Keratoconjunctivitis sicca or dry eye disease (DED) is a condition that many providers see on a day-to-day basis. In fact, using the TFOS DEWS II diagnostic study criteria, it was estimated that the global prevalence of DED is 29.5%, nearly 1 in 3 people.1
Treatment for DED usually involves a long-term regimen including multiple therapies rather than a single, one-time treatment. In addition to lifestyle modifications, prescription medications, and procedures aimed at restoring ocular surface homeostasis, most regimens include the use of topical lubricants or artificial tears (ATs).
Although artificial tears are often available over the counter, optometrists should treat them with the same care as prescription medications, carefully selecting and troubleshooting drops based on the patient's specific type and subtype of DED.
Types of artificial tears
Artificial tears are commonly available in three main formulations: liquid drops, gels, and ointments. These lubricants differ in their ingredients, thickness, duration of effect, and appropriateness for specific dry eye conditions.
Liquid drops, which typically contain components such as carboxymethylcellulose, glycerin, or polyethylene glycol (PEG), are thin and act quickly.2 They can be beneficial in the management of mild dry eye and can be used frequently throughout the day without significantly affecting vision.
It is ideal to use preservative-free drops, especially when using them frequently. Using preserved drops too frequently can have negative effects on the ocular surface. In contrast, gel-based drops have a thicker consistency, allowing for longer-lasting relief in moderate dry eye cases; however, they may cause temporary blurred vision upon application.2
Ointments, which are semisolid and melt at body temperature, offer prolonged hydration and are especially beneficial for overnight use. Due to their thickness, they often result in pronounced blurring of vision immediately after use.2
For a deeper dive into the differences between liquid, gel, and oil emulsion drops, check out A Comparative List of Artificial Tears—with Download!
Taking a closer look at the composition of artificial tears
Artificial tear components are regulated under the FDA’s over-the-counter (OTC) drug monograph system, specifically 21 CFR Part 349, which outlines the conditions under which ophthalmic products are considered generally recognized as safe and effective (GRASE).3 This includes a defined list of approved active ingredients and permissible concentrations.
As a result, the composition of OTC artificial tears tends to follow a similar foundation. Most artificial tear formulations include a demulcent, a preservative (unless preservative-free), emollients, and/or inactive ingredients. Depending on the formulation, demulcents and emollients can be categorized as either active or inactive ingredients.
Demulcents
Demulcents are the components of ATs that lubricate and protect the ocular surface, usually serving as the active ingredient. They alleviate dryness and irritation by enhancing tear viscosity and increasing the retention time of the tear film on the eye.3,4
While the FDA regulates active ingredients, the specific molecular weight or chain length of the polymers is not regulated.3 This means that two products that have the same polymer in the same concentration can have different clinical effects based on the structure of the polymer itself.5
For example, it has been shown that the polymer hyaluronic acid (HA) has different properties at different molecular weights.6 While brand-specific information regarding molecular weight is often proprietary, it is worth considering when determining the right AT.
Cellulose derivatives
Cellulose derivatives include carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (hypromellose), hydroxyethyl cellulose, and methylcellulose. They are known for their mucoadhesive properties, ability to enhance tear viscosity, and prolong ocular surface residence time.4
CMC has also been shown to promote corneal epithelial cell migration and reepithelialization when there is damage.7,8
Polyols
This category comprises glycerin, polyethylene glycol (PEG) 300, PEG 400, and polysorbate 80. These substances also act as humectants, retaining moisture on the ocular surface.9
Dextran 70
Dextran 70 increases the mechanical strength of the tear film and is often combined with other demulcents due to its low viscosity.4 Demulcents are often combined in artificial tear formulations to enhance efficacy, providing lubrication, moisture retention, and protection for individuals suffering from dry eye symptoms.10
Other demulcents include:10
- Gelatin: Reliable viscosity agent for ophthalmic formulary purposes, though it is more commonly used for intracanalicular implants to inhibit tear drainage in dry eye patients
- Polyvinyl alcohol (PVA): A synthetic polymer with moderate viscosity that enhances tear film stability and has good spreading and wetting properties
- Povidone (polyvinylpyrrolidone): Increases tear film residence time and interacts with mucins on the ocular surface to improve lubrication and comfort
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Comparative List of Artificial Tears
Use this master list of artificial tears to stay on top of recalled drops and compare the active ingredients and preservatives in various tears on the market.
Emollients
Most artificial tears are formulated to supplement either the lipid layer or aqueous layer of the tear film.11 However, some eye drops are formulated as emulsions, which contain aqueous lubricants such as hydroxypropyl guar (HP guar), PEG, propylene glycol (PG), and emollient lipid ingredients.
Lipid-based artificial tears have been shown to stabilize the tear film lipid layer, reduce tear evaporation, and improve the signs of meibomian gland dysfunction (MGD) and evaporative dry eye (EDE).12 A recent study compared the PG-HP guar nanoemulsion drop Systane Complete to the non-lipid-based aqueous drop Systane Ultra.13
The study found that while both drops provided symptom relief within 1 month, the tear film lipid layer grades increased only with the PG-HP-guar nanoemulsion drop (after 90 days). Furthermore, the study found that when using the lipid-based drop, there was significantly greater improvement in patients with a low lipid layer thickness at baseline.13
Other results, however, have been less compelling. For example, another study found that using a PG-HP-guar nanoemulsion was only associated with short-term changes in lipid layer thickness, and had no effects after over 1 month of use.14 This is an area where additional studies are needed to gain a more complete picture of the clinical effects of this type of drop formulation.
Preservatives
Preservatives are added to multi-dose artificial tear bottles to inhibit microbial contamination.9 However, repeated exposure to preservatives can cause toxicity to the ocular surface, particularly in patients with chronic dry eye or those using drops more frequently.15
Symptoms may include epithelial cell loss, inflammation, and tear film instability.9,16,17 Consequently, many modern artificial tear formulations are moving away from preserved versions and toward preservative-free alternatives, which help minimize surface damage and improve tolerability in long-term use.
Benzalkonium chloride
A widely used preservative known for its antimicrobial properties, benzalkonium chloride (BAK) has been associated with significant ocular surface toxicity, including decreased epithelial cell viability, increased pro-inflammatory mediators, and loss of goblet cells.18
Polyquaternium-1 (polyquad)
A quaternary ammonium compound similar to BAK but approximately 27 times larger in size, polyquad's size reduces its ability to penetrate mammalian cells, making it less toxic.16
In vitro and animal studies have shown that polyquad is remarkably safer than BAK, causing less ocular surface toxicity.16,18 However, studies have demonstrated that polyquad can induce cytotoxicity and enhance inflammation in human corneal epithelial cells.16
Sodium perborate (GenAqua and Dequest)
An oxidative, “vanishing” preservative that decomposes into oxygen and water upon eye instillation, sodium perborate is less toxic than BAK but not completely innocuous.18 Studies indicate that sodium perborate can induce DNA damage and reactive oxygen species (ROS) generation in conjunctival cells at higher concentrations.17,19
Purite
Purite is another "vanishