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

Murari, J.; Gautier, J.; Daout, J.; Krafft, L.; Senee, P.; Mece, P.; Seiple, W.; Grieve, K.; Sheynikhovich, D.; Meimon, S.; Paques, M.; Arleo, A.

doi:10.1101/2023.10.09.560481

bioRxiv · 10.1101/2023.10.09.560481

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

Murari, J.·Gautier, J.·Daout, J.·Krafft, L.·Senee, P.·Mece, P.·Seiple, W.·Grieve, K.·Sheynikhovich, D.·Meimon, S.·Paques, M.·Arleo, A.

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Abstract

PurposeThis study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic Age-related Macular Degeneration (AMD). MethodsWe recruited 7 young controls, 4 older controls and 16 presymptomatic AMD patients with foveal drusen from the Silversight Cohort. A high speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) 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. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. ResultsFEM were measured with high precision (RMS-S2S=0.0015{degrees} on human eyes) and small foveal drusen (median=60{micro}m) 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. 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. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

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Murari, J., Gautier, J., Daout, J., Krafft, L., Senee, P., Mece, P., Seiple, W., Grieve, K., Sheynikhovich, D., Meimon, S., Paques, M., Arleo, A.. 2023-10-10. Foveal drusen increase fixation instability: fixational eye movements as biomarkers for pre-symptomatic AMD. https://doi.org/10.1101/2023.10.09.560481

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