|Year : 2019 | Volume
| Issue : 2 | Page : 102-111
Understanding and evaluating diplopia
Ani Sreedhar1, Ashok Menon2
1 Department of Ophthalmology, Divisions of Oculoplasty and Neuro-Ophthalmology, Little Flower Hospital and Research Centre, Angamaly, Kerala, India
2 Department of Neurology and Clinical Research, Little Flower Hospital and Research Centre, Angamaly, Kerala, India
|Date of Web Publication||27-Aug-2019|
Dr. Ani Sreedhar
Department of Ophthalmology, Divisions of Oculoplasty and Neuro-Ophthalmology, Little Flower Hospital and Research Centre, Angamaly - 683 572, Kerala
Source of Support: None, Conflict of Interest: None
Diplopia or double vision is a frequent reason for ophthalmology consultation. Monocular diplopia is usually ocular or retinal in origin, whereas binocular diplopia is often due to neurological causes. Detailed history beginning with any childhood visual disorders or head tilt and covering comorbid conditions and drug intake is essential. The alignment of images and direction of maximum separation point to the muscle(s) are involved. Temporal profile including onset, progression, and fluctuations along with comorbid conditions helps to narrow down the etiology. Refraction, ocular examination, and fundoscopy can identify ocular and retinal conditions; meticulous examination of ocular ductions and versions is mandatory to localize the cause of diplopia and to initiate investigations for the underlying disease process. Isolated ocular motor palsies are mostly due to microvascular ischemia; in the absence of red flags, investigation may be deferred for 6–8 weeks. Large vertical fusional amplitudes may be a clue to a decompensated congenital trochlear palsy. A partial third nerve palsy with early pupillary involvement, progressive signs, involvement of multiple cranial nerves, and elderly patients with rapid Erythrocyte Sedimentation Rate (ESR) are some situations warranting early imaging and other investigation. Myasthenia gravis and thyroid disease may present with diplopia and ophthalmic manifestations alone without systemic symptomatology. Immunoglobulin G4-related orbital myositis and anti-GQ1b antibody-mediated ocular neuropathies are relatively recently recognized immune-mediated conditions that may present with diplopia to an ophthalmologist. Ophthalmoplegic migraine has been renamed recurrent ophthalmoplegic neuropathy and is a diagnosis of exclusion at initial presentation.
Keywords: Binocular diplopia, monocular diplopia, ocular nerve palsy
|How to cite this article:|
Sreedhar A, Menon A. Understanding and evaluating diplopia. Kerala J Ophthalmol 2019;31:102-11
| Introduction|| |
Diplopia (from Greek, diploos = double, opsis = vision) or double vision refers to a disorder of vision where single objects appear double. It is essential for the ophthalmologist to be familiar and comfortable with the evaluation of diplopia as a symptom as it is among the most common reasons for patient consultation and referral. In this review, we seek to provide an introduction to the understanding and evaluation of diplopia in the clinic, emergency, or ward. Readers interested in greater detail are directed to more comprehensive textbooks or review articles that have been extensively quoted by us.,,,,,
| Monocular Versus Binocular Diplopia|| |
The most important initial question to be addressed in the evaluation of diplopia is whether the diplopia is uniocular or binocular. If diplopia persists on occlusion of either eye (i.e., monocular diplopia), the causes are likely to be ophthalmological, drug related, or functional. On the other hand, if diplopia disappears on occlusion of either eye (i.e., binocular diplopia), the causes are much more likely to be neuro-ophthalmological or neurological.
| Monocular Diplopia|| |
Monocular diplopia may be a symptom of refractive errors, corneal or lenticular disease, or retinal dysfunction. Diplopia due to disease of the refractive apparatus of the eye (cornea, aqueous humor, lens, and vitreous body) is due to diffraction of light such that it falls both on the fovea and the extrafoveal parts of the retina of the same eye. This results in the appearance of a “ghost image” overlapping or adjacent to the true foveal image and can often be corrected by viewing through a pinhole. The patient may experience other ocular symptoms such as glare or haze. Astigmatism, dry eyes, cataracts, or poorly centered intraocular lenses may all be associated with this kind of monocular diplopia. Diplopia due to retinal disease will not resolve with pinhole correction and may be associated with metamorphopsia or distortion of the image. Exceptions to the maxim that “monocular diplopia is usually ophthalmological” are encountered rarely in disorders of the primary or secondary visual cortex. Suspicion of this situation may be engendered when diplopia is bilateral (i.e., bilateral monocular diplopia) or when more than two images are seen (cerebral polyopia). There may be associated palinopsia or persistence of the image after gaze has been shifted. Cerebral monocular diplopia or polyopia has been described in occipital infarction, migraine,, and occipital epilepsy.
