磁共振T2-mapping评估Graves眼病活动性的价值

目的探讨磁共振T_(2)-mapping在Graves眼病(GO)活动性评估方面的价值。方法收集2019年7月-2021年1月于重庆医科大学附属第一医院内分泌科就诊的GO患者64例,使用计算机对其进行简单随机分组,其中49例作为观察研究对象,另外15例进行诊断试验评价。按照临床活动性评分(CAS)将49例GO患者分为活动组(CAS≥3分,48只患眼)与非活动组(CAS<3分,50只患眼)。同期招募31名健康志愿者作为正常对照组,共62只眼。所有人均行3.0T眼眶磁共振T_(2)-mapping成像。在T_(2)-mapping冠状位图像上测量上直肌、下直肌、内直肌、外直肌眼球后5个层面的T_(2)弛豫时间(T_(2)RT),每块眼外肌分别取眼球后5个层面的T_(2)RT最大值来代表该眼外肌的T_(2)RT,最后取4块眼外肌T_(2)RT中的最大值,以眼外肌最大T_(2)RT表示。比较活动组、非活动组与正常对照组间上述5个指标(上直肌T_(2)RT、下直肌T_(2)RT、内直肌T_(2)RT、外直肌T_(2)RT、眼外肌最大T_(2)RT)的差异;采用受试者工作特征(ROC)曲线分析上述5个指标对GO活动性评估的诊断价值,得出诊断阈值,然后利用另外15例GO患者进行诊断试验评价,确定诊断效能较高的指标及其诊断活动性的阈值。结果活动组所有眼外肌的T_(2)RT均明显高于非活动组及正常对照组,差异有统计学意义(P<0.001)。ROC曲线分析显示,上直肌、下直肌、内直肌、外直肌、眼外肌的最大T_(2)RT判断活动性的截断值分别为80.200 ms、97.045 ms、94.355 ms、85.750 ms、101.385 ms。利用另外15例GO患者进行诊断试验评价,综合评估敏感度、特异度、阳性预测值、阴性预测值较高的指标为下直肌T_(2)RT、眼外肌最大T_(2)RT,其判断活动性的截断值分别为97.045 ms、101.385 ms;敏感度分别为91.7%、93.8%;特异度均为80.0%。结论磁共振T_(2)-mapping序列对评估GO的活动性具有良好价值。临床上可选择测量下直肌T_(2)RT或眼外肌最大T_(2)RT协助评估GO的活动性。

中重度活动性Graves眼病药物治疗新进展

Graves眼病(GO)为Graves病的甲状腺外表现,是由细胞免疫介导的复杂的自身免疫性疾病,眼眶成纤维细胞和眼眶脂肪细胞是免疫反应的靶细胞,促甲状腺激素受体和胰岛素样生长因子-1是关键的自身靶抗原。除吸烟、放射性碘治疗后等危险因素外,高胆固醇血症被发现为GO新的危险因素。糖皮质激素至今在中重度活动性GO的治疗中有不可撼动的地位,但部分患者经治疗后并没有反应,或出现了复发。生物靶向制剂、细胞因子抑制剂以及具有抗炎作用的他汀类药物等已逐步研究并应用于GO的临床治疗。文章对GO主要发病机制及目前中重度活动性GO药物治疗的新进展进行综述。

