Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Optical Coherence Tomography Thickness Measurements of the Extraocular Rectus Muscle Tendons in Graves' Ophthalmopathy

Lucía De-Pablo-Gómez-de-Liaño, MD, PhD; José Ignacio Fernández-Vigo, MD, PhD; Néstor Ventura-Abreu, MD; Juan Troyano-Rivas, MD; Cristina Niño-Rueda, MD, PhD; Ángel Romo-López, MD; Rosario Gómez-de-Liaño, MD, PhD

Abstract

Purpose:

To examine extraocular rectus muscle tendons in patients with Graves' ophthalmopathy using optical coherence tomography (OCT).

Methods:

This was a cross-sectional observational study conducted with 55 healthy controls, 45 patients with clinically inactive Graves' ophthalmopathy, and 12 patients with clinically active Graves' ophthalmopathy. Scanning was performed at the 3- and 9-o'clock positions. The medial rectus tendon thickness was measured at 7.2 and 9.2 mm from the limbus and the lateral rectus tendon thickness was measured at 8.5 and 10.5 mm from the limbus.

Results:

The 9.2-mm medial rectus, 8.5-mm lateral rectus, and 10.5-mm lateral rectus tendons were thicker in the inactive Graves' ophthalmopathy group than the control group (240 ± 70, 231 ± 63, and 228 ± 54 µm vs 201 ± 71, 199 ± 53, and 200 ± 32 µm, respectively; P ≤ .011), whereas the 8.5-mm lateral rectus and 9.2-mm medial rectus tendons were thicker in patients with active Graves' ophthalmopathy than patients with inactive Graves' ophthalmopathy (274 ± 77 and 283 ± 68 µm vs 231 ± 63 and 240 ± 70 µm, respectively; P ≤ .048). A correlation was detected between lateral rectus and medial rectus tendon thicknesses and the Graves' ophthalmopathy clinical activity score (R = 0.252, P = .035; and R = 0.291, P = .013, respectively).

Conclusions:

OCT emerged as an accurate method for measuring medial rectus and lateral rectus tendon thicknesses in patients with Graves' ophthalmopathy. The imaging tool was able to detect thicker horizontal rectus tendons in patients with inactive Graves' ophthalmopathy than in controls, and in patients with active compared to inactive disease.

[J Pediatr Ophthalmol Strabismus. 2018;55(6):356–362.]

Abstract

Purpose:

To examine extraocular rectus muscle tendons in patients with Graves' ophthalmopathy using optical coherence tomography (OCT).

Methods:

This was a cross-sectional observational study conducted with 55 healthy controls, 45 patients with clinically inactive Graves' ophthalmopathy, and 12 patients with clinically active Graves' ophthalmopathy. Scanning was performed at the 3- and 9-o'clock positions. The medial rectus tendon thickness was measured at 7.2 and 9.2 mm from the limbus and the lateral rectus tendon thickness was measured at 8.5 and 10.5 mm from the limbus.

Results:

The 9.2-mm medial rectus, 8.5-mm lateral rectus, and 10.5-mm lateral rectus tendons were thicker in the inactive Graves' ophthalmopathy group than the control group (240 ± 70, 231 ± 63, and 228 ± 54 µm vs 201 ± 71, 199 ± 53, and 200 ± 32 µm, respectively; P ≤ .011), whereas the 8.5-mm lateral rectus and 9.2-mm medial rectus tendons were thicker in patients with active Graves' ophthalmopathy than patients with inactive Graves' ophthalmopathy (274 ± 77 and 283 ± 68 µm vs 231 ± 63 and 240 ± 70 µm, respectively; P ≤ .048). A correlation was detected between lateral rectus and medial rectus tendon thicknesses and the Graves' ophthalmopathy clinical activity score (R = 0.252, P = .035; and R = 0.291, P = .013, respectively).

Conclusions:

OCT emerged as an accurate method for measuring medial rectus and lateral rectus tendon thicknesses in patients with Graves' ophthalmopathy. The imaging tool was able to detect thicker horizontal rectus tendons in patients with inactive Graves' ophthalmopathy than in controls, and in patients with active compared to inactive disease.

[J Pediatr Ophthalmol Strabismus. 2018;55(6):356–362.]

