Eye movements - an overview

In order for the eyes to move fully, together and in a co-ordinated way, there has to be correct functioning at three levels in the visual system:

• The six extraocular muscles: these are the four rectus muscles and the two obliques. When the eyes are looking straight ahead, they are said to be in the primary position. The extraocular muscles enable them to be moved into one of the six so-called cardinal positions of gaze (i.e. directed to one side or the other, either looking out and up, straight out or out and down) or into one of the two midline vertical positions (looking directly up or directly down). Deviations from these positions of gaze provide the basis for diagnosis of a squint.
• The three cranial nerves: all the movements of the eyes are enabled by the third cranial nerve other than lateral abduction (lateral rectus) which is generated by the sixth (abducent) cranial nerve and a downward, inward gaze (such as looking where to put your feet when going down a flight of steps - superior oblique) which is generated by the fourth (trochlear) cranial nerve.
• The higher brain centres including the three cranial nerve nuclei: the third, fourth and sixth brainstem nuclei ensure the correct functioning of their relevant cranial nerves and connections between the nuclei ensure that the eyes move together in a co-ordinated way. The higher cortical centres control the speed of eye movements either when following a moving target (pursuit) or jumping from one target to another (saccades).

Overview of eye movement disorders¹

Eye movement disorders can fall into four categories. Some disorders can belong to more than one category:

• Non-paralytic (concomitant) squint - both eye movements are full but only one eye is directed towards the target. There is a constant angle of deviation which is unrelated to the direction of gaze. This tends to be the squint of childhood.
• Paralytic (incomitant) squint - there is under-action of at least one of the extraocular muscles and the degree of squint is dependent on the direction of gaze (being largest when the globe is rotated towards the field of action of the relevant muscles or their associated nerve).
• Disorder of input into brainstem nuclei - this may result in abnormal eye movement co-ordination or in oscillating eye movements (nystagmus).
• Gaze palsies - these occur when there is a problem at the level of the higher cortical centres and may be associated with abnormal pursuit or saccadic eye movements.

Squints

Description²

Otherwise known as strabismus, squint refers to a misalignment of the eyes. The image is therefore not in corresponding areas of both eyes, which may result in eventual amblyopia in childhood or diplopia in adulthood. It is actually pretty unusual for eyes to be perfectly aligned (orthophoria) and most people have a very slight tendency to deviate their direction of gaze, so resulting in mild heterophoria (latent squint). A latent squint can sometimes be seen as the individual gazes into the distance or when tired or daydreaming.³ Heterotropia refers to a manifest squint. A 'phoria' can develop into a 'tropia' if:

• Muscle strength is inadequate to maintain alignment.
• Stimulus to maintain alignment is weak (e.g. blurred vision).
• There is a problem with the neurological pathway.

Intermittent squints are common in neonates but the eyes should be fully aligned by about 3 months of age.

Terminology

The prefixes 'eso' and 'exo' before a 'phoria' or a 'tropia' refer to an inward and outward ocular deviation respectively (e.g. exotropia refers to a manifest squint where there is an outward turning of the eye). Alphabet patterns are ascribed to incomitant horizontal deviations if they vary significantly when measured from the upward to the downward gaze. If the deviation is greater in the upward gaze than the downward gaze, it is said to follow a 'V' pattern. If it is greater in the downward gaze than the upward gaze, it is said to follow an 'A' pattern. These terms can be applied to both esotropias and exotropias.

Finally, the prefixes 'hypo' and 'hyper' refer to a downward or upward deviation respectively. This form of squint is less common.⁴

Classification

There are a number of ways of classifying squints but, for practical purposes, it is helpful to consider whether it is congenital (onset before six months of age) or acquired and then use the above terminology to describe whether the eyes permanently or intermittently turn in, out, up or down and whether this is concomitant or not. Infantile (congenital or essential) esotropia refers to the common condition characterised by a squint (of various sorts as described above) in an otherwise normal infant with no refractive error. There are more elaborate systems used by ophthalmologists which combine the elements described above with whether the problem is on near or distant gaze, whether there is accommodative ability or not, whether the problem changes over time (e.g. exotropia becoming an esotropia), etc. However, using the above terminology is perfectly fine in the primary care setting.

