Orbital Disease of Neuro-Ophthalmic Significance

Orbital Disease of Neuro-Ophthalmic Significance

Jurij R. Bilyk


Graves’ disease is defined as the triad of hyperthyroidism (diffuse thyroid enlargement), orbitopathy, and pretibial myxedema.


• Thyroid eye disease (TED) is an autoimmune process. However, the exact mechanism by which the changes in the orbit take place remains elusive.

• TED is associated with other autoimmune disorders, such as myasthenia gravis (MG), which is present in 1% to 2% of the patients.

• Orbital findings are due to chronic inflammation and glycosaminoglycan deposition in the soft tissues (extraocular muscles, fat, lacrimal gland) that in turn causes edema and eventual fibrosis. Secondary orbital congestion from decreased venous outflow potentiates the clinical findings.


• Thyroid disease is common, occurring in about 2% of the general population, with a female preponderance of 6 to 7:1. TED is seen to some degree in 30% to 70% of patients with thyroid dysfunction, with the female to male ratio narrowing to 4:1.

• There is also controversial evidence that patients treated for hyperthyroidism with radioactive iodine rather than medically or surgically may develop TED more frequently and to a more severe degree. Pretreatment with corticosteroid has been suggested to decrease this problem but remains unproven.

• Although periocular findings usually manifest within 18 months of the thyroid disease, they can either precede or follow the thyroid diagnosis by several years or even decades. Patients are typically hyperthyroid, but a minority of cases are hypo- or euthyroid. The presence of the characteristic eye disease without any thyroid abnormalities is termed euthyroid TED.
These patients eventually develop thyroid dysfunction in 70% of cases within 2 years of the orbitopathy. Approximately, 5% to 25% of patients will present initially to the ophthalmologist without evidence of systemic disease.


• Systemic: Depending on the specific type of thyroid dysfunction (hyper-, hypo-, eu-), initial symptoms include:

  • Weight loss or gain

  • Increased appetite Sweating

  • Heat/cold intolerance

  • Fatigue

  • Tremors

  • Heart palpitations

  • The thyroid gland may be enlarged

  • Up to 50% may have a family history of thyroid dysfunction

• Periocular and orbital: Many patients experience two distinct phases of the disease. Early in the course, the patient presents with symptomatic, inflammatory signs called “active” (Fig. 13-1). During this phase, patients have a variety of nonspecific complaints, often misdiagnosed as allergy or dry eye syndrome. As additional orbital inflammation develops, the clinical diagnosis becomes more obvious.

  • Six months to 3 years later (mean 12 months), the progressive changes either arrest or abate, and the patient enters a long-term “inactive” or “burnt-out” phase. At this point, the chance of reentering an inflammatory phase is about 5%. TED may present either unilaterally or bilaterally and may be asymmetric.

• Symptoms

  • Eyelid: A variety of lid abnormalities occur including upper lid retraction in primary gaze (“thyroid stare”), edema (“puffy eyelid”), and lagophthalmos (inability to close the eyelids completely).

  • A foreign body sensation, which may be asymmetric, and is either due to corneal exposure from proptosis or lid retraction.

  • Double vision is due to infiltration of the extraocular muscles, which become inflamed and subsequently become fibrotic.

  • Loss of vision can be found on the basis of anterior segment disease (corneal exposure, drying, infection, or perforation) or a compressive optic neuropathy.

• Signs

  • Upper eyelid retraction is a typical and highly sensitive sign of TED and is seen mostly in the hyperthyroid state (Fig. 13-2A). Upper scleral show should always be considered abnormal and should prompt thyroid function testing. Lid edema may occur in the hyper- or hypothyroid state. The upper lid may lag behind the movement of the globe in downgaze (von Graefe sign) (Fig. 13-2B).

  • Proptosis may be unilateral or bilateral. The most frequent cause of proptosis in adults is TED.

  • Increased resistance to attempted retropulsion of the globes is found in some patients. Patients with little or no proptosis and increased resistance to retropulsion are at greater risk of developing optic neuropathy.

  • Exposure keratopathy due to lagophthalmos.

  • Ocular injection. Conjunctival injection is most prominent over the horizontal rectus muscle. Conjunctival chemosis is commonly noted inferolaterally (Fig. 13-3).

  • Ocular misalignment in any form may occur. However, the muscles most commonly involved are the medial and inferior rectus muscles. Therefore, esotropias and hypotropias are most frequently encountered (Fig. 13-4).

  • Increased intraocular pressure, especially in upgaze: This is usually due to restrictive inferior rectus myopathy or a congested orbit (Fig. 13-5A). Because this is a mechanical form of increased intraocular pressure, topical antiglaucomatous therapy is often ineffective.

  • Optic neuropathy occurs in approximately 5% of patients with TED and is due to compression of the optic nerve by large indurated muscles at the orbital apex. The clinical risk factors for the development of thyroid-related optic neuropathy are as follows:

    • ▶ Lack of proptosis

    • ▶Increased resistance to ocular retropulsion

    • ▶Involvement of the medial rectus muscles with complaints of diplopia and evidence of restrictive strabismus


• The clinical appearance of the patient with lid retraction is sufficient to establish the diagnosis of TED (Fig. 13-5A). In a typical clinical setting, imaging of the orbit is not required but may reveal enlarged extraocular muscles with sparing of the tendinous insertions. The medial and inferior rectus muscles are most frequently involved (Fig. 13-5B). The orbital fat may appear inflamed on MRI and have a diffuse reticular pattern (“dirty fat”) on CT.

• Endocrinologic investigation to detect any thyroid dysfunction should be carried out in patients without a history of thyroid disease. Although a battery of tests is available, in general a selective (sensitive, third generation) TSH is the only screening test needed. This test is especially helpful in patients who are systemically asymptomatic, since it is effective in detecting subtle degrees of hyperthyroidism. In cases where the patient is euthyroid, a thyroid-stimulating antibody (TSI) test may reveal a markedly elevated titer. Although the predictive utility of TSI is unclear, a high titer supports the diagnosis of TED in a euthyroid patient.

• Imaging of the orbit should be performed if the diagnosis is in doubt (e.g., absence of upper eyelid retraction, isolated unilateral proptosis, etc.) or in preparation for surgical intervention (see the following discussion).

• Follow-up schedules depend on the clinical setting. Patients with risk factors for optic neuropathy (see previous discussion) should be examined every 2 to 3 months initially to detect decreasing vision or color perception, and the patient should be instructed on how to monitor for red desaturation on a weekly basis between examinations. Patients with no ocular misalignment and normal retropulsion may be seen every 6 to 12 months.


• A detailed description is found in Table 13-1.

Jul 14, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Orbital Disease of Neuro-Ophthalmic Significance

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