Anatomy and function
Chronic progressive external ophthalmoplegia
Orbital inflammatory disorders
Orbital Graves disease
Other restrictive syndromes
DISORDERS OF THE NEUROMUSCULAR JUNCTION
Disorders of the extraocular muscles and neuromuscular junction can produce a virtually unlimited variety of disordered ocular motility patterns because their clinical manifestations are not limited by the scope of a single cranial nerve or supranuclear process. These disorders are frequently bilateral and often involve the levator palpebrae and orbicularis oculi (but not the pupil), and in some cases can result in total bilateral ophthalmoplegia. Not surprisingly, many of these disorders have systemic manifestations.
Diseases of the extraocular muscles can produce motility disturbances in two ways: (1) the disease process can affect the muscle’s ability to contract and thus cause weakness and, (2) the muscle may be stiffened by disease, causing a restriction of muscle movement by tethering. Occasionally both processes are present to some degree, as weak muscles can become fibrotic and restricted over time. Myasthenia gravis and related disorders cause muscle weakness by affecting transmission at the neuromuscular junction with an otherwise normal nerve and muscle.
Six extraocular muscles insert on the globe. In the horizontal plane, the lateral rectus muscle abducts and the medial rectus muscle adducts the eye. Vertical movement is more complicated because two muscles (superior rectus and inferior oblique) elevate the eye, and two muscles (inferior rectus and superior oblique) depress the eye. The actions of the oblique muscles on the globe may seem mysterious, but they are easily remembered with a clear understanding of how they insert on the globe and the direction of their action (Figure 8–1). Table 8–1 lists the primary and secondary actions of the extraocular muscles. Note that the vertically acting muscles also tort the eye, but the torsional forces are balanced when both elevators (superior rectus and inferior oblique) or both depressors (inferior rectus and superior oblique) are active.
The extraocular muscles and their innervation.
The medial rectus muscle has been sectioned and retracted in this drawing of the right eye to show the position of the extraocular muscles. The course of cranial nerves (CNs) III (oculomotor, superior and inferior divisions), IV (trochlear), and VI (abducens) are shown as they enter the orbit through the superior orbital fissure to innervate the extraocular muscles. Note that CN IV enters the orbit outside of the annulus of Zinn. The action of each of the extraocular muscles is a logical consequence of its insertion on the globe and direction of action. The medial and lateral rectus muscles insert anterior to the equator of the globe and pull directly posteriorly, rotating the globe in the horizontal plane. Similarly, the superior and inferior rectus muscles move the eye in the vertical plane. However, the superior and inferior rectus muscles insert at a slight angle relative to the visual axis, so they also cause some torsion and adduction of the globe (inset). The oblique muscles insert posterior to the equator and pull anteromedially (inset). Thus, the superior oblique depresses and the inferior oblique elevates. The torsional forces generated by the oblique muscles should be evident from this diagram.
PRIMARY AND SECONDARY ACTIONS OF THE EXTRAOCULAR MUSCLESa
|Extraocular Muscle||Primary Action||Secondary Action||Tertiary Action|
|Horizontally acting muscles||Lateral rectus||Abducts|
|Vertically acting muscles||Superior rectus||Elevates||Adducts||Intorts|
Neuromuscular disorders often defy classification as being primarily neural or muscular in origin. For example, the pathological changes in muscle tissue with disorders such as chronic progressive external ophthalmoplegia suggests a muscle disease, but denervation can also cause secondary myopathic changes. With this disclaimer in mind, disorders will be discussed that appear primarily to affect the extraocular muscles.
Chronic progressive external ophthalmoplegia (CPEO) is characterized by symmetric and slowly progressive bilateral ptosis and limitation of eye movements. Ptosis usually precedes the other ocular motility defects. Usually, patients do not complain of diplopia (Figure 8–2). CPEO is a mitochondrial myopathy: The muscle disease is the result of dysfunction of the mitochondria in the muscle cells. Light microscopy of limb or extraocular muscle biopsies reveals “ragged red fibers” (with modified Gomori trichrome stain), which consists of subsarcolemmal aggregates of degenerated mitochondria. Electron microscopy shows giant malformed mitochondria and also proliferation of normal-appearing mitochondria. Mitochondrial dysfunction in CPEO is usually the result of mitochondrial DNA deletions, which can be sporadic or heritable in a pattern similar to Leber hereditary optic neuropathy (LHON). There are also autosomal dominant and recessive forms of CPEO, which occur as a result of nuclear DNA mutations that affect production of mitochondrial components. Thus, this clinical entity encompasses a heterogeneous group of sporadic and genetic disorders with different inheritance patterns and presentations, many with systemic signs and symptoms.
