therapeutic insights
Old Problem, New Twist
Alcon's new over-the-counter dry eye product addresses the mucin layer.
Christina S. Wilmer, O.D., F.A.A.O.

How many dry eye patients do you have in your practice? For many practitioners, the number is high and our treatment regimen is often inadequate. Treatment may only improve symptoms temporarily, leaving patients frustrated.

Aqueous replacement is key

Our diagnosis of dry eye depends on the evaluation of the tear components and on choosing a treatment appropriate to the deficient portion of the tear film. Currently our mainstay of dry eye therapy is aqueous replacement via non-preserved artificial tear supplements.

Aqueous replacement keeps the corneal surface hydrated and the patient comfortable. Individual vial droppers may have a place in dry eye therapy but as always, creating a regimen that our patients can incorporate into daily life is crucial. The development of dissipating preservatives in bottled products such as Refresh, Genteal and Thera Tears has made aqueous replacement therapy patient friendly, thereby enhancing compliance and results. Patients are more likely to use a product that they can carry in a purse or briefcase -- not if it's a leaky, single-dose vial.

In addition to adding lubrication, we also try to retain the presence of aqueous with punctal occlusion via temporary collagen and semi-permanent silicone plugs. Although punctal occlusion can be a powerful treatment, it's sometimes not a feasible solution. I've found that the results are often temporary, with the patient initially experiencing a significant reduction in symptoms only to find that the effects diminish over time. So it's back to the bottle for many, frustrated by the temporary freedom they've experienced.

Identify the problem

Lipid layer dysfunction is a common cause of dry eye symptoms. Identifying the offending lid disease and meibomian gland dysfunction can lead to a successful, symptom-reducing treatment. As we know, the surface lipid layer is crucial in diminishing evaporation while maintaining a stable surface. By reducing evaporation between blinks, we effectively minimize our patient's symptoms.

Lid hygiene and medical treatment of meibomianitis gives the patient (and us) a degree of relief. Medical treatment has conditioned our patients to desire the "quick fix" with prescription medication; I find that initial compliance in treating lid disease is consistent with high patient motivation.

In addition to drops and plugs, patients' symptoms often dictate that we add ointments and gels to help improve symptoms and surface dryness.

Targeting the mucin

Hydrophilic mucin, a component of the tear film, coats the inherently hydrophobic corneal surface. The mucin creates a hydrophilic field compatible with the aqueous. The hydration of the corneal epithelium is obviously crucial for cell health. On surface corneal epithelial cells, microvilli protrude into the tear film and create the surface structure crucial to stable tear film adherence.

Glycocalyx is produced by the epithelial cell, which interacts with the mucin to create a hydrophilic mucin-glycocalyx-microvilli complex. When these complexes are compromised, surface drying causes damage and loss of the corneal epithelial microvilli. Tear stability is also diminished. This instability remains as the epithelium continues to dry prematurely between blinks. We see this as dry spots develop during tear break-up measurements.

Alcon offers a solution

A new over-the-counter product by Alcon targets this tear component. Systane is a mucomimetic that is designed to protect corneal cells that have been damaged during dry eye disease. The product is designed to create a "bandage" that surrounds the damaged microvilli of the surface corneal epithelium. This bandage effectively fills in the missing cell structure and produces a hydrophilic surface, allowing the aqueous and lipid tear components to maintain stability over the damaged cell and minimize dehydration between blinks. As the corneal surface maintains hydration, the epithelial microvilli are able to repair; eventually, normal mucin binding resumes.

Systane is available in a drop form consisting of the main component 0.18% Hp-Guarpolysacha-ride, essential ions in a boric buffer system and preserved with Polyquad. The solution exits the bottle with a pH of 7; on contact with the ocular surface, it shifts to a pH of 7.4. This pH shift increases the viscosity of the drop by enhancing crosslinks within the solution. The result is what the company describes as a "lubricious soft gel." It's bioadhesive, prolonging ocular surface protection.

Systane studies

In-house studies enrolled patients who were symptomatic enough that they were either willing to spend money on a dry eye product or were currently using a dry eye product. The cost of a therapy is an interesting criterion to consider because the financial implications of dry eye therapy are often prohibitive and may be a predictor of symptom intensity. Most patients are unlikely to purchase expensive drops on a continuous basis if the perceived symptoms don't warrant the expense.

The second criterion for enrollment was practitioner evaluation of NaFl staining on the corneal surface. The study investigators used The National Eye Institute corneal grid to stand-ardize the staining locations of each of the subjects. They scored each subject on a 0 to 3 scale within each grid area. For a subject to gain enrollment in the study, investigators required a minimum score of three.

The investigators pre-treated the subjects with saline to equalize their entry point into the study. They then assigned groups to Systane or the well-established drop Refresh.

Significant findings in the Systane group were a decrease in conjunctival staining assessed with Lissamine Green dye. Investigators also observed a decrease in corneal staining using NaFl dye, which was placed in the patient's eye five minutes before examination. This delay in exam time was crucial to allow for maximum determination of corneal staining.

Starting with the subjective

Objective findings and the health of the ocular tissue are important to us as practitioners; they are crucial in our treatment decision making. Yet, ironically, one of the first things that we do when our patients arrive and take a seat in our exam chair is to determine their subjective response to therapy.

Study participants on Systane had a positive change in subjective dry eye symptoms. Patients noted a reduction in morning dryness, afternoon dryness and foreign body sensation. There was improvement of signs and symptoms in both study groups, however, the Systane group showed a statistically significant edge over Refresh.

Meeting treatment's goal

Although both groups showed improvement, the investigators determined a significant and intriguing outcome with Systane. When they evaluated patients for tear break-up time, they noted that the Systane group had a prolonged result. The active polymer remained in the tear film throughout the 45 to 60 minute evaluation period. The substance had peak concentration and effect on the tear break-up time at the 20-minute evaluation.

Increased tear stability is the goal of dry eye treatment, which in turn minimizes patient symptoms between blinks.

Sizing up the side effect

As in most treatment, there's often an Achilles' heel, which Systane has not escaped. Not surprisingly, because of the lubricious soft gel nature of the product, 50% of study participants experienced blurring of vision. The blurring subsided after approximately 90 seconds.

What's of interest is that the study participants noted a decrease in blurring over prolonged use (Alcon defined this as 42 days). If this product is to become a viable option in dry eye treatment, then we as practitioners will need to walk our patients through the side effects and keep them focused on the goal of therapy.

Looking toward the future

For our contact lens patients who are often plagued with dry eye symptoms it is unclear what role if any Systane will play. Systane has not been tested with contact lenses and it will be interesting to see if the "bandage effect" on corneal epithelial cells, which may work well in dry eye, will cause adverse effects with excessive contact lens depositing and build up. Possibly we will have greater success with this product if we use it in concert with daily disposable lenses.

As the dry eye therapy arena expands, we will gladly accept new treatment options. The results of patient-tested therapy will tell the story. I look forward to Systane's introduction to our expanding repertoire of dry eye therapy.

Dr. Wilmer is assistant clinical professor at the University of California, Berkeley School of Optometry. She's also chief at the Tang Eye Center. You can reach her via e-mail at cwilmer@spectacle.berkeley.edu.