In 2003, a group in Dresden, Germany, published preliminary studies demonstrating that a crosslinking (CXL) technique could increase the stiffness or rigidity of corneas and suggested this method might be helpful in treating thinning corneas and keratoconus (KC). KC is a non-inflammatory, typically bilateral but asymmetric, corneal thinning. It usually first shows up in patients in their 20s and 30s, but diagnosis can range from 10-50 years old or older; it can be progressive but often stabilizes in later years. Treatments range from glasses and contact lenses for mild cases to corneal transplantation in more severe cases. A second, rarer cause of corneal thinning happens after refractive laser surgery, where abnormal biochemical reactions lead to progressive corneal thinning.

Research has shown that keratoconus corneas have increased levels of degradative enzyme activity that make the cornea thinner. These corneas also have oxidative damage that causes breakdown of the cornea due to harmful free radicals and superoxides. More recent studies show KC corneas lack important structural supporting fibers, so the anterior cornea is destabilized, weakened and thinned.

CXL involves treating the thin cornea with Riboflavin and ultraviolet A light, which increases the crosslinking of the corneal collagens and makes the cornea more resistant to enzyme degradation. This corneal CXL treatment has been used in Europe, South America, Australia and Asia on hundreds of patients, delaying the need for corneal transplant in many. In the United States, there are ongoing clinical trials investigating the CXL treatment.

DEF is supporting research on CXL in several ways, including the following projects:

• DEF-supported researchers M. Cristina Kenney, MD, PhD, and James V. Jester, PhD, have shown there is a relationship between stretching corneal cells and oxidative stress that causes damage to cells and tissues. They have also shown that stretching corneal cells stimulates them to produce reactive oxygen species (free radicals), which can lead to increased activity of degradative enzymes and cell death. Scientists theorize that crosslinking makes the cornea more firm, the cells are not stretched and there is less enzymatic degradation and cell death.

• DEF-supported researchers Ronald N. Gaster, MD, and James V. Jester, PhD, of UC Irvine participated in an international meeting of physicians and scientists who were presenting their laboratory and clinical results using the CXL procedure for patients with KC and post-laser corneal thinning. Cathy Warren, RN, executive director of the National Keratoconus Foundation, also attended and brought back vital information for KC patients.

• DEF-supported researchers Ronald N. Gaster, MD, and Ezra Maguen, MD, are conducting clinical trials in Orange County and Los Angeles to study the efficacy and safety of the CXL technique for their patients.

• Jester is collaborating with Tibor Juhasz, PhD, to develop an instrument to measure the microscopic mechanical strength of the corneal fibers. They use a femtosecond laser to make microscopic bubbles that can deform the collagen fibers in the cornea, allowing them to measure the changes in firmness of the fibers before and after treatment. This work recently received a grant from the National Eye Institute.