Viscosity, or fluid thickness, has been considered one of the most important properties of an AT. Higher viscosity leads to longer retention of the agent in the ocular surface, which is beneficial in terms of relieving the signs and symptoms related to dry eye or dysfunctional tear syndrome. However, the thicker constitution is prone to cause blurring of vision after instillation and may leave runoff residues on the eyelashes or lids as the solution dries out. The challenge for AT preparations is to accomplish a certain level of viscosity that maximizes its retention time and maintains visual clearness, thereby augmenting clinical efficacy (Bhojwani et al. 2011).

Demulcents are lubricating compounds contained in AT that have a mucilaginous consistency, which provides lubricity for protecting and smoothing the ocular surface, thereby minimizing abrasive actions of the eyelids. The US Food and Drug Administration (FDA) recognizes six categories of ophthalmic demulcents (Table 4.1).

To be allowed in “over-the-counter” (OTC) preparations, the demulcents should fall within certain concentration ranges according to international standards. An AT may contain up to three demulcents in its preparations. An ophthalmic vasoconstrictor or a vasoconstrictor with astringent combination could be included to provide the AT with additional redness- or discomfort-reducing properties.

Cellulose derivatives are the most common demulcents found in modern tear substitutes. Their concentration range goes from 0.2 to 2.5 %. The two main cellulose derivatives available for AT preparations are hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC). Cellulose derivatives also function as viscosity agents if its concentration is increased, which prolongs its retention time in the ocular surface. Similarly, CMC preparations, typically presented in 0.5 or 1.0 % CMC, have different viscosity, with the higher concentration forming a thicker, gel-like liquid. In addition, cellulose-based demulcents can be combined with an oil in order to enhance its mucoadhesive properties, which improves either the mucin and lipid components of the tear film (Rieger 1990). CMC can also be combined with osmoprotectants such as glycerin, L-carnitine, and erythritol, which are biocompatible solutes that aim to protect cells from the physiological stress of exposure to hyperosmotic conditions. Altering these characteristics may be a strategy for deciding the concentration and composition of cellulose-derived AT in accordance with the type and severity of TDS. It has also been demonstrated in a recent study that CMC can have biological effects as it appears to stimulate the closure of epithelial cell wounds in vitro as well as re-epithelization in rabbit corneas in vivo (Garrett et al. 2008).

Liquid polyols (polyhydric alcohols) are allowable in concentrations of 0.2–1.0 %. Polyols do not have viscosity properties and are only used as lubricants. Interestingly, a comparative study demonstrated that AT containing propylene glycol 0.3 % (PG) and polyethylene glycol 0.4 % (PEG 400) provided better lubricity and longer visual acuity maintenance than a tear containing cellulose-based demulcents. Polyols can be combined with mineral oil and phospholipids to create a stable emulsion and promote stabilization of the lipid layer, especially in patients with meibomian gland dysfunction. These patients can also benefit from lipid only containing artificial tears, such as castor oil and mineral oil.