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An Update on Thyroid Eye Disease



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Am Fam Physician. 2005 Jun 1;71(11):2197-2200.

The prevalence of Graves’ disease in the United Kingdom is estimated at 1 to 2.7 percent of the population, and eye complications occur in one fourth to one half of cases. Changes in the eyes may develop before the onset of Graves’ disease, and occasionally only one eye is involved. Although it rarely causes vision loss, thyroid eye disease can be painful and distressing with significant visual and cosmetic sequelae. Cawood and colleagues examined the clinical features of thyroid eye disease to clarify the pathophysiology of the condition and potential treatments.

Histologically, circulating sensitized orbital tissue-specific T lymphocytes and a local inflammatory cellular infiltrate are present in thyroid eye disease. The orbital fibroblasts appear key to the hypertrophy of adipose tissue and accumulation of glycosaminoglycans in the orbit. Despite recent research, the pathophysiology of Graves’ disease remains unclear.

The clinical features of thyroid eye disease include ocular pain, photophobia, chemosis, diplopia, exophthalmos, and eye irritation (“gritty eyes”). Physical signs include proptosis, edema of the eyelid and conjunctiva, and diplopia (Table 1). The NO SPECS mnemonic often is used as a scoring system for severity of eye change (Table 2). Patients who develop blurred vision, reduced visual acuity or color perception, pupillary signs, or visual field defects may have optic neuropathy and must be referred to an ophthalmologist immediately. The clinical features of thyroid eye disease may persist after the phase of acute inflammation because of residual scarring of orbital tissues. Thyroid eye disease also may be accompanied by skin changes in the lower legs (pretibial myxedema), finger nails (acropachy), and at sites of previous skin trauma.

TABLE 1
Clinical Activity Score

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Smoking appears to be a major risk factor in developing eye symptoms in Graves’ disease, because patients with eye involvement are four times more likely to be smokers than never-smokers. The risk also is associated with the number of cigarettes smoked per day. Other risk factors for thyroid eye disease are less well established. Older men may have a higher risk of more severe disease. Radioiodine therapy may cause a flare-up of eye disease.

Full ophthalmic assessment including computed tomography or magnetic resonance imaging can indicate the degree of involvement of the extraocular muscles and soft tissues. Orbital biopsy is required occasionally to establish the diagnosis.

In mild cases, only symptomatic care to protect the eyes from drying is required. Up to 35 percent of patients require high-dose steroids or orbital decompression therapy. The response rates to steroid therapy range from 33 to 66 percent. The dosage and regimen are individualized because no large randomized placebo-controlled trials have been conducted. Orbital radiotherapy also has been suggested for reducing progression of thyroid eye disease, but clinical trials have not demonstrated improvements, and adverse effects include cataracts, retinopathy, and risk of malignancy. Surgical decompression is indicated for severe cases during the acute phase and to improve function and appearance in later stages of the condition. Overall, outcomes of all treatments for thyroid eye disease are disappointing. More than one half of patients report persistent diplopia, about one third are dissatisfied with the cosmetic result, and more than one fourth have low visual acuity.

Potential future treatments include anti-cytokine therapy, particularly anti–tumor necrosis factor-alpha agents. Side effects limit use of these agents. Octreotide and colchicine have given disappointing results in recent clinical trials. [NOTE: Colchicine is no longer available in the United States.] The authors conclude that increased understanding of thyroid eye disease will likely lead to improvement of treatments in the future.

TABLE 2
NO SPECS Classification of Thyroid Eye Disease

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Cawood T, et al. Recent developments in thyroid eye disease. BMJ. August 14, 2004;329:385–90.


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