Thyroid orbitopathy. Review of key points for diagnosis and treatment
Abstract Introduction and objective: Thyroid orbitopathy (TO) is an autoimmune disease of unknown etiology. It is a chronic and sometimes subacute or acute edematous and inflammatory disease, the main characteristics of which are eyelid edema, corneal ulcers, ocular hypertension, generally bilateral exophthalmos, restrictive strabismus, diplopia and optic neuropathy. To review and to update the current diagnostic and therapeutic approaches. Objective: To propose a practical, basic and precocious approach based in the knowledge of the TO. Methods: Literature review and exposition of our experience in the management of TO. Results: TO is an inflammatory orbital disease that probably has an autoimmune origin and most of the time is related to systemic disorders of the thyroid gland. Pathogenesis of the disease is not yet fully understood. Women are more likely to develop TO, and the disease is clearly affected by several factors such as smoking, age, sex and race. It is crucial to determine TO severity and activity for a correct management. Conclusions: Clinical knowledge is essential for the early diagnosis of this disorder, and it is the most important factor for the proper management of the disease. The medical treatment must be initiated promptly and should be aggressive and based in the current phase of the disease, in order to avoid the severe damage that follows TO. The surgical approach must be logical and sequential, but, on the other hand, must be rapid and aggressive in order to return the patient to his/her labour, social and familiar environment.
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Li Z, Cestari DM, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018;29(6):528–34.
Al-Sharif E, Alsuhaibani AH. Fat-removal orbital decompression for thyroid associated orbitopathy: The right procedure for the right patient. Saudi J Ophthalmol. 2017;31(3):156–61.
Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J. 2016;5(1):9–26.
Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008;158(3):273–85.
Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020;16(2):104–16.
Ludgate M. Fibrosis in dysthyroid eye disease. Eye. 2020;34(2):279–84.
Marcinkowski P, Hoyer I, Specker E, Furkert J, Rutz C, Neuenschwander M, et al. A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of graves’ orbitopathy. Thyroid. 2019;29(1):111–23.
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–61.
Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, et al. A questionnaire survey on the management of Graves’ orbitopathy in Europe. Eur J Endocrinol. 2006;155(2):207–11.
Effraimidis G. MANAGEMENT OF ENDOCRINE DISEASE: Predictive scores in autoimmune thyroid disease: are they useful? Eur J Endocrinol. 2019;181(3):R119–31.
Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, et al. Clinical assessment of patients with Graves’ orbitopathy: The European Group on Graves’ orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155(3):387–9.
Ramli N, Kala S, Samsudin A, Rahmat K, Zainal Abidin Z. Proptosis - Correlation and Agreement between Hertel Exophthalmometry and Computed Tomography. Orbit. 2015;34(5):257–62.
Fayers T, Dolman PJ. Validity and reliability of the TED-QOL: A new three-item questionnaire to assess quality of life in thyroid eye disease. Br J Ophthalmol. 2011;95(12):1670–4.
Nkenke E, Benz M, Maier T, Wiltfang J, Holbach LM, Kramer M, et al. Relative en-and exophthalmometry in zygomatic fractures comparing optical non-contact, non-ionizing 3D imaging to the Hertel instrument and computed tomography. J Cranio-Maxillofacial Surg. 2003;31(6):362–8.
Alper MG. Pioneers in the history of orbital decompression for Graves’ ophthalmopathy. Doc Ophthalmol. 1995;89(1–2):163–71.
Graham SM, Thomas RD, Carter KD, Nerad JA. The transcaruncular approach to the medial orbital wall. Laryngoscope. 2002;112(6):986–9.
Hernández-García E, San-Román JJ, González R, Nogueira A, Genol I, Stoica B, et al. Balanced (endoscopic medial and transcutaneous lateral) orbital decompression in Graves’ orbitopathy. Acta Otolaryngol. 2017;137(11):1183–7.
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Kacker A, Kazim M, Murphy M, Trokel S, Close LG. «Balanced» orbital decompression for severe Graves’ orbitopathy: Technique with treatment algorithm. Otolaryngol-Head Neck Surg. 2003;128(2):228–35.
