The relationship between mechanical properties, ultrastructural changes, and intrafibrillar bond formation in corneal UVA/riboflavin cross-linking treatment for keratoconus

Shao Hsuan Chang, Ashkan Eliasy, Kai Jung Chen, You Ren Ji, Tai Horng Young, Tsung Jen Wang, Colin E. Willoughby, Kevin J. Hamill, Ahmed Elsheikh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE: To determine the relationship between mechanical behavior in cross-linked corneas and changes in the corneal ultrastructure after corneal cross-linking (CXL). METHODS: Porcine corneas were treated following the “Dresden” protocol, the current gold standard for clinical treatment, consisting of dropwise application of 0.1% riboflavin in 20% dextran followed by 30 minutes of ultraviolet-A (UVA) irradiation. The effect of CXL was assessed using uniaxial tensile testing, transmission electron microscopy, and Fourier transform infrared spectroscopy, with results compared against corneas treated with each of the treatment solution components individually. RESULTS: UVA/riboflavin cross-linked corneas displayed 28% ± 17% increase in the material tangent modulus compared with dextran treatment alone, and altered collagen architecture within the first 300 µm of stromal depth consisting of 5% increase in the thickness of collagen fibrils, no significant changes to interfibrillar spacing, and an 8% to 12% decrease in number of fibrils per unit area. Fourier transform infrared spectroscopy confirmed formation of interfibrillar bonds (P = .012) induced by UVA-mediated CXL. CONCLUSIONS: The data support a model wherein collagen fibril diameter and structural density are fundamental parameters in defining tissue stiffening following UVA/riboflavin CXL and provide benchmarks against which modifications to the Dresden CXL protocol can be evaluated.

Original languageEnglish
Pages (from-to)264-272
Number of pages9
JournalJournal of Refractive Surgery
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Keratoconus
Riboflavin
Cornea
Collagen
Fourier Transform Infrared Spectroscopy
Dextrans
Benchmarking
Transmission Electron Microscopy
Swine

ASJC Scopus subject areas

  • Surgery
  • Ophthalmology

Cite this

The relationship between mechanical properties, ultrastructural changes, and intrafibrillar bond formation in corneal UVA/riboflavin cross-linking treatment for keratoconus. / Chang, Shao Hsuan; Eliasy, Ashkan; Chen, Kai Jung; Ji, You Ren; Young, Tai Horng; Wang, Tsung Jen; Willoughby, Colin E.; Hamill, Kevin J.; Elsheikh, Ahmed.

In: Journal of Refractive Surgery, Vol. 34, No. 4, 01.04.2018, p. 264-272.

Research output: Contribution to journalArticle

Chang, Shao Hsuan ; Eliasy, Ashkan ; Chen, Kai Jung ; Ji, You Ren ; Young, Tai Horng ; Wang, Tsung Jen ; Willoughby, Colin E. ; Hamill, Kevin J. ; Elsheikh, Ahmed. / The relationship between mechanical properties, ultrastructural changes, and intrafibrillar bond formation in corneal UVA/riboflavin cross-linking treatment for keratoconus. In: Journal of Refractive Surgery. 2018 ; Vol. 34, No. 4. pp. 264-272.
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abstract = "PURPOSE: To determine the relationship between mechanical behavior in cross-linked corneas and changes in the corneal ultrastructure after corneal cross-linking (CXL). METHODS: Porcine corneas were treated following the “Dresden” protocol, the current gold standard for clinical treatment, consisting of dropwise application of 0.1{\%} riboflavin in 20{\%} dextran followed by 30 minutes of ultraviolet-A (UVA) irradiation. The effect of CXL was assessed using uniaxial tensile testing, transmission electron microscopy, and Fourier transform infrared spectroscopy, with results compared against corneas treated with each of the treatment solution components individually. RESULTS: UVA/riboflavin cross-linked corneas displayed 28{\%} ± 17{\%} increase in the material tangent modulus compared with dextran treatment alone, and altered collagen architecture within the first 300 µm of stromal depth consisting of 5{\%} increase in the thickness of collagen fibrils, no significant changes to interfibrillar spacing, and an 8{\%} to 12{\%} decrease in number of fibrils per unit area. Fourier transform infrared spectroscopy confirmed formation of interfibrillar bonds (P = .012) induced by UVA-mediated CXL. CONCLUSIONS: The data support a model wherein collagen fibril diameter and structural density are fundamental parameters in defining tissue stiffening following UVA/riboflavin CXL and provide benchmarks against which modifications to the Dresden CXL protocol can be evaluated.",
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