Amblyopia, commonly termed “lazy eye,” is a neurodevelopmental disorder characterized by reduced best-corrected visual acuity (BCVA) in one or both eyes without identifiable structural ocular pathology. It typically arises from strabismus, anisometropia, or visual deprivation during the critical period of visual development. Amblyopia affects approximately 1%–5% of the population and remains the most prevalent cause of monocular visual impairment in children and young adults.1

Traditionally, amblyopia has been linked to cortical abnormalities within the visual pathway, including the lateral geniculate body (LGB) and visual cortex. With advances in imaging—particularly optical coherence tomography (OCT)—attention has turned to subtle retinal changes that may accompany the condition. Several reports suggest increased macular thickness or retinal nerve fiber layer thickness (RNFLT) in amblyopic eyes, raising the possibility that retinal involvement contributes to visual deficits.2,3 OCT provides high-resolution, cross-sectional images of the retina and choroid, while OCT angiography (OCTA) offers non-invasive visualization of retinal and choroidal microvasculature. These modalities have enabled evaluation of macular thickness, ganglion cell complex (GCC), foveal morphology, and vascular density in the context of amblyopia.4–6

Despite increasing use of OCT and OCTA, findings remain inconsistent: some studies report thicker foveae or increased RNFLT in amblyopic eyes, whereas others find no significant differences compared with fellow or control eyes. Discrepancies also extend to inner nuclear layer (INL) thickening, outer nuclear layer (ONL) thinning, and the direction of change in choroidal thickness. Variability in amblyopia subtype, age, axial length (AL), refractive status, and imaging protocols likely contributes to these differences, and it is not yet clear whether observed retinal changes are primary features of amblyopia or secondary to visual deprivation.7,8 Histologic work further suggests that reduced postnatal apoptosis of retinal ganglion cells could underlie increased RNFLT in some amblyopic eyes.9

In light of these inconsistencies, this systematic review consolidates and critically appraises current evidence on retinal and choroidal alterations in amblyopia detected by OCT and OCTA, with particular attention to differences among subtypes (strabismic, anisometropic, and deprivational), the effects of occlusion therapy, and the interpretation of thickness and vascular parameters. By clarifying these structural findings, we aim to inform understanding of amblyopia pathophysiology and guide future clinical and research directions.

OCTA provides additional insight into retinal perfusion. Liu et al. demonstrated reduced SCP vessel density in multiple macular sectors in severe hyperopic anisometropic amblyopia, accompanied by increased regional retinal thickness.3 Hamurcu et al. reported reduced SCP density without central macular or choroidal thickness differences.8

In previously amblyopic eyes, Salerni et al. observed higher outer-macular vessel density and macular perfusion compared with untreated amblyopic and normal eyes; perfusion metrics predicted BCVA in both amblyopic and ex-amblyopic groups.17 Reflectivity mapping studies further suggest choroidal involvement, with reduced reflectivity in the choriocapillaris and Sattler’s layer in unilateral amblyopia.20 While OCTA findings remain heterogeneous, vascular parameters may demonstrate greater sensitivity to disease state and treatment history than structural thickness alone.

To avoid interpretative duplication, all biometric influences are synthesized here.

Rather than reiterating subtype-specific findings across multiple sections, the structural variations in amblyopia are synthesized here to emphasize key distinctions and shared mechanisms.

In anisometropic amblyopia, several studies report mild central or inner macular thickening, sometimes accompanied by increased RNFLT.10,15,16 However, these observations should be interpreted with caution, as RNFLT measurements are influenced by axial length–related ocular magnification effects. Optical coherence tomography angiography (OCTA) studies further suggest reduced superficial capillary plexus (SCP) density in untreated cases.3

Strabismic amblyopia demonstrates more heterogeneous macular findings, with no consistent or reproducible pattern in ganglion cell complex (GCC) measurements across studies.11,17

In combined amblyopia, current evidence indicates that after appropriate correction for axial length, there is no distinct additive OCT phenotype beyond that observed in individual subtypes.11

Deprivational amblyopia remains relatively underexplored; preliminary reports suggest increased FT and RNFLT measurements, although the evidence base is limited and requires further validation.11,17

In contrast, high myopic amblyopia is characterized predominantly by generalized retinal and choroidal thinning, largely attributable to axial elongation rather than amblyopia-specific mechanisms.19

Collectively, these findings support a subtype-dependent and biometry-modulated model of retinal structural variation in amblyopia, rather than a single unifying retinal structure. Notably, structural alterations—particularly RNFLT in anisometropic amblyopia—are modest and partially confounded by axial length and magnification effects. Furthermore, available longitudinal data suggest that structural changes following therapy are limited, reinforcing the concept that amblyopia is primarily a functional visual disorder with subtle anatomical correlates.3,10,11

Across cohorts, OCT/OCTA demonstrate subtype- and region-specific alterations rather than a uniform retinal signature of amblyopia. Anisometropic amblyopia frequently shows thicker macular or foveal measurements in amblyopic eyes compared with fellow or control eyes,3,15 although these differences are often attenuated or absent after axial-length and magnification correction.7,12 In contrast, high-myopic amblyopia is more consistently associated with choroidal thinning while macular thickness may remain comparable to controls,18 suggesting a stronger influence of refractive status and axial elongation. Pediatric and mixed cohorts remain heterogeneous, with reports ranging from thicker central macula and foveola.2,21–23 to null or region-limited changes.24,25 In special phenotypes such as myelinated retinal nerve fiber with myopic amblyopia, atypical macular profiles further emphasize the role of etiology and ocular biometry in shaping structural findings.26 Strabismic amblyopia also demonstrates inconsistent findings, with some studies reporting increased macular thickness,6 although such differences may be overestimated in the absence of biometric correction.6

RNFLT findings are similarly variable. Several anisometropic cohorts report thicker RNFLT, occasionally accompanied by larger rim area and smaller cup-to-disc ratio without corresponding ganglion cell complex (GCC) thinning.2,9,10 These observations support the hypothesis of altered postnatal retinal maturation with reduced physiological apoptosis of retinal ganglion cells. However, studies incorporating axial-length and magnification correction often demonstrate attenuated or absent RNFLT or GCC differences,11–13 underscoring the importance of biometric adjustment in OCT interpretation.

