Overview

Various definitions have been put forward to describe amblyopia. 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.¹

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 (i.e. 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. Organic amblyopia refers to irreversible amblyopia.²

It has been described as a disorder 'in which the patient sees nothing and the doctor sees nothing'.³ 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 normal² (although microscopic abnormalities have been found in retina, lateral geniculate bodies and visual cortex).^4,5 It is the most frequently treated paediatric disorder in ophthalmic and orthotic practice¹ and it is the most common cause of monocular visual loss.³

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

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) causes 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 1-3% of healthy children¹ and up to about 5% of children with ocular co-pathology².
• It is more common in premature babies.⁷
• Failure of detection or of treatment efforts in children means prevalence rates are similar in adults as shown by a study of nearly 4,000 adults in Australia.⁸
• 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

• 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 2 or more Snellen or logMAR lines difference between eyes.⁵ 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.¹
    • 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.
  • 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 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,² e.g. 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 record on Vision Testing and Screening in Young Children for more detail.

Treatment

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.⁹ However, this partly perhaps reflects paucity and difficulty of research and therefore evidence. Clinical beliefs that children with amblyopia do improve during treatment are supported by evidence. However, without sound evidence on the natural history of these conditions, this evidence falls short of showing that treatment works. One analysis has shown substantial lifetime gains from childhood treatment of amblyopia.¹⁰ Reduction in unilateral visual acuity precludes entry to certain professions (e.g. the fire service and armed forces because they cannot hold a class II professional driving license).⁶ In addition, there is the increased risk of damage to the good eye and consequent major visual handicap.¹¹

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 (e.g. remove a cataract and then prescribe glasses). Thereafter, intermittent occlusion of the healthy eye (e.g. 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.¹ It is also guided by the type of amblyopia:

• In deprivation amblyopia, the cause (e.g. 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.⁶
• Conversely, in the case of strabismic amblyopia, amblyopia should be treated first with occlusion and refraction,¹² then the strabismus corrected. Debate surrounds timing of surgery.^13,14 Sometimes realignment helps to reverse the amblyopia and amblyopia treatment is not needed.¹⁴
• Anisometropic amblyopia is corrected with glasses or contact lenses. Research shows progressive improvement in acuity for up to 18 weeks in some patients after correction of refractive error alone (refractive adaption). Refractive correction is all that is needed in a quarter of children with amblyopia.⁵

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. Practice is very variable¹⁵ but, generally, treatment starts with short patching periods and is titrated up according to response. A 6 month-old baby may do well with patching for 10 minutes a day whereas a dense amblyopia in a six year-old child may require full-time patching.⁷ There is evidence to suggest that there may be a maximal dose per day beyond which further patching confers no extra benefit.¹⁶ The duration of treatment is variable but tends to be long,¹⁷ in the order of months, the most improvement generally being obtained in the first 6 weeks.¹⁶ 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.¹ This is only effective if the amblyopic eye has a visual acuity of > 6/18. The same principle applies of closely monitoring the healthy eye to avoid inducing amblyopia.
• Other methods of treatment (levodopa and citicoline, visual stimulation) are being investigated. Combination treatments may be used more in the future.⁵

The key to success is compliance.^7,18 This may also be the greatest challenge.¹⁷ It is worth noting that, although it is unpleasant for both child and parent, standard psychological assessments have detected no significant psychological distress.¹ However, prescriptions should take the difficulty of following treatment into account and minimise the amount of hours of patching prescribed.¹⁶ Parents need good information and education, as does the child when they are old enough to understand.^17,18 Whilst both patching and penalisation are as effective as each other, atropine has the advantage of better compliance to treatment.¹⁹

Children need regular follow-up until the age of 8. Initially, this is frequent (as a rule of thumb: every week per year of age)² but as the amblyopia reverses, the frequency reduces. Traditionally, there was not thought to be any benefit in treating children older than 10²⁰ but recent evidence challenges this²¹ and there are ongoing studies looking at the effect of treating young people up to the age of 18.² 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 but are not currently in use in the UK.²²

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.¹

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 2 consecutive 3-monthly assessments¹

Does amblyopia treatment work?

