Thyroid Eye Disease and Glaucoma: A Cross-Sectional Study Comparing Clinical Characteristics and Disease Severity.

Background and Objectives: This study investigates the relationship between thyroid eye disease (TED) and open-angle glaucoma (OAG), focusing on disease severity and clinical features. Materials and Methods: Conducted at the Timis County Emergency Clinical Hospital, the research included 106 patients, with 53 having both conditions and 53 having only OAG. Key metrics analyzed included intraocular pressure (IOP) using a Goldmann applanation tonometer, the retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) characteristics evaluated using optical coherence tomography (OCT). Results: Results indicated that patients with both TED and OAG experienced a 6.09% reduction in RNFL thickness and showed more rapid disease progression, with 48.35% having active TED. The mean IOP in TED patients was 27.5 ± 4.9 mmHg, which was similar to those with only OAG. Demographic factors, including age and gender, influenced the clinical course and disease severity. Conclusions: These findings underscore the importance of specialized monitoring and treatment strategies for patients with coexisting TED and OAG to prevent vision loss.

Optical coherence tomography angiography in thyroid associated ophthalmopathy: a systematic review.

PURPOSE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters. METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ). RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients. CONCLUSION: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.

Biomechanical changes of the cornea after orbital decompression in thyroid-associated orbitopathy measured by corvis ST.

This study aims to investigate the changes in ocular biomechanical factors in patients with inactive thyroid eye disease (TED) who undergo orbital decompression surgery. This observational prospective study include 46 eyes of 31 patients with inactive TED undergoing orbital decompression at a tertiary university hospital from October 2021 to September 2023. All participants underwent a full ophthalmic examination, and a biomechanical examination was performed using corvis ST at baseline, 1 month, and 3 months postoperatively. The study participants had a mean age of 45 ± 11.6 years, and 58.1% of them were female. The second applanation time (A2T) increased from baseline to postoperative month 1 and continued to increase to postoperative month 3 (P < 0.001). The first applanation velocity (A1V), highest concavity (HC) peak distance, and pachymetry parameters also increased from postoperative month 1 to postoperative month 3 (P = 0.035, P = 0.005, and P = 0.031, respectively). The HC time increased from baseline to postoperative month 3 (P = 0.027). Other changes were statistically insignificant. The P-values were adjusted according to biomechanically corrected intraocular pressure (bIOP). Baseline Hertel significantly influenced A2 time (P < 0.001). Our findings suggest that ocular biomechanical parameters may change following decompression surgery in patients with inactive TED. Specifically, an increase in A2T, A1V, and HC peak distance suggests a decrease in corneal stiffness, although the increased HC time contradicts this. It is recommended to postpone keratorefractive or intraocular lens implantation surgeries until corneal biomechanics stabilize after decompression surgery for optimal results.

Alterations in dynamic regional homogeneity within default mode network in patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a significant autoimmune eye disease known for causing exophthalmos and substantial optic nerve damage. Prior investigations have solely focused on static functional MRI (fMRI) scans of the brain in TAO patients, neglecting the assessment of temporal variations in local brain activity. This study aimed to characterize alterations in dynamic regional homogeneity (dReHo) in TAO patients and differentiate between TAO patients and healthy controls using support vector machine (SVM) classification. Thirty-two patients with TAO and 32 healthy controls underwent resting-state fMRI scans. We calculated dReHo using sliding-window methods to evaluate changes in regional brain activity and compared these findings between the two groups. Subsequently, we employed SVM, a machine learning algorithm, to investigate the potential use of dReHo maps as diagnostic markers for TAO. Compared to healthy controls, individuals with active TAO demonstrated significantly higher dReHo values in the right angular gyrus, left precuneus, right inferior parietal as well as the left superior parietal gyrus. The SVM model demonstrated an accuracy ranging from 65.62 to 68.75% in distinguishing between TAO patients and healthy controls based on dReHo variability in these identified brain regions, with an area under the curve of 0.70 to 0.76. TAO patients showed increased dReHo in default mode network-related brain regions. The accuracy of classifying TAO patients and healthy controls based on dReHo was notably high. These results offer new insights for investigating the pathogenesis and clinical diagnostic classification of individuals with TAO.

Blink Lagophthalmos in Graves Orbitopathy.

