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Overview of diplopia

Author: Don C Bienfang, MD

Section Editor: Paul W Brazis, MD
Deputy Editor: Janet L Wilterdink, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2018. | This topic last updated: Jun 20, 2017.

INTRODUCTION — Dysfunction of the extraocular muscles may be the result of an abnormality of the muscle
itself or an abnormality of the motor nerve to the muscle. The major symptom associated with this dysfunction is
diplopia. The evaluation of neuromuscular diplopia is reviewed here.

NEUROANATOMY — Three pairs of extraocular muscles move each eye in three directions: vertically (superior
and inferior), horizontally (medial and lateral), and torsionally (intorsion when the eye rotates toward the patient's
nose and extorsion when the eye rotates toward the patient's shoulder). The following muscles are responsible
for these movements (table 1 and figure 1 and figure 2):

● The superior rectus and inferior oblique muscles are responsible for upward vertical movements. The
superior rectus acts in all fields of gaze and the inferior oblique on medial gaze.

● The inferior rectus and superior oblique muscles are responsible for downward vertical movement. The
inferior rectus acts in all fields of gaze, and the superior oblique on medial gaze.

● The lateral rectus is responsible for abduction.

● The medial rectus is responsible for adduction.

● The superior oblique is responsible for intorsion.

● The inferior oblique is responsible for extorsion.

The superior oblique muscle is innervated by cranial nerve IV, the lateral rectus muscle by cranial nerve VI, and
all others by cranial nerve III (table 1).

Details of the neurologic examination with regard to eye movements are discussed separately. (See "The
detailed neurologic examination in adults".)

PRESENTATION/HISTORY

Diplopia — Be sure to determine that the diplopia is present only with both eyes open and absent when either
eye is closed (binocular diplopia). Binocular diplopia suggests that the underlying problem is due to ocular
misalignment; generally, patients will choose to close the eye with the dysfunctional muscle unless that is the eye
with much better vision. Monocular diplopia (persists with one eye closed) suggests local eye disease or
refractive error; this is generally a problem that should be referred to an ophthalmologist and is not discussed
further here. Triple vision or triplopia is a rare complaint in patients with extraocular paresis, usually as a transient
phenomenon in patients with superimposed nystagmus or oscillopsia [1]. Multiple images with one or both eyes
is also a common complaint in patients with nuclear sclerotic cataract.

Important questions to ask the patient with binocular diplopia include:

● In which field of gaze is the double vision worst? The worst position of gaze represents the field of action of
a paretic muscle (eg, with a right lateral rectus palsy, diplopia is greatest on right lateral gaze). If a muscle is
restricted however, as in thyroid disease, the double vision is worst when trying to stretch the muscle, that is,
opposite to its field of action. Thus, a patient with thyroid ophthalmopathy cannot look up because the
inferior rectus is tight, not because the superior rectus is weak.

● In which field of gaze are the double images closest together?

● Is the separation of images vertical, horizontal, or oblique?

● Is there any corrective head position that makes the double vision tolerable?

● Is the double vision worse at a distance (typical of a sixth nerve palsy) or is it worse at near (typical of a
medial rectus palsy)?

Some patients lack diplopia despite obvious ocular misalignment. There may be a number of explanations for
this finding:

● Vision may be suppressed in one eye because of an old strabismus. Some patients with strabismus can
develop a type of peripheral double vision if they have anomalous retinal correspondence, which is then
followed by the original angle of the double vision changing because of neuromuscular disease or a change
in the angle of the strabismus with age.

● Patients may have decreased vision in one eye, in which case the double vision will only be for objects large
enough to see by the eye with poor vision.

● Some patients have such a wide separation of the images that they are able to ignore one of the images
because it is far out of alignment with the true straight-ahead image.

● Some patients have such a minimal separation of the images that they cannot appreciate that they are
seeing two images. They complain, instead, of "blurred vision", which is really a combination of two images.

● Some patients will have a misalignment only when the eyes are moving. However, vision is suppressed
when the eyes are moving so that they are not aware of a double vision.

Pain — Ask the patient about the presence or absence of any ocular, orbital, or periorbital pain and request that
the patient point to the location of the pain. Painful ophthalmoplegia has a specific differential diagnosis that is
distinct from painless ophthalmoplegia (table 2).

● Diffuse intracranial pathology is suggested by complaints of a generalized headache or pain in the area of
the temple. In contrast, it is most likely that the patient has an isolated lesion of one of the cranial nerves if
the pain is localized to the area just above the eyebrow on the side of the weak muscle.

● Intraorbital pathology should be considered in patients with pain localized directly to the eye.

● Sudden onset of head pain described as the worst ever experienced should be a cause for concern and
suggests an intracranial aneurysm. (See "Clinical manifestations and diagnosis of aneurysmal subarachnoid
hemorrhage".)
 ● Another worrisome type of pain is one that is severe, requires heavy opiate-type medication, and is
distributed to the area of the first or second division of the fifth cranial nerve. It is important in such cases to
carefully test for sensory loss in the area of the forehead and cheek; such a symptom often indicates that
there is a tumor pressing on the fifth cranial nerve as well as the affected nerve to the eye muscle.

● Pain on eye movement suggests a myopathy or an orbital process. Pain on eye movement but without
double vision is also typical of optic neuritis.

Tempo of the problem — Ask the duration of the problem. Sometimes old photographs are useful in doubtful
cases. Old photographs are particularly helpful in cases of lid ptosis, fourth nerve palsy, and pupillary
abnormalities.

Was the onset sudden and has now plateaued, or gradual with steady worsening? Did the pain precede the
palsy and resolve shortly after the palsy started? This is a particularly good sign; it is typical of idiopathic or
ischemic etiologies (eg, due to diabetes mellitus).

