Subscribe to RSS
DOI: 10.1055/a-2186-5548
Aktuelle Therapieansätze der endokrinen Orbitopathie – sind die zielgerichteten Therapien die Zukunft?
Article in several languages: deutsch | EnglishZusammenfassung
Die endokrine Orbitopathie (EO) ist eine Autoimmunerkrankung der Augenhöhle, die am allerhäufigsten im Zusammenhang mit einer Schilddrüsenautoimmunerkrankung vom Typ Basedow auftritt. Für die Diagnose spezifisch und für die Pathogenese von zentraler Bedeutung ist das Auftreten von gegen den TSH-Rezeptor gerichteten Autoantikörpern (TRAK). Diese Autoantikörper, zumeist mit stimulierender Wirkung, induzieren eine unkontrollierte Schilddrüsenüberfunktion und in der Augenhöhle einen Gewebeumbau und eine mehr oder weniger ausgeprägte Entzündung. In Folge kommt es zu einer periokulären, entzündlichen Schwellung in variablem Ausmaß, Exophthalmus und Fibrose der Augenmuskeln und dadurch zu einer Störung der symmetrischen Augenbeweglichkeit mit Doppelbildwahrnehmung. In den letzten Jahrzehnten umfassten die therapeutischen Anstrengungen für die entzündliche Orbitopathie allgemein immunsuppressive Maßnahmen und für die Schilddrüsenüberfunktion die symptomatische Therapie durch Hemmung der Schilddrüsenhormonproduktion. Mit dem Bekanntwerden, dass durch die TRAK auch ein wichtiger Wachstumsfaktorrezeptor aktiviert wird, der IGF1R (Insulin-like-Growth-Factor-1-Rezeptor), wurden Biologika entwickelt, die diesen blockieren. Teprotumumab ist bereits in den USA zugelassen, und die Therapieeffekte sind v. a. hinsichtlich der Exophthalmusreduktion enorm. Nebenwirkungen, v. a. Hyperglykämie und Hörstörungen, sind zu beachten. Inwieweit die Autoimmunreaktionen (Produktion der TRAK/Anlocken von immunkompetenten Zellen) durch diese Therapien auch beeinflusst werden, ist noch nicht ausreichend geklärt. Rezidive nach der Therapie zeigen, dass die Hemmung der Autoimmunreaktion im Therapiekonzept insbesondere bei schwerem Verlauf mit enthalten sein muss.
Schlüsselwörter
endokrine Orbitopathie - Pathogenese - Risikofaktoren - Klassifikation - Leitlinien - zielgerichtete TherapienPublication History
Received: 08 July 2023
Accepted: 05 October 2023
Accepted Manuscript online:
05 October 2023
Article published online:
19 January 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References/Literatur
- 1 Davies TF, Andersen S, Latif R. et al. Gravesʼ disease. Nat Rev Dis Primers 2020; 6: 52 DOI: 10.1038/s41572-020-0184-y.
- 2 Krieger CC, Neumann S, Gershengorn MC. TSH/IGF1 receptor crosstalk: Mechanism and clinical implications. Pharmacol Ther 2020; 209: 107502 DOI: 10.1016/j.pharmthera.2020.107502.
- 3 Smith TJ, Janssen J. Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy. Endocr Rev 2019; 40: 236-267 DOI: 10.1210/er.2018-00066.
- 4 Smith TJ, Hegedus L, Douglas RS. Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Gravesʼ orbitopathy. Best Pract Res Clin Endocrinol Metab 2012; 26: 291-302 DOI: 10.1016/j.beem.2011.10.002.
- 5 Smith TJ. Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease. J Clin Endocrinol Metab 2022; 107 (Suppl. 01) S13-S26 DOI: 10.1210/clinem/dgac328.
- 6 Krause G, Eckstein A, Schulein R. Modulating TSH Receptor Signaling for Therapeutic Benefit. Eur Thyroid J 2020; 9: 66-77 DOI: 10.1159/000511871.
- 7 Kumar S, Coenen MJ, Scherer PE. et al. Evidence for enhanced adipogenesis in the orbits of patients with Gravesʼ ophthalmopathy. J Clin Endocrinol Metab 2004; 89: 930-935 DOI: 10.1210/jc.2003-031427.
- 8 Kumar S, Nadeem S, Stan MN. et al. A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Gravesʼ ophthalmopathy. J Mol Endocrinol 2011; 46: 155-163 DOI: 10.1530/JME-11-0006.
- 9 Fang S, Huang Y, Liu X. et al. Interaction Between CCR6+ Th17 Cells and CD34+ Fibrocytes Promotes Inflammation: Implications in Gravesʼ Orbitopathy in Chinese Population. Invest Ophthalmol Vis Sci 2018; 59: 2604-2614 DOI: 10.1167/iovs.18-24008.
- 10 Fang S, Lu Y, Huang Y. et al. Mechanisms That Underly T Cell Immunity in Gravesʼ Orbitopathy. Front Endocrinol (Lausanne) 2021; 12: 648732 DOI: 10.3389/fendo.2021.648732.
- 11 Fang S, Zhang S, Huang Y. et al. Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy. J Clin Endocrinol Metab 2020; 105: dgaa124 DOI: 10.1210/clinem/dgaa124.
- 12 Sonderegger I, Iezzi G, Maier R. et al. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med 2008; 205: 2281-2294 DOI: 10.1084/jem.20071119.
- 13 Görtz GE, Philipp S, Bruderek K. et al. Macrophage-Orbital Fibroblast Interaction and Hypoxia Promote Inflammation and Adipogenesis in Gravesʼ Orbitopathy. Endocrinology 2022; 164: bqac203 DOI: 10.1210/endocr/bqac203.
- 14 Eckstein AK, Plicht M, Lax H. et al. Thyrotropin receptor autoantibodies are independent risk factors for Gravesʼ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 2006; 91: 3464-3470 DOI: 10.1210/jc.2005-2813.