Olivari N. Transpalpebral decompression of endocrine ophthalmopathy (graves’ disease) by removal of intraorbital fat: Experience with 147 operations over 5 years. Plast Reconstr Surg. 1991 DOI: 10.1097/00006534-199104000-00004
Anthony Wolfe S. Transpalpebral decompression of endocrine ophthalmopathy (graves’ disease) by removal of intraorbital fat: Experience with 147 operations over 5 years. Plast Reconstr Surg. 1991;87(4):642–3.
Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5(3):164–70.
Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011 DOI: 10.1056/NEJMoa1012985
Calero-Bernal ML, Martin-Garrido I, Donazar-Ezcurra M, Limper AH, Carmona EM. Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patients. Can Respir J. 2016;2016. DOI: 10.1155/2016/2464791
Viani GA, Boin AC, De Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy for graves’ ophthalmopathy: A systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75(5):324–32.
Kim JW, Han SH, Son BJ, Rim TH, Keum KC, Yoon JS. Efficacy of combined orbital radiation and systemic steroids in the management of Graves’ orbitopathy. Graefe’s Arch Clin Exp Ophthalmol. 2016;254(5):991–8.
Laurberg P, Berman D, Bülow Pedersen I, Andersen S, Malling S, Carlé A. Triple therapy (glucocorticoid + ciclosporin + orbital irradiation) for diplopia (DIP) of moderate-to-severe graves’ orbitopathy (MSGO). A prospective follow-up study. Thyroid. 2015
Bartalena L. What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf). 2010;73(2):149–52.
Stan MN, Salvi M. Rituximab therapy for Graves’ orbitopathy - Lessons from randomized control trials. Eur J Endocrinol. 2017;176(2):R101–9.
Patel A, Yang H, Douglas RS. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019 Dec;208:281–8.
Chatterjee, Nimrat Walker G. Teprotumumab for Thyroid-Associated Ophthalmopathy. Physiol Behav. 2017;176(10):139–48.
Choe CH, Cho RI, Elner VM. Comparison of lateral and medial orbital decompression for the treatment of compressive optic neuropathy in thyroid eye disease. Ophthal Plast Reconstr Surg. 2011;27(1):4–11.
Delfino L, Gauna A, Yampey J. Oftalmopatía de Graves y tratamiento con I131. Rev Argent Endocrinol Metab. 2015
Vannucchi G, Covelli D, Campi I, Currò N, Dazzi D, Rodari M, et al. Prevention of orbitopathy by oral or intravenous steroid prophylaxis in short duration Graves’ disease patients undergoing radioiodine ablation: A prospective randomized control trial study. Thyroid. 2019;29(12):1828–33.
Li Z, Cestari DM, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018;29(6):528–34.
Al-Sharif E, Alsuhaibani AH. Fat-removal orbital decompression for thyroid associated orbitopathy: The right procedure for the right patient. Saudi J Ophthalmol. 2017;31(3):156–61.
Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J. 2016;5(1):9–26.
Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008;158(3):273–85.
Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020;16(2):104–16.
Ludgate M. Fibrosis in dysthyroid eye disease. Eye. 2020;34(2):279–84.
Marcinkowski P, Hoyer I, Specker E, Furkert J, Rutz C, Neuenschwander M, et al. A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of graves’ orbitopathy. Thyroid. 2019;29(1):111–23.
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–61.
Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, et al. A questionnaire survey on the management of Graves’ orbitopathy in Europe. Eur J Endocrinol. 2006;155(2):207–11.
Effraimidis G. MANAGEMENT OF ENDOCRINE DISEASE: Predictive scores in autoimmune thyroid disease: are they useful? Eur J Endocrinol. 2019;181(3):R119–31.
Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, et al. Clinical assessment of patients with Graves’ orbitopathy: The European Group on Graves’ orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155(3):387–9.
Ramli N, Kala S, Samsudin A, Rahmat K, Zainal Abidin Z. Proptosis - Correlation and Agreement between Hertel Exophthalmometry and Computed Tomography. Orbit. 2015;34(5):257–62.
Fayers T, Dolman PJ. Validity and reliability of the TED-QOL: A new three-item questionnaire to assess quality of life in thyroid eye disease. Br J Ophthalmol. 2011;95(12):1670–4.
