Abstract

Objective: To evaluate the contribution and application of orbital fat-to-muscle ratio (FMR) in Thyroid Eye Disease related restrictive strabismus.

Design: Retrospective cross-sectional study.

Subjects, participants: Adult patients (≥18 years) with a confirmed diagnosis of TED evaluated at a tertiary referral thyroid eye disease clinic between 2017 and 2025 who had high-resolution orbital CT imaging available for quantitative analysis.

Methods: Orbital CT scans were analyzed using three-dimensional (3D) volumetric segmentation to quantify orbital fat and extraocular muscle (EOM) volumes. The FMR was calculated for each orbit. A simplified single-slice two-dimensional (2D) FMR was also measured for comparison. Clinical data included presence and magnitude of strabismus, restrictive ocular motility, Clinical Activity Score (CAS), thyroid-stimulating immunoglobulin (TSI) levels, and surgical history. Associations were assessed using correlation analyses, multivariable logistic regression, intraclass correlation coefficients (ICC), and receiver operating characteristic (ROC) analysis.

Main outcome measures: Association of FMR with TED factors associated with disease severity, restrictive ocular motility and strabismus presence.

Results: Of 579 screened patients, 197 met inclusion criteria (mean age 54.9 ± 16.3 years; 69.7% female). Restrictive ocular motility was present in 39.1% and was associated with significantly lower FMR compared with nonrestrictive disease (0.69 ± 0.36 vs. 0.91 ± 0.42; p < 0.001). Strabismus angle correlated inversely with FMR (r = -0.169; p = 0.030), as did the number of EOMs operated during strabismus surgery (r = -0.160; p = 0.027). FMR was negatively correlated with CAS (r = -0.186; p = 0.010) and TSI (r = -0.188; p = 0.047). In multivariable analysis, lower FMR remained an independent predictor of restrictive motility. An FMR cutoff of 0.66 best discriminated the presence of strabismus (sensitivity 0.59; specificity 0.72). Agreement between 2D and 3D measurements was good (ICC = 0.77).

Conclusions: Quantitative FMR derived from CT segmentation is a clinically relevant imaging biomarker in TED that reflects a continuous spectrum of muscle and fat involvement. Lower FMR identifies patients at increased risk for restrictive motility, strabismus, and inflammatory activity. Three-dimensional FMR provides superior anatomical and clinical relevance compared with 2D measurements and may enhance risk stratification and longitudinal assessment in TED.