Does the motility problem change as the day goes on? This is a typical sign of myasthenia gravis but myasthenia
gravis is not necessarily the only cause of this symptom.

Finally, one should ask a broad question about any other symptoms, particularly neurologic symptoms, that
occurred with the double vision.

EXAMINATION

Pupil — When the parasympathetic fibers of the third nerve are involved, resulting in pupillary dilation in
association with other dysfunction of the third cranial nerve, it is a warning sign of a compressive lesion of the
third nerve, typically an aneurysm or, less commonly, a tumor. (See "Approach to the patient with anisocoria".)

Other cranial nerves — The second important observation is the possible involvement of any other cranial
nerves. Mononeuropathies (dysfunction of only one cranial nerve) are often idiopathic. However,
polyneuropathies require a full and extensive neuroradiologic and laboratory workup. Of particular importance
are processes that involve the nerves near the third, fourth, and sixth cranial nerves. As examples: the second
cranial nerve is concerned with vision, the pupillary light reaction, and visual fields; the fifth cranial nerve is
responsible for facial and corneal sensation; abnormalities of the seventh cranial nerve may cause facial droop
or weakness of the orbicularis oculi muscle; pathology of the eighth cranial nerve can be suggested by dizziness
or loss of hearing. (See "The detailed neurologic examination in adults", section on 'Cranial nerve examination'.)

Globe — Another important associated observation is the presence or absence of any forward protrusion of the
eye, exophthalmos (suggestive of Grave's disease). To assess for the presence of exophthalmos, I like to have
the patient look down while I retract the upper lids and I look down past the patient's brow to compare the
forward location of the two corneas. A small amount of upper lid ptosis, often present in these cases, will mask
the appearance of exophthalmos as viewed from straight ahead. In testing for orbital resiliency, that is how easily
can one retroplace the globe digitally, I stand to the side of the patient and observe the eye going back when I
press with my finger. This gives me a visual and tactile input.

Observe whether the eyeball is congested. Ask the patient to assume the head position that maximizes the
double vision and the one that minimizes the double vision. Is there any droopiness of the lid?

Ocular motility — Details of the neurologic examination with regard to eye movements are discussed
separately. (See "The detailed neurologic examination in adults".)

It is often enough merely to observe the eye movement in the right, left, up, and down gaze (figure 2). In the
more profound expressions of ocular motility disturbance, the astute observer can determine which muscle is
dysfunctional by making these observations alone. The following are some simple rules:

● If the double vision is worse on looking to one side and better looking to the other, and if the eyes appear
crossed, the problem is most likely that the lateral rectus muscle is not working. Usually this is due to a sixth
nerve palsy.

● If there is some droopiness of the lid and if any combination of the following things is present — poor inward
turning, poor elevation, or poor depression of the eye, then there is probably at least a partial third nerve
palsy.

● If the patient likes to tilt his head to get better vision and if the double vision is primarily vertical and worst
looking to one side and down, there is probably a fourth nerve palsy.

With most patients one can hold a finger vertically or horizontally and move it into different fields of gaze asking
in which field of gaze the image separation is the worst and in which it is the best. While you hold the finger in the
field of gaze with the worst double vision, cover one eye and ask which image disappears. With a vertical
diplopia, when the higher image disappears the eye you covered is lower in position than its partner is and vice-
versa. With horizontal diplopia, when the image to the right of the other image disappears, the eye you covered
is pointed to the left of its partner. Crossed diplopia means uncrossed eyes and vice-versa.

A relatively simple office test that can be helpful is use of a red glass over one eye. This device helps the patient
identify the two images more clearly and helps the clinician identify from which eye each image is coming.
However, the results of this test should be interpreted with caution; some patients seem to be able to fuse the red
and white light with effort. Also, some patients give interpretations which I find confusing, saying for instance, that
they see one light on top of the other when they mean that the lights are superimposed.

Restrictive ophthalmoplegia — If a patient has a tight and fibrous or entrapped muscle, attempted gaze in
the direction away from the field of action of the muscle will result in a rise in intraocular pressure. A rise of 7
mmHg is considered diagnostic of restrictive ophthalmopathy. On examination, the patient will appear to have a
weakness of the opponent muscle due to failure of relaxation of the restricted muscle. A patient with Graves'
disease will frequently have this problem due to fibrosis of the inferior rectus muscle. In such cases, on
attempted upward gaze the intraocular pressure will rise.

Quantitation — There are several ways to precisely measure the amount of eye deviation. Prism
measurements are commonly used since this number is necessary if the ultimate goal is to correct the deviation
with a prism in the glasses, or at least to help the patient with a prism.

ETIOLOGY/DIAGNOSIS — Neuromuscular diplopia may arise due to a number of causes, including a

neurogenic lesion (supra-, inter-, or infranuclear), a neuromuscular transmission defect, myopathy, or mechanical
restriction in the orbit. An exhaustive summary of these etiologies is the subject of other reviews [2,3]. Some
helpful clues in patients with vertical or horizontal diplopia and some of the more common acquired causes of
diplopia are discussed here.

Vertical diplopia — Patients with vertical diplopia complain of seeing two diagonally displaced images, one atop
the other. There are many causes of vertical diplopia (table 3).

Vertical diplopia in primary gaze suggests underactivity of the right or left inferior rectus, superior rectus, inferior
oblique, or superior oblique [3]. If vertical separation is worse on right gaze, the right superior or inferior rectus or
the left inferior or superior oblique may be underactive; separation that is worse looking to the right and down
suggests underactivity of the right inferior rectus or left superior oblique. Torsional abnormalities due to oblique
muscle involvement should be suspected in patients who complain of image separation that worsens or improves
with left or right head tilt.
The direction of compensatory head tilt may provide further diagnostic clues. Underaction of the superior or
inferior rectus muscles is compensated by chin flexion or extension. Torsional diplopia due to underaction of the
oblique muscles may be associated with an angular head tilt.

