Long-term database analysis of conventional and accelerated crosslinked keratoconic mid-European eyes

  • Efstathios Vounotrypidis
  • Alexis Athanasiou
  • Karsten Kortüm
  • Daniel Kook
  • Mehdi Shajari
  • Siegfried Priglinger
  • Wolfgang J. Mayer



To investigate the long-term efficacy of accelerated corneal collagen cross-linking (CXL) in a large mid-European cohort with progressive keratoconus.


Four hundred thirteen eyes of 316 patients with progressive keratoconus were enrolled and treated with conventional (group A) or accelerated (group B) CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), slit lamp, and Pentacam® examinations were performed before and 12, 24, and 36 months after surgery. Maximum and mean anterior keratometry (Kmax, Kmf), corneal topography indices, and corneal pachymetry (TCT) were examined within each group and between groups. Further subgroup analysis of mild and moderate keratoconic eyes was performed.


One hundred thirty-one eyes of 101 patients were treated in group A, 282 eyes of 215 patients in group B. (UDVA, CDVA) and Kmax improved within each group, but not statistically significantly between groups after 36 months (p = 0.081, p = 0.344, p = 0.113, respectively). Kmf remained stable in both groups. TCT decreased significantly in group A (p = 0.014), but remained stable in group B (p = 0.063). Subgroup analysis showed similar results with improvement in visual acuity and keratometry and decrease of TCT. Corneal topography indices showed no differences between the groups after 36 months, but developed differently in the subgroup analysis. No correlation was detected between the change of corneal topography indices and TCT with regard to preoperative Kmax.


In a large mid-European study population including subgroup analysis of mild and moderate keratoconus, accelerated CXL showed similar results to conventional CXL regarding keratometry, corneal topography indices, and CDVA, but further improvement of UDVA. Preoperative Kmax did not affect the postoperative course of corneal topography indices and TCT.


CXL Corneal collagen crosslinking Accelerated crosslinking Keratoconus Corneal topography 



A part of this work was presented at the 114th DOG Congress in September 2016 (Berlin) and at the XXXV ESCRS Congress in October 2017 (Lisbon).


No funding was received for this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Institutional Review Board from the Department of Ophthalmology, University Hospital, LMU Munich) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, a formal consent is not required.

