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Posted on 04/15/2003 4:09:24 AM PDT by RJCogburn
little-known operation restores hope for people who lose sight from chemical or heat burns of the eye or certain rare diseases. The procedure, 50 to 100 percent effective in healing corneal damage, is used worldwide, including Iran, where it helps restore sight for victims of Iraqi mustard gas attacks.
A variation on corneal transplants, the surgery grafts stem cells from a donor or a patient's good eye to the injured eye. The cells are from the limbus, a rim around the cornea. The cells resheath the cornea's surface, the 50-micron-thick epithelium, to maintain it as a transparent window. When burns or disease wipe out the limbal stem cells, the epithelium clouds over with scar tissue, causing blindness.
Grafting even a small piece of limbus can lead the stem cells to regrow clear epithelium — and keep it clear — thus restoring sight. The cells even recover transplanted corneas. Stem cell transplants and corneal transplants are frequently performed one after the other if corneal damage extends below the epithelium.
The discovery of the cells 17 years ago and clinical proof that they keep working in any eye with an intact tear system has opened a new era in eye surgery.
"It's an outstanding breakthrough and has, at least in the short run, cured a number of patients," said Dr. Richard S. Fisher, director of the corneal disease program at the National Eye Institute in Bethesda, Md.
The stem cells are adult, not fetal tissue, and join bone marrow and skin as the third adult stem cell in wide use to repair organs.
In the United States, officials estimate that 300 a year are performed and that the transplants are increasing because they are the sole alternative to plastic corneas for desperate burn cases, industrial accidents, damage from contact lenses and a few rare diseases that cause blindness. In operations on one eye, 90 percent to 100 percent restore vision, because the patients' own stem cells from the good eye can be transplanted without rejection.
In one eye, the surgery is "basically a slam dunk," said its originator, Dr. Kenneth R. Kenyon of Boston.
"When we first saw a number of challenging cases of mostly chemical burns," he said, "the eyes were chronically inflamed, with ulcers and blood vessels growing into the cornea, hallmarks, we now know, of limbal stem cell deficiency."
In a paper in 1989, Dr. Kenyon and Dr. Scheffer C. G. Tseng reported that ulcers and inflammation healed and invading blood vessels withdrew after the surgery. Vision improved immediately for many patients. Patients who later needed the entire cornea transplanted because other layers were scarred also had better prognoses. Those transplants were more accepted because the new stem cells resurfaced the new corneas, keeping them transparent.
"I have some patients 20 years out with good vision," Dr. Kenyon said. "I believe these last a lifetime."
Stem cell transplants on one eye are now standard, said Dr. R. Doyle Stulting, editor of the journal Cornea. "They are clearly successful and they are permanent," Dr. Stulting said.
For patients blind in both eyes, stem cell transplants remain effective in half the cases after five years, principally because of rejection. Donor cells from eye banks or relatives are used, and patients require extensive antirejection drugs. In addition, injuries to both eyes from diseases like aniridia, an iris condition; Stevens Johnson syndrome, an allergic reaction to medication; and ocular cicatricial pemphigoid, an inflammatory disease, often damage lower corneal layers and require multiple operations before sight is restored.
Surgeons report progress in those cases. Dr. Edward J. Holland, director of corneal services at the Cincinnati Eye Institute, has written the lone textbook on reconstructing the ocular surface. Last year, he announced results from 74 blind patients who received donor stem cells in both eyes.
Seventy-three percent developed clear new corneal surfaces. In patients with no other problems, that would have meant great vision. But for those complicated cases, half of whom had aniridia, the mean vision improved, from 20/1700 before surgery to 20/200 after surgery.
Twenty/200 is legal blindness, but most aniridics can't get better vision," Dr. Holland said, because their retinas have genetic damage that cannot be repaired. "At 20/200, they can get around and read large print books with functional aids."
This year in the journal Ophthalmology, Dr. Holland reported on 23 more people blind in both eyes from aniridia. Their vision had improved from an average of 20/1000 to 20/165 four years after stem cell and cornea transplants.
