Triglyceride-driven pathogenesis in thyroid-associated ophthalmopathy: a dual approach of clinical correlation and genetic causality.

Objective: To explore the application value of 99Tcm-diethylenetriaminepentaacetic acid (DTPA) orbital single photon emission computed tomography/computed tomography (SPECT/CT) in staging evaluation of thyroid associated ophthalmopathy (TAO). Methods: A case-control study. A total of 40 patients with binocular TAO were recruited from May 2019 to December 2019 in the Second Hospital of Dalian Medical University. According to the clinical activity score (CAS) standard, 40 TAO patients were divided into the active group (15 cases) and the inactive group (25 cases), and 10 healthy volunteers were recruited as the control group. All subjects underwent 99Tcm-DTPA orbital SPECT/CT examination, and each subject's CAS, reading results and maximum standardized uptake value (SUVmax) were recorded. The Kruskal-Walis H test was used for the CAS comparison among the three groups. The analysis of variance was used for the SUVmax comparison among the three groups. The comparison between CAS and SUVmax before and after treatment was performed by paired samples Wilcoxon signed rank test and paired-sample t test, and Spearman correlation analysis was performed between SUVmax and CAS. The Kappa test was used to check the consistency between the reading result and CAS's judgment of TAO activity. The receiver operating characteristic curve was used to analyze the diagnostic value of the reading results and SUVmax for TAO. Results: The age difference among the three groups was not statistically significant, and the gender difference was not statistically significant (all P>0.05). The difference in CAS among the three groups was statistically significant (H=39.894; P<0.01). Patients with active TAO showed abnormal concentration and enhancement of nuclides in the orbital tissue, and the uptake of radionuclides was significantly increased, while patients with inactive TAO had a slight increase, and healthy volunteers had no significant or only mild uptake. The SUVmax of the active group (2.24±0.47) was highest, and that of the inactive group (1.57±0.43) was higher than the healthy control group (0.67±0.22). After pairwise comparison, there were statistical differences between groups (all P<0.05). According to Spearman correlation analysis, the SUVmax of all TAO patients was linearly, positively correlated with their CAS (r=0.753; P<0.05). In assessing the clinical activity of TAO, the reading results were consistent with CAS (Kappa value=0.737; P<0.05). Taking the reading results as the standard, the area under the receiver operating characteristic curve (AUC) of SUVmax was 0.992, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 86.70% and a specificity of 76.00%. Taking CAS results as the standard, the AUC of SUVmax was 0.853, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 100.00% and a specificity of 87.50%. Five patients had inconsistent SUVmax and CAS. The CAS was ≥3, but the orbits did not show any inflammatory lesions in two of them; the CAS was<3, but the orbits showed inflammatory lesions in three of them. Thirteen active TAO patients with 99Tcm-DTPA orbital SPECT/CT showing significant accumulation of nuclides were given hormone shock therapy 12 times. After treatment, the CAS 2.00 (2.00) was lower than the pre-treatment 3.00 (1.50) score, and the difference was statistically significant (Z=-3.100, P<0.01). The SUVmax after treatment (1.60±0.20) was lower than the pre-treatment value (2.17±0.34), and the difference was statistically significant (t=10.197, P<0.01). Conclusion: 99Tcm-DTPA orbital SPECT/CT can relatively accurately determine the state of orbital inflammation in patients with TAO, and can be used as a useful supplement to evaluate the clinical activity of TAO, helping to guide clinical treatment. (Chin J Ophthalmol, 2021, 57: 830-836).