Non-paralytic squint

Epidemiology

• Ocular misalignments are common in newborns: one study found the prevalence of these to be about 73% in one month-old babies, reducing to 50% in two month-old babies and virtually disappearing in normal four month-olds.⁵
• Pathological misalignment is prevalent among older children, affecting about 5% of 5 year-olds⁶ (of these, 60% have eso-deviations and 20% have exo-deviations). This drops to ~3% in the 13-24 year-old age group.⁴
• Esotropias appear to be more common among Caucasians but, in the few studies looking at prevalence of this problem among non-white populations, the reverse appears to be true in West Indian children and patients of oriental descent.
• Intermittent exotropias are more common than constant exotropias, which tend to be associated with other abnormalities.

Presentation^1,4

• Parental concern due to the presence of a manifest squint.
• Motor skills may be reduced in amblyopic children but particularly those with strabismus (manual dexterity tasks requiring speed and accuracy are affected the greatest).⁶
• Detection at a preschool screening clinic.
• Compensatory head tilt or chin lift to minimise diplopia and enable binocular viewing.
• There may be a history of risk factors including:
  • Family history.
  • Prematurity.
  • Neonatal jaundice.
  • Encephalitis.
  • Meningitis.
  • Cerebral palsy.
  • Craniofacial abnormalities.
  • Learning disabilities ± syndromes, e.g. Down's syndrome and Turner's syndrome.
  • A febrile illness may occasionally precede accommodative esotropia.
  There may also be associated ocular pathology including:
  • Refractive error, particularly anisometropia (the refractive error is different in both eyes) and high hypermetropia (very long-sighted).
  • Media opacities such as cataract.
  • Retinal abnormalities such as retinoblastoma.
• The majority of children have no associated disorders.

Examination

• A young baby should be examined for the presence of epicanthic folds (crescenteric folds of skin on each side of the nose) which could give rise to pseudoesotropia: the impression that the eyes are turned inwards when in fact they are not. The corneal reflection test (Hirschberg's test) can help to rule this out.
  

  Hirschberg's test This gives a rough estimate of the degree of strabismus. Hold a pen torch about an arm's length (~33 cm) away from the patient and shine it in front of their eyes. If the patient is able to understand instructions, ask them to look at the light (babies will tend to look towards it anyway, even if briefly). Observe where the reflection of the pen torch lies with respect to the cornea. It should be central bilaterally. If it lies at the inner margin of the pupil, there is an outward deviation (exotropia) of the eye. If it lies at the outer margin, an esotropia is present. When the reflection is at the margin of the pupil, there is approximately 15° deviation and, if it lies at the edge of the cornea, there is ~45° deviation.

• Look for facial asymmetry (either craniofacial abnormalities or head tilt) and obvious eye abnormalities, e.g. ptosis or proptosis.
• Perform the cover/uncover test. If this appears to be normal, try the alternate cover test.
  

  Cover/uncover test An object to focus on is held in front of the patient who is instructed to focus on it. One eye is completely occluded for several seconds and the uncovered eye is observed for movement as it focuses on the object. This eye is then covered and the other eye is observed for movement. Movement of the eye outwards confirms that there is an esotropia (i.e. the eye was turned inwards initially) and vice versa for exotropia. The test is repeated for objects at 6 metres and far distance, which may also reveal a vertical squint. Alternate cover test This is done in a similar fashion to the previous test but the occluder is rapidly switched from one eye to the other. There is now no longer bifoveal stimulation (so each eye is seeing a separate image). Observing the eye movement as the occluder is removed, note whether it moves inwards (i.e. there is a latent exophoria and the eye has to move in to see again) or outwards (revealing a latent esophoria).

• Assess the patient for evidence of any other ocular abnormality or systemic abnormality (see risk factors and associations under 'Presentation', above).

Investigation

In the eye unit, the patient will undergo a series of tests aimed at pinpointing the problem.⁷ This may include assessment of motility, accommodation, fixation, binocularity, stereopsis, refraction and a number of other tests.⁸ If there is suspicion of associated diseases, the relevant investigations will be carried out according to clinical findings.

