CT features of exophthalmos in Chinese subjects with thyroid-associated ophthalmopathy

AIM: To investigate computed tomography (CT) features of exophthalmos in Chinese subjects with thyroid-associated ophthalmopathy (TAO). METHODS: A total of 605 eyes of 325 patients with exophthalmos due to TAO were classified as grade Ⅰ (mild exophthalmos) or Ⅱ (severe exophthalmos) based on orbital CT imaging. The increased orbital volume features, such as changes from extraocular muscles, orbital fat, or both, were analyzed. RESULTS: A total of 605 eyes were analyzed, among them 62.98% presented grade Ⅰ exophthalmos, while 36.02% showed grade Ⅱ exophthalmos. In grade Ⅰ, 56.69% showed orbital fat change, and in grade Ⅱ, 89.29% exhibited extraocular muscle enlargement. CONCLUSION: Orbital fat and extraocular muscle enlargement are likely to be observed on CTs of subjects with mild and severe exophthalmos, respectively. Our results suggest that CT findings may guide TAO clinical therapy recommendations and prognosis.

The role of cell mediated immunopathogenesis in thyroid-associated ophthalmopathy

Currently, thyroid-associated ophthalmopathy (TAO) lacks effective treatment due to our lack of clarity in its immunopathogenesis. Orbital fibroblasts play a key role in altering inflammation and immune response in TAO, and are considered as the key target and effector cells in its pathogenesis. The orbit infiltrating CD34+ fibrocytes add on to the process by expressing high levels of autoantigens and inflammatory cytokines, while also differentiating into myofibroblasts or adipocytes. This review focuses on the role of orbital fibroblasts and CD34+ fibrocytes in the pathogenesis of TAO, highlighting the basis of emerging treatments.

The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy

AIM: To report the effects of intravenous high-dose glucocorticoids(iv GC) and orbital decompression(OD) surgery for treatment of sight-threatening thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective review of medical records from patients with sight-threatening TAO [definite or highly suspected dysthyroid optic neuropathy(DON)] treated with iv GC(60 cases) and OD(25 cases) was conducted at the Zhongshan Ophthalmic Center between January 2001 and January 2009. Patients were initially treated with iv GC(iv GC group). If no significant improvement in visual function was obtained, they then received OD surgery(OD group). The pre-versus post-treatment efficacies of either iv GC or OD in these patients were assessed using several indices, including visual acuity, intraocular pressure, ocular alignment, ocular motility, and exophthalmos. RESULTS: Nighty-one eyes had definite DON while 79 were considered to have highly suspected DON. In the iv GC group, 51 individuals(85.0%) eventually demonstrated normal vision, while 10 patients(16.7%) demonstrated a reduction in deviation(P<0.01), and 35 cases(58.3%) showed slight improvements in ocular motility(P<0.01). In OD group, visual acuity improved in 24 cases(96.0%, P<0.01) and all patients showed varying reductions of exophthalmos(mean: 4.35±1.13 mm, P<0.01). Eight cases(32.0%) experienced an 8-15 PD reduction of deviation and ocular motility improved in 12 cases(48.0%), while 3 patients(12.0%) developed new-onset strabismus with diplopia post-surgically(P<0.01). Patients were followed up at an average of 1.55±1.07 y. CONCLUSION: Both iv GC and OD show good therapeutic efficacy in the treatment of sight-threatening TAO. Thepresence of extremely poor eyesight(≥0.5 log MAR) was corrected in some patients with iv GC alone, thus sparing these patients from subsequent OD surgery. In patients who were refractory to steroids, subsequent OD surgery often provided satisfactory outcomes, however, new-onset strabismus with diplopia was observed in 12.0% of these cases.

