Diplopia

AUTHORS: Benjamin Kartub, MD and Nicholas J. Inman, MD

Definition

Diplopia is the perception of two images of a single object that may be displaced horizontally, vertically, or obliquely. Diplopia may be monocular or binocular. Monocular diplopia is double vision in one eye and persists when the unaffected eye is covered. It is an ophthalmologic problem that results from abnormal light transmission to the retina. Binocular diplopia results from ocular misalignment and resolves when either eye is covered. There are multiple possible causes that can be localized along the visual pathway, from the eye to the brainstem.

Synonym

Double vision

ICD-10CM CODE
H53.2		Diplopia

Epidemiology & Demographics

Diplopia represents 1.4% of ophthalmologic emergencies.
The majority of cases are binocular.

Risk Factors

Risk factors for diplopia include risk factors for vasculopathies (e.g., hypertension, diabetes mellitus, smoking, cerebrovascular accident), trauma, ocular surgery, presence of cataracts, alcohol abuse, as well as autoimmune conditions such as myasthenia gravis and Grave disease.

Genetics

Some diseases that may present with diplopia have a genetic basis, such as Marfan syndrome and homocystinuria (dislocation of lens) or, to a lesser degree, autoimmune conditions (myasthenia gravis , Graves’) that have a possible genetic link.

Physical Findings & Clinical Presentation

Monocular diplopia: Persists when the unaffected eye is covered and, unless caused by a retinal defect, resolves when a pinhole is used.
Restrictive, mechanical orbitopathy: Restriction of eye movement away from affected muscle, typically gradual in onset with a sensation of mass effect/discomfort/pain in a single eye. It may be the result of rectus muscle entrapment secondary to orbital blowout fracture or may be accompanied by fever if infectious in etiology. When caused by thyroid disease, it may be unilateral or bilateral; be worse in the morning; and may have notable proptosis, periorbital swelling, edema, palpebral swelling, and conjunctival or scleral injection. Depending on the pathology, the patient may complain of pain.
Cranial nerve (CN; III, IV, or VI) palsy: May occur as an isolated nerve palsy as a result of microvascular ischemia, or in combination in the case of cavernous sinus, central, or posterior orbital pathologies.
1. CN III (oculomotor) palsy: Vertical and horizontal diplopia. Complete CN III palsy will have ptosis; large unreactive pupil; and paralysis of adduction, elevation, and depression so eye rests in position of abduction, depression, and intorsion.
2. CN IV (trochlear) palsy: Vertical and/or torsional diplopia that worsens looking down and toward the nose; difficulty descending stairs, reading, or watching television in bed.
3. CN VI (abducens) palsy: Horizontal diplopia that worsens on lateral gaze toward the affected side.
Neuraxial process: D iplopia may occur in isolation or may be accompanied by multiple neurologic signs and symptoms depending on the location of the lesion and specific pathology.
Neuromuscular disorder: Muscle atrophy/weakness, weakness on forced eyelid closure, normal reflexes, and no sensory deficits.

Etiology

The etiology of diplopia differs between monocular and binocular diplopia. Monocular diplopia (Box E1) is caused by primary ophthalmologic structural problems in the transmission of light to the retina and generally should be referred to an ophthalmologist. Binocular diplopia, when not caused by trauma, is most often a vascular lesion (small-vessel vasculopathy or aneurysmal disease) or occasionally due to endocrinopathy, neuromuscular, neoplastic, or autoimmune sources.
Table E1 summarizes important causes of diplopia.

