New artificial tear formulas, advances in punctal occlusion provide hope for dry eye

Issue: May 2000

The treatment plan for dry eye has been relatively straightforward: use rewetting drops to help keep the ocular surface moist. If that is not sufficient, have punctum plugs inserted into the lower puncta and, if necessary, the upper puncta. A more permanent solution would be punctal cautery.

Today, ophthalmic companies are devising new ways of providing relief from ocular dryness, and more options than ever are available to people suffering from dry eye, no matter how mild or severe the condition. New artificial tears have higher viscosity and disappearing preservatives and they are even designed specifically for contact lens wearers. More often than not, the goal today is to heal the dry eye, not simply re-wet it.

The “disappearing” preservative

While the concept is not brand new, certain drops that have successfully treated dry eye are joining the ranks of the disappearing-preservative products. Previously available only in unpreserved single-unit doses, TheraTears (0.25% sodium carboxymethylcellulose, Advanced Vision Research) is branching out into a bottled version that features the solution in a preserved form that breaks down into oxygen and water upon contact with the eye.

After patients have gone through the “saturation dosing” period with the single-unit doses, said Jeffrey P. Gilbard, MD, founder and chief executive officer of Advanced Vision Research, they can continue treatment in smaller amounts when the eyes begin to experience less dryness. “With saturation, we can lower tear film osmolarity faster and get these patients comfortable faster,” said Dr. Gilbard. “As they continue to use TheraTears, their eyes start to feel better and better. So, rather than using the entire contents of a single-unit container for both eyes, they’ll be able to graduate to TheraTears in a bottle, where they can use one or two drops at a time.”

Dr. Gilbard said that the product is unique in that it promotes the healing process in dry eye, restoring conjunctival goblet cells as opposed to simple lubrication of the ocular surface. “We were able to patent the electrolyte balance of the tear film by showing that this balance is crucial for the maintenance of conjunctival goblet cells,” he said. “Lowering osmolarity and providing this electrolyte balance permits the reblossoming of conjunctival goblet cells that provide the natural lubrication for the ocular surface.”

TheraTears in a bottle began shipment on March 31 and arrived in drugstores on May 1.

New item from CIBA

Similarly, CIBA Vision has introduced a new addition to its dry eye armamentarium. The company that created the GenTeal (hydroxypropyl methylcellulose) line and Hypo Tears drops is launching Hypo Tears Select (polyvinyl alcohol 1%). This drop’s disappearing preservative also breaks down into components of water and oxygen upon eye contact.

“It takes literally seconds for that preservative to disappear once it hits the tear film and the ocular tissue,” said Robert D. Houdek, OD, the director of optometric services for CIBA Vision Corp. “So you don’t have to worry about developing a toxic reaction to the preservatives of the product, which is one of the biggest problems with preserved tears.”

Hypo Tears Select, which was launched in April, expands the current sodium perborate family of dry eye products, said Dr. Houdek. “Hypo Tears Select has a fairly thin viscosity with the disappearing preservative,” he said. “If you need a slightly more viscous tear, you can recommend the GenTeal, but you still have the disappearing preservative. If you need an even more viscous preparation, you can use the GenTeal gel, which also has sodium perborate as a preservative. If a patient requires further assistance, they can be fit with the Tear Saver punctum plugs.”

Drops for contact lenses

The RefreshTears Comfort Drop (carboxymethylcellulose sodium, Allergan), launched at the Southern Council of Optometrists meeting in Atlanta in February, is an artificial tear formulated specifically for use with contact lenses. Michael Stern, PhD, research investigator for Allergan, said that such a drop aids dry eye patients, particularly those who suffer dry eye from wearing contact lenses.

“It allows contact lenses to sit on the cushion of these tears — the tear film — and it makes them more comfortable,” said Dr. Stern. “One problem for people with borderline dry eye — those who are fine normally, but are uncomfortable wearing contact lenses — is that their tear film becomes more compromised with time, making them unable to wear contacts for extended periods. So contact lenses do require a stable tear film to sit on so they can feel comfortable.”

While the tear provides some symptomatic relief, said Dr. Stern, it also has a preservative that breaks down once it comes in contact with the eye. “This tear has a purite preservative, which means it’s essentially nonpreserved when it hits the ocular surface,” he said. “The advantage of this is that you can have it in a single bottle, in a multi-dose container, yet it does not present the eye with a potent surface-active preservative such as benzalkonium chloride.”

