Thyroid-Associated Orbitopathy: Evaluating Microstructural Changes of Extraocular Muscles and Optic Nerves Using Readout-Segmented Echo-Planar Imaging-Based Diffusion Tensor Imaging

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.

Clinical Study of Ocular Manifestations of Thyroid Disease in Tertiary Eye Care Center

Introduction: Thyroid eye disease (TED), Graves’ ophthalmopathy, or Thyroid associated orbithopathy (TAO) are an immunemediated inflammatory disorder that produces expansion of the extraocular muscles and fat in the orbit. TED is most commonlyassociated with Graves’ hyperthyroidism but can also be noted in hypothyroid and euthyroid states.Aim: The aim of the study is to evaluate the ocular manifestation of thyroid dysfunction (TD).Materials and Methods: A prospective non-randomized observational study was carried out on 106 patients of TD. They wereexamined in detail for demography, systemic, and ocular examination and laboratory investigation. Period of study was 1 year.Results: In this study, average age of presentation of TD was 42.54 years. Female-to-male ratio was 3.1:1. Lid retractionwas the most common (82.4%) lid sign in patients of hyperthyroidism while in patients of hypothyroidism, it was lid edema(28.9%). The second most common lid sign was lid lag which was present 70.6% cases. Proptosis was present in 52.9%hyperthyroid patients. Three patients had unilateral proptosis. Corneal ulcer (due to exposure keratopathy) was present in17.6% of hyperthyroid patients.Conclusion: Females were more commonly affected. However, ocular manifestations were more severe in male. Hence, it isimportant to rule out TD in patient with other ocular symptom.

The Clinical Result of Medial Orbital Decompression in Patients with Thyroid-associated Orbitopathy

PURPOSE: To evaluate the clinical effects of medial orbital decompression in patients with thyroid orbitopathy. METHODS: Forty-three orbits of 28 patients who underwent medial orbital decompression for cosmetic purposes between January 2014 to January 2017 were retrospectively reviewed. Changes in visual acuity, intraocular pressure, exophthalmos, strabismus, and diplopia were checked before, 3 months, and 1 year after surgery. RESULTS: The average exophthalmos reduction was −2.99 ± 0.96 mm at postoperative 3 months and −3.07 ± 1.24 mm after 1 year (both, p < 0.001). In patients who underwent unilateral orbital decompression, the mean difference in exophthalmometry between the two eyes was significantly reduced from 3.06 ± 0.78 mm to 0.38 ± 0.44 mm after 3 months, and to 0.50 ± 0.46 mm after 1 year (p = 0.011 and p = 0.012, respectively). After surgery, the final postoperative intraocular pressure decreased significantly at postoperative 3 months and 1 year (both, p < 0.001). The mean preoperative horizontal deviation was 0.88 ± 4.85 prism diopters (PD) and 5.50 ± 6.74 PD at postoperative 3 months, which demonstrated significant esodeviation postoperatively (p = 0.007). Three patients had new onset esotropia (8.33%), but no surgical treatment was needed. CONCLUSIONS: Medial orbital decompression is a less invasive and safe surgical procedure for patients with asymmetric or mild thyroid-associated orbitopathy, which can be beneficial for reducing proptosis.

Development of Thyroid-Associated Ophthalmopathy in Patients Who Underwent Total Thyroidectomy

PURPOSE: To report clinical characteristics of thyroid-associated ophthalmopathy (TAO) in patients who previously underwent total thyroidectomy for thyroid cancer or a benign mass of the thyroid. MATERIALS AND METHODS: Of the patients who were diagnosed with TAO from March 2008 to March 2012, we performed a retrospective chart review on those who had undergone total thyroidectomy for thyroid cancer or a benign mass of the thyroid before the occurrence of ophthalmopathy. RESULTS: Of the 206 patients diagnosed with TAO, seven (3.4%) met the inclusion criteria. The mean age of the subjects was 47.4 years, and all were female. Six patients were diagnosed with papillary thyroid cancer, and one was diagnosed with a benign mass. The duration between total thyroidectomy and onset of TAO ranged from 3-120 months (median 48 months). Ophthalmic manifestations varied among cases. Except for the patient who was diagnosed with a benign mass, all patients showed hyperthyroid status and were under Synthroid hormone treatment at the time of TAO development. Five of these six patients had positive levels of thyroid-stimulating hormone (TSH) receptor autoantibodies. CONCLUSION: TAO rarely develops after total thyroidectomy, and the mechanism of TAO occurrence is unclear. However, most patients showed abnormalities in thyroid function and TSH receptor autoantibodies.

