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Corneal epithelial stem cell transplant may offer promise
Functional vision is being restored long-term in patients with severe ocular surface disorders who undergo corneal epithelial stem cell transplantation.
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---Eye before stem cell transplantation. Conditions that destroy the limbal area of the peripheral cornea, such as Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium, resulting in scarring and opacification of the cornea.
---Eye after stem cell transplantation. Corneal epithelial stem cell transplantation has restored functional vision in legally blind patients for at least 1 year postoperatively.
TOKYO – Corneal epithelial stem cell transplantation has restored functional vision in legally blind patients for at least 1 year postoperatively, according to a study led by Kazuo Tsubota, MD, of the Department of Ophthalmology, Tokyo Dental College. “This procedure gives us the opportunity to treat disorders, such as Stevens-Johnson syndrome, ocular pemphigoid and chemical/thermal burns, which have never been treatable before,” Dr. Tsubota told Ocular Surgery News.
Dr. Tsubota’s study was published recently in the New England Journal of Medicine. “I have published [my findings] on very severe cases; however, aniridia patients, who also lack stem cells, are good candidates,” Dr. Tsubota said. “The ideal patient is one who does not have corneal epithelial stem cells.”
Conditions that destroy the limbal area of the peripheral cornea, such as Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium, resulting in scarring and opacification of the cornea. “Many of these patients have previously had several routine cornea transplants that have not worked,” said Edward J. Holland, MD, director of Cornea Service in the Department of Ophthalmology at the University of Minnesota. “Now that we know how stem cell disease works, it turns out that if you have stem cell failure, a routine corneal transplant is doomed to failure eventually.”
With the stem cell transplantations, however, 50% to 75% of these patients, according to Dr. Holland, are “doing reasonably well.” He told Ocular Surgery News that there are a lot of people who have been in the “ophthalmology system” for a long time, who have given up after many failures and who probably can benefit from this procedure. “For instance, we’ve done about 20 aniridia patients, and they have a very good success rate with stem cell transplantation,” Dr. Holland said, “and there are a lot of aniridia patients out there.”
Dr. Holland has performed a total of approximately 60 epithelial stem cell transplantations, with outcomes similar to that of Dr. Tsubota. In an Associated Press interview, Dr. Holland said, “Dr. Tsubota’s study shows how two improvements are increasing surgeons’ success: transplanting more limbus tissue so patients get more stem cells and giving patients immune-suppressing drugs to prevent transplant rejection.”
Possible reasons for stem cell transplantation failure, according to Dr. Holland, include the use of stem cells that are not healthy enough; lack of sufficient number of cells so that they do not replicate sufficiently enough to repopulate the ocular surface; and rejection. “This tissue is highly likely to reject because of its location near the limbal vessels close to the vasculature of the patient and also because these eyes are typically in flamed, and inflamed eyes have in creased risk of rejection,” he explained.
Dr. Tsubota used an immunosuppressive regimen of cyclosporine and a short course of corticosteroids. Dr. Holland typically uses cyclosporine, azathioprine and corticosteroids. “We have seen stem-cell transplantations fail more than 1 year after surgery,” Dr. Holland said. “The failure could represent chronic low-grade rejection or stem-cell death from non-immunologic causes. The reason cannot be determined by clinical examination; rather it will probably require histologic study.”
Elderly patients usually do well with topical immune-suppressing drugs, which lack some of the significant side effects of systemic immune-suppressing drugs, Dr. Holland said. Younger patients with stronger immune systems usually need the added boost of systemic immune-suppressing agents, he added.
The study
---Illustration of transplantation process from diseased host eye to host eye after corneal transplantation and suturing of limbal graft.
Dr. Tsubota and his colleagues performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaver eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 D in the affected eyes. In 28 eyes, he also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on one eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least 1 year after transplantation.
A mean of 1,163 days after stem-cell transplantation, 22 of the 43 eyes (51%) had corneal epithelialization; of the 22 eyes, seven eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 D to 0.02 D. The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 D. Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes.
For Your Information:Reference:
- Kazuo Tsubota, MD, can be reached at the Department of Ophthalmology, Tokyo Dental College, Chiba, 11-13 Sugano 5 Chome, Ichikawa-shi, Chiba 272-8513, Japan; (81) 47-322-0151; fax: (81) 47-322-6786. Dr. Tsubota has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Edward J. Holland, MD, can be reached at the University of Minnesota, Department of Ophthalmology, Box 493, 420 Delaware St. SE, Minneapolis, MN 55455-0501; (612) 625-3233; fax: (612) 625-7107. Dr. Holland has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Tsubota K, Satake Y, Kaido M, et al. Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med. 1999:340(2):1697-1703. Copyright 1999 Massachusetts Medical Society. All rights reserved.