Understanding How Corneal Cross-Linking Treatment for Keratoconus Works

Authors: Chang, S.H., Eliasy, A., Chen, K.J., Ji, Y.R., Young, T.H., Wang, T.J., Willoughby, C.E., Hamill, K.J., Elsheikh, A.

Journal: Journal of Refractive Surgery

Publication Date: April 2018

DOI: https://dx.doi.org/10.3928/1081597X-20180220-01

Transmission electron microscopy (TEM) images of porcine corneas imaged at a depth of 80 to 150 µm. (A) Representation TEM images of phosphate-buffered saline (PBS), riboflavin in dextran, and dextran only and riboflavin/dextran/ultraviolet-A (UVA) cross-linked corneas. Bar = 500 nm. (B) An area of 300 × 300 dpi (yellow dashed square) is shown at higher magnification with an example of the measurement of the area and density of collagen fibrils.

Summary:

Keratoconus is an eye condition where the cornea thins, leading to reduced visual function, and in severe cases, may require corneal transplantation. Corneal cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is an established treatment for this condition, but the way it works remains unclear.

Our study aimed to understand the relationship between the mechanical changes and the ultrastructural changes in the cornea following CXL treatment, as well as the contribution of individual components of the treatment protocol. To do this, we treated porcine corneas using the Dresden protocol, which involves removing the corneal epithelium, applying riboflavin in dextran, and then exposing the cornea to UVA light.

Our findings revealed that the increase in corneal stiffness following the Dresden protocol is a result of both dextran-induced dehydration and UVA/riboflavin-induced bond formation within the cornea. These new bonds, along with changes in collagen fibril diameter and overall structure, contribute to the increased mechanical strength of the treated cornea.

While our study provides valuable insights into how CXL treatment works, it also highlights the need for a better understanding of the roles of various stromal proteins and their interactions in the treatment process. This knowledge will be critical in evaluating modifications to the Dresden protocol and developing new treatments for keratoconus.

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