisms are currently under development. This activity in the TAO therapeutic space portends even greater improvements in patient care.