Options broaden for treating dry eye

Issue: May 1999

While dry eye can be a stubborn condition for both patients and practitioners, treatment options are expanding. The most commonly used topical treatment is artificial tears, which soothe the nonlubricated ocular surface and — for the most part — are well tolerated. Gel-like ophthalmic lubricants form an occlusive film over the ocular surface and protect the eye from drying, but these are associated with blurred vision and are typically reserved for nighttime use. Practitioners may also recommend that patients avoid specific environmental factors that could be associated with dry eye and eye rubbing. On the other end of the treatment spectrum, some practitioners are using short bursts of mild steroids to quell the inflammatory response in severe dry eye patients and to provide some subjective relief.

A new therapy is also on the horizon. Cyclosporine, typically known as an immunosuppressant to prevent organ rejection, has been studied as a potential treatment for dry eye, with the possibility as an effective longer-term aid. According to investigators, the fact that cyclosporine is approved for treating dry eye in dogs prompted human clinical trials. Allergan is conducting phase 3 trials, and Allergan research investigator, Michael Stern, PhD, said that a premarket approval application is expected to be filed this year.

Common treatment: artificial tears

When considering tear substitutes, clinicians have a choice of preserved or preservative-free varieties; the latter is usually preferred. Artificial tears that contain preservatives may actually worsen symptoms rather than alleviate them.

James Lanier, OD, in private practice in Jacksonville, Fla., told Primary Care Optometry News that he prefers nonpreserved artificial tears for his patients to avoid potential allergic reactions to preservatives, which could complicate the diagnosis. He generally uses TheraTears (0.25% carboxymethylcellulose, Advanced Vision Research), BionTears (hydroxypropyl methylcellulose, Alcon) and Refresh Plus (carboxymethylcellulose sodium 0.5%, Allergan).

Monica L. Monica, MD, PhD, in private practice in New Orleans, said that she has switched 50% of her dry eye patients to GenTeal (hydroxypropyl methylcellulose, Ciba Vision). “I am really happy with the GenTeal product because of the dosing and price. Although Refresh Plus is a single dose, GenTeal is a little more user friendly,” Dr. Monica said, “and GenTeal is priced competitively when compared with Refresh Plus in our area.”

Dr. Lanier noted that some patients may respond better to a preserved drop. “For those patients who have an issue with unidose, which is what drops such as TheraTears and BionTears are, I like GenTeal, which is preserved, but has a self-neutralizing formula that doesn’t seem to be abrasive,” he said.

GenTeal contains a preservative, sodium perborate, which changes into water and oxygen upon contact with the tear film and ocular tissue. Refresh Plus restores eye moisture with a special formula that has some of the qualities of natural tears.

Improve lid hygiene

In conjunction with recommending artificial tears, Dr. Lanier also suggests evaluating the lid margin hygiene, which could be a causative factor for dry eye.

“Heating the margin of the lid, scrubbing the margin and the lid area and putting compresses on the lid cause the oil glands to secrete oil in a more normal fashion. A lot of patients are deficient in that oil. They make a lot of tears, but they don’t make enough oil to seal the tear against the eye. We try hygiene first, and if that doesn’t work we go to plugs,” he said.

Tears good, but not first line

William J. Rand, MD, in private practice in Pompano Beach, Fla., agrees that both GenTeal and Refresh Plus are good therapies but said they are not first-line therapies. “I don’t start with nonpreserved drops,” Dr. Rand said. “I try preserved drops such as HypoTears (hydroxypropyl methylcellulose, dextran 70, Ciba Vision) or Tears Naturale (hydroxypropyl methylcellulose, dextran 70, Alcon), then I would try Refresh or something similar afterward.”

If a patient has severe dry eye, and artificial tears used four times a day are not working, perhaps switching to a higher viscosity tear that seems to last longer would help. “One that really works is Celluvisc (carboxymethylcellulose sodium 1%, Allergan),” said Anne Ricks Sumers, MD, a private practitioner in Ridgewood, N.J. “It is very thick, so it coats your eye. It really does blur your vision for 1 to 5 minutes, but it lasts a lot longer.” Dr. Sumers said if Celluvisc or Refresh Plus lubricant eye drops do not provide adequate relief, she then investigates patients’ environments to see if their surroundings could be the culprit causing dry eye.

