27th December 2023

Diplopia

Background

Epidemiology

Diplopia (seeing double) is a common presentation estimated to represent 1.4% of ocular emergencies. There are many potential causes, which could be neurological or ophthalmological. Differentiating between diagnoses relies on thorough and careful history-taking and clinical examination.

Pathophysiology

Diplopia is the symptom of seeing double, either in the horizontal, vertical or diagonal plane, and can be constant or intermittent. It can be monocular or binocular, each with its own set of possible underlying causes. Characterising if the diplopia is monocular or binocular is the first step towards identifying a cause. To provide an idea of how many causes there could be for this symptom, consider the complexity of binocular vision. Each eye is moved by six extraocular muscles, each controlled by one of three cranial nerves which arise from the midbrain and pons. These cranial nerves, via the medial longitudinal fasciculus, carry information about the direction in which the eye should move, all of which are coordinated by the supranuclear gaze centres. In normal sight, each eye sends a slightly different image to the visual processing centre, where complex mechanisms converge the two images together. When images from the eyes are too dissimilar, diplopia is experienced.

Monocular diplopia

This is double vision, which resolves only when the affected eye is covered. The majority of monocular diplopia presentations are intraocular, and common pathologies include uncorrected refractive errors, cataracts, corneal irregularities such as dry eye and keratoconus, vitreous opacities or abnormalities of the iris. Rarely disorders of the primary or secondary visual cortex can cause monocular diplopia.

Binocular diplopia

This is double vision, which resolves by covering either eye. Binocular diplopia is due to misalignment of the visual axes, the cause of which is many. There are three general categories which cover the causes of binocular diplopia relating to nerves, muscles and those conditions which may affect the neuromuscular junction.

1. Nerve: supranuclear, nuclear or infranuclear causes, infarct, infection, compression, inflammation, demyelination, degeneration
2. Muscle: pathologies within the extraocular muscles, such as thyroid eye disease
3. NMJ: primarily myasthenia gravis

Physiological diplopia

Normal double vision is when objects behind or in front of a visual target are seen in double. This is normal, where true diplopia has been excluded. In true diplopia, whatever the patient is fixating on will be in double. A simple test is to ask the patient to fixate on something in the distance, with a target in near vision, such as a thumb. When looking at an object in the distance, the thumb will be in double, and when looking at the object in near vision, the items in the distance will be in double. Everyone has an element of double vision, but the visual centres amalgamate images from each eye into one, so you will likely not appreciate it in normal vision. Some patients are very astute to this normal double vision and may present for evaluation.

References

• Walker, J. R. & Earl Corley, J. (2021) ‘Diplopia’, in Ferri’s Clinical Advisor 2021. [Online]. pp. 477.e11–477.e14.
• Danchaivijitr C, Kennard C. Diplopia and eye movement disorders. Journal of Neurology, Neurosurgery & Psychiatry. 2004 Dec 1;75(suppl 4):iv24-31.
• Iliescu DA, Timaru CM, Alexe N, Gosav E, De Simone A, Batras M, Stefan C. Management of diplopia. Romanian journal of ophthalmology. 2017 Jul;61(3):166.

Presentation

Both monocular and binocular diplopia can present in the same way with a history of double vision, where single objects appear as double in the horizontal, vertical, or oblique plane. Binocular diplopia tends to present as two clearly separated images, whereas monocular presentations describe a ‘ghost image’ or a second slightly faded image, which may partly overlap the true image.

The onset of diplopia is almost always sudden and, depending on the underlying cause, can worsen or improve over time. Because of its sudden onset, diplopia can often be presumed to have a vascular cause, but it is important to keep a broad differential list. The progression of the diplopia can be quite telling; for example, changes in the pattern and intensity of diplopia point towards pathology such as compression, whereas intermittent diplopia with diurnal variation points more towards neuromuscular junction disorders like myasthenia gravis.

Patients may also present with compensatory mechanisms such as head tilts, which they do to reduce the double vision phenomenon. When the diplopia is secondary to uncorrected strabismus, patients may present with obvious squint, which is not necessarily the presenting complaint.

In cases of diplopia secondary to pathologies such as myasthenia gravis or thyroid eye disease, patients may present with diplopia later in the day or worse in the morning, respectively. Patients with Parkinson’s Disease can present with diplopia secondary to convergence insufficiency, where there is a horizontal diplopia after prolonged periods of near vision tasks such as reading. These patients may present with letters that ‘mix together’ on the page or screen.

