Teprotumumab Reduces Orbital Fat, Extraocular Muscle Volume in Thyroid Eye Disease

Graves’ ophthalmopathy (also known as thyroid eye disease (TED), dysthyroid/thyroid-associated orbitopathy (TAO), Graves’ orbitopathy) is an autoimmune inflammatory disorder affecting the orbit around the eye, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exopthalmos). It is part of a systemic process with variable expression in the eyes, thyroid, and skin, caused by autoantibodies that bind to tissues in those organs, and, in general, occurs with hyperthyroidism. The most common form of hyperthyroidism is Graves’ disease. About 10% of cases do not have Graves’ disease, but do have autoantibodies.
Investigators show 2 ways in which teprotumumab can reduce inflammation for patients with thyroid eye disease.

Researchers say teprotumumab, a  novel human monoclonal antibody, can address the orbital and periorbital inflammation in the eyes of patients with thyroid eye disease (TED) in 2 ways. This treatment can reverse the inflammation that causes tissue remodeling, extraocular muscle enlargement, and orbital fat expansion in these patients, according to a study published in British Journal of Ophthalmology.  

Researchers examined the use of teprotumumab in patients with TED, a progressive autoimmune disease with vision-threatening implications. The medication was previously found to decrease proptosis, diplopia, and inflammation following 24 weeks of treatment in 2 multicenter, randomized placebo-controlled trials. The current retrospective review used orbital imaging from 1 of these phase III teprotumumab clinical trials (OPTIC, NCT03298867) to determine volumetric and inflammatory changes, before and after teprotumumab treatment.

In the current review, investigators looked at results of 6 patients with active TED who had received 24 weeks of teprotumumab and orbital imaging (CT or MRI). A comparative control group of 24 orbits of 12 patients who did not have TED was also reviewed.

Researchers used 3D volumetric calculations of the extraocular muscles, orbital fat, and bony orbit measurements from image processing software that was previously validated. Clinical measurements of TED were compared with 3D volumetric results and changes in extraocular muscle inflammation.

They found that total extraocular muscle volume within each orbit was “markedly reduced post-teprotumumab in all patients (n=6 patients, 12/12 orbits, P <.02).” In addition, researchers found a reduction in total orbital fat volume in 11 of 12 studied orbits (n=6 patients, P =.04). In 8 out of 8 orbits (n=4 patients, P <.01), overall extraocular muscle inflammation based on MRI signal intensity ratio was reduced. 

No statistical difference was found in post-treatment extraocular muscle volume compared with the control group.

“Teprotumumab markedly reduces the clinical signs and soft tissue changes that occur with TED,” according to investigators. “The resolution of diplopia, striking reduction in orbital soft tissue volume, and proptosis underscores the growing body of evidence that suggests a paradigm shift from surgical to less morbid medical therapies in the management of TED in patients in the active stage of the disease.”


Jain AP, Gellada N, Ugradar S, Kahaly G, Douglas R. Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease. Bri J Ophthalmol. Published online November 10, 2020. doi: 10.1136/bjophthalmol-2020-317806.