Nkenke E, Benz M, Maier T, Wiltfang J, Holbach LM, Kramer M, et al. Relative en-and exophthalmometry in zygomatic fractures comparing optical non-contact, non-ionizing 3D imaging to the Hertel instrument and computed tomography. J Cranio-Maxillofacial Surg. 2003;31(6):362–8.
Alper MG. Pioneers in the history of orbital decompression for Graves’ ophthalmopathy. Doc Ophthalmol. 1995;89(1–2):163–71.
Graham SM, Thomas RD, Carter KD, Nerad JA. The transcaruncular approach to the medial orbital wall. Laryngoscope. 2002;112(6):986–9.
Hernández-García E, San-Román JJ, González R, Nogueira A, Genol I, Stoica B, et al. Balanced (endoscopic medial and transcutaneous lateral) orbital decompression in Graves’ orbitopathy. Acta Otolaryngol. 2017;137(11):1183–7.
Sagiv O, Satchi K, Kinori M, Fabian ID, Rosen N, Ben Simon GJ, et al. Comparison of lateral orbital decompression with and without rim repositioning in thyroid eye disease. Graefe’s Arch Clin Exp Ophthalmol. 2016;254(4):791–6.
Kacker A, Kazim M, Murphy M, Trokel S, Close LG. «Balanced» orbital decompression for severe Graves’ orbitopathy: Technique with treatment algorithm. Otolaryngol-Head Neck Surg. 2003;128(2):228–35.
Olivari N. Transpalpebral decompression of endocrine ophthalmopathy (graves’ disease) by removal of intraorbital fat: Experience with 147 operations over 5 years. Plast Reconstr Surg. 1991 DOI: 10.1097/00006534-199104000-00004
Anthony Wolfe S. Transpalpebral decompression of endocrine ophthalmopathy (graves’ disease) by removal of intraorbital fat: Experience with 147 operations over 5 years. Plast Reconstr Surg. 1991;87(4):642–3.
Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5(3):164–70.
Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011 DOI: 10.1056/NEJMoa1012985
Calero-Bernal ML, Martin-Garrido I, Donazar-Ezcurra M, Limper AH, Carmona EM. Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patients. Can Respir J. 2016;2016. DOI: 10.1155/2016/2464791
Viani GA, Boin AC, De Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy for graves’ ophthalmopathy: A systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75(5):324–32.
Kim JW, Han SH, Son BJ, Rim TH, Keum KC, Yoon JS. Efficacy of combined orbital radiation and systemic steroids in the management of Graves’ orbitopathy. Graefe’s Arch Clin Exp Ophthalmol. 2016;254(5):991–8.
Laurberg P, Berman D, Bülow Pedersen I, Andersen S, Malling S, Carlé A. Triple therapy (glucocorticoid + ciclosporin + orbital irradiation) for diplopia (DIP) of moderate-to-severe graves’ orbitopathy (MSGO). A prospective follow-up study. Thyroid. 2015
Bartalena L. What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf). 2010;73(2):149–52.
Stan MN, Salvi M. Rituximab therapy for Graves’ orbitopathy - Lessons from randomized control trials. Eur J Endocrinol. 2017;176(2):R101–9.
Patel A, Yang H, Douglas RS. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019 Dec;208:281–8.
Chatterjee, Nimrat Walker G. Teprotumumab for Thyroid-Associated Ophthalmopathy. Physiol Behav. 2017;176(10):139–48.
Choe CH, Cho RI, Elner VM. Comparison of lateral and medial orbital decompression for the treatment of compressive optic neuropathy in thyroid eye disease. Ophthal Plast Reconstr Surg. 2011;27(1):4–11.
Delfino L, Gauna A, Yampey J. Oftalmopatía de Graves y tratamiento con I131. Rev Argent Endocrinol Metab. 2015
Vannucchi G, Covelli D, Campi I, Currò N, Dazzi D, Rodari M, et al. Prevention of orbitopathy by oral or intravenous steroid prophylaxis in short duration Graves’ disease patients undergoing radioiodine ablation: A prospective randomized control trial study. Thyroid. 2019;29(12):1828–33.
Galindo-Ferreiro, A., & Marqués-Fernández, V. E. (2021). Thyroid orbitopathy. Review of key points for diagnosis and treatment. Revista ORL, 12(4), 381–391. https://doi.org/10.14201/orl.23829
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