The past medical and family history may include vascular risk factors such as hypertension, diabetes or cardiac disease, and specific ophthalmology questions may highlight issues in childhood or even ongoing in adulthood, such as strabismus corrected with prisms or surgery. It is important to explore ocular trauma, headache history, control of any comorbidities such as hypertension and diabetes, and a drug history such as citalopram, lamotrigine, and gabapentin have been associated with diplopia.

Signs

Source: Wikimedia Commons (2019). StrabismusVL2, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?curid=81253483 (Accessed on: 13 February 2023).

Source: Wikimedia Commons (2017). Proptosis and lid retraction from Graves’ Disease, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?curid=16115992 (Accessed on: 13 February 2023).

Source: Wikimedia Commons (2009). Congenitalptosis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Congenitalptosis.JPG (Accessed on: 13 February 2023).

References

• Iliescu DA, Timaru CM, Alexe N, Gosav E, De Simone A, Batras M, Stefan C. Management of diplopia. Romanian journal of ophthalmology. 2017 Jul;61(3):166.
• Jitander Dudee MD. Diplopia (Double Vision) clinical presentation [Internet]. History, Physical, Causes. Medscape; 2022 [cited 2023Feb9]. Available from: https://emedicine.medscape.com/article/1214490-clinical

Diagnosis

As with many presentations in medicine, an accurate history and examination is crucial and can reveal the cause of the diplopia in the majority of cases. There are two types of diplopia, monocular and binocular, and differentiating between these is a crucial first step. Refractive errors or lens diseases should be suspected in monocular diplopia when it can be resolved with a pinhole, whereas binocular diplopia requires the clinician to determine the underlying cause of the ocular misalignment.

Monocular or binocular assessment

Monocular diplopia is diagnosed when the double vision does not resolve upon closing or covering either eye and, therefore present with monocular viewing. Monocular diplopia can be bilateral, which is not the same as binocular diplopia, which requires both eyes to be open and have the symptom of double vision. In binocular diplopia, covering either eye will eliminate the diplopia.

Use of a pinhole device

Where monocular diplopia is confirmed, a pinhole device should be utilised to identify whether the cause may be related to anterior structures such as the cornea or the lens. The pinhole will block peripheral light rays, only allowing central light to pass through the cornea and pupil, improving acuity and eliminating diplopia secondary to an optical cause. If the diplopia persists, one should consider issues with the macula, such as oedema or problems with the cortex. The symptom of multiple images (> 2) is known as cerebral polyopia and is a rare occurrence of monocular diplopia secondary to structural disorders of the cerebral cortex.

Assess the brainstem

Diplopia can be a symptom seen in stroke patients where structures in the brainstem are affected. Therefore, when monocular diplopia is excluded, the logical next step would be to assess the brainstem and organise urgent imaging where indicated. Structures which may be affected include:

1. The diencephalon, a primary relay and processing centre for sensory (including visual) information
2. Nuclei or fascicles of the 3ʳᵈ, 5ᵗʰ, or 6ᵗʰ cranial nerves, each responsible for extraocular muscle function
3. The medial longitudinal fasciculus – a specialised nerve bundle involved in extraocular function
4. The vestibulo-ocular pathway – important in the gaze-stabilising reflex

Assess the diplopia axis

Purely vertical diplopia is caused by 3ʳᵈ or 4ᵗʰ nerve palsy, myasthenia gravis, skew deviation (acquired vertical misalignment not due to any single muscle or ocular motor nerve) or processes related to the orbital tissues such as thyroid eye disease. Purely horizontal diplopia is usually related to abduction (6ᵗʰ cranial nerve) and adduction (third cranial nerve) deficits. Identifying problems with extraocular motility can be difficult and requires a detailed examination, observing each eye separately. Whilst assessing the axis, it is important to observe any signs of thyroid eye disease, such as proptosis or lid lag and for signs of myasthenia, such as fatigable ptosis.

Assess eye misalignment

Cover and alternate cover testing is an efficient and quick way to assess the alignment of the eyes and establish if a diplopia may be due to strabismus. Cover tests can help identify and quantify ocular misalignment, and there are three types of cover test, two of which can be performed at the bedside with little equipment.

Begin with the monocular cover-uncover test, which differentiates between tropias, where a deviation is always present, and phorias, where a deviation is present when one eye is closed or covered. Ask the patient to fixate on a point ahead, roughly 50cm or further away, and observe for any deviations. If placing an occluder over the non-affected eye causes the affected eye to fixate, this is known as a tropia. A phoria would be seen when the covered eye deviates on occlusion and returns to fixation on removal of the occluder.

