Search Results (82)

Background/Objective: Dysthyroid Optic Neuropathy (DON) is a severe complication of Thyroid Eye Disease (TED) leading to irreversible visual impairment. Its pathogenesis remains unclear, and early predictive tools are lacking. The study aims to investigate peripheral immune characteristics associated with DON, focusing on the IL-2⁺Th1/CD4⁺Tregs axis. Methods: A retrospective study was conducted in 37 TED patients, including DON (n = 22) and non-DON (n = 15) groups. Peripheral blood immune cell subsets were quantified using flow cytometry. Clinical data and peripheral blood immune indicators including T cell subsets, B cell subsets, T helper (Th) cell subsets, and regulatory T (Treg) cells populations were analyzed. Correlation and logistic regression analyses were applied to evaluate associations between immune indicators and DON. Receiver operating characteristic (ROC) analysis was used to assess the discriminatory performance of candidate variables and exploratory combined models. Results: Patients with DON showed higher IL-2⁺Th1 levels and lower CD4⁺Tregs levels compared with non-DON patients, along with an increased IL-2⁺Th1/CD4⁺Tregs ratio. Age and clinical activity score also differed significantly between groups. The IL-2⁺Th1/CD4⁺Tregs axis showed significant alterations associated with DON. The exploratory logistic regression model combining immune and clinical indicators showed potential discriminatory ability in differentiating DON from non-DON patients. Conclusions: This study identifies an imbalance between IL-2⁺Th1 and CD4⁺Tregs as a potential immune signature associated with DON. Integration of immune and clinical features may provide an exploratory framework for risk stratification in TED. Further prospective studies with larger cohorts are warranted to validate these findings. Full article

Introduction: Teprotumumab (Tepezza^®), an insulin-like growth factor-1 receptor (IGF-1R) antagonist, is the first FDA-approved targeted therapy for thyroid eye disease (TED). While effective for reducing proptosis and inflammation, increasing post-marketing evidence has linked teprotumumab to auditory adverse events. IGF-1 signaling is essential for cochlear maintenance and neuroprotection; therefore, systemic IGF-1R inhibition presents a biologically plausible mechanism for ototoxicity. Despite growing recognition of these effects, no standardized approach exists for audiologic assessment or monitoring of patients receiving teprotumumab. This review aimed to (1) summarize proposed mechanisms and the reported spectrum of teprotumumab-related auditory effects, (2) evaluate current methods used to assess and monitor these patients, and (3) identify areas of consensus and ongoing uncertainty. Methods: An updated narrative review of the literature was conducting using PubMed, CINAHL, and Google Scholar using Boolean strings targeting teprotumumab exposure and hearing-related outcomes. Studies from 2022 onward were identified using Boolean search strings targeting teprotumumab exposure and hearing-related outcomes. Peer-reviewed English language studies reporting audiometric findings were eligible for inclusion. Results: Ten studies met inclusion criteria. Reported effects most commonly included bilateral high-frequency SNHL, tinnitus, and aural fullness, typically emerging after three to six infusions. Many cases demonstrated persistent deficits despite drug discontinuation. Baseline audiometric assessment was not uniformly reported across studies, and monitoring protocols varied considerably, with inconsistent incorporation of speech testing and immittance measures. Conclusions: Teprotumumab-associated ototoxicity is increasingly recognized and potentially irreversible. Current evidence is insufficient to guide standardized monitoring. Prospective studies are urgently needed to establish evidence-based audiologic surveillance protocols. Full article

Background: Selenium (Sel) supplementation has been proposed as an antioxidant adjunct in Graves’ orbitopathy (GO), with early randomized evidence suggesting benefits in quality of life (QoL), ocular involvement, and disease progression in mild GO. However, subsequent trials across populations with different Sel status and disease severity have yielded inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) reassessed the efficacy of Sel supplementation in GO. Methods: PubMed, Scopus, and the Cochrane Library were searched from inception to 1 May 2026 for RCTs, comparing Sel supplementation with placebo or no Sel supplementation in patients with GO (PROSPERO “CRD420261395074”). Heterogeneity was assessed using I² statistics and Cochran’s Q test. Risk ratios (RRs) were calculated using the Mantel–Haenszel method, and mean differences (MDs) using the Inverse-Variance method. Random-effects models with restricted maximum-likelihood estimation were applied. Results: Five RCTs including 303 patients were analyzed, of whom 165 (56%) received Sel. Sel supplementation was associated with a significant reduction in clinical activity score (MD −1.05; 95% CI −1.61 to −0.48; I² = 52%; p < 0.01). No significant differences were observed in palpebral aperture (MD −0.12; 95% CI −1.22 to 0.98; I² = 58%; p = 0.83), although this anatomical parameter should be interpreted cautiously because it may be influenced by thyroid functional status and hyperthyroidism-related Müller muscle hyperfunction. No significant differences were observed in QoL improvement (RR 1.72; 95% CI 0.43 to 6.92; I² = 86%; p = 0.24) or visual function (MD 6.31; 95% CI −1.40 to 14.03; I² = 45%; p = 0.11). Conclusions: Sel supplementation may improve clinical activity score in patients with Graves’ orbitopathy, but this finding should be interpreted cautiously given the small number of trials, limited sample size, and clinically relevant heterogeneity. Current evidence does not show consistent benefits for palpebral aperture, quality of life, or visual function. Larger RCTs stratified by baseline Sel status and disease severity are needed before firm conclusions can be drawn. Full article

