Radiotherapy for Nonmalignant Eye Diseases: Graves' Ophthalmopathy - Pseudotumor Orbitae.

Objective: To investigate the association between lipid levels and the risk of Graves' ophthalmopathy (GO). Methods: This study employed Mendelian randomization (MR) with a retrospective cross-sectional analysis. Summary data for lipids and GO were obtained from the genome-wide association studies (GWAS) released between 2013 and 2023, and two-sample MR was used to explore the causal relationship between lipids and GO. Inverse-variance weighting (IVW) served as the primary estimator, with MR-Egger regression and the weighted median (WM) as auxiliary methods. A series of sensitivity analyses were conducted to ensure the validity and stability of the findings. In parallel, lipid data were collected from inpatients with GO and contemporaneous healthy controls in the Department of Ophthalmology, the Third Xiangya Hospital of Central South University, from April 2022 to November 2024, and differences in lipid levels were analyzed using independent-samples t tests and non-parametric tests. Results: In the forward MR analysis for HDL-C, two GWAS datasets were used. Both the ieu-b-109 data (OR=0.644,95%CI=0.388-1.070,P=0.089) and the ieu-b-4844 data (OR=1.349,95%CI=0.848-2.146,P=0.206) indicated that HDL-C had no significant causal association with the risk of GO. the low-density lipoprotein cholesterol (LDL-C) was evaluated using four GWAS data sources. The ieu-a-300 data (OR=0.686,95%CI=0.352-1.335,P=0.267), the ieu-a-781 data (OR=0.467,95%CI=0.116-1.886,P=0.285), the ieu-b-110 data (OR=0.734,95%CI=0.380-1.419,P=0.358), and the ieu-b-4846 data (OR=1.311,95%CI=0.634-2.714,P=0.465) were not statistically significant, and the effect directions were inconsistent, suggesting that LDL-C had no clear causal effect on the risk of GO. Triglycerides were evaluated using five data sources. The ieu-a-783 data (OR=1.101,95%CI=0.461-2.626,P=0.829), the ieu-b-4849 data (OR=0.657,95%CI=0.203-2.128,P=0.483), the ieu-b-4850 data (OR=1.144,95%CI=0.568-2.305,P=0.707), the met-d-Total_TG data (OR=1.630,95%CI=0.309-8.600,P=0.565), and the ukb-bub35-TRIG data (OR=0.906,95%CI=0.572-1.436,P=0.674) showed no causal association between triglyceride levels and the risk of GO. the total cholesterol was evaluated using the ieu-a-782 dataset (OR=0.672,95%CI=0.103-4.399,P=0.678), which suggested no significant causal effect on the risk of GO. The effect directions of all these analyses were consistent across IVW, MR-Egger, and WM methods, suggesting that the results were relatively robust. No clear causal relationship between lipids and GO was found. In the reverse MR analysis, no causal relationship was found between GO and HDL-C, triglycerides, or total cholesterol (P>0.05). Although the ieu-b-4846 data suggested a slight inverse association between Graves' ophthalmopathy and LDL-C (OR=0.983,95%CI=0.968-0.998,P=0.027), it was not significant after FDR correction (FDR=0.081). An observational study included 102 patients with GO, including 45 males (44.1%) and 57 females (55.9%), with an average age of 43.50 (33.00, 53.00) and a BMI of 23.55±3.50. There were 102 healthy controls, including 46 males (45.1%) and 56 females (54.9%), with an average age of 42.50 (34.00, 56.00) and a BMI of 23.20±3.67. The results showed no statistically significant differences in HDL-C (P=0.487), LDL-C (P=0.186), triglycerides (P=0.391), or total cholesterol (P=0.168) between the two groups. Conclusion: Both MR and observational studies indicate that lipid levels may not be significantly associated with the risk of GO. There is a need for large sample and in-depth clinical studies in China.

