Lacrimal gland enlargement in inactive thyroid eye disease: a case series and literature review.

PURPOSE: This study aimed to evaluate the morphometric and volumetric dimensions of the lacrimal gland in patients with inactive thyroid eye disease and compare them with the values reported in the literature. METHODS: This case series evaluated consecutive patients with inactive thyroid eye disease treated at a tertiary eye hospital from 2015 to 2020. The patients' baseline demographics and clinical characteristics were obtained. The axial and coronal length, width, and volume of the lacrimal gland were measured on computed tomography scan images, and the results were statistically analyzed. RESULTS: A total of 21 patients (42 orbits) with inactive thyroid eye disease were evaluated. Their mean age was 49.0 ± 14.6 years, and 12 (57.1%) of them were men. The main complaint was dryness, and the majority of the patients had good vision and mild proptosis. The mean axial length and width of the lacrimal gland were 19.3 ± 3.9 mm and 7.5 ± 2.1 mm, respectively; coronal length and width, 20.4 ± 4.5 mm and 7.5 ± 2.1 mm, respectively; and lacrimal gland volume, 0.825 ± 0.326 mm3. Age, sex, or laterality were not found to be determinants of lacrimal gland enlargement. CONCLUSION: Patients with thyroid eye disease have enlarged lacrimal gland even in the nonactive phase of the disease multifactorial aspects influence the lacrimal gland in thyroid eye disease, making it difficult to establish a clear correlation with predisposing factors. Further studies are warranted to better understand the association between thyroid eye disease and the lacrimal gland.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

AIMS: To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS: Multiple 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. RESULTS: Compared 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. CONCLUSION: The 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.

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.

Superficial ocular vascular changes after orbital decompression in patients with thyroid ophthalmopathy measured by anterior segment OCT angiography; an observational study.

Thyroid eye disease (TED) is a common ophthalmologic manifestation of thyroid dysfunction. Despite various imaging techniques available, there hasn't been a widely adopted method for assessing the anterior segment vasculature in TED patients. Our study aimed to evaluate alterations in ocular surface circulation following orbital decompression surgery in TED patients and investigate factors influencing these changes. Using anterior segment optical coherence tomography-angiography (AS-OCTA), we measured ocular surface vascularity features, including vessel density (VD), vessel diameter index (VDI), and vessel length density (VLD), both before and after decompression surgery, alongside standard ophthalmic examinations. Our AS-OCTA analysis revealed a significant decrease in most of the temporal vasculature measurements six weeks post-surgery (p < 0.05). However, differences in the nasal region were not statistically significant. These findings indicate notable changes in ocular surface circulation following orbital decompression in TED patients, which may have implications for intraocular pressure (IOP) control and ocular surface symptoms management. AS-OCTA holds promise as a tool for evaluating the effectiveness of decompression surgery and assessing the need for further interventions.

Effect of orbital decompression surgery on the choroidal profile in patients with thyroid eye disease.

This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in patients with thyroid eye disease (TED). Fifty-one eyes from 38 patients with controlled TED and proptosis were enrolled in this study. The majority of the patients (50.9%) had a clinical activity score (CAS) of zero, and none had a CAS greater than 2. The patients underwent a complete baseline ophthalmologic examination, and their choroidal profile alterations were monitored using enhanced depth imaging optical coherence tomography (EDI-OCT) before and during the three months after surgery. Changes in SFCT, luminance area (LA), total choroidal area (TCA), and the choroidal vascularity index (CVI) were measured as the ratio of LA to TCA in EDI-OCT images. The participants had an average age of 46.47 years, and 22 were female (57.9%). The SFCT of the patients exhibited a significant reduction over the follow-up period, decreasing from 388 ± 103 to 355 ± 95 µm in the first month (p < 0.001) and further decreasing to 342 ± 109 µm by the third month compared to baseline (p < 0.001). The CVI exhibited a drop from 0.685 ± 0.037 at baseline to 0.682 ± 0.035 and 0.675 ± 0.030 at 1 and 3 months post-surgery, respectively. However, these changes were not statistically significant, indicating comparable decreases in both LA and TCA. There was a significant correlation between improved proptosis and reduction in SFCT (p < 0.001) but not with CVI (p = 0.171). In conclusion, during the three months of follow-up following orbital wall decompression, CVI did not change, while SFCT reduced significantly. Additionally, SFCT was significantly correlated with proptosis reduction, whereas CVI was not.

