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Principles of Accelerated Corneal Collagen Cross-Linking

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Management of Early Progressive Corneal Ectasia

Abstract

Prior to the advent of the corneal collagen cross-linking procedure, no conservative treatment for corneal ectasia existed, with 20% of keratoconus patients progressing to eventually require penetrating keratoplasty [1].

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References

  1. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66(1):97–103.

    Article  CAS  PubMed  Google Scholar 

  2. Seiler T, Spoerl E, Huhle M, Kamouna A. Conservative therapy of keratoconus by enhancement of collagen cross-links. Invest Ophthalmol Vis Sci. 1996;37:S1017.

    Google Scholar 

  3. Maurice DM. The structure and transparency of the cornea. J Physiol. 1957;136(2):263–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Hart RW, Farrell RA. Light scattering in the cornea. J Opt Soc Am. 1969;59(6):766–74.

    Article  CAS  PubMed  Google Scholar 

  5. Benedek GB. Theory of transparency of the eye. Appl Opt. 1971;10(3):459–73.

    Article  CAS  PubMed  Google Scholar 

  6. Twersky V. Transparency of pair-related, random distributions of small scatterers, with application to the cornea. J Opt Soc Am. 1975;65(5):524–30.

    Article  CAS  PubMed  Google Scholar 

  7. Meek KM. The cornea and sclera. Structure. Chapter 13. p. 359–96, 2008 from Collagen structure and mechanics (isbn:978-0-387-73905-2 (Print) 978-0-387-73906-9 (Online)).

    Google Scholar 

  8. Meek KM, Quantock AJ. The use of X-ray scattering techniques to determine corneal ultrastructure. Prog Retin Eye Res. 2001;20(1):95–137.

    Article  CAS  PubMed  Google Scholar 

  9. Winkler M, Chai D, Kriling S, Nien CJ, Brown DJ, Jester B, Juhasz T, Jester JV. Nonlinear optical macroscopic assessment of 3-D corneal collagen organization and axial biomechanics. Invest Ophthalmol Vis Sci. 2011;52(12):8818–27.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Pauling L, Corey RB. The structure of fibrous proteins of the collagen-gelatin group. Proc Natl Acad Sci U S A. 1951;37(5):272–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Ramachandran GN, Kartha G. Structure of collagen. Nature. 1954;174(4423):269–70.

    Article  CAS  PubMed  Google Scholar 

  12. Ramachandran GN, Kartha G. Structure of collagen. Nature. 1955;176(4482):593–5.

    Article  CAS  PubMed  Google Scholar 

  13. Baldwin SJ, Quigley AS, Clegg C, Kreplak L. Nanomechanical mapping of hydrated rat tail tendon collagen I fibrils. Biophys J. 2014;107(8):1794–801.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Aghamohammadzadeh H, Newton RH, Meek KM. X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus. Structure (London, England: 1993). 2004;12(2):249–56.

    Article  CAS  Google Scholar 

  15. Abahussin M, Hayes S, Knox Cartwright NE, Kamma-Lorger CS, Khan Y, Marshall J, Meek KM. 3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology. Invest Ophthalmol Vis Sci. 2009;50(11):5159–64.

    Article  PubMed  Google Scholar 

  16. Fraser SA, Ting YH, Mallon KS, Wendt AE, Murphy CJ, Nealey PF. Sub-micron and nanoscale feature depth modulates alignment of stromal fibroblasts and corneal epithelial cells in serum-rich and serum-free media. J Biomed Mater Res A. 2008;86(3):725–35.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Holmes DF, Gilpin CJ, Baldock C, Ziese U, Koster J, Kadler KE. Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organization. Proc Natl Acad Sci U S A. 2001;98(13):7307–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Hayes S, Kamma-Lorger CS, Boote C, Young RD, Quantock AJ, Rost A, Khatib Y, Harris J, Yagi N, Terrill N, Meek KM. The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS One. 2013;8(1):e52860.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Meek KM, Tuft SJ, Huang Y, Gill PS, Hayes S, Newton RH, Bron AJ. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005;46(6):1948–56.