3 T MRI定量测量眼眶结构在Graves眼病分期中的诊断价值

目的应用3 T眼眶MRI技术评估Graves眼病(Graves ophthalmopathy,GO)患者泪腺参数与临床活动性评分(clinical activity score,CAS)的相关性。材料与方法前瞻性纳入2020年2月至2023年6月安徽医科大学附属阜阳医院和安徽医科大学第一附属医院确诊的GO患者40例80只眼作为GO组,选取与GO组性别与年龄段匹配的健康人群40例80眼作为对照组。根据CAS评分将GO患者分为活动期GO组、非活动期GO组。分别对三组进行MRI常规图像及读出分段平面回波弥散加权成像(readout segmentation of long variable echo-trains diffusion weighted imaging,RESOLVE DWI)图像采集,横断位T2加权成像脂肪抑脂(T2-weighted imaging fat suppression,T2WI-FS)获得眼球突出度、泪腺突出度,横断位及冠状位T2WI-FS测量获得泪腺最大截面时的长径、短径、面积,记录横断位泪腺表观扩散系数(apparent dispersion coefficient,ADC)平均值。使用SPSS 24.0软件进行统计学分析,P<0.05为差异有统计学意义。定量资料组间比较采用两独立样本t检验,性别、吸烟史、饮酒史、CAS评分的组间差异采用卡方检验。采用受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under the curve,AUC)评价GO活动性的诊断效能。采用Spearman’s相关分析泪腺各定量参数与CAS评分的相关性。结果(1)活动期GO组眼球突出度、横断位泪腺各参数,包含泪腺突出度、长径、短径、面积及ADC平均值,均较非活动期GO组、对照组增大,非活动期GO组较对照组升高(P均<0.05)。(2)ROC曲线结果显示,眼球突出度、横断位泪腺面积对GO患者的诊断效能最高(AUC为0.906、0.905),泪腺突出度、横断位泪腺ADC平均值对GO患者也有一定的诊断价值(0.793、0.702)。RESOLVE DWI ADC值预测GO活动性的最佳截断点为1.181×10^(-3)mm^(2)/s,其敏感度高达95.00%,特异度76.30%。(3)眼球突出度(r=0.734,P<0.05)、泪腺突出度(r=0.719,P<0.05)、泪腺ADC值(r=0.742,P<0.05)与CAS呈高度相关。结论横断位泪腺突出度、泪腺DWI ADC平均值可作为GO诊断及分期的重要参考指标。

阿托伐他汀钙片有效降低短病程Graves眼病患者的血清肿瘤坏死因子水平

目的分析阿托伐他汀治疗对于Graves眼病(GO)患者血清肿瘤坏死因子α(TNF-α)水平的影响,探索阿托伐他汀钙片对GO患者疗效及安全性。方法选取2022年8月至2023年3月在南昌大学第一附属医院内分泌科门诊就诊或住院的60例GO患者作为研究对象,按其病程长短分为长病程组(病程>2年,n=30)和短病程组(病程<2年,n=30)。2组均在抗甲状腺药物治疗同时服用阿托伐他汀钙片20 mg·d^(-1),观察比较2组治疗前及治疗后2个月的血清TNF-α水平、突眼度,以及甲状腺功能、促甲状腺激素受体抗体、肝功能、空腹血糖、血脂的变化情况及药物相关不良反应。结果与治疗前短病程组患者的血清TNF-α均值高于长病程组(9.43±0.52 pg·mL^(-1)vs7.53±0.27pg·mL^(-1),P<0.05)。治疗后2个月,短病程组TNF-α水平较治疗前下降(9.43±0.52 pg·mL^(-1)vs 8.17±0.41 pg·mL^(-1),P<0.05),而长病程组患者的TNF-α水平无明显变化(7.53±0.27 pg·mL^(-1)vs8.18±0.54pg·mL^(-1),P=0.173)。治疗前后两组突眼度均无明显变化(P>0.05)。短病程组患者FT4降低(1.53±1.16 ng·dL^(-1)vs1.17±0.08ng·dL^(-1),P=0.016),FT3、TSH、TRAb均无明显变化(P>0.05),长病程组患者FT3、FT4、TSH、TRAb均无明显变化(P>0.05)。长病程组出现转氨酶升高的患者比例高于短病程组,长病程5例(16.7%,5/30),短病程组1例(3.3%,1/30),但均在正常值上限范围之内,所有患者治疗过程中均未出现肌肉酸痛、肌痛、无力、僵硬和肌肉痉挛症状。结论阿托伐他汀钙片联合抗甲状腺药物治疗可显著降低短病程Graves眼病患者血清TNF-α水平,但突眼度改善并不显著,对长病程(病程>2年)患者血清TNF-α无影响。

Tea Polyphenols Reduce Inflammation of Orbital Fibroblasts in Graves’Ophthalmopathy via the NF-κB/NLRP3 Pathway

