Skip to main content
View expanded cover

Controversies in Neuro-Ophthalmic Management pp 261–271Cite as

Graves Ophthalmopathy

  • 336 Accesses

Abstract

Graves ophthalmopathy is an autoimmune disease that affects the orbit and the adnexa. During the active phase, usually lasting from 6 months to 2 years, there is enlargement and fibrosis of the orbital fat and extraocular muscles, which can lead to ocular surface disease, abnormal extraocular motility, compressive optic neuropathy, and cosmetic impairment. Management can be divided into three broad categories: supportive, immunomodulatory, and reconstructive. When a patient’s disease reaches a level of severity that requires treatment beyond supportive measures such as lubrication, immunomodulatory therapies and surgical intervention may be necessary. Methods to treat the active disease include radiation and medical treatments, with steroids or the insulin-like growth factor 1 receptor inhibitor, teprotumumab, which was FDA approved in January of 2020. Reconstructive procedures may be used to manage optic nerve compression, proptosis, eyelid malposition, and ocular misalignment. In this chapter, we address presentation, diagnosis, and management of Graves ophthalmopathy.

Keywords

  • Graves disease
  • Thyroid eye disease
  • Graves ophthalmopathy
  • Compressive optic neuropathy
  • Orbital decompression
  • Intravenous steroids
  • Orbital radiation
  • Teprotumumab

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-030-74103-7_25
  • Chapter length: 11 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   89.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-74103-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   119.99
Price excludes VAT (USA)
Hardcover Book
USD   169.99
Price excludes VAT (USA)
Learn about institutional subscriptions
Fig. 25.1
Fig. 25.2
Fig. 25.3
Fig. 25.4

References

  1. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477–588.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 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(1):9–26.

    CAS  CrossRef  Google Scholar 

  3. Bartley GB. Rundle and his curve. Arch Ophthalmol. 2011;129(3):356–8.

    CrossRef  Google Scholar 

  4. Sahli E, Gunduz K. Thyroid-associated ophthalmopathy. Turk J Ophthalmol. 2017;47(2):94–105.

    CrossRef  Google Scholar 

  5. Minakaran N, Ezra DG. Rituximab for thyroid-associated ophthalmopathy. Cochrane Database Syst Rev. 2013;5:CD009226.

    Google Scholar 

  6. Mohyi M, Smith TJ. IGF1 receptor and thyroid-associated ophthalmopathy. J Mol Endocrinol. 2018;61(1):T29–43.

    CAS  CrossRef  Google Scholar 

  7. Abraham-Nordling M, Byström K, Törring O, Lantz M, Berg G, Calissendorff J, Nyström HF, Jansson S, Jörneskog G, Karlsson FA, Nyström E. Incidence of hyperthyroidism in Sweden. Eur J Endocrinol. 2011;165(6):899–905.

    CAS  CrossRef  Google Scholar 

  8. Tanda ML, 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(4):1443–9.

    Google Scholar 

  9. Dolman PJ. Evaluating Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;26(3):229–48.

    Google Scholar 

  10. Shan SJC, Douglas RS. The pathophysiology of thyroid eye disease. J Neuroophthalmol. 2014;34(2):177–85.

    CrossRef  Google Scholar 

  11. Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol. 1996;121(3):284–90.

    CAS  CrossRef  Google Scholar 

  12. Zhao J, et al. Thyroid eye disease-related epiblepharon: a comparative case study. Asia-Pacific J Ophthal. 2020;9(1):44–7.

    Google Scholar 

  13. Victores AJ, Takashima M. Thyroid eye disease: optic neuropathy and orbital decompression. Int Ophthalmol Clin. 2016;56(1):69–79.

    CrossRef  Google Scholar 

  14. Fishman DR, Benes SC. Upgaze intraocular pressure changes and strabismus in Graves’ ophthalmopathy. J Clin Neuroophthalmol. 1991;11(3):162–5.

    CAS  PubMed  Google Scholar 

  15. Bothun ED, et al. Update on thyroid eye disease and management. Clin Ophthalmol. 2009;3:543–51.

    PubMed  PubMed Central  Google Scholar 

  16. Mourits MP, et al. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 1997;47(1):9–14.

    CAS  CrossRef  Google Scholar 

  17. Ponto KA, et al. Clinical relevance of thyroid-stimulating immunoglobulins in Graves’ ophthalmopathy. Ophthalmology. 2011;118(11):2279–85.

    Google Scholar 

  18. Diana T, Ponto KA, Kahaly GJ. Thyrotropin receptor antibodies and Graves’ orbitopathy. J Endocrinol Invest. 2020;44(4):703–12. https://doi.org/10.1007/s40618-020-01380-9.

    CAS  CrossRef  PubMed  Google Scholar 

  19. Takasu N, Oshiro C, Akamine H, et al. Thyroid-stimulating antibody and TSH-binding inhibitor immunoglobulin in 277 Graves’ patients and in 686 normal subjects. J Endocrinol Investig. 1997;20(8):452–61.

    CAS  CrossRef  Google Scholar 

  20. Planck T, et al. Smoking induces overexpression of immediate early genes in active Graves’ ophthalmopathy. Thyroid. 2014;24(10):1524–32.

    CAS  CrossRef  Google Scholar 

  21. Nita M, Grzybowski A. Smoking and eye pathologies. A systemic review. Part II. Retina diseases, uveitis, optic neuropathies, thyroid-associated orbitopathy. Curr Pharm Des. 2017;23(4):639–54.