The alternate cover test involves the patient fixating on a point ahead of them whilst the examiner moves an occluder from one eye to the other whilst focusing on the movement of the uncovered eye. This test allows the examiner to note whether the deviation is worse in specific gazes, i.e. when looking to the left, right, up, down or on a diagonal plane. A deviation which remains the same in all positions of gaze is classed as concomitant and incomitant if it is affected. Incomitant squints should raise concern for neurological, myogenic or neuromuscular junction disorders and may involve specialist input from neurology, whereas concomitant squint should be referred to ophthalmology and may not require further investigation.

Investigations

Blood pressure, blood glucose, urine analysis and erythrocyte sedimentation rate should be performed in cases where a microvascular pathology is suspected. Where thyroid or myasthenia causes are suspected, thyroid function tests, anti-acetylcholine receptor antibodies and single fibre electromyography (EMG) of the orbicularis muscles should be considered. The ice test is a simple bedside investigation which is highly sensitive and specific to myasthenia. The test is interpreted as positive when a ptotic lid is improved after ice application for 2-5 minutes. Acute CT or MRI scans should be obtained when the onset of diplopia is acute and/or present with neurological signs or papilloedema.

Differential Diagnoses

Parkinson’s Disease

Ophthalmological signs in Parkinson’s can arise from efferent or afferent dysfunction due to the decreased levels of dopamine in the CNS. In normal physiology, dopamine is a neurotransmitter in the retina and is theorised to control the activity of several cell types. Ocular symptoms can include horizontal diplopia (mono or binocular), convergence insufficiency where a patient struggles to read or clearly see items at close distance, photosensitivity, and subjective reductions in visual quality.

Skew deviation

This is a vertical and oblique diplopia which cannot be localised to a single extraocular muscle or cranial nerve and is, therefore, a diagnosis of exclusion. Suspicion for skew deviation should be raised if a 3-step test does not highlight a problem with the 4th cranial nerve, i.e. the problematic muscle is not superior oblique. Further testing can be performed via Maddox Rod; however, this requires specialist input and interpretation.

6ᵗʰ nerve palsies

The abducens nerve has a long course from its source in the pons to the terminus at the lateral rectus muscle. Innervation of the lateral rectus allows for abduction (lateral gaze) of the eye. Understanding the anatomy of the abducens nerve helps in highlighting the key pathologies which can result in 6ᵗʰ nerve palsies.

Nuclear – a nuclear sixth nerve palsy can present as a horizontal gaze palsy where the patient is unable to abduct the ipsilateral eye and adduct the contralateral eye. The 6ᵗʰ nerve nucleus intermixes with the contralateral 3ʳᵈ nerve nucleus via the medial longitudinal fasciculus, allowing for gaze to one direction or another (i.e. both eyes moving in the same direction at the same time.) When the 6ᵗʰ nerve nucleus has been affected by such processes as brainstem demyelination, compression secondary to a neoplasm or micro-ischaemia, then the contralateral 3ʳᵈ nerve can also be affected. Cranial nerve VII may also be affected as the nerve fascicle loops around the nucleus of cranial nerve 6. The medial longitudinal fasciculus can be damaged by any lesion or ischaemia as it is supplied by branches of the basilar artery; this can cause internuclear ophthalmoplegia (INO). INO is an ocular movement disorder characterised by partial or complete loss of adduction on the same side as the lesion/ischaemia and contralateral nystagmus on abduction. The MLF passes through the pons into the midbrain, meaning the location of the lesion can be in both. If the patient is able to converge their eyes (i.e. become cross-eyed), then that means the 3ʳᵈ nerve nucleus is functioning via communications from the convergence centre in the midbrain, meaning the lesion is likely in the pons.

Fascicle – The nerve fascicle can be affected as it travels towards its exit point at the pontomedullary junction. This often presents with contralateral hemiparesis due to involvement of the pyramidal tract.

The subarachnoid space – the abducens nerve is anchored at its exit at the pontomedullary junction and to the petroclinoid ligament, where the nerve turns 90 degrees after following the slope of the clivus. Between these two anchoring points, the nerve exists in the subarachnoid space, and changes in intracranial pressure (ICP), either increased or decreased, may result in downward displacement of the brainstem, causing stretching of the nerve.

Petrous – as it passes under the petroclinoid ligament, the nerve contacts the tip of the petrous pyramid, making it susceptible to pathologies related to the temporal bone. These can be neoplastic, inflammatory, via compression and often involve the 8ᵗʰ, 7ᵗʰ or 5ᵗʰ nerves due to their close proximity.

