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Review
. 2008 Nov;19(6):499-506.
doi: 10.1097/ICU.0b013e3283131557.

The eye and thyroid disease

Ajay E Kuriyan  1 , Richard P Phipps, Steven E Feldon
Affiliations
Review

The eye and thyroid disease

Ajay E Kuriyan et al. Curr Opin Ophthalmol. 2008 Nov.

Abstract

Purpose of review: The pathophysiology and optimal management of thyroid eye disease (TED) have not yet been elucidated. Recent studies have increased our knowledge of the disease process and different diagnostic and therapeutic options. This review highlights the recent progress in TED research and identifies areas requiring further advancements.

Recent findings: The pathophysiology of TED likely involves genetic and environmental factors, which may potentiate cellular and humoral-mediated inflammation within the orbit. Despite progress in TED research, a target antigen has not been established with certainty. New diagnostic methods and questionnaires are being developed that potentially provide information regarding inflammatory activity of TED. Corticosteroids alone or in combination with orbital radiation may be effective in improving TED symptoms. New immunomodulating therapies may also have a role TED management. Surgery is highly effective for treatment of TED-induced optic nerve compression and for managing the chronic soft tissue changes of TED.

Summary: A unifying hypothesis of TED pathophysiology is elusive. Further bench research into the autoimmune process is needed. In addition, large, prospective, randomized clinical trials based on the inflammatory activity of disease, while difficult to design, are essential to develop a consensus regarding the proper timing and use of anti-inflammatory medications.

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Conflict of interest statement

Conflict of Interest: No conflicting relationships exist.

Figures

Figure 1
Figure 1. Pathophysiology of TED
According to one current model, TED is triggered by binding and activation of orbital fibroblasts by autoantibodies. These autoantibodies could be specific for antigens such as TSH-R and/or IGF-1R. Activated orbital fibroblasts release chemokines, including IL-16, RANTES, and CXCL10, which recruit T lymphocytes into the orbit. These lymphocytes then interact with fibroblasts, potentially activating each other, further promoting cytokine production (IFNγ, TNFα, PGD2, and 15d-PGJ2) and secretion of T cell-activating factors by the fibroblasts (IL-8 and CXCL10). Fibroblasts are also stimulated to secrete IL-6 (promoting B cell differentiation) and to increase autoantigen presentation, both of which amplify the overall response. The interactions of fibroblasts with T cells result in the deposition of extracellular matrix molecules, fibroblast proliferation, and fat accumulation. See Lehmann, GM [5].
Figure 2
Figure 2. Management of Graves' orbitopathy
Rehabilitative surgery includes orbital decompression, squint surgery, lid lengthening, and blepharoplasty/browplasty. i.v. GCs, intravenous glucocorticoids; OR, orbital radiotherapy; DON, dysthyroid optic neuropathy. See Bartalena L. [45]
See this image and copyright information in PMC

References

    1. Garrity JA, Bahn RS. Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment. American Journal of Ophthalmology. 2006;142:147–147. - PMC - PubMed
    1. Prummel M, Bakker A, Wiersinga W, et al. Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience. Eur J Endocrinol. 2003;148:491–495. - PubMed
    1. Schotthoefer EO, Wallace DK. Strabismus associated with thyroid eye disease. Curr Opin Ophthalmol. 2007;18:361–365. - PubMed

    2. This article reviews methods for the treatment and evaluation of strabismus associated with TED, with a focus on the developments in 2006.

    1. Eckstein AK, Lax H, Losch C, et al. Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol. 2007;67:607–612. - PubMed

    2. This retrospective observational study of 158 TED patients reports that patients with more severe TED and with higher levels of TSH-R autoantibodies were less likely to go into remission.

    1. Lehmann GM, Garcia-Bates TM, Smith TJ, et al. Regulation of Lymphocyte Function by PPARgamma: Relevance to Thyroid Eye Disease-Related Inflammation. PPAR Res. 2008;2008:895. - PMC - PubMed

    2. This article reviews TED pathophysiology, with an emphasis on PPARγ's potential dual anti-inflammatory and pro-adipogenic roles.

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