OBJECTIVE: We aimed to investigate the ability of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in assessing the microstructural change of extraocular muscles (EOMs) and optic nerves in patients with thyroid-associated orbitopathy (TAO) as well as in evaluating disease activity.MATERIALS AND METHODS: We enrolled 35 TAO patients and 22 healthy controls (HCs) who underwent pre-treatment rs-EPI-based DTI. Mean, axial, and radial diffusivity (MD, AD, and RD) and fractional anisotropy (FA) of the medial and lateral EOMs and optic nerve for each orbit were calculated and compared between TAO and HC groups and between active and inactive TAO groups. Factors such as age, sex, disease duration, mediation, and smoking history between groups were also compared. Logistic regression analysis was used to evaluate the predictive value of significant variables for disease activity.RESULTS: Disease duration was significantly shorter in active TAOs than in inactive ones (p < 0.001). TAO patients showed significantly lower FA and higher MD, AD, and RD than HCs for both medial and lateral EOMs (p < 0.001), but not the AD value of lateral EOMs (p = 0.619). Active patients had significantly higher FA, MD, and AD than inactive patients for medial EOMs (p < 0.005), whereas only FA differed significantly in the lateral EOMs (p = 0.018). The MD, AD, and RD of optic nerves were significantly lower in TAO patients than HCs (p < 0.05), except for FA (p = 0.129). Multivariate analysis showed that the MD of medial EOMs and disease duration were significant predictors for disease activity. The combination of these two parameters showed optimal diagnostic efficiency for disease activity (area under the curve, 0.855; sensitivity, 68.4%; specificity, 96.9%).CONCLUSION: rs-EPI-based DTI is promising in assessing microstructural changes of EOMs and optic nerves and can help to indicate the disease activity of TAO, especially through the MD of medial EOMs.
Anisotropy ; Diffusion Tensor Imaging ; Diffusion ; Echo-Planar Imaging ; Humans ; Logistic Models ; Multivariate Analysis ; Muscles ; Negotiating ; Optic Nerve ; Orbit ; Sensitivity and Specificity ; Smoke ; Smoking ; Troleandomycin

PURPOSE: To compare the intraocular pressure (IOP) measured using Goldmann-applanation tonometry (GAT) and Tonopen® tonometry and to evaluate the factors influencing the measurement difference in patients with thyroid-associated ophthalmopathy (TAO)-related restrictive strabismus. METHODS: In 50 eyes of 50 patients who were diagnosed with TAO, IOP measurements were taken using both GAT and a Tonopen® and were subsequently compared between the devices. Factors influencing the measurement difference between the devices were determined, including the restriction of eyeball movement, eyeball deviation, exophthalmometry, central corneal thickness, refractive errors, and blood thyroid hormone levels. RESULTS: In the TAO patients, the GAT-measured IOP was higher than for Tonopen® (16.1 ± 4.7 vs. 13.8 ± 4.5 mmHg, respectively, p < 0.001). As the restriction of vertical eyeball movement increased, the IOP difference between the devices also increased (p = 0.037). The absolute IOP difference between the devices was positively correlated with restrictions in vertical eyeball movement (p = 0.027), degree of vertical strabismus (p = 0.021), and central corneal thickness (p ≤ 0.031). CONCLUSIONS: In patients with TAO accompanying vertical eyeball movement restriction, potential errors in IOP measurements should be considered between the different IOP-measuring devices.
Graves Ophthalmopathy* ; Humans ; Intraocular Pressure* ; Manometry* ; Refractive Errors ; Strabismus* ; Thyroid Gland ; Troleandomycin

PURPOSE: To compare the macular choroidal thickness in patients with thyroid-associated ophthalmopathy (TAO) with those with normal tension glaucoma (NTG). METHODS: A total of 70 normal eyes, 74 eyes with TAO and 60 eyes with NTG were enrolled in this study. All patients underwent spectral-domain optical coherence tomography (SD-OCT) (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA). Macular choroidal thickness was assessed using enhanced depth imaging. The average macular choroidal thickness was defined as the average value of three measurements: at the fovea and at the points located 1.5 mm in the nasal and temporal directions from the fovea. Generalized estimating equations were used to uncover factors affecting the average macular choroidal thickness. RESULTS: The average, superior and inferior quadrant retinal nerve fiber layer thicknesses were significantly thinner in the NTG group compared with the TAO and control groups (p < 0.001). The average macular choroidal thickness of the TAO group, NTG group and controls was 281.01 ± 60.06 µm, 241.66 ± 55.00 µm and 252.07 ± 55.05 µm, respectively, which were significantly different (p = 0.013). The subfoveal, nasal and temporal side choroidal thicknesses were significantly thinner in the NTG group compared with the TAO group (p = 0.014, 0.012 and 0.034, respectively). Subjects with TAO were associated with a thicker average macular choroidal thickness compared with the NTG group after adjusting for age, sex, spherical equivalent and intraocular pressure (β = 32.61, p = 0.017). CONCLUSIONS: Macular choroidal thickness was significantly thicker in patients with TAO compared with those with NTG. Further evaluation is required to determine if a thick choroid in subjects with TAO has any role in glaucomatous optic neuropathy.
Choroid* ; Graves Ophthalmopathy* ; Humans ; Intraocular Pressure ; Low Tension Glaucoma* ; Nerve Fibers ; Optic Nerve Diseases ; Retinaldehyde ; Tomography, Optical Coherence* ; Troleandomycin

