International Journal of Keratoconus and Ectatic Corneal Diseases

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VOLUME 7 , ISSUE 2 ( July-December, 2018 ) > List of Articles

Surgical Technique

Pachymetry-based Accelerated Crosslinking: The “M Nomogram” for Standardized Treatment of All-thickness Progressive Ectatic Corneas

Cosimo Mazzotta, Andrea Romani, Alessandro Burroni

Keywords : Crosslinking, Keratoconus, M nomogram, Pachymetry, Thin corneas

Citation Information : Mazzotta C, Romani A, Burroni A. Pachymetry-based Accelerated Crosslinking: The “M Nomogram” for Standardized Treatment of All-thickness Progressive Ectatic Corneas. Int J Kerat Ect Cor Dis 2018; 7 (2):137-144.

DOI: 10.5005/jp-journals-10025-1171

License: CC BY-NC 4.0

Published Online: 01-08-2013

Copyright Statement:  Copyright © 2018; The Author(s).


Purpose: To assess the safety and efficacy of a new customized epithelium-off accelerated crosslinking (ACXL) nomogram “M nomogram” based on preoperative corneal optical thinnest point for progressive keratoconus and iatrogenic corneal ectasia. Methods: Comparative analysis including the measured depths of the demarcation lines by in vivo confocal microscopy (IVCM) and corneal OCT in 20 eyes treated with conventional 3 mW/cm2 CXL, 20 eyes treated with 30 mW/cm2 ACXL with continuous (10 eyes) and pulsed (10 eyes) UV-A exposure (1 sec on, 1 sec off), 20 eyes treated with 15 mW/cm2 pulsed light ACXL and 20 eyes using the 9 mW/cm2 ACXL protocol. IVCM was performed by the HRT II Rostock Cornea Module (Heidelberg, Germany) and corneal OCT by the OptoVue (Freemont, Irvine, USA). The mathematical cross-linking profile was determined according to a calculated depth of the demarcation line and the threshold cross-link concentration adopting the conventional 3 mW/cm2 protocol as a benchmark. Results: The average demarcation depths were 350 ± 50 μm for the 3 mW/cm2 conventional protocol, 200 ± 50 μm for the 30 mW/cm2 continuous light ACXL, 250 ± 50 μm for the 30 mW/cm2 pulsed light ACXL and 280 ± 30 μm for the 15 mW/cm2 pulsed light ACXL. There was a very high correlation between the depth of the demarcation line between the measured and calculated data with a slope of m = 1.03 and an R2 value 0.73. Conclusion: ACXL M nomogram allows safe and efficacious CXL parameters setting based on preoperative minimum corneal thickness also including a more standardized treatment of thin ectatic corneas between 250 μm and 400 μm.

