Abstract
Purpose :
UVA-Crosslinking (CXL) is a treatment to halt the progression of keratoconus by inducing chemical bonds between collagen fibrils in the tissue. Riboflavin solutions (RS) of different osmolarities are used to influence corneal hydration during CXL. Furthermore, UV radiation intensity (UVI) may be increased to reduce exposure times. The aim of this study was to use nanoindentation (NI) to quantify the CXL effects of seven different CXL protocols.
Methods :
Human donor corneas not suitable for transplantation were equilibrated in cell culture medium supplemented with 15% dextran, clamped in an artificial anterior chamber and exposed to a retro-corneal fluid pressure (20 mmHg). To measure the elastic modulus (EM) and creep (CP), a measure of fluid displacement within tissue under load, spatially resolved NI in the center of the Cornea was performed in the native state and after CXL. The CXL was performed with either one of three RS (0.1% riboflavin(A); 0.1% riboflavin+1.1% HPMC(B); 0.1% riboflavin+20% dextran(C)) and a UVI of 3mW/cm2 or one of five different UVI ((a)3, (b)6, (c)9, (d)18, (e)30 mW/cm2) with RS (B). Each of the seven different CXL protocols was applied to 10 corneas. The EM and CP values were compared using a linear mixed model and examined for significant treatment effects.
Results :
Mean donor age was 74.8±11.9 years (range 37-93 years; 16 females, 54 males). In the comparison of three RS, native EM was 113kPa and CP was 17.2%. CXL increased EM by (A)28kPa, (B)24kPa, (C)35kPa and reduced the CP by (A)1.5%, (B)1.8% and (C)4.5%, respectively. In the UVI comparison, native EM was 128 kPa and CP was 15.8%. Following CXL treatment, an increase in EM by (a)24kPa, (b)28kPa, (c)19kPa, (d)24kPa, (e)14kPa and a reduction in CP by (a)1.7%, (b)1.5%, (c)1.4%, (d)1.2%, (e)0.6% were observed. Analysis in a linear mixed model revealed p-values < 0.0001 for all described treatment effects.
Conclusions :
This approach allows for quantitative investigation of biomechanical properties of the human cornea by absolute force measurements under almost physiological conditions. All CXL methods show both a significant increase in EM and a reduction in CP. CXL appears enhanced with hyperosmotic riboflavin and diminished when high radiation intensity is used for short times.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.