Inflammation of the extraocular muscles (EOM), or myositis, results in an enlargement and thickening of the muscle. This disorder is encountered in orbital inflammation syndrome due to thyroid-associated orbitopathy (TAO) or systemic disease. The goal of this study was to evaluate the significance of T2 hyperintensity on MRI in the case of EOM myositis.

In this retrospective study, we focused our data collection on the presence or absence of MRI-T2 hyperintensity in the EOMs and criteria described in the ophthalmologist's record, such as ocular pain, motility restriction, proptosis and redness. MRI examinations were performed on a 3.0T system with a 16-channel head coil, with Gadolinium injection prior to the scan. Conventional structural imaging included axial T1 weighted imaging, axial T2-weighted imaging, and axial, coronal, and oblique sagittal T2-weighted imaging with fat-suppression sequences.

In total, 26 patients (42 orbits) were included in this study. Eighteen patients (31 orbits) showed T2 hyperintensity in at least one muscle. Thirty of 31 orbits with T2 hyperintensity showed EOM hypertrophy (P
                     ≤0.0001). The mean number of hypertrophied EOMs was 2.67±2.47. Ten patients underwent MRI prior to and after the conclusion of treatment. Interestingly, 50% of all patients with a history of oral corticosteroid treatment for myositis still had T2 hyperintensity on their MRI scans.

T2 hyperintensity is strongly correlated with enlargement of the muscle. The persistence of a T2 hypersignal after corticosteroid treatment requires another study to better understand the clinical significance of this parameter.

L’inflammation d'un muscle extra-oculaire ou myosite se traduit par une hypertrophie/épaississement du muscle. On observe surtout cette anomalie dans le syndrome d’inflammation orbitaire dû à une orbitopathie dysthyroïdienne ou dans le syndrome inflammatoire orbitaire idiopathique (SIOI). Le but de l’étude était d’évaluer l’intérêt de l’hypersignal T2 en IRM dans le cas d’une myosite de l’orbite.

Dans cette étude rétrospective, nous avons focalisé nos données sur la présence d’un hypersignal T2 en IRM des muscles oculo-moteurs associés à la douleur oculaire, la restriction de la motilité, l’exophtalmie et la rougeur. Les examens IRM ont été réalisés sur un système 3.0T avec une bobine de tête à 16 canaux avec injection de Gadolinium. L’imagerie structurelle conventionnelle comprenait une imagerie axiale pondérée en T1, une imagerie axiale pondérée en T2 et une imagerie sagittale axiale, coronale et oblique pondérée en T2 avec des séquences de suppression de la graisse.

Au total, 26 patients dont 42 orbites ont été retenus pour cette étude. Dix-huit patients (31 orbites) présentaient des signaux d’hypersignal T2 dans au moins un muscle. Trente des 31 orbites présentaient un hypersignal T2 avec une hypertrophie du muscle (p
                     ≤0,0001). La mesure de l’hypertrophie musculaire était de 2,67±2,47. Dix patients ont bénéficié d’une IRM avant et après la fin du traitement.

L’hypersignal T2 dans les myosites des muscles oculo-moteurs est corrélé à l’augmentation de la taille du muscle. La persistance d’un hypersignal T2 après traitement corticoïde nécessite une autre étude pour mieux comprendre l’intérêt clinique.

# Introduction

Orbital inflammation is an inclusive term that characterizes inflammatory pathologies affecting all structures within the orbit. It has highly variable clinical features targeting diverse orbital tissues, such as the lacrimal gland, intra- and/or extraconal fat tissues surrounding the orbit and extraocular muscles (EOM) which is called orbital myositis [1]. Thyroid-associated orbitopathy (TAO) is by far the commonest cause of inflammation of EOM but inflammation of EOM may also occur in the setting of systemic inflammatory, autoimmune, or idiopathic.

Inflammation of EOM results in an enlargement and thickening of the muscle that leads to multiple symptoms such as orbital pain, ocular motility limitation, diplopia, eyelid swelling, ptosis and/or chemosis, or proptosis [2]. The assessment of orbital inflammation can be very challenging because of the clinical diversity of this presentation. Magnetic resonance imaging (MRI) plays an important role in understanding and diagnosing EOM inflammation. On MRI, fatty infiltration causes the EOM T1 hyperintensity whereas oedema causes the EOM T2 hyperintensity. This T2 hyperintensity reflects the transverse relaxation characteristics of the tissues that enhance the inflammation [3,4].

The main purpose of this study is to analyze the association between the T2 hyperintensity MRI's signal and the EOM clinical inflammation.

# Materials and methods

The retrospective study protocol was approved by the CHU (# 2023-6842). The CHU MRI database of the epidemiology center was asked to extract all the MRI's report from august 2015 to October 2022 that contained these keywords: Graves’ disease; myositis; EOM inflammation; height of EOM; thickness of EOM; proptosis; diplopia; ocular pain; eye mobilization pain; EOM pain.

