麻豆传媒

The first-ever corneal stem-cell transplants in the U.S. proved feasible and safe, allowed patients to receive new corneas, and in some cases improved vision as a solo procedure, a small preliminary clinical study showed.

Four patients who had corneal limbal stem cell deficiency after ocular burns underwent the procedure using healthy stem cells from the patients' uninjured or less injured eye. Two of the four subsequently underwent corneal transplants, and the other two had vision improvement without cornea replacement.

The landmark development was made possible by a technologic innovation (cultivated autologous limbal epithelial cells, or CALEC) that facilitated transplantation without xenobiotics, serum, or antibiotics, reported Ula V. Jurkunas, MD, of Mass Eye and Ear in Boston, and co-authors in .

"Our early results suggest that CALEC might offer hope to patients who had been left with untreatable vision loss and pain associated with major cornea injuries," Jurkunas said in a . "Cornea specialists have been hindered by a lack of treatment options with a high safety profile to help our patients with chemical burns and injuries that render them unable to get an artificial cornea transplant. We are hopeful with further study, CALEC can one day fill this crucially needed treatment gap."

Jurkunas estimated that 1,000 people a year in the U.S. might benefit from the transplant procedure.

Transplants have been used for some time to treat limbal cell deficiency. The key advance with CALEC relates to cell processing, said Stephen Pflugfelder, MD, of Baylor College of Medicine in Houston.

"It's definitely an advance in our field," he told 麻豆传媒. "I do limbal stem cell transplants, but currently we have to take several small pieces [of tissue] from the other eye. I think one of their patients had some damage to the other eye, so there may be a very small area where you can take the stem cells. This offers the opportunity to expand one small area into a larger sheet, as opposed to taking three or four biopsies from the other eye, which would pretty much exhaust all of the stem cells in the good eye."

The procedure might have broader application, beyond instances involving ocular injuries, added Pflugfelder, who was not involved in the study. An increasingly common cause of limbal cell deficiency involves patients who wear contact lenses long term.

A key question about future use of the transplant procedure is whether the technique will be broadly available to ophthalmologists or limited to specialized eye centers. One possible scenario would involve development of processing centers that would perform the cell expansion on tissue sent by ophthalmologists in the community and then return the finished cellular sheet for transplantation, said Pflugfelder.

The four patients described in the study had irreversible loss of limbal stem cells, which replenish and maintain the outer layer of the cornea. Although the therapeutic potential of CALEC was described , no clinical studies in the U.S. had evaluated limbal stem cell grafting, Jurkunas and colleagues noted in their report.

FDA requirements for manufacturing and quality control in tissue engineering posed a major obstacle to limbal stem cell transplantation. involves harvesting a patient's own limbal stem cells from a small corneal biopsy and then expanding the cell population in a two-step process to create a sheet of cells that provide a surface for growth of normal corneal tissue after transplantation.

The authors described the first four patients who underwent limbal stem cell transplants. A fifth patient had a biopsy but the stem cells did not expand sufficiently for transplantation.

The four patients who underwent transplantations had limbal stem cell deficiency caused by chemical burns. The patients were all men, ranging in age from 31 to 52.

The first patient had corneal opacity clearance at 3, 9, and 12 months after transplantation. The patient still had limited vision in the affected eye at 12 months because of intrastromal opacity, but subsequently underwent a corneal transplant. The second patient had ocular surface reconstruction 8 years before enrolling in the CALEC study, but still had corneal opacification. Opacity persisted to 9 months after the limbal stem cell transplant, but had improved by 12 months. The patient's best corrected visual acuity (BCVA) improved from 20/40 to 20/30.

The third patient had complete corneal opacification at enrollment, 5 months after the chemical burn. Following CALEC transplant, corneal opacification improved during follow-up visits at 3, 9, and 12 months. The epithelial defect had resolved by 12 months, and the patient's vision had improved from hand motion to 20/30.

The fourth patient enrolled in the study 30 years after an acid burn. He had complete opacification, extensive neovascularization, and lagophthalmos. After an initial biopsy did not lead to a viable limbal stem cell construct, the patient underwent a successful biopsy 3 years later. BCVA improved from hand motion at baseline to finger counting at 12 months. Conjunctivalization resolved and neovascularization and corneal staining improved, allowing the patient to prepare for a corneal transplant.

The next phase of clinical evaluation for CALEC will be a 15-patient study with 18-month follow-up to get a better assessment of the procedure's efficacy and durability.

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