Clinical Study on Therapy of Soothing Liver and Strengthening Spleen in the Treatment of Active Thyroid-Associated Ophthalmopathy Complicated with Dry Eye / 广州中医药大学学报

Objective To investigate the efficacy of the therapy of soothing liver and strengthening spleen(shortened as Shugan Jianpi therapy)in the treatment of active thyroid-associated ophthalmopathy(TAO)complicated with dry eye,and to provide a reference basis for clinical treatment.Methods A total of 108 patients with active TAO complicated with dry eye of liver depression and qi stagnation type were randomly divided into observation group and control group,54 patients in each group.Both groups were given conventional treatment for intervention of Graves'disease,and additionally the control group was given hormone shock therapy by intravenous injection of Methylprednisolone Sodium Succinate,and the observation group was treated with Chinese medicine prescription for soothing liver and strengthening spleen orally and intravenous injection of Methylprednisolone Sodium Succinate.The treatment period lasted for 12 weeks,and then the patients were followed up till to the 6th month.The changes of clinical activity score(CAS),proptosis,ocular surface disease index(OSDI),corneal fluorescein staining(FL),Schirmer I test(SIT)and tear film break-up time(BUT)in the two groups were observed before and after the treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate in the observation group was 94.44%(51/54)and that in the control group was 74.07%(40/54),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the CAS,OSDI score and proptosis of the patients in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the indicators of tear secretion function such as SIT,FL score and BUT of patients in the two groups were improved compared with those before treatment(P＜0.01),and the improvement in the observation group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).Conclusion Shugan Jianpi therapy exerts certain clinical efficacy in treating patients with active TAO complicated with dry eye of liver depression and qi stagnation type,which can effectively relieve the proptosis,prolong the tear film break-up time,promote the secretion of tears and the repair of corneal epithelium,improve the visual function,and enhance the quality of life of the patients.

Value of evaluating Graves ophthalmopathy motiliny by MRI T2-mapping / 解放军医学杂志

Objective To investigate the value of magnetic resonance imaging(MRI)T2-mapping in evaluating the activity of Graves ophthalmopathy(GO).Methods A total of 64 patients with GO in the Department of Endocrinology,the First Affiliated Hospital of Chongqing Medical University from July 2019 to January 2021 were collected.Simple random grouping was performed by computer,with 49 cases as observation subjects,and 15 patients for diagnostic test.According to clinical activity score(CAS),49 GO patients were divided into active group(CAS≥3 points,48 eyes)and inactive group(CAS<3 points,50 eyes).Normal control group(NC group)included 31 patients(62 eyes).All subjects underwent 3.0T orbital MRI T2-mapping.Measuring the T2 relaxation time(T2RT)of superior rectus,inferior rectus,medial rectus,and lateral rectus on five layers behind the eyeball on T2-mapping coronal images,and select the maximum value of T2RT in the five layers for each extraocular muscle to represent the T2RT of this extraocular muscle.Finally,select the maximum T2RT values of the four extraocular muscles,expressed as extraocular muscle maximum T2RT.Compare the differences of the above 5 indicators(superior rectus T2RT,inferior rectus T2RT,medial rectus T2RT,lateral rectus T2RT,extraocular muscle maximum T2RT)between active group,inactive group and NC group.ROC curve was used to analyze the diagnostic value of the above 5 indicators for GO activity assessment,and the diagnostic threshold was obtained.Then,another 15 GO patients were performed for diagnostic tests evaluation to determine the indicators of high diagnostic efficacy and the threshold of diagnostic activity.Results The T2RT of all extraocular muscles in active group were significantly higher than those in inactive group and NC group,the difference was statistically significant(P<0.001).The threshold value of the five indicators were obtained by ROC curve analysis.The maximum T2RT cut-off values of superior rectus muscle,inferior rectus muscle,medial rectus muscle,lateral rectus muscle and extraocular muscles for judging activity were 80.200 ms,97.045 ms,94.355 ms,85.750 ms and 101.385 ms respectively.Another 15 GO patients were performed for diagnostic tests,the indexes with relatively high sensitivity,specificity,positive predictive value and negative predictive value were inferior rectus T2RT and extraocular muscle maximum T2RT,the cut-off values of GO activity were 97.045 ms and 101.385 ms,respectively;the sensitivity were 91.7％and 93.8％,respectively;the specificity all were 80.0％.Conclusions MRI T2-mapping sequence has a good value in assessment of GO activity.The inferior rectus T2RT and extraocular muscle maximum T2RT can be choosed to evaluate the activity of GO.

