Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC6858302 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Thyroid eye disease (TED) is a complex inflammatory disease that can have a long clinical course with sight-threatening and debilitating ocular sequelae. Until recently, there were limited therapeutic options available. In the last decade we have gained a deeper understanding of the underlying pathophysiology, which has led to the development of novel effective targeted therapies. This article discusses the challenges encountered in the clinical evaluation and treatment of TED patients, with the goal to empower endocrinologists and ophthalmologists to work together to provide effective multidisciplinary care. We will review recommendations of past clinical guidelines around evaluation and management of TED patients, discuss the randomized controlled trials of new biologic therapies, and explore how to navigate the emerging therapeutic landscape.
| S-EPMC8078830 | biostudies-literature
Project description:Graves disease is an autoimmune thyroid disease classically characterised by a clinical triad consisting of hyperthyroidism, diffuse goitre, and thyroid eye disease. Thyroid eye disease is an immunologically mediated condition in which humoral immunity is thought to play a central role. Thyroid eye disease is traditionally treated with high-dose glucocorticosteroids and surgical orbital decompression. However, responses are inadequate and alternative treatment options are needed. Rituximab, an anti-CD20 monoclonal antibody, shows promise as a novel therapeutic option for thyroid eye disease. There are 43 cases of thyroid eye disease treated with rituximab in the medical literature, and larger studies are warranted to determine the long-term effectiveness of rituximab. Rituximab may represent an attractive new treatment option for thyroid eye disease, especially in the case of disease that is refractory to current treatment strategies.
| S-EPMC5123122 | biostudies-other
Project description:BackgroundThyroid eye disease (TED) is an autoimmune disorder that constitutes a major clinical and therapeutic challenge. Current treatment options for moderate-to-severe TED include immunotherapy, orbital radiotherapy and decompression surgery. Limited drugs of proven efficacy are available for the treatment of people with TED. Given the role in the pathogenesis of TED of interleukin (IL)-6 expression in adipocytes, fibroblasts and macrophages, the proposed theory is that inhibition of IL-6 by tocilizumab may be an effective treatment in TED by directly reducing the inflammatory response. In addition, there is an unmet need for a new treatment that can modify the natural course of the disease and reduce the incidence of late complications that can occur as a result of fibrosis following inflammation.ObjectivesTo investigate the efficacy and harms of tocilizumab for the treatment of people with TED.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase Ovid; LILACS BIREME; OpenGrey; the ISRCTN registry; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the EU Clinical Trials Register. The date of the search was 31 July 2018.Selection criteriaWe searched for trials of tocilizumab administered by intravenous infusion using any dosage regimen, compared with placebo or intravenous glucocorticoid therapy for people with TED.Data collection and analysisWe planned to use standard methods recommended by Cochrane. The primary outcome was change in TED score (as defined by investigators). Secondary outcomes included measurement of the following parameters: change in proptosis, change in extraocular motility, change in palpebral aperture measurements, number of relapses, development of optic neuropathy and change in quality of life score. We planned to measure these outcomes at three months (range two to six months) and 12 months (range six to 18 months) post-treatment. Adverse outcomes included any adverse effects identified in the trials at any time point.Main resultsNo studies met the inclusion criteria of this review. We found one randomised, placebo-controlled, double masked study (NCT01297699). This study plans to evaluate the efficacy and harms of tocilizumab administration in people with moderate-to-severe or sight-threatening graves' ophthalmopathy (GO), that had not responded adequately to treatment with intravenous corticosteroid pulses. It was completed in December 2015 and will be assessed for inclusion in the review when data become available.Authors' conclusionsThere is currently no evidence from randomised controlled trials evaluating the efficacy and harms of tocilizumab for the treatment of people with TED.
