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La Tunisie Medicale Feb 2021Graves' disease (GD) is a common autoimmune disorder. Graves'orbitopathy (GO) is its most common extrathyroidal manifestation. It is rare but may reveal the disease.
INTRODUCTION
Graves' disease (GD) is a common autoimmune disorder. Graves'orbitopathy (GO) is its most common extrathyroidal manifestation. It is rare but may reveal the disease.
AIM
To describe the demographic, clinical and therapeutic features of GO.
METHODS
We carried out a retrospective and descriptive analysis of 82 patients with GO. This study was conducted in Ophthalmology and Endocrinology departments of Taher Sfar University Hospital in Mahdia, between January 2010 and December 2017. GD patients diagnosed with GO were included.
RESULTS
The mean age was 36.17 years ± 12.81. Patients aged 19-40 years had the highest rate of GO. The male-to-female ratio was 0.49. Family history of autoimmune thyroid disease was present in 15% and associated autoimmune disease in 4% of cases. Smoking was seen in 71% of patients. The onset of GO was simultaneous with onset of GD in 45%, before in 21% and after the onset of GD in 34% of cases. GO was bilateral in 76% of patients. The most common ocular symptoms were prominent eyes (55% of patients), ocular pain (11%) and diplopia (41%). Proptosis and upper eyelid retraction were the most common clinical signs (93% and 90% respectively). Dysthyroid optic neuropathy was present in one eye, keratitis in one eye and glaucoma in five eyes. Severe disease was noted in 11% and active disease was present in 7% of patients. CT-scan and magnetic resonance imaging scan (MRI) were performed in 48% and 42% of cases respectively. Proptosis was the most common radiological sign. Thyroid dysfunction was managed with anti-thyroid medication only (59%), thyroxine replacement (37%), radioactive iodine (35%) and thyroidectomy (6%). 20% of patients received corticosteroids. One patient required immunosuppressive therapy.
CONCLUSION
GO is a complex disease, which is associated with impaired quality of life and can potentially result in sight-threatening complications. Appropriate diagnosis, convenient therapy and a regular follow-up are necessary to improve results and avoid the aesthetic and functional sequelae.
Topics: Adult; Female; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Male; Quality of Life; Retrospective Studies; Thyroid Neoplasms
PubMed: 33899194
DOI: No ID Found -
Journal of Neuro-ophthalmology : the... Mar 2024Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients... (Review)
Review
BACKGROUND
Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab.
METHODS
A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration.
RESULTS
Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2-15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms.
CONCLUSIONS
Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.
Topics: Female; Humans; Infant; Male; Diplopia; Quality of Life; Optic Nerve Diseases; Graves Ophthalmopathy; Exophthalmos; Antibodies, Monoclonal, Humanized
PubMed: 37751310
DOI: 10.1097/WNO.0000000000001994 -
Neurosciences (Riyadh, Saudi Arabia) Jan 2023A 65-year-old male patient presented with a rare arterio-venous fistula (AFV). The symptoms included congestion, decreased visual acuity, and proptosis. Further...
A 65-year-old male patient presented with a rare arterio-venous fistula (AFV). The symptoms included congestion, decreased visual acuity, and proptosis. Further investigation revealed a non-traumatic intra orbital AFV with ophthalmic vein thrombosis. The management strategy was craniotomy and the prescription of anticoagulants. The patient recovered 2 months after surgery demonstrating successful resolution of his presenting symptoms and an alternative approach to complicated cases of embolization.
Topics: Male; Humans; Aged; Arteriovenous Fistula; Exophthalmos; Venous Thrombosis; Embolization, Therapeutic
PubMed: 36617457
DOI: 10.17712/nsj.2023.1.20220012 -
The Journal of Clinical Endocrinology... Apr 2022
Topics: Graves Disease; Humans; Thyrotoxicosis; Weather
PubMed: 34928376
DOI: 10.1210/clinem/dgab909 -
Cells Mar 2022Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive... (Review)
Review
Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulate a range of functional processes at the cellular, tissue, and systemic levels in healthy humans. Conversely, excess ROS or RNS activity can disrupt function, impairing the performance of daily activities. This article analyzes the impact of redox mechanisms on extreme task performance. Such activities (a) require complex motor skills, (b) are physically demanding, (c) are performed in an extreme environment, (d) require high-level executive function, and (e) pose an imminent risk of injury or death. The current analysis utilizes race car driving as a representative example. The physiological challenges of this extreme task include physical exertion, g loading, vibration, heat exposure, dehydration, noise, mental demands, and emotional factors. Each of these challenges stimulates ROS signaling, RNS signaling, or both, alters redox homeostasis, and exerts pro-oxidant effects at either the tissue or systemic levels. These redox mechanisms appear to promote physiological stress during race car driving and impair the performance of driver athletes.