Dr. Rand does not commonly recommend thicker drops. “The difference is minimal — the drops are too thick, and they blur vision. Patients’ acceptance is marginal,” he said.

Eschewing therapeutics for plugs

Because of the success he has had with collagen and permanent punctal and lacrimal plugs, John L. Schachet, OD, in private practice in Englewood, Colo., told Primary Care Optometry News that he rarely uses therapeutics when treating dry eye patients.

After evaluating the patient’s history and conducting the phenol red thread, tear break-up time and Schirmer’s tests, then performing a lissamine green or rose bengal staining, Dr. Schachet will immediately opt to use four collagen implants to begin his treatment.

“I’d much rather go right to the plugs than require patients to continually have to use drops,” he said. “We became aggressive and realized that plugs worked. We have had positive patient responses, where they say the treatment has literally changed their lives, or that for the first time in years they are not aware of their eyes. When you hear that over and over again, you realize the plugs work.”

Steroids for severe damage

For patients who have severe tissue damage and are in a great deal of discomfort as a result of prolonged dry eye, Eric Schmidt, OD, in private practice in Elizabethtown, N.C., turns to a brief dosage of a mild steroid to allow the inflammatory response to subside.

“Many times, a topical steroid such as Eflone (fluorometholone, Ciba Vision) or FML (fluorometholone, Allergan) will really calm down the inflammatory response and quiet down the tissue damage that has been occurring for so long,” Dr. Schmidt told Primary Care Optometry News.

Typically, Dr. Schmidt will prescribe a topical steroid to be administered at least four times daily for a period of 10 days. In some cases, a longer course may be required, but he does not prescribe a steroid for more than 2 weeks. Ten days is usually sufficient to provide subjective relief for the patient and allow artificial tears to be effective for more long-term relief.

A steroid-antibiotic combination also can be helpful for patients who experience irritation or inflammation as a result of the insertion of a silicone plug, Dr. Schachet said. “Usually, irritation will occur in the first 24 to 72 hours. At that point, we will use a therapeutic steroid antibiotic combination drug to quiet it down,” he said.

In these cases, prescribing the combination drug for 3 to 4 days will relieve the inflammation, he said.

Cyclosporine on the horizon

Currently, the Food and Drug Administration (FDA) has not approved the use of cyclosporine in the human eye. “Cyclosporine controls immune-based inflammatory conditions in the eye, so some doctors are having it compounded for use in these conditions,” Dr. Stern said. “They are treating certain types of severe allergies as well as other immune-based inflammatory diseases.”

Dr. Schmidt generally uses cyclosporine for patients who have not sufficiently responded to occlusion therapy.

“The reason cyclosporine works so well is it helps reverse some of the tissue damage that has occurred,” he said. “For example, one of the big anatomical changes we see in ocular surface disease is goblet cell death. Cyclosporine quiets down the immune system and the inflammatory reaction subsequent to it, and it allows the goblet cells to regenerate quite nicely. It helps prevent cell death if used properly.”

Because the long-term safety and efficacy of cyclosporine in the eye has not been studied, Dr. Schmidt limits dosage to four times daily. He closely follows patients on cyclosporine to monitor potential side effects.

Other uses of cyclosporine

Joseph Tauber, MD, who has conducted research involving cyclosporine during the past 10 years, has used the drug for ocular ailments in addition to dry eye. “I’ve used it for high-risk cornea transplantations, some allergic conditions, uveitis and other immunologic problems,” Dr. Tauber said. “I have had a fair amount of experience with the drug in a variety of formulations.”

Dr. Tauber said approximately 22 patients in a phase 3 study took cyclosporine for a year and approximately 28 patients in a phase 2 trial took cyclosporine for 2 years in an open-label extension study. He was impressed by the improvement experienced by these patients being treated for dry eye.

