Researchers recently discovered that corneal collagen crosslinking (CXL) may cause permanent keratocyte loss or altered keratocyte repopulation, resulting in clinical complications, such as corneal opacification and perforation.

The team compared the corneal buttons of eight keratoconus corneas (five to 114 months after CXL) with five keratoconus specimens without CXL and five normal corneas for morphological alterations. They evaluated the corneal buttons by transmission electron microscopy, light microscopy and immunohistochemistry using antibodies against CD34, PGP 9.5, nestin, telomerase reverse transcriptase and Ki67.

The investigators found that the majority of keratoconus corneas that had CXL showed a significant keratocyte loss that was clinically correlated with corneal opacification and perforation; keratoconus corneas without CXL, however, revealed a higher keratocyte density compared with healthy controls. They noted that the remaining keratocytes in post-CXL corneas appeared more polymorphic and revealed a different expression of surface markers similar to keratocytes in corneal scars. The presence of proteoglycans, nerves and endothelial cells was unaffected by CXL, they added.

“Our findings indicate that corneal CXL has the potential to cause persistent structural and functional damage with loss of keratocytes and/or altered repopulation of keratocytes years after the procedure,” the study authors wrote in their paper. “Despite its good safety profile and high effectiveness in progressive keratoconus, CXL should be performed in accordance with current guidelines strictly adhering to protocol and safety standards.”

Müller P, Loeffler KU, Messmer E, et al. Histological corneal alterations in keratoconus after crosslinking—expansion of findings. Cornea. September 9, 2019. [Epub ahead of print].