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Navigating the Controversies in the Treatment of Keratoconus

  • Adel Barbara
  • Paul R. Meredith
  • Ramez Barbara
Chapter

Abstract

Keratoconus significantly impacts upon the life of patients suffering from this frustrating disease. Quality of life is negatively affected at a young age, an age of learning and professional formation. The associated astigmatism, both regular and more significantly the irregular, reduces visual acuity and impairs the quality of vision.

Until two decades ago the only treatment options were rigid gas permeable contact lenses or penetrating keratoplasty. More recently deep anterior lamellar keratoplasty has been replacing penetrating keratoplasty as the treatment of choice in cases of very advanced and scarred keratoconic corneas. New innovations in contact lens design include soft contact lenses for keratoconus, hybrid lenses. Scleral-and semi-scleral contact lenses, enable more patients to wear contact lenses.

Early detection of keratoconus is enabled by the availability of various corneal topographies and tomographies. Collagen corneal cross-linking has proven to be effective in arresting keratoconus and has revolutionized the way we face keratoconus.

The cornea can be remolded by intrastromal corneal rings or photorefractive keratectomy, with or without combined collagen corneal cross-linking.

Phakic intraocular lenses, in particular toric lenses, are an additional means of improving visual acuity.

All the previously mentioned treatment approaches may be combined either simultaneously or sequentially.

Advancements in diagnosis and treatment has led to the emergence of keratoconus as a new subspecialty in ophthalmology. With so many new treatment modalities available and the potential to combine approaches it is easy for the clinician to become confused. This chapter will act as a guide in the ‘what’, ‘when’ and ‘how’ of the management of keratoconus.

Keywords

Keratoconus Ectasia Post lasik Intrastromal rings ISCR Intacs Ferrara ring Keraring Barbara ring Collagen cross linking CXL Intraocular lens Penetrating keratoplasy PKP Deep anterior lamellar keratoplasty DALK Vernal kerato-conjunctivitis Eye rubbing Photorefractive keratectomy Phototherapeutic keratectomy PRK Astigmatism Myopia Proud nudule Hydrops 

References

  1. 1.
    Parker JS, van Dijk K, Melles GRJ. Treatment options for advanced keratoconus: a review. Surv Ophthalmol. 2015;60:459–80.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Reinhart WJ, Musch DC, Jacobs DS, Lee WB, Kaufman SC, Shtein RM. Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty. Ophthalmology [Internet]. 2011 [cited 2017 Mar 19];118(1):209–18. Available from: http://www.ncbi.nlm. nih.gov/pubmed/21199711.
  3. 3.
    Henein C, Nanavaty MA. Systematic review comparing penetrating keratoplasty and deep anterior lamellar keratoplasty for management of keratoconus. Contact Lens Anterior Eye [Internet]. 2017 [cited 2017 Mar 19];40(1):3–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27802912.
  4. 4.
    Williams KA, Lowe M, Bartlett C, Kelly T-L, Coster DJ, et al. Risk factors for human corneal graft failure within the australian corneal graft registry. Transplantation [Internet]. 2008 [cited 2017 Nov 25];86(12):1720–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19104411.
  5. 5.
    Al-Mohaimeed MM. Penetrating keratoplasty for keratoconus: visual and graft survival outcomes. Int J Health Sci (Qassim) [Internet]. 2013 [cited 2016 Nov 26];7(1):67–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23559907.
  6. 6.
    Troutman RCSC. Relaxing incision for control of postoperative astigmatism following keratoplasty. Ophthalmic Surg. 1980;11:117–20.PubMedGoogle Scholar
  7. 7.
    Troutman RC, Gaster RN. Surgical advances and results of keratoconus. Am J Ophthalmol [Internet]. 1980 [cited 2017 Nov 4];90(2):131–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6999909.
  8. 8.
    Feizi S, Zare M, Feizi S, Zare M. Current approaches for management of postpenetrating keratoplasty astigmatism. J Ophthalmol [Internet]. 2011[cited 2016 Nov 26];2011:708736. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21811668.
  9. 9.
    de Toledo JA, de la Paz MF, Barraquer RI, Barraquer J. Long-term progression of astigmatism after penetrating keratoplasty for keratoconus: evidence of late recurrence. Cornea [Internet]. 2003 [cited 2017 Dec 16];22(4):317–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12792474
  10. 10.
    Patel SV, Malta JB, Banitt MR, Mian SI, Sugar A, Elner VM, et al. Recurrent ectasia in corneal grafts and outcomes of repeat keratoplasty for keratoconus. Br J Ophthalmol [Internet]. 2009 [cited 2017 Dec 16];93(2):191–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19019928.
  11. 11.
    Barbara R, Barbara A. Recurrent keratoconus. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis [Internet]. [Cited 2017 Mar 26];22(22):65–6865. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=5070&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=391&isPDF=YES.
  12. 12.
    Bergmanson JPG, Goosey JD, Patel CK, Mathew JH. Recurrence or re-emergence of keratoconus – what is the evidence telling us? Literature review and two case reports. Ocul Surf [Internet]. 2014 [cited 2017 Dec 16];12(4):267–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25284772.
  13. 13.
    Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea [Internet]. 2008 [cited 2017 Sep 22];27(10):1109–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19034122.
  14. 14.
    Pearson AR, Soneji B, Sarvananthan N, Sandford-Smith JH. Does ethnic origin influence the incidence or severity of keratoconus? Eye [Internet]. 2000 [cited 2017 Jul 12];14(4):625–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11040911.
  15. 15.
    Georgiou T, Funnell CL, Cassels-Brown A, O’Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye (Lond) [Internet]. 2004 [cited 2016 Aug 13];18(4):379–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15069434.
  16. 16.
    Slim EA, Jarade EF, Charanek BM, Antoun JS, Hemade AI, Awada SH, et al. Acute corneal hydrops mimicking infectious keratitis as initial presentation of keratoconus in a 10-year-old child. Case Rep Ophthalmol Med [Internet]. 2015 [cited 2017 Nov 4];2015:1–4. Available from: http://www.hindawi.com/journals/criopm/2015/308348/
  17. 17.
    Rehany U, Rumelt S. Corneal hydrops associated with vernal conjunctivitis as a presenting sign of keratoconus in children. Ophthalmology [Internet]. 1995 [cited 2017 Nov 4];102(12):2046–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9098316.
  18. 18.
    Kaimbo WKD. Corneal hydrops associated with vernal conjunctivitis as a presenting sign of keratoconus in a Congolese child. Bull Soc Belge Ophtalmol [Internet]. 2002. [Cited 2017 Nov 4];(283):29–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12058484.
  19. 19.
    Al Suhaibani AH, Al-Rajhi AA, Al-Motowa S, Wagoner MD. Inverse relationship between age and severity and sequelae of acute corneal hydrops associated with keratoconus. Br J Ophthalmol [Internet]. 2007 [cited 2017 Sep 22];91(7):984–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17576720.
  20. 20.
    Reeves SW, Stinnett S, Adelman RA, Afshari NA. Risk factors for progression to penetrating keratoplasty in patients with keratoconus. Am J Ophthalmol [Internet]. 2005 [cited 2017 Sep 22];140(4):607. e1-607.e6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16226512
  21. 21.
    Wagner H, Barr JT, Zadnik K, Group the CLE of K (CLEK) S. Collaborative longitudinal evaluation of keratoconus (clek) study: methods and findings to date. Cont Lens Anterior Eye [Internet]. 2007 [cited 2017 Nov 19];30(4):223–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17481941.
  22. 22.
