Post CxL Haze

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Post Crosslinking Haze

Introduction

In 2003 Wollensack et al. introduced Corneal Cross Linking. In the last past years, based on the combined use of the photosensitizer riboflavin and UVA light of 370 nm, it has become in a treatment of choice to improve biomechanical stability in eyes with progressive keratectasia. Several long-term and short-term complications of CXL have been studied and documented over the years. One of the most common complications is stromal corneal haze.

Pathophysiology

In vitro and ex vivo studies show that CXL leads to an immediate loss of keratocytes in the corneal stroma. In a confocal microscopy study, Mazzotta et al. ound that in eyes with keratoconus, activated keratocytes repopulated the corneal stroma starting at 2 months and that the repopulation was almost complete at 6 months. It is possible that these activated keratocytes contribute to the development of CXL-associated corneal haze.

Other factors that may contribute to CXL-associated corneal haze include stromal swelling pressure changes, proteoglycan-collagen interactions and glycosamino-glycan hydration.

In addition, it was reported that the intact corneal epithelium may play an important role in prevention of corneal haze. Based on this evidence, Razmjoo and collaborates, proposed that partial removal of the cornea and leaving the central portion of the cornea intact could improve the outcome of CXL, but finally they founded that keeping the central corneal epithelium intact was not beneficial for decreasing corneal haziness, however, this method caused better improvement in corrected vision.

PRK haze vs CXL haze

There are some differences between PRK haze and CXL haze, the most important may be the depth of the haze, in the the case of PRK haze, it is founded strictly sub epithelial while CXL haze extends into the anterior stroma to approximately 300 um of depth.

Treatment

As we said above, first months after CXL we expected some grade of haze depending on the depth of treatment into the stroma as well as the amount of keratocyte loss. From the third month after procedure, the cornea began to clear and there was a significant decrease in CXL-associated corneal haze which usually does not require treatment except for some low dose steroid medication in some cases. From 6 months to 1 year postoperatively, there continued to be a decrease in haze measurements. Typically late permanent scarring should be differentiated from the early postoperative temporary haze which is often paracentral and compatible with good visual results. It may not be actually related to CXL itself but rather to the ongoing disease process and corneal remodeling.

References

  1. C.A Benatti, "Corneal Crosslinking and Types of Riboflavin", "Apectasias 2015" - I International Ectasia Meeting, Mexico City, Oct 2015.
  2. C. Mazzotta, A. Balestrazzi, S. Baiocchi, C. Traversi, and A. Caporossi, “Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus: in vivo confocal microscopic evaluation,” Clinical and Experimental Ophthal- mology, vol. 35, no. 6, pp. 580–582, 2007.
  3. Greenstein SA, Fry KL, Bhatt J, Hersh PS: Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicro- scopic analysis. J Cataract Refract Surg 2010; 36:2105–2114.
  4. Raiskup F, Hoyer A, Spoerl E: Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg 2009;25:S824–S828.
  5. F. Raiskup-Wolf, A. Hoyer, E. Spoerl, and L. E. Pillunat, “Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results,” Journal of Cataract and Refractive Surgery, vol. 34, no. 5, pp. 796–801, 2008. 

  6. A. Caporossi, C. Mazzotta, S. Baiocchi, and T. Caporossi, “Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena Eye Cross Study,” American Journal of Ophthalmology, vol. 149, no. 4, pp. 585–593, 2010. 

  7. G. Wollensak, E. Spoerl, M. Wilsch, and T. Seiler, “Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/ UVA treatment,” Cornea, vol. 23, no. 1, pp. 43–49, 2004.
  8. 
J. S. Dhaliwal and S. C. Kaufman, “Corneal collagen cross- linking: a confocal, electron, and light microscopy study of eye bank corneas,” Cornea, vol. 28, no. 1, pp. 62–67, 2009.
  9. T. Koller, M. Mrochen, and T. Seiler, “Complication and failure rates after corneal crosslinking,” Journal of Cataract and Re- fractive Surgery, vol. 35, no. 8, pp. 1358–1362, 2009.

  10. H. Razmjoo, B. Rahimi, M. Kharraji, N. Koosha, A Peyman. Corneal haze and visual outcome after collagen crosslinking for keratoconus: A comparison between total epithelium off and partial epithelial removal methods. Adv Biomed Res. 2014 Nov 29;3:221.
  11. C. H. Dohlman, B. O. Hedbys, S. Mishima, “The swelling pressure of the corneal stroma,” Investigative Ophthalmology, vol. 1, pp. 158–162, 1962. 

  12. Y. M. Michelacci, “Collagens and proteoglycans of the corneal extracellular matrix,” Brazilian Journal of Medical and Biological Research, vol. 36, no. 8, pp. 1037–1046, 2003. 

  13. L. S. Lim, R. Beuerman, L. Lim, and D. T. H. Tan, “Late-onset deep stromal scarring after riboflavin—UV-A corneal collagen cross-linking for mild keratoconus,” Archives of Ophthalmology, vol. 129, no. 3, pp. 360–362, 2011.