Customized Corneal Cross-Linking

  • Cosimo Mazzotta
  • Miguel Rechichi
  • Marco Ferrise


Personalized accelerated crosslinking nomograms for the management of corneal ectasia were conceived after comparative analysis of demarcation lines and cell viability observed after customized accelerated epithelium-off crosslinking CXL treatments by spectral domain corneal OCT and scanning laser in vivo confocal microscopy matching all the clinical and instrumental data with mathematical models. Accelerated high-fluence Topography-guided CXL at 30 mW/cm2 UV-Power and Accelerated epithelium-off CXL with 9 and 15 mW/cm2 UV-A power with standardized Fluence of 5.4 J/cm2 were safe and effective demostrating a keratocytes apoptosis and demarcation line depth between 280 and 340 μm. The 30 mW ACXL showed a penetration with continuous and pulsed light between 150 and 200 μm. No endothelial damage was reported in any case. In vivo morphological studies demonstrated that Accelerated CXL allow a pachymetry-guided cutomization of CXL maintainig the standard Fluence of 5.4 J/cm2 and a total treatment time under 20 min. Moreover a pachymetry-guided ACXL nomogram (M nomogram) developed by Mazzotta C and Friedman M matching the physical and mathematical calculations with the miscostructural IVCM and OCT observations of demarcation lines depths allow an efficacous CXL management of primary and iatrogenic ectatic corneas also allowing a safe management of thin ectatic corneas.


Accelerated crosslinking Pachymetry-guided CXL Customized CXL Customized crosslinking nomogram M nomogram 


  1. 1.
    Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297–319.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Godefrooij DA, de Wit GA, Uiterwaal CS, et al. Age-specific incidence and prevalence of keratoconus: a nationwide registration study. Am J Ophthalmol. 2017;175:169–72.Google Scholar
  3. 3.
    Ambrosio R Jr, Klyce SD, Wilson SE. Corneal topographic and pachymetric screening of keratorefractive patients. J Refract Surg. 2003;19:24–9.PubMedGoogle Scholar
  4. 4.
    Pearson AR, Soneji B, et al. Does ethnic origin influence the incidence or severity of keratoconus? Eye (Lond). 2000;14:625–8.Google Scholar
  5. 5.
    Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric corneal collagen cross-linking in children and adolescents. J Refract Surg (Thorofare, N.J.: 1995). 2012;28:753–8. Scholar
  6. 6.
    Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol. 2010;149(4):585–93.Google Scholar
  7. 7.
    Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35(8):1358–62.Google Scholar
  8. 8.
    Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A–induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–7.Google Scholar
  9. 9.
    Roberts CJ, Dupps WJ Jr. Biomechanics of corneal ectasia and biomechanical treatments. J Cataract Refract Surg. 2014;40(6):991–8.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Roy AS, Dupps WJ Jr. Patient-specific computational modeling of keratoconus progression and differential responses to collagen cross-linking. Invest Ophthalmol Vis Sci. 2011;52:9174–87.Google Scholar
  11. 11.
    Nordström M, Schiller M, Fredriksson A, et al. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol. 2017;101:920–5.PubMedGoogle Scholar
  12. 12.
    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; Article ID 2031031. 10 pages.Google Scholar
  13. 13.
    Meek KM, Hayes S. Corneal cross-linking—a review. Ophthalmic Physiol Opt. 2013;33:78–93.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Vinciguerra P, Albe E, Trazza S, et al. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology. 2009;116:369–78.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Kanellopoulos AJ. Novel myopic refractive correction with transepithelial very high-fl uence collagen cross-linking applied in a customized pattern: early clinical results of a feasibility study. Clin Ophthalmol. 2014;8:697–702.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, Wong TY, Naduvilath TJ, Resnikoff S. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123:1036–42.PubMedGoogle Scholar
  17. 17.
    Kanellopoulos AJ, Dupps WJ, Seven I, Asimellis G. Toric topographically customized transepithelial, pulsed, very high-fl uence, higher energy and higher riboflavin concentration collagen cross-linking in keratoconus. Case Rep Ophthalmol. 2014;5(2):172–80.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kanellopoulos AJ, Asimellis G. Hyperopic correction: clinical validation with epithelium-on and epithelium-off protocols, using variable fl uence and topographically customized collagen corneal crosslinking. Clin Ophthalmol. 2014;8:2425–33.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Kanellopoulos J, Asimellis G. Presbyopic PiXL crosslinking. Curr Ophthalmol Rep. 2015. Scholar
  20. 20.