Introduction

Graves' ophthalmopathy affects 0.4% of the population.1 It is symptomatic in 30% to 50% of affected patients, and may be subclinical in up to 90% of cases.2 The disease most commonly occurs in individuals with hyperthyroidism (90%), but may also appear in patients with Hashimoto's thyroiditis, hypothyroidism, or euthyroidism.3 It usually occurs bilaterally but with some asymmetry,4 and is more frequent in women.5

Graves' ophthalmopathy is an autoimmune inflammatory disorder of the orbital and periorbital tissues. Although the pathogenesis of Graves' ophthalmopathy is still poorly understood, it is thought that autoantibodies target the thyroid-stimulating hormone receptor (TSH-R) expressed by epithelial cells of the thyroid and orbital tissues.6 In response to the autoimmune assault, fibroblasts in the eye muscles may differentiate into mature adipocytes. In consequence, there is an expansion of intraorbital fat and myofibroblasts, which produce glycosaminoglycans. The latter absorb water, producing edema and fibrosis in the active, or wet, stage of the disease, which may affect ocular motility.7 Thickening of the extraocular muscles occurs through the expansion of connective tissue at the level of the perimysium and endomysium, leaving the muscle fibers intact.8 The inferior and medial recti are usually the most affected.9 Because of increased intraorbital pressure, veins become compressed and are unable to drain the fluid, producing chemosis.

Imaging techniques are useful for the diagnosis and management of Graves' ophthalmopathy, mainly in patients with asymmetric Graves' ophthalmopathy or prior to decompression or strabismus surgery. Thus, through magnetic resonance imaging (MRI), computed tomography (CT), and ultrasonography, it is possible to observe enlarged extraocular muscles and increased orbital fat in patients with Graves' ophthalmopathy.10 Although MRI and CT are currently the best techniques to diagnose Graves' ophthalmopathy, these devices have drawbacks: they are not readily available for routine practice, they are time-consuming, and they are expensive. CT is also limited by the hazards associated with radiation. Ultrasonography requires an experienced examiner who shows high interobserver variability.11

The use of optical coherence tomography (OCT) to visualize the extraocular rectus muscles has been recently described in the literature.12–19 In a previous study, we measured medial and lateral rectus thicknesses in healthy individuals employing different OCT devices and observed good agreement and reproducibility.14 Using enhanced-depth OCT, Häner et al.20 described medial rectus muscle thickening in 15 patients with Graves' ophthalmopathy. However, extraorbital muscle thicknesses have not yet been compared in patients with active and inactive disease. Therefore, the purpose of this study was to use OCT to assess horizontal rectus muscle thickening in patients with active and inactive Graves' ophthalmopathy compared to healthy controls.

Patients and Methods

For this cross-sectional observational study, we examined the right eyes of 55 healthy patients (control group), 45 patients with clinically inactive Graves' ophthalmopathy, and 12 patients with active Graves' ophthalmopathy at the Hospital Clínico San Carlos, Madrid, Spain, from November 2016 to July 2017. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the institutional review board of the Hospital Clínico San Carlos. Signed informed consent was obtained from each participant.

Active and inactive disease were defined according to the clinical activity score (CAS) of Mourits in which 10 items were assessed to give a score out of 10: (1) chemosis; (2) caruncle inflammation; (3) conjunctival redness; (4) eyelid erythema; (5) eyelid swelling; (6) spontaneous orbital pain; (7) gaze-evoked orbital pain; (8) exophthalmos of 2 mm or greater; (9) affected ocular motility; and (10) loss of visual acuity. The cut-offs used to differentiate between active and inactive disease were a CAS value of 4 or greater or less than 4 on a scale of 10, respectively.21

A complete clinical history was obtained and an ophthalmologic examination was performed for all patients. Patients were excluded if they had an ocular disease making it difficult to define the limbus (as the measurement reference point), if they were not able to easily collaborate, or if they had undergone strabismus surgery. Patients with active Graves' ophthalmopathy were examined before commencing treatment (both naïve or with a new active episode).

Further data collected from all participants were gender, age, thyroid state, Graves' ophthalmopathy disease duration, and CAS.

Images were obtained using the anterior segment module of the Spectralis (Heidelberg Engineering Inc., Heidelberg, Germany). This system takes 40,000 axial scans per second and has a 7-µm axial resolution. The examination was guided by a fixation light. Scans were performed parallel to the long axis of the tendon as 5 parallel line scans 16.7 µm long and 5.7 µm high at 278-µm intervals, and the best quality image was selected. Cross-section photographs were obtained using the software's sclera mode, and we selected the line raster scanning protocol, enhanced depth imaging, and high-resolution in that mode. The image acquisition for all of the horizontal rectus muscles lasted approximately 3 to 5 minutes.