Management

• Referral - a neonate with a constant squint or with a squint that is worsening from two months of age should be referred to an ophthalmologist.⁵ Any older child with a suspected squint should be seen in the Eye Clinic. Refer to your local protocol but, generally, this will be to the orthoptist team who will liaise with the ophthalmologists. The earlier the referral, the better chance the child has of avoiding the possibility of amblyopia.
• Assessment - there will be both an orthoptic assessment (to assess the visual acuity and ascertain the presence and nature of the squint) as well as a medical review to ensure that the eye is otherwise healthy.
• General approaches:
  • Treatment is guided by the exact nature of the squint and by the patient's age.
  • Correction of refractive errors will be the (important) first step in the management of these individuals.
  • If the patient is less than 8 years old, any concurrent amblyopia will need treating too⁷ (e.g. eye patching ± cycloplegic drops).
  • Some patients are treated with prisms (placed on spectacle lenses) too.⁴
  • Patients may go on to have surgical alignment (particularly for esotropias) if previous treatment attempts have failed or if the squint is large enough. A combination of muscle recession (it is moved backwards on the globe and so its action is weakened) and antagonistic muscle resection (a segment of muscle is removed, so strengthening its action) is used with the aim to restore binocular function. Sometimes, adjustable sutures are used to enable minor corrections to be made without having to go through a further full surgical procedure. These have traditionally been used in older patients but there has been some recent success in applying these methods to children and infants.⁹ There is not always a consensus as to whether a unilateral or bilateral procedure is best - this depends on your local eye unit practices and on the operating surgeon. Sometimes, it takes more than one procedure to get the satisfactory result but few surgeons would operate more than two or three times.
• Esotropia:
  • Infantile esotropia is best managed with early surgical intervention to optimise outcome.¹⁰ This is ideally carried out before the child's first birthday but there is a risk of subsequent exotropia.⁷
  • There have been new developments in the management of esotropia, including chemodenervation by injection of botulinum toxin type A in one or more extraocular muscles. There is a paucity of good-quality research into this and a recent Cochrane review suggested only a modest (if any) benefit while highlighting the high rate of complications (found in a quarter to half of patients).¹¹ However, this may play a valuable diagnostic role in certain cases and may help plan surgery, particularly if the esotropia has arisen as a result of over-correction of exotropia.
  • Another approach with esotropia has been to use miotic agents (e.g. cholinesterase inhibitors) which reduce accommodative effort and convergence by stimulating ciliary muscle convergence but the side-effects of the miotic drugs limit this use.⁴
• Exotropia:³
  • Where this is intermittent, treatment is more commonly sought by the patient or parents than due to a visual need to realign the eyes. If there is a concern about visual acuity in the child, surgery should be performed by about 5 years of age.⁸ There has been evidence suggesting that monocular surgery is better for these patients. If the problem is subtle, eye exercises may suffice.

Children should be followed up at regular intervals (younger children more frequently than older ones due to the risk of developing amblyopia). This will typically be in the order of every few weeks to months, initially depending on the exact problem and treatment used.

Complications²

• An uncorrected squint can lead to amblyopia (lazy eye).
• Surgical under- or over-correction may happen during the initial procedure, necessitating further surgery.¹²
• Inferior oblique overaction may sometimes occur (usually at about 2 years of age) so patients may need further surgery despite an apparently good initial result.
• Dissociated vertical vision (the eye drifts up and out during periods of inattention) can occur years after initial surgery and may warrant surgical intervention if it becomes cosmetically unacceptable.
• There is work being done in the assessment of the psychological consequences of these visual disorders and their effect on quality of life.¹³ There are no firm conclusions yet but it would seem that there is a significantly increased risk of strabismic children going on to develop adult mental health problems¹⁴ and there are social ramifications, such as poorer chances of success in job interviews (see 'Psychosocial aspects of squints', below).¹⁵

Prognosis⁴

This depends on the nature and degree of the squint and whether there are any associated underlying problems. Generally, early intervention should produce good alignment and limit any amblyopia but perfect stereopsis (3-D vision) is rarely achieved.

Paralytic squint¹⁶

This refers to the group of conditions characterised by disease of the III, IV and VI cranial nerves. A nerve palsy may be isolated or there may be multiple nerves involved. Each nerve may be affected at any point along its course from the brainstem to the orbit. Myopathies may give rise to diplopia and restriction of eye movement; in severe cases there may be a degree of paralytic squint. Myopathies, unlike neuropathies, tend to be bilateral. Below is an overview of diplopia and cranial nerve palsies; you will find more detail about these conditions in the separate article Diplopia and III, IV and VI Cranial Nerve Lesions.

Diplopia

This is the term used when a patient sees an image in two different places. They are most commonly side by side (horizontal diplopia) but may be one on top of the other (vertical diplopia) or, unusually, oblique to each other. It is important to distinguish monocular diplopia from binocular diplopia. A patient presenting with diplopia should be advised to stop driving and inform the Driver and Vehicle Licensing Agency (DVLA).

