Overview^[1]

Amblyopia can be defined as a decrease of vision for which no physical cause can be found on eye examination. It can be unilateral or bilateral. It is sometimes subdivided into:

• Functional - potentially responsive to occlusive therapy.
• Organic - irreversible.

In essence, it is a developmental failure of the immature neuroretina during early childhood that occurs as a result of visual deprivation or abnormal binocular interaction. It is therefore an effect of another ocular pathology.

During the first 2-3 years of life, the neuroretina develops rapidly in response to visual stimuli. This continues, albeit more slowly, until 7 or 8 years of age, after which the neuroretinal map is complete and set. If there is sensory deprivation, or if the brain receives a degraded image from abnormal ocular alignment (ie a squint), this developmental process is slowed or halted, resulting in decreased vision in one or both eyes. However, if the sensory input or image quality is restored, the development runs its course again - rapidly in the first 2 or 3 years and more slowly until 7 or 8 years old. So, 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 has stopped.

A memorable aphorism is that amblyopia a disorder 'in which the patient sees nothing and the doctor sees nothing'.^[2] This is not quite true, as there may be varying degrees of visual function left but it is a useful reminder that clinical examination of amblyopes is normal^[1] (although microscopic abnormalities have been found in retina, lateral geniculate bodies and visual cortex).^[3] It is one of the most significant paediatric disorders in ophthalmic and orthotic practice^[4] and it is the most common cause of monocular visual loss.^[1]

Patients often refer to the term 'lazy eye' but, if this is mentioned, be sure to specify what they mean, as patients also occasionally use this term for a squint.

Aetiology^[1][5]

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.^[6]

Amblyopia can arise from combinations of these problems, such as a squint and a refractive error.

Epidemiology

• Amblyopia affects about 2 in every 100 children in the UK.^[4]
• It is more common in premature babies.^[7]
• One Chinese study found that prevalence rates in adults mirrored those of children.^[8] 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 anisometropia and a further third due to a combination of the two. Other causes are relatively rare.

Presentation^[1]

A unilateral (rarely bilateral) decrease in visual acuity in the absence of an organic lesion provides the diagnosis. Presentation can be in a number of ways:

• Strabismus:
  • 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.^[9] However, this can be a complex assessment for several reasons:
    • 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.^[10]
    • Some of the visual acuity tests used are insensitive to amblyopia. For example, visual acuity in amblyopia is often better when reading single letters than a row ('crowding phenomenon'). This is seen to a certain extent in everybody but more marked in amblyopes. So, using tests with single images or letters may miss a mildly affected child.
    • There is a range of typical 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.
    There are more advanced visual acuity tests (neutral density filter and grating acuity) available to confirm the diagnosis in more difficult cases. These are carried out in more specialist settings but the suspicion of amblyopia has to be raised first before the child can be referred for the test.
    
    Functional MRI is a recent development which can assist in evaluating the relationship between cortex function and visual acuity.^[11] Combined with another technique called pattern-reversal visual evoked potential (PR-VEP), functional MRI can detect different types of cortical activity in different types of amblyopia.^[12]
  • Detection by screening programme. 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 of other pathology
  • Anything obstructing the vision, such as a cataract or a marked ptosis, should immediately 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 in various ways,^[1] eg prolonged lid swelling, presence of a vitreous haemorrhage or traumatic cataract. Prolonged occlusive dressing would have the same effect.

It is worth noting that visual fields and colour vision are normal.

Screening for amblyopia

See separate article Vision testing and screening in young children for more detail.

Treatment^[1]

Is amblyopia worth treating?

Some have questioned the value of treatment, 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.^[13] 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.^[4]

Reduction in unilateral visual acuity precludes entry to certain professions (eg the fire service and armed forces). Ostensibly this is 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.^[14]

Treatment aims

The essence of treating amblyopia is stimulating the amblyopic eye back on to its normal developmental path before the developmental stage stops. In the first instance, any pathology causing the amblyopia in that eye needs to be rapidly addressed and there needs to be optimisation of vision of the amblyopic eye (eg remove a cataract and then prescribe glasses). Thereafter, 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 vigorous an attempt to occlude the healthy eye can lead to amblyopia in this side so the process has to be carefully monitored in an eye unit.

Treatment

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.^[4] It is also guided by the type of amblyopia:

• In deprivation amblyopia, the cause (eg ptosis, cataract) should first be treated, followed by the amblyopia. This is the hardest type of amblyopia to treat and optimum treatment regimens are unclear.
• Conversely, in the case of 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:

• Patching (occlusion): 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. Opaque contact lenses have also been used. There is no definitive consensus on the amount of patching required.^[4] 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 at least partial benefit up to the age of 12.
  
  The duration of treatment is variable but tends to be long, in the order of months, the most improvement generally being obtained in the first six weeks.^[15] Due attention is paid to the healthy eye, which runs the risk of developing amblyopia itself if sensory deprivation is too prolonged in the younger child (particularly less than 2½ years of age).
• Penalisation: a similar effect to patching can be achieved by optical penalisation of the healthy eyes with atropine drops (pupil dilation which makes the vision go blurred). This may be better tolerated than patching but has the disadvantages of potential systemic side-effects, including flushing, hyperactivity and tachycardia which can particularly affect children with Down's syndrome.^[10] A Cochrane review suggests that penalisation is as effective as occlusion and can be considered 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.^[4] The same principle applies of closely monitoring the healthy eye to avoid inducing amblyopia.
• Other methods of treatment (levodopa^[16], citicoline^[17] and visual stimulation in adults^[18]) are being investigated. Combination treatments (occlusion and atropine) may be used more in the future.^[19]

The key to success is compliance.^[20] This may also be the greatest challenge.^[15] It is worth noting that, although it is unpleasant for both child and parent, standard psychological assessments have detected no significant psychological distress.^[10] However, prescriptions should take the difficulty of following treatment into account and minimise the amount of hours of patching prescribed.^[13] Parents need good information and education, as does the child when they are old enough to understand.^[10][20] Whilst both patching and penalisation are as effective as each other, atropine has the advantage of better compliance to treatment.^[21]

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.^[1] Traditionally, there was not thought to be any benefit in treating children older than 10^[22] but recent evidence challenges this^[23] and there are ongoing studies looking at the effect of treating young people up to the age of 18.^[1] 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.^[24]

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.^[10]

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.^[10]

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.^[1] 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.^[10] Subtle ocular and cerebral pathologies may explain these failures, as may inaccurate refractive correction and lack of compliance. Factors suggesting a good outcome include:^[1]

• Young age at start of therapy.
• Strabismic amblyopia.
• Better initial visual acuity prior to treatment.

Practice tips

• Refer a squint early.
• Be aware of local screening programmes.