Amblyopia

Amblyopia is diagnosed when there is reduced BCVA not explained by ocular structural disease, typically with two or more Snellen lines of interocular difference, or reduced acuity below accepted age/context thresholds after appropriate refractive correction.

• Amblyopia is a diagnosis of exclusion: corneal, lenticular, retinal, optic nerve, and neurological pathology must be ruled out.
• The critical or sensitive period of visual development extends from birth to approximately 7–8 years, with peak plasticity in the first 2–3 years.
• Thresholds vary by context: UK screening pathways may use 6/9 as a referral threshold, while many clinical texts use BCVA worse than 6/12 or a ≥2-line interocular difference as the diagnostic threshold. In exams, state the context clearly.

1. Strabismic Amblyopia

Strabismic amblyopia results from constant unilateral ocular deviation. To avoid diplopia and visual confusion, the visual cortex suppresses the image from the deviating eye, leading to reduced cortical representation and disuse amblyopia.

• Constant deviation is more amblyogenic than intermittent deviation.
• Esotropia is more amblyogenic than exotropia.
• Alternating strabismus usually does not cause amblyopia because each eye is used for fixation at different times.

2. Anisometropic Amblyopia

Anisometropic amblyopia occurs when unequal refractive error causes one eye to receive a chronically defocused retinal image, while the fellow eye receives a clearer image and becomes dominant.

3. Meridional Amblyopia

Meridional amblyopia is caused specifically by uncorrected astigmatism and produces orientation-selective visual loss. It is a mechanistic subtype within refractive amblyopia, but it is not synonymous with ametropic amblyopia, which is the broader category of amblyopia due to significant refractive error.

4. Deprivation Amblyopia

Deprivation amblyopia is the most severe form because patterned retinal stimulation is blocked during the most plastic period of visual development.

• Causes include congenital or infantile cataract, dense vitreous haemorrhage, corneal opacity, complete ptosis occluding the visual axis, and uncorrected unilateral aphakia.
• Dense unilateral congenital cataract requires urgent surgery in early infancy, followed immediately by optical rehabilitation and amblyopia therapy.
• Over-patching after surgery may cause iatrogenic reverse amblyopia in the fellow eye.

5. Bilateral Refractive Amblyopia

Bilateral amblyopia may occur when high bilateral refractive error is left uncorrected during the sensitive period, such as high hypermetropia, high myopia, or high bilateral astigmatism.

Amblyopia is primarily a cortical disorder involving abnormal activity-dependent visual development. The neural substrate lies mainly in the lateral geniculate nucleus and primary visual cortex, especially V1.

Critical Period and Cortical Competition

• During early development, thalamocortical projections from the LGN compete for cortical representation in V1.
• Abnormal visual input shifts cortical dominance toward the better-seeing eye.
• Ocular dominance columns representing the amblyopic eye shrink, while those representing the fellow eye expand.
• Hebbian activity-dependent synaptic competition explains why clear, consistent retinal input is essential during early childhood.

Cellular Mechanisms

• Reduced size and density of LGN cells corresponding to the amblyopic eye, especially in parvocellular layers.
• Reduced cortical neuronal responsiveness to amblyopic-eye input.
• Excess GABAergic inhibition contributing to suppression of the amblyopic eye.
• Reduced NMDA receptor activity and lower BDNF-related plasticity in visual cortex.

Suppression vs Amblyopia

Suppression is an active cortical inhibition of the amblyopic eye under binocular viewing and is potentially reversible. Frank amblyopia represents deeper cortical reorganisation that persists even during monocular viewing. Dichoptic therapies aim to reduce interocular suppression and rebalance binocular input.

Visual Acuity Assessment

• Always use crowded or linear acuity charts when possible.
• Record acuity separately for each eye with appropriate occlusion.
• Assess fixation: central, steady, and maintained (CSM), especially in preverbal children.

Refraction

• Cycloplegic refraction is mandatory.
• Cyclopentolate 1%, two doses 5 minutes apart, is appropriate for children aged ≥1 year.
• Use cyclopentolate 0.5% in infants under 1 year to reduce systemic toxicity risk.
• Atropine 1% for 3 days may be reserved for dark irides or inadequate cycloplegia with cyclopentolate.
• Full hypermetropic correction is important; partial correction can perpetuate anisometropic blur.

