Proptosis, Diplopia Severity Affects Thyroid Eye Disease-Related Quality of Life

Symptom severity of thyroid eye disease can reduce quality of life and utility values for patients with moderate to severe thyroid eye disease.

Moderate to severe thyroid eye disease (TED) can be a significant burden on quality of life, with increasing severity of proptosis and diplopia having greater effects on quality of life (QOL), according to an investigation published in JAMA Ophthalmology

The researchers defined 6 health states based on 2 prior clinical trials that involved a total of 171 participants with active TED, and discussed the states with 6 patients experiencing this inflammatory condition. The 6 health states were validated in meetings with a comprehensive ophthalmologist, oculoplastic surgeon, endocrinologist, and 3 patient advisory council members diagnosed with moderate to severe TED.

Next, a healthy general cohort was enrolled to represent a diverse demographic and geographic population sample. Using the health state explanations, the newly enrolled participants answered QOL questions. Ten individuals took part in pilot interviews that checked language, and 101 responded in main formal interviews. All 111 contributed to final statistical results. The time trade-off (TTO) approach used in interviews asked respondents to estimate how many years they would trade life with poorer QOL for fewer years living in best health. 

Participants gauged utility value on a scale between perfect health (1) and death (0) based on trade-offs. The resulting mean (SD) utility score was 0.44 (0.34). Correspondingly, mean (SD) utility fell with worsening health states, including the following:

  1. No diplopia and small proptosis (<3 mm), utility 0.60 (0.34)
  2. No diplopia, large proptosis (≥3 mm), 0.46 (0.32)
  3. Intermittent (or inconstant) diplopia, small proptosis, 0.52 (0.33)
  4. Intermittent diplopia, large proptosis, 0.43 (0.33)
  5. Constant diplopia, small proptosis, 0.34 (0.31)
  6. Constant diplopia, large proptosis, 0.30 (0.31)
Both the presence of large proptosis and constant diplopia drove health state scores lower.

“These values decreased (worsened) as severity of diplopia increased; however, the decrement in those health states with large proptosis and milder diplopia was more modest,” according to the researchers. “Both the presence of large proptosis and constant diplopia drove health state scores lower.”

Participants had initially been trained in health state evaluation by expressing their overall health in a visual analog scale (VAS), between 0 for worst health to 100 as best health. The average VAS score for own health was 77.64 (80.00), comparable to that in the general population, 80.4. Then, average VAS for TED health states converted to utility score resulted as 0.38 (0.20). In the VAS exercise, values ranged between 51.71(21.44) for the first state of no diplopia and small proptosis, to 27.42 (16.04) in the most severe category — constant diplopia and large proptosis. 

The qualitative investigation was conducted between April 2020 and April 2021. A limitation of the analysis was the 10-year time horizon, considering inflammatory symptoms can be variable across time. Second, these data may not apply to those with less active or mild disorder. The sample included more women, older participants, and more with visual impairment than the overall US population, but reflected the proportion of Americans with TED. This study is the first to assess utility value in moderate to severe TED using TTO and a general population sample.

Disclosures: This research was supported by Horizon Therapeutics plc. Several study authors have disclosed affiliations with the biotech, pharmaceutical, and/or device companies. . Please see the original reference for a full list of disclosures.


Smith TJ, Cockerham K, Lelli G, et al. Utility assessment of moderate to severe thyroid eye disease health StatesJAMA Ophthalmol. Published online December 29, 2022. doi:10.1001/jamaophthalmol.2022.3225