Study subjects
Thirty-six consecutive patients with TAO who underwent MRI for assessment of disease severity in the Department of Ophthalmology at Beijing Tongren Hospital between March 2019 and May 2020 were enrolled in the study. All patients had bilateral orbital involvement.
The study inclusion criteria were as follows: fulfillment of the European Group on Graves’ Orbitopathy diagnostic criteria for TAO [8]; no prior history of immunosuppressive therapy, retrobulbar radiotherapy, or surgical decompression of the orbit; and complete orbital MRI data available for assessment. The following exclusion criteria were applied: other disease involving the intraorbital structures regardless of the etiology, other autoimmune disease, any ferromagnetic or electronic material in the body, and claustrophobia.
A modified version of the Clinical Activity Score (CAS) [9] was used to assess the activity of TAO. The CAS includes scores for the following seven items: pain on attempted up or down gaze, spontaneous retrobulbar pain, redness of the conjunctiva, inflammation of the caruncle and/or plica, redness of the eyelids, swelling of the eyelids, and conjunctival edema. We obtained the CAS for each eye. Based on the CAS, the 72 eyes of the 36 patients were categorized into an inactive TAO group (43 orbits, CAS < 3) and an active TAO group (29 orbits, CAS ≥3).
Previous researchers found no significant difference in lacrimal gland parameters measured for the left and right sides in patients with TAO [10]. Therefore, in this study, we combined the measurements for the left and right eyes for the analyses.
MRI examinations
Orbital MRI scans were obtained for all patients using a 3.0-T scanner (Signa HDx; General Electric Healthcare, Milwaukee, WI, USA) with an eight-channel phased-array head coil. Foam cushions were placed between the head and the coil to stabilize the head in the supine position. Throughout the scanning procedure, patients needed to remain stationary and keep their eyes closed to minimize the impact of ocular movements.
The orbital MRI protocol involved both sagittal and axial turbo spin echo (TSE) T1-weighted imaging (T1WI), axial and coronal TSE T2-weighted imaging (T2WI), and T2WI with fat suppression (T2WI-FS). The parameters used for T1WI were as follows: an echo time (TE) of 9 ms and a repetition time (TR) of 456.5 ms. The following parameters were used for T2WI and T2WI-FS: TR/TE 1621.5 ms/90 ms, two excitations, 384 × 256 matrix, field of view 180 × 180 mm, section thickness 3 mm; and section gap 0 mm.
Imaging processing
Measurement of LGP severity
The degree of LGP was measured on axial T2WI-FS sequences using ImageJ software (National Institutes of Health, Bethesda, MD, USA, http://rsbweb.nih.gov/ij/index.html). Using the method described by Gagliardo et al. [11], a line was drawn on the maximum delineated LGP level of the ventral zygomatic border (interzygomatic line) bilaterally, after which a perpendicular line was taken to measure the degree of herniation of the lacrimal gland parenchyma (Fig. 1).
Measurement of proptosis
We measured the severity of proptosis on axial T2WI using ImageJ software. At the level showing the maximum convexity of the lens, the vertical distance from the interzygomatic line to the top of the cornea was defined as the proptosis value (Fig. 1).
Measurement of extraocular muscle volume (EOM)
The volume of each EOM measured on MRI was similar to that in previous studies [12,13,14]. For each orbit, the EOM volumes of the lateral rectus, medial rectus, inferior rectus, and superior oblique muscles were assessed; those for the superior rectus complex, the superior rectus and levator palpebrae muscles were measured together because they were difficult to separate on the magnetic resonance images (Fig. 2). Regions of interest were delineated using the Image J polygon selection tool and their cross-sectional areas were measured. The areas of the medial rectus, lateral rectus, and superior oblique muscles were obtained from axial images and those of the superior rectus complex and inferior rectus from the sagittal images. The EOM volumes were obtained from the sum of cross-sectional areas with a slice thickness of 3 mm. All data were determined independently in masked mode by one radiologist and one senior ophthalmologist; the average measurements were used for the statistical analyses.
Statistical analysis
The Shapiro-Wilk test was used to evaluate the normality of continuous variables. Data are summarized as the mean ± standard deviation or as the median and interquartile range depending on whether they were continuous and normally distributed. The chi-squared test and Student’s t-test were used to evaluate differences in sex and age between the two groups. All quantitative measurements were compared between the two groups using the Student’s t-test. Linear regression analysis with Pearson’s or Spearman’s test was performed to explore the correlation between the LGP and CAS, proptosis, EOM volumes, and age in all patients with TAO.
Receiver-operating characteristic (ROC) curve analysis was used to estimate the value of LGP in discriminating active from inactive TAO. The intraclass correlation coefficient (ICC) was used to evaluate the consistency of the quantitative parameters measured by the two observers. All statistical analyses were performed using SPSS software version 19.0 (IBM Corp., Armonk, NY, USA). A P-value of < 0.05 was considered statistically significant.