Commonly prescribed drugs that may be associated with diplopia or polyopia, sometimes uniocular, include the antiepileptic drugs such as carbamazepine, lacosamide, lamotrigine, zonisamide, and phenytoin.
Monocular diplopia may occasionally be psychogenic or a symptom of a functional eye movement disorders such as convergence spasm. Absence of any change in the position of the image on tilting the head may raise suspicion of nonorganic etiology.
| Binocular Diplopia|| |
Binocular diplopia is the more common symptom and usually occurs when the visual target stimulates noncorresponding points on the retina of either eye, and the retinal images cannot be fused by the brain to form a single image. It is reported most frequently by patients with neuro-ophthalmological/neurological problems causing abnormalities in eye movement. It may be a consequence of lesions of the cranial ocular motor nuclei (III, IV, or VI) in the midbrain and pons or of the medial longitudinal fasciculus (MLF) which connects these nuclei. Involvement of the MLF leads to internuclear ophthalmoplegia (INO). More often, binocular diplopia results from extra-axial lesions of these cranial nerves in the subarachnoid or orbital segments after the nerves exit the brainstem and from diseases of the neuromuscular junction or extraocular muscles.
The history and a quick examination may help localization as well as provide pointers toward the etiology. Childhood squint, surgical procedures in the eye or evidence of head tilt, and posturing from the history or old photographs could suggest a decompensated infantile strabismus. Associated motor or sensory involvement, cerebellar or long tract signs offer clues to central nervous system lesions. Fatigability of the lid, ocular, or other muscles is the hallmark of diseases of the neuromuscular junction such as myasthenia gravis. Inflammatory conditions of the orbit, thyroid ophthalmopathy, orbital neoplasms, and trauma may all affect extraocular muscles and result in diplopia. Orbital inflammation may be idiopathic or associated with systemic illnesses such as sarcoidosis, SLE, giant cell arteritis, or the relatively recently described immunoglobulin G4-related orbital inflammatory disease., Enlargement of the infraorbital nerve may suggest the latter condition. Inflammatory conditions are often associated with headache or pain on eye movement. Red eye with tortuous “corkscrew” limbic-conjunctival vessels raises the specter of a caroticocavernous fistula.
Other questions to be probed in the history include the alignment of the images and the direction of gaze where diplopia is most pronounced (i.e., images are maximally separated). Horizontally separated parallel images suggest weakness of medial or lateral rectus muscles or an INO. A diplopia on looking to the right would imply weakness of the right medial rectus, left lateral rectus, or right INO. A clue that might help differentiating between them is that diplopia from medial rectus dysfunction is usually worse for nearer objects whereas that due to lateral rectus weakness is worse for distant objects. Pure vertical diplopia may result from weakness of the superior or inferior rectus, the superior or inferior obliques, or skew deviation. In practice, pure vertical diplopia is most likely to be due to superior oblique dysfunction as the other three muscles are all innervated by the oculomotor nerve and are seldom affected in isolation. Worsening of vertical diplopia in upgaze suggests a third nerve palsy with weakness of both superior rectus and inferior oblique. Worsening while looking down suggests inferior rectus weakness or a trochlear palsy leading to superior oblique paresis. Diplopia with the images obliquely aligned to each other may occur in oculomotor palsies where both the recti and the inferior oblique are affected or in conditions that can affect multiple muscles such as myasthenia gravis or orbital disease.
| Examination and Evaluation of Diplopia|| |
Clues to the presence and cause of diplopia may be evident even as the patient enters the clinic and narrates the history. Any head tilt, face turn, and elevation or depression of the chin should be remarked as should spontaneous occlusion of one eye to avoid diplopia. A suggestion of limb weakness or ataxia, facial deviation, abnormal head or eye movements, asymmetrical prominence of the eyes, drooping of the lids, hoarseness of voice, or decreased blink frequency may all suggest underlying neurological illness.
Ocular motility has to be tested carefully, individually (ductions), and both eyes together (versions) in all nine cardinal positions. Testing of torsional motility can be aided by observing conjunctival vessels. Convergence and divergence may be assessed by tracking objects from distance to near and back. The approaching target may be seen as double when fusion breaks down. If the patient is blind, his/her own fingers can be used as a fixation target and brought from far to near so that he/she can use his/her sense of proprioception to track. Convergence occurs when both medial recti are activated through the supranuclear pathways. Therefore, convergence is not affected in a pure INO even though adduction deficit is present. In patients with convergence insufficiency, diplopia may occur following continuous near work. In orbital disease including thyroid ophthalmopathy, restriction of eye movement may be due to infiltration, entrapment, or fibrosis rather than a true paralysis. Diplopia worsening in upgaze along with inadequate elevation in a patient with thyroid eye disease is more likely to be due to inferior rectus restriction than superior rectus paresis. If this is suspected, a forced duction test may be carried out by anesthetizing the cornea and passively attempting to move the eyeball gently using forceps. Failure to move the eye passively in the affected direction would suggest a restrictive etiology. Craniofacial trauma may be followed by diplopia due to inferior oblique muscle entrapment or an acquired Brown's syndrome [Figure 1], which may also be differentiated by a forced duction test and imaging.
