The probability of blindness due to the serious eye disease glaucoma has decreased by nearly half since 1980, according to a study published this month in Ophthalmology. The researchers speculate that advances in diagnosis and therapy are likely causes for the decrease, but caution that a significant proportion of patients still progress to blindness.
A leading cause of irreversible blindness worldwide, glaucoma affects more than 2.7 million individuals aged 40 and older in the United States and 60.5 million people globally. Significant changes in diagnostic criteria, new therapies and tools as well as improvements in glaucoma management techniques have benefited individual patients; however their effect on the rates of visual impairment on a population level has remained unclear. This study, conducted by a team based at the Mayo Clinic, was the first to assess long-term changes in the risk of progression to blindness and the population incidence of glaucoma-related blindness. By identifying epidemiologic trends in glaucoma, the researchers hope to gain insight into best practices for the distribution of health and medical resources, as well as management approaches for entire populations.
The researchers reviewed every incident case (857 cases total) of open-angle glaucoma diagnosed from 1965 to 2009 in Olmsted County, Minn., one of the few places in the world where long-term population-based studies are conducted. They found that the 20-year probability and the population incidence of blindness due to OAG in at least one eye had decreased from 25.8 percent for subjects diagnosed between 1965 and 1980 to 13.5 percent for those diagnosed between 1981 and 2000. The population incidence of blindness within 10 years of diagnosis also decreased from 8.7 per 100,000 to 5.5 per 100,000 for those groups, respectively. Yet, 15 percent of the patients diagnosed in the more recent timeframe still progressed to blindness.
“These results are extremely encouraging for both those suffering from glaucoma and the doctors who care for them, and suggest that the improvements in the diagnosis and treatment have played a key role in improving outcomes,” said Arthur J. Sit, MD, associate professor of ophthalmology at the Mayo Clinic College of Medicine and lead researcher for the study. “Despite this good news, the rate at which people continue to go blind due to OAG is still unacceptably high. This is likely due to late diagnosis and our incomplete understanding of glaucoma, so it is critical that research into this devastating disease continues, and all eye care providers be vigilant in looking for early signs of glaucoma during routine exams.”
Diabetics Losing Vision Despite Advances
Despite recent advances in prevention and treatment of most vision loss attributed to diabetes, a new study shows that less than half of Americans with damage to their eyes from diabetes are aware of the link between the disease and visual impairment, and only six in 10 had their eyes fully examined in the year leading up to the study.
The research, described online on Dec. 19 in JAMA Ophthalmology, also found that nearly half of those with diabetes and eye damage had not visited a clinician charged with managing their disease in that same time period.
“As a nation, we are woefully inadequate as health-care providers in explaining to our patients with diabetes that the condition can have a detrimental effect on their eyes,” says study leader Neil M. Bressler, MD, a professor of ophthalmology at the Johns Hopkins University School of Medicine and chief of the retina division at the Johns Hopkins Wilmer Eye Institute. “The earlier we catch diabetic eye disease, the greater the likelihood that we can help patients keep their good vision. Clearly, this research shows how far we have to go to educate people about this frequent and feared complication.”
People with diabetes have at least a 10-percent risk of developing diabetic macular edema during their lifetime, and estimates suggest that close to 745,000 of them in the United States have swelling in the macula.
Until recently, 15 percent of patients who developed the condition and were treated for it with the standard laser therapy still lost their vision. Dr. Bressler says that ocular injections reduce the swelling and risk of vision loss to less than 5 percent. With treatment, moreover, half of patients find their vision improves, making prompt diagnosis critical.
For the study, the Johns Hopkins-led team of researchers used data collected between 2005 and 2008 from Americans enrolled in the National Health and Nutrition Examination Survey (NHANES). Among the 798 people over the age of 40 with a self-reported diagnosis of type 2 diabetes and who had retinal imaging done, 48 had diabetic macular edema and were asked in the survey whether a physician had told them about the link between diabetes and vision problems (44.7 percent were).
They were also asked whether they had seen a heath-care provider about their diabetes in the previous year (46.7 percent had), and whether they had received an eye examination, including pupil dilation, in the previous year (59.7 percent had). Some 30 percent of the individuals with diabetic macular edema already had some type of vision loss related to the disease.
