Amblyopia in 2026: A State-of-the-Art Review of Multidimensional Phenotyping, Response Heterogeneity, and Clinical...

Amblyopia is increasingly conceptualized as a neurodevelopmental visual disorder that often arises from discordant binocular visual experience during early life and is associated with abnormal binocular interactions, interocular suppression, orientation-dependent developmental abnormalities in selected refractive phenotypes, and experience-dependent plasticity, consistent with a distributed-network perspective rather than a purely monocular acuity deficit. We performed a structured state-of-the-art narrative synthesis of peer-reviewed reviews, randomized controlled trials, and key mechanistic human studies indexed in PubMed/MEDLINE, Web of Science, and Scopus (1 January 2016-28 February 2026; last search 28 February 2026), prioritizing recent evidence from 2021-2026. Literature supports consideration of clinically trackable constructs beyond best-corrected visual acuity (BCVA), including quantified suppression/imbalance, binocular function, and functionally meaningful outcomes such as reading-related limitation and broader functional impact. Across established and emerging intervention classes, treatment effects are heterogeneous across ages and etiologies. Evidence is strongest for conventional penalization and selected active training-based approaches, whereas newer protocol-standardized approaches remain investigational and require prospective evaluation with transparent exposure/dose reporting. Based on these findings, we outline a clinically oriented, core outcome set for amblyopia and strabismus (COSAMS)-aligned framework that combines quantified binocular imbalance with multidimensional phenotyping and a hypothesis-driven, prospectively testable therapeutic model intended to structure (not replace) clinical decision-making. Priorities for precision-oriented amblyopia care include standardization of suppression metrics, adoption of core outcome sets, transparent reporting of 'not measurable' outcomes and missingness, and prospective validation of phenotype-driven, prediction-ready frameworks.