Stem cells reverse blindness caused by burns

Procedure restored sight in 75 percent of patients, researchers reported

By ALICIA CHANG

updated 5:03 p.m. ET, Wed., June 23, 2010

LOS ANGELES - Dozens of people who were blinded or otherwise suffered severe eye damage when they were splashed with caustic chemicals had their sight restored with transplants of their own stem cells — a stunning success for the burgeoning cell-therapy field, Italian researchers reported Wednesday.

The treatment worked completely in 82 of 107 eyes and partially in 14 others, with benefits lasting up to a decade so far. One man whose eyes were severely damaged more than 60 years ago now has near-normal vision.

"This is a roaring success," said ophthalmologist Dr. Ivan Schwab of the University of California, Davis, who had no role in the study — the longest and largest of its kind.

Stem cell transplants offer hope to the thousands of people worldwide every year who suffer chemical burns on their corneas from heavy-duty cleansers or other substances at work or at home.

The approach would not help people with damage to the optic nerve or macular degeneration, which involves the retina. Nor would it work in people who are completely blind in both eyes, because doctors need at least some healthy tissue that they can transplant.

In the study, published online by the New England Journal of Medicine, researchers took a small number of stem cells from a patient's healthy eye, multiplied them in the lab and placed them into the burned eye, where they were able to grow new corneal tissue to replace what had been damaged. Since the stem cells are from their own bodies, the patients do not need to take anti-rejection drugs.

Adult stem cells have been used for decades to cure blood cancers such as leukemia and diseases like sickle cell anemia. But fixing a problem like damaged eyes is a relatively new use. Researchers have been studying cell therapy for a host of other diseases, including diabetes and heart failure, with limited success.

Adult stem cells, which are found around the body, are different from embryonic stem cells, which come from human embryos and have stirred ethical concerns because removing the cells requires destroying the embryos.

Currently, people with eye burns can get an artificial cornea, a procedure that carries such complications as infection and glaucoma, or they can receive a transplant using stem cells from a cadaver, but that requires taking drugs to prevent rejection.

The Italian study involved 106 patients treated between 1998 and 2007. Most had extensive damage in one eye, and some had such limited vision that they could only sense light, count fingers or perceive hand motions. Many had been blind for years and had had unsuccessful operations to restore their vision.

The cells were taken from the limbus, the rim around the cornea, the clear window that covers the colored part of the eye. In a normal eye, stem cells in the limbus are like factories, churning out new cells to replace dead corneal cells. When an injury kills off the stem cells, scar tissue forms over the cornea, clouding vision and causing blindness.

In the Italian study, the doctors removed scar tissue over the cornea and glued the laboratory-grown stem cells over the injured eye. In cases where both eyes were damaged by burns, cells were taken from an unaffected part of the limbus.

Most patients regained sight
Researchers followed the patients for an average of three years and some as long as a decade. More than three-quarters regained sight after the transplant. An additional 13 percent were considered a partial success. Though their vision improved, they still had some cloudiness in the cornea.

Patients with superficial damage were able to see within one to two months. Those with more extensive injuries took several months longer.

"They were incredibly happy. Some said it was a miracle," said one of the study leaders, Graziella Pellegrini of the University of Modena's Center for Regenerative Medicine in Italy. "It was not a miracle. It was simply a technique."

The study was partly funded by the Italian government.

Researchers in the United States have been testing a different way to use self-supplied stem cells, but that work is preliminary.

One of the successful transplants in the Italian study involved a man who had severe damage in both eyes as a result of a chemical burn in 1948. Doctors grafted stem cells from a small section of his left eye to both eyes. His vision is now close to normal.

In 2008, there were 2,850 work-related chemical burns to the eyes in the United States, according to the Bureau of Labor Statistics.

Schwab of UC Davis said stem cell transplants would not help those blinded by burns in both eyes because doctors need stem cells to do the procedure.

"I don't want to give the false hope that this will answer their prayers," he said.

Dr. Sophie Deng, a cornea expert at the UCLA's Jules Stein Eye Institute, said the biggest advantage was that the Italian doctors were able to expand the number of stem cells in the lab. This technique is less invasive than taking a large tissue sample from the eye and lowers the chance of an eye injury.

"The key is whether you can find a good stem cell population and expand it," she said.

Macular degeneration is a major cause of gradual, painless, central vision loss in the elderly. Previously known as "senile macular degeneration," the name has been changed to age-related macular degeneration, (ARMD), due to the unflattering reference to advanced age. The average age at onset of visual loss is about 75 years. After the age of 50 years, the incidence steadily increases; over one-third of people in their ninth decade of life are affected. Researchers have implied that certain conditions may contribute to the disorder. Some of these are arteriosclerosis, oxidative damage, photic damage, inflammation, diet, vitamin and rare element deficiencies, and genetics. The genetic factors that are suspected in being involved are hard to quantify due to the fact that parents and siblings may not be alive, and children may be too young to display any symptoms that could be traced leading to the disease.

The term "stroke" or "paralytic stroke" is commonly used to describe a sudden problem with the brain that is usually related to its blood supply. A "stroke," therefore, can be due to ischemia (decreased blood supply), infarction (interrupted blood supply), or hemorrhage (severe bleeding), and usually means that there is some kind of permanent problem with the nervous system. All three of these causes (ischemia, infarction, or hemorrhage) would be due to cerebrovascular disease (disease related to the blood supply to the brain).

A population-based cohort study from Taiwan investigated the relationship between age-related macular degeneration and stroke risk over a five year period. The study included 209 patients receiving care for ARMD between 1999 and 2001. Researchers then randomly selected 1,045 control subjects who were matched for age and gender for comparison. It was found that 142 patients involved in the study had strokes during the five year follow-up period. There were 38 patients (18.2% of those with AMRD) from the study group and 104 (9.9%) from the control group. After adjusting for age, gender, income, level of urbanization, geographic location and comorbidities, it was found that patients with AMRD, who were 65 years and over, had a risk of stroke that was 2.21 times greater than the control subjects. There was no significant difference in the risk of stroke between patients with AMRD who were younger than 65 years of age and the control patients in the same group. It can be concluded that AMRD is associated with an increased risk of stroke in patients with ARMD who are 65 years or older.¹ 

¹ Hu CC, Ho JD, Lin HC. Neovascular age-related macular degeneration and the risk of stroke: a 5-year population-based follow-up study. Stroke. 2010.41(4):613-7.

1. Individuals from 49 to 65 years old who have/had at least one parent with macular degeneration. Spouses or partners will be included.
2. The parent(s) who have Age-Related Macular degeneration or have a first-degree relative with the disease (siblings).

Arch Ophthalmol. 2009;127(11):1483-1493.

Objective  To evaluate the relationships between the amount and type of dietary fat and intermediate age-related macular degeneration (AMD).
 

Author Affiliations: Department of Nutrition, Food Studies, and Public Health, New York University, New York, New York (Dr Parekh); Departments of Ophthalmology and Visual Sciences (Drs Voland, Blodi, and Mares) and Statistics and Biostatistics (Dr Chappell), University of Wisconsin, Madison; Department of Prevention and Healthy Lifestyles, American Medical Association, Chicago, Illinois (Dr Moeller); Department of Family and Community Medicine, University of Arizona, Tucson (Dr Ritenbaugh); and Department of Epidemiology, The University of Iowa, Iowa City (Dr Wallace).

Design  Women aged 50 to 79 years with high and low lutein intake from 3 sites of the Women's Health Initiative Observational Study were recruited into the Carotenoids in Age-Related Eye Disease Study. Fat intake from 1994 through 1998 was estimated using food frequency questionnaires, and AMD was assessed photographically from 2001 through 2004.

Results  Intakes of -6 and -3 polyunsaturated fatty acids, which were highly correlated (r = 0.8), were associated with approximately 2-fold higher prevalence of intermediate AMD in high vs low quintiles. However, monounsaturated fatty acid intake was associated with lower prevalence. Age interactions were often observed. In women younger than 75 years (n = 1325), total fat and saturated fatty acid intakes were associated with increased prevalence of AMD (multivariate adjusted odds ratios [95% confidence interval] for intermediate AMD, 1.7 [1.0-2.7] for quintile 5 vs quintile 1 for total fat [P = .10 for trend] and 1.6 [0.7-3.6] for saturated fatty acids [P = .23 for trend]). The associations were reversed in older women.

Conclusions  These results support a growing body of evidence suggesting that diets high in several types of fat may contribute to the risk of intermediate AMD and that diets high in monounsaturated fatty acids may be protective.

Nationwide AMD Genetics Study Recruiting Participants

New Treatments Hold Hope for Failing Eyes

SUNDAY, Sept. 27 (HealthDay News) -- Already a leading cause of vision loss among people older than 60, age-related macular degeneration is expected to skyrocket in numbers over the coming decades as the U.S. population grows older.

However, a series of new treatments now under study or in development should mean that eye specialists will be well-prepared to treat the coming surge of macular degeneration cases.

These include refinements of treatments that have proven effective against some forms of the disease as well as new therapies targeting forms of macular degeneration that have so far proven impossible to treat.

