Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.

<h4>Purpose</h4>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.<h4>Methods</h4>Using small-angle X-ray scattering, measur...

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Main Authors: Sally Hayes, Craig Boote, Christina S Kamma-Lorger, Madhavan S Rajan, Jonathan Harris, Erin Dooley, Nicholas Hawksworth, Jennifer Hiller, Nick J Terill, Farhad Hafezi, Arun K Brahma, Andrew J Quantock, Keith M Meek
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0022405
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author Sally Hayes
Craig Boote
Christina S Kamma-Lorger
Madhavan S Rajan
Jonathan Harris
Erin Dooley
Nicholas Hawksworth
Jennifer Hiller
Nick J Terill
Farhad Hafezi
Arun K Brahma
Andrew J Quantock
Keith M Meek
author_facet Sally Hayes
Craig Boote
Christina S Kamma-Lorger
Madhavan S Rajan
Jonathan Harris
Erin Dooley
Nicholas Hawksworth
Jennifer Hiller
Nick J Terill
Farhad Hafezi
Arun K Brahma
Andrew J Quantock
Keith M Meek
author_sort Sally Hayes
collection DOAJ
description <h4>Purpose</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.
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spelling doaj-art-89fddd5996a94c0ebac34ce4b5a4beef2025-08-20T02:08:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2240510.1371/journal.pone.0022405Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.Sally HayesCraig BooteChristina S Kamma-LorgerMadhavan S RajanJonathan HarrisErin DooleyNicholas HawksworthJennifer HillerNick J TerillFarhad HafeziArun K BrahmaAndrew J QuantockKeith M Meek<h4>Purpose</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0022405
spellingShingle Sally Hayes
Craig Boote
Christina S Kamma-Lorger
Madhavan S Rajan
Jonathan Harris
Erin Dooley
Nicholas Hawksworth
Jennifer Hiller
Nick J Terill
Farhad Hafezi
Arun K Brahma
Andrew J Quantock
Keith M Meek
Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
PLoS ONE
title Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
title_full Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
title_fullStr Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
title_full_unstemmed Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
title_short Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma.
title_sort riboflavin uva collagen cross linking induced changes in normal and keratoconus corneal stroma
url https://doi.org/10.1371/journal.pone.0022405
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