Laser Induced Collagen Crosslinking in Tissue

Abstract

The presently disclosed subject matter provides techniques for inducing collagen cross-linking in human tissue, such as cartilage or cornea, without using a photosensitizer (e.g., riboflavin), by inducing ionization of the water contained in the tissue to produce free radicals that induce chemical cross-linking in the human tissue. In an embodiment, a femtosecond laser operates at sufficiently low laser pulse energy to avoid optical breakdown of tissue. In an embodiment, the femtosecond laser operates in the infrared frequency range.

1 . A method of reshaping curvature of a region of a cornea having an initial curvature, the method comprising:
 inducing partial ionization in a region of the cornea by applying laser light energy below optical breakdown, wherein a majority of the laser light is in wavelengths, or integral fractions thereof, that are not absorbed directly by amino acids in collagen of the cornea.   
     
     
         2 . The method of  claim 1 , further comprising:
 projecting an illumination pattern on the cornea;   recording a pattern of reflection from the cornea with a camera; and   converting the pattern of reflection into a topography of the cornea.   
     
     
         3 . The method of  claim 1 , wherein the laser light energy is applied in an illumination pattern generated by a continuous wave laser. 
     
     
         4 . The method of  claim 1 , wherein the initial curvature is reshaped to a curvature corresponding to a desired topography. 
     
     
         5 . The method of  claim 1 , wherein the region of the cornea to be modified is based at least in part on a deformation map. 
     
     
         6 . The method of  claim 1 , wherein the inducing partial ionization comprises scanning a laser over the region of the cornea to be modified. 
     
     
         7 . The method of  claim 6 , wherein the scanning comprises scanning a femtosecond laser. 
     
     
         8 . The method of  claim 6 , wherein the scanning comprises scanning a femtosecond laser having an average power output from about 10 mW to about 100 mW. 
     
     
         9 . The method of  claim 6 , wherein the scanning comprises scanning a femtosecond laser having a pulse energy of from about 0.1 nJ to about 10 nJ. 
     
     
         10 . The method of  claim 6 , wherein the laser is scanned in a pattern of exposure selected from the group consisting of: a circle and an ellipse. 
     
     
         11 . The method of  claim 6 , wherein the laser is scanned in a pattern of exposure comprising an annulus. 
     
     
         12 . The method of  claim 6 , wherein the laser is scanned in multiple layers of the cornea. 
     
     
         13 . A method of reshaping a patient's cornea from a first shape to a second shape, the method comprising:
 irradiating the cornea with a laser light in the absence of a photosensitizer in or on the cornea, the laser light having energy sufficient to cause ionization of water without causing optical breakdown of molecules of the tissue;   generating reactive oxygen species by ionizing water molecules in or on the cornea; and   inducing cross-linking in the cornea by the generated reactive oxygen species,   wherein the induced cross-linking changes the cornea from the first shape to the second shape.   
     
     
         14 . The method according to  claim 13 , wherein the second shape has a steeper curvature than the first shape. 
     
     
         15 . The method according to  claim 13 , wherein the second shape has a less steep curvature than the first shape. 
     
     
         16 . The method according to  claim 13 , wherein the induced cross-linking has a pattern selected from the group consisting of: a circle and an ellipse. 
     
     
         17 . The method according to  claim 13 , wherein the induced cross-linking has an annular pattern. 
     
     
         18 . A system for reshaping curvature of a region of a cornea having an initial curvature, the system comprising:
 illumination optics configured to project an illumination pattern onto at least a portion of the cornea;   a camera configured to record a reflection pattern from the at least a portion of the cornea;   a control system, coupled to the camera, the control system configured to:
 convert the reflection pattern to a corneal topography, and 
 compare the corneal topography to a desired corneal topography to determine a deformation map; 
   a laser system, configured to induce ionization in the region of the cornea according to the deformation map to reshape the region from the initial curvature to a new curvature; and   a coupling device, configured to stabilize the laser system with respect to the cornea.   
     
     
         19 . The system of  claim 18 , wherein the laser system is configured to cross-link collagen in the cornea according to the deformation map. 
     
     
         20 . The system of  claim 18 , wherein the laser system comprises a femtosecond laser. 
     
     
         21 . The system of  claim 20 , wherein the femtosecond laser is a Nd:Glass femtosecond laser. 
     
     
         22 . The system of  claim 21 , wherein the femtosecond laser has a pulse width of from about 50 to 150 fs. 
     
     
         23 . The system of  claim 21 , wherein the femtosecond laser has an average power from about 11 mW to about 100 mW. 
     
     
         24 . The system of  claim 21 , wherein the femtosecond laser emits light in the wavelength range from about 600 nm to about 1600 nm. 
     
     
         25 . The system of  claim 21 , wherein the femtosecond laser emits light in the infrared frequency range. 
     
     
         26 . The system of  claim 18 , wherein the laser system comprises:
 a high magnification objective lens and   a galvanometer configured to raster a laser beam.   
     
     
         27 . The system of  claim 18 , wherein the laser system further comprises an attenuator. 
     
     
         28 . An apparatus for adapting a laser system for reshaping curvature of a region of a cornea having an initial curvature, the apparatus comprising:
 a control system, adapted to be coupled to the laser system and configured to compare an existing corneal topography of at least a portion of the cornea to a desired corneal topography to determine a deformation map; and   laser modification optics, coupled to the control system and configured to adjust laser output of the laser system, to modify a region of the cornea according to the deformation map.   
     
     
         29 . The apparatus of  claim 28 , wherein the laser modification optics are configured to cross-link collagen in the region of the cornea according to the deformation map. 
     
     
         30 . The apparatus of  claim 28 , wherein the laser modification optics further comprise an attenuator to reduce laser output power.