PurposeWe conducted a clinical study to characterize fine spatiotemporal alterations of FEM in controls and patients with pre-clinical signs of age-related macular degeneration (AMD).MethodsTwenty-seven participants were recruited from the SilverSight cohort of the Vision Institute - Quinze-Vingts National Vision Hospital, Paris. Subjects were included in three groups: healthy young, healthy aging controls, and aging subjects with drusen. Detection of microdrusen was done using gaze-dependent adaptive optics ophthalmology. Monocular retinal tracking was based on adaptive optics flood illumination ophthalmoscopy (AO-FIO). The system allows for sub-arcminute resolution, high-speed, distortion-free imaging of the foveal area. Local stimulation through digital micromirror (DMD) projection from a near infrared source enabled projection of optotypes. Eye movements were estimated using a phase-correlation registration algorithm.ResultsCompared to controls, patients with foveal drusen showed higher microsaccade amplitude, higher drift diffusion coefficient, and worse fixation stability -i.e. higher isoline area. Among the drusen group, the increase of microsaccade amplitude and ISOA was correlated with drusen eccentricity; the closer the drusen were to the center of the fovea, the more unstable were FEM.ConclusionsWe demonstrate the clinical interest of a novel high-precision retinal tracking technique to characterize FEM changes at the microscopic level. We found significant differences between the drusen group and both healthy young and older adult groups. Central drusen altered fixation stability characteristics, resulting in compensatory FEM changes. High speed, high resolution FEM analysis may help to define the functional signatures of early age-related changes.