Dry eye therapy more effective when disease mechanism recognized

Issue: May 1998

Clinicians who can determine which layer of the tear film - aqueous, mucus or lipid - specifically needs treatment will likely have happier, more comfortable dry eye patients, said Cristina M. Schnider, OD, FAAO.

"The term 'dry eye' is so broad that if you're really going to treat it, you need to know more about its mechanism," Dr. Schnider said.

Dr. Schnider, director of professional relations and clinical affairs at Menicon, advises clinicians to think about all three layers of the tear film when treating dry eye.

Dr. Schnider recommends that clinicians try to narrow down the actual mechanism of dry eye so they can tailor therapy to minimize symptoms. "There are tests for both the tear volume and the mucous layer, and you can observe the lipid layer pretty easily with specular reflection on the slit-lamp," she said.

Don't overlook lipid layer

Dr. Schnider feels the lipid layer is most often overlooked. "Regardless of how many tears you have, if the lipid layer is not functioning the tears will evaporate more quickly," she said.

With the exception of a few pathological conditions and Sjögren's syndrome, Dr. Schnider said, many people suffer from dry eye as a result of eyelid problems. "Their lipid glands are not producing the right kind of lipids," she said. "I find that tetracycline - or erythromycin if the patient is tetracycline-sensitive - can be tremendously helpful, not because of the antibiotic effect but because it actually alters lipid chemistry. It can help keep the viscosity of the lipid in a more natural state."

Therapy that restores the balance of the lipid layer, she said, will help whatever tears are present simply remain more stable for the patient's comfort. In these instances, she also has patients use vitamin A drops "because they have that little bit of oil that just seems to stabilize the drop in the eye," she said.

The vitamin A drops, Dr. Schnider said, as well as nonpreserved drops, offer patients relief without exposing the cornea to traditional preservatives known to be toxic.

The most challenging patient to treat is one who is mucus-deficient, she said, in which case a treatment that offers high viscosity is needed. "I think this condition is fairly rare, but moving toward an electrolyte-rich drop is appropriate," she said.

Case history helpful

"I tell clinicians that when they do a case history it is important to learn about a patient's environment. Ask a contact lens wearer, in particular, if he or she has problems at work," said Dr. Schnider.

Clinicians who believe the typical dry eye patient is elderly or suffers from an autoimmune disorder may be surprised to learn that dry eye patients do not always fit that profile. Research from Scotland and Canada has shown, in fact, that younger patients who wear contact lenses and work with a computer can suffer from dry eye symptoms more often than elderly patients.

"Two studies I've seen found an association between dry eye symptoms in people younger than 45 and office work and contact lens wear," said Dr. Schnider.

"There have also been studies that show that most computers in an office are at eye level or above, so the aperture is a lot wider and you get enhanced evaporation as compared to reading. It's been shown that when people look at computers, their blink rate goes way down, to 20 seconds or longer."

Dr. Schnider said clinicians are often surprised to think of younger patients suffering from dry eye symptoms "when, in fact, they can have more problems due to contact lens wear and office work."

Rigid lenses disrupt the lipid layer, enhancing evaporation, while soft lenses actively deplete the aqueous layer to maintain their hydration levels, she said.

If contact lens wear is a factor, carefully consider the type of contact lens material you choose for the dry eye patient. "You can make a little problem bigger by selecting the wrong contact lens," she said. "The main reason people fail with dry eye therapy is that there's a shotgun approach instead of addressing the underlying cause."

A place for preservatives?

"If there's a place for the preserved eye drop today, it really depends on what the preservative is," Dr. Schnider said. "GenTeal (Ciba Vision), for example, has peroxide, which I consider natural. If patients are going to be using drops more than once or twice a day or if they wear soft lenses, they should use nonpreserved drops or those with a more natural preservative."

Jeffrey P. Gilbard, MD, now in a solo private practice dedicated to corneal and external disease, and president and CEO of Advanced Vision Research, directed a National Institutes of Health-sponsored research program on dry eyes for 18 years.

He has developed an eye drop that he says goes beyond just being preservative free. "TheraTears (Advanced Vision Research) has been shown in preclinical studies to actually promote healing of the changes seen in dry eye," Dr. Gilbard said.

TheraTears has been shown to restore conjunctival goblet cells in dry eye, and it works by "being hypotonic enough to lower tear osmolarity and rehydrate the eye and by providing the patented electrolyte balance the ocular surface needs for growth, maintenance and repair," said Dr. Gilbard.