Ocular Examination

• Cover-uncover and alternate cover tests to detect and quantify strabismus.
• Hirschberg and Krimsky tests in preverbal or poorly cooperative children.
• Slit-lamp examination to exclude corneal opacity and cataract.
• Fundus examination to exclude optic nerve, macular, and retinal pathology.
• Pattern VEP may show reduced amplitude and prolonged latency in the amblyopic eye when behavioural visual acuity is unreliable.

Management has three core pillars: treat the cause, provide full optical correction, and enforce use of the amblyopic eye by occlusion or penalisation.

Step 1: Treat the Underlying Cause

• Deprivation amblyopia: urgent removal of the obstructing lesion such as cataract surgery, ptosis repair, or corneal intervention.
• Strabismic amblyopia: prescribe appropriate spectacles first; strabismus surgery improves alignment but does not directly treat amblyopia.
• Refractive amblyopia: prescribe full cycloplegic correction, especially full hypermetropic correction when indicated.

Step 2: Refractive Adaptation

Spectacle or contact lens correction alone can improve visual acuity by 1–3 Snellen lines in anisometropic amblyopia over approximately 16–18 weeks. A period of optical correction should precede patching unless urgent deprivation amblyopia requires immediate combined management.

Step 3: Occlusion Therapy

Patching the fellow, better-seeing eye forces use of the amblyopic eye and remains a cornerstone of treatment.

Step 4: Pharmacological Penalisation

Atropine 1% in the fellow eye induces cycloplegia and blurs near vision, encouraging use of the amblyopic eye.

• PEDIG ATS1 showed atropine penalisation is comparable to patching for moderate amblyopia.
• Weekend atropine can be as effective as daily atropine for moderate amblyopia.
• Useful when patching compliance is poor.
• Less effective in severe amblyopia unless the penalised fellow eye becomes functionally worse than the amblyopic eye for the relevant task.

Step 5: Optical Penalisation

Over-plus lenses, usually around +2.0 to +3.0 D over full correction in the fellow eye, may blur near vision and act as an alternative or adjunct to atropine in selected patients.

Step 6: Dichoptic Therapy

Dichoptic therapy presents different images to the two eyes, typically a high-contrast stimulus to the amblyopic eye and a lower-contrast stimulus to the fellow eye, aiming to reduce interocular suppression and restore binocular balance.

• Examples include I-BiT and game-based binocular systems.
• PEDIG BRIITE 2019 found binocular iPad game therapy was not superior to part-time patching in children aged 5–12 years.
• It remains an evolving option, especially for older children and residual amblyopia, but is not a replacement for established therapy.

Step 7: Neuroplasticity Enhancement

Levodopa-carbidopa and citicoline have been studied as adjuncts to enhance cortical plasticity, but benefits are modest or transient and these are not routine first-line treatments.

Deprivation Amblyopia from Congenital Cataract

Dense unilateral congenital cataract is one of the most time-critical problems in paediatric ophthalmology. Surgery is usually required within 6–10 weeks of birth, with some advocating 4–6 weeks for dense unilateral cataract, followed by immediate optical rehabilitation and aggressive amblyopia treatment.

• Optical rehabilitation may involve contact lens correction, aphakic spectacles, or later IOL depending on age and case selection.
• The Infant Aphakia Treatment Study (IATS) found comparable grating acuity outcomes between contact lens and primary IOL correction in infancy, but more adverse events with IOL implantation.
• Many centres defer IOL implantation until after age 2 years in suitable cases.

Treatment Beyond the Traditional Critical Period

Amblyopia treatment should not be dismissed solely because the child is older than 7–8 years. PEDIG studies demonstrate that meaningful improvement can occur up to 17 years, although response is slower and usually less complete than in younger children.

Amblyopia is a neurodevelopmental disorder caused by abnormal visual experience during the sensitive period. Classification includes strabismic, anisometropic, meridional, deprivation, and bilateral refractive forms. Management requires correction of the cause, full optical correction with refractive adaptation, and forced use of the amblyopic eye through patching or penalisation. PEDIG trials provide the evidence base for modern treatment regimens and show that treatment should still be attempted in older children and teenagers with appropriate counselling.