Clinical characteristics and risk factors of thyroid-associated ophthalmopathy with liver injury / 眼科新进展

Objective To explore the clinical characteristics and liver injury-related risk factors of thyroid-associated ophthalmopathy(TAO)patients with liver function impairment.Methods In this retrospective cohort study,the clinical data of 1 030 TAO patients who visited Henan Provincial People's Hospital from July 2017 to May 2023 was collected.These patients were divided into TAO patients with liver injury(Group A,132 patients)and TAO patients with normal liver func-tion(Group B,898 patients).The age,gender,smoking history,liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(γ-GT),total bilirubin(TBil),direct bilirubin(DBil),and alkaline phosphatase(ALP)],thyroid function-related indicators[free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),thyrotropin receptor antibody(TRAb),thyroid peroxidase antibody(TPO-Ab),and thyroglobulin antibody],and eye signs[eye protrusion degree,intraocular pressure,absence or occurrence of upper eyelid retraction,NOSPECS grading,clinical activity score(CAS),and number of affected ocular muscles of both eyes]of two groups were collected and compared.Multivariate logistic regression analysis was used to identify the risk fac-tors for liver injury in TAO patients.Results The proportion of liver injury in patients who were initially diagnosed with TAO and received no treatment was 12.82％.There was no statistically significant difference in the gender distribution and the proportion of smokers between the two groups(both P＞0.05).The age of patients in Group A[(44.63+13.64)years]was higher than that in Group B[(40.25±14.04)years],and the difference was statistically significant(t=3.718,P＜0.05).The levels of ALT,AST,γ-GT,ALP,TBil and DBil in Group A were higher than those in Group B,and the differences were statistically significant(allP＜0.01).The FT3,FT4,TPOAb and TRAb levels in Group A were higher than those in Group B,while the TSH level was lower than that in Group B(all P＜0.01).The number of affected ocular mus-cles of both eyes and the proportion of patients with a CAS score≥3 in Group A were higher than those in Group B(both P＜0.05).The regression analysis results showed that the higher the FT4 and TRAb levels,the older the age,and the lower the TSH level,the higher the risk of liver injury in TAO patients.Conclusion High levels of FT4 and TRAb,as well as low TSH level and advanced age,are independent risk factors for liver injury in TAO patients.The direct toxic effects of immune factors and high thyroxine level on the liver are jointly involved in the mechanism of liver injury in TAO patients.

Research progress of biological agents in thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Thyroid-associated ophthalmopathy(TAO)is a rare organ-specific autoimmune disease with an unclear pathogenesis. At present, the treatment still relies mainly on glucocorticoids and traditional immunosuppressants. However, some patients respond poorly to these drugs and experience treatment-related adverse reactions, highlighting the urgent need for novel drugs for TAO treatment. In recent years, with the deepening of research on the pathogenesis of TAO, a multitude of biologics targeting specific targets have emerged. Among them, teprotumumab, which targets the insulin-like growth factor-I receptor(IGF-IR), has been approved by the Food and Drug Administration for the treatment of TAO, and several other biologics are currently in clinical trials. This review provides the latest reference for the clinical prevention, treatment, and research of TAO by summarizing the current clinical research status of biologics targeting IGF-IR, neonatal Fc receptor(FcRn), thyroid-stimulating hormone receptor(TSHR), B cells, cytokines, and other biological agents in TAO and analyzing their impact on clinical treatment and future research trends.

Apical bleeding: a rare cause of blindness after orbital decompression / Sangramento apical: uma causa rara de cegueira pós descompressão orbitária

ABSTRACT Orbital decompression is widely performed for the management of proptosis for cosmetic and functional cases of Graves orbitopathy. The main side effects include dry eye, diplopia, and numbness. Blindness after orbital decompression is extremely rare. The mechanisms of vision loss after decompression are not well described in the literature. Considering the devastating effect and rarity of this complication, this study presented two cases of blindness after orbital decompression. In both cases, vision loss was provoked by slight bleeding in the orbital apex.