|Figure 1: Brown syndrome – Defective elevation in adduction mimicking inferior oblique palsy|
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Ocular misalignment can cause diplopia even if ocular motility is apparently full. This may be seen in congenital strabismus, skew deviation, or subtle ocular motor palsies. When misalignment is present with both eyes open, it is called a tropia; if apparent only with one eye closed, it is a phoria. Tropias and phorias can be detected in co-operative patients with sufficient vision in each eye using the cover tests. The cover–uncover test is useful in differentiating tropias from phorias. The patient is asked to fixate on a target, and one eye is occluded. Movement of the open eye to pick up fixation suggests that it was deviated and a tropia is present. If, on the other hand, the occluded eye moves when uncovered, it suggests a phoria. In the alternate cover test, both eyes are alternately covered and then uncovered within seconds while fixating on a target and the movement made by the eye to regain fixation is noted. An esotropic eye moves out to regain fixation and an exotropic eye moves in to fixate. The amount of deviation can be measured by placing prism over the eyes till movements are negated. Primary deviation is the deviation of the affected eye when the normal eye is fixating and secondary deviation occurs when the paretic eye is fixating, and the patient looks in the direction of the paresis. Secondary deviation when the paretic eye is fixing is always more the primary deviation. For example, in a patient with right lateral rectus palsy, the primary deviation when the left eye is occluded is less than the secondary deviation when the right eye is occluded and fixation reverts to the left eye. This follows from Hering's law of motor correspondence which states that the yoke muscles of both eyes are equally innervated.
A measure of the deviation can be obtained by shining a torchlight when the eyes are in primary position and measuring the displacement of the light reflex from the pupil. Each mm of decentration from the pupil equals 7° of ocular deviation. This is called the Hirschberg test.
Charting of the direction of maximum separation of the images (Hess chart) can be carried out by dissociating the eyes using a red filter over the right eye (by convention) and a green filter over the left eye. The red and green images as seen by the patient are recorded. Note should be taken of (i) the position of greatest displacement of red and green images, (ii) any tilt of the images and the position in which it is seen maximally, and (iii) whether the images are crossed or uncrossed while remembering that the fainter image belongs to the palsied eye.
Superior oblique weakness, either isolated or in conjunction with an oculomotor palsy, is often difficult to diagnose, and the Parks–Bielschowsky test is useful in the former context. This test assumes that only one vertically acting muscle is paretic and involves three sequential steps. Step 1 involves identifying the hypertropic eye, from which it could be inferred that the depressors on that side or the elevators of the opposite eye are weak. For example, a hypertropic right eye would suggest that the inferior rectus or superior oblique on the right or the left superior rectus or inferior oblique is weak. In Step 2, the patient is asked to move the eye horizontally to either side, and the hypertropia is assessed. Before drawing inferences, one has to remember that the superior and inferior recti act better in the abducted position while the obliques act better with the eye adducted. In our example, if the right hypertropia is more pronounced while looking toward the left than the right, it would point toward weakness of the right superior oblique or the left superior rectus. The patient can also be asked to look up and down in this position. If the hypertropia is more pronounced on looking down, it suggests that it is the right superior oblique and not the left superior rectus that is weak. Finally, in Step 3, the hypertropia is assessed while tilting the head to either side. Hypertropia in superior oblique palsy worsens on head tilt to the affected side. To understand this, one has to recall that the superior oblique and superior rectus are primarily intorters while the inferior rectus and inferior oblique are extorters of the eyeball. In a normal person, head tilt to one side is countered by a torsional movement of the eye to the opposite side mediated by the vestibulo-ocular reflex. Tilt to the right would, therefore, be associated with intorsion of the right eye and extorsion of the left eye. Since the obliques and recti act in opposite directions vertically (e.g., the superior rectus is an elevator while the superior oblique is a depressor), the vertical actions of these muscles would be canceled out, and there would be no movement of the eye in the vertical plane during torsion. In the situation where the superior oblique is weak, however, the action of the superior rectus in elevating the eyeball is unopposed and the eye becomes more hypertropic [Figure 2].
|Figure 2: Parks–Bielschowsky test in a patient with right superior oblique palsy showing right hypertropia increasing on opposite gaze and on right head tilt|
Click here to view
Superior oblique palsy in conjunction with a third nerve palsy is also important to detect and may be missed. Isolated involvement of one of the ocular motor nerves is most often due to microvascular infarction, which is a relatively benign condition. Involvement of more than one nerve, however, may be due to more sinister inflammatory, infiltrating, or compressive causes requiring more emergent treatment. The affected eye in a third nerve palsy is often exotropic because of medial rectus weakness, and superior oblique action can be assessed by observing for intorsion when asking the patient to look down.
