Orbital asymmetry degree: a potential 99mTc-DTPA SPECT/CT imaging marker for diplopia in thyroid-associated ophthalmopathy

Background 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 99m Tc-DTPA SPECT/CT, and diplopia in patients with TAO. Methods A1:1 matched case–control study was conducted, including 22 matched pairs of patients with TAO with or without diplopia. Patients were matched for sex, age, and smoking history. All participants underwent thyroid function testing, measurement of thyroid-related antibodies, and 99m Tc-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. Full-sample ROC analysis and leave-one-pair-out cross-validation were used to evaluate model discriminatory performance. Results After adjustment for age, both OAD (OR = 2.084, 95% CI: 1.040–4.174, P = 0.038) and dEMa(OR = 1.615, 95% CI: 1.044–2.497, P = 0.031) 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). Adding dEMa to the OAD + age model only slightly increased the AUC to 0.952, and Leave-one-pair-out cross-validation supported the relatively stronger internal performance of the OAD + age model, while the addition of dEMa did not provide meaningful improvement. Conclusions Inter-orbital inflammatory asymmetry assessed by 99m Tc-DTPA SPECT/CT was significantly associated with diplopia in TAO.OAD showed relatively strong discriminatory performance and may represent a promising quantitative imaging marker. Further studies in larger prospective cohorts with independent external validation are needed to confirm these findings and clarify the clinical utility of OAD.