MRI examinations were performed on a 3.0T system with a 16-channel head coil. Patients were required to lie in a supine position with their eyes closed naturally. They were also instructed to look forward and to keep their eyes still. Conventional structural imaging included axial T1 weighted imaging, axial T2-weighted imaging and axial, coronal, and oblique sagittal T2-weighted imaging with fat-suppression sequences. Double DIXON was used in 19 orbits (11 patients) whereas FATSAT was used in 23 orbits (15 patients). All the orbits were analyzed on axial and coronal imaging. All patients had MRI with Gadolinium injection prior to their scan. MRI data were first evaluated by 1 senior radiologist using the AGFA IMPAX 6 software and revised by a well-trained senior ophthalmologist and oculoplastic specialist from the Quebec Ophthalmology University Center (CUO).

We then focused our data on 2 criteria described in the MRI: presence of T2 hyperintensity signal of EOM and enlargement (hypertrophic) of EOM. The EOM T2 hyperintensity analysis was performed by the radiologist and was based on a dichotomous 3 steps scale (light-moderate-severe) using T2FS or double Dixon on coronal and axial sections. When there was only a unilateral involvement the contralateral EOM were used to compare and describe the pathology. We also focused our data on criteria described in the ophthalmologist record such as: ocular pain, motility restriction, proptosis and redness.

In this study, all the affected eyes have been considered independently. Only qualitative data have been extracted from patient's record to perform statistical analysis. Categorical variables were reported as counts and percentages with 95% confidence interval and descriptive statistics (median and quartiles) are reported for continuous variables. Exact Chi square tests was used to determine whether there is an association between the T2 hyperintensity signal and the signs and symptoms of extraocular muscle inflammation. The calculations of sensitivity, specificity, and predictive values were performed considering the unit of analysis as the orbits (n
                     =42), rather than the patients (n
                     =26). In other words, each orbit was evaluated separately based on the presence or absence of a hyperT2 signal and hypertrophy of the extraocular muscles. This approach assumes that the orbits were treated as independent observations, even when they originate from both eyes of the same patient. SAS 9.4 software was used to perform the statistical tests.

# Results

## Patient's demographics and clinical characteristics

In total, 26 patients (7 men, 19 women; age, 56.52; SD=24.66 years; range, 8–98 years) from which 42 orbits have been included in this study. Among the 26 patients, MRI was requested for thyroid-associated orbitopathy (n
                        =13), clinical orbital myositis without thyroid disease (n
                        =5), autoimmune disease (n
                        =3), motility restriction of eye muscles (n
                        =3), suspicion of orbital cavernous vascular malformation (n
                        =1) and suspicion of peri-orbital infection (n
                        =1). The final IRM diagnosis was thyroid-associated orbitopathy for 13 patients, SIOI for 10 patients, and autoimmune disease for 3 patients.

Eighteen patients (31 orbits, 73.8%) (5 men, 13 women; age, 58.5; SD=25.7 years) showed T2 hyperintensity signals in at least one muscle and 8 patients (11 orbits, 26.2%) (2 men, 6 women; age, 47.8; SD=29.2 years) showed no evidence of T2 hyperintensity signals. Analysis has been performed on MRI-T2 hyperintensity signal in association with patient's characteristics (Table 1
                        ). Interestingly, a correlation between proptosis and T2 hyperintensity was observed.

## EOM hypertrophy and T2 hyperintensity

Thirty of 31 orbits with T2 hyperintensity showed EOM hypertrophy (P
                        ≤0.0001). The mean number of EOM hypertrophy was 2.67±2.47. The location of EOM is described in Table 2
                        . Not surprisingly, oblique muscle rarely showed EOM hypertrophy. We calculated the sensitivity, specificity and predictive values between the T2 hyperintensity and EOM hypertrophy (Table 3
                        ).

## T2 hyperintensity and treatment by corticosteroids

Treatment history of these patients included oral corticosteroids (n
                        =9), radiotherapy at 20 grays (n
                        =6) and immunotherapy (n
                        =3) consisting of nivolumab, ipilimumab or infliximab. Patients with oral corticosteroid history received prednisone between 5 and 30mg or dexamethasone between 8 and 12mg daily for a mean treatment duration of 15 (SD=27) days.

Eight patients had MRI before and after the end of corticosteroid treatment. All those patients had bilateral EOM involvement. Response to treatment and delay between the end of the treatment and the MRI is reported on Table 4
                        . Interestingly, half of all patients with oral corticosteroid treatment history for myositis still had T2 hyperintensity signal on their MRI scans.