    Nawaz S, Gupta S, Gogia V, Sasikala NK, Panda A. Trans-epithelial versus Conventional corneal collagen cross-linking: a randomized trial in keratoconus. Oman J Ophthalmol. 2015;8(1):9–13.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S, Yun SH. Brillouin microscopy of collagen crosslinking: noncontact depth-dependent analysis of corneal elastic modulus. Invest Ophthalmol Vis Sci. 2013;54:1418–25.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Lim WK, et al. Epithelium-on photorefractive intrastromal cross-linking (PiXL) for reduction of low myopia. Clin Ophthalmol. 2017;11:1205–11. Scholar
  23. 23.
    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. Trans Vis Sci Technol. 2013;2(7):6.Google Scholar
  24. 24.
  25. 25.
  26. 26.
    O’Brart DPS, Patel P, Lascaratos G, Wagh VK, Tam C, Lee J, O’Brart NA. Keratoconus and corneal ectasia: seven-year follow-up. Am J Ophthalmol. 2015;160:1154–63. 3.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Schumacher S, Oeftiger L, Mrochen M. Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking using riboflavin and ultraviolet radiation. Invest Ophthalmol Vis Sci. 2011;52:9048–52.PubMedPubMedCentralGoogle Scholar
  28. 28.
    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;40:353–7.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Kling S, Richoz O, Hammer A, Tabibian D, Jacob S, Agarwal A, Hafezi F. Increased biomechanical efficacy of corneal cross-linking in thin corneas due to higher oxygen availability. J Refract Surg. 2015;31:840–6.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Cınar Y, Cingü AK, Türkcü FM, Çınar T, Yüksel H, Özkurt ZG, Çaça I. Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol. 2014;33(3):218–22.Google Scholar
  31. 31.
    Cınar Y, Cingü AK, Turkcu FM, Yüksel H, Sahin A, Yıldırım A, Caca I. Accelerated corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol. 2014;33(2):168–71.PubMedGoogle Scholar
  32. 32.
    Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg. 2011;37:149–60.Google Scholar
  33. 33.
    Legare ME, Iovieno A, Yeung SN, et al. Corneal collagen cross-linking using riboflavin and ultraviolet A for the treatment of mild to moderate keratoconus: 2-year follow-up. J Ophthalmol. 2013;48:63–8.Google Scholar
  34. 34.
    Kymionis GD, Tsoulnaras KI, Grentzelos MA, Liakopoulos DA, Tsakalis NG, Blazaki SV, Paraskevopoulos TA, Tsilimbaris MK. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol. 2014;158(4):671–5.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Shetty R, Nagaraja H, Jayadev C, Pahuja NK, Kurian Kummelil M, Nuijts RM. Accelerated corneal collagen cross-linking in pediatric patients: two-year follow-up results. Biomed Res Int. 2014;2014:894095.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Elbaz U, Shen C, Lichtinger A, Zauberman NA, Goldich Y, Chan CC, Slomovic AR, Rootman DS. Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow up. Cornea. 2014;33(8):769–73.Google Scholar
  37. 37.
    Jain V, Gazali Z, Bidayi R. Isotonic riboflavin and HPMC with accelerated cross-linking protocol. Cornea. 2014;33(9):910–3.PubMedGoogle Scholar
  38. 38.
    Pahuja N, Kumar NR, Francis M, Shanbagh S, Shetty R, Ghosh A, Roy AS. Correlation of clinical biomechanical outcomes of accelerated crosslinking (9 mW/cm2 in 10 minutes) in keratoconus with molecular expression of ectasia-related genes. Curr Eye Res. 2016;41(11):1419–23.PubMedGoogle Scholar
  39. 39.
    Marino GK, Torricelli AA, Giacomin N, Santhiago MR, Espindola R, Netto MV. Accelerated corneal collagen crosslinking for postoperative LASIK ectasia: two-year outcomes. J Refract Surg. 2015;31(6):380–4.PubMedGoogle Scholar
  40. 40.
    Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M. Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol. 2018;38(1):67–74.Google Scholar
  41. 41.
