Post CxL Haze

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 by Nichelle Warren MD on January 15, 2023.

Post Crosslinking Haze


In 2003 Wollensack et al. introduced Corneal Collagen Cross-Linking. In the past few years, based on the combined use of the photosensitizer, riboflavin, and UVA light of 370 nm, it has become 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.


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. found 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 glycosaminoglycan 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.


As we said above, in the 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.


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