EyeWorld Asia-Pacific September 2011 Issue

54 EW CORNEA September 2011 Human trials show promise for bioengineered corneas by Rich Daly EyeWorld Contributing Editor The first non-prosthetic corneal substitute implanted in human eyes restored optical- mechanical function and some physiologic function among recipients in a recent Phase I clinical trial T he 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 normal eye pressure, according to May Griffith, PhD, researcher, clinical and experimental medicine department, Linkoping University, Linkoping, Sweden, and colleagues. Most importantly, vision was restored in the patients while immune rejection was avoided without prolonged immunosuppressive therapy. Such findings bear out the early promise of artificial corneas developed as an alternative to donor corneas. “The main advantage to bioengineered or artificial corneas is that there should not be an immune response because there is no donor,” said Christopher N. Ta, MD, associate professor of ophthalmology, Stanford University School of Medicine, Stanford, Calif., USA, who has implanted the corneas. “The inflammatory response may depend on how it is engineered and the types of material used.” Additionally, such corneas eliminate the possibility of donor- to-recipient 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 supplementing the human donor cornea supply with a tissue- engineered alternative,” wrote Dr. Griffith and her colleagues in the February issue of Expert Review of Medical Devices. Despite the early positive results, 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 replacements of damaged corneas, which stand at about 10 million worldwide. Among the advantages of the biosynthetic cornea is that its material 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 advantages over traditional replacement corneas: implantability using standard surgical tools and procedures with no additional surgical training required. Limited corneas studied So far, researchers have implanted the bioengineered corneas in patients with keratoconus and central scarring, which are conditions that spare the recipient corneal endothelium. This allows the use of the anterior lamellar keratoplasty (ALK) technique they have used to implant the bioengineered corneas. Researchers plan to extend the use of biosynthetic corneas to conditions affecting the entire stroma, such as dystrophies or extensive scarring. Transplants in these corneas would use deep ALK to replace the full stromal thickness. Such use of the bioengineered lenses “could provide the added benefit of minimizing vision- limiting 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-thickness penetrating keratoplasty. However, humans’ non-regenerating endothelium would require use of cultivated endothelial cells or an alternative approach. Among the unanswered questions surrounding biosynthetic corneas is why the superficial corneal nerve regeneration and partial sensitivity returning in recipients 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 regeneration is necessary”, they noted. Also unresolved so far by the research is whether keratocyte repopulation—necessary to constitute a true “regeneration” of the stroma—is required within the initial cell-free biosynthetic material. They found keratocyte invasion of the central implanted region began only 12 to 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 repopulation of the biosynthetic material is needed or even desirable. Rapid regeneration may be incompatible with corneal stability, transparency, good visual outcome, and a predictable postoperative course. We may not want to tinker too much with a good thing,” Dr. Griffi th and her colleagues noted. EW Editors’ note: Dr. Griffith has a financial interest with Eyegenix Inc. (Honolulu, Hawaii, USA), a subsidiary of Cellular Bioengineering Inc. and is the holder of a patent application related to the formulation of the biomaterials for use in corneal transplantation. Dr. Ta has no financial interests related to his comments. Contact information Griffith: may.griffith@liu.se Ta: 650-725-6995 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 Ophthalmology presentation, May 1, 2011 A) Biosynthetic cornea; B) surgical implantation by lamellar keratoplasty; C) 1 day post-op; D) 24 months post-op Source: May Griffith, PhD