Proptosis Measures Miss Many Other Improvements in Thyroid Eye Disease at Week 12

Many patients with thyroid eye disease who fail to meet the conventional two-millimeter proptosis threshold after twelve weeks of teprotumumab N01 therapy still show meaningful improvement in inflammatory activity and quality of life, according to a multicenter prospective registry study conducted at four centers in China.

The study, published in BMC Ophthalmology, examined the coexistence of what researchers call discordance: a situation in which the study eye shows less than two millimeters of reduction in Hertel exophthalmometry, the standard anatomical measure of eye protrusion, while other measured clinical domains improve at the same early assessment point.

In this registry, patients were treated at four Chinese centers; the safety set included 98 participants with safety documentation, and the Week-12 full analysis set included 64 participants who had reached the early assessment window.

The protocol specified that measurements be taken in a single predefined study eye, selected by greater baseline proptosis and fixed during follow-up. Hertel exophthalmometry and the 7-item Clinical Activity Score (CAS) were assessed in that same predefined study eye. The Graves Ophthalmopathy Quality of Life (GO-QOL) instrument captured patient-reported outcomes, and diplopia was tracked separately.

The paired Week-12 data told a layered story. Hertel response, defined as proptosis reduction of at least two millimeters, occurred in 23 of 58 participants, or 39.7 percent. In contrast, CAS response occurred in 42 of 58, or 72.4 percent, diplopia improved in 23 of 56, or 41.1 percent, and GO-QOL improved in 32 of 44, or 72.7 percent. Inflammatory and quality-of-life measures improved far more often than the anatomical measure alone.

When the researchers combined the domains, Hertel nonresponse coexisted with CAS and/or GO-QOL improvement in 29 of 54 participants classifiable for the combined analysis, or 53.7 percent. Among the 33 Hertel nonresponders who had at least one evaluable CAS or GO-QOL result, 29, or 87.9 percent, had improvement in one or both domains. The authors emphasized that this 87.9 percent figure is a conditional composite estimate and not an overall response rate.

Separate paired analyses sharpened the picture further. Hertel nonresponse with CAS improvement occurred in 24 of 52 participants, or 46.2 percent, and Hertel nonresponse with GO-QOL improvement occurred in 16 of 41, or 39.0 percent.

Safety data from the full treated cohort showed that any adverse event was recorded in 64 of 98 participants, or 65.3 percent. This was a prospective observational registry without investigator-assigned treatment allocation; therefore, no interventional trial registration was required.

The clinical implication the authors draw is that early anatomical classifications based on the two-millimeter Hertel threshold should be interpreted alongside other measured clinical domains rather than in isolation.

The study’s conclusions carry important limitations. The registry was conducted at four Chinese centers using teprotumumab N01, a ready-to-use liquid formulation, and the paired analyses used outcome-specific available-case denominators, so the numbers of participants differ across comparisons. Still, the finding that more than half of classifiable participants showed this discordance pattern offers a concrete, quantified argument for broadening how early treatment response is assessed in thyroid eye disease beyond proptosis measurements alone.

Subject of Research: Discordance between proptosis response and other clinical improvements during teprotumumab N01 therapy for thyroid eye disease

Article Title: Discordance between proptosis response and other clinical improvements at week 12 during teprotumumab N01 therapy for thyroid eye disease: a multicenter prospective registry study

Article References: Gao, W., Yan, B., Hu, J., Li, D., & Luo, L. (2026). Discordance between proptosis response and other clinical improvements at week 12 during teprotumumab N01 therapy for thyroid eye disease: a multicenter prospective registry study. BMC Ophthalmology. https://doi.org/10.1186/s12886-026-05476-3

Image Credits: AI Generated

DOI: 10.1186/s12886-026-05476-3

Keywords: thyroid eye disease, teprotumumab N01, IBI311, proptosis, Hertel exophthalmometry, Clinical Activity Score, GO-QOL, prospective registry, Week 12 assessment, discordance, BMC Ophthalmology, between