AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Thyroid-associated orbitopathy (TAO), frequently termed Graves ophthalmopathy, is part of an autoimmune process that can affect the orbital and periorbital tissue, the thyroid gland, and, rarely, the pretibial skin or digits (thyroid acropachy). 

The first description of an individual with possible TAO was Bodhidharma (Daruma), the founder of Zen Buddhism and Kung Fu, in the 6th century.  

The association of goiter and exophthalmos has been recognized by many clinicians, including Sayyid Ismail Al-Jurjani in Persia in the 12th century, the Irish doctor Robert Graves in 1835, and the German physician Karl Adloph von Basedow in 1840.^{1, 2}

TAO may precede, coincide, or follow the systemic complications of dysthyroidism. The ocular manifestations of TAO include eyelid retraction, proptosis, chemosis, periorbital edema, and altered ocular motility with significant functional, social, and cosmetic consequences. Of those patients affected, 20% indicate the ocular morbidity of TAO is more troublesome than the systemic complications of dysthyroidism. 

Although most cases of TAO do not result in visual loss, TAO can cause vision-threatening exposure keratopathy, troublesome diplopia, and compressive optic neuropathy; therefore, all clinicians should be able to recognize TAO.

Pathophysiology

In simplest terms, the underlying pathophysiology of TAO is thought to be an antibody-mediated reaction against the TSH receptor with orbital fibroblast modulation of T-cell lymphocytes. T-cell lymphocytes are believed to react against thyroid follicular cells with shared antigenic epitopes in the retroorbital space.  An active phase of inflammation is initially present. 

Lymphocytic infiltration of the orbital tissue causes a release of cytokines (eg, tumor necrosis factor, interleukin 1 [IL-1]) from CD4+ T cells stimulating the orbital fibroblasts to produce mucopolysaccharides, which, by hyperosmotic shift, cause tissue edema in the extraocular muscles.  Fibroblasts are believed to be the target and effector cells in TAO. Fibroblasts are extremely sensitive to stimulation by cytokines and other soluble proteins and immunoglobulins that are released in the course of an immune reaction. The cytokines activate previously quiescent fibroblasts to secrete hyaluronic acid, a glycosaminoglycan. Doubling the hyaluronic acid content in the orbital tissue causes a 5-fold increase in the tissue osmotic load.  In addition, preadipocyte fibroblasts are influenced to transform into adipocytes, especially in young patients. 

The orbit can be described as a pear-shaped box with an anterior opening; the stalk of the pear represents the optic nerve.  In TAO, the increase in orbital volume from the extraocular muscles and fat causes forward protrusion (proptosis or exophthalmos) and, occasionally, optic nerve compression at the narrow posterior apex of the orbit.  The edema results in tissue damage and fibrosis, with restriction in extraocular motility and lagophthalmos. 

Usually within 1-2 years of the onset of orbital involvement, the inflammation settles to a more quiescent, fibrotic phase predominated by scarring of the orbital tissues.

TAO may be part of a more generalized disorder of connective tissue and striated muscle.

A more extensive discussion on the pathoimmunology of TAO is beyond the scope of this article. Some of the more recent research in this field is outlined below.

The insulin-like growth factor 1 receptor is an autoantigen that may be important in TAO because of its aberrant expression by TAO fibroblasts, the promotion of T-cell recruitment, and the presence of circulating activating autoantibodies. T helper 2 cytokines (IL-4 and IL-13) may induce the expression of 15-lipoxygenase-1, with up-regulation in the production of 15-hydroxyeicosatetraenoic acid (15-HETE), causing tissue activation and remodeling.

Cyclooxygenase 2 (COX-2) is expressed at higher levels in the orbital fibroadipose tissues of TAO. There is a positive correlation with increasing severity of orbital disease, suggesting a possible relationship with COX-2 expression and orbital inflammation in TAO.

Variants in the IL-23R gene are strongly associated with Graves ophthalmopathy (or TAO). These variants may predispose to Graves ophthalmopathy (or TAO) by changing the expression and/or the function of IL-23R, thereby promoting a proinflammatory signaling cascade.

