New hope for repairing eye damage once thought untreatable

A Mass Eye and Ear-led clinical trial of a procedure that took stem cells from a healthy eye and transplanted them into a damaged eye safely restored corneal surfaces in 14 patients who were followed for 18 months. 

The stem cell treatment for blinding cornea injuries — called cultivated autologous limbal epithelial cells, or CALEC — was developed at Mass Eye and Ear. It consists of removing stem cells from a healthy eye with a biopsy, expanding them into a cellular tissue graft in a novel manufacturing process that takes two to three weeks, and then surgically transplanting the graft into the eye with a damaged cornea.

“Our first trial showed that CALEC was safe and the treatment was possible,” said principal investigator Ula Jurkunas, associate director of the Cornea Service at Mass Eye and Ear and professor of ophthalmology at Harvard Medical School. “Now we have this new data supporting that CALEC is more than 90 percent effective at restoring the cornea’s surface, which makes a meaningful difference in individuals with cornea damage that was considered untreatable.”

The cornea is the clear, outermost layer of the eye. Its outer border, the limbus, contains a large volume of healthy stem cells called limbal epithelial cells, which maintain the eye’s smooth surface.

When a person suffers a cornea injury, such as a chemical burn, infection, or other trauma, it can deplete the limbal epithelial cells, which can never regenerate. The resulting limbal stem cell deficiency renders the eye with a permanently damaged surface where it can’t undergo a corneal transplant, the current standard of care for vision rehabilitation. People with these injuries often experience persistent pain and visual difficulties.

This need led Jurkunas and Reza Dana, director of the Cornea Service at Mass Eye and Ear, to explore a new approach for regenerating limbal epithelial cells. Nearly two decades later, following preclinical studies and collaborations with researchers at Dana-Farber and Boston Children’s, it was possible to consistently manufacture CALEC grafts that met stringent quality criteria needed for human transplantation. The clinical trial was approved by the U.S. Food and Drug Administration and Mass General Brigham Institutional Review Board, and the first patient was treated in 2018 at Mass Eye and Ear. Successful completion of the trial was accomplished through close coordination between Jurkunas’ surgical team and the cell manufacturing facility at Dana-Farber. 

One limitation of this approach is that it is necessary for the patient to have only one involved eye so a biopsy can be performed to get starting material from the unaffected normal eye.

“Our future hope is to set up an allogeneic manufacturing process starting with limbal stem cells from a normal cadaveric donor eye,” said Jerome Ritz of Dana-Farber Cancer Institute’s Connell and O’Reilly Families Cell Manipulation Core Facility, where the stem cell grafts are manufactured. “This will hopefully expand the use of this approach and make it possible to treat patients who have damage to both eyes.”

Researchers showed the procedure completely restored the cornea in 50 percent of participants at their three-month visit, and that the rate of complete success increased to 79 percent and 77 percent at their 12- and 18-month visits, respectively. With two participants meeting the definition of partial success at 12 and 18 months, the overall success was 93 percent and 92 percent at 12 and 18 months. Three participants received a second transplant, one of whom reached complete success by the end visit. An additional analysis of the procedure’s impact on vision showed varying levels of improvement of visual acuity in all 14 patients.

CALEC displayed a high safety profile, with no serious events in either the donor or recipient eyes. One adverse event, a bacterial infection, occurred in one participant eight months after the transplant, due to chronic contact lens use. Other adverse events were minor and resolved quickly following the procedures. 

The procedure remains experimental and is currently not offered at Mass Eye and Ear or any U.S. hospital, and additional studies will be needed before the treatment is submitted for federal approval.

The trial is the first human study of a stem cell therapy to be funded by the National Eye Institute, a part of the National Institutes of Health, and was the first stem cell therapy in the eye in the U.S. Other research collaborators include Jia Yin at Mass Eye and Ear; Myriam Armant of Boston Children’s Hospital; and the JAEB Center for Health Research. 

In the interim, future CALEC studies should include larger numbers of patients at multiple centers, with longer follow-ups and a randomized-control design. 

“We feel this research warrants additional trials that can help lead toward FDA approval,” said Jurkunas. “While we are proud to have been able to bring a new treatment from the lab bench to clinical trials, our guiding objective was and always will be for patients around the country to have access to this effective treatment.”

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This research is funded by National Eye Institute of the National Institutes of Health.

Disclosures: CALEC is patent-pending. Jurkunas and Dana have financial interest in OcuCell, a company developing living ophthalmic cell-based therapies for treating eye disease. Armant serves on the scientific advisory board for OcuCell. Ritz receives research funding from Kite/Gilead, Novartis, and Oncternal, and serves on Scientific Advisory Boards for Astraveus, Garuda Therapeutics, Smart Immune, Tolerance Bio, and TriArm Therapeutics. The remaining authors declare no competing interests.