Isolated nerve palsies

Third cranial nerve:

• Presentation: there may be external ophthalmoplegia where there are partial or complete motility problems resulting in varying degrees of squint or internal ophthalmoplegia (partial or complete impairment of pupillary reactions). There may also be a ptosis.
• Aetiology: pupil-sparing causes tend to relate to ischaemic microvascular disease (and rarely, cavernous sinus syndrome). Pupil-involving disease usually arises as a result of an aneurysm but can also occur as a result of a tumour, trauma, pituitary apoplexy, herpes zoster and leukaemia. Children may exhibit this as part of an ophthalmoplegic migraine.

• Presentation: binocular vertical diplopia, difficulty in reading and the sense that things appear to be tilted.
• Aetiology: trauma, vasculopathy (often related to diabetes and hypertension) and demyelinating disease. This may also be congenital or idiopathic.

• Presentation: horizontal diplopia which is worse for distance than near vision and most pronounced on lateral gaze on the affected side.
• Aetiology: vasculopathy (usually diabetic, hypertensive or atherosclerotic) and trauma are the most common causes but it is also often idiopathic. Less common causes include an increase in intracranial pressure, cavernous sinus mass, multiple sclerosis, giant cell arthritis, inflammation and infection. Children may also get this as a benign, post-viral (or post-vaccination) condition as well as due to increased intracranial pressure and Gradenigo's syndrome (multiple cranial nerve palsies associated with complicated otitis media).

Multiple nerve palsies

• Presentation: there may be a combination of unilateral III, IV and VI cranial nerves resulting in limitation of eye movement (and therefore diplopia), facial pain corresponding to one or more branches of the V cranial nerve, a ptosis and small pupil (Horner's syndrome) or a dilated pupil if the III cranial nerve is affected.
• Aetiology: there are a number of conditions and syndromes which can give rise to this clinical picture:
  • Arteriovenous fistula (carotid-cavernous or dural-cavernous).
  • Tumours within the cavernous sinus (primary or metastatic).
  • Intracavernous aneurysm.
  • Mucormycosis (particularly in uncontrolled diabetic and immunocompromised patients).
  • Pituitary apoplexy.
  • Herpes zoster.
  • Cavernous sinus thrombosis.
  • Tolosa-Hunt syndrome.
  • Rare causes: sarcoidosis, Wegener's granulomatosis, tuberculosis.

Ocular myopathies^1,2

Ocular myositis
This is an idiopathic, nonspecific inflammation of one or more of the extraocular muscles, usually presenting early in adult life and associated with acute pain on moving the eye. It is treated with non-steroidal anti-inflammatory drugs (NSAIDs) or steroids but, ultimately, either spontaneously resolves after six weeks or follows a protracted course of recurring episodes.

Ocular myopathy (progressive external ophthalmoplegia)¹⁷
This rare condition is characterised by progressive, bilateral reduction in eye movement, associated with a ptosis, usually before the age of 20. It occurs as a result of mutations in the mitochondrial DNA. Although it may occur in the absence of any other clinical sign, it is usually associated with skeletal muscle weakness. Ultimately, ocular movement may be lost altogether. Treatment options are limited and the remit of specialist centres.

Brown's syndrome
This condition may be congenital or acquired (iatrogenic or inflammatory: rheumatoid arthritis, pansinusitis or scleritis) and is characterised by malfunction of the trochlear nerve or the superior oblique. Congenital cases are occasionally treated with surgery and acquired cases may respond to a course of steroids along with treatment of the underlying cause.

Duane's syndrome
In this condition, there is unilateral or bilateral lateral rectus activity during adduction and reduced activity in abduction. This results in a limited ability to abduct the eye and a narrowing of the palpebral aperture on adduction (as, effectively, both medial and lateral recti are acting simultaneously). Most cases are managed conservatively, as there is no amblyopia due to the eyes being straight in the primary position. If this is not the case, surgery will be performed to correct it.

Myopathies due to systemic disease¹⁶

Dysthyroid eye disease
See separate Thyroid Eye Disease article. Hallmarks of advanced disease are a painful red eye with diplopia, a reduced visual acuity, proptosis, lid retraction and lid lag. These patients may also have restricted eye movements (particularly elevation and abduction) giving rise to a squint - this is known as restrictive thyroid myopathy, exophthalmic ophthalmoplegia, dysthyroid eye disease or Graves' disease.