    Chatzis N, Hafezi F. Progression of keratoconus and efficacy of corneal collagen cross-linking in children and adolescents. J Refract Surg [Internet]. 2012 [cited 2017 Jul 2];28(11):753–8. Available from: http://www.healio.com/doiresolver?doi=10.3928/1081597X-20121011-01.
  23. 23.
    Wollensak G, Spoerl EST. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–7.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cart Refract Surg. 2015;41:41–6.Google Scholar
  25. 25.
    Kumar Kodavoor S, Arsiwala AZ, Ramamurthy D. One-year clinical study on efficacy of corneal cross-linking in indian children with progressive keratoconus. Cornea [Internet]. 2014 [cited 2017 Jul 2];33(9):919–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25055145.
  26. 26.
    Bakshi E, Barkana Y, Goldich Y, Isaac Avni DZ. No titlecorneal cross-linking for progressive keratoconus in children: our experience. Int J Keratoconus Ectatic Corneal Dis. 2012;1(1):53–6.Google Scholar
  27. 27.
    Barbara R, Pikkel J, Garzozi H, Barbara A. Collagen cross-linking and keratoconus in pediatric patients. Int J Keratoconus Ectatic Corneal Dis Int J Keratoco Ectatic Corneal Dis [Internet]. [cited 2017 Mar 26]. 11(11):57–6057. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=2674&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=211&isPDF=YES.
  28. 28.
    Arora R, Gupta D, Goyal JL, Jain P. Results of corneal collagen cross-linking in pediatric patients. J Refract Surg [Internet]. 2012 [cited 2017 Sep 22];28(11):759–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23347368.
  29. 29.
    Hanna R, Berkwitz E, Jamyl Habib Castillo BT. Collagen cross-linking for the treatment of keratoconus in pediatric patients. [Cited 2017 Mar 26]; Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=8430&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=651&isPDF=YES.
  30. 30.
    Vinciguerra P, Albé E, Frueh BE, Trazza S, Epstein D. Two-year corneal cross-linking results in patients younger than 18 years with documented progressive keratoconus. Am J Ophthalmol [Internet]. 2012 [cited 2017 Sep 22];154(3):520–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22633357.
  31. 31.
    Magli A, Forte R, Tortori A, Capasso L, Marsico G, Piozzi E. Epithelium-off corneal collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. Cornea [Internet]. 2013 [cited 2017 Sep 22];32(5):597–601. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23132450.
  32. 32.
    Luca Buzzonetti MD, Gianni Petrocelli M. No title transepithelial corneal cross-linking in pediatric patients: early results. J Refract Surg. 2012;28(November):763–7.PubMedGoogle Scholar
  33. 33.
    Badawi AE. Accelerated corneal collagen cross-linking in pediatric keratoconus: one year study. Saudi J Ophthalmol Off J Saudi Ophthalmol Soc. 2017[Internet] [cited 2017 Nov 1];31(1):11–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28337057.
  34. 34.
    Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol [Internet]. [Cited 2017 Mar 19];28(4):293–322. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6230745.
  35. 35.
    Gautam V, Chaudhary M, Sharma AK, Shrestha GS, Rai PG. Topographic corneal changes in children with vernal keratoconjunctivitis: a report from Kathmandu, Nepal. Contact Lens Anterior Eye [Internet]. 2015 [cited 2017 Nov 4];38(6):461–5. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1367048415300035.
  36. 36.
    Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol [Internet]. 2000 [cited 2016 Aug 13];84(8):834–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10906086.
  37. 37.
    McMonnies CW, Boneham GC. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin Exp Optom [Internet]. 2003 [cited 2016 Aug 13];86(6):376–84. Available from: http://doi.wiley.com/10.1111/j.1444-0938.2003.tb03082.x.
  38. 38.
    Hawkes E, Nanavaty MA. Eye rubbing and keratoconus : a literature review. Int J Keratoconus Ectatic Corneal Dis. 2014;3(3):118–21.Google Scholar
  39. 39.
    Gatinel D. Eye rubbing, a sine qua non for keratoconus? Int J Keratoconus Ectatic Corneal Dis. 2016;5(1):6–12.Google Scholar
  40. 40.
    Elizabeth Hawkes MAN. Eye rubbing and keratoconus: a literature review. Cor Dis. 2014;3(3):118–21.Google Scholar
  41. 41.
    CW McMonnies. Cornea. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea. 2009;28(6):607–l.Google Scholar
  42. 42.
    McConnies CW. Eye rubbing type and prevalence including contact lens “removal-relief” rubbing. Clin Exp Optom [Internet]. 2016 [cited 2017 Sep 30];99(4):366–72. Available from http://www.ncbi.nlm.nih.gov/pubmed/27306478.
  43. 43.
    Pucci N, Novembre E, Cianferoni A, Lombardi E, Bernardini R, Caputo R, et al. Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol [Internet]. 2002 [cited 2017 Nov 8];89(3):298–303. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12269651.
  44. 44.
    Tesse R, Spadavecchia L, Fanelli P, Rizzo G, Procoli U, Brunetti L, et al. Treatment of severe vernal keratoconjunctivitis with 1% topical cyclosporine in an Italian cohort of 197 children. Pediatr Allergy Immunol [Internet]. 2010 [cited 2017 Nov 8];21(2p1):330–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19840298.
  45. 45.
    Leonardi A. Management of vernal keratoconjunctivitis. Ophthalmol Ther [Internet]. 2013 [cited 2017 Sep 30];2(2):73–88. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25135808.
  46. 46.
    Sangwan VS, Jain V, Vemuganti GK, Murthy SI. Vernal keratoconjunctivitis with limbal stem cell deficiency. Cornea [Internet]. 2011 [cited 2017 Sep 22];30(5):491–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21598432.
  47. 47.
    Cameron JA, Al-Rajhi AA, Badr IA. Corneal ectasia in vernal keratoconjunctivitis. Ophthalmology [Internet]. 1989 [cited 2017 Sep 22];96(11):1615–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2616147.
  48. 48.
    Gomes JAP, Tan D, Rapuano CJ, Belin MW, Ambrósio R, Guell JL, et al. Global consensus on keratoconus and ectatic diseases the group of panelists for the global delphi panel of keratoconus and ectatic diseases. Cornea. 2015 [Cited 2017 Jul 2];34(4):359–69. Available from: http://www.corneasociety.org/sites/default/files/global_consensus_on_keratoconus_and_ectatic.1.pdf.
  49. 49.
    Sykakis E, Karim R, Evans JR, Bunce C, Amissah-Arthur KN, Patwary S, et al. Corneal collagen cross-linking for treating keratoconus. In: Hamada S, editor. Cochrane database of systematic reviews [Internet]. Chichester: Wiley; 2015 [cited 2017 Jul 2]. p. CD010621. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25803325.
  50. 50.
    Galvis V, Tello A, Ortiz AI, Escaf LC. Patient selection for corneal collagen cross-linking: an updated review. Clin Ophthalmol [Internet]. 2017 [cited 2017 Jul 2];11:657–68. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28435217.
  51. 51.
    Wang Q, Savini G, Hoffer KJ, Xu Z, Feng Y, Wen D, et al. A comprehensive assessment of the precision and agreement of anterior corneal power measurements obtained using 8 different devices. Wedrich A, editor. PLoS One [Internet]. 2012 [cited 2017 Jul 5];7(9):e45607. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23049823.
  52. 52.
    Shetty R, Arora V, Jayadev C, Nuijts RMMA, Kumar M, Puttaiah NK, et al. Repeatability and agreement of three scheimpflug-based imaging systems for measuring anterior segment parameters in Keratoconus. Investig Ophthalmol Vis Sci. 2014;55(8):5263.Google Scholar
  53. 53.
