PURPOSE: Improved understanding of thyroid eye disease (TED) pathogenesis has 
facilitated identification of a targeted molecular approach for TED treatment 
offering the potential to halt or slow disease progression in a nonsurgical 
manner. Herein, we provide a summary of the current knowledge of TED management, 
followed by discussion of a novel insulin-like growth factor-1 receptor (IGF-1R) 
antagonist antibody and its potential to change the course of the disease.
DESIGN: Perspective.
METHODS: Review of the literature and authors' experience.
RESULTS: Many publications demonstrate IGF-1R overexpression in TED, and its 
activation as an autoantigen as a critical factor in TED pathogenesis. Several 
in vitro studies demonstrate that IGF-1R inhibition attenuates downstream 
molecular events including cytokine and hyaluronan production, and cellular 
differentiation. These observations led to the hypothesis that blocking IGF-1R 
may abrogate the clinical progression of TED. The recent completion of phase 2 
and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety 
of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in 
patients with moderate-to-severe, active TED. Both the phase 2 and the recent 
phase 3 study results demonstrate that more patients with active TED receiving 
teprotumumab experienced a meaningful improvement in proptosis.
CONCLUSIONS: Current TED treatment strategies target inflammation and symptoms, 
but do not modify the disease course. Therefore, proptosis as well as strabismus 
and its resulting diplopia often remain, impacting patient well-being and 
quality of life over the long term. Targeted molecular therapy using 
teprotumumab demonstrates disease-modifying benefits with the potential to shift 
the paradigm for TED treatment.