Sarah Cheng, MD, PhD, a clinical oculoplastic fellow at the University of California, San Diego, discusses findings from an exploratory study examining the biological changes in orbital tissue associated with Tepezza (teprotumumab-trbw) treatment. The findings were presented at the 2026 American Academy of Ophthalmology (AAO) Annual Meeting in New Orleans, Louisiana.
Understanding Thyroid Eye Disease
Thyroid eye disease (TED), commonly associated with Graves’ disease, is a rare, autoimmune condition diagnosed in an estimated 19 to 24 people per 100,000 in the United States each year. The condition impacts the muscles, fat, and soft tissues in and around the eyes, resulting in redness, inflammation, eyelid changes, pain, and pressure. Many patients also experience proptosis (bulging eyes).
Teprotumumab is a fully human monoclonal antibody that binds to and blocks the insulin-like growth factor-1 receptor (IGF-1R), a protein overexpressed in orbital fibroblasts of patients with TED. Blocking this receptor reduces common manifestations of TED, such as inflammation and changes in orbital tissues, but the drug’s full mechanism of action isn’t fully understood.
Key Findings from the 2026 AAO Annual Meeting
At the 2026 AAO Annual Meeting, author Dr. Cheng, presented exploratory findings offering insight into the molecular features of TED and changes observed following treatment with teprotumumab.
The study, titled The Molecular Basis of Proptosis Reduction in TED Patients After Teprotumumab Therapy, used single-nuclear multiomics sequencing to compare orbital tissue from 28 patients with active, chronic, reactivated, or teprotumumab-treated TED and 10 control patients, examining 281,085 nuclei.
Key findings included:
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Inflammation was Higher in Active and Reactivated TED
Tissue samples from patients with either active and reactivated TED showed increased inflammatory signals, including higher proportions of T-cells and macrophages than tissues from patients with chronic disease.
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Chronic TED Showed Signs of Fat Cell Expansion and Tissue Remodeling
Tissue samples from patients with chronic TED had a higher proportion of adipocytes (fat cells) and increased expression of genes related to extracellular matrix production. Fibroblasts in patients with active, reactivated, and chronic TED showed increased expression of collagen-related genes, while HA-related gene expression was highest in chronic TED1.
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Teprotumumab Treatment was Associated with Changes in Orbital Tissue
Samples from patients treated with teprotumumab had fewer adipocytes and reduced expression of immediate early genes associated with cellular responses. The study also found lower expression of genes related to collagen and hyaluronic acid in treated patients. Immediate early gene expression in treated patients looked similar to those in control samples.
Findings Offer Insights into Teprotumumab’s Effects
The exploratory study’s findings offer insights into the biological changes associated with TED as well as teprotumumab treatment. Dr. Cheng and her team plan to use spatial transcriptomics to better understand where specific genes are expressed within orbital tissue so they can validate the findings from the single-nucleus analysis.
The researchers also plan to conduct experiments with cultured orbital fibroblasts to determine whether specific genes identified in the study play a functional role in TED-related tissue changes.
For more information, visit: https://aao.apprisor.org/apsSession.cfm?id=PO145
To learn more about TED and other ophthalmology/eye diseases, visit: https://checkrare.com/diseases/ophthalmology-eye-diseases/
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