    Article  PubMed  Google Scholar 

  20. Meek KM. Corneal shape supported by collagen organization. Presented at the 8th Annual CXL Congress. Geneva; Dec 2012.

    Google Scholar 

  21. Daxer A, Fratzl P. Collagen fibril orientation in the human corneal stroma and its implications in keratoconus. Invest Ophthalmol Vis Sci. 1997;38(1):121–9.

    CAS  PubMed  Google Scholar 

  22. Newton RH, Meek KM. The integration of the corneal and limbal fibrils in the human eye. Biophys J. 1998;75(5):2508–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Roberts CJ, Dupps WJ. Biomechanics of corneal ectasia and biomechanical treatments. J Cataract Refract Surg. 2014;40:991–8.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Roy AS, Dupps WJ. Patient-specific computational modeling of keratoconus progression and differential responses to collagen cross-linking. Invest Ophthalmol Vis Sci. 2011;52(12):9174–87.

    Article  Google Scholar 

  25. Scarcelli G, Besner S, Pineda R, Yun SH. Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. Invest Ophthalmol Vis Sci. 2014;55(7):4490–5.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Scarcelli G, Besne S, Pineda R, Kalout P, Yun SH. In vivo biomechanical mapping of normal and keratoconic corneas. JAMA Ophthalmol. 2015;133(4):480–2.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319.

    Article  CAS  PubMed  Google Scholar 

  28. McMonnies CW. Abnormal rubbing and keratectasia. Eye Contact Lens. 2007;33(6 Pt 1):265–71.

    Article  PubMed  Google Scholar 

  29. Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M, McMahon TT, Shin JA, Sterling JL, Wagner H, Gordon MO. Baseline findings in the collaborative longitudinal evaluation of keratoconus (CLEK) study. Invest Ophthalmol Vis Sci. 1998;39(13):2537–46.

    CAS  PubMed  Google Scholar 

  30. Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea. 2008;27(10):1109–13.

    Article  PubMed  Google Scholar 

  31. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;115(1):37–50.

    Article  PubMed  Google Scholar 

  32. Knox Cartwright NE, Tyrer JR, Marshall J. Age-related differences in the elasticity of the human cornea. Invest Ophthalmol Vis Sci. 2011;52(7):4324–9.

    Article  PubMed  Google Scholar 

  33. Malik NS, Moss SJ, Ahmed N, Furth AJ, Wall RS, Meek KM. Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta. 1992;1138(3):222–8.

    Article  CAS  PubMed  Google Scholar 

  34. Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci. 1998;39(3):644–8.

    CAS  PubMed  Google Scholar 

  35. Seiler T, Huhle S, Spoerl E, Kunath H. Manifest diabetes and keratoconus: a retrospective case-control study. Graefes Arch Clin Exp Ophthalmol. 2000;238(10):822–5.

    Article  CAS  PubMed  Google Scholar 

  36. McCall AS, Kraft S, Edelhauser HF, Lundquist RR, Bradshaw HE, Dedeic Z, Dionne MJ, Clement EM, Conrad GW. Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). Invest Ophthalmol Vis Sci. 2010;51(1):129–38.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Brummer G, Littlechild S, McCall S, Zhang Y, Conrad GW. The role of nonenzymatic glycation and carbonyls in collagen cross-linking for the treatment of keratoconus. Invest Ophthalmol Vis Sci. 2011;52(9):6363–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Zhang Y, Mao X, Schwend T, Littlechild S, Conrad GW. Resistance of corneal RFUVA–cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases. Invest Ophthalmol Vis Sci. 2013;54(2):1014–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Meek KM, Hayes S. Corneal cross-linking—a review. Ophthalmic Physiol Opt. 2013;33(2):78–93.

    Article  PubMed  Google Scholar 

  40. Spoerl E, Seiler T. Techniques for stiffening the cornea. J Refract Surg. 1999;15(6):711–3.

    CAS  PubMed  Google Scholar 

  41. Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye (Lond). 2004;18(7):718–22.

    Article  CAS  Google Scholar 

  42. Wollensak G, Spoerl E, Reber F, Pillunata L, Funk R. Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro. Ophthalmic Res. 2003;35(6):324–8.

