Our new series takes you through presentation, examination, investigation, diagnosis and treatment of a patient- describing the key principles of care before offering a take home message.
A 32-year-old woman complains of eye symptoms that began three to six months earlier. She first experienced increased lacrimation and a gritty feeling in the eyes. In recent weeks, she has noticed prominence of her eyes in the sockets, redness of the conjunctivae and eyelids, and occasional pain behind the eyes on eye movement. Although the changes in appearance have bothered her somewhat, it is the pain that has prompted her to seek medical attention.
Last year, she was diagnosed with hyperthyroidism. She completed a course of antithyroid medication with resolution of her symptoms of tachycardia, tremor, weight loss despite good appetite, and mild goitre. She is otherwise healthy; her only medication is a hormonal patch for contraception.
Temperature is normal; heart rate is 84 beats per minute. Scalp hair is normal. The eyelids are retracted, and the conjunctivae and eyelids are red bilaterally; eyelid retraction and exophthalmos is less than 2 mm. There is no diplopia on gaze testing, and fluorescein examination reveals no corneal involvement. No goitre is palpable. Chest is clear and heart is normal. She has no tremor. The remaining physical findings are normal.
Results of a full blood count, biochemistry screen and thyroid function tests are all normal.
Which statement about this patient is most accurate?
A. She should receive additional therapy for hyperthyroidism with radioactive iodine.
B. Immunosuppressive therapies are unlikely to benefit her.
C. She should undergo prompt surgical orbital decompression.
D. Her risk of progression to severe disease is 25%.
Correct answer (D).
This patient has Graves ophthalmopathy, or ocular manifestations of autoimmune origin. The ocular symptoms are thought to be caused by autoreactive T lymphocytes that react with antigens common to thyroid and orbital tissues. The activated T cells then elicit cytokines; these, in turn, induce the cellular proliferation and secretion that expand orbital content and result in the clinical findings.1 Symptoms include, in declining incidence, eyelid contraction, exophthalmos, extraocular muscle dysfunction, ocular pain, and lacrimation.
Most patients with Graves ophthalmopathy (85% to 90%) have associated hyperthyroid Graves disease. However, not all patients are hyperthyroid. About 10% or so may be euthyroid (like this woman) or even hypothyroid; often, their ophthalmopathy appears some time after a former hyperthyroid state has resolved.2,3 About 20% to 30% of cases of ophthalmopathy are “clinically relevant,” and 3% to 5% are considered sight-threatening.2,3
When evaluating a patient with Graves ophthalmopathy, two questions need to be answered. First, is the disease in an active phase, or is it inactive? This distinction is important because active ophthalmopathy will respond to immunosuppressive therapies, whereas inactive disease will not. The most frequently used tool for office-based assessment of disease activity is the clinical activity score.2 This tool assigns one point to each of the following:
• Pain with eye movement.
• Redness of eyelids.
• Redness of conjunctivae.
• Swelling of eyelids.
• Swelling of caruncle.
A score of three or more indicates active ophthalmopathy.
The second question is how severe is the patient’s disease? This question is important because mild disease can be conservatively treated, whereas severe disease may need more aggressive methods—in some cases, surgical decompression of the orbit. Severity is determined by evaluating the degree of lid retraction, exophthalmos, soft tissue and extra ocular muscle involvement, and corneal involvement.2,4 In addition, any optic nerve involvement is considered a sign of severe disease. In 25% of patients, mild or moderate disease may progress to severe disease2; thus, good follow-up is needed.
Principles of therapy
The approach to therapy for Graves ophthalmopathy involves the following principles2,4:
• Risk factors must be addressed and euthyroid status should be attained. Most often this means treating hyperthyroidism. Antithyroid drugs are preferred because radioiodine worsens ocular signs and symptoms in 15% of patients—although concomitant treatment with glucocorticoids seems to prevent this complication.3,4 Smoking cessation also ameliorates Graves ophthalmopathy.
• Immunosuppressive therapies are effective when active disease is present. Options include glucocorticoid regimens (by far the most common), orbital radiotherapy, cyclosporine and, recently, rituximab.
• When a patient’s sight is threatened (eg, when there is optic nerve involvement or corneal breakdown), orbital decompression techniques may be required.
• In mild cases, conservative, local therapies may be sufficient; signs and symptoms ameliorate over time.
What treatment for this patient?
Treating this woman with radioactive iodine (choice A) would not be appropriate on 2 counts. First, she is clinically and biochemically euthyroid and thus requires no further therapy for hyperthyroidism at this time. Second, radioactive iodine could cause progression of the ophthalmopathy, as noted above.2
This patient manifests enough components of the clinical activity score (redness of eyelids, redness of conjunctivae, and retrobulbar pain) to be considered as having active ophthalmopathy—which is a reasonable predictor of positive response to immunosuppressive therapy. Thus, choice B is incorrect.
Surgical orbital decompression (choice C) is probably too aggressive. Orbital decompression is indicated for sight-threatening ophthalmopathy, which is suggested by optic neuropathy or imminent corneal breakdown. Neither of these conditions is present here; moreover, these lesions are usually treated with an immediate 2-week course of high-dose corticosteroids before surgery. In severe cases, cosmetic considerations can also be an indication for surgery, but ideally surgery is performed only after a patient’s ophthalmopathy has been consistently inactive for at least six months. Cosmetically, this patient’s condition was not severe enough to warrant surgery, nor had her ophthalmopathy been inactive long enough.
Outcome of this case
The patient’s Graves ophthalmopathy was characterized as active but mild. She was treated with nonspecific ophthalmic ointments and lubricants and dark lenses. After three months, her condition had significantly improved but had not entirely resolved. She remained clinically and biochemically euthyroid. However, because of the 25% risk of progression to severe disease in patients with mild or moderate ophthalmopathy (choice D), she will be carefully followed up at 3-month intervals.
This article was written by Ronald N Rubin, MD and first appeared in our US sister publication Consultant Live http://www.consultantlive.com/home but has been reviewed for UK relevance.
What’s the take home? The Take Home Message The Take Home Message
Suspect Graves ophthalmopathy in patients with a history of hyperthyroidism in whom ocular symptoms develop.