{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:09:08Z","timestamp":1792598948288,"version":"4.5.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to evaluate and compare the efficacy of intravenous (iv) glucocorticoids (GCs) with and without orbital radiotherapy (ORT) in a retrospective analysis of patients with active, moderate-to-severe Graves\u2019 orbitopathy (GO). Since diplopia has the strongest impact on quality of life, a careful work up of motility and binocular single vision (BSV) has been performed. The Essen-EUGOGO-Center database (n=3655) was screened for patients with untreated moderate-to-severe, active GO, onset \u226412 months. The inclusion criteria were met by 148 patients (n=76 ivGC, n=72 ivGC + ORT). We analyzed CAS (inactivation: \u22642), NOSPECS, lid-width, proptosis, motility, and field of BSV. To score the overall ophthalmic outcome, a severity-weighted-score (SOS) was compared with an established EUGOGO inflammation-weighted-score (IOS). Cumulative ivGCs dosages and duration of GO did not differ between the groups. Patients with combination therapy had a significantly more severe GO at baseline. Therefore, a subgroup with matched severity was additionally compared. In the IOS, both groups reached similar improvement rates (55.2 vs. 63.9%; p=0.31). However, in the SOS, the rates differed significantly (46.1 vs. 61.1%; p=0.03- unmatched and p=0.03 matched), despite similar rates of inactivation (65.8 vs. 63.8%). Impaired motility improved significantly more often after combination therapy (p=0.01 matched, p=0.004 unmatched). Treatment responders showed only partial improvement (proptosis: 2.5\u00b10.5\u2009mm; motility: 11.3\u00b110.9\u00b0). In our retrospective analysis, combination therapy (ivGCs + ORT) was significantly more effective in reduction of severity and should therefore always be considered in moderate-to-severe GO stages, especially in the presence of motility disorders. However, the limited improvement in clinical parameters, despite the promising effect on inactivation of inflammation, has to be outlined to the patients.<\/jats:p>","DOI":"10.1055\/s-0043-116945","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T22:57:51Z","timestamp":1505775471000},"page":"739-747","source":"Crossref","is-referenced-by-count":45,"title":["Combination Therapy of Intravenous Steroids and Orbital Irradiation is More Effective Than Intravenous Steroids Alone in Patients with Graves\u2019 Orbitopathy"],"prefix":"10.1055","volume":"49","author":[{"given":"Michael","family":"Oeverhaus","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen (EUGOGO Center Essen), Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Witteler","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen (EUGOGO Center Essen), Essen, Germany"},{"name":"Department of Medical Oncology, Kliniken Essen-Mitte, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegard","family":"Lax","sequence":"first","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Esser","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen (EUGOGO Center Essen), Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-4192","authenticated-orcid":false,"given":"Dagmar","family":"F\u00fchrer","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, University Hospital Essen, (EUGOGO Center Essen) University Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Eckstein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen (EUGOGO Center Essen), Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,9,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/WNO.0000000000000132","article-title":"The pathophysiology of thyroid eye disease","volume":"34","author":"S J Shan","year":"2014","journal-title":"J Neuroophthalmol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1055\/s-0035-1555762","article-title":"Current Insights into the Pathogenesis of Graves\u2019 Ophthalmopathy","volume":"47","author":"R S Bahn","year":"2015","journal-title":"Horm Metab Res"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1055\/s-0035-1555956","article-title":"Modeling Graves\u2019 Orbitopathy in Experimental Graves\u2019 Disease","volume":"47","author":"J P Banga","year":"2015","journal-title":"Horm Metab Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1210\/jc.2016-1315","article-title":"TSH\/IGF-1 Receptor Cross Talk in Graves\u2019 Ophthalmopathy Pathogenesis","volume":"101","author":"C C Krieger","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1055\/s-0035-1559633","article-title":"Graves\u2019 disease mechanisms: The role of stimulating, blocking, and cleavage region tsh receptor antibodies","volume":"47","author":"S A Morshed","year":"2015","journal-title":"Horm Metab Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.4049\/jimmunol.181.6.4397","article-title":"Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves\u2019 disease","volume":"181","author":"S