Amblyopia is a decrease of vision arising from dysfunctional processing of visual information due to degradation of the retinal image during a sensitive period of visual development. It causes a range of abnormalities and is the result of other pathologies affecting the eye. The most common underlying causes are refractive error, strabismus and early-onset cataract. The approach to treatment is to improve the quality of the visual input during the visual developmental period. The method will vary according to the underlying cause.
Amblyopia is one of the most significant paediatric disorders in ophthalmic and orthotic practice and it is the most common cause of monocular visual loss. It is usually unilateral. It can be bilateral, usually where there is high bilateral refractive error or other binocular pathology. It is sometimes subdivided into:
- Functional - potentially responsive to occlusive therapy.
- Organic - irreversible.
The most common causes are
- Constant strabismus.
- Asymmetric refractive errors.
- Any orbital pathology affecting ocular growth or clarity.
During the first 2-3 years of life, the neuro-retina develops rapidly in response to visual stimuli. This continues, more slowly, until 7 or 8 years of age, after which the neuro-retinal map is complete and set.
If there is sensory deprivation, or if the brain receives a degraded image from abnormal ocular alignment (squint), during this period then this developmental process is slowed or halted, resulting in decreased vision in one or both eyes. If the sensory input or image quality is restored, the development runs its course again - rapidly in the first two or three years and more slowly until the age of 7 or 8 years. The importance of amblyopia is that if it is detected early and managed appropriately, vision can be restored. After this critical development period, no further treatment will help, as the development process is complete. Clinical examination is often normal (although microscopic abnormalities have been found in retina, lateral geniculate bodies and visual cortex). Visual fields and colour vision are also normal.
Amblyopia has been colloquially termed 'lazy eye', although the same phrase is occasionally used to refer to squint so it is important to clarify which a patient means.
Conditions that can lead to amblyopia are:
- Strabismic amblyopia: strabismus (squint) results in amblyopia because the images at the fovea are different.
- Ametropic amblyopia: bilateral moderate-to-high refractive errors can result in amblyopia.
- Anisometropic amblyopia: differences in refraction (anisometropia) cause one image to be more blurred than the other, leading to amblyopia on that side.
- Meridional amblyopia: amblyopia arises in an uncorrected astigmatic eye.
- Stimulus deprivation amblyopia: deprivation or physical obstruction of the image (for example, by a cataract or marked ptosis) causes amblyopia. This is a relatively rare cause, accounting for just 3% of amblyopia cases.
- Combinations: amblyopia can arise from combinations of these problems, such as a squint and a refractive error.
The degree of refractive error thought capable of leading to amblyopia is 1.50-4.50, varying by type and whether or not both eyes are affected. Symmetrical refractive error is less likely to lead to amblyopia than unilateral error - eg, in the case of myopia, amblyopia is likely with a symmetrical refractive error of 3.00 but an asymmetric error of 2.00. For hypermetropes the asymmetrical disease may lead to amblyopia at a refractive error of 1.50, whereas for symmetrical refractive error the figure is 4.50.
- Amblyopia is common, with estimated prevalence of 1-3% in the UK. It is the most frequently treated disorder in paediatric ophthalmology.
- It is more common in premature babies.
- One Chinese study found that prevalence rates in adults mirrored those of children. This is thought to be due to failure of early detection or of treatment efforts in childhood.
- About a third of cases are due to strabismus, a third due to anisometropia and a further third due to a combination of the two. Other causes are relatively rare.
A unilateral (rarely bilateral) decrease in visual acuity in the absence of an organic lesion provides the diagnosis. However, a finding of reduced visual acuity is not diagnostic of amblyopia. If no causative factor (eg, strabismus) is found then other ocular pathology (or misdiagnosis of reduced acuity) should be considered.
Presentation can be in a number of ways:
- Amblyopia caused by strabismus tends to present earlier, as the squint is more easily detected by parents.
- Strabismus may also be picked up by screening programmes (where employed).
Visual acuity testing
An accepted definition of amblyopia based on visual acuity is two or more Snellen or LogMAR lines difference between eyes. The Royal College of Ophthalmologists recommend LogMAR testing where possible. A LogMAR chart comprises rows of letters and is considered to estimate acuity more accurately than the Snellen chart. The acronym stands for Logarithm of the Minimum Angle of Resolution.
