International Ophthalmology

, Volume 38, Issue 6, pp 2509–2517 | Cite as

Transepithelial accelerated corneal collagen cross-linking with higher oxygen availability for keratoconus: 1-year results

  • Ling Sun
  • Meng Li
  • Xiaoyu Zhang
  • Mi Tian
  • Tian Han
  • Jing Zhao
  • Xingtao ZhouEmail author
Original Paper



To investigate the safety and efficacy of a new protocol for transepithelial accelerated corneal collagen cross-linking with higher oxygen availability for keratoconus treatment.


There were 26 patients (26 eyes) diagnosed with keratoconus enrolled in the study and treated with transepithelial accelerated corneal collagen cross-linking. The corneas were irradiated using UVA light for 5 min and 20 s with 45 mW/cm2 irradiance and pulsed illumination (1:1). The follow-up examinations were performed at 1 day, 1 month, 3 months, 6 months, and 1 year postoperatively. At each follow-up, the patients received a complete ophthalmologic examination that included visual acuity, manifest refraction, corneal topography, endothelial cell density, and ORA.


The operations were uneventful, and there were no complications during follow-up. At 1 year after the procedure, the uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) of the treated eyes were significantly improved compared to the pretreatment values (P = 0.012, 0.041, respectively). Additionally, 65.4% of eyes gained at least 1 line in CDVA, and 42.3% of eyes showed a reduction in at least 0.5D in astigmatism. The maximum keratometry (K max), corneal thickness, corneal endothelial cell density and corneal biomechanics were stable at each visit.


Transepithelial accelerated corneal collagen cross-linking with higher oxygen availability was safe for keratoconus treatment and partially prevented disease progression. Therefore, further studies with large patient cohorts and longer follow-up periods are recommended.


Transepithelial accelerated corneal collagen cross-linking Keratoconus Pulsed illumination Safety Efficacy 



This study was funded by the National Natural Science Foundation of China (Grant No. 81570879), the National Natural Science Foundation of China for Young Scholars (Grant No. 81600762). The sponsors and funding organizations had no role in the design or conduct of this research.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethical Committee of the Fudan University EENT Hospital Review Board and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Vinciguerra R, Romano MR, Camesasca FI et al (2013) Corneal cross-linking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age. Ophthalmology 120(5):908–916CrossRefGoogle Scholar
  2. 2.
    Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135(5):620–627CrossRefGoogle Scholar
  3. 3.
    Lytle G (2014) Advances in the technology of corneal cross-linking for keratoconus. Eye Contact Lens 40(6):358–364CrossRefGoogle Scholar
  4. 4.
    Wittig-Silva C, Chan E, Islam FM, Wu T, Whiting M, Snibson GR (2014) A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results. Ophthalmology 121(4):812–821CrossRefGoogle Scholar
  5. 5.
    O’Brart DP, Kwong TQ, Patel P, McDonald RJ, O’Brart NA (2013) Long-term follow-up of riboflavin/ultraviolet A (370 nm) corneal collagen cross-linking to halt the progression of keratoconus. Br J Ophthalmol 97(4):433–437CrossRefGoogle Scholar
  6. 6.
    Zamora KV, Males JJ (2009) Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea 28(4):474–476CrossRefGoogle Scholar
  7. 7.
    Koppen C, Vryghem JC, Gobin L, Tassignon MJ (2009) Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus. J Refract Surg 25(9):S819–S823CrossRefGoogle Scholar
  8. 8.
    Vinciguerra P, Randleman JB, Romano V et al (2014) Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg 30(11):746–753CrossRefGoogle Scholar
  9. 9.
    Filippello M, Stagni E, Buccoliero D, Bonfiglio V, Avitabile T (2012) Transepithelial cross-linking in keratoconus patients: confocal analysis. Optom Vis Sci 89(10):e1–e7CrossRefGoogle Scholar
  10. 10.
    Gatzioufas Z, Richoz O, Brugnoli E, Hafezi F (2013) Safety profile of high-fluence corneal collagen cross-linking for progressive keratoconus: preliminary results from a prospective cohort study. J Refract Surg 29(12):846–848CrossRefGoogle Scholar
  11. 11.
    Kanellopoulos AJ (2012) Long-term safety and efficacy follow-up of prophylactic higher fluence collagen cross-linking in high myopic laser-assisted in situ keratomileusis. Clin Ophthalmol 6:1125–1130CrossRefGoogle Scholar
  12. 12.
    Raiskup F, Spoerl E (2013) Corneal crosslinking with riboflavin and ultraviolet A. I. Principles. Ocul Surf 11(2):65–74CrossRefGoogle Scholar
  13. 13.
    Hallahan KM, Rocha K, Roy AS, Randleman JB, Stulting RD, Dupps WJ Jr (2014) Effects of corneal cross-linking on ocular response analyzer waveform-derived variables in keratoconus and postrefractive surgery ectasia. Eye Contact Lens 40(6):339–344CrossRefGoogle Scholar
  14. 14.
    Alnawaiseh M, Rosentreter A, Bohm MR, Eveslage M, Eter N, Zumhagen L (2015) Accelerated (18 mW/cm2) corneal collagen cross-linking for progressive keratoconus. Cornea 34(11):1427–1431CrossRefGoogle Scholar
  15. 15.
    Al Fayez MF, Alfayez S, Alfayez Y (2015) Transepithelial versus epithelium-off corneal collagen cross-linking for progressive keratoconus: a prospective randomized controlled trial. Cornea 34(Suppl 10):S53–S56CrossRefGoogle Scholar
  16. 16.
    Soeters N, Wisse RP, Godefrooij DA, Imhof SM, Tahzib NG (2015) Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol 159(5):821–828CrossRefGoogle Scholar
  17. 17.
    Kamaev P, Friedman MD, Sherr E, Muller D (2012) Photochemical kinetics of corneal cross-linking with riboflavin. Investig Ophthalmol Vis Sci 53(4):2360–2367CrossRefGoogle Scholar
  18. 18.
    Bowes O, Coutts S, Ismailjee A et al (2017) Pulsed light accelerated corneal collagen cross-linking: 1-year results. Cornea 36(6):e15–e16CrossRefGoogle Scholar
  19. 19.
    Bagga B, Pahuja S, Murthy S, Sangwan VS (2012) Endothelial failure after collagen cross-linking with riboflavin and UV-A: case report with literature review. Cornea 31(10):1197–1200CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Ling Sun
    • 1
  • Meng Li
    • 1
  • Xiaoyu Zhang
    • 1
  • Mi Tian
    • 1
  • Tian Han
    • 1
  • Jing Zhao
    • 1
  • Xingtao Zhou
    • 1
    Email author
  1. 1.Key Laboratory of Myopia, Ministry of Health, Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghaiChina

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