# Discussion

EOM inflammation has been studied with A-mode ultrasonography in early 2000 and it showed interesting results: it had a decent positive predictive value but a rather poor negative predictive value that forced the authors to preclude its use as a sole activity parameter [5]. Nowadays, T2 hyperintensity signal is often used to demonstrate muscle inflammation in myocarditis, Crohn's disease and skeletal muscle myositis [6–9]. In general, the intensity of T2 signal is related to the amount of extracellular water related to a large amount of glycosaminoglycans as seen in most edematous tissues [10,11]. Furthermore, Liu et al. suggested that tissues with greater T2 signal may indicate more tissue components and complex environment which mean a more glycosaminoglycan's rich environment could be more amenable to response than tissues containing less soluble fibrotic compounds [12]. In this study, we found, for a specific target population of patients with clinical myositis symptoms such as EOM hypertrophy, motility restriction, ocular pain, and proptosis that EOM hypertrophy seems correlated with T2 hyperintensity signal on orbits MRI. Moreover sensibility (100%) and specificity (92%) for our target population show a strong association between EOM inflammation and T2 hyperintensity signal. These and other previous findings confirm that T2 signal may be useful in the assessment of the inflammatory state of EOMs [13–15].

In our study, we tried to elucidate the relevance of T2 hyperintensity signal towards post-corticosteroids treatment. Accordingly, we asked ourselves if treatment such as steroids would erase/decrease the T2 hyperintensity signal since it's associated with EOM inflammation. To treat orbital myositis, corticosteroids are the first-line drug as patients generally dramatically improve within the first days of treatment [16,17]. Usually, oral prednisone (1mg/kg/day for 2 weeks, followed by gradual tapering over 6–12 weeks) is the corticosteroid of choice, but intravenous methylprednisolone (500–1000mg/day) has been effectively used in some patients [18]. Moreover, suppression of the inflammatory activity of orbital myositis by corticosteroids is rarely long lasting once treatment doses have been tapered off [19,20]. Unfortunately, there are no uniformly valid markers to predict the curative efficacy of corticosteroid, and these conventional measures are either qualitative in nature or based on morphologic changes [12]. Moreover, analysis of T2 sequence MRI after corticosteroids must be associated with clinical evaluation. In our study, half of orbits showed evidence of a persistent T2 hyperintensity signal on their orbits MRI despite the corticosteroid treatment. Since T2 hyperintensity signal can illustrate the EOM inflammation, a persistent T2 hyperintensity signal could indicate the need to pursue the anti-inflammatory treatment for a prolonged time or to increase the regimen [20]. However, we cannot tell if the corticosteroid treatment could suppress the T2 hyperintensity signal because some patients of our study received a low dose of oral corticosteroid on a short period of time. Moreover, unfortunately we were not able to provide the outcome (remission or not) due to lack of follow-up. Interestingly, our results support other studies that suggest the lack of efficiency of corticosteroid to improve orbital inflammation and erase/decrease T2 hyperintensity signal [12,21]. In fact, the heterogenous T2 signal among the EOM may be more effective to indicate the corticosteroid efficiency as described by Liu et al. [12]. This point should be confirmed by the MRI T1 values which can reflect the pathological status of the extraocular muscle. Moreover, T1 mapping could help to quantitatively assess the clinical activity of TAO and the response to corticosteroid therapy in active TAO patients [22].

In this study, we also wanted to associate T2 hyperintensity signal to proptosis and pain since these are two frequent symptoms of orbital myositis [1]. First, our results showed that proptosis is also associated with T2 hyperintensity signal, but EOM enlargement is already known to cause eye proptosis. In fact, extraocular muscle involvement and prominence of the retrobulbar fat contribute to proptosis [23]. So, we cannot conclude on T2 hyperintensity signal and proptosis pertinent clinical of interest. Second, myositis is one of the most common causes of painful orbital mass in adult population [23]. In our study, ocular pain was also reported quite often (59.5%) and it has been correlated to T2 hyperintensity signal for up to 54.8% of the studied orbits. However, ocular pain and T2 hyperintensity signal had poor statistical association rate (P
                     =0.48). To explain this poor relation, orbital pain reported by the patients could be due to other factors then EOM inflammation such as other ocular involvement [1,23]. This process causes the rise of orbital pressure, and it often generates ocular pain. Otherwise, orbital pain is a subjective patient related data, we would need a bigger pool of patients to determine and conclude on the association of T2 hyperintensity signal and ocular pain.

Nevertheless, our work has some limitations to evaluate the effectiveness of MRI in measuring the activity of orbital myositis under corticosteroids (CS): a low-powered study involving a small sample size; cumulative dosage of corticosteroids varying from one patient to another; RI being performed at different time points after treatment; absence of gold standard for defining remission, i.e., lack of follow-up.

Moreover, our study encompassed TAO's and non-TAO's myositis suggesting non-homogeneous groups. Such a comparison group would bring a lot of value to this study, and it would enhance the T2 hyperintensity signal interest in EOM inflammation. Finally, because Dixon-T2WI showed higher sensitivity and specificity and showed fewer artifacts than a conventional protocol when assessing thyroid eye disease, in addition to higher self-reported confidence, Dixon-T2WI would be of accuracy for all our patients [24].

In conclusion, analysis of MRI-T2 signal is essential in the analysis of orbital myositis. T2 hyperintensity is strongly correlated with enlargement of the muscle and means active or non-active inflammation.

# Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

We would like to acknowledge SCIENTA, a health data valorization and exploitation center and Johanne Doucet, a former CUO nurse from which this project could not have been done.