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.

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.

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.

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.

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.

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.

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.

Global research on artificial intelligence in thyroid-associated ophthalmopathy:A bibliometric analysis

Purpose:To provide an overview of global publications on artificial intelligence(AI)in thyroid-associated oph-thalmopathy(TAO)through bibliometric analysis.Methods:Publications related to AI in TAO from inception until April 2023 were retrieved from the Web of Science database.The trends of publications and citations,publishing performance,collaboration among countries and institutions,and the funding agencies,relevant research domains,leading journals,hotspots and their evolution were identified.Results:A total of 55 publications were included for analysis.The number of publications and citations continued to grow since 1998,with a significant acceleration of growth after 2020.China is the most productive country with the highest number of productive institutions,followed by the United States.European countries have the most extensive collaboration.The most relevant research domain was radiology,nuclear medicine&medical imaging.The European Journal of Radiology was one of the most productive journals,with the most influential articles published."Thyroid-associated ophthalmopathy"and"neural network"maintain hotspots during the entire period.Studies were more focused on clinical features during 1998 and 2016,clinical features and medical data during 2017 and 2020,and medical data and AI techniques during 2021 and 2023.Conclusions:This study summarized the global research status regarding AI in TAO in terms of trends,countries,institutions,research domains,journals,and key topics.AI has shown great potential in TAO.Sponsored by funding agencies such as NSFC,China has become the most productive country in the field of AI in TAO.Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.

The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid optic neuropathy

Thyroid-associated orbitopathy （TAO） is an inflammatory autoimmune disorder. The most serious complication of TAO is dysthyroid optic neuropathy （DON）, which can lead to permanent vision loss because of volume expansion in the orbital apex. Orbital radiation therapy （ORT） is an anti-inflammatory treatment used in the treatment of active TAO. Clinical studies support radiotherapy as having a modest effect on DON, and early radiotherapy may protect against disease progression to DON. Current studies suggest that radiotherapy is generally safe. However, risks still exist in some cases. The possible effects of radiotherapy on TAO, especially complicated with DON, are reviewed. The effects of radiotherapy on DON are not completely known, and evidence from standardized, prospective, and multicenter clinical trials is still lacking.

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.

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.

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。

Choroidal vascularity index in thyroidassociated ophthalmopathy:a crosssectional study

Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-associated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association Was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,genderorage(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.

Reduced macular inner retinal thickness and microvascular density in the early stage of patients with dysthyroid optic neuropathy

Background:The goal was to investigate changes of the inner intra-retinal layer thicknesses and retinal capillary density(RCD)around the macula in thyroid-associated ophthalmopathy(TAO)patients with or without dysthyroid optic neuropathy(DON).Methods:Forty-four TAO patients including 23 non-DON and 21 DON patients,and 38 healthy participants were enrolled.Spectral domain optical coherence tomography equipped with Angiovue was used to obtain threedimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary layers(SRCL and DRCL,respectively)around the macula.Quantitative analyses were performed using a custom automated algorithm.Results:The thicknesses of the nerve fiber layer,ganglion cell layer+inner plexiform layer,and ganglion cell complex(GCC)as well as the RCDs in the SRCL and DRCL in both TAO groups were significantly decreased compared to the controls.In addition,the RCDs in DRCL of the DON group were further decreased compared to the non-DON group.GCC thickness in both TAO groups was positively correlated with the RCDs of the SRCL in the total annular zone and in the temporal,inferior,and nasal sectors.The areas under the receiver operating characteristic curves for the GCC thickness combined with the RCD were generally larger than those of each single indicator.Conclusions:Thinned inner intra-retinal layers and decreased RCDs in the TAO patients without DON revealed that morphological changes might precede visual dysfunction.The composite index of the retinal structure and the microvascular density might be valuable in the diagnosing,monitoring,and intervention for early DON.

Modified endoscopic transnasal orbital apex decompression in dysthyroid optic neuropathy

Background:To describe the surgical technique and assess the clinical efficacy and safety of modified endoscopic transnasal orbital apex decompression in the treatment of dysthyroid optic neuropathy.Methods:In this retrospective research,forty-two subjects(74 orbits)who underwent modified endoscopic transnasal orbital apex decompression for the treatment of dysthyroid optic neuropathy were enrolled.Preoperative and postoperative best-corrected visual acuity(BCVA),visual field mean deviation(MD),Hertel exophthalmometry,and new onset diplopia were assessed before and after the intervention.The Wilcoxon test was used for differential analysis.Linear mixed-models’analyses were conducted to assess the potential predictors for BCVA change.Results:Postoperatively,the mean BCVA improved from 0.70±0.62 logMAR to 0.22±0.33 logMAR.BCVA significantly improved in 69 eyes(93%),remained stable in 4 eyes(5%)and deteriorated in 1 eye(1%).MD of visual fields improved from−13.73±9.22 dB to−7.23±7.04 dB.Proptosis decreased from 19.57±3.38mm to 16.35±3.01mm.Preoperative BCVA,MD of visual fields and medical rectus diameter were independent factors associated with improvements in BCVA(P<0.05)by linear mixed-models’analyses.Eighteen patients(42.9%)developed new diplopia postoperatively.Conclusion:Modified endoscopic transnasal orbital apex decompression effectively restores vision in dysthyroid optic neuropathy.

Reduced macular inner retinal thickness and microvascular density in the early stage of patients with dysthyroid optic neuropathy

Background:The goal was to investigate changes of the inner intra-retinal layer thicknesses and retinal capillary density(RCD)around the macula in thyroid-associated ophthalmopathy(TAO)patients with or without dysthyroid optic neuropathy(DON).Methods:Forty-four TAO patients including 23 non-DON and 21 DON patients,and 38 healthy participants were enrolled.Spectral domain optical coherence tomography equipped with Angiovue was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary layers(SRCL and DRCL,respectively)around the macula.Quantitative analyses were performed using a custom automated algorithm.Results:The thicknesses of the nerve fiber layer,ganglion cell layer and inner plexiform layer,and ganglion cell complex(GCC)as well as the RCDs in the SRCL and DRCL in both TAO groups were significantly decreased compared to the controls.In addition,the RCDs in DRCL of the DON group were further decreased compared to the non-DON group.GCC thickness in both TAO groups was positively correlated with the RCDs of the SRCL in the total annular zone and in the temporal,inferior,and nasal sectors.The areas under the receiver operating characteristic curves for the GCC thickness combined with the RCD were generally larger than those of each single indicator.Conclusions:Thinned inner intra-retinal layers and decreased RCDs in the TAO patients without DON revealed that morphological changes might precede visual dysfunction.The composite index of the retinal structure and the microvascular density might be valuable in the diagnosing,monitoring,and intervention for early DON.

Choroidal vascularity index in thyroidassociated ophthalmopathy:a crosssectional study

Background:Hemodynamic changes have been observed in patients with Graves’disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVI)in patients with thyroidassociated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,gender or age(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.