    Article  CAS  PubMed  Google Scholar 

  43. Wollensak G, Spoerl E, Wilsch M, Seiler T. Endothelial cell damage after riboflavin-ultraviolet-A treatment in the rabbit. J Cataract Refract Surg. 2003;29(9):1786–90.

    Article  PubMed  Google Scholar 

  44. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg. 2003;29(9):1780–5.

    Article  PubMed  Google Scholar 

  45. Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA. Cornea. 2004;23(5):503–7.

    Article  PubMed  Google Scholar 

  46. Spoerl E, Wollensak G, Dittert D, Seiler T. Thermomechanical behavior of collagen-cross-linked porcine cornea. Ophthalmologica. 2004;218(2):136–40.

    Article  CAS  PubMed  Google Scholar 

  47. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004;29(1):35–40.

    Article  CAS  PubMed  Google Scholar 

  48. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620–7.

    Article  CAS  PubMed  Google Scholar 

  49. NDA 203324: (Keratoconus Approved 4/15/16) (Ectasia Approved 7/15/16).

    Google Scholar 

  50. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Bunsen R, Roscoe H. Photochemische Untersuchungen, Poggendorff’s Annalen; 1855.

    Google Scholar 

  52. Krueger RR, Ramos-Esteban JC, Kanellopoulos AJ. Staged intrastromal delivery of riboflavin with UVA cross-linking in advanced bullous keratopathy: laboratory investigation and first clinical case. J Refract Surg. 2008;24(7):S730–6.

    PubMed  Google Scholar 

  53. 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. 2014;40(6):353–7.

    Article  PubMed  Google Scholar 

  54. Jaycock PD, Lobo L, Ibrahim J, Tyrer J, Marshall J. Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery. J Cataract Refract Surg. 2005;31(1):175–84.

    Article  PubMed  Google Scholar 

  55. Ford MR, Dupps WJ, Rollins AM, Roy AS, Hu Z. Method for optical coherence elastography of the cornea. J Biomed Opt. 2011;16(1):016005.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006;32(2):279–83.

    Article  PubMed  Google Scholar 

  57. Kanellopoulos AJ, Krueger RR, Asimellis G. Cross-linking and corneal imaging advances. Biomed Res Int. 2015;2015:306439.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Kling S, Remon L, Pérez-Escudero A, Merayo-Lloves J, Marcos S. Corneal biomechanical changes after collagen cross-linking from porcine eye inflation experiments. Invest Ophthalmol Vis Sci. 2010;51(8):3961–8.

    Article  PubMed  Google Scholar 

  59. Elsheikh A, Anderson K. Comparative study of corneal strip extensometry and inflation tests. J R Soc Interface. 2005;2(3):177–85.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Pallikaris IG, Kymionis GD, Ginis HS, Kounis GA, Tsilimbaris MK. Ocular rigidity in living human eyes. Invest Ophthalmol Vis Sci. 2005;46(2):409–14.

    Article  PubMed  Google Scholar 

  61. Asejczyk-Widlicka M, Pierscionek BK. The elasticity and rigidity of the outer coats of the eye. Br J Ophthalmol. 2008;92(10):1415–8.

    Article  CAS  PubMed  Google Scholar 

  62. Jue B, Maurice DM. The mechanical properties of the rabbit and human cornea. J Biomech. 1986;19(10):847–53.

    Article  CAS  PubMed  Google Scholar 

  63. Hjortdal JO. Regional elastic performance of the human cornea. J Biomech. 1996;29(7):931–42.

    Article  CAS  PubMed  Google Scholar 

  64. Cabrera Fernández D, Niazy AM, Kurtz RM, Djotyan GP, Juhasz T. Finite element analysis applied to cornea reshaping. J Biomed Opt. 2005;10(6):064018.

    Article  PubMed  Google Scholar 

  65. Chai D, Gaster RN, Roizenblatt R, Juhasz T, Brown DJ, Jester JV. Quantitative assessment of UVA-riboflavin corneal cross-linking using nonlinear optical microscopy. Invest Ophthalmol Vis Sci. 2011;52(7):4231–8.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Kamaev P, Friedman MD, Sherr E, Muller D. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012;53(4):2360–7.