Objective To explore the value of magnetic resonance fat quantification technology (MR mDixon-quant) in evaluating thyroid-associated ophthalmopathy (TAO) activity. Methods Case control study was performed.Fifty patients (100 eyes) with TAO which met Mourits criterion were enrolled from September 2016 to March 2018 in Ningxia Hui Autonomous Region People's Hospital.The TAO patients were grouped by clinical activity score (CAS). Twenty nine patients (58 eyes) with CAS≥3 served as TAO active group, twenty one patients (42 eyes) with CAS<3 served as TAO non-active group.Twenty three healthy subjects (46 eyes) were collected as normal control group at the same time.All subjects underwent orbital MR mDixon-quant and MR imaging.Orbital fat content (FF values) and exophthalmus was calculated on MR work-station.FF values and degree of exophthalmus were analyzed by analysis of variance.The correlation of FF values and CAS in TAO patients was conducted by Spearman rank correlation analysis.The cut-off values of FF in predicting TAO activity was determined by receiver operating characteristics (ROC) curve.The Kappa consistency test was chosen to assess the consistency of CAS and FF values.Intraclass correlation coefficient (ICC) were used to analyze the intra-observer and inter-observer repeatability of the FF values and the degree of exophthalmus.This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region People's Hospital (No.20160718). All the candidates signed informed consent. Results The FF values were (85.190±4.346)%, (88.715±5.686)% and (82.345±5.445)% in TAO active group, TAO inactive group and normal control group, respectively, with a significant difference among the 3 groups (F=17.072, P<0.001). The FF values of TAO active group and TAO inactive group were significantly higher than that of control group, and the FF value of TAO active group was significantly lower than that of TAO inactive group (all at P<0.01). The degrees of exophthalmos were (20.221±1.714), (20.855±2.103) and (15.363±1.667)mm in TAO active group, TAO inactive group and normal control group, respectively, with a significant difference among the three groups (F=126.298, P<0.01). The degrees of exophthalmos in TAO active group and TAO inactive group were significantly higher than that in normal control group (both at P<0.01), there was no statistical difference in degrees of exophthalmos between TAO active group and TAO inactive group (P<0.05). Spearman rank correlation revealed that FF value was negative correlated with CAS (rs=-0.443, P<0.01). The cut-off value of FF value was 87.180%, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 74.14%(43/58), 66.67%(28/42), 75.44%(43/57), 65.12%(28/43) and 71.00%(71/100), respectively.There were consistencies of FF values with the CAS (Kappa=0.431, P<0.001). The intra-observe and inter-observer reproducibility were fairly good for FF value (ICC=0.953, 0.920) and degree of exophthalmus (ICC=0.935, 0.917). Conclusions MR mDixon-quant can quantitative measure orbital fat with good measurement repeatability.Fat quantification technology by MR is valuable in evaluating TAO activity. Key words: Thyroid-associated ophthalmopathy; mDixon-quant; Fat quantification; Activity

Objective To evaluate visual quality and related factors in patients with thyroidassociated ophthalmopathy (TAO).Methods This was a prospective case-control study.A total of 38patients (72 eyes) with TAO and 35 healthy adults (70 eyes) underwent testing with OQAS Ⅱ,which uses a double-pass technique to evaluate the modulation transfer function (MTF),objective scatter index (OSI) and visual acuity at different contrast sensitivities (100％,20％,9％).Some clinical data was recorded in the patients with TAO,including best corrected visual acuity (BCVA),the disease duration,clinical activity scores (CAS),NOSPECS,proptosis,smoking habits,etc.Data were statistically analyzed with an independent samples t test,pearson or Spearman correlation analysis and a multiple regression analysis.Results The visual quality of patients with TAO showed decreases,with lower MTF (TAO 29.35±11.65,controls 42.97±7.38,t=-8.344,P＜0.01),higher OSI (TAO 0.89±0.84; controls 0.33±0.14,t=5.551,P＜0.01),lower VA100％ (TAO 0.96±0.40,controls 1.43±0.25,t=-8.522,P＜0.01),lower VA20％ (TAO 0.70±0.31,controls 1.05±0.26,t=-7.269,P＜0.01),and lower VA9％ (TAO 0.42±0.18,controls 0.64±0.19,t=-6.948,P＜0.01).The MTF in patients with TAO was correlated significantly with age,CAS,NOSPECS,proptosis,palpebral fissure height,intraorbital pressure and smoking (r=-0.281,-0.485,-0.489,-0.277,-0.469,-0.332,-0.502,P＜0.05).OSI in patients with TAO was correlated significantly with age,CAS,NOSPECS,intraorbital pressure and smoking (r=0.368,0.476,0.418,0.268,0.535,P＜0.05).There were no statistically significant differences in MTF or OSI for BCVA,duration of disease,thyroid function,intraocular pressure,diplopia or average amount of sleep.Multiple regression analysis revealed that CAS,NOSPECS,smoking and palpebral fissure height are risk factors for the MTF (R2=0.497,F=16.567,P＜0.01),while CAS and smoking were risk factors for OSI (R2=0.405,F=23.501,P＜0.01).Conclusion Visual quality of patients with TAO is reduced,with higher OSI,lower MTF,VA100％,VA20％ and VA9％.MTF is negatively correlated with CAS,NOSPECS,proptosis,palpebral fissure height,intraorbital pressure and smoking,while OSI is positively correlated with CAS,NOSPECS,intraorbital pressure and smoking.CAS,NOSPECS,palpebral fissure height and smoking are significant risk factors for the MTF (R2=0.497,F=16.567,P＜0.01); CAS and smoking are significant risk factors for the OSI (R2=0.405,F=23.501,P＜0.01). Key words: Thyroid associated ophthalmopathy; Visual quality; Double-pass technique ; Related factors