Macular structural findings appear to be layer-specific rather than generalized. Increased central and inner macular thickness has been reported in anisometropic amblyopia even after adjustment for age and axial length, whereas outer retinal layers, including the outer nuclear layer and cone density, are generally preserved.15 Conversely, some studies demonstrate no significant macular differences despite functional visual improvement,7,12 while sub-foveal thinning has been observed in eyes with high refractive error, particularly in association with choroidal alterations.19,21,24,27,28

OCTA studies provide additional evidence for microvascular involvement in amblyopia. Reduced superficial capillary plexus (SCP) vessel density has been reported in untreated anisometropic amblyopia, sometimes without significant foveal avascular zone (FAZ) changes and occasionally correlating with reduced visual evoked potential (VEP) amplitude.3,8 Magnification-corrected pediatric analyses indicate that reduced vessel density may coexist with localized retinal thickening.3,5 Some treated cohorts demonstrate increased macular perfusion, particularly in outer retinal regions, with perfusion indices correlating with best-corrected visual acuity, suggesting adaptive or compensatory vascular remodeling after therapy.27 Importantly, OCTA may reveal perfusion abnormalities even when retinal thickness parameters remain unchanged.8

Axial length and image magnification consistently emerge as critical methodological determinants across studies. Failure to account for these variables may lead to overestimation of structural and vascular differences, particularly in pediatric and anisometropic populations.5,29 This consideration is especially relevant in high-myopic amblyopia, where retinal and choroidal thinning closely parallels axial elongation, supporting a choroid-first susceptibility model.10,19,27 In contrast, hyperopic anisometropic amblyopia more commonly demonstrates thicker RNFLT and foveal parameters with relatively preserved central macular thickness.10,27 Additional variability across studies likely reflects differences in scan protocols, segmentation algorithms, sample size, subtype composition, and the relatively limited inclusion of deprivational amblyopia.11,17 Emerging techniques such as mean reflectivity mapping may further improve the detection of choroidal compartment alterations beyond conventional thickness-based assessment.20

Clinically, OCT and OCTA are useful for phenotyping amblyopia subtypes and documenting baseline retinal and vascular characteristics; however, their predictive value for individual visual recovery remains limited, as anatomical parameters do not consistently correlate with treatment outcomes.12,16,17,30 Among emerging biomarkers, OCTA-derived perfusion indices—particularly macular and outer-ring vessel density—appear promising as adjunctive indicators of treatment response, although standardized acquisition methods and routine axial-length correction are essential before broader clinical application.5,17

Future research should prioritize longitudinal, subtype-stratified studies using standardized and biometrically corrected imaging protocols. Integration of layer-specific retinal analysis, choroidal assessment, wide-field OCTA, electrophysiology, and behavioral visual measures may help clarify structure–function relationships and improve mechanistic understanding of amblyopia.4,8,15 Advanced analytical approaches will be necessary to disentangle the contributions of neurodevelopmental maturation, refractive error, and visual deprivation, ultimately improving prognostic modeling and determining whether structural or vascular normalization directly mediates therapy-related visual improvement.

Optical Coherence Tomography (OCT) and OCT Angiography (OCTA) demonstrate that structural and microvascular alterations in amblyopia are subtype dependent. The most consistent pattern is observed in anisometropic amblyopia, characterized by thicker retinal nerve fibre layer and inner macular measurements with reduced superficial capillary plexus density, while high-myopic amblyopia more often shows diffuse choroidal thinning. In contrast, strabismic, combined, and deprivational subtypes exhibit variable findings that frequently diminish after axial-length correction, highlighting the importance of biometric adjustment and standardized imaging protocols.

Longitudinal evidence indicates that conventional therapy improves visual acuity reliably, whereas structural changes are modest, region specific, and not strongly correlated with functional recovery. OCTA-derived perfusion parameters may show earlier normalization and hold promise as potential biomarkers of treatment response; however, current evidence remains constrained by methodological heterogeneity and limited sample sizes.

While OCT and OCTA are powerful diagnostic tools, their effective integration into routine amblyopia management requires a clear understanding of both their current capabilities and their significant limitations. This section provides the clinical "bottom line" for practitioners seeking to leverage advanced imaging in their practice.

Based on the current evidence, OCT and OCTA can be valuable in the following clinical scenarios:

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  Baseline assessment: Use OCT/OCTA at diagnosis to document structural patterns and exclude coexisting macular pathology.

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  Atypical or stalled cases: Consider imaging when recovery is unexpected or limited to detect subtle structural contributors.

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  Monitoring adjunct: OCTA may help track microvascular changes during therapy, but it is not yet a validated prognostic tool.

Confounding Factors are mentioned below:

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  Axial length: Failure to correct for axial length can create magnification artifacts that exaggerate or eliminate apparent differences.

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  Subtype heterogeneity: Imaging findings vary by amblyopia subtype and refractive status, so results must always be interpreted in clinical context.

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