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      Corticosteroids for Graves' Ophthalmopathy: Systematic Review and Meta-Analysis

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      BioMed Research International
      Hindawi

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          Abstract

          Background

          Graves' ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids (GCs) therapy is the mainstay of treatment especially for active moderate to severe patients, which needs evidence-based support.

          Method

          We searched all the randomized controlled trials (RCTs) involving corticosteroid treatment for patients diagnosed with GO from EMBASE, Medline, and the Cochrane library and then conducted a system review and meta-analysis. The electronic search covered the period from April 1966 to March 2018.

          Result

          Twenty-nine trials were included. GCs were proved to be beneficial for GO patients [response rate, risk ratio (RR) = 1.72, 95% confidence interval (CI): 1.28~2.31, P=0.0003], and intravenous corticosteroids worked significantly better than oral corticosteroids as ever reported. When compared with the single treatment of GCs, the combination of radiotherapy and GCs showed similar effects on response rate (RR=1.25, 95%CI: 0.91~1.73). A study proved the advantage of mycophenolate mofetil over GCs in three outcomes (response rate, RR=0.74, 95%CI: 0.63~0.88). Additional treatments such as technetium-99 methylene diphosphate ( 99Tc-MDP) or cyclosporine enhanced the effect of GCs on proptosis reduction, respectively (P<0.00001 and P=0.02).

          Conclusion

          Our meta-analysis confirmed the effects of GCs in the management of GO and intravenous GCs are proved to be better than oral GCs as ever reported. Combination of radiotherapy and GCs did not enhance the effects of GCs. However, if proptosis is the main issue, combination of 99Tc-MDP or cyclosporine with GCs may be taken into consideration. The reported advantages of mycophenolate mofetil over GCs are noteworthy and need more RCTs to confirm.

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          Most cited references34

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          The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy

          Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients. In mild GO, a watchful strategy is usually sufficient, but a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms. High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO. The optimal cumulative dose appears to be 4.5-5 g of methylprednisolone, but higher doses (up to 8 g) can be used for more severe forms. Shared decision-making is recommended for selecting second-line treatments, including a second course of intravenous GCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab or watchful waiting. Rehabilitative treatment (orbital decompression surgery, squint surgery or eyelid surgery) is needed in the majority of patients when GO has been conservatively managed and inactivated by immunosuppressive treatment.
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            Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

            Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them. The objective of this study was to optimize glucocorticoid application in GO. The study design was a randomized trial over 12 wk with 6-month follow-up. The study was performed at university joint thyroid and ophthalmic clinics. Seventy euthyroid out-patients with untreated, active, and severe GO were studied. Patients received either once weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. At 3 months, the primary end point was a composite of improvements in proptosis, lid fissure width, and rate of diplopia in primary gaze, visual acuity, eye muscle thickness, and patient's quality of life. Intravenous glucocorticoid therapy resulted in rapid, significant, and sustained improvement. At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the iv group. TSH receptor antibody titers decreased during iv steroid administration (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001). Additional treatment was required less frequently in the iv group. Intravenous steroids were safe, with different rates of adverse events between the two groups (P < 0.001). In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.
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              Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy.

              Optimal doses of i.v. glucocorticoids for Graves' orbitopathy (GO) are undefined.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                22 November 2018
                : 2018
                : 4845894
                Affiliations
                Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
                Author notes

                Academic Editor: Timothy Y. Lai

                Author information
                http://orcid.org/0000-0002-4068-7017
                http://orcid.org/0000-0001-7945-1258
                Article
                10.1155/2018/4845894
                6282115
                ada2edc2-7562-48d9-a741-61cd74bf46d1
                Copyright © 2018 Xiaofang Tu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2018
                : 12 November 2018
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81300642
                Categories
                Research Article

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