Accurate measure of visual acuity can be complicated:
- The children in the most vulnerable stage - before the age of 2 - are the most difficult to test. A dense amblyopia can be diagnosed if the child protests when the healthy eye is patched but, otherwise, diagnosis can be difficult.
- Some visual acuity tests are insensitive to amblyopia. For example, visual acuity in amblyopia is often better when reading single letters than a row ('crowding phenomenon'). This effect is more marked in amblyopes and means a diagnosis can be missed.
- There is a range of visual acuity in a given population and this range changes with age according to development of the nervous system. Thus, in 4-year-old children, the range is from 6/6 to 6/9 and this confounds the diagnosis of amblyopia.
More advanced visual acuity tests (neutral density filter and grating acuity) can be used to confirm the diagnosis in more difficult cases. These are carried out in more specialist settings once the suspicion of amblyopia has been raised.
Functional MRI can assist in evaluating the relationship between cortical function and visual acuity. Combined with a technique called pattern-reversal visual evoked potential (PR-VEP), functional MRI can detect different types of cortical activity in different types of amblyopia.
Presentation on screening
Screening tests to detect refractive errors and strabismus exist and they are sensitive and reliable. However, screening is not widely employed and debate surrounds methods, benefit and cost. Follow the link below for more information about vision screening.
Presence due to other pathology
- Anything obstructing the vision, such as a cataract or a marked ptosis, should raise concern about the development of amblyopia in a young child. Babies and young children need urgent referral and treatment.
- A very large strawberry naevus can press on the cornea, so distorting it and causing a refractive error.
- Trauma can lead to amblyopia through various processes - eg, prolonged lid swelling, presence of a vitreous haemorrhage or traumatic cataract. Prolonged occlusive dressing would have the same effect.
Screening for amblyopia
See separate Vision Testing and Screening in Young Children article for more detail.
Amblyopia is treated by modifying the visual input into the affected eye. In the case of stimulus deprivation amblyopia, the cause of the visual deprivation (eg, cataract) needs to be dealt with. Significant refractive errors need to be corrected. Any remaining visual deficit may be treated by obscuring or degrading the visual input to the fellow eye. Commonly used methods are patching (occlusion), instillation of atropine drops and occasionally, occlusive contact lenses.
Some have questioned the value of treatment of amblyopia, as it causes little functional disability and treatments (patching particularly) can sometimes be psychologically distressing. However, the Amblyopia Treatment Studies have provided valuable evidence which enables treatment to be tailored to the needs of individual patients (eg, a reduction in the duration and/or frequency of treatment), thus increasing the likelihood of compliance. One analysis has shown substantial lifetime gains from childhood treatment of amblyopia. It should be recognised, however, that a significant number of children do not respond to treatment - either conventional or reduced.
Reduction in unilateral visual acuity precludes entry to certain professions (eg, the fire service and armed forces). This is said to be because the unaffected eye is at risk from trauma in these high-risk occupations and the individual may have to rely on vision from the amblyopic eye.
Any pathology causing the amblyopia in the affected eye needs to be rapidly addressed: there needs to be optimisation of vision of the amblyopic eye. After this, intermittent occlusion of the healthy eye (eg, patching or pharmacologically) should help the amblyopic eye back on to its developmental course. It is worth noting that too prolonged an attempt to occlude the healthy eye can lead to amblyopia in this side so the process has to be carefully monitored.
This is guided by the degree of amblyopia and the age of the child (the two of which are often linked). It should only be initiated in children whose visual acuity falls below the normal acuity expected of a child of that age. It is also guided by the type of amblyopia:
- In deprivation amblyopia, the cause (eg, cataract) should first be treated, followed by the amblyopia. This is the most difficult type of amblyopia to treat - optimum treatment regimens are unclear.
- In strabismic amblyopia, amblyopia should be treated first with occlusion and refraction. The aim is to have freely alternating fixation with equal vision in both eyes. Surgical correction of the strabismus is then usually undertaken.
- Anisometropic amblyopia is corrected with glasses or contact lenses. Refractive correction may be all that is needed.