PURPOSE: To investigate the relationship between the kinematics of spontaneous blinks and the anterior area of the levator palpebrae superioris muscle in patients with Graves orbitopathy (GO). METHODS: This is a case-control study. The authors measured the margin reflex distance of the upper eyelid (margin reflex distance 1), the kinematics of spontaneous blinks, and the anterior area of levator palpebrae superioris muscle in CT coronal scans of patients with Graves upper eyelid retraction (GO) and a control group. The eye with the greatest margin reflex distance 1 was selected for analysis in each group. RESULTS: A total of 68 participants were included, with 36 in the GO group and 32 in the control group. In the GO group, the mean margin reflex distance 1 measured 6.5 mm, while in the control group, it was 3.9 mm. Almost all parameters related to the closing phase of spontaneous blinking activity, including amplitude, velocity, blinking rate, and interblink time, did not differ between the two groups. However, the effectiveness of the blink's amplitude (ratio of blink amplitude to margin reflex distance 1) and the main sequence (relationship between amplitude and velocity) were significantly reduced in the GO group compared with the control group. The area of the levator palpebrae superioris muscle was significantly larger in GO than in controls, with 71.4% of patients' muscles outside of the maximum range of the controls. CONCLUSIONS: In patients with GO, there is a reduction in blinking effectiveness, also known as blink lagophthalmos, which is a factor in the common occurrence of ocular surface symptoms. The increase in velocity with amplitude is also reduced in GO.

Inferior Rectus Muscle Y-Split for Thyroid-Related Vertical Strabismus.

Incomitant hypotropia in thyroid eye disease can be difficult to manage, especially in the presence of orthotropia with fusion in down gaze and reading position. Recessing the affected ipsilateral inferior rectus muscle may result in an undesirable downgaze diplopia secondary to a hypertropia in downgaze. Various surgical techniques have been described to manage this potential complication including asymmetric recession of both inferior rectus muscles, posterior myoscleropexy operation, and the Scott recess/resect procedure of the contralateral inferior rectus. In 2004, Hoerantner et al. introduced the y-split recession of the medial rectus muscle for near esotropic deviations. The anterior portion of muscle is split and secured in a y-shaped configuration, which reduces the muscle lever arm and helps minimize incomitance and muscle slippage. Unlike the traditional Cüppers Faden, a y-split recession results in torque reduction in all gaze positions. In addition, a y-split recession does not involve scleral passes posteriorly reducing the risk of globe perforation. We report a patient with incomitant strabismus secondary to thyroid eye disease who underwent a combination of traditional recession and y-splitting recession of the contralateral inferior rectus muscle, resulting in good functional alignment in primary gaze and in the reading position.

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Teprotumumab improves light sensitivity in patients with thyroid eye disease.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. METHODS: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. RESULTS: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p <  0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). CONCLUSION: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.

Central and peripheral contrast sensitivity in thyroid eye disease.

PURPOSE: Assessment of central and peripheral contrast sensitivity (CS) in thyroid eye disease (TED) with and without dysthyroid optic neuropathy (DON). METHODS: This cross-sectional study enrolled 33 eyes of 18 treatment-naïve TED patients and 18 age- and sex-matched healthy controls for comparative analysis. A detailed ophthalmic examination included visual acuity (VA), intraocular pressure measurement, slit-lamp biomicroscopy, and CS testing (central and four peripheral regions) using Spaeth-Richman Contrast Sensitivity test was done. RESULTS: The average age of TED patients was 47.17 ± 13.99 years and a female preponderance was noted (66.66%, n = 12). Twenty-five eyes (75.8%) were diagnosed as TED without DON, while eight eyes (24.2%) had DON. Nine eyes (27.2%) were in the active stage of disease and 29 eyes (87.8%) had proptosis. The difference in mean logMAR visual acuities between TED patients and controls was statistically insignificant ( P = 0.189), but a significant difference was noted in central and total CS score ( P < 0.001, Wilcoxon-Mann-Whitney test). On CS comparison between DON and non-DON eyes, a significant difference in average scores was noted in central and all peripheral areas ( P < 0.05, Wilcoxon-Mann-Whitney test). With increasing clinical activity score, a statistically significant reduction was noted in CS in three out of four peripheral regions (Spearman correlation, P < 0.05). CONCLUSION: Visual function compromise can be detected in TED in the presence of intact VA, by testing CS. Peripheral CS deteriorates with increasing inflammation and in DON. Serial monitoring of both central and peripheral CS may help in diagnosing DON early.

Altered Static and Dynamic Brain Functional Topological Organization in Patients With Dysthyroid Optic Neuropathy.

