Cornea Day delves into Fuchs topics

In the first session of ASCRS Cornea Day, Francis Price Jr., MD, and Winston Chamberlain, MD, led a session focusing on Fuchs dystrophy. We’ve seen a change in the last 20 years in how we treat Fuchs, Dr. Francis Price said, and the next 20 years will likely see changes as well.

DMEK: the current gold standard

To begin the session, Marianne Price, PhD, presented on DMEK, which she said is the gold standard at this time for corneal endothelial dysfunction. Compared with PK and DSAEK, DMEK provides faster and better visual recovery and low risk of rejection episodes, she said.

In terms of the fast visual recovery, many patients recover 20/40 to 20/50 vision by the 5-day visit. DMEK provides rapid and durable visual recovery, she added.

DMEK is performed with a small 2.2 mm incision, and it can be combined with cataract surgery. There is minimal risk of rejection, and this allows for early steroid reduction.

The rate of cell loss slows over time and plateaus sooner after DMEK than DSAEK. DMEK also has a lower graft failure rate from 6 months to 10 years compared with DSEK or PK for Fuchs, Dr. Marianne Price said.

DMEK cost is around $4,000 for corneal tissue and around a $1,000–2,000 surgeon fee. One EK per eye usually lasts lifetime. She added that the Fuchs average age is around 68 years old.

Cell therapy – AURN001

Getting into corneal endothelial cell therapy, Zaina Al-Mohtaseb, MD, highlighted AURN001 (Aurion Biotech) therapy.

She first spoke about some of the limitations of DSEK/DMEK. There is limited worldwide donor cornea supply, she said, adding that there is one donor for every 70 diseased eyes worldwide. It’s also a challenging and complex surgery, which is performed by a limited number of qualified corneal surgeons. There is potential for transplant failures or rejections. These options can also be onerous for patient recovery. Patients must lie flat on their back for up to 5 days, and there is a 10–15% detachment rate. Finally, there are also poor physician economic incentives because there is a fixed fee for reimbursement, despite variations in the procedure times and required patient visits.

Dr. Al-Mohtaseb shared details on the AURN001 investigational combination drug product, which features human corneal endothelial cells (HCECs) plus a ROCK inhibitor (small molecule). These are fully differentiated, allogeneic human corneal endothelial cells, where no donor matching is required, no gene engineering, and are optimal donor endothelial cell quality.

This option features a single dose with intracameral administration of the HCECs + ROCK inhibitor. The HCECs are designed to restore vision, while the ROCK inhibitor (Y-27632) is designed to enable rapid endothelial cell engraftment. This therapy is designed to be administered through the anterior chamber of the eye and is a minimally invasive procedure, Dr. Al-Mohtaseb said.

AURN001 has the potential to address the unmet need for donor corneal tissue, she said, with one donor having the potential to provide up to 1,000 doses. General ophthalmologists can do this procedure. It’s also straightforward and minimally invasive. Patient postop recovery is 3 hours lying face down. There are potentially favorable physician economics, although Dr. Al-Mohtaseb said reimbursement is not known at this time.

She shared some results, noting that Aurion’s product candidate has been evaluated in multiple clinical trial globally in more than 225 patients so far. She showed data from Japan, El Salvador, as well as the U.S. and Canada.

Dr. Al-Mohtaseb went into detail on the CLARA trial in the U.S. and Canada, a Phase 1/2 study, which was a prospective, parallel-arm, dose ranging, multicenter, randomized, double-masked study. The primary endpoint of the study was proportion of responders with a ≥15-letter improvement from baseline in best corrected visual acuity (BCVA) at 6 months. Secondary endpoint was the change from baseline BCVA and CCT at each timepoint.

The study was broken into several arms:

• Arm 1 – AURN001 High Dose: 1.0 × 10⁶ neltependocel + 100 μM Y-27632
• Arm 2 – AURN001 Medium Dose: 5.0 × 10⁵ neltependocel + 100 μM Y-27632 
• Arm 3 – AURN001 Low Dose: 2.5 × 10⁵ neltependocel + 100 μM Y-27632
• Arm 4 – Y-27632 Solution: 100 μM Y-27632 with Endothelial Polishing
• Arm 5 – Neltependocel Suspension: 1.0 × 10⁶ neltependocel with Endothelial Polishing

With this trial, Dr. Al-Mohtaseb said goals of the trial were to look at efficacy and safety and to find the correct dosage of the corneal endothelial cells and comparing the parts (the different arms). The goal was to get 20 patients in each of these arms.

Outcomes were excellent, Dr. Al-Mohtaseb said. There was dose response improvement and 3-line gain at 6 months. In the high-dose arm, 50% of patients had a 3-line gain.

She noted that the high-dose arm with ROCK had no rescues at 6 months, while those with the cell-only treatment did have some rescues.

Dr. Al-Mohtaseb said that some patients improved very quickly, and she showed BCVA improvement from 20/50 to 20/20 at month 1 sustained to month 6 in some cases.

In terms of safety, there were no treatment-related systemic or ocular severe adverse events and no graft rejections. Ocular hypertension was the most common adverse event but did not occur in the high-dose group.

Corneal endothelial cell therapy across all trials in Japan, El Salvador, the U.S., and Canada generally showed clinically meaningful improvement in BCVA and CCT. Therapy was well tolerated with a favorable safety profile across all trials with no graft rejections observed to date. Corneal endothelial cell therapy was commercially launched in Japan in September 2024. AURN001 is being evaluated in a Phase 1/2 clinical trial in the U.S. and Canada with 12-month data planned to be presented in 2025.

Looking to the future

To conclude the Fuchs session, Dr. Francis Price asked session participants for their opinions on what the future (in 5–10 years) will look like in terms of available treatments in corneal transplantation.

Jennifer Rose-Nussbaumer, MD, said she thinks cell injection will be an option, but that EK and PK will still be used. She noted that she still uses PK and thinks there will still be a place for all procedures but that cell injection will play a role.

Dr. Marianne Price noted that new options will allow further personalization of treatment for patients. However, she said that one thing that is not being factored in is patient compliance, and that will be important to consider.

David Verdier, MD, noted that it remains to be seen if the quality of vision with cell injection will approach what has been seen with DMEK, and he said that 25 years ago, none of these things were on the table. They came up swiftly, and there could be a completely different option in 10 years.

Dr. Al-Mohtaseb is optimistic about the use of human endothelial cell therapy in the future and said decreasing cell rejection is huge. It’s about the patient in the end, she said.

She added that she doesn’t like picking one therapy over the other and thinks there’s room for different treatment to elevate the field and personalize treatment. There’s always going to be PK for stromal scarring, she added.

“We’re conditioned to look for the next thing,” said Gregory Moloney, MD. He noted that physicians are always hearing about these options and keeping track of how they compare to each other. But he thinks it’s beyond the point where one thing will come in and be the gold standard.

He wants to know how the options are going to deal with guttae, and he said he hopes that “in 10 years we’re not stripping Descemet’s anymore.”

Financial disclosures

Al-Mohtaseb: Alcon
Marianne Price: EyeYon