    Article  PubMed  Google Scholar 

  67. Aldahlawi NH, Hayes S, O’Brart DP, Meek KM. Standard versus accelerated riboflavin-ultraviolet corneal collagen crosslinking: resistance against enzymatic digestion. J Cataract Refract Surg. 2015;41(9):1989–96.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Aldahlawi NH, Hayes S, O’Brart DP, Akhbanbetova A, Littlechild SL, Meek KM. Enzymatic resistance of corneas crosslinked using riboflavin in conjunction with low energy, high energy, and pulsed UVA irradiation modes. Invest Ophthalmol Vis Sci. 2016;57(4):1547–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Rood-Ojalvo S, Kamaev P, Friedman M, Sherr E, Muller D. Papain digestion method for analysis of cross-linking in corneal flaps. ARVO. 2013;5280:C0199.

    Google Scholar 

  70. Verzijl N, DeGroot J, Oldehinkel E, BanK RA, Thorpe SR, Baynes JW, Bayliss MT, Bijlsma JW, Lafeber FP, Tekoppele JM. Age-related accumulation of Maillard reaction products in human articular cartilage collagen. Biochem J. 2000;350(Pt 2):381–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Zhang Y, Conrad AH, Conrad GW. Effects of ultraviolet-A and riboflavin on the interaction of collagen and proteoglycans during corneal cross-linking. J Biol Chem. 2011;286(15):13011–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Criado S, Ma’rtire D, Allegretti P, Furlong J, Bertolotti SG, La Falce E, Garcia NA. Singlet molecular oxygen generation and quenching by the antiglaucoma ophthalmic drugs, Timolol and Pindolol. Photochem Photobiol Sci. 2002;1(10):788–92.

    Article  CAS  PubMed  Google Scholar 

  73. Friedman M, Kamaev P, Eddington W, Smirnov M, Sherr E, Peterson S, Muller D. Photochemical reactions during CXL. CXL Congress. Boston; 2015.

    Google Scholar 

  74. Chace KV, Carubelli R, Nordquist RE, Rowsey JJ. Effect of oxygen free radicals on corneal collagen. Free Radic Res Commun. 1991;12–13(Pt 2):591–4.

    Article  Google Scholar 

  75. Massey V. Activation of molecular oxygen by flavins and flavoproteins. J Biol Chem. 1994;269(36):22459–62.

    CAS  PubMed  Google Scholar 

  76. Kato Y, Uchida K, Kawakishi S. Aggregation of collagen exposed to UVA in the presence of riboflavin: a plausible role of tyrosine modification. Photochem Photobiol. 1994;59(3):343–9.

    Article  CAS  PubMed  Google Scholar 

  77. Lu CY, Wang WF, Lin WZ, Han ZH, Yao SD, Lin NY. Generation and photosensitization properties of the oxidized radicals of riboflavin: a laser flash photolysis study. J Photochem Photobiol B Biol. 1999;52(1–3):111–6.

    Article  CAS  Google Scholar 

  78. Görner H. Oxygen uptake after electron transfer from amines, amino acids and ascorbic acid to triplet flavins in air-saturated aqueous solution. J Photochem Photobiol B. 2007;87(2):73–80.

    Article  PubMed  Google Scholar 

  79. Lu C, Bucher G, Sander W. Photoinduced interactions between oxidized and reduced lipoic acid and Riboflavin (Vitamin B2). Phys Chem. 2004;5:47–56.

    CAS  Google Scholar 

  80. Ahmad I, Fasihullah Q, Noor A, Ansari IA, Ali QNM. Photolysis of riboflavin in aqueous solution: a kinetic study. Int J Pharm. 2004;280(1–2):199–208.

    Article  CAS  PubMed  Google Scholar 

  81. Flavins: photochemistry and photobiology. Comprehensive Series in Photochemical and Photobiological Sciences. In: Silva E, Edwards AM, editors. Santiago: P. Universidad Catolica de Chile; Cambridge: Royal Society of Chemistry; 2006. isbn:0-85404-331-4.

    Google Scholar 

  82. Görner H. Oxygen uptake induced by electron transfer from donors to the triplet state of methylene blue and xanthene dyes in air-saturated aqueous solution. Photochem Photobiol Sci. 2008;7(3):371–6.