Orbital decompression surgery and horse chestnut seed extract improved superior orbital vein blood flow in patients with thyroid-associated ophthalmopathy

AIM： To evaluate the efficacy and safety of orbital decomposition （OD） surgery in combination with horse chestnut seed extract （HCSE）, as compared to OD atone, in patients with thyroid-associated ophthalmopathy （TAO）. METHODS： Sixty-two orbits from 62 TAO patients were randomly assigned to OD or OD＋HCSE at 1：1 ratio （31 received OD alone, 31 received OD ＋HCSE）. Forty-two orbits from 21 healthy subjects were used as controls. Complete ophthalmic examination and color Doppler flow imaging （CDFI） were performed before surgery and 3mo post-surgery on all 62 orbits from the TAO patients. CDFI were also performed on the 42 control orbits, The effect of OD ＋HCSE and OD alone on TAO orbits was compared on several endpoints, including superior ophthalmic vein blood flow （SOVBF） parameters, subjective assessment, soft tissue involvement, lid retraction, diplopia, eye movement restriction, degree of exophthalmos, and intraocular pressure. The control orbits were used as reference for the SOVBF parameters. RESULTS： OD surgery with or without HCSE improved SOVBF, symptoms and soft tissue involvement, decreased degree of exophthalmos and intraocular pressure in orbits of TAO patients. The OD ＋HCSE combination led to significantly better improvement of SOVBF than OD alone. The differences between the reductions of SOVBF in the two groups are 1.26 cmls in max-volecity and 0.52 cm/s in min-voiecity （P〈0.0001）. CONCLUSION： SOVBF is significantly reduced in the orbits affected with TAO, indicating that congestion may be an important factor contributing to TAO pathogenesis. OD surgery improves the SOVBF, and combination of HCSE medication and OD surgery further improved venous return than OD surgery alone.

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis

·AIM: To determine the prevalence of ophthalmopathy in Hashimoto’s patients and to make a comparison in subgroups of patients·METHODS: The study involved 110 Hashimoto’s thyroiditis patients and 50 control subjects attending to the endocrinology department of the hospital. Subgroup classification of patients was made as euthyroid,subclinic and clinic in Hashimato’s thyroiditis. All patients were evaluated by a single experienced ophthalmologist for the prevalence and characteristics of eye signs.·RESULTS:Theoverallprevalencesofeyechanges were22.7%(25 patients) in patients and 4%(2 persons) in control subjects respectively(P =0.002). In patients the most common symptom was retrobulbar eye pain with or without any eye movement. Thirteen patients had significant upper eyelid retraction(11.8%). Six patients had eye muscle dysfunction as reduced eye movements in up gaze. In control patients one person had proptosis and another had lid retraction. The clinical activity score and classification of the ophthalmopathy did not show any significant differences among subgroups.·CONCLUSION:Theeyesignsweremostlymild(22.7%)and the most common eye sign was the presence of upper eyelid retraction(11.8%). Additionally six patients had eye muscle dysfunction as reduced eye movements in up gaze. Therefore we recommend to make a routine ophthalmic examination in Hashimoto’s thyroiditis patients in order not to omit the associated ophthalmopathy.

Epigenetics effect on pathogenesis of thyroid-associated ophthalmopathy

Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease.Recent studies have found the aberrant epigenetics in TAO,including DNA methylation,noncoding RNAs,and histone modification.Many genes have an aberrant level of methylation in TAO.For example,higher levels are found in CD14,MBP,ANGLE1,LYAR and lower levels in DRD4 and BOLL.Non-coding RNAs are involved in the immune response(miR-146a,miR-155,miR-96,miR-183),fibrosis regulation(miR-146a,miR-21,miR-29),adipogenesis(miR-27)and are thought to play roles in TAO.MicroRNA is also related to the clinical activity score(miR-Let7d-5p)and may be a predictor of glucocorticoid therapy(miR-224-5p).The quantities of H4 in TAO are increased compared with euthyroid control subjects,and the role of histone modifications in Graves*disease may lead to better understanding of its role in TAO.More studies are needed to explain the role of epigenetics in TAO and provide potential therapeutic strategies.

Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy

AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroidassociated ophthalmopathy(TAO) could be an early sign to detect dysthyroid optic neuropathy(DON). METHODS: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography(OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries(RPC), retinal nerve fiber layer(RNFL), and macular ganglion cell complex(GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. RESULTS: Whole choroidal RPC was significantly reduced in DON(48.24%±0.4978%) compared to normal(50.33%±0.3173%) and TAO without DON(49.16%±0.5463%;P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field(VF) defect in DON(r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed.CONCLUSION: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.