Drugs usually do not prevent extraocular muscle fibrosis in Graves’ ophthalmopathy (GO), and surgical treatment has complications and does not cure extraocular muscle fibrosis. Triptolide (TPL) has shown antifibrotic effects; however, the mechanism by which it treats extraocular muscle fibrosis in GO remains unclear. The aim of this study was to investigate the therapeutic effect and potential mechanism of TPL through a combination of network pharmacology and experimental validation. Network pharmacology identified 10 potential therapeutic targets, 1767 gene ontology terms, and 95 signaling pathways, including the PI3K/AKT pathway. Molecular docking revealed a strong affinity between core targets on the PI3K/AKT pathway and TPL. The experimental results showed that TPL inhibited the proliferation of OFs in vitro in a concentration-dependent manner. It significantly inhibited the expression of TGF-β1-induced fibrosis-related markers, such as FN, CTGF, α-SMA, and TIMP-1, while significantly down-regulating the expression of PI3K/AKT signaling proteins. The use of inhibitors of the PI3K/AKT pathway inhibited the expression of fibrosis-related markers. These findings suggest that TPL can resist extraocular muscle fibrosis in GO through multiple pathways, in which the PI3K/AKT pathway plays a key role.

BackgroundThis study aimed to describe and compare eyelid contours before and after orbital fat decompression in patients with Graves’ ophthalmopathy (GO) by measuring their midpupil lid distances (MPLDs).MethodsA retrospective comparative study of patients with GO who underwent orbital fat decompression was performed. Standard digital images of primary gaze were analyzed using a self-designed software. Radial MPLDs of the upper and lower eyelids were measured from 0° (nasal) to 180° (temporal) with 15° spacing. Pre- and postoperative MPLDs were compared and the relationship between MPLD changes and Hertel exophthalmometric value changes were analyzed. Eyelid contour symmetries were assessed using the nasal-to-temporal MPLD ratios.ResultsA total of 31 eyes from 17 patients and 25 eyes from 17 normal participants (control) were included. The mean postoperative Hertel value change was 3.8 ± 1.1 mm. After orbital fat decompression, MPLDs in the lower eyelids decreased, more significantly on the nasal sectors (nasal 30°, 45°, 60°, 75°, and 90°, p = 0.030, 0.024, 0.036, 0.040, and 0.042, respectively). Conversely, MPLDs slightly increased in the upper eyelids but was not statistically significant. Changes in MPLDs did not correlate with the extent of proptosis reduction.ConclusionsOrbital fat decompression effectively improves lower eyelid retraction in patients with GO, especially on the nasal sectors. This effect is independent from the amount of proptosis reduction. Upper eyelid contour remains unchanged after the surgery.

Disclosure: Z. Roe-Zurz: None. L. Madrigal: None.Graves’ ophthalmopathy (GO) is a serious complication of autoimmune hyperthyroidism, affecting approximately 30% of patients. It is characterized by immune-mediated inflammation of retro-orbital tissues, which can lead to sight-threatening complications. Recent evidence suggests that obesity and related metabolic factors—including hyperinsulinemia, insulin resistance (HOMA-IR), and elevated high-sensitivity C-reactive protein (hs-CRP)—are associated with both the presence and severity of GO. Here, we present a case of chronic GO that significantly improved following BMI reduction after sleeve gastrectomy. A 49-year-old woman with class III obesity and a complex thyroid disease history—including Graves’ ophthalmopathy (GO) previously managed with orbital decompression and lid surgery in 2012, as well as papillary thyroid carcinoma status post-thyroidectomy with post-ablative hypothyroidism—presented in the Fall of 2023 with progressive frontal headaches, orbital pain, and upward gaze diplopia. Examination revealed proptosis, lateral lid fullness, and 1+ scleral show. Hertel ophthalmometry, which measures the distance between the corneal apex and lateral orbital rim, showed slight, but objective, progression to 25/25 mm at a 105 mm base. Orbital CT demonstrated asymmetric enlargement of the medial and inferior rectus muscles with bilateral proptosis. Her TSH and free T4 were within normal limits, and thyroglobulin antibodies were undetectable.Despite multiple obesity therapies, including daily liraglutide, her ocular symptoms worsened over several months. She was referred for bariatric surgery, and following a postoperative BMI reduction from 35 to 30, her ocular symptoms rapidly improved. Hertel measurements returned to baseline at 23/23 mm and later improved further to 17/17 mm at a 105 mm base.Understanding how obesity and its associated factors—particularly its pro-inflammatory state—influence the pathophysiology and progression of GO may help define metabolic and weight-loss management for Graves’ disease and other autoimmune disorders. While we hypothesize that a reduction in systemic inflammation, rather than direct orbital fat loss, contributed to our patient’s improvement in her thyroid orbitopathy, this case presents an intriguing possibility that warrants further investigation.Presentation: Monday, July 14, 2025

