Update on thyroid eye disease: Regional variations in prevalence,diagnosis, and management

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.     

Changes of saccadic eye movements in thyroid‐associated ophthalmopathy

Purpose: To establish whether or not the dynamics of saccadic eye movements are significantly changed in patients with different stages of thyroid‐associated ophthalmopathy (TAO) and, subsequently, if analysis of saccades could serve as an additional diagnostic tool for early detection of inflammatory activity in TAO. Methods: Thirty‐seven patients with TAO and 10 age‐ and gender‐matched control subjects were investigated. The patients were divided into four groups according to the stage of the disease: (i) early mild disease (n = 10), (ii) early severe disease (n = 11), (iii) long‐standing restrictive disease (n = 10) and (iv) proven auto‐immune hyperthyroidism without any signs of TAO (n = 6). Horizontal and vertical saccades with amplitudes of 10°, 20°, 30° and 40° were recorded binocularly using the induction scleral search coil technique. The two main sequence constants V_max and C were calculated for each eye. Repeated measurement analysis of variance was carried out to test for differences between different gaze directions, eyes and groups. Results: In horizontal saccades, significant differences were found between groups but not between abduction and adduction. In vertical saccades, differences between groups and the interaction between groups and up‐ and down‐gaze saccades were significant. Compared with the control group, analysis of the main sequence curves revealed larger differences in patients of group 3 and 4 than in those of group 1 and 2. Whereas in the control group down‐gaze saccades were faster than up‐gaze saccades, the opposite behaviour was found in all patient groups. The largest differences were detected among those patients who had no signs of TAO (group 4). Conclusions: In this study, significant saccade differences were detected in all patients with TAO. In contrast to our earlier studies where evaluation of multiple individual saccade parameters did not reveal significant differences, analysis of the main sequence constants and mathematical reconstruction of the main sequence curves turned out to be a sensitive technique for reliable detection of subtle ocular motility changes. Significant differences were detected even in patients with auto‐immune thyroiditis where no clinical signs of TAO were apparent.     

Serum CYR61 Is Associated with Disease Activity in Graves’ Orbitopathy

Purpose: To investigate the clinical implications of cysteine-rich angiogenic inducer 61 (CYR61) in Graves’ orbitopathy (GO).

Methods: Sera from 52 GO patients, 23 Graves’ disease (GD) patients, and 20 healthy controls, and orbital fat tissue samples from 12 of 52 GO patients and 8 control subjects were included for analysis. Concentrations of CYR61 were measured from sera with an enzyme-linked immunosorbent assay, and CYR61 mRNA expression levels were evaluated from orbital fat tissue with polymerase chain reaction.

Results: Serum CYR61 levels were higher in GO patients than in controls (p = 0.001). Patients with active GO showed higher CYR61 levels than those with inactive GO (p < 0.001) or GD (p = 0.004). Expression of CYR61 mRNA was 7.4-fold higher in patients with GO than in healthy controls (p < 0.001).

Conclusions: CYR61 could be an adjuvant biomarker associated with the inflammatory activity of GO.     

Role of Botulinum Toxin A in Diplopia following Orbital Decompression

Diplopia following orbital decompression is a common complication in Graves' ophthalmopathy. Strabismus surgery is often required to treat the persistent diplopia. The author presents a successful treatment with botulinum toxin A injection in a case of diplopia following orbital decompression. Treatment with botulinum toxin A in the management of new-onset diplopia following orbital decompression has been suggested in a case that is not amenable to prism treatment and may eliminate strabismus surgery in some cases.     

CD40-CD40配体共刺激通路在甲状腺相关性眼病发病中作用研究进展

甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)是器官特异性自身免疫性疾病,其发病机制涉及T细胞对几种自身抗原的耐受丧失及以T细胞为主的免疫细胞不适当活化。T细胞活化需要识别共刺激信号,其中CD40-CD40L作为T细胞活化的共刺激信号之一,在TAO的发病机制中起重要作用。本文就CD40-CD40L分子细胞学特征、功能及近年关于其在TAO发病机制中的作用研究进展作一综述。     

甲状腺相关眼病免疫学发病机理的研究进展

甲状腺相关眼病目前被认为是一种与Graves病关系密切的器官特异性自身免疫性疾病,其具体发病机制至今仍未明确。已有研究发现:自身抗原、眶内成纤维细胞、免疫细胞、细胞因子及免疫介质等都是该病发病过程中的重要因素。     

Medical management of thyroid eye disease

Thyroid eye disease (TED) is the most common cause of orbital disease in adults. The immunologic pathogenesis of TED has been an area of active research and considerable progress has resulted in an expansion of therapeutic options. Although surgical intervention may be required, a majority of TED patients can be managed with medical therapies. Of medical therapies, glucocorticoids remain the agent of choice in the control of TED activity. The objective of this review is to discuss the paradigm and options in medical management of TED.     

替妥木单抗在甲状腺相关眼病治疗中的不良反应及预防策略

甲状腺相关眼病(TAO)是一种与甲状腺功能异常相关的自身免疫性疾病，会显著影响患者的生活质量，可导致视力障碍和容貌损毁。传统的治疗方法往往不尽如人意。研究发现，替妥木单抗(teprotumumab)是一种可抑制胰岛素样生长因子1受体(IGF-1R)的人源单克隆抗体，目前已成为TAO的新兴靶向治疗药物。尽管此药已证明在TAO治疗中有效且相对安全，但随着临床应用的不断推广，关于此药引发的不良反应值得引起广大眼科医师的重视，包括听力损害、高血糖、腹泻、肌肉痉挛、输液反应、认知功能减退、甲状腺功能抑制、脱发、恶心和疲劳等。此药总体耐受性良好，大多数不良事件的严重程度为轻度或中度。本文对当前替妥木单抗在TAO治疗中的不良反应及预防策略进行了综述。     

生长抑素对人球后成纤维细胞增殖的影响

目的　探讨生长抑素 1 4 (SS1 4 )治疗 Graves眼病的机理 ,为临床应用提供实验依据。方法　培养人球后成纤维细胞 (hum an retro- ocular fibroblast,HROFb) ,用 MTT比色法测定细胞增殖状况 ,并观察 SS1 4 对HROFb的生长、增殖的影响。结果　所测光吸收值与成纤维细胞的数目呈正相关 (r=0 .996,P<0 .0 0 1)。SS1 4 在低浓度下 (<0 .2 5 nmol/ L)可促进 HROFb 增殖 ,当浓度 >2 5 nm ol/ L 时则可抑制 HROFb的增殖 ,且具剂量效应关系。HROFb的增殖率与 SS1 4 浓度呈负相关 (r=- 0 .90 5 4,P<0 .0 0 1)。结论　生长抑素对人成纤维细胞增殖有双相作用。