Use of ultra-high-resolution optical coherence tomography to detect in vivo characteristics of Descemet's membrane in Fuchs' dystrophy

Abstract

Purpose: To demonstrate the capability of ultra-high-resolution (UHR) anterior segment optical coherence tomography (OCT) to image Descemet's membrane (DM) and measure its thickness in vivo. (2) To evaluate the use of DM characteristics and thickness in the diagnosis of Fuchs' dystrophy.

Design: Case-control study.

Participants: Twenty eyes of 12 Fuchs' dystrophy patients, 20 eyes of 13 young normal, and 20 eyes of 15 elderly normal subjects.

Methods: Subjects were imaged using novel, custom-built UHR-OCT. Images were used to describe the characteristics of DM. Custom-made software was used to measure DM thickness and central corneal thickness (CCT). Specimens of DM obtained from Fuchs' dystrophy patients who underwent endothelial keratoplasty (EK) were histopathologically examined. Regression analyses were used to assess the correlation of DM thickness measured by UHR-OCT in vivo and by light microscopy and to determine the intergroup correlations between age, CCT, and DM thickness.

Main outcome measures: We assessed DM characteristics and thickness, CCT, and age.

Results: Using UHR-OCT, the DM seemed in normal young subjects as a single, opaque, smooth line and in normal elderly subjects as a band of 2 smooth opaque lines with a translucent space in between. In Fuchs' dystrophy, DM appeared as a thickened band of 2 opaque lines; the anterior line was smooth whereas the posterior line had a wavy and irregular appearance with areas of localized thickenings. The DM thickness measured in vivo by UHR-OCT correlated significantly with that measured by light microscopy in 5 Fuchs' dystrophy eyes that underwent EK. The average central thicknesses of DM in normal young, in normal elderly and in Fuchs' dystrophy eyes were 10+/-3, 16+/-2, and 34+/-11 microm, respectively (P<0.001). There was a significant correlation between age and DM thickness only in normal groups. In Fuchs' dystrophy patients, there was a significant correlation between CCT and DM thickness that was not significant for normal groups.

Conclusions: Ultra-high-resolution OCT is an innovative technique for the in vivo imaging of DM. Determining DM characteristics and thickness by UHR-OCT could be a new approach for the diagnosis of Fuchs' dystrophy.

Figure 1. Ultra high resolution optical coherence tomography (UHR-OCT) images of the central cornea

The epithelium (a), Bowman's layer (b), and stroma (c) are readily seen in each image and Descemet's membrane (d) is enlarged in the inset. (A) Descemet's membrane of a normal young subject appeared as a single smooth opaque line on the back surface of the cornea. (B) Descemet's membrane in a normal elderly subject appeared as a band formed of two smooth opaque lines with a translucent space in between. (C) In UHR-OCT image of the right eye of Fuchs' dystrophy patient number 5, Descemet's membrane consisted of a thickened band composed of two opaque lines separated by a translucent space. The anterior line was smooth while the posterior line had a wavy irregular appearance with areas of localized thickenings. Bars are 50 μm.

Figure 2. Reflectivity profiles of ultra high resolution optical coherence tomography (UHR-OCT) images of young normal, elderly normal and Fuchs' dystrophy corneas

Each profile was created by averaging the UHR-OCT A-scan data for the central 2 mm of the corneas shown in Figure 1. Peaks were identified and correlated to the different corneal layers. The interval from (a) to (b) represents epithelium, while from (b) to (c) represents Bowman's layer. The stroma is represented by the interval from (c) to (d). The thickness of Descemet's membrane was calculated as the distance from (d) to (e). The measured thicknesses of Descemet's membrane were 9 μm for the normal young subject (A), 17 μm for the normal elderly subject (B), and 55 μm for the right eye of Fuchs' dystrophy patient number 5 (C). For the Fuchs' dystrophy patient (C), the reflectivity profile of the corneal stroma was greater than that in the normal subjects (A and B), probably due to corneal edema. The posterior line of the Descemet's membrane in (C) had multiple small spikes that correlated with its irregular appearance on the UHR-OCT image.

Figure 3. Comparison of corneal histological analysis and ultra high resolution optical coherence tomography (UHR-OCT) images of a Fuchs' dystrophy patient

Image (A) shows the photomicrograph of the pathology section of the same Descemet's membrane in image (B) obtained by Descemet's stripping automated endothelial keratoplasty (DSAEK) of the right eye of Fuchs' dystrophy patient number 5. Image (A) discloses thickened Descemet's membrane with areas of nodular excrescences correlating with cornea guttae. The average central thickness of the Descemet's membrane measured histopathologically by light microscope was 31μm (Periodic acid-Schiff stain; original magnification X400). UHR- OCT image (B) of the same Descemet's membrane appears as a thickened band formed of two opaque lines. The anterior line is smooth while the posterior line has a wavy irregular appearance with areas of localized thickenings that can be correlated to cornea guttae. In vivo UHR-OCT measurements of this Descemet's membrane was 55 μm. Bar is 50 μm.

Figure 4. Fuchs' dystrophy Descemet's membrane thickness measured by ultra high resolution optical coherence tomography (UHR-OCT) was significantly correlated with light microscopic histopathological measurements

For Fuchs' dystrophy corneas that underwent Descemet's stripping automated endothelial keratoplasty (DSAEK), preoperative UHR-OCT measured thicknesses showed a significant correlation with that measured by light microscopic histopathological examination. In Vivo Descemet's membrane thickness of the central 2 mm of the cornea was measured using custom-made software that created a reflectivity profile form UHR-OCT raw images. Different peaks of the reflectivity profile were correlated to corresponding layers of the cornea and the distance between the last two peaks were used to calculate the thickness of Descemet's membrane. Light microscopy mean thicknesses of Descemet's membrane were determined by averaging thickness measurements that included and excluded guttae in one representative randomly selected central high power field per slide.

Figure 5. In normal subjects, Descemet's membrane tends to become thicker with age

There was a highly significant positive correlation (r = 0.75; P< 0.001) between the thickness of Descemet's membrane and age in the healthy young and elderly groups.

Figure 6. In Fuchs' dystrophy, Descemet's membrane thickness correlates significantly with the central cornea thickness

There was a significant non-linear power correlation (r = 0.5; P < 0.05) correlation between the thickness of Descemet's membrane and the central corneal thickness in Fuchs' dystrophy patients.