Background: In managing active, moderate-to-severe Graves' Ophthalmopathy (GO), a notable gap often exists between treatment efficacy in controlled trials and effectiveness in real-world practice. High-dose corticosteroids are standard, but the choice between intravenous (IV) and oral routes involves a complex trade-off between efficacy, tolerability, and practicality, particularly in diverse populations. Methods: This single-center, pragmatic, prospective cohort study was conducted at a tertiary hospital in Indonesia from March 2023 to March 2024. Thirty-six GO patients were treated with either IV pulse or daily oral methylprednisolone based on a shared clinical decision-making process. The primary outcome was the change in proptosis. To address the non-randomized design and control for selection bias, a propensity score-adjusted Analysis of Covariance (ANCOVA) was used to compare treatment effectiveness. Results: Baseline analysis revealed that patients selected for IV therapy had significantly more severe proptosis. Both unadjusted and adjusted analyses showed that each regimen resulted in a significant reduction in proptosis from baseline (p < 0.01). In the primary, propensity score-adjusted analysis, no statistically significant difference was detected in the degree of proptosis reduction between the IV and oral groups. However, the tolerability profiles were profoundly different; patients in the oral group experienced a significantly higher incidence of adverse events, including dyspepsia (66.7%) and Cushingoid features (55.6%), compared to a single case of transient hypokalemia in the IV group. Conclusion: In this real-world setting, after statistically controlling for baseline severity, both IV and oral methylprednisolone demonstrated comparable effectiveness in reducing proptosis. However, the intravenous route was associated with a vastly superior safety profile. These findings underscore the critical importance of tolerability in clinical decision-making and support the continued recommendation of IV pulse therapy as the first-line treatment.

Graves' ophthalmopathy (GO) is an autoimmune disorder marked by orbital inflammation and tissue remodeling, leading to irreversible disfigurement and vision loss. The current first‐line glucocorticoid therapy remains palliative, underscoring the critical need for mechanism‐based interventions. Autoantibodies against thyrotropin receptor (TSHR) in GO patients highlight its therapeutic potential, yet TSHR inhibitor development faces challenges, including low potency, off‐target effects, and mechanistic constraints. To overcome this therapeutic void, YC3, a TSHR‐targeting nucleic acid aptamer, has been developed through an innovative approach that combines protein‐targeting cell‐SELEX with functional selection. YC3 exhibits nanomolar affinity alongside robust pharmacodynamic efficacy. In vitro, YC3 significantly reverses thyroid‐stimulating antibodies (TSAbs)‐driven hyperactivation in primary human orbital fibroblasts, thereby suppressing pathogenic hallmarks of fibroblasts. In vivo, therapeutic administration of YC3 significantly alleviates ocular symptoms in a GO mouse model. Mechanistic investigations reveal that YC3 binds to a previously unidentified allosteric site within the leucine‐rich repeat domain of TSHR, consequently inhibiting receptor activation. Collectively, this study not only identifies YC3 as a promising TSHR‐targeting therapeutic candidate but also unveils a novel allosteric site for next‐generation inhibitors. These findings highlight the potential of aptamers in both dissecting receptor mechanisms and uncovering cryptic druggable sites, thereby bridging structural biology with targeted drug development.