PURPOSE: This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Korean patients with thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Genetic analyses were conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48) to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of each genetic variant on the transcription or expression of these genes was examined. Additionally, correlations between functional haplotypes of ST3GAL5 or ST8SIA1 and clinical characteristics of the patients were investigated. RESULTS: Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified, and four major promoter haplotypes were assembled. Additionally, three promoter variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and ST8SIA1 variants identified in TAO patients were also found in healthy controls. Promoter activity was significantly decreased in three promoter haplotypes of ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors activating protein-1, NKX3.1, and specificity protein 1 were revealed as having roles in transcriptional regulation of these haplotypes. The nonsynonymous variant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no differences in clinical characteristics were detected in patients possessing the functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly lower in patients with the ST8SIA1 haplotype, which showed a significant increase in promoter activity. CONCLUSION: These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoter haplotype and the clinical severity of TAO. However, further studies with larger sample sizes are warranted.
DNA ; Exophthalmos ; Graves Ophthalmopathy* ; Haplotypes ; Healthy Volunteers ; Humans ; Korea ; Polymorphism, Single Nucleotide ; Sample Size ; Sensitivity and Specificity ; Sialyltransferases ; Transcription Factors ; Troleandomycin

PURPOSE: To evaluate the clinical outcomes of balanced deep lateral and medial orbital wall decompression and to estimate surgical effects using computed tomography (CT) images in Korean patients with thyroid-associated ophthalmopathy (TAO). METHODS: Retrospective chart review was conducted in TAO patients with exophthalmos who underwent balanced deep lateral and medial orbital wall decompression. Exophthalmos was measured preoperatively and postoperatively at 1 and 3 months. Postoperative complications were evaluated in all study periods. In addition, decompressed bone volume was estimated using CT images. Thereafter, decompression volume in each decompressed orbital wall was analyzed to evaluate the surgical effect and predictability. RESULTS: Twenty-four patients (48 orbits) with an average age of 34.08 ± 7.03 years were evaluated. The mean preoperative and postoperative exophthalmos at 1 and 3 months was 18.91 ± 1.43, 15.10 ± 1.53, and 14.91 ± 1.49 mm, respectively. Bony decompression volume was 0.80 ± 0.29 cm3 at the medial wall and 0.68 ± 0.23 cm3 at the deep lateral wall. Postoperative complications included strabismus (one patient, 2.08%), upper eyelid fold change (four patients, 8.33%), and dysesthesia (four patients, 8.33%). Postsurgical exophthalmos reduction was more highly correlated with the deep lateral wall than the medial wall. CONCLUSIONS: In TAO patients with exophthalmos, balanced deep lateral and medial orbital wall decompression is a good surgical method with a low-risk of complications. In addition, deep lateral wall decompression has higher surgical predictability than medial wall decompression, as seen with CT analysis.
Decompression* ; Exophthalmos ; Eyelids ; Graves Ophthalmopathy ; Humans ; Orbit* ; Paresthesia ; Postoperative Complications ; Retrospective Studies ; Strabismus ; Troleandomycin

PURPOSE: To evaluate the effect of orbital decompression surgery on quality of life in thyroid-associated ophthalmopathy (TAO) patients. METHODS: From August 2014 to December 2015, 80 patients diagnosed with TAO at our clinic were retrospectively analyzed. The patients were divided into 2 groups: 30 patients who underwent orbital decompression surgery and 50 patients who did not receive surgery. The Korean version of the Grave's ophthalmopathy specific quality of life (GO-QoL) questionnaire was completed by all patients. We compared questionnaire scores between groups and analyzed demographic and clinical factors affecting change in GO-QoL. RESULTS: The patients who underwent orbital decompression had lower mean GO-QoL score for appearance in comparison with patients without orbital decompression (p < 0.001). The mean GO-QoL score for appearance was increased from 28.8 ± 17.1 to 51.5 ± 18.8 after orbital decompression (p = 0.024). The mean GO-QoL score for visual function was not different between the patients who did not receive surgery and the orbital decompression group. The mean GO-QoL score for visual function was not changed after orbital decompression. There was a significant relation between postoperative proptosis degree and change in GO-QoL score for appearance after orbital decompression. CONCLUSIONS: GO-QoL score for appearance was significantly improved after orbital decompression surgery, and psychological interventions should be considered to enhance the quality of life outcomes.
Decompression* ; Exophthalmos ; Graves Ophthalmopathy* ; Humans ; Orbit* ; Quality of Life* ; Retrospective Studies ; Troleandomycin

