Recent Advances in Amblyopia Management

INTRODUCTION Amblyopia is a neurodevelopmental disorder characterised by reduced vision resulting from abnormal visual experience during the sensitive period of visual development. It results from defective processing of visual information in the brain, despite the absence of any structural abnormality that directly correlates with the degree of visual loss.[1] The condition affects 1%–5% of the global paediatric population and presents in various forms, including strabismic, anisometropic and deprivation amblyopia.[2,3] Amblyopia is classified into anisometropic, strabismic, mixed and stimulus deprivation types. Anisometropic amblyopia is defined as the difference between the two eyes of one dioptre or more in the sphere or cylindrical power without the presence of strabismus. Strabismic amblyopia is defined as the presence of heterotropia or microtropia is present with no associated high refractive error or anisometropia. Mixed amblyopia is present when both anisometropic and strabismic amblyopia coexist. Stimulus deprivation is defined as the presence of an obstruction to vision during the sensitive period of visual development (high refractive errors are generally classified separately).[2] The critical period is a vital phase in early life when the visual system is particularly sensitive to deprivation, allowing for potential reversal of its effects. This period begins around 4 months of age, peaks by 2 years and significantly declines by 5 years, eventually ceasing by around 12 years. Vision deprivation leads to reduced synaptic activity and altered neuronal connectivity within the primary visual cortex. Cortical neurons become preferentially responsive to the dominant eye, while those linked to the amblyopic eye show decreased responsiveness. Consequently, deficits occur in visual acuity, contrast sensitivity and binocular vision, reflecting impaired cortical processing of visual information.[1] Ocular evaluation includes a detailed ophthalmic history regarding the onset and duration of ocular symptoms (diminution of vision, diplopia, nystagmus and head posture). Any history of use of spectacles, past ocular surgery, treatment for amblyopia or strabismus and family history of strabismus. Best corrected visual acuity (BCVA) using a 4 m logMAR ETDRS chart (Good-Lite Co.), cycloplegic refraction (under atropine sulphate 1% eye ointment in children older than 7 years and homatropine hydrobromide 2% eye drops in children younger than 7 years) and anterior segment evaluation by slit-lamp biomicroscopy. Cover–uncover test to rule out phoria and tropia. Levels of binocular function are assessed using the Randot Preschool test (stereopsis), Titmus stereoacuity test (stereopsis), Worth 4 dot test (assess fusion) and Bagolini striated glasses test (binocularity). Subsequently, amblyopia is divided into three grades: mild (BCVA 0.17–0.30 logMAR eq), moderate (BCVA > 0.30–0.77 logMAR eq), and severe (BCVA > 0.77 logMAR eq).The management of amblyopia has traditionally relied on correcting refractive errors, patching the better eye and using cycloplegic penalisation. However, about 25%–50% of patients demonstrate incomplete resolution or recurrence even after standard therapy. With improved understanding of visual neuroplasticity, recent years have witnessed substantial research into pharmacological agents, binocular-based approaches, perceptual learning techniques and game-based digital therapies. These advancements seek to target binocular dysfunction and cortical suppression, which are now recognised as central mechanisms of amblyopia. This review compiles current evidence on established treatment modalities as well as emerging therapies and their implications for clinical practice. OPTICAL CORRECTION IN AMBLYOPIA Refractive correction is the cornerstone of amblyopia therapy. The primary objective is to provide a clear and focused retinal image in the amblyopic eye by prescribing accurate spectacles. Full cycloplegic refraction is essential, as improper refraction can itself contribute to amblyopia.[1] Cycloplegia should be performed objectively. In children younger than 8 years, atropine 1% ointment may be used thrice daily for 3 days. In children older than 8 years, Homide 0.5% may be instilled as two drops at 15-minute intervals, followed by retinoscopy after 30–40 minutes. Age-appropriate logMAR Visual Acuity (VA) assessment and spectacle prescription help minimise residual amblyogenic refractive error. In anisometropic amblyopia, spectacle correction is the first-line treatment. Objective refraction is preferred because subjective responses may be unreliable in younger children. In infants with high hyperopia or astigmatism, waiting until 1 year of age may be reasonable, as physiological refractive changes often reduce refractive error during infancy. The Amblyopia Treatment Study (ATS-5) reported that refractive correction alone resolved amblyopia in 27% of children with moderate amblyopia, and 77% showed ≥2-line improvement on the VA chart with spectacles alone.