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.

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.

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.

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.

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.

Treatment of moderate to severe orbitopathy: Current modalities and perspectives.

Graves' orbitopathy (GO) is the primary cause of exophthalmos in adults. It appears in 30 to 50% of patients with Graves' disease. About 5% are moderate-to-severe cases that might be see-threatening or lead to long term disabling sequelae. Recommendations have been established in 2016 by the European thyroid association (ETA) and the European group on Grave's orbitopathy (EUGOGO), suggesting a wide use of corticosteroids in moderate to severe forms. However, disappointing results have been reported in 20 to 30% of cases. Improved understanding of pathophysiological mechanisms has allowed the use of non-specific immunomodulatory agents, currently under evaluation, and which place in the therapeutic strategy remains to be determined. Very recently, new promising therapeutic advances have emerged with the identification of new therapeutic targets, such as the TSH receptor and IGF-1 receptor complex.

Thermal Imaging of the Ocular Surface in Thyroid Eye Disease: A Comparison between Active, Inactive and Healthy Eyes.

Aim: To report the temperature differences on the ocular surface using infrared thermal imaging (TI) in thyroid eye disease (TED) and healthy eyesMethods: Prospective, consecutive, comparative case series comparing TI parameters between active and inactive TED with healthy controls. The data captured included baseline demography, activity of TED and the TI parameters. Area under the receiver operating characteristic curves (AUROC) were calculated for the temperature values to determine the sensitivity and specificity in distinguishing active from inactive TED. The Youden index and the predictor cut off values were also reported.Results: The study included 11 eyes with active TED, 46 eyes with inactive TED and 40 eyes healthy patients. Temperatures of pre-determined points on the ocular surface in degrees were compared between the three groups. Temperature at the caruncle, medial and lateral conjunctiva was noted to be significantly higher in the active TED group compared to inactive TED and healthy eyes. The most favorable Youden index (0.7) was noted for the caruncle with an AUROC value of 0.91, a sensitivity of 91% and a specificity of 79%. Correlation coefficient for the caruncular temperature with the corresponding CAS (clinical activity score) was 0.65 (95% C.I. 0.45 to 0.78, p < .0001).Conclusion: Thermal imaging in TED is an objective way of documenting surface inflammation by the surrogate marker of temperature change. It supplements CAS in clinically evident cases and could be useful in staging eyes with subtle clinical signs as well as those where signs have reduced following initiation of treatment.

Bulbar Conjunctival Microvascular Alterations in Thyroid-Associated Ophthalmopathy Patients with Different Activities.

Purpose: To evaluate the morphologic and hemodynamic changes of bulbar conjunctival vessels in thyroid-associated ophthalmopathy (TAO) patients and the correlations with the activity.Methods: Patients diagnosed as TAO with different clinical activity scores (CAS) and healthy participants were recruited. All subjects underwent a complete ophthalmic examination and functional slit-lamp biomicroscope. Vascular variables including the vessel density, vessel complexity, average diameter, blood flow velocity and blood flow rate in microvascular networks were measured. The correlations among microvascular parameters, CAS and exophthalmos were analyzed. Areas under the receiver operating characteristic curves (AUROCs) were applied to evaluate the diagnostic accuracy of microvascular alterations for active TAO.Results: A total of 46 eyes were enrolled in our study. The vessel complexity and blood flow velocity increased in the active TAO group significantly compared with the inactive group and healthy controls (P < .05). Meanwhile, the vessel complexity and blood flow rate were positively correlated with CAS (r = 0.641 and r = 0.526). Bulbar conjunctival microvascular parameters performed a good ability in distinguishing the active stage of TAO (AUROC = 0.793).Conclusions: Increasing bulbar conjunctival vessel complexity and blood flow were evident in TAO with severe inflammation. The measurements of bulbar conjunctival microvasculature could be a reference to evaluate activity in TAO.

Comparison of 2-wall versus 3-wall orbital decompression against dysthyroid optic neuropathy in visual function: A retrospective study in a Chinese population.

ABSTRACT: To compare visual function of 2-wall (medial and lateral) versus 3-wall (medial, lateral, and inferior) orbital decompression in patients with dysthyroid optic neuropathy (DON).A total of 52 eyes of 37 patients underwent orbital decompression for DON between 2013 and 2019 were retrospectively reviewed. Two- or 3-wall decompression was performed in 31 eyes of 23 patients and 21 eyes of 14 patients, respectively. We examined best-corrected visual acuity (BCVA), visual field mean deviation (MD) and pattern standard deviation (PSD), pattern-reversed visual evoked potential (PVEP) for P100 latency and amplitude at 60 and 15 arcmin stimulation checkerboard size, as well as proptosis using Hertel exophthalmometry.Whether 2-wall or 3-wall decompression, all parameters of visual function were improved after surgery (all P < .05). The improvement in BCVA, MD, and PSD was not statistically significant between groups (all P > .05). Proptosis reduction was higher after 3-wall decompression (P = .011). Mean increase in P100 amplitude after 3-wall decompression was statistically higher than that of after 2-wall decompression at 60 and 15 arcmin (P = .045 and .020, respectively), while the mean decrease in P100 latency was similar between the groups (P = .821 and .655, respectively). Six patients (66.67%) had persistent postoperative diplopia and 1 patient (20%) had new-onset diplopia in 3-wall decompression group, which were higher than in 2-wall decompression group (46.15% persistent postoperative diplopia and no new-onset diplopia).Both 2-wall and 3-wall decompression can effectively improve visual function of patients with DON. Three-wall decompression provides better improvement in P100 amplitude and proptosis, however new-onset diplopia is more common with this surgical technique.

