Enabling In Vivo Longitudinal Evaluation of Descemet's Membrane Thickness in Wild-type and FECD Mice Using Self-Referenced Optical Coherence Microscopy.

Purpose: Descemet's membrane (DM) remodeling is a key factor in the etiology of early-onset Fuchs endothelial corneal dystrophy (FECD). Although various mouse models have been developed to replicate major FECD phenotypes, including DM thickening, there is currently no imaging technique capable of evaluating changes in mice DM thickness in vivo. This work proposed a novel self-referenced optical coherence microscope (OCM) to longitudinally evaluate age-dependent and FECD-dependent changes in DM thickness in mice. Methods: The self-referenced OCM used the mouse corneal surface as the reference to mitigate artifacts from breathing-induced motion, steep corneal curvature, and dispersion mismatch, that often compromise the delineation of the DM in vivo. The approach was validated by longitudinally evaluating the DM thickness in four wild-type (WT) and five FECD mice at two time points-5 weeks of age and 16 weeks of age. Results: Unlike standard OCM, the self-referenced approach enabled the delineation of the DM with an axial resolution of 1.6 µm in the living eyes of WT and FECD mice. A significant increase in DM thickness was observed in FECD mice (2.74 ± 0.12 µm) compared with WT mice (1.85 ± 0.22 µm) at 5 weeks of age. A similar trend was observed at 16 weeks of age (3.20 ± 0.20 µm in FECD mice vs 2.21 ± 0.32 µm in WT mice). No age-dependent increase in DM thickness was observed in either group between 5 weeks of age and 16 weeks of age. Conclusions: This study represents the first longitudinal in vivo evaluation of age-dependent changes in DM thickness in both WT and FECD mice using self-referenced OCM.