Science Behind Today's Artificial Tears
The science and mechanism of action behind today's most unique formulations.
DAVID MEADOWS, Ph.D., WILLIAM TRATTLER, M.D., JEFFREY P. GILBARD, M.D., PETER A. SIMMONS, Ph.D.

Recent research has demonstrated that the tear film is far more complex than was initially understood. Each of the primary constituents in the tear film – mucins, proteins, ions, water and lipids – play a crucial and interconnected role in maintaining tear stability. Environmental or physiologic changes that upset the equilibrium between these functional components can disrupt the tear film stability and result in a loss of structural "memory" that may ultimately lead to dry eye symptoms and signs.

The treatment strategies for dry eye continue to get more exciting, as we better understand the underlying causes of dry eye and as well are able to tailor our treatments for dry eye.

Formulations of Artificial Tears

SYSTANE

Systane Lubricant Eye Drops (Alcon Laboratories) are designed to deliver immediate, long-lasting relief from the signs and symptoms of dry eye and help restore memory to the tear film.

The pH of Systane Lubricant Eye Drops in the bottle is approximately 7.0, slightly less than the pH of human tears (approximately 7.5 to 7.8). The product is fairly non-viscous and droppable and contains the demulcents propylene glycol and polyethylene glycol 400, as well as the inactive ingredients borate and the polymer hydroxypropyl-guar (HP-Guar), which acts as a gelling agent.

When Systane is instilled in the eye, it immediately spreads over the tear film by the eyelid. The drop replaces much of the existing tear film and any excess product is quickly drained out of the eye. Upon instillation, the components of Systane rapidly diffuse to the corneal surface where they can begin interacting with other key components of the patient's natural tear film. During this process, HP-Guar becomes increasingly viscous and binds with the borate ions and active demulcents to form a gel-like consistency that is able to mimic the form and function of the soluble ocular mucins and glycocalyx.

This soft gel provides additional lubrication to the eye's surface and acts as a corneal bandage over unprotected, or dry and irritated, portions of the epithelium so that when the eyelid blinks over the surface of the eye, it is protected from further dryness and irritation. Systane also helps the aqueous portion of the tear film flush out any soluble inflammatory agents and irritants that may be present.

Soothe

Soothe (Alimera Sciences) is a new lubricating drop that contains Restoryl, a lipid supplement that can increase the lipid layer within the tear film by 50% to 120%. Soothe is considered a metastable emulsion. Metastability describes how within a few blinks, Soothe rapidly separates into its multiple oil and water phases. This is in contrast to ordinary emulsions, where the oil and water phases are uniformly mixed, and remain mixed when applied to the eye.

Once applied to the eye, this oil in-water emulsion separates into:

• Restoryl, which rapidly rebuilds the lipid layer

• Interfacial molecules, which work to attach the lipid layer to the aqueous and support the mucin layer

• Water, which restores the aqueous layer of tear film.

Soothe benefits dry eye patients by stabilizing the tear film, which reduces tear evaporation. One study found that one-drop of Soothe can provide up to 8 hours of relief from discomfort. Soothe is effective on its own as a treatment for dry eye. Soothe also works well in combination with other agents, such as Restasis, in patients with dry eyes.

TheraTears

Hypotonic TheraTears (Advanced Vision Research) is the only artificial tear shown to lower elevated tear film osmolarity. The hypotonicity of TheraTears was established in a series of experiments that examined how hypotonic an eyedrop needs to be to lower elevated tear film osmolarity. Subsequent studies showed that q.i.d. dosing was effective in producing a statistically significant lowering of elevated tear film osmolarity in 8 weeks. In addition, TheraTears contains the exact same electrolyte balance of the human tear film, and this electrolyte balance was able to be patented by showing "electrolyte imbalance toxicity" from solutions outside patent range, and a therapeutic effect on goblet cells from patented formulation. Subsequent prospective, randomized, placebo-controlled clinical studies have shown that TheraTears provides unsurpassed immediate and cumulative relief of symptoms while decreasing rose Bengal staining and restoring conjunctival goblet cells. TheraTears now provides complete dry-eye relief for everyone with TheraTears preservative free, TheraTears in a bottle (disappearing preservative), TheraTears Liquid Gel, TheraTears Contact Lens Comfort Drops and TheraTears Nutrition (omega-3 supplement).

Refresh

Allergan's artificial tear formulations contain multiple electrolytes in proportions similar to those found in natural tears, including sodium, potassium, calcium, magnesium and chloride ions. These ions have been found to be essential for normal corneal function. The buffers used in Allergan's formulations are either the naturally occurring buffer lactate (in nonpreserved products), or a borate buffer (in preserved products), which in addition to being nonirritating and nontoxic to ocular tissues, also has antimicrobial activity.

Allergan preserved dry eye formulations contain Purite, a purified form of sodium chlorite, which acts as an oxidizing agent to eliminate microbial cells. It is nontoxic to ocular cells as they contain natural anti-oxidant mechanisms lacking in microbes.

Overall, Allergan�s dry eye formulations contain an optimum balance of ingredients to maximize benefit to the compromised ocular surface. This is accomplished in both preserved and nonpreserved dosing forms to provide safety and convenience to the patient without inclusion of any potential iritants.