[4,5] Spectacle adaptation for 4–6 weeks is typically advised before adding occlusion or penalisation. For bilateral refractive amblyopia, spectacles remain the primary intervention. ATS-7 demonstrated significant improvement in binocular VA with spectacles alone.[6] More recent studies confirm the benefit even in strabismic amblyopes treated with refractive correction alone.[7] OCCLUSION THERAPY Occlusion of the better eye (‘patching’) remains the gold standard in amblyopia therapy. It forces the amblyopic eye to function and reduces inhibitory neural input from the dominant eye. Success rates vary from 30% to 92%, depending on age, compliance, severity and type of amblyopia. The ATS provided important evidence on appropriate patching regimens: ATS-2A: In severe amblyopia (20/100–20/400), 6 h of daily patching was found to be equally effective as full-time patching.[8] In ATS-2B, moderate amblyopia, 2 h/day was as effective as 6 h/day.[9] Despite these findings, some clinicians still prescribe full-time patching due to concern for poor outcomes, though actual compliance in real-world settings often differs from prescribed hours. VA must be recorded using the same chart and under consistent conditions. The amblyopic eye should be allowed 5–10 min to adapt after patch removal before VA assessment. Stopping patching is recommended when: VA becomes equal in both eyes, fixation becomes alternating and no improvement is observed after 3–6 months of compliant therapy. Tapering is essential to prevent recurrence. Recurrence rates can reach 25% in the first year after stopping therapy. Complications include occlusion amblyopia, allergic skin reactions, poor cosmetic acceptability and risk of strabismus development (3% develop significant deviation).[10] Evidence suggests that patching offers no significant advantage over spectacles alone in bilateral ametropic amblyopia. Patching may be added only to correct residual interocular difference once the better eye reaches ~ 20/30 vision.[11] AMBLYOPIA TREATMENT IN ADOLESCENTS AND ADULTS Although neuroplasticity declines with age, improvement is still possible. ATS-3 showed: age 7–12 years: patching significantly improves VA regardless of prior treatment, and age 13–17 years: benefit occured primarily in those not previously treated.[12] Thus, therapy should not be denied solely based on age. AMBLYOPIA TREATMENT IN PATIENTS WITH ECCENTRIC FIXATION A study compared conventional and inverse occlusion in the treatment of amblyopia with eccentric fixation at a tertiary care centre over a period of 1 year. Sixty patients with amblyopia (refractive or strabismic) with eccentric fixation, older than 12 years were divided into two groups by systematic randomisation: conventional occlusion (occlusion of the sound eye for 6 h/day) and inverse occlusion (occlusion of the amblyopic eye for 6 h/day). Stereoacuity improved significantly in both the conventional and inverse occlusion groups (P = 0.013 and 0.016, respectively). Improvement in fixation function was statistically significant only in the inverse occlusion group I (P = 0.002). They concluded that both conventional and inverse occlusion therapy are effective in the treatment of amblyopia with eccentric fixation in adults in terms of improvement of VA and stereopsis. However, for the prevention and improvement of anomalous fixation pattern, inverse occlusion is preferred with no issues of compliance and functional limitation.[13] SEQUENTIAL VERSUS SIMULTANEOUS TREATMENT APPROACHES his approach involves spectacle adaptation followed by patching or atropine if residual amblyopia remains. Advantages include: some children improve with spectacles alone, when patching begins, VA is already improved, enhancing compliance and reducing parental burden. Some clinicians initiate spectacles and patching (or atropine) together. This may allow earlier suppression reduction and faster improvement, particularly in younger children. A PEDIG trial has been undertaken / was designed to determine which strategy yields better long-term outcomes. (ATS-22) Shivani et al. conducted a study in 2025 at a tertiary care centre to compare visual outcomes and stereoacuity between sequential and simultaneous refractive correction and patching in 70 patients with amblyopia aged 3–14 years over a period of 1 year. The study concluded that no statistically significant difference in BCVA was observed between groups (P = 0.58). However, stereopsis was significantly better in the sequential group (P < 0.01), suggesting a potential functional advantage despite similar visual acuity outcomes.[14] PENALISATION THERAPY Penalisation reduces the dominant eye’s visual advantage either optically or pharmacologically. Atropine 1% induces cycloplegia and mydriasis in the better eye, resulting in blur, particularly in hyperopic eyes, thereby forcing use of the amblyopic eye. Key findings from ATS-1 included that atropine was equally effective as 6 hours of patching in moderate amblyopia.