Purpose: To evaluate the clinical features of dry eye in thyroid-associated ophthalmopathy (TAO) according to disease activity and analyze the related factors. Methods: This study included 157 patients diagnosed with TAO and dry eye between March 2009 and March 2015. According to the clinical activity score (CAS), TAO patients were divided into inactive (CAS < 3) and active (CAS ≥ 3) groups. Clinical features included age, sex, visual acuity, proptosis, palpebral fissure width, orbital computed tomography (CT) findings, thyroid hormones, and ocular surface parameters including tear film break-up time (TFBUT), Schirmer tests, keratoepitheliopathy scores, and ocular surface disease index (OSDI) were obtained and compared between the groups. In addition, correlations between clinical features and ocular surface parameters were analyzed in both groups. Results: In the inactive and active TAO groups, CAS was 1.24 ± 0.69 and 4.23 ± 1.13, respectively (p = 0.001). Thyrotropin-binding inhibitory immunoglobulin was significantly higher in the active TAO group than in the inactive TAO group (p = 0.048). On orbital CT, extraocular muscle hypertrophy was more common in the active TAO group than the inactive TAO group (p = 0.020). No significant difference was found in age, sex, visual acuity, free T4, and thyroid-stimulating hormone between the two groups. During analysis of the tear film and ocular surface parameters, TFBUT (p = 0.006) was shorter and OSDI score (p = 0.028) was higher in the active TAO group than the inactive TAO group. TFBUT was negatively correlated with proptosis (r = -0.432, p = 0.001; r = -0.308, p = 0.032) and palpebral fissure width (r = -0.367 p = 0.012; r = -0.312, p = 0.031) in both groups. OSDI was positively correlated with proptosis in the active TAO group (r = 0.301, p = 0.033). Conclusions: TFBUT was shorter and OSDI score higher in dry eye patients with active TAO than in patients with inactive TAO. The TFBUT was negatively correlated with proptosis and palpebral fissure width in both groups. J Korean Ophthalmol Soc 2016;57(7):1037-1043