Hypertropia refers to an upward vertical displacement of one eye in primary gaze. A right hypertropia occurs with
paresis of the right eye depressors (right inferior rectus or superior oblique) or left eye elevators (left superior
rectus or inferior oblique). If the right hypertropia increases in left gaze, either the right superior oblique or the left
superior rectus muscle is underacting. If the vertical deviation increases with right head tilt, the right superior
oblique muscle is weak [3].

A skew eye deviation presenting with hypertropia and vertical diplopia can result from an imbalance in the
vestibular system. In such patients, the diplopia typically does not match ocular muscle function and the
deviation changes when the patient is tested sitting versus lying down. These features can distinguish a skew
eye deviation from extraocular paresis.

Horizontal diplopia — Horizontal diplopia is usually due to disease processes that affect the medial or lateral
rectus muscles or the innervation of these muscles [2]. The images appear side by side; as mentioned above,
image separation that is worse at a distance is typical of a sixth nerve palsy, while image separation that is worse
at near is typical of a medial rectus palsy. An esotropia refers to a medial deviation of the eye at primary gaze, an
exotropia refers to lateral deviation in primary gaze. There are many causes of horizontal diplopia (table 4) [2].

Fourth cranial nerve palsy — Cranial nerve IV palsy is a common cause of vertical diplopia [3]. Most fourth
nerve palsies are either traumatic or idiopathic.

Congenital — Patients with congenital fourth nerve palsy are often able to compensate for the double vision
with a head tilt that minimizes symptoms. Over time, however, they may have increasing difficulty controlling the
symptoms and present with diplopia. The patient may insist that this is a new problem, although old photos
frequently demonstrate a head tilt [4]. A peculiar feature of congenital fourth nerve palsy is that the amount of
hypertropia in the primary position is very large (deviations as high as 20 or 30 prism diopters). A true acquired
fourth nerve palsy of recent onset will have a hypertropia that measures prism diopters in the mid-teens in the
primary position at the most [5].

Traumatic — Traumatic fourth nerve palsies, in contrast to traumatic third and sixth nerve palsies, may occur
with a relatively mild blow to the head that is not associated with loss of consciousness or a skull fracture [6].
Some traumatic fourth nerve palsies improve with time, but most do not. Careful examination is important to
exclude bilateral fourth nerve palsies which can be very asymmetrical; it is unfortunate for a surgeon to have
corrected a fourth nerve palsy by weakening the ipsilateral inferior oblique muscle, only to find a contralateral
fourth nerve palsy now uncovered and obvious to the patient [7-9].

Idiopathic — Idiopathic fourth nerve palsies, like idiopathic third and sixth nerve palsies, often present with
pain over the eyebrow of the affected eye that stops shortly after the diplopia starts [10-12]. When asked to point
to the pain, patients usually indicate an area just above the brow on the side of the muscle weakness. Rarely
does the pain require medication. The best time to diagnose a third, fourth, or sixth nerve palsy is early in its
course. If the palsy does not resolve there is a tendency for the deviation to become more "comitant." This
means the hypertropia, esotropia, or exotropia that was once limited largely to one field of gaze will creep into
the opposite field due to the contraction and thus overaction of the antagonistic muscle [13].

Other — Rarely a fourth nerve palsy can be due to raised intracranial pressure [14]. It is important to look
carefully at the optic nerve head to be sure that there is no papilledema.

The fourth nerve exits from the dorsum of the brainstem. Thus, neurologic signs of cerebellar disease may be
present if a tumor in that region is causing the fourth nerve palsy.
Most fourth cranial nerve palsies are either idiopathic or traumatic. The idiopathic ones usually resolve in a few
weeks. I typically postpone neuroradiologic testing until two months have passed without improvement as long
as the other cranial nerves are normal [15,16].

Third cranial nerve palsy — Third cranial nerve palsies may cause both vertical and horizontal diplopia.
Patients with a complete unilateral third nerve palsy have ptosis, a large unreactive pupil, and paralysis of
adduction, elevation, and depression; the eye rests in a position of abduction, slight depression, and intorsion [3].
The asymmetry of pupil size is greater in the light than in the dark.

Absence of pupillary involvement suggests a benign process that can be observed over a couple of weeks. A
fixed, dilated pupil requires extensive neurologic evaluation. Partial involvement of the pupil (defined in one
report as anisocoria greater than 0.5 but less than 2.0 mm in room light, and whose affected pupil maintained
reactivity to light) may be associated with either serious or benign underlying pathologies; neuroimaging is
indicated in these individuals [17].

This topic is discussed separately. (See "Third cranial nerve (oculomotor nerve) palsy in adults" and "Third
cranial nerve (oculomotor nerve) palsy in children".)

Sixth nerve palsy — Patients with sixth cranial nerve palsies primarily complain of horizontal diplopia, although
they may also complain of slight vertical diplopia. On examination there is an esotropia (inward deviation) that is
worsened with gaze into the field of the weak lateral rectus muscle. To limit diplopia, patients may assume a
compensatory face turn in the direction of the paralyzed muscle [2]. Abduction is commonly limited on the side of
the lesion.

Patients with idiopathic sixth nerve palsy often present with the sudden onset of horizontal diplopia that is better
at near and worse at a distance. There may be minor pain over the affected eyebrow at the onset of the double
vision, but no disturbing pain distributed over the forehead or face. The remainder of the neurologic examination
is normal [18]. Poorly controlled diabetes is a predisposing factor, and one population-based study found that
patients with isolated six nerve palsy had a six-fold increase in the odds of diabetes compared with controls [19].
Other causes of sixth nerve palsy are shown in the Table (table 5).

