Strabismus in Thyroid Eye Disease

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Article initiated by:

Chantal Josee Boisvert, MD, Kevin Gustafson

All contributors:

Chantal Josee Boisvert, MD, S. Grace Prakalapakorn, MD, MPH, Kara M. Cavuoto, M.D.

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Review:

Assigned status Update Pending

 by Chantal Josee Boisvert, MD on March 1, 2016.

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Disease Entity

Strabismus in Thyroid Eye Disease (TED)

Disease

Thyroid eye disease (or thyroid-related orbitopathy or Graves’ ophthalmopathy) has numerous ophthalmologic clinical sequelae including lid retraction, proptosis, periorbital edema, decreased vision, and strabismus. These occur more commonly in patients with hyperthyroidism but can also occur in patients with normal or low thyroid levels. Among those with Graves’ hyperthyroidism, approximately 20-25% of patients will have clinically obvious Graves’ ophthalmopathy at the time of diagnosis. Many more patients will have evidence of enlargement of extraocular muscles on various imaging modalities. Strabismus, or misalignment of the eyes, can be horizontal, vertical, torsional, or a combination of the three. In TED, the inferior rectus and medial rectus muscles are most commonly involved, leading to hypotropia and esotropia. The superior and lateral rectus muscles are the next most commonly involved, though isolated enlargement of the superior or lateral recti is highly atypical of TED. The oblique muscles are rarely involved.

Etiology

Graves’ disease is caused by an abnormal antibody production against normal tissue. The same antibody can attack the thyroid gland and the extraocular muscles. This likely occurs because these tissues contain proteins that appear similar to the immune system as those of the thyroid gland. Strabismus in thyroid eye disease is a result of swelling and thickening of the extraocular muscles, which restricts eye movement and causes the eyes to move out of alignment. The resulting asymmetry between the two eyes can cause double vision (diplopia).

Risk Factors

Women are six times more likely than men to develop thyroid eye disorders (86% versus 14% of cases, respectively). Radioactive iodine carries a 15-20% increased risk for exacerbation of thyroid eye disease. Smokers who have Graves’ disease are also at increased risk of developing thyroid eye disease, and when they do, often have more severe and prolonged active disease that can threaten vision.

General Pathology

Inflammation and lymphocytic infiltration of the extraocular muscles and orbital tissues followed by fibrosis.

Pathophysiology

The pathogenesis of TED involves cellular proliferation, inflammation, and accumulation of glycosaminoglycans (GAG) in extraocular muscles and orbital connective and adipose tissue. Thyroid-stimulating antibodies and T-cell cytokines like TNF-alpha and interferon gamma stimulate retroorbital fibroblast production of GAG. The buildup of GAG leads to an increase in fluid accumulation and pressure within the orbit. The progression of TED leads to further swelling and eventual fibrosis of the extraocular muscles and orbital tissue.

Primary prevention

Smoking cessation, management of thyroid dysfunction

Diagnosis

History

Onset of diplopia, duration and progression of symptoms, known thyroid disease, family history of thyroid disease or thyroid eye disease, smoking history, previous thyroid/orbital/eye surgeries, medications

Physical examination

Complete eye examination including:

• Visual acuity

• Head posture

• Stereoacuity

• Extraocular movements and eye alignment

• Pupillary exam

• Intraocular pressure (IOP) (needs to be checked in both primary and upgaze, as an increase in IOP in upgaze correlates with the severity of inferior rectus muscle enlargement)

• Slit lamp examination

• Optic nerve evaluation

Signs

• Ocular misalignment and/or extraocular movement restrictions (elevation and abduction are commonly affected)

• Abnormal head positioning

• Resistance on forced duction testing

• Conjunctival erythema over the insertions of the horizontal recti

• Other signs of thyroid eye disease (lid retraction, proptosis, lid lag, etc)

Symptoms

• Diplopia

• Decrease in stereovision or depth perception

• Ocular or retroorbital discomfort or pain

Clinical diagnosis

Strabismus can be confirmed with a comprehensive eye examination. The acute phase of TED results in variable strabismus and diplopia. Proptosis is also a feature of the acute phase. As the disease progresses, the strabismus and proptosis worsens. Assessment of the severity of strabismus in the setting of other ocular findings consistent with Graves’ ophthalmopathy (lid retraction, stare, lid lag, proptosis, periorbital edema) should prompt a work-up of thyroid function. Because the ophthalmopathy associated with thyroid dysfunction may occur at any time during the course of the disease and may precede other systemic findings, it is important to begin the thyroid work-up and continue with routine follow-ups.

Diagnostic procedures

CT/MRI orbit without contrast or Ultrasound: enlargement of the extraocular muscles without involvement of the tendons

Laboratory test

• Thyroid function tests: T3, T4, TSH. These may be low, normal, or high.

• Thyrotropin receptor autoantibody (TSI). Circulating TSI levels correlate strongly with the clinical activity score of the eye disease.

• Acetylcholine receptor antibody to rule-out co-existent myasthenia gravis (5% of patients).

Differential diagnosis

• Cranial nerve palsies

• Inflammatory conditions like myositis and idiopathic orbital inflammation

• Myasthenia gravis in patients with fluctuating double vision and ptosis

• Chronic progressive external ophthalmoplegia

• Space-occupying lesions of the orbit

• Trauma to extraocular muscles (orbital fracture, orbital/intranasal surgeries, etc)

Management

General treatment

If the patient is not experiencing diplopia in primary gaze or reading position, observation may be all that is required. Patching one eye will immediately relieve diplopia. Surgery should be performed only after the acute phase subsides, and the angle of strabismus is stable for at least 6 months. Management of the patient’s thyroid dysfunction and smoking cessation are also very important.

Medical therapy

There is no medication that will improve the ability of extraocular muscles to move. Patients may benefit from placement of a Fresnel or ground-in prisms in their spectacles. It can be used as a definitive treatment for small amounts of strabismus or as a temporary treatment while waiting for the strabismus to stabilize.

Medical follow up

Patients need continued follow-up with eye examinations to determine degree of strabismus and progression of TED. Ophthalmopathy tends to stabilize over a course of months.

Surgery

Most cases of strabismus in TED require surgical correction. 6 months of stable measurements is typically the goal prior to performing surgery. However, it may be appropriate to perform surgery earlier in patients with severely debilitating double vision or strabismus (patients with extreme head posturing to compensate for the misalignment). Surgical correction consists of recession of the restricted extraocular muscles. Vertical muscle surgery can affect the eyelid position, therefore strabismus repair should be performed before any eyelid procedure. A more thorough discussion of strabismus surgery can be found here.

Surgical follow up

Frequency of reoperation in adults with TED is as high as 50%. This can be due to unstable strabismus that changes over time or due to the unpredictable nature of the surgical correction itself. The amount of recession necessary is difficult to predict and a correction in one gaze may result in a misalignment in another gaze (ex. correction for deviation in primary gaze may result in deviation in down gaze).

Complications

Worsening double vision is the primary complication of strabismus in TED. Abnormal head positioning may develop as the patient tries to compensate for the ocular misalignment. There is a high rate of late overcorrection after strabismus surgery for TED. The most likely explanation is a stretched insertion scar or dehiscence, which occurs as the suture dissolves.

Prognosis

The prognosis for strabismus in TED is favorable. Surgical correction is typically well-tolerated and successful in most patients. Control of the thyroid dysfunction remains a key part of the treatment plan and coordination with an endocrinologist is vital for disease management.

Additional Resources

Thyroid Eye Disease

Strabismus Surgery, Horizontal

Massachusetts Eye and Ear - Thyroid Eye Disease: FAQ

References

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