Lenticules for intrastromal corneal implantation

Abstract

Decellularized and shaped corneal tissue lenticules from allograft and/or xenograft sources and methods of obtaining such lenticules are disclosed. The lenticules are particularly useful as intrastromal lenticular implants in keratoplasty procedures, in which a hinged flap is formed in a patient's cornea and folded back along its hinge to expose the stromal bed of the cornea. The shaped lenticule is then applied to the stromal bed and the flap returned to its original position yielding a new curvature for the cornea and resulting in a desired refractive correction. Fine-tuning of the new refractive power can be achieved by laser ablation either at the same time as implantation or at later time in the event of regression or tonus changes. Methods of decellularizing cornea tissue are disclosed to reduce potential immunogenic reactions on the part of the patient to the implanted lenticule. The lenticules can be further treated to remove immunogenic epitopes. In addition, the posterior and/or anterior surfaces of the lenticule can be treated to assist in intrastromal seating of the lenticule and/or to reduce the likelihood of dislodgement. The methods of forming lenticules can further include preserving at least a portion of the Bowman's membrane. The smoothness of the Bowman's membrane surface also makes it less likely that reopening the flap will dislodge the lenticule.

1 . A decellularized corneal lenticule comprising:
 a lenticular body derived from donor corneal tissue having an anterior surface that includes a Bowman's membrane from the donor corneal tissue and a posterior surface that is formed to provide the lenticule with a desired shape; and   wherein the corneal tissue is decellularized.   
     
     
         2 . The lenticule of  claim 1 , wherein the tissue of the lenticule is from 60% to 100% free of cellular material. 
     
     
         3 . The lenticule of  claim 1 , wherein the posterior surface is cut to a desired shape such that the lenticule can be implanted into a stromal region of a patient's eye to change the refractive power of the cornea. 
     
     
         4 . The lenticule of  claim 1 , wherein the lenticule has a diameter of about 0.5 mm to about 10 mm. 
     
     
         5 . The lenticule of  claim 1 , wherein the lenticule has a thickness of less than or about 350 micrometers. 
     
     
         6 . The lenticule of  claim 1 , wherein the lenticule exhibits low immunoreactivity due to degradation of immunogenic epitopes. 
     
     
         7 . The lenticule of  claim 6 , wherein the lenticule is substantially free of alpha-GAL epitopes. 
     
     
         8 . The lenticule of  claim 6 , wherein the lenticule is substantially free of neu5GC epitopes. 
     
     
         9 . The lenticule of  claim 1 , wherein the posterior surface of the lenticule further comprises a crosslinking agent to promote adherence of the lenticule to a stromal bed when implanted intrastromally into a patient's stromal bed. 
     
     
         10 . The method of  claim 1 , further comprising sterilizing the lenticule using a technique selected from the group consisting of wet agents, gamma radiation, and electron beam. 
     
     
         11 . A method of forming a lenticule from donor corneal tissue comprising:
 removing a portion of tissue from a central region of a donor corneal tissue together with at least a portion of Bowman's membrane of the donor corneal tissue; and   shaping a posterior surface of said donor corneal tissue to provide a lenticule body of a desired shape.   
     
     
         12 . The method of  claim 11 , wherein the steps of removing and shaping are performed simultaneously. 
     
     
         13 . The method of  claim 11 , further comprising removing cellular material from the lenticule. 
     
     
         14 . The method of  claim 11 , further comprising treating the lenticule with a surfactant to remove cellular material from the lenticule. 
     
     
         15 . The method of  claim 11 , further comprising removing at least one immunogenic epitope from the lenticule. 
     
     
         16 . The method of  claim 15 , further comprising removing at least one epithelial or endothelial cell layer from the lenticule. 
     
     
         17 . The method of  claim 14 , wherein the lenticule is enzymatically treated to remove the at least one immunogenic epitope, and wherein the at least one immunogenic epitope is selected from a group consisting of alpha-GAL and neu5GC. 
     
     
         18 . The method of  claim 11 , further comprising treating the posterior surface of the lenticule with a crosslinking agent to promote adherence of the lenticule to a stromal bed when implanted intrastromally into a patient's stromal bed. 
     
     
         19 . A method of forming a lenticule from donor corneal tissue comprising:
 removing a portion of tissue from a central region of a donor corneal tissue by small incision lenticule extraction; and   removing cellular material from the lenticule.   
     
     
         20 . The method of  claim 19  wherein the small incision lenticule extraction is performed with a femtosecond laser. 
     
     
         21 . The lenticule of  claim 1 , wherein the lenticule has a thickness less than or about 200 micrometers. 
     
     
         22 . The lenticule of  claim 1 , wherein the lenticule has a thickness less than or about 100 micrometers.