Dysthyroid Optic Neuropathy Research Articles

Lacrimal gland enlargement in thyroid eye disease.

This study aimed to investigate lacrimal gland (LG) enlargement in thyroid eye disease (TED) patients on magnetic resonance imaging (MRI). A retrospective review was conducted on TED patients who had undergone fat-suppressed contrast-enhanced T1-weighted MRI of the orbits. The lacrimal gland was segmented on OsiriX in consecutive axial and coronal slices to determine its volume. Enlargement was defined as a volume greater than 1100mm3, based on previous normative data. Asymmetric enlargement was defined if one side was enlarged but the contralateral side was not. Clinical data including presentation (active/inactive) and presence or absence of dysthyroid optic neuropathy was evaluated. The study population consisted of 88 orbits from forty-four patients with a mean age of 53 ± 15years, with 29 (65%) being female. Twelve patients (27%) had LG enlargement, with eight (18%) having bilateral enlargement and four (9%) having asymmetric enlargement. There was no significant difference in age (p = 0.17) or sex (p = 0.44) between the LG enlarged and non-enlarged groups. There was also no significant difference in the clinical activity (p = 0.46) or prevalence of dysthyroid optic neuropathy (p = 0.63) between the LG enlarged orbits and non-LG enlarged orbits. Lacrimal gland enlargement may be observed in approximately thirty percent of TED patients, with asymmetric enlargement in approximately ten percent of cases.

Clinical Characteristics and Underlying Pathophysiology in 4 Subtypes of Dysthyroid Optic Neuropathy Patients

Objective: To analyze different subtypes, clinical characteristics, and pathophysiologies of dysthyroid optic neuropathy (DON) based on orbital fat and extraocular muscle (EOM) volume increases on orbital CT images. Methods: The author retrospectively reviewed the medical records of 80 patients (152 eyes) who were diagnosed with DON and treated at Anam, Guro, or Ansan hospitals of the Korea University College of Medicine from February 2006 to December 2023. Clinical features, ophthalmic examination, demographic characteristics, thyroid status, and radiographic findings from computed tomography scans (prevalence of fat or muscle volume increases) were analyzed. Results: Four groups were designated based on EOM volume (MV) and orbital fat volume (FV). Group 1 had no increase in MV or FV (5.3%, 8 eyes), group 2 had increased FV only (8.66%, 13 eyes), group 3 had an increase in MV only (52.6%, 80 eyes), while group 4 had both MV and FV increase (33.6%, 51 eyes). Patients in group 1 were younger and had low diplopia scores than patients in the other groups. Decreases in visual acuity, color vision abnormalities, diplopia score, and apical crowding were less frequent in groups 1 and 2 than groups 3 and 4 (P=0.000). Patients in groups 3 and 4 had significantly more apical crowding and higher diplopia scores and CAS scores than patients in groups 1 and 2 (P=0.000 and 0.013, respectively). The number of patients who underwent decompression surgery was significantly higher in groups 3 and 4 than groups 1 and 2 (P=0.000). Conclusion: Extraocular muscle enlargement occurred in 86% of DON patients and compression of the optic nerve due to enlargement of EOMs at the orbital apex is the main cause of DON. Optic nerve stretch and vascular insufficiency due to increased orbital pressure are other potential mechanisms underlying DON in groups without an increase in FV or MV. Although decreased visual acuity, color vision abnormalities, and diplopia were less frequent in these groups, greater attention should be paid to the timely diagnosis of DON.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath.

This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.

Optic nerve compression associated with visual cortex functional alteration in dysthyroid optic neuropathy: A combined orbital and brain imaging study

AbstractAimsTo investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED).MethodsMultiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low‐frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented.ResultsCompared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON.ConclusionThe combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

Graves' orbitopathy as the cause of diplopia in old age-Differences between young and old