Informed consent

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


  1. 1.
    Spoerl E, Huhle M, Seiler T (1998) Induction of cross-links in corneal tissue. Exp Eye Res 66:97–103. CrossRefPubMedGoogle Scholar
  2. 2.
    Hashemi H, Seyedian MA, Miraftab M, Fotouhi A, Asgari S (2013) Corneal collagen cross-linking with riboflavin and ultraviolet a irradiation for keratoconus: long-term results. Ophthalmology 120:1515–1520. CrossRefPubMedGoogle Scholar
  3. 3.
    Raiskup F, Theuring A, Pillunat LE, Spoerl E (2015) Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg 41:41–46. CrossRefPubMedGoogle Scholar
  4. 4.
    Ehmke T, Seiler TG, Fischinger I, Ripken T, Heisterkamp A, Frueh BE (2016) Comparison of corneal riboflavin gradients using dextran and HPMC solutions. J Refract Surg 32:798–802. CrossRefPubMedGoogle Scholar
  5. 5.
    Schumacher S, Oeftiger L, Mrochen M (2011) Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Invest Ophthalmol Vis Sci 52:9048–9052. CrossRefPubMedGoogle Scholar
  6. 6.
    Wernli J, Schumacher S, Spoerl E, Mrochen M (2013) The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time. Invest Ophthalmol Vis Sci 54:1176–1180. CrossRefPubMedGoogle Scholar
  7. 7.
    Tomita M, Mita M, Huseynova T (2014) Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg 40:1013–1020. CrossRefPubMedGoogle Scholar
  8. 8.
    Shetty R, Pahuja NK, Nuijts RM, Ajani A, Jayadev C, Sharma C, Nagaraja H (2015) Current protocols of corneal collagen cross-linking: visual, refractive, and tomographic outcomes. Am J Ophthalmol 160:243–249. CrossRefPubMedGoogle Scholar
  9. 9.
    Kymionis GD, Grentzelos MA, Kankariya VP, Liakopoulos DA, Portaliou DM, Tsoulnaras KI, Karavitaki AE, Pallikaris AI (2014) Safety of high-intensity corneal collagen crosslinking. J Cataract Refract Surg 40:1337–1340. CrossRefPubMedGoogle Scholar
  10. 10.
    Bozkurt E, Ozgurhan EB, Akcay BI, Kurt T, Yildirim Y, Gunaydin ZK, Demirok A (2017) Refractive, topographic, and aberrometric results at 2-year follow-up for accelerated corneal cross-link for progressive keratoconus. J Ophthalmol 2017:5714372. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Choi M, Kim J, Kim EK, Seo KY, Kim TI (2017) Comparison of the conventional Dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea 36:523–529. CrossRefPubMedGoogle Scholar
  12. 12.
    Brittingham S, Tappeiner C, Frueh BE (2014) Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes. Invest Ophthalmol Vis Sci 55:8371–8376. CrossRefPubMedGoogle Scholar
  13. 13.
    Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrosio R Jr, Guell JL, Malecaze F, Nishida K, Sangwan VS (2015) Global consensus on keratoconus and ectatic diseases. Cornea 34:359–369. CrossRefPubMedGoogle Scholar
  14. 14.
    Greenstein SA, Fry KL, Hersh PS (2011) Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. Journal of Cataract & Refractive Surgery 37: 1282–1290 DOI doi:
  15. 15.
    Krumeich JH, Daniel J, Knulle A (1998) Live-epikeratophakia for keratoconus. J Cataract Refract Surg 24:456–463CrossRefPubMedGoogle Scholar
  16. 16.
    Elbaz U, Shen C, Lichtinger A, Zauberman NA, Goldich Y, Chan CC, Slomovic AR, Rootman DS (2014) Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus—a 1-year follow-up. Cornea 33:769–773. CrossRefPubMedGoogle Scholar
  17. 17.
    Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M (2016) Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol.
  18. 18.
    Cummings AB, McQuaid R, Naughton S, Brennan E, Mrochen M (2016) Optimizing corneal cross-linking in the treatment of keratoconus: a comparison of outcomes after standard- and high-intensity protocols. Cornea 35:814–822. CrossRefPubMedGoogle Scholar
  19. 19.
    Razmjoo H, Rahgozar A, Shirani K, Abtahi SH (2015) Pentacam topographic changes after collagen cross-linking in patients with keratoconus. Adv Biomed Res 4:62. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Giacomin NT, Netto MV, Torricelli AA, Marino GK, Bechara SJ, Espindola RF, Santhiago MR (2016) Corneal collagen cross-linking in advanced keratoconus: a 4-year follow-up study. J Refract Surg 32:459–465. CrossRefPubMedGoogle Scholar
  21. 21.
    Chan TC, Chow VW, Jhanji V, Wong VW (2015) Different topographic response between mild to moderate and advanced keratoconus after accelerated collagen cross-linking. Cornea 34:922–927. CrossRefPubMedGoogle Scholar
  22. 22.
    Greenstein SA, Fry KL, Hersh PS (2011) Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg 37:1282–1290. CrossRefPubMedGoogle Scholar
  23. 23.
    Kymionis GD, Kontadakis GA, Hashemi KK (2017) Accelerated versus conventional corneal crosslinking for refractive instability: an update. Curr Opin Ophthalmol 28:343–347. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity Hospital, Ludwig-Maximilians-University MunichMunichGermany
  2. 2.Department of OphthalmologyGoethe UniversityFrankfurt am MainGermany

Personalised recommendations