Randomized Trial of Oxygen-Enriched Epithelium-On CXL for Keratoconus

Key Takeaways

• At month 12, least squares mean Kmax improved by 0.5 D with treatment and worsened by 0.4 D with sham/placebo, with a significant between-group difference of -1.0 D.
• The phase 3, multicenter, sham procedure/placebo-controlled, double-masked trial enrolled patients aged 13 to 51 years, with eyes assigned 2:1 to treatment or sham/placebo.
• No serious ocular adverse events or severe treatment-related adverse events were reported in the study eye, and punctate keratitis was the most common adverse event.

A phase 3 randomized keratoconus trial found a month 12 between-group Kmax advantage of -1.0 D with oxygen-enriched epithelium-on corneal collagen cross-linking versus sham/placebo. The comparison included patients aged 13 to 51 years in a randomized, double-masked setting. This month 12 Kmax result was the prespecified primary efficacy endpoint, and the month 12 analysis met that endpoint.

The multicenter randomized clinical trial enrolled patients with keratoconus who were 13 to 51 years old and used a sham procedure/placebo-controlled, double-masked design. Eyes were assigned in a 2:1 ratio, with 200 eyes receiving oxygen-enriched epithelium-on CXL and 112 eyes receiving sham/placebo. The active protocol used riboflavin 5′-phosphate ophthalmic solutions 0.239% and 0.177%, ultraviolet A irradiation, and supplemental oxygen, while controls received placebo solutions and sham irradiation. The primary efficacy endpoint was the between-group difference in least squares mean change from baseline in maximum corneal curvature at month 12.

At month 12, least squares mean Kmax improved by 0.5 D in the treatment group and worsened by 0.4 D in the sham/placebo group. The between-group difference was -1.0 D with p<0.0001. The corresponding confidence intervals were 0.7 to 0.3 for the treatment-group change, 0.1 to 0.8 for the sham/placebo-group change, and -1.3 to -0.6 for the between-group difference. Within-group p values were p<0.0001 for treatment and p=0.0045 for sham/placebo, and the prespecified month 12 efficacy criterion was met.

At month 12, there were no serious ocular adverse events and no severe treatment-related adverse events in the study eye. Punctate keratitis was the most common adverse event, occurring in 6.5% of CXL-treated eyes and 1.8% of sham/placebo eyes.