PURPOSE: To describe the change of lacrimal gland volumes in Korean patients with thyroid-associated ophthalmopathy (TAO) via computed tomography (CT). METHODS: A retrospective review of CT images from 217 TAO patients and 135 control subjects was performed. The TAO patients were diagnosed between May 2005 and May 2014 and had a CT performed on initial presentation (330 orbital CT scans). These images were compared with 270 orbital CT scans from the control group, obtained between May 2013 and May 2014. An open source DICOM viewer was used to calculate the volume of the lacrimal gland. RESULTS: The mean volume of the lacrimal gland in TAO patients was 0.816 cm³ in the right orbit (standard deviation [SD], 0.048) and 0.811 cm3 in the left orbit (SD, 0.051), with no significant difference between right and left (p = 0.192). However, significant differences were observed between TAO patients and healthy individuals (p < 0.001). There was no significant difference between mean lacrimal gland volumes of males (0.812 cm³; SD, 0.037) and females (0.816 cm³; SD, 0.029) (p = 0.513). There was a negative correlation between gland volume and age in TAO patients (Pearson r = -0.479, p = 0.00). The subjective tearing (right: r = 0.244, p = 0.018; left: r = 0.226, p = 0.024), corneal superficial punctate keratopathy (right: r = 0.192, p = 0.040; left: r = 0.206, p = 0.036), and exophthalmometry (right: r = 0.182, p = 0.032; left: r = 0.180, p = 0.046) correlated with lacrimal gland volume. CONCLUSIONS: This study is the first to use CT images to calculate the lacrimal gland volume of Korean TAO patients. In TAO patients, the lacrimal gland volume was notably increased compared to control subjects. The lacrimal gland volume decreased with age, but there was no difference between gender and no difference between left and right. The lacrimal gland volume correlated with subjective tearing, corneal superficial punctate keratopathy and exophthalmometry.
Computer Communication Networks ; Female ; Graves Ophthalmopathy* ; Humans ; Lacrimal Apparatus* ; Male ; Orbit ; Retrospective Studies ; Tears ; Tomography, X-Ray Computed ; Troleandomycin

PURPOSE: To evaluate the clinical features of dry eye in thyroid-associated ophthalmopathy (TAO) according to disease activity and analyze the related factors. METHODS: This study included 157 patients diagnosed with TAO and dry eye between March 2009 and March 2015. According to the clinical activity score (CAS), TAO patients were divided into inactive (CAS < 3) and active (CAS ≥ 3) groups. Clinical features included age, sex, visual acuity, proptosis, palpebral fissure width, orbital computed tomography (CT) findings, thyroid hormones, and ocular surface parameters including tear film break-up time (TFBUT), Schirmer tests, keratoepitheliopathy scores, and ocular surface disease index (OSDI) were obtained and compared between the groups. In addition, correlations between clinical features and ocular surface parameters were analyzed in both groups. RESULTS: In the inactive and active TAO groups, CAS was 1.24 ± 0.69 and 4.23 ± 1.13, respectively (p = 0.001). Thyrotropin-binding inhibitory immunoglobulin was significantly higher in the active TAO group than in the inactive TAO group (p = 0.048). On orbital CT, extraocular muscle hypertrophy was more common in the active TAO group than the inactive TAO group (p = 0.020). No significant difference was found in age, sex, visual acuity, free T4, and thyroid-stimulating hormone between the two groups. During analysis of the tear film and ocular surface parameters, TFBUT (p = 0.006) was shorter and OSDI score (p = 0.028) was higher in the active TAO group than the inactive TAO group. TFBUT was negatively correlated with proptosis (r = -0.432, p = 0.001; r = -0.308, p = 0.032) and palpebral fissure width (r = -0.367 p = 0.012; r = -0.312, p = 0.031) in both groups. OSDI was positively correlated with proptosis in the active TAO group (r = 0.301, p = 0.033). CONCLUSIONS: TFBUT was shorter and OSDI score higher in dry eye patients with active TAO than in patients with inactive TAO. The TFBUT was negatively correlated with proptosis and palpebral fissure width in both groups.
Exophthalmos ; Graves Ophthalmopathy* ; Humans ; Hypertrophy ; Immunoglobulins ; Orbit ; Tears ; Thyroid Hormones ; Thyrotropin ; Troleandomycin ; Visual Acuity