Hertel Exophthalmometry and Computed Tomography for the Evaluation of Exophthalmos in Patients with Thyroid-Associated Ophthalmopathy

Objective: To compare the values of exophthalmos measured by computed tomography (CT) and Hertel exophthalmometry (HE) in patients with thyroid-associated ophthalmopathy (TAO). Material and Methods: One hundred and seventy eyes were examined in 85 patients with TAO. Each patient underwent a complete ophthalmic examination, Hertel exophthalmometry, and CT of the orbits through a 16-slice CT scanner (Bright Speed, General Electric), measuring the extraocular muscles, the total muscle thickness sum (MTS), and proptosis. The patients were divided into two groups-with activity and without TAO activity, the activity being assessed by means of the Clinical Activity Score (CAS) and the severity-according to the EUGOGO classification. Results: TAO activity was detected in 45 patients (90 eyes, 53%) with MTS of 23.54 ± 5.73 mm, IOP of 19.78 ± 4.49 mm Hg, Hertel exophthalmos of 23.08 ± 4.19 mm and measured by CT-23.32 ± 4.33 mm. Forty patients (80 eyes, 47%) were without TAO activity, with MTS of 19.28 ± 4.03, IOP of 16.6 ± 4.51 mm Hg, Hertel exophthalmos of 20.03 ± 3.84 mm and measured by CT-19.84 ± 4.47 mm. A correlation was detected between exophthalmos and: MTS, IOP, the activity and severity of TАО. High congruence was established between the two methods of measuring exophthalmos-CT and HE (Pearson correlation, r = 0.690, p = 0.000). Conclusion: Our results showed a high degree of consistency between Hertel exophthalmometry and multidetector CT for the evaluation of exophthalmos in patients with TAO. Exophthalmos is an important clinical feature and its measurement and monitoring over time assess the clinical course and outcome of treatment.

Role of Peripheral Regulatory T Lymphocytes in Patients with Thyroid Associated Ophthalmopathy During Systemic Glucocorticoid Treatment:A Prospective Observational Study

Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.

疏肝健脾法治疗活动期甲状腺相关眼病并发干眼症的临床研究

【目的】探讨疏肝健脾法治疗活动期甲状腺相关眼病(TAO)并发干眼症的疗效,为临床治疗提供参考依据。【方法】将108例活动期TAO并发干眼症肝郁气滞证患者随机分为观察组和对照组,每组各54例。2组患者均给予维持Graves病的常规治疗,在此基础上,对照组给予激素冲击疗法(注射用甲泼尼龙琥珀酸钠静脉滴注)治疗,观察组在对照组的基础上联合中药疏肝健脾方治疗,疗程为12周并复诊随访至6个月。观察2组患者治疗前后临床活动性分级评分(CAS)、突眼度、眼表疾病指数(OSDI)评分、角膜荧光素染色(FL)评分、泪液分泌试验(SIT)和泪膜破裂时间(BUT)的变化情况,并评估2组患者的临床疗效。【结果】(1)疗效方面,治疗6个月后,观察组的总有效率为94.44%(51/54),对照组为74.07%(40/54),组间比较(χ2检验),观察组的疗效明显优于对照组(P<0.05)。(2)活动性、突眼度和OSDI方面,治疗后,2组患者的CAS评分、OSDI评分和突眼度均较治疗前降低(P<0.01),且观察组的降低幅度均明显优于对照组(P<0.1)。(3)泪液分泌功能方面,治疗后,2组患者的SIT、FL评分、BUT均较治疗前改善(P<0.01),且观察组的改善幅度均明显优于对照组,差异均有统计学意义(P<0.01)。【结论】疏肝健脾法治疗活动期TAO并发干眼症肝郁气滞证患者具有较好的临床疗效,可有效减轻突眼度,延长泪膜破裂时间,增加泪液分泌,促进角膜上皮修复,改善视功能,提高生活质量。

眼眶减压术后新发复视的研究进展

甲状腺相关眼病(thyroid-associated ophthalmopathy,TAO),又称Graves眼病,是与甲状腺疾病密切相关的一种器官特异性自身免疫性疾病。眼球突出是TAO的主要临床表现之一,也是临床上多数患者就诊的原因。眼球突出一方面会影响美观,另一方面可因眼睑闭合不全导致暴露性角膜炎或因眼眶压力增大导致压迫性视神经病变。眼眶减压术用于重度TAO已有过百年历史,从最早经外眦皮肤切开的传统外部切口入路进行骨性眼眶减压及脂肪减压到内镜下经鼻入路眼眶减压术,其安全性和有效性均已得到肯定。术后复视是眼眶减压术常见的并发症。近年来,随着眼眶减压术的发展,其越来越多地用于美容目的以矫正眼球突出。然而术后的新发复视仍然是困扰众多相关眼科医疗工作者的难题。近年来,多项研究对术后新发复视的相关因素进行了探讨,并由此对眼眶减压术进行改良,在对术后新发复视的减少方面取得不同程度的进展。该文对眼眶减压术后新发复视的研究进展进行综述,旨在促进专科医生更精准地开展TAO的手术,进而提高手术患者术后的生活质量及手术满意度。

