First-in-Class Therapy for Diabetic Retinopathy Shows Six-Month Benefit | ASRS 2025

A single dose of a new class of medications that blocks the action of endothelin has been shown to be safe and well tolerated, and resulted in durable improvements in patients with diabetic retinopathy, according to the results of a phase 2a study presented today at the American Society of Retina Specialists (ASRS) annual meeting being held in Long Beach, California.

Diabetic retinopathy is characterized by damage to the blood vessels in the retina, often caused by poor blood sugar control in people with diabetes. Diabetic retinopathy affects almost 10 million people in the United States. It can lead to diabetic macular edema, which is a leading cause of vision loss.

Endothelin levels have been demonstrated to be elevated in patients with diabetic retinopathy. Endothelin is involved in inflammation and cell death through its receptors expressed in retinal vascular and neuroretinal cells.

The current standard of care for diabetic retinopathy focuses on blocking vascular endothelial growth factor (VEGF) and/or destroying peripheral retina via laser procedures to reduce VEGF production and oxygen consumption with hopes to preserve central retinal function. Current therapies do not address the underlying cause of the disease, and many patients continue to lose vision.

Justis Ehlers, M.D.

Justis Ehlers, M.D., who is the Norman C. and Donna L. Harbert Endowed Chair of Ophthalmic Research at the Cole Eye Institute of the Cleveland Clinic, presented late-breaking research on PER-001, which is a novel, first-in-class small molecule endothelin receptor antagonist.

Developed by Perfuse Therapeutics, the therapy is delivered through a slow-release, dissolvable implant in the vitreous cavity of the eye. It is designed to provide a sustained release of PER-001, allowing for dosing every six months. It is specifically designed to block endothelin signaling to increase ocular blood flow.

Researchers conducted a sham-controlled and center-masked study. In the study, 27 patients with non-proliferative diabetic retinopathy without diabetic macular edema were randomized to receive a single intravitreal injection of PER-001 on day 1 of low dose, high dose, or sham control, followed monthly for six months.

Researchers found that eyes treated with PER-001 showed reductions in macular ischemia, vascular leakage, and microaneurysms. These structural benefits were accompanied by measurable improvements in visual function under low luminance conditions and improved peripheral visual fields.

Specifically, PER-001 treatment led to improvements in ultra-widefield color fundus photography evaluation of macular ischemia, vascular leakage, and microaneurysm (MA) count at months 3 and 6 compared with control.

“There was some specific functional testing that was carried out to look for any signs of changes,” Ehlers said. “In this case, low luminance contrast sensitivity was looked at across all of the study arms, showing potential improvements in both the low-dose and high-dose groups and worsening in the sham groups. When looking at low luminance, low contrast, and central visual acuity, there was also a signal towards improvements compared with the sham, with about a five-letter difference between both groups and in peripheral vision. The low-dose group was seeing the high dose, and the control group was stable.

“Overall, the drug was well tolerated, with no evidence of ventricular inflammation or signs of retinal vasculitis. BCBA [best-corrected visual acuity] overall was stable in all groups,” Ehlers said.

He said phase 2b/3 trials are expected to begin later this year in patients with diabetic retinopathy.

PER-001 is also being studied in patients with glaucoma. The phase 2a glaucoma trial showed that after a single intravitreal administration of PER-001 released for six months, added to existing standard-of-care IOP-reducing therapies, it improved compared with the natural history of the disease.