The thicknesses of the horizontal rectus muscle tendons were measured using the OCT's caliper function. The posterior limbus was readily identified, marked on the external view of the eye, and the software generated a vertical line on the OCT image to mark it as the point of reference for the measurements.19 Medial rectus thickness was measured at 7.2 and 9.2 mm from the limbus, and lateral rectus thickness was measured at 8.5 and 10.5 mm from the limbus (Figure 1).14,15 Chemosis was identified as a hyporeflective area inside the conjunctiva and was measured in the temporal quadrant 6 mm from the limbus (Figure 2). All scans were taken by a well-trained examiner and were analyzed by a single well-trained reviewer of images (LD-P-G-L).

Medial rectus muscle thickness measurements. Medial rectus thickness measured 7.2 and 9.2 mm from the limbus by optical coherence tomography in a (A) healthy control, (B) patient with inactive Graves' ophthalmopathy, and (C) patient with active Graves' ophthalmopathy.

Figure 1.

Medial rectus muscle thickness measurements. Medial rectus thickness measured 7.2 and 9.2 mm from the limbus by optical coherence tomography in a (A) healthy control, (B) patient with inactive Graves' ophthalmopathy, and (C) patient with active Graves' ophthalmopathy.

Chemosis observed by optical coherence tomography. (A–B) Chemosis measured 6 mm from the limbus in two patients with active Graves' ophthalmopathy. (C) Large cysts or spaces observed in the conjunctiva due to chemosis.

Figure 2.

Chemosis observed by optical coherence tomography. (A–B) Chemosis measured 6 mm from the limbus in two patients with active Graves' ophthalmopathy. (C) Large cysts or spaces observed in the conjunctiva due to chemosis.

A subgroup of 15 eyes (15 patients) with Graves' ophthalmopathy (10 with inactive and 5 with active disease) were randomly selected to assess intraobserver and interobserver reproducibility of the OCT thickness measurements. We also examined the reproducibility of the chemosis measurements in 5 patients with active Graves' ophthalmopathy. To ensure interobserver reproducibility, two independent examiners (LD-P-G-L and JIF-V) inspected the same images, and a second measurement on the same image was taken by the same examiner 1 week after the first measurement.

Statistical Analysis

Statistical tests were performed using Statistical Package for Social Sciences software (version 18.0; SPSS, Inc., Chicago, IL). Quantitative data are provided as the mean and standard deviation, and qualitative data as their frequency distributions. Controls were paired by age and sex. Differences in muscle tendon thicknesses among groups were assessed by analysis of variance (ANOVA) using the post-hoc Tukey's test in the multiple pair comparisons. To assess agreement as a measure of the interobserver and intraobserver reproducibility of the OCT measurements in patients with Graves' ophthalmopathy, intraclass correlation coefficients (ICCs) were calculated for quantitative variables. Pearson's test was used to correlate CAS with muscle tendon thickness. Significance was set at a P value of less than .05.

Results

The baseline characteristics of the three study groups are provided in Table 1. There were no differences in age or sex among groups (P ≥ .245). The average disease duration was 57.3 ± 56.2 months in the group of patients with inactive Graves' ophthalmopathy and 14.6 ± 11.6 months in the group of patients with active Graves' ophthalmopathy. Eighty-seven percent of patients had hyperthyroidism and 13% were euthyroid.

Baseline Characteristics of the Different Groupsa

Table 1:

Baseline Characteristics of the Different Groups

In the control group, lateral rectus tendon thickness measurements could be made at 8.5 mm from the limbus in 93% of patients and at 10.5 mm in 78% of patients, whereas the 7.2- and 9.2-mm medial rectus tendons could be measured in 95% and 86% of patients, respectively. In the inactive Graves' ophthalmopathy group, the 8.5- and 10.5-mm lateral rectus tendons could be measured in 87% and 73% of patients, respectively, whereas the 7.2- and 9.2-mm medial rectus tendons could be measured in 98% and 87% of patients, respectively. In the active Graves' ophthalmopathy group, 8.5-mm lateral rectus tendon measurements could be made in 75%, but the more posterior measurements could only be taken in 42% of cases (10.5-mm lateral rectus due to the difficulty in maximum inward gaze from pain and chemosis, whereas both medial rectus measurements could be obtained in 92% of patients).

