Depth-Dependent Reduction of Biomechanical Efficacy of Contact Lens-Assisted Corneal Cross-linking Analyzed by Brillouin Microscopy

Abstract

Purpose: To determine the relative impact of contact lens- assisted corneal cross-linking (CACXL) and standard protocol CXL (CXL) on regional corneal stiffness using Brillouin microscopy.

Methods: CXL and CACXL were performed on 30 intact fresh porcine eyes (15 per group). Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by Brillouin maps. Corneas were cut into strips to conduct mechanical stress-strain tests after Brillouin microscopy to evaluate stiffness difference between CXL and CACXL. Each eye served as its own control.

Results: CXL had a greater impact on corneal stiffness, with a maximum increase of 5.74% compared to 3.99% for CACXL (P < .001). CXL increased longitudinal modulus by 7.8% in the anterior, 1.7% in the middle, and -0.7% in the posterior regions compared to CACXL, which increased longitudinal modulus by 5.5% in the anterior (P < .001), 1.2% in the middle (P = .15), and -0.4% in the posterior regions (P = .60). Mechanical stress-strain tests showed that at 10% strain averaged Young's modulus was 5 MPa for CXL and 2.97 MPa for CACXL (P < .001).

Conclusions: Both CACXL and standard protocol CXL induced significant corneal stiffening primarily concentrated in the anterior cornea. CACXL leads to less stiffening compared with CXL. An attenuated but continuous stiffening effect can be observed through the whole cornea for both CACXL and CXL, although CACXL has a smaller stiffness gradient. [J Refract Surg. 2019;35(11):721-728.].

Copyright 2019, SLACK Incorporated.

Figures

Figure 1.

CXL protocols for standard CXL and CACXL. Hydrophilic contact lenses were used to make riboflavin solution penetrate through contact lenses and diffuse into the stroma. Thus, there was no need to lift contact lenses during UV irradiation.

Figure 2.

Representative Brillouin results for the standard CXL group. (a) Distribution of Brillouin shifts in an untreated eye. Aqueous humor is the bottom part of the color map. (b) Distribution of Brillouin shifts in the same eye after standard CXL. According to Eq. (1), a higher Brillouin shift correlates to a larger longitudinal modulus. Increase of longitudinal modulus is elucidated with different colors. (c) Profiles of Brillouin shifts in (a) and (b) along the depth, averaged in lateral direction. The way to divide the cornea into 3 segments is also shown.

Figure 3.

Representative Brillouin results for the CACXL group. (a) Distribution of Brillouin shifts for an untreated eye. Though thickness of this cornea is different from the one in Figure 2(a), similar stiffness distribution can be seen. (b) Distribution of Brillouin shifts for the same eye after CACXL. (c) Lateral averaged depth profiles of Brillouin shifts in (a) and (b).

Figure 4.

Percentage change of mean longitudinal modulus of the anterior, middle and posterior for the standard CXL (N=15) versus CACXL (N=15). ***=P<0.001.

Figure 5.

Stress-strain curves fitted by mean values at strains of 4%, 6%, 8% and 10%. Standard CXL had greater stiffness than CACXL at all selected Strains.