Laird Harrison

May 01, 2015

SAN DIEGO — Injected cultivated cells can heal corneal endothelial damage, according to initial results from a small trial.

"Overall, the short-term results are excellent," said Shigeru Kinoshita, MD, from the Kyoto Prefectural University of Medicine in Japan.

He described his team's research here at the American Society of Cataract and Refractive Surgery 2015 Symposium, after receiving the society's Charles D. Kelman Innovator's Award for this work.

The novel treatment would provide another option for the treatment of conditions such as Fuchs' dystrophy and endothelial cornea damage related to cataract surgery, said Edward Holland, MD, from the Cincinnati Eye Institute, who presented the award to Dr Kinoshita.

Currently patients with severe endothelial cornea dysfunction depend on cornea transplants, and these are difficult to obtain, he told Medscape Medical News.

This research "is going to totally change the paradigm of corneal endothelial disease," said Dr Holland. "It's a totally outside-the-box idea." The approach could one day allow ophthalmologists to treat these conditions in the clinic rather than the operating room, he said.

The researchers began by cultivating corneal endothelial cell sheets on type 1 collagen; however, experiments in monkeys were unsatisfactory. They then decided to inject the cells directly into the anterior chamber in hope that the cells would organize themselves into new tissue.

Although the cells are difficult to cultivate, one donor cornea could provide enough cells to treat 243 patients, said Dr Kinoshita. "And the procedure is minimally invasive."

It's a totally outside-the-box idea.

The researchers combined the cells with a Rho kinase inhibitor, mesenchymal-conditioned medium, and an inhibitor of transforming growth-factor beta signaling.

This appeared to work in both monkeys and rabbits, but "especially in the monkeys," Dr Kinoshita explained. "Three months after injection with the Rho kinase inhibitor, we could see the beautiful endothelial cell sheet on the backside of the cornea."

From there, the researchers moved to initial experiments in humans with Fuchs' dystrophy, and completely restored patients' vision.

They counted 2000 cells/mm², an amount comparable to that seen with Descemet's stripping endothelial keratoplasty, Descemet's membrane endothelial keratoplasty, and penetrating keratoplasty.

In the initial stages of an unpublished clinical trial of 11 patients with bullous keratopathy or Fuchs' dystrophy, most attained 20/20 vision and thinner corneas, Dr Kinoshita reported.

While waiting on longer-term results with the injected cells, the researchers are experimenting with eye drops containing a Rho kinase inhibitor.

The eye drops reduced edema only slightly in four eyes with diffuse edema related to pseudoexfoliation or to bullous keratopathy secondary to laser iridotomy.

"But for four cases of central corneal edema in Fuchs' corneal dystrophy, we did get a very good effect," said Dr Kinoshita. The procedure decreased the central cornea thickness in addition to restoring vision.

Patients with damage related to surgery might also benefit from the eye drops, he said. He described the case of an 84-year-old woman who lost two-thirds of her Descemet's membrane during cataract surgery, but her best corrected visual acuity returned to 20/25.

Neither the injected cells nor the Rho kinase inhibitor eye drops have caused any increase in intraocular pressure or overgrowth of corneal endothelial cells, Dr Kinoshita reported.

In fact, both the procedures look like promising supplements to current therapies, he concluded.

Dr Kinoshita reports relationships with Abbott Medical Optics, Alcon Laboratories, HOYA, JCR Pharmaceuticals, Otsuka Pharmaceutical, Pfizer, Santen Pharmaceutical, and Senju Pharmaceutical. Dr Holland reports relationship with Alcon, Bausch + Lomb, Kala Pharmaceuticals, Mati Therapeutics, PRN–Physician Recommended Nutriceuticals, Rapid Pathogen Screening, Senju Pharmaceuticals, TearLab, and TearScience.

American Society of Cataract and Refractive Surgery (ASCRS) 2015 Symposium. Presented April 19, 2015.


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