    Mehravaran S, Asgari S, Bigdeli S, Shahnazi A, Hashemi H. Keratometry with five different techniques: a study of device repeatability and inter-device agreement. Int Ophthalmol [Internet]. 2014 [cited 2017 Jul 5];34(4):869–75. http://www.ncbi.nlm.nih.gov/pubmed/24562593.
  54. 54.
    Hashemi H, Yekta A, Khabazkhoob M. Effect of keratoconus grades on repeatability of keratometry readings: comparison of 5 devices. J Cataract Refract Surg [Internet]. 2015 [cited 2017 Jul 5];41(5):1065–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26049838.
  55. 55.
    Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006;17(4):356–60.PubMedGoogle Scholar
  56. 56.
    Raiskup F, Spoerl E. Corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Am J Ophthalmol. 2011;152(1):28–32.PubMedGoogle Scholar
  57. 57.
    Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg [Internet]. 2009 [cited 2017 Mar 3];35(4):621–4. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0886335009000625.
  58. 58.
    Kymionis G, Diakonis V, Coskunseven E, Jankov M, Yoo S, Pallikaris I. Customized pachymetric guided epithelial debridement for corneal collagen cross linking. BMC Ophthalmol. 2009;9(1):10.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35(8):1358–62.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Raiskup F, Hoyer A, Spoerl E. Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg [Internet]. 2009 [cited 2017 Jul 15];25(9):S824–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19772259.
  61. 61.
    Pollhammer M, Cursiefen C. Bacterial keratitis early after corneal crosslinking with riboflavin and ultraviolet-A. J Cataract Refract Surg. 2009;35(3):588–9.PubMedGoogle Scholar
  62. 62.
    Sharma N, Maharana P, Singh G, Titiyal JS. < i> Pseudomonas</i> keratitis after collagen crosslinking for keratoconus: case report and review of literature. J Cataract Refract Surg. 2010;36(3):517–20.PubMedGoogle Scholar
  63. 63.
    Rama P, Di Matteo F, Matuska S, Paganoni G, Spinelli A. < i> Acanthamoeba</i> keratitis with perforation after corneal crosslinking and bandage contact lens use. J Cataract Refract Surg. 2009;35(4):788–91.PubMedGoogle Scholar
  64. 64.
    Demirci G, Ozdamar A. Case of corneal perforation as a complication after uneventful cxl without Infection. Int J Keratoconus Ectatic Corneal Dis J Kerat Ect Cor Dis [Internet]. [Cited 2017 Mar 26];22(33). Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=5598&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=425&isPDF=YES.
  65. 65.
    Al-Qarni A, AlHarbi M. Herpetic keratitis after corneal collagen cross-linking with riboflavin and ultraviolet-A for keratoconus. Middle East Afr J Ophthalmol [Internet]. 2015 [cited 2017 Jul 15];22(3):389–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26180483.
  66. 66.
    Goldich Y, Uri Elbaz DSR. Anterior uveitis after collagen cross-linking for keratoconus. Int J Kerat Ect Cor Dis. 2015;4(3):110–4.Google Scholar
  67. 67.
    Kymionis GD, Grentzelos MA, Kounis GA, Diakonis VF, Limnopoulou AN, Panagopoulou SI. Combined transepithelial phototherapeutic keratectomy and corneal collagen cross-linking for progressive keratoconus. Ophthalmology [Internet]. 2012 [cited 2012 Oct 27];119(9):1777–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22683058.
  68. 68.
    Comparison of combined transepithelial phototherapeutic keratectomy and mechanical debridement during corneal cross-linking. J Refract Surg @BULLET [Internet]. 2017;[Cited 2017 May 19];33(4). Available from: https://www.healio.com/ophthalmology/journals/jrs/2017-4-33-4/%7Bb57dd521-f228-4280-9b88-5d1c1ca2ee8a%7D/comparison-of-combined-transepithelial-phototherapeutic-keratectomy-and-mechanical-debridement-during-corneal-cross-linking.pdf.
  69. 69.
    Wollensak G, Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. J Cataract Refract Surg. 2009;35(3):540–6.PubMedGoogle Scholar
  70. 70.
    Raiskup F, Hillen M. Corneal cross-linking can halt the progression of keratoconus, but what is the best approach. Int J Keratoconus Ectatic Corneal Dis. 4(2):47–51.Google Scholar
  71. 71.
    Caporossi A, Mazzotta C, Baiocchi S, Caporossi T, Paradiso AL. Transepithelial corneal collagen crosslinking for keratoconus: qualitative investigation by in vivo HRT II confocal analysis. Eur J Ophthalmol [Internet]. 2012 [cited 2012 Oct 27];22(Suppl 7):S81–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22344471.
  72. 72.
    Barbara R, Abdelaziz L, Barua A, Garzozi H, Barbara A. Collagen corneal cross-linking and the epithelium. Int J Keratoconus Ectatic Corneal Dis Ep Int J Kerat Ect Cor Dis. 11(33):179–84.Google Scholar
  73. 73.
    Lombardo M, Pucci G, Barberi R, Lombardo G. Interaction of ultraviolet light with the cornea: clinical implications for corneal crosslinking. J Cataract Refract Surg. 2015;41.Google Scholar
  74. 74.
    Leccisotti A, Islam T. Transepithelial corneal collagen cross-linking in keratoconus. J Refract Surg (Thorofare, NJ 1995). 2010;26(12):942.Google Scholar
  75. 75.
    Stojanovic A, Chen X, Jin N, Zhang T, Sten SF. Safety and efficacy of epithelium-on corneal collagen cross-linking using a multifactorial approach to achieve proper stromal riboflavin saturation. J Cataract Refract Surg. 2012;38(2):283–91.Google Scholar
  76. 76.
    Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg. 2012;283–91.Google Scholar
  77. 77.
    Cruzat A, Shukla AN, Arafat SN, Alageel S, Colon C, Chodosh J, et al. Ex vivo study of transepithelial corneal cross-linking. J Refract Surg [Internet]. 2017 [cited 2017 Mar 15];33(3):171–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28264131.
  78. 78.
    Gore DM, O’Brart D, French P, Dunsby C, Allan BD. Transepithelial riboflavin absorption in an ex vivo rabbit corneal model. Investig Opthalmology Vis Sci [Internet]. 2015 [cited 2017 Mar 18];56(8):5006. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26230765.
  79. 79.
    Kaya V, Utine CA, Yilmaz OF. Efficacy of corneal collagen cross-linking using a custom epithelial debridement technique in thin corneas: a confocal microscopy study. J Refract Surg [Internet]. 2011 [cited 2017 Mar 3];27(6):444–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21162472.
  80. 80.
    Samaras K, O’brart DP, Doutch J, Hayes S, Marshall J, Meek KM. Effect of epithelial retention and removal on riboflavin absorption in porcine corneas. J Refract Surg [Internet]. 2009 [cited 2017 Mar 3];25(9):771–5. Available from: http://www.healio.com/doiresolver?doi=10.3928/1081597X-20090813-03.
  81. 81.
    Vinciguerra P, Randleman JB, Romano V, Legrottaglie EF, Rosetta P, Camesasca FI, et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg [Internet]. 2014 [cited 2017 Mar 3];30(11):746–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25375847.
  82. 82.
    Vinciguerra P, Romano V, Rosetta P, Legrottaglie EF, Kubrak-Kisza M, Azzolini C, et al. Iontophoresis-assisted corneal collagen cross-linking with epithelial debridement: preliminary results. Biomed Res Int [Internet]. 2016 [cited 2017 Mar 3];2016:1–5. Available from: http://www.hindawi.com/journals/bmri/2016/3720517/.
