A Biosynthetic Alternative to Human Donor Tissue for Inducing Corneal Regeneration: 24-Month Follow-Up of a Phase 1 Clinical Study

Sci Transl Med 25 August 2010:
Vol. 2, Issue 46, p. 46ra61
DOI: 10.1126/scitranslmed.3001022
Research Article
A Biosynthetic Alternative to Human Donor Tissue for Inducing Corneal Regeneration: 24-Month Follow-Up of a Phase 1 Clinical Study
Per Fagerholm1,*, Neil S. Lagali1,*, Kimberley Merrett2, W. Bruce Jackson2, Rejean Munger2, Yuwen Liu3, James W. Polarek4, Monica Söderqvist5 and May Griffith1,2,†

+ Author Affiliations

1Departments of Clinical and Experimental Medicine, and Ophthalmology, Faculty of Health Sciences, Linköping University, Cell Biology Building, Level 10, SE-581 83 Linköping, Sweden.
2University of Ottawa Eye Institute, Ottawa, Ontario, Canada K1H 8L6.
3CooperVision Inc., 5870 Stoneridge Drive, Suite 1, Pleasanton, CA 94588, USA.
4FibroGen Inc., 409 Illinois Street, San Francisco, CA 94158, USA.
5Synsam Opticians, Box 362, Trädgårdstorget 2, 581 03 Linköping, Sweden.

1Departments of Clinical and Experimental Medicine, and Ophthalmology, Faculty of Health Sciences, Linköping University, Cell Biology Building, Level 10, SE-581 83 Linköping, Sweden.
2University of Ottawa Eye Institute, Ottawa, Ontario, Canada K1H 8L6.
3CooperVision Inc., 5870 Stoneridge Drive, Suite 1, Pleasanton, CA 94588, USA.
4FibroGen Inc., 409 Illinois Street, San Francisco, CA 94158, USA.
5Synsam Opticians, Box 362, Trädgårdstorget 2, 581 03 Linköping, Sweden.
†To whom correspondence should be addressed. E-mail: may.griffith@liu.se
AbstractCorneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.