    Cingü AK, Sogutlu-Sari E, Cınar Y, Sahin M, Türkçü FM, Yüksel H, Sahin A, Caça I. Transient corneal endothelial changes following accelerated collagen cross-linking for the treatment of progressive keratoconus. Cutan Ocul Toxicol. 2014;33(2):127–31.PubMedGoogle Scholar
  42. 42.
    Hashemi H, Fotouhi A, Miraftab M, Bahrmandy H, Seyedian MA, Amanzadeh K, Heidarian S, Nikbin H, Asgari S. Short-term comparison of accelerated and standard methods of corneal collagen crosslinking. J Cataract Refract Surg. 2015;41(3):533–40.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Hashemi H, Miraftab M, Seyedian MA, Hafezi F, Bahrmandy H, Heidarian S, Amanzadeh K, Nikbin H, Fotouhi A, Asgari S. Long-term results of an accelerated corneal cross- linking protocol (18 mW/cm2) for the treatment of progressive keratoconus. Am J Ophthalmol. 2015;160(6):1164–70.Google Scholar
  44. 44.
    Chow VW, Chan TC, Yu M, Wong VW, Jhanji V. One year outcomes of conventional and accelerated collagen crosslinking in progressive keratoconus. Sci Rep. 2015;5:14425.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Asri D, Touboul D, Fournié P, Malet F, Garra C, Gallois A, Malecaze F, Colin J. Corneal collagen crosslinking in progressive keratoconus: multicenter results from the French National Reference Center for keratoconus. J Cataract Refract Surg. 2011;37(12):2137–43.Google Scholar
  46. 46.
    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.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Gatzioufas Z, Richoz O, Brugnoli E, Hafezi F. Safety profile of high-fluence corneal collagen cross-linking for progressive keratoconus: preliminary results from a prospective cohort study. J Refract Surg. 2013;29(12):846–8.PubMedGoogle Scholar
  48. 48.
    Wernli J, Schumacher S, Spoerl E, Mrochen M. The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time. Invest Ophthalmol Vis Sci. 2013;54(2):1176–80.Google Scholar
  49. 49.
    Hammer A, Richoz O, Arba Mosquera S, Tabibian D, Hoogewoud F, Hafezi F. Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Invest Ophthalmol Vis Sci. 2014;55(5):2881–4.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Chan TC, Chow VW, Jhanji V, Wong VW. Different topographic response between mild to moderate and advanced keratoconus after accelerated collagen cross-linking. Cornea. 2015;34(8):922–7.PubMedGoogle Scholar
  51. 51.
    Shetty R, Pahuja NK, Nuijts RM, Ajani A, Jayadev C, Sharma C, Nagaraja H. Current protocols of corneal collagen crosslinking—visual, refractive and tomographic outcomes. Am J Ophthalmol. 2015;160(2):243–9.Google Scholar
  52. 52.
    Kymionis GD, Tsoulnaras KI, Grentzelos MA, Plaka AD, Mikropoulos DG, Liakopoulos DA, Tsakalis NG, Pallikaris IG. Corneal stroma demarcation line after standard and high- intensity collagen crosslinking determined with anterior segment optical coherence tomography. J Cataract Refract Surg. 2014;40(5):736–40.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Kymionis GD, Grentzelos MA, Plaka AD, Tsoulnaras KI, Diakonis VF, Liakopoulos DA, Kankariya VP, Pallikaris AI. Correlation of the corneal collagen cross-linking demarcation line using confocal microscopy and anterior segment optical coherence tomography in keratoconic patients. Am J Ophthalmol. 2014;157(1):110–5.PubMedGoogle Scholar
  54. 54.
    Kurt T, Ozgurhan EB, Yildirim Y, Akcay BI, Cosar MG, Bozkurt E, Taskapili M. Accelerated (18mW/cm2) corneal cross-linking for progressive keratoconus: 18-month results. J Ocul Pharmacol Ther. 2016;32(4):186–91.PubMedGoogle Scholar
  55. 55.
    Razmjoo H, Peyman A, Rahimi A, Modrek HJ. Cornea collagen cross-linking for keratoconus: a comparison between accelerated and conventional methods. Adv Biomed Res. 2017;6:10.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Mazzotta C, Traversi C, Paradiso AL, Latronico ME, Rechichi M. Pulsed light accelerated crosslinking versus continuous light accelerated crosslinking: one-year results. J Ophthalmol. 2014;2014:604731.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Touboul D, Efron N, Smadja D, et al. Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. J Refract Surg (Thorofare, N.J.: 1995). 2012;28(11):769–76.Google Scholar
  58. 58.