- 15 Stöhr M, Oeverhaus M, Lytton SD. et al. Predicting the Course of Gravesʼ Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay. Horm Metab Res 2021; 53: 435-443 DOI: 10.1055/a-1525-2070.
- 16 Stöhr M, Oeverhaus M, Lytton SD. et al. Predicting the Relapse of Hyperthyroidism in Treated Gravesʼ Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies. Horm Metab Res 2021; 53: 235-244 DOI: 10.1055/a-1373-5523.
- 17 Wiersinga W, Zarkovic M, Bartalena L. et al. Predictive score for the development or progression of Gravesʼ orbitopathy in patients with newly diagnosed Gravesʼ hyperthyroidism. Eur J Endocrinol 2018; 178: 635-643 DOI: 10.1530/EJE-18-0039.
- 18 Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs. lifetime cigarette consumption. Clin Endocrinol (Oxf) 1996; 45: 477-481 DOI: 10.1046/j.1365-2265.1996.8220832.x.
- 19 Eckstein A, Quadbeck B, Mueller G. et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol 2003; 87: 773-776 DOI: 10.1136/bjo.87.6.773.
- 20 Oeverhaus M, Winkler L, Stahr K. et al. Influence of biological sex, age and smoking on Gravesʼ orbitopathy – a ten-year tertiary referral center analysis. Front Endocrinol (Lausanne) 2023; 14: 1160172 DOI: 10.3389/fendo.2023.1160172.
- 21 Lanzolla G, Sabini E, Profilo MA. et al. Relationship between serum cholesterol and Gravesʼ orbitopathy (GO): a confirmatory study. J Endocrinol Invest 2018; 41: 1417-1423 DOI: 10.1007/s40618-018-0915-z.
- 22 Stein JD, Childers D, Gupta S. et al. Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. JAMA Ophthalmol 2015; 133: 290-296 DOI: 10.1001/jamaophthalmol.2014.5103.
- 23 Nilsson A, Tsoumani K, Planck T. Statins Decrease the Risk of Orbitopathy in Newly Diagnosed Patients with Graves Disease. J Clin Endocrinol Metab 2021; 106: 1325-1332 DOI: 10.1210/clinem/dgab070.
- 24 Laurberg P, Wallin G, Tallstedt L. et al. TSH-receptor autoimmunity in Gravesʼ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008; 158: 69-75 DOI: 10.1530/EJE-07-0450.
- 25 Bartalena L, Marcocci C, Bogazzi F. et al. Relation between therapy for hyperthyroidism and the course of Gravesʼ ophthalmopathy. N Engl J Med 1998; 338: 73-78 DOI: 10.1056/NEJM199801083380201.
- 26 Tallstedt L, Lundell G, Torring O. et al. Occurrence of ophthalmopathy after treatment for Gravesʼ hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992; 326: 1733-1738 DOI: 10.1056/NEJM199206253262603.
- 27 Iwama S, Kobayashi T, Yasuda Y. et al. Immune checkpoint inhibitor-related thyroid dysfunction. Best Pract Res Clin Endocrinol Metab 2022; 36: 101660 DOI: 10.1016/j.beem.2022.101660.
- 28 Wong V, Fu AX, George J. et al. Thyrotoxicosis induced by alpha-interferon therapy in chronic viral hepatitis. Clin Endocrinol (Oxf) 2002; 56: 793-798 DOI: 10.1046/j.1365-2265.2002.01553.x.
- 29 Medic F, Bakula M, Alfirevic M. et al. Amiodarone and Thyroid Dysfunction. Acta Clin Croat 2022; 61: 327-341 DOI: 10.20471/acc.2022.61.02.20.
- 30 Lee HJ, Li CW, Hammerstad SS. et al. Immunogenetics of autoimmune thyroid diseases: A comprehensive review. J Autoimmun 2015; 64: 82-90 DOI: 10.1016/j.jaut.2015.07.009.
- 31 Lee HJ, Stefan-Lifshitz M, Li CW. et al. Genetics and epigenetics of autoimmune thyroid diseases: Translational implications. Best Pract Res Clin Endocrinol Metab 2023; 37: 101661 DOI: 10.1016/j.beem.2022.101661.
- 32 Topcu CB, Celik O, Tasan E. Effect of stressful life events on the initiation of Gravesʼ disease. Int J Psychiatry Clin Pract 2012; 16: 307-311 DOI: 10.3109/13651501.2011.631016.
- 33 Matos-Santos A, Nobre EL, Costa JG. et al. Relationship between the number and impact of stressful life events and the onset of Gravesʼ disease and toxic nodular goitre. Clin Endocrinol (Oxf) 2001; 55: 15-19 DOI: 10.1046/j.1365-2265.2001.01332.x.
- 34 Winsa B, Adami HO, Bergstrom R. et al. Stressful life events and Gravesʼ disease. Lancet 1991; 338: 1475-1479 DOI: 10.1016/0140-6736(91)92298-g.
- 35 Uddin JM, Rubinstein T, Hamed-Azzam S. Phenotypes of Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg 2018; 34: S28-S33 DOI: 10.1097/IOP.0000000000001147.
- 36 Eckstein AK, Lösch C, Glowacka D. et al. Euthyroid and primarily hypothyroid patients develop milder and significantly more asymmetrical Graves ophthalmopathy. Br J Ophthalmol 2009; 93: 1052-1056 DOI: 10.1136/bjo.2007.137265.
- 37 Garip Kuebler A, Halfter K, Reznicek L. et al. Evaluating the interreader agreement and intrareader reproducibility of Visual Field Defects in Thyroid Eye Disease-Compressive Optic Neuropathy. Eye (Lond) 2022; 36: 724-732 DOI: 10.1038/s41433-021-01504-2.
- 38 Garip Kuebler A, Halfter K, Reznicek L. et al. A pathological indicator for dysthyroid optic neuropathy: tritan color vision deficiency. Graefes Arch Clin Exp Ophthalmol 2021; 259: 3421-3426 DOI: 10.1007/s00417-021-05227-8.