  83. 83.
    Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol [Internet]. 2014 [cited 2017 Mar 3];92(1):e30–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23848196.
  84. 84.
    Cantemir A, Alexa A-I, Galan BG, Anton N, Ciuntu RE, Danielescu C, et al. Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus – 3 years follow-up study. Acta Ophthalmol [Internet]. 2017 [cited 2017 Nov 22];95(7):e649–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29110439.
  85. 85.
    Aldahlawi NH, Hayes S, O’Brart DPS, O’Brart ND, Meek KM. An investigation into corneal enzymatic resistance following epithelium-off and epithelium-on corneal cross-linking protocols. Exp Eye Res [Internet]. 2016 [cited 2017 Mar 3];153:141–51. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0014483516303529.
  86. 86.
    Buzzonetti L, Petrocelli G, Valente P, Iarossi G, Ardia R, Petroni S. Iontophoretic transepithelial corneal cross-linking to halt keratoconus in pediatric cases: 15-month follow-up. Cornea. 2015;34(5):512–5.PubMedGoogle Scholar
  87. 87.
    Gore DM, O’Brart DP, French P, Dunsby C, Allan BD, Meek KM. A comparison of different corneal iontophoresis protocols for promoting transepithelial riboflavin penetration. Investig Opthalmol Vis Sci [Internet]. 2015 [cited 2017 Mar 3];56(13):7908. Available from: http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.15-17569.
  88. 88.
    Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, et al. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Investig Opthalmol Vis Sci [Internet]. 2016 [cited 2017 Mar 18];57(2):594. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24644053.
  89. 89.
    Wernli J, Schumacher S, Spoerl E, Mrochen M, C B, S GR. The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment. Time Investig Opthalmol Vis Sci [Internet]. 2013 [cited 2017 Mar 7];54(2):1176. Available from: http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.12-11409.
  90. 90.
    Schumacher S, Oeftiger L, Mrochen M. Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Investig Opthalmol Vis Sci [Internet]. 2011 [cited 2017 Mar 7];52(12):9048. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22025568.
  91. 91.
    Lin J-T, Cheng D-C. Modeling the efficacy profiles of UV-light activated corneal collagen crosslinking. PLoS One [Internet]. 2017 [cited 2017 May 14];12(4):e0175002. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28384251.
  92. 92.
    Krueger RR, Herekar S, Spoerl E. First proposed efficacy study of high versus standard irradiance and fractionated riboflavin/ultraviolet a cross-linking with equivalent energy exposure. Eye Contact Lens Sci Clin Pract [Internet]. 2014 [cited 2017 Mar 15];40(6):353–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25365552.
  93. 93.
    Hammer A, Richoz O, Mosquera SA, Tabibian D, Hoogewoud F, Hafezi F. Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Investig Opthalmol Vis Sci [Internet]. 2014 [cited 2017 Mar 15];55(5):2881. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24677109.
  94. 94.
    Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg [Internet]. 2014 [cited 2017 Mar 7];40(6):1013–20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24857442.
  95. 95.
    Alnawaiseh M, Rosentreter A, Böhm MRR, Eveslage M, Eter N, Zumhagen L. Accelerated (18 mW/cm2) corneal collagen cross-linking for progressive keratoconus. Cornea. 2015;34(11):1427–31.PubMedGoogle Scholar
  96. 96.
    Hashemi H, Fotouhi A, Miraftab M, Bahrmandy H, Seyedian MA, Amanzadeh K, et al. Short-term comparison of accelerated and standard methods of corneal collagen crosslinking. J Cataract Refract Surg. 2015;41(3):533.PubMedGoogle Scholar
  97. 97.
    Razmjoo H, Peyman A, Rahimi A, Modrek H. Cornea collagen cross-linking for keratoconus: a comparison between accelerated and conventional methods. Adv Biomed Res [Internet]. 2017 [cited 2017 Mar 18];6(1):10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28299302.
  98. 98.
    Elbaz U, Shen C, Lichtinger A, Zauberman NA, Goldich Y, Chan CC, et al. Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus—A 1-year follow-up. Cornea [Internet]. 2014 [cited 2017 Mar 15];33(8):769–73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24937167.
  99. 99.
    Marino GK, Torricelli AAM, Giacomin N, Santhiago MR, Espindola R, Netto MV. Accelerated corneal collagen cross-linking for postoperative LASIK ectasia: two-year outcomes. J Refract Surg [Internet]. 2015 [cited 2017 Mar 15];31(6):380–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26046704.
  100. 100.
    Bozkurt E, Ozgurhan EB, Akcay BIS, Kurt T, Yildirim Y, Günaydin ZK, et al. Refractive, topographic, and aberrometric results at 2-year follow-up for accelerated corneal cross-link for progressive keratoconus. J Ophthalmol. 2017[Internet] [cited 2017 Mar 18];2017:1–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28197339.
  101. 101.
    Piñero DP, Artola A, Ruiz-Fortes P, Soto-Negro R, Pérez-Cambrodi RJ. Clinical outcomes at 1 year following corneal ectasia treatment with accelerated transepithelial cross-linking. Int J Keratoco Ectatic Corneal Dis. 2016;(3):93–6.Google Scholar
  102. 102.
    Henriquez MA, Rodríguez AM, Izquierdo L. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients. Cornea [Internet]. 2017 [cited 2017 Nov 3];36(12):1503–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28938381.
  103. 103.
    Ozgurhan EB, Kara N, Cankaya KI, Kurt T, Demirok A. Accelerated corneal cross-linking in pediatric patients with keratoconus: 24-month outcomes. J Refract Surg [Internet]. 2014 [cited 2017 Mar 18];30(12):843–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25437484.
  104. 104.
    Zhang X, Sun L, Chen Y, Li M, Tian M, Zhou X. One-year outcomes of pachymetry and epithelium thicknesses after accelerated (45 mW/cm(2)) transepithelial corneal collagen cross-linking for keratoconus patients. Sci Rep [Internet]. 2016 [cited 2017 Jul 12];6:32692. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27597655.
  105. 105.
    Kymionis GD, Tsoulnaras KI, Grentzelos MA, Liakopoulos DA, Tsakalis NG, Blazaki SV, et al. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol [Internet]. 2014 [cited 2017 Mar 3];158(4):671–5. e1. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25034113.
  106. 106.
    Brittingham S, Tappeiner C, Frueh BE. Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes. Invest Ophthalmol Vis Sci. 2014;55(12):8371–6. doi:10. Invest Ophthalmol Vis Sci [Internet]. 2014 Dec 23 [cited 2017 Mar 15];55(12):8371–6. Available from http://iovs.arvojournals.org/Article.aspx?doi=10.1167/iovs.14-15444.
  107. 107.
    Ozgurhan EB, Sezgin Akcay BI, Yildirim Y, Karatas G, Kurt T, Demirok A. Evaluation of corneal stromal demarcation line after two different protocols of accelerated corneal collagen cross-linking procedures using anterior segment optical coherence tomography and confocal microscopy. J Ophthalmol. 2014;2014:981893.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Badawi A. Corneal endothelial changes after accelerated corneal collagen cross-linking in keratoconus and postLASIK ectasia. Clin Ophthalmol [Internet]. 2016 [cited 2017 Mar 15];10:1891–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27757009.
  109. 109.
    Cingü AK, Sogutlu-Sari E, Çınar Y, Şahin M, Türkçü FM, Yüksel H, et al. Transient corneal endothelial changes following accelerated collagen cross-linking for the treatment of progressive keratoconus. Cutan Ocul Toxicol [Internet]. 2014 [cited 2017 Mar 15];33(2):127–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23859485.
