Eyeworld

72 | EYEWORLD | DECEMBER 2022 C ORNEA expand and enlarge to form tight junctions with remaining endothelial cells. "Thus, by stripping Descemet's membrane in the cornea's central area, the remaining endothelial cells at the periphery will likely enlarge and gravitate to the center," he said. "However, in some cases, enlarged corneal endothelial cells may cease to maintain their pump and barrier functions, thereby increasing corneal edema and poten- tially resulting in hazy vision in the long term." He added that this procedure is limited to those corneas with a small area of central guttata, and there can be a long recovery period. Dr. Berdahl said it's unknown exactly how cell redistribution works with DSO. It is likely at least partially driven by contact inhibition. Endothelial cells stop growing when they touch other endothelial cells, and by removing an area of endothelial cells, the endothelial cells migrate to cover the cells that have been removed be- cause there is no longer an adjacent contact. Dr. Berdahl said that he has not used DSO in clinical practice and thinks the majority of en- dothelial dysfunction treated surgically is with DMEK or DSAEK, with the exception of some cases where only central guttata are present. Dr. Yeu also noted that patients have a longer recovery with DSO; it could take up to 8 weeks for vision to recover with a lot of corneal swelling in the interim. However, she does see its potential in the future because it doesn't have the allograft rejection. "If we could do DSO with a ROCK inhibitor, there may be patients who would consider that versus scraping and cells," she said. Moving forward Dr. Giegengack stressed the potential for cell therapy, not just in the U.S. but also internation- ally. Noting that he's done humanitarian work in developing countries, Dr. Giegengack said that corneal transplants tend to have lower success rates there than in the U.S. "I think cell therapy has the potential to decrease that discrepancy," he said. "Because cell therapy is a less complex procedure, I think it will potentially require less follow-up and have fewer complications. [These are] especially important benefits for patients in underserved parts of the world." Dr. Yeu mentioned the possibility of having the option to cryopreserve. This isn't a foreign idea, she said, noting that it's used for amniot- ic membranes. She said it would "change the way we think" to be able to use these cells and defrost them when you need them. She added that it's been promising to see patients in studies so far who had significant visual issues, vision worse than 20/40 and up to 20/800, some with worse than 600-micron corneas. "To see these types of cornea patients at the level they're at is very promising," Dr. Yeu said. "It is heartening to know that corneal endothelial dystrophies are now the focus of multiple avenues of research and development," Dr. Holland said. "I think these innovations will yield safe and efficacious options for patients suffering from corneal endothelial diseases. For example, I think that cell therapy might be used across the entire disease spectrum, which would potentially mean the ability for us to treat pa- tients earlier in the course of their disease. I do think endothelial cell therapy will become the treatment of choice for the majority of patients with endothelial disease." continued from page 71 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 antiprolif- erative factors that naturally prevent endo- thelial 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 injec- tions 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 effective- ness of the body's own endothelial cells. This helps to decrease the chances of rejection. Relevant disclosures Berdahl: Aurion Biotech Giegengack: Aurion Biotech Holland: Aurion Biotech Yeu: Aurion Biotech Contact Berdahl: john.berdahl@ vancethompsonvision.com Giegengack: mgiegeng@wakehealth.edu Holland: eholland@holprovision.com Yeu: eyeulin@gmail.com

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