"If you don't show that your treatment is restoring conjunctival goblet cells to the ocular surface, your technology is obsolete," he said.

Research and cyclosporine drops

Michael Stern, PhD, is helping lead some of the newest technology in dry eye treatment. As a research investigator at Allergan, Dr. Stern oversees the ocular surface disease program. "We've been looking at the pathophysiology of dry eye for a long time, and we believe there is an immune-based inflammation of the ocular surface and lacrimal glands," he said.

In a healthy environment, he said, the neural traffic between the lacrimal glands, ocular surface and the brain works to secrete normal amounts of tears. In dry eye, however, an inflammation occurs in the lacrimal gland and ocular surface. Dr. Stern said, "The tears that are secreted contain pro-inflammatory cytokines," Dr. Stern said. "These tears inflame the ocular surface, which also manufactures these pro-inflammatory cytokines, and you end up with this positive feedback loop."

Research has also indicated that when there is a drop-off in androgen levels, such as those seen in peri- and postmenopausal women and in men who are on anti-androgen treatment for prostatic problems, the anti-inflammatory environment of the ocular surface is compromised and results in the ability of these tissues to become inflamed.

"Artificial tears are a palliation of the symptoms for short periods of time, but they don't really address the problem," Dr. Stern said. His research team has been studying topical cyclosporine as a dry eye therapy. The agent is currently approved for preventing solid organ transplant rejection, and Allergan is involved in phase 3 clinical trials to show that cyclosporine drops can improve the signs and symptoms of dry eye.

"Cyclosporine has two modes of action," Dr. Stern said. "First, it's an immunomodulator, so it tends to prevent the activation of T cells, which are some of the primary secretors of these cytokines. Second, it acts as an anti-inflammatory. Based on my findings and those of my colleagues and various labs, we've shown there is an immune-based inflammation occurring with dry eye, and that's why cyclosporine is important."

Most of the patients currently enrolled in the phase 3 clinical trials are elderly, peri- and postmenopausal woman, Dr. Stern said. "For the symptoms, we're looking at subjective parameters and have an ocular surface disease index, which is a series of questions that address a patient's functionality."

Results so far, he said, have shown that cyclosporine drops "essentially knock out the inflammation and T cell infiltration in these patients. It takes 3 or 4 weeks for the real effect to kick in, but then these patients can do things they haven't been able to do for years."

That, Dr. Stern said, is what matters most to the dry eye patient. "If you speak with people who suffer from dry eye, they walk around all day thinking of nothing but their eyes," he said. "They're in pain all the time; having moderate to severe dry eye is very debilitating."

Post-refractive surgery

Another group of patients who can benefit from artificial tears are those who have undergone refractive surgery, said Drs. Schnider and Gilbard.

"In surgery and medical treatments, a balanced salt solution is used," said Dr. Schnider, "and the theory is that if you bathe the cornea in its natural balance of electrolytes, you'll add tear volume and the less the cornea will have to adapt."

Keeping the cornea hydration balanced after surgery to allow the epithelium to heal is the goal of postoperative treatment, she said. "It makes sense, particularly in that first week or so following surgery, for the friction to stay at a minimum, and I would recommend using something fairly viscous."

Dr. Gilbard said some patients opt for refractive surgery because they are unable to wear contact lenses due to dry eye. "Postoperatively, these patients may have borderline dry eye conditions," he said, and a therapeutic adjunct may be helpful.

For Your Information:

Cristina M. Schnider, OD, FAAO, may be contacted at Menicon USA, 335 West Pontiac Way, Clovis, CA 93612-5613; (209) 292-2020; fax: (209) 292-2021. Dr. Schnider has no direct financial interest in the products mentioned in the article, nor is she a paid consultant for any companies mentioned.

Jeffrey P. Gilbard, MD, may be contacted at Advanced Vision Research, 7 Alfred St., Suite 330, Woburn, MA 01801; (800) 979-8327; fax: (781) 935-5075; e-mail: jgilbard@mediaone.net. Dr. Gilbard is president and CEO of Advanced Vision Research.

Michael Stern, PhD, is a research investigator at Allergan. He may be contacted there at 2525 DuPont Drive, Irvine, CA 92612; (714) 246-5817; fax: (714) 246-5578.