  110. 110.
    Medeiros CS, Giacomin NT, Bueno RL, Ghanem RC, Moraes HV, Santhiago MR. Accelerated corneal collagen crosslinking: technique, efficacy, safety, and applications. J Cataract Refract Surg [Internet]. 2016 [cited 2017 Mar 7];42(12):1826–35. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0886335016305132.
  111. 111.
    Richoz O, Hammer A, Tabibian D, Gatzioufas Z, Hafezi F. The biomechanical effect of corneal collagen cross-linking (CXL) with riboflavin and UV-A is oxygen dependent. Transl Vis Sci Technol. 2013[Internet] [cited 2017 Mar 4];2(7):6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24349884.
  112. 112.
    Santhiago MR. Accelerated corneal cross-linking: we must acquire knowledge as fast. J Refract Surg [Internet]. 2016 [cited 2017 Mar 12];32(6):362–3. Available from: http://www.healio.com/doiresolver?doi=10.3928/1081597X-20160519-01.
  113. 113.
    Turkcu UO, Yuksel N, Novruzlu S, Yalinbas D, Bilgihan A, Bilgihan K. Protein oxidation levels after different corneal collagen cross-linking methods. Cornea [Internet]. 2016 [cited 2017 Jul 8];35(3):388–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26751992.
  114. 114.
    Yuksel N, Ozel-Turkcu U, Yalinbas D, Novruzlu S, Bilgihan A, Bilgihan K. Comparison of aqueous humor nitric oxide levels after different corneal collagen cross-linking methods. Curr Eye Res. 2016[Internet] [cited 2017 Jul 8];41(12):1539–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27216990.
  115. 115.
    Mazzotta C, Traversi C, Paradiso AL, Latronico ME, Rechichi M. Pulsed light accelerated crosslinking versus continuous light accelerated crosslinking: one-year results. J Ophthalmol [Internet]. 2014 [cited 2017 Jul 8];2014:604731. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25165576.
  116. 116.
    Mazzotta C, Traversi C, Caragiuli S, Rechichi M. Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye (Lond). 2014;28(10):1179.Google Scholar
  117. 117.
    Moramarco A, Iovieno A, Sartori A, Fontana L. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg. 2015[Internet] [cited 2017 Mar 4];41(11):2546–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26703505.
  118. 118.
    Mazzotta C, Baiocchi S, Bagaglia SA, Fruschelli M, Meduri A, Rechichi M. Accelerated 15 mW pulsed-light crosslinking to treat progressive keratoconus: Two-year clinical results. J Cataract Refract Surg. 2017[Internet] [cited 2017 Nov 4];43(8):1081–8. Available from. http://www.ncbi.nlm.nih.gov/pubmed/28917411.
  119. 119.
    Choi M, Kim J, Kim EK, Seo KY, Kim T. Comparison of the conventional dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea [Internet]. 2017 [cited 2017 Mar 18];36:523. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28230557.
  120. 120.
    Toker E, Çerman E, Özcan DÖ, Seferoğlu ÖB. Efficacy of different accelerated corneal crosslinking protocols for progressive keratoconus. J Cataract Refract Surg [Internet]. 2017 [cited 2017 Nov 2];43(8):1089–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28917412.
  121. 121.
    Yıldırım Y, Olcucu O, Gunaydin ZK, Ağca A, Ozgurhan EB, Alagoz C, et al. Comparison of accelerated corneal collagen cross-linking types for treating keratoconus. Curr Eye Res [Internet]. 2017 [Cited 2017 Jul 12];42(7):1–5. Available from: https://www.tandfonline.com/doi/full/10.1080/02713683.2017.1284241.
  122. 122.
    Greenstein SA, Fry KL, Hersh PS. In vivo biomechanical changes after corneal collagen cross-linking for keratoconus and corneal ectasia: 1-year analysis of a randomized, controlled, clinical trial. Cornea [Internet]. 2012 [cited 2017 Nov 4];31(1):21–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21993470.
  123. 123.
    Kymionis GD, Tsoulnaras KI, Grentzelos MA, Liakoppoulos DA, et al. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol [Internet]. 2014 [Cited 2017 Nov 22];158(4):671–5.e1. Available from: http://www.sciencedirect.com/science/article/pii/S0002939414003961.
  124. 124.
    Kling S, Hafezi F. Biomechanical stiffening: slow low-irradiance corneal crosslinking versus the standard Dresden protocol. J Cataract Refract Surg [Internet]. 2017 [cited 2017 Nov 2];43(7):975–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28823446.
  125. 125.
    Seiler TG, Fischinger I, Koller T, Zapp D, Frueh BE, Seiler T. Customized corneal cross-linking: one-year results. Am J Ophthalmol [Internet]. 2016 [cited 2017 May 19];166:14–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26944278.
  126. 126.
    Mazzotta C, Moramarco A, Traversi C, Baiocchi S, Iovieno A, Fontana L. Accelerated corneal collagen cross-linking using topography-guided UV-A energy emission: preliminary clinical and morphological outcomes. J Ophthalmol [Internet]. 2016 [cited 2017 May 19];2016:1–10. Available from: https://www.hindawi.com/journals/joph/2016/2031031/.
  127. 127.
    Cassagne M, Pierné K, Galiacy SD, Asfaux-Marfaing M-P, Fournié P, Malecaze F. Customized topography-guided corneal collagen cross-linking for keratoconus. J Refract Surg. 2017[Internet] [cited 2017 Nov 14];33(5):290–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28486719.
  128. 128.
    Nordström M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol [Internet]. 2017 [cited 2017 Nov 14];101(7):920–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27899371.
  129. 129.
    Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea. 2006;25(9):1057–9.PubMedGoogle Scholar
  130. 130.
    Kymionis GD, Grentzelos MA, Plaka AD, Tsoulnaras KI, Diakonis VF, Liakopoulos DA, et al. Correlation of the corneal collagen cross-linking demarcation line using confocal microscopy and anterior segment optical coherence tomography in keratoconic patients. Am J Ophthalmol [Internet]. 2014 [cited 2017 Mar 3];157(1):110–5. e1. Available from: http://linkinghub.elsevier.com/retrieve/pii/S000293941300617X.
  131. 131.
    Spadea L, Tonti E, Vingolo EM. Corneal stromal demarcation line after collagen cross-linking in corneal ectatic diseases: a review of the literature. Clin Ophthalmol [Internet]. 2016 [cited 2017 Apr 12];10:1803–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27695286.
  132. 132.
    Tian M, Ma P, Zhou W, Feng J, Mu G. Outcomes of corneal crosslinking for central and paracentral keratoconus. Medicine (Baltimore) [Internet]. 2017 [cited 2017 Mar 18];96(10):e6247. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28272223.
  133. 133.
    Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet A. I. Principles. Ocul Surf [Internet]. 2013 [cited 2017 Jul 7];11(2):65–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23583042.
  134. 134.
    Rathi VM, Mandathara PS, Dumpati S. Contact lens in keratoconus. Indian J Ophthalmol [Internet]. 2013 [cited 2017 Jun 3];61(8):410–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23925325.
  135. 135.
    Moodaley L, Liu C, Woodward EG, O’Brart D, Muir MK, Buckley R. Excimer laser superficial keratectomy for proud nebulae in keratoconus. Br J Ophthalmol [Internet]. 1994 [cited 2017 Jun 3];78(6):454–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8060928.
  136. 136.
    Jorge L, PS-Díez A. Phakic intraocular lenses in keratoconus. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis. 2015;44(33):103–6.Google Scholar
  137. 137.