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  1. Wollensak G, Spoerl E, Seiler Th. Riboflavin/ultraviolet-Ainduced collagen crosslinking for the treatment of keratoconus. Am J Ophtalmol 2003;135(5):620-627.
  2. Caporossi A, Baiocchi S, Mazzotta C, et al. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A-induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg 2006;32(5):837-845.
  3. Hafezi F, Kanellopoulos J, Wiltfang R, et al. Corneal collagen crosslinking with riboflavin and ultraviolet A to treat induced keratectasia after laser in situ keratomileusis. J Cataract Refract Surg 2007;33(12):2035-2040.
  4. Raiskup F, Theuring A, Pillunat LE, et al. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg 2015;41(1):41-46.
  5. Mazzotta C, Traversi C, Baiocchi S, et al. Corneal Collagen Cross-Linking with Riboflavin and Ultraviolet A Light for Pediatric Keratoconus: Ten-Year Results. Cornea 2018;37(5):560-566.
  6. O'Brart DP, Patel P, Lascaratos G, et al. Corneal Crosslinking to Halt the Progression of Keratoconus and Corneal Ectasia: Seven-Year Follow-up. Am J Ophthalmol 2015;160(6): 1154-1163.
  7. Caporossi A, Mazzotta C, Baiocchi S, et al. 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):585-593.
  8. Wittig-Silva C, Chan E, Islam FM, et al. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results. Ophthalmology 2014;121(4):812-821.
  9. Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998;42(4):297- 319.
  10. Godefrooij DA, Gans R, Imhof SM, et al. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking. Acta Ophthalmol 2016;94(7):675-678.
  11. Sandvik GF, Thorsrud A, Råen M, et al. Does Corneal Collagen Cross-linking Reduce the Need for Keratoplasties in Patients With Keratoconus? Cornea 2015;34(9):991-995.
  12. Tabibian D, Mazzotta C, Hafezi F. PACK-CXL: Corneal crosslinking in infectious keratitis. Eye Vis (Lond) 2016;3:11.
  13. Spoerl E, Mrochen M, Sliney D, et al. Safety of UVA-riboflavin cross-linking of the cornea. Cornea 2007;26(4):385-389.
  14. Hagem AM, Thorsrud A, Sandvik GF, et al. Randomized Study of Collagen Cross-Linking With Conventional Versus Accelerated UVA Irradiation Using Riboflavin With Hydroxypropyl Methylcellulose: Two-Year Results. Cornea 2019;38(2):203-209.
  15. Elbaz U, Shen C, Lichtinger A, et al. Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow-up. Cornea 2014;33(8):769-773.
  16. Ulusoy DM, Göktaþ E, Duru N, et al. Accelerated corneal crosslinking for treatment of progressive keratoconus in pediatric patients. Eur J Ophthalmol 2017;27(3):319-325.
  17. Marino GK, Torricelli AA, Giacomin N, et al. Accelerated corneal collagen crosslinking for postoperative LASIK ectasia: two-year outcomes. J Refract Surg 2015;31(6):380-384.
  18. Chow VW, Chan TC, Yu M, et al. One year outcomes of conventional and accelerated collagen crosslinking in progressive keratoconus. Sci Rep 2015;5:14425.
  19. Hashemian H, Jabbarvand M, Khodaparast M, et al. Evaluation of corneal changes after conventional versus accelerated corneal cross-linking: a randomized controlled trial. J Refract Surg 2014;30(12):837-842.
  20. Shetty R, Pahuja NK, Nuijts RM, et al. Current protocols of corneal collagen crosslinking - visual, refractive and tomographic outcomes. Am J Ophthalmol 2015;160(2):243-249.
  21. Hashemi H, Miraftab M, Seyedian MA, et al. Long-term Results of an Accelerated Corneal Cross-linking Protocol (18mW/cm2) for the Treatment of Progressive Keratoconus. Am J Ophthalmol 2015;160(6):1164-1170.
  22. Mazzotta C, Traversi C, Paradiso AL, et al. Pulsed light accelerated crosslinking versus continuous light accelerated crosslinking one-year results. J Ophthalmol 2014;2014:1-6.
  23. Sadoughi MM, Einollahi B, Baradaran-Rafii A, et al. Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol 2016:1-8.
  24. Brindley GS. The Bunsen-Roscoe law for the human eye at very short durations. J Physiol 1952;118(1):135-139.
  25. Scarcelli G, Kling S, Quijano E, et al. Brillouin microscopy of collagen crosslinking: non-contact depth-dependent analysis of corneal elastic modulus. Invest Ophthalmol Vis Sci. 2013;54(2):1418-1425.
  26. Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of progressive keratoconus by riboflavin-UVA-induced crosslinking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea 2007;26(4):390-397.
  27. 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(4): 527-533.
  28. Mazzotta C, Traversi C, Baiocchi S, et al. Conservative treatment of keratoconus by riboflavin-UVA-induced crosslinking of corneal collagen: qualitative investigation. Eur J Ophthalmol 2006;16(4):530-535.