Age-related macular degeneration involves the breakdown of the macula, which is located in the retina and helps provide clear central vision. As the macula deteriorates, people see a blurred spot in the center of their vision that grows over time.

Macular degeneration comes in two forms, wet and dry. Current treatments for the wet form of the disease -- in which abnormal new blood vessels in the eye cause leakage and bleeding -- have proven quite successful. The wet form is more rare but can cause rapid vision loss if not caught early.

Researchers have discovered a combination therapy of vitamins and antioxidants that reduces the risk of progressive vision loss by more than 20 percent, said Dr. David W. Parke II, executive vice president and chief executive of the American Academy of Ophthalmology.

Other progress against the wet form of the disease has come through the use of drugs that target vascular endothelial growth factor, or VEGF, a substance in the body that promotes the growth of new blood vessels.

"We now have treatments where, when we catch people early in the course of the disease, the chance of vision loss is less than 10 percent over a two-year period," said George Williams, chairman of ophthalmology and director of the Eye Institute at William Beaumont Hospital in Royal Oak, Mich. Those treatments also provide a 20 to 30 percent chance of significant vision improvement over the same period.

No effective treatments have been found for the dry form of macular degeneration, which causes less catastrophic vision loss but accounts for 85 percent of all macular degeneration cases, according to the U.S. National Eye Institute. The dry form occurs when the light-sensitive cells in the macula begin to slowly break down.

New advances in the treatment of the wet form involve further research into vitamin combinations that can help slow the progress of macular degeneration, Parke said. An ongoing trial is looking into whether diet or supplements can better improve a person's chances of retaining clear vision late in life.

"Around the world, there are culturally different rates of progression," Parke said. "The question becomes, how much of this is dietary?"

Research also has focused on the two drugs currently used to target VEGF, with a head-to-head study now looking into which of the two is more effective. "It's a very important trial, and I think all involved are looking forward to seeing if these drugs have a lot of differences," Parke said.

Other anti-VEGF drugs are in the pipeline, Williams said, and studies are testing ways to combine anti-VEGF medications with radiation or laser therapy to produce better results.

Cutting-edge research also may have found another way to tackle the wet form of macular degeneration. In the June 14 issue of Nature, doctors reported that blocking the activity of a specific protein can reduce the same blood vessel growth that leads to the wet form.

"We now have the opportunity to develop drugs that target this protein that may be safer and more effective than our current treatments," Parke said.

As far as the dry form of macular degeneration, eye experts are exploring ways that drugs used to treat other nerve-damaging diseases such as Alzheimer's might be able to help save people's eyesight, Williams said.

"We're fairly optimistic that within three to five years we'll have a treatment for the dry form of macular degeneration," he said. "We know what happens is the nerve cells that sense the light are dying off. The thought here is if we attack the process that makes them die, we can save the vision."

At one time or another, we've all heard our mothers say: “You are what you eat.” At no time has this been truer than today. The Standard American Diet (S.A.D.), or Western Diet, is characterized by high intakes of red meats, processed sugars, saturated fats, refined grains, dairy fat and eggs.

Just a generation ago, it wasn't uncommon for families to raise their own fresh fruits, vegetables and meats. Most produce was fresh and grown locally. Today, however, 70% to 80% of all food consumed is processed, according to the British organization, Nutrition Matters. These changes have led to a lack of proper nutrition and health problems in all age groups. Specifically, processed foods lose much of the vitamins and minerals necessary for normal growth, function and health. Those vitamins and minerals are essential to aid and maintain a strong immune system.

Where you're needed

As optometrists, we have an obligation to share with our patients the importance of acquiring and maintaining good nutrition, as valid clinical evidence reveals it plays a vital role in ocular conditions, such as age-related macular degeneration (AMD), diabetes, dry eye and cataracts. In the case of cataracts, for instance, we know that antioxidants and vitamins, such as C, play a role in their prevention and formation.

Still, despite all the nutritional information we can provide patients, many will never change their dietary habits. By incorporating nutraceuticals and vitamins into our practices, however, we can provide the vitamins, antioxidants and the essential fatty acids/omega 3s (which may be lacking in a patient's diet) that promote good eye health, while at the same time creating an additional revenue stream for our practices.

Willing patients

I've found that when you educate patients that supplements are available to help prevent or reduce their risk of eye disease or alleviate a current ocular condition, many are eager to learn about them.

For example, patients with family members or friends who have AMD are willing to do anything to prevent the onset of the disease, as they see the toll it has taken and continues to take on their close ones.

Further, dry eye patients are eager to find ways to increase their comfort and alleviate their symptoms.

