First proposed efficacy study of high versus standard irradiance and fractionated riboflavin/ultraviolet a cross-linking with equivalent energy exposure

Ronald R. Krueger, Satish Herekar, Eberhard Spoerl

Research output: Contribution to journalArticle

23 Scopus citations


Purpose: To document the first presented report in December 2008 of high irradiance riboflavin/ultraviolet A (UVA) corneal cross-linking in comparison with that of standard irradiance and of fractionated exposure to increase the time for oxygen diffusion into the cornea. Methods: After in vitro studies of oxygen depletion and cross-linking density using type 1 human collagen gels, 36 ex vivo porcine globes were deepithelialized and exposed to 0.1% riboflavin drops in carboxymethylcellulose solution every 5 min for 3 initial doses and then throughout irradiation afterward. Six eyes each were irradiated with 370-nm UVA light at 2, 3, 9, and 15 mW/cm2 continuously and 15 mW/cm2 fractionated (with alternate cycles of 30 s "ON" and 30 s "OFF" exposure) using an equivalent radiant exposure of 5.4 mJ/cm. The final six eyes received no UVA exposure as a control. The exposed corneas were then dissected and subjected to extensiometry. Analysis of variance with Bonferroni post hoc test was performed between groups. Results: The stress required to induce a 10% strain for the control eyes (no UVA) was 100.6±20.9×103 N/m2 in comparison with the stress of 3 mW/cm2 (standard irradiation) at 146.7±17.6·103 N/m2 (P=0.009). The stress at the other equidose irradiances of 2, 9, 15 continuously, and 15 mW/cm2 fractionated were 140±21.9, 162.8±70, 154.1±70, and 163.0±64×103 N/m2, respectively. When comparing the irradiances of 15 mW/cm2 continuously and fractionated to the standard irradiation, the stress was not statistically different (P=0.799 and 0.643), respectively. Conclusion: High irradiance riboflavin/UVA cross-linking with equivalent energy exposure demonstrates comparable efficacy in stiffening corneal collagen with standard irradiance, but with considerably less exposure time. Over the past 6 years, since this report was first presented, the use of high irradiance cross-linking has been gaining popularity.

Original languageEnglish (US)
Pages (from-to)353-357
Number of pages5
JournalEye and Contact Lens
Issue number6
StatePublished - Jan 1 2014



  • Cross-linking
  • High irradiance
  • Oxygen
  • Riboflavin

ASJC Scopus subject areas

  • Ophthalmology

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