Tracer techniques have emerged as pivotal tools in ophthalmology, offering unprecedented capabilities for visualizing and quantifying complex biological processes within the eye. These techniques—spanning optical, isotopic, and metal-based tracers—have significantly enhanced our ability to detect and monitor ocular diseases, from early-stage pathologies to therapeutic responses. By providing molecular-level specificity, improved signal sensitivity, and real-time dynamic imaging, tracers enable precise analysis of ocular fluid dynamics, retinal and vascular abnormalities, and neural connections between the eye and brain. Furthermore, these technologies are advancing our understanding of the systemic connections between the eye and other organs, such as the brain, thyroid, and lymphatic systems. Tracers are helping to uncover new pathways for understanding these relationships and their impact on both ocular and systemic diseases. Despite challenges in clinical translation, biosafety, and specificity, advances in tracer design, particularly at the nanoscale, are driving the development of multimodal imaging platforms. As these technologies continue to evolve, they will increasingly support the development of tailored treatment regimens, improve early detection, and facilitate the monitoring of therapeutic outcomes. Full article

Background and Clinical Significance: Bilateral carotid-cavernous fistulas are rare clinical entities characterized by heterogeneous clinical presentations and variable outcomes. Case presentation: We report the case of a 69-year-old woman with a three-month history of progressive bilateral conjunctival hyperemia, proptosis, intermittent diplopia, and a left eye abduction deficit. Her systemic history included long-standing arterial hypertension and previous thyroidectomy with stable substitutive therapy. Comprehensive ophthalmologic, neurologic, and endocrine evaluations excluded more common causes of orbital congestion, including thyroid eye disease, orbital cellulitis, cavernous sinus thrombosis, and idiopathic orbital inflammation. The patient denied any history of recent trauma. Digital subtraction angiography (DSA) confirmed a bilateral, low-flow, indirect Barrow type D carotid–cavernous fistula (CCF) supplied by dural branches of both the internal and external carotid arteries, with marked reflux into dilated superior ophthalmic veins. DSA was essential, as prior CT and MRI studies did not identify any vascular abnormalities. The patient was scheduled for transvenous embolization; however, during the follow-up she noted gradual improvement in her condition. Repeat pre-procedural angiography performed approximately two months later demonstrated complete spontaneous closure of all shunts, accompanied by full clinical resolution. Conclusions: Owing to the exceptional rarity of bilateral indirect CCFs and the added occurrence of spontaneous closure, this case expands the limited existing literature and emphasizes the diagnostic challenges and the need for individualized treatment timing supported by multidisciplinary evaluation in low-flow dural carotid–cavernous fistulas. Full article

Background/Objectives: To investigate the scleral inferior rectus–optic nerve distance (SIROND) and its association with intraocular pressure (IOP) elevation during upward gaze in patients with thyroid eye disease (TED), based on magnetic resonance imaging (MRI) examinations. Methods: This prospective study included 20 eyes (13 patients) diagnosed with active TED. All patients underwent orbital MRI in both primary and upward gaze positions before and 6 months after steroid pulse therapy. The SIROND was measured on MRI. IOP was recorded in both gazes. Changes in SIROND, inferior rectus (IR) muscle volume, proptosis, optic disc and scleral morphology, and IOP were analyzed pre- and post-treatment. Results: SIROND significantly decreased from primary gaze to upward gaze both before and after treatment (p < 0.001). Following steroid pulse therapy, there were significant reductions in IR muscle volume and proptosis (p < 0.05). Correspondingly, SIROND significantly increased in both primary and more in upward gaze post-treatment (p < 0.05). Although IOP during upward gaze was significantly higher than that in primary gaze both before and after treatment (p < 0.001), the gaze-related difference in IOP (p = 0.059), as well as SIROND, tended to be smaller after treatment (p < 0.001). A larger reduction in gaze-related pre-treatment SIROND was associated with greater IOP elevation in upward gaze (p = 0.038). MRI showed no evidence of globe compression by the IR muscle, and optic disc morphology remained unchanged following treatment. Conclusions: SIROND may serve as supportive radiological evidence for IOP elevation induced by upward gaze in patients with TED. Full article