RESUMO A descompressão orbitária é uma cirurgia amplamente empregada para correção da proptose em casos cosméticos e funcionais da orbitopatia de Graves. Os principais efeitos colaterais induzidos pela descompressão são olho seco, diplopia e parestesias. Amaurose pós descompressão é uma complicação extremamente rara e cujos mecanismos são pouco discutidos na literatura. Considerando o efeito devastador representado pela perda visual e a escassez de relatos dessa complicação, os autores apresentam dois relatos de amaurose após descompressão orbitária. Nos dois casos a perda visual ocorreu devido a sangramento de pequena monta no ápice orbitário.

Quality of life in patients with Graves' orbitopathy submitted to orbital decompression: comparison between balanced and inferomedial techniques

ABSTRACT Purpose: To compare inferomedial wall orbital decompression to balanced medial plus lateral wall orbital decompression in patients with Graves' orbitopathy in the inactive phase with regard to exophthalmos reduction and the effects on quality of life. Methods: Forty-two patients with inactive Graves' orbitopathy were randomly divided into two groups and submitted to one of two orbital decompression techniques: inferomedial wall orbital decompression or medial plus lateral wall orbital decompression. Preoperative and postoperative assessments included Hertel's exophthalmometry and a validated Graves' orbitopathy quality of life questionnaire. The results of the two groups were compared. Results: Compared to preoperative measurement, exophthalmos reduction was statistically significant in both groups (p<0.001) but more so in patients undergoing medial plus lateral wall orbital decompression (p=0.010). Neither orbital decompression techniques increased the visual functioning subscale score on the Graves' orbitopathy quality of life questionnaire (inferomedial wall orbital decompression p=0.362 and medial plus lateral wall orbital decompression p=0.727), but a statistically significant difference was observed in the score of the appearance subscale in patients submitted to medial plus lateral wall orbital decompression (p=0.006). Conclusions: Inferomedial wall orbital decompression is a good alternative for patients who do not require large exophthalmos reduction. However, medial plus lateral wall orbital decompression offers greater exophthalmos reduction and greater improvement in appearance (higher Graves' orbitopathy quality of life questionnaire scores), making it a suitable option for esthetic-functional rehabilitation.

Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Patologías Oftalmológicas en lactantes menores de 6 meses en un servicio de oftalmopediatría de un hospital de referencia

Introducción: Las afecciones oftalmológicas en niños menores de 6 meses pueden producir alteraciones visuales e incluso la ceguera total. Objetivos: Describir la frecuencia y los tipos de patologías oftalmológicas en lactantes menores de 6 meses en un servicio de oftalmopediatría de un hospital infantil. Materiales y Métodos: estudio observacional, descriptivo, retrospectivo. Se revisó la base de datos del servicio de oftalmopediatría. Por muestreo de casos consecutivos fueron incluidos lactantes con edad ≤6 meses, que consultaron en el periodo de marzo a septiembre del 2022, en cuyas fichas figuraban el número telefónico. Variables: edad, sexo, motivo de consulta, antecedentes perinatales y de patologías oftalmológicas, resultado del examen oftalmológico y tratamiento. Los datos fueron analizados en SPSS con estadísticas descriptivas. El comité de ética aprobó el protocolo con consentimiento de los padres. Resultados: Ingresaron 137 lactantes con edad 2,9 ± 1,8 meses, peso de nacimiento 2995 ± 621, edad gestacional 38 ± 2,1 semanas, 53% varones, 31% para control, el 83%, con antecedente de patología ocular. Presentaron patología ocular el 32% (44/137), 59% (26/44) de origen congénito y 41%(18/44) adquiridas. El 18% (8/44) de las alteraciones oculares recibieron tratamiento quirúrgico. Conclusión: El 32% de los lactantes atendidos en el servicio de oftalmopediatria presentaron patologías oculares, de las cuales el 59% fueron congénitas, las dos más frecuentes la catarata congénita y la obstrucción del conducto nasolagrimal.