- 39 North VS, Freitag SK. A Review of Imaging Modalities in Thyroid-associated Orbitopathy. Int Ophthalmol Clin 2019; 59: 81-93 DOI: 10.1097/IIO.0000000000000289.
- 40 Starks VS, Reinshagen KL, Lee NG. et al. Visual field and orbital computed tomography correlation in dysthyroid optic neuropathy due to thyroid eye disease. Orbit 2020; 39: 77-83 DOI: 10.1080/01676830.2019.1600150.
- 41 Mourits MP, Koornneef L, Wiersinga WM. et al. Clinical criteria for the assessment of disease activity in Gravesʼ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73: 639-644 DOI: 10.1136/bjo.73.8.639.
- 42 Dolman PJ, Rootman J. VISA Classification for Graves orbitopathy. Ophthalmic Plast Reconstr Surg 2006; 22: 319-324 DOI: 10.1097/01.iop.0000235499.34867.85.
- 43 European Group on Gravesʼ Orbitopathy (EUGOGO). Wiersinga WM, Perros P, Kahaly GJ. et al. Clinical assessment of patients with Gravesʼ orbitopathy: the European Group on Gravesʼ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol 2006; 155: 387-389 DOI: 10.1530/eje.1.02230.
- 44 Burch HB, Perros P, Bednarczuk T. et al. Management of Thyroid Eye Disease: A Consensus Statement by the American Thyroid Association and the European Thyroid Association. Thyroid 2022; 32: 1439-1470 DOI: 10.1089/thy.2022.0251.
- 45 Terwee CB, Prummel MF, Gerding MN. et al. Measuring disease activity to predict therapeutic outcome in Gravesʼ ophthalmopathy. Clin Endocrinol (Oxf) 2005; 62: 145-155 DOI: 10.1111/j.1365-2265.2005.02186.x.
- 46 Salvi M, Vannucchi G, Curro N. et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Gravesʼ orbitopathy: a randomized controlled study. J Clin Endocrinol Metab 2015; 100: 422-431 DOI: 10.1210/jc.2014-3014.
- 47 Ponto KA, Merkesdal S, Hommel G. et al. Public health relevance of Gravesʼ orbitopathy. J Clin Endocrinol Metab 2013; 98: 145-152 DOI: 10.1210/jc.2012-3119.
- 48 Bartalena L, Wiersinga WM. Proposal for Standardization of Primary and Secondary Outcomes in Patients with Active, Moderate-to-Severe Gravesʼ Orbitopathy. Eur Thyroid J 2020; 9: 3-16 DOI: 10.1159/000510700.
- 49 Ponto KA, Hommel G, Pitz S. et al. Quality of life in a German graves orbitopathy population. Am J Ophthalmol 2011; 152: 483-490 e481 DOI: 10.1016/j.ajo.2011.02.018.
- 50 Bahn RS, Gorman CA. Choice of therapy and criteria for assessing treatment outcome in thyroid-associated ophthalmopathy. Endocrinol Metab Clin North Am 1987; 16: 391-407
- 51 Campi I, Curro N, Vannucchi G. et al. Quantification of Global Ocular Motility Impairment in Gravesʼ Orbitopathy by Measuring Eye Muscle Ductions. Thyroid 2021; 31: 280-287 DOI: 10.1089/thy.2020.0165.
- 52 Jellema HM, Saeed P, Mombaerts I. et al. Objective and subjective outcomes of strabismus surgery in Gravesʼ orbitopathy: a prospective multicentre study. Acta Ophthalmol 2017; 95: 386-391 DOI: 10.1111/aos.13367.
- 53 Kahaly GJ, Pitz S, Hommel G. et al. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Gravesʼ orbitopathy. J Clin Endocrinol Metab 2005; 90: 5234-5240 DOI: 10.1210/jc.2005-0148.
- 54 Kahaly GJ, Riedl M, König J. et al. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Gravesʼ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol 2018; 6: 287-298 DOI: 10.1016/S2213-8587(18)30020-2.
- 55 Zang S, Ponto KA, Kahaly GJ. Clinical review: Intravenous glucocorticoids for Gravesʼ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 2011; 96: 320-332 DOI: 10.1210/jc.2010-1962.
- 56 Bartalena L, Krassas GE, Wiersinga W. et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Gravesʼ orbitopathy. J Clin Endocrinol Metab 2012; 97: 4454-4463 DOI: 10.1210/jc.2012-2389.
- 57 Rajendram R, Taylor PN, Wilson VJ. et al. Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol 2018; 6: 299-309 DOI: 10.1016/S2213-8587(18)30021-4.
- 58 Kahaly G, Schrezenmeir J, Krause U. et al. Ciclosporin and prednisone v. prednisone in treatment of Gravesʼ ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest 1986; 16: 415-422 DOI: 10.1111/j.1365-2362.1986.tb01016.x.
- 59 Prummel MF, Mourits MP, Berghout A. et al. Prednisone and cyclosporine in the treatment of severe Gravesʼ ophthalmopathy. N Engl J Med 1989; 321: 1353-1359 DOI: 10.1056/NEJM198911163212002.
- 60 Stan MN, Garrity JA, Carranza Leon BG. et al. Randomized controlled trial of rituximab in patients with Gravesʼ orbitopathy. J Clin Endocrinol Metab 2015; 100: 432-441 DOI: 10.1210/jc.2014-2572.
- 61 Ceballos-Macías José J, Rivera-Moscoso R, Flores-Real Jorge A. et al. Tocilizumab in glucocorticoid-resistant graves orbitopathy. A case series report of a Mexican population. Ann Endocrinol (Paris) 2020; 81: 78-82 DOI: 10.1016/j.ando.2020.01.003.
- 62 Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR. et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol 2018; 195: 181-190 DOI: 10.1016/j.ajo.2018.07.038.
- 63 Pérez-Moreiras JV, Varela-Agra M, Prada-Sánchez MC. et al. Steroid-Resistant Gravesʼ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience. J Clin Med 2021; 10: 706 DOI: 10.3390/jcm10040706.