    Merwald H, Klosner G, Kokesch C, Der-Petrossian M, Hönigsmann H, Trautinger F. UVA- induced oxidative damage and cytotoxicity depend on the mode of exposure. J Photochem Photobiol B. 2005;79(3):197–207.PubMedGoogle Scholar
  59. 59.
    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):1179–83.Google Scholar
  60. 60.
    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;41(11):2546–51.Google Scholar
  61. 61.
    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. 2014;30(12):843–9.PubMedGoogle Scholar
  62. 62.
    Ozgurhan EB, Akcay BI, Kurt T, Yildirim Y, Demirok A. Accelerated corneal collagen cross linking in thin keratoconic corneas. J Refract Surg. 2015;31(6):386–90.PubMedGoogle Scholar
  63. 63.
    Mita M, Waring GO 4th, Tomita M. High-irradiance accelerated collagen crosslinking for the treatment of keratoconus: six-month results. J Cataract Refract Surg. 2014;40(6):1032–40.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Spoerl E, Terai N, Scholz F, Raiskup F, Pillunat LE. Detection of biomechanical changes after corneal cross-linking using ocular response analyzer software. J Refract Surg. 2011;27:452–7.PubMedGoogle Scholar
  65. 65.
    Mazzotta C, Traversi C, Baiocchi S, et al. Corneal healing after riboflavin ultraviolet-A collagen cross-linking determined by confocal laser scanning microscopy in vivo: early and late modifications. Am J Ophthalmol. 2008;146:527–33.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Mazzotta C, Caporossi T, Denaro R, Bovone C, Sparano C, Paradiso A, Baiocchi S, Caporossi A. Morphological and functional correlations in riboflavin UV A corneal collagen crosslinking for keratoconus. Acta Ophthalmol. 2012;90:259–65.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014;40(6):1013–20.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Sherif AM. Accelerated versus conventional corneal collagen cross-linking in the treatment of mild keratoconus: a comparative study. Clin Ophthalmol. 2014;8:1435–40.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Mazzotta C, Baiocchi S, Simone AB, Fruschelli M, Alessandro M, Rechichi M. Accelerated 15 mW pulsed-light crosslinking in treatment of progressive keratoconus: two year clinical results. J Cataract Refract Surg. 2017;43:1081.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Mazzotta C, Hafezi F, Kymionis G, Caragiuli S, Jacob S, Traversi C, Barabino S, Randleman B. In vivo confocal microscopy after corneal collagen cross-linking. Ocul Surf. 2015;13(4):298–314.PubMedGoogle Scholar
  71. 71.
    Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of progressive keratoconus by riboflavin- UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea. 2007;26(4):390–7.PubMedGoogle Scholar
  72. 72.
    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;4:313.Google Scholar
  73. 73.
    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. 2012;22(Suppl 7):S81–8.PubMedGoogle Scholar
  74. 74.
    Bao F, et al. Changes in corneal biomechanical properties with different corneal cross-linking irradiances. J Refract Surg. 2018;34:51–8.PubMedGoogle Scholar
  75. 75.
    Kling S, Hafezi F. Biomechanical stiffening: slow low-irradiance corneal crosslinking versus the standard Dresden protocol. J Cataract Refract Surg. 2017;43:975–9. Scholar
  76. 76.
    Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea. 2006;25:1057–9.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Kymionis GD, Grentzelos MA, Plaka AD, et al. Evaluation of the corneal collagen crosslinking demarcation line profile using anterior segment optical coherence tomography. Cornea. 2013;32:907–10.PubMedGoogle Scholar
  78. 78.
    Bouheraoua N, Jouve L, El Sanharawi M, et al. Optical coherence tomography and confocal microscopy following three different protocols of corneal collagen-crosslinking in keratoconus. Invest Ophthalmol Vis Sci. 2014;55:7601–9.PubMedGoogle Scholar
  79. 79.
