International Ophthalmology

, Volume 39, Issue 11, pp 2675–2683 | Cite as

The efficacy of standard versus accelerated epi-off corneal cross-linking protocols: a systematic review and sub-group analysis

  • Mohammad Miraftab
  • Hassan HashemiEmail author
  • Mohammad Abdollahi
  • Shekoufeh Nikfar
  • Soheila Asgari



To compare the one-year efficacy of accelerated and standard 5.4 J/cm2 protocols of cross-linking (CXL) in the treatment of progressive keratoconus.


In this systematic review, two members of the research team searched Scopus, Pubmed, ISI, Ovid, Science Direct, and Cochrane databases independently for publications between January 2010 and December 2016. The majority of retrieved studies were not randomized clinical trials (RCT), or the second arm of the RCT was either untreated or customized CXL. The outcomes of interest were uncorrected distance visual acuity, corrected visual acuity, manifest refraction spherical equivalent, maximum keratometry in the central 3 mm, minimum keratometry in the central 3 mm, and corneal thickness in the apex or thinnest point at baseline and 1 year after CXL.


Of the 453 papers found in the preliminary search, 23 papers were included in the final analysis. Analysis of variance of one-year changes showed that longer irradiation times were associated with a greater corneal flattening effect, although there was no difference in terms of improvement in vision or refraction.


In other words, efficacy is comparable among different CXL protocols, so it is recommended to use the standard method in cases where maximum flattening is expected, such as young people and severe cases.


Standard cross-linking Accelerated cross-linking Systematic review 



No funding was received for this research.

Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mohammad Miraftab
    • 1
  • Hassan Hashemi
    • 2
    Email author
  • Mohammad Abdollahi
    • 3
  • Shekoufeh Nikfar
    • 4
    • 5
  • Soheila Asgari
    • 1
  1. 1.Noor Ophthalmology Research CenterNoor Eye HospitalTehranIran
  2. 2.Noor Research Center for Ophthalmic EpidemiologyNoor Eye HospitalTehranIran
  3. 3.The Institute of Pharmaceutical Sciences (TIPS), Faculty of PharmacyTehran University of Medical SciencesTehranIran
  4. 4.Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  5. 5.The Institute of Pharmaceutical Sciences (TIPS)Tehran University of Medical SciencesTehranIran

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