Objective:This study aimed to explore the effects of tea polyphenols(TP)on inflammation of orbital fibroblasts in Graves’ophthalmopathy(GO)and to provide new ideas for GO treatment.Methods:Primary orbital fibroblasts were extracted from orbital adipose/connective tissues of patients with and without GO.Real-time quantitative PCR(RT-qPCR)was used to detect the expression of interleukin(IL)-6,IL-1β,and monocyte chemotactic protein(MCP)-1 in non-GO and GO orbital fibroblasts.The CCK-8 assay was used to determine the appropriate concentration of TP for subsequent experiments.RT-qPCR and enzyme-linked immunosorbent assay(ELISA)were performed to investigate the effects of TP on lipopolysaccharide(LPS)-induced production of inflammatory cytokines.Nuclear factor-κB(NF-κB)expression was measured using Western blotting analysis.NOD-like receptor 3(NLRP3)expression was detected using both Western blotting analysis and immunofluorescence staining.Results:The mRNA levels of IL-6,IL-1β,and MCP-1 in GO orbital fibroblasts were significantly higher than those in non-GO cells.TP treatment significantly inhibited LPS-induced production of inflammatory factors,including IL-6,IL-1β,and MCP-1.TP also inhibited the expression levels of NF-κB and NLRP3.Inflammation in the GO orbital fibroblasts was higher than that in non-GO cells.TP inhibited the production of inflammatory cytokines in GO orbital fibroblasts in vitro through the NF-κB/NLRP3 pathway.Conclusion:These findings suggest that TP may have a potential role in GO treatment.

甲泼尼龙联合吗替麦考酚酯治疗中重度活动性Graves眼病

目的 评估甲泼尼龙联合吗替麦考酚酯治疗中重度活动性Graves眼病(GO)的疗效及安全性,并对比该联合治疗与单独使用甲泼尼龙的疗效差异。方法 回顾性选取中重度活动性GO患者,分为联合组(甲泼尼龙联合吗替麦考酚酯)和单药组(甲泼尼龙)。比较两组患者之间的视觉评分、外貌评分、临床活动性评分(CAS)、突眼度、眼裂宽度及眼球活动度方面的变化,记录不良事件。结果 研究共纳入98例患者,其中联合组32例患者,单药组61例患者。两组治疗后的生活质量评分、CAS、突眼度较治疗前改善。在治疗12周时,两组治疗前后视觉评分、外貌评分、CAS、突眼度、眼裂宽度的差值及眼球活动度减少比例的比较差异无统计学意义(P> 0.05)。联合组眼球运动时疼痛及眼睑充血改善比例高于单药组(P <0.001)。在治疗终点,两组治疗前后外貌评分、突眼度、眼裂宽度的差值及眼球活动度减少比例比较差异无统计学意义(P> 0.05),联合组视觉评分及CAS改善幅度高于单药组(P <0.05),其中眼睑水肿改善比例高于单药组(P <0.05)。12周时,单药组有效率为65.0%,联合组有效率为66.7%。24周时,联合组有效率为80.0%。两组在第12周及各自治疗终点的总体有效率差异无统计学意义(P> 0.05)。联合组未出现白细胞减少或严重感染的情况。结论 甲泼尼龙联合吗替麦考酚酯治疗中重度活动性GO是有效、可耐受且安全的,联合治疗的总体有效率可能并不优于单用激素治疗,但联合用药在视觉评分、眼睑充血、眼睑水肿及眼球运动性疼痛的改善上可能优于单用激素。

