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  • Review Article
  • Published:

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy

Nature Reviews Endocrinology volume 16, pages 104–116 (2020)Cite this article

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Abstract

Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient’s quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required. Clinical trials have shown that considerable benefit can be derived from the addition of antiproliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab, which reduces proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. The pathophysiology of Graves orbitopathy has also been revised with identification of new potential therapeutic targets. In this Review we provide an up-to-date overview of the field, outline the optimal management of Graves orbitopathy and summarize the research developments in this area to highlight future research questions and direct future clinical trials.

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Fig. 1: Proposed management of Graves orbitopathy.
Fig. 2: Overview of potential therapeutic targets in Graves orbitopathy.

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Author notes

  1. These authors contributed equally: Peter N. Taylor, Lei Zhang.

  2. These authors share senior authorship: George J. Kahaly, Marian Ludgate.

Authors and Affiliations

  1. Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK

    Peter N. Taylor, Lei Zhang, Ilaria Muller, Colin M. Dayan & Marian Ludgate

  2. Moorfields Eye Hospital NHS Foundation Trust, London, UK

    Richard W. J. Lee & Daniel G. Ezra

  3. University of Bristol, Bristol, UK

    Richard W. J. Lee

  4. Fondazione IRRCS Ca’ Granda Ospedale Maggiore Policinico, Department of Endocrinology, Milan, Italy

    Ilaria Muller

  5. Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

    George J. Kahaly

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Competing interests

The Johannes Gutenberg University (JGU) Medical Center and the JGU Thyroid Laboratory received research grants from Novartis, Germany, and River Vision, USA, when performing the MINGO and teprotumumab trials.

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Glossary

Proptosis

Abnormal protrusion of the eyeball.

Diplopia

Double vision.

Observer masked

The observer assessing outcomes does not know the treatment allocation (the same as “blinded” in clinical trials); masked is used instead of blinded in ophthalmology trials to not alarm patients.

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Taylor, P.N., Zhang, L., Lee, R.W.J. et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol 16, 104–116 (2020). https://doi.org/10.1038/s41574-019-0305-4

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