A sudden onset distinguishes idiopathic sixth cranial nerve palsies from tumor or myasthenia gravis.
Spontaneous improvement over several weeks to months is expected, and failure to improve suggests more
serious intracranial pathology. As an example, in a study of 213 patients with unilateral isolated sixth nerve
palsies in whom trauma was excluded, 78 percent experienced spontaneous recovery of their palsy, 37 percent
recovering by 8 weeks and 74 percent by 24 weeks [20]. Only 16 percent failed to recover; of this group,
however, almost 40 percent had serious underlying pathology accounting for their palsy.

Patients with bilateral sixth nerve palsy will have progressive horizontal double vision as a presenting symptom.
The point of least inward turn will always be to the side of the stronger lateral rectus. One may have to depend
upon observation of the abducting eye to decide if both lateral recti are weak. This decision is very important. An
ominous sign in any cranial nerve palsy is the involvement of any other cranial nerve, even its partner on the
other side [21]. The sixth nerve is a case in point because it has a long and relatively isolated course after it exits
the brainstem, climbs up the clivus, and passes through the cavernous sinus. This allows certain tumors to affect
both sixth nerves before any other parts of the brain are affected [22-24].

Other nerves to pay particular attention to when dealing with sixth nerve palsies are the fifth nerve, pointing to a
lesion in the cavernous sinus, and papilledema, suggesting a mass lesion causing raised intracranial pressure
and displacement of the brainstem and thus stretching of one or both sixth nerves. Involvement of cranial nerve
V causes reduced facial sensation, often around the upper face and cornea. Despite the anesthesia in this area,
however, patients with mass lesions may complain of severe pain around the eye (often requiring opiates).
Internuclear ophthalmoplegia — Internuclear ophthalmoplegia is a specific gaze abnormality characterized by
impaired horizontal eye movement with weak adduction of the affected eye and abduction nystagmus of the
contralateral eye. This results from a lesion (usually stroke or demyelination) in the medial longitudinal fasciculus
in the dorsomedial brainstem tegmentum of either the pons or the midbrain. (See "Internuclear
ophthalmoparesis".)

Myasthenia gravis — The extraocular eye muscles are often involved in myasthenia gravis (MG). The clinical
manifestations vary from subtle blurring of vision to severe diplopia. MG-induced diplopia can mimic an
internuclear ophthalmoplegia. Weakness of the eye muscles in MG can also produce ptosis, the degree of which
is variable, switching from one eye to the other on separate examinations and occasionally increasing with
sudden exposure to bright light. Most patients with MG do not complain of eye pain or headache. Fatigability and
variability of clinical findings are characteristic.

Physical examination may reveal unusual eye movements that do not conform to the anatomy of one nerve or
muscle. The pupils are always spared in MG, helping in the differentiation from other disorders such as botulism.
The diagnosis and treatment of myasthenia gravis is discussed separately. (See "Ocular myasthenia gravis".)

Thyroid ophthalmopathy — Thyroid ophthalmopathy is a common cause of horizontal or vertical diplopia.

Restriction of extraocular movement preferentially affects the inferior rectus, medial rectus, and superior rectus,
in that order [3]. Because the process causes muscle tightness or restriction, the diplopia is worse in the direction
opposite that of the involved muscle action [2]. Thus, hypertropia (upward vertical deviation) and esotropia
(medial deviation) are common in patients with thyroid ophthalmopathy, but exotropia (lateral deviation) is
uncommon because the lateral rectus muscle is usually not involved.

Limitation in elevation of one or both eyes with vertical misalignment is the most common defect of ocular motility
in these individuals. The other characteristic signs of thyroid ophthalmopathy include proptosis and periorbital
edema. (See "Clinical features and diagnosis of Graves' orbitopathy (ophthalmopathy)".)

Ophthalmoplegic migraine — Ophthalmoplegic migraine is rare and most often seen in children and young
adults. It is a diagnosis that should be made only after other disorders have been ruled out. It may affect the third
(most common), fourth, or sixth cranial nerves. Extraocular muscle paralysis can occur with the first attack of
headache or, rarely, precede it. Permanent damage to the third nerve has been reported [25]. Other causes of
painful ophthalmoplegia (eg, aneurysm) should be excluded with neuroimaging studies.

Ophthalmoplegic migraine is now considered a cranial neuralgia because MRI gadolinium enhancement of the
cisternal segment of the affected cranial nerve has been demonstrated in patients with a typical clinical
presentation, suggesting that the condition may be a recurrent demyelinating neuropathy. (See "Pathophysiology,
clinical manifestations, and diagnosis of migraine in adults".)

Wernicke's syndrome — Wernicke's syndrome is caused by thiamine deficiency and is typically associated with
alcohol abuse. Patients with Wernicke's encephalopathy may complain of vertical diplopia due to a supranuclear
or nuclear lesion [3]. (See "Wernicke encephalopathy".)

Orbital myositis — Orbital myositis is an idiopathic inflammation of an extraocular muscle. The diagnosis should
be considered in patients who have seemingly isolated extraocular muscle dysfunction, especially in the
distribution of cranial nerve III.

Patients present with acute or subacute orbital pain and horizontal diplopia; absence of pain suggests an
alternate diagnosis [26,27]. On physical examination there may be conjunctival chemosis and injection, ptosis,
and proptosis. The process can be unilateral or bilateral. Neuroimaging reveals a focal or diffuse inflammatory
lesion. The disorder usually resolves with corticosteroids [28], particularly in severe cases, although in my
experience corticosteroids tend to prolong the course of what might otherwise be a self-limited illness.
Tolosa-Hunt syndrome — The Tolosa-Hunt syndrome is a rare syndrome, which is characterized by painful
ophthalmoplegia and is caused by an idiopathic granulomatous inflammation of the cavernous sinus. This
syndrome responds to corticosteroid therapy.