Frequency

United States

In a rural Minnesota community, the annual incidence rate was estimated at 16 cases per 100,000 women and 2.9 cases per 100,000 men.

Mortality/Morbidity

Monitoring of thyroid exophthalmos may help prevent corneal and optic nerve damage.

Sex

• Various studies suggest that TAO affects women 2.5-6 times more frequently than men.
• Severe cases of TAO occur more often in men than in women.

Age

• TAO mostly affects patients aged 30-50 years.
• Severe cases of TAO are believed to be more frequent in patients who are older than 50 years.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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History

• TAO usually has a self-limited course over 1 or more years. Stable TAO can occasionally reactivate, but this is uncommon.
• Signs and symptoms may vary and depend on the stage that the patient is experiencing. Initially, an acute or subacute stage of active inflammation occurs. Later, the patient progresses to a more quiescent stage, which is characterized by fibrosis.
• Patients may complain of the following ocular symptoms:
• • Dry eyes
  • Puffy eyelids
  • Angry-looking eyes
  • Bulging eyes
  • Diplopia
  • Visual loss
  • Field loss
  • Dyschromatopsia
  • Photopsia on upgaze
  • Ocular pressure or pain
• Symptoms of hyperthyroidism include the following:
• • Tachycardia/palpitations
  • Nervousness
  • Diaphoresis
  • Heat intolerance
  • Skeletal muscle weakness
  • Tremor
  • Weight loss
  • Hair loss
  • Irritability
  • Goiter
• Symptoms of hypothyroidism include the following:
  
  
  • Bradycardia
  • Drowsiness
  • Poor mentation
  • Muscle cramps
  • Weight gain
  • Dry skin
  • Husky voice
  • Depression
  • Cold intolerance

