Researchers have reported encouraging preclinical results for a novel rexinoid-based eye drop they say could offer a new approach to treating dry eye disease while potentially avoiding some of the long-term risks associated with steroid therapy.
The researchers from Baylor College of Medicine in the US and Okayama University in Japan published their findings in the April 2026 edition of Investigative Ophthalmology & Visual Science.
The study investigated the effects of the experimental compound NEt-3IB in a mouse model of desiccating stress-induced dry eye disease. The research found the topical treatment reduced inflammation, protected the ocular surface and preserved conjunctival goblet cells, which are essential for tear stability and lubrication.
The researchers said the findings support further investigation in human clinical studies.
“Dry eye disease is a common condition that causes irritation, redness and blurred vision,” said corresponding author Dr Stephen Pflugfelder, professor and James and Margaret Elkins Chair in Ophthalmology at Baylor College of Medicine. “People with the condition tend to have it for the rest of their lives. There is a need for improved treatments.”
Current therapies commonly rely on corticosteroids to suppress inflammation, but prolonged steroid use can increase the risk of glaucoma and cataracts.
The team focused on modulating immune cells called macrophages. They said resident macrophages normally helped maintain ocular surface health by clearing debris, supporting tissue repair and suppressing inflammation. But during dry eye disease these protective cells became dysfunctional while inflammatory monocytes infiltrated the tissue.
They hypothesised that restoring the protective function of resident macrophages could improve ocular surface health.
The study evaluated a rexinoid compound developed by Dr Hiroki Kakuta’s laboratory at Okayama University. Rexinoids are synthetic molecules related to vitamin A signalling pathways and designed to regulate immune responses without some of the adverse effects associated with steroids.
The team in Japan modified NEt-3IB to improve its water solubility, enabling it to be formulated as an eye drop.
Mice treated with NEt-3IB three times daily for five days showed significantly lower corneal permeability, indicating better corneal barrier integrity, along with larger and more numerous goblet cells compared with controls.
Using single-cell RNA sequencing, researchers also found the treatment suppressed inflammatory gene expression while stimulating homeostatic and anti-inflammatory pathways in conjunctival monocyte and macrophage populations. Importantly, NEt-3IB increased expression of protective factors including Igf1 and Il10, effects not observed with dexamethasone.
The investigators said NEt-3IB produced much smaller increases in intraocular pressure than dexamethasone, suggesting it may prove safer for long-term use.
“This study suggests that redirecting immune cells to reduce inflammation and enhance protective functions could offer an improved treatment option for dry eye disease,” Dr Pflugfelder said.