While some people fail to see eye doctors or diabetes educators because they lack insurance, Dr. Bressler says that most of the problem is likely a lack of understanding about the risks, and most people probably aren’t referred to eye-care specialists who can quickly determine retinal vulnerability.
“We can prevent a lot of vision impairment or blindness if we can just get these people into the medical system,” he says. Now that the extent of the problem is known, strategies can be developed to address issues of patient education, access to specialists and costs.
Available Drug May Treat Aniridia
University of British Columbia and Vancouver Coastal Health scientists have developed a potential cure for a rare eye disease, showing for the first time that a drug can repair a birth defect.
They formulated the drug Ataluren into eye drops, and found that it consistently restored normal vision in mice who had aniridia, a condition that severely limits the vision of about 5,000 people in North America. A small clinical trial with children and teens is expected to begin next year in Vancouver, the United States and the United Kingdom.
Aniridia is caused by the presence of a “nonsense mutation”—an extra “stop sign” on the gene that interrupts production of a protein crucial for eye development.
Ataluren is believed to have the power to override the extra stop sign, thus allowing the protein to be made. The UBC-VCH scientists initially thought the drug would work only in utero—giving it to a pregnant mother to prevent aniridia from ever arising in her fetus. But then they gave their specially formulated Ataluren eye drops, which they call START, to two-week-old mice with aniridia, and found that it actually reversed the damage they had been born with.
“We were amazed to see how malleable the eye is after birth,” said Cheryl Gregory-Evans, PhD, an associate professor of ophthalmology and visual sciences and a neurobiologist at the Vancouver Coastal Health Research Institute. “This holds promise for treating other eye conditions caused by nonsense mutations, including some types of macular degeneration. And if it reverses damage in the eye, it raises the possibility of a cure for other congenital disorders. The challenge is getting it to the right place at the right time.”
Molecule Could Be Key to Corneal Transplant Success
For the estimated 10 percent of patients whose bodies reject a corneal transplant, the odds of a second transplant succeeding are poor. All that could change, however, based on a UT Southwestern Medical Center study that has found a way to boost the corneal transplant acceptance rate.
In the study, researchers found that corneal transplants in mice were accepted 90 percent of the time when the action of an immune system molecule called interferon-gamma (IFN-γ) was blocked and when the mice shared the same major histocompatibility complex (MHC) genotype as the donor cornea. MHC matching is not typically done with human corneal transplants because of a high acceptance rate.
“Our findings indicate that neither MHC matching alone nor administration of anti-IFN-γ antibody alone enhances graft survival. However, we found that when MHC matching is combined with anti-IFN-γ therapy, long-term corneal transplant survival is almost guaranteed,” said Dr. Jerry Niederkorn, a professor of ophthalmology and microbiology at UT Southwestern and senior author of the study.
The study findings, reported in the December issue of the American Journal of Transplantation, suggest an option to improve the odds of a subsequent corneal transplant’s success for those patients whose first transplant was rejected.
More than 40,000 corneal transplants are performed annually in the United States, making this surgical procedure one of the most common and successful in transplantation. But out of that total, about 4,000 fail, with the recipient’s body rejecting the corneal graft and requiring a second operation.
A surprising finding of the study was learning that IFN-γ can act both as an immune system suppressor or activator, depending on the context of the histocompatibility antigens perceived by the immune system, Dr. Niederkorn said. Earlier studies indicated that this molecule only activated immune system rejection of transplants and that disabling IFN-γ would improve the acceptance rate. But that was not necessarily the case; researchers found that when there was no MHC matching between the mice and the transplants, and IFN-γ was disabled, the transplant rejection rate was 100 percent.
“Under those conditions, IFN-γ was needed to maintain the T regulatory cells, which suppress the immune response,” Dr. Niederkorn said.
Rather than recommend transplant matching and inactivation of IFN-γ for all first-time corneal transplant recipients, Dr. Niederkorn said this strategy would make the most sense for those who have already rejected a cornea, or for those individuals believed to be at risk for a corneal transplant rejection. But before a clinical trial can be launched to verify the results obtained in mice, further study is needed.
“We are working to develop an IFN-γ antibody in eye-drop form,” Dr. Niederkorn said. “Then we need to test whether this antibody will work in animal models.”
The lead author of the study was Khrishen Cunnusamy, PhD, a former postdoctoral researcher in Dr. Niederkorn’s lab and current UT Southwestern medical student.