蒺藜皂苷对Graves眼病眼眶组织纤维化的作用机制研究

目的:研究蒺藜提取物蒺藜皂苷对Graves眼病眼眶组织纤维化的作用及其机制。方法:采用人hTSHR重组质粒结合电穿孔免疫BALB/c雌性小鼠的方法构建Graves眼病模型,分为对照组、模型组、蒺藜皂苷组。RT-PCR、免疫荧光法观察三组小鼠眼眶组织α-SMA、CollagenⅠ和CollagenⅢ水平。采用马松和天狼星红染色观察三组小鼠眼眶组织细胞外基质(ECM)沉积水平;采用ELISA检测三组小鼠血清PDGF、INF-γ和TGF-β1水平。TGF-β1刺激原代分离小鼠眼球后成纤维细胞,对照组PBS给药处理。蒺藜皂苷分别设置5、10、20、40、80μg/ml浓度进行给药。CCK-8检测不同组细胞增殖能力变化;RT-PCR、免疫荧光观察不同组细胞α-SMA、CollagenⅠ和CollagenⅢ水平;ELISA检测不同组细胞上清中PDGF、INF-γ水平;Western blotting检测不同组细胞PI3K/AKT和Smad2通路变化。结果:蒺藜皂苷能抑制小鼠眼眶组织α-SMA、CollagenⅠ和CollagenⅢ以及炎症因子PDGF、INF-γ、TGF-β1的表达。蒺藜皂苷显著抑制小鼠眼眶组织ECM的沉积。蒺藜皂苷抑制TGF-β1刺激后小鼠眼球后成纤维细胞增殖,α-SMA、CollagenⅠ、CollagenⅢ、PDGF、INF-γ的分泌。蒺藜皂苷能抑制纤维化经典通路PI3K/AKT和Smad2磷酸化。结论:蒺藜皂苷能够抑制PI3K/AKT和Smad2通路,阻滞Graves眼病眼球组织纤维化,可有效治疗Graves眼病。

外周血CD4^(+)T、CD8^(+)T细胞及免疫活化分子CD38、IL-2R表达水平在Graves眼病患者中的临床意义

目的研究Graves眼病(GO)患者外周血CD4^(+)T、CD8^(+)T细胞及免疫活化分子CD38、IL-2R水平的临床意义。方法选取2022年1月至2023年1月我院收治的80例Graves病(GD)患者为GD组,65例GO患者为GO组,根据CAS评分将GO组患者分为活动期组(26例)和非活动期组(39例),另选50例体检中心健康者为对照组。比较各组血清甲状腺功能、甲状腺相关抗体及外周血各细胞因子水平,分析GO患者外周血各细胞因子水平与甲状腺功能、甲状腺相关抗体、CAS评分的相关性,并分析外周血各细胞因子对GO疾病活动性的预测价值。结果GO组FT3、FT4低于GD组,高于对照组,GD组高于对照组(P<0.05);GO组TSH高于GD组,低于对照组,GD组低于对照组(P<0.05);GO组、GD组TGAb、TPOAb、TRAb、CD4^(+)T高于对照组(P<0.05);GO组、GD组CD8^(+)T低于对照组(P<0.05);GO组CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R高于GD组和对照组,GD组高于对照组(P<0.05)。GO患者活动期组CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R高于非活动期组(P<0.05)。CD4^(+)/CD8^(+)T、CD8^(+)CD38^(+)T与CAS评分呈正相关(P<0.05);CD4^(+)CD38^(+)T与TRAb、CAS评分呈正相关(P<0.05);IL-2R与FT4、TRAb、TPOAb、CAS评分呈正相关(P<0.05)。CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R联合检测预测GO患者疾病活动性的AUC值为0.930,高于外周血四者单独检测(AUC=0.736、0.749、0.668、0.699,P<0.05)。结论外周血CD4^(+)/CD8^(+)T、CD4^(+)CD38^(+)T、CD8^(+)CD38^(+)T、IL-2R联合预测GO活动性的临床价值更高。