- 64 Marcocci C, Kahaly GJ, Krassas GE. et al. Selenium and the course of mild Gravesʼ orbitopathy. N Engl J Med 2011; 364: 1920-1931 DOI: 10.1056/NEJMoa1012985.
- 65 Mourits MP, van Kempen-Harteveld ML, Garcia MB. et al. Radiotherapy for Gravesʼ orbitopathy: randomised placebo-controlled study. Lancet 2000; 355: 1505-1509 DOI: 10.1016/S0140-6736(00)02165-6.
- 66 Prummel MF, Terwee CB, Gerding MN. et al. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Gravesʼ ophthalmopathy. J Clin Endocrinol Metab 2004; 89: 15-20 DOI: 10.1210/jc.2003-030809.
- 67 Marcocci C, Bartalena L, Bogazzi F. et al. Orbital radiotherapy combined with high dose systemic glucocorticoids for Gravesʼ ophthalmopathy is more effective than radiotherapy alone: results of a prospective randomized study. J Endocrinol Invest 1991; 14: 853-860 DOI: 10.1007/BF03347943.
- 68 Bartalena L, Marcocci C, Chiovato L. et al. Orbital cobalt irradiation combined with systemic corticosteroids for Gravesʼ ophthalmopathy: comparison with systemic corticosteroids alone. J Clin Endocrinol Metab 1983; 56: 1139-1144 DOI: 10.1210/jcem-56-6-1139.
- 69 Kim JW, Han SH, Son BJ. et al. Efficacy of combined orbital radiation and systemic steroids in the management of Gravesʼ orbitopathy. Graefes Arch Clin Exp Ophthalmol 2016; 254: 991-998 DOI: 10.1007/s00417-016-3280-7.
- 70 Oeverhaus M, Witteler T, Lax H. et al. Combination Therapy of Intravenous Steroids and Orbital Irradiation is More Effective Than Intravenous Steroids Alone in Patients with Gravesʼ Orbitopathy. Horm Metab Res 2017; 49: 739-747 DOI: 10.1055/s-0043-116945.
- 71 Marquez SD, Lum BL, McDougall IR. et al. Long-term results of irradiation for patients with progressive Gravesʼ ophthalmopathy. Int J Radiat Oncol Biol Phys 2001; 51: 766-774 DOI: 10.1016/s0360-3016(01)01699-6.
- 72 Wakelkamp IM, Tan H, Saeed P. et al. Orbital irradiation for Gravesʼ ophthalmopathy: Is it safe? A long-term follow-up study. Ophthalmology 2004; 111: 1557-1562 DOI: 10.1016/j.ophtha.2003.12.054.
- 73 Lanzolla G, Maglionico MN, Comi S. et al. Sirolimus as a second-line treatment for Gravesʼ orbitopathy. J Endocrinol Invest 2022; 45: 2171-2180 DOI: 10.1007/s40618-022-01862-y.
- 74 Zhang M, Chong KK, Chen ZY. et al. Rapamycin improves Gravesʼ orbitopathy by suppressing CD4+ cytotoxic T lymphocytes. JCI Insight 2023; 8: e160377 DOI: 10.1172/jci.insight.160377.
- 75 Douglas RS, Kahaly GJ, Patel A. et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020; 382: 341-352 DOI: 10.1056/NEJMoa1910434.
- 76 Kahaly GJ, Douglas RS, Holt RJ. et al. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol 2021; 9: 360-372 DOI: 10.1016/S2213-8587(21)00056-5.
- 77 Smith TJ, Kahaly GJ, Ezra DG. et al. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med 2017; 376: 1748-1761 DOI: 10.1056/NEJMoa1614949.
- 78 Douglas RS, Kahaly GJ, Ugradar S. et al. Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study. Ophthalmology 2022; 129: 438-449 DOI: 10.1016/j.ophtha.2021.10.017.
- 79 Furmaniak J, Sanders J, Sanders P. et al. TSH receptor specific monoclonal autoantibody K1–70 targeting of the TSH receptor in subjects with Gravesʼ disease and Gravesʼ orbitopathy-Results from a phase I clinical trial. Clin Endocrinol (Oxf) 2022; 96: 878-887 DOI: 10.1111/cen.14681.
- 80 Le Moli R, Malandrino P, Russo M. et al. Corticosteroid Pulse Therapy for Gravesʼ Ophthalmopathy Reduces the Relapse Rate of Gravesʼ Hyperthyroidism. Front Endocrinol (Lausanne) 2020; 11: 367 DOI: 10.3389/fendo.2020.00367.
- 81 Bartalena L, Baldeschi L, Dickinson A. et al. Consensus statement of the European Group on Gravesʼ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008; 158: 273-285 DOI: 10.1530/EJE-07-0666.
- 82 Bartalena L, Baldeschi L, Boboridis K. et al. The 2016 European Thyroid Association/European Group on Gravesʼ Orbitopathy Guidelines for the Management of Gravesʼ Orbitopathy. Eur Thyroid J 2016; 5: 9-26 DOI: 10.1159/000443828.
- 83 Bartalena L, Kahaly GJ, Baldeschi L. et al. The 2021 European Group on Gravesʼ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Gravesʼ orbitopathy. Eur J Endocrinol 2021; 185: G43-G67 DOI: 10.1530/EJE-21-0479.
- 84 Kahaly GJ, Bartalena L, Hegedus L. et al. 2018 European Thyroid Association Guideline for the Management of Gravesʼ Hyperthyroidism. Eur Thyroid J 2018; 7: 167-186 DOI: 10.1159/000490384.
- 85 Schott M, Morgenthaler NG, Fritzen R. et al. Levels of autoantibodies against human TSH receptor predict relapse of hyperthyroidism in Gravesʼ disease. Horm Metab Res 2004; 36: 92-96 DOI: 10.1055/s-2004-814217.
- 86 Meyer Zu Horste M, Pateronis K, Walz MK. et al. The Effect of Early Thyroidectomy on the Course of Active Gravesʼ Orbitopathy (GO): A Retrospective Case Study. Horm Metab Res 2016; 48: 433-439 DOI: 10.1055/s-0042-108855.