CONTEXT: Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. OBJECTIVE: We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional magnetic resonance imaging with the graph theory method. METHODS: A cross-sectional study was conducted at a grade A tertiary hospital with 66 TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). Main outcome measures included topological properties of functional networks. RESULTS: For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. DON and non-DON patients both exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in the orbitofrontal cortex and visual network (VN). For dynamic properties, the DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in the DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. CONCLUSION: Functional network alterations were observed both in DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON.

The changing landscape of thyroid eye disease: current clinical advances and future outlook.

AIMS: This review aims to provide an overview of the current understanding of TED and its pathophysiology. To describe the evidence base for current consensus treatment recommendations and newer biological therapies available as well as to present future therapeutic research. METHODS: We reviewed and assessed the peer-reviewed literature placing particular emphasis on recent studies evaluating the pathophysiology of TED, landmark trials forming the basis of current management and recent clinical trials informing future therapeutics. Searched were made in MEDLINE Ovid, Embase Ovid, US National Institutes of Health Ongoing Trials Register and EU Clinical Trials Register. Keywords included: "Thyroid Eye Disease", "Graves Orbitopathy", "Thyroid Orbitopathy" and "Graves' Ophthalmopathy". RESULTS AND CONCLUSIONS: The pathophysiology of TED involves a complex array of cellular and humoral based autoimmune dysfunction. Previous therapies have been broad-based acting as a blunt instrument on this mechanism with varying efficacy but often accompanied with a significant side effect profile. The recent development of targeted therapy, spearheaded by Teprotumumab has led to an array of treatments focusing on specific components of the molecular pathway optimising their impact whilst possibly minimising their side effect profile. Future challenges involve identifying the most effective target for each patient rather than any single agent being a panacea. Long-term safety profiles will require clarification as unintended immunological consequence downstream may become manifest as seen in other diseases. Finally, future novel therapeutics will entail significant expenditure and may lead to a divergence of available treatment modalities between healthcare systems due to funding disparities.

Reactivation After Teprotumumab Treatment for Active Thyroid Eye Disease.

PURPOSE: To determine the recurrence and reactivation rates after teprotumumab therapy for active thyroid eye disease. DESIGN: Retrospective consecutive case series. METHODS: This was a study of all patients followed for active thyroid eye disease at the Cole Eye Institute, Cleveland Clinic, treated with teprotumumab between May 2020 and May 2021. Patients with less than 6 months follow-up after completion of infusions were excluded. The primary outcome measure was reactivation, defined as a regression in proptosis (increase of ≥2 mm in either eye and to within ≤2 mm of pre-treatment level and Clinical Activity Score [CAS] worsening of 2 points or greater). Secondary outcome was diplopia response. RESULTS: A total of 21 patients were included in the study. The average long-term improvement in proptosis in the eye with more proptosis after teprotumumab was 1.57mm (range, -3 to 4 mm). Of the 17 initial responders, there were 8 reactivations (47%) and 2 isolated proptosis regressions (12%); Overall, 7 of 21 patients (33%) responded throughout the study period. Average time to regression was 12.25 months (range, 2-22.5 months). There was no statistically significant change in diplopia at final visit in any subgroup (P = 0.68 to >.99). CONCLUSIONS: At most, 33% of patients demonstrate continued response 2 years after teprotumumab treatment. The proptosis and CAS regression occurs in the setting of disease reactivation in 80% of regressions. Teprotumumab treatment appears to offer minimal long-term improvement in diplopia.

Revision orbital decompression for thyroid eye disease.

OBJECTIVE: To compare the indications, surgical techniques and outcomes for revision orbital decompression surgery for thyroid eye disease in open, endoscopic, and combined open and endoscopic approaches. METHODS: A retrospective review of all revision orbital decompression procedures for thyroid eye disease from a single large academic institution over a 17-year period (01/01/2004-01/01/2021) was performed. Patient demographics, as well as indications and types of surgery were reviewed. Outcome measures included changes in proptosis, intraocular pressure, visual acuity and diplopia. RESULTS: Thirty procedures were performed on 21 patients. There was a median of 9.4 months between primary orbital decompression and revision decompression surgery. There were 6 bilateral procedures, and 2 of these patients underwent additional revision surgeries due to decreased visual acuity with concern for persistent orbital apex compression or sight-threatening ocular surface exposure in the setting of proptosis. Twenty-five procedures were performed as open surgeries with 5 endoscopic/combined cases. Combined Ophthalmology/Otolaryngology surgery via combined open/endoscopic approaches was favoured for persistent orbital apex disease. Visual acuity remained preserved in all patients. The overall median reduction in proptosis was 2 mm and intraocular pressure change was 1 mmHg regardless of surgical approach. The overall rate of new onset diplopia after surgery was 15%. These patients had open approaches. All endoscopic/combined approach patients had pre-existing diplopia. There were no statistically significant differences between the open and endoscopic/combined groups in regard to change in visual acuity, reduction in proptosis or intraocular pressure. CONCLUSION: Revision orbital decompression is an uncommon procedure indicated for those patients with progressive symptoms despite previous surgery and intensive medical management. Both endoscopic and non-endoscopic techniques offer favourable outcomes with respect to visual acuity, decrease in intraocular pressure, and improvement in proptosis and overall lead to a low incidence of new onset diplopia. LEVEL OF EVIDENCE: Level IV.