Tsui","year":"2008","journal-title":"J Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1210\/jc.2014-3566","article-title":"Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by Graves\u2019 disease immunoglobins","volume":"100","author":"C C Krieger","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1089\/thy.1997.7.885","article-title":"Quality of life in patients with Graves\u2019 ophthalmopathy is markedly decreased: Measurement by the medical outcomes study instrument","volume":"7","author":"M N Gerding","year":"1997","journal-title":"Thyroid"},{"key":"ref9","first-page":"747","article-title":"Graves\u2019 ophthalmopathy: current concepts regarding pathogenesis and management","volume":"14","author":"H B Burch","year":"1993","journal-title":"Endocr Rev"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ajo.2011.02.018","article-title":"Quality of life in a german graves orbitopathy population","volume":"152","author":"K A Ponto","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1365-2265.2005.02352.x","article-title":"Psychosocial morbidity of Graves' orbitopathy","volume":"63","author":"G J Kahaly","year":"2005","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","article-title":"Teprotumumab for thyroid-associated ophthalmopathy","volume":"376","author":"T J Smith","year":"2017","journal-title":"N Engl J Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1055\/s-0035-1555901","article-title":"Future prospects for the treatment of graves\u2019 hyperthyroidism and eye disease","volume":"47","author":"S Neumann","year":"2015","journal-title":"Horm Metab Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1055\/s-0035-1554721","article-title":"Medical treatment of graves' orbitopathy","volume":"47","author":"M Salvi","year":"2015","journal-title":"Horm Metab Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S0140-6736(00)02165-6","article-title":"Radiotherapy for Graves\u2019 orbitopathy: Randomised placebo-controlled study","volume":"355","author":"M P Mourits","year":"2000","journal-title":"Lancet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1210\/jc.2003-030809","article-title":"A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves\u2019 ophthalmopathy","volume":"89","author":"M F Prummel","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00417-009-1214-3","article-title":"A retrospective study on the efficacy of total absorbed orbital doses of 12, 16 and 20\u2009Gy combined with systemic steroid treatment in patients with Graves\u2019 orbitopathy","volume":"248","author":"K T Johnson","year":"2010","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"853860","DOI":"10.1007\/BF03347943","article-title":"Orbital radiotherapy combined with high dose systemic glucocorticoids for Graves' ophthalmopathy is more effective than radiotherapy alone: Results of a prospective randomized study","volume":"14","author":"C Marcocci","year":"1991","journal-title":"J Endocrinol Invest"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1210\/jcem-56-6-1139","article-title":"Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: Comparison with systemic corticosteroids alone","volume":"56","author":"L Bartalena","year":"1983","journal-title":"J Clin Endocrinol Metab"},{"key":"ref20","first-page":"102","article-title":"Low- versus high-dose radiotherapy for Graves' ophthalmopathy: A randomized, single blind trial","volume":"85","author":"G J Kahaly","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1530\/EJE-07-0666","article-title":"Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO","volume":"158","author":"L Bartalena","year":"2008","journal-title":"Eur J Endocrinol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000443828","article-title":"The 2016 European Thyroid Association\/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy","volume":"5","author":"L Bartalena","year":"2016","journal-title":"Eur Thyroid J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5234","DOI":"10.1210\/jc.2005-0148","article-title":"Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy","volume":"90","author":"G J Kahaly","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"ref24","first-page":"322","article-title":"Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: A preliminary study","volume":"11","author":"C M Ng","year":"2005","journal-title":"Hong Kong Med J"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00417-016-3280-7","article-title":"Efficacy of combined orbital radiation and systemic steroids in the management of Graves' orbitopathy","volume":"254","author":"J W Kim","year":"2016","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1210\/jc.2012-2758","article-title":"Efficacy and safety of orbital radiotherapy for graves' orbitopathy","volume":"97","author":"M L Tanda","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4454","DOI":"10.1210\/jc.2012-2389","article-title":"Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy","volume":"97","author":"L