The thickness measurements obtained in controls, patients with inactive Graves' ophthalmopathy, and patients with active Graves' ophthalmopathy, respectively, were: 7.2-mm medial rectus = 173 ± 39, 188 ± 46, and 193 ± 44 µm (P = .039; ANOVA) (Table 2) and 9.2-mm medial rectus = 201 ± 71, 240 ± 70, and 283 ± 68 µm (P < .001); 8.5-mm lateral rectus = 199 ± 53, 231 ± 63, and 274 ± 77 µm (P < .001) and 10.5-mm lateral rectus = 200 ± 32 and 228 ± 54 µm (only for controls and patients with inactive Graves' ophthalmopathy) (P = .021). Thus, 9.2-mm medial rectus and 7.2- and 9.2-mm lateral rectus measurements were greater in the inactive Graves' ophthalmopathy group than in controls (P ≤ .011). In the active Graves' ophthalmopathy group, 9.2-mm medial rectus and 8.5-mm lateral rectus tendons were thicker again compared with the patients with inactive Graves' ophthalmopathy (P ≤ .048). However, there were no differences between controls and patients with inactive Graves' ophthalmopathy or between patients with inactive and active Graves' ophthalmopathy in the more anterior medial rectus measurements (P ≥ .062). Posterior lateral rectus thickness measurements could not be compared between patients with inactive and active Graves' ophthalmopathy due to the small size of our active Graves' ophthalmopathy group.

Medial and Lateral Rectus Tendon Thickness Measurementsa

Table 2:

Medial and Lateral Rectus Tendon Thickness Measurements

Intraobserver and interobserver reproducibility of the tendon thickness measurements were ICC = 0.920 (range: 0.785 to 0.972) and ICC = 0.894 (range: 0.719 to 0.963), respectively, for the lateral rectus, and higher at ICC = 0.954 (range: 0.904 to 0.978) and ICC = 0.939 (range: 0.859 to 0.972), respectively, for the medial rectus. Best intraobserver and interobserver reproducibility values were recorded for the chemosis measurements (ICC = 0.995 [range: 0.925 to 0.999] and 0.993 [range: 0.921 to 0.999], respectively).

Mean CAS scores were 0.6 ± 0.8 in the inactive Graves' ophthalmopathy group and 4.7 ± 1.4 in the active Graves' ophthalmopathy group (Table 1). A weak significant correlation was detected between the lateral rectus (8.5) and CAS (R = 0.252, P = .035), and also between the medial rectus (9.2) and CAS (R = 0.291, P = .013). On the contrary, no significant correlation was observed between the CAS and 7.2-mm medial rectus (7.2) (R = 0.156, P = .146) or between this score and the 10.5-mm lateral rectus (R = 0.143, P = .112).

Conjunctival swelling was observed in 7 of 12 patients with active Graves' ophthalmopathy, with a mean thickness of 322 ± 202 µm (range: 55 to 610 µm). In two patients, large cysts (spaces) were observed in the conjunctiva due to chemosis using this instrument.

Discussion

Muscle thickening is one of the classic findings in patients with Graves' ophthalmopathy, and it is because of this that imaging techniques are important for diagnosing and treating affected patients. In the current study using OCT, we detected a significant thickening of the lateral rectus and medial rectus muscle tendons (at the more posterior measurement points) in patients with inactive Graves' ophthalmopathy compared to controls. We also observed further thickening of the medial rectus at the posterior measurement point (9.2 mm from the limbus) and lateral rectus at the anterior measurement point (8.5 mm from the limbus) in patients with active Graves' ophthalmopathy compared to those with inactive disease. However, at the more anterior medial rectus measurement point (7.2 mm from the limbus), no significant thickening was observed when we compared controls and patients with inactive or active Graves' ophthalmopathy. We also observed the excellent reproducibility of OCT measurements in patients with Graves' ophthalmopathy.

