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.

Systematic review of ocular surface treatments in the setting of thyroid eye disease.

Introduction: Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Methods: Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Results: Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. Conclusion: This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

A novel nomogram to predict glucocorticoid response in thyroid-associated ophthalmopathy: findings from a pilot study.

PURPOSE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. CONCLUSION: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Thyroid-associated ophthalmopathy: the role of oxidative stress.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition affecting the eyes, characterized by proptosis, extraocular muscle involvement, and in severe cases, vision impairment including diplopia, optic neuropathy, and potential blindness. The exact etiology of TAO remains elusive; however, increased oxidative stress and decreased antioxidant capacity are pivotal in its pathogenesis. Elevated oxidative stress not only directly damages orbital tissues but also influences thyroid function and autoimmune responses, exacerbating tissue destruction. This review explores the role of oxidative stress in TAO, elucidates its mechanisms, and evaluates the efficacy and limitations of antioxidant therapies in managing TAO. The findings aim to enhance understanding of oxidative stress mechanisms in TAO and propose potential antioxidant strategies for future therapeutic development.

Assessing the relationship between levator palpebrae superioris and thyroid-associated ophthalmopathy using the Dixon-T2WI sequence.

Background: The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI. Methods: The retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS_T) and signal intensity ratio (LPS_SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS_T and LPS_SIR. Results: In the TAO group, LPS_T and LPS_SIR were higher than those in the normal group (p < 2.2e-16). The upper lid retraction (ULR) ≥ 2 mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505 mm) and 0.81 for LPS_SIR (cutoff: 1.170). LPS_T (p = 2.8e-07) and LPS_SIR (p = 3.9e-12) in the active phase were higher than in the inactive phase. LPS_T and LPS_SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups (p < 0.05). ROC showed an AUC of 0.70 for LPS_T (cutoff: 2.095 mm) in judging the active phase, and 0.78 for LPS_SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS_T (cutoff: 2.095 mm) and 0.78 for LPS_SIR (cutoff: 1.197). Conclusion: The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

A comprehensive epigenetic network can influence the occurrence of thyroid-associated ophthalmopathy by affecting immune and inflammatory response.

The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncRNA/circRNA/mRNA sequencing data, as well as several RNA methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding RNA, and RNA methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding RNA. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by RNA epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.

Dixon MRI-based quantitative parameters of extraocular muscles, intraorbital fat, and lacrimal glands for staging thyroid-associated ophthalmopathy.

OBJECTIVE: To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). METHODS: Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. RESULTS: Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p < 0.05). The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were independently associated with active TAO (all p < 0.05). The combination of the EOM-SIRmean, LG-SIRmean, and LG-FFmean values showed better performance than the EOM-SIRmean value alone in staging TAO in both the training (AUC, 0.820 vs 0.793; p = 0.016) and validation (AUC, 0.751 vs 0.733, p = 0.341) cohorts. CONCLUSION: Dixon MRI-based parameters of EOMs, LGs, and IF are useful for differentiating active from inactive TAO. The integration of multiple parameters can further improve staging performance. CRITICAL RELEVANCE STATEMENT: In this study, the authors explored the combined value of quantitative parameters of EOMs, IF, and LGs derived from Dixon MRI in staging TAO patients, which can support the establishment of a proper therapeutic plan. KEY POINTS: The quantitative parameters of EOMs, LGs, and IF are useful for staging TAO. The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were found to independently correlate with active TAO. Joint evaluation of orbital tissue improved the ability to assess TAO activity.

Potential role of IGF-1R in the interaction between orbital fibroblasts and B lymphocytes: an implication for B lymphocyte depletion in the active inflammatory phase of thyroid-associated ophthalmopathy.

BACKGROUND: Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED. METHODS: Orbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA. RESULTS: IGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients. CONCLUSIONS: IGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.

