Selenium supplementation in thyroid associated ophthalmopathy: an update

·The therapeutic effect of selenium(Se)has already been proven in thyroid disease and thyroid associated ophthalmopathy(TAO).In spite of clear scientific proof of its benefits in TAO,there appears to be no clear agreement among the clinicians regarding its optimum dose,duration of the treatment,efficacy and safety to date.In this review,the author summarises the findings of 135 English language articles published on this subject over the past four decades from 1973 to 2013.The regulation and metabolism of thyroid hormones require a steady supply of Se and recent studies have revealed several possible mechanisms by which Se improves the severity of thyroid disease and TAO.These mechanisms include 1)inhibitory effect of HLA-DR molecule expression on thyrocytes;2)profound reductions of thyroid stimulating hormone(TSH)receptor antibodies(TSHR-Ab)and TPO antibodies(TPO-Ab);3)prevention of dysregulation of cell-mediated immunity and B cell function;4)neutralising reactive oxygen species(ROS)and inhibition of redox control processes required for the activation,differentiation and action of lymphocytes,macrophages,neutrophils,natural killer cells involved in both acute and chronic orbital inflammation in TAO;5)inhibition of expression of proinflammatory cytokines and 6)inhibition of prostaglandin and leukotriene synthesis.An increased oxidative stress has been observed in both acute and chronic phases of thyroid disease with raised tissue concentrations of ROS.The benefits of Se supplementation in individuals with TAO appear to be proportionate to the degree of systemic activity of the thyroid disease.The maximal benefit of Se supplementation is therefore seen in thesubjects who are hyperthyroid.Restoration of euthyroidism is one of the main goals in the management of TAO and when anti-thyroid drugs are combined with Se,the patients with Graves’disease(GD)and autoimmune thyroiditis(AIT)achieved euthyroidism faster than those treated with anti-thyroid drugs alone.Se status of normal adult humans can vary widely and Se supplementation may confer benefit only if serum Se levels are insufficient.The author recommends that serum Se levels of patients with TAO to be assessed prior to and during Se supplementation at regular intervals to avoid potential iatrogenic chronic Se overdose.

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.

Biomarker identification of thyroid associated ophthalmopathy using microarray data

AIM： To uncover the underlying pathogenesis of thyroid associated ophthalmopathy（TAO） and explore potential biomarkers of this disease.METHODS： The expression profile GSE9340, which was downloaded from Gene Expression Omnibus database, included 18 specimens from 10 TAO patients and 8 hyperthyroidism patients without ophthalmopathy. The platform was HumanRef-8 v2 Expression BeadChip. Raw data were normalized using preprocess. Core package and the differentially expressed genes（DEGs） were identified based on t-test with limma package of R. Functional enrichment analyses were performed recruiting the DAVID tool. Based on STRING database, a protein-protein interaction（PPI） network was constructed, from which a module was extracted. The functional enrichment for genes in the module was performed by the BinGO plugin.RESULTS： In total, 861 DEGs（433 up-regulated and 428 down-regulated） between TAO patients and hyperthyroidism patients without ophthalmopathy were identified. Crucial nodes in the PPI network included TPX2, CDCA5, PRC1, KIF23 and MKI67, which were also remarkable in the module and all enriched in cell cycle process. Additionally, MKI67 was highly correlated with TAO. Besides, the DEGs of GTF2 F1, SMC3, USF1 and ZNF263 were predicted as transcription factors（TFs）. CONCLUSION： Several crucial genes are identified such as TPX2, CDCA5, PRC1 and KIF23, which all might play significant roles in TAO via the regulation of cell cycle process. Regulatory relationships between TPX2 and CDCA5 as well as between PRC1 and KIF23 may exist.Additionally, MKI67 may be a potent biomarker of TAO, and SMC3 and ZNF263 may exert their roles as TFs in TAO progression.

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.

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.

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.

