Eyeworld Daily News

20 | EYEWORLD DAILY NEWS | MAY 6, 2023 ASCRS ANNUAL MEETING DAILY NEWS D uring an ASCRS Cornea Day session about updates in sur- gical cornea, Deepinder Dhaliwal, MD, gave an over- view of injectable cell therapy and devices for endothelial dysfunction. She spoke about endothelial keratoplasty. Challenges with this are that there is a limited donor cornea supply (1 for every 70 disease eyes); keratoplasty can be challenging, complex, and invasive; post-surgi- cal complications can occur (both graft-related and steroid related); there are unfavorable economics; and there are lengthy procedure times. There are opportunities, how- ever. It's an efficient procedure; it increases availability and accessibil- ity; there is high surgeon adoption; and it reduces post-surgical compli- cations. What are the current and future options? Dr. Dhaliwal mentioned cor- neal "rejuvenation" (DSO), injecting human corneal endothelial cells, and using a device instead of cells. DSO is available, but one issue is there needs to be a faster and more predicable recovery. Dr. Dhaliwal said she loves using DSO in the right patient. She noted that there are medical therapies in the works that can stimulate migration and prolifer- ation of endothelial cells. Next, Dr. Dhaliwal discussed injectable human corneal endothe- lial cells, noting technology being developed by Aurion and Emmecell. These are fully differentiated cells that are produced from other ma- ture, differentiated cells. They have all the inherent properties of specific, differentiated cells with minimal im- mune issues. They are cost efficient to produce at scale. But this is a finite option, she said, as proliferation requires new donor cells after a spe- cific number of passages. One donor could potentially treat upwards of 100 patients. The Emmecell technology involves human corneal endothelial cells that are expanded in culture, and donor HCECs are combined with magnetic nanoparticles. The magnet- ic cells are injected in the anterior chamber, and an external magnetic eye patch facilitates localization and integration of the magnetic HCECs into the endothelial layer. This option addresses the root problem of too few HCECs. It's a non-surgical proce- dure and easy to perform, with rapid recovery, no donor limits, and it's safe and repeatable. First-in-human clinical trial data showed an excellent safety and efficacy profile, and a Phase 1b trial showed no safety issues and early signs of efficacy (no inflammation, no infection, no IOP elevation). An FDA IND has been approved for a second U.S. protocol, and random- ized, double-masked study is being initiated. The Aurion approach uses en- dothelial cells that are stripped from a healthy donor cornea, cultured, and expanded in a proprietary manufacturing process. Degener- ated endothelium is mechanically removed from the recipient cornea. Cultured cells are placed in sus- pension with a ROCK inhibitor and loaded into a syringe. The cell sus- pension is injected into the patient's anterior chamber, and the patient is placed in a prone position for 3 hours to enable settling of endothelial cells. This method comes from the work of Shigeru Kinoshita, MD, PhD. Aurion received PMDA approv- al in Japan in March 2023, and 130 subjects have been treated via multiple trials and surgeons so far in Japan and El Salvador. They are targeting the first clinical trial in the U.S. for this method in summer 2023. Dr. Dhaliwal wrapped up by discussing the EndoArt (EyeYon Medical), an optically clear, flexible, biocompatible, dome-shaped im- plant. It's 6.5 mm in diameter and 50 microns thick and is made from a non-biodegradable synthetic poly- mer. It provides a mechanical barrier between the aqueous and the cornea. It's an impermeable barrier to fluid. It decreases aqueous going into the corneal stroma, but nutrients enter from the periphery, she said. This product has FDA breakthrough designation and is CE approved and approved in India. John Berdahl, MD, also discussed endothelial cell therapy clinical trials. He first stressed the hurdles with keratoplasty: challenging, complex, invasive surgery; limited worldwide donor cornea supply; and onerous patient recovery. Cell therapy would offer an ample cell supply with a minimally invasive procedure that is less onerous for patients in postop recovery. Dr. Berdahl noted the trial from Emmecell and several from Aurion. The work in Japan and El Salvador from Aurion has seen more than 150 procedures performed, he said. Across all completed trials, Dr. Berdahl said endothelial cell ther- apy has shown improvement in BCVA and central corneal thickness. Therapy was well tolerated with a favorable safety profile, he said. Sim- ilar results have been demonstrated regardless of surgeon or geographic location. Editors' note: Dr. Dhaliwal has financial interests with a variety of ophthalmic companies. Dr. Berdahl has financial interests with a variety of ophthalmic companies. Examining corneal cell therapy

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