Abstract
The aim of this study was to investigate corneal enzymatic resistance following epithelium off and on riboflavin/UVA cross-linking (CXL). One hundred and fourteen porcine eyes were divided into four non-irradiated control groups and seven CXL groups. The latter comprised; (i) epithelium-off, 0.1% iso-osmolar riboflavin, 9 mW UVA irradiation for 10 min, (ii) disrupted epithelium, 0.1% hypo-osmolar riboflavin, 9 mW UVA for 10 min, (iii) epithelium-on, 0.25% hypo-osmolar riboflavin with 0.01% benzylalkonium chloride (BACS), 9 mW UVA for 10 min, (iv) epithelium-on, 5 min iontophoresis at 0.1 mA for 5 min with 0.1% riboflavin solution, 9 mW UVA for 10 min or (v) 12.5 min, (vi) epithelium-on, prolonged iontophoresis protocol of 25 min with 1.0 mA for 5 min and 0.5 mA for 5 min with 0.25% riboflavin with 0.01% BACS, 9 mW UVA for 10 min or (vii) 12.5 min. Enzymatic resistance was assessed by daily measurement of a corneal button placed in pepsin solution and measurement of corneal button dry weight after 11 days of digestion. This study revealed that the enzymatic resistance was greater in CXL corneas than non-irradiated corneas (p < 0.0001). Epithelium-off CXL showed the greatest enzymatic resistance (p < 0.0001). The prolonged iontophoresis protocol was found to be superior to all other trans-epithelial protocols (p < 0.0001). A 25% increase in UVA radiance significantly increased corneal enzymatic resistance (p < 0.0001). In conclusion, although epithelium-on CXL appears to be inferior to epithelium-off CXL in terms of enzymatic resistance to pepsin digestion, the outcome of epithelium-on CXL may be significantly improved through the use of higher concentrations of riboflavin solution, a longer duration of iontophoresis and an increase in UVA radiance.
Highlights
Over the past decade, riboflavin/UVA corneal cross-linking (CXL) has become an established treatment to halt the progression of keratoconus and other corneal ectasias
Riboflavin acts as a photo-sensitizer for the production of oxygen free radicals, which drive the CXL process (McCall et al, 2010) and as a result insufficient stromal absorption may result in treatment failure (Wollensak et al, 2003; Wollensak and Iomdina, 2009)
Epi-off-CXL is considered to be the gold standard procedure, with multiple prospective and randomized controlled studies demonstrating its efficacy in terms of cessation of keratoconus progression and improvements in keratometric and visual parameters (Caporossi et al, 2006; Gkika et al, 2011; O'Brart et al, 2011; Richoz et al, 2013; Wittig-Silva et al, 2014; Wollensak et al, 2003), new methods of epi-on-CXL
Summary
Riboflavin/UVA corneal cross-linking (CXL) has become an established treatment to halt the progression of keratoconus and other corneal ectasias. In the “goldstandard” CXL protocol the epithelium is removed from the central corneal to allow adequate stromal absorption of riboflavin prior to UVA irradiation. Spoerl et al confirmed this need for epithelial removal, reporting no changes in corneal biomechanics when CXL was performed with the epithelium intact (Spoerl et al, 1998). On this basis, the epithelium was removed in the first published clinical studies (Caporossi et al, 2006; Gkika et al, 2011; O'Brart et al, 2011; Richoz et al, 2013; Wittig-Silva et al, 2014; Wollensak et al, 2003). Epithelial debridement is associated with a number of adverse events, including severe ocular pain in the immediate post-operative period, delayed visual rehabilitation and the risks of scarring, infectious and non-infectious keratitis (Koller et al, 2009)
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