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

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).

A literature review using search terms, including fibrocytes, IGF-IR, TSHR, TAO, and thyroid eye disease.

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.

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.