Endocrine orbitopathy (EO) is an autoimmune disease mostly associated with a disease of the thyroid gland, which leads to inflammation, adipogenesis and fibrosis. The severity of EO can vary greatly between individuals, which makes it difficult to exactly predict the natural course of the disease; however, this is important to be able to individually adapt the treatment. The aim of this study was to compare the clinical features, course, treatment and prognosis for patients with EO under 50 years old with older patients. The results of the study with a focus on motility are presented in this special issue. The hospital records of a randomly selected sample of 1000 patients from the EO databank in Essen (GODE), which includes 4260 patients, were analyzed. The patients were divided into two groups: group 1 ≤50 years and group 2 >50 years. Only patients with complete data sets were included in the statistical analyses. Younger patients (n = 484) presented significantly more frequently with milder EO (53% vs. 33%, p < 0.0001), whereas older patients (n = 448) more frequently suffered from moderate or severe forms (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility and clinical activity scores (5.9 vs. 2.3 prism diopters, PD/310° vs. 330°, both p < 0.0001, CAS 2.1 vs. 1.7, p = 0.001). Proptosis and the occurrence of optic nerve compression showed no significant differences between the groups (3% each). Multiple logistic regression showed that the necessity for a second eye muscle surgery was most strongly associated with a previous decompression (OR = 0.12, 95 % CI 0.1-0.2, p < 0.0001), followed by orbital irradiation and age. In summary, younger patients with EO presented with milder clinical features, such as a lower rate of restrictive motility disorders and weaker expression of signs of inflammation. Therefore, older patients needed steroids, irradiation, eyelid and eye muscle surgery more frequently; however, the risk of dysthyroid optic neuropathy and the necessity of a second eye surgery were not or only slightly associated with age.

A multifactorial screening model based on the Graves ophthalmopathy quality of life scores in dysthyroid optic neuropathy.

To validate the Graves ophthalmopathy quality of life (GO-QOL) questionnaire in screening DON and to construct an effective model. A total of 194 GO patients were recruited and divided into DON and non-DON (mild and moderate-to-severe) groups. Eye examinations were performed, and quality of life was assessed by the GO-QOL questionnaire. The random forest, decision tree model, receiver operator characteristic (ROC) curve, accuracy and Brier score were determined by R software. In GO-QOL, age, best corrected visual acuity (BCVA), exophthalmos, CAS, severity, and Gorman score were found to be factors related to visual function scores. On the appearance scale, gender, duration of GO, BCVA, exophthalmos, CAS and severity of GO were relevant. Both the visual function scores and appearance scores were significantly lower in DON groups than in non-DON groups (33.18 ± 24.54 versus 81.26 ± 17.39, 60.08 ± 24.82 versus 76.14 ± 27.56). The sensitivity, specificity, and AUC of the visual function scores were 91.1%, 81.7% and 0.939, respectively Visual function scores were used to construct a decision tree model. The sensitivity, specificity, and AUC of the model were 92.9%, 88.0% and 0.941, respectively, with an accuracy of 89.7% and a Brier score of 0.024. Visual function scores were qualified as a screening method for DON, with a cutoff point of 58. A multifactorial screening model based on visual function scores was constructed.

Efficacy of rituximab in treating steroid-resistant Graves’ orbitopathy in active moderate-to-severe and sight-threatening forms: A retrospective observation from China

Background and objectivesThe efficacy of rituximab (RTX) in treating steroid-resistant Graves’ orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. MethodsData from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. ResultsThe median follow-up time was 22 (8–34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves’ Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. ConclusionA single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

Tocilizumabuse for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort.

To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.

White Matter Alterations of Visual Pathway in Thyroid Eye Disease: A Fixel-Based Analysis.

Thyroid eye disease (TED), particularly its sight-threatening complication, dysthyroid optic neuropathy (DON), profoundly impacts patients' visual health. The pathological changes in the white matter (WM) fibers within the intracranial visual pathway in TED have been infrequently studied. Understanding these changes holds crucial importance for exploring the pathogenesis and prognosis of TED. To utilize fixel-based analysis (FBA) to clarify the type of microstructural damage occurring in the visual pathway in TED. Prospective. 28 TED with DON patients (11 males and 17 females), 28 TED without DON (non-DON) patients (12 males and 16 females), and 28 healthy controls (HCs) (12 males and 16 females). 3 T; multishell diffusion MRI using echo planar imaging. Fiber density (FD) and fiber-bundle cross-section (FC) were calculated to characterize WM microstructural alteration in TED visual pathway. The correlations between FBA metrics and visual field index and mean deviation were examined. One-way analysis of variance, Kruskal-Wallis, t-tests, Mann-Whitney U, Chi-square, and Pearson correlation, were conducted with false discovery rate and family wise error corrections. Significance was set at P < 0.05. Both DON and non-DON groups showed significant FD loss in the right optic tract compared with HCs, with DON patients experiencing more severe FD loss. Only DON patients had FD loss in the right optic radiation (OR) compared with the non-DON patients and HCs, with no FC difference across groups. FD in DON patients' ORs significantly correlated with visual field index (r = 0.857) and mean deviation (r = 0.751). Both DON and non-DON affect the WM microstructure of the visual pathway to varying extents. Visual field metrics can reflect the severity of FD damage to the OR in the visual pathway of DON patients. 2. Stage 3.

