CORNEA EWAP MARCH 2023 35 in that we have very good treatment options for endothelial dysfunction, DSAEK and DMEK, both of which set a high bar for cell therapy,” Dr. Giegengack said. “For patients in the U.S. who qualify for DMEK/DSAEK procedures, increasingly we are opting for DMEK since patients are generally able to see better and recover more rapidly than with DSAEK. But due to the complexity of surgery, we cannot perform DMEK on all patients, so DSAEK is still a viable option.” Dr. Giegengack said that for cell therapy to be a viable treatment option, it would need to be at least as good as DMEK. “In my experience with the cell therapy patients I’ve treated (and who I’ve observed my colleagues treat) in the OUS studies, the preliminary findings are promising,” Dr. Giegengack said, noting that corneal edema is reduced, and visual acuity is improved significantly. He added that cell therapy is a less complex procedure to perform than DMEK, and postop recovery for patients is shorter. “I’m hopeful that cell therapy will ultimately enable ‘DMEK-like’ improvements in vision to a larger group of patients,” Dr. Giegengack said. This new cell therapy option could also be beneficial on a global scale by enabling easier access worldwide. Globally, corneal tissue supply is a big challenge, Dr. Giegengack said. “Even in the U.S., with an upswing in DMEK procedures, surgeons are requiring more specific donor tissue, so tissue supplies are running short,” he said. “Cell therapy can alleviate these supply challenges. Dr. Kinoshita’s exciting discovery was to get corneal endothelial cells to replicate in vitro (they do not regenerate naturally in vivo).” Dr. Yeu said that seeing this work in action has been incredibly gratifying. “It’s exciting because it’s just cells plus a formulation of ROCK inhibitor.” It allows for limbus-to-limbus adhesion of cells. With allograft transplants, “we’re only able to replace the central 80%.” As a result, there are problems with peripheral edema, Dr. Yeu said, and those patients with peripheral pathology can’t be treated well. “So far with the work we’ve done, these patients are able to have corneal thinning that gets them to the same type of results that we see with DSAEK and DMEK by month 1 to month 6,” Dr. Yeu said. She added that being able to get patients off steroids, or at least to minimal steroid use, is another benefit. This helps reduce some issues with ocular hypertension and glaucoma. “Not only are rejection rates lower, but the IOP issues are much lower, and these corneas look incredible,” she said, adding that the possibility for patients to be able to survive on one transplant would be amazing. Dr. Yeu also commented on the technique used with corneal endothelial cell therapy, noting that it’s even easier than DSAEK and DMEK because instead of a stripping, it’s a polishing to remove residual endothelium using a silicone tip on a cannula. It’s a familiar technique that any anterior segment surgeon can do. “It also opens up the opportunity to treat everything from early corneal edema to severe corneal edema as a first-line therapy,” she said. Dr. Berdahl agreed that surgical accessibility is an advantage of endothelial cell therapy. Endothelial keratoplasty is a highly technical procedure that’s performed primarily by corneal surgeons, but endothelial cell therapy would be a more accessible technique. It would also likely have a decreased rejection risk because the cells are antigenically more neutral. “The procedure can control exactly how many endothelial cells are injected, the surgical technique is less technical, and we can avoid an air bubble in the anterior chamber and avoid the potential complications of flattening the chamber.” In addition to Aurion Biotech, Dr. Berdahl mentioned that Emmecell is exploring endothelial cell therapy options. Other treatments Another advancement is Descemet’s stripping only (DSO). Corneal endothelial cells will naturally expand to form tight junctions with other corneal endothelial cells, Dr. TTHX1114 growth factor Another interesting option in this space is TTHX1114 growth factor, currently in studies from Trefoil Therapeutics. “We know that the eye contains antiproliferative factors that naturally prevent endothelial cell regeneration in vivo,” Dr. Holland said. These factors keep those cells in cell cycle “arrest” mode, which prevents cell regeneration in vivo. Trefoil Therapeutics has a novel approach for injecting growth factor into the anterior chamber of the eye to stimulate endothelial cell reproduction in vivo. This treatment requires weekly injections over a 4-week course. “If this approach works, it would have significant benefits as compared to endothelial keratoplasty,” Dr. Holland said. This is not the injection of endothelial cells, rather injection of a pharmaceutical growth factor, Dr. Berdahl said. The benefit of this approach is that this pharmaceutical growth factor could increase the effectiveness of the body’s own endothelial cells. This helps to decrease the chances of rejection.
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