肥大细胞在甲状腺相关眼病脂肪组织中的分布

目的 研究甲状腺相关眼病(TAO)患者,眼眶脂肪结缔组织中肥大细胞的分布特点.方法 对10例TAO患者和6例正常对照的眼眶脂肪结缔组织进行大体观察、HE染色和肥大细胞甲苯胺蓝法染色.结果 TAO患者较对照组的脂肪结缔组织有韧性,脂肪结缔组织中偶见肥大细胞、可见淋巴细胞等炎症细胞浸润及纤维组织增生,而对照组未见明显的炎症细胞.结论 静止期TAO患者的球后脂肪结缔组织中仍然有淋巴细胞及肥大细胞,还存在轻微的炎症反应,反应中的肥大细胞与其免疫性炎症的特点相符合.     

Significance of orbital fatty tissue for exophthalmos in thyroid-associated ophthalmopathy

PURPOSE: To correlate exophthalmos with the volume of extraocular muscle and orbital fatty tissue in thyroid-associated ophthalmopathy (TAO), using MRI that enables the orbital soft tissues to be well defined. METHODS: Thirty-three orbits, 20 from 10 patients with TAO and 13 from 13 controls, were employed. T1-weighted orbital MR slices 2 or 3 mm thick were obtained in axial, coronal and sagittal planes. Tracing the outlines of each structure, we measured the total sectional areas. Volumes of the extraocular muscle, of the fatty tissue and of the bony orbital cavity were calculated by multiplying the slice thickness. Exophthalmos was also measured using axial MRI. RESULTS: In TAO the volume increment of orbital fatty tissue (6.19 cm(3)) was much greater than that of extraocular muscle (1.16 cm(3)). Increase of exophthalmos by 1 mm needed a total orbital volume increment of 0.92 cm(3). The total orbital fatty tissue volume (correlation coefficient 0.70, P=0.06%) and the anterior orbital fatty tissue volume (0.64, P=0.23%) were more closely correlated with the degree of exophthalmos than was extraocular muscle volume (0.58, P=0.8%). Moreover, the volume increment of extraocular muscle and orbital fatty tissue was not always proportional. CONCLUSION: The results show that the orbital fatty tissue involvement is closely related to the degree of exophthalmos. For studying exophthalmos in TAO, the volumetric change, not only in ocular muscles, but also in orbital fatty tissue, should be taken into consideration.     

Immunohistochemical evidence for IgA1 involvement in Graves ophthalmopathy.

Orbital muscle, adipose tissues, and periorbital muscle from 11 patients with Graves ophthalmopathy were studied with in situ assays using monoclonal antibodies for IgA1, IgA2, IgM, and IgG. Tissue biopsies were taken from varied extraocular muscles and orbital sites. All cases were from patients with severe disease or disease of long duration. Control specimens of extraocular muscle tissues were obtained from nine patients treated for unrelated orbital disorders. Only connective tissue associated with the extraorbital muscles and periorbital muscles showed any reactivity. Of the muscle tissue obtained from patients with Graves disease all exhibited IgA1 positive staining of the endomysium and perimysium, without staining of the muscle fibers themselves. Parallel sections of orbital muscles reacted with anti-IgA2 or anti-IgM antibody failed to demonstrate staining. Control extraocular muscle tissue did not stain with anti-IgM and one control muscle of seven reacted minimally with anti-IgA2. Some reactivity with anti-IgA1 was seen in four of the seven control muscles but this was qualitatively much less than that of muscle tissue from patients with Graves disease. Monoclonal anti-IgG did not stain tissue from the six Graves specimens and three control specimens tested.     

甲状腺相关眼病眼外肌组织黏附分子表达的研究

目的探讨黏附分子ICAM-1、ELAM-1、CD44（HCAM）在甲状腺相关眼病（TAO）眼外肌的表达水平。方法手术获得的眼外肌分为两组：正常组和TAO组。分别运用免疫荧光技术、免疫组织化学和流式细胞学测定11例TAO患者14条眼外肌标本和10例正常者眼外肌标本ICAM-1、ELAM-1、CD44表达水平。结果正常组ICAM-1、CD44少量表达,未见ELAM-1的表达。TAO组ICAM-1在眼外肌束膜结缔组织、成纤维细胞、单核细胞、血管内皮细胞表达上调。ELAM-1在间质增生血管内皮细胞表达。CD44在淋巴细胞、成纤维细胞、血管内皮细胞表达上调。肌细胞本身未见黏附分子表达。CD44在眼外肌束膜结缔组织、成纤维细胞、单核细胞表达水平最高。两组间表达差异具有统计学意义。结论ICAM-1、ELAM-1、CD44在TAO患者炎性细胞中表达上调。     