Advances in artificial intelligence in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), also referred to as Graves' ophthalmopathy, is a medical condition wherein ocular complications arise due to autoimmune thyroid illness. The diagnosis of TAO, reliant on imaging, typical ocular symptoms, and abnormalities in thyroid function or thyroid-associated antibodies, is generally graded and staged. In recent years, Artificial intelligence(AI), particularly deep learning(DL) technology, has gained widespread use in the diagnosis and treatment of ophthalmic diseases. This paper presents a discussion on specific studies involving AI, specifically DL, in the context of TAO, highlighting their applications in TAO diagnosis, staging, grading, and treatment decisions. Additionally, it addresses certain limitations in AI research on TAO and potential future directions for the field.

Triamcinolone injection in the treatment of lid retraction for thyroid-associated ophthalmopathy: A systematic review.

INTRODUCTION AND OBJECTIVES: Lid retraction is one of the most common symptoms of Thyroid-Associated Ophthalmopathy (TAO), which potentially precipitates various complications, such as dry eyes, exposure keratopathy, and cosmetic concerns. Local corticosteroid injections, such as triamcinolone, have been proposed as a choice of treatment for TAO. This approach may be a favorable alternative for patients intolerant to the systemic effects of high-dose methylprednisolone. However, the efficacy of this intervention remains unestablished. Hence, our review aims to evaluate the efficacy of triamcinolone injection in reducing lid retraction. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted in three databases (PubMed, Science Direct, and ProQuest). This review included studies that use local triamcinolone injections for patients with thyroid-associated ophthalmopathy. The outcome of interest in this review is lid retraction parameters. RESULTS: From six studies, a total of 392 patients were included. All studies showed significant improvement in lid retraction in the patient who received triamcinolone (all p < 0.05) as shown by ΔMRD (-0.93 mm in 1 month and -1.38 mm in 3 months), ΔMLD (-1.98 mm at 6 months), and Δpalpebral fissure height (-1.68 in 1 month). The majority of studies showed rapid improvement in lid retraction in the first month of therapy. CONCLUSION: Triamcinolone injection is an effective therapy for lid retraction related to thyroid-associated ophthalmopathy.

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.

Long-term surgical outcome and impact on daily life activities of strabismus surgery in thyroid-associated ophthalmopathy with and without previous orbital decompression.

BACKGROUNDS: To report the long-term surgical outcomes and the impact on daily life activities of strabismus surgery in patients with Thyroid Associated Orbitopathy (TAO) with and without previous orbital decompression. METHODS: Patients who underwent strabismus surgery for TAO were retrospectively reviewed. The primary outcome was to evaluate the influence of orbital decompression on the outcomes of TAO related strabismus surgery. Surgical success was defined by the resolution of diplopia and a post-operative deviation < 10 prism diopters (PD). The secondary outcomes were the clinical features, surgical approaches, and impact on daily life activities. RESULTS: A total of 45 patients were included in the study. The decompression surgery group (DS) included 21 patients (46.7%), whereas the non-decompression surgery group (NDS) patients were 24 (53.3%). The mean follow-up time from the last strabismus surgery was 2,8 years (range 8-200 months). Successful surgical outcome was achieved in 57,1% of patients in the DS, and 75% of patients in the NDS (p = 0,226). DS patients required almost twice the number of surgical interventions for strabismus compared to the NDS (1,95 vs. 1,16 respectively, p = 0,006), a higher number of extraocular muscles recessed in the first surgery (2,67 vs. 1,08 respectively, p < 0.001), and a lower rate of unidirectional surgery compared to NDS (23% vs. 95%, p < 0,001). At the pre-operative assessment, 71.4% of DS patients had eso-hypotropia, while no patients had this type of strabismus in the NDS group (p < 0.001). On the other hand, the hypotropia rate was 79.2% in NDS patients and only 4.8% in DS patients (p < 0.001). Moreover, 21,8% of NDS patients used prism lenses in daily life activities, compared to 42.9% of patients that used prism lenses to reduce the impairment in their daily life activities (p = 0.016). CONCLUSIONS: The results of our study showed that DS patients required almost twice the number of strabismus surgical procedures, a higher number of extraocular muscles recessed in the first surgery, and an increased need for prism lenses to correct the residual deviation compared to the NDS, but with similar long-term surgical outcomes.

