| Peer-Reviewed

Collagen Cross Linking in Keratoconus: A Review

Received: 31 October 2016     Accepted: 29 November 2016     Published: 3 January 2017
Views:       Downloads:
Abstract

Corneal collagen cross-linking (CXL) is a therapeutic procedure that helps in increasing the corneal stiffness in the keratoconus eyes. It increases the collagen cross linking within the extracellular matrix (ECM). Ultraviolet-A (370 nm) irradiation of the cornea after saturation with the photosensitizer riboflavin is used. A minimum deepithelialized corneal thickness of 400 μm is recommended to avoid potential irradiation damage to the corneal endothelium but in advanced cases this is not achieved which limits the application of CXL in that category. Modifications have been done in the conventional CXL procedure to be applicable in thin corneas. The current review discusses different techniques employed to achieve this end and their results. The modifications in CXL halt the progression of keratectasia without postoperative complications. However, the evidence of safety and efficacy in the use of modified CXL protocols is still limited to few studies with few patients involved. Controlled studies with long-term follow-up are required to confirm the safety and efficacy of the modified protocols.

Published in International Journal of Ophthalmology & Visual Science (Volume 1, Issue 1)
DOI 10.11648/j.ijovs.20160101.13
Page(s) 20-24
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Keratoconus, Collagen Cross Linking, Thin Cornea