The Clinical Characteristics of Thyroid Orbitopathy in Thyroid Dysfunction Pediatric Patients

PURPOSE: To investigate the clinical characteristics and treatment methods for pediatric thyroid-associated orbitopathy in pediatric patients with thyroid disorders. METHODS: To determine the prevalence and clinical characteristics of pediatric thyroid-associated orbitopathy, we retrospectively analyzed the medical records of 34 patients admitted to the Pediatrics Department of our institution between September 2010 and September 2012. The patients had been diagnosed with autoimmune thyroid disorder and were admitted for treatment of thyroid-associated orbitopathy. RESULTS: In the 24.1 months of follow-up observation, 14 patients were diagnosed with Graves' disease (41.2%) and 20 patients with Hashimoto's thyroiditis (58.8%). Of the 34 patients, 15 (44.1%) developed eye symptoms. Among the eye symptoms, lid swelling was the most prevalent in 41.2% of patients, followed by eyelid retraction in 23.5%, lid lag in 17.6%, conjunctival injection in 14.7%, proptosis in 8.8%, and extraocular muscle hypertrophy in 17.6%. Severe impairment of visual acuity, visual field, and ocular motility were not observed in our study. Although eyelid surgery was performed in 3 cases, most patients were treated conservatively. CONCLUSIONS: Pediatric thyroid-associated orbitopathy was frequently observed in patients with Graves' disease and Hashimoto's thyroiditis. Compared to adults, children showed milder disease manifestation and progression, and the disease could be managed with conservative treatment.

Radiographic Analysis of Extraocular Muscle Volumetric Changes Following Orbital Decompression in Thyroid-Associated Orbitopathy: Comparison of Nunery Types 1 and 2

PURPOSE: To evaluate the radiographic volume change in extraocular muscles (EOM) following orbital wall decompression for Nunery type 1 and type 2 thyroid-associated orbitopathy (TAO). METHODS: Medical records of 31 orbits in 20 patients undergoing postoperative orbital CT after orbital decompression for TAO were retrospectively reviewed. The patients were divided according to Nunery classifications. A type 1 classification was assigned to patients who had no diplopia and essentially normal versions. A type 2 classification was assigned to patients with restrictive motility loss and diplopia within 20 degrees of the primary position. EOM volumes were determined by the summation of each EOM's cross-sectional areas in the coronal plane of the CT scans and multiplying the sum by the slice thickness. Main outcome measure was a comparison of EOM volume changes between types 1 and 2 TAO and a relationship between EOM volume and change in proptosis. RESULTS: In type 2 TAO, a significant increase in the volume of the medial rectus muscle, lateral rectus, and total EOM was detected postoperatively (p = 0.044, 0.022, 0.049), whereas no significant changes were found in the EOM's volume changes in type 1 TAO. The reduction of proptosis after orbital decompression in type 1 TAO was significantly greater than in type 2 TAO (p = 0.025). A significant positive association was observed between the preoperative EOM volumes and the reduction of proptosis following orbital wall decompression (r = 0.505). CONCLUSIONS: The postoperative EOM volumes following orbital wall decompression was significantly increased in Nunery type 2 patients who had restrictive myopathy.

Bilateral Extraocular Muscle Metastasis of Nasal Rhabdomyosarcoma Mimicking a Thyroid Associated Orbitopathy: A Case Report

Metastases to the orbit usually affect the intraorbital fat and bone than the extraocular muscles. Metastasis to the extracoular muscles commonly occurs unilaterally, and diffuse enlargement of the bilateral extraocular muscles due to metastasis is extremely rare. In this report, we will describe a case of diffuse metastasis to the bilateral extraocular muscles from nasal rhabdomyosarcoma masquerading as thyroid associated orbitopathy. We will also discuss about the MR imaging findings helpful for differential diagnosis from thyroid associated orbitopathy.

Risk Factors Associated with the Severity of Thyroid-Associated Orbitopathy in Korean Patients

PURPOSE: The purpose of this study is to identify risk factors for severe thyroid-associated orbitopathy (TAO) and compressive optic neuropathy in Korean patients. METHODS: This study was a retrospective comparative case series. All TAO patients who were first seen at our institution between 2005 and 2009 and who had follow-up periods of at least 6 months were included. Patients were divided into mild or moderate and severe TAO groups. Cases were also segregated based on the presence or absence of optic neuropathy. Demographics, smoking status, comorbidities, thyroid hormonal status, thyroid autoantibody levels, and clinical presentations were assessed. RESULTS: A total of 99 patients (83 with mild to moderate courses and 16 with severe courses; 90 without optic neuropathy and 9 with optic neuropathy) were included in this study. On multiple logistic regression analysis, smoking status was a predictive risk factor for a severe course of TAO and the development of optic neuropathy (odds ratios = 6.57 and 10.00, respectively). Other factors such as age, gender, free T4 level, thyroid binding-inhibiting immunoglobulin, and a history of diabetes were not predictive of severe TAO or optic neuropathy. CONCLUSIONS: Although various factors may influence the severity of TAO and the development of optic neuropathy, this study showed that smoking was a risk factor for severe TAO and the development of optic neuropathy. Therefore, it is important for patients with Graves' disease to refrain from smoking. Frequent and careful observation should also be performed in current smokers, as TAO patients who smoke are susceptible to a severe course and/or optic neuropathy.

