Diplopia

Kurt Brueggemann and James A. Comes

Diplopia is an uncommon and frightening emergency department (ED) complaint. The differential diagnosis is complex and evaluation may require neuroimaging or consultation with subspecialists who may not be immediately available. Diplopia can be the sentinel finding of an insidious neurologic or metabolic disease, the sole symptom of a benign and self-limited microvascular (diabetic) mononeuropathy, or the lone warning sign of an impending intracranial aneurysm rupture. Diplopia can result from a unilateral ocular problem or binocular misalignment. It may present in isolation or as part of a constellation of findings.

Management varies from expectant to emergent depending on the presumed etiology. A comprehensive emergent management strategy has not been thoroughly established. Guiding principles and available evidence favor a meticulous, systematic, and conservative approach.

CLINICAL PRESENTATION

Diplopia has a wide variety of presentations, depending upon the neuroanatomic location of the lesion (if present) (1,2). Diplopia can be categorized as horizontal, vertical, or oblique/diagonal, and it may be noted to be worse with a particular direction of gaze. Strabismus may be evident at rest (-tropia) or upon provocation (-phoria). For example a medial deviation of the eye at rest is termed an esotropia.

Diplopia can be confused with a variety of other symptoms, including dizziness, lightheadedness, blurry vision, ghost-like images, and partial or full vision loss (3).

Diplopia, colloquially “double vision,” is the result of an inability to integrate the signals received by two retinas into a single sensible visual perception. This can result from a refractive error of an individual eye (monocular diplopia) or an extraocular cause producing misalignment of the eyes (binocular diplopia).

Monocular diplopia is almost invariably due to a problem with the single involved eye, and rarely requires emergent management. It can be distinguished from binocular diplopia by having the patient alternately close one eye and then the other. If diplopia persists with monocular vision, misalignment of the eyes is not the problem (3) and further attention should be directed to the affected eye. The focus of the remainder of this chapter is binocular diplopia.

During normal vision the brain integrates the sensory input from each eye into a single stereoscopic worldview (visual acuity and depth perception). The two eyes are normally entrained and aligned to place any object of interest over the fovea (central vision) of each retina. The inability of one eye to accurately “acquire the target” produces two distinct retinal projections which cannot be fused by the visual cortex, resulting in “double vision.”

Diplopia (pathologic binocular diplopia) results from dysfunction of the extraocular muscles (EOMs), also called ophthalmoplegia. This dysfunction can result from disorders and diseases anywhere from the orbit to the CNS including the muscles, their neuromuscular junctions, cranial nerve(s) or nuclei up through their respective interneurons. These neurons make possible the complex coordination of head and eye movements involving cortical, vestibular, proprioceptive, and cerebellar circuits.

Extraocular motility is provided by six EOMs; the medial rectus (EOM-MR) and lateral rectus (EOM-LR) adduct and abduct the eye, the superior rectus (EOM-SR) and inferior oblique (EOM-IO) elevate the eye while the inferior rectus (EOM-IR) and superior oblique (EOM-SO) depress the eye.

The abducens nerve (CN-VI) innervates the EOM-LR. The trochlear nerve (CN-IV) innervates the EOM-SO. The oculomotor nerve (CN-III) innervates the remainder of the EOMs, the major muscle of the eye lid, levator palpebrae superioris (LPS), and also carries autonomic parasympathetic fibers to the pupillary constrictor muscle.

Individual cranial nerve palsies present with typical clinical presentations. A patient may adopt several coping strategies to deal with the deficits. These coping strategies can help guide the identification of the palsy. If a compensatory head position is present, it mirrors the function of the inactive muscle(s).

The clinical presentation may also vary considerably secondary to the underlying cause. For example, a lesion in the cavernous sinus may involve all three extraocular cranial nerves as well as the ophthalmic and maxillary branches of the trigeminal nerve. Lesions of the carotid artery up through the cavernous sinus may produce a Horner syndrome (ipsilateral ptosis, miosis, and anhidrosis). A lesion of the pituitary may involve a characteristic visual field deficit and endocrinologic signs and symptoms. Diseases involving the orbit may be painfully obvious (e.g., an orbital fracture with EOM entrapment) or quite subtle (e.g., thyroid myopathy). Brainstem or other central lesions often involve other neurologic deficits including hemiparesis, anesthesia, discoordination or vertigo, facial weakness or anesthesia, dysphonia, dysphagia, or visual field deficits. Neuromuscular junction disorders can be elusive but may exhibit historical features such as fatigability, temporal variation, dysphagia, proximal muscle weakness, and dyspnea. CNS infection may also produce fever, headache, meningismus, or altered mental status.

Oculomotor (CN-III) Palsy

A complete CN-III nerve palsy will produce a “down and out” pupil, and ipsilateral ptosis with variable but critical pupillary involvement. The patient may complain of a diagonal diplopia which is worse in near-field gaze when looking inward and upward. The accompanying ptosis (effectively closing the “bad” eye) may minimize the associated disability by obliterating the diplopia.

