Cornea
Spring 2026

by Liz Hillman
Editorial Co-Director

Biologics may dominate in the retina subspecialty, but cornea is beginning to see interest with these products as well, especially for immune-mediated or severe ocular surface diseases and even corneal dystrophies.

“Pharmacological options to date, such as corticosteroids, have limited scope of action in reducing inflammation. On the other hand, biologics can replace diseased or damaged cells or can supplement natural pathways, and they have the potential to heal, restore, or regenerate the cornea,” said Stephen Pflugfelder, MD. “I think it is the consequence of greater knowledge about cornea physiology, cellular constituents, and pathways that promote homeostasis, healing, and suppress damaging inflammation.”

Biologics are already being used for some conditions affecting the cornea, but many of them are systemic or subconjunctival. The emergence of topical biologics for conditions affecting the cornea is exciting, said Anat Galor, MD.

“They’re going for diseases that we currently use topical therapy for but may not be super happy with the options we have, like dry eye disease and chronic uveitis,” Dr. Galor said, explaining that chronic use of steroids, for example, is not ideal, and having a steroid-sparing option for conditions like chronic uveitis would be great.

“We need to find biologics that work and make them accessible and affordable. The benefit will be that they will be more targeted approaches to disease. A lot of the current therapies we throw at the ocular surface fall into categories of either generating tears or suppressing inflammation, which are shotgun approaches,” said Winston Chamberlain, MD, PhD.

If dry eye/ocular surface disease is the target issue, Dr. Chamberlain acknowledged that while inflammation is a strong component, there are multiple other variables that could drive symptoms. “What’s appealing about biologics is that we may be targeting very specific chemical pathways in certain patients, which may reduce ocular side effects and be more targeted to actually address the needs of patients.”

While biologics for ocular surface disease are attractive for their potential to target root causes, there are some hurdles that need to be overcome. Dr. Chamberlain said biologics are usually macromolecules, recombinant proteins, or “soups of proteins” that can have storage challenges, delivery issues due to the mucosal surface of the eye, especially in drop form. In addition, they’re expensive to produce.

“I think refrigeration is a key component that would be required for some of the biologic therapies that we consider,” Dr. Chamberlain said. “Then there are other variables like overall stability … the kind of material they’re stored in and how that might interact with the biologic’s chemistry. … How easy is it for a patient to acquire, store and administer the medications?”

He gave the example of cenegermin (Oxervate, Dompé), which is a recombinant nerve growth factor that is shipped to patients periodically over the 8-week course of treatment. “Patients get two to three shipments directly from a distribution pharmacy during that time, so there’s logistical issues associated with applying those, getting them to the patient, and keeping them stable so that they’re effective when the patient uses them in their eye,” Dr. Chamberlain said.

Then there’s the issue of diagnostics—is diagnostic technology advanced enough to detect the very specific pathways that would make biologics beneficial? According to Dr. Chamberlain, “we’re getting there, but we certainly aren’t there yet for many aspects of ocular surface disease. There are still aspects of disease that we don’t understand. Molecular and cellular mechanisms may not be obvious from patient complaints or what we’re seeing on the surface.”

Dr. Chamberlain said there are modalities that can help piece together some of the diagnostic deficiencies on the surface, such as tear film osmolarity, interferometers that can detect how much lipid is in the tear film, meibomian gland imaging, and infrared imaging that can look at healing processes. “I think we’re getting better at making observations about deficiencies, but we still don’t have a great understanding of what some of the underlying cellular and molecular mechanisms are that drive symptoms in a particular patient,” he said.

In addition to cenegermin, the cornea subspecialty has a long history of using biologics such as serum tears, platelet-enriched plasma, and amniotic membrane. Dr. Pflugfelder also mentioned insulin drops for epithelial defects, neurotrophic keratitis, and dry eye.

The success other medical specialties have had with biologics has ophthalmology looking for additional options.

Thymosin β-4

Thymosin β-4, which is being developed by RegeneRx Biopharmaceuticals and its partner ReGenTree as RGN-259 eye drops, Dr. Chamberlain said, is following a similar path to cenegermin in that it’s being studied as a treatment for NK, but it drives a different cellular signal—a signal for cell migration. “Breakdown of epithelial layers on the ocular surface or a break in intracellular adhesion molecules can lead to geographic defects or small, microscopic fissures on the surface that promote inflammation. Thymosin β-4 has the potential to drive migration across denuded areas and cause these cells to integrate with each other, which will drive healing on the surface,” he explained. Additional applications for the ocular surface could be targeted with thymosin β-4 as well. RGN-259 has completed one Phase 3 clinical trial for neurotrophic keratopathy and is conducting additional Phase 3 clinical trials for this indication. It has also investigated the drop for moderate to severe dry eye disease.