- 87 Lanzolla G, Menconi F, Nicoli F. et al. Beneficial effect of low-dose radioiodine ablation for Gravesʼ orbitopathy: results of a retrospective study. J Endocrinol Invest 2021; 44: 2575-2579 DOI: 10.1007/s40618-021-01544-1.
- 88 Menconi F, Leo M, Vitti P. et al. Total thyroid ablation in Gravesʼ orbitopathy. J Endocrinol Invest 2015; 38: 809-815 DOI: 10.1007/s40618-015-0255-1.
- 89 Menconi F, Marino M, Pinchera A. et al. Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Gravesʼ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 2007; 92: 1653-1658 DOI: 10.1210/jc.2006-1800.
- 90 Oeverhaus M, Koenen J, Bechrakis N. et al. Radioiodine ablation of thyroid remnants in patients with Gravesʼ orbitopathy. J Nucl Med 2023; 64: 561-566 DOI: 10.2967/jnumed.122.264660.
- 91 Traisk F, Tallstedt L, Abraham-Nordling M. et al. Thyroid-associated ophthalmopathy after treatment for Gravesʼ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009; 94: 3700-3707 DOI: 10.1210/jc.2009-0747.
- 92 Torring O, Tallstedt L, Wallin G. et al. Gravesʼ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine–a prospective, randomized study. Thyroid Study Group. J Clin Endocrinol Metab 1996; 81: 2986-2993 DOI: 10.1210/jcem.81.8.8768863.
- 93 Vannucchi G, Covelli D, Campi I. et al. Prevention of Orbitopathy by Oral or Intravenous Steroid Prophylaxis in Short Duration Gravesʼ Disease Patients Undergoing Radioiodine Ablation: A Prospective Randomized Control Trial Study. Thyroid 2019; 29: 1828-1833 DOI: 10.1089/thy.2019.0150.
- 94 Vannucchi G, Campi I, Covelli D. et al. Gravesʼ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab 2009; 94: 3381-3386 DOI: 10.1210/jc.2009-0506.
- 95 Tanda ML, Lai A, Bartalena L. Relation between Gravesʼ orbitopathy and radioiodine therapy for hyperthyroidism: facts and unsolved questions. Clin Endocrinol (Oxf) 2008; 69: 845-847 DOI: 10.1111/j.1365-2265.2008.03417.x.
- 96 Dederichs B, Dietlein M, Jenniches-Kloth B. et al. Radioiodine therapy of Gravesʼ hyperthyroidism in patients without pre-existing ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy?. Exp Clin Endocrinol Diabetes 2006; 114: 366-370 DOI: 10.1055/s-2006-924321.
- 97 Bartalena L, Piantanida E, Gallo D. et al. Epidemiology, Natural History, Risk Factors, and Prevention of Gravesʼ Orbitopathy. Front Endocrinol (Lausanne) 2020; 11: 615993 DOI: 10.3389/fendo.2020.615993.
- 98 Tanda ML, Piantanida E, Liparulo L. et al. Prevalence and natural history of Gravesʼ orbitopathy in a large series of patients with newly diagnosed Gravesʼ hyperthyroidism seen at a single center. J Clin Endocrinol Metab 2013; 98: 1443-1449 DOI: 10.1210/jc.2012-3873.
- 99 Perros P, Zarkovic M, Azzolini C. et al. PREGO (presentation of Gravesʼ orbitopathy) study: changes in referral patterns to European Group On Gravesʼ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012. Br J Ophthalmol 2015; 99: 1531-1535 DOI: 10.1136/bjophthalmol-2015-306733.
- 100 Schuh A, Ayvaz G, Baldeschi L. et al. Presentation of Gravesʼ orbitopathy within European Group On Gravesʼ Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III). Br J Ophthalmol 2023; DOI: 10.1136/bjo-2022-322442.
- 101 Eckstein A, Schittkowski M, Esser J. Surgical treatment of Gravesʼ ophthalmopathy. Best Pract Res Clin Endocrinol Metab 2012; 26: 339-358 DOI: 10.1016/j.beem.2011.11.002.
- 102 Marino M, Morabito E, Brunetto MR. et al. Acute and severe liver damage associated with intravenous glucocorticoid pulse therapy in patients with Gravesʼ ophthalmopathy. Thyroid 2004; 14: 403-406 DOI: 10.1089/105072504774193276.
- 103 Negro R, Hegedus L, Attanasio R. et al. A 2018 European Thyroid Association Survey on the Use of Selenium Supplementation in Gravesʼ Hyperthyroidism and Gravesʼ Orbitopathy. Eur Thyroid J 2019; 8: 7-15 DOI: 10.1159/000494837.
- 104 Broen JCA, van Laar JM. Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology. Nat Rev Rheumatol 2020; 16: 167-178 DOI: 10.1038/s41584-020-0374-8.
- 105 Quah Qin Xian N, Alnahrawy A, Akshikar R. et al. Real-World Efficacy and Safety of Mycophenolate Mofetil in Active Moderate-to-Sight-Threatening Thyroid Eye Disease. Clin Ophthalmol 2021; 15: 1921-1932 DOI: 10.2147/OPTH.S305717.
- 106 Zhang L, Grennan-Jones F, Draman MS. et al. Possible targets for nonimmunosuppressive therapy of Gravesʼ orbitopathy. J Clin Endocrinol Metab 2014; 99: E1183-E1190 DOI: 10.1210/jc.2013-4182.
- 107 Roos JCP, Eglitis V, Murthy R. Inhibition of Fibrotic Contraction by Sirolimus (Rapamycin) in an Ex Vivo Model of Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg 2021; 37: 366-371 DOI: 10.1097/IOP.0000000000001876.
- 108 Chang S, Perry JD, Kosmorsky GS. et al. Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy. Ophthalmic Plast Reconstr Surg 2007; 23: 225-226 DOI: 10.1097/IOP.0b013e3180500d57.