Culture and Differentiation of Human Orbital Preadipocytes in Thyroid-associated Ophthalmopathy

Purpose: To identify whether there are preadipocytes in the orbits of thyroid-associated ophthalmopathy (TAO) patients and whether they possess the capacity to undergo adipocytic differentiation.Methods: Orbital fat tissue from TAO patients was placed in primary culture and proliferating cells were sub-passaged. The preadiocytes were identified with immunohistochemistry. Confluent preadipocytes were subjected to a differentiation protocol. And Peroxisome proliferators-associated receptorγ (PPARγ)transcript levels were determined before and after differentiation.Result: In primary culture, cells were spindly and showed positive immunostaining for preadipocyte factor-1 (pref-1 ) protein. During the process of differentiation, orbital cells showed evidence of adipogenesis and relatively greater PPARγ gene expression with differentiation.Conclusion: There are active preadipocytes in the orbital tissue of TAO patients which might be able to undergo adipocyte differentiation. These observations suggest that the preadipocytes differentiation contributed to excess orbital adipose tissue volume in TAO.

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.

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.

Frequency of IL-10-producing regulatory B cells associated with disease activity in thyroid-associated orbitopathy

AIM： To investigate the association between IL-10-producing regulatory B（B10） cells and the clinical features of thyroid-associated orbitopathy（TAO）. METHODS： A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center from May 2015 to December 2015. Peripheral blood mononuclear cells（PBMCs） were separated from blood samples of 30 TAO patients and 16 healthy controls and stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10＋ B cells was examined by flow cytometry and the correlation between the frequency of IL-10＋ B cells and clinical features of TAO was analyzed by SPSS. RESULTS： The frequency of IL-10＋ B cells among CD19＋ B cells in TAO patients was significantly lower than in healthy controls（TAO： 4.66%±1.88% vs healthy control： 6.82%±2.40%, P〈0.01）. The frequency of IL-10＋ B cells showed a positive correlation with disease activity of TAO measured by Clinical Activity Score（CAS）（r=0.50, P〈0.01）, and became higher in TAO patients with family history of Graves＇ disease（GD）（P=0.04）. CONCLUSION： The decrease of the frequency of IL-10＋ B cells in TAO patients indicates the deficiency of B10 cells in TAO, and the positive association with disease activity suggests its important role in TAO inflammation regulation.

Evaluation of retinal nerve fiber layer thickness profile in thyroid ophthalmopathy without optic nerve dysfunction

AIM： To evaluate retinal nerve fiber layer（RNFL）thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction.METHODS： A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of： biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement;or a clinical activity score（CAS）〉3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart.RESULTS： Mean age of the sample was 38.75y（range13-70y） with 18 males and 22 females. Average RNFL thickness at first visit was 92.06 ±12.44 μm, significantly lower than control group（101.28±6.64 μm）（P =0.0001）.Thickness of inferior quadrant decreased from 118.2 ±21.27 μm to 115.0 ±22.27 μm after 6mo（P =0.02）. There was no correlation between the change in CAS and RNFL thickness. CONCLUSION： Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave＇s disease and active intervention may be warranted in the presence of significant damage.

CD19^(+)CD27^(+)IgD^(+)B细胞与甲状腺相关性眼病患者疾病活动度相关性研究

目的:探讨甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者外周血CD19^(+)CD27^(+)IgD^(+)B细胞比例变化与病情活动度的关系。方法:采用流式细胞术检测TAO患者和健康对照组CD19^(+)CD27^(+)IgD^(+)B细胞比例,分析TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例与健康对照组的差异,并分析CD19^(+)CD27^(+)IgD^(+)B细胞比例与TAO疾病活动度之间的相关性。结果:TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例明显低于健康对照(P<0.05);活动性TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例细胞显著低于非活动性TAO患者;CD19^(+)CD27^(+)IgD^(+)B细胞比例与TAO患者CAS评分呈显著负相关(r=-0.7128,P<0.001)。结论:TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例降低,与疾病活动度呈负相关。