To explore the serum lipids levels in healthy pregnant women, and to establish the reference intervals of serum lipids in middle and late pregnancy. Triglyceride (TG), total cholesterol (TCH), high density lipoprotein (HDL), low density lipoprotein (LDL), apo-lipoprotein-A(APO-A) and apo-lipoprotein-B (APO-B) were measured in 3 200 pregnant women and 3 200 healthy women of childbearing age(the control group) from January 2014 to Febuary 2015 in Obstetrics and Gynecology Hospital of Fudan University. In the healthy pregnant women, serum lipids were measured at 14-20, 24-28 and 37-40 gestational weeks, respectively. All the parameters were detected by Hitachi 7180 automatic biochemical analyzer. The test results were calculated and determined by the C28-A3 standard of the National Clinical and Laboratory Standards Institute. And the normal reference intervals of serum lipids in middle and late pregnancy were defined as 2.5%-97.5%. (1) The levels of TG, TCH, HDL, LDL, APO-A and APO-B in the control group were 0.8, 4.2, 1.0, 2.7 mmol/L and 1.1, 0.8 g/L, respectively. The levels of TG, TCH, HDL, LDL, APO-A and APO-B in middle and late pregnancy were significantly higher than those in the control group (P<0.05). (2) The serum lipids levels at 14-20, 24-28 and 37-40 gestational weeks in healthy pregnant women were compared with the control group as following. The TG levels were 1.9, 3.8 and 4.4 folds of the control group; the TCH levels were 1.1, 1.5 and 1.5 folds of the control group; the HDL levels were 1.2, 1.6 and 1.5 folds of the control group; the LDL levels were 1.1, 1.4 and 1.4 folds of the control group; the APO-A levels were 1.3, 1.4 and 1.5 folds of the control group; and the APO-B levels were 1.1, 1.5 and 1.5 fold of the control group respectively. The TG level was the most increased, and it increased gradually with gestational age (P<0.01). (3) The median of LDL to HDL cholesterol ratio in the healthy pregnancy group at 14-20, 24-28 and 37-40 gestational weeks were 2.7, 2.5, 2.6, respectively, which were significantly lower than that of the control group (2.8; P<0.05). (4) Reference intervals of serum lipids at 14-20, 24-28 and 37-40 gestational weeks in healthy pregnant women were as following. The TG levels were 0.7-3.9, 1.7-6.3 and 1.6-8.1 mmol/L, respectively; the TCH were 3.3-6.9, 4.3-8.3, 4.3-8.7 mmol/L, respectively; the HDL were 0.8-1.8, 1.0-2.1 and 1.0-2.1 mmol/L, respectively; the LDL were 2.1-4.5, 2.7-5.1 and 2.6-5.2 mmol/L, respectively; the APO-A were 1.1-1.8, 1.2-1.9 and 1.1-2.4 g/L, respectively; and the APO-B were 0.6-1.4, 0.9-1.8 and 0.8-2.1 g/L, respectively. The LDL/HDL ratios were 2.3-3.1, 2.2-2.9 and 2.1-3.0, respectively. Serum lipids increased physiologically with gestational age in middle and late pregnancy. The establishment of reference intervals for serum lipids in pregnancy will help to distinguish abnormal serum lipid levels in middle and late pregnancy.

Objective: To compare the differences in the central macular choroidal thickness (CMCT) between thyroid-associated ophthalmopathy (TAO) patients in active and inactive stages, and the healthy subjects used spectral-domain optical coherence tomography (SD-OCT) and assess the potential of using CMCT as an indicator for follow-up of TAO patients. Methods: Cross-sectional study. Eleven active stage TAO patients (22 eyes, active TAO group) and 21 inactive stage TAO patients (42 eyes, inactive TAO group) who received treatment at the Department of Ophthalmology, First People's Hospital of Nantong during January 2015 and December 2017 were enrolled. Twenty-three healthy subjects (46 eyes) with comparable ages to the two TAO groups were enrolled in the healthy control group. TAO activity was assessed using the TAO clinical activity score (CAS) system. All subjects underwent best corrected visual acuity, slit lamp examination, Goldmann tonometer for intraocular pressure measurement, direct ophthalmoscopy, A-superelocular measurement, ocular protrusion measurement, and SD-OCT detection of CMCT. The variance analysis was used to compare the differences of intraocular pressure, eyeball protrusion and CMCT between the three groups. The correlation between CMCT and various clinical indicators was analyzed by univariate linear regression analysis and multivariate linear regression analysis. Results: The intraocular pressure and eyeball protrusion indicators of the active TAO group, the inactive TAO group, and the control group were (20.16±3.49) mmHg (1 mmHg=0.133 kPa) and (18.68±1.64) mm, (15.42±2.49) mmHg and (15.64±1.01) mm, (15.72±2.38) mmHg and (12.02±0.83) mm, respectively. The intraocular pressure and ocular protrusion of the active TAO group were higher than those of the inactive TAO group and the healthy control group, the differences between the groups are of statistical significance (all P<0.001). The CMCT value of the active TAO group, the inactive TAO group and the healthy control group were (391.27±33.89) μm, (317.31±29.62) μm, and (304.26±42.26) μm, respectively. The CMCT of the active TAO group was significantly higher than the inactive group and the healthy control group, the differences between the groups are of statistical significance (all P<0.001). Based on univariate analysis, thicker CMCT was significantly associated with intraocular pressure (t=4.600, P<0.001); after correction of intraocular pressure, thicker CMCT was significantly associated with CAS (β=0.848, 95%CI 15.608-21.499, P<0.001). Multivariate analysis showed a correlation between thicker CMCT and CAS scores (P<0.001), thyroid function (P<0.001), and intraocular pressure(P=0.039). Conclusions: The CMCT in the eyes of active TAO patients is higher than that of the inactive TAO patients and healthy people. The CMCT examination is of referential value, and may be used as a tool for assessing the activity of lesions in patients with TAO and clinical follow-up. (Chin J Ophthalmol, 2018, 54: 688-693).