Efficacy and safety of tripterygium glycosides for active moderate to severe Graves' ophthalmopathy: a randomised, observer-masked, single-centre trial.

BACKGROUND: Tripterygium glycosides (TG) has been used to treat a spectrum of inflammatory and autoimmune diseases. Our preliminary studies have shown that TG is effective in the treatment of active Graves' ophthalmopathy (GO). OBJECTIVE: We aimed to compare the efficacy and tolerability of TG with intravenous methylprednisolone (iv.MP) in patients with active moderate-to-severe GO. METHODS: This study was an observer-masked, single-centre, block-randomised trial. Patients with active moderate-to-severe GO were randomly assigned to receive iv.MP (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) or with TG (20 mg tablet three times per day for 24 weeks). The primary endpoints were the overall response rate and the patients' quality of life at 12 and 24 weeks. RESULTS: In this study, 161 patients were enrolled and randomised from 2015 to 2019. A total of 79 were randomly assigned to receive iv.MP and 82 to receive TG. A greater overall response rate was found in the TG group compared with the iv.MP group at week 24 (90.2% vs 68.4%, P = 0.000). Similarly, the patients' quality of life of the TG group showed a significantly higher response than the iv.MP group at week 24 (89.02% vs 72.15%, P = 0.001). The TG therapy showed a better CAS response than the iv.MP (91.5% vs 70.9% improved, P < 0.05), and up to 91.2% of patients were inactive. Also, the TG group showed a significantly higher improved rate of diplopia, proptosis, visual acuity, soft tissue involved and the decrease of eye muscle motility than the iv.MP group at week 24. Significantly more patients in the iv.MP group than the TG group experienced adverse events. CONCLUSION: Compared with iv.MP treatment, TG therapy is more effective and safer for patients with active moderate to severe GO.

Primary and secondary superior rectus recessions to correct vertical deviations in Graves' orbitopathy patients.

PURPOSE: Patients with vertical strabismus and consecutive diplopia due to Graves' orbitopathy (GO) might need recession of the rectus superior muscle. The aim of this retrospective analysis is to provide dose-effect values and motility analysis for these patients. METHODS: Dose-effect relations (deviation reduction in primary position per amount of recession in mm), monocular excursions and size of the field of binocular single vision (BSV) were evaluated in three different groups of patients. Group 1 (n = 33) patients with primary fibrosis of superior rectus muscle undergoing recession of the ipsilateral rectus superior, Group 2 (n = 14) superior rectus muscle recession after recession of inferior rectus on the contralateral eye and Group 3 (n = 15) simultaneous ipsilateral superior rectus recession and contralateral inferior rectus muscle recession. Surgery was performed using the dose-effect for inferior rectus recession of 4 prism dioptre (PD,Δ ) reduction/per mm recession and the intraoperative traction test. RESULTS: Restoration of BSV in the central 20° of gaze could be reached in 88%, 79% and 67% of patients in the three groups, respectively. Restoration of BSV in downgaze (up to 30°) was a little less successful, 79%, 57% and 53%, respectively. The median dose-effect was 3.2Δ reduction/mm recession in Group 1 (Spearman correlation r = 0.75, p < 0.0001) and 3.3Δ /mm in Group 2 (n.s.) and 4Δ /mm in Group 3 (r = 0.67, p = 0.016). The basis for the improvement was the symmetrization of ductions. CONCLUSION: If superior rectus recession is necessary in GO, higher dosing around 3Δ reduction/per mm recession should be applied. In case of large deviations, combined vertical surgery (inferior rectus and superior rectus contralateral) is required and reasonable (low cyclotorsion). Single-step or two-step procedures lead to similar results.

Quantification of Global Ocular Motility Impairment in Graves' Orbitopathy by Measuring Eye Muscle Ductions.

Background: The overall changes of ocular motility in Graves' orbitopathy (GO) are not easily quantifiable with the methods currently available, especially in clinical studies. The aim of the present study was to calculate parameters that quantify the changes of ocular motility in GO in relation to the Gorman score for diplopia. Methods: We studied 100 GO patients (Group 1) and 100 controls (Group 2). We also included 30 patients treated with intravenous methylprednisolone (iv-MP), assessed at baseline and after 12 and 24 weeks (Group 3), and 66 patients submitted to squint surgery, assessed at baseline and after 12 weeks (Group 4). Ocular ductions were measured in four gaze directions by a perimeter arc and were used to calculate a total motility score (TMS) as the sum of ductions in each direction; a biocular TMS (b-TMS) as the sum of the TMS of two eyes; and an asymmetry ratio (AR) as the sum of the differences of the corresponding ductions between the two fellow eyes divided by the mean difference found in controls. Quality of life was accessed by a specific questionnaire (Graves' orbitopathy quality of life [GO-QoL] questionnaire). Results: TMS and b-TMS were lower, while AR was higher, in Group 1 compared with controls (p < 0.001). In Group 1, TMS and b-TMS were inversely correlated with the Gorman score (p < 0.001) and AR was higher in patients with constant diplopia compared with the others (p < 0.001). In Group 3, TMS and b-TMS increased after treatment in responders to iv-MP (p < 0.001). In Group 4, TMS and b-TMS improved in all patients after surgery (p < 0.01), while AR and GO-QoL score improved only in those without residual constant diplopia (p < 0.001). Conclusion: We describe a quantitative method to assess eye motility dysfunction in any stage of GO to be used as an outcome measure in clinical studies.