Graves' ophthalmopathy (GO) is an orbital inflammatory autoimmune disease with limited treatment options. Advances in understanding of disease pathogenesis, particularly the dysregulated insulin-like growth factor-1 receptor (IGF-1R) signaling network in the orbital fibroblasts, have led to the development of targeted therapies against IGF-1R for GO. In this study, we aimed to evaluate the preclinical therapeutic potential of CT102, an IGF-1R-targeting antisense oligonucleotide. Antisense oligonucleotides represent a promising class of therapeutics due to their direct regulation of disease-causing genes and their variants, providing a compelling alternative to traditional "protein-specific" therapies. A GO-related rat model was established via intraperitoneal injection of bovine thyroglobulin and validated via the elevated serum thyroid peroxidase antibodies and suppressed serum thyroid-stimulating hormone levels. The GO-related rat model exhibited stable and consistent pathologic alterations of the extraocular muscles. Ocular administration of CT102 is well tolerated, and high-dose CT102 treatment showed therapeutic benefits as illustrated by the downregulation of IGF-1R level in ocular muscle tissue and reduction in pathologic abnormalities. Restoration of GO-associated biomarkers, including serum thyroid peroxidase antibody and serum thyroid-stimulating hormone levels, was observed in the high-dose CT102 group compared with normal controls. Furthermore, CT102 demonstrates superior modulation of GO-associated biomarkers relative to 2 positive controls: teprotumumab, the only anti-IGF-1R antibody approved by the US Food and Drug Administration, and miR-143, an RNA therapeutic targeting IGF-1R. To our knowledge, this study provides, for the first time, a rationale for clinical trials of CT102 in patients with GO and highlights the potential of anti-IGF-1R antisense oligonucleotides as a therapeutic strategy for GO. SIGNIFICANCE STATEMENT: To our knowledge, this study is the first to describe the therapeutic potential of anti- insulin-like growth factor-1 receptor antisense oligonucleotides in Graves' ophthalmopathy (GO), providing the rationale for future clinical trials in patients with GO and highlighting the potential of anti-insulin-like growth factor-1 receptor antisense oligonucleotide as a therapeutic strategy for GO.

Conventional definitive treatments of relapsed Graves' disease (GD) include surgery and radioiodine therapy (RAI). Recently, radiofrequency ablation (RFA) has emerged as a potential novel treatment option. This study compared the health-related quality of life (HRQOL) at 2years after treatment of relapsed GD with RFA, surgery, and RAI. Patients with persistent/relapsed GD who underwent RFA, surgery (total thyroidectomy), or RAI at the same tertiary endocrine surgery unit from 2020 to 2022 were recruited to complete the disease-specific (ThyPRO-39) and generic (SF-12V2, SF-6D and EQ-5D-5L) HRQOL questionnaires at two years after each of the above respective treatments. Composite and domain specific scores were compared after propensity score matching for baseline age, sex, thyroid function, and comorbidities. Patients with moderate to severe Graves ophthalmopathy were excluded. Eighty-five patients completed the questionnaires. In the matched cohort, 45 patients (RFA: 15, Surgery: 15, RAI: 15) were analyzed. Their median age was 34 (30 - 44), and majority were female patients (91%). For the thyroid disease-specific ThyPRO-39 questionnaire, the RFA group had significantly lower (better) scores for depressive symptoms than the RAI and surgery groups (p=0.046 and 0.009, respectively). The RFA group also had lower (better) scores for anxiety symptoms, hypothyroid symptoms, tiredness, overall quality of life impact scale, and composite scale, albeit differences being not statistically significant. In generic questionnaires, comparable composite scores were observed. These include the physical component score and mental component score in SF-12v2, the SF-6D utility score, EQ-5D-5L utility score, and EQ-VAS score. Sensitivity analysis with inverse probability of treatment weighting yielded consistent results. At 2years after treatment of relapsed GD, single-session RFA achieved significantly better outcomes in terms of less depressive symptoms and at least comparable outcomes in most HRQOL domains when compared to surgery and RAI, when a disease-specific questionnaire (ThyPRO-39) was used. Comparable outcomes from generic HRQOL questionnaires were noted across RFA, surgery, and RAI.

