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Ocular Lubrication vs. Viscosity of Ophthalmic Products
BY JOSEPH G. VEHIGE, OD, AND PETER A. SIMMONS, PHD, FAAO

One of the essential functions of the tear film is to lubricate the ocular surface during blinking and eye movement. The eyes are constantly in motion and/or blinking, and the ocular surface is delicate. Without adequate lubrication, ocular surface damage occurs and symptoms of discomfort develop or increase.

Ocular lubrication is also essential for contact lens wear. It offsets friction, which results when relative motion occurs between two surfaces that are in physical contact. Friction increases as relative speed and load (the force pushing surfaces together) increase.

Figure 1. Ocular viscosity testing of three current products: carbomer-containing Genteal Gel (HPMC-CB), Novartis Ophthalmics), 1% CMC Refresh Liquigel (CMC, Allergan) and Systane with HP-guar (PG-HPG, Alcon). The results illustrate the effect of two levels of dilution with a simulated tear fluid and a change to ocular pH and temperature.

Lens Wear and Lubrication

Contact lens wear should reduce corneal friction because the magnitude of a lens's movement against the cornea (a low-shear movement) is less than the magnitude of the eyelid's movement against the cornea (a high-shear movement) when a contact lens isn't in place. In addition, lens wear may favorably redistribute load forces over a larger area. These two features of lens wear make bandage hydrogel lenses suitable for protecting the corneal surface.

However, when a contact lens is in place, compromise to the lid margin and palpebral conjunctiva may increase if lubrication from the tear film is inadequate or if the lens surface becomes compromised.

Ideally, the surfaces involved should rarely experience direct physical contact because a minimal, but critical, fluid layer remains between them.

Ocular Lubrication Mechanics

Large, water-loving molecules primarily lubricate the eye by creating and maintaining a thin boundary layer of water between moving surfaces. Mucin bound to surface epithelial cells and soluble mucin in the aqueous component of the tears facilitate this process. The superficial lipid layer at the aqueous-air interface also contributes some lubrication.

In artificial tears and contact lens rewetting drops, water-soluble polymers provide lubrication. They:

• dissolve into and hold onto water
• remain on the ocular surface for a reasonable time period

The ability to attract, hold and release water promotes water retention on the ocular surface (humectant property), allowing these agents to serve double duty in treating dry eye.

Relative to retention on the ocular surface and potentially of great merit to the maintenance of a critical boundary layer is an agent's ability to adhere to ocular surface cells and the overlying mucin layer. This property is referred to as mucoadhesion and has been recognized in this context for many years. Some of the best agents in this regard are anionic in that they carry a large number of negatively charged sites along the polymer backbone. Carboxymethylcellulose, polyacrylic acids (carbomers) and hyaluronic acid are classic examples of anionic polymers that have enhanced mucoadhesive force.

Considering Viscosity

Increased viscosity of an ocular agent generally increases both lubrication and retention in the tear film. However, when adding supplements to the tears, a practical upper limit for viscosity exists, driven primarily by blur and also by unpleasant sensations or even discomfort. Also, to produce a higher viscosity, a product usually contains a higher total concentration of ingredients that may solidify on drying to produce crusting and flaking on the eyelids and lashes.

To help predict the behavior of an artificial tear on-eye, researchers can measure its viscosity under simulated ocular surface conditions that include temperature, pH and presence of salts and other components of natural tears. Also, because the tear film must act as an effective lubricant under both low- and high-speed movement, researchers should measured it under both high- and low-shear conditions.

Beware High Viscosity Claims

When measuring the viscosity of ocular agents critically under these simulated ocular conditions, researchers may note a surprising finding. Gels that contain carbomer rapidly "melt" into a thin, low-viscosity fluid when mixed with tear salts. Figure 1 demonstrates this dramatic thinning. The surprise is that the resultant "ocular" viscosity is actually lower than that of some liquid artificial tears.

A recently available product contains a novel modified carbohydrate polymer (HP Guar) that purportedly thickens on-eye as a result of an alkaline shift in pH. To examine this claim, researchers measured the viscosity of the product under simulated ocular conditions that included increased pH, temperature, shear effects and two levels of possible dilution with simulated tear fluid (researchers mixed it with simulated tears to model initial [zero minutes to five minutes] and final [five minutes to 20 minutes] equilibration of the eye drop with the ocular surface fluid).

Figure 1 also shows the results of these experiments, in which any increase in viscosity that resulted from pH change was more than offset by dilution with the natural tears. In regard to this product, note that thickening (if it did occur) without adhesion to the ocular surface doesn't ensure enhanced duration of benefit, and furthermore this nonionic polymer hasn't demonstrated muco-adhesion.

A rational approach to managing dry eye includes providing adequate lubrication and, thus, protection to the ocular surface. The initial or "in-package" viscosity of ophthalmic products influences ocular lubrication less than does the final or "ocular" viscosity, regardless of the change in viscosity from the starting point. In addition, you should consider the ability of the polymer to adhere to ocular tissue as an essential feature that increases lubrication, protection and hydration of the ocular surface.

Dr. Vehige is a senior director at Allergan, Inc. working in Eye Care Research and Development, with a current emphasis on the clinical development and testing of new artificial tears and ophthalmic drugs.

Dr. Simmons conducts research and development projects within the Eye Care Research group at Allergan, Inc., with particular interests in the area of dry eye disease and treatment.