Magnetic cell therapy for corneal endothelial dysfunction

Cells obtained from one donor cornea could treat hundreds of patients, with a nonsurgical procedure performed in a clinical setting. Image credit: ©New Africa – stock.adobe.com

Magnetic cell delivery of human corneal endothelial cells (HCECs) to the anterior chamber seems to be a safe cell-based treatment that is exhibiting early signs of efficacy for corneal endothelial cell dysfunction, Sumit Garg, MD, ABO, reported at the American Society of Cataract and Refractive Surgery 2024 annual meeting in Boston, Massachusetts. Garg is with the University of California Irvine Gavin Herbert Eye Institute, UCI Health, California.

Study design

Garg reported on a phase 1 multicentre study (NCT04894110) to determine the safety and tolerability of a single injection of magnetic HCECs (EO2002; Emmecell) in patients who had symptomatic corneal oedema secondary to Fuchs corneal dystrophy or pseudophakic bullous keratopathy. All patients have a best-corrected visual acuity (BCVA) of 20/40 or worse. The study was designed to enrol up to 42 patients in the two groups.

The first part included 21 patients (group 1) with whom four treatment doses were tested (ie, injection of 50,000, 150,000, 500,000, and 1 million cells with or without endothelial brushing or Descemet stripping). Patients were followed for 6 months.

Part two included 21 additional participants in a randomised, double-masked trial of the three highest doses identified previously. The primary outcome is safety. Secondary end points are decreased corneal thickness and improved BCVA.

The technologic steps

Garg described the steps in the cell preparation process. First, the HCECs from a donor cornea are expanded in culture. One donor cornea can yield enough cells for the treatment of hundreds of patients. Donor HCECs are combined with magnetic nanoparticles, and the magnetised HCECs are injected into the anterior chamber without the need for endothelial brushing or disruption. The patient wears a magnetic eye patch for up to 3 hours. This step facilitates localisation and integration of magnetic HCECs into the endothelial layer.

Treatment effect

A representative case was that of a patient injected with 500,000 cells during the 5-minute procedure, requiring no endothelial brushing or Descemet stripping. At 26 weeks postoperatively, the patient had a central corneal thickness decrease of 217 µm and an increase in the BCVA of 18 letters, Garg explained.

In another representative example in a case without endothelial brushing or Descemet stripping, the baseline BCVA was 20/50 with a pachymetry value of 651. At 1 year of follow-up, the BCVA was 20/30 with a pachymetry value of 601.

Among the 4 doses originally tested, no associated adverse effects of the treatment were recorded. The IOP was stable in the treated patients. No infections or inflammation developed. Early signs of efficacy were apparent with the 150,000, 500,000, and 1 million cell doses. Greater efficacy was associated with the two higher doses, which were associated with higher increases in the BCVA.

Part 2

Twenty-one patients have been enrolled in a randomised and double-masked fashion. Participants are randomly assigned 1:1:1 and received one injection of EO2002 at one of the three most effective doses: 150,000, 500,000, or 1 million HCECs. This part of the study aims to continue ensuring safety and to pinpoint the most effective dose.

“Magnetic corneal cell therapy is a novel technology that is well tolerated,” Garg said. “Cells obtained from one donor cornea can treat hundreds of patients in a simple procedure that can be performed in the clinical setting without surgery. Further studies are warranted to continue the development of this product for corneal endothelial dysfunction.”

Another clinical investigation

The effect of EO2002 is also being evaluated in association with cataract surgery. Two groups of patients are included in this clinical trial. Group 1 includes 6 patients who received an injection of the cells during cataract surgery; Group 2 includes 6 patients who received an injection 1 week after cataract surgery.

The study end points are safety; increased or stable endothelial cell density; no decrease in the BCVA that is expected to improve due to the cataract surgery; and a stable central corneal thickness in patients who are at risk for corneal endothelial dysfunction.

Sumit Garg, MD, ABO | E: gargs@hs.uci.edu

Garg is a consultant/adviser to Emmecell. He presented “Treatment of Corneal Endothelial Dysfunction With Magnetic Cell Therapy” at the American Society of Cataract and Refractive Surgery 2024 annual meeting in Boston, Massachusetts.