Impacts of physical, metabolic, and immunological factors on the exophthalmometry values of a contemporary Japanese population with/without Graves’ disease

Proptosis, a key clinical manifestation of thyroid eye disease (TED), serves as an objective indicator of this disease's severity. Although body compositions and the prevalences of myopia and tobacco smoking have changed in Japan, no updated reference exophthalmometry values have been reported since the 1980s. To determine normal values for exophthalmometry in a contemporary Japanese general population and identify factors associated with exophthalmos in people with/without Graves' disease (GD), we conducted a cross-sectional study using a general population cohort and a GD cohort, from October 2023 to October 2024. We used a Hertel exophthalmometer to measure the exophthalmometry values in both cohorts, and we obtained clinical data from medical records and/or questionnaires. Eighty-six patients with GD and 502 general population controls were included. The GD cohort's mean exophthalmometry value (17.0 ± 3.3 mm) was significantly higher than the general population (15.6 ± 2.8 mm), which was larger than the upper limit of the normal references (15.0 mm) defined by the Japan Thyroid Association based on a 1970s' report. Multiple regression analyses revealed that age, BMI, myopia, and dyslipidemia remained independently associated with exophthalmometry values in the general population cohort, whereas height, smoking, and anti-thyroglobulin autoantibody negativity were associated with the GD cohort's exophthalmometry values. Our findings suggest a possible increase in mean exophthalmometry values in the contemporary Japanese general population. They highlight the need to update normative exophthalmometry values, accounting for body-composition including metabolic profiles and myopia, which could lead to accurate assessments of proptosis severity and appropriate therapeutic strategies for patients with TED. Clinical Trials Registry (CTR) registration: UMIN-CTR no. 000051753.