Low serum levels of high-density lipoprotein (HDL) are commonly encountered in patients with coronary artery disease (CAD). An example of this type of patient is a 42-year-old white man with a history of sudden-onset angina secondary to a 90% obstructive lesion along the proximal left anterior descending coronary artery. The family history was significant for his father, who died of a myocardial infarction (MI) at age 44 years. The patient underwent percutaneous transluminal angioplasty with stenting but developed in-stent restenosis. He underwent cutting balloon angioplasty and brachytherapy and was asymptomatic for approximately 6 months. The stent then developed a high-grade occlusion with recurrence of angina, and the patient required single-vessel bypass surgery. The patient’s baseline serum lipid profile revealed low-density lipoprotein (LDL) 128 mg/dL, HDL 27 mg/dL, and triglycerides 92 mg/dL. His lipoprotein(a), C-reactive protein, and homocysteine levels were normal. He was not hypertensive, had no impairment of glycemic control, and did not smoke. With a combination of simvastatin 40 mg and niacin (Niaspan; Kos Pharmaceuticals) 1000 mg daily, the patient’s lipid profile improved, with LDL 78 mg/dL, HDL 43 mg/dL, and triglycerides 60 mg/dL. Follow-up stress testing demonstrated normal myocardial perfusion, and the patient has been asymptomatic for 2 years. With few exceptions, low HDL is an independent risk factor for CAD in case-control and prospective observational studies. In contrast, high HDL levels are associated with longevity and are protective against the development of atherosclerotic disease. In the Framingham Study, risk for CAD increases sharply as HDL levels fall progressively below 40 mg/dL.1 In the Quebec Cardiovascular Study, for every 10% reduction in HDL, risk for CAD increased 13%.2 Many clinicians believe that low HDL is associated with increased CAD risk because it is a marker for hypertriglyceridemia and elevated remnant particle concentrations. The Prospective Cardiovascular Munster …

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.

Objective To explore the distribution of serum TRAb IgG subtypes in patients with thyroid-associated ophthalmopathy(TAO) at different stages and its value in assessing TAO activity. Methods Forty-three patients with TAO, 30 patients with Graves′ disease (GD group), 19 patients with Hashimoto′s thyroiditis (HT group), and 50 healthy subjects (NC group)admitted to the First Affiliated Hospital of Zhengzhou University were collected from August 2018 to February 2019. According to the clinical activity score (CAS), the patients with TAO were further divided into the active period group (AP group, CAS≥3 points, 22 cases) and the inactive period group (IP group, CAS<3 points, 21 cases). The basic clinical data of subjects in each group were collected. The serum concentrations of FT3, FT4, TSH, thyroperoxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid-stimulating hormone receptor antibody (TRAb) were detected by chemiluminescence immunoassay and the binding rate in percentage (B) of serum TRAb IgG and IgG subtypes were detected by ELISA. The positive rate in each group and relative content of positive samples were compared. Results (1)Compared with HT group, the positive rates of IgG1 and IgG2 in TAO group and GD group were significantly decreased (P 0.05). (2)Compared with the IP group, IgG1(B) and the positive rates of IgG1 in the AP group were increased while IgG4(B) and the relative contents of IgG4 were reduced (P<0.05). (3)IgG1(B)was positively correlated with TAO activity (B=6.190, P=0.007), and higher IgG4(B)indicated more inclinations to the inactive period (B=-16.390, P=0.052). (4) The area under the curve of receiver operating characteristic (ROC) for TAO developing into active period assessed by activity rate was 0.859 (95%CI 0.746-0.973, P<0.05). When the activity rate was 4.29, the Jordon index showed the largest, with sensitivity of 81.8% and specificity of 81.0%. Conclusions Elevated levels of TRAb IgG1 in the patients with TAO indicate a tendency to active period, while elevated levels of TRAb IgG4 indicate a tendency to inactive period. The activity rate can provide a reference for assessing whether TAO is active or not. Key words: Thyroid-associated ophthalmopathy; IgG subtype; Clinical activity score

