Treatment Options for Graves' Ophthalmopathy

The Challenge

Clinically evident Graves' ophthalmopathy (GO) occurs in approximately 20 percent of unselected patients with Graves' disease and in approximately 70 percent of Graves' patients if computed tomography (CT) or magnetic resonance imaging (MRI) are used to establish the diagnosis.

Management of Graves' ophthalmopathy requires a carefully integrated approach involving the endocrinologist and ophthalmologist, with the goal of preserving the patient's vision and restoring favorable self-perception and quality of life.

Patient with Graves' ophthalmopathy

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Multimodal Management

Less than 5 percent of patients with Graves' disease have severe GO. Overall, 66 percent of untreated patients with mild to moderate Graves' ophthalmopathy show spontaneous improvement over a 12-month period, while about 10 percent deteriorate.

Several studies have noted a striking association between cigarette smoking and Graves' ophthalmopathy. In addition, smoking has been shown to be associated with progression of eye disease after radioiodine therapy and to adversely influence the course of GO during treatment with corticosteroids and orbital radiotherapy.

Patient with active inflammatory Graves' ophthalmopathy

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Hyperthyroidism Treatment

Early and accurate control of hyperthyroidism and counseling patients to quit smoking are keys to preventing development or progression of GO. The modality of treatment of hyperthyroidism is less important than effective restoration and maintenance of the euthyroid state.

In patients with moderately severe, active eye disease, especially those who are smokers, antithyroid drugs or the combined use of radio-iodine and corticosteroids should be considered. To avoid hypothyroidism, thyroid status should be monitored every four to six weeks in the initial phases of treatment, when changes in thyroid status are expected.

Patients with particularly active and severe GO are best managed initially with antithyroid drugs until their eye disease is inactive and then should be treated with either combined radioiodine and corticosteroids or thyroidectomy.

Ophthalmopathy Treatment

The majority of patients with Graves' ophthalmopathy have mild, self-limited disease course requiring only local measures for symptomatic relief. Instilling artificial tears and taping the eyelids shut at night can prevent nocturnal corneal drying. Worsening of diplopia and soft tissue changes during the night often occur secondary to dependent edema. This edema may respond to nighttime elevation of the head. Sunglasses or tinted lenses may assist in decreasing photophobia. Prisms are occasionally useful for the correction of mild diplopia.

Patients with moderate to severe GO may experience severe periorbital edema, proptosis, eye pain, changes in visual acuity or color vision, or severe restriction of ocular motion. These patients should be assessed by an ophthalmologist to determine whether they require emergent treatment for compressive optic neuropathy or corneal ulceration. If no early surgical intervention is needed, the patient may benefit from a course of immunosuppressive therapy.

While approximately 66 percent of patients with active Graves' ophthalmopathy benefit from oral corticosteroids, evidence is mounting that intravenous corticosteroids may be somewhat more effective in providing relief from pain, injection and conjunctival edema.

Pulse therapy with intravenous methylprednisolone acetate may be considered. However, this therapy should be undertaken only in centers with appropriate GO expertise, given the small risk for fatal hepatotoxicity. In addition, orbital radiotherapy, alone or in combination with corticosteroids, may be beneficial to patients with active GO, especially those with extra-ocular muscle dysfunction.

Surgical Options

Orbital decompression is generally considered for patients with Graves' ophthalmopathy who have severe proptosis, orbital congestion, or ocular exposure or for patients who desire an improvement in appearance. In addition, orbital decompression is effective for treatment of optic neuropathy and as adjunctive therapy for corneal ulceration related to excess proptosis.

Patients with active disease who have shown intolerance or insufficient response to immunosuppressive therapy or who have debilitating retrobulbar or periorbital pain may also benefit from decompression surgery. It is important to restore thyroid hormone levels to normal before any type of orbital surgery is performed. An exception to this occurs when severe GO threatens vision and requires urgent orbital decompression.

Eye muscle surgery (strabismus surgery) is typically performed after decompression if the patient has diplopia postoperatively. In patients not requiring decompression, strabismus surgery may be performed after at least 6 months of stable eye deviation measurements without concurrent corticosteroid therapy. The goal of strabismus surgery is single vision in primary gaze and the reading position; diplopia with looking left or right may persist after surgery.

Eyelid surgery for GO usually follows orbital decompression and strabismus procedures. Upper and lower eyelid retraction is relieved by weakening (recessing) the muscles. Blepharoplasty (removal of excess eyelid and orbital tissue that prolapses anteriorly from the increase in orbital volume) may be indicated in selected patients.

Points to Remember

• The most important factors in prevention of development or progression of Graves' ophthalmopathy (GO) appear to be early and accurate control of thyroid dysfunction and counseling patients to quit smoking.
• Determining the appropriate treatment for patients with GO depends on assessing whether the eye disease is active (inflammatory) or inactive (quiescent) and defining the severity of the ocular symptoms.