The distinction between muscle and tendon can be difficult when using OCT. In previous studies, we used OCT to measure the distance from the limbus to the muscle insertions as 5.2 mm for the medial rectus and 6.5 mm for the lateral rectus.14 For these distances, we would need to add the mean lengths of the tendons, approximately 4 mm for the medial rectus and 8 mm for the lateral rectus.22 According to these mean values, the true muscles begin at approximately 9 mm from the limbus for the medial rectus and 14 to 15 mm for the lateral rectus. Thus, because current thickness measurements were made at 7.2 and 9.2 mm from the limbus for the medial rectus and at 8.5 mm and 10.5 mm for the lateral rectus, we assumed we were measuring the thickness of the muscle tendons rather than the muscles themselves. A possible exception was the 9.2-mm medial rectus tendons, which could correspond to the muscle–tendon junction point.

In a recent OCT study, Häner et al.20 compared lateral rectus and medial rectus muscle thicknesses in 15 patients with Graves' ophthalmopathy, 5 of whom had active disease, with 12 controls. These authors observed a mean thickness of the medial rectus muscle in the Graves' ophthalmopathy group of 256.4 ± 17 µm, which was significantly thicker than in their control group (214.7 ± 5.5 µm). However, lateral rectus thickness was not significantly different between the patients with Graves' ophthalmopathy (263.8 ± 57.7 µm) and controls (254.9 ± 8.6 µm). The device used by these authors was the same as in our study. Although their medial rectus measurements were taken at 8.7 mm from the limbus and lateral rectus thicknesses at 9.8 mm from the limbus, means were similar in both studies, except for the control lateral rectus thickness, which was greater in their study.

Although the muscles most involved in Graves' ophthalmopathy are the inferior and medial recti, besides 9.2-mm medial rectus thickening, we also noted lateral rectus thickening in patients with Graves' ophthalmopathy compared to controls. In contrast, Häner et al.20 only detected differences in medial rectus thickness. As recognized by the authors, limitations of their study were the small number of patients and the low CAS scores, which were both lower than our study.

Classically, spindle-shaped spreading of more than one extraocular muscle (> 4 mm) without involvement of the tendon is considered pathognomonic for Graves' ophthalmopathy,11 whereas tendon involvement is thought to be more characteristic of myositis.21,23 However, in 6.4% of cases, enlargement of the tendons has been observed by CT and MRI in patients with Graves' ophthalmopathy.24 Interestingly, in the current OCT study, we observed thickening of the anterior portion of the muscle in Graves' ophthalmopathy. The increased thickness was approximately 15 to 80 µm, which may not be detected through CT or MRI, due to their lower resolution. Häner et al.20 found that OCT could show that the tendinous area of the insertion site is affected in Graves' ophthalmopathy. According to Jaggi et al.,25 who evaluated extraocular muscle–tendon junction anatomy by immunohistochemistry, there is no “true” tendon; instead muscle fibers transition into the tendon and may reach all the way to the sclera in up to 75% of cases. So it is not unreasonable that, in some cases with more muscle fibers in the proximal tendon, we might see some thickening with extraocular muscle enlargement related to Graves' ophthalmopathy. Even with the high resolution of the SD-OCT employed, we found it difficult to determine where the tendons ended and, therefore, to confirm their real involvement in Graves' ophthalmopathy.

Several studies have shown a good linear correlation between MRI signal intensity values obtained for the rectus muscles and CAS.26,27 Thus, MRI scans could be a useful measurement of disease activity and help monitor and treat the condition. Further, lower muscle reflectivity was described in patients with Graves' ophthalmopathy than in controls in an ultrasonography study.28 This was also lower in responders to immunosuppressive treatment than in nonresponders (P = .02). However, in a later study, the negative predictive value of this indicator was only 60%.29 Hence, despite the low cost, short examination time, and lack of irradiation of ultrasonography, no clear classification of disease activity seems possible. The technique has drawbacks because it is insufficiently accurate and shows high interobserver variability.11,28 Häner et al.20 was able to correlate CAS with OCT-determined muscle thickness (R2 = 0.5; P = .0027). In agreement, we detected a significantly weak correlation between CAS and muscle thickness for the lateral rectus and the posterior portion of the medial rectus (9.2 mm from the limbus).