To compare diagnostic value of 4 kinds of target-to-nontarget ratio (T/NT), and to choose a better one to assess thyroid associated ophthalmopathy (TAO) activity. Methods: The clinical data were collected for 29 newly-diagnosed patients (58 eyes) with TAO who underwent orbital 99mTc-DTPA single photon emission computed tomography/computed tomography (SPECT/CT) fusion images according to the clinical activity score (CAS). They were divided into an active group (18 cases, 36 eyes), an inactive group (11 cases, 22 eyes), and a control group (9 cases, 18 eyes). Diagnostic value of orbital/occipital lobe radioactive uptake count ratio (T/NT1), orbital/occipital radioactive uptake count ratio (T/NT2), orbital/thalamus radioactive uptake count ratio (T/NT3), and orbital/cerebellar radioactivity uptake count ratio (T/NT4) were calculated, and the CAS of Spearman rank correlation and receiver operating characteristic (ROC) curve were analyzed. Results: T/NT1, T/NT2 and CAS were correlated (r1=0.873, r2=0.527; P<0.001), with the better correlation between T/NT1 and CAS and there was no correlation between T/NT3, T/NT4 and CAS (r3=0.039, r4=0.090; P>0.05). Area under the ROC curve of T/NT1 was 0.860, area under the ROC curve of T/NT2 was 0.581, and the accuracy for T/NT1 on TAO activity was good. T/NT1=9.74 could be used as active threshold for judge of TAO in patients. Conclusion: There is a good correlation between T/NT1 and CAS. TAO activity assessment possesses high diagnostic value, and SPECT/CT together with imaging anatomical location is more accurate.

Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.

ObjectiveThis prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO).Materials and MethodsA total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO.ResultsPatients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively; all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001).ConclusionMTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

To investigate the levels of seven inflammatory cytokines and one chemokine in tears of patients with thyroid-associated ophthalmopathy (TAO) and asymptomatic control subjects, and determine the correlations between tear inflammatory mediators and clinical parameters. Prospective observational cohort study. The study involved 21 patients with TAO and ten asymptomatic controls. TAO patients were divided into active TAO and inactive TAO on the basis of 7-point modified formulation of the clinical activity score (CAS). Ocular Surface Disease Index (OSDI) score, tear film break-up time (BUT) was obtained, and the Schirmer test and fluorescein staining were performed in all participants. Ten microliters of tears were collected for analysis the concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, IL-17 interferon (IFN)-γ, tumor necrosis factor (TNF)-α and one chemokine (IL-8) by multiplex bead analysis. Fluorescein staining scores were higher, BUT scores were shorter, and Schirmer test scores were lower in patients with active TAO and inactive TAO than in control subjects. IL-1β, IL-6, and IL-8 concentrations in tears were significantly higher in active TAO than inactive TAO and the controls. TNF-α concentration was significantly higher in both active and inactive TAO compared with the controls. IL-17 was significantly higher in active TAO than the controls, and the level of IL-2 was significantly higher in inactive TAO compared with the controls. There were significantly positive correlations between tear IL-1β, IL-6 and IL-8 levels and CAS in TAO. No significant correlations were found between other cytokine concentrations and clinical parameters in TAO. The differences of tear inflammatory cytokines between patients with active and inactive TAO indicated that orbital inflammation may be involved in the ocular surface damage of TAO.