Chronic progressive external ophthalmoplegia.
A 27-year-old woman described progressive ptosis over her lifetime. Bilateral ptosis is evident. The patient also had a complete ophthalmoplegia, with inability to move the eyes well in any direction on command or with oculocephalic maneuvers.
In addition to ptosis and ophthalmoplegia, patients with mitochondrial myopathies frequently have weakness of facial and systemic muscles, cardiac conduction abnormalities (potentially fatal), pigmentary retinopathies, and other systemic signs. Kearns-Sayre syndrome (KSS) is a type of CPEO associated with a mitochondrial chromosomal defect recognized as a distinct syndrome (Table 8–2). This disorder is most often diagnosed before 20 years of age. Management should include consultation with a cardiologist because KSS is associated with cardiac conduction defects (including heart block and sudden death).
KEARNS-SAYRE SYNDROME: DIAGNOSTIC CRITERIA
The diagnosis of CPEO or KSS can be made in some patients by genetic testing or muscle biopsy (deltoid or quadriceps muscle). Treatment is largely supportive. Ptosis surgery may be helpful, but the risk of exposure keratopathy must be considered.
Progressive supranuclear palsy (PSP) and ocular myasthenia gravis may be difficult to clinically distinguish from CPEO. However, unlike CPEO, PSP (discussed in Chapter 10) usually occurs in patients 60 years or older, and the oculocephalic reflexes are intact, proving that the extraocular muscles are not the source of the ophthalmoplegia. Patients with myasthenia may have ocular symptoms that vary significantly over time, unlike the steady progression of CPEO.
Myotonic dystrophy is an autosomal dominant systemic myopathy that can cause bilateral ptosis and limited ocular motility. Additional ocular signs include a characteristic polychromatic cataract (present in most adults with the disorder) and a pigmentary maculopathy and retinopathy. Visible (and palpable) wasting of the temporalis and sternocleidomastoid muscles, frontal balding, bilateral ptosis, and facial weakness produce a very characteristic and distinctive appearance (Figure 8–3). Systemic findings include diffuse weakness and atrophy of the muscles of the arms and legs, cognitive deficiencies, hearing loss, testicular atrophy, and cardiac abnormalities. Myotonic contraction, typically worsened by cold or excitement, becomes evident before 20 years of age. The presence of action myotonia (difficulty voluntarily relaxing a muscle after contraction) and percussion myotonia (localized contraction of a muscle when a sharp tap is applied) can distinguish myotonic dystrophy from other myopathies. Clinically, action myotonia may be evident as difficulty releasing after a handshake. With electromyography, the myotonic signature is diagnostic: “Divebomber” discharges demonstrate continued activation of the muscle after attempted relaxation.
Myotonic dystrophy facial appearance.
This photoillustration of a patient with myotonic dystrophy type 1 shows characteristic temporal, jaw, and facial muscle atrophy, with frontal balding. (Reproduced, with permission, from Amato A, Russell J: Neuromuscular Disorders. New York: McGraw-Hill; 2008.)
Oculopharyngeal dystrophy is a hereditary autosomal dominant condition affecting patients of French-Canadian heritage. Patients usually present between 40 and 60 years of age with progressive bilateral ptosis, limited ocular motility, and weakness of the bulbar musculature with dysphagia. Aspiration pneumonia is common and can be prevented by cricomyotomy.
Orbital inflammation can be caused by a wide range of infectious, vasculitic, and idiopathic conditions (Table 8–3). The extraocular muscles are often ivolved, resulting in painful diplopia. Obviously, orbital inflam-matory disorders will also frequently involve other orbital structures, causing optic neuropathy, proptosis, and other ocular signs and symptoms.
