Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma

Hayes, Sally ORCID: https://orcid.org/0000-0001-8550-0108, Boote, Craig ORCID: https://orcid.org/0000-0003-0348-6547, Kamma-Lorger, Christina S., Rajan, Madhavan S., Harris, Jonathan L., Dooley, Erin Patricia, Hawksworth, Nicholas, Hiller, Jennifer, Terill, Nick J., Hafezi, Farhad, Brahma, Arun K., Quantock, Andrew James ORCID: https://orcid.org/0000-0002-2484-3120 and Meek, Keith Michael Andrew ORCID: https://orcid.org/0000-0002-9948-7538 2011. Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma. PLoS ONE 6 (8) , e22405. 10.1371/journal.pone.0022405

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Abstract

Purpose To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas. Methods Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin). Results Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (p<0.001); an increase in fibril diameter was also seen in two out of four unswollen normal corneas and one unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a decrease in tissue hydration in the swollen normal corneas only. Although there was no consistent treatment-induced change in hydration in the unswollen normal samples, iso-osmolar cross-linking of these corneas did result in a compaction of collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not seen in the swollen normal corneas. Collagen D-periodicity was not affected by either treatment. Conclusion The observed structural changes following Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
Publisher:	PLoS
ISSN:	1932-6203
Last Modified:	09 Oct 2023 09:43
URI:	https://orca.cardiff.ac.uk/id/eprint/18883

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