- 109 Roos JCP, Murthy R. Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Gravesʼ orbitopathy. Eye (Lond) 2019; 33: 679-682 DOI: 10.1038/s41433-019-0340-3.
- 110 Prummel MF, Mourits MP, Blank L. et al. Randomized double-blind trial of prednisone versus radiotherapy in Gravesʼ ophthalmopathy. Lancet 1993; 342: 949-954
- 111 Johnson KT, Wittig A, Loesch C. et al. A retrospective study on the efficacy of total absorbed orbital doses of 12, 16 and 20 Gy combined with systemic steroid treatment in patients with Gravesʼ orbitopathy. Graefes Arch Clin Exp Ophthalmol 2010; 248: 103-109 DOI: 10.1007/s00417-009-1214-3.
- 112 Tanda ML, Bartalena L. Efficacy and safety of orbital radiotherapy for Gravesʼ orbitopathy. J Clin Endocrinol Metab 2012; 97: 3857-3865 DOI: 10.1210/jc.2012-2758.
- 113 Kahaly GJ, Rösler HP, Pitz S. et al. Low- versus high-dose radiotherapy for Gravesʼ ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metab 2000; 85: 102-108 DOI: 10.1210/jcem.85.1.6257.
- 114 Sterker I, Tegetmeyer H, Papsdorf K. et al. Effect of combined intravenous glucocorticoids and orbital radiotherapy in restoring driving competency in patients with Gravesʼ orbitopathy. Horm Metab Res 2009; 41: 391-396 DOI: 10.1055/s-0028-1128141.
- 115 Shams PN, Ma R, Pickles T. et al. Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease. Am J Ophthalmol 2014; 157: 1299-1305 DOI: 10.1016/j.ajo.2014.02.044.
- 116 Gold KG, Scofield S, Isaacson SR. et al. Orbital Radiotherapy Combined With Corticosteroid Treatment for Thyroid Eye Disease-Compressive Optic Neuropathy. Ophthalmic Plast Reconstr Surg 2018; 34: 172-177 DOI: 10.1097/IOP.0000000000001003.
- 117 Marcocci C, Bartalena L, Rocchi R. et al. Long-term safety of orbital radiotherapy for Gravesʼ ophthalmopathy. J Clin Endocrinol Metab 2003; 88: 3561-3566 DOI: 10.1210/jc.2003-030260.
- 118 Godfrey KJ, Kazim M. Radiotherapy for Active Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg 2018; 34 (4S Suppl. 1): S98-S104 DOI: 10.1097/IOP.0000000000001074.
- 119 Chen J, Chen G, Sun H. Intravenous rituximab therapy for active Gravesʼ ophthalmopathy: a meta-analysis. Hormones (Athens) 2021; 20: 279-286 DOI: 10.1007/s42000-021-00282-6.
- 120 Vannucchi G, Campi I, Covelli D. et al. Efficacy Profile and Safety of Very Low-Dose Rituximab in Patients with Gravesʼ Orbitopathy. Thyroid 2021; 31: 821-828 DOI: 10.1089/thy.2020.0269.
- 121 Gillespie EF, Raychaudhuri N, Papageorgiou KI. et al. Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-kappaB. Invest Ophthalmol Vis Sci 2012; 53: 7746-7753 DOI: 10.1167/iovs.12-9861.
- 122 Ueland HO, Ueland GA, Lovas K. et al. Novel inflammatory biomarkers in thyroid eye disease. Eur J Endocrinol 2022; 187: 293-300 DOI: 10.1530/EJE-22-0247.
- 123 Leszczynska A, Molins B, Fernandez E. et al. Cytokine production in thyroid eye disease: in vitro effects of dexamethasone and IL-6 blockade with tocilizumab. Graefes Arch Clin Exp Ophthalmol 2019; 257: 2307-2314 DOI: 10.1007/s00417-019-04419-7.
- 124 Dorado Cortez O, Grivet D, Perrillat N. et al. Treatment of corticosteroid-resistant Gravesʼ orbitopathy with tocilizumab: a single-centre prospective study. Orbit 2023; 42: 411-417 DOI: 10.1080/01676830.2022.2119262.
- 125 Moi L, Hamedani M, Ribi C. Long-term outcomes in corticosteroid-refractory Gravesʼ orbitopathy treated with tocilizumab. Clin Endocrinol (Oxf) 2022; 97: 363-370 DOI: 10.1111/cen.14655.
- 126 Sanchez-Bilbao L, Martinez-Lopez D, Revenga M. et al. Anti-IL-6 Receptor Tocilizumab in Refractory Gravesʼ Orbitopathy: National Multicenter Observational Study of 48 Patients. J Clin Med 2020; 9: 2816 DOI: 10.3390/jcm9092816.
- 127 Philipp S, Horstmann M, Hose M. et al. An Early Wave of Macrophage Infiltration Intertwined with Antigen-Specific Proinflammatory T Cells and Browning of Adipose Tissue Characterizes the Onset of Orbital Inflammation in a Mouse Model of Gravesʼ Orbitopathy. Thyroid 2022; 32: 283-293 DOI: 10.1089/thy.2021.0464.
- 128 de Lacerda AM, de Souza SAL, Gutfilen B. et al. Technetium-99 m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Gravesʼ ophthalmopathy. Clin Physiol Funct Imaging 2019; 39: 135-142 DOI: 10.1111/cpf.12548.
- 129 Paridaens D, van den Bosch WA, van der Loos TL. et al. The effect of etanercept on Gravesʼ ophthalmopathy: a pilot study. Eye (Lond) 2005; 19: 1286-1289 DOI: 10.1038/sj.eye.6701768.
- 130 Durrani OM, Reuser TQ, Murray PI. Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit 2005; 24: 117-119 DOI: 10.1080/01676830590912562.
- 131 Komorowski J, Jankiewicz-Wika J, Siejka A. et al. Monoclonal anti-TNFalpha antibody (infliximab) in the treatment of patient with thyroid associated ophthalmopathy. Klin Oczna 2007; 109: 457-460
- 132 Ayabe R, Rootman DB, Hwang CJ. et al. Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease. Ophthalmic Plast Reconstr Surg 2014; 30: 415-419 DOI: 10.1097/IOP.0000000000000211.