“There were some patients who had benefits lasting a month following cessation of therapy, and some had benefits lasting longer,” Dr. Tauber said. “I don’t believe we can say that cyclosporine cures, but I think the effect certainly lasts at least some period of time after discontinuing treatment.”

Animal use prompts human trials

According to Dr. Stern, data generated in the dry eye dog resulted in important evidence of the disease mechanism and prompted the human clinical trials. “We have been attempting to determine what ocular surface disease really is and what dry eye is,” he said.

Dr. Stern cited new research showing that dry eye involves an immune-based inflammation of the ocular surface and lacrimal glands. That research found significant T cell and other immune cell involvement. “The tears that are secreted out of the eye carry many pro-inflammatory cytokines,” Dr. Stern said. “The ocular surface cells themselves become very much inflamed, and it is our belief that this ocular inflammation is what is bothering the patient. Artificial tears are lubricating and do not eliminate the underlying inflammatory process.”

Cyclosporine works by preventing T cell activation and by acting as an anti-inflammatory. It restores the ocular surface to a more normal configuration, thereby relieving the symptoms, according to Dr. Stern.

In researching the pathology of dry eye, Dr. Stern found that the ocular surface, lacrimal glands and interconnecting innervation dysfunction. In a normal individual, stimulation of the ocular surface goes through a neural pathway to the central nervous system and then back to the lacrimal gland, which results in a secretion of normal tears to the ocular surface.

“It is believed that the glands themselves are kept in a noninflammatory environment by circulating androgens,” Dr. Stern said. “In certain patients, when these levels of androgens drop below a protective threshold, you can get a neurogenic-based inflammation of the lacrimal gland.”

He explained that the tears secreted onto the ocular surface contain pro-inflammatory cytokines that were produced by inflammatory cells within the lacrimal glands, causing the ocular surface to become inflamed. Cyclosporine works by eliminating the immune-based inflammation on the ocular surface.

“There are several lacrimal glands,” Dr. Stern said. “There is the main one, but there are also accessory glands that sit in the superior conjunctiva. It is those glands that may be responsible for normal tear flow and are affected in dry eye just as the main lacrimal gland is affected.”

For Your Information:

Michael Stern, PhD, can be reached at Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612; (714) 246-4500; fax: (714) 246-5578; e-mail: stern_michael@allergan.com. Dr. Stern is a research investigator for Allergan Inc.

James Lanier, OD, can be reached at 1500 Riverside Ave., Jacksonville, FL 32204; (904) 356-7101; fax: (904) 356-7947; e-mail: jclanier1@ mediaone.net. Dr. Lanier has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Monica L. Monica, MD, PhD, can be reached at 143 Robert E. Lee Blvd., New Orleans, LA 70124; (504) 282-8172; fax: (504) 282-6701; e-mail: mlong511@aol.com. Dr. Monica has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

William J. Rand, MD, can be reached at 5 W. Sample Rd., Pompano Beach, FL 33064; (954) 782-1700; fax: (954) 782-7490; e-mail: wjr@randeye.com. Dr. Rand has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Anne Ricks Sumers, MD, can be reached at 1200 E. Ridgewood Ave., Ridgewood, NJ 07450; (201) 612-0044; fax: (201) 612-9446; e-mail: asumers@ bellatlantic.net. Dr. Ricks Sumers has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

John L. Schachet, OD, can be reached at 8586 E. Arapahoe, Ste. 100, Englewood, CO 80112; (303) 771-4221; fax: (303) 721-7759; e-mail: Jschachet@aol.com. Dr. Schachet has no direct financial interest in the products mentioned, nor is he a paid consultant for any companies mentioned.

Eric Schmidt, OD, can be reached at PO Box 2589, Elizabethtown, NC 28337; (910) 862-4268; fax: (910) 862-2057. Dr. Schmidt did not disclose if he has a direct financial interest in the products mentioned in this article or if he is a paid consultant for any companies mentioned.

Joseph Tauber, MD, can be reached at 11213 Nall, Leawood, KS 66211; (913) 261-2020; fax: (913) 261-2090; e-mail: jtauber@microlink.net. Dr. Tauber has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.