    Google Scholar 

  22. Marcocci C, Kahaly GJ, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364(20):1920–31.

    Google Scholar 

  23. Kahaly GJ, Pitz S, Hommel G, et al. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab. 2003;90(9):5234–40.

    CrossRef  Google Scholar 

  24. Aktaran S, Akarsu E, Erbagci I, et al. Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves’ ophthalmopathy. Int J Clin Pract. 2007;61(1):45–51.

    CAS  CrossRef  Google Scholar 

  25. Wang Y, Patel A, Douglas RS. Thyroid eye disease: how a novel therapy may change the treatment paradigm. Ther Clin Risk Manag. 2019;15:1305–18.

    CAS  CrossRef  Google Scholar 

  26. Salvi M, Vannucchi G, Curro 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(2):422–31.

    CAS  CrossRef  Google Scholar 

  27. 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(2):432–41.

    CAS  CrossRef  Google Scholar 

  28. Slowik M, Urbaniak-Kujda D, Bohdanowicz-Pawlak A, et al. CD8+CD28-lymphocytes in peripheral blood and serum concentrations of soluble interleukin 6 receptor are increased in patients with Graves’ orbitopathy and correlate with disease activity. Endocr Res. 2012;37(2):89–95.

    CAS  CrossRef  Google Scholar 

  29. Russell DJ, Wagner LH, Seiff SR. Tocilizumab as a steroid sparing agent for the treatment of Graves’ orbitopathy. Am J Ophthalmol Case Rep. 2017;7:146–8.

    CrossRef  Google Scholar 

  30. 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;195:181–90.

    CAS  CrossRef  Google Scholar 

  31. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–61.

    CAS  CrossRef  Google Scholar 

  32. Douglas RS, Sile S, Thompson EHZ, et al. Teprotumumab treatment effect on proptosis in patients with active thyroid eye disease: results from a phase 3, randomized, double-masked, placebo-controlled, parallel-group, multicenter study. Proceedings American Association of Clinical Endocrinologists. Endocr Pract. 2019;25.

    Google Scholar 

  33. Douglas RS, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341–52.

    CAS  CrossRef  Google Scholar 

  34. Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves’ ophthalmopathy. Ophthalmology. 2001;108:1523–34.

    CAS  CrossRef  Google Scholar 

  35. Tanda ML, Bartalena L. Efficacy and safety of orbital radiotherapy for Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97(11):3857–65.

    CAS  CrossRef  Google Scholar 

  36. Bradley EA, Gower EW, Bradley DJ, et al. Orbital radiation for Graves ophthalmopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2008;115(2):398–409.

    Google Scholar 

  37. Mourits MP, et al. (2000) Radiotherapy for Graves’ orbitopathy: randomised placebo-controlled study. Lancet. 2000;355(9214):1505–9.

    CAS  CrossRef  Google Scholar 

  38. Marcocci C, Bartalena L, Bogazzi F, et al. Orbital radiotherapy combined with high dose systemic glucocorticoids for Graves’ ophthalmopathy is more effective than radiotherapy alone: results of a prospective randomized study. J Endocrinol Investig. 1991;14(10):853–60.

    CAS  CrossRef  Google Scholar 

  39. Ng CM, Yuen HK, Choi KL, et al. Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves’ ophthalmopathy: a preliminary study. Hong Kong Med J. 2005;11(5):322–30.

    CAS  PubMed  Google Scholar 

  40. Shams PN, Ma R, Pickles T, Rootman J, et al. Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease. Am J Ophthalmol. 2014;157(6):299–1305.

    CrossRef  Google Scholar 

  41. Rootman DB, Golan S, Pavlovich P, et al. Postoperative changes in strabismus, ductions, exophthalmometry, and eyelid retraction after orbital decompression for thyroid orbitopathy. Ophthalmic Plast Reconstr Surg. 2017;33(4):289–93.

    CrossRef  Google Scholar 

  42. Yoon MK, McCulley TJ. Autologous dermal grafts as posterior lamellar spacers in the management of lower eyelid retraction. Ophthal Plast Reconstr Surg. 2014;30:64–8.

    CrossRef  Google Scholar 

  43. Fichter N, Guthoff RF, Schittkowski MP. Orbital decompression in thyroid eye disease. ISRN Ophthalmol. 2012;2012:739236.

    CAS  CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Oculoplastics, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Emma C. McDonnell

  2. Division of Oculoplastics and Division of Neuro-Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Timothy J. McCulley

Authors
  1. Emma C. McDonnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy J. McCulley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy J. McCulley .

Editor information

Editors and Affiliations

  1. Division of Neuro-Ophthalmology Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    MD Amanda D. Henderson

  2. Division of Neuro-Ophthalmology Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    MD Andrew R. Carey

Rights and permissions

Reprints and Permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

McDonnell, E.C., McCulley, T.J. (2021). Graves Ophthalmopathy. In: Henderson, A.D., Carey, A.R. (eds) Controversies in Neuro-Ophthalmic Management. Springer, Cham. https://doi.org/10.1007/978-3-030-74103-7_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-74103-7_25

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-74102-0

  • Online ISBN: 978-3-030-74103-7

  • eBook Packages: MedicineMedicine (R0)