Thyroid associated orbitopathy

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Abstract

Thyroid associated orbitopathy, also known as Graves’ orbitopathy, is typically a self-limiting autoimmune process associated with dysthyroid states. The clinical presentation may vary from very mild disease to severe irreversible sight-threatening complications. Despite ongoing basic science and clinical research, the pathogenesis and highly effective therapeutic strategies remain elusive. The present article reviews the pathophysiology, clinical presentation, and management of this common, yet poorly understood disease, which remains a challenge to the ophthalmologist.

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Most cited references 55

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Epidemiology and prevention of Graves' ophthalmopathy.

W. Wiersinga, Luigi Bartalena (2002)

Graves' ophthalmopathy is clinically relevant in approximately 50% of patients with Graves' disease, severe forms affecting 3%-5% of patients. Two age peaks of incidence are observed in the fifth and seventh decades of life, with slight differences between women and men. The disease is more frequent in women than in men, although the female-to-male ratio is only 1:4 in severe forms of eye disease. The natural history of Graves' ophthalmopathy is incompletely defined, but in many instances, especially in mild forms, the disease may remit or improve spontaneously. The onset of the ophthalmopathy is in most cases concomitant with the onset of hyperthyroidism, but eye disease may precede or follow hyperthyroidism. Cigarette smoking plays an important role in the occurrence of the ophthalmopathy, and is also associated with a higher degree of disease severity and a lower effectiveness of its medical treatment. Primary prevention (i.e., avoidance of the occurrence of the ophthalmopathy) is presently not feasible, but smoking withdrawal in relatives of patients with Graves' disease might be important. In terms of secondary prevention (i.e., avoidance of progression of subclinical eye disease into overt and severe ophthalmopathy) in addition to refraining from smoking, early and accurate control of thyroid dysfunction (both hyperthyroidism and hypothyroidism), as well as early diagnosis and treatment of mild eye disease are important. As to the role that management of hyperthyroidism may play in the course of Graves' ophthalmopathy, while antithyroid drugs and thyroidectomy are not disease-modifying treatments, radioiodine therapy causes a progression of the ophthalmopathy in approximately 15% of patients, especially high-risk patients, who smoke, have severe hyperthyroidism or uncontrolled hypothyroidism, high levels of thyrotropin (TSH)-receptor antibody, or preexisting eye disease. However, the risk of radioiodine-associated progression of the opthalmopathy can be eliminated by concomitant treatment with middle-dose glucocorticoids. In terms of tertiary prevention (i.e., avoidance of deterioration and complications of overt disease) early immunosuppressive treatment or orbital decompression, as appropriate, are essential tools. Smoking withdrawal may increase the effectiveness of immunosuppressive treatment.

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Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

George J. Kahaly, Manuela Dittmar, G Hommel … (2005)

Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them. The objective of this study was to optimize glucocorticoid application in GO. The study design was a randomized trial over 12 wk with 6-month follow-up. The study was performed at university joint thyroid and ophthalmic clinics. Seventy euthyroid out-patients with untreated, active, and severe GO were studied. Patients received either once weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. At 3 months, the primary end point was a composite of improvements in proptosis, lid fissure width, and rate of diplopia in primary gaze, visual acuity, eye muscle thickness, and patient's quality of life. Intravenous glucocorticoid therapy resulted in rapid, significant, and sustained improvement. At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the iv group. TSH receptor antibody titers decreased during iv steroid administration (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001). Additional treatment was required less frequently in the iv group. Intravenous steroids were safe, with different rates of adverse events between the two groups (P < 0.001). In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.

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Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.

Lois E. H. Smith, B. Prabhakar, S Bahn … (2003)

Graves' disease (GD) is a very common autoimmune disorder of the thyroid in which stimulatory antibodies bind to the thyrotropin receptor and activate glandular function, resulting in hyperthyroidism. In addition, some patients with GD develop localized manifestations including ophthalmopathy (GO) and dermopathy. Since the cloning of the receptor cDNA, significant progress has been made in understanding the structure-function relationship of the receptor, which has been discussed in a number of earlier reviews. In this paper, we have focused our discussion on studies related to the molecular mechanisms of the disease pathogenesis and the development of animal models for GD. It has become apparent that multiple factors contribute to the etiology of GD, including host genetic as well as environmental factors. Studies in experimental animals indicate that GD is a slowly progressing disease that involves activation and recruitment of thyrotropin receptor-specific T and B cells. This activation eventually results in the production of stimulatory antibodies that can cause hyperthyroidism. Similarly, significant new insights have been gained in our understanding of GO that occurs in a subset of patients with GD. As in GD, both environmental and genetic factors play important roles in the development of GO. Although a number of putative ocular autoantigens have been identified, their role in the pathogenesis of GO awaits confirmation. Extensive analyses of orbital tissues obtained from patients with GO have provided a clearer understanding of the roles of T and B cells, cytokines and chemokines, and various ocular tissues including ocular muscles and fibroblasts. Equally impressive is the progress made in understanding why connective tissues of the orbit and the skin in GO are singled out for activation and undergo extensive remodeling. Results to date indicate that fibroblasts can act as sentinel cells and initiate lymphocyte recruitment and tissue remodeling. Moreover, these fibroblasts can be readily activated by Ig in the sera of patients with GD, suggesting a central role for them in the pathogenesis. Collectively, recent studies have led to a better understanding of the pathogenesis of GD and GO and have opened up potential new avenues for developing novel treatments for GD and GO.

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Author and article information

Journal

Journal ID (nlm-ta): Indian J Ophthalmol

Journal ID (iso-abbrev): Indian J Ophthalmol

Journal ID (publisher-id): IJO

Title: Indian Journal of Ophthalmology

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0301-4738

ISSN (Electronic): 1998-3689

Publication date (Print): Mar-Apr 2012

Volume: 60

Issue: 2

Pages: 87-93

Affiliations

[1 ]Department of Ophthalmology, Royal Alexendra Hospital, University of Alberta, Edmonton, Alberta, Canada T5H 3V9

[2 ]Orbit, Oculoplasty and Ocular Oncology, Netraseva Eye Associates, Jalna, Maharashtra, India

Author notes

Correspondence to: Dr. Rajat Maheshwari, Orbit, Oculoplasty and Ocular Oncology, Netraseva Eye Associates, Jalna – 431 203, Maharashtra, India. E-mail: rajat.oculoplasty@ 123456gmail.com

Article

Publisher ID: IJO-60-87

DOI: 10.4103/0301-4738.94048

PMC ID: 3339094

PubMed ID: 22446901

SO-VID: 5b9b7caf-41a9-4a0b-8c35-f6697dbbe73b

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Thyroid associated orbitopathy

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Clinical Virtual Research Center Journal of Ophthalmology

Most cited references 55

Epidemiology and prevention of Graves' ophthalmopathy.

Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.

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