Diplopia first experienced in adulthood may, on occasion, be due to decompensation of a childhood strabismus because of age, disease, drugs, or intoxicants. Infantile strabismus may be seen in conditions such as Brown's syndrome, Duane's syndrome, congenital trochlear nerve palsy, or inferior oblique overaction. If a decompensated congenital trochlear nerve palsy is suspected, testing of vertical fusional amplitudes using prisms is useful. Vertical fusional amplitudes in normal individuals may vary between 1 and 4 prism diopters, but patients with congenital trochlear nerve palsy have a vertical fusional amplitude of >6 diopters.
| Accessory Examination|| |
Examination of the fundus and the afferent visual pathway may also disclose signs that point to the diagnosis. Apart from papilledema, fundoscopy can pick up retinitis pigmentosa in mitochondrial disorders such as Kearns–Sayre syndrome or evidence of retinal artery occlusion or ischemic optic neuropathy in temporal arteritis. Cyclotorsion and saccadic intrusions such as square-wave jerks may also be better appreciated under the magnifying lens of the ophthalmoscope.
Pupillary size in light and in darkness, constriction in response to light and accommodation, and the “swinging torch test” complete the assessment of the afferent pathway.
Ptosis may accompany motility defects in the third nerve paresis or myasthenia gravis. Fatigability of the ptosis and improvement with ice-pack application may further strengthen suspicion of myasthenia. Mild ptosis with enophthalmos and miosis may be seen in lesions of sympathetic pathway causing Horner's syndrome.
Orbital examination for proptosis, periorbital edema, pulsations, and resistance to gentle pressure should be carried out, and the margins palpated for masses in all cases of diplopia or ptosis. Proptosis associated with lid retraction, lid lag, conjunctival injection, and tenderness over ocular muscle-tendon insertions suggest thyroid ophthalmopathy. Although the medial rectus is frequently affected, exotropia is rarely seen. If present, coexistent myasthenia must be sought; in contrast to myasthenia, diplopia in thyroid ophthalmopathy is usually worse in the morning.
Diplopia may be iatrogenic resulting from trauma to the extraocular muscles after cataract (0.17%–0.85%), retina, orbital, or sinus surgery. Diplopia after cataract surgery could also be because of the prismatic effect of the implanted intraocular lens or unmasking of a congenital phoria following resumption of binocular vision.
| Cranial Neuropathies|| |
Neuropathy involving the third (oculomotor), fourth (trochlear), or sixth cranial nerves is the most common neurological causes of diplopia. Ischemia of the nerve due to the involvement of the microvasculature is the most frequent cause of isolated third or sixth nerve palsy in adults. This is the mechanism postulated to be responsible for diabetic cranial neuropathies. Isolated fourth nerve palsy may, more commonly, be congenital or traumatic. Aneurysms of the posterior communicating artery and tumors are more sinister causes of isolated third nerve palsy and should be considered, especially if there is early pupillary involvement. In children, isolated third and fourth nerve palsies are most commonly congenital or traumatic. In the absence of this history, third or sixth nerve palsies mandate investigation for tumors. Isolated pediatric sixth nerve palsies are often reported to be postviral.
The ocular motor nerves are commonly divided into nuclear, fascicular, subarachnoid, cavernous, and superior orbital fissure and orbital segments for ease of anatomical localization of the lesion. Without reviewing the anatomy in great detail, only a few aids to clinical localization are mentioned here.
| Third Nerve (Oculomotor) Palsy|| |
The third nerve supplies the superior rectus, levator complex, inferior rectus, medial rectus, and the inferior oblique muscles as well as carrying the parasympathetic supply to the pupillary sphincter. A palsy of the nerve causes the eye to be pulled down and out due to unopposed action of lateral rectus and superior oblique [Figure 3]. If there is complete ptosis, diplopia will not be a complaint. The pupillary size can vary from a completely dilated, blown pupil to one that is slightly larger than the other.
|Figure 3: Right third nerve palsy: the patient has ptosis and restricted elevation, depression, and adduction|
Click here to view
The third nerve nuclear complex straddles the midline just beneath the periaqueductal gray matter at the level of superior colliculus. The central caudal nucleus supplies both right and left levator palpebrae superioris muscles. The superior rectus fascicles decussate and supply the superior rectus of the opposite side. The parasympathetic Edinger–Westphal nucleus innervates the pupillary constrictors, and nuclei to all other extraocular muscles supply their ipsilateral muscles.
