The Athens Protocol: Perform a Partial Topography-Guided Normalization Treatment Separate or Together with Corneal Cross-Linking? Cross-Linking and PRK: Sequential Versus Combined Strategy

  • A. John Kanellopoulos


Corneal cross-linking (CXL) has established a new paradigm for the treatment of progressive ectasia and keratoconus [1–3]. The visual rehabilitation of patients who achieve stability after CXL can be challenging if they were intolerant of rigid gas permeable contact lenses or if they had poor vision with glasses and/or soft contact lenses prior to treatment. The problem led my colleagues and me to introduce the topography-guided normalization of corneas that remain highly irregular despite some flattening effect from CXL [4, 5].


Financial Disclosure

Consultant for Alcon, Avedro, Allergan, i-Optics, Keramed, Zeiss, ISP Surgical.


  1. 1.
    Kanellopoulos AJ. Post-LASIK ectasia. Ophthalmology. 2007;114(6):1230.CrossRefGoogle Scholar
  2. 2.
    Hafezi F, Kanellopoulos AJ, Wiltfang R, Seiler T. Corneal collagen crosslinking with riboflavin and ultraviolet A to treat induced keratectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2007;33:2035–40.CrossRefGoogle Scholar
  3. 3.
    Krueger RP, Kanellopoulos AJ. Stability of simultaneous topography-guided photorefractive keratectomy and riboflavin/UVA cross-linking for progressive keratoconus: case reports. J Refract Surg. 2010;26(10):S827–32.CrossRefGoogle Scholar
  4. 4.
    Kanellopoulos AJ, Asimellis G. OCT corneal epithelial topographic asymmetry as a sensitive diagnostic tool for early and advancing keratoconus. Clin Ophthalmol. 2014;8:2277–87.CrossRefGoogle Scholar
  5. 5.
    Kanellopoulos AJ, Asimellis G. OCT- derived comparison of corneal thickness distribution and asymmetry differences between normal and keratoconic eyes. Cornea. 2014;33(12):1274–81.CrossRefGoogle Scholar
  6. 6.
    Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg. 2009;25(9):S812–8.CrossRefGoogle Scholar
  7. 7.
    Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014;30(2):88–92.CrossRefGoogle Scholar
  8. 8.
    Kanellopoulos AJ. Sequential versus simultaneous CXL and topography-guided PRK. Cover story – cataract & refractive surgery today Europe. 2009.Google Scholar
  9. 9.
    Kanellopoulos AJ, Asimellis G. Comparison of Placido disc and Scheimpflug image derived topography-guided excimer laser surface normalization combined with higher fluence CXL: the Athens Protocol, in progressive keratoconus. Clin Ophthalmol. 2013;7:1385–96.CrossRefGoogle Scholar
  10. 10.
    Kanellopoulos AJ, Asimellis G. Epithelial remodelling after partial topography-guided normalization and high-fluence short-duration crosslinking (Athens Protocol); results up to 1 year. J Cataract Refract Surg. 2014;40:1597–602.CrossRefGoogle Scholar
  11. 11.
    Kanellopoulos AJ. Long-term results of a prospective randomized bilateral eye comparison trial of higher fluence, shorter duration ultraviolet A radiation, and riboflavin collagen cross linking for progressive keratoconus. Clin Ophthalmol. 2012;6:97–101.CrossRefGoogle Scholar
  12. 12.
    Kanellopoulos AJ, Pamel GJ. Review of current indications for combined very high fluence collagen cross-linking and laser in situ keratomileusis surgery. Indian J Ophthalmol. 2013;61(8):430–2.CrossRefGoogle Scholar
  13. 13.
    Kanellopoulos AJ, Moustou V, Asimellis G. Evaluation of visual acuity, pachymetry and anterior-surface irregularity in keratoconus and crosslinking intervention follow-up in 737 cases. J Kerat Ect Cor Dis. 2013;2(3):95–103.Google Scholar
  14. 14.
    Kanellopoulos AJ, Loukas YL, Asimellis G. Cross-linking biomechanical effect in human corneas by same energy, different UV-A fluence: an enzymatic digestion comparative evaluation. Cornea. 2016;35(4):557–61.CrossRefGoogle Scholar
  15. 15.
    Kanellopoulos AJ, Skouteris V. Secondary ectasia due to forceps injury at childbirth: management with combined topography-guided partial PRK and collagen cross-linking (Athens Protocol) and subsequent phakic IOL implantation. J Refract Surg. 2011;27(9):635–6.CrossRefGoogle Scholar
  16. 16.
    Kanellopoulos AJ, Perry S. Binder: management of corneal ectasia after LASIK with combined, same –day, topography-guided partial transepithelial PRK and collagen cross-linking: the Athens Protocol. J Refract Surg. 2011;27(5):323–31.CrossRefGoogle Scholar
  17. 17.
    Kanellopoulos AJ, Khan J. Topography-guided hyperopic LASIK with and without high irradiance collagen cross-linking: initial comparative clinical findings in a contralateral eye study of 34 consecutive patients. J Refract Surg. 2012;28(11 Suppl):S837–40.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • A. John Kanellopoulos
    • 1
    • 2
  1. Eye InstituteAthensGreece
  2. 2.New York University School of MedicineNew YorkUSA

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