[15] Improvement persisted over 2 years, though residual amblyopia remained common.[16] Advantages include easy administration, lower cost and better acceptability. Disadvantages include slower response and potential effects on binocularity. Weekend-only atropine was shown to be equally effective as daily atropine.[17] Adding plus lenses to the dominant eye blurs the near image. Optical penalisation is a useful alternative in patch-resistant children.[18] Studies have shown comparable outcomes between atropine alone, optical penalisation alone and combined atropine and optical penalisation (COAT).[19] LIQUID CRYSTAL GLASSES/INTERMITTENT OCCLUSION THERAPY Recently, liquid crystal glasses have been introduced as an innovative modality in the treatment of amblyopia to overcome the limitations of patching.[20–24] LCG is an electronically controlled device in which a pre-programmed microchip is incorporated into the optical refractive lens. The occlusion process is electronically controlled by a device that comprises a microprocessor with a memory and is powered by rechargeable coin batteries. The rate and duration of each viewing state are pre-programmed at a defined, controlled pace. It is child-friendly and cosmetically acceptable. However, its use remains limited by cost. Yuan et al. conducted a randomised comparative trial evaluating an alternative flicker glass therapy (LCG at 7 Hz, 1 h/day) versus conventional patching (2 h/day) in 40 patients aged 7–13 years. After 12 weeks, both groups demonstrated comparable gains in BCVA (P < 0.01), with no statistically significant difference between the two treatments (P = 0.82).[22] PHARMACOLOGICAL AUGMENTATION THERAPY Pharmacotherapy aims to enhance cortical plasticity and supplement traditional therapy. Dopamine is essential for retinal neurotransmission and cortical visual processing. Levodopa crosses the blood–brain barrier and increases central dopamine levels. Various dose regimens have been tried, ranging from high-dose short courses to low-dose longer therapy.[25] Findings include: some studies show ≥2-line VA improvement, especially in children <8 years, side effects are dose-dependent, improvements may regress after discontinuation in some patients and a large PEDIG trial found no clinically significant benefit in residual amblyopia.[26] A study conducted by Dadeya et al. included 30 patients with strabismic amblyopia aged 3–12 years.[25] The patients were divided into two groups: one group received L-DOPA, while the other received a placebo for 6 months. The authors found that improvement in VA was greater in the levodopa group (15 of 15 patients) compared with the placebo group (9 of 15 patients) (P < 0.005). Due to inconsistent efficacy and adverse effects, levodopa is not routinely recommended. However, available evidence is currently insufficient to show that augmenting amblyopia therapy with L-DOPA and carbidopa will result in meaningful improvement in visual acuity. Citicoline enhances phospholipid synthesis and increases norepinephrine and dopamine in the CNS.[27] A comparative study conducted by Pawar et al. included 84 patients with amblyopia to evaluate the effectiveness of adding citicoline to patching therapy. There was an improvement in VA and contrast sensitivity in both young and adult amblyopes. Oral citicoline (500 mg/day for 12 weeks) improved VA and refractive status. Enhanced efficacy when combined with patching compared to patching alone.[27] Citicoline appears promising, but larger trials are needed. Animal studies show that fluoxetine restores ocular dominance plasticity. Human trials, however, have produced mixed outcomes: A multicentre phase II trial conducted by Huttunen et al. included 42 patients aged 18–60 years with moderate to severe amblyopia over a period of 10 weeks. The patients were divided into two groups receiving either fluoxetine or placebo in addition to patching and perceptual learning. The study found no additional benefit of fluoxetine (20 mg) compared with placebo (P = 0.524). Citalopram demonstrated no added benefit.[28] Thus, evidence remains inconclusive. Donepezil increases cortical acetylcholine levels. While it enhances perceptual learning in healthy subjects, a pilot study in adults with amblyopia showed no improvement and possible interference with learning transfer.[29] BINOCULAR SIMULATION, PERCEPTUAL LEARNING AND GAME-BASED THERAPIES Loss of binocularity and interocular suppression are key mechanisms in amblyopia. Modern therapies aim to reduce suppression and enhance binocular cooperation. Perceptual learning includes repeated visual tasks that lead to improved neural efficiency and visual performance. This process operates through a reduction in internal neural noise and through more efficient use of stimulus information by retuning the weighting of that information. It is based on the principle that repeated practice of challenging visual tasks can induce long-lasting neural plasticity within the visual cortex. Studies have demonstrated enhanced contrast sensitivity and VA using near-threshold Gabor patches, with improvement even in adult amblyopes. This is typically a monocular therapy targeting the amblyopic eye.