Asymmetric proptosis in thyroid eye disease

PurposePatients with thyroid eye disease (TED) can present with asymmetric disease. The purpose of this study was to evaluate the prevalence of asymmetric TED in an Australian cohort and investigate clinical, biochemical, and radiological associations of asymmetric TED.MethodsThis was a retrospective study of patients with TED who underwent Hertel exophthalmometry and orbital computed tomography (CT) scans. Asymmetry was defined as a difference in the globe protrusion of ≥ 3 mm using Hertel exophthalmometry. Data was collected on patient demographics, clinical disease presentation, thyroid function tests and antibody levels. Muscles volumes were determined by manually segmenting the extraocular muscles on CT scans using a commercially available software.Results172 orbits from 86 patients were included in the study. 28 (33%) patients had asymmetric TED. No significant differences were observed in age, gender, thyroid hormone status, anti-thyroid peroxidase levels, thyroid stimulating hormone receptor antibodies, disease activity status, or dysthyroid optic neuropathy between the asymmetric and non-asymmetric groups. The extraocular muscle volumes were significantly higher in the asymmetric orbit compared to its contralateral orbit.ConclusionAsymmetric TED is a reasonably common occurrence in the course of TED. It is associated with higher extraocular muscle volumes, suggesting muscle enlargement as one of the underlying contributors to asymmetric proptosis. Thyroid eye disease should be considered in the differential of asymmetric orbital inflammatory disease.

Central and peripheral contrast sensitivity in thyroid eye disease.

Assessment of central and peripheral contrast sensitivity (CS) in thyroid eye disease (TED) with and without dysthyroid optic neuropathy (DON). 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. 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). 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.

Orbital CT scan parameters in dysthyroid optic neuropathy: a systematic review and meta-analysis.

Addressing Dysthyroid Optic Neuropathy (DON) is crucial due to its debilitating impact in thyroid eye disease (TED). Prompt treatment can preserve vision. Despite lacking definitive diagnostic criteria, computed tomography's (CT) parameters are commonly used for diagnosis. However, these parameters exist without consensus on their diagnostic performance. Systematic review and meta-analysis. We conducted a meta-analysis of studies assessing orbital CT diagnostic performance for DON in adults with TED. We searched various databases including Medline, PubMed, Scopus, and EMBASE, and others electronic databases, until July 2023. Evaluated CT parameters includes Barrett index (BI), fat prolapse via superior-orbital-fissure (SOF), superior-ophthalmic-vein-dilatation (SOVD), and the Nugent score. Diagnostic Test Accuracy analysis (DTA) was performed using R. A total of 9 articles with documented target parameters, collectively analysed 212 orbits with DON. Nugent score exhibited highest diagnostic ability with a log diagnostic odd ratio (logDOR) of 2.64 (95% CI, 2.02, 3.25). Another significant DON indicator was a BI ≥ 50%, with a logDOR of 1.97 (95% CI, 1.17; 2.77). Conversely, fat prolapse via SOF and SOVD proved less sensitive, with a logDOR of 1.42 and 1.09 respectively. Regarding the SROC curve, Nugent score and the BI have the greatest AUC. Variations in study locale, participant demographics, and measurement methods accounted for heterogeneity in meta-analysis. Nugent score and a BI ≥ 50% prove to be significant diagnostic parameters for DON, distinguishing them from fat prolapse via SOF and SOVD. Prioritizing these parameters can lead to prompt treatment and thus enhanced visual outcomes. CRD42023446376.

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

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. 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. 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. 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. 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.

Three-dimensional soft tissue reconstruction and volume measurement used for the diagnosis of dysthyroid optic neuropathy.