Isolated nuclear involvement is rarely seen but would cause either bilateral or no ptosis since a single central nucleus innervates both the levator palpebrae superioris. Furthermore, a nuclear lesion would cause either contralateral or bilateral superior rectus palsy. Fascicular lesions would cause a complete third nerve palsy that may or not be associated with contralateral hemiplegia, ataxia, or tremor through involvement of the proximate pyramidal tracts, superior cerebellar peduncles, or red nucleus. The pupillomotor fibers being situated superficially are more vulnerable to compression in the subarachnoid and cavernous segments. In the orbit, either the superior division supplying the superior rectus and the lid or the inferior division supplying the inferior rectus, inferior oblique, and the pupil may be involved in isolation.
| Clinical Scenarios and Tips|| |
- Acute onset of severe headache in a young patient without other comorbidities, presence of neck stiffness, and an evolving third nerve palsy with pupillary involvement should prompt immediate consideration and emergent investigation for aneurysms at the junction of posterior communicating artery and middle cerebral artery with potential subarachnoid hemorrhage. Less commonly, compression can occur when the nerve travels between the superior cerebellar and posterior cerebral arteries
- Subacute onset of the third nerve palsy without much pain in an elderly patient with other comorbidities is likely to be ischemic in origin. Pupils are usually spared as ischemia initially affects the central watershed zone within the nerve. Temporal arteritis needs to be kept in mind and investigated in the relevant setting
- Pupillary monitoring is important during consultations in the neurology or neurosurgery intensive care unit. A large, unresponsive pupil in neurosurgical patients may be a sign of raised intracranial pressure causing uncal herniation and compression of the third nerve against the tentorial edge (Hutchinson pupil). This may or not be associated with other features of the third or sixth nerve palsy, but these may not be easily detected in an unconscious patient. It is crucial to remember to assess the pupils before instilling mydriatics for fundoscopy
- Signs of aberrant regeneration of the third nerve suggest a chronic process but are not necessarily benign. It may be the consequence of imperfect repair following an old injury but may also be due to slow-growing masses such as meningioma which breach the perineurium. Reinnervation never occurs in a setting of ischemia. The most common accompaniments of aberrant regeneration involve lid retraction on attempted adduction or depression, ptosis on attempted abduction, or pupillary constriction on attempted eye movement [Figure 4].
|Figure 4: Aberrant regeneration of the third nerve: right lid has retracted on adduction|
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| Fourth Nerve (Trochlear) Palsy|| |
The trochlear nerve supplies the superior oblique muscle which intorts, depresses, and abducts the eye. The depressor action is best with the eye in the adducted position. Due to its dorsal position and very short fascicular course in the midbrain, the fourth nerve palsy only rarely results from intrinsic brainstem lesions such as multiple sclerosis, glioma, or infarcts. Fibers from the fourth nerve nucleus decussate and exit dorsally from the midbrain at the level of the inferior colliculus. A nuclear fourth nerve lesion, therefore, causes involvement of the contralateral superior oblique. Ipsilateral sympathetic involvement and INO may be seen in midbrain lesions before the decussation. Rarely, a contralateral afferent pupillary defect may also be seen due to the involvement of pupillary afferent fibers in the superior colliculus. After entering the subarachnoid space, the nerve curves around the pons between the superior cerebellar and posterior cerebral arteries and then runs along the free margin of the tentorium cerebelli. The long subarachnoid course of this slender nerve renders it vulnerable to trauma. Unilateral or bilateral fourth nerve palsy as a consequence of trauma may never recover.
In the cavernous sinus, the fourth nerve lies in the lateral wall between the third nerve above and the ophthalmic division of the trigeminal below. It enters the orbit through the superior orbital fissure outside the Annulus of Zinn and muscle cone. Lesions in the cavernous sinus and superior orbital fissure are unlikely to cause isolated fourth nerve palsy. As with other cranial nerves, ischemic mononeuropathy may affect the fourth nerve. It is usually sudden in onset and associated with periorbital pain; the diplopia typically resolves completely in 4–6 weeks. Tumors, meningitis, and metastatic disease are uncommon causes of isolated fourth nerve palsy. Congenital fourth nerve palsy is common, can decompensate, and presents in adulthood with acute onset of diplopia. Diagnosis is made only from old photographs which may show a compensatory contralateral head tilt and presence of large fusional amplitudes.
Fourth nerve palsy causes hypertropia and a small convergent squint of the affected eye. The patient complains of diplopia when the eye is depressed toward the opposite side with a tilt of the image. Patients tilt their head toward the opposite side and depress their chin to avoid diplopia by moving the eye out of the field of action of the affected muscle [Figure 5].
Bilateral trochlear nerve palsy can be diagnosed if >10° of cyclotorsion is measured using Maddox rod, and both eyes go into hypertropia on opposite gaze.
