Assessment of a preclinical dry eye model using ultrahigh-resolution optical coherence tomography

Abstract

Purpose : This study employs ultrahigh-resolution optical coherence tomography (UHR-OCT) to characterize a dry eye mouse model. Additionally, OCT images are compared to fluorescein staining cornea photographs.

Methods : Fifty-seven C57BL/6 mice with scopolamine induced desiccating stress dry eye disease (DED) were included in this study. Corneal OCT images were acquired after induction of the disease on two consecutive study days using a custom-built UHR-OCT system (central wavelength 850 nm, axial resolution 1.38 µm in tissue). Epithelial and stromal thickness was assessed in the central region of the cornea. In addition, defects within epithelium and deeper corneal layers were evaluated. Fluorescein photographs were taken on the second study day immediately after OCT imaging.

Results : The mean thickness of epithelium, stroma and whole cornea increased significantly from 38.0 ± 1.80 µm, 67.1 ± 3.47 µm and 105.1 ± 4.22 µm on the first day to 39.3 ± 2.57 µm, 69.5 ± 3.46 µm and 108.8 ± 4.81 µm on the second day (p = 0.001 for epithelium and stroma, p < 0.001 for the whole cornea), respectively. Thirty-eight percent of the corneas did not show defects in any layer on both days. Epithelial defects were the ones most commonly observed and could be found in 50% of the eyes on at least one day. In cases where no epithelial lesions were revealed by OCT imaging, distinct defects were found in only 6% of fluorescein images, with 51% showing diffuse markings and 43% showing no markings at all. All the corneas showing an epithelial lesion in OCT on the second day showed alteration in fluorescein staining with 50% being diffuse and 50% distinct local marks. Mean fluorescein intensity showed a weak correlation to epithelial thickness (r = 0.389; p = 0.023), but none to stromal thickness (r = -0.104; p = 0.557).

Conclusions : Our study showed that structural defects of the epithelium can easily be evaluated using UHR-OCT. Furthermore, OCT delivers information about structural changes and provides quantitative thickness data of all corneal layers. It thus provides an excellent addition to fluorescein staining for investigation of morphological changes in the cornea due to DED. In addition, it might help to explore possible causative mechanisms of defects as observed using fluorescein staining.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Corneal defects revealed by fluorescein staining (a), en-face projection of epithelium from 3D OCT data (b) and OCT tomogram (c).