TABLE E1 Important Causes of Diplopia

Diplopia-Causing Entity	Mechanism and Mortality	Distinguishing Features
Tier 1-Critical
Basilar artery thrombosis	Impending thrombosis of the basilar artery with brainstem ischemia; untreated mortality, 70%-90%	Vertigo, dysarthria, other cranial nerve involvement; risk factors for stroke
Botulism	Toxin inhibits release of acetylcholine (ACh) at cholinergic synapses and presynaptic myoneural junctions; untreated mortality, 60%	Dysarthria, dysphagia, autonomic dysreflexia, pupillary dysfunction
Basilar meningitis	Infection; untreated mortality, close to 100% if bacterial (15%-20% if treated)	Headache, meningismus, fever
Aneurysm	Enlarging aneurysm directly compresses cranial nerve; untreated rupture risk = 1%/yr (3.5%/yr for previously ruptured); mortality, 26%-67%/rupture	CN III palsy with pupillary involvement
Tier 2-Emergent
Vertebral dissection	Dissection causes vertebrobasilar ischemia; acute untreated mortality, 28% (2%-5% if neurologically asymptomatic)	Neck pain, vertigo; risk factors for vertebral dissection
Myasthenia gravis	Autoantibodies develop against ACh nicotinic postsynaptic receptors; untreated crisis mortality, 42% (5% if treated)	Fluctuating muscle weakness, ptosis, and diplopia worsen with activity and improve with rest
Wernicke encephalopathy	Thiamine-dependent metabolic failure and tissue injury; untreated mortality, 20%	Nystagmus, ataxia, altered mental status, and ophthalmoplegia; alcoholism and nutritional deficiency
Orbital apex syndrome, cavernous sinus process	Inflammation or infection in the orbital apex or cavernous sinus directly affects oculomotor cranial nerves; acute mortality low unless infectious and complicated by meningitis	A combination of palsies of CN III, IV, or VI, with retro-orbital pain, conjunctival injection, possible periorbital, facial numbness
Tier 3-Urgent
Brainstem tumor	Tumor involvement at the supranuclear level; acute mortality low (long-term mortality variable)	Skew deviation-vertical diplopia, internuclear ophthalmoplegia
Miller-Fisher syndrome	Autoantibodies develop to a cranial nerve ganglioside, GQ1b; acute mortality low (if fully differentiated from GBS; mortality, 2%-12% if GBS)	Ophthalmoplegia, ataxia, areflexia
Multiple sclerosis	Demyelinating lesions; acute mortality low	Internuclear ophthalmoplegia
Thyroid myopathy (Graves’ disease)	Autoimmune myopathy; acute mortality low in regard to ocular complaints	Proptosis, restriction of elevation and abduction of the eye, signs of Graves’ disease
Ophthalmoplegic migraine	Inflammatory cranial neuropathy; low mortality, self-limited disease	Ipsilateral headache, CN (usually III) palsy
Ischemic neuropathy	Microvascular ischemia; mortality low, self-limited disease	Isolated CN palsy (pupil-sparing if CN III)
Orbital myositis, pseudotumor	Autoimmune or idiopathic myositis; acute mortality low in regard to ocular complaints	Eye pain, restriction of movement, periorbital edema; exophthalmos and chemosis when more severe
Orbital apex mass	Tumor, infiltration, or mass effect in orbital apex or cavernous sinus directly compresses oculomotor cranial nerves; acute mortality low	A combination of palsies of CN III, IV, or VI, and possible periorbital, facial numbness, with retro-orbital pain, proptosis, signs of venous congestion

CN, Cranial nerve; GBS, Guillain-Barré syndrome.

From Walls RM et al: Rosen’s emergency medicine, ed 9, Philadelphia, 2018, Elsevier.

BOX E1 Causes of Monocular Diplopia

Uncorrected refractive error
Equipment failure (defective contact lens, ill-fitting bifocals in patients with dementia)
Corneal disease (e.g., astigmatism, dry eye, keratoconus)
After surgery for long-standing tropia (eccentric fixation)
Corrected long-standing tropia (eccentric fixation)
Foreign body in aqueous or vitreous media
Iris abnormalities (polycoria, trauma)
Lens: Multirefractile (combined cortical and nuclear) cataracts, subluxation
Occipital cortex (bilateral monocular): Migraine, epilepsy, stroke, tumor, trauma (palinopsia, polyopia)
Psychogenic
Retinal disease (rare)

From Jankovic J et al: Bradley and Daroff’s neurology in clinical practice, ed 8, Philadelphia, 2022, Elsevier.

Differential Diagnosis (Box E2

BOX E2 Signs Associated With Diplopia

Extraocular muscle or lid fatigue, suggests myasthenia gravis (MG)
Cogan lid twitch, suggests MG
Weakness of other muscles (e.g., orbicularis oculi, other facial muscles, neck flexors, bulbar muscles), suggests MG or oculopharyngeal dystrophy
Narrowing of the palpebral fissure and retraction of the globe on adduction, associated with an abduction deficit, suggests Duane retraction syndrome
Paradoxical elevation of upper lid on attempted adduction or downgaze, and pupil constriction on attempted adduction or downgaze, occurs with aberrant reinnervation of the third cranial nerve, which is nearly always a result of trauma or compression caused by tumor or aneurysm
Ptosis with elevation of deep upper lid creases, baggy eyelids, superior sulcal enlargement or deformity, and previous eyelid surgical repair, suggest sagging eye syndrome
Miosis accompanying intermittent esotropia with a variable abduction deficit, occurs with spasm of the near reflex (also called convergence spasm)
Horner syndrome, ophthalmoplegia, and impaired sensation in the distribution of the first division of the trigeminal nerve occur with superior orbital fissure and anterior cavernous sinus lesions; Horner syndrome with a contralateral superior oblique palsy occurs with a lower midbrain trochlear nucleus lesion
Proptosis, suggests an orbital lesion such as thyroid eye disease, inflammatory or infiltrative orbital disease (tumor, orbital pseudotumor, or amyloidosis), or a carotid-cavernous sinus fistula (in which case it may be pulsatile)
Ocular bruits, often heard by both patient and doctor, occur with carotid-cavernous or dural shunt fistulas
Ophthalmoplegia, ataxia, nystagmus, and confusion, suggest Wernicke encephalopathy
Facial pain, hearing loss, and ipsilateral lateral rectus weakness, indicate the Gradenigo syndrome
Myotonia and retinal pathology in the setting of diplopia and ophthalmoplegia, suggest more widespread disorders such as mitochondrial disease