- 133 Girnita L, Smith TJ, Janssen J. It Takes Two to Tango: IGF-I and TSH Receptors in Thyroid Eye Disease. J Clin Endocrinol Metab 2022; 107 (Suppl. 01) S1-S12 DOI: 10.1210/clinem/dgac045.
- 134 Ugradar S, Kang J, Kossler AL. et al. Teprotumumab for the treatment of chronic thyroid eye disease. Eye (Lond) 2022; 36: 1553-1559 DOI: 10.1038/s41433-021-01593-z.
- 135 Diniz SB, Cohen LM, Roelofs KA. et al. Early Experience With the Clinical Use of Teprotumumab in a Heterogenous Thyroid Eye Disease Population. Ophthalmic Plast Reconstr Surg 2021; 37: 583-591 DOI: 10.1097/IOP.0000000000001959.
- 136 Ozzello DJ, Dallalzadeh LO, Liu CY. Teprotumumab for chronic thyroid eye disease. Orbit 2022; 41: 539-546 DOI: 10.1080/01676830.2021.1933081.
- 137 Stan MN, Krieger C. Teprotumumab – A Review of Its Adverse Effects Profile. J Clin Endocrinol Metab 2023; 108: e654-e662 DOI: 10.1210/clinem/dgad213.
- 138 Kay-Rivest E, Belinsky I, Kozlova A. et al. Prospective Assessment of Otologic Adverse Events due to Teprotumumab: Preliminary Results. Otolaryngol Head Neck Surg 2023; 168: 1164-1169 DOI: 10.1002/ohn.174.
- 139 Roemer A, Staecker H, Sasse S. et al. Biological therapies in otology. HNO 2017; 65: 87-97 DOI: 10.1007/s00106-016-0306-8.
- 140 Yamahara K, Yamamoto N, Nakagawa T. et al. Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells. Hear Res 2015; 330: 2-9 DOI: 10.1016/j.heares.2015.04.009.
- 141 Jain AP, Gellada N, Ugradar S. et al. Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease. Br J Ophthalmol 2022; 106: 165-171 DOI: 10.1136/bjophthalmol-2020-317806.
- 142 Evans M, Sanders J, Tagami T. et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf) 2010; 73: 404-412 DOI: 10.1111/j.1365-2265.2010.03831.x.
- 143 Furmaniak J, Sanders J, Young S. et al. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1–70). Auto Immun Highlights 2012; 3: 19-25 DOI: 10.1007/s13317-011-0025-9.
- 144 Furmaniak J, Sanders J, Clark J. et al. Preclinical studies on the toxicology, pharmacokinetics and safety of K1–70 a human monoclonal autoantibody to the TSH receptor with TSH antagonist activity. Auto Immun Highlights 2019; 10: 11 DOI: 10.1186/s13317-019-0121-9.
- 145 Pearce SHS, Dayan C, Wraith DC. et al. Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Gravesʼ Hyperthyroidism: A Phase I Study. Thyroid 2019; 29: 1003-1011 DOI: 10.1089/thy.2019.0036.
- 146 Marcocci C, Bartalena L, Panicucci M. et al. Orbital cobalt irradiation combined with retrobulbar or systemic corticosteroids for Gravesʼ ophthalmopathy: a comparative study. Clin Endocrinol (Oxf) 1987; 27: 33-42 DOI: 10.1111/j.1365-2265.1987.tb00836.x.
- 147 Ebner R, Devoto MH, Weil D. et al. Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone. Br J Ophthalmol 2004; 88: 1380-1386 DOI: 10.1136/bjo.2004.046193.
- 148 Lee SJ, Rim TH, Jang SY. et al. Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy using subconjunctival triamcinolone injections. Graefes Arch Clin Exp Ophthalmol 2013; 251: 261-270 DOI: 10.1007/s00417-012-2153-y.
- 149 Duan M, Xu DD, Zhou HL. et al. Triamcinolone acetonide injection in the treatment of upper eyelid retraction in Gravesʼ ophthalmopathy evaluated by 3.0 Tesla magnetic resonance imaging. Indian J Ophthalmol 2022; 70: 1736-1741 DOI: 10.4103/ijo.IJO_2228_21.
- 150 Young SM, Kim YD, Lang SS. et al. Transconjunctival Triamcinolone Injection for Upper Lid Retraction in Thyroid Eye Disease-A New Injection Method. Ophthalmic Plast Reconstr Surg 2018; 34: 587-593 DOI: 10.1097/IOP.0000000000001120.
- 151 Xu DD, Chen Y, Xu HY. et al. Long-term effect of triamcinolone acetonide in the treatment of upper lid retraction with thyroid associated ophthalmopathy. Int J Ophthalmol 2018; 11: 1290-1295 DOI: 10.18240/ijo.2018.08.07.
- 152 Lee JM, Lee H, Park M. et al. Subconjunctival injection of triamcinolone for the treatment of upper lid retraction associated with thyroid eye disease. J Craniofac Surg 2012; 23: 1755-1758 DOI: 10.1097/SCS.0b013e3182646043.
- 153 Rana HS, Akella SS, Clabeaux CE. et al. Ocular surface disease in thyroid eye disease: A narrative review. Ocul Surf 2022; 24: 67-73 DOI: 10.1016/j.jtos.2022.02.001.
- 154 Eckstein AK, Finkenrath A, Heiligenhaus A. et al. Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies. Acta Ophthalmol Scand 2004; 82: 291-297 DOI: 10.1111/j.1395-3907.2004.00268.x.
- 155 Ismailova DS, Fedorov AA, Grusha YO. Ocular surface changes in thyroid eye disease. Orbit 2013; 32: 87-90 DOI: 10.3109/01676830.2013.764440.
- 156 Sullivan BD, Whitmer D, Nichols KK. et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010; 51: 6125-6130 DOI: 10.1167/iovs.10-5390.