眼眶脂肪与甲状腺相关眼病

甲状腺相关眼病（thyroid associated ophthalmopathy，TAO）是最常见的眼眶病，主要临床表现为眼球前突，暴露性角膜炎，压迫性视神经病变，视力下降甚至失明等。发病机理不明，目前对眼外肌、眼眶纤维组织研究较多，对眼眶脂肪研究较少，而眼眶脂肪增多又是眼球前突的重要原凶之一，眼眶脂肪也参与了TAO的发生和发展，故有必要对TAO眼眶脂肪进行组织病理学和实验室研究，根据患者的临床表现，对治疗也进行探讨。     

甲状腺相关性眼病眶内组织的病理改变

目的 观察甲状腺相关性眼病（TAO）患者结膜、眼外肌、pulley等组织的组织病理学改变特点。设计 实验研究。研究对象 16例临床确诊为TAO且行斜视矫正术患者,其中男性8例,女性8例,年龄32~65岁,平均（50.3±6.7）岁;12例手术治疗的非TAO共同性斜视患者,其中男性6例,女性6例,年龄6~52岁,平均（28.8±7.4）岁。方法 收集上述患者手术中的结膜、眼外肌、pulley等组织标本。TAO组留取结膜标本16例,眼外肌标本12例, pulley标本9例;对照组留取结膜标本12例,眼外肌标本8例,pulley标本8例。以术中所见及采集标本的HE染色、Masson、Van Gieson及免疫组化染色,对比两组之间病理学改变的差异。主要指标 结膜、眼外肌、pulley的病理改变。结果 与对照组相比,TAO组14例结膜上皮层肥厚,2例可见上皮层萎缩,16例结膜标本均显示固有层纤维化,组织结构紊乱,血管壁周围可见少量炎性细胞浸润;10例眼外肌标本病理改变表现为眼外肌肌纤维增粗,2例为肌纤维变性萎缩,12例标本均显示眼外肌肌纤维不同程度断裂、纤维化,胶原纤维明显增多,空泡形成;9例pulley标本均显示pulley肌纤维断裂,结构紊乱,弹力纤维断裂,胶原纤维明显增多,空泡形成。结论 TAO患者不仅是眼外肌,结膜组织及眶内结缔组织可能均经历了由炎性反应到纤维化的退行性变过程,由此引起眼部各种临床表现。（眼科,2014, 23： 130-134）     

甲状腺相关性眼病眼球突出CT影像分析

目的 探讨甲状腺相关性眼病眼球突出时眼外肌肥厚、眶脂肪增多等相关性CT影像学分析.方法 回顾性分析58例甲状腺相关性眼病CT影像资料,男22例,女36例,行横轴位和冠状位检查,层厚和层距2mm.结果 58例甲状腺相关性眼病眼球突出CT影像观察,单纯眼外肌肌腹肥厚(n=54),肌腹及肌腱、肌止点均受累及(n=3);眶脂防增多(n=16);眼外肌肥厚伴眼上静脉增粗(n=3);眼外肌肥大伴视神经增粗(n=1);眼肌肥大伴泪腺增大(n=2);眼睑肿胀(n=39).结论 在对甲状腺相关性眼病眼球突出的研究中眼外肌、眼眶脂肪容积的改变都应加以考虑;CT对该病的诊断具有重要的价值.     

Immunohistochemical evidence for C3bi involvement in Graves ophthalmopathy.