Introduction: Ophthalmological conditions in children under 6 months can cause visual disturbances and even total blindness. Objectives: To describe the frequency and types of ophthalmological pathologies in infants under 6 months of age in a pediatric ophthalmology service at a children's hospital. Materials and Methods: this was an observational, descriptive and retrospective study. The database of the ophthalmopediatric service was reviewed. By sampling consecutive cases, infants aged ≤6 months, who consulted from March to September 2022 and whose records included the telephone number were included. Variables: age, sex, chief complaint, perinatal history and ophthalmological pathologies, result of ophthalmological examination and treatment. Data were analyzed in SPSS with descriptive statistics. The ethics committee approved the protocol and parental consent was obtained. Results: 137 infants, aged 2.9 ± 1.8 months, birth weight 2995 ± 621, gestational age 38 ± 2.1 weeks, of which 53% were male were selected for this study. 31% presented for a routine follow-up, 83% had a history of ocular pathology. 32% (44/137) presented ocular pathology, 59% (26/44) congenital and 41% (18/44) acquired. 18% (8/44) of the ocular alterations received surgical treatment. Conclusions: 32% of the infants seen in the ophthalmopediatric service presented ocular pathologies, of which 59% were congenital, the two most frequent being congenital cataracts and nasolacrimal duct obstruction.

Role of interleukin-6 in ocular inflammatory diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Interleukin-6(IL-6)is a pleiotropic cytokine produced by monocytes, macrophages, T lymphocytes and other cell types. It is significantly up-regulated in the process of infection and inflammation, and is the core cytokine of the host's defense against environmental stresses(such as injury and infection). Abnormal and persistent IL-6 production is closely associated with the development of various autoimmune and inflammatory diseases. A growing number of studies have shown that IL-6 plays a critical role in ocular inflammation and angiogenesis in the conjunctiva, cornea, uvea and retina. Blockade of IL-6 ameliorates chronic and refractory intraocular inflammation. This article aims to review the role as well as the mechanism of IL-6 in ocular inflammatory diseases, attempting to have a deep and systematic understanding of the role of IL-6 in ocular inflammatory diseases.

Effect of orbital decompression on choroidal thickness in patients with thyroid associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of orbital decompression on the central macular choroidal thickness(CMCT)in patients with thyroid-associated ophthalmopathy(TAO).METHOD: Prospective clinical studies. A total of 29 TAO patients(42 eyes)treated in our department from January 2021 to January 2022 were analyzed, and they were divided into 20 cases(30 eyes)in the moderate and severe group and 9 cases(12 eyes)in the extremely severe group. Both groups of patients received orbital decompression, and the changes of CMCT, visual acuity, intraocular pressure, exophthalmos, and clinical activity score(CAS)at 3 and 6mo before and after surgery were compared between the two groups.RESULTS: All patients completed follow-up. The CMCT, exophthalmos, intraocular pressure, and CAS of the extremely severe group at 3 and 6mo were 355.13±15.59 and 339.61±13.17μm, 19.33±2.23 and 17.83±1.70mm, 18.86±3.05 and 18.09±1.37mmHg, 3.75±0.87 and 2.42±1.00 points, respectively. The moderate and severe group was 325.00±10.48 and 321.04±11.34μm, 16.07±1.74 and 15.6±1.98mm, 16.65±2.04 and 16.03±2.3mmHg, 1.50±0.51 and 1.43±0.50 points, and there was differences with those before operation(extremely severe group: 396.46±17.61μm, 22.00±2.3mm, 21.85±2.82mmHg, 5.33±1.44 points; moderate and severe group: 335.77±11.60μm, 19.07±1.84mm, 18.89±3.06mmHg, 1.63±0.49 points; all P&#x003C;0.001). The best corrected visual acuity(LogMAR)before surgery was 0.64±0.22 in the extremely severe group, and 0.43±0.20 and 0.34±0.15 at 3 and 6mo after operation, respectively, which were different from those before surgery(all P&#x003C;0.001)CONCLUSION: Orbital decompression can effectively reduce CMCT, intraocular pressure and exophthalmos in TAO patients, relieve orbital vein stasis, and effectively improve vision and reduce mobility in patients with extremely severe disease.

