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Autoimmune thyroid eye disease

Autoimmune thyroid eye disease

The symptoms of this complex eye condition range from mild to severe. Accurate assessment of disease activity is important

Lid retraction, causing a staring appearance, can occur in any form of hyperthyroidism and results from sympathetic overactivity. However, autoimmune hyperthyroidism – autoimmune thyroid eye disease or orbitopathy – is associated with specific eye signs.

Thyroid eye disease occurs without hyperthyroidism in 10% of patients (most of whom have autoimmune hypothyroidism or thyroid antibodies). In 75% of patients, onset of thyroid eye disease occurs within the year before or after thyrotoxicosis diagnosis. However, it can precede or follow thyrotoxicosis by several years, accounting for some cases of euthyroid thyroid eye disease.

Many patients with immune hyperthyroidism have little clinical evidence of thyroid eye disease. However, the enlarged extraocular muscles typical of the disease, and other subtle features, can be detected in almost all patients using ultrasound or computed tomography imaging of the orbits. Unilateral signs are found in up to 10% of patients.

Clinical features of thyroid eye disease vary from a mild grittiness of the eyes to severe diplopia, disfiguring proptosis and vision loss. There is a natural tendency towards spontaneous improvement that depicts an active phase, which slowly abates, then an inactive phase.

The most common symptoms of thyroid eye disease are eyelid retraction (90%), soft tissue involvement (80%), proptosis (50–60%), dry eye syndrome (50%), motility disorders (40%), optic neuropathy (3–5%) and superior limbic keratitis (2%).

The autoimmune process leads to an accumulation of collagen and hydrophilic glycosaminoglycans within the orbit. Inflammatory changes of the eyelids cause visible oedema and erythema.

If extraocular muscles are affected, motility disorders may occur. Patients with these motility disturbances, diplopia, severe and active disease have severely impaired health-related quality of life.

The earliest clinical manifestations of thyroid eye disease are a sensation of grittiness, eye discomfort and excessive tearing.

Proptosis occurs in about a third of patients. Optimal detection is by visualization of the sclera between the lower border of the iris and the lower eyelid, with the eyes in the primary position. Proptosis can be measured using an exophthalmometer. It may cause corneal exposure and damage in severe cases – especially if the lids fail to close during sleep.

Periorbital oedema, scleral injection and chemosis are frequent. In 5–10% of patients, the muscle swelling is so severe that diplopia results, typically, but not exclusively, when the patient looks up and laterally.

The most serious manifestation is optic nerve compression at the apex of the orbit, leading to papilloedema, peripheral field defects and permanent loss of vision if untreated.

Clinical evaluation

Many scoring systems have been used to gauge the extent and severity of the orbital changes in thyroid eye disease. Thyroid eye disease is classified as severe if corneal involvement, severe proptosis, constant diplopia or optic neuropathy are present.

By evaluating the activity of thyroid eye disease, the most effective and stage-adjusted therapy can be administered. Immunomodulatory therapies target the oedematous, lymphocyte infiltration and the activated fibroblasts. Thyroid eye disease is active when inflammatory symptoms (e.g. redness and swelling) are dominating.

Methods to assess activity of thyroid eye disease include:

  • Purely clinical assessment (i.e. Clinical Activity Score)
  • Laboratory measurements (cytokines, glycosaminoglycan excretion, thyroid stimulating immunoglobulins)
  • Imaging techniques.

The clinical evaluation of the Clinical Activity Score together with the measurement of thyroid stimulating immunoglobulin serum levels can accurately document disease activity.

General ophthalmic assessment should include examination of anterior and posterior eye segment, applanation tonometry, Hertel exophthalmometry and motility tests.

Additionally, the presence of optic disc oedema or disc pallor is assessed and the existence, or otherwise, of choroidal folds recorded. As well as fundoscopy, relative afferent pupillary defects, vision field defects, colour vision abnormalities, visual evoked potentials and visual acuity are also tested, in order to exclude optic neuropathy.