An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

A TSHR-Targeting Aptamer in Monocytes Correlating with Clinical Activity in TAO.

Background: Manifestations of thyroid-associated ophthalmopathy (TAO) vary greatly. Few tools and indicators are available to assess TAO, restricting personalized diagnosis and treatment. Aim: To identify an aptamer targeting thyroid-stimulating hormone receptor (TSHR) and utilize this aptamer to evaluate clinical activity in patients with TAO. Methods: An aptamer targeting TSHR was developed by exponential enrichment and systematic evaluation of TSHR ligands. After truncation and optimization, the affinity, equilibrium dissociation constant, and serum stability of this aptamer were evaluated. The affinity of the TSHR-targeting aptamer to isolated fibrocytes was assessed, as was aptamer internalization by fibrocytes. The mechanism of binding was determined by molecular docking. The correlation between disease manifestations and the percentage of TSHR-positive cells was assessed by correlation analysis. Results: The aptamer TSHR-21-42 was developed to bind to TSHR, with the equilibrium dissociation constant being 71.46 Kd. Isolated fibrocytes were shown to bind TSHR-21-42 through TSHR, with its affinity maintained at various temperatures and ion concentrations. TSHR-21-42 could compete with anti-TSHR antibody, both for binding site to TSHR and uptake by cells after binding. In addition, TSHR-21-42 could bind to leukocytes in peripheral blood, with this binding differing in patients with TAO and healthy control subjects. The percentage of TSHR-positive monocytes, as determined by binding of TSHR-21-42, correlated positively with clinical activity score in patients with TAO, indicating that TSHR-21-42 binding could assess the severity of TAO. Conclusion: This aptamer targeting TSHR may be used to objectively assess disease activity in patients with TAO, by evaluating the percentages of TSHR positive cells in peripheral blood.

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.

A meta-analysis of the efficacy of two-wall orbital decompression operations for thyroid-associated ophthalmopathy.

BACKGROUND: The main treatment for the symptoms of proptosis and optic nerve compression caused by thyroid-associated ophthalmopathy is orbital decompression surgery. Medial inferior wall decompression and balanced decompression are two frequently used surgical procedures. However, there is no unified consensus on how to choose different surgical options for orbital decompression in clinical practice. AIMS: To compare the effects of medial inferior wall decompression and balanced decompression surgery through meta-analysis and to provide reference for clinical optimal decision making. METHODS: Databases, including PubMed, Web of Science, Ovid, Cochrane Library, and ClinicalTrials.gov, were searched for randomized controlled trials and cohort studies on decompression surgery for thyroid-associated ophthalmopathy published from inception to March 21, 2023. Using RevMan 5.3 software, a meta-analysis was conducted based on the following outcome indicators: proptosis, diplopia rate, intraocular pressure, visual acuity, and complication rate. RESULTS: Two randomized controlled trials and five cohort studies with a total of 377 patients were included in this analysis. After balanced decompression surgery, patients with thyroid-associated ophthalmopathy experienced a significant decrease in proptosis [MD = 4.92, 95% CI (4.26, 5.58), P < 0.0001]. Balanced decompression can improve postoperative visual acuity [MD = - 0.35, 95% CI (- 0.56, - 0.13), P = 0.001] and intraocular pressure [MD = 5.33, 95% CI (3.34, 7.32), P < 0.0001]. The rates of proptosis [MD = 0.33, 95% CI (- 1.80, 2.46), P = 0.76] and diplopia [OR = 1.20, 95% CI (0.38, 3.76), P = 0.76] did not differ between patients who underwent medial inferior wall decompression and those who underwent balanced decompression. CONCLUSION: Balanced decompression and medial inferior wall decompression are both effective options for surgical treatment of thyroid-associated ophthalmopathy in clinical practice.

Statins and thyroid eye disease (TED): a systematic review.

PURPOSE: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED. METHODS: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2). RESULTS: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy. CONCLUSION: Statin therapy could be a potential adjunctive modality for preventing and treating TED. TRIAL REGISTRATION: PROSPERO registration number: CRD42022315522.

