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Morphological and immunohistochemical changes after corneal cross-linking.

Elisabeth M Messmer1, Peter Meyer, Martina C Herwig

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|May 15, 2012
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Summary

Corneal cross-linking (CXL) for keratoconus may cause lasting keratocyte loss in the anterior and middle corneal stroma. This study highlights potential long-term corneal damage, advising careful adherence to protocols.

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Area of Science:

  • Ophthalmology
  • Corneal Science
  • Histopathology

Background:

  • Keratoconus is a progressive thinning disorder of the cornea.
  • Corneal cross-linking (CXL) is a treatment aimed at stiffening the cornea to halt keratoconus progression.
  • The long-term morphologic effects of CXL on human corneal tissue require detailed investigation.

Purpose of the Study:

  • To investigate the light and electron microscopic and immunohistochemical changes in human corneas following corneal cross-linking (CXL).

Main Methods:

  • Examination of six post-CXL keratoconus corneas, twelve non-CXL keratoconus corneas, and seven normal corneas.
  • Utilized light microscopy, transmission electron microscopy, and indirect immunohistochemistry for BAX, survivin, BCL-2, and smooth muscle actin.
  • Quantified keratocyte density using direct immunofluorescence in different corneal stromal regions.

Main Results:

  • Post-CXL corneas showed significant reductions in keratocyte counts, particularly in the anterior and middle stroma (P = 0.014, P = 0.024).
  • Keratocyte loss was observed in both central and peripheral regions of CXL-treated corneas (P = 0.028, P = 0.047).
  • Increased proapoptotic BAX and/or antiapoptotic survivin expression was noted in some post-CXL keratocytes and endothelium.

Conclusions:

  • Corneal cross-linking (CXL) can induce significant and potentially permanent morphologic changes in human keratoconus corneas up to 30 months post-procedure.
  • A notable finding is the long-lasting keratocyte loss in the anterior and middle corneal stroma.
  • Given the potential for long-term corneal damage, CXL should be performed cautiously, adhering strictly to investigational protocols.