ObjectiveTo examine the factors influencing 131I-refractory Graves’ disease (GD) hyperthyroidism in patients, develop a nomogram prediction model, and conduct its validation.MethodsA total of 272 hyperthyroidism patients who received initial 131I treatment at our hospital from January 2021 to January 2022 were randomly selected. Patients were divided into refractory hyperthyroidism group (92 cases) and non-refractory hyperthyroidism group (180 cases) based on whether they were cured after one course of 131I treatment. They were randomly divided into a training group (n=190) and an internal validation group (n=82) in a 7:3 ratio. Multiple factors that might affect the efficacy of 131I treatment were collected, including 16 variables such as clinical characteristics, laboratory, and imaging examinations. LASSO regression was used for optimization and selection, and a multivariate logistic regression model was constructed to create a nomogram prediction model. The model’s discrimination, calibration, and clinical validity were evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow calibration curve, and decision curve analysis (DCA).ResultsThere were no statistically significant differences (P>0.05) in the comparison of the 16 variables between the training and validation groups. Following LASSO regression analysis, six predictive variables associated with 131I-refractory hyperthyroidism were identified: the duration of hyperthyroidism, nighttime sleep quality, the presence of Graves' ophthalmopathy (GO), the effective half-life of thyroid 131I, thyroid uptake 99mTc value, and thyroid mass. The area under the ROC curve (AUC) for the risk of 131I refractory hyperthyroidism in the training group was 0.943 (95% CI: 0.909-0.977), and the AUC for the validation group was 0.926 (95% CI: 0.870-0.983). The Hosmer-Lemeshow calibration curve showed good fit (training group P=0.876; validation group P=0.202). DCA demonstrated that when the threshold probability for equal patients ranged from 0.04 to 0.86 in the training group and from 0.09 to 0.87 in the validation group, using the nomogram prediction model to predict the risk of refractory hyperthyroidism after 131I treatment was more beneficial.ConclusionThis study found that the duration of GD hyperthyroidism, nighttime sleep quality, GO, effective half-life of thyroid 131I, thyroid uptake 99mTc value, and thyroid mass are independent influencing factors of 131I refractoriness. A risk prediction model including these six factors was established. This model provides guidance for the diagnosis and treatment decisions of 131I refractory GD hyperthyroidism, offers a quantitative tool for clinical assessment of 131I efficacy, and aids in personalized treatment decisions, reducing the burden of ineffective or inefficient treatments.

Exploring the link between Co-stimulatory gene polymorphisms and clinical manifestations in Graves' ophthalmopathy.

Purpose: To identify predictive factors for non-shrinking extraocular muscles (EOMs) after retrobulbar injection of glucocorticoids (GCs) in patients with Graves’ ophthalmopathy (GO).Methods: This retrospective cohort study included 60 GO patients (102 eyes) who received retrobulbar GC injections. We used univariate analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate logistic regression to identify factors associated with non-shrinking EOMs. The primary outcome was the change in EOM volume assessed by orbital computed tomography (CT) scans before and after treatment.Results: After retrobulbar injection of GCs, 36 eyes (35.3%) showed a reduction in EOM volume, while 66 eyes (64.7%) did not. Multivariate analysis revealed that age (OR = 1.09, 95% CI: 1.01-1.18, p = 0.03) and Clinical Activity Score (CAS)≥3 (OR = 0.11, 95% CI: 0.02-0.59, p = 0.008) were independent predictors of non-shrinking EOMs. Higher age increased the odds of non-shrinking EOMs by 9% per year, while higher disease activity (CAS≥3) was associated with a better treatment response. Other factors, like proptosis and axial orbit depth, showed trends but did not reach statistical significance.Conclusion: Age and disease activity (CAS≥3) are significant predictors of non-shrinking EOMs after retrobulbar GCs injection in GO patients. These findings can help clinicians better assess treatment outcomes and optimize therapeutic strategies for GO patients. Future research should focus on expanding the sample size and exploring underlying biological mechanisms to further validate these findings and improve treatment precision.