RefreshTears, first launched in May 1997, and Refresh Plus both contain carboxymethylcellulose (CMC), an advanced polymer that provides strong mucoadhesion. The result, says Allergan, is prolonged retention without increased viscosity or blurring. The company states that CMC possesses strong mucoadhesive bonding groups that promote adherence to the epithelial surface, and it is a negatively charged polymer that mimics the mucin layer in natural tears.

Custom-fit punctal occlusion

Alcon is currently seeking approval from the Food and Drug Administration (FDA) to commercially sell the Tears Naturale PORT Punctal Occluder, a gold-filled matrix of heat-responsive polymer material that is inserted through the punctum as a liquid and solidifies within seconds to conform to the patient’s drainage duct. The company looks to have the PORT occluder move to commercialization late in 2000.

Currently, the company’s primary dry eye treatment is Bion Tears Lubricant Eye Drops (hydroxypropyl methylcellulose), launched in 1992. This product’s composition is similar to natural tears because it includes essential ions containing both bicarbonate and zinc, said Stuart Raetzman, marketing director in consumer products for Alcon. “Corneal epithelial cells, with the help of carbonic anhydrase, produce bicarbonate (the natural buffering agent for the eye), and Bion Tears augments this,” said Mr. Raetzman.

“Furthermore, zinc is important in the development and differentiation of new cells and is essential in the mechanism of bicarbonate production by corneal cells because it is an essential part of the carbonic anhydrase molecule,” he continued.

In addition, the drops maintain the tight junctions of the corneal epithelium and help stabilize the mucin, said Mr. Raetzman. “This is important in helping treat dry eye because the corneal epithelium forms a barrier between the environment and the corneal stroma and provides a smooth surface to allow comfortable blinking and wettability,” he said.

The wait for Restasis

Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan), a topical formulation recommended for the treatment of keratoconjunctivitis sicca, awaits word from the FDA after receiving an approvable letter Aug. 24, 1999. Dr. Stern said that the approval of Restasis could be a breakthrough for moderate to severe dry eye sufferers.

“This would be the first actual therapeutic for dry eye; there’s nothing else on the market,” he said. “It could be a very big benefit to the patient with more moderate to severe forms of the disease. In clinical trials, we performed more scientific tests looking at the immune cells in these patients. We have shown a benefit there — these immune cells are decreased and the markers of inflammation decrease.”

Allergan resubmitted the approvable letter on Dec. 9, 1999, based on questions posed by the FDA regarding the efficacy of the drug. The 6-month period allotted for the review ends June 9, by which time the FDA is required to inform Allergan of its decision.

The role of androgens

Dr. Stern said that a theory regarding the possible role of androgens in dry eye cases is behind a new supplement undergoing clinical trials at Allergan. “Androgens tend to suppress inflammation: they’re anti-inflammatory hormones,” he said. “They act through TGF-beta, which is a growth factor that suppresses inflammation, and they provide this anti-inflammatory environment in the lacrimal glands.”

When these androgens decrease —often at the time of menopause in women or in men undergoing anti-androgen-type therapies for prostate diseases, Dr. Stern said — abnormalities in the tear film often develop, inciting dry eye. “So we believe that by topically supplying the androgens to the accessory lacrimal glands and the ocular surface, and potentially the meibomian glands, we can prevent this inflammation from progressing and, in fact, resolve it and restore the tear film,” he said.

Phase II trials for the supplement have not yet begun, said Dr. Stern.

For Your Information:

Jeffrey P. Gilbard, MD, is the medical director of the Cornea & Vision Correction Center, clinical assistant professor at Harvard Medical School and founder and chief executive officer of Advanced Vision Research. He may be reached at 7 Alfred Street, Suite 330, Woburn, WA 01801; (800) 979-8327; fax: (781) 935-5075; e-mail: info@theratears.com.

Robert D. Houdek, OD, is the director of optometric services for CIBA Vision Corporation. He may be reached at 11460 Johns Creek Parkway, Duluth, GA 30097-1556; (800) 533-1676, ext. 3168; fax: (678) 415-4202.

Michael Stern, PhD, is a research investigator for Allergan. He may be reached at 2525 Dupont Drive, Irvine, CA 92713; (714) 246-4500; fax: (714) 246-4374.

Stuart Raetzman is the marketing director in consumer products for Alcon Laboratories Inc. He may be reached at 6201 South Freeway, Fort Worth, TX 76134; (817) 293-0450; (800) 757-9195; fax: (817) 568-7177.