A skew deviation may possibly be confused with a fourth nerve palsy. A skew is a vertical misalignment of the eyes due to dysfunction of the vestibulo-ocular connections in the brainstem. The fibers connecting the medial vestibular nucleus to the ocular motor nuclei decussate in the pons and then join the MLF. Medullary lesions (i.e., before the decussation) are associated with the ipsilateral eye being lower, whereas lesions in the midbrain are associated with ipsilateral hypertropia. Unlike a trochlear palsy, the hypertropia in skew deviation may improve in the supine position. Furthermore, the degree of misalignment is usually the same in each direction in skew deviation while in trochlear palsy, it is nonconcomitant.
Diplopia may rarely be a consequence of superior oblique myokymia which is a disorder characterized by paroxysmal bursts of contraction of the superior oblique muscle leading to diplopia, particularly when looking down.
| Sixth Nerve (Abducens) Palsy|| |
A Nuclear Sixth Nerve Lesion is Associated with Restricted Gaze Toward the Same Side since the abducens nucleus also sends fibers to the contralateral medial rectus through the Mlf. A fascicular lesion would be associated with only restricted ipsilateral restriction of abduction that may or not be associated with facial palsy and contralateral hemiplegia. Infarctions, demyelination from multiple sclerosis, brainstem gliomas, metastatic lesions, or extension of cerebellar tumors are likely possibilities. After exiting the brainstem at the pontomedullary junction, the sixth nerve runs along the clivus before piercing the dura at the dorello canal. Clival meningiomas and metastases to the clivus, particularly from the prostate, can result in isolated sixth nerve palsy.
In its passage over the petrous apex and under the petroclinoid ligament, the nerve is close to the termination of the infe
rior petrosal sinus; therefore, venous engorgement in caroticocavernous fistulas (CCF) can result in the sixth nerve palsy. Involvement of the petrous apex in severe otitis media can present with facial pain due to fifth nerve involvement, reduced hearing, and sixth nerve palsy (Gradenigo's syndrome). Similar signs may be seen in nasopharyngeal carcinoma in adults. Temporal bone fractures involving the petrous apex can present with bleeding through the external ear and ecchymosis around the mastoid (Battle sign).
The sixth nerve lies in the middle of the cavernous sinus between the carotid artery and the fourth nerve and may be the first to be affected in lesions such as CCF, cavernous sinus thrombosis, and intracavernous aneurysms. Metastasis to the cavernous sinus and extension of sellar tumors can also initially present as sixth nerve palsy. The other cranial nerves (third, fourth, and fifth) are relatively protected in the lateral wall of the sinus. The sympathetic fibers innervating the pupil and Muller's muscle run along with the sixth nerve in the cavernous sinus.
The patient with abducens palsy typically complains of horizontal diplopia worse when gazing toward the palsied rectus muscle [Figure 6]. The head is turned toward the palsied eye to minimize the strabismus. Diplopia is present for distant objects and may be even absent for near. The external ear has to be examined for discharge, and fundoscopy is mandatory in every case.
| Clinical Scenarios and Tips|| |
- Isolated sixth nerve palsy of sudden onset in a person above 50 years of age is most likely an ischemic mononeuropathy. Comorbidities such as diabetes or hypertension may be present. The patient has to be monitored periodically, and imaging is advisable if there is any progression or involvement of any other cranial nerve or pupil or if there is no recovery after 3 months. The possibility of myasthenia would have to be evaluated, especially if there is any diurnal variation since it can mimic any nerve palsy or even an INO
- Unilateral or bilateral sixth nerve palsy may occur in children following viral infections and may resolve spontaneously. However, the possibility of brainstem gliomas or cerebellar tumors must not be forgotten in this age group.
| Mimics of Sixth Nerve Palsy|| |
- Divergence insufficiency in the elderly may present with convergent squint for distance due to small infarcts in the divergence center in the brainstem. The ocular movements are full in these patients
- Medial rectus inflammation and fibrosis can limit abduction and mimic sixth nerve palsy in Graves thyroid ophthalmopathy, but other signs and symptoms of hyperthyroidism are usually present
- Medial rectus entrapment limiting abduction and mimicking sixth nerve palsy may accompany fracture of the ethmoid bone [Figure 7]. A history of epistaxis in a traumatized patient would suggest this possibility
- It is possible to confuse convergence spasm with bilateral sixth nerve palsy, and latent hypermetropia or presbyopia needs to be evaluated
- Duane's syndrome (Types I and III) may be associated with restriction of abduction. Narrowing of the palpebral aperture and enophthalmos on attempted adduction are clues to the diagnosis.