PURPOSE: To determine by immunohistochemical methods if components of the complement system are present in Graves ophthalmopathy extraocular and periocular tissues compared with non-Graves ophthalmopathy ocular tissues, and, if so, whether a qualitative difference exists. METHODS: Orbital muscle, periorbital muscle, and adipose tissue from 10 Graves ophthalmopathy patients were studied with in situ assays using monoclonal antibodies for C3bi and C5b-9 (the terminal attack complex) complement components. Extraocular muscle, periocular muscle, and adipose tissue from 12 patients treated for unrelated orbital disorders were used as controls. RESULTS: All nine Graves extraocular and periocular muscle tissues exhibited C3bi positive staining in an intense, localized oval- to spindle-shaped reaction that appeared to represent cells on a diffuse staining background of the endomysial and perimysial connective tissues with no staining of the muscle fibers themselves. Some reactivity was seen in 6 of the 12 control muscles, but this was much less intense than that of Graves ocular muscle tissue. Only two Graves muscle samples stained minimally with the monoclonal antibody for the C5b-9 terminal attack complex while none of the control muscle samples demonstrated reactivity. Orbital fat from Graves and control patients did not demonstrate any reactivity for C3bi or C5b-9. CONCLUSION: C3bi and not C5b-9 (the terminal attack complex) is present in Graves ophthalmopathy extraocular and periocular tissues in a qualitatively greater way than in control non-Graves ophthalmopathy ocular tissue. Consequently, C3bi may contribute to the pathophysiology of Graves ophthalmopathy.     

甲状腺相关眼病眼眶组织透明质酸合成酶表达的研究

目的探讨透明质酸合成酶2（HAS2）mRNA在甲状腺相关眼病（TAO）患者球后脂肪组织及眼外肌中的表达。方法收集四川大学华西医院眼科2000—2005年确诊并行眼眶减压术或斜视矫正术的TAO患者21例为TAO组,获得眼外肌标本18个,脂肪标本17个;Ⅱ期义眼台植入患者、眼袋整形者及共同性斜视患者18例作为对照组,共获得眼外肌组织标本17个,脂肪组织标本11个。所有标本通过原位杂交的方法,测量吸光度（A）值,计算HAS2mRNA的表达。依据活动期的临床表现对TAO患者进行临床活动性评分（CAS）,采用Spearman秩相关分析对HAS2mRNA在待测眼组织标本中的表达量与TAO患者CAS的相关性进行评估。结果 TAO组患者眼外肌和脂肪间质组织HAS2明显黄染,对照组均呈轻度黄染。TAO组和对照组的眼外肌组织中HAS2mRNAA值分别为191.133±48.898和133.200±48.933,差异有统计学意义（P=0.001）（95%CI：24.275～91.590）;TAO组和对照组眶脂肪组织中HAS2mRNAA值分别为50.430±26.812和33.048±11.690,差异有统计学意义（t=2.350,P=0.028）（95%CI：2.099～32.664）;CAS与TAO脂肪组织中HAS2mRNA的表达无明显相关性（r=0.044,P=0.868）,与肌肉组织中HAS2mRNA的表达呈弱正相关性（r=0.496,P=0.036）。结论 TAO患者HAS2mRNA的高表达是造成眶后透明质酸堆积的原因之一。     

Graves' hyperthyroidism,ophthalmopathy and pretibial myxedema may be components of a multi-system autoimmune disorder

The authors have used the indirect immunofluorescence test to investigate reactivity of sera from patients with Graves' disease with porcine extraocular muscle and other tissue substrates. Sera from 75% of patients with thyroid-associated ophthalmopathy (TAO) contained one or more antibodies reactive with extraocular muscle, compared to 32% of those with Graves' hyperthyroidism without the eye disorder, 41% of patients with Hashimoto's thyroiditis, and 16% of normals. Antibodies reactive with a non-organ specific connective tissue antigen(s), seen as fluorescence of the interstitium and endomysium, were found in sera from 10% of patients with TAO and 16% of those with Graves' hyperthyroidism, but not from any patient with Hashimoto's thyroiditis or normal subject. Antinuclear antibodies were detected in sera from 31% of patients with TAO, but from only 8% with Hashimoto's thyroiditis, in no patient with Graves' hyperthyroidism and in only 3% of normal subjects. The finding of a high prevalence of antinuclear antibodies and, less often, anti-connective tissue antibodies in patients with thyroid autoimmunity and ophthalmopathy, is consistent with Graves' disease being a ‘collagen-like disorder’. The possible reasons why inflammation and resulting tissue damage are mainly found in the thyroid, connective tissue of the skin and orbit, and skeletal muscle are discussed.     

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 of605 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.#$TAB 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.     