The cranial nerves supplying EOMs exit the brainstem and traverse the dura, subarachnoid space, and cavernous sinus before funneling into the superior orbital fissure. CN-III travels alongside the posterior communicating artery soon after it exits the brainstem. CN-III innervates four EOMs and includes fibers supplying pupillary and palpebral muscles.

A complete CN-III palsy with pupillary involvement is a posterior circulation aneurysm until proven otherwise. Pupillary involvement is particularly worrisome because the parasympathetic fibers lie in the periphery of the nerve sheath, making them more susceptible to external compression. Aneurysm and diabetic neuropathy are the two leading causes of CN-III palsy. An isolated, unilateral, atraumatic complete CN-III palsy sparing the pupil is often due to diabetic neuropathy. Cavernous sinus lesions can produce CN-III palsies with a concurrent Horner syndrome which can make the pupillary findings very ambiguous.

Partial, incomplete, or inconsistent palsies of CN-III are substantially more complicated and require neuroimaging and consideration of neuromuscular disease (4). A dysfunctional EOM-MR raises several diagnostic possibilities including internuclear ophthalmoplegia (INO), myopathy, and neuromuscular disease. These last examples serve to illustrate the point that any findings not consistent with a complete unilateral cranial nerve III palsy sparing the pupil require a very meticulous appraisal.

Trochlear (CN-IV) Palsy

A complete CN-IV nerve palsy may have a more subtle presentation. The patient may complain of a vertical diplopia with a torsional (rotational) component. Owing to the inaction of the functionally denervated EOM-SO the globe may appear elevated (hypertropia) and extorted. The diplopia will worsen with nasal deviation and downgaze, thus activities like reading, descending stairs or watching TV in bed may be difficult. The patient may adopt a compensatory head posture or tilt consisting of the head tilted forward and away from the affected eye (mirroring the depression and intorsion action of the EOM-SO).

CN-IV exits the brainstem dorsally and passes alongside the edge of the cerebellar tentorium making it vulnerable in the setting of closed head injury. It has a long intracranial course, so diseases affecting the subarachnoid space should be strongly considered. CN-IV palsies are very unlikely to be aneurysmal.

The critical diagnostic consideration in patients presenting with vertical diplopia is skew deviation. Skew deviation results from a central lesion and can mimic a CN-IV palsy but is often distinguished by the presence of other neurologic findings. It results from a supranuclear lesion of the interneurons connecting the vestibular and ocular circuits and frequently presents with vertical diplopia present in all gaze directions.

Abducens (CN-VI) Palsy

Although the abducens nerve (CN-VI) innervates only a single muscle, EOM-LR, the associated diplopia is often the most severe. Horizontal diplopia is the rule and a compensatory head rotation (toward the affected side) may be present. The patient may close the eye “pseudoptosis” or cover it to minimize the symptoms.

CN-VI travels near the cavernous portion of the internal carotid artery and may be the first cranial nerve involved in vascular disease in this area. The abducens nerve ascends the clivus in a near vertical fashion and is tethered at the apex across the sharp ridge of the petrous portion of the temporal bone. This anatomic anchoring makes the abducens nerve very susceptible to increased intracranial pressure (ICP). Thus the examiner should look for headache and papilledema and have a low threshold for obtaining imaging to exclude obstructive hydrocephalus, mass lesions, idiopathic intracranial hypertension, or sagittal venous thrombosis.

Internuclear Ophthalmoplegia

Internuclear ophthalmoplegia (INO) clinically presents as an EOM-MR palsy. In normal abduction the medial longitudinal fasciculus (MLF) activates the contralateral EOM-MR to keep the eyes aligned. A lesion of the MLF manifests as an inability to adduct the eye on attempted contralateral abduction. The abducting eye will exhibit nystagmus as a response to the divergence. INO is by definition a central lesion requiring neuroimaging and consideration of neuromuscular disease. Bilateral INO is a hallmark of multiple sclerosis (MS). As the EOM-MR itself is not impaired, convergence should remain intact in an INO and be impaired in a neuromuscular disease affecting the EOM-MR.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of binocular diplopia can be simplified based on whether the findings suggest an isolated cranial nerve palsy. If an isolated unilateral cranial nerve palsy is present, and there is no history of antecedent trauma or orbital findings, the differential diagnosis can be narrowed considerably. CN-III palsy is most likely due to a posterior circulation aneurysm or diabetic neuropathy. CN-IV palsy must be differentiated from central causes of vertical diplopia and the physical examination may not be adequate to do so (5,6). The patient with CN-VI palsy must be evaluated for disease processes producing elevated ICP.

If the diplopia is not attributable to an individual cranial nerve palsy, the diagnostic considerations include myopathy or myositis (7), neuromuscular disease, demyelinating disease, descending paralytic disorders, or a CNS lesion including infection, inflammation, neoplasm, ischemia, thrombosis, aneurysm, hemorrhage, dissection, or demyelination.