| Multiple Ocular Motor Nerve Palsies|| |
When more than one nerve is involved, the pathology is usually in the cavernous sinus/superior orbital fissure or a meningeal-based inflammatory or infiltrative process affecting the nerves in the subarachnoid space or base of skull. The third, fourth, and sixth nerves along with the ophthalmic and mandibular branches of the trigeminal (V1 and V2) and sympathetic fibers may be affected in cavernous sinus lesions including cavernous sinus thrombosis and the steroid-responsive inflammatory condition called the Tolosa–Hunt syndrome. Periorbital sensation mediated by the lacrimal branch of V1 has to be carefully tested. The optic nerve may additionally be involved at the orbital apex. Chronic meningitis and skull base tumors, commonly nasopharyngeal carcinomas or metastases, may be responsible for multiple cranial nerve palsies without long tract signs. Polyneuropathies such as Miller–Fisher syndrome and neuromuscular junction disorders such as myasthenia gravis have also to be considered in the differential diagnosis. Isolated ocular motor palsies mediated by GQ1b antibodies may occur even without the complete triad of Miller–Fisher syndrome (ophthalmoplegia, ataxia, and areflexia). Acetylcholine receptor antibodies may be present in only 50% of patients with pure ocular myasthenia; MUSK antibodies are even less common.
The condition previously known as ophthalmoplegic migraine has recently been renamed recurrent ophthalmoplegic neuropathy by the International Headache Society because its demographic profile and pathophysiology are distinct from migraine. It typically affects children under 10 years and manifests with headache occasionally associated with nausea or vomiting followed up to 2 weeks later by the development of ipsilateral ophthalmoplegia involving one or more nerves. The ophthalmoplegia may persist for over a month but typically reverses. There may be a family history of migraine. It is a diagnosis of exclusion, especially when it occurs for the first time, and imaging is mandatory to exclude aneurysm.
| Investigation|| |
In the absence of trauma, systemic disease, other symptoms such as severe headache, and other neurological deficits, most isolated ocular motor nerve palsies are likely to be ischemic in etiology. In these situations, imaging and other investigations for compressive or inflammatory lesions may be deferred for 3 months by which time at least partial improvement should be evident. Vertical fusional amplitude measurement may be useful in isolated fourth nerve palsies to exclude or diagnose a decompensated congenital trochlear palsy. Immediate investigation may still be advisable in these patients if:
- More than one of the nerves is involved
- He/she is over 50 years old
- If the pupil is involved early in a third nerve palsy
- Partial third nerve palsy.
In the last two of these situations, immediate vascular imaging, either computed tomography (CT) angiography or magnetic resonance angiography, has to be carried out to evaluate the possibility of aneurysmal compression. The other two scenarios require brain imaging with administration of contrast focusing, especially on the cavernous sinus and superior orbital fissure. Skull base and pyriform fossa imaging and evaluation for nasopharyngeal cancers may be needed if nonocular cranial nerves are also affected. In the elderly patient, if the blood ESR is >50 mm in the 1st h, investigations for temporal arteritis may be pursued further. Lumbar puncture and CSF study may have to be carried out for the evaluation of chronic meningitis and neurosarcoidosis. The latter condition may also require chest CT scan and Angiotensin Converting Enzyme (ACE) assay. As previously mentioned, myasthenia gravis may present with eye movement abnormalities in various combinations and can be investigated with a neostigmine test and assays for acetylcholine receptor antibodies.
| Management|| |
The treatment of diplopia is beyond the purview of this review but is, in essence, directed to the cause. Symptomatic measures include temporary monocular patching if the condition is expected to be self-limiting, optic prisms, strabismus surgery, and botulinum toxin injection into the antagonist of the paralyzed muscle.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Miller NR, Newman NJ, Biousse V, Kerrison JB, editors. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th
ed. Philadelphia: Lippincott Williams and Wilkins; 2005.
Glaser JS. Neuro-Ophthalmology. 3rd
ed. Philadelphia: Lippincott Williams and Wilkins; 1999.
Wright KW, Strube YN. Pediatric Ophthalmology and Strabismus. 3rd
ed. New York: Oxford University Press Inc.; 2012.
Leigh RJ, Zee DS. The Neurology of Eye Movements. 5th
ed. Oxford: Oxford University Press; 2015.
Miller N, Subramanian PS, Patel V. Walsh and Hoyt's Clinical Neuro-Ophthalmology: The Essentials. 3rd
ed. Alphen aan den Rijn: Wolters Kluwer; 2016.
Dinkin M. Diagnostic approach to diplopia. Continuum (Minneap Minn) 2014;20:942-65.
Tan A, Faridah H. The two-minute approach to monocular diplopia. Malays Fam Physician 2010;5:115-8.
Coffeen P, Guyton DL. Monocular diplopia accompanying ordinary refractive errors. Am J Ophthalmol 1988;105:451-9.
Lepore FE, Yarian DL. Monocular diplopia of retinal origin. J Clin Neuroophthalmol 1986;6:181-3.
Meadows JC. Observations on a case of monocular diplopia of cerebral origin. J Neurol Sci 1973;18:249-53.
