UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of Graves' orbitopathy (ophthalmopathy)

Author
Terry F Davies, MD, FRCP, FACE
Section Editor
Douglas S Ross, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Graves' orbitopathy (ophthalmopathy) is an autoimmune disease of the retro-orbital tissues. This topic review will provide an overview of the treatment of this disorder; its pathogenesis and clinical features are discussed separately. (See "Pathogenesis and clinical features of Graves' ophthalmopathy (orbitopathy)".)

NATURAL HISTORY

The natural history of Graves' orbitopathy is variable and must be considered in the context of concomitant hyperthyroidism therapy [1-3]. (See 'Direct effect of type of therapy' below.)

In some patients, orbitopathy changes little for many years. In others, it may worsen or improve or, in a few patients, follow a course characterized by exacerbations and remissions. These variations make it especially difficult to reach conclusions about the efficacy of treatment. (See 'Efficacy' below.)

One study, as an example, evaluated 237 patients with newly diagnosed Graves' hyperthyroidism who were treated with thionamides [1]. At initial presentation, the majority (73.7 percent) of patients had no ocular involvement, whereas mild, moderate-to-severe, and sight-threatening orbitopathy were present in 20, 5.8, and 0.3 percent of patients, respectively. During the 18-month follow-up period, progression to moderate-to-severe orbitopathy occurred in 2.6 percent of patients with no orbitopathy at baseline and in 2.4 percent of patients with mild activity at baseline. In contrast, 58 percent of patients with mild disease at baseline experienced complete remission.

APPROACH TO TREATMENT

Treatment of patients with Graves' orbitopathy includes:

                       

