Drug Backed Even Though It Turns Blue Eyes Brown

SILVER SPRING, Md. - A new type of drug to battle vision-stealing glaucoma works significantly better than standard therapy - but has the startling side effect of turning blue eyes brown.

Despite not understanding the cause or significance of the eye-color change, the Food and Drug Administration should approve latanoprost, a panel of scientific advisers decided yesterday.

But the FDA panel insisted that manufacturer Pharmacia & Upjohn Inc. continue to study the drug's long-term safety and clearly label that it can cause the eye color change so doctors and patients understand the risk.

"This could turn out to be a major public-health hazard for glaucoma patients," said Dr. Alexander Brucker of the University of Pennsylvania, who opposed the drug.

Other panelists countered that there is no proof of such danger and voted 4-2 to approve the drug. "It is very effective" at fighting glaucoma, said Dr. Emily Chew of the National Eye Institute.

The FDA is not bound by advisory-panel decisions but usually follows them.

Glaucoma blinds 80,000 Americans a year and steals some sight from 900,000 others. It is caused when fluid builds up inside the eyeball and causes dangerous pressure. Over time that pressure pushes against the delicate optic nerve until it is damaged and the person begins to lose eyesight.

Standard therapy is a drug called timolol. This eye drop makes the eye produce less fluid, thus keeping the pressure down. But it has numerous side effects, from breathing problems to irregular heartbeat. And people with heart or respiratory problems cannot use it.

Latanoprost is the first of a new class of drugs based on a natural chemical called prostaglandin, which helps the eye drain its fluid.

In a study of 829 patients, those who took latanoprost had a 37-percent greater drop in inner-eye pressure than timolol patients. They also had significantly fewer side effects.

But some had a startling side effect: blue eyes turned brown, as did green, hazel and even yellowish ones. The color change hit 15.5 percent of patients after a year of latanoprost use.

"This is a very strange side effect," acknowledged Dr. Johan Stjernschantz, the company's lead researcher. "There is no other drug or agent that can cause this side effect."

And it is not a reversible change, even when patients stop taking the drug. The question is whether the change is cosmetic or dangerous.

The company theorizes that latanoprost increased the amount of melanin in people's eyes. Melanin is a chemical that gives people skin color, and everybody's eyes have some. But lighter-colored eyes don't produce as much of the pigment, allowing light to better diffuse through the eye and reflect back as, for example, a blue color.

The company gave high levels of latanoprost to monkeys for a year and counted the number of melanin-producing cells, finding no increase. But these cells were producing more of the kind of melanin that causes a dark color than the kind that causes yellower colors.

The company notes that 10 percent of the population experiences an unexplained eye-color change by adulthood anyway.

But critical panelists asked whether the melanin-producing cells would eventually get so full that they burst.

The company noted that if a patient's eye color does not change by 18 months of therapy, it probably will not change.