Eyeworld

SUMMER 2025 | EYEWORLD | 51 C CHANGING MINDSETS by Liz Hillman Editorial Co-Director About the physicians Marjan Farid, MD Director of Cornea, Cataract, and Refractive Surgery Gavin Herbert Eye Institute University of California, Irvine Irvine, California John Sheppard, MD Professor of Ophthalmology Eastern Virginia Medical School Medical Director Lions Eye Bank of Eastern Virginia Regional Medical Director EyeCare Partners Norfolk, Virginia F or about 7 years, there has been one FDA approved treatment for neurotroph- ic keratitis (NK): Oxervate (cenerger- min-bkbj ophthalmic solution, 0.002%, 20 mcg/mL, Dompe). Before that, there was nothing. Now pharmaceutical options for NK—and persistent corneal epithelial defect (PCED) more generally—in the pipeline number about a half dozen. "Oxervate did an amazing job in terms of opening this whole space for the treatment of non-healing ocular surface epithelial defects," Dr. Farid said. "Since that therapeutic became available, our knowledge in this space has evolved. We're understanding more about the pathophysiology of the ocular surface intricacies of the interplay between the epithelial cells, the limbal stem cells, the corneal nerves, and this complex interdigitation that creates a smooth corneal surface that's important for the immuni- ty of the eye as well as vision." Dr. Farid said this area has expanded with a lot of other potential mechanisms of action that are being looked at for the management of these ocular surface wounds. "The interesting thing," said John Sheppard, MD, "is that with DEWS I, no one mentioned a neurogenic component to dry eye. We like to think that the previous century was the era of tear replacement. The first decade of this century was the decade of inflammation in dry eye and surface disease in general. The second decade was the decade of meibomian gland dysfunction. This decade has become the decade of neurogenic ocular surface disease." Dr. Farid and Dr. Sheppard shared their insights and opinions about some of the options in the pipeline for NK and PCED. But first … Is NK the only etiology for persistent corneal epithelial defect? Dr. Farid said the discussion about NK and PCED treatment needs to start with the differ- ence between the two. Dr. Farid said PCED is the larger umbrella definition of many things that can impact corneal healing, and it encompasses neurotrophic keratitis. "Neurotrophic keratitis is one form of persistent corneal epithelial defect, but there are others. You look at neurotrophic keratitis as a difficulty of the corneal nerves specifically; when you look at persistent corneal epitheli- al defect, it's not just about the nerves of the cornea but also the ability of the epithelium to migrate to regenerate the epithelial cells to communicate and interact with each other as well as with stromal fibroblasts and their ability to adhere to the underlying basement mem- brane of the cornea. Where does the epitheli- um of the cornea transform into disease of the nerves of the cornea? You need healthy epitheli- um to release trophic factors to keep the nerves healthy and vice versa; you also need the nerves to release trophic factors to keep the cornea healthy." Dr. Sheppard said PCED is "clearly not monolithic in terms of its etiology." "It's a multi-factorial situation with many overlapping features," he said, calling it a significant diagno- sis that is actively being pursued. But he called the PCED market "elusive." Patients with PCED are "wandering or- phans," and once you find one, you develop a long-term relationship with that patient to help them in their healing journey, he said. "It's not like they're coming in the door all the time, and there are so many companies with high hopes for this," Dr. Sheppard said. As a cornea specialist, he thinks the space for treat- ment development is exciting. As an investor, he's wary. He said he hopes for the best for the The robust NK and PCED pharmaceutical pipeline continued on page 52 Anterior basement membrane dystrophy-associated recurrent corneal erosion syndrome causing persistent epithelial defect and painful foreign body sensation Source: John Sheppard, MD

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