Orbital Disease of Neuro-Ophthalmic Significance
Jurij R. Bilyk
THYROID EYE DISEASE
Graves’ disease is defined as the triad of hyperthyroidism (diffuse thyroid enlargement), orbitopathy, and pretibial myxedema.
ETIOLOGY AND EPIDEMIOLOGY
• 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.
INCIDENCE
• 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.
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.
CLINICAL CHARACTERISTICS
• 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
DIAGNOSTIC EVALUATION
• 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.
TREATMENT
• General
Control the dysthyroid state. Note that control of thyroid function has little effect on the progression of TED.
Cigarette smoking adversely affects the ocular signs of TED. All patients with Graves’ disease should be advised strongly to stop smoking. The patient should be reminded in no uncertain terms that cessation of tobacco use is important in the management of their disease; these conversations should be clearly documented in the medical record.
TABLE 13-1. Etiology of Orbital Inflammation | ||||||||||||||||||||||||||||||||||||||||||
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• Specific
Systemic corticosteroids: TED often responds to the systemic administration of corticosteroids. Treatment may improve orbital congestion, acute ocular misalignment, and optic neuropathy. Some patients will respond to this treatment, others will not. Prolonged steroid therapy is not indicated because of the risks of long-term steroid use. In the majority of patients, cessation of corticosteroids will result in a recurrence of inflammation. Recent studies from Europe suggest that the use of high-dose pulsed intravenous corticosteroids may lead to an arrest of progressive orbitopathy. Whether this therapy is effective in long-term disease control is controversial.
Orbital radiation: There is controversy about the efficacy of orbital radiation. Many reports indicate that it is effective in the treatment of the inflammatory phase of TED. Other studies as well as a recent meta-analysis of available data indicate that it may not be effective except perhaps in the stabilization of progressive external ophthalmoplegia. However, some criticism about the patient selection and duration of the ocular disease keeps the controversy regarding radiation therapy alive. We still employ radiation therapy in select patients with TED. Orbital radiation is usually given over 10 to 12 sessions (200 cGy each session) for a total dose of 2000 cGy. It should not be repeated because of the risk of additive radiation, and many experts avoid radiation in patients who smoke or have other vasculopathic risk factors (e.g., diabetes mellitus). It is only indicated in patients who are in the inflammatory phase. Of note, orbital radiation is advocated by some experts in
the management of TED compressive optic neuropathy. While the authors certainly utilize this treatment modality in patients who present with early optic neuropathy, the treating physician should also be aware that radiation therapy frequently has a significant lag of several weeks before any anti-inflammatory effect is seen. The optic neuropathy may progress significantly in the interim. Therefore, advanced or rapidly progressive compressive optic neuropathy is best treated with timely orbital decompression. Patients with early optic neuropathy who undergo orbital radiation therapy should be monitored closely for any progressive visual loss.
Surgery usually progresses in a staged, sequential fashion. Orbital abnormalities are addressed first, followed by strabismus and eyelid repair. Not all patients require each step, but the order is important to maximize predictability of the final result.
▶ Orbital decompression is indicated when proptosis must be reduced or when optic neuropathy occurs. For the relief of proptosis, an anterior decompression may suffice; for the optic neuropathy, a posterior orbital decompression that involves the medial wall of the orbit is usually required. Some experts have reported reversal of optic neuropathy with bony decompression of the deep lateral orbital wall. During the inflammatory phase, surgery is reserved for emergent cases of compressive optic neuropathy. Once the inflammation has subsided, surgery is typically safer and more predictable.
▶ Extraocular muscle surgery: Surgical attempts to realign the eyes should be performed only after the ocular misalignment has been stable for several months (we use 3 months as a minimum). Recessions (typically with adjustable suture technique) are recommended rather than muscle resection.
▶ Eyelid surgery is aimed at first correcting upper and lower eyelid retraction and then debulking edematous skin and fat. Avariety of techniques are employed, including levator recession, full-thickness blepharotomy, Müllerectomy, and eyelid spacers.
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