Endothelial keratoplasty is the current gold standard for treating corneal endothelial diseases, achieving excellent visual outcomes and rapid rehabilitation.
There are, however, severe limitations to donor tissue supply and uneven access to surgical teams and facilities across the globe.
The corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration.
This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal over-hydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency.
Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity.
The cornea is the transparent anterior part of the eye and is composed of five different layers. The outermost layer is the corneal epithelium, followed by Bowman’s membrane, corneal stroma, Descemet’s membrane (DM), and the innermost corneal endothelium.
The adult human cornea is about 550 μm thick and serves 3 major functions:
- as a mechanical and chemical barrier to protect the inner ocular tissues,
- as a transparent medium for light passage, and
- light refraction (providing two thirds of the eye’s refractive power).
Inside the corneal stroma, the orderly arrangement and interfibrillar spacing of collagen fibrils regulate the light transmission through the cornea.
Increased light scattering occurs when the spatial arrangement, diameter, and densities of collagen fibrils are altered and when an alteration in the refractive index ratio between fibrils and the extrafibrillar matrix is encountered.
All these factors are influenced by the stromal hydration status, as fluid sequestration within the stroma is expected to separate the constituent collagen fibrils, altering the fibrillar spacing and alignment.
A cell therapy developed by a team of Japanese researchers has driven Aurion Biotech’s IOTA trial. The company recently released early results from the study, which focuses on corneal endothelial cell therapy.
This is an innovative biologic therapy developed by Shigeru Kinoshita, MD, PhD, and colleagues that has come to fruition with the propagation of healthy corneal cells from 2 donors used to treat 50 patients with corneal endothelial disease.
A cell therapy developed by a team of Japanese investigators has driven Aurion Biotech’s IOTA trial, and the company recently released early results from the study.
The treatment, corneal endothelial cell therapy, is an innovative biologic therapy developed by Shigeru Kinoshita, MD, PhD, a professor and chair of ophthalmology at Kyoto Prefecture University of Medicine in Japan, and colleagues and has come to fruition with the propagation of healthy corneal cells from 2 donors used to treat 50 patients with corneal endothelial disease.
According to the company, the preliminary fi ndings from the IOTA trial showed improvements in visual acuity and central corneal thickness. Corneal edema is the result of death or degradation of corneal endothelial cells.
Because these cells do not regenerate, loss of vision can occur. Up to now, transplantation procedures such as Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) have been performed but are limited by their disadvantages—namely, they are complex surgeries that few surgeons perform and the supply of donor corneas is limited.
In contrast, corneal endothelial cell therapy has several potential advantages: The supply of corneal endothelial cells is abundant. Endothelial cells from one donor can replicate to treat up to 100 eyes.
The procedure is straightforward, can be performed relatively quickly, and is less complex than DMEK and DSAEK procedures. The procedure is patient friendly, with postoperative recovery in several hours as opposed to several days for the DSAEK and DMEK procedures.
The corneal endothelial cell procedure involves 3 steps. First, the diseased endothelium is removed from the recipient cornea. Second, the cultured cells are loaded into syringes, and the cell suspension is injected into the patient’s anterior chamber, where the cells rapidly self-align.
Third, the patient recovers for approximately 3 hours while in a prone position. To date, Kinoshita and his team have performed cell therapy procedures in 65 patients in Japan, with excellent clinical outcomes.
Key findings from these studies have been published in the New England Journal of Medicine and a follow-up 5-year study in Ophthalmology.
In the IOTA trial, conducted from November 2020 to May 2021, at the Clínica Quesada in San Salvador, El Salvador, the investigators injected the cells into the aff ected eyes with the goals of reducing corneal edema and restoring vision.
The IOTA trial was conducted as a proof of concept of previous studies of the cell therapy procedure developed by Kinoshita and colleagues. The results showed that the procedure was safe, well tolerated, and efficacious.
This is the fi rst trial of the corneal endothelial cell therapy procedure to be conducted outside of Japan. Investigators are Gabriel Quesada, MD, and Rodrigo Quesada, MD, in El Salvador and Edward Holland, MD; Elizabeth Yeu, MD; John Berdahl, MD; Matt Giegengack, MD; John Vukich, MD; and Kevin Waltz, MD, in the US.
“This is a landmark moment for the treatment of corneal endothelial disease,” said Holland, who is chief medical advisor and medical advisory board chair at Aurion Biotech. Holland reported that in part 1 of the trial, the investigators treated 16 patients with cells garnered from 1 donor.
In the second part of the trial, they treated 34 patients from 1 donor. Moreover, Holland pointed out that the study confi rmed the procedure is accessible for surgeons and minimally invasive for patients.
“The initial readout from this proof-of-concept trial is promising. Patients have demonstrated improvements in visual acuity and central corneal thickness,” Holland said.
Greg Kunst, Aurion Biotech’s chief executive officer, said the IOTA trial has provided insights and confirms that the procedure can restore vision to patients suff ering from blindness resulting from corneal endothelial disease.
“Until Professor Kinoshita’s astonishing innovations in corneal endothelial cell therapy, vision loss caused by corneal edema has remained largely underserved,” he said.
“That is because of a chronic undersupply of donor corneas and current standards of care that involve exceptionally complex procedures. Because we have acquired this intellectual property, we look forward to advancing this cell therapy through regulatory approval in the US and elsewhere to restore vision to patients throughout the world.”
The patients will be followed for 12 months to assess the longer-term safety and efficacy of the treatment and after the study ends.