References
[1] J. H. Krachmer, R. S. Feder, M. W. Belin. Keratoconus and related non-inflammatory corneal thinning disorders. Surv Ophthalmol, 28 (1984), pp. 293-322.
[2] Y. S. Rabinowitz. Keratoconus. Surv Ophthalmol, 42 (1998), pp. 297-319.
[3] W. Hammerstein. Zur genetic des keratoconus. Albrecht Von Graefes Arch Klin Exp Ophthalmol, 190 (1974), pp. 293-308.
[4] R. H. Kennedy, W. M. Bourne, J. A. Dyer. A 48-year clinical and epidemiological study of keratoconus. Am J Ophthalmol, 101 (1986), pp. 267-273.
[5] E. Spoerl, M. Huhle, T. Seiler. Induction of cross-links in corneal tissue Exp Eye Res, 66 (1998), pp. 97-103.
[6] G. Wollensak, E. Spoerl, T. Seiler. Riboflavin/ultraviolet-A-induced collagen cross-linking for the treatment of kertatoconus. Am J Ophthalmol, 135 (2003), pp. 620-627.
[7] A. S. Mc Call, S. Kraft, H. F. Edelhauser. Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). Invest Ophthalmol Vis Sci, 51 (2010), pp. 129-138.
[8] S. Hayes, C. S. Kamma-Lorger, C. Boote. The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma PLoS ONE, 8 (2013), pp. e52860.
[9] Kymionis GD, Portaliou DM, Diakonis VF, Kounis GA, Panagopoulou SI, Grentzelos MA. Corneal collagen cross-linking with riboflavin and ultraviolet-A irradiation in patients with thin corneas. Am J Ophthalmol. 2012; 153: 24–8. doi: 10.1016/j.ajo.2012.01.012.
[10] Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. J Cataract Refract Surg. 2010; 36: 114–20. doi: 10.1016/j.jcrs.2009.07.044.
[11] Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009; 35: 621–4. doi: 10.1016/j.jcrs.2008.10.060.
[12] Raiskup F, Spoerl E. Corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Am J Ophthalmol. 2011; 152: 28–32. doi: 10.1016/j.ajo.2011.01.016.
[13] Wu H, Luo S, Dong N, Lin Z, Liu Z, Shang X. The clinical study of corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Zhonghua Yan Ke Za Zhi. 2014; 50: 681–6.
[14] Gu SF, Fan ZS, Wang LH, Tao XC1, Zhang Y, Wang CQ, et al. A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas. Int J Ophthalmol. 2015; 8: 94–7.
[15] Kaya V, Utine CA, Yilmaz OF. Intraoperative corneal thickness measurements during corneal collagen cross-linking with hypoosmolar riboflavin solution in thin corneas. Cornea. 2012; 31: 486–90. doi: 10.1097/ICO.0b013e31821e4286.
[16] Soeters N, Tahzib NG. Standard and hypoosmolar corneal cross-linking in various pachymetry groups. Optom Vis Sci. 2015; 92: 329–36. doi: 10.1097/OPX.0000000000000486.
[17] Vetter JM, Brueckner S, Tubic-Grozdanis M, Vossmerbaumer U, Pfeiffer N, Kurz S. Modulation of central corneal thickness by various riboflavin eyedrop compositions in porcine corneas. J Cataract Refract Surg. 2012; 38: 525–32. doi: 10.1016/j.jcrs.2011.09.045.
[18] Chang SW, Chi RF, Wu CC, Su MJ. Benzalkonium chloride and gentamicin cause a leak in corneal epithelial cell membrane. Exp Eye Res. 2000; 71: 3–10. doi: 10.1006/exer.2000.0849.
[19] Majumdar S, Hippalgaonkar K, Repka MA. Effect of chitosan, benzalkonium chloride and ethylenediaminetetraacetic acid on permeation of acyclovir across isolated rabbit cornea. Int J Pharm. 2008; 348: 175–8. doi: 10.1016/j.ijpharm.2007.08.017.
[20] Koppen C, Wouters K, Mathysen D, Rozema J, Tassignon MJ. Refractive and topographic results of benzalkonium chloride-assisted transepithelial crosslinking. J Cataract Refract Surg. 2012; 38: 1000–5. doi: 10.1016/j.jcrs.2012.01.024.
[21] Soeters N, Wisse RP, Godefrooij DA, Imhof SM, Tahzib NG. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol. 2015; 159: 821–8. doi: 10.1016/j.ajo.2015.02.005.
[22] Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg. 2012; 38: 283–91. doi: 10.1016/j.jcrs.2011.08.030.
[23] Spadea L, Mencucci R. Transepithelial corneal collagen cross-linking in ultrathin keratoconic corneas. Clin Ophthalmol. 2012; 6: 1785–92. doi: 10.2147/OPTH.S37335.
[24] Wollensak G, Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. J Cataract Refract Surg. 2009; 35: 540–546. doi: 10.1016/j.jcrs.2008.11.036.
[25] Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea. 2006; 25: 1057–9. doi: 10.1097/01.ico.0000225720.38748.58.
[26] Bonnel S, Berguiga M, De Rivoyre B, Bedubourg G, Sendon D, Froussart-Maille F, et al. Demarcation line evaluation of iontophoresis-assisted transepithelial corneal collagen cross-linking for keratoconus. J Refract Surg. 2015; 31: 36–40. doi: 10.3928/1081597X-20141218-04.
[27] Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens-assisted collagen cross-linking (CACXL): a new technique for cross-linking thin corneas. J Refract Surg. 2014; 30: 366–72. doi: 10.3928/1081597X-20140523-01.
[28] Iseli HP, Popp M, Seiler T, Spoerl E, Mrochen M. Laboratory measurement of the absorption coefficient of riboflavin for ultraviolet light (365 nm) J Refract Surg. 2011; 27: 195–201.
[29] Ozgurhan EB, Akcay BI, Kurt T, Yildirim Y, Demirok A. Accelerated corneal collagen cross-linking in thin keratoconic corneas. J Refract Surg. 2015; 31: 386–90. doi: 10.3928/1081597X-20150521-11.
[30] Lin JT, Cheng DC. Optimal focusing and scaling law for uniform photo-polymerization in a thick medium using a focused UV laser. Polymers. 2014; 6: 552–64.
[31] Lin JT, Liu HW, Cheng DC. On the dynamic of UV-light initiated corneal cross linking. J Med Biolog Eng. 2014; 34: 247–50.
Cite This Article
  • APA Style