Impact of Graves Disease on Ocular Surface and Corneal Epithelial Thickness in Patients With and Without Graves Orbitopathy.

PURPOSE: Our aim was to assess ocular surface and tear film stability and corneal epithelial thickness (CET) in patients with Graves disease (GD) with and without Graves orbitopathy (GO). METHODS: This study included healthy age-matched controls and patients with GD. Symptoms (Ocular Surface Disease Index questionnaire) and signs (schirmer test and tear breakup time test) of dry eye disease were determined, according to the International Dry Eye Workshop II criteria of DED. CET map was also assessed. RESULTS: Twenty-four eyes were included in the control group, with a mean age of 41.00 ± 13.65 years, and 34 in the GD group, 18 with GO and 16 without GO, with a mean age of 44.44 ± 13.95 and 45.75 ± 10.59 years, respectively. All patients with GO had inactive disease (mean clinical activity score: 1.33 ± 0.69). Patients with GD had higher proportion of clinical diagnosis of dry eye disease (GO vs. GD without GO vs. controls: 77.77% vs. 75.00% vs. 4.17%), with higher Ocular Surface Disease Index (GO vs. GD without GO vs. controls: 15.44 vs. 15.06 vs. 9.88) and lower tear breakup time test (GO vs. GD without GO vs. controls: 6.33 s vs. 7.25 s vs. 11.63 s). Superior CET was lower in patients with GD (P < 0.05). No differences were found between patients with and without GO (P > 0.05). CONCLUSIONS: GD negatively influenced ocular surface and CET, with a higher level of eye dryness and corneal thinning regardless of GO status, suggesting that subclinical chronic inflammation may play a role in the pathogenesis of tear film and ocular surface stability.

Quantitative evaluation of activity of thyroid-associated Ophthalmopathy using short-tau inversion recovery (STIR) sequence.

OBJECTIVE: Quantitatively staging TAO using MRI remains limited. Our study aims to identify the cut-off signal intensity value for staging TAO using STIR sequence scan. METHODS: Between June 2018 and July 2020, a number of 51 patients with TAO (102 eyes) and 19 volunteer controls (38 eyes) were recruited. The clinical and biochemical parameters were measured in each patient. Disease activity was diagnosed based on the Clinical Activity Score (CAS). The signal intensities of extraocular muscles were scanned using short-tau inversion recovery (STIR) sequences from MRI. RESULTS: Compared to the inactive TAO patients and the controls, the signal intensity ratios (SIRs) of the superior rectus, inferior rectus, medial rectus, lateral rectus on STIR images were significantly increased in the active TAO patients. After adjustment for age and smokers, the SIRs of four extraocular muscles showed strong associations with CAS. By receiver operator characteristic (ROC) curve analysis, all four muscle SIRs demonstrated good efficiency for predicting disease activity [area under curve (AUC) 0.75-0.83, all P < 0.01]. The identified cut-off SIR values were further validated in a new group of TAO patients (30 eyes) enrolled between September 2020 and January 2021. The cut-off SIR value of > 2.9 in the inferior rectus showed optimal diagnostic value for staging the active TAO. CONCLUSIONS: the signal intensity of extraocular muscles on STIR sequence was a good predictor for TAO activity. A cut-off SIR value of > 2.9 in the inferior rectus could be applied to evaluate the active stage of TAO.

Spontaneous brain activity alterations in thyroid-associated ophthalmopathy patients using amplitude of low-frequency fluctuation: A resting-state fMRI study.

