Foveal drusen increase fixation instability: fixational eye movements as biomarkers for pre-symptomatic AMD

Abstract

AbstractPurposeTo link changes of fixational eye movements (FEM) in controls and patients with foveal drusen using adaptive optics retinal imaging to find biomarkers for pre-symptomatic AMD.DesignA nationwide population-based cohort study.Participants7 young controls, 4 older controls and 16 pre-symptomatic dry-AMD patients with foveal drusen.MethodsOn one side monocular retinal tracking was performed on a research-grade adaptive optics flood illumination ophthalmoscope. The system allows for sub-arcminute resolution, high-speed, and distortion-free imaging of the foveal area. We extracted then compared microsaccade and drift characteristics across individuals and groups. On the other side, screening of foveal drusen was performed on older subjects using gaze-dependent protocol on a clinical-grade AO-FIO. We then annotated drusen from resulting images to determine their location and size.Main outcome measuresThe difference in microsaccade amplitude, drift diffusion coefficient and fixation stability with ISOline Area (ISOA) between groups. For the drusen group, the relationship between these variables and retinal structure characteristics: drusen size and eccentricity in the fovea.ResultsFEM were measured with high precision (RMS-S2S=0.001°) and small drusen (median=60µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient and ISOA were significantly larger for patients with drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea.ConclusionsA 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.