From Jankovic J et al: Bradley and Daroff’s neurology in clinical practice, ed 8, Philadelphia, 2022, Elsevier.

Monocular diplopia:
1. Refractive error: High refractive error, irregular astigmatism
2. Eyelid: Mechanical compression on cornea (chalazion, tumor, hematoma, edema)
3. Tear film: Abnormalities of tear film causing light diffraction (mucus strand, foreign body, oil droplets)
4. Cornea: Opacity causing light diffraction (scar, edema, corneal dystrophies), corneal irregularities
5. Lens: Opacities (cataract, vacuoles, water cleft), shape (lenticonus, spherophakia), position (ectopia lentis, lens subluxation)
6. Iris and pupil: Iridodialysis, polycoria, peripheral iridotomy/ iridectomy
7. Vitreous: Foreign bodies
8. Retina: Macular edema, central serous retinopathy
9. Cerebral polyopia: Trauma, migraine, multiple sclerosis, encephalitis, seizure
10. Psychogenic (functional deficit)
Binocular diplopia:
1. Restrictive, mechanical orbitopathy
  1. Infection (abscess)
  2. Trauma
  3. Orbital myositis (may be associated with Wegener granulomatosis, giant cell arteritis, systemic lupus erythematosus, dermatomyositis, sarcoidosis, rheumatoid arthritis, or orbital pseudotumor)
  4. Grave ophthalmopathy
  5. Craniofacial mass
2. Cranial nerve (III, IV, or VI) palsy
  1. Isolated mononeuropathy of a single nerve
    1. Demyelination (e.g., multiple sclerosis)
    2. Hypertensive or diabetic vasculopathy
    3. Nerve compression (e.g., aneurysm, tumor)
  2. Unilateral palsy of multiple oculomotor nerves
    1. Infection
    2. Mass
    3. Vasculitis affecting cavernous sinus or posterior orbit
3. Neuraxial process involving the brainstem
  1. Multiple sclerosis may manifest as a focal brainstem lesion.
  2. A more diffuse but localized brainstem lesion may result from brainstem tumor, brain stem lacunar stroke, basilar artery thrombosis, vertebral artery dissection, ophthalmoplegic migraine, infection, Guillain-Barré syndrome, Wernicke encephalopathy, meningoencephalitis, or botulism.
4. Neuromuscular disorder
  1. Myasthenia gravis
  2. Lambert-Eaton syndrome
Psychogenic (functional deficit)

Workup

Full neurologic examination with careful attention to the cranial nerves is indicated in all patients presenting with diplopia (Box E3).
Full ocular examination is also indicated and includes testing of visual acuity, visual field, external eye examination, extraocular movements, pupillary examination, intraocular pressure, and slit-lamp examination.
The first step is to determine if the diplopia is monocular or binocular. Present an image to the patient and sequentially cover each of the patient’s eyes. In monocular diplopia, double vision persists when one eye is covered and, except in the case of bilateral monocular diplopia, resolves when the opposite eye is covered. In binocular diplopia, double vision resolves when either eye is covered.
Monocular diplopia:
1. After monocular diplopia has been confirmed, evaluate the patient’s vision through a pinhole.
2. If diplopia persists through the pinhole, the likely cause is a macular defect. If diplopia is resolved with the use of a pinhole, the cause is an error in light diffraction (high ametropia, astigmatism, tear film abnormalities, lens dislocations, etc.).
3. Fundoscopic examination can be performed as an adjunct.
4. Ophthalmologic referral is indicated in most cases.
Binocular diplopia:
1. As binocular diplopia is frequently caused by neuromuscular dysfunction it requires further evaluation in the emergency department to rule out neurological insult. The presence of additional neurological symptoms should prompt expedited neuroimaging and neurology consultation.
2. Compensatory head positions for diplopia are illustrated in Fig E1. Extraocular movements should be assessed to determine the responsible muscle or nerve. In restrictive pathologies, the diplopia will be worse and the extraocular movements impaired in the direction away from the pathology. Otherwise, the pathology lies on the side with worsening diplopia and impaired extraocular movement.
3. Imaging is the mainstay of the workup and is indicated in most cases of undifferentiated binocular diplopia.
4. Laboratory studies are rarely helpful but can be used in certain scenarios (infectious etiologies, CSF analysis in meningitis, and thyroid panel).
Fig. E2 describes an algorithm for the diagnostic approach to diplopia.