OBJECTIVES: Previous studies demonstrated that thyroid-associated ophthalmopathy (TAO) patients were accompanied by cognitive decline. However, The exact neural mechanisms of cognitive decline in TAO patients remain unclear. Our study aimed to investigate the spontaneous brain activity alterations using amplitude of low-frequency fluctuation (ALFF) method and their relationships with clinical features in TAO patients. MATERIALS AND METHODS: In total, twenty-one patients with TAO (14 men and 7 women) and 21 healthy control (HC) subjects (14 men and 7 women) were enrolled in this study. The ALFF method was used to assess the spontaneous brain activity changes. Meanwhile, receiver operating characteristic (ROC) curve was used to distinguish TAO group and HCs group. And Pearson correlation was performed to calculate the relationship between the observed mean ALFF values of the altered regions in patients with TAO and their clinical features. RESULTS: Compared with the HCs, TAO patients had significantly lower ALFF values in the right superior occipital gyrus (SOG) and bilateral precuneus (preCUN). In contrast, TAO patients showed higher ALFF values in the left cerebellum (CER) and left insula (INS). CONCLUSION: our result highlighted that TAO patients showed altered intrinsic brain activities in the preCUN, left CER, left INS and right SOG, which might provide useful information for explaining neural mechanisms in patients with TAO.

Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study.

This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.

Insulin-Like Growth Factor Pathway and the Thyroid.

The insulin-like growth factor (IGF) pathway comprises two activating ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six IGF binding proteins (IGFBP) and nine IGFBP related proteins. IGF-I and the IGF-IR share substantial structural and functional similarities to those of insulin and its receptor. IGF-I plays important regulatory roles in the development, growth, and function of many human tissues. Its pathway intersects with those mediating the actions of many cytokines, growth factors and hormones. Among these, IGFs impact the thyroid and the hormones that it generates. Further, thyroid hormones and thyrotropin (TSH) can influence the biological effects of growth hormone and IGF-I on target tissues. The consequences of this two-way interplay can be far-reaching on many metabolic and immunologic processes. Specifically, IGF-I supports normal function, volume and hormone synthesis of the thyroid gland. Some of these effects are mediated through enhancement of sensitivity to the actions of TSH while others may be independent of pituitary function. IGF-I also participates in pathological conditions of the thyroid, including benign enlargement and tumorigenesis, such as those occurring in acromegaly. With regard to Graves' disease (GD) and the periocular process frequently associated with it, namely thyroid-associated ophthalmopathy (TAO), IGF-IR has been found overexpressed in orbital connective tissues, T and B cells in GD and TAO. Autoantibodies of the IgG class are generated in patients with GD that bind to IGF-IR and initiate the signaling from the TSHR/IGF-IR physical and functional protein complex. Further, inhibition of IGF-IR with monoclonal antibody inhibitors can attenuate signaling from either TSHR or IGF-IR. Based on those findings, the development of teprotumumab, a ß-arrestin biased agonist as a therapeutic has resulted in the first medication approved by the US FDA for the treatment of TAO. Teprotumumab is now in wide clinical use in North America.

Effect of systemic steroid therapy in Graves' orbitopathy on regulatory T cells and Th17/Treg ratio.

PURPOSE: Glucocorticoids are a mainstay treatment for Graves' orbitopathy, yet their exact mechanisms of action remain unclear. We aimed to determine whether the therapeutic effects of systemic steroid therapy in Graves' orbitopathy are mediated by changes in regulatory T lymphocytes (Tregs) and T helper 17 lymphocytes (Th17). METHODS: We assessed Treg and Th17 levels in the peripheral blood of 32 patients with active, moderate-to-severe Graves' orbitopathy who received 12 weekly pulses of methylprednisolone, and determined their association with disease severity, disease activity, and treatment outcomes. The acute orbitopathy phase was confirmed based on clinical evaluation and magnetic resonance imaging, and assessed using the clinical activity score (CAS). The severity of the disease was classified according to ETA/EUGOGO guidelines, and quantified based on the total eye score. Treatment response was determined based on specific criteria (e.g., changes in CAS score, diplopia grade, visual acuity, etc.). Treg and Th17 cells were identified using flow cytometry. RESULTS: Methylprednisolone treatment improved the activity of the disease and altered the Th17/Treg balance (i.e., the percentage of Tregs decreased while the number of Th17 cells remained unchanged). There was no association between the Treg/Th17 ratio and the activity and severity of the disease or the treatment response. CONCLUSIONS: Therapeutic effects of steroid therapy in Graves' orbitopathy are not mediated by Treg and Th17 alterations in the peripheral blood. The decrease in peripheral Treg percentage is likely a consequence of the non-specific effects of steroids and does not impact clinical outcome.