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‘Remarkable’ transitions underway in corneal transplantation
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According to Eye Bank Association of America statistics, endothelial keratoplasty is the most frequently performed corneal transplant in the U.S. The transition from penetrating keratoplasty to endothelial keratoplasty occurred over the last 10 years. In 2005, 42,063 PK procedures vs. 1,398 EK procedures were performed in the U.S. In 2014, PK accounted for 19,294 transplants and EK for 25,965.
This remarkable transition to EK for endothelial failure, whether from Fuchs’ dystrophy or postsurgical bullous keratopathy, is quite impressive in speed and magnitude, and it is worldwide in scope. Corneal surgeons are now in the midst of a transition from thicker endothelial transplants containing endothelium, Descemet’s membrane and stroma (DSEK) to those containing Descemet’s membrane and endothelium alone (DMEK). The next logical step is to develop a technique for endothelial regeneration or replacement.
In my laboratory at the University of Minnesota between 1980 and 1990, working with brilliant cell biologist Debra Skelnik, we learned to culture human endothelial cells. We learned that in vitro in a culture dish these endothelial cells could be plated onto a human cornea denuded of endothelium and the endothelium would attach and function. We learned that a central 4 mm to 5 mm endothelial injury induced by freezing in the central cornea would heal through endothelial sliding over a month or two. In endothelial cell cultures from younger corneas, endothelial mitosis was observed. We learned to fortify donor corneas with additional cultured endothelium to create donor corneas with routine cell counts of more than 3,000. We learned that under the influence of some growth factors, the endothelium could be induced to undergo mitosis. A summary of this work is published in the Transactions of the American Ophthalmological Society, representing the then-required thesis for membership.
Twenty years later, research into endothelial regeneration and replacement continues with evidence that cultured endothelial cells might be transplanted into a patient’s anterior chamber, adhere and function, restoring vision. This would be the ultimate endothelial transplant, and one can imagine using a patient’s own stem cells in culture to generate a replacement endothelium that would never reject.
Rho kinase inhibitors are showing superior promise to growth factors for inducing mitosis when corneal failure is secondary to a reduced cell count, such as occurs following surgical trauma. Those of us who have performed transplants for decades have all observed late clearing of a primary donor failure, presumably from migration of peripheral host endothelial cell onto the donor graft. This observation suggests that a simple removal of Descemet’s membrane in patients with Fuchs’ dystrophy with a localized central patch of guttata might be effective. A small number of successful cases encourages more research into this approach and further search for agents such as the promising Rho kinase inhibitor work pioneered by Shigeru Kinoshita to induce mitosis and return central endothelial cell counts to normal.
Progress continues, limited only by human and capital resources. I can imagine eye banks in another decade offering cultured endothelial cells as a donor alternative to the EK approaches of today, as well as medical therapy to replace the endothelium lost in a routine cataract operation. Both would represent disruptive advances, and both are very likely to transition from research bench to bedside.