PURPOSE: To evaluate the clinical features of dry eye in thyroid-associated ophthalmopathy (TAO) according to disease activity and analyze the related factors. METHODS: This study included 157 patients diagnosed with TAO and dry eye between March 2009 and March 2015. According to the clinical activity score (CAS), TAO patients were divided into inactive (CAS < 3) and active (CAS ≥ 3) groups. Clinical features included age, sex, visual acuity, proptosis, palpebral fissure width, orbital computed tomography (CT) findings, thyroid hormones, and ocular surface parameters including tear film break-up time (TFBUT), Schirmer tests, keratoepitheliopathy scores, and ocular surface disease index (OSDI) were obtained and compared between the groups. In addition, correlations between clinical features and ocular surface parameters were analyzed in both groups. RESULTS: In the inactive and active TAO groups, CAS was 1.24 ± 0.69 and 4.23 ± 1.13, respectively (p = 0.001). Thyrotropin-binding inhibitory immunoglobulin was significantly higher in the active TAO group than in the inactive TAO group (p = 0.048). On orbital CT, extraocular muscle hypertrophy was more common in the active TAO group than the inactive TAO group (p = 0.020). No significant difference was found in age, sex, visual acuity, free T4, and thyroid-stimulating hormone between the two groups. During analysis of the tear film and ocular surface parameters, TFBUT (p = 0.006) was shorter and OSDI score (p = 0.028) was higher in the active TAO group than the inactive TAO group. TFBUT was negatively correlated with proptosis (r = -0.432, p = 0.001; r = -0.308, p = 0.032) and palpebral fissure width (r = -0.367 p = 0.012; r = -0.312, p = 0.031) in both groups. OSDI was positively correlated with proptosis in the active TAO group (r = 0.301, p = 0.033). CONCLUSIONS: TFBUT was shorter and OSDI score higher in dry eye patients with active TAO than in patients with inactive TAO. The TFBUT was negatively correlated with proptosis and palpebral fissure width in both groups.
Exophthalmos ; Graves Ophthalmopathy* ; Humans ; Hypertrophy ; Immunoglobulins ; Orbit ; Tears ; Thyroid Hormones ; Thyrotropin ; Troleandomycin ; Visual Acuity

PURPOSE: To determine immunochemical and clinical differences in thyroid-associated ophthalmopathy (TAO) patients with restrictive strabismus and without strabismus. METHODS: A retrospective chart review of 15 TAO patients with strabismus (25 eyes) and 24 TAO patients without strabismus (39 eyes) who presented to the Ophthalmology Clinic between August 2011 and December 2013 was performed. Visual acuity, intraocular pressure (IOP), Hertel exophthalmometry, soft tissue score, and enlargement of extraocular muscles on computed tomography (CT) were obtained and compared in each group. Thyroid related autoantibody (thyroid-stimulating hormone receptor antibody, TRAb; thyroid peroxidase antibody, TPOAb; anti-thyroglobulin antibody, TgAb) titers and positive rates were obtained at the time of diagnosis or before treatment and analyzed. RESULTS: The gender and smoking proportion were not significantly different between the 2 groups. The mean age of TAO patients with strabismus was 52.53 years and of TAO patients without strabismus 40.33 years (p = 0.004). The differences in visual acuity and IOP between the 2 groups were not significant. Hertel exophthalmometry showed less proptotis in the TAO with strabismus group than the TAO without strabismus group (16.84 mm versus 18.67 mm). The soft tissue score was not significantly different. The extraocular muscle enlargement rate of TAO with strabismus was significantly higher than in TAO without strabismus group. In the TAO with strabismus group, TRAb level was higher than in the TAO without strabismus group (p = 0.021). CONCLUSIONS: The TAO with strabismus group was older and had higher positive rate, level of TRAb, and extraocular muscle enlargement rate on CT than the TAO without strabismus group. Furthermore, proptosis was less definite in the TAO with strabismus group.
Diagnosis ; Exophthalmos ; Graves Ophthalmopathy* ; Humans ; Intraocular Pressure ; Iodide Peroxidase ; Muscles ; Ophthalmology ; Retrospective Studies ; Smoke ; Smoking ; Strabismus* ; Thyroid Gland ; Troleandomycin ; Visual Acuity