透明质酸与甲状腺相关眼病研究进展

甲状腺相关眼病(TAO)是成人常见的眼眶疾病,眶周脂肪结缔组织中糖胺聚糖沉积是其主要的病理特征之一.透明质酸是糖胺聚糖的主要成分,具有高亲水性和黏弹性的特性,可大量吸水膨胀,其在眼眶组织聚集导致眶周结缔组织及眼外肌水肿和纤维化,进而出现TAO特征性的临床表现.眼眶成纤维细胞是透明质酸的主要来源,患者体内自身抗体和多种细胞因子可与成纤维细胞上促甲状腺激素受体(TSHR)及胰岛素样生长因子-1受体(IGF-1R)等结合,在透明质酸合成酶的作用下促进眼眶成纤维细胞合成透明质酸,导致眶周组织、外周血及体液中透明质酸含量增加,并在一定程度上为疾病诊断、病情判断及疗效和预后评估提供参考.     

以眼外肌肥大为主要CT征的眼眶病分析

目的 多种眼眶病表现为以眼外肌肥大为主要的临床特征,根据不同的眼外肌肥大CT表现特点,可为临床诊断和治疗提供依据.方法 自2004年1月至2007年12月,对CT表现有不同特征的眼外肌肥大的连续就诊患者共225例,据其表现特点,明确病因并鉴别诊断.结果 计有8种眼眶病.甲状腺相关眼病(TAO)175例,肌炎型炎性假瘤26例,颈动脉海绵窦漏(CCF)8例,转移性眼外肌肿瘤4例,肌肉静脉血管瘤4例,眶内恶性淋巴瘤6例,眼外肌血肿1例,眼外肌植物性异物1例.结论 根据眼外肌肥大的CT特征,结合病史及临床表现能做出正确的诊断.     

甲状腺相关眼病合并眼压升高106例临床分析

目的 观察甲状腺相关眼病(Thymid—associated Ophthalmopathy，TAO)合并眼压升高的临床特征和影响因素。方法 对1994年～2001年间收治的339例(597眼)TAO患者中106例(188眼)眼压升高患者的临床资料进行分析。结果 本组TAO患者眼压升高的发生率为31．3％，男性略高于女性。眼压升高的发生与TAO患者眼肌肥大对眼球壁的压迫、眶内结缔组织增生及眼肌肥大和水肿致眶压增高、以及TAO病变的严重程度有关，与TAO病程无明显关系。甲强龙冲击和开眶减压手术控制TAO病情和眶压后，绝大部分患者眼压可以控制。结论 TAO眼压升高有其独自的临床特点，应与原发性青光眼鉴别。积极有效的TAO治疗措施可使绝大部分患者的眼压得到控制。     

甲状腺相关眼病患者眼眶组织糖皮质激素受体mRNA的表达

目的探讨糖皮质激素受体（GR）α和β mRNA在甲状腺相关眼病（TAO）患者眼眶组织中的表达。方法眼外肌和（或）眼眶脂肪组织标本取自在我科行手术治疗的17例严重TAO患者,意外死亡的10例健康成年人眼外肌和（或）眼眶脂肪组织标本作为对照。提取眼外肌或眶脂肪组织总RNA,将RNA逆转录为cDNA,用荧光定量聚合酶链反应（PCR）方法实时检测GRα和GRIβ的PCR扩增全过程,计算各个样本GRα和GRIβ mRNA的表达量。结果眼外肌和眶脂肪组织均表达GRα和GRβ mRNA。TAO患者GRα mRNA表达量为（40．15±11．37）拷贝／μ1,正常对照为（20．64±7．07）拷贝／μl。TAO患者GRα mRNA表达量与GRβ mRNA表达量的比值（GRα／GRβ比值）为77．76±18．77,正常对照为148．34±23．86,差异具有统计学意义（P＜0．05）。眼外肌与眶脂肪组织之间,甲状腺机能正常、亢进及低下患者之间,使用糖皮质激素治疗与未使用糖皮质激素患者之间GRα mRNA表达量和GRα／GRβ比值比较,差异均无统计学意义（P＞0．05）。结论TAO患者眼眶组织GRα mRNA的表达增强;GRα／GRβ比值降低可能在TAO的病理发生和糖皮质激素的治疗反应中起一定作用。     

Clinical Analysis of 106 Cases with Elevated Intraocular Pressure in Thyroid-associated Ophthalmopathy