Dietary recommendations are a key element in the management of cardiovascular disease. Evidence is mounting that certain dietary patterns can influence cardiovascular health by modifying risk factors such as obesity, dyslipidemia, and hypertension, as well as factors involved in systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiac rhythm.1,2 In recent years, numerous dietary fads have emerged, in part as a response to the rising prevalence of obesity in the United States.3 In the present study, we review the various dietary portfolios that have emerged in the literature and the major studies that investigated their effectiveness in modifying cardiovascular risk. Currently, the typical American diet is estimated to derive 49% of its calories from carbohydrates, 34% from fat, and 12% to 16% from protein.4 Proposals to alter the proportions and/or types of macronutrients in this diet have been made for weight loss and cardiovascular health (Table 1).5–12 For weight management, for example, the strategy recommended by most medical groups entails the intake of a low-calorie, low-fat diet. The concept of fat restriction for weight management stems from traditional calorimetric measurements, which assign greater energy values to fat (&9 kcal/g) and less to carbohydrate and protein (&4 kcal/g). The low-calorie concept, on the other hand, is an intuitive technique to induce negative energy balance and has been adopted by some commercialized weight loss programs such as Weight Watchers International. View this table: TABLE 1. Various Dietary Patterns, Including Those Popularized Commercially and Those Investigated by Observational Studies and Clinical Trials One alternative proposed for weight loss is the low-carbohydrate diet. This was first described by William Banting13 in the 1860s and recently has received much attention in the form of the Atkins’, Stillman, Protein Power Lifeplan, and Zone diets. The Atkins’ diet begins with a weight-loss …

Objective To investigate the efficacy of 99Tcm-Octreotide Scintigraph in directing the treatment of thyroid associated ophthalmopathy (TAO) with periocular injection of Octreotide or Triamcinolone Acetonide. Methods Of 71 patients with active TAO (clinical activity score (CAS) ≥3 and positive 99Tcm-Octreotide Scintigraph) were divided into two groups treated with Octreotide (Octreotide Group, 21 cases) or Triamcinolone Acetonide (Triamcinolone Acetonide Group, 50 cases), respectively. And 12 normal volunteers were enrolled as the control. CAS score, 99Tcm-Octreotide Scintigraph and uptake ratio (UR) were detected before and after the treatment. Exophthalmometry measurements, intraocular pressure and TAO related ocular signs, including von-Graeve's sign, Dalrymple's sign and Eniroth's sign were recorded during the treatment. The incidence of adverse reactions was also evaluated. Results Before treatment, the patients UR levels were significantly higher than the control (F =22.517, P ＜0.001) and no difference was found between Octreotide Group and Triamcinolone Acetonide Group (P ＞0.05). After treatment, the UR levels in patients were decreased significantly (toT=5.31, P ＜0.01; tTA=4.34, P ＜0.01), and approximate to the normal (P ＞0.05). Accordingly, the patients CAS scores were obviously declined after treatment (toT=4.21, P ＜0.01; tTA=3.89, P ＜0.01). In addition, exophthalmia was obviously alleviated after treatment (Octreotide Group: 3.48 mm; Triamcinolone Acetonide Group: 2.61mm). As to the TAO related ocular signs, only the occurrence of Eniroth's sign showed a substantial decline in Octreotide Group (χ2=11.958, P ＜0.01). While, all signs fiequency, including von-Graeve's, Dalrymple's and Eniroth's signs were significantly declined in Triamcinolone Acetonide Group (X 2: 32.19, 41.36 and 26.27, P ＜0.01). The intraocular pressure showed no obvious change in both treated groups. But higher fiequency of adverse reactions were found in Triamcinolone Acetonide Group compared with Octreotide Group (X 2=5.396, P ＜0.05). Conclusions 99Tcm-Octreotide Scintigraph plays a critical role in evaluating the clinical activity of TAO. The patients with positive 99Tcm-Octreotide Scintigraph show better therapeutic efficacy of Octreotide or Triamcinolone Acetonide. Both drugs decrease the exophthalmia degree without elevating the intraocular pressure. Compared with Octreotide, Triamcinolone Acetonide could more efficiently invert the ocular signs, but with higher frequency of adverse reactions. Key words: Thyroid associated ophthalmopathy; Receptors; Technetium; Octreotide; Somatostatin analogues