Objectives: To validate claims-based algorithms for identifying thyroid eye disease (TED) cases and assess whether machine learning can improve case identification in a large, linked real-world dataset. Methods: Using a large, linked database from Komodo Health^® and Academy IRIS^® Registry, we evaluated six rule-based algorithms incorporating Graves’ disease (GD), eye symptoms and signs. The IRIS Registry’s curated data, based on confirmed TED diagnoses from medical notes, served as the reference standard. Additionally, we developed supervised machine learning models using demographic, diagnostic, procedural, and medication data. Feature selection was performed using recursive feature elimination to rank predictive codes and construct a simplified, interpretable model. Cross-validation was used to assess model performance and compare performance with the rule-based algorithms. Results: The rule-based algorithms demonstrated a trade-off between sensitivity and specificity, with some achieving high specificity but limited sensitivity. Algorithm 1 had the highest sensitivity (48.7%) but lower specificity (59.9%) and PPV (75.8%). Algorithms 2–5 demonstrated higher specificity (87.2–93.5%) but lower sensitivity (17.8–27.0%). Algorithm 6 improved sensitivity (33.4%) compared to Algorithms 2–5 while maintaining high specificity (86.8%) and a strong PPV (86.7%). Machine learning models demonstrated similar trade-offs. One model achieved improved specificity (77.2%) with sensitivity of 49.3%, outperforming Algorithm 1 in specificity while matching its sensitivity. Another model maximized specificity (91.7%) and PPV (89.8%) at a reduced sensitivity of 28.5%. These results highlight the flexibility of machine learning models in adjusting performance to address different research objectives. Conclusions: This study evaluated existing rule-based algorithms for identifying TED cases in claims data, revealing trade-offs between sensitivity and specificity. Machine learning models provide additional flexibility, allowing performance to be tailored to specific research use cases. While no single method consistently outperformed others across all metrics, both rule-based and machine learning approaches demonstrated value in improving TED case identification using real-world data sources. Full article

Background/Objectives: Dry eye disease (DED) is now widely considered to be the most prevalent ocular surface-related disease and has attracted increasing clinical attention in recent years. DED is well-studied in thyroid orbitopathy, but scarce data are available in patients with papillary thyroid carcinoma (PTC). Methods: We analyzed 29 PTC cases with radioactive iodine (RAI) treatment (Group 1), 22 PTC cases without RAI (Group 2), and 26 normal control individuals (Group 3). All participants were evaluated with the Ocular Surface Disease Index (OSDI), meibomian gland secretion quality, and lid margin grading. Non-contact meibography and non-invasive tear breakup time measurements were completed using the Sirius Scheimpflug camera. Thyrotropin (TSH), free thyroxine, and free triiodothyronine were measured. Results: TSH values were significantly lower in both patient groups than in controls (p < 0.001). The proportion of participants with a lower meibomian gland secretion quality score ≥ 1 was 34.5% in Group 1, 22.7% in Group 2, and 7.1% in Group 3 (p = 0.002). There was a higher proportion of a meibomian gland atrophy score ≥ 1 in Groups 1 and 2 than in controls (p = 0.007). No differences were found between groups in lower lid margin score, Oxford values, upper meibomian gland expressibility or upper meibography scores (p = 0.485, p = 0.064, p = 0.256, p = 0.069). OSDI scores were higher in both PTC groups than in controls (6.25 and 8.12 vs. 2.52), with borderline overall significance (p = 0.050) and higher pairwise scores versus controls (both p = 0.034). Conclusions: Meibomian gland dysfunction was observed in PTC patients regardless of RAI treatment, suggesting that TSH suppression itself may contribute to the development of ocular surface changes. Full article

Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article

Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability. Full article

Autoimmune thyroid diseases (AITDs) represent T cell-mediated, organ-specific autoimmune disorders caused by immune dysregulation, culminating in an immune-mediated attack on thyroid tissue. AITD etiopathogenesis is the result of the interplay between a genetic susceptibility and environmental factors; hypothyroidism and thyrotoxicosis are the respective clinical hallmarks of autoimmune thyroiditis and Graves’disease, the two main forms of AITD. The application of nanomedicine in the context of thyroid disorders ranges from nanodiagnosis and nanotherapy to nanotheranostics. Nanomedicine has been used to develop new sensitive methods for the determination of the TSH, iodine and TSAb. Furthermore, other studies have used nanomedicine to explore new treatments of autoimmune thyroiditis, Graves’disease and also thyroid eye disease. In the future, the application of nanomedicine will be personalized in accordance with individual genetic profiles, thus improving the therapeutic effectiveness and reducing the undesirable side effects with improved patient outcomes. Full article

