Gene variants tied to progression of eye disease

Age-related macular degeneration is the most common cause of vision loss in people over 60, but only some of the people who have the early or intermediate stages of the eye disease develop its more serious form, losing so much of their central vision that they can no longer drive or read.

Researchers led by Dr. Johanna M. Seddon of Tufts-New England Medical Center report in tomorrow’s Journal of the American Medical Association that people with variations in two common genes have a two- to four-times higher risk of developing advanced AMD. When combined with smoking and obesity, already known risk factors for advanced AMD, the gene variations pushed the risk of advanced AMD 19 times higher.

"We have shown how genetic variations do add to progression," Seddon said in an interview about the clinical trial, which followed 1,466 people for about six years. "Genetic factors, smoking and obesity are all independent factors related to progression of AMD and they seem to be additive."

But Seddon and her co-authors, who include Sarah George and Bernard Rosner of Harvard, say it's too early to call for genetic screening. Many, but not all, people with the gene variations progress to advanced AMD, but so do some people without the gene variation."The story is unfolding and we have a lot more to learn," Seddon said. "Genetic screening is premature at this point."

They do recommend that people exercise, eat a healthy diet and not smoke, based on previous work implicating the same risk factors for cardiovascular disease in AMD. Seddon showed in 1994 that diet is linked to AMD, and in 1996 that smoking is related.
Dr. Bruce P. Rosenthal of Lighthouse International, a non-profit organization established to help people with vision loss, said the study will be valuable as researchers continue to seek the root causes of the disease.

"While we have known for many years that smoking and being overweight contributes to the risk of macular degeneration, the findings of a genetic link for the progression of macular degeneration from early or intermediate stages to advanced disease are indeed significant and will have a major impact on future study and possible treatment of AMD," he said in a statement.

Rosenthal was not involved in the study, which was funded by the National Eye Institute and other grants.