Physical

• TAO is the most common cause of unilateral and bilateral proptosis in adults.
• • Proptosis or exophthalmos occurs because the orbital contents are confined within the bony orbit, and decompression can only occur anteriorly.
  • Unilateral proptosis of TAO usually reflects asymmetric muscle involvement.
  • Retropulsion (digital palpation of the globes through closed eyelids) is a useful test.  Patients with severe TAO have decreased retropulsion. Various exophthalmometers can be used to measure orbital protrusion.
  • Lacrimal gland enlargement is not uncommon.
• Normally, the upper lid is located 1-1.5 mm below the superior limbus, and the lower lid is located at the inferior limbus.
• • Upper lid retraction (Dalrymple sign), often with temporal flare and scleral show, is the most common ocular sign of TAO. This sign is an important differentiating feature to note in all patients with proptosis.
  • Mechanisms for upper lid retraction include proptosis, sympathetic drive of the Muller muscle, upgaze restriction, fibrosis of the levator muscle, and contralateral ptosis (myasthenia).
  • Lid retraction may occur in both the upper and lower lids because of a sympathetically innervated tarsal muscle in both lids. Upgaze restriction, levator fibrosis, and very severe proptosis are other possible causes of lid retraction.
  • If eyelid retraction is absent, then TAO may be diagnosed only if (1) proptosis, optic nerve involvement, or restrictive extraocular myopathy is associated with thyroid dysfunction or abnormal regulation, and (2) no other confounding ophthalmic features are apparent.
  • Lid lag on downgaze (von Graefe sign) is another important feature of TAO. While slowly moving the fixation object from upward to downward, the examiner should observe if the eyelid lags behind the globe on downgaze.
  • Pseudoptosis and true ptosis may be seen in patients with TAO. Pseudoptosis may be observed if contralateral lid retraction is present. Ptosis may occur with TAO if levator dehiscence is present. Patients with TAO may have concurrent myasthenia gravis, which may lead to ptosis.
  • Other TAO lid signs include lid edema and glabellar furrows.
• Anterior segment signs in TAO include superficial punctate keratitis, superior limbic keratoconjunctivitis, conjunctival injection usually over the rectus muscle insertions, and conjunctival chemosis.
• With severe proptosis, corneal exposure with frank corneal ulceration may occur. Superior limbic keratoconjunctivitis is a chronic, often recurrent condition of ocular irritation, which some attribute to mechanical trauma transmitted from the upper eyelid to the superior bulbar and tarsal conjunctiva. Superior limbic keratoconjunctivitis has been a purported prognostic marker for severe TAO.
• Strabismus is common with TAO, and it often presents as hypotropia or esotropia because the inferior rectus muscle and the medial rectus muscle are the most commonly involved extraocular muscles.
• • The corneal light reflexes should be examined closely because asymmetric proptosis and lid retraction may mask the true relative positions of the globes.
  • The restrictive myopathy sometimes can be confirmed with forced ductions or elevated intraocular pressure with eye movement (eg, upgaze in hypotropic patients) if a diagnosis of TAO is not revealing.
  • Inferior rectus muscle restriction may mimic double elevator palsy.
  • Pseudo-fourth nerve palsies have been described with TAO.
  • Although esotropia is a more common finding with TAO, convergence insufficiency has been described.
  • In patients with TAO and exotropia, the possibility of concurrent myasthenia gravis should be considered.
• Optic nerve compression may occur with seemingly mild proptosis. Also, most cases of compressive thyroid optic neuropathy occur without visible optic nerve edema. For this reason, documenting visual acuity, color vision, and the presence or absence of a relative afferent pupillary defect is important during each visit.
• Glaucoma may result from decreased episcleral venous outflow. Because of restrictive myopathy, intraocular pressure may rise more than 8 mm Hg on upgaze.
• Choroidal folds may be seen with thyroid ophthalmopathy.
• Numerous other eponymous signs are associated with TAO, including the following:
• • Vigouroux sign (eyelid fullness)
  • Stellwag sign (incomplete and infrequent blinking)
  • Grove sign (resistance to pulling down the retracted upper lid)
  • Goffroy sign (absent creases in the forehead on superior gaze)
  • Möbius sign (poor convergence)
  • Ballet sign (restriction of one or more extraocular muscles)
• A statistically significant association of deep glabellar rhytids with thyroid ophthalmopathy has been described. This is presumably caused by hypertrophy of brow depressor muscles compensating for lid retraction.
• Pretibial dermopathy and thyroid acropachy (which mimics the appearance of clubbing) are less commonly encountered dramatic, cutaneous signs of dysthyroidism.
• Numerous classification systems for TAO exist, but they all have shortcomings.
• • The simplest classification for TAO is type I and type II.
  • • Type I is characterized by minimal inflammation and restrictive myopathy.
    • Type II is characterized by significant orbital inflammation and restrictive myopathy.
    • Type I and type II orbitopathy are not mutually exclusive.
  • Werner's NOSPECS classification system (and its modifications) is one of the most commonly known systems and is used in many endocrine studies.
    • Unfortunately, patients may fall into more than one particular class.
    • Patients may not progress in an orderly fashion from class 1 to class 6. Patients with visual loss from compressive optic neuropathy may not show marked proptosis or other signs of severe disease.
    • As with other classification systems, it may be of limited prognostic value.

Causes

• Relationship of thyroid status and TAO
• • The thyroid gland per se does not cause TAO. Instead, the thyroid gland, eye muscles, and pretibial skin are especially subject to the autoimmune attack. Regulation of thyroid function does not abort TAO. However, restoration of the euthyroid state (with antithyroid drugs and thyroxine) may improve the eye status to some extent.
  • Many patients with TAO are hyperthyroid, but the following also are associated with TAO: euthyroidism (20%), Hashimoto thyroiditis, thyroid carcinoma, and neck irradiation. Even if the patient is euthyroid, TAO may progress. In patients who are hyperthyroid, the eye signs of TAO usually develop within 18 months of dysthyroidism; very often, they develop concurrently.
• Radioactive iodine and TAO
• • Although somewhat controversial, several publications have suggested that thyroid ablation with orally ingested radioactive iodine (RAI; I-131) may exacerbate TAO compared to antithyroid drugs or surgical ablation.
• • • I-131 is believed to result in a release of thyroid antigens.
    
