Dry-eye syndrome presents many challenges to both the patients experiencing ocular discomfort and the practitioners attempting to alleviate their symptoms. Patients are subject to a broad variety of environmental challenges that can exacerbate the symptoms of irritation, burning and grittiness, and this continual discomfort can be indicative of eventual ocular damage.

The severity of dry-eye discomfort is often heightened in windy, smoky or dusty conditions. Additionally, activities that require prolonged staring, such as watching TV, computer use or reading, also worsen dry-eye symptoms.

Certain medications, such as oral antihistamines and antidepressants, can cause ocular drying as well.^1,2

The practitioner is faced with the challenge of alleviating the symptoms of a condition that can originate from a variety of causes. These may involve not only the ocular surface but its interaction with other factors and structures

An example of tear film breakup time that leads to an unprotected ocular surface.

affecting the tear film such as blinking, lacrimal and meibomian glands, hormones, mucins and oils. We are now aware that a simple deficiency in tear volume is not necessarily the only problem, but that the problem could be in a deficiency or malfunction of any one of these components necessary for the formation of normally functioning system.

Tear Film
The tear film comprises three layers: the lipid layer, the aqueous layer and the mucin layer. The lipid layer, the 0.1 mm thick outermost layer of the tear film, is secreted primarily by meibomian glands and functions to prevent evaporation and maintain structural integrity of the film.

The middle aqueous layer is produced primarily by the lacrimal glands and functions to deliver essential nutrients and protectants including secreted immune-system proteins that help prevent microbial or toxic substances from reaching the ocular surface.

The mucin layer, adjacent to the ocular surface, is produced by goblet cells in the conjunctiva and cornea and serves to coat the hydrophobic corneal epithelium with a hydrophilic layer. The mucin layer also contributes to prevention of pathogens reaching the ocular surface and maintenance of ocular surface hydration.^3,4,5 This three-layered anatomy of the tear film is crucial to maintaining the integrity of the ocular surface.

A broad variety of physiological origins affecting any one of these three layers can lead to a compromised tear film, causing ocular discomfort and ocular surface damage.⁶ With such varied causes, development of an effective therapy can be challenging.

A primary goal of dry-eye therapies today is to achieve an extension in the time the tear film remains intact. The reasoning behind this goal is made clear by examining the relationship between tear film breakup time and the time between blinks. Just after a blink, the ocular surface has been “re-coated” with an intact tear film. As the eye remains open, this film will break. In dry-eye sufferers, the time to tear film breakup is typically significantly less than in non-dry eye patients.⁷ Upon tear film breakup, the surface of the eye becomes exposed and unprotected for the remainder of time that the eye remains open, until the next blink. Repeated intermittent exposures of a tear film deficient cornea such as this can lead to ocular discomfort and clinically significant redness and keratitis.⁸

In developing new dry-eye therapies and comparing currently available ones, this picture of what happens to the eye between each blink is a key evaluator. It verifies that a difference of just seconds in the duration of tear film integrity can make a difference in the clinical profile of a dry-eye patient. A tear substitute that causes even a small elongation of tear film breakup time may bridge the gap between breakup time and blink time, thus achieving improvement in ocular surface protection.

Artificial Tears
The ideal artificial tear, therefore, would be able to achieve a lengthening of tear film breakup time, while also being comfortable in the eye. This is a difficult balance to strike, as in attempts to increase the duration of tear film integrity can often decrease the overall comfort of a drop. As dry-eye sufferers often use such medications several times per day at work, study or travel, it is essential to also minimize any vision-blurring or caking of medication.
Additionally, an ideal drop would have a long retention time in the eye, as this would allow dry-eye patients to dose less frequently.

There are many different over-the-counter artificial tear preparations available to treat dry-eye symptoms. Most preparations consist of a solution containing electrolytes, surfactants, viscosity agents and preservatives. This combination of ingredients strives to strike an ideal balance between maximizing tear film stability and ocular surface retention while simultaneously minimizing vision-blurring or caking. Hydroxypropyl methylcellulose (HPMC), glycerin, carboxymethyl cellulose, and polyvinyl alcohol are all examples of current artificial tear components. Some artificial tears employ a combination of two or more such agents. The preservative chosen for multi-dose units of artificial tears is also an important ingredient.

Historically, older preservatives used in artificial tears, such as benzalkonium chloride, have been associated with provocation of allergic reactions or cellular toxicity. This, in particular, is a concern in dry-eye patients who use eye drops on a very frequent basis.

More recently developed preservatives though have circumvented this difficulty with novel compounds. Polyquaternium-1 (Polyquad), sodium perborate (GenAqua), and stabilized oxychloro complex (Purite) are all newer, more comfortable preservatives. Polyquad has been shown to avoid the epithelial cell toxicity and sensitivity sometimes associated with older preservatives. Sodium perborate degrades into water and oxygen, and Purite is also purported to degrade into innocuous by-products from its initial oxychloro complex.

Therapy Comparisons
Clinical research trials are able to evaluate the relative effect of artificial tears on tear film breakup time. This can be accomplished by recording a baseline tear film breakup time, instilling one artificial tear eye drop in one eye and another in the contralateral eye, and then evaluating tear film breakup time again at several time points post-medication instillation. The change in tear film breakup time from baseline to post-medication instillation time points can then be evaluated.

One example of such a study is an ongoing research trial evaluating the relative tear film breakup times of available artificial tear eye drops. Two of those under comparison are Tears Naturale Forte and Refresh Tears. The comparison (15 eyes per group) was made using six tear film evaluations: 0, 5, 10, 15, 20 and 30 minutes post medication instillation. Data showed that tear film breakup times were extended (as compared to baseline) only at the earlier time points (5 and 10 minutes) with use of Refresh. With Tears Naturale Forte, tear film breakup extensions were seen at several time points, including 20 and 30 minutes.

There are two factors to examine in this clinical picture: the extension of tear film breakup time and the duration of this capability. We can see in the above study that tear film breakup time can be elongated with both artificial tears, but the duration of this capability, after one drop of medication instillation, was not

An example of keratitis that is a result of an unprotected ocular surface. Tear substitutes that extend tear film breakup time may be useful in minimizing the signs and symptoms of dry eye.

equal for both. The efficacy at the later time points in eyes dosed with Tears Naturale Forte indicates a longer retention time in the eye, one of the properties most desirable in an artificial tear. With longer lasting relief of symptoms allowing for decreased dosing frequency, patient compliance increases, thus a healthy, protected ocular surface is maintained.

The primary goal is to prevent ocular surface damage before it occurs. The challenges in achieving this must first be surmounted by the practitioner, in diagnosing a somewhat elusive condition and then working with each patient to find appropriate treatment. The patients are also presented with obstacles in achieving satisfactory ocular protection. Many unavoidable environmental and lifestyle conditions exacerbate the symptoms of dry-eye syndrome, and patients must religiously adhere to a regimen of eye drop dosing to keep their eyes comfortable and healthy.

The tools to meet these challenges are at our fingertips though, with instruments such as tear film breakup time evaluations, comparative clinical analyses, and ever-improving artificial tear eye drops like Tears Naturale Forte that allow patients the freedom to dose less frequently while still adequately protecting the ocular surface. 

Dr. D’Arienzo is a clinical assistant professor of ophthalmology at New York Medical Center and St. Vincent’s Medical Center. He reports no financial interest in any of the products mentioned.

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