| S-EPMC6517231 | biostudies-literature
Project description:Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease. Incomplete understanding of its pathogenesis has hindered development of targeted therapies that might alter the natural course of disease. Smoking cessation and maintenance of euthyroidism appear to reduce the rate of onset and severity of TED. Recent evidence suggests that selenium may lessen the inflammatory symptoms in mild disease. Corticosteroids remain the primary treatment for patients with moderate to severe active TED. Surgical decompression is commonly undertaken in the chronic stable phase, and only rarely in the active phase when vision is threatened by compressive optic neuropathy. Orbital radiotherapy remains an adjunctive strategy during active disease. Targeted immunotherapies have the potential to alter disease progression, but further evidence is needed to establish safety and efficacy. In this article, we review evidence from prospective therapeutic trials of several treatment modalities. We focus on moderate to severe active TED.
| S-EPMC3463137 | biostudies-other
Project description:Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of Sovaldi™, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977. It was subsequently acquired and advanced through phase 3 development by Gilead Sciences, Inc. In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious. Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR), curing patients in excess of 80% in all genotypes and >90% in treatment-naïve subjects being administered combination therapy with other agents. Harvoni(®) is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet, and it has demonstrated high SVR rates in patients infected with HCV genotype 1, without the need for exogenous interferon and/or ribavirin. Here, we discuss the discovery, development, pharmacologic characterization, and results from the phase 3 trials of sofosbuvir. Hepatitis C is a chronic disease, for which most patients have been undiagnosed, are unwilling to start treatment, or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy. Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care, thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines.
| S-EPMC4542085 | biostudies-literature
Project description:Blepharoplasty for thyroid eye disease (TED) has been indicated for the purpose of improving upper and lower eyelid retraction caused by exophthalmos. Both aponeurotic blepharoptosis and aging lower eyelid are common conditions that require plastic surgeries and could be complicated with other disease conditions, such as TED. This is the first report of planned and staged treatment of the contradictory pathophysiologies of aging changes of upper and lower eyelids associated with TED. A 59-year-old woman suffered complicated bilateral asymmetric aponeurosis blepharoptosis of the lower and upper eyelids, caused by both advanced aging and TED. To achieve aesthetic improvement, three-stage surgical treatments were planned, as follows: (1) Orbital decompression for exophthalmos; (2) Extraocular muscle surgery, if necessary; (3) Blepharoplasty for functional and aesthetic abnormalities due to loosening of the upper and lower eyelids. After medial and lateral orbital floors were opened bilaterally, the patient did not need extraocular surgery. As the final step, levator aponeurosis advancement procedure was performed in the upper eyelids for bilateral asymmetrical aponeurotic blepharoptosis, and transitional lower blepharoplasty using a skin-muscle flap technique via a sub-ciliary incision was performed in the lower eyelids for age-related loosening. The typical face displayed by Graves' disease disappeared, and the symptoms associated with loosening of the upper and lower eyelids improved substantially. Improvement of exophthalmos by orbital decompression revealed the severity of the blepharoptosis and the aging change of lower eyelid. Step-by-step planning from decompression surgery to upper and lower blepharoplasty could lead to sufficient improvement in the facial appearance in TED.
| S-EPMC8294927 | biostudies-literature
Project description:The clinical features of thyroid eye disease are dictated by the orbit's compartmentalisation; particularly, the muscle cone, which is delimited by the rectus muscles, their inter-muscular septa and the posterior sclera. The cone is anchored to the orbit apex and contains the posterior globe, the muscle bellies, a fat pad, and the blood circulation, optic nerve, and CSF sheath. It is surrounded by mobile extraconal fat, retained by the orbital septum.Thyroid eye disease is caused by expansion of muscle bellies and fat within the cone. Mechanical properties of the cone determine that the disease partitions into three phases: circumferential expansion, with forward displacement of extraconal fat; axial elongation, with increasing cone pressure; impedance of posterior venous outflow, with cone oedema and venous flow reversal.Venous flow reversal can be observed in the conjunctival circulation. It is initially transient, accompanying rises in cone pressure caused by eye movements, but later becomes permanent. It is a useful clinical sign that locates diseased muscles and anticipates venous compressive crises.Strabismus arises when inflamed rectus muscles, swollen by hydrated glycosaminoglycans, lose contractility and compliance. The incomitance is moderated by increasing stiffness affecting all the rectus muscles, as they are stretched during cone expansion.Immunomodulation, which rapidly reduces cone volume, relieving muscle elongation and stiffness, may paradoxically unmask strabismus. However, ciclosporin A suppresses late post-inflammatory fibrosis and only 4 of 71 patients so-treated required strabismus surgery.The cone model also accounts for the variety of clinical presentations of thyroid eye disease.