- 157 Gilbard JP, Farris RL. Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol (Copenh) 1983; 61: 108-116 DOI: 10.1111/j.1755-3768.1983.tb01401.x.
- 158 Iskeleli G, Karakoc Y, Abdula A. Tear film osmolarity in patients with thyroid ophthalmopathy. Jpn J Ophthalmol 2008; 52: 323-326 DOI: 10.1007/s10384-008-0545-7.
- 159 Takahashi Y, Lee PAL, Vaidya A. et al. Tear film break-up patterns in thyroid eye disease. Sci Rep 2021; 11: 5288 DOI: 10.1038/s41598-021-84661-4.
- 160 Xu N, Cui Y, Fu D. et al. Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids. J Endocrinol Invest 2020; 43: 901-910 DOI: 10.1007/s40618-019-01174-8.
- 161 Mandic JJ, Kozmar A, Kusacic-Kuna S. et al. The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs. euthyreosis. Graefes Arch Clin Exp Ophthalmol 2018; 256: 845-852 DOI: 10.1007/s00417-017-3892-6.
- 162 Huang D, Luo Q, Yang H. et al. Changes of lacrimal gland and tear inflammatory cytokines in thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci 2014; 55: 4935-4943 DOI: 10.1167/iovs.13-13704.
- 163 Huang D, Xu N, Song Y. et al. Inflammatory cytokine profiles in the tears of thyroid-associated ophthalmopathy. Graefes Arch Clin Exp Ophthalmol 2012; 250: 619-625 DOI: 10.1007/s00417-011-1863-x.
- 164 Park J, Baek S. Dry eye syndrome in thyroid eye disease patients: The role of increased incomplete blinking and Meibomian gland loss. Acta Ophthalmol 2019; 97: e800-e806 DOI: 10.1111/aos.14000.
- 165 Gurdal C, Genc I, Sarac O. et al. Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings, conjunctival epithelial apoptosis, and MMP-9 expression. Curr Eye Res 2010; 35: 771-777 DOI: 10.3109/02713683.2010.490320.
- 166 Sun R, Yang M, Lin C. et al. A clinical study of topical treatment for thyroid-associated ophthalmopathy with dry eye syndrome. BMC Ophthalmol 2023; 23: 72 DOI: 10.1186/s12886-023-02805-8.
- 167 Kim YS, Kwak AY, Lee SY. et al. Meibomian gland dysfunction in Gravesʼ orbitopathy. Can J Ophthalmol 2015; 50: 278-282 DOI: 10.1016/j.jcjo.2015.05.012.
- 168 Ebner R. Botulinum toxin type A in upper lid retraction of Gravesʼ ophthalmopathy. J Clin Neuroophthalmol 1993; 13: 258-261
- 169 Traisk F, Tallstedt L. Thyroid associated ophthalmopathy: botulinum toxin A in the treatment of upper eyelid retraction–a pilot study. Acta Ophthalmol Scand 2001; 79: 585-588 DOI: 10.1034/j.1600-0420.2001.790608.x.
- 170 Uddin JM, Davies PD. Treatment of upper eyelid retraction associated with thyroid eye disease with subconjunctival botulinum toxin injection. Ophthalmology 2002; 109: 1183-1187 DOI: 10.1016/s0161-6420(02)01041-2.
- 171 Dintelmann T, Sold J, Grehn F. [Botulinum toxin injection-treatment of upper lid retraction in thyroid eye disease]. Ophthalmologe 2005; 102: 247-250 DOI: 10.1007/s00347-004-1091-4.
- 172 Wabbels B. [Botulinumtoxin in Ophthalmology]. Klin Monbl Augenheilkd 2019; 236: 825-836 DOI: 10.1055/a-0885-2107.
- 173 Olver JM. Botulinum toxin A treatment of overactive corrugator supercilii in thyroid eye disease. Br J Ophthalmol 1998; 82: 528-533 DOI: 10.1136/bjo.82.5.528.
- 174 Dagi LR, Elliott AT, Roper-Hall G. et al. Thyroid eye disease: honing your skills to improve outcomes. J AAPOS 2010; 14: 425-431 DOI: 10.1016/j.jaapos.2010.07.005.
- 175 Saeed P, Tavakoli Rad S, Bisschop P. Dysthyroid Optic Neuropathy. Ophthalmic Plast Reconstr Surg 2018; 34 (4S Suppl. 1): S60-S67 DOI: 10.1097/IOP.0000000000001146.
- 176 Görtz GE, Horstmann M, Aniol B. et al. Hypoxia-Dependent HIF-1 Activation Impacts on Tissue Remodeling in Gravesʼ Ophthalmopathy-Implications for Smoking. J Clin Endocrinol Metab 2016; 101: 4834-4842 DOI: 10.1210/jc.2016-1279.
- 177 Curro N, Covelli D, Vannucchi G. et al. Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy. Thyroid 2014; 24: 897-905 DOI: 10.1089/thy.2013.0445.
- 178 Sears CM, Azad AD, Dosiou C. et al. Teprotumumab for Dysthyroid Optic Neuropathy: Early Response to Therapy. Ophthalmic Plast Reconstr Surg 2021; 37 (3S): S157-S160 DOI: 10.1097/IOP.0000000000001831.
- 179 Sears CM, Wang Y, Bailey LA. et al. Early efficacy of teprotumumab for the treatment of dysthyroid optic neuropathy: A multicenter study. Am J Ophthalmol Case Rep 2021; 23: 101111 DOI: 10.1016/j.ajoc.2021.101111.
- 180 Hwang CJ, Nichols EE, Chon BH. et al. Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab. Eur J Ophthalmol 2022; 32: NP46-NP49 DOI: 10.1177/1120672121991042.
- 181 Lopez MJ, Herring JL, Thomas C. et al. Visual Recovery of Dysthyroid Optic Neuropathy With Teprotumumab. J Neuroophthalmol 2022; 42: e491-e493 DOI: 10.1097/WNO.0000000000001298.