UC Irvine

Ectatic disorders of the cornea such as Keratoconus or post-LASIK ectasia are characterized by mechanical weakening and thinning of the corneal stroma, leading to distortion of its shape and severely impacting the vision of those affected. Though temporary vision correction can be achieved, advanced cases often require corneal transplants. A new method, recently approved by the FDA, has the potential to stop or reverse the progression of disease. For this procedure the cornea is presoaked in the photosensitizer riboflavin and irradiated with ultraviolet-A (UVA) light. The riboflavin then generates oxygen free radicals, causing covalent bonds to form between corneal collagen molecules, mechanically stiffening the tissue. In order to avoid the potential cellular damage associated with UVA irradiation specific parameters have been selected for this procedure which minimize exposure to deeper structures, especially to the corneal endothelium which is not regenerative in humans. Unfortunately these parameters limit crosslinking (CXL) to the anterior cornea and allow for very little control over the treated area.

We have hypothesized that the substitution of nonlinear excitation for UVA irradiation would greatly increase the precision of this procedure, thereby improving its safety and efficacy. We have termed this technique nonlinear optical crosslinking or ‘NLO CXL.’ NLO CXL uses highly focused 760 nm femtosecond laser light to induce two photon excitation of the riboflavin soaked within the corneal tissue, limiting photo activation to the focal volume, and allowing for highly controllable crosslinking in the x, y, and z directions. Also, near infrared light is generally not harmful to cellular structures and naturally penetrates much deeper into corneal tissue than UVA light. Because of this the focal volume can be positioned much deeper into the tissue without taking the risk of damaging the endothelium.

This body of work details, first and foremost, the development of a system that is capable of producing a nonlinearly crosslinked volume of corneal collagen, with highly controllable dimensions. It also presents the results of studies intended to develop a better crosslinking procedure overall, including general exploration of the effects of crosslinking on corneal collagen or shape.