Rituximab in the Treatment of Thyroid Eye Disease: A Review.
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ABSTRACT:
SUBMITTER: Ostrowski RA
PROVIDER: S-EPMC5123122 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
Publications
Rituximab in the Treatment of Thyroid Eye Disease: A Review.
Ostrowski Rochella A RA Bussey Melissa R MR Shayesteh Yasmin Y Jay Walter M WM
Neuro-ophthalmology (Aeolus Press) 20150617 3
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 a ...[more]
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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:Orbital decompression is a surgical procedure aimed at increasing the orbital volume and/or decreasing the volume of the orbital fat. The indications for orbital decompression are determined in the course of thorough eye examination. An important objective of examination of a patient with thyroid eye disease (TED) is determination of inflammation activity and severity. Orbital decompression is a surgical procedure that can be performed in both the active and nonactive stages of the disease. However, the indications for the surgery in these cases are different. Optic neuropathy and severe corneal disease are threatening complications that may lead to permanent visual loss and generally occur in the presence of active orbital inflammation. If treatment with high-dose corticosteroids has proven ineffective, an urgent surgical procedure consisting of orbital decompression and, in case of involvement of the cornea, eyelid and corneal surgery has to be performed. Owing to significant progress in technology, improvement of methods and accumulated experience over the past decade, the indications for bone orbital decompression have extended compared to the time when this procedure was used only in patients with extremely severe TED. The most common complication of the orbital decompression is the development or deterioration of previously existing binocular diplopia and strabismus. In addition, other parameters may change as well, including the position of the globe, the eyelids, the angle of deviation of the eye, and intraocular pressure. Thus, bone orbital decompression is a major step of a comprehensive, often multistage, system of rehabilitation of patients with severe refractory TED.
| S-EPMC6171517 | 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.
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Project description:Thyroid eye disease (TED) is a complex, debilitating autoimmune disease that causes orbital inflammation and tissue remodeling, resulting in proptosis, diplopia, and in severe cases, loss of vision. TED can lead to facial disfigurement and severely impact patients' quality of life. Although the course of TED was identified over 60 years ago, effective treatment options have proved to be challenging. Current treatments such as glucocorticoid therapy and orbital radiation focus on reducing orbital inflammation. However, these therapies fail to modify the disease outcomes, including proptosis and diplopia. Recent advances in the understanding of the molecular basis of TED have facilitated the development of targeted molecular therapies such as teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody. In recent phase 2 and phase 3 randomized placebo-controlled trials, teprotumumab rapidly achieved improvement in clinical endpoints defining TED, including improved proptosis and diplopia. Dramatic improvement in clinical outcomes achieved after teprotumumab therapy during active TED are heretofore singular and comparable only to surgical therapies achieved during the inactive phase of TED. The advent of effective medical therapy can lead to a paradigm shift in the clinical management of TED. This review will provide an overview of TED, its epidemiology, insight into the molecular biology of the disease, clinical characteristics and diagnosis, and current and emerging treatment modalities.
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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: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:BACKGROUND:Thyroid eye disease is an autoimmune disorder of the orbital retrobulbar tissue commonly associated with dysthyroid status. The most frequent condition is hyperthyroidism, although it is also present in hypothyroid and euthyroid patients. The prevalence of thyroid conditions in patients with thyroid eye disease had been previously evaluated; however, there is no consensus on a global prevalence. The study aims to estimate the prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in patients with TED, through a systematic review of literature. METHODS:We conducted a systematic review of the literature following the PRISMA guidelines, in MEDLINE, COCHRANE, EMBASE, Science Direct, and LILACS databases. Inclusion criteria were primary studies of patients with a diagnosis of thyroid eye disease made by an ophthalmologist or with diagnosis criteria, with measurement of thyroid function (TSH, T3, and free T4), and diagnosis of the primary thyroid condition. A quality assessment was made through the Joanna Briggs Institute Quality tools. Finally, we extracted relevant details about the design, the results, and the prevalence of thyroid disorders in thyroid eye disease. RESULTS:The initial search revealed 916 studies, of which finally thirteen met inclusion criteria. Six studies were performed in Europe (Germany, Wales, and Spain), five in Asia (Iran, South Korea, Japan, and Singapore), one in North America (USA), and one in Africa (Ghana). The global prevalence, in patients of thyroid eye disease, was 10.36% for hypothyroidism, 7.9% for euthyroidism, and 86.2% for hyperthyroidism. CONCLUSIONS:Professionals should be aware that thyroid eye disease can be present in patients with a normal thyroid function. The assessment for these patients is based on orbital images; serum TSH, T3, and free T4; antibody levels as thyrotropin receptor antibodies; and thyroperoxidase levels. Additionally, we want to encourage research in this field in other regions of the world such as Latin America. SYSTEMATIC REVIEW REGISTRATION:PROSPERO ID CRD42020107167.
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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.
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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.
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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.
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