Twelve years ago, Shawn Smith, a jewelry designer, was cleaning 100 carats of rough emeralds in acid when the beaker exploded, splashing acid and emeralds into his eyes. Suddenly, he was blinded.
Two years ago, Mr. Smith sought help from Dr. Holland.
"He could only sense light," Dr. Holland recalled. "Both his eyes were covered with a thick dense scar we couldn't see under."
Dr. Holland peeled back the white scar tissue with scissors and scalpel to find the intact eye. He sutured four crescents of limbus donated by Mr. Smith's half-brother. In a week, the stem cells had grown a new transparent surface, indicating that they were up and running. Three months later, Dr. Holland transplanted other layers of the cornea. That night, Mr. Smith watched television. The next day, he could read the fourth line on the eye chart.
"It's an awesome world out there," Mr. Smith said, "and you just don't know it until you lose it. Then I went to school to see if I could recognize my son. I did."
Mr. Smith's sight is now 20/50.
Dr. Holland also reports success with Stevens Johnson patients, those with the worst prognoses. Stem cell transplants give them a 50-50 chance at sight, he theorizes.
Dan Merton was a union representative in Detroit until he contracted the syndrome a year ago. His skin peeled off, his lung collapsed and his kidneys stopped working. But worst of all, he could not see. "All I could do was sit on the bed," Mr. Merton said. "I didn't have the motivation to get up."
Dr. Holland grafted stem cells from the daughter of Mr. Merton onto his left eye, and he regained very low vision. That improved considerably after Dr. Holland transplanted his cornea. "I am so happy I don't know what to do," Mr. Merton said. "I can see everything. I can't see it clear. But I can see my kids. I am just so blessed."
Some ophthalmologists, however, say they will not accept limbal stem cell transplants as a breakthrough until studies on hundreds of patients confirm the results.
"This is so new we don't know if this will have later complications that'll revert or if it's a temporary solution or a permanent cure," said Dr. Kirk R. Wilhelmus at the Baylor College of Medicine in Houston.
Others, like Dr. Stulting, see the procedure as life-changing. "Someone who is seeing like midnight in a coal mine and can't find anything or move anywhere without being led, who tomorrow can see enough to tell where a door is or a truck is," he said, "is functionally different. They can walk, they can protect themselves. They're not even close to 20/20. They're maybe 20/400. Counting fingers instead of barely seeing light.
"People with stem cell deficiencies who have severe inherited disease or disease from birth or chemical injuries do have a big difference made in their lives if an operation suddenly enables them to read with a magnifying glass and work."
More could be helped, advocates say, if rejection could be eliminated or if donated corneas matched recipients' tissue types. Researchers have grown limbus in the laboratory, but the Food and Drug Administration recently stopped transplants of the bioengineered stem cells in humans, calling for lengthy clinical trials.
Work, however, continues in Italy, Japan and Taiwan as scientists try to find limbus cells that are pure stem cells. The goal is to grow sheets and sheets of limbus, making it a commercial product like bioengineered skin.
In Iran, dozens of victims of mustard gas in the Iraq-Iran war, most of them soldiers, can see after these operations, said Prof. M. A. Javadi, head of ophthalmology at the Shahid Beheshti University of Medical Sciences in Tehran.
The effects of invisible mustard gas are not felt for at least 30 minutes. It burns the skin, lungs and, above all, eyes. Soldiers who think they have survived an attack often blind themselves by wiping saturated uniforms across their faces. The chemical denatures proteins on the epithelium, melting if off. The effects can appear 10 or even 30 years later.
The delayed effects of the gas destroy the limbal stem cells, making corneal transplants alone useless, said Professor Javadi, who has treated hundreds of gas victims. "Currently," he said, "stem cell transplanation with or without corneal transplants seem the most promising treatment."
People with mild cases can regain some sight, said Dr. Ali Khodadoust of Yale, who consults on hard cases in Shiraz, Iran, where he grew up. Half regain some or most of their sight, but severe cases cannot be reversed, because the gas has stopped the tear system.
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