Treatment of the amblyopia itself involves intermittently depriving the healthy eye of vision in order to stimulate visual development in the amblyopic eye. Deprivation may be in the form of:
An adhesive patch is used on a pair of glasses or directly on the periorbital skin, so causing total (light and form) deprivation of the healthy eye. Patches with an adhesive rim, applied to the skin, are most commonly used. Opaque contact lenses have also been used. Because they cover the child's good eye, they limit their visual ability to the level of the amblyopic eye. They are easy for a child to remove, and may cause allergy. As it is the parent/s or carer/s who will have to deal with the distressed, uncomfortable, visually impaired child who is wearing the patch, it is clearly important that such adults are convinced of the need for treatment and appropriately motivated to carry it out. Giving older children a stake in their own treatment - for example, with the use of patching diaries and star charts - helps.
Evidence provided from research sources such as the Amblyopia Treatment Studies suggest that the number of hours per day should be dictated by the degree of amblyopia - ie severe cases may require patching for most of the waking day, whereas moderate degrees may require one hour or less. It is known that the amount of patching is often far less than prescribed, due to poor patient concordance.
The age at which occlusion should be prescribed is also under review. Most studies suggest that children are unlikely to benefit over the age of 7, although there is some evidence of partial benefit up to the age of 12.
The duration of treatment is variable but tends to be in the order of months. Most improvement is obtained in the first six weeks. Attention is paid to the healthy eye, due to the risk of developing amblyopia secondary to sensory deprivation (particularly in children less than 2½ years of age).
The US Pediatric Eye Disease Investigator Group (PEDIG) tested two patching regimens for the treatment of moderate amblyopia in 3- to 7-year-old children: two hours vs six hours per day (plus one hour per day of near visual activities during patching). Visual acuity in the amblyopic eye improved a similar amount in both groups. In a further study of severe amblyopia, no significant difference was found in the visual outcome in the amblyopic eye following full time (all but one hour per day) compared to six hours of patching per day (each combined with at least one hour of near visual activity during patching). Both studies reported significant rates of residual acuity deficit following four months of treatment.[11, 12]
A similar effect to patching can be achieved by optical penalisation of the healthy eye with atropine drops (pupil dilation which makes the vision go blurred). The advantages of atropine are that the treatment is not cosmetically obtrusive and that compliance is not an issue once the drops or ointment are instilled. This may be better tolerated than patching but has the disadvantages of potential systemic side-effects, including flushing, hyperactivity and tachycardia. This can particularly affect children with Down's syndrome. A Cochrane review suggests that penalisation is as effective as occlusion and can be considered an an alternative first-line option for most cases of amblyopia. It has the advantage of being more cosmetically acceptable but is less controllable, as blurring can last for up to two weeks after instillation. The same principle applies of closely monitoring the healthy eye to avoid inducing amblyopia.
The key to success is compliance. This may also be the greatest challenge. It is worth noting that, although it is unpleasant for both child and parent, standard psychological assessments have detected no significant psychological distress. However, prescriptions should take the difficulty of following treatment into account and minimise the amount of hours of patching prescribed. Parents need good information and education, as do children when they are old enough to understand. Whilst both patching and penalisation are as effective as each other, atropine has the advantage of better compliance to treatment.
Because amblyopia can recur within the first year after treatment, regular monitoring is advised during this period. The evidence suggests that there is a better outcome if treatment is tailed off rather than stopped suddenly. Traditionally, there was not thought to be any benefit in treating children older than 10.However, recent evidence challenges this.There are ongoing studies looking at the effect of treating young people up to the age of 18. The outcome of these is not known yet. More recently, different treatment approaches have been investigated to address untreated amblyopia in adulthood. Novel lenses have been implanted with success.
If the visual acuity drops again, patching or optical penalisation needs to be restarted until the visual acuity improves again. However, if the deterioration is progressive despite treatment, a neurological cause should be ruled out.
The end point of treatment is equal visual acuity in both eyes. Treatment can be tailed off once visual acuity in an amblyopic eye has been stable for two consecutive three-monthly assessments.
Does amblyopia treatment work?
