Concocting the recipe for natural teardrops

To most of us, tears are those wet, salty drops that come out of our eyes when we cry. To scientists who study them, they're those wet, salty, oily, mucous, protein-filled drops that lubricate our eyes and protect them from dust, debris and infection.

For the most part, tears go unnoticed - until something goes wrong. Eyes sting, burn, itch or turn red. They feel like they're full of sand or being poked with a stick.


These symptoms, grouped under the general label "dry eye," can develop when a person doesn't make enough tears, when tears evaporate too fast, or their intricate chemical balance is knocked out of kilter.

Scientists are working to find more - and more effective - approaches to treating the problem. Several new products have entered the market in recent years and are jockeying for position with older remedies, sometimes with only unpublished trials to support them. More strategies are under development.


The task is tricky, because tears are more complex than pure water. The lacrimal glands, just below the eyebrow, produce them continuously. Salty water forms the middle - aqueous - layer of a three-layered tear film that lubricates and protects our eyes.

Below it lies the sticky mucous layer, secreted by the conjunctiva, a transparent membrane covering the surface of the eyeball. Mucus "glues" the film in place. Third is the lipid, or oily, layer produced by tiny sebaceous glands, the meibomians, lined up along the edges of the eyelids. The lipids get squirted onto the eye surface when we blink, and float on the top of the aqueous layer, like oil on a puddle, minimizing evaporation.

The tear film is constantly being renewed. The old batch drains out into our nose and throat through tiny holes called puncta, and the eyelids spread a new batch smoothly and evenly across the surface of our eyes. This happens every time we blink - and we blink 12,000 to 15,000 times a day.

There are many causes of dry eye, including an autoimmune disease called Sjogren's syndrome that attacks the tear-producing glands of the eye, side effects of Lasik surgery, taking antihistamines or spending too much time at a computer. Women and older people are most prone.

Experts estimate that 20 million Americans have mild symptoms, while for 6 million women and 3 million men, the symptoms are moderate to severe.

"Our aging population of baby boomers is resulting in a very significant increase in the number of people who suffer from dry eye," says Doug MacHatton, vice president of investor relations and strategic communications for Alcon Laboratories in Fort Worth, Texas.

Because dry eye is getting more prevalent, over-the-counter treatments are big business.

Among the recent entrants into the market is Optive, introduced by Allergan last month, designed to fight the problem of over-salty tears. It contains two key ingredients in addition to water - carboxymethylcellulose, a lubricant with a unique binding effect, and glycerin, which helps keep the eye hydrated.


Complicated mix

"The glycerin goes into cells, takes water with it and keeps it there," says Joe Vehige, Allergan's senior director of consumer eye care research and development. In an unpublished, 90-day study of about 300 subjects with dry eye symptoms, he says, Optive outperformed two other popular artificial tear products: Refresh, also made by Allergan, and Systane, made by Alcon. Performance was rated on six common measures, including needed frequency of use and comfort rating. MacHatton's company's product, Systane, introduced in 2003, improves comfort by increasing lubrication between the eyelid and the cornea. It does so by combining a substance called hydroxypropyl guar (HP-Guar), a gelling agent that works to hold Systane on the eye surface, with polyethylene glycol 400 and propylene glycol, two lubricants.

Kim Fisher, Alcon's senior product manager for dry eye, says that several controlled, double-blind studies have shown that Systane outperforms other solutions on four of the main patient symptoms - burning, dryness, grittiness and the feeling that something is in the eye.

New developments came also from a better understanding of what happens to eyes when they're dry. In the late 1980s, Stephen Pflugfelder, professor and director of the ocular surface center in the department of ophthalmology at Baylor College of Medicine in Houston, discovered high levels of inflammatory mediators in the tear film of dry eye patients - chemicals, that is, involved in the inflammation process. One of the first he identified was Interleukin-1, part of the body's response in fighting infection.

"This showed there was inflammation going on in dry eye," Pflugfelder says. Indeed, scientists believe that dry eye can be caused by inflammation of the lacrimal and meibomian glands, resulting, respectively, in insufficient tear production or too much tear evaporation. Three treatments intended to fight inflammation have either come on the market recently or are in clinical trials.

One is Restasis, introduced by Irvine, Calif.-based Allergan in 2003. It contains the anti-inflammatory chemical cyclosporine. Restasis has been shown in clinical trials to increase tear production and is the only prescription eye drop approved by the Food and Drug Administration for that purpose.


More than 4 million prescriptions for Restasis have been written so far. It is most effective in treating chronic dry eye early in the disease, Allergan's Vehige says.

Also in 2003, a company called Advanced Vision Research, makers of an older dry eye remedy called TheraTears, introduced TheraTears Nutrition, an oral supplement designed, like Restasis, to counter inflammation, but with all-natural ingredients that didn't require FDA approval.

TheraTears Nutrition is a blend of vitamin E with flaxseed oil and fish oil - providing short- and long-chain omega-3 fatty acids, respectively, says Jeffrey Gilbard, a clinical assistant professor at the Harvard Medical School, director of the Dry Eye Clinic at the New England Eye Center, and founder and chief scientific officer of Advanced Vision.

His studies, he says, have shown that short-chain omega-3s thicken the oily layer of the tear film, but do not suppress inflammation, while long-chains do the opposite. At a scheduled meeting of the Association for Research in Vision and Ophthalmology in May, Athena Papas, professor of dental research at Tufts University, says she will present evidence that TheraTears Nutrition makes patients with dry eye (and dry mouth) feel significantly better.

Hormone help

David Sullivan, a senior scientist at Schepens Eye Research Institute and an associate professor of ophthalmology at Harvard Medical School, is attacking inflammation with still a different weapon: hormones.


He originally hypothesized a connection between dry eye and hormones because dry eye is much more common in women, and because the occurrence of dry eye goes up as people get older - as the production of the sex hormones estrogen and androgen is going down.

Sullivan has studied the effects of estrogen and androgen on dry eye. Perhaps surprisingly, he found that upping estrogen levels may actually make dry eye worse. But he has found that topical treatment with androgen suppresses inflammation in both the lacrimal and meibomian glands in patients with Sjogren's syndrome.

Researchers in Italy have shown that androgen has a positive effect on the mucous layer too, he says. Androgen drops are in a second round of clinical trials at Allergan.

Researchers at Alcon have been developing a very different product, based on a "mucin secretagogue," a substance that increases the secretion of a particular mucin. MacHatton says initial test results were good, but they haven't been able to prove its effectiveness in clinical trials.

As a dry eye patient himself, MacHatton notes that there's something unpredictable about the phenomenon of dry eye that may make the perfect remedy hard to pin down.

Although he believes that Systane is the best artificial tears product, he says, "There are times when I'm using it, and it's just wonderful. There are other times when it's not."


Karen Ravn wrote this article for the Los Angeles Times.