In the current study, OCT proved useful to accurately measure conjunctival swelling in patients with active Graves' ophthalmopathy. The method used currently in clinical practice for detecting chemosis is a slit-lamp examination. However, this subjective method could soon be superseded by more objective OCT measurements. OCT has also been employed in patients with Graves' ophthalmopathy to assess subfoveal choroidal thickness, which is increased in patients with active Graves' ophthalmopathy. This variable has thus been proposed as an objective criterion to assess disease activity.30

OCT has several advantages over MRI and CT because it is a rapid, noninvasive, and readily available technique. We propose that OCT should be considered a complementary technique to MRI, which is clearly the gold standard for examining the entire length of the muscle and its interrelations within the orbit. In daily practice, we recommend an OCT examination in patients with Graves' ophthalmopathy, mainly in cases of dubious diagnosis or during follow-up to establish if there is thickening of the rectus muscles and the presence of chemosis. This measure acquires special interest because no muscle thickness cut-offs have yet been established to classify patients according to disease activity. In future studies, it would also be interesting to assess the benefits of OCT for monitoring treatment responses in patients with Graves' ophthalmopathy. The learning curve for the OCT exploration of the horizontal muscles is short, similar to an exploration of the macula or the optic nerve.

Our study has several limitations. OCT allows visualization of the anterior part of the muscle but not of the muscle belly, making it especially difficult to examine in patients with motility restrictions. The vertical rectus muscles are also difficult to examine because of interference from the eyelids and motility restrictions, mainly in the inferior rectus. However, it is also true that previous studies using different OCT devices achieved good visualization of the vertical rectus in patients with strabismus.13,18 In addition, because muscle insertion distances vary between individuals, the muscle measurement points used here may not have been equivalent. Future studies are needed to explore the inferior rectus in patients with Graves' ophthalmopathy because it is the most affected extraocular muscle, and also to compare OCT findings with MRI findings. Further limitations of our study were the relatively small number of patients with active Graves' ophthalmopathy, and the fact that the posterior portion of the lateral rectus could be measured only in a few cases. Accordingly, studies including larger patient populations are needed to confirm the results of the current study.

Our OCT measurements revealed thicker horizontal rectus muscle tendons in patients with Graves' ophthalmopathy than in controls, and thicker measurements in patients with active Graves' ophthalmopathy compared to those with inactive disease. If these results are confirmed, OCT could be useful to establish the severity of Graves' ophthalmopathy.

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Baseline Characteristics of the Different Groupsa

CharacteristicControls (n = 55)Inactive Graves' Ophthalmopathy (n = 45)Active Graves' Ophthalmopathy (n = 12)
Age (years)50.4 ± 20 (17 to 82)52.6 ± 14 (17 to 80)55.6 ± 12 (38 to 81)
Sex (female)72.7%79.5%75%
CAS00.6 ± 0.8 (0 to 3)4.7 ± 1.4 (4 to 8)
Disease duration (months)N/A57.3 ± 56.2 (1 to 240)14.6 ± 11.6 (2 to 40)

Medial and Lateral Rectus Tendon Thickness Measurementsa

TendonMeasurement Site from LimbusControls (µm)Inactive GO (µm)Active GO (µm)Pb
Medial rectus7.2 mm173 ± 39 (94 to 273)188 ± 46 (101 to 325)193 ± 44 (134 to 299)Controls vs inactive 0.062; Inactive vs active 0.904
9.2 mm201 ± 71 (82 to 386)240 ± 70 (130 to 457)283 ± 68 (144 to 414)Controls vs inactive 0.011; Inactive vs active 0.048
Lateral rectus8.5 mm199 ± 53 (104 to 342)231 ± 63 (119 to 398)274 ± 77 (127 to 443)Controls vs inactive 0.006; Inactive vs active 0.039
10.5 mm200 ± 32 (112 to 269)228 ± 54 (121 to 335)278 ± 88 (145 to 389)Controls vs inactive 0.021; Inactive vs active N/A
Authors

From the Department of Ophthalmology, Hospital Universitario 12 de Octubre, Madrid, Spain (LD-P-G-L); and the Department of Ophthalmology, Hospital Universitario Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain (JIF-V, NV-A, JT-R, CN-R, AR-L, RG-D-L).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Lucía De-Pablo-Gómez-de-Liaño, MD, PhD, Department of Ophthalmology, Hospital Universitario, C/ Avenida de Córdoba 0, 28041 Madrid, Spain. E-mail: depablo.lucia@gmail.com

Received: November 29, 2017
Accepted: June 20, 2018
Posted Online: August 29, 2018

10.3928/01913913-20180802-01

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