Retrospective case studies show that 73% of children are successfully treated with patching but this drops to about 50% of children after three years. About 25% of successfully treated children experience a recurrence within a year of tailing off treatment; this is more likely to occur if treatment is stopped abruptly. Subtle ocular and cerebral pathologies may explain these failures, as may inaccurate refractive correction and lack of compliance. Factors suggesting a good outcome include:
- Young age at start of therapy.
- Strabismic amblyopia.
- Better initial visual acuity prior to treatment.
- Children should be reviewed within three months of commencing treatment with glasses or patching/atropine.
- In children wearing glasses, treatment with patching/atropine can be deferred until no further improvement occurs.
- Once treatment with patching/atropine is commenced, review should take place at least three-monthly - more frequently in smaller children who are having higher doses of patching.
- Atropine should be offered at the outset and should be considered in children who have difficulty complying with patching.
- Around 25% of successfully treated amblyopic children experience a recurrence within the first year off treatment. Risk of recurrence is greater when patching is stopped abruptly.
- Many children will have a residual visual deficit despite compliance with treatment.
- Failure of visual acuity to improve within six months of the commencement of amblyopia treatment should prompt re-refraction and re-examination of the fundus, looking in particular for optic nerve hypoplasia and subtle macular pathology.
- Progression of visual deficit during treatment, in the absence of obvious ocular pathology, raises the possibility of progressive cerebral pathology.
Further reading and references
; Interventions for unilateral and bilateral refractive amblyopia. Cochrane Database Syst Rev. 2012 Apr 184:CD005137.
; Abnormal cortical processing of pattern motion in amblyopia: evidence from fMRI. Neuroimage. 2012 Apr 260(2):1307-15. Epub 2012 Jan 24.
; The effect of sensory uncertainty due to amblyopia (lazy eye) on the planning and PLoS One. 20127(2):e31075. Epub 2012 Feb 17.
; Decreased gray matter concentration in the lateral geniculate nuclei in human Invest Ophthalmol Vis Sci. 2010 Mar51(3):1432-8. Epub 2009 Oct 29.
; Interventions for unilateral and bilateral refractive amblyopia, The Cochrane Library, 2012.
; Interventions for stimulus deprivation amblyopia. Cochrane Database Syst Rev. 2006 Jul 193:CD005136.
; Prevalence and causes of amblyopia in a rural adult population of Chinese the Ophthalmology. 2011 Feb118(2):279-83. Epub 2010 Sep 24.
; Amblyopia. Lancet. 2006 Apr 22367(9519):1343-51.
; Relationship of visual cortex function and visual acuity in anisometropic Int J Med Sci. 20129(1):115-20. Epub 2011 Dec 17.
; Combination of blood oxygen level-dependent functional magnetic resonance imaging Mol Vis. 201218:909-19. Epub 2012 Apr 11.
; Royal College of Ophthalmologists (2012)
; Amblyopia treatment studies. Curr Opin Ophthalmol. 2004 Oct15(5):432-6.
; Lessons from the amblyopia treatment studies. Ophthalmology. 2012 Apr119(4):657-8. doi: 10.1016/j.ophtha.2011.12.003.
; An audit of the outcome of amblyopia treatment: a retrospective analysis of 322 Br J Ophthalmol. 2010 Aug94(8):1007-11. Epub 2009 Dec 2.
; Conventional occlusion versus pharmacologic penalization for amblyopia. Cochrane Database Syst Rev. 2009 Oct 7(4):CD006460.
; Video-game play induces plasticity in the visual system of adults with amblyopia. PLoS Biol. 2011 Aug9(8):e1001135. Epub 2011 Aug 30.
; Reverse amblyopia with atropine treatment. Binocul Vis Strabismus Q. 200924(1):25-31.
; Psychological causes of non-compliance with electronically monitored occlusion Br J Ophthalmol. 2009 Nov93(11):1499-503. Epub 2009 Aug 5.
; Amblyopia: diagnostic and therapeutic options. Am J Ophthalmol. 2006 Jan141(1):175-184.
; Effect and sustainability of part-time occlusion therapy for patients with Br J Ophthalmol. 2010 Jun 7.
; Implantation of the multifocal ReSTOR apodised diffractive intraocular lens in Br J Ophthalmol. 2009 Oct93(10):1296-301.
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