The Short-Term Safety Evaluation of Corneal Crosslinking Agent-Genipin

Background: Genipin( GP) is a safe method for corneal crosslinking, even for very thin corneas. However, there have been no reports on the optimal GPconcentration range to use in vivo for corneal crosslinking. Objectives: To investigate the safety of corneal crosslinking after a 24-h incubation with different concentrations of GP. Methods: Twenty New Zealand white rabbitswere divided into a phosphate-buffered saline(PBS) group, 0.2% GPcrosslinking ( GP-CXL) group, 0.25% GP-CXL group, and 0.3% GP-CXL group. Before and after surgery, the operated eyes of each group were characterized by confocal microscopy, and corneal buttons were excised for endothelium staining and electron microscopy. Results: The keratocyte structures in each GPgroup appeared to be similar to those in the PBS group. Through the confocal microscopy, the changes in corneal endothelial cell density also did not significantly differ among groups. There was a significant difference in apoptosis between the 0.3% GP-CXL and PBS groups (p < 0.05) and between the 0.3% GP-CXL and 0.25% GP-CXL groups (p < 0.05), but there were no significant differences between the 0.2 and 0.25% GP-CXL groups compared to the PBS group. Transmission electron microscopy showed endothelial cell damagein the 0.3% GP-CXL group, with minimal endothelial cell damagein the other groups. Conclusions: Treatment of rabbit corneas with ≤0.25% GPresulted in minimal toxicity to keratocytes and endothelial cells, suggesting that it is a safe crosslinking agent at those concentrations.