Orbital Asymmetry Degree: A Potential 99mTc-DTPA SPECT/CT Imaging Marker for Diplopia in Thyroid-Associated Ophthalmopathy

Diplopia is a common and clinically important manifestation of thyroid-associated ophthalmopathy (TAO), often related to asymmetric orbital involvement. This study investigated the association between orbital asymmetry degree (OAD), a novel quantitative imaging index derived from 99mTc-DTPA SPECT/CT, and diplopia in patients with TAO. A total of 22 matched pairs of patients with TAO with or without diplopia were included in the study. All participants underwent thyroid function testing, measurement of thyroid-related antibodies, and 99mTc-DTPA SPECT/CT imaging. The maximum standardized uptake values (SUVmax) of the lacrimal glands, orbital soft tissues, and extraocular muscles were measured bilaterally. OAD was calculated from the absolute inter-orbital differences in SUVmax across these three orbital components and was used to quantify overall inter-orbital inflammatory asymmetry. Age-adjusted conditional logistic regression was performed to assess the associations of imaging and clinical variables, including OAD, the absolute inter-orbital difference in extraocular muscle SUVmax (dEMa), thyrotropin receptor antibody (TRAb), and CT-based mean extraocular muscle thickness, with diplopia. The results showed that both OAD and dEMa were significantly associated with diplopia, whereas TRAb and CT-based mean extraocular muscle thickness were not. In the full-sample ROC analysis, the OAD + age model showed the highest discriminatory performance (AUC = 0.940), compared with the dEMa + age model (AUC = 0.890) and the TRAb + age model (AUC = 0.785). The findings suggest that inter-orbital inflammatory asymmetry assessed by 99mTc-DTPA SPECT/CT may represent a promising quantitative imaging marker for diplopia in TAO. However, further studies in larger prospective cohorts with independent external validation are needed to confirm these findings and clarify the clinical utility of OAD.