    Article  PubMed  Google Scholar 

  83. Ahmed S. Effect of complexing agents on the photodegradation of riboflavin in aqueous solution. PhD Thesis. Karachi: Baqai Medical University; 2009.

    Google Scholar 

  84. Kamaev P, Smirnov M, Friedman M, Sherr E, Muller M. Aggregation and photoreduction in anaerobic solutions of flavin mononucleotide. J Photochem Photobiol A Chem. 2015;310:60–5.

    Article  CAS  Google Scholar 

  85. Spikes JD, Shen HR, Kopecková P, Kopecek J. Photodynamic crosslinking of proteins. III. Kinetics of the FMN- and rose bengal-sensitized photooxidation and intermolecular crosslinking of model tyrosine-containing N-(2 hydroxypropyl) methacrylamide copolymers. Photochem Photobiol. 1999;70(2):130–7.

    Article  CAS  PubMed  Google Scholar 

  86. Silva E, Godoy J. Riboflavin sensitized photooxidation of tyrosine. Int J Vitam Nutr Res. 1994;64:253–6.

    CAS  PubMed  Google Scholar 

  87. Bastian M, Sigel H. The self-association of flavin mononucleotide (FMN (2-)) as determined by (1) H NMR shift measurements. Biophys Chem. 1997;67(1–3):27–34.

    Article  CAS  PubMed  Google Scholar 

  88. Mazzotta C, Hafezi F, Kymionis G, Caragiuli S, Jacob S, Traversi C, Barabino S, Randleman JB. In vivo confocal microscopy after corneal collagen crosslinking. Ocul Surf. 2015;13(4):298–314.

    Article  PubMed  Google Scholar 

  89. Friedman MD, Kamaev P, Smirnov M, Mrochen M, Lytle G, Muller D. Can we safely cross-link thinner corneas? Pathways for optimized CXL treatment planning. Barcelona: ESCRS; 2015.

    Google Scholar 

  90. Yam JC, Chan CW, Cheng AC. Corneal collagen cross-linking demarcation line depth assessed by Visante OCT After CXL for keratoconus and corneal ectasia. J Refract Surg. 2012;28(7):475–81.

    Article  PubMed  Google Scholar 

  91. Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Skatharoudi CA, Grentzelos MA, Tsakalis NG. Corneal stromal demarcation line depth following standard and a modified high intensity corneal cross-linking protocol. J Refract Surg. 2016;32(4):218–22.

    Article  PubMed  Google Scholar 

  92. Zygoura V, del Barrio JA, Gatzioufas Z, Saw V, Raiskup F. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol. 2015;159(1):211–2.

    Article  PubMed  Google Scholar 

  93. Fontana L, Moramarco A. Esperienze personali con CXL accelerato. UOC Oculistica ASMN-IRCCS Reggio Emilia. CXL Course, Roma; 20 settembre 2014.

    Google Scholar 

  94. Mazzotta C. In vivo corneal micro-structural analysis in accelerated corneal collagen X-linking. CXL Course, Roma; 20 Sept 2014.

    Google Scholar 

  95. Mazzotta C, Paradiso AL, Baiocchi S, Caragiuli S, Caporossi A. Qualitative investigation of corneal changes after accelerated corneal collagen cross-linking (A-CXL) by in vivo confocal microscopy and corneal OCT. J Clin Exp Ophthalmol. 2013;4:6.

    Article  Google Scholar 

  96. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  97. Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Grentzelos MA, Paraskevopoulos TA, Zacharioudaki ME, Zivkovic M, Kouroupaki AI, Tsilimbaris MK. Corneal stromal demarcation line determined with anterior segment optical coherence tomography following a very high intensity corneal collagen cross-linking protocol. Cornea. 2015;34(6):664–7.

    Article  PubMed  Google Scholar 

  98. Peyman A, Nouralishahi A, Hafezi F, Kling S, Peyman M. Stromal demarcation line in pulsed versus continuous light accelerated corneal cross-linking for keratoconus. J Refract Surg. 2016;32(3):206–8.