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.

Performance of T2 mapping in the staging of Graves' ophthalmopathy based on different region of interest selection methods.

BACKGROUND: Discriminating the stage of Graves' ophthalmopathy (GO) is crucial for clinical decision. Application of conventional T2-weighted imaging in the staging is still limited. PURPOSE: To evaluate the performance of T2 mapping based on two different regions of interest (ROIs) for staging GO. MATERIAL AND METHODS: In total, 56 GO patients were retrospectively enrolled and divided into two groups according to the clinical activity score (CAS). T2 relaxation time (T2RT) of extraocular muscle (EOM) on T2 mapping based on two different ROIs (T2RTROI-1: ROIs were drawn separately in the four EOMs; T2RTROI-2: ROI was drawn in the most inflamed EOM) was measured and compared between active and inactive groups. RESULTS: Both T2RTROI-1 and T2RTROI-2 values in the active GO were significantly higher than those of inactive GO (P <0.001). T2RTROI-1 and T2RTROI-2 values were positively correlated with CAS (rs=0.73, 0.69; P <0.001). When the T2RTROI-1 value of 83.3 ms and T2RTROI-2 value of 106.3 ms were used as cutoff values for staging GO, respectively, the best results were obtained with areas under the curve (AUCs) of 0.822 and 0.827. There was no significant difference for AUCs between T2RTROI-1 and T2RTROI-2 (P = 0.751). Excellent and good inter-observer agreements were achieved in quantitative measurements for T2RTROI-1 and T2RTROI-2 values, respectively, with intraclass correlation coefficients of 0.954 and 0.882. CONCLUSION: The T2RT values derived from two different ROIs were useful for assessment of disease activity. Taking reproducibility and diagnostic performance into consideration, T2RTROI-1 would be an ideal image biomarker for staging GO compared to T2RTROI-2.

Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

Deep-Learning Based Automated Segmentation and Quantitative Volumetric Analysis of Orbital Muscle and Fat for Diagnosis of Thyroid Eye Disease.

Purpose: Thyroid eye disease (TED) is characterized by proliferation of orbital tissues and complicated by compressive optic neuropathy (CON). This study aims to utilize a deep-learning (DL)-based automated segmentation model to segment orbital muscle and fat volumes on computed tomography (CT) images and provide quantitative volumetric data and a machine learning (ML)-based classifier to distinguish between TED and TED with CON. Methods: Subjects with TED who underwent clinical evaluation and orbital CT imaging were included. Patients with clinical features of CON were classified as having severe TED, and those without were classified as having mild TED. Normal subjects were used for controls. A U-Net DL-model was used for automatic segmentation of orbital muscle and fat volumes from orbital CTs, and ensemble of Random Forest Classifiers were used for volumetric analysis of muscle and fat. Results: Two hundred eighty-one subjects were included in this study. Automatic segmentation of orbital tissues was performed. Dice coefficient was recorded to be 0.902 and 0.921 for muscle and fat volumes, respectively. Muscle volumes among normal, mild, and severe TED were found to be statistically different. A classification model utilizing volume data and limited patient data had an accuracy of 0.838 and an area under the curve (AUC) of 0.929 in predicting normal, mild TED, and severe TED. Conclusions: DL-based automated segmentation of orbital images for patients with TED was found to be accurate and efficient. An ML-based classification model using volumetrics and metadata led to high diagnostic accuracy in distinguishing TED and TED with CON. By enabling rapid and precise volumetric assessment, this may be a useful tool in future clinical studies.