    
    • In a study by Bartalena, approximately 15% of patients treated with only RAI developed or had worsening of TAO.³ In contrast, none of the patients treated with both RAI and prednisone had progression of TAO, and two thirds showed improvement. Only 3% of patients treated with methimazole showed worsening of TAO.
  • To prevent progression of TAO from RAI, pretreating and posttreating the patient with low-dose steroids (eg, 0.5 mg/kg/d up to 2 mo posttreatment) has been suggested if no contraindications for steroids exist and agreed to by the patient. Post-RAI, the patient should be monitored closely for the development of hypothyroidism. Several studies have not shown that radioiodine is a significant risk for initiation or progression of mild TAO. 
• Other diagnostic considerations
• • In orbital cellulitis, the onset of proptosis is often quicker, and the patient has other evidence of infection (eg, fever, leukocytosis). See Cellulitis, Orbital. On neuroimaging, the paranasal sinuses often are opacified.
  • Carotid cavernous fistula: The patient may have a cranial bruit, and the dilated episcleral vessels extend to the limbus.
  • Orbital inflammatory syndrome (orbital pseudotumor)
• • • Orbital inflammatory syndrome is often more painful than TAO and progresses faster; the tendons are involved in orbital myositis.
    • Orbital pseudotumor is associated more often with ptosis than lid retraction.
    • Isolated enlargement of the lateral rectus muscle is more likely to represent a process such as orbital inflammatory syndrome rather than TAO.
  • Other causes of thickened muscles (sarcoidosis, metastases, lymphoma, amyloid, and acromegaly)
  • Dorsal midbrain syndrome (Parinaud syndrome)
  • • Patients may present with lid retraction and upgaze problems.
    • In contrast to TAO, the globes elevate on the doll's head maneuver in Parinaud syndrome.
    • The eye tends not to be injected or proptotic in Parinaud syndrome.
• • Diseases associated with TAO
• • • Other autoimmune diseases, such as myasthenia gravis, Addison disease, vitiligo, and pernicious anemia, have been described with TAO.
    • Yersinia enterocolitica infection has been associated with TAO.
    • In one study, 8% of patients with TAO had positive acetylcholine receptor antibodies. At 4.5-year follow-up visits, none of the patients with positive serology were identified clinically to have myasthenia gravis.
  • Smoking: TAO is associated strongly with smoking; the more severe the eye disease, the stronger the association. In one study, smokers of European ethnicity had a 2.4 times increased risk for TAO compared to their Asian counterparts.
  • The oral hypoglycemic pioglitazone has been suggested to cause adipocyte proliferation in patients with TAO. Until definitive studies are performed, alternatives to the thiazolidinediones might be considered in patients with TAO.

DIFFERENTIALS

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Follow-up
• Miscellaneous
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Lab Studies

• Blood
  
  
  • In screening for thyroid disease, the combination of free T4 (thyroxine) and TSH (thyroid-stimulating hormone) or serum TSH (thyrotropin) are highly sensitive and specific. However, because of cost, some recommend initially only using the TSH to screen for thyroid disease.
  • Serum TSH (thyrotropin) is useful to establish a diagnosis of hyperthyroidism or hypothyroidism. Usually, the TSH is low in hyperthyroidism and high in hypothyroidism.
  • There is a confusing and inconsistent nomenclature for the various TSH receptor assays. Assays that measure the binding of TSH to a solubilized receptor are often referred to as TRAb (thyroid receptor antibody), TBII (TSH-binding inhibitor immunoglobulin), and LATS (long-acting thyroid stimulator) assays. Assays that measure the ability of immunoglobulin G (IgG) to bind to the TSH receptor on cells and to stimulate adenylate cyclase production have generally been referred to as the TSI (thyroid-stimulating immunoglobulin) assays.
  • Other blood tests that may be useful include calculated free T4 (thyroxine) index, thyroid-stimulating immunoglobulin, antithyroid antibodies, and serum T3 (triiodothyronine). The introduction of direct assays for TSH, free T4, and free T3 has superseded the usefulness of total T4 and T3 resin uptake testing.
  • Thyroid peroxidase antibodies and antibodies to thyroglobulin may be useful when trying to associate eye findings with a thyroid abnormality, such as euthyroid Graves disease.
  • The thyroid peroxidase test is also called the antimicrosomal antibody test and the antithyroid microsomal antibody test.
  • The antithyroglobulin test is also called the antithyroid antibody test.
  • The serum level of hyaluronan is not a sensitive indicator of its presence within the extraocular muscles.