    Article  PubMed  Google Scholar 

  99. Mrochen M, Friedman MD, Kamaev P, Smirnov M, Lytle G, Muller D. Consistency, consistency, consistency: treatment standardization requirements for corneal cross-linking (CXL). Barcelona: ESCRS; 2015.

    Google Scholar 

  100. Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. J Cataract Refract Surg. 2010;36(1):114–20.

    Article  PubMed  Google Scholar 

  101. Ng AL, Kwok PS, Wu RT, Jhanji V, Woo VC, Chan TC. Comparison of the demarcation line on ASOCT after simultaneous LASIK and different protocols of accelerated collagen crosslinking: a bilateral eye randomized study. Cornea. 2017;36(1):74–7.

    Article  PubMed  Google Scholar 

  102. Rajpal RK, Wisecarver CB, Williams D, Rajpal SD, Kerzner R, Nianiaris N, Lytle G, Hoang K. Lasik Xtra® provides corneal stability and improved outcomes. Ophthalmol Ther. 2015;4(2):89–102.

    Article  PubMed Central  Google Scholar 

  103. Tan J, Lytle GE, Marshall J. Consecutive laser in situ keratomileusis and accelerated corneal crosslinking in highly myopic patients: preliminary results. Eur J Ophthalmol. 2014.

    Google Scholar 

  104. Mazzotta C, Balestrazzi A, Traversi C, Caragiuli S, Caporossi A. In vivo confocal microscopy report after Lasik with sequential accelerated corneal collagen cross-linking treatment. Case Rep Ophthalmol. 2014;5(1):125–31.

    Article  PubMed Central  PubMed  Google Scholar 

  105. Lee H, Kang DS, Ha BJ, Choi JY, Kim EK, Seo KY, Kim TI. Changes in posterior corneal elevations after combined transepithelial photorefractive keratectomy and accelerated corneal collagen cross-linking: retrospective, comparative observational case series. BMC Ophthalmol. 2016;16:139.

    Article  PubMed Central  PubMed  Google Scholar 

  106. Nguyen MK, Chuck RS. Corneal collagen cross-linking in the stabilization of PRK, LASIK, thermal keratoplasty, and orthokeratology. Curr Opin Ophthalmol. 2013;24(4):291–5.

    Article  PubMed  Google Scholar 

  107. Ng AL, Chan TC, Cheng GP, Jhanji V, Ye C, Woo VC, Lai JS. Comparison of the early clinical outcomes between combined small-incision lenticule extraction and collagen cross-linking versus SMILE for myopia. BMC Ophthalmol. 2016;16:139.

    Article  Google Scholar 

  108. Seven I, Sinha Roy A, Dupps WJ. Patterned corneal collagen crosslinking for astigmatism: computational modeling study. J Cataract Refract Surg. 2014;40(6):943–53.

    Article  PubMed Central  PubMed  Google Scholar 

  109. 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. 2016;2016:2031031. https://doi.org/10.1155/2016/2031031.

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Siena University, Ophthalmology Speciality School Siena University and Siena Crosslinking Center, Siena, Italy

    Cosimo Mazzotta

  2. Carl Gustav Carus University, Department of Ophthalmology Carl Gustav Carus University, Dresden, Germany

    Frederik Raiskup

  3. Siena University, Ophthalmology Speciality School Siena University, Siena, Italy

    Stefano Baiocchi & Claudio Traversi

  4. University of Maryland, Department of Bioengineering University of Maryland, College Park, Maryland, USA

    Giuliano Scarcelli

  5. Avedro, Waltham, Massachusetts, USA

    Marc D. Friedman

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  1. Cosimo Mazzotta
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  4. Giuliano Scarcelli
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  5. Marc D. Friedman
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  6. Claudio Traversi
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Mazzotta, C., Raiskup, F., Baiocchi, S., Scarcelli, G., Friedman, M.D., Traversi, C. (2017). Principles of Accelerated Corneal Collagen Cross-Linking. In: Management of Early Progressive Corneal Ectasia. Springer, Cham. https://doi.org/10.1007/978-3-319-61137-2_1

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  • DOI: https://doi.org/10.1007/978-3-319-61137-2_1

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