While considered a benign condition, permanent neurologic deficits can occur, and relapses are common, often
requiring prolonged immunosuppressive therapy. Tolosa-Hunt syndrome must also be carefully differentiated
from more commonly occurring malignancies and infections involving the cavernous sinus, a task made difficult
by the lack of a specific diagnostic test abnormality. (See "Tolosa-Hunt syndrome".)

Others — A number of other pathologies can lead to diplopia and/or ophthalmoplegia [29].

● Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) can affect the extraocular
muscle function as a presenting manifestation. This is often referred to as the Fisher or Miller Fisher variant.
Typically, deep tendon reflexes are also absent. (See "Guillain-Barré syndrome in adults: Clinical features
and diagnosis".)

● Tick bite paralysis and botulism are neuromuscular junction pathologies that can lead to extraocular muscle
weakness. (See "Botulism" and "Tick paralysis".)

● Structural lesions (metastases, infections) affecting the skull base cavernous sinus can lead to a cranial
polyneuropathy with diplopia as the primary manifestation.

● Giant cell arteritis can present with diplopia, usually with other suggestive clinical features. (See "Clinical
manifestations of giant cell arteritis".)

DIAGNOSTIC APPROACH — It is difficult to establish a standard guideline for the evaluation of diplopia.
Multiple possible etiologies exist, many of which can be serious. Some important caveats are helpful:

● The first rule is to determine if a single nerve is involved. Involvement of other nerves, even the opposite
cranial nerve (eg, bilateral sixth nerve palsy), suggests a more serious underlying disorder and requires
more extensive evaluation, including neuroimaging (See "Tolosa-Hunt syndrome", section on 'Differential
diagnosis' and "Tolosa-Hunt syndrome", section on 'Diagnostic evaluation'.)

● The second question is whether there is a medical excuse for the problem. As an example, one is more
likely to work up a young person with a sixth nerve palsy than an older person in his seventies.

● Signs of improvement over time almost always means the process is benign. Isolated fourth or sixth never
palsies can be observed for a few weeks. More extensive work-up should be done if the palsy does not
resolve or if other symptoms appear.

● The presence of severe headache of sudden onset demands an urgent evaluation for cerebral aneurysm.

SUMMARY AND RECOMMENDATIONS

● Binocular diplopia (double vision with both eyes open and absent when either eye is closed) often results
from dysfunction of one or more of the extraocular muscles. In contrast monocular diplopia, which persists
when one eye is closed, suggests local eye disease or a refractive problem. (See 'Presentation/history'
above.)

● Three pairs of extraocular muscles move each eye in three directions: vertically (superior and inferior),
horizontally (medial and lateral), and torsionally (intorsion when the eye rotates toward the patient's nose
and extorsion when the eye rotates toward the patient's shoulder) (table 1 and figure 1 and figure 2). (See
'Neuroanatomy' above.)
● The presence or absence of pain is an important distinguishing feature in considering a differential diagnosis
(table 2). (See 'Presentation/history' above.)

● The examination should focus on establishing which particular extraocular muscle or muscles may be weak.
The presence of pupillary or other cranial nerve abnormality and other ocular findings are also important.
(See 'Examination' above.)

● When the pattern of muscle weakness suggests that the problem is isolated to a single cranial nerve, the
differential diagnosis is specific to the individual nerve:

• For third nerve palsies, the presence or absence of pupillary involvement and other associated signs is
critical to localization and diagnosis (table 6) (See "Third cranial nerve (oculomotor nerve) palsy in
adults" and "Third cranial nerve (oculomotor nerve) palsy in children".)

• Most fourth cranial nerve palsies are idiopathic or traumatic in etiology. (See 'Fourth cranial nerve palsy'
above.)

• Sixth nerve palsies cause isolated weakness of abduction, and may result from poorly controlled
diabetes, among other causes (table 5). Bilateral sixth nerve palsies may be seen in elevated
intracranial pressure. (See 'Sixth nerve palsy' above.)

● Internuclear ophthalmoplegia is a specific gaze abnormality characterized by impaired horizontal eye

movement with weak adduction of the affected eye and abduction nystagmus of the contralateral eye. This
results from a lesion (usually stroke or demyelination) in the medial longitudinal fasciculus in the
dorsomedial brainstem tegmentum of either the pons or the midbrain. (See "Internuclear
ophthalmoparesis".)

● The extraocular eye muscles are often involved in myasthenia gravis (MG). Multiple extraocular muscles in
both eyes are typically involved and ptosis is also often present. Fatigability and variability of clinical findings
are characteristic clues to this diagnosis. (See "Ocular myasthenia gravis".)

● Thyroid ophthalmopathy leads to muscle tightness and restriction of movement. Proptosis is usually also
present. (See "Clinical features and diagnosis of Graves' orbitopathy (ophthalmopathy)".)

● Other causes of binocular diplopia affecting multiple, bilateral extraocular muscles include: orbital myositis,
Tolosa-Hunt syndrome, Miller Fisher variant of acute inflammatory demyelinating polyneuropathy, and
structural and/or inflammatory lesions involving the skull base cavernous sinus, or basilar meninges. (See
'Etiology/diagnosis' above.)