Imaging Studies

• Ultrasound
• • Orbital ultrasound can quickly confirm if the patient has thickened muscles or an enlarged superior ophthalmic vein.
  • The author of this article prefers other imaging modalities. 
• CT scan and MRI
• • If the diagnosis of TAO can be established clinically, then it is not necessary to routinely order a CT scan or an MRI.
  • If the above studies are required, obtain axial and coronal views.
  • Neuroimaging usually reveals thick muscles with tendon sparing.
  • • The inferior rectus muscle and the medial rectus muscle usually are involved.
    • Isolated rectus muscle involvement may occur in up to 6% of patients. In this subgroup of patients, the superior rectus muscle may be the most frequently involved muscle.
    • Isolated lateral rectus muscle enlargement without other evidence of muscle enlargement is uncommon in TAO but suggests another disease process (eg, orbital myositis).
    • Bilateral muscle enlargement is the norm; unilateral cases usually represent asymmetric involvement rather than normality of the less involved side.
  • Neuroimaging may show a dilated superior ophthalmic vein.
  • Apical crowding of the optic nerve is well visualized on neuroimaging.
  • MRI is more sensitive for showing optic nerve compression.
  • CT scan is performed prior to bony decompression because it shows better bony architecture.
  • Occasionally, the proptosis of TAO results in straightening of the optic nerve.

Histologic Findings

• Lymphocytic cell infiltration
• Enlargement of fibroblasts
• Accumulation of mucopolysaccharides
• Interstitial edema
• Increased collagen production
• Fibrosis with degenerative changes in the eye muscles