Dysthyroid optic neuropathy (DON) leads to vision loss. This study aimed to investigate a new method that can directly evaluate the change in muscle cone inner volume (MCIV) and distinguish DON orbits from non-DONs. This study included 54 patients (108 orbits) who were diagnosed with thyroid eye disease and treated at the Beijing Tongren Hospital between December 2019 and September 2021. The extraocular muscle volume (EOMV), orbital fat volume (OFV), and bony orbit volume (BOV) of the patients were measured using three-dimensional reconstruction. MCIV was measured using artificially defined boundaries. The associations between these volumes and clinical indicators were studied, and the diagnostic efficacy of these volumes for DON was described using receiver operating characteristic (ROC) curves. The ROC curve showed that the area under the curve of MCIV/BOV (%) combined with EOMV/BOV (%) reached 0.862 (p < 0.001), with a sensitivity of 85.7% and a specificity of 76.1%. The combination of MCIV/BOV (%) and EOMV/BOV (%) is a good indicator for the diagnosis of DON, which aids in the early detection and intervention of DON.

Diagnosis of dysthyroid optic neuropathy: combined value of orbital MRI and intracranial visual pathway diffusion kurtosis imaging.

To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI-based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy.

Long-term outcomes of inferomedial orbital wall decompression in Graves' ophthalmopathy in an Asian population: A 30-year retrospective study.

This study aims to evaluate the long-term outcomes of inferomedial orbital wall decompression (IMOD) in Graves' ophthalmopathy (GO). A retrospective review of 422 eyes of 226 patients with GO-related cosmetically disfiguring proptosis (COS), dysthyroid optic neuropathy (DON), or exposure keratopathy (EXP) who received IMOD from 1989 to 2020 was conducted. Hertel value (HE) and corrected visual acuity (CVA) were evaluated at baseline and regularly thereafter. Proptosis recurrence, diplopia, and adjuvant surgeries were assessed. Complete success was defined as proptosis reduction over 2 mm without recurrence and improved diplopia. Partial success was defined as proptosis reduction without recurrence but with persistent or new-onset diplopia, and failure as proptosis recurrence. After follow-up for 40.1 ± 39.6 months (range, 6-239 months), 236 eyes (55.9%) achieved complete success, 175 eyes (41.5%) achieved partial success, and 11 eyes (2.6%) had failure. Significant CVA improvement was observed in both DON and COS groups (P < 0.001 and P = 0.045, respectively). Average proptosis reduction was 5.2 ± 2.2 mm, with a significant increase of 0.5 mm after long-term follow-up (P < 0.001). Incidence of proptosis recurrence was 2.6%. Surgical success rate of COS group was positively correlated with preoperative HE. IMOD demonstrated excellent success rate in all three subgroups with a low proptosis recurrence rate and improved visual outcome in both DON and COS groups. Delayed proptosis reduction effect of IMOD may result in delayed-onset asymmetry, especially in the unilateral group.

3.0 T multi-parametric MRI reveals metabolic and microstructural abnormalities in the posterior visual pathways in patients with thyroid eye disease.

We aim to explore the microstructural and metabolic changes in visual pathways in patients with thyroid eye disease (TED) using 3T multi-parametric MRI. Thirty-four TED patients (inactive group = 20; active group = 14; acute group = 18; chronic group = 16) and 12 healthy controls (HC) were recruited from November 2020 to July 2021. Proton magnetic resonance spectroscopy (1H-MRS), glutamate chemical exchange saturation transfer (GluCEST) and diffusion kurtosis imaging (DKI) were performed on 3.0T MR scanner. Data analysis and group comparisons were performed after MR data processing. As compare to HC group, the levels of total choline (tCh) in optic radiation (OR) in active group ([1.404 ± 0.560] vs. [1.022 ± 0.260]; p < 0.05), together with tCh ([1.415 ± 0.507] vs. [1.022 ± 0.260]; p < 0.05) in OR in acute group were significantly increased. Glutamine (Gln) levels were higher in OR in the chronic group than those in HCs and were positively correlated with the levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3) and FT4 in chronic group. Glutamate (Glu) levels by 1H-MRS did not show significant differences between any two groups. Interestingly, MTRasym (3.0 ppm) was higher in OL in inactive group, active group, acute group and chronic group than those in HCs, and was positively correlated with Glu levels in OL in 1H-MRS. Fractional anisotropy (FA) values from DKI in OR in acute group were significantly lower than those in HCs. Our initial study demonstrate that GluCEST performs better than 1H-MRS to monitor Glu alterations in visual pathway in TED patients. Changes of brain glutamine levels in TED patients are closely related to their associated hormones alterations, indicating that disease injury status could be reflected through non-invasive metabolites detection by brain 1H-MRS. FA is the most sensitive DKI index to reveal the visual pathway impairment in TED patients. Altogether, our study revealed that 3T multiparametric MR techniques are useful to demonstrate metabolic and microstructural alterations in visual pathways in TED patients. We found that damage to visual pathways occurs in mild TED cases, which not only offers a new approach to the diagnosis of dysthyroid optic neuropathy, but also demonstrates neuropathy in TED is a gradual and continuous spatio-emporal progression.