Graves' orbitopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD) and manifests itself in symptoms and signs of involvement of the orbits and neighboring tissues. Approximately 15% of patients with GD who do not present clinical signs of GO at the onset of the disease will develop it in the first 3 to 6 months. TSH receptors are also expressed in several extrathyroidal tissues, especially in the retroorbital tissues. For this reason, complaints such as strabismus, diplopia, proptosis (exophthalmos) and eyelid retraction are common in this ophthalmopathy. Its incidence is higher in women, as it is an autoimmune disease, but it is still considered relatively rare, with 5-6% of cases classified as moderate to severe. Therefore, as it is a less frequent condition, this case series aims to report the diagnosis and management of Graves' orbitopathies in two male patients with moderate activity of severe disease in a large endocrinology service. By considering and expanding the dissemination around this diagnosis, it may be possible to improve the prognosis of these patients, preventing fibrosis and sequelae such as changes in appearance, proptosis and dysfunction of the extrinsic ocular muscles. The objective of this study is to highlight possible errors in the diagnosis and treatment of Graves' disease and ophthalmopathy that may lead to future consequences.

Graves' ophthalmopathy (GO), also known as thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease and a leading cause of visual morbidity. The disease primarily affects the orbital tissue and is characterized by inflammation, expansion of extraocular muscles, and remodeling of orbital fat, resulting in proptosis, diplopia, and even vision loss. Active GO poses significant therapeutic challenges and often requires prompt intervention to preserve visual function and improve quality of life. Over the past decade, considerable progress has been made in understanding the immunopathogenesis of GO, leading to the development of targeted pharmacological therapies that extend beyond traditional systemic corticosteroids. This review summarizes recent advances in the drug therapy of active GO, focusing on novel immunomodulators, biological agents such as monoclonal antibodies targeting CD20, IL-6 R, and insulin-like growth factor-1 receptor (IGF-1R), and evolving treatment strategies based on disease activity and severity. We also discuss current clinical practice guidelines, emerging therapeutic targets under investigation, and future perspectives in the individualized management of this vision-threatening autoimmune condition.

Graves' ophthalmopathy (GO) is an autoimmune-inflammatory condition affecting about 25% of patients with Graves' disease (GD). Oxidative stress (OS) increases the production of inflammatory cytokines, the production of free radicals (ROS) and insulin resistance modulating IGF-1r/TSHr cross-talk in GO. Selenium is a component of selenoproteins and promotes the suppression of ROS production. We aim to evaluate the effects of the Mediterranean diet (MD) naturally enriched with selenium in patients with GD and active mild GO on thyroid function parameters, nutritional state, autoimmunity and the clinical course of GO. 40 GD patients with untreated mild active GO and stable thyroid function were randomly assigned to the Mediterranean diet (MD) naturally enriched with selenium (MD group) or a free diet (FD group). The selenium content of the MD was increased by approximately 30% according to the reference levels of nutrient and energy intake for the Italian population (LARN 2014). The combined endocrinological-ophthalmological evaluation was carried - out at baseline and after 12 and 24 weeks from the beginning of the MD or FD. The MD contained 178.1 ± 15.1 mcg of SE, and the diet was balanced with respect to the macronutrient composition. The Clinical Activity Score (CAS) improved significantly at visit 1 in the MD group compared to the FD group (p = 0.03). Hertel measurements and eyes motility were not different at visits 1 and 2 in either group of patients. Soft tissue involvement improved in the MD group compared to the FD group at visit 1 and 2 (p = 0.03 and 0.04). The absolute value (mm) of the eyelid aperture was significantly lower at visit 2 in the MD group than in the FD group (9.3 ± 0.6 vs. 10.5 ± 0.5, p = 0.01). The relative change in BMI was significantly lower in the MD group than in the FD group at visit 2 (2.5 [(-9.4) -10.1)] vs. 5.1 [(-0.4) -15)] kg, p = 0.04). TRABs values and thyroid function did not differ and decreased to a similar degree in both groups of patients during the observation period. No cases of GO exacerbation were observed in the two groups of patients. The MD is a versatile dietary style and should be a component of the dietary treatment plan in patients with GD and mild GO to reduce weight regain and the inflammation and insulin resistance, which in turn contribute to the autoimmune-inflammatory processes of GO.