CXCR4 MFAP2 KLF4在分化型甲状腺癌中的表达及对预后的预测价值研究

目的:研究趋化因子4受体(CXCR4)、微纤维相关蛋白2(MFAP2)、Krüppel样因子4(KLF4)在分化型甲状腺癌(DTC)中的表达及对预后的预测价值。方法:选择我院2019年7月至2020年7月收治的113例DTC患者,术中留取其肿瘤组织及癌旁正常组织。采用蛋白免疫印迹法检测DTC组织及癌旁正常组织中CXCR4、MFAP2、KLF4表达水平,分析CXCR4、MFAP2、KLF4表达水平与DTC临床病理特征的关系。对DTC患者进行3年随访,统计3年总生存情况,比较死亡组与存活组CXCR4、MFAP2、KLF4表达水平,采用ROC曲线分析CXCR4、MFAP2、KLF4对DTC预后的预测价值,采用Cox回归模型进行DTC预后单因素和多因素分析。结果:与癌旁正常组织比较,DTC组织CXCR4、MFAP2蛋白表达量显著升高(P<0.05),KLF4蛋白表达量显著降低(P<0.05)。TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者CXCR4、MFAP2蛋白表达量显著高于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05),TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者KLF4蛋白表达量显著低于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05)。113例DTC患者随访3年期间失访8例,最终获得随访者105例。死亡组患者CXCR4、MFAP2蛋白表达量显著高于存活组(P<0.05),KLF4蛋白表达量显著低于存活组(P<0.05)。绘制ROC曲线发现,CXCR4、MFAP2、KLF4单独或联合预测DTC预后的AUC(95%CI)分别为0.692(0.562~0.823)、0.729(0.590~0.869)、0.766(0.622~0.910)、0.832(0.690~0.975),联合预测的效能显著优于单项检测(P<0.05)。Cox回归分析显示,淋巴结转移、TNM分期Ⅲ期、肿瘤低分化、CXCR4表达升高、MFAP2表达升高、KLF4表达降低是DTC预后的危险因素(P<0.05)。结论:分化型甲状腺癌患者肿瘤组织中CXCR4、MFAP2呈高表达,KLF4呈低表达,其表达水平与淋巴结转移、肿瘤分化程度、TNM分期及3年总生存率相关,三者联合检测有助于预测分化型甲状腺癌预后。

血脂联合磁共振参数在甲状腺相关性眼病糖皮质激素治疗疗效预测中的价值

目的:评估血清脂代谢指标联合眼眶磁共振成像(magnetic resonance imaging,MRI)定量参数在预测中重度活动期甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者糖皮质激素(glucocorticoid,GC)治疗疗效中的价值。方法:回顾性纳入44例接受GC治疗的中重度活动期TAO患者,根据GC疗效将患者分为敏感组(n=28)和抵抗组(n=16)。收集两组患者在GC治疗前的血清脂代谢指标和基于眼眶MRI测得的泪腺突出度/眼眶脂肪厚度(lacrimal gland herniation/orbital fat thickness,LGH/OFT)及其他临床参数,并比较两组间各参数差异。采用Logistic回归和受试者工作特征曲线分析与GC治疗疗效相关的独立预测因子并评估其预测价值。结果:敏感组患者血清总胆固醇和低密度脂蛋白胆固醇水平显著低于抵抗组(P=0.005,P=0.019),且敏感组病程更短(P=0.037)。敏感组患者LGH/OFT显著高于抵抗组(P<0.001)。总胆固醇和LGH/OFT是TAO患者激素是否敏感的独立预测因子(OR值分别为0.230、1.395_(每0.1单位),P均<0.05)。联合血清总胆固醇≤4.8 mmol/L和LGH/OFT≥1.51预测GC治疗敏感性,可以获得最佳预测效能(曲线下面积为0.838,灵敏度为87.5%,特异度为65.6%)。结论:血脂参数和眼眶MRI定量参数均可预测中重度活动期TAO患者GC治疗敏感性,两者联合可进一步提高预测效能。

生物制剂在甲状腺相关眼病中的研究进展

甲状腺相关眼病(TAO)是一种罕见的器官特异性自身免疫性疾病,发病机制尚未明确。目前治疗仍主要依赖糖皮质激素和传统免疫抑制剂,部分患者对这些药物反应不佳,同时存在治疗相关不良反应,因此迫切需要治疗TAO的新型药物。近年来,随着对TAO发病机制研究的不断深入,针对特定靶点研发的生物制剂层出不穷,其中靶向胰岛素样生长因子-Ⅰ受体(IGF-IR)的替妥木单抗已被美国食品和药物管理局批准用于治疗TAO,还有多种生物制剂处于临床试验阶段。本文通过总结针对IGF-IR、新生儿Fc受体(FcRn)、促甲状腺激素受体(TSHR)、B细胞、细胞因子等的生物制剂在TAO中的临床研究现状,分析其对临床治疗及未来研究趋势的影响,为TAO临床防治和研究提供最新参考。

