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      Intravenous Glucocorticoid Treatment for Korean Graves' Ophthalmopathy Patients

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          Abstract

          Background

          High-dose intravenous steroids are the first-line treatment for patients with moderate-to-severe and active Graves' ophthalmopathy (GO). We aimed to investigate the response rate of methylprednisolone (MPD) treatment among Korean patients with active moderate-to-severe GO and to identify predictive factors of treatment response.

          Methods

          This is a retrospective observational study. We included 54 active moderate-to-severe GO patients treated with 4.5 g intravenous MPD over 12 weeks between November 2011 and November 2018. Response was defined as an improvement in at least two of five indicators (clinical activity score [CAS], soft-tissue involvement, exophthalmos, diplopia, and visual acuity) at immediate and 3 months after treatment completion. We examined predictive factors for response using logistic regression analysis.

          Results

          Twenty-four (44.4%) and 22 (40.7%) patients showed response at immediate and 3 months after intravenous (IV) steroid treatment. Of the five ophthalmic parameters, all patients in the responsive group (100.0%) showed a decrease in CAS and 90.9% showed less soft tissue involvement after IV steroid treatment. Among variables, the sum of extraocular muscle width was positively (odds ratio [OR], 1.163; 95% confidence interval [CI], 0.973–1.389; P = 0.096) associated with treatment response. While, the OR of age was 0.918 (95% CI, 0.856–0.985; P = 0.017) and thyrotropin binding inhibitory immunoglobulin (TBII) was 0.921 (95% CI, 0.864–0.982; P = 0.012).

          Conclusion

          In Korean active moderate-to-severe GO patients, intravenous steroid treatment is not as effective as previously reported. Parameters associated with CAS and soft-tissue involvement were found to be influenced by IV MPD treatment. Extraocular muscle enlargement, younger age and lower TBII are predictive factors for a good steroid treatment response.

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          Most cited references24

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          Graves' ophthalmopathy.

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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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              Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy.

              Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double-blind, prospective study. The CAS was determined by an opthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade. Responders (22) and non-responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non-responders. Twelve of 22 responders and three of 21 non-responders had a CAS > or = 4 (55% vs 14%; P or = 4 had a similar duration of Graves' ophthalmopathy as patients with a CAS < 4. The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                04 May 2020
                15 June 2020
                : 35
                : 23
                : e177
                Affiliations
                [1 ]Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
                [2 ]Department of Ophthalmology, Chung-Ang University College of Medicine, Seoul, Korea.
                Author notes
                Address for Correspondence: Jeong Kyu Lee, MD, PhD. Department of Ophthalmology, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea. LK1246@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-2737-6759
                https://orcid.org/0000-0001-9797-9945
                Article
                10.3346/jkms.2020.35.e177
                7295605
                32537950
                b3cfc9e0-4c05-4f06-8fd6-e02fd9c199e0
                © 2020 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 December 2019
                : 13 April 2020
                Funding
                Funded by: Korean Thyroid Association Young Investigator Award;
                Categories
                Original Article
                Endocrinology, Nutrition & Metabolism

                Medicine
                graves' ophthalmopathy,glucocorticoids,clinical activity score,response rate
                Medicine
                graves' ophthalmopathy, glucocorticoids, clinical activity score, response rate

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