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REFERENCES

1. Keane JR. Triplopia: thirteen patients from a neurology inpatient service. Arch Neurol 2006; 63:388.
2. Brazis PW, Lee AG. Acquired binocular horizontal diplopia. Mayo Clin Proc 1999; 74:907.
3. Brazis PW, Lee AG. Binocular vertical diplopia. Mayo Clin Proc 1998; 73:55.
4. Brazis PW. Palsies of the trochlear nerve: diagnosis and localization--recent concepts. Mayo Clin Proc
1993; 68:501.
5. Mittelman D, Folk ER. The evaluation and treatment of superior oblique muscle palsy. Trans Sect
Ophthalmol Am Acad Ophthalmol Otolaryngol 1976; 81:893.
 6. Sydnor CF, Seaber JH, Buckley EG. Traumatic superior oblique palsies. Ophthalmology 1982; 89:134.
7. Helveston EM, Mora JS, Lipsky SN, et al. Surgical treatment of superior oblique palsy. Trans Am
Ophthalmol Soc 1996; 94:315.
8. Kushner BJ. The diagnosis and treatment of bilateral masked superior oblique palsy. Am J Ophthalmol
1988; 105:186.
9. Lee J, Flynn JT. Bilateral superior oblique palsies. Br J Ophthalmol 1985; 69:508.
10. Coppeto JM, Lessell S. Cryptogenic unilateral paralysis of the superior oblique muscle. Arch Ophthalmol
1978; 96:275.
11. von Noorden GK, Murray E, Wong SY. Superior oblique paralysis. A review of 270 cases. Arch Ophthalmol
1986; 104:1771.
12. Beard CM, Benson RC Jr, Kelalis PP, Elveback LR. Incidence of malignant testicular tumors in the
population of Rochester, Minnesota, 1935 through 1974. Mayo Clin Proc 1977; 52:8.
13. Ellis FD, Helveston EM. Superior oblique palsy: diagnosis and classification. Int Ophthalmol Clin 1976;
16:127.
14. Halpern JI, Gordon WH Jr. Trochlear nerve palsy as a false localizing sign. Ann Ophthalmol 1981; 13:53.
15. Bagolini B, Campos EC, Chiesi C. Plagiocephaly causing superior oblique deficiency and ocular torticollis.
A new clinical entity. Arch Ophthalmol 1982; 100:1093.
16. Keane JR. Fourth nerve palsy: historical review and study of 215 inpatients. Neurology 1993; 43:2439.
17. Jacobson DM. Relative pupil-sparing third nerve palsy: etiology and clinical variables predictive of a mass.
Neurology 2001; 56:797.
18. Bixenman WW, von Noorden GK. Benign recurrent VI nerve palsy in childhood. J Pediatr Ophthalmol
Strabismus 1981; 18:29.
19. Patel SV, Holmes JM, Hodge DO, Burke JP. Diabetes and hypertension in isolated sixth nerve palsy: a
population-based study. Ophthalmology 2005; 112:760.
20. King AJ, Stacey E, Stephenson G, Trimble RB. Spontaneous recovery rates for unilateral sixth nerve
palsies. Eye (Lond) 1995; 9 ( Pt 4):476.
21. Gutman I, Levartovski S, Goldhammer Y, et al. Sixth nerve palsy and unilateral Horner's syndrome.
Ophthalmology 1986; 93:913.
22. Insel TR, Kalin NH, Risch SC, et al. Abducens palsy after lumbar puncture. N Engl J Med 1980; 303:703.
23. Kline LB, Glaser JS. Bilateral abducens nerve palsies from clivus chordoma. Ann Ophthalmol 1981; 13:705.
24. Neuberger J, Bone I. Bilateral sixth cranial nerve palsy in infectious mononucleosis. Postgrad Med J 1979;
55:433.
25. Bartleson JD. Transient and persistent neurological manifestations of migraine. Stroke 1984; 15:383.
26. Slavin ML, Glaser JS. Idiopathic orbital myositis: report of six cases. Arch Ophthalmol 1982; 100:1261.
27. Smith JL, Taxdal DS. Painful ophthalmoplegia. The Tolosa-Hunt syndrome. Am J Ophthalmol 1966;
61:1466.
28. Mombaerts I, Koornneef L. Current status in the treatment of orbital myositis. Ophthalmology 1997;
104:402.
29. Keane JR. Bilateral ocular paralysis: analysis of 31 inpatients. Arch Neurol 2007; 64:178.

Topic 5238 Version 7.0

GRAPHICS

Actions of extraocular muscles

Nerve and Tertiary

Primary action Secondary action
muscle action

Cranial nerve III

Superior rectus Elevation (maximal on lateral Intorsion Adduction

gaze)

Inferior rectus Depression (maximal on lateral Extorsion Adduction

gaze)

Medial rectus Adduction None None

Inferior oblique Excyclotorsion Elevation (maximal on medial Abduction

gaze)

Cranial nerve IV

Superior oblique Incyclotorsion Depression (maximal on medial Abduction

gaze)

Cranial nerve VI

Lateral rectus Abduction None None

Graphic 72952 Version 1.0

Extraocular muscles

Each eye has six extraocular muscles, which are yoked in pairs.

Reproduced with permission from: Lavin, PJM. Eye movement disorders and diplopia.
In: Neurology in Clinical Practice: Principles of Diagnosis and Management, 2nd ed,
Bradley, WG (Ed), Butterworth-Heinemann, Boston 1996. p. 185. Copyright © 1996
Elsevier.

Graphic 75770 Version 1.0

Diagnostic positions of gaze

The nine diagnostic positions of gaze, used for testing versions (saccades and
pursuit). Pure elevation (supraduction) and depression (infraduction) of the eyes
are predominantly functions of the superior and inferior rectus muscles,
respectively, with some help from the oblique muscles. The eyes are rotated
directly upward primarily by the superior rectus with some help from the inferior
oblique; the eyes are rotated directly downward primarily by the inferior rectus
with some help from the superior oblique.