ABSTRACT Purpose To analyze the correlation between a magnetic resonance imaging (MRI) score, we proposed in a previous report, and conventional quantitatively evaluated MRI findings, and to evaluate the clinical utility of the MRI score in patients with Graves’ ophthalmopathy (GO). Methods Using ImageJ, we retrospectively re-analyzed magnetic resonance images of 25 patients with GO who were evaluated in the previous study. The signal intensity and area measured by ImageJ were normalized for each affected extraocular muscle (EOM) in each patient (normalized quantified inflammation and enlargement). Furthermore, the ratio of the value for the affected EOM to the normal values was calculated in each patient (quantified inflammation and enlargement compared to normal values). We analyzed the correlations between MRI scores and quantitative MRI finding before and after 6 g of intravenous methylprednisolone (IVMP). Results The correlation coefficient between the normalized MRI score and normalized quantified inflammation and enlargement was 0.59 before IVMP and 0.69 after IVMP. The correlation coefficient between the MRI score and quantified inflammation and enlargement compared to normal values was 0.58 before IVMP and 0.73 after IVMP. The correlation coefficients for all items were statistically significant (P-value < .05). Conclusion This study found a high correlation between the MRI score, which is our proposed semiquantitative method for assessing EOM swelling and inflammation, and the results of conventional quantitative evaluation methods. This suggests that the MRI score, which can be more readily used in clinical practice, may be as reliable as quantitative evaluation methods.

Purpose: evaluating relationship between serum level of TSH Receptor Antibody (TRAb) and severity of Graves’ ophthalmopathy (GO). Methods: prospective interventional follow up study included 35 newly diagnosed untreated patients with GO was carried at Ain Shams University Hospital, Cairo. patients were subjected to full ophthalmological examination, measuring proptosis degree by Hertel’s Exophthalmometer, measuring TRAb serum level. patients were classified according to clinical activity score into 2 groups: Inactive [CAS &amp;lt; 3]: 23 patients received only antithyroid therapy and Active [CAS ≥ 3]: 12 patients received intravenous methylprednisolone at a dose of 0.5gm for 6 weeks, injected weekly. 6 weeks after treatment severity of (GO), proptosis, and TRAb serum level were reassessed. Results: study found the mean CAS was 2.11±1.13, the mean proptosis measured (23.26 ±3.19) and (22.42 ± 3.27) in right and left eye respectively while mean of TRAb was 11.19 ±6.45. After 6 weeks of treatment, CAS was regressed significantly in relation to TRAb level as TRAb measurement decreased by -62.7%, -14.06% in group II and group I respectively while proptosis measurement of right and left eyes in group II significantly decreased, with mean changes of -10.3% and -10.7%, respectively. And, in group I (-4.5% and -3.8%) in right and left eyes respectively, but not significant to TRAb level. Conclusion TRAb level can be used as monitor to activity of Grave’s Ophthalmopathy (GO) and in follow up but not directly related to proptosis degree.