A Preliminary Evaluation of the Diagnostic Performance of a Smartphone-Based Machine Learning-Assisted System for Evaluation of Clinical Activity Score in Digital Images of Thyroid-Associated Orbitopathy.

Background: We previously developed a machine learning (ML)-assisted system for predicting the clinical activity score (CAS) in thyroid-associated orbitopathy (TAO) using digital facial images taken by a digital single-lens reflex camera in a studio setting. In this study, we aimed to apply this system to smartphones and detect active TAO (CAS ≥3) using facial images captured by smartphone cameras. We evaluated the performance of our system on various smartphone models and compared it with the performance of ophthalmologists with varying clinical experience. Methods: We applied the preexisting ML architecture to classify photos taken with smartphones (Galaxy S21 Ultra, iPhone 12 pro, iPhone 11, iPhone SE 2020, Galaxy M20, and Galaxy A21S). The performance was evaluated with smartphone-captured images from 100 patients with TAO. Three ophthalmology residents, three general ophthalmologists with <5 years of clinical experience, and three oculoplastic specialists independently interpreted the same set of images taken under a studio environment and compared their results with those generated by the smartphone-based ML-assisted system. Reference CAS was determined by a consensus of three oculoplastic specialists. Results: Active TAO (CAS ≥3) was identified in 28 patients. Smartphone model used in capturing facial images influenced active TAO detection performance (F1 score 0.59-0.72). The smartphone-based system showed 74.5% sensitivity, 84.8% specificity, and F1 score 0.70 on top three smartphones. On images from all six smartphones, average sensitivity, specificity, and F1 score were 71.4%, 81.6%, and 0.66, respectively. Ophthalmology residents' values were 69.1%, 55.1%, and 0.46. General ophthalmologists' values were 61.9%, 79.6%, and 0.55. Oculoplastic specialists' values were 73.8%, 90.7%, and 0.75. This smartphone-based ML-assisted system predicted CAS within 1 point of reference CAS in 90.7% using facial images from smartphones. Conclusions: Our smartphone-based ML-assisted system shows reasonable accuracy in detecting active TAO, comparable with oculoplastic specialists and outperforming residents and general ophthalmologists. It may enable reliable self-monitoring for disease activity, but confirmatory research is needed for clinical application.

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.

T2 Relaxation Time in Extraocular Muscles of Patients with Mild Thyroid- Associated Ophthalmopathy: Comparing T2 Mapping With and Without Fat Suppression Using Different Measurement Methods.

OBJECTIVE: This study aimed to compare the parametric value of T2 with and without fat suppression (FS) on T2 mapping for the evaluation of extraocular muscles (EOMs) in mild thyroid-associated ophthalmopathy (TAO). METHODS: We prospectively recruited 44 consecutive patients with mild TAO seen between May 2020 and October 2022 and 26 healthy controls with no history of eye- or thyroid-related or other autoimmune diseases. Patients with mild TAO were subdivided into active and inactive groups based on their clinical activity scores. The T2 of each EOM was measured over a large and small area of interest on T2-mapping images with and without FS. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of T2 for detecting TAO activity. RESULTS: The T2 was significantly and heterogeneously higher in the active group than in the inactive and control groups (P < 0.05). FS-T2-mapping images had better signal display within and at the edges of the EOMs than those without FS. It was possible to observe high-signal aggregation visible in the periphery of some EOMs, and the central part showed relatively low signals. The maximum T2 measured in small or large areas with and without FS had good diagnostic efficacy for TAO activity, with that of no-FS being better (the area under the ROC curve of the maximum T2 measured in a small area and a large area without FS was 1.0 and 1.0 and P values of < 0.001 and < 0.001, respectively). CONCLUSION: Maximal T2 with or without FS can facilitate the early clinical detection of mild TAO activity. The maximum T2 in a small area can facilitate active staging of patients with mild TAO.