    Budo C, Bartels MC, van Rij G. Implantation of Artisan toric phakic intraocular lenses for the correction of astigmatism and spherical errors in patients with keratoconus. J Refract Surg. 2005;21:218–22.PubMedGoogle Scholar
  138. 138.
    Kato N, Toda I, Hori-Komai Y, Sakai C, Arai H, Tsubota K. Phakic intraocular lens for keratoconus. Ophthalmology [Internet]. 2011 [cited 2017 Mar 26];118(3):605–5. e2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21376252.
  139. 139.
    Gupta S. Implantable contact lenses in keratoconus. Int J Keratoconus Ectatic Corneal Dis Keratoconus Int J Kerat Ect Cor Dis [Internet]. 2016;55(11):17–2017. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=9480&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=723&isPDF=YES.Google Scholar
  140. 140.
    Levy J, Pitchkhadze A, Lifshitz T. Treatment of stable keratoconus by cataract surgery with toric IOL implantation. Int J Kerat Ect Cor Dis. 2012;1(2):128–30.Google Scholar
  141. 141.
    Parikakis EA, Chatziralli IP, Peponis VG, David G, Chalkiadakis S, Mitropoulos PG. Toric intraocular lens implantation for correction of astigmatism in cataract patients with corneal ectasia. Case Rep Ophthalmol [Internet]. 2013 [cited 2017 Nov 29];4(3):219–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24348406.
  142. 142.
    Barbara A. Textbook on keratoconus, new insights. 2012.Google Scholar
  143. 143.
    Nosé W, Neves RA, Burris TE, Schanzlin DJ, Belfort Júnior R. Intrastromal corneal ring: 12-month sighted myopic eyes. J Refract Surg. 1996;12(1):20–8.PubMedGoogle Scholar
  144. 144.
    Zare MA, Hashemi H, Salari MR. Intracorneal ring segment implantation for the management of keratoconus: safety and efficacy. J Cataract Refract Surg. 2007;33(11):1886–91.PubMedGoogle Scholar
  145. 145.
    Burris TE, Ayer CT, Evensen DA, Davenport JM. Effects of intrastromal corneal ring size and thickness on corneal flattening in human eyes. Refract Surg. 1991;7(1):46–50.Google Scholar
  146. 146.
    Siganos CS, Kymionis GD, Kartakis N, Theodorakis MA, Astyrakakis N, Pallikaris IG. Management of keratoconus with Intacs. Am J Ophthalmol. 2003;135(1):64–70.PubMedGoogle Scholar
  147. 147.
    Colin JVS. Implantation of Intacs and a refractive intraocular lens to correct keratoconus. J Cataract Refract Surg. 2003;29:832–4.PubMedGoogle Scholar
  148. 148.
    Colin J. European clinical evaluation: use of Intacs prescription inserts for the treatment of keratoconus. J Cataract Refract Surg. 2006;32:747–55.PubMedGoogle Scholar
  149. 149.
    Kymionis GD, Bouzoukis DI, Portaliou DMPI. New Intacs SK implantation in patients with post-laser in situ keratomileusis corneal ectasia. Cornea. 2010;29(2):214–6.PubMedGoogle Scholar
  150. 150.
    Shetty R, Narayana KM, Mathew K, Anand D, Mhaske P, Shetty B. Safety and efficacy of Intacs in Indian eyes with keratoconus: an initial report. Indian J Ophthalmol. 2009;57(2):115–9.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Salgado-Borges JM, Costa-Ferreira C, Monteiro M, Guilherme-Monteiro J, Torquetti L, Ferrara P, et al. Refractive, tomographic and biomechanical outcomes after implantation of ferrara ICRS in keratoconus patients.Google Scholar
  152. 152.
    Siganos D, Ferrara P, Chatzinikolas K, Bessis N, Papastergiou G. Ferrara intrastromal corneal rings for the correction of keratoconus. J Cataract Refract Surg. 2002;28(11):1947–51.PubMedGoogle Scholar
  153. 153.
    Peris-Martinez C, Menezo Rozalen JL. Keratoconic corneas after ferrara rings implantation: histopathological findings. Acta Ophthalmol. 2008;86:0.Google Scholar
  154. 154.
    Barbara A, Barbara R. Long-term follow-up of ferrara rings segments for the treatment of keratoconus. Int J Kerat Ect Cor Dis [Internet]. 2013 [cited 2017 Dec 13];2(1):34–9. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=4549&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=354&isPDF=YES.
  155. 155.
    El Dib RP, de Freitas D. A systematic review of Ferrara’s ring in the treatment of keratoconus. J Refract Surg. (Thorofare, NJ 1995. 2008;24(9):865.PubMedGoogle Scholar
  156. 156.
    Leonardo Torquetti J, Torquetti L, Ferrara G, Ferrara P. Predictors of clinical outcomes after intrastromal corneal ring segments implantation. Int J Keratoco Ectatic Corneal Dis. 2012;1(1):26–30.Google Scholar
  157. 157.
    Coskunseven E, Kymionis GD, Tsiklis NS, Atun S, Arslan E, Jankov MR, et al. One-year results of intrastromal corneal ring segment implantation (KeraRing) using femtosecond laser in patients with keratoconus. Am J Ophthalmol. 2008;145(5):775.PubMedGoogle Scholar
  158. 158.
    Daxer B, Mahmood H, Daxer A. MyoRing treatment for keratoconus: DIOPTEX PocketMaker vs Ziemer LDV for corneal pocket creation. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis. 11(33):151–2.Google Scholar
  159. 159.
    Daxer A. MyoRing treatment of keratoconus. Int J Kerat Ect Cor Dis. 2015;4(2):76–83.Google Scholar
  160. 160.
    Daxer A. Corneal thickness after myoring implantation for keratoconus. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis. 2014;33(11):15–9.Google Scholar
  161. 161.
    Daxer A. MyoRing for central and noncentral keratoconus. Int J Keratoconus Ectatic Corneal Dis Noncentral Keratoconus Int J Kerat Ect Cor Dis [Internet]. 2012 [Cited 2017 Apr 10];11(22):117–9. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=3338&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=258&isPDF=YES.
  162. 162.
    Ys R. Intacs for keratoconus. Ophthalmol Clin. 2006;46(3):91–103.Google Scholar
  163. 163.
    Brenner LF, Alió JL, Vega-Estrada A, Baviera J, Beltrán J, Cobo-Soriano R. Indications for intrastromal corneal ring segments in ectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2012;38:2117.PubMedGoogle Scholar
  164. 164.
    Suiter BG, Twa MD, Ruckhofer JSD. A comparison of visual acuity, predictability, and visual function outcomes after intracorneal ring segments and laser in situ keratomileusis. Trans Am Ophthalmol Soc. 2000;98:51–5.PubMedPubMedCentralGoogle Scholar
  165. 165.
    Carrasquillo KG, Rand J, Talamo J. Intacs for keratoconus and post-LASIK ectasia: mechanical versus femtosecond laser-assisted channel creation. Cornea. 2007;26(9):956–62.PubMedGoogle Scholar
  166. 166.
    Sharma M, Boxer WBS, et al. Comparison of single-segment and double-segment Intacs for keratoconus and post-LASIK ectasia. Am J Ophthalmol. 2006;141(5):891–5.PubMedGoogle Scholar
  167. 167.
    Tan BU, Purcell TL, Torres LF, Schanzlin DJ. New surgical approaches to the management of keratoconus and post-LASIK ectasia. Trans Am Ophthalmol Soc. 2006;104:212.PubMedPubMedCentralGoogle Scholar
  168. 168.
