We have recently shown that photo-activation of riboflavin and mechanical stiffening of the cornea can be achieved using 760 nm infrared Femtosecond laser light through a two photon, nonlinear optical (NLO) process. The primary advantage of NLO over the existing technology is that cross linking occurs only within the two-photon focal volume of the FS laser light, providing precise control over the area, depth and geometry of the mechanically stiffened cornea that can be easily tailored to the patient's corneal topography. We have further patented an FS laser delivery system and shown that can vary the two-photon focal volume by changing the numerical aperture (NA) of the focusing lens to greatly expand the lateral and axial dimensions of the CXL region up to 150 μm of the corneal thickness. This greatly speeds up the NLO process, providing a more rapid procedure compared to that of standard treatments. We have also established that using regeneratively amplified FS laser pulses, mechanical stiffening of rabbit corneas can be achieved with an overall power of <46.1 mW, below the ANSI thermal limits for laser exposure to the eye. Additionally, we have shown in a live rabbit model that our NLO CXL device can crosslink a 4 mm diameter central corneal region in 5 minutes and produce 1-2 diopters of corneal flattening. We have further developed an FS corneal epithelial micromachining method to enhance penetration of chemicals through the epithelium without producing epithelial damage before or after the procedure, thus avoiding the major adverse effects of standard protocols. With this novel technology now in hand, we are ready to develop a clinical prototype that will allow for the testing of this device to treat keratoconus and low degrees of myopia, hyperopia, presbyopia and astigmatism.

Project Narrative: Keratoconus is a corneal thinning disorder affecting 1 in 375 individuals in the United States. In addition, other refractive errors represent the most common vision-related disorder affecting over 200 million Americans and costing over $16 billion annually. Over 60 million people suffer from low degrees of myopia (nearsighted) and astigmatism, while an additional 30 million individuals have low degrees of presbyopia (farsighted) requiring correction for good vision. The long-range goal of this project is to develop a laser based device to non-invasively modify corneal stiffness and precisely alter corneal curvature to correct keratoconus and other refractive errors.