Some selected diseases which can mimic or aggregate extraocular cranial nerve dysfunction include:

Cavernous Sinus Thrombosis: May involve all three extraocular cranial nerves as well as the ophthalmic and maxillary branches of the trigeminal nerve. It should be strongly considered in the thrombophilic or immunocompromised patient as the associated infection can be bacterial or fungal. Diseases of the cavernous internal carotid artery including aneurysm or rupture may present similarly.

Giant Cell/Temporal Arteritis: Should be considered in any elderly patient complaining of unilateral headache and vacillating vision abnormalities (including diplopia). Ophthalmoplegic migraine must be considered a diagnosis of exclusion in all age groups.

Miller–Fisher Syndrome (MFS): Is a descending demyelinating inflammatory polyneuropathy which typically begins with diplopia and then progresses to ataxia, areflexia and potentially proximal muscle weakness, paresthesias, and respiratory failure from diaphragmatic insufficiency (8).

Botulism: Often begins with bilateral ophthalmoplegia but it can potentially involve any cranial nerve (e.g., dysphagia may be the presenting complaint). It progresses to symmetric descending weakness.

Myasthenia Gravis (MG): Can initially present with ocular symptoms of diplopia and ptosis. The ophthalmoplegia producing diplopia can involve any combination of EOMs and mimic any of the CN palsies described above. The pupils, however, are never affected in ocular myasthenia.

Multiple Sclerosis (MS): Patients may present with ophthalmoplegia resulting from cranial nerve palsies or INO.

Idiopathic Intracranial Hypertension (IIH): (Formerly pseudotumor cerebri) is an important diagnostic consideration as it can result in vision loss if left untreated. Since CN-VI is sensitive to increased ICP it is the EOM palsy associated with this condition. Funduscopic examination reveals papilledema and nonpulsatile distended retinal veins. Emergent neuroimaging is warranted to exclude obstructive hydrocephalus, venous sinus thrombosis or mass lesion.

Thyroid Extraocular Myopathy: It can produce diplopia in clinically euthyroid patients without alarming signs of an orbital process. The inferior rectus is most commonly the first muscle involved in this restrictive myopathy. Orbital findings can include exophthalmos, ptosis, periocular inflammation, lid lag, and lid retraction.

Wernicke Encephalopathy: Must be considered in any patient presenting with altered mental status, ataxia, and oculomotor aberrations from ophthalmoplegia to nystagmus (9).

ED EVALUATION

The diagnostic approach must be guided by the overall condition of the patient and the associated signs and symptoms. Thus, if the patient is strongly suspected to have meningitis, the diagnostic and management process is governed by the preliminary diagnosis, regardless of diplopia.

The history and physical examination can be critical in lesion localization and establishing the diagnostic approach. In a stable and cooperative patient the examiner should first focus on the eyes, including tests of visual acuity, visual field integrity, pupillary reactivity, afferent defects and appearance (size and symmetry), extraocular movements, and alignment (looking for strabismus, gaze deviation, or nystagmus). The patient should be asked to report any changes in their symptoms with these maneuvers. Visual acuity and EOM testing should be performed with each eye individually and together. The examiner should then proceed to consideration of the face, looking for ptosis (if not already noted) and facial, orbital or ocular asymmetry (e.g., unilateral conjunctival injection). The presence of pain at rest or pain with movement should be noted (7,10–12). A full cranial nerve examination must be performed, as well as a complete cerebellar examination, gait testing, and evaluation of deep tendon reflexes, and extremity motor or sensory function.

Even with a careful physical examination in a cooperative patient the localization of the lesion may prove difficult (1,2). Consequently, consider broad neuroimaging and early subspeciality consultation if available. Patients with binocular diplopia without clinically evident ophthalmoplegia require careful evaluation as this can be a sign of MS.

Monocular diplopia, once identified, should prompt a thorough examination of the eye including cornea, lens, anterior/posterior chambers, retina, and possibly the optic nerve. Consideration should be given to disease processes producing monocular vision impairment or loss (13), monocular visual field deficits, and a monocular painful red eye. Ophthalmologic consultation is recommended.

In the setting of trauma, computed tomography (CT) should be the first choice for diagnostic imaging. In the absence of trauma, CT can be performed initially as it is often the most accessible, though a negative result may be falsely reassuring (14–16). If resources are available patients should be evaluated with magnetic resonance imaging, with angiography or venography, depending on the clinical picture.

Neurologic findings attributable to more than one cranial nerve (II to XII) or any other neurologic findings should prompt neuroimaging and consideration of neuromuscular disease, restrictive myopathy, demyelinating disease, or other causes of descending weakness (17). If aneurysm is strongly suspected, some authorities consider that a negative CT or MR angiogram is inadequate to exclude aneurysmal disease and thus suggest formal angiography in this setting (3).

Some authors have argued that all patients presenting with binocular diplopia require advanced neuroimaging because the potential etiologies may be life-threatening and there are no established clinical criteria for safely identifying the subset of patients who do not require an extensive workup.