Foveolar drusen decrease fixation stability in pre-symptomatic AMD

Purpose To link changes of fixational eye movements (FEM) in controls and patients with foveal drusen using adaptive optics retinal imaging to find anatomo-functional markers for pre-symptomatic Age-related Macular Degeneration (AMD). Design A population-based cohort study. Participants 7 young controls, 4 older controls and 16 presymptomatic AMD patients with foveal drusen. Methods A high speed research-grade adaptive optics flood illumination ophthalmoscope was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, high-speed and distortion-free imaging of the foveal area. Early signs of AMD were documented using gaze-dependent imaging on a clinical-grade AO-FIO. Main outcome measures Microsaccade amplitude, drift diffusion coefficient and fixation stability across participants, and in the case of presymptomatic AMD participants, the relationship between these variables and retinal structure characteristics such as drusen size and eccentricity. Results FEM were measured with high precision (RMS-S2S=0.0015° on human eyes) and small foveal drusen (median=60µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient and ISOline Area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. Conclusions A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Eye movement analysis with flood imaging provides robust description of both functional and structural signs of early age-related changes. ### Competing Interest Statement The authors have declared no competing interest. * FEM : fixational eye movements AMD : age-related macular degeneration RPE : retinal pigment epithelium AO-FIO : adaptive optics flood illumination ophthalmoscope RMS-S2S : root mean square sample-to-sample ISOA : isoline area SD-OCT : spectral domain optical coherence tomography