Eyeworld

EW FEATURE 52 by Rich Daly EyeWorld Contributing Editor Human trials show promise for bioengineered corneas T he first non-prosthetic corneal substitute im- planted in human eyes re- stored optical-mechanical function and some physio- logic function among recipients in a recent Phase I clinical trial. The recently completed Swedish clinical study on the safety and functionality of a biosynthetic cornea in 10 recipient patients found it supported the in-growth of endogenous cells and nerves, as well as functions like touch sensation, development of tear film, and nor- mal eye pressure, according to May Griffith, Ph.D., researcher, clinical and experimental medicine depart- ment, Linkoping University, Linkop- ing, Sweden, and colleagues. Most importantly, vision was re- stored in the patients while immune rejection was avoided without pro- longed immunosuppressive therapy. Such findings bear out the early promise of artificial corneas devel- oped as an alternative to donor corneas. "The main advantage to bio- engineered or artificial corneas is that there should not be an immune response because there is no donor," said Christopher N. Ta, M.D., asso- ciate professor of ophthalmology, Stanford University School of Medi- cine, Stanford, Calif., who has im- planted the corneas. "The inflammatory response may depend on how it is engineered and the types of material used." Additionally, such corneas elimi- nate the possibility of donor-to-recip- ient pathogen transmission, which is another serious risk inherent to the use of human donor tissue, he said. The early human trial results "brought us one step closer to sup- plementing the human donor cornea supply with a tissue-engi- neered alternative," wrote Dr. Griffith and her colleagues in the February issue of Expert Review of Medical Devices. Despite the early positive re- sults, Dr. Griffith and her colleagues doubt the bioengineered corneas will replace human donor corneas in "the foreseeable future." But the biosynthetic corneal replacements could help meet the demand for re- placements of damaged corneas, which stand at about 10 million worldwide. Among the advantages of the biosynthetic cornea is that its mate- rial can be mass-produced, so it's far less expensive than human donor tissue. Traditional donor corneas, which have been used for more than 100 years, have numerous built-in expenses linked to their procuring, storing, handling, and testing for pathogens and biocompatibility. "The ideal world would have off-the-shelf bioengineered artificial corneas so that we don't need eye banks and don't need to harvest donor tissue," Dr. Ta said. "They have a much longer shelf life and could be implanted anywhere in the world without the infrastructure needed for donor tissue." For surgeons, the artificial cornea offers the following advan- tages over traditional replacement corneas: implantability using stan- dard surgical tools and procedures with no additional surgical training required. Limited corneas studied So far, researchers have implanted the bioengineered corneas in pa- tients with keratoconus and central scarring, which are conditions that spare the recipient corneal endothe- lium. This allows the use of the ante- rior lamellar keratoplasty (ALK) technique they have used to implant the bioengineered corneas. Researchers plan to extend the use of biosynthetic corneas to condi- tions affecting the entire stroma, such as dystrophies or extensive scarring. Transplants in these corneas would use deep ALK to re- place the full stromal thickness. Such use of the bioengineered lenses "could provide the added benefit of minimizing vision-limit- ing posterior interface haze that was present, to varying degrees, in the patients in our recent study," wrote Dr. Griffith and colleagues. Additionally, the ability to tailor biosynthetic materials for specific applications may allow implantation of biosynthetic corneas in full-thick- ness penetrating keratoplasty. How- ever, humans' non-regenerating endothelium would require use of cultivated endothelial cells or an al- ternative approach. Among the unanswered ques- tions surrounding biosynthetic corneas is why the superficial corneal nerve regeneration and par- tial sensitivity returning in recipi- ents is "gradual and variable." Similarly, slow reinnervation often takes place in human donor corneas, and regeneration of deeper stromal nerves into human donor tissue is "a very slow to nonexistent process," Dr. Griffith and colleagues noted. However, the positive visual outcomes and clinical success of the implant "raise the question of whether complete nerve regenera- tion is necessary," they noted. Also unresolved so far by the re- search is whether keratocyte repopula tion—necessary to consti- tute a true "regeneration" of the stroma—is required within the ini- tial cell-free biosynthetic material. They found keratocyte invasion of the central implanted region began only 12-18 months post-op and was still limited at the 3-year post-op limits of the study. "From a clinical perspective, it is questionable whether rapid, total reinnervation or keratocyte repopu- lation of the biosynthetic material is needed or even desirable. Rapid re- generation may be incompatible with corneal stability, transparency, good visual outcome, and a pre- dictable postoperative course. We may not want to tinker too much with a good thing," Dr. Griffith and her colleagues noted. EW Editors' note: Dr. Griffith has a financial interest with Eyegenix Inc. (Honolulu), a subsidiary of Cellular Bioengineering Inc. and is the holder of a patent application related to the for- mulation of the biomaterials for use in corneal transplantation. Dr. Ta has no financial interests related to his com- ments. February 2011 CORNEA May 2011 AT A GLANCE Three-year post-op results in first Stage I trial of bioengineered corneas: • Central corneal thickness remained constant • No transparency change for 2 years, after which transparency was altered • Slow repopulation of keratocytes • Partial ocular surface sensitivity was restored after 3 years Source: Abstract, Association for Research in Vision and Ophthalmol- ogy presentation, May 1, 2011 A) Biosynthetic cornea; B) surgical implantation by anterior lamellar keratoplasty; C) 1 day post-op; D) 24 months post-op Source: May Griffith, Ph.D.

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