The Epidemiologic and Clinical Characteristics of Thyroid-Associated Orbitopathy

PURPOSE: To determine the epidemiologic and clinical characteristics of thyroid-associated orbitopathy (TAO). METHODS: We retrospectively studied the clinical data of 385 patients from the New York City area diagnosed with TAO from January 1990 to December 2000. The total cases were divided into male and female groups and age-adjusted relative incidence rates were obtained to plot the incidence curve and clinical characteristics. Statistical analysis was applied to the collected data. RESULTS: The average age of patients with TAO was 46.3 years for females and 50.1 years for males. The female-male ratio was 5.31:1. In 23.3% of patients, the diagnosis of TAO was made simultaneously with their thyroid disease. In 75% of cases, the diagnosis was made within 18 months of the presentation of thyroid disease. Soft tissue involvement was noted most frequently in 311 (80.8%), eyelid retraction in 306 (79.5%), proptosis in 278 (72.2%), restrictive myopathy in 234 (60.8%), and compressive optic neuropathy in 43 (11.2%) of 385 patients. CONCLUSIONS: TAO has variable and different epidemiologic and clinical characteristics according to sex and age.

The Clinical Phenotype of Thyroid-Associated Orbitopathy related to Underlying Thyroid Status

PURPOSE: Thyroid-Associated Orbitopathy (TAO) presents with highly variable clinical characteristics. We hypothesize that the underlying thyroid status predisposes a patient to different clinical characteristics of TAO. METHODS: We retrospectively studied the clinical data of 385 patients from the New York area who were referred to our clinic and diagnosed with TAO from Jan 1990 to Dec 2000. We divided the 385 patients into three groups: Graves' hyperthyroid, euthyroid, and hypothyroid, and analyzed them statistically. RESULTS: Three hundred thirty-one (86%) patients were hyperthyroid, 25 (6.5%) were euthyroid, and 29 (7.5%) were hypothyroid. The average age of TAO presentation in each group was 46.7, 46.1, and 49.9 years, respectively. The female-male ratio in each group was 5.25, 3.17, 13.5:1, respectively (p>0.05). The average time from thyroid disease to TAO in the hyperthyroid and hypothyroid groups was 16.6 and 38 months, respectively (p<0.05). The hyperthyroid group had more proptosis (76.1 vs. 41.4%, p=0.0001<0.05) than the hypothyroid group. CONCLUSIONS: TAO has different clinical characteristics depending on thyroid status. The hyperthyroid group has a short disease interval and more severe clinical course of TAO than the hypothyroid group.

Thyroid Associated Orbitopathy following Periocular Surgery

PURPOSE: To descirbe a series of patients in which Thyroid Associated Orbitopathy (TAO) occurred after periocular surgery. METHODS: A retrospective case review of patients who developed TAO in close temporal association with periocular surgical interventions and presented at the orbital clinic from 1997 to 2004. History of previous thyroid abnormality and the lack of TAO signs and symptoms before surgery were reviewed and analyzed. RESULTS: Nine patients that developed TAO in association with periocular surgery were identified. All were women with an average age of 59.3years. (range: 45-75 years). The patients divided into two groups. Group 1 consisted of four patients who had previously been diagnosed with Graves' hyperthyroidism (GH). They ranged in age from 48 to 75 years (average: 58.8 years). The diagnosis of GH had been made an average of 50.5 months (range: 12-96 months) before presentation with TAO. Group 2 consisted of five patients who had no previous history of thyroid abnormality. They ranged in age from 45 to 74 years (average: 60.2 years). No patients had any signs or symptoms of TAO before their recent presentation. CONCLUSIONS: Periocular surgery may lead to local inflammatory events that may contribute to the instigation of TAO in predisposed individuals.

The Risk Factors for Severe Thyroid-Associated Orbitopathy

PURPOSE: To determine risk factors for severe Thyroid-Associated Orbitopathy (TAO). METHODS: We retrospectively studied the clinical data of 385 patients of the New York City area diagnosed with TAO from January 1990 to December 2000. We reviewed clinical characteristics and tried to identify several risk factors. The statistical analysis was applied to the collected data. RESULTS: Men more frequently had proptosis, restrictive myopathy, and optic neuropathy than women. Patients older than 50 years presented more frequently with proptosis, restrictive myopathy, and optic neuropathy than younger than 50 years. Patients with a family history of thyroid disease had similar clinical characteristics compare to those without family history. Smokers more often had proptosis, restrictive myopathy, and compressive optic neuropathy than nonsmokers. Patients who had received radioactive iodine (RAI) treatment were older, and were more frequently smokers. If patients were smokers and treated with radioactive iodine treatment, they were more likely to have proptosis, restrictive myopathy, and compressive optic neuropathy than if not treated with radioactive iodine. However, the RAI treatment did not seem to be associated with severe characteristics of TAO in non-smokers. CONCLUSIONS: The risk factors for severe TAO are: male, age older than 50, smoking, treated with RAI in smokers.