Thyroid eye disease: From pathogenesis to targeted therapies

Area of Science:

• Ophthalmology
• Endocrinology
• Immunology

Background:

• Thyroid eye disease (TED) is the primary extrathyroidal manifestation of Graves' hyperthyroidism.
• Its pathogenesis involves autoimmune reactions targeting orbital fibroblasts, leading to orbital tissue expansion and swelling.
• Current understanding of TED's molecular mechanisms is rapidly evolving.

Purpose of the Study:

• To review recent advancements in understanding the molecular pathogenesis of TED.
• To identify promising therapeutic targets and drugs for TED treatment.

Main Methods:

• Literature review of studies on TED pathogenesis and therapeutics.
• Analysis of molecular pathways involving the thyroid-stimulating hormone receptor and IGF-1R.
• Evaluation of clinical trial data for novel biologics.

Main Results:

• Autoantibodies to TSHR and IGF-1R activate orbital fibroblasts, driving TED pathology.
• Teprotumumab, an IGF-1R inhibitor, demonstrated high efficacy and safety in moderately severe active TED patients.
• Novel biologics represent a paradigm shift in TED treatment.

Conclusions:

• Understanding TED's molecular pathogenesis has led to targeted therapies.
• Inhibition of IGF-1R with teprotumumab offers a promising treatment option.
• Emerging biologics are transforming TED management.