Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy

AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.