Amblyopia Severity Predicts Fixation Dysfunction Independent of Nystagmus and Foveation Disruption in Fusion Maldevelopment Nystagmus

Purpose: Fixation instability in amblyopia, with or without strabismus, reflects abnormalities in physiologic fixational eye movements (FEMs) and, in some individuals, fusion maldevelopment nystagmus (FMN), a pathognomonic marker of early binocular disruption. We quantified time and frequency domain FEM characteristics across amblyopic and strabismic cohorts to determine how amblyopia severity, strabismus, and FMN influence FEM abnormalities, binocular disconjugacy, and foveation across viewing conditions. Methods: FEMs were recorded under binocular and monocular viewing in controls (n = 64) and patients with anisometropic amblyopia (n = 30), strabismic/mixed amblyopia (n = 40), and strabismus without amblyopia (n = 27) using high-resolution video-oculography. Time domain FEM metrics (amplitude, velocity, and amplitude disconjugacy), foveation times, and frequency domain analyses were performed. Linear mixed-effects models assessed the effects of amblyopia subtype and severity, strabismus, and nystagmus on eye-specific FEM characteristics across viewing conditions. Results: Fast FEM amplitudes correlated strongly with visual acuity deficits, independent of amblyopia subtype and FMN presence. Greater interocular differences in viewing-eye fast FEM amplitude and slow FEM velocity were observed in amblyopic patients, indicating a sensory rather than alignment-driven effect. In patients with FMN and moderate to severe amblyopia, amblyopic-eye viewing was associated with reduced foveation time and increased spectral power, along with increased fast FEM amplitude disconjugacy, whereas these differences and disconjugacies were attenuated in other groups. Conclusions: Time and frequency domain FEM analyses reveal that fixation abnormalities are a marker of amblyopia. FEM and nystagmus metrics thus serve as sensitive, quantitative biomarkers of binocular sensorimotor integrity and may support objective detection and monitoring of amblyopia.