糖皮质激素不同用药途径对Graves突眼患者疗效、复发和病情稳定时间的影响

目的探究糖皮质激素不同用药途径对Graves突眼(GO)患者疗效、复发和病情稳定时间的影响。方法收集2020年1月至2021年12月接受治疗的60例GO患者为研究对象,按照区组随机化分组法将其分为口服组和静脉组,各30例。口服组服用醋酸泼尼松片进行治疗,静脉组选用醋酸泼尼松龙注射液治疗。比较两组的临床疗效、复发和病情稳定时间;分析影响GO复发的因素。结果静脉组的临床疗效显著优于口服组(P<0.05)。两组停药后12个月内的复发率比较,差异无统计学意义(P>0.05);静脉组的病情稳定时间长于口服组(P<0.05)。复发者的年龄明显小于未复发者,病情重度占比、高碘饮食占比及治疗结束时游离三碘甲腺原氨酸(FT3)水平明显高于未复发组(P<0.05)。Logistic回归分析结果显示,年龄是停药后GO复发的保护因素,高碘饮食和治疗结束时FT3水平是GO复发的危险因素(P<0.05)。结论与口服用药相比,糖皮质激素静脉冲击疗法能更好地治疗GO,延长病情稳定时间,但糖皮质用药途径并不会对复发率产生明显影响,停药后是否复发主要受患者年龄、是否高碘饮食和停药时机体FT3水平等影响。

经鼻内镜内下壁减压术治疗Graves眼病压迫性视神经病变的效果

目的 探讨经鼻内镜内下壁减压术治疗Graves眼病压迫性视神经病变的临床效果。方法 选取医院2017年1月至2022年6月收治的92例Graves眼病压迫性视神经病变患者,根据随机数字表法分为研究组和常规组,各46例。研究组接受经鼻内镜内下壁减压术,常规组接受眼眶平衡减压术,比较两组治疗前后眼球突出度及视力变化情况、术中出血量和手术时间、生活质量,比较两组并发症发生情况。结果 治疗后,两组眼球突出度较治疗前下降,且研究组低于常规组(P<0.05),两组最佳矫正视力均上升,且研究组高于常规组(P<0.05)。研究组术中出血量少于常规组,手术时间短于常规组(P<0.05)。治疗后研究组社会功能、认知功能、心理状态、健康状态评分和总分均高于常规组(P<0.05)。两组并发症总发生率比较差异无统计学意义(P>0.05)。结论 经鼻内镜内下壁减压术治疗Graves眼病压迫性视神经病变可以缓解患者眼球突出问题,帮助患者更好恢复视力,减少术中出血量并缩短手术时间,提高生活质量,且安全性高。

Graves眼病患者血浆细胞因子浓度与临床活动度的相关性分析

目的Graves眼病(Graves ophthalmopathy,GO)是一种器官特异性自身免疫疾病,是成人最常见的眼眶疾病之一,其导致的眼部损害给患者带来了沉重的身心负担。GO的发病机制包括炎症细胞(淋巴细胞、浆细胞、肥大细胞和巨噬细胞)增多,分泌多种细胞因子导致炎症反应。在本研究中,测定活动期及非活动期GO患者血浆12种细胞因子的浓度,探讨其与疾病临床活动度的相关性。方法选取2021年1月-2023月1月在首都医科大学附属北京同仁医院内分泌科诊断为GO患者27例,并按照其临床活动性评分(Clinical Activity Score,CAS)将其划分为活动期组(CAS≥3)14例及非活动期组(CAS<3)13例。采用多重微球流式免疫荧光发光法检测血浆12项细胞因子[包括白细胞介素(interleukin,IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-17、IL-12P70,干扰素(interferon,IFN)-α、IFN-γ、肿瘤坏死因子(tumor necrosis factor,TNF)-α]浓度,同时收集所有研究对象的性别、年龄、肝肾功能、甲状腺功能及抗体等临床指标。结果与非活动期组相比,活动期GO患者的IL-1、IL-4、IL-5、IL-8、IL-10、IL-17、TNF-α及IFN-γ浓度明显升高,差异均有统计学意义(P<0.05)。Spearman相关性分析显示IL-1、IL-4、IL-5、IL-8、IL-10、IL-17、TNF-α及IFN-γ与CAS评分呈现显著正相关。单因素Logistic回归分析显示IL-1、IL-4、IL-5和IL-17升高会增加活动期风险。结论(1)活动期GO患者IL-1、IL-4、IL-5、IL-8、IL-10、IL-17、TNF-α及IFN-γ浓度明显高于非活动期组,提示这些细胞因子可能参与了GO的免疫反应。(2)单因素回归分析显示,IL-1、IL-4、IL-5和IL-17升高会增加活动期风险,推测这4种细胞因子有望作为评判GO病情活动性的指标。