Graves’ disease (GD) and Thyroid Eye Disease (TED) are autoimmune disorders characterized by significant heterogeneity in treatment response. Up to 50% of GD patients relapse after antithyroid drug (ATD) withdrawal, and a substantial portion of TED patients (20–50%) are resistant to first-line glucocorticoid (GC) therapy. This review evaluates the current evidence on epigenetic modifications as predictive biomarkers to guide personalized treatment. We synthesized recent findings (up to 2025) from PubMed, focusing on DNA methylation and microRNAs (miRNAs). For GD, ATD relapse risk is linked to a persistent “epigenetic memory” in T cells, notably the hypomethylation of Th17-associated genes. Circulating miRNA signatures, including miR-346, miR-23b-5p, and miR-92a-3p, also show promise in predicting remission. For TED, GC sensitivity is strongly correlated with specific circulating miRNAs. High pre-treatment levels of miR-146a predict a positive response (100% positive predictive value), while low levels of miR-224-5p predict non-responsiveness. While DNA methylation is confirmed in TED pathogenesis, its predictive role is unstudied. Major research gaps persist, particularly the near-total absence of data on histone modifications as predictive markers and the lack of epigenetic predictors for new biologics treatments, which currently rely on genetic or pharmacokinetic markers. Epigenetic biomarkers represent a promising frontier for stratifying patients and optimizing therapeutic strategies in Graves’ autoimmunity. Full article

Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R² = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R² = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article

Background: Thyroid eye disease (TED), or Graves’ orbitopathy, is the most common extra-thyroidal manifestation of Graves’ disease, but it has only rarely been reported after SARS-CoV-2 vaccination. Autoimmune thyroid disease, including subacute thyroiditis and Graves’ disease, has been described following COVID-19 vaccination; we present a case series of TED occurring shortly after different COVID-19 vaccines to provide clinical data on this potential safety signal. Case presentation: We describe five women (mean age 47 years; range 27–69) who developed TED 3–20 days after COVID-19 vaccination with mRNA or adenoviral vector vaccines, three of whom had pre-existing thyroid disease. Presentations included ocular and retro-orbital pain, exophthalmos, headache, goiter, tremor, depressive symptoms, and, in one case, anterior neck pain and fever. TED severity (ETA/EUGOGO) ranged from mild to severe, with frequent findings of suppressed TSH, elevated thyroid autoantibodies, and inflammatory markers, as well as imaging evidence of exophthalmos, extraocular muscle enlargement, and diffuse or multinodular goiter. Management with intravenous corticosteroids, selenium, levothyroxine adjustment, and/or intramuscular corticosteroids led to improvement in thyroid function and inflammation by 3 months, although mild TED often persisted. Conclusions: This case series supports a temporal association between COVID-19 vaccination and new-onset or exacerbated TED in individuals with autoimmune thyroid disease. Although vaccination benefits outweigh potential risks, clinicians should remain alert to ocular and thyroid symptoms after immunization to ensure timely diagnosis and management. Full article

Eyelid retraction, cicatricial entropion, and deformities associated with facial nerve palsy are among the eyelid malpositions most detrimental to the ocular surface, as they cause exposure, tear film instability, inflammation, and potentially significant visual impairment. These conditions present major functional and esthetic challenges, underscoring the need for a clear understanding of their mechanisms and management. A narrative review was conducted using PubMed, MEDLINE, Embase, and Google Scholar to identify English and non-English studies (with English abstracts) addressing eyelid malpositions related to thyroid eye disease, cicatricial processes, and facial nerve palsy. Screening and cross-referencing yielded 115 relevant publications. Studies were excluded if they lacked clinical relevance, did not address the target disorders, involved animals, consisted of insufficient case reports, lacked an English abstract, or were non–peer-reviewed or duplicated. Extracted information included patient demographics, clinical presentations, diagnostic methods, treatments, complications, and outcomes. In thyroid eye disease, eyelid retraction results from adrenergic overstimulation, increased Müller muscle tone, and fibrosis involving the levator–superior rectus complex. Temporary improvement may be achieved with botulinum toxin, corticosteroids, or soft-tissue fillers, whereas sustained correction requires individualized surgical approaches. Cicatricial entropion arises from posterior lamellar contraction caused by inflammatory or iatrogenic injury and is best treated with lamellar repositioning or grafting procedures. In facial nerve palsy, incomplete blinking, punctal malposition, and lacrimal pump dysfunction contribute to tearing and ocular surface instability; management prioritizes corneal protection, eyelid rebalancing, and adjunctive measures such as botulinum toxin or physiotherapy. Across all conditions, tailored, multidisciplinary care is essential to maintain ocular surface integrity, restore eyelid function, and preserve quality of life. Full article