ORBTIAL INFLAMMATORY DISORDERS
Idiopathic orbital inflammatory syndrome (IOIS; previously called orbital inflammatory pseudotumor) is characterized by the rapid onset of orbital congestion, proptosis, diplopia, pain, and the lack of identifiable infectious, neoplastic, or other causes (Figure 8–4). IOIS can present as a focal process, primarily affecting the extraocular muscles (orbital myositis), optic nerve, lacrimal gland, or sclera, or may present as a diffuse orbital inflammation (see Table 8–3; subtypes of IOIS). A single extraocular muscle or combination of muscles can be affected. The affected muscles constrict poorly and restrict free movement of the globe. They are usually enlarged on neuroimaging and may enhance with contrast. Systemic vasculitic conditions, sarcoidosis, orbital Graves disease, orbital cellulitis, carotid-cavernous fistulas, and neoplastic processes should be specifically sought and considered because idiopathic orbital inflammatory syndrome is a clinical diagnosis of exclusion (see Table 8–3). The appearance of the tendonous muscle insertion on the globe seen with neuroimaging may help distinguish idiopathic orbital inflammatory syndrome from the muscle enlargement of orbital Graves disease: thickened, involved tendons with IOIS; thin, normal-appearing tendons with orbital Graves disease (although they do sometimes enhance). Patients with IOIS usually experience prompt relief of symptoms with high-dose oral corticosteroids. Failure to respond promptly to corticosteroids should lead the physician to consider other diagnoses with additional testing, such as an orbital biopsy. Patients can usually be successfully tapered off corticosteroids over several months. Recurrence after a slow taper should also prompt reinvestigation of other diagnoses. Non-steroidal anti-inflammatory agents (NSAIDs) may be effective in less severe cases. Radiation treatment of the orbit and steroid-sparing immunosuppressives (cyclophosphamide, cyclosporine, or methotrexate) are a consideration for patients who recur on repeated attempts to taper corticosteroids. This idiopathic inflammatory condition of the orbit is likely a similar process to the painful inflammatory syndrome of the cavernous sinus—the Tolosa-Hunt syndrome (discussed in Chapter 9).
Idiopathic orbital inflammatory syndrome.
A 48-year-old woman presented with 4 months of bilateral periocular pain. One month prior to presentation she developed diplopia in upgaze and redness of the right eye. Her examination showed normal visual acuities and visual fields, but she had focal injection of the medial bulbar conjunctiva of the right eye and a right hypotropia in upgaze. An extensive evaluation did not reveal any systemic, vasculitic, infectious, or neoplastic cause. The patient’s symptoms quickly resolved on oral prednisone, without recurrence after tapering off the medication. (A) At presentation, conjunctival injection of the right eye is evident (1). A right hypotropia in upgaze is identified (2),(3). (B) Magnetic resonance imaging of the orbit at presentation showed abnormal T2 hyperintensity with reticulation in the retro-orbital fat (arrows), seen in this coronal section. (C) An axial T1 sequence with contrast shows prominent enhancement of the insertions of the bilateral superior oblique muscles on the globe (arrows). (D) Coronal view of T1 sequence with enhancement of bilateral superior oblique muscle insertions (arrows).
Restrictive myopathies/orbitopathies cause motility disturbances by mechanically restricting globe movement. The most common restrictive processes include trauma (blowout fractures) and orbital Graves disease; less common entities include inflammatory, infiltrating, and space-occupying lesions. In some orbital processes, a combination of neuropathic, myopathic, and restrictive processes are present and are impossible to separate.
Orbital Graves disease is a common orbital myopathy that has a confusing number of clinical names: Graves orbitopathy, Graves ophthalmopathy, thyroid eye disease, thyroid-associated orbitopathy or ophthalmopathy, and dysthyroid myopathy. Some authorities have reservations regarding the use of the name thyroid eye disease, since thyroid abnormalities are not invariably present and this condition is not caused by thyroid dysfunction. The term Graves disease is unpopular with those who prefer not to use eponyms, and the orbit disease must be distinguished from Graves disease of the thyroid, since these two disorders do not always occur together. In this book, the term orbital Graves disease (or Graves orbitopathy) will be used because this term acknowledges that Graves disease of the thyroid and orbital Graves disease likely have the same (immunological) root cause, and it has historic precedent. The use of orbitopathy is preferred rather than ophthalmopathy because the disease affects the entire orbit, not only the eye.