TREATMENT

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Medical Care

• Inform patients that TAO usually runs a self-limited but prolonged course over 1 or more years. Patients also should realize that no immediate cure is available.
• Most patients with TAO can be observed; the follow-up interval depends on disease activity.
• • Monitor for visual loss from corneal exposure and optic neuropathy and for strabismus development.
  • Visual field and color vision testing may help in early detection of visual loss.
• If a patient has dry eye symptoms, consider using artificial tears during the day, lubricating ointment at night, and punctal plugs.
• Sleeping with the head of the bed elevated may decrease morning lid edema.
• Encourage patients to stop smoking to decrease the risk of congestive orbitopathy.
• In patients with diplopia, prisms may be beneficial to those with small-angle and relatively comitant deviations.
• • Tape occlusion of one lens or segment of the glasses may be helpful. If this does not work, try an occluder or eye patch (with care not to compress the orbit).
  • The author does not recommend the use of eye exercises for patients with severe restrictive strabismus; doing so may elevate intraocular pressure.
  • Oral steroids usually are reserved for patients with severe inflammation or compressive optic neuropathy. Steroids may decrease the production of mucopolysaccharides by the fibroblasts. Pulse intravenous steroids (eg, methylprednisolone 1 g every other day for 3 cycles) can be considered.
  • Antitumor necrosis factor drugs, such as etanercept, infliximab, and daclizumab, have been used in patients with TAO, but more studies are required to determine their adverse effect profile as compared to steroids. Octreotide, pentoxifylline, nicotinamide, plasmapheresis, and intravenous immunoglobulin are not mainstream medical treatments of TAO.
  • • Octreotide, a potent synthetic somatostatin analogue, has a beneficial effect in TAO, especially in patients with a positive Octreoscan-111. Lanreotide is a longer-acting somatostatin analogue, which is administered only once every 2 weeks; it may provide some benefit.
    • Pentoxifylline and nicotinamide may be useful. Both agents are believed to inhibit cytokine-induced glycosaminoglycan synthesis by the retroorbital fibroblasts.
    • The role of plasmapheresis and intravenous immunoglobulin (IV Ig) is not well delineated. One randomized trial of IV Ig (1 g Ig/kg body weight for 2 consecutive d q3wk) versus oral prednisolone (for 20 wk with initial dose of 100 mg/d) showed both treatments to be equally effective in patients with active TAO. Fewer adverse effects were observed in the IV Ig treatment group.
• Orbital radiation
• • This procedure sometimes is prescribed for moderate-to-severe inflammatory symptoms, diplopia, and visual loss in patients with TAO.
  • The radiation (1500-2000 cGy fractionated over 10 d) usually is administered via lateral fields with posterior angulation. Radiation is believed to damage orbital fibroblasts or perhaps lymphocytes.
  • Radiation requires several weeks to take effect, and it may transiently cause increased inflammation. Thus, most patients are maintained on steroids during the first few weeks of treatment.
  • Better response to radiation is observed in patients with active inflammation who are treated within 7 months of TAO onset.  Radiation may be more effective if combined with steroid treatment.  Studies that suggest that radiotherapy is ineffective in TAO must be scrutinized to ensure that the radiation was administered to appropriate candidates at the appropriate time. (Gorman's study used serum thyroid-stimulating immunoglobulin as a surrogate of active eye disease. Although the blood test is an indicator of immunologic activity, it may not reflect the clinical progression of TAO. Furthermore the patients in Gorman's study were enrolled at a median of 1.3 y after onset of eye symptoms, suggesting that many of the patients in the study would not have progressive eye symptoms or signs indicative of an ongoing orbital process.⁴)
  • Cataract, radiation retinopathy, and radiation optic neuropathy are possible risks. They are not common if treatment is appropriately fractionated and the eyes are shielded. In Marquez's study, 12% of patients developed cataracts after irradiation with median follow-up of 11 years.⁵
  • Wakelkamp also believed that orbital irradiation for TAO is a safe treatment modality, except possibly for patients with diabetes mellitus.⁶ Radiation may be a relative contraindication for patients with diabetes mellitus because of the risk of worsening retinopathy.
  • Although improvement of motility disturbances can occur with radiotherapy, radiation is limited when used in isolation to treat diplopia.
• Optic nerve compression
• • Compressive optic neuropathy may present with blurry vision, visual loss, dyschromatopsia, or field loss. Patients may not have marked proptosis, but they usually show markedly decreased retropulsion (tight orbits).
  • If necessary, high-dose steroids and higher intravenous doses are given. If no response occurs after 24 hours, steroids probably will not work; at this point, the patient should have surgical decompression and maintain steroids.
  • Adjunctive cyclosporine, octreotide, and IV Ig are less common modalities of medical treatment.
  • If a good steroid response occurs, orbital radiation may be considered. In severe cases of TAO, combined steroids, radiation, and surgery may be required.

Surgical Care

Approximately 5% of patients may require surgical intervention. The patient should know that multiple-staged procedures may be required. In elective cases, listen carefully to what the patient desires; the patient's expectations may not be realistic. The timing of surgery is important. Unless compressive optic neuropathy or severe corneal exposure is present, surgery generally is delayed during the active inflammatory phase of TAO. Surgery usually is performed during the quiescent cicatricial phase of the disease. Taking preoperative photographs is advised. With strabismus surgery, document prism measurements or fields of single binocular vision. Recording baseline-automated perimetry also is useful. The sequence of surgery is important. If the patient has marked proptosis, strabismus, and lid deformity, perform surgery in the following order:

• Orbital decompression
• • Thoroughly explain the potential complications of orbital decompression (eg, blindness, hemorrhage, diplopia, periorbital numbness, globe malposition, sinusitis, lid malposition) to the patient before surgery.
  • Orbital decompression may be performed as the initial treatment of compressive optic neuropathy or used if medical treatment is ineffective. A combination of medical and surgical treatment may be required in compressive optic neuropathy.
  • Following bony orbital decompression, open the periorbita. Little reduction in proptosis occurs until the periorbita is slit.
  • To decompress the optic nerve, at least 2 orbital walls usually are decompressed (traditionally, the medial wall and floor of the orbit). Medial decompression for compressive neuropathy must be taken posteriorly all the way to the apex of the optic canal. Surgery can be approached from a transorbital or trans-sinus route. Transorbital routes include subciliary incisions, lid crease incisions, medial incisions (cutaneous, transcaruncular), and coronal incisions. Trans-sinus routes include transantral approaches and endoscopy.
  • Medial wall removal should not extend above the frontoethmoidal suture. This averts bleeding from the ethmoidal arteries and prevents cerebrospinal fluid (CSF) leaks.
  • When the orbital floor is removed, preservation of a strut of bone between the ethmoid and maxillary bones may reduce strabismus from inferomedial shift in the globe position.
  • Balanced decompression of the medial and lateral orbital walls frequently is described. Avoiding decompression of the orbital floor theoretically decreases the risk of postoperative diplopia and lid retraction.
  • Lateral wall decompression does little to relieve apical compression but helps to reproduce proptosis. Valgus repositioning of the orbital wall and orbital rim-onlay, porous-polyethylene grafts are adjunctive techniques to reduce proptosis.
  • Four-wall decompression (with decompression of the orbital roof) requires a neurosurgical approach.
  • Orbital fat decompression without bony removal has been described for TAO without apical compression. Candidates for orbital fat decompression should show predominant enlargement of the orbital fat compartment, rather than the rectus muscles on orbital imaging. Unlike cosmetic blepharoplasty, with orbital fat decompression, fat also is removed posterior to the equator of the globe. Inferiorly, the fat is removed through a transconjunctival approach, which may be facilitated with lateral canthotomy and cantholysis. Superiorly, fat removal is through a lid crease incision, usually confined to the nasal quadrant.
• Strabismus surgery
• • Successful, early strabismus surgery during active thyroid ophthalmopathy has been described, but strabismus surgery generally is delayed until TAO is inactive and the prism measurements have been stable for at least 6 months.
  • Patients should realize that the goal of surgery is to minimize diplopia in primary and reading positions. Expecting binocular single vision in all positions of gaze may not be realistic. Patients also should realize that multiple strabismus surgeries and prisms may be required.
  • Because of the restrictive myopathy of TAO, recessions, rather than resections, predominantly are performed. Whenever feasible, adjustable suture surgery is recommended. In patients intolerant of conscious suture adjustment, hang-back sutures can be adjusted using the corneal light reflexes. In select patients with TAO, strabismus surgery can be performed using topical anesthesia. To prevent ocular ischemic syndrome, do not operate simultaneously on more than 2 muscles per eye.
  • Surgery of the inferior rectus muscle deserves special mention. Inferior rectus muscle recession may decrease upper lid retraction, but it often results in lower lid retraction despite dissection of the lower lid retractors. Because the inferior rectus muscle has subsidiary actions (excyclotorsion and adduction), inferior rectus muscle recessions may lead to a component of intorsion and A-pattern strabismus.
  • If visualization during strabismus surgery is difficult, especially for the superior rectus muscle, a vertical lid split technique may be considered.
  • Botulinum toxin injections are used by some clinicians during the acute phase of TAO as a temporizing measure until orbital decompression can be completed.  Optic neuropathy following a botulinum toxin injection for strabismus in a patient with TAO has been reported.
• Lid-lengthening surgery
• • If restoration of the euthyroid state does not improve lid retraction, consider lid-lengthening surgery. This surgery decreases corneal exposure and can be used to camouflage mild-to-moderate proptosis.
  • Lateral tarsorrhaphies can decrease upper and lower lid retraction, but the author does not prefer this method.
  • Two to three millimeters of upper lid retraction can be ameliorated with a Müller muscle excision. Lateral levator tenotomy is often helpful to decrease the temporal flare. If further amounts of lid recession are required, levator recession can be considered.
  • Lower lid-lengthening usually requires a spacer material. Graft materials include human acellular dermis, tarsus, and conjunctiva from the upper lid, hard palate, and ear cartilage.
  • Horizontal tightening procedures (eg, lateral tarsal strip) increase scleral show in patients with proptosis.
  • In the horizontally tight eyelid, lateral canthal advancement is a useful adjunct to enhance the effect of retractor recession and reduction of temporal flare.
• Blepharoplasty
• • This is the last phase of restorative surgery in TAO. Lower lid blepharoplasty can be approached transconjunctivally if no excess lower lid skin is present.
  • Upper lid blepharoplasty is performed transcutaneously with conservative skin excision. Brow fat resection may be considered. Dacryopexy may be required if lacrimal gland prolapse occurs.