Drake ME Jr. Migraine as an organic cause of monocular diplopia. Psychosomatics 1983;24:1024-7.
Smith SV. Neuro-ophthalmic symptoms of primary headache disorders: Why the patient with headache may present to neuro-ophthalmology. J Neuroophthalmol 2019;39:200-7.
Zakaria A, Lalani I, Belorgey L, Jay Foreman P. Focal occipital seizures with cerebral polyopia. Epileptic Disord 2006;8:295-7.
Gräf M, Lorenz B. How to deal with diplopia. Rev Neurol (Paris) 2012;168:720-8.
Rucker JC, Tomsak RL. Binocular diplopia. A practical approach. Neurologist 2005;11:98-110.
Berry-Brincat A, Rose GE. Idiopathic orbital inflammation: A new dimension with the discovery of immunoglobulin G4-related disease. Curr Opin Ophthalmol 2012;23:415-9.
Chwalisz BK, Stone JH. Neuro-ophthalmic complications of igG4-related disease. Curr Opin Ophthalmol 2018;29:485-94.
Hardy TG, McNab AA, Rose GE. Enlargement of the infraorbital nerve: An important sign associated with orbital reactive lymphoid hyperplasia or immunoglobulin g4-related disease. Ophthalmology 2014;121:1297-303.
Henderson AD, Miller NR. Carotid-cavernous fistula: Current concepts in aetiology, investigation, and management. Eye (Lond) 2018;32:164-72.
Lee JE, Yang HK, Kim JH, Hwang JM. Diagnostic utility of the three-step test according to the presence of the trochlear nerve in superior oblique palsy. J Clin Neurol 2018;14:66-72.
Keane JR. Multiple cranial nerve palsies: Analysis of 979 cases. Arch Neurol 2005;62:1714-7.
Brazis PW. Palsies of the trochlear nerve: Diagnosis and localization – Recent concepts. Mayo Clin Proc 1993;68:501-9.
Rao R, MacIntosh PW, Yoon MK, Lefebvre DR. Current trends in the management of thyroid eye disease. Curr Opin Ophthalmol 2015;26:484-90.
Golnik KC, West CE, Kaye E, Corcoran KT, Cionni RJ. Incidence of ocular misalignment and diplopia after uneventful cataract surgery. J Cataract Refract Surg 2000;26:1205-9.
Nayak H, Kersey JP, Oystreck DT, Cline RA, Lyons CJ. Diplopia following cataract surgery: A review of 150 patients. Eye (Lond) 2008;22:1057-64.
Cornblath WT. Diplopia due to ocular motor cranial neuropathies. Continuum (Minneap Minn) 2014;20:966-80.
Kung NH, Van Stavern GP. Isolated ocular motor nerve palsies. Semin Neurol 2015;35:539-48.
Holmes JM, Mutyala S, Maus TL, Grill R, Hodge DO, Gray DT. Pediatric third, fourth, and sixth nerve palsies: A population-based study. Am J Ophthalmol 1999;127:388-92.
Jacobson DM, Trobe JD. The emerging role of magnetic resonance angiography in the management of patients with third cranial nerve palsy. Am J Ophthalmol 1999;128:94-6.
Tamhankar MA, Biousse V, Ying GS, Prasad S, Subramanian PS, Lee MS, et al.
Isolated third, fourth, and sixth cranial nerve palsies from presumed microvascular versus other causes: A prospective study. Ophthalmology 2013;120:2264-9.
Morillon P, Bremner F. Trochlear nerve palsy. Br J Hosp Med (Lond) 2017;78:C38-C40.
Eggenberger ER. Supranuclear eye movement abnormalities. Continuum (Minneap Minn) 2014;20:981-92.
Wong AM. Understanding skew deviation and a new clinical test to differentiate it from trochlear nerve palsy. J AAPOS 2010;14:61-7.
Hernowo A, Eggenberger E. Skew deviation: Clinical updates for ophthalmologists. Curr Opin Ophthalmol 2014;25:485-7.
Elder C, Hainline C, Galetta SL, Balcer LJ, Rucker JC. Isolated abducens nerve palsy: Update on evaluation and diagnosis. Curr Neurol Neurosci Rep 2016;16:69.
Margolin E, Lam CTY. Approach to a patient with diplopia in the emergency department. J Emerg Med 2018;54:799-806.
Odaka M, Yuki N, Hirata K. Anti-GQ1b igG antibody syndrome: Clinical and immunological range. J Neurol Neurosurg Psychiatry 2001;70:50-5.
Al-Haidar M, Benatar M, Kaminski HJ. Ocular myasthenia. Neurol Clin 2018;36:241-51.
Smith SV, Schuster NM. Relapsing painful ophthalmoplegic neuropathy: No longer a “Migraine,” but still a headache. Curr Pain Headache Rep 2018;22:50.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]