    Bhavesh Makkar, Deepak Mishra. (2017). Collagen Cross Linking in Keratoconus: A Review. International Journal of Ophthalmology & Visual Science, 1(1), 20-24. https://doi.org/10.11648/j.ijovs.20160101.13

    Copy | Download

    ACS Style

    Bhavesh Makkar; Deepak Mishra. Collagen Cross Linking in Keratoconus: A Review. Int. J. Ophthalmol. Vis. Sci. 2017, 1(1), 20-24. doi: 10.11648/j.ijovs.20160101.13

    Copy | Download

    AMA Style

    Bhavesh Makkar, Deepak Mishra. Collagen Cross Linking in Keratoconus: A Review. Int J Ophthalmol Vis Sci. 2017;1(1):20-24. doi: 10.11648/j.ijovs.20160101.13

    Copy | Download

  • @article{10.11648/j.ijovs.20160101.13,
      author = {Bhavesh Makkar and Deepak Mishra},
      title = {Collagen Cross Linking in Keratoconus: A Review},
      journal = {International Journal of Ophthalmology & Visual Science},
      volume = {1},
      number = {1},
      pages = {20-24},
      doi = {10.11648/j.ijovs.20160101.13},
      url = {https://doi.org/10.11648/j.ijovs.20160101.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijovs.20160101.13},
      abstract = {Corneal collagen cross-linking (CXL) is a therapeutic procedure that helps in increasing the corneal stiffness in the keratoconus eyes. It increases the collagen cross linking within the extracellular matrix (ECM). Ultraviolet-A (370 nm) irradiation of the cornea after saturation with the photosensitizer riboflavin is used. A minimum deepithelialized corneal thickness of 400 μm is recommended to avoid potential irradiation damage to the corneal endothelium but in advanced cases this is not achieved which limits the application of CXL in that category. Modifications have been done in the conventional CXL procedure to be applicable in thin corneas. The current review discusses different techniques employed to achieve this end and their results. The modifications in CXL halt the progression of keratectasia without postoperative complications. However, the evidence of safety and efficacy in the use of modified CXL protocols is still limited to few studies with few patients involved. Controlled studies with long-term follow-up are required to confirm the safety and efficacy of the modified protocols.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Collagen Cross Linking in Keratoconus: A Review
    AU  - Bhavesh Makkar
    AU  - Deepak Mishra
    Y1  - 2017/01/03
    PY  - 2017
    N1  - https://doi.org/10.11648/j.ijovs.20160101.13
    DO  - 10.11648/j.ijovs.20160101.13
    T2  - International Journal of Ophthalmology & Visual Science
    JF  - International Journal of Ophthalmology & Visual Science
    JO  - International Journal of Ophthalmology & Visual Science
    SP  - 20
    EP  - 24
    PB  - Science Publishing Group
    SN  - 2637-3858
    UR  - https://doi.org/10.11648/j.ijovs.20160101.13
    AB  - Corneal collagen cross-linking (CXL) is a therapeutic procedure that helps in increasing the corneal stiffness in the keratoconus eyes. It increases the collagen cross linking within the extracellular matrix (ECM). Ultraviolet-A (370 nm) irradiation of the cornea after saturation with the photosensitizer riboflavin is used. A minimum deepithelialized corneal thickness of 400 μm is recommended to avoid potential irradiation damage to the corneal endothelium but in advanced cases this is not achieved which limits the application of CXL in that category. Modifications have been done in the conventional CXL procedure to be applicable in thin corneas. The current review discusses different techniques employed to achieve this end and their results. The modifications in CXL halt the progression of keratectasia without postoperative complications. However, the evidence of safety and efficacy in the use of modified CXL protocols is still limited to few studies with few patients involved. Controlled studies with long-term follow-up are required to confirm the safety and efficacy of the modified protocols.
    VL  - 1
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

  • Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

  • Sections