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Oct 14 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Tanda ML, Piantanida E, Liparulo L, et al. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. J Clin Endocrinol Metab 2013; 98:1443.
  2. Piantanida E, Tanda ML, Lai A, et al. Prevalence and natural history of Graves' orbitopathy in the XXI century. J Endocrinol Invest 2013; 36:444.
  3. Menconi F, Profilo MA, Leo M, et al. Spontaneous improvement of untreated mild Graves' ophthalmopathy: Rundle's curve revisited. Thyroid 2014; 24:60.
  4. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26:1343.
  5. Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J 2016; 5:9.
  6. Tallstedt L, Lundell G, Tørring O, et al. Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992; 326:1733.
  7. Bartalena L, Marcocci C, Bogazzi F, et al. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 1989; 321:1349.
  8. Sridama V, DeGroot LJ. Treatment of Graves' disease and the course of ophthalmopathy. Am J Med 1989; 87:70.
  9. Gwinup G, Elias AN, Ascher MS. Effect on exophthalmos of various methods of treatment of Graves' disease. JAMA 1982; 247:2135.
  10. Marcocci C, Bruno-Bossio G, Manetti L, et al. The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case-control study. Clin Endocrinol (Oxf) 1999; 51:503.
  11. Hall R, Smith BR, Mukhtar ED. Thyroid stimulators in health and disease. Clin Endocrinol (Oxf) 1975; 4:213.
  12. Weetman AP. The immunomodulatory effects of antithyroid drugs. Thyroid 1994; 4:145.
  13. Träisk F, Tallstedt L, Abraham-Nordling M, et al. Thyroid-associated ophthalmopathy after treatment for Graves' hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009; 94:3700.
  14. Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med 2003; 139:346.
  15. Kurihara H. Total thyroidectomy for the treatment of hyperthyroidism in patients with ophthalmopathy. Thyroid 2002; 12:265.
  16. Järhult J, Rudberg C, Larsson E, et al. Graves' disease with moderate-severe endocrine ophthalmopathy-long term results of a prospective, randomized study of total or subtotal thyroid resection. Thyroid 2005; 15:1157.
  17. Menconi F, Marinò M, Pinchera A, et al. Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Graves' orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 2007; 92:1653.
  18. Moleti M, Violi MA, Montanini D, et al. Radioiodine ablation of postsurgical thyroid remnants after treatment with recombinant human TSH (rhTSH) in patients with moderate-to-severe graves' orbitopathy (GO): a prospective, randomized, single-blind clinical trial. J Clin Endocrinol Metab 2014; 99:1783.
  19. Wiersinga WM. Advances in treatment of active, moderate-to-severe Graves' ophthalmopathy. Lancet Diabetes Endocrinol 2016.
  20. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, et al. Treatment modalities for Graves' ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab 2009; 94:2708.
  21. http://www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/books/NBK279098/ (Accessed on June 30, 2016).
  22. Salvi M, Campi I. Medical Treatment of Graves' Orbitopathy. Horm Metab Res 2015; 47:779.
  23. Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med 2011; 364:1920.
  24. Zang S, Ponto KA, Kahaly GJ. Clinical review: Intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 2011; 96:320.
  25. Prummel MF, Wiersinga WM. Medical management of Graves' ophthalmopathy. Thyroid 1995; 5:231.
  26. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy. J Clin Endocrinol Metab 2005; 90:5234.
  27. Chang TC, Huang KM, Hsiao YL, et al. Relationships of orbital computed tomographic findings and activity scores to the prognosis of corticosteroid therapy in patients with Graves' ophthalmopathy. Acta Ophthalmol Scand 1997; 75:301.
  28. Salvi M, Vannucchi G, Campi I, et al. Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. Eur J Endocrinol 2006; 154:511.
  29. El Fassi D, Nielsen CH, Hasselbalch HC, Hegedüs L. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option. Eur J Endocrinol 2006; 154:623.
  30. Salvi M, Vannucchi G, Campi I, et al. Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur J Endocrinol 2007; 156:33.
  31. Hegedüs L, Smith TJ, Douglas RS, Nielsen CH. Targeted biological therapies for Graves' disease and thyroid-associated ophthalmopathy. Focus on B-cell depletion with Rituximab. Clin Endocrinol (Oxf) 2011; 74:1.
  32. Salvi M, Vannucchi G, Currò N, et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: a randomized controlled study. J Clin Endocrinol Metab 2015; 100:422.
  33. El Fassi D, Banga JP, Gilbert JA, et al. Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies. Clin Immunol 2009; 130:252.
  34. Salvi M, Vannucchi G, Campi I, et al. Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: effects on orbital lymphocytic infiltrates. Clin Immunol 2009; 131:360.
  35. Stan MN, Garrity JA, Carranza Leon BG, et al. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. J Clin Endocrinol Metab 2015; 100:432.
  36. Stan MN, Garrity JA, Bradley EA, et al. Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy. J Clin Endocrinol Metab 2006; 91:4817.
  37. Dickinson AJ, Vaidya B, Miller M, et al. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2004; 89:5910.
  38. Wémeau JL, Caron P, Beckers A, et al. Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. J Clin Endocrinol Metab 2005; 90:841.
  39. Prummel MF, Mourits MP, Blank L, et al. Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy. Lancet 1993; 342:949.
  40. Mourits MP, van Kempen-Harteveld ML, García MB, et al. Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study. Lancet 2000; 355:1505.
  41. Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy. Ophthalmology 2001; 108:1523.
  42. Bartalena L, Marcocci C, Chiovato L, et al. Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: comparison with systemic corticosteroids alone. J Clin Endocrinol Metab 1983; 56:1139.
  43. Wiersinga WM, Prummel MF. An evidence-based approach to the treatment of Graves' ophthalmopathy. Endocrinol Metab Clin North Am 2000; 29:297.
  44. Marcocci C, Bartalena L, Tanda ML, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab 2001; 86:3562.
  45. Prummel MF, Terwee CB, Gerding MN, et al. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy. J Clin Endocrinol Metab 2004; 89:15.
  46. Marcocci C, Bartalena L, Rocchi R, et al. Long-term safety of orbital radiotherapy for Graves' ophthalmopathy. J Clin Endocrinol Metab 2003; 88:3561.
  47. Nygaard B, Specht L. Transitory blindness after retrobulbar irradiation of Graves' ophthalmopathy. Lancet 1998; 351:725.
  48. Lyons CJ, Rootman J. Orbital decompression for disfiguring exophthalmos in thyroid orbitopathy. Ophthalmology 1994; 101:223.
  49. Ogura JH, Thawley SE. Orbital decompression of exophthalmos. Otolaryngol Clin North Am 1980; 13:29.
  50. Shorr N, Seiff SR. The four stages of surgical rehabilitation of the patient with dysthyroid ophthalmopathy. Ophthalmology 1986; 93:476.
  51. Jernfors M, Välimäki MJ, Setälä K, et al. Efficacy and safety of orbital decompression in treatment of thyroid-associated ophthalmopathy: long-term follow-up of 78 patients. Clin Endocrinol (Oxf) 2007; 67:101.
  52. Wakelkamp IM, Baldeschi L, Saeed P, et al. Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized controlled trial. Clin Endocrinol (Oxf) 2005; 63:323.
  53. Garrity JA. Orbital lipectomy (fat decompression) for thyroid eye disease: an operation for everyone? Am J Ophthalmol 2011; 151:399.