Functional decoding and meta-analytic connectivity modeling in thyroid-associated ophthalmopathy.

Background: Thyroid-associated ophthalmopathy (TAO) is an orbital disease closely related to thyroid disease with a long-lasting duration that can be blinding and disabling. Recently, structural and functional neuroimaging studies have been performed in TAO patients, but studies have reported inconsistent results. This quantitative meta-analysis was conducted to identify convergent patterns of abnormal brain function among different studies in TAO. Methods: We searched PubMed, EMBASE, Cochrane, and Web of Science, performed reference tracking, and retrieved 15 eligible studies. Peak coordinates were extracted from these studies and subsequently tested for convergence using activation likelihood estimation (ALE). Results: Compared to healthy subjects, resting-state brain activity in the whole brain of TAO patients was significantly increased in the left superior frontal gyrus (SFG) and decreased in the left cuneus/precuneus. Functional decoding analysis of the BrainMap database revealed that these regions are predominantly associated with cognitive and emotional impairment. In this study, task-related meta-analytic connectivity modeling (MACM) analysis was used to describe the connectivity and function of the two seed regions. Significant coactivation of these regions was found primarily in the bilateral superior parietal lobule, medial frontal gyrus, left fusiform gyrus, left cingulate gyrus, supplementary motor area and thalamus. Conclusion: Our findings underscore the role of the SFG and the cuneus/precuneus in the pathophysiology of TAO, highlighting the crucial impact of working memory deficits.

Global research on artificial intelligence in thyroid-associated ophthalmopathy: A bibliometric analysis.

Purpose: To provide an overview of global publications on artificial intelligence (AI) in thyroid-associated ophthalmopathy (TAO) through bibliometric analysis. Methods: Publications related to AI in TAO from inception until April 2023 were retrieved from the Web of Science database. The trends of publications and citations, publishing performance, collaboration among countries and institutions, and the funding agencies, relevant research domains, leading journals, hotspots and their evolution were identified. Results: A total of 55 publications were included for analysis. The number of publications and citations continued to grow since 1998, with a significant acceleration of growth after 2020. China is the most productive country with the highest number of productive institutions, followed by the United States. European countries have the most extensive collaboration. The most relevant research domain was radiology, nuclear medicine & medical imaging. The European Journal of Radiology was one of the most productive journals, with the most influential articles published. "Thyroid-associated ophthalmopathy" and "neural network" maintain hotspots during the entire period. Studies were more focused on clinical features during 1998 and 2016, clinical features and medical data during 2017 and 2020, and medical data and AI techniques during 2021 and 2023. Conclusions: This study summarized the global research status regarding AI in TAO in terms of trends, countries, institutions, research domains, journals, and key topics. AI has shown great potential in TAO. Sponsored by funding agencies such as NSFC, China has become the most productive country in the field of AI in TAO. Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.

Early diagnosis of thyroid-associated ophthalmopathy using label-free Raman spectroscopy and multivariate analysis.

Thyroid-associated ophthalmopathy (TAO) is the most common orbital disease in adults, with complex clinical manifestations and significant impacts on the life quality of patients. The current diagnosis of TAO lacks reliable biomarkers for early and non-invasive screening and detection, easily leading to poor prognosis. Therefore, it is essential to explore new methods for accurately predicting TAO development in its early stage. In this study, Raman spectroscopy, with non-destructive, label-free, and high-sensitivity characteristics, was used to analyze the differences in biochemical components of orbital adipocyte and tear samples between TAO and control groups. Furthermore, a multivariate analysis method (i.e., Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA)) was applied for data processing and analysis. Compared with controls, PCA-LDA yielded TAO diagnostic accuracies of 72.7% and 75.0% using orbital adipocytes and tears, respectively. Our proof-of-concept results suggest that Raman spectroscopy holds potential for exploring the underlying pathogenesis of TAO, and its potential application in early screening of other thyroid-associated diseases can be further expanded.