Clinical application of botulinum toxin type A in the treatment of thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Thyroid-associated ophthalmopathy(TAO)is an autoimmune inflammatory disease involving multiple orbital tissues with a variety of clinical manifestations, which has serious effects on the life quality of patients.Interventions of TAO mainly include medical treatment to stabilize thyroid function, reduce inflammation and regulate immune function, as well as surgical treatment to relieve ocular symptoms. Botulinum toxin type A can paralyze muscles by blocking nerve impulse conduction at the neuromuscular junction, which is of certain therapeutic value for restrictive strabismus due to extraocular muscle involvement and upper eyelid retraction due to involvements of levator palpebrae superioris and Müller's muscle in TAO patients, especially when they have surgical contraindications, lack surgical opportunity, or refuse surgery. This paper reviews the application of botulinum toxin type A in the treatment of TAO, focusing on its pharmacological mechanism, dosage, effectiveness, and possible complications when treating restrictive strabismus and upper eyelid retraction, and discussing potential therapeutic values of botulinum toxin type A for intraocular pressure elevation, glabellar frown lines and dry eye caused by extraocular muscle compression in TAO patients, in order to provide a reference for clinical intervention.

New drug for thyroid-associated ophthalmopathy——Teprotumumab-trbw / 国际眼科杂志(Guoji Yanke Zazhi)

Teprotumumab-trbw,a monoclonal antibody that acts on the insulin growth factor-Ⅰ receptor, was approved in 2020 for the treatment of thyroid-associated ophthalmopathy, but little is known about it in China. It is hoped to provide guidance for clinical use through the review of its molecular structure, pharmacokinetics, therapeutic mechanism, clinical research and safety. It inhibits immune inflammation by blocking thyroid-stimulating hormone receptor /insulin growth factor-Ⅰ receptor crosstalk signaling, so as to reduce the production of hyaluronic acid and inflammatory factors in response. It can also promote the apoptosis of retro-orbital fibroblasts/adipocytes and inhibit the expression of genes related to the synthesis of thyroid hormones, thereby significantly improving the clinical symptoms such as exophthalmos and diplopia. The common adverse reactions of Teprotumumab-trbw are muscle spasm, hyperglycemia, hearing loss and so on. Teprotumumab-trbw is effective and durable in the treatment of thyroid-associated ophthalmopathy, and patients with secondary treatment can also benefit from it, which provides a new way and hope for the treatment of thyroid-associated ophthalmopathy.

Clinical evaluation of lacrimal gland parameters in patients with thyroid-associated ophthalmopathy using orbital magnetic resonance imagining / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the lacrimal gland parameters and their correlation with clinical examination in patients with thyroid-associated ophthalmopathy(TAO)using orbital magnetic resonance imaging(MRI).METHODS: A total of 38 patients(76 eyes)with TAO were selected as case group, and 26 patients(52 eyes)who matched the gender and age with case group and volunteered to accept examination were selected as normal control group. Patients in case group were categorized into active TAO group and inactive TAO group according to the modified clinical activity score(CAS). The exophthalmos was evaluated on T1WI after obtaining the MRI images, the longest lacrimal gland length, width, and the biggest area in axial and coronal images were evaluated on T2WI, and the maximum T2 value and mean T2 value of the lacrimal gland were recorded.RESULTS: There were no significant differences in age, gender and exophthalmos between active TAO and inactive TAO(P&#x0026;#x003E;0.05). The area of lacrimal gland was higher in active TAO than that in inactive TAO, and was higher in inactive TAO than that in control group in coronal and axial section(all P&#x0026;#x003C;0.01). The length of lacrimal gland in coronal and axial section was higher in the active TAO than that in the inactive TAO and the control group(all P&#x0026;#x003C;0.05). The width of lacrimal gland in coronal and axial section was higher in active TAO and inactive TAO than that in the control group(all P&#x0026;#x003C;0.05). The maximum T2 value in the active TAO was higher than that in the inactive TAO and control group, and the inactive TAO was higher than that in the control group(all P&#x0026;#x003C;0.05). The average T2 value in the active TAO was higher than that in the inactive TAO and control group(all P&#x0026;#x003C;0.05). CAS was positively correlated with lacrimal gland area in axial, coronal section and maximum T2 value(all P&#x0026;#x003C;0.01).CONCLUSION: The lacrimal gland is significantly enlarged in patients with TAO, especially in active TAO. The lacrimal gland area in axial, coronal section and maximum T2 value could be potentially utilized as valuable radiographic biomarkers for the activity of TAO.