FIG E1 Compensatory Head Positions for Diplopia

A, Right Lateral Rectus Palsy. A Right Esotropia is Present in Primary Gaze; However, by Turning the Head to the Right (in the Direction of Action of the Weak Right Lateral Rectus Muscle), the Patient Can Move the Eyes into Left Gaze and Maintain Both Eyes on Target (Orthotropia), Thereby Achieving Binocular Single Vision. B, Acute Right Superior Oblique Muscle Palsy. The Right Eye Extorts (Excycloduction) Because of the Unopposed Action of the Right Inferior Oblique Muscle. When the Patient Tilts the Head to the Left and Forward (in the Direction of Action of the Weak Muscle), the Right Eye is Passively Intorted While the Left Eye Actively Intorts to Compensate and Maintain Binocular Single Vision. The Head Also Tilts Forward to Compensate for the Weak Depressor Action of the Weak Right Superior Oblique.

From Jankovic J et al: Bradley and Daroff’s neurology in clinical practice, ed 8, Philadelphia 2022, Elsevier.

Figure E2 Algorithm for the Diagnostic Approach to Diplopia in the Emergency Department-a Guideline

Cn, Cranial Nerve; CT, Computed Tomography; CTA, CT Angiogram; Dsa, Digital Subtraction Angiography (Conventional Angiography); Dwi, Diffusion-Weighted Imaging; Gad, Gadolinium; Hi-Res, High-Resolution; Lp, Lumbar Puncture; MRA, Magnetic Resonance Angiography; MRI, Magnetic Resonance Imaging.

From Walls RM et al: Rosen’s emergency medicine, ed 9, Philadelphia, 2018, Elsevier.

BOX E3 Assessment of the Patient With Diplopia

History

Monocular or binocular?
Horizontal, vertical, or oblique separation of the images?
Effect of distance of target (worse at near or far)?
Effect of fatigue? Worse in morning or evening?
Transient or persistent? If transient, effect of gaze direction or truly transient (consider giant cell arteritis)?
Tilting of one image?
Is there is a history of head trauma, cancer, “lazy eye,” eye surgery, or botulinum toxin?
What other symptoms are present (i.e., headache, eye pain, dizziness, weakness)?

Observation

Head tilt or turn? (“FAT ^1∗ scan”)
Ptosis (fatigue)?
Pupil size? Anisocoria?
Proptosis?

Eye Examination

Visual acuity (each eye separately, and binocularly if primary position nystagmus present)
Versions (pursuit, saccades, and muscle overaction)
Convergence (does miosis occur?)
Ductions
Ocular alignment (muscle balance) in the “forced primary position” and comitance pattern
Pupils
Lids (examine palpebral fissures, levator function, fatigue)
Vestibulo-ocular reflexes (doll’s eye reflex)
Bell phenomenon
Prism measurements
Stereopsis (Titmus stereo test)
Optokinetic nystagmus

General Neurological Examination

Other Tests Where Indicated

Listen for bruits
Forced ductions
Edrophonium (Tensilon) test
Lights on-off test for the dragged-fovea diplopia syndrome
Ice-pack test for ptosis

From Jankovic J et al: Bradley and Daroff’s neurology in clinical practice, ed 8, Philadelphia, 2022, Elsevier.

Laboratory Tests

Thyroid panel may be useful in cases of suspected thyroid disease.
Lumbar puncture for meningitis or Miller-Fischer syndrome.

Imaging Studies

Magnetic resonance imaging (MRI) of the orbits with gadolinium is the test of choice in patients with suspected restrictive, mechanical orbitopathy; cavernous sinus; or posterior orbit pathology. Computed tomography (CT) of the head with contrast is a second-line option.
For an isolated mononeuropathy, MRI of the brain and orbits with gadolinium is preferred. CT angiography (CTA) or magnetic resonance angiography (MRA) should be obtained in cases of suspected aneurysm. MRA should be used with caution when aneurysm is highly suspected because the sensitivity of MRA decreases with aneurysm size less than 5 mm.
MRI with and without gadolinium is recommended for detection of brainstem lesions. The addition of a diffusion-weighted imaging protocol may be useful when ischemia is suspected.

1∗ FAT, Family album tomography-review of old photographs for head tilt, pupil size, lids, ocular alignment, etc. For magnification, use an ophthalmoscope, magnifying glass, or slit lamp.

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