Cavernous sinus – as the nerve passes through the cavernous sinus, it can be associated with the 3ʳᵈ, 4ᵗʰ and V1/2 branches of the 5ᵗʰ cranial nerve. Cavernous sinus thrombosis, most commonly due to infection, can produce cranial nerve palsies, the most affected being the abducens nerve. The internal carotid artery also passes through the cavernous sinus, giving rise to the possibility of aneurysms and fistulas, which again can lead to cranial nerve palsies.

Superior orbital fissure – pathologies involved in the cavernous sinus can also affect the superior orbital fissure due to its mixed contents of cranial nerves and vessels. Problems at this point of the abducens nerve length are often associated with proptosis and decreasing vision.

The most likely aetiology of isolated six nerve palsy in adults is ischaemia. This can be due to a host of comorbidities, including diabetes, hypertension, temple arthritis or anaemia.

3ʳᵈ nerve palsies

The oculomotor nerve has three main functions: innervation to the pupil and lens, innervation to the upper eyelid and innervation of the extraocular muscles (SR, MR, IR, IO). Complete third nerve palsies are likely to present with ptosis, a dilated pupil with sluggish to no reactions and a down-and-out eye with an inability to adduct, infraduct or supraduct. Partial third nerve palsies are more common, and these can present with a mix of the previously mentioned signs to varying degrees of severity.

The third nerve originates from two nuclei in the midbrain and exits near the midline at the base of the midbrain. From here, the nerve passes through the cavernous sinus towards and through the superior orbital fissure and to the orbit of the eye. Therefore, the same pathologies which can affect the 6ᵗʰ cranial nerve in the cavernous sinus or orbital fissure can also affect the 3ʳᵈ nerve. Patients presenting with new signs and symptoms of 3ʳᵈ nerve palsy raise suspicion for aneurysms, which may be compressing the nerve between it exiting the midbrain and entering the cavernous sinus, mainly an aneurysm of the posterior communicating artery. Also, CN III has parasympathetic fibres controlling pupil constriction running along the outside of the nerve. Therefore, external compression of the 3ʳᵈ nerve may lead to pupil dilation. If any ocular motility examination suggests involvement of CN III + deficits of duction with or without a dilated pupil, urgent non-contrast CT head with possibility of additional CT angiogram should be discussed. MRA should be discussed for patients who are pregnant, with poor renal function or allergy to contrast agents.

Lesions affecting the 3ʳᵈ nerve nucleus in the midbrain can present with bilateral complete ptosis due to there being only one sub-nucleus innervating both levator palpebrae superioris muscles. If the corticospinal tract has been affected, patients can present with contralateral hemiplegia or ataxia if the superior cerebellar peduncle is involved. The 3rd nerve partly exists within the subarachnoid space and is therefore at risk of damage secondary to infections, inflammation or masses within the subarachnoid space. In patients presenting and not requiring urgent CT imaging of the brain, it is not unreasonable to consider an MRI  with contrast to evaluate the entire path of the 3rd nerve to rule out lesions/processes along its course.

4ᵗʰ nerve palsies

As mentioned earlier, a palsy of the trochlear nerve will result in vertical diplopia. Superior oblique intorts and depresses the eye in the adducted position. So, clinical examination of a patient with a 4ᵗʰ nerve palsy may reveal abnormal head posture (torticollis) in an attempt to compensate for the diplopia, strabismus in the affected eye where there would be a hypertropia and in some cases an esotropia. The trochlear nerve is the only cranial nerve which crosses the midline to innervate the contralateral side and exits the brainstem dorsally. This means that in cases of trauma to the dorsal aspect of the brainstem, a patient can have a bilateral 4th nerve palsy, which presents with vertical diplopia and strabismus.

The Parks 3 Step test can be utilised as a gross bedside test to help determine which extraocular muscle is causing a vertical diplopia. Understanding why the test works requires an in-depth understanding of how the extraocular muscles rotate the eye on 3 axes, which is not covered in this section. The test will not be diagnostic if more than one extraocular muscle is affected.

1. Identify the hypertrophic eye in primary position – ask the patient to gaze ahead and see which eye is hypertrophic. If, for example, the right eye is higher, then the muscles affected are narrowed to either the depressors of the right eye (IR + SO) or the elevators (SR + IO) of the left eye.
2. Identify if the hypertropia worsens in left or right gaze – in a trochlear nerve palsy, hypertropia of the paretic eye will increase on the opposite gaze.
3. Identify if the hypertropia is worse on head tilt to the left or right – in a trochlear nerve palsy, the hypertropia will worsen on tilting to the same side.