Cigarette smoking can profoundly influence the occurrence and course of thyroid eye disease; it also impairs response to conservative treatment. Accordingly, patients should be strongly urged to stop smoking. Emotional distress and stressful life events are risk factors for thyroid eye disease and should be minimized.

Diagnosis and clinical course

Magnetic resonance imaging is the optimal imaging procedure for the differential diagnosis of thyroid eye disease.

The clinical course of thyroid eye disease does not follow that of the thyroid disease itself. Thyroid eye disease typically worsens over the initial 3–6 months, followed by a plateau phase (the next 12–18 months), with spontaneous improvement, particularly in the soft tissue changes. The course is more fulminant in up to 5% of patients, requiring intervention in the acute phase where optic nerve compression or corneal ulceration occur.

Diplopia may appear late in the disease due to fibrosis of the extraocular muscles. Radioiodine treatment for hyperthyroidism worsens the eye disease in approximately 15–20% of patients (especially smokers). Antithyroid drugs or surgery have no adverse effects on the clinical course of thyroid eye disease.

Further reading

  1. Lazarus J, Marino M. Orbit-thyroid relationship. In: Wiersinga WM, Kahaly GJ (Editors): Graves’ orbitopathy – A multidisciplinary approach – Questions and answers, 2nd revised edition, Karger, Basel, pp 26-32.
  2. Bahn RS. Graves’ opthalmopathy. N Engl J Med. 2010; 362: 726-38.
  3. Orgiazzi J, Ludgate M. Pathogenesis. In: Wiersinga WM, Kahaly GJ (Editors): Graves’ orbitopathy – A multidisciplinary approach – Questions and answers, 2nd revised edition, Karger, Basel, pp 40-56.
  4. Bartalena L, Tanda ML. Clinical practice. Graves' ophthalmopathy. N Engl J Med. 2009; 360: 994-1001.
  5. Kahaly GJ. Imaging in thyroid-associated orbitopathy. Eur J Endocrinol. 2001; 145: 107-18.
  6. Hales IB, Rundle FF. Ocular changes in Graves' disease. A long-term follow-up study. Q J Med. 1960; 29: 113-26.
  7. Ponto KA, Kahaly GJ. Quality of life in patients suffering from thyroid orbitopathy. Pediatr Endocrinol Rev. 2010; 7: 245-9.
  8. Werner SC. Modification of the classification of the eye changes in Graves´ disease. Am J Ophthalmol. 1977; 83: 725-7.
  9. Dickinson AJ. Clinical Manifestation. In: Wiersinga WM, Kahaly GJ (Editors): Graves’ Orbitopathy - A multidisciplinary Approach - Questions and Answers, 2nd revised edition, Karger, Basel, 2010, pp 1-25.
  10. Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid. 2008; 18: 333-46.
  11. Mourits MP, Koornneef L, Wiersinga WM, et al. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach. Br J Ophthalmol. 1989; 73: 639-44.
  12. Bartalena L, Martino E, Marcocci C, et al. More on smoking habits and Graves' ophthalmopathy. J Endocrinol Invest. 1989; 12: 733-7.
  13. Bartalena L, Marcocci C, Tanda ML, et al. Cigarette smoking and treatment outcomes in Graves’ ophthalmopathy. Ann Intern Med. 1998; 129: 632-5.
  14. Mourits MP. Diagnosis and Differential Diagnosis of Graves´ Orbitopathy. In: Wiersinga WM, Kahaly GJ (Editors): Graves’ orbitopathy – A multidisciplinary approach – Questions and answers, 2nd revised edition, Karger, Basel, pp 66-76.
  15. Ponto KA, Zang S, Kahaly GJ. The tale of radioiodine and Graves' orbitopathy. Thyroid. 2010; 20: 785-93.

George J. Kahaly

Professor of Medicine and Endocrinology / Metabolism, Chief of the endocrine outpatient clinic
Dept of Medicine
Gutenberg University Medical Center
Mainz, Germany
autoimmune thyroid eye disease
diagnostic testing