Expert Opinion - Diagnosing thyroid eye disease

Know how to diagnose and manage thyroid eye disease. By Professor Caroline MacEwen

Exophthalmos is one of the more readily recognisable signs of TED
Exophthalmos is one of the more readily recognisable signs of TED

Thyroid eye disease (TED) is an orbital inflammation affecting up to 40% of patients with autoimmune thyroid gland disease, meaning some 0.25m may be affected in the UK. However, research shows the diagnosis of TED is often delayed.1,2

Nearly half of respondents to a recent survey reported a delay of at least six months between onset of symptoms and a diagnosis of TED; the delay was a year or more in a quarter of these patients.2

Missed diagnoses
In most cases TED is related to Graves' hyperthyroidism, although some patients will have no measurable abnormality of thyroid gland function.

The diagnosis is missed for two main reasons. First, the very common presentation with red, uncomfortable and watery eyes is often misdiagnosed as the more common conjunctivitis or allergic eye disease.

Second, the thyroid gland disorder and ocular symptoms can occur at different times and may not be recognised as associated. Heightened awareness of TED and its presentation is therefore paramount.

TED can rarely lead to permanent loss of vision, but more commonly causes chronic discomfort, double vision and marked facial disfigurement. It has a major impact on quality of life, with adverse effects on employment and self-confidence, frequently leading to a withdrawal from social interaction that is often underappreciated by healthcare professionals.

Moreover, TED is associated with significant psychological effects and carries a considerable socioeconomic burden.3,4

Early diagnosis expedites referral to specialised clinics able to provide symptomatic relief; early immunomodulation of TED has been shown to reduce incidence of symptoms and progression.5

Diagnosing TED
Women, especially those aged 30-50 years, have a four to five times greater risk of developing TED than men; most present with concurrent thyroid dysfunction. About 20% present with eye disease many years before and another 20% after thyroid gland disease.

The ocular disease is more common, more severe and more refractory to treatment in smokers. The most common symptoms (see box, below) are persistently red, irritable and watering eyes that may mimic infective or allergic conjunctivitis, but without the stickiness of infective conjunctivitis or the itching of allergic conjunctivitis.

When to consider TED

Consider TED in those with:

  • Red, uncomfortable eyes with no discharge or itch.
  • Aching behind the eyes.
  • Proptosis and/or lid retraction.
  • Double vision.
  • A personal or family history of thyroid disease.

Aching behind the eyes - more intense in the morning or on upward gaze - is also common, but is often identified only on direct questioning. Subconjunctival oedema, or eyelid puffiness due to orbital fat prolapse, is common and often misattributed to the swelling of allergic eye disease.

Patients often note a change in facial appearance, particularly due to upper eyelid retraction or exophthalmos; these signs are more readily recognised as being due to TED and generally trigger a specialist referral.

Double or reduced vision suggests advanced disease.

The diagnosis of TED is clinical and is simplest where lid retraction or proptosis is present in a patient with a history of thyroid gland dysfunction. It is more difficult where these key ophthalmic signs are absent or where thyroid gland dysfunction is absent or unrecognised.

The diagnosis is assisted by investigations including TSH, and T3 and T4 measurements, although in a small number of cases there is no biochemical abnormality. Presence of thyroid auto-antibodies is almost universal and measurement of TSH receptor antibodies is most useful.6

Orbital imaging (CT or MRI) can confirm proptosis and show enlargement of the extraocular muscles or fat compartments; STIR (short tau inverse recovery) MRI sequences also give an indication of disease activity, based on water content of the extraocular muscles.

Case Study

A 48-year-old woman presents to her GP with red and aching eyes that are irritable and tend to water. There is no discharge or itch.

She was treated for hyperthyroidism with radioiodine four years ago.

She has somewhat red eyes and slightly puffy lids, but no obvious proptosis.

Intermittent upper eyelid retraction is evident during examination and the eyelids remain about 1mm open during gentle closure.

Thyroid functions are normal on replacement therapy.

Managing TED
Ideally, all patients with TED, except for the mildest cases, should be referred to and managed by a specialist with expertise in TED, or a combined thyroid eye clinic where ophthalmologists and endocrinologists work collaboratively.

Early correction of any thyroid gland disturbance is vital and all patients should be supported to stop smoking - continued smoking increases the risk of more severe disease and reduces response to treatment.7

The natural history of TED varies, most patients having mild, self-limiting disease that might only require temporary use of ocular lubricants. Left untreated, orbital inflammation and scarring in severe cases can remain active for three to four years; such patients justify systemic immunosuppression.

Low-dose orbital radiotherapy can also be used to suppress orbital inflammation. Orbital decompression may be required early in the disease if visual failure due to optic neuropathy is not reversed with medical therapy.

Once the inflammatory phase has been suppressed and the thyroid gland disease is stable, surgical rehabilitation should be planned to correct significant proptosis, eyelid malpositions or diplopia. These surgical procedures improve facial appearance and have important quality of life benefits for those with severe TED.

In all cases, patients should be provided with information about the disease, its duration and likely outcomes.

  • Professor MacEwen is a consultant ophthalmologist at Ninewells Hospital, Dundee. TEAMeD is the Thyroid Eye Disease Amsterdam Declaration implementation group
1. Estcourt S, Hickey J, Perros P et al. The patient experience of services for thyroid eye disease in the United Kingdom. Eur J Endocrinol 2009; 161: 483-7.

2. Perros P, Baldeschi L, Boboridis K et al. A questionnaire survey on the management of Graves' orbitopathy in Europe. Eur J Endocrinol 2006; 155: 207-11.

3. Estcourt S, Vaidya B, Quinn A et al. The impact of thyroid eye disease upon patients' wellbeing. Clin Endocrinol (Oxf) 2008; 68: 635-9.

4. Coulter I, Frewin S, Krassas GE et al. Psychological implications of Graves' orbitopathy. Eur J Endocrinol 2007; 157: 127-31.

5. Wiersinga WM, Smit T, Schuster-Uittenhoeve AL et al. Therapeutic outcome of prednisone medication and of orbital irradiation in patients with Graves' ophthalmopathy. Ophthalmologica 1988; 197: 75-84.

6. Schott M, Hermsen D, Broecker-Preuss M et al. Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves' disease. Clin Endocrinol (Oxf) 2009; 71: 566-73.

7. Thornton J, Kelly SP, Harrison RA et al. Cigarette smoking and thyroid eye disease. Eye (Lond) 2007; 21: 1135-45.

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