Myasthenia gravis
See separate Myasthenia Gravis article. About 40% of patients may show involvement of the extraocular muscles where there is extraocular muscle fatigue resulting in intermittent diplopia ± squint.

Management and prognosis of paralytic squint

These patients should be referred to the local ophthalmology team (occasionally, clinical indicators would suggest a neurologist's opinion would be more appropriate) for further investigation and treatment. Depending on clinical suspicion, this is likely to involve orthoptic confirmation of the paralytic squint, blood tests and imaging with subsequent management of the underlying cause. If no cause is found or whilst the underlying problem is being corrected, these patients may be fitted with prisms (fixed on to their glasses) to alleviate the diplopia. Prognosis depends on the primary problem.

Psychosocial aspects of squints

Strabismus is usually managed with the aim of correcting double vision in the adult or preventing amblyopia in the child. Whilst these functional outcomes are obviously important, the psychosocial consequences of strabismus are arguably as important. A recent study has found that both adults and children find strabismus disturbing to look at (regardless of gender, age or whether the respondents had strabismus in their own family).¹⁸ Curiously, adults found a squinting right eye more disturbing than a squinting left eye. In the same study, children perceived esotropia as more disturbing than exotropia. But the psychosocial aspects go beyond a subjective appreciation of an individual's appearance: Durnian and colleagues suggest that affected individuals are adversely affected in many aspects of their lives, including finding a partner, job prospects and interaction with peers.¹⁹ As such, a strabismus-specific quality of life questionnaire has been devised but is not widely used.

Document references

1. James B, Chew C, Bron A. Lecture notes on Ophthalmology, 9th ed. Blackwell Publishing (2003)
2. Kanski J. Clinical Ophthalmology, A Systematic Approach, 5th ed. Butterworth Heinemann (2003)
3. Hatt S, Gnanaraj L.; Interventions for intermittent exotropia. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003737. DOI: 10.1002/14651858.CD003737.pub2.
4. Preferred Practice Pattern: Esotropia and Exotropia (updated 2007), American Academy of Ophthalmology
5. Horwood AM, Riddell PM; Can misalignments in typical infants be used as a model for infantile esotropia? Invest Ophthalmol Vis Sci. 2004 Feb;45(2):714-20. [abstract]
6. Ocampo VVD et al; Esotropia, Infantile, Medscape, Feb 2010
7. Jackson TL; Moorfields Manual of Ophthalmology, Mosby (2008)
8. Denniston AKO, Murray PI. Oxford Handbook of Ophthalmology (OUP), 2008
9. Awadein A, Sharma M, Bazemore MG, et al; Adjustable suture strabismus surgery in infants and children. J AAPOS. 2008 Oct 8. [abstract]
10. Elliott S, Shafiq A.; Interventions for infantile esotropia. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004917. DOI: 10.1002/14651858.CD004917.pub2.
11. Rowe FJ, Noonan CP; Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006499. [abstract]
12. Schutte S, Polling JR, van der Helm FC, et al; Human error in strabismus surgery: quantification with a sensitivity analysis. Graefes Arch Clin Exp Ophthalmol. 2008 Oct 25. [abstract]
13. Hatt SR, Leske DA, Bradley EA, et al; Development of a Quality-of-Life Questionnaire for Adults with Strabismus. Ophthalmology. 2008 Nov 17. [abstract]
14. Mohney BG, McKenzie JA, Capo JA, et al; Mental illness in young adults who had strabismus as children. Pediatrics. 2008 Nov;122(5):1033-8. [abstract]
15. Mojon-Azzi SM, Mojon DS; Strabismus and employment: the opinion of headhunters. Acta Ophthalmol. 2008 Oct 30. [abstract]
16. Kunimoto DY, Kanitkar KD, Makar MS; The Wills Eye Manual (4th ed.) 2004. Lippincott, Williams and Wilkins
17. Roy H Sr; Chronic Progressive External Ophthalmoplegia, Medscape, Dec 2008
18. Mojon-Azzi SM, Kunz A, Mojon DS; The perception of strabismus by children and adults. Graefes Arch Clin Exp Ophthalmol. 2010 Nov 10. [abstract]
19. Durnian JM, Noonan CP, Marsh IB; The psychosocial effects of adult strabismus: a review. Br J Ophthalmol. 2010 Sep 18. [abstract]

Acknowledgements