Eyeworld

52 | EYEWORLD | SUMMER 2025 C ORNEA Reference 1. Linsey K. Use of an eyelid pressure patch concomitantly with a decellularized dehydrated amniotic membrane for ocular surface disease management. Ophthalmol Ther. 2025;14:573– 584. companies that are working toward treatments for PCED and NK indications, but he knows get- ting a product approved and bringing it success- fully to the market can be a challenge. The 'Cinderella story' Dr. Sheppard called Oxervate the "Cinderel- la story" that motivated other companies to develop their molecules for the indication of PCED and/or NK. "The idea of treating PCED has become more sophisticated in that people are looking for drugs that target a meaningful pathway." Oxervate, a recombinant human nerve growth factor, became the first FDA-approved targeted therapy for NK. Dr. Sheppard said it has worked well for these patients, tremendous- ly boosting prescriber awareness of NK, but the expense and prior approvals have been chal- lenges for the drug. Dr. Farid said Oxervate has been "one of the most impactful therapies for corneal disease" in the last decade, addressing unmet need in re- generating corneal nerves, especially in patients with post-herpetic eye disease and severe dia- betes. "It's the best thing we have right now for a lot of these non-healing neurotrophic ulcers," she said, but added, "We've seen there are areas where it goes beyond the nerves, where there's limbal stem cell disease, where there's underly- ing inflammatory disease, mechanical trauma, where Oxervate may not be 100% effective in these corneas. … I think there is room for therapeutics that offer a broader action to the epithelium and the basement membrane matrix to allow epithelial adhesion, migration, and proliferation." Dr. Sheppard said with reasonable patient selectivity, Oxervate can have great success. That being said, patients who are not as se- vere or who are not appropriate candidates for Oxervate have physicians and pharmaceutical companies "looking for the next echelon of potential success." The PCED, NK pharmaceutical pipeline What's great about the pharmaceuticals in the development for PCED and NK, Dr. Farid said, is they all have different mechanisms of action. Some are looking to improve the health of epi- thelial cells so they can migrate and proliferate better, while others are another human recom- binant growth factor that can help with regener- ation of nerves/epithelium, and still others are stem cells. "I think there's going to be space for all of these therapeutics to work in different types of patients and different etiologies," Dr. Farid said. "I think some of that is going to need to be worked out in terms of what was the initial in- citing problem. Was it an issue with the nerves, was this related to mechanical trauma, was this related to chemical burn of the eye? I think a bit of that is going to get teased out, and we may potentially be able to target different types of etiologies with different medications." Here's a brief look at some of the compa- nies working on a PCED or NK pharmaceutical therapy. (This is not an exhaustive list of every company working on a PCED or NK product.) Amber Ophthalmics: NEXAGON (lufepirs- en ophthalmic gel), an unmodified antisense oligonucleotide, inhibits the protein connex- in43, which, according to the company, stops an "exaggerated inflammatory cascade" particular- ly relevant to chemical burns, and helps restore continued from page 51 Persistent Mackie Stage 2 central corneal epithelial defect in chronic herpes zoster ophthalmicus Source: John Sheppard, MD Acute neurotrophic central epithelial defect immediately postop cataract surgery with toric IOL in dominant eye; occult herpetic reactivation Source: John Sheppard, MD

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