[30] Dichoptic therapy presents different stimuli to each eye, thereby reducing suppression by adjusting contrast levels. It can unlock plasticity in the adult visual cortex by directly reducing suppression of the amblyopic eye, resulting in greater functional gains than those achieved with monocular occlusion alone. These stimuli can be delivered using red–green anaglyph glasses, which present stereoscopic images through separate red and green lenses; shutter glasses that alternately darken and brighten in synchrony with a monitor to present dynamic images selectively to the amblyopic eye; polarised glasses; virtual reality headsets; or low-pass filters that decrease luminance in the dominant eye. Various approaches include the Interocular Binocular Treatment System, Lazy Eye Shooter, Falling Blocks, Dig Rush and Vivid Vision.[31] Key studies: Hess et al. used a dichoptic version of Tetris in patients aged 13–50, showing improvement.[31] Birch et al. reported improvement after 4 weeks of binocular iPad games in children aged 4–12.[32] However, large trials such as BRAVO and others found no superiority over patching, largely due to poor compliance.[33] Video games enhance prolonged visual engagement. Some studies show improvements in acuity, contrast sensitivity and global motion perception. Playing action video games while the fellow eye is patched has been shown to accelerate improvement. Television-assisted therapy has also shown some benefit. A study conducted by Dadeya et al. included 40 patients aged 4–7 years with unilateral amblyopia. The subjects were randomly divided into two groups of 20 each. Patients in the first group, Group A (control), were prescribed patching alone. Patients in the second group, Group B (study), were asked to play action video games for up to 12 weeks. Improvement in BCVA and stereoacuity was significantly greater in Group B at all visits, with statistical significance observed at 12 weeks (P = 0.002). Overall improvements typically range from 0.1 to 0.2 logMAR across digital therapies.[34,35] ROLE OF NEAR ACTIVITIES Near-visual activities (crafts, reading, and games) have long been recommended during patching. While early studies suggested benefits, a large ATS-6 trial showed no difference between near and distance activities during patching. Thus, near tasks are optional rather than essential. A summary of the major amblyopia treatment modalities and their advantages is presented in Table 1.[36]Table 1: Summary of amblyopia treatment modalities, principles, and advantagesROLE OF ARTIFICIAL INTELLIGENCE IN FUTURE Artificial Intelligence (AI) can transform amblyopia management by enhancing early detection, treatment personalisation and accessibility. AI-driven screening tools can identify subtle risk factors using multimodal data, enabling earlier diagnosis in diverse settings, including remote and resource-limited areas. Machine-learning models can predict treatment response, optimise therapy intensity and monitor adherence through digital platforms. Advanced algorithms may also refine binocular and VR-based therapies by adapting stimuli in real time. As AI continues to integrate with tele-ophthalmology and portable screening devices, it promises faster, more accurate and cost-effective amblyopia care, significantly improving outcomes for children worldwide. CONCLUSION Significant progress has been made in understanding amblyopia as a binocular disorder rather than purely monocular visual failure. Early detection, precise refractive correction and good compliance remain the foundation of successful therapy. Patching continues to be the gold standard, particularly in younger children. Penalisation serves as a valuable alternative, offering good efficacy with better acceptability. Emerging therapies such as binocular training, perceptual learning and digital game-based platforms hold promise but have produced inconsistent results in large trials, largely due to compliance challenges. Pharmacologic augmentation with citicoline appears encouraging, whereas levodopa, SSRIs and cholinesterase inhibitors require further evidence. A comprehensive, individualised approach combining refractive correction, evidence-based adjunct therapies and close monitoring – is essential to optimise outcomes. Treatment should not be denied based on age alone, as meaningful improvement may occur even in adolescents and adults. Future research should aim to refine binocular therapies, enhance compliance and better understand neuroplastic mechanisms to develop targeted treatments. Data availability statement A comprehensive literature search is available on using the amblyopia stereopsis and patching versus Data associated is available in and can be provided – – review and and Dadeya Data and of There are no of