Increased efficacy of accelerated corneal collagen crosslinking in rabbit ectasia models due to higher oxygen availability.

The purpose of this study was to comprehensively investigate the efficacy and safety of accelerated corneal collagen crosslinking (A-CXL) in a normoxic or hyperoxic environment. The collagenase type Ⅱ solution was applied to both the left and right eyes of the rabbit after epithelial debridement. Two weeks after collagenase treatment, the corneal morphology parameters (by Pentacam) and biomechanical parameters (by Corvis ST) in vivo were assessed to determine whether corneal ectasia had occurred. Subsequently, these eyes were randomly divided into three groups. The first group did not receive any treatment. The second and third groups underwent A-CXL surgery (30 mW/cm2, 4 min) in normoxic environment (21 % oxygen) or hyperoxic environment (>90 % oxygen), respectively. Four weeks later, changes in the corneal morphology parameters and biomechanical parameters in vivo were evaluated. Moreover, the elastic modulus (by biaxial stretch test) and histology of corneal tissues were also assessed ex vivo. Morphological and biomechanical parameters in vivo suggest the occurrence of corneal ectasia after collagenase treatment. No significant differences were found in morphological parameters changes obtained by Pentacam among three groups at 4 weeks after A-CXL surgery. However, the results of SD-OCT revealed that the corneal thickness change at the peripheral position along the nasal-temporal direction in the hyperoxic A-CXL group was lower compared with the other two groups. Biomechanical tests showed that, compared with the ectatic cornea group, the ability of the cornea to resist deformation increased only in the hyperoxic A-CXL group, with lower A1V and IR in vivo and higher elastic modulus ex vivo, while the normoxic A-CXL exhibited similar postoperative outcomes to untreated ectatic cornea. The histological results showed that no obvious signs of apoptosis were observed in all groups. In conclusion, hyperoxic A-CXL may be more effective than normoxic A-CXL in the aspect of delaying further cornea ectasia. This confirms the positive role of oxygen application in A-CXL in keratoconus clinic treatment.