Bartalena","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1530\/EJE-07-0558","article-title":"Methylprednisolone pulse therapy for patients with moderately severe Graves' orbitopathy: A prospective, randomized, placebo-controlled study","volume":"158","author":"R J van Geest","year":"2008","journal-title":"Eur J Endocrinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4103\/2230-8210.152770","article-title":"Efficacy and safety of low dose oral prednisolone as compared to pulse intravenous methylprednisolone in managing moderate severe Graves' orbitopathy: A randomized controlled trial","volume":"19","author":"A Roy","year":"2015","journal-title":"Indian J Endocrinol Metab"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1136\/bjo.73.8.639","article-title":"Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: A novel approach","volume":"73","author":"M P Mourits","year":"1989","journal-title":"Br J Ophthalmol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1365-2265.1997.2331047.x","article-title":"Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy","volume":"47","author":"M P Mourits","year":"1997","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/j.1365-2265.2004.02143.x","article-title":"Clinical results of anti-inflammatory therapy in Graves' ophthalmopathy and association with thyroidal autoantibodies","volume":"61","author":"A K Eckstein","year":"2004","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1530\/eje.0.1480491","article-title":"Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: The first European Group on Graves' Orbitopathy experience","volume":"148","author":"M F Prummel","year":"2003","journal-title":"Eur J Endocrinol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1056\/NEJMoa1012985","article-title":"Selenium and the course of mild Graves' orbitopathy","volume":"364","author":"C Marcocci","year":"2011","journal-title":"N Engl J Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1210\/jc.2010-1962","article-title":"Clinical review: Intravenous glucocorticoids for Graves' orbitopathy: Efficacy and morbidity","volume":"96","author":"S Zang","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0161-6420(92)31931-1","article-title":"A functional scoring method for the field of binocular single vision","volume":"99","author":"T J Sullivan","year":"1992","journal-title":"Ophthalmology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1210\/jc.2014-3014","article-title":"Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: A randomized controlled study","volume":"100","author":"M Salvi","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00417-016-3280-7","article-title":"Efficacy of combined orbital radiation and systemic steroids in the management of Graves' orbitopathy","volume":"254","author":"J W Kim","year":"2016","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0140-6736(93)92001-A","article-title":"Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy","volume":"342","author":"M F Prummel","year":"1993","journal-title":"Lancet"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1055\/s-0042-108855","article-title":"The effect of early thyroidectomy on the course of active graves' orbitopathy (GO): A retrospective case study","volume":"48","author":"H M Meyer Zu","year":"2016","journal-title":"Horm Metab Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/S0039-6060(96)80049-3","article-title":"Surgical treatment of Graves' disease: Subtotal or total thyroidectomy?","volume":"120","author":"P Miccoli","year":"1996","journal-title":"Surgery"},{"key":"ref42","first-page":"307","article-title":"Graves' ophthalmopathy and 131I therapy","volume":"43","author":"C Marcocci","year":"1999","journal-title":"Q J Nucl Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.ophtha.2003.12.054","article-title":"Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study","volume":"111","author":"I M Wakelkamp","year":"2004","journal-title":"Ophthalmology"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/thy.1998.8.439","article-title":"Orbital radiotherapy for Graves' ophthalmopathy","volume":"8","author":"L Bartalena","year":"1998","journal-title":"Thyroid"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0028-1128141","article-title":"Effect of combined intravenous glucocorticoids and orbital radiotherapy in restoring driving competency in patients with Graves' orbitopathy","volume":"41","author":"I Sterker","year":"2009","journal-title":"Horm Metab Res"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-116945.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T23:15:23Z","timestamp":1628118923000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-116945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,18]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10,5]]},"published-print":{"date-parts":[[2017,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-116945","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,18]]}}}