Reproduced with permission from: Lavin, PJM. Eye movement disorders and diplopia.
In: Neurology in Clinical Practice: Principles of Diagnosis and Management, 2nd ed,
Bradley, WG (Ed), Butterworth-Heinemann, Boston 1996. p. 185. Copyright © 1996
Elsevier.

Graphic 58849 Version 1.0

Causes of painful ophthalmoplegia

(1) Trauma:

(2) Vascular:

Intracavernous carotid artery aneurysm

Posterior cerebral artery aneurysm

Carotid-cavernous fistula

Carotid-cavernous thrombosis

Posterior communicating artery aneurysm

Internal carotid artery dissection

(3) Neoplasm:

Primary intracranial tumour

Pituitary adenoma

Meningioma

Craniopharyngioma, others

Primary cranial tumour

Chordoma, others

Local metastases

Nasopharyngeal tumour

Squamous cell carcinoma

Distant metastases

Lymphoma

Multiple myeloma

Carcinomatous metastases

(4) Inflammation, infection:

Bacterial

Contiguous sinusitis

Mucocele (sphenoid sinus)

Periostitis

Abcess

Viral

Herpes zoster

Fungal

Mucormycosis, Actinomycosis

Spirochetal

Treponema pallidum

Mycobacterial

Mycobacterium tuberculosis

Others

Sarcoidosis

Wegener's granulomatosis

Eosinophilic granuloma

Tolosa-Hunt syndrome
 Orbital pseudotumor

(5) Miscellaneous:

Diabetic ophthalmoplegia

Ophthalmoplegic migraine

Giant cell arteritis

Data from: Kline LB, Hoyt WF. The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry 2001; 71:577.

Graphic 77825 Version 3.0

Causes of binocular vertical diplopia and hypertropia-hyperphoria
Supranuclear causes
Supranuclear monocular elevation paresis (congenital
or acquired)
Skew deviation
Vertical one-and-a-half syndrome
Wernicke's syndrome
Paroxysmal superior rectus and levator palpebrae
spasm with multiple sclerosis
Ocular motor nerve dysfunction
Third cranial nerve palsy
Fourth cranial nerve palsy
Superior oblique myokymia
Ocular neuromyotonia
Ophthalmoplegic migraine
Wernicke's syndrome
Fisher's syndrome
Guillain-Barré syndrome
Sixth cranial nerve palsy
Decompensation of a long-standing phoria
Neuromuscular junction disease
Myasthenia gravis
Botulism
Diseases of eye muscle
Isolated paresis of a vertical-acting extraocular
muscle, superior oblique, inferior oblique, superior
rectus, or inferior rectus (for example, due to
congenital causes, myasthenia gravis, Graves' disease,
botulism, trauma, postoperative sequelae, trochleitis,
orbital metastasis, orbital pseudotumor, and muscle
ischemia resulting from giant cell arteritis)
Decompensation of a long-standing phoria
Graves' disease
Chronic progressive external ophthalmoplegia
syndromes
Postsurgical (eg, cataract operation)
Congenital strabismus syndromes
Dissociated vertical deviation
Congenital "double elevator" palsy (monocular
elevation deficiency)
Double depressor paralysis (unilateral paralysis of the
inferior rectus and superior oblique) (congenital or
acquired)
Physiologic hyperdeviation on lateral gaze
Mechanical processes causing vertical eye
misalignment
Graves' disease
Brown's superior oblique tendon sheath syndrome
Congenital
Acquired (for example, due to superomedial orbital
trauma, tenosynovitis or myositis, adhesions, metastasis
to the superior oblique muscle, frontal sinus osteoma,
pansinusitis, peribulbar anesthesia, blepharoplasty,
maxillofacial or sinus surgery, and superior oblique tuck)
Acquired Brown's syndrome associated with
underaction of the ipsilateral superior oblique muscle
("canine tooth syndrome")
Orbital floor blow-out fracture
Direct trauma to the extraocular muscles (for
example, intramuscular hematoma)
Congenital inferior rectus fibrosis
Strabismus fixus (generalized fibrosis of extraocular
muscles)
Postoperative sequelae (including retinal detachment
surgery, orbital surgery, strabismus surgery, and
cataract surgery)
Orbital inflammation (myositis) and pseudotumor
Metastatic infiltration of extraocular muscles
Orbital tumors Fallen eye syndrome (patient with long-
standing superior oblique muscle paresis who
habitually fixates with the paretic eye may have
development of hypodeviation of the uninvolved eye
caused by contracture of the contralateral inferior
rectus muscle)
Rising eye syndrome (long-standing inferior oblique
muscle palsy may result in contracture and fibrosis of
the contralateral superior rectus muscle)
Hemifield slip, retinal disease, and
fictitious diplopia
Hemifield slip phenomenon resulting from dense
bitemporal hemianopsia or heteronymous altitudinal
field defects
Foveal displacement syndrome (eg, due to subretinal
or preretinalneovascular membranes)
Fictitious (nonorganic) vertical diplopia
 (asymptomatic)

Reproduced with permission from: Lee AG, Brazis PW. Clinical Pathways in Neuro-Ophthalmology: An Evidence-Based
Approach. Thieme, New York 2002. Copyright © 2002 Thieme Medical Publishers.