Anti-TNFα

Dr. Galor talked about topical anti-TNFα being developed as licaminlimab by Oculis for treatment of dry eye and potentially uveitis.

“What they have found is that there is a genetic polymorphism in the TNF1 receptor that predicts whether you’re going to respond better to this biologic,” she said. “It doesn’t mean that if you don’t have this polymorphism, you won’t respond. But instead of saying, ‘We’re going to go after the entire pie of dry eye,’ they’re saying … ‘We’re going to try to help you identify the people who may need our product.’”

Dr. Galor said, at least at present, ophthalmology isn’t quite geared toward this level of precision medicine, but she hopes it’s trending in that direction. “Oncology is showing us what is possible. Now with these bioinformatics and AI, it should be possible to do a better job in drug selection,” she said.

Oculis has completed Phase 2 clinical trials with licaminlimab and is expected to begin a registrational trial.

IL-1 receptor antagonists

IL-1 receptor antagonists have been researched for corneal conditions like dry eye and allergic conjunctivitis but haven’t gotten much momentum, Dr. Chamberlain thinks, in part due to limited trial designs. Dr. Chamberlain explained that IL-1 is an early mediator of inflammation, so blocking it can have beneficial downstream effects.

“In my mind, that’s a true target for a biologic,” he said. “IL-1 receptor antagonists act on an upstream protein to block an early signal in inflammation.”

Lacripep

“Lacripep, a first-in-class topical therapy based on the lacritin protein, being developed by Tear Solutions, is a trophic peptide that seems to drive survival, proliferation, and wound healing actions of epithelial cells,” Dr. Chamberlain said. It is being investigated for Sjögren’s dry eye and more generalized, moderate to severe dry eye.

Epithelial and endothelial cell therapies

Cell therapies for corneal conditions, such as endothelial disease and epithelial disorders, have caused excitement in recent years. Allogenic corneal endothelial cell therapy by Aurion has provided positive topline results from its Phase 1/2 study.

CALEC (cultivated autologous limbal epithelial cells) being developed at Mass Eye and Ear has completed a Phase 1/2 study, restoring the corneal surface in patients who had surface damage or limbal stem cell deficiency.

Though not a cell therapy but related to regeneration of corneal endothelial cells, work is being done by Trefoil Therapeutics to develop TTHX1114, fibroblast growth factor 1. Phase 1/2 research has been completed with Phase 2 data showing positive regenerative and visual outcomes.

Exosomes

“There is a long list of biologics that are used for non-ocular conditions that may be useful for ocular conditions, and we just don’t know because we don’t use them that often.”

Anat Galor, MD

Dr. Chamberlain brought up exosomes, extracellular vesicles that can carry proteins, lipids, or mRNA, which are being explored as a cell-free regenerative therapy that could help with inflammation, wound healing, and more. Some of the companies exploring exosomes for ocular surface conditions at preclinical and clinical stages include Kimera Labs, ExoCoBio, EV Therapeutics, and some in academia.

“There is a long list of biologics that are used for non-ocular conditions that may be useful for ocular conditions, and we just don’t know because we don’t use them that often,” Dr. Galor said about the ripe future for the field of biologics in cornea.

Editors’ note: This is not an exhaustive list of all biologic options or companies working on biologics for corneal conditions.

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About the physicians

Winston Chamberlain, MD, PhD
Affiliate Professor of Ophthalmology
Northwest Permanente, P.C.
Casey Eye Institute
Oregon Health & Science University
Portland, Oregon

Anat Galor, MD
Professor of Ophthalmology
Bascom Palmer Eye Institute
Miami, Florida

Stephen Pflugfelder, MD
Professor and James and Margaret Elkins Chair in Ophthalmology
Baylor College of Medicine
Houston, Texas

Relevant disclosures

Chamberlain: ReGenTree site investigator
Galor: Alcon, Bausch + Lomb, Dompé, Oculis
Pflugfelder: None

Contact

Chamberlain: wdchamberlain@gmail.com
Galor: AGalor@med.miami.edu
Pflugfelder: stevenp@bcm.edu