Gut microbiota and thyroid-associated ophthalmopathy / 中南大学学报(医学版)

Thyroid-associated ophthalmopathy(TAO)is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults.Due to the complex clinical manifestations and prolonged course,TAO seriously affect the physical and mental health of patients.The pathogenesis of TAO has not been fully elucidated and the treatment lacks specificity.Therefore,in-depth research on the pathogenesis of TAO is to find effective treatments.In recent years,studies have suggested that there is gut microbiota disorder in TAO,and the risk factors of TAO can promote gut microbiota disorder.Disordered gut microbiota can participate in the occurrence and development of TAO via influencing T cell differentiation,mimicking autoantigens,and influencing host non-coding RNA expression.Modulating the gut microbiota also has therapeutic effects on TAO and is a promising therapeutic approach.

Discussion on the Treatment of Thyroid associated ophthalmopathy from"Liver Opens at the Eyes"Based on the Imbalance of"Th17/Treg" / 世界科学技术-中医药现代化

Thyroid associated ophthalmopathy(TAO)is a refractory disease,which is related to Th17/Treg cellular immune imbalance."liver opens at the eyes"is a systematic summary of the theories of liver disease affecting the eye and eye disease affecting the liver in traditional Chinese medicine,which can guide the clinical diagnosis and treatment of TAO in traditional Chinese medicine.Studies have shown that the treatment of TAO from the perspective of"liver opens at the eyes"can regulate the immune imbalance of Th17/Treg cells to a certain extent,so as to achieve the purpose of disease prevention and treatment.This paper discusses the role of Th17/Treg cellular immune imbalance in TAO,from the aspects of Th17/Treg imbalance promoting the occurrence and development of TAO,the role of"liver opens at the eyes"theory in the etiology and pathogenesis of TAO,and the consistency between"liver opens at the eyes"physiology and Th17/Treg immune balance.In order to reveal the scientific connotation of traditional Chinese medicine in preventing and treating TAO by regulating Th17/Treg imbalance.

Dedifferentiation and regulation mechanism of TNF-α on orbital fibroblasts in thyroid-associated ophthalmopathy / 中华实验眼科杂志

Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.

Progress in the treatment of thyroid-associated ophthalmopathy with teprotumumab / 中华实验眼科杂志

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease of complex etiology and pathogenesis, which can cause a variety of ocular manifestations and even threaten vision.Glucocorticoids are often used as the first-line treatment in the clinic, but some patients become resistant to them.The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in the development of TAO.Teprotumumab is an anti-IGF-1R monoclonal antibody that can specifically bind to the IGF-1R and block its binding to the α-subunit of IGF-1 to exert biological effects.Clinical trials have shown that teprotumumab has good efficacy in reducing proptosis (decrease≥2 mm) and inflammatory activity (CAS decrease≥2 points) of active moderate-to-severe TAO.Most side effects are mild or moderate.Hyperglycemia is currently an identifiable adverse event associated with teprotumumab that can be controlled with medication.Pregnancy and inflammatory bowel disease are contraindications for teprotumumab due to its teratogenicity to the fetus and its ability to severely exacerbate inflammatory bowel disease.The US FDA has officially approved teprotumumab for the treatment of active moderate-to-severe TAO in January 2020.This article reviews the progress of clinical trials on the mechanism, efficacy and safety of teprotumumab in the treatment of TAO.

Rapamycin restores CD4 + T cell subsets imbalance in Graves′ ophthalmopathy mice model / 中华内分泌代谢杂志

Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.

Interleukin-6 mediates the association of low density lipoprotein-cholesterol with thyroid associated ophthalmopathy / 中华内分泌代谢杂志

Objective:To investigate the mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Construction of predictive ceRNA network and identification of the patterns of immune cells infiltrated in Graves ' ophthalmopathy / 中南大学学报(医学版)

OBJECTIVES@#Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO.@*METHODS@#The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software.@*RESULTS@#A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8+ T cells and CD4+ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5.@*CONCLUSIONS@#This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4+ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.