Graphic 52647 Version 9.0

Causes of acquired binocular horizontal diplopia

Causes of esotropia Causes of exotropia

Childhood strabismus syndromes (see Table 2) Childhood strabismus syndromes (see Table 2)

Change of angle of preexisting childhood strabismus or Change of angle of preexisting childhood strabismus or
loss of suppression scotoma loss of suppression scotoma

Decompensation of a long-standing esophoria Decompensation of a long-standing exophoria

Consecutive esotropia (after strabismus surgery) Consecutive exotropia (after strabismus surgery)

Optical (eg, optical center change in glasses, Optical factors

overminus in accommodative esophoria)
Sensory exotropia (usually not associated with
Sensory esotropia (usually not associated with diplopia)
diplopia)
Disorders of the muscle
Disorders of muscle and restrictive syndromes Orbital myositis (orbital pseudotumor)
Orbital myositis (orbital pseudotumor) Thyroid eye disease (uncommon)
Thyroid eye disease Myasthenia gravis
Myasthenia gravis Medial orbital wall fracture
Medial orbital wall fracture Postsurgical exotropia
Postsurgical esotropia Isolated weakness of medial rectus muscle
Isolated weakness of lateral rectus muscle Muscle trauma
Muscle trauma Progressive external ophthalmoplegia syndromes
Progressive external ophthalmoplegia syndromes Other orbital disease processes
Other orbital disease processes
Disorders of cranial nerves
Disorders of cranial nerves Third nerve palsy
Sixth nerve palsy Ocular neuromyotonia
Ocular neuromyotonia
Central disorders
Central disorders Acquired motor fusion deficiency
Cyclic esotropia Internuclear ophthalmoplegia (INO) (wall-eyed
Periodic alternating esotropia monocular INO syndrome and wall-eyed bilateral INO
syndrome) and the one-and-a-half syndrome (paralytic
Divergence insufficiency or paralysis
Pontine exotropia)
Acute acquired comitant esotropia
Vitamin E deficiency (eg, abetalipoproteinemia)
Spasm of the near reflex
Convergence insufficiency and paralysis
Midbrain pseudo-sixth nerve palsy
Hemifield slide phenomena
Thalamic esotropia
Acquired motor fusion deficiency
Hemifield slide phenomena

Reproduced with permission from: Brazis PW, Lee AG. Acquired binocular horizontal diplopia. Mayo Clin Proc 1999; 74:907.
Copyright © 1999 Mayo Clinic.

Graphic 56887 Version 3.0

Causes of sixth nerve palsy

Nuclear lesions Petrous apex lesions

Congenital (eg, Mobius syndrome) Neoplasm

Demyelinating Nasopharyngeal carcinoma

Ischemic Infection or inflammatory

Complicated otitis media or mastoiditis
Neoplastic
Thrombosis of inferior petrosal sinus
Traumatic
Traumatic
Metabolic (Wernicke's disease)
Basilar skull fracture
Fascicular lesions
Cavernous sinus lesions
Demyelination
Cavernous sinus thrombosis
Infarction
Cavernous sinus fistula
Neoplasm
Neoplasm
Traumatic
Nasopharyngeal cancer
Subarachnoid space lesions Pituitary adenoma

Aneurysm or other vascular abnormalities Plasmacytoma

Sixth nerve neuroma
Carcinomatous meningitis
Skull base tumors
Damage following procedures
Sphenoid sinus tumors
Cervical traction
Squamous cell cancer of the pterygopalatine fossa
Shunting for hydrocephalus
Ischemic lesions
Spinal or epidural anesthesia
Inflammatory or infectious
Lumbar puncture
Myelography, radiculography Internal carotid artery aneurysm or dissection

Inflammatory lesions Orbital lesions

Vasculitis
Neoplastic
Sarcoidosis
Inflammatory
Systemic lupus erythematosus
Infectious
Infectious
Traumatic
Lyme disease
Syphilis
Tuberculosis
Cryptococcal and other meningitis
Cysticercosis
HIV-CMV encephalitis

Neoplastic
Abducens nerve tumor
Leukemia
Metastatic
Trigeminal nerve tumor

Modified from: Lee AG, Brazis PW. Clinical pathways in Neuro-ophthalmology: An evidence-based approach, Theime, New
York, 1999.

Graphic 80526 Version 4.0

Acquired third nerve lesions: most common causes

Location of
Associated symptoms/signs Most common causes
the lesion

Nucleus Complete ipsilateral third plus contralateral ptosis and Infarction

contralateral superior rectus weakness Hemorrhage
Tumor

Fascicles Contralateral hemiparesis (Weber's syndrome) Infarction

Contralateral tremor (Benedikt's syndrome) Hemorrhage
Ipsilateral ataxia (Nothnagel's syndrome) Tumor
Demyelination

Subarachnoid Typically isolated ICA/Pcom A/Basilar/PCA

space May present with headaches or orbital pain Aneurysm
Microvascular (ischemic)
Tumor (pituitary,
carcinomatous meningitis)
Meningitis
Herniation
Trauma

Cavernous sinus Cranial nerves IV, VI, V1, V2 Tumor

Oculosympathetic dysfunction (Horner) Inflammation
Pain may be prominent Carotid aneurysm
Microvascular (ischemic)
Thrombosis
Arteriovenous fistula

Orbital apex Proptosis Trauma

Visual loss Tumor
Cranial nerves IV, VI, V1, V2 Inflammation
Oculosympathetic dysfunction (Horner) Infection (fungus)
Pain may be prominent

ICA: internal carotid artery; Pcom A: posterior communicating artery; PCA: posterior cerebral artery.

Reproduced with permission from: Biousse V, Newman NJ. Third Nerve Palsies. Semin Neurol 2000; 20:55. Copyright © 2000
Theime Medical Publishers.

Graphic 56375 Version 6.0

Contributor Disclosures
Don C Bienfang, MD Nothing to disclose Paul W Brazis, MD Nothing to disclose Janet L Wilterdink,
MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
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