Retrospective case studies show that 73% of children are successfully treated with patching² but this drops to about 50% of children after 3 years.⁵ 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.¹ Subtle ocular and cerebral pathologies may explain these failures as may inaccurate refractive correction and lack of compliance. Factors suggesting a good outcome include:²

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

Practice tips

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

Document references

1. Guidelines for the Management of Amblyopia, Royal College of Ophthalmologists (2006)
2. Yen KG; Amblyopia, eMedicine, Dec 2008
3. von Noorden GK, Campos E. Binocular vision and ocular motility, 6th edition. St Louis,MO:Mosby 2002
4. Anderson SJ, Swettenham JB; Neuroimaging in human amblyopia. Strabismus. 2006 Mar;14(1):21-35. [abstract]
5. Holmes JM, Clarke MP; Amblyopia. Lancet. 2006 Apr 22;367(9519):1343-51. [abstract]
6. Hatt S, Antonio-Santos A, Powell C, et al; Interventions for stimulus deprivation amblyopia. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005136. [abstract]
7. Jackson TL. Moorfields Manual of Ophthalmology, Mosby (2008)
8. Attebo K, Mitchell P, Cumming R, et al; Prevalence and causes of amblyopia in an adult population. Ophthalmology. 1998 Jan;105(1):154-9. [abstract]
9. Snowdon SK, Stewart-Brown SL; Preschool vision screening. Health Technol Assess. 1997;1(8):i-iv, 1-83. [abstract]
10. Membreno JH, Brown MM, Brown GC, et al; A cost-utility analysis of therapy for amblyopia. Ophthalmology. 2002 Dec;109(12):2265-71. [abstract]
11. Tommila V, Tarkkanen A; Incidence of loss of vision in the healthy eye in amblyopia. Br J Ophthalmol. 1981 Aug;65(8):575-7. [abstract]
12. Shotton K, Elliott S; Interventions for strabismic amblyopia. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006461. [abstract]
13. Williams C, Harrad R; Amblyopia: contemporary clinical issues. Strabismus. 2006 Mar;14(1):43-50. [abstract]
14. Lam GC, Repka MX, Guyton DL; Timing of amblyopia therapy relative to strabismus surgery. Ophthalmology. 1993 Dec;100(12):1751-6. [abstract]
15. Denniston AKO, Murray PI. Oxford Handbook of Ophthalmology, OUP (2008)
16. Stewart CE, Stephens DA, Fielder AR, et al; Objectively monitored patching regimens for treatment of amblyopia: randomised BMJ. 2007 Oct 6;335(7622):707. Epub 2007 Sep 13. [abstract]
17. Awan M, Proudlock FA, Grosvenor D, et al; An audit of the outcome of amblyopia treatment: a retrospective analysis of 322 Br J Ophthalmol. 2010 Aug;94(8):1007-11. Epub 2009 Dec 2. [abstract]
18. Loudon SE, Passchier J, Chaker L, et al; Psychological causes of non-compliance with electronically monitored occlusion Br J Ophthalmol. 2009 Nov;93(11):1499-503. Epub 2009 Aug 5. [abstract]
19. Li T, Shotton K; Conventional occlusion versus pharmacologic penalization for amblyopia. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006460. [abstract]
20. Wu C, Hunter DG; Amblyopia: diagnostic and therapeutic options. Am J Ophthalmol. 2006 Jan;141(1):175-184. [abstract]
21. Hwang DJ, Kim YJ, Lee JY; Effect and sustainability of part-time occlusion therapy for patients with Br J Ophthalmol. 2010 Jun 7. [abstract]
22. Petermeier K, Gekeler F, Spitzer MS, et al; Implantation of the multifocal ReSTOR apodised diffractive intraocular lens in Br J Ophthalmol. 2009 Oct;93(10):1296-301. [abstract]

Internet and further reading

• LEA test for ambylopia screening

Acknowledgements