    Kymionis GD, Siganos CS, Kounis G, Astyrakakis N, Kalyvianaki MI, Pallikaris IG. Management of post-LASIK corneal ectasia with Intacs inserts: one-year results. Arch Ophthalmol. 2003;121(3):322.PubMedGoogle Scholar
  169. 169.
    Kymionis GD, Tsiklis NS, Pallikaris AI, Kounis G, Diakonis VF, Astyrakakis N, et al. Long-term follow-up of Intacs for post-LASIK corneal ectasia. Ophthalmology. 2006;113:1909–17.PubMedGoogle Scholar
  170. 170.
    Ramez Barbara J, Barbara R, Zadok D, Pikkel J, Marcovich A, Garzozi H, et al. Collagen corneal cross-linking followed by intac implantation in a case of post-PRK ectasia. Int J Keratoco Ectatic Corneal Dis [Internet]. 2012 [cited 2017 Mar 26];1(1):68–72. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=2677&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=211&isPDF=YES.
  171. 171.
    Barbara A, Shehadeh-Masha’our R, Zvi F, Garzozi H. Management of pellucid marginal degeneration with intracorneal ring segments. J Refract Surg. 2005;21:296–8.PubMedGoogle Scholar
  172. 172.
    Ruckhofer J, Stoiber J, Twa MD, Grabner G. Correction of astigmatism with short arc-length intrastromal corneal ring segments: preliminary results. Ophthalmology. 2003;110(3):516–24.PubMedGoogle Scholar
  173. 173.
    Rodríguez LA, Guillén PB, Benavides MA, Garcia L, Porras D, Daqui-Garay RM. Penetrating keratoplasty versus intrastromal corneal ring segments to correct bilateral corneal ectasia: preliminary study. J Cataract Refract Surg. 2007;33(3):488–96.PubMedGoogle Scholar
  174. 174.
    Barbara R, Barbara A. Intrastromal corneal ring segments with and without collagen corneal crosslinking vs penetrating keratoplasty for the treatment of keratoconus. Int J Kerat Ect Cor Dis [Internet]. 2014 [cited 2017 Mar 26];3(2):88–94. Available from: http://www.jaypeejournals.com/ejournals/ShowText.aspx?ID=6724&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=506&isPDF=YES.
  175. 175.
    Dauwe C, Touboul D, Roberts CJ, Mahmoud AM, Kérautret J, Fournier P, et al. Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus. J Cataract Refract Surg. 2009;35(10):1761–7.PubMedPubMedCentralGoogle Scholar
  176. 176.
    Barbara R, Garzozi H, Barbara A. Combined intacs SK and collagen corneal crosslinking for the treatment of keratoconus. Int J Keratoconus Ectatic Corneal Dis pages. 2012;1(2):109–16.Google Scholar
  177. 177.
    Coskunseven E, Jankov MR, Hafezi F, Atun S, Arslan E, Kymionis GD. Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg. 2009;35(12):2084–91.PubMedGoogle Scholar
  178. 178.
    Ertan A, Karacal H, Kamburoğlu G. Refractive and topographic results of transepithelial cross-linking treatment in eyes with intacs. Cornea [Internet]. 2009;28(7):719–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19574920.
  179. 179.
    Nicula C, Pop RN, Nicula D V. Comparative results in a combined procedure of intrastromal corneal rings implantation and cross-linking in patients with keratoconus: a retrospective study. Ophthalmol Ther [Internet]. 2017 [Cited 2017 Nov 4];313–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29086187.
  180. 180.
    Alió JL, Vega-Estrada A, Sanz-Díez P, Peña-García P, Durán-García ML, Maldonado M. Keratoconus management guidelines. Int J Keratoconus Ectatic Corneal Dis. 2015;4(1):1–39.Google Scholar
  181. 181.
    Piñero DP, Alio JL. Intracorneal ring segments in ectatic corneal disease – a review. Clin Exp Ophthalmol. 2010;38(2):154–67.PubMedGoogle Scholar
  182. 182.
    Intrastromal corneal ring segments in children with keratoconus. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis [Internet]. 2017;66(22):45–8. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=13121&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=1022&Value=26&isPDF=YESGoogle Scholar
  183. 183.
    Al-Tuwairqi W, Sinjab MM. Intracorneal ring segments implantation followed by same-day topography-guided PRK and corneal collagen CXL in low to moderate keratoconus. J Refract Surg. 2013;29(1):59–63.PubMedGoogle Scholar
  184. 184.
    Coskunseven E, Jankov MR, Grentzelos MA, Plaka AD, Limnopoulou AN, Kymionis GD. Topography-guided transepithelial PRK after intracorneal ring segments implantation and corneal collagen CXL in a three-step procedure for keratoconus. J Refract Surg. 2013;29(1):54–8.PubMedGoogle Scholar
  185. 185.
    Al-Tuwairqi W, Sinjab MM. Intracorneal ring segments implantation followed by same-day Topography-guided PRK and corneal collagen CXL in low to moderate keratoconus. J Refract Surg [Internet]. 2013 [cited 2016 Aug 13];29(1):59–64. Available from: http://www.healio.com/doiresolver?doi=10.3928/1081597X-20121228-04.
  186. 186.
    Adel Barbara RB. How to improve visual acuity after intrastromal corneal ring segments? implantation for keratoconus and post-LASIK ectasia. Int J Keratoconus Ectatic Corneal Dis Int J Kerat Ect Cor Dis [Internet]. [Cited 2017 Mar 26];33(22):69–75. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=6721&Type=FREE&TYP=TOP&IN=~/eJournals/images/JPLOGO.gif&IID=506&isPDF=YES.
  187. 187.
    El-Raggal TM, Abdel Fattah AA. Sequential intacs and verisyse phakic intraocular lens for refractive improvement in keratoconic eyes. J Cataract Refract Surg. 2007;33(6):966–70.PubMedGoogle Scholar
  188. 188.
    Kamburoglu G, Ertan A, Bahadir M. Implantation of Artisan toric phakic intraocular lens following intacs in a patient with keratoconus. J Cataract Refract Surg. 2007;33:528–30.PubMedGoogle Scholar
  189. 189.
    Moshirfar MF, Carlton R, Meyer JJ, Neuffer MC, Espandar L, Mifflin M. Simultaneous and sequential implantation of intacs and verisyse phakic intraocular lens for refractive improvement in keratectasia. Cornea. 2011;30(2):158–63.PubMedGoogle Scholar
  190. 190.
    Özertürk Y, Sari ES, Kubaloglu A, Koytak A, Piñero D, Akyol S, et al. J Cataract Refract Surg [Internet]. 2012 [cited 2017 Nov 5];38(2):324–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22322167.
  191. 191.
    Lisa C, García-Fernández M, Madrid-Costa D, Torquetti L, Merayo-Lloves J, Alfonso JF. Femtosecond laser–assisted intrastromal corneal ring segment implantation for high astigmatism correction after penetrating keratoplasty. J Cataract Refract Surg [Internet]. 2013 [cited 2016 Nov 26];39(11):1660–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0886335013008742.
  192. 192.
    Arantes JCD, Coscarelli S, Ferrara P, Araújo LPN, Ávila M, Torquetti L. Intrastromal corneal ring segments for astigmatism correction after deep anterior lamellar keratoplasty. J Ophthalmol [Internet]. 2017 [cited 2017 Nov 4];2017:8689017. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28951784.
  193. 193.
    Arriola-Villalobos P, Díaz-Valle D, Güell JL, Iradier-Urrutia MT, Jiménez-Alfaro I, Cuiña-Sardiña R, et al. Intrastromal corneal ring segment implantation for high astigmatism after penetrating keratoplasty. J Cataract Refract Surg [Internet]. 2009 [cited 2016 Nov 26];35(11):1878–84. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0886335009007652.
