• Written By:
    Cornea/External Disease, Refractive Mgmt/Intervention

    Review of: Histological Corneal Alterations in Keratoconus After Crosslinking—Expansion of Findings

    Mùˆller P, Loeffler K, Messmer E, et al. Cornea, March 2020

    This basic science study describes the histologic findings in corneas with a history of corneal collagen crosslinking (CXL) for keratoconus.

    Study design

    Researchers examined morphological alternations in the corneal buttons of 8 keratoconus corneas (5–114 months after CXL), 5 keratoconus specimens without CXL and 5 healthy corneas. Five of the cases were new while the remaining 3 were previously published. Samples were evaluated by light microscopy and immunohistochemistry—using antibodies against CD34, PGP 9.5, nestin, telomerase reverse transcriptase and Ki67—as well as by transmission electron microscopy.


    Seven of the corneas that underwent CXL experienced significant keratocyte loss. Conversely, corneas that did not undergo CXL had a higher keratocyte density compared with healthy controls. Keratocyte loss might clinically correlate with corneal opacification and corneal perforation. After CXL, the remaining keratocytes tended to be more polymorphic and expressed different surface markers that were similar to keratocytes in corneal scars. The procedure did not affect proteoglycans, nerves and endothelial cells.


    The overall sample size was small. Since comparisons were only possible in eyes that failed CXL and required transplantation, it is unclear if these results would be similar in eyes undergoing successful CXL without the need for future transplantation. In vivo data, such as from confocal microscopy, might differ from histological findings for reasons such as tissue shrinkage during histopathological processing.

    Clinical significance

    CXL may lead to permanent keratocyte loss or repopulation of altered keratocytes. Though the clinical impact of these histologic findings is uncertain, they are similar to findings from corneal scar formation.