Crosslinking came to the fore in 2003, when a group in Dresden, Germany, published preliminary studies demonstrating that a CXL technique could increase the stiffness or rigidity of corneas and suggested this method might be helpful in treating thinning corneas and KC. CXL involves treating the thin cornea with riboflavin and ultraviolet light, which increases the crosslinking of the corneal collagens and makes the cornea more resistant to enzyme degradation. (For more on this, see the spring 2010 DEF newsletter.)

The next step is trying to improve the way in which the cornea is crosslinked; determining how to monitor the collagen crosslinking in a noninvasive way is the key to doing this. "Noninvasively assessing corneal mechanics allows us to more accurately diagnose patients with KC and establish the effects of CXL and other potential modalities to therapeutically correct the disease," Jester says. "As we develop modalities to assess methods of crosslinking, we can also look at new ways of crosslinking."

Jester and Tibor Juhasz, a professor of biomedical engineering and ophthalmology at UCI, are employing new imaging technologies to monitor CXL (for more on this, see the Thanksgiving 2009 DEF newsletter), as well as a new approach in measuring corneal elasticity. Jester explains: "This is a nonlinear optical approach where we generate small bubbles in the cornea and push them with acoustic waves. This moves the bubbles, then we track them using lower energy to see where the bubbles move and how fast they come back. From that, we can calculate the elastic modulus, which is a measure of whether the cornea stiffens after crosslinking.

"We have developed several approaches to assess crosslinking, assess corneal structure and see how the structure of the keratoconic cornea differs from that of the normal cornea. We know KC individuals have softer corneas than normal individuals and lack the normal structural elements. Collagen structure controls the mechanics of the cornea; crosslinking can stiffen the KC cornea and make it similar to the stiffness of a normal adult cornea."

Ultimately, the goal is to use these techniques to identify and treat those patients who will develop KC prior to cone formation. "That's the beauty of the crosslinking," Jester says. "Those who have had crosslinking show partial regression and stability in progression of disease over extended periods of time. If you identified susceptible individuals early, you could crosslink them, and they would not develop cone formation."

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