How Age Affects Graves' Orbitopathy-A Tertiary Center Study.

Graves' orbitopathy (GO) is an autoimmune disorder leading to inflammation, adipogenesis, and fibrosis. The severity of GO can vary widely among individuals, making it challenging to predict the natural course of the disease accurately, which is important for tailoring the treatment approach to the individual patient. The aim of this study was to compare the clinical characteristics, course, treatment, and prognosis of GO patients under 50 years with older patients. We reviewed the medical records of a random sample of 1000 patients in our GO database Essen (GODE) comprising 4260 patients at our tertiary referral center. Patients were divided into two groups: Group 1 (≤50 years) and Group 2 (>50 years). Only patients with a complete data set were included in the further statistical analysis. The results showed that younger patients (n = 484) presented significantly more often with mild GO (53% vs. 33%, p < 0.0001), while older patients (n = 448) were more likely to experience moderate-to-severe disease (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility, and clinical activity scores (5.9 vs. 2.3 PD/310° vs. 330° both p < 0.0001, CAS: 2.1 vs. 1.7, p = 0.001). Proptosis and occurrence of dysthyroid optic neuropathy (DON) showed no significant difference between groups (both 3%). Multiple logistic regression revealed that the need for a second step of eye muscle surgery was most strongly associated with prior decompression (OR = 0.12, 95% CI: 0.1-0.2, p < 0.0001) followed by orbital irradiation and age. The model showed good fitness regarding the area under the curve (AUC = 0.83). In conclusion, younger GO patients present with milder clinical features such as a lower rate of restrictive motility disorders and less pronounced inflammatory signs. Therefore, older patients tend to need more steroids, irradiation, and lid and eye muscle surgery. Still, the risk of DON and the necessity of secondary eye muscle surgery are not or only slightly associated with age, respectively.

Exacerbation of Thyroid Eye Disease and Dysthyroid Optic Neuropathy During Pregnancy: A Case Report.

A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.

Transition from hypothyroidism to Graves' disease, development of thyroid eye disease, progression to optic neuropathy after inpatient pulse therapy, and long-term administration of outpatient pulse therapy: a case report with review of literature.

A 55-year-old woman transitioned from hypothyroidism to Graves' disease (GD) and then developed thyroid eye disease (TED) with proptosis and diplopia. After three cycles of daily methylprednisolone pulse therapy, her condition progressed to dysthyroid optic neuropathy with decreased visual acuity in both eyes. Her clinical activity score (CAS) was 7 points. Orbital magnetic resonance imaging (MRI) showed that the enlarged extraocular muscles were compressing the optic nerve in the area of the cones. Although her visual acuity recovered during two further cycles of daily pulse therapy, disease activity persisted for 4 years. TED exacerbated five times. Each time, the patient received weekly pulse therapy with no adverse reactions until her ophthalmopathy was relieved. The total cumulative dose of methylprednisolone was 59.5 g. Thyroid-stimulating antibody (TSAb) was positive from the time of hypothyroidism onset and became strongly positive with the onset of GD and the progress of TED. In addition, MRI was useful for the evaluation of the pathophysiology of ophthalmopathy. This case report suggests that careful monitoring by both endocrinologists and ophthalmologists using CAS, ophthalmological assessments, TSAb measurement, and orbital MRI are useful for making treatment decisions for TED.