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As risk factors increase, so does dry eye syndrome
Today's dry eye remedies concentrate on treating inflammation; tomorrow's aim is to prevent it.
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HOUSTON — An aging population, medication side effects and increasing computer use are just a handful of reasons why up to 10 million Americans qualify as keratoconjunctivitis sicca patients.
“There are numerous factors that promote dry eye,” said dry eye specialist Stephen Pflugfelder, MD, of the Baylor College of Medicine. “For instance, more people are having cosmetic facial surgery, more people are having LASIK, which causes dry eye, and people are taking more and more medications with side effects that cause dry eye, like hormone replacements and antidepressants.”
As the dry-eye patient population grows, so do the number of studies regarding its pathogenesis and possible cure.
“In studies of dry eye, people have found that inflammation is a key factor,” Dr. Pflugfelder said. “As we know more about which inflammatory factors are responsible, there may be therapies that are specifically targeted at those factors. It's probably going to turn out that there won't be one factor. There may be a multitude of factors. Any single therapy might only decrease the inflammation by 50%, but that would be good enough for the patients who are really bothered.”
Tears and therapeutics
Improvements in artificial tears have made it easier for most dry eye patients to find relief in over-the-counter products. Bottled formulations such as Refresh Tears (Allergan), GenTeal (Novartis Ophthalmics) and TheraTears (Advanced Vision Research) work well, according to dry eye specialists. The preservative “disappears” when the drop contacts the eye, minimizing the amount of irritation the patient experiences. There are also preservative-free single-dose artificial tear formulations that are appropriate for patients with more sensitive eyes. Celluvisc (carboxymethylcellulose sodium 1%, Allergan), is another artificial tear option. Its extra-thick formula is available only in single-dose preservative-free units. For patients with more severe dryness, nighttime eye ointments such as Refresh PM (Allergan) can work well.
Many patients require something stronger, like the therapeutic cyclosporine, which targets the inflammatory process.
“The goal of therapeutics is to provide patients with long-lasting relief. Artificial tears might last 10 to 15 minutes, whereas an effective therapeutic would provide hours or days of relief from a single instillation. Any therapeutic that is effective will have a great impact on the tens of millions of people with dry eye; essentially right now the only option they have is artificial tears,” Dr. Pflugfelder said.
Restasis, Allergan's cyclosporine compound, was slated to undergo a second round of clinical trials this spring in response to the Food and Drug Administration's request for confirmatory data, according to Marian S. Macsai, MD, of Evanston Hospital in Illinois.
“Restasis decreases the inflammatory cyctokines on the ocular surface, which in turn stops a lot of irritation. And it has a wonderful safety profile,” she said. Meanwhile, until FDA approval is obtained for Restasis, some physicians may be prescribing cyclosporine eye drops on an off-label basis, although there are a limited number of pharmacies presently compounding these drops.
Antibiotics, steroids and occlusion
Topical steroids are another option for treating especially severe dry eye.
“I usually reserve topical steroids for patients who are still symptomatic after using artificial tears or having punctal occlusion, if they can't function or if they have intolerable irritation symptoms,” Dr. Pflugfelder said. Alrex (lodeprednol etabonate 0.2%, Bausch & Lomb) is a good choice for long-term use, he said.
“It's a ‘soft steroid' that is activated by enzymes as it passes through the cornea. Theoretically it doesn't have much intraocular activity. Increased IOP can still occur, but it occurs at a much lower frequency than other steroids and the safety profile is much better,” he said.
Currently, Alrex is indicated for treatment of seasonal allergic conjunctivitis
Another option is tetracycline, an antibiotic with a potent anti-inflammatory effect. In the future there may be a tetracycline compound developed specifically for ocular inflammation, he said.
In cases of aqueous deficiency, punctal occlusion may be the answer. Collagen or silicone plugs, argon laser punctoplasty and thermal punctoplasty may be useful if ocular lubricants are not effective in an aqueous deficiency. One note of caution is to avoid punctal occlusion in blepharitis patients who are mistakenly diagnosed as having dry eye.
“There are some people who get classified as having dry eye although they really have blepharitis and inflammation. In some cases when they get punctal occlusion they actually get worse, because it prevents the drainage of these inflammatory factors,” Dr. Pflugfelder said. He recommends using a tear clearance test rather than a tear production test to diagnose dry eye, because in most cases of dry eye clearance of tears is reduced.
Androgens and dry eye
Studies are underway regarding the connection between androgens and dry eye.
“Statistics show that there is a much higher incidence of dry eye in women, and more than 90% of Sjögren's syndrome patients are female. Clearly there is some imbalance,” Dr. Macsai said. Several studies have suggested that androgen deficiencies result in dry eye syndrome. Dr. Macsai says the question is: “Will androgen replacement work?” She believes the answer is yes, but only if it is started in a preemptive manner.
“If we knew which androgen was the protective one and could measure it in women in the premenopausal years and then supplement that and only that androgen, then perhaps we could protect against dry eye,” she said.
A lesser known theory is that of the role of nutrition in dry eye syndrome. Dr. Macsai says that anecdotal evidence in her practice shows that a diet rich in Omega-3 fatty acids and low in Omega-6 fatty acids and carbohydrates has a positive effect on dry eye patients.
“There are supplements they can take to increase Omega-3 fatty acids like fish oils, flax seed oil and olive oil. It shifts their metabolism somewhat to decrease inflammation,” she said.
She also recommends Vitamin A and Vitamin E supplements for dry eye, but cautions against overuse of these supplements. She says patients who have run out of options — they've been occluded, they're on steroids or cyclosporine, they're doing lid hygiene and wearing moisture goggles — say after making the dietary changes their eyes feel dramatically better.
“At this point, I think that diet should be the first step in treatment rather than the last resort,” she said.
For Your Information:
- Stephen C. Pflugfelder, MD, can be reached at the Cullen Eye Institute, 6565 Fannin, Houston, TX 77030; (713) 798-4944; fax: (713) 798-8739. Dr. Pflugfelder is a paid consultant for Allergan.
- Marian S. Macsai, MD, can be reached at Evanston Northwestern Healthcare, Division of Ophthalmology, Evanston, IL. 60201; (847) 657-1936; fax: (847) 657-1949; e-mail: mmacsai@enh.org. Dr. Macsai has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.
- Bausch & Lomb Pharmaceuticals can be reached at 8500 Hidden River Pkwy., Tampa, FL 33637; (800) 323-0000; fax: (813) 975-7762.