    Kymionis GD. Corneal collagen cross linking-Plus. Open Ophthalmol J. 2011;5:10.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Kymionis GD, Grentzelos MA, Kankariya VP, Pallikaris IG. Combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for ectatic disorders: Cretan protocol. J Cataract Refract Surg. 2013;39:1939.PubMedGoogle Scholar
  81. 81.
    Kymionis GD, Grentzelos MA, Portaliou DM, Kankariya VP, Randleman JB. Corneal collagen cross-linking (CXL) combined with refractive procedures for the treatment of corneal ectatic disorders: CXL plus. J Refract Surg. 2014;30(8):566–76.Google Scholar
  82. 82.
    Alfonso JF, Fernandez-Vega L, Lisa C, Fernandes P, Gonzalez-Meijome JM, Montes-Mico R. Collagen copolymer toric posterior chamber phakic intraocular lens in eyes with keratoconus. J Cataract Refract Surg. 2010;36(6):906–16. 43.Google Scholar
  83. 83.
    Alio JL. Advances in phakic intraocular lenses: indications, efficacy, safety, and new designs. Curr Opin Ophthalmol. 2004;15(4):350–7.PubMedGoogle Scholar
  84. 84.
    Burris TE, Ayer CT, Evensen DA, Davenport JM. Effects of Instrastromal corneal ring size and thickness on corneal flattening in human eyes. Refract Corneal Surg. 1991;7(1):46–50.PubMedGoogle Scholar
  85. 85.
    de Ferrara A, Cunha P. Tecnica cirurgica para correçao de miopia; Anel corneano intra- estromal. Rev Bras Oftalmol. 1995;54:577–88.Google Scholar
  86. 86.
    Baiocchi S, Mazzotta C, Cerretani D, Caporossi T, Caporossi A. Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg. 2009;35(5):893–9.PubMedGoogle Scholar
  87. 87.
    Belin MW, Khachikian SS, Ambrosio R Jr. Elevation based corneal tomography. 2nd ed. New Delhi: Jaypee-Highlights Medical Publishers, Inc; 2011.Google Scholar
  88. 88.
    Colin J. Intacs safe and viable long-term treatment for keratoconus. Eurotimes. 2009;16.Google Scholar
  89. 89.
    Samimi S, Leger F, Touboul D, Colin J. Histopathological findings after intracorneal ring segment implantation in keratoconic human corneas. J Cataract Refract Surg. 2007;33(2):247–53.PubMedGoogle Scholar
  90. 90.
    Sansanayudh W, Bahar I, Kumar NL, Shehadeh-Mashour R, Ritenour R, Singal N, Rootman DS. Intrastromal corneal ring segment SK implantation for moderate to severe keratoconus. J Cataract Refract Surg. 2010;36(1):110–3. 19.PubMedGoogle Scholar
  91. 91.
    Alio JL, Agdeppa MC, Pongo VC, El Kady B. Microincision cataract surgery with toric intraocular lens implantation for correcting moderate and high astigmatism: pilot study. J Cataract Refract Surg. 2010;36(1):44–52.PubMedGoogle Scholar
  92. 92.
    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. 2013;4:219–28.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Lee SJ, Kwon HS, Koh IH. Sequential intrastromal corneal ring implantation and cataract surgery in a severe keratoconus patient with cataract. Korean J Ophthalmol. 2012;26(3):226–9.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Hoffmann PC, Auel S, Hutz WW. Results of higher power toric intraocular lens implantation. J Cataract Refract Surg. 2011;37(8):1411–8.PubMedGoogle Scholar
  95. 95.
    Mazzotta C, Bagaglia S, Vinciguerra R, Ferrise M, Vinciguerra P. Enhanced-fluence pulsed-light iontophoresis corneal cross-linking: 1-year morphological and clinical results. J Refract Surg. 2018;34(7):438–44.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cosimo Mazzotta
    • 1
    • 2
  • Miguel Rechichi
    • 3
    • 4
  • Marco Ferrise
    • 2
    • 3
    • 5
  1. 1.Post-Graduate Ophthalmology SchoolUniversity of SienaSienaItaly
  2. 2.Siena Crosslinking Center®, OcuMedical VisionSienaItaly
  3. 3.Eye Center®CatanzaroItaly
  4. 4.Centro Polispecialistico MediterraneoCatanzaroItaly
  5. 5.Studio Oculistico FerriseLamezia TermeItaly

Personalised recommendations