Differential dose-response relationships of collagen cross-linking in the cornea and sclera

This study aimed to systematically compare the enhancing effects of different UVA irradiation intensities on the biomechanical properties of ex vivo porcine cornea and sclera, to clarify the differences in the "dose-response" relationships between the two tissues during cross-linking, and to provide a parametric basis for extending cross-linking technology to the treatment of scleral diseases such as pathological myopia.

Eighty fresh ex vivo porcine eyes were used. The cornea and sclera were each randomly divided into 4 groups according to irradiation intensity: a control group (no irradiation), and experimental groups treated at 3,15and 30 mW/cm² (total energy 5.4 J/cm²). Following infiltration with a 0.1% riboflavin solution, irradiation was performed with 370 nm UVA light, the procedure was assisted by pure oxygen blowing. Key parameters extracted included the secant modulus (at 2%, 6%, and 10% strain points), the tangent modulus (slope of the linear elastic region), and the Yeoh hyperelastic model parameters (C₁, C₂).

In the cornea, both the secant modulus and tangent modulus showed a increase with rising irradiation intensity, with the 30 mW/cm² group exhibiting the greatest enhancement magnitude (approximately a 146.2% increase in secant modulus at 10% strain). For the sclera, the modulus enhancement displayed a non-linear relationship, the 15 mW/cm² group showed the optimal reinforcement effect (approximately a 176.13% increase in secant modulus), while the effect diminished in the 30 mW/cm² group. Analysis of model parameters indicated that the increase in C₂ (governing nonlinear stiffening) after cross-linking was far greater than that in C₁ (governing initial stiffness), suggesting that cross-linking primarily enhances the tissue's resistance under large deformations. Inter-group comparisons revealed that under identical parameters at low to medium intensities (3 and 15 mW/cm²), the sclera exhibited a higher modulus increase rate than the cornea; at high intensity (30 mW/cm²), the cornea showed more significant enhancement.

The responses of the cornea and sclera to cross-linking intensity are fundamentally different: the reinforcement effect in the cornea increases with intensity, whereas the sclera has an optimal intensity (15 mW/cm²), beyond which further intensity increase leads to diminishing returns.