| S-EPMC6367424 | biostudies-literature
Project description:Thyroid eye disease (TED; also known as thyroid-associated ophthalmopathy) is an autoimmune condition with disabling and disfiguring consequences. Teprotumumab is the first and only medication approved by the United States Food and Drug Administration for the treatment of TED. We review the efficacy and safety of teprotumumab in TED, highlighting results from the 2 randomized, double-masked, placebo-controlled trials. Post-approval case reports of teprotumumab use in patients with compressive optic neuropathy (CON) and inactive TED were similarly favorable to those from the trials. The preliminarily results of teprotumumab for CON and inactive TED should be investigated in formal clinical trials. Teprotumumab should be avoided in pregnancy. Evidence also suggests that teprotumumab may exacerbate pre-existing inflammatory bowel disease, worsen hyperglycemia, and be associated with hearing impairment. Patients at risk for these adverse events need to be closely monitored with baseline and periodic assessments.
| S-EPMC8630371 | biostudies-literature
Project description:Evaluation of tear film break-up pattern (TFBUP) is the main diagnostic method for tear film-oriented therapy (TFOT) of dry eye. This prospective, observational study examined TFBUPs in 154 eyes/sides from 78 patients with thyroid eye disease (TED) who met the diagnostic criteria for dry eye in Japan. TFBUPs were classified as area, line, spot, dimple, and random breaks. Results for the status of TED and dry eye were compared between the TFBUPs. Consequently, line, spot, dimple, and random breaks were observed in 80 (51.9%), 29 (18.8%), 10 (6.5%), and 35 eyes (22.7%) while no eyes showed area breaks. The random break group had the highest incidence of lid lag/Graefe sign and superior limbic keratoconjunctivitis (SLK) (P < 0.050). Although the incidence of each TFBUP is almost equal in patients with simple dry eye without TED, line breaks were more frequently observed in TED. In addition, while random breaks in simple dry eye are usually only associated with minor ocular surface damages, those in TED were associated with a higher incidence of concomitant SLK. These results will be helpful for understanding the etiology of dry eye in TED and for TFOT in TED.
| S-EPMC7935998 | biostudies-literature
Project description:ObjectivesThe clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the longitudinal association between changes in serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels and course of disease activity and severity over time.DesignThis was a multicentre, prospective, observational study.SettingFifteen tertiary care oculoplastic service centres in Korea.ParticipantsSeventy-six patients with newly diagnosed TED were included and followed up for 12 months.MethodsWe evaluated clinical characteristics and serum TRAb levels at baseline, 6 and 12 months of TED diagnosis. Additionally, we analysed longitudinal associations between the serum TRAb levels and clinical activity score (CAS), no signs or symptoms, only signs, soft tissue involvement, proptosis, extraocular muscle involvement, corneal involvement, sight loss (NOSPECS) score and proptosis.ResultsThyroid-stimulating immunoglobulin (TSI) and TSH-binding inhibitory immunoglobulin (TBII) levels decreased during the 1-year follow-up, whereas disease activity measured using CAS decreased mainly in the first 6 months. Disease severity measured using NOSPECS score and proptosis remained unchanged. Moreover, inter-person differences in TBII levels were associated with CAS, NOSPECS score and proptosis over time, whereas inter-person differences in TSI levels were associated with NOSPECS score. Subgroup analysis of patients with a baseline CAS≥4 demonstrated that within-person changes in TSI levels affected the CAS and NOSPECS score.ConclusionsFollow-up measurement of serum TSI and TBII levels may help evaluate TED prognosis and enable accurate clinical decision-making.
| S-EPMC9214404 | biostudies-literature