Key Takeaways

• Two trials at the University of Cologne are evaluating antisense oligonucleotide eye drops targeting IRS-1 in patients with aniridia-associated keratopathy and high-risk corneal transplantation
• The Olisens-Aniridia study is expected to enroll 20 participants for 12 weeks of treatment, while Olisens-Precon is expected to enroll 10 participants for a 4-week treatment period

A European research consortium has begun recruiting patients for 2 clinical trials evaluating gene-silencing eye drops as a potential treatment for abnormal corneal blood vessel growth associated with rare ocular diseases, according to Restore Vision, a Horizon Europe-funded research project coordinated by the University of Galway, Ireland.¹

The studies, underway at the University Hospital Cologne in Germany, will evaluate antisense oligonucleotide eye drops targeting insulin receptor substrate 1 (IRS-1) in patients with aniridia-associated keratopathy and patients undergoing or who have undergone high-risk corneal transplantation. The trials mark the first use of the treatment in patients with these rare diseases, according to the EU-funded Restore Vision consortium.

The investigational eye drops, known as Olisens, are designed to inhibit expression of IRS-1, a protein involved in signaling pathways associated with the growth of blood and lymphatic vessels into the cornea. Corneal neovascularization can compromise corneal transparency and visual function and, among patients receiving corneal transplants, substantially increase the risk of graft rejection.

“Currently there is no adequate targeted treatment option for corneal neovascularization in clinical routine,” said Mert Mestanoglu, MD, study physician in the Department of Ophthalmology at the University of Cologne. He added that treatment options for aniridia-associated keratopathy are particularly limited because of the disease's complexity and rarity.

The Olisens-Aniridia and Olisens-Precon studies are recruiting at the Department of Ophthalmology at the University of Cologne. The consortium describes the studies as phase 2 trials evaluating a new indication for a product that already has marketing authorization.

Olisens-Aniridia is expected to enroll 20 participants and will include a 12-week treatment period. The Olisens-Precon study is expected to enroll 10 participants and will have a 4-week treatment period. Recruitment for both studies is planned over 12 months.

Eligible participants include patients with aniridia-associated keratopathy and patients scheduled for or who have previously undergone high-risk corneal transplantation. Restore Vision lists the indications under investigation as aniridia-associated keratopathy and corneal neovascularization resulting from herpetic keratopathy.

Aniridia is a rare genetic disorder affecting approximately 1 in 100,000 people, according to the consortium. Beyond the characteristic absence or incomplete development of the iris, patients can develop progressive ocular surface disease. In aniridia-associated keratopathy, abnormal vessels can grow across the normally avascular cornea, contributing to loss of transparency and deterioration of vision.

Rather than delivering conventional antiangiogenic therapy, the Olisens approach uses antisense oligonucleotides to interfere with expression of the IRS-1 target. By reducing the relevant molecular signal, investigators hope to limit the pathologic blood and lymphatic vessel growth that can damage the cornea.

The topical route could also be important for diseases of the cornea and ocular surface because the medication can be administered directly to the eye without an intraocular procedure. Restore Vision reported that the eye drops have received orphan drug designation. The Cologne studies will provide early clinical evidence on the safety and potential efficacy of the approach in the targeted rare-disease populations.

For high-risk corneal transplantation, controlling neovascularization is particularly relevant because vascularization of the recipient cornea increases the likelihood of immune-mediated graft rejection. In aniridia-associated keratopathy, meanwhile, clinicians face limited options for addressing progressive corneal surface deterioration and neovascularization.

The trials are part of Restore Vision, a Horizon Europe-funded program coordinated by the University of Galway in Ireland. The consortium includes 10 research institutions, small and medium-sized enterprises, and patient organizations working on therapies for rare corneal and ocular surface diseases.

The broader program is developing treatments for 7 rare eye diseases estimated to affect approximately 500,000 people across Europe.

Reference

1. Restore Vision. European consortium launches first human trial of gene-silencing eye drops for rare eye diseases. Restore Vision. Published August 11, 2026. Accessed August 14, 2026. https://restorevision-project.eu/european-consortium-launches-first-human-trial-of-gene-silencing-eye-drops-for-rare-eye-diseases/.