  194. 194.
    Coscarelli S, Ferrara G, Alfonso JF, Ferrara P, Merayo-Lloves J, Araújo LPN, et al. Intrastromal corneal ring segment implantation to correct astigmatism after penetrating keratoplasty. J Cataract Refract Surg [Internet]. 2012 [cited 2016 Nov 26];38(6):1006–13. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0886335012003690.
  195. 195.
    Coskunseven E, Kymionis GD, Tsiklis NS, Atun S, Arslan E, Siganos CS, et al. Complications of intrastromal corneal ring segment implantation using a femtosecond laser for channel creation: a survey of 850 eyes with keratoconus. Acta Ophthalmol [Internet]. 2011 [cited 2017 Nov 4];89(1):54–7. Available from http://www.ncbi.nlm.nih.gov/pubmed/19681760.
  196. 196.
    Barbara A, Barbara R. Intacs intracorneal ring segments complications in patients suffering from keratoconus. Int J Keratoconus Ectatic Corneal Dis J Kerat Ect Cor Dis. 22(33):121–8.Google Scholar
  197. 197.
    Sadigh AL, Aali TA, Sadeghi A. Outcome of intrastromal corneal ring segment relative to depth of insertion evaluated with scheimpflug image. J Curr Ophthalmol [Internet]. 2016 [cited 2017 Nov 5];27:25–31. Available from: www.sciencedirect.com.
  198. 198.
    Barbara R, Barbara A, Naftali M. Depth evaluation of intended vs actual intacs intrastromal ring segments using optical coherence tomography. Eye [Internet]. 2016 [cited 2017 Nov 5];30(1):102–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26493037.
  199. 199.
    Gorgun E, Kucumen RB, Yenerel NM, Ciftci F. Assessment of intrastromal corneal ring segment position with anterior segment optical coherence tomography. Ophthal Surg Lasers Imaging [Internet]. 2012 [cited 2017 Dec 15];43(3):214–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22390964.
  200. 200.
    Kouassi FX, Buestel C, Raman B, Melinte D, Touboul D, Gallois A, et al. Comparison of the depth predictability of intra corneal ring segment implantation by mechanical versus femtosecond laser-assisted techniques using optical coherence tomography (OCT Visante ({\textregistered})). J Fr Ophtalmol. 2011;94–9.Google Scholar
  201. 201.
    Kubaloglu A, Sari ES, Cinar Y, Cingu K, Koytak A, Coşkun E, et al. Comparison of mechanical and femtosecond laser tunnel creation for intrastromal corneal ring segment implantation in keratoconus: prospective randomized clinical trial. J Cataract Refract Surg [Internet]. 2010 [cited 2017 Dec 15];36(9):1556–61. Available from: http://www.sciencedirect.com/science/article/pii/S0886335010008497.
  202. 202.
    Torquetti L, Sandes J, Ferrara G, Ferrara P. Ferrara intrastromal corneal ring segments. Barbara A, editor. Int J Keratoconus Ectatic Corneal Dis [Internet]. 2016 [cited 2017 Mar 26];5(3):114–27. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=10529&Type=FREE&TYP=TOP&IN=~/eJournals/images/JPLOGO.gif&IID=807&isPDF=YES.
  203. 203.
    Bedi R, Touboul D, Pinsard L, Colin J. Refractive and topographic stability of intacs in eyes with progressive keratoconus: five-year follow-up. J Refract Surg [Internet]. 2012 [cited 2017 Dec 15];28(6):392–6. Available from: http://www.healio.com/doiresolver?doi=10.3928/1081597X-20120509-01.
  204. 204.
    Fernández-Vega Cueto L, Lisa C, Madrid-Costa D, Merayo-Lloves J, Alfonso JF. Long-term follow-up of intrastromal corneal ring segments in paracentral keratoconus with coincident corneal keratometric, comatic, and refractive axes: stability of the procedure. J Ophthalmol [Internet]. 2017 [cited 2017 Dec 15];2017:4058026. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28948045.
  205. 205.
    Vega-Estrada A, Alió JL, Plaza-Puche AB. Keratoconus progression after intrastromal corneal ring segment implantation in young patients: five-year follow-up. J Cataract Refract Surg [Internet]. 2015 [cited 2017 Sep 20];41(6):1145–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26189375.
  206. 206.
    Mortensen J, Ohrstrom A. Excimer laser photorefractive keratectomy for treatment of keratoconus. J Refract Surg. 1994;10:368–74.Google Scholar
  207. 207.
    Mortensen J, Carlsson K, Öhrstrom A. Excimer laser surgery for keratoconus. J Cataract Refract Surg. 1998;24(7):893–8.PubMedGoogle Scholar
  208. 208.
    Tambe DS, Ivarsen A, Hjortdal J. Photorefractive keratectomy in keratoconus. Case Rep Ophthalmol [Internet]. 2015 [cited 2017 Mar 26];6(2):260–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26327912.
  209. 209.
    Koller T, Iseli HP, Donitzky C, Papadopoulos N, Seiler T, et al. Topography-guided surface ablation for forme fruste keratoconus. Ophthalmology. 2006;113(12):2198–202.PubMedGoogle Scholar
  210. 210.
    Alpins N, Stamatelatos G. Customized photoastigmatic refractive keratectomy using combined topographic and refractive data for myopia and astigmatism in eyes with forme fruste and mild keratoconus. J Cataract Refract Surg. 2007;33(4):591–602.PubMedGoogle Scholar
  211. 211.
    Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M, et al. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg. 2009;25(9):807.Google Scholar
  212. 212.
    Kanellopoulos AJ. Short and long term complications of combined topography guided PRK and CXL (the Athens Protocol) in 412 keratoconus eyes (2–7 years follow-up). Investigative Ophth & Vis Sci. 2011;52:5202.Google Scholar
  213. 213.
    Kankariya V, Kymionis G, Kontadakis G, Yoo S. Update on simultaneous topo-guided photorefractive keratectomy immediately followed by corneal collagen cross-linking for treatment of progressive keratoconus. Int J Keratoconus Ectatic Corneal Dis Ect Cor Dis. 11(33).Google Scholar
  214. 214.
    Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg [Internet]. 2009 [cited 2017 May 19];25(9):S812–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19772257.
  215. 215.
    Siqueira JA, Dias LC, Siqueira R, Valbon B, Santos R, Dawson D, et al. Long-term improvement after the athens protocol for advanced keratoconus with significant ectasia progression in the fellow eye long- term improvement after the athens protocol for advanced keratoconus with significant ectasia progression in the fellow. Int J Keratoconus Ectatic Corneal Dis Eye J Kerat Ect Cor Dis [Internet]. [cited 2017 Mar 26];22(33):1025–68. Available from: http://www.jaypeejournals.com/eJournals/ShowText.aspx?ID=5599&Type=FREE&TYP=TOP&IN=_eJournals/images/JPLOGO.gif&IID=425&isPDF=YES.
  216. 216.
    Shah S, Mohan S, Rajan M, John B, Badlani V. Our experience with Athens protocol -simultaneous topo-guided photorefractive keratectomy followed by corneal collagen cross linking for keratoconus. Int J Res Med Sci Int J Res Med Sci Shah S Int J Res Med Sci [Internet]. 2016 [cited 2017 May 19];44(77):2639–44. Available from: www.msjonline.org.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Adel Barbara
    • 1
  • Paul R. Meredith
    • 2
  • Ramez Barbara
    • 2
  1. 1.Medical Director of IVISION, Refractive Surgery and Keratoconus Treatment CenterHaifaIsrael
  2. 2.Southampton Eye Unit, Southampton General HospitalSouthamptonUK

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