Graves眼病患者血清中性粒细胞计数、CRP、ESR、NLR及甲状腺自身抗体的表达和意义

目的探讨Graves眼病(Graves ophthalmopathy)患者活动期血清的甲状腺自身抗体、炎性指标水平与临床意义及患者突眼度与血清甲状腺自身抗体、炎症指标水平的相关性。方法选取2018年6月至2020年3月就诊的Graves眼病患者103例,按临床活动度评分(CAS)分为非活动组(CAS<3,n=53)和活动组(CAS≥3,n=50),收集患者的临床资料,完善血常规、C-反应蛋白(CRP)、血沉(ESR)、甲状腺抗体检查。结果活动组患者的突眼度、NOSPECS分级、CRP、ESR、中性粒细胞计数、中性粒细胞与淋巴细胞比值(NLR)均高于非活动组(P<0.05)。活动组的促甲状腺素受体抗体(TRAb)、抗甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)水平高于非活动组(P<0.05)。Pearson相关性分析显示,Graves眼病患者突眼度与中性粒细胞计数、CRP、ESR、NLR、TRAb、TGAb、TPOAb、NOSPECS分级均呈正相关(P<0.05)。结论通过监测患者的甲状腺自身抗体及中性粒细胞计数、CRP、ESR、NLR炎性指标水平可为评估Graves眼病活动性和临床疗效提供重要的参考依据。

基于郁火理论探讨Graves眼病的病理改变

Graves眼病是弥漫性毒性甲状腺肿最常见、最复杂的并发症,Graves眼病的基本病机为郁火之邪上炎眼目,因此郁火理论在Graves眼病病理改变方面有着重要应用。Graves眼病眼睑征乃脾营亏虚,中焦气机郁遏生火上炎所致;眼眶结缔组织增生乃痰浊湿滞,壅塞生火灼目所致;球结膜充血和水肿乃瘀血阻于眼络,郁热不得布散所致;泪膜功能下降,角膜炎症或溃疡穿孔乃肾阴不足,相火离位上扰所致;脉络膜及视网膜血流改变乃肝气怫郁于内,日久化火所致。基于郁火与眼部病理改变的理论联系,在治疗方面,可采用局部辨证与整体辨证相结合的方式,使用益营散火、化形解火、培肾透火、理气清火等治法,以达到疏解郁火,宣畅气机之效。

Orbital decompression surgery for the treatment of Graves＇ ophthalmopathy：comparison of different techniques and long-term results

AIM： To evaluate the long-term results of different orbital decompression techniques performed in patients with Graves＇ ophthalmopathy（GO）.METHODS： Totally 170 cases with GO underwent orbital decompression between 1994 and 2014. Patients were divided into 4 groups as medial-inferior, mediallateral（balanced）, medial-lateral-inferior, and lateral only according to the applied surgical technique. Surgical indications, regression degrees on Hertel exophthalmometer, new-onset diplopia in the primary gaze and new-onset gaze-evoked diplopia after surgery and visual acuity in cases with dysthyroid optic neuropathy（DON） were compared between different surgical techniques.RESULTS： The study included 248 eyes of 149 patients. The mean age for surgery was 42.3±13.2 y. DON was the surgical indication in 36.6% of cases, and three-wall decompression was the most preferred technique in these cases. All types of surgery significantly decrease the Hertel values（P〈0.005）. Balanced medial-lateral, and only lateral wall decompression caused the lowest rate of postoperative new-onset diplopia in primary gaze. The improvement of visual acuity in patients with DON did not significantly differ between the groups（P=0.181）. CONCLUSION： The study show that orbital decompression surgery has safe and effective long term results for functional and cosmetic rehabilitation of GO. It significantly reduces Hertel measurements in disfiguring proptosis and improves visual functions especially in DON cases.

Association of Graves’ disease and Graves’ ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene

Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.

Hypoxia increases adipogenesis and affects adipocytokine production in orbital fibroblasts-a possible explanation of the link between smoking and Graves' ophthalmopathy

AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves’ophthalmopathy(GO)and from patients without known thyroid diseases undergoing blepharoplasty.The OF were cultured separately under normoxic and hypoxic conditions.Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.RESULTS:There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions.This was not observed in OF from normal controls.Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.CONCLUSION:Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO.We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process.

