Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation of corneal epithelium and subepithelial nerve plexus regeneration by in vivo HRT II system confocal microscopy in humans

PURPOSE. To assess corneal tissue modifications after riboflavin-UVA- induced cross-linking of corneal collagen in patients with progressive keratoconus as well as regeneration of epithelium and subepithelial nerve plexus by in vivo HRT II system confocal microscopy in humans. METHODS. Ten patients with progressive keratoconus were treated by riboflavin-UVA-induced cross-linking of corneal collagen, involving assessment of ultrastructural modifications of the corneal epithelium and subepithelial nerve plexus by HRT II system confocal microscopy. Treatment included instillation of 0.1% riboflavin-20% dextrane solution 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. Radiant energy was 3 mW/cm2 or 5.4 Joule/cm2 and the source was dual UVA (370 nm) light-emitting led. The protocol included the operation followed by antibiotic medication and eye dressing with a soft therapeutic contact lens. Changes in epithelium and subepithelial and stromal nerve plexus were assessed by HRT II system confocal microscopy in vivo. RESULTS. After 5 days of soft contact lens wearing corneal epithelium has a regular morphology and density. Disappearance of subepithelial stromal nerve fibers was observed in the central irradiated area where, 1 month after the operation, initial reinnervation was microscopically observed. No changes in nerve fibers were observed in the peripheral untreated with a clear lateral transition between the two areas. Six months after the operation, the anterior subepithelial stroma was recolonized by nerve fibers with restoration of corneal sensitivity. CONCLUSIONS. HRT II system confocal microscopy confirms corneal epithelium restore and re-innervation after riboflavin-UVA-induced collagen cross-linking directly in vivo in humans.