·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 ...·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.展开更多
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 Expres...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.展开更多
·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...·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.展开更多
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 TA...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.展开更多
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 revie...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.展开更多
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 cl...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.展开更多
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 ...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.展开更多
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 se...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.展开更多
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 t...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.展开更多
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...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.展开更多
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 c...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.展开更多
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 report...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.展开更多
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 Zh...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.展开更多
文摘·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.
文摘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.
文摘·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.
基金Supported by National Natural Science Foundation of China(No.81200719)China Postdoctoral Science Foundation(No.2013M543579+1 种基金 No.2014T71013)Key Specialized Projects in Nanjing(No.SZDZK2016008)
文摘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.
基金Supported by the National Natural Science Foundation of China (No.81670885)the Science and Technology Program of Guangdong Province, China (No.2013B020400003)the Science and Technology Program of Guangzhou, China (No.15570001)
文摘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.
基金Sichuan Science and Technology Department the Tackling Key Project Fund, China (No.05SG022-014-1)
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by the National Natural Science Foundation of China(No.81470664No.81670887No.81700875)
文摘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.