Three Dimensional Orbital Magnetic Resonance T2-Mapping in the Evaluation of Patients with Graves'Ophthalmopathy

The clinical application of orbital magnetic resonance（MR） T2-mapping imaging in detecting the disease activity of Graves＇ ophthalmopathy（GO）, and the predictive values of therapy response to intravenous glucocorticoid（iv GC） were investigated. Approved by the local institutional review board（IRB）, 106 consecutive patients with GO were included in this prospective study. All subjects were divided into two groups according to the patients＇ clinical activity score（CAS）： the CAS positive group（CAS ≥3） or the CAS negative group（CAS 〈3）. T2 relaxation time of extraocular muscles（T2RT; ms） and the areas of four extra-ocular muscles（AEOMs; mm2） were measured by 3D T2-mapping MR sequence before and after methylprednisolone treatment, so as the CAS and some ophthalmic examinations including visual acuity, intra-ocular pressure, eyeball movement, diplopia and proptosis. In addition, 24 healthy volunteers were recruited as the control group. The mean T2RT and AEOMs in CAS positive group were higher than those in CAS negative group. Both CAS positive and negative groups had significantly higher mean T2RT and AEOMs than the control group（P〈0.01）. There was a positive correlation between T2RT and AEOMs values in GO patients, both of them had a positive correlation with CAS and the ophthalmic examinations. It was concluded that to evaluate the activity of GO, CAS was mostly related to inflammation symptoms of ocular surface, more than that, T2RT and AEOMs were also related to abnormal findings of the ophthalmic examinations including high ocular pressure, impaired eyeball movement, diplopia and proptosis. T2RT and AEOMs can reflex the inflammation state of ocular muscles better. CAS combined with 3D T2-mapping MR imaging could improve the sensitivity of detection of active GO so as the prediction and evaluation of the response to methylprednisolone treatment.

Intravenous glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: a systematic review and Meta-analysis

AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trials(RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score(CAS), and adverse events.RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence(one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio(RR) 7.50, 95% confidence interval(CI) 1.14 to 49.26]. Moderate quality evidence(four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids(OGC), with of RR being 1.51(95%CI 1.25 to 1.83). There was low quality evidence(one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response(RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lowerresponse compared to participants using rituximab(RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil(MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF(RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence(one trial) showed that participants with dysthyroid optic neuropathy(DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression(RR 3.33, 95%CI 0.51 to 21.89).CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.

Ocular surface changes in Graves’ophthalmopathy

Many patients with Graves’ophthalmopathy(GO)suffer from dry eye syndrome(DES),and this is one of the most common reasons of eye discomfort in patients with GO.The prevalence of DES in patients with GO is significantly higher than normal subjects.The ocular surface changes involving changes in tears,cornea,conjunctiva and glands occur in GO patients.However,the mechanism of how DES occurs in GO still remains unclear.In this review,the ocular surface changes were illustrated and analyzed the reasons for high prevalence of DES in GO patients.

Paracentral Corneal Dellen:A Rare Sign of Graves Ophthalmopathy

Purpose: To report a rare sign, paracentral corneal dellen that developed in a middleaged female patient with Graves ophthalmopathy.Methods:A paracentral corneal dellen developed in the left eye in a 42-year-old woman who was diagnosed as Graves ophthalmopathy. The patient had remarkable upper eyelid retraction, upper eyelid lag and upward motility restriction. The Graves ophthalmopathy was classified as Grade V according to NOSPECS classification.Results:Local artificial tear film and 0.3% Tobramycin eye drops were administered to both eyes.Twenty-four hours later, the left corneal dellen disappeared.Conclusions:Graves ophthalmopathy can lead to paracentral corneal dellen because of severe upper eyelid retraction and upward motility restriction of the eye in spite of the lack of lagophthalmos. Artificial tear drop and antibiotic eye drop therapy helped even though the patient did not have corneal exposure.