  29. Mazzotta C, Hafezi F, Kymionis G, et al. In Vivo Confocal Microscopy after Corneal Collagen Crosslinking. Ocul Surf. 2015 Oct;13(4):298-314.
  30. Mazzotta C, Traversi C, Caragiuli S, et al. Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye (Lond) 2014;28(10):1179-1183.
  31. Mazzotta C, Traversi C, Mellace P, et al. Keratoconus Progression in Patients with Allergy and Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test. Eye Contact Lens 2018;44 Suppl 2: S48-S53.
  32. Kohlhaas M, Spoerl E, Schilde T, et al. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg 2006;32(2):279-283.
  33. Schumacher S, Mrochen M, Wernli J, et al. Optimization model for UV-riboflavin corneal cross-linking. Invest Ophthalmol Vis Sci 2012;53(2):762-769.
  34. Krueger R, Herekar MS, 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;40:353-357.
  35. Kamaev P, Friedman MD, Sherr E, et al. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci 2012;53(4):2360-2367.
  36. Kling S, Richoz O, Hammer A, et al. Increased Biomechanical Efficacy of Corneal Cross-linking in Thin Corneas Due to Higher Oxygen Availability. J Refract Surg 2015;31(12):840- 846.
  37. Moramarco A, Iovieno A, Sartori A, et al. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg 2015;41(11):2546-2551.
  38. Peyman A, Nouralishahi A, Hafezi F, et al. Stromal Demarcation Line in Pulsed Versus Continuous Light Accelerated Corneal Cross-linking for Keratoconus. J Refract Surg 2016;32(3):206-208.
  39. Jiang LZ, Jiang W, Qiu SY. Conventional vs. pulsed-light accelerated corneal collagen cross-linking for the treatment of progressive keratoconus: 12-month results from a prospective study. Exp Ther Med 2017;14(5):4238-4244.
  40. Friedman MD, Kamaev P, Smirnov M, et al. Can we safely cross-link thinner corneas? Pathways for optimized CXL treatment planning, ESCRS 2015, Barcelona, Spain.
  41. Mazzotta C, Paradiso AL, Baiocchi S, et al. 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.
  42. Touboul D, Efron N, Smadja D, Praud D, et al. Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. J Refract Surg 2012;28(11): 769-776.
  43. Mazzotta C, Baiocchi S, Bagaglia SA, et al. Accelerated 15 mW pulsed-light crosslinking to treat progressive keratoconus: Two-year clinical results. J Cataract Refract Surg 2017;43(8):1081-1088.
  44. Hashemi H, Fotouhi A, Miraftab M, et al. Short-term comparison of accelerated and standard methods of corneal collagen crosslinking. J Cataract Refract Surg 2015;41(3):533-540.
  45. Hafezi F, Mrochen M, Iseli HP, et al. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg 2009;35(4):621-624.
  46. Raiskup F, Spoerl E. Corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Am J Ophthalmol 2011;152(1):28-32.e1.
  47. Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelialcornealcollagencrosslinking for progressive keratoconus: 24-month clinicalresults. J Cataract Refract Surg 2013 Aug;39(8):1157-1163.
  48. Mazzotta C, Ramovecchi V. Customized epithelial debridement for thin ectatic corneas undergoing corneal crosslinking: epithelial island cross-linking technique. Clin Ophthalmol 2014;8:1337-1343.
  49. Kymionis GD, Portaliou DM, Diakonis VF, et al. Corneal collagen cross-linking with riboflavin and ultraviolet-A irradiation in patients with thin corneas. Am J Ophthalmol 2012; 153(1):24-28.
  50. Jacob S, Kumar DA, Agarwal A, et al. Contact lens-assisted collagen cross-linking (CACXL): A new technique for crosslinking thin corneas. J Refract Surg 2014;30(6):366-372.
  51. Mazzotta C, Jacob S, Agarwal A, et al. In Vivo Confocal Microscopy After Contact Lens-Assisted Corneal Collagen Cross-linking for Thin Keratoconic Corneas. J Refract Surg. 2016;32(5):326-331.
  52. Sachdev MS, Gupta D, Sachdev G, et al. Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea. J Cataract Refract Surg 2015;41(5):918-923.
  53. Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea 2006;25(9):1057-1059.
  54. Spadea L, Di Genova L, Tonti E. Corneal stromal demarcation line after 4 protocols of corneal crosslinking in keratoconus determined with anterior segment optical coherence tomography. J Cataract Refract Surg 2018;44(5):596-602.
  55. Richoz O, Hammer A, Tabibian D, et al. The biomechanical effect of corneal collagen cross-linking (CXL) with riboflavin and UV-A is oxygen dependent. Trans Vis Sci Tech 2013;2(7):6.
  56. Mazzotta C, Wollensak G, Raiskup F, et al. The meaning of the demarcation line after riboflavin-UVA corneal collagen crosslinking. Expert Review of Ophthalmology 2019;14(2):115-131.
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