Topics: Abnormalities, Multiple; Athletes; Cleft Palate; Exophthalmos; Humans; Microcephaly; Osteosclerosis; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 35269521
DOI: 10.3390/cells11050899 -
The British Journal of Ophthalmology Jun 2022Teprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Teprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in recent clinical trials. Given its specificity, we expect it to demonstrate greater efficacy on the worse affected orbit, in patients with asymmetric TED. Herein, we investigate the differential impact of teprotumumab on the orbits of such patients.
METHODS
In this pooled analysis of patients who were enrolled in the recent phase 2 (NCT01868997) and phase 3 (NCT03298867) trials, all patients with asymmetric TED (difference in exophthalmometry of ≥3 mm) were screened for eligibility. The primary outcomes of the trials, proptosis, diplopia and Clinical Activity Score (CAS) response, were evaluated in both orbits of patients who had received treatment or placebo, to examine the differential response from baseline to week 24.
RESULTS
From a pooled group of 84 patients randomised to receive teprotumumab and 87 randomised to placebo, 10 (12%) and 12 (14%), respectively, met the inclusion criteria. The teprotumumab-treated patients demonstrated significant reductions in proptosis, CAS and diplopia in both orbits of each patient and this was not seen with placebo. The reduction in proptosis and CAS was significantly greater in the worse affected orbit, improving symmetry. In the placebo arm, while the mean CAS in the study eye reduced over time, proptosis and diplopia did not change in either orbit.
CONCLUSION
The findings in this study suggest the differential impact of teprotumumab on orbits that are clinically more affected by TED, suggesting that teprotumumab reduces asymmetry.
Topics: Antibodies, Monoclonal, Humanized; Diplopia; Exophthalmos; Graves Ophthalmopathy; Humans
PubMed: 33579690
DOI: 10.1136/bjophthalmol-2020-318314 -
Frontiers in Endocrinology 2023The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.
METHODS
To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.
RESULTS
A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.
CONCLUSIONS
Based on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/prospero, identifier CRD42023398170.
Topics: Humans; Antibodies, Monoclonal; Immunoglobulins, Intravenous; Diplopia; Rituximab; Graves Ophthalmopathy; Exophthalmos
PubMed: 37288301
DOI: 10.3389/fendo.2023.1160936 -
Journal of General Internal Medicine Apr 2017
Topics: Carotid-Cavernous Sinus Fistula; Exophthalmos; Humans; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 27612485
DOI: 10.1007/s11606-016-3860-6 -
Eye (London, England) Feb 2020Dysthyroid eye disease is a rare condition, mainly found in people with Graves' hyperthyroidism. Autoimmune responses to thyroid/orbit shared antigens drive extensive...
Dysthyroid eye disease is a rare condition, mainly found in people with Graves' hyperthyroidism. Autoimmune responses to thyroid/orbit shared antigens drive extensive tissue remodelling. This includes excess adipogenesis and over-production of extra-cellular matrix, which both tend to occur in the earlier 'active' inflammatory stages of disease. With time these give way to fibrosis, which has a profound impact on eye motility and may be life-long. Progress has been made in identifying the shared autoantigen(s) and the role of specific T cells and autoantibodies in remodelling, which have facilitated development of novel therapies. However relatively little is known of the autoimmune processes under-pinning fibrosis and currently there are no adequate medical treatments.
Topics: Autoantibodies; Fibrosis; Graves Disease; Graves Ophthalmopathy; Humans
PubMed: 31844169
DOI: 10.1038/s41433-019-0731-5 -
JAMA Ophthalmology Apr 2022Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in... (Meta-Analysis)
Meta-Analysis
Proptosis and Diplopia Response With Teprotumumab and Placebo vs the Recommended Treatment Regimen With Intravenous Methylprednisolone in Moderate to Severe Thyroid Eye Disease: A Meta-analysis and Matching-Adjusted Indirect Comparison.
IMPORTANCE
Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition.
OBJECTIVE
To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo.
DATA SOURCES
Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP.
STUDY SELECTION
PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged.
DATA EXTRACTION AND SYNTHESIS
Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes.
MAIN OUTCOMES AND MEASURES
Changes in proptosis by millimeter and diplopia response (percentage with ≥1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo, and to week 24 in patients receiving teprotumumab.
RESULTS
The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03).
CONCLUSIONS AND RELEVANCE
This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.
Topics: Antibodies, Monoclonal, Humanized; Diplopia; Exophthalmos; Graves Ophthalmopathy; Humans; Methylprednisolone
PubMed: 35175308
DOI: 10.1001/jamaophthalmol.2021.6284