甲状腺相关性眼病患者眼表及肠道菌群的研究进展

甲状腺相关性眼病(TAO)是一种自身免疫性疾病,其病因和发病机制尚未完全明确,目前普遍认为其发生是免疫、遗传、环境等因素共同作用的结果。近年来,学者们开始关注微生物对TAO的影响,认为眼表及肠道菌群失调后能激发免疫系统发生一系列的免疫应答,诱发TAO的自身免疫反应。“肠-眼轴”可能是TAO发病的重要因素之一,肠道菌群及其代谢物可能通过血液循环和淋巴系统影响眼表组织,这种“肠-眼轴”的相互作用可能通过多种途径影响TAO的发生和发展,包括免疫细胞的迁移、交叉免疫反应和代谢物的循环。本文就眼表菌群及肠道菌群失调与TAO的研究进展进行综述,探讨其菌群参与TAO发生发展的可能机制,为TAO的诊断与治疗提供新的思路。

OCTA定量分析甲状腺相关性眼病和甲状腺功能亢进患者黄斑及视盘旁血管密度变化

目的:应用光学相干断层扫描血管成像(OCTA)定量分析甲状腺相关性眼病(TAO)及甲状腺功能亢进患者黄斑及视盘旁血管密度(VD)的变化,探索能够早期反映TAO发生发展的无创监测指标。方法:采用横断面临床研究。纳入2023-02-2023-06于武汉大学人民医院就诊的活动期TAO患者24例(TAO组)、甲状腺功能亢进无眼部改变患者24例(甲亢组)和体检健康者24例(对照组)。三组受检者均接受黄斑HD 6mm×6mm和视盘HD 4.5mm×4.5mm扫描模式的OCTA检查,并测量浅层及深层视网膜VD、视盘旁放射状毛细血管网VD(ppVD)、视盘周围视网膜神经纤维层(RNFL)厚度及中心凹无血管区(FAZ)面积,比较三组受检眼上述指标的差异。结果:与对照组比较,TAO组和甲亢组浅层视网膜VD显著降低(P<0.05或P<0.01);与甲亢组比较,TAO组整体、N2及I2区域浅层视网膜VD显著降低(P<0.05或P<0.01)。甲亢组和TAO组中心凹区域深层视网膜VD明显低于对照组(P<0.05或P<0.01)。三组间大部分区域ppVD及RNFL厚度的差异均无统计学意义(P>0.05)。甲亢组和TAO组FAZ面积较对照组均显著扩大(P<0.05或P<0.01)。结论:甲状腺功能亢进患者在尚未发展为TAO之前已经出现浅层视网膜VD降低及FAZ面积扩大,TAO患者的相关变化较甲状腺功能亢进患者更甚,OCTA有助于早期无创监测相关指标变化。

健脾利湿化痰祛瘀法治疗活动期甲状腺相关性眼病临床研究

目的 观察健脾利湿化痰祛瘀法治疗活动期甲状腺相关性眼病(TAO)临床疗效。方法 将90例TAO患者按照随机数字表法分为2组,对照组45例予注射用甲泼尼龙琥珀酸钠针静脉滴注治疗,治疗组45例予健脾利湿化痰祛瘀法治疗。疗程12周。比较2组治疗前后中医证候评分,2组治疗前后及第24周随访突眼度、临床活动度评分(CAS)、胰岛素样生长因子-1(IGF-1)、透明质酸(HA)水平,统计2组疗效及不良反应情况。结果 治疗组总有效率93.3%(42/45),对照组总有效率68.9%(31/45),治疗组临床疗效优于对照组(P<0.05)。治疗组治疗后中医证候各项评分均较本组治疗前降低(P<0.05),且治疗组治疗后均低于对照组(P<0.05),对照组治疗后畏光流泪、眼睑肿胀评分均较本组治疗前降低(P<0.05)。2组治疗后及随访时突眼度均较本组治疗前降低(P<0.05),且治疗组随访时突眼度低于对照组同期(P<0.05)。2组治疗后及随访时CAS评分均较本组治疗前降低(P<0.05),且治疗组随访时CAS评分低于对照组同期(P<0.05)。2组治疗后及随访时IGF-1、HA水平均较本组治疗前降低(P<0.05),且治疗组治疗后及随访时IGF-1、HA水平均低于对照组同期(P<0.05)。治疗组不良反应发生率低于对照组(P<0.05)。结论 健脾利湿化痰祛瘀法治疗TAO患者疗效显著,能改善眼部症状。

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。