Thyroid鄄associatedophthalmopathy(TAO)isachronicautoimmuneprocessthataffectstheretrobulbarspaceandhasstrongetiologiclinkswithautoimmunethyroiddisease.Itisreportedtobethemostcommonorbitaldiseaseinadultsandthemostprevalentorbitaldiseases[1].Somepatientsarefoundtohavethediseasecompli鄄catedwithocularhypertension.ThecontributingfactorforocularhypertensioninTAOiscomplex.Inthispaperwehavesummarizedandanalyzedtheclinicmanifestationsof106cases(188eyes)ofocularhypertensionin339cases(597eyes)withTAO…     

Graves眼病眼眶组织病理与IgA、IgE表达的研究

目的 观察Ｇｒａｖｅｓ眼病患者眼部组织免疫球蛋白的表达及组织病理学的改变。方法 收集Ｇｒａｖｅｓ眼病患者眼餐肌及眶脂肪１９例,采用免疫组化、ＨＥ及特殊染色方法观察眼眶组织中ＩｇＡ和ＩｇＥ的表达,粘多糖的堆积及眼外肌受损情况。结果 Ｇｒａｖｅｓ眼病外肌肌内膜、肌外膜有ＩｇＡ阳性染色,其表达程度与治疗有关,差异有显著性;肌细胞、浸润的浆细胞及多形核白细胞ＩｇＥ染色阳改天人表达程度与病程和治疗均有关,差     

A型肉毒毒素在甲状腺相关眼病治疗中的应用

甲状腺相关眼病(TAO)是一种累及多种眼眶组织的自身免疫性炎症性疾病,临床表现多样,严重影响患者的生活质量。TAO的治疗主要包括稳定甲状腺功能、抗炎、免疫调节等内科治疗以及缓解眼部症状的手术治疗。A型肉毒毒素通过阻断神经肌肉接头处的神经冲动传导起到麻痹肌肉的作用,对于TAO患者因眼外肌受累出现的限制性斜视以及因提上睑肌和Müller肌受累出现的上睑退缩具有一定的治疗价值,特别是当患者存在手术禁忌证、缺乏手术时机及手术意愿时。本文就A型肉毒毒素在TAO治疗中的应用作一综述,着重总结A型肉毒毒素治疗TAO限制性斜视和上睑退缩的作用机制、剂量、有效性及可能的并发症,并探讨A型肉毒毒素对于TAO患者出现的眼外肌压迫所致眼压升高、眉间皱纹、干眼等潜在的治疗价值,以期为临床干预提供参考。     

医学影像学评估甲状腺相关性眼病活动度的价值

甲状腺相关性眼病（thyroid associated ophthalmopathy,TAO）是一种器官特异性自身免疫性疾病,其治疗方案的确定及疗效观察依赖于临床活动度的评估。临床多以临床活动度评分（clinical activity score,CAS）作为TAO活动度的评价标准,但有一定的局限性。CT成像眼外肌形态学的定量分析（眼外肌总横截面积/眼眶面积比值）结果与CAS评分呈正相关;通过眼外肌T2 mapping MRI定量分析提示眼外肌T2值与TAO免疫抑制疗效密切相关,有助于评估TAO免疫抑制疗效; 99mTc-DTPA 眼眶SPECT/CT采用图像融合技术,一次显像可获得功能信息与解剖信息,可作为CAS的有效补充。现代医学影像学特别是功能影像学对TAO活动度的评估具有较大的应用价值。（眼科,2018, 27： 321-324）     

The role od adhesion molecules in the pathogenesis of Graves ophthalmopathy

Graves' ophthalmopathy (GO) is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles and/or orbital connective tissue. Adhesion molecules play an important role in the initiation and maintenance of the inflammatory immune process. Cellular activation and local expression of adhesion molecules lead to leucocyte recruitment, migration to inflammatory sites and targeting in the extravascular space. Vascular endothelium in retroocular connective tissues of patients with GO is strongly positive for EMAL-1 and VCAM-1, whereas VCAM-1 immunoreactivity is minimal and ELAM-1 immunoreactivity is generally absent in normal retroocular tissue. Interactions between matched activated T lymphocytes and orbital endothelial cells are mediated by integrin dependent ICAM-1/LFA-1 and VCAM-1/VLA-4 pathways and reveal marked differences when comparing GO orbital endothelial cells to normal ones. Higher soluble ICAM-1 volumes in patients with Graves' disease with GO than those in patients with Graves' disease without ophthalmopathy can reflect the degree of inflammatory activity. Increased soluble ELAM-1 concentration only in patients with GO suggests that soluble ELAM-1 could be a specific marker of endothelium activation in GO.