There is a very quick and easy diagram you can utilise when identifying which extraocular muscle may be the culprit in presentations of vertical diplopia.

In this example, the patient presents with vertical diplopia and a right-sided hypertropia on examination. Step 1 is to circle the muscles on the bottom of the eye, which is deviated, and circle the muscles on the top on the contralateral side (highlighted in green). The next step of the test is to examine when the deviation worsens in left or right gaze. In this example, the patient’s vision worsens in left gaze, so you circle the muscles utilised for left gaze (amber). The final step is to identify which direction of head tilt worsens the deviation; in this case, it is right-sided head tilt. Highlight the muscles on the diagonal, which corresponds to whichever direction the deviation is greatest. The extraocular muscle, which has been circled 3 times, is the muscle causing the deviation, which in this example is the right superior oblique.

Thyroid eye disease

The position of the lid must be observed when diagnosing thyroid eye disease. Pathological signs include lid lag, where the upper lid lags behind the limbus when the patient rapidly diverts their eye from superior to inferior gaze, and lid retraction, where the sclera is visible above and below the iris. Thyroid eye disease causes enlargement of the extraocular muscles, which restricts their movement and causes diplopia.

Myasthenia gravis

Patients may complain of associated symptoms such as dysphagia, dysarthria and dyspnoea, which worsen as the day goes on and improve with rest. Ocular signs include ptosis, sometimes beginning as unilateral, which frequently shifts from one eye to the other to eventually become bilateral. Pupils are never involved in myasthenia.

References

• Margolin E. Approach to patients with diplopia. Journal of the Neurological Sciences. 2020 Oct 15;417:117055.
• Crumbie L. Diencephalon [Internet]. Kenhub. 2022. Available from: https://www.kenhub.com/en/library/anatomy/diencephalon
• Kanukollu VM, Sood G. Strabismus.
• Danchaivijitr C, Kennard C. Diplopia and eye movement disorders. Journal of Neurology, Neurosurgery & Psychiatry. 2004 Dec 1;75(suppl 4):iv24-31.
• The Cavernous Sinus – Contents – Borders – Thrombosis – TeachMeAnatomy [Internet]. Available from: https://teachmeanatomy.info/neuroanatomy/vessels/cavernous-sinus/
• ‌ Nguyen V, Reddy V, Varacallo M. Neuroanatomy, cranial nerve 6 (abducens). InStatPearls [Internet] 2021 Nov 29. StatPearls Publishing.
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• Joyce C, Le PH, Peterson DC. Neuroanatomy, Cranial Nerve 3 (Oculomotor) [Updated 2022 Mar 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
• Elkington AR, Frank HJ. 2nd ed. Oxford: Blackwell Science; 1991. Clinical Optics p.94-98
• Tan AK, Faridah HA. The two-minute approach to monocular diplopia. Malaysian Family Physician: the official journal of the Academy of Family Physicians of Malaysia. 2010;5(3):115.

Management

General advice

All patients should be advised to stop driving and report their visual symptoms to the DVLA, who may perform their own assessment or advise on criteria to be met prior to driving again. Suspected underlying pathologies should be appropriately investigated and managed, which is often driven by ophthalmology after routine or urgent referrals.

Monocular diplopia

Close examination and use of a pinhole will confirm monocular diplopia, the causes of which are often uncorrected refractive errors and cataracts. Routine referrals to optometry or ophthalmology are suggested for treatments such as glasses, contact lenses, cataract surgery and even simple measures like artificial tears.

Binocular diplopia

Acute management is aimed at relieving any debilitating symptoms due to the diplopia. The aim is to regain single binocular vision by unilateral occlusion of the poorer eye. In younger patients, there is a risk of developing amblyopia, and so the occlusion is alternated between each eye. Other options include using prisms to realign the visual axis in vertical or horizontal diplopia. When the binocular diplopia is long-standing or an underlying cause cannot be identified or managed, then surgery can be considered. Some cases are managed with botulinum injections into the antagonistic muscle to the paretic one, i.e. MR to LR in a 6ᵗʰ nerve palsy.

References

• Mashige KP, Munsamy AJ. Diplopia. South African Family Practice. 2016 Aug 26;58(sup1):S12-7.
• Margolin E. Approach to patients with diplopia. Journal of the Neurological Sciences. 2020 Oct 15;417:117055.