To evaluate the quality of life, depression, and anxiety levels of Turkish patients with Graves' Ophthalmopathy (GO) of different disease activity and severity, using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire and to compare these findings with healthy controls. This study was designed as a cross-sectional clinical study. The study population included 25 patients with active GO, 25 patients with inactive GO, and 25 patients with non-ophthalmopathy Graves' disease. A group of 30 age- and sex-matched healthy volunteers was included as a control group. All participants underwent a comprehensive ophthalmological examination followed by the administration of the GO-QOL, BDI, and BAI questionnaires. No statistically significant difference was found among the four groups in terms of age or gender (p = 0.752, p = 0.981, respectively). BDI and BAI scores were significantly higher in the Active GO group compared to the Control group (p = 0.001, p = 0.024, respectively). In the Inactive GO group, BDI scores were also higher than the Control group (p = 0.017), while no significant difference was observed in BAI scores (p = 0.087). A comparison of GO-QOL scores revealed that both Active GO and Inactive GO groups had significantly lower scores compared to both the Non-Ophthalmopathy Graves' group (p < 0.001, p = 0.003) and the Control group (p < 0.001, p < 0.001). The present study identified a decrease in quality of life and an increase in depression and anxiety scores in both active and inactive Turkish GO patients.

PurposeHigh intraocular pressure (IOP) is a frequent clinical manifestation of Graves' ophthalmopathy (GO), but little is known about the mechanism by which thyroid function alters IOP in GO.Materials and MethodsThe relationships between IOP and clinical manifestations of GO were determined by simple linear correlation analysis and the Kruskal-Wallis test. Factors significantly associated with changes in IOP were evaluated by multiple linear regression analysis. The relationships between IOP and thyroid function were verified using data from the National Health and Nutrition Examination Survey, and causative relationships between thyroid function and IOP were assessed using summary-data-based Mendelian randomization analysis. Gene expression was compared in patients with and without GO using analysis of a Gene Expression Omnibus dataset, and associated GO pathways were identified.ResultsClinical data were obtained from 392 hospitalizations of 270 patients, including 142 hospitalizations with increased IOP and 250 with normal IOP. IOP was linearly associated with GO duration, clinical activity score (CAS), and concentrations of free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin receptor antibodies. Multiple linear regression analysis yielded a model including CAS, FT3 concentration, and sex (r=0.46). Analysis of 3848 samples from the dataset showed that FT3 and FT4 levels differed between the increased and normal IOP groups. Increased expression of the LOXL-AS1 gene was identified as a contributor to increased IOP, with LOXL-AS1 expression increased in GO.ConclusionIncreased thyroid function is a risk factor for elevated IOP in patients with GO, with higher expression of LOXL-AS1 in GO contributing to this effect.

PurposeThe purpose of this study was to investigate fibroblast markers and histone deacetylase (HDAC) 4 in orbital tissues and orbital fibroblasts from patients with Graves’ ophthalmopathy (GO) and healthy controls.MethodsHematoxylin and eosin (H&E), Masson's trichrome, and Verhoeff's Van Gieson (VVG) staining were performed on GO and control orbital tissues. Immunohistochemistry on fibroblast markers were investigated. GO orbital fibroblasts (GOFs) and control orbital fibroblasts (COFs) stimulated with platelet-derived growth factor (PDGF)-BB were assessed for collagen type I alpha I (COL1A1), elastin (ELN), and fibrillin-2 (FBN2) mRNA expression. HDAC4 knockdown in GOF and COF were assessed to study its impact on elastin expression. GO orbital tissues and GOF treated with either LMK-235 or tasquinimod were examined.ResultsOrbital tissues exhibited accumulation of adipocytes, orbital fibroblasts, collagen, and elastin. After 2 hours, PDGF-BB stimulation induced an 8-fold increase of ELN in GOF and a 5-fold increase of ELN in COF compared to no treatment, whereas COL1A1 and FBN2 mRNA levels were later induced after 24 hours. Elastin protein expression was significantly higher in GOF compared to COF at both the basal level and after PDGF-BB stimulation. HDAC4 knockdown significantly reduced PDGF-BB-induced ELN mRNA expression in GOF but not in COF. LMK-235 inhibited ELN mRNA expression in GOF. However, LMK-235 and tasquinimod did not decrease ELN mRNA level in GO orbital tissues.ConclusionsOrbital tissues exhibit shared and unique characteristics from other tissues. Our in vitro studies showed that elastin mRNA and protein expression increased in response to PDGF-BB stimulation in GOF which might be due to aberrant HDAC4 levels.