Alice Goodman

November 18, 2013

NEW ORLEANS — Rho kinase inhibitor eyedrops stimulate the growth of corneal epithelium, according to a preliminary study in patients with Fuchs dystrophy.

"Think outside the box," said Shigeru Kinoshita, MD, from Kyoto Prefectural University of Japan. The drops, also known as rock inhibitors, could become a treatment reality in the future. "This is just the beginning," Dr. Kinoshita said. "We may be heading toward minimally invasive surgery for Fuchs dystrophy and other forms of corneal problems."

Dr. Kinoshita and his team pioneered the technique as part of research on new therapies for corneal endothelial diseases, as well as for the early stages of Fuchs dystrophy. The first approach is aimed at using cultivated corneal endothelial cells plus a rock inhibitor to promote cell adhesion, proliferation, and inhibition of apoptosis of corneal endothelial cells.

The second effort — to develop a novel medical treatment for early phases of corneal endothelial disease using rock inhibitor eyedrops — was the focus of talk here at the American Academy of Ophthalmology 2013 Annual Meeting.

Dr. Kinoshita explained that in the early stages of Fuchs dystrophy, the center of the cornea is more damaged because that is where the disease process starts. In the early stages, the peripheral cornea still has functioning endothelial cells.

The idea that we could treat corneal endothelial disease without surgery is intriguing and exciting.

The technique involves transcorneal freezing to remove the damaged endothelial cells and then adding the eyedrops to promote cell proliferation. First, the investigators demonstrated that the technique could result in cell proliferation and corneal wound healing in the rabbit model; next, they replicated their results in monkeys and showed that the eyedrops could effectively treat corneal endothelial damage and promote corneal cell proliferation.

They received approval from the university to treat 8 patients with corneal edema. Four had Fuchs dystrophy and 4 had pseudophakic bullous keratophy. Patients were treated with eyedrop applications of 10 mmol/L 6 times per day for 7 days.

In the 4 patients with Fuchs dystrophy, corneal healing and restored visual acuity were observed. Three months after treatment with the rock inhibitor, corneal thickness was reduced to 563 cells/mm² from 700 cells/mm².

"The patients were quite happy," Dr. Kinoshita said.

His team treated another patient with corneal injury resulting from cataract surgery. That patient's eye also showed corneal healing and visual improvement after treatment with rock inhibitor eyedrops.

The technique was not effective in the 4 patients with pseudophakic bullous keratophy.

"The eyedrops are very effective for focal edema, but less so for diffuse edema," he explained at the meeting.

In an interview with Medscape Medical News, Dr. Kinoshita said he is in discussions with a Japanese drug company about making the eyedrops commercially available. He also said that other compounds might be useful in stimulating corneal regrowth.

Kathryn Colby, MD, noted that "these are exciting new data suggesting that a specific compound, delivered via eyedrops, can restore the corneal epithelium." Dr. Colby is a corneal surgeon at Massachusetts Eye and Ear Infirmary and Boston Children's Hospital.

"The idea that we could treat corneal endothelial disease without surgery is intriguing and exciting. The concept that medications can be given topically to stimulate growth of a patient's own corneal endothelial cells deserves further research. We look forward to clinical trials of the rock inhibitor and similar products."

Dr. Kinoshita holds a patent on the rock inhibitor eyedrops. Dr. Colby reports financial ties with Novartis.

American Academy of Opthalmology 2013 Annual Meeting. Presented November 16, 2013.

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