We Must See Eye to Eye on Eye Drops

Drops and artificial tears are the mainstay of dry eye disease treatment. In terms of options for our patients, we have a significant armamentarium, arguably more than in any other subspecialty in ophthalmology (1). But do we know what the components of these drops are, and does it matter when it comes to prescribing them?

Artificial tears work through a number of mechanisms including increasing tear volume, changing the surface tension of tears, increasing the viscosity of tears in order to increase the duration of the drops, and preventing tear evaporation (2).

Before we explore the components of drops and how we use them, we need to first consider the different targets for treatment in context of the “vicious circle” of the disease. The vicious circle, first proposed by Baudouin et al. (3), showed that the rapid break-up of the tear film after blinking (tear film instability) leads to local drying and hyperosmolarity of the epithelial surface. This leads to apoptosis, inflammation, and a loss of mucin-producing goblet cells. The cascade of mechanisms, involving osmotic, mechanical and inflammatory stress, destroys goblet cells and defence systems of the ocular surface, which leads to further damage of the tear film closing the circle.

Clinically, what do we want from artificial tears? We want a product that supports water retention, that has the right level of viscosity to address the patient’s needs. We want a product that has a surface tension greater than that of tears, an effective concentration level of active ingredients, and that acts on the different mechanisms of actions of dry eye disease (2).

There are many categories of tear substitutes that range in terms of viscosity, from saline to lipids. 

Key components of tear substitutes:

• Carbomers. Synthetic, high molecular weight polymers of acrylic acid. They form a long-lasting, transparent, lubricated film on the eye surface. They also increase the retention time on the ocular surface, thus providing improved hydration and alleviation of dry eye symptoms (5).

• Hyaluronic acid (HA). The most commonly used constituent of artificial tears is a naturally occurring glycosaminoglycan, found in and around body cells and tissues – for example, in synovial fluid and vitreous and aqueous humor (6). Hyaluronic acid is water soluble and capable of binding large quantities of water compared to its own weight, but its physical properties vary depending upon its molecular weight (7). There is some evidence to suggest that high molecular weight HA is clinically superior in the treatment of DED compared to its low molecular weight counterpart. Uniquely, HA exhibits non-Newtonian properties – in other words it is able to mimic natural tears and change its viscosity, reducing for example at higher shear rates such as during blinking, and increasing when the eye remains open, stabilizing the tear film (6). High molecular weight HA is also known to have anti-inflammatory effects.

• Lipid layer supplements. Most of us use these products in our meibomian gland dysfunction patients (MGD), a disease characterized by disruption of the tear film lipid layer and an increase in the tear film evaporation rate. In clinical practice choosing a lipid is not so simple. The lipid layer is complex, comprising a hydrophobic outer layer, which prevents evaporation and an interface layer, which anchors the lipid to the aqueous interface. Therefore, when treating our patients we need to look at the components of the different drops and decide which are the most appropriate for the specific clinical need. While not an oil nor a lipid, perfluorohexyl octane is an effective hydrophobic with a low viscosity that spreads very quickly and thinly on the ocular surface, preventing evaporation (7).

• Mucous layer supplements. This is a key area of unmet need in the treatment of dry eye diseases. Secretagogues can stimulate mucin secretion. Topical secretagogue formulations are applied to the ocular surface to induce aqueous and/or mucin secretion. They are currently only available in Asia (8).

• Additional components. There are a number of additional targets in artificial tears, including osmoprotectants, which may protect cells against hyperosmolarity; bioprotectants which protect cell membranes and proteins from dehydration; antioxidants, which have been shown to decrease the effects of oxidative stress, and autophagy inducers, which promote the process of evacuating inflammatory response products (6,9).

A recent addition to our arsenal of treatments for dry eye disease is ARTELAC Complete/Nereya (Bausch + Lomb), a preservative free, non-aqueous, multicomponent tear substitute (10). Containing a mixture of 0.24% sodium hyaluronate, carbomer and medium chain triglycerides, this product allows us to treat all three layers of the tear film. Results from a recent multicentre, investigator-masked non-inferiority study comparing the safety of ARTELAC Complete/Nereya and VISMED (TRB Chemidica) over a 90 day period showed that at both one and three months on corneal staining ARTELAC Complete was non-inferior to VISMED (11). Interestingly, tear break up time, interferometry and tear evaporation showed a statistically significant improvement in the ARTELAC Complete group compared to the VISMED group. 

We are very fortunate that there are a large number of effective tear substitutes available for our patients and that these treatments work on multiple aspects of dry eye diseases. However, compliance remains a key problem when treating dry eye disease. Sometimes this may be our fault. A recent survey revealed that almost 90 percent of patients surveyed did not administer their drops as per the prescribed regime, and over 80 percent did not know how frequently they needed to instill their drops (12). As clinicians we need to counsel our patients carefully and ensure they thoroughly understand their drops regimes to avoid worsening of their disease. 

This article was presented at the Bausch + Lomb Dry Eye Summit, Italy, October 2024