To educate yourself about nutritional requirements, talk to a dietician or nutritionist. These professionals can provide an overall picture of the daily nutrition requirements for most patients. Also, consider inviting one of these supplement specialists to give a nutrition presentation at your next staff meeting.

Don't overlook the importance of a knowledgeable staff. Staff may spend more time with patients than with you. Provide each employee with the same knowledge — it reflects an office that is well educated and well run.

Now, follow these steps to educate patients about supplements and your ability to dispense them:

• Ask supplement providers for educational brochures and displays to help better educate your patients. Display POP-printed materials in exam rooms and the reception area. Further, consider placing visual systems that broadcast educational videos in your reception room — another great way to present information while patients wait for their appointments.

• Invest a couple of minutes of your chair time to discuss the benefits of specific supplements, and encourage patients to use their favorite search engine to read pertinent studies, such as the Age-Related Eye Disease Study (AREDS) and AREDS II.

• Provide educational handouts or follow-up e-mails to patients that include links to appropriate nutrition-related Web sites.

The practice benefit

Half of all Americans reach for some form of dietary supplement on a daily basis. In fact, last year, American consumers spent $23 billion on nutritional supplements.

If patients are going to spend money on supplements, we, as their primary-care optometrist, can help them make informed decisions about products, using, for instance, formularies in addressing their unique nutritional needs. Since so many supplements are available on the market, they'll greatly appreciate our expertise and recommendations. And, this appreciation won't only likely lead to increased practice revenue, but also increased patient loyalty and referrals.

In terms of practice revenue garnered from the sales of supplements alone, consider the following scenario: One patient purchases one supplement bottle each day at a profit of $20. If an average work month has 22 days, the practice would realize a $440 monthly profit, or $5,280 per year. If the single bottle supply lasts two months, each patient would return six times per year to make purchases, thus increasing the bottom line by $31,680 per year. These benefits multiply in a model that includes multi-doctor or group practices.

Choose the right product

Currently, many nutritional products target ocular health alone. Many of these were developed based on the research that came out of FDA-sponsored studies, such as AREDS. As a result recommend products based on solid clinical evidence, and make sure they meet the highest standards and are of pharmaceutical grade. Remember, not all products are created equal, so caution patients about generic and “big box” brands, which may contain “fillers.” Finally, stand behind the product(s) you recommend and sell. Assure patients you'll offer a refund for any that may cause problems, such as gastric distress.

Don't forget the basics

While dietary supplements are useful, it's crucial you encourage patients to maintain a good, healthy diet of whole foods, especially fruits and vegetables (e.g. the dark leafy greens and deeper-colored varieties) and to eat lean meats and fish when possible. After all, a few moments of prevention may mean a lifetime of good health and vision. OM

Taking B vitamins could lower the risk for a leading cause of blindness in older Americans, a study reports.

"This is the first randomized trial to indicate a possible benefit of folic acid, B-6 and B-12 vitamin supplements in reducing the risks of age-related macular degeneration," says study author William Christen, an associate professor of medicine at Brigham and Women's Hospital in Boston.

Christen and his colleagues collected data from a cardiovascular disease trial involving more than 5,200 women over 40 who reported they did not have macular degeneration at the study's start.

The women had been randomly assigned to take either a daily combination of folic acid, B-6, and B-12 supplements or a placebo. They answered yearly questionnaires for about seven years to track pill adherence and the development of new diseases. At study's end, 55 cases of age-related macular degeneration were confirmed in the vitamin group and 82 were confirmed in the placebo group.

Those who took the supplements had a 41% lower risk of being diagnosed with the disease. Even though the study involved only women, the researchers say, the findings probably apply to all older Americans.

"These finding are the first to suggest a possible early prevention measure," Christen says.

The study, paid for by the National Eye Institute, appears in this week's Archives of Internal Medicine.

An estimated 1.75 million people have advanced age-related macular degeneration, and 7.3 million are in early stages of the disease, he says. Few treatments exist, and they are only for advanced forms.

High blood levels of an amino acid, homocysteine, have been linked to a greater risk for age-related macular degeneration, Christen says. "It's fairly well-established that folic acid, B-6 and B-12 can reduce blood levels of homocysteine, so there's a reason to suspect a possible benefit."

More research is warranted, partly to determine the amounts of vitamins necessary to benefit eye health, Christen says. The doses taken in the study were higher than the daily recommended doses, he says.

Another drawback: "The study did not include rigorous eye examinations or retinal photos," says Sophie Bakri, associate professor of ophthalmology, vitreoretinal diseases and surgery at the Mayo Clinic. The macular degeneration diagnoses were obtained by reviewing the participants' questionnaires and medical records.

"We also need future rigorous clinical trials in other populations," Bakri says.