An ensemble deep learning diagnostic system for determining Clinical Activity Scores in thyroid-associated ophthalmopathy: integrating multi-view multimodal images from anterior segment slit-lamp photographs and facial images.

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

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

PURPOSE: 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. DESIGN: Systematic review and meta-analysis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PROSPERO REGISTRATION NUMBER: CRD42023446376.

New Multi-Parameters Combination of Technetium-99m-Diethylene-Triamine-Pentaacetate Orbital Single-Photon Emission Computed Tomography/Computed Tomography for the Evaluation of Graves' Orbitopathy Activity.

PURPOSE: This study investigates the new combined parameters of 99mTc-DTPA orbital single-photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of Graves' orbitopathy (GO) activity. METHODS: A retrospective analysis was performed on 41 patients. All the patients undergone the 99mTc-DTPA orbital SPECT/CT and were categorized into active and inactive group based on the standard combined by the clinical active score (CAS), magnet resonance imaging (MRI) and/or follow-up results. Quantitative parameters of lacrimal gland (LG) including the protruding degree of lacrimal gland herniation (LGH) and uptake ratios (URs) of region of interest (ROI) drawn on lacrimal gland and occipital bone. SPECT/CT reading results were based on visual analysis. Parameters were compared between the two groups and the diagnostic value on discrimination of GO activity was also evaluated. RESULTS: All parameters of SPECT/CT for active GO groups were significantly higher than those of the inactive groups (p<.05). There were notable linear positive correlations between the assumption standard and readings as well as combination models 2 and 3 (r = .794, r = .772, r = .760, respectively). ROC analysis indicated that model 2 provided the highest diagnostic performance, exhibiting an area under the curve (AUC) of .947, a sensitivity of 92.7%, and a specificity of 88.6%. CONCLUSIONS: The combined use of SPECT/CT reading results and DTPA uptake parameters of LG offers a more objective and precise evaluation of active GO. This study further recommends 99mTc-DTPA SPECT/CT might be serving as a supplementary beneficial approach for CAS in evaluating GO activity.

Artificial Intelligence-based quantitative evaluation of retinal vascular parameters in thyroid-associated ophthalmopathy.

PURPOSE: Thyroid-associated ophthalmopathy (TAO) may result in increased metabolism and abnormalities in microcirculation. The fractal dimension (Df) of retinal vessels has been shown to be related to the pathology of a number of ophthalmic disorders, but it hasn't been investigated in TAO. METHODS: We analyzed 1078 participants aged 18 to 72 (548 healthy volunteers and 530 TAO). Images were captured using a non-mydriatic 45-degree fundus camera. Baseline retinal characteristics, such as vessel width, tortuosity, and Df were measured using semiautomated software from fundus images. The average retinal parameters were compared between the two groups. The receiver operation curve (ROC) was used to assess the diagnostic efficacy of various retinal vascular parameters for TAO. RESULTS: Despite controlling for potential confounding variables, Df, vessel width, and tortuosity significantly increased in TAO compared to healthy volunteers. Compared to active TAO, patients in the inactive phase had a larger retinal venous caliber (p < 0.05), but there was no difference in Df or arterial caliber. Moderate and severe cases had a higher Df compared with mild cases (EUGOGO guidelines). The area under the ROC for Df, tortuosity, and vascular caliber in the diagnosis of TAO was 0.904 (95% CI: 0.884-0.924), 0.638 (95% CI: 0.598-0.679), and 0.617 (95% CI: 0.576-0.658), respectively. CONCLUSIONS: Due to its accessibility, affordability, and non-invasive nature, retinal vascular Df may serve as a surrogate marker for TAO and might be used to identify severe cases. With relatively high diagnostic performance, the Df is of some utility for the detection of TAO.

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.

Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease.

BACKGROUND: Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. METHODS: In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. RESULTS: The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. CONCLUSIONS: The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

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

OBJECTIVES: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). METHODS: 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. RESULTS: 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). CONCLUSION: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. CLINICAL RELEVANCE STATEMENT: 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. KEY POINTS: • 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.