Consultations

• Patients with TAO benefit from consultation and follow-up care with an endocrinologist.
• Orbital decompression can be performed in conjunction with an otorhinolaryngologist, especially when endoscopic procedures are contemplated.
• Neurosurgical consultation is required when decompression of the orbital roof is performed.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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Further Outpatient Care

• Patients should receive follow-up care as needed.

Complications

• With thyroid exophthalmos, corneal exposure can occur.

Prognosis

• Prognosis is generally favorable for patients with this condition. Most patients do not require surgical intervention.

Patient Education

• See Surgical Care and Medical Care.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 11  

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• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• TAO can be asymmetric.
• Optic nerve compression in TAO can occur in the absence of obvious proptosis.  For this reason, always check for retropulsion. 
• TAO should not be mistaken for a dural arteriovenous malformation or a carotid cavernous fistula.
• Early diagnosis and appropriate monitoring of TAO may decrease corneal exposure and compressive optic neuropathy.
• In patients with TAO who have proptosis and inferior scleral show, simple horizontal tightening of the lower lid will result in increased globe exposure.
• Prior to bony orbital decompression, a CT scan should be obtained because it delineates bony anatomy better than an MRI.

Special Concerns

• Pregnancy and TAO  
• • The incidence of hyperthyroidism in women who are pregnant has been reported to be approximately 0.2%. Information on the management of TAO during pregnancy is not widely available.
  • The author is not aware of literature that supports caesarean delivery over vaginal delivery in women with TAO who are pregnant. If a pregnant woman with TAO has compressive optic neuropathy, steroids can usually be administered in consultation with the obstetrician and an endocrinologist. Ideally, surgery should be deferred until after delivery when possible. However, if emergent orbital decompression is required, nonabdominal surgery may not impose the same risks to the fetus as that of abdominal surgery.
• Childhood TAO  
• • In general, children with TAO tend to have a more benign disease course, with less ophthalmoplegia, than adults. In comparison with adults, surgical intervention is infrequently required with children. 
  • Children and their parents should be counseled to avoid smoking. Secondhand smoke seems to exacerbate autoimmune thyroid disease, and passive smoking may have a deleterious effect on childhood TAO.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Long-standing thyroid ophthalmopathy with typical features of lid retraction (upper and lower) and scleral show with proptosis. This patient's chief complaint was binocular vertical diplopia. A small right hypotropia was observed on alternate cover testing.
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Media type:  Photo

Media file 2:  Axial CT scan of a patient with congestive thyroid orbitopathy. The recti muscles are thickened with apical compression. The tendons are spared.
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Media type:  CT

Media file 3:  Thyroid acropachy imitates the appearance of clubbing and is an uncommon finding in patients with thyroid ophthalmopathy. This patient required bilateral orbital decompression and strabismus surgery.
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Media type:  Photo

Media file 4:  Pretibial myxedema and thyroid acropachy in the same patient as in Image 3.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: Apr 30, 2008