Strabismus in Thyroid Eye Disease

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Article initiated by:

Chantal Josee Boisvert, MD, Kevin Gustafson

All contributors:

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

Assigned editor:

Kara M. Cavuoto, M.D.

Review:

Assigned status Up to Date

 by Kara M. Cavuoto, M.D. on September 12, 2024.

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Disease Entity

Strabismus in Thyroid Eye Disease

Disease

Thyroid eye disease (TED) manifests more commonly in hyperthyroid patients (90% of cases) but can occur in hypothyroid and even euthyroid patients. It is important to note that the course of TED does not necessarily parallel thyroid gland activity in levels of triiodothyronine (T3) or free thyroxine (T4) and only approximately 20-25% of patients have clinically apparent Graves’ ophthalmopathy.

TED has numerous ophthalmologic clinical signs and symptoms including lid retraction, proptosis, periorbital edema, decreased vision and strabismus. It typically affects both eyes but can be asymmetric. The inferior rectus muscle is most commonly involved, followed by the medial rectus, superior rectus and then lateral rectus. While oblique muscles are rarely thought to be involved, more recent research suggests it is not so uncommon. In one study, 96% of TED patients demonstrated significant SO enlargement.

Etiology

Strabismus in thyroid eye disease is a result of inflammation and subsequent fibrosis that causes swelling and thickening of the extraocular muscles. This can restrict eye movement, causing misalignment and possibly result in double vision.

Risk Factors

Women are six times more likely than men to develop thyroid eye disorders (86% versus 14%, respectively). While TED is a common cause of acquired vertical deviation in adults, children rarely acquire motility problems. Radioactive iodine carries a 15-20% increased risk for exacerbation of thyroid eye disease. Smokers who have Graves’ disease are at increased risk of developing thyroid eye disease, often with more severe and prolonged active disease that can threaten vision.

Pathophysiology

The pathogenesis of TED involves cellular proliferation, inflammation, and accumulation of glycosaminoglycans in extraocular muscles and orbital connective as well as expansion of adipose tissue. Orbital fibroblasts express CD40 receptors which is unique from other fibroblasts throughout the body. These receptors, generally on B-cells, can be engaged by T-cells bound to CD154. This leads to the upregulation of orbital fibroblast production of inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2. This subsequently leads to increased synthesis of hyaluronan and glycosaminoglycans causing inflammation of orbital contents. Since orbital fibroblasts are also derived from embryological neural crest lineage, a subpopulation of orbital fibroblasts possesses the ability to undergo adipocyte differentiation. This leads to the expansion of orbital fat and further increased pressure within the orbital cavity.

Diagnosis

History

A thorough history should be obtained, which includes the 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 and medications.

Physical examination

A complete eye examination should be performed, which can include:

• Visual acuity
• Head posture
• Stereoacuity
• Extraocular movements
• Sensorimotor exam
• Double Maddox rod
• Pupil exam
• Intraocular pressure in both primary and upgaze
• Slit lamp examination
• Optic nerve evaluation
• Hertel exophthalmometer
• Forced ductions

Diagnostic procedures

TED diagnosis requires 2 of the following 3 signs:

• Concurrent thyroid disease, recently treated immune-related thyroid dysfunction or the presence of thyroid antibodies (including thyroid-stimulating hormone–receptor (TSH-R) antibodies, thyroid-binding inhibitory immunoglobulins, thyroid-stimulating immunoglobulins, antimicrosomal antibodies) in a euthyroid patient
• Typical ocular signs:
  • Chemosis and/or caruncular edema
  • Restrictive strabismus
  • Eyelid retraction with typical lateral flare
  • Proptosis
  • Compressive optic neuropathy
  • Fluctuating eyelid edema and/or erythema
• Evidence of any rectus or levator muscle enlargement on radiology (unilateral or bilateral)

Laboratory test

• Thyroid function tests, including T3, T4, TSH levels, which may be low, normal or high due to discordance between systemic disease and TED

• Thyrotropin receptor autoantibody (TSI) or total antibodies against TSH-R (thyrotropin-binding inhibitory immunoglobulin [TBII] test) which more strongly correlate with the clinical activity score of the eye disease

• Acetylcholine receptor antibody to rule out co-existing 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 recommended. In patients with symptomatic diplopia, patching one eye will immediately relieve double vision. Strabismus surgery should be performed only after the acute phase subsides and the magnitude of deviation remains stable for at least six months. Management of the patient’s thyroid dysfunction and smoking cessation are also very important.

Medical therapy

Once patients become symptomatic with TED, acute phase treatment includes smoking cessation and supportive care such as topical ocular lubricants. Other possible therapies include topical cyclosporine to reduce ocular surface irritation, a reduced-salt diet and/or sleeping with the head elevated to reduce edema, sunglasses to relieve dry eye, selenium supplementation or botulinum toxin for restrictive strabismus. In cases of severe orbital congestion and inflammation, glucocorticoids, biologics and/or radiotherapy may be used.

Patients may also benefit from placement of a Fresnel or ground-in prisms in their spectacles which can be used as a definitive treatment for small angles of strabismus, as a temporary treatment while the strabismus stabilizes or after decompression surgery while awaiting surgical correction of strabismus.

Statin therapy has been reported as a possible medical therapy useful in prevention of TED in Graves’ disease patients. One study found statin therapy significantly reduced the number of orbital decompressions and trended toward reducing the number and amount of strabismus surgeries, although these trends did not meet statistical significance.

Surgery

Surgery is indicated in cases of diplopia, abnormal head positioning or severe acute orbital inflammation. If surgery is needed, orbital decompression is typically performed first, followed by strabismus surgery and then eyelid retraction repair. Before surgery is considered, it is recommended for patients to achieve stabilization in the degree of strabismus and thyroid function tests. It may be appropriate to perform surgery earlier in patients with severely debilitating double vision or strabismus, such as in patients with extreme head posturing compensating for misalignment. Surgical correction typically consists of recession of the restricted extraocular muscles, although resections can be safely performed. As vertical muscle surgery can affect the eyelid position, strabismus repair should be performed before any eyelid procedure. The primary goal of surgery is to achieve single binocular vision in primary position and downgaze. A more thorough discussion of strabismus surgery can be found here.

Surgical success rates

Success rates of TED-strabismus surgery overall is variable with reoperation rates reported as high as 50%. While surgery may eliminate diplopia in the primary gaze, normal motility is rarely restored. This is due to the restrictive myopathy, large recessions necessary in some cases to return the eye to primary position and progression of underlying disease.

In a recent study, motor success was achieved in 69% of surgeries with success defined as vertical deviation of ≤5Δ and horizontal deviation of ≤10Δ in primary gaze at distance at final follow-up. Of the 27 surgeries that did not achieve motor success, 59% were undercorrected and 41% were overcorrected. In correcting for diplopia, 58% met the success criteria for sensory outcome postoperatively defined as the absence of diplopia in primary position.

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, most likely explained by stretching of the insertion which can occur as the suture dissolves.

Prognosis

The prognosis for strabismus in TED is favorable. TED is self-limited, lasting about one year on average in nonsmokers and two to three years in smokers. Recurrence of inflammation occurs in 5-10% of 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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