基于DSE-Net的甲状腺相关眼病患病区域轻量型分割算法

临床活动性评分(Clinical activity score,CAS)是临床诊断甲状腺相关眼病(Thyroid associated ophthalmopathy,TAO)的重要评估方法之一。由于TAO症状的多样性和非患病区域的影响,人工诊断TAO容易受医生的主观经验影响。精准获取TAO患者脸部关键区域是早期诊断TAO的重要前提之一。因此,本文提出了一种基于DSE-Net的TAO患病区域自动分割的轻量型算法。DSE-Net采用U-Net作为主干模型,设计的密集型挤压-激励(Dense squeeze-and-excitation,DSE)通道注意力模块逐层提取编码结构的低级特征并融合解码结构的高级特征,进一步增强模型的特征提取能力。在巩膜、眼睑和泪阜数据集上的测试证明了DSE-Net的有效性,其中Dice系数分别达到了84.8%、84.7%和92.7%,IoU分别达到了74.0%、74.7%和86.5%。同时经过大量的对比实验证明了DSE-Net的优越性。提出的模型具有参数少、结构简单和特征提取能力强等特点,为TAO的早期诊断和预后治疗提供了重要信息。

Resolution of Pseudoptosis after Anti-inflammatory Treatment of the Contralateral Eye in Thyroid-associated Ophthalmopathy

Thyroid-associated ophthalmopathy （TAO） is an autoimmune inflammatory disease. Pseudoptosis （or ptosis）, which involves a reduction in the opening of the upper eyelid with a normal levator muscle, is rarely reported in TAO patients. In this article, we reported three cases of unilateral pseudoptosis due to inflammation of the levator in the contralateral eye. The effect of the unilateral use of triamcinolone acetonide （TA） on contralateral lid position and contour was also investigated.

球后脂肪体积测定对甲状腺相关性眼病治疗时机的判定价值

目的探讨商业化软件计算球后脂肪体积,分析其与甲状腺相关性眼病(TAO)进展及预后的关系。方法收集2016年1月~2016年12月在我院内分泌科确诊的35例(70个眼眶)TAO患者的临床资料。测量1.5T眼眶MRI球后脂肪体积及眼外肌信号强度比值(SIR)分析其与临床各项指标的相关性,并收集12例(24个眼眶)健康人测量球后脂肪体积,初步比较TAO组及健康组体积的差异。结果脂肪体积与病程成正相关(r=0.480,P<0.01),病程6个月以内组与6~12个月组相比,脂肪体积差异不显著(P=0.084)。病程6个月以内组及病程6~12个月组球后脂肪体积均显著低于病程大于12个月组(P<0.01,P<0.05)。脂肪体积与突眼度存在相关性(r=0.622,P<0.01),突眼度每增加1 mm,球后脂肪体积将增加0.88 m L。临床活动性评分(CAS)与SIR值及促甲状腺素受体抗体(TRAb)存在相关性(r=0.536,r=0.416,P<0.01)。TAO组球后脂肪体积显著高于正常组(P<0.01)。结论 TAO病程1年以上可能是球后脂肪组织增多的高峰阶段,球后脂肪体积结合SIR值的测量有助于最佳激素治疗时机的探索及预后分析。

甲状腺自身抗体与甲状腺相关性眼病的关系

目的:探讨甲状腺自身抗体与甲状腺相关性眼病(Thyroid-associated ophthalmopathy,TAO)、甲状腺机能亢进症突眼(甲亢突眼)及甲状腺机能亢进(甲亢)的关系。方法:甲状腺相关性眼病35例,甲亢突眼37例,甲亢83例,正常对照90例,分别检测其甲状腺球蛋白抗体(TGA)、甲状腺微粒体抗体(TMA)、促甲状腺受体抗体(TRAb)。结果:四组的TGA阳性数(率)分别为3(8.6%)、6(16.2%)、16(19.3%)、6(6.7%),TMA阳性数(率)分别为6(17.2%)、7(18.9%)、32(38.6%)、12(13.3%),TGA、TMA双阳性数(率)分别为1(2.6%)、4(10.8%)、11(13.8%)、0(0.0%),TRAb阳性数(率)分别为22(62.9%)、31(83.8%)、70(84.3%)、6(6.7%)。结论:TGA、TMA与TAO的相关性不大,诊断意义很小,TRAb与TAO有较好的相关性,对其早期诊断、治疗和随访有很大价值。

陈如泉从肝风论治甲状腺相关眼病眼睑退缩经验

陈如泉教授结合多年临床经验,把整体辨证与局部辨证结合起来,提出了甲状腺相关眼病眼睑退缩病位在肝,本病的基本病机系肝风内动,确立了平肝熄风、缓急止痉、搜风剔络的基本治疗方法,将辨证施治与经验用药相结合,取得较好疗效,丰富了从"肝"论治的学术观点。

雷公藤多甙片治疗甲状腺相关眼眶病变的临床观察

目的 探讨雷公藤多甙片对甲状腺相关眼眶病变的疗效。方法 86例 ( 86只眼 )甲状腺功能正常的甲状腺相关眼眶病变患者分为观察组 60例和对照组 2 6例。观察组口服雷公藤多甙片 2 0mg,每日 3次 ;对照组口服维生素B1 2 0mg和维生素C片 2 0 0mg ,每日 3次 ,分别观察两组的疗效。结果 观察组 54例患者眼部异常表现消失或减轻 ,3例无变化 ,3例患者眼部异常表现加重。对照组中 4例患者眼部部分异常表现减轻 ,1 0例患者眼部异常表现无变化 ,1 2例患者眼部部分异常表现加重。结论 雷公藤多甙片对甲状腺功能正常的中轻度甲状腺相关眼眶病变患者具有较好的疗效 。

甲状腺相关性眼病的发病机制及治疗进展

格雷夫斯病(GD)是一种由于促甲状腺激素受体(TSHR)抗体增多而引起甲状腺功能亢进的自身免疫性疾病。甲状腺相关性眼病(TAO)是GD最常见的甲状腺外表现,临床表现多样,如眼睑退缩、眼球突出、视神经受累等。目前国内外学者对TAO关注较多,本文主要对TAO发病机制及治疗新进展进行简要综述。

DNA修复基因XRCC1-Arg399Gln多态位点与壮族甲状腺相关眼病的相关性分析

目的探讨DNA修复基因XRCC1-Arg399Gln多态性与甲状腺相关眼病（TAO）的相关性。方法用PCR-RFLP法检测182例TAO患者和182例健康对照者的XRCC1-Arg399Gln多态性。结果TAO组和对照组的等位基因分布有差异,TAO组突变等位基因（A）频率高于健康对照组（P〈0.001）;与野生型（GG）相比,携带变异基因的个体（GA＋AA）可增加TAO的发病风险（OR值为1.863,95%CI为1.228～2.826,P〈0.05）。对于TAO,携带变异基因或吸烟单一因素的OR值分别为1.343（95%CI 0.764～2.36）和2.0274（95%CI 1.121～3.667）,但携带变异基因者如果吸烟,OR值则高达4.981（95%CI 2.697～9.1998）。结论XRCC1-Arg399G1n位点A等位基因（Gln）可能是TAO的易感基因,其多态性与吸烟可能存在联合作用。

雷公藤多甙对体外培养的眼眶成纤维细胞增殖和透明质酸分泌的影响

①目的观察雷公藤多甙对体外培养的正常人眼眶后成纤维细胞生长的抑制作用以及对细胞分泌透明质酸的影响,为雷公藤多甙治疗甲状腺相关眼病提供实验室依据。方法用组织块培养技术建立眼眶后成纤维细胞系,用MTT比色法及放射免疫法测定雷公藤多甙对正常人眼眶成纤维细胞增殖和透明质酸分泌的影响。结果雷公藤多甙可明显抑制正常人眼眶成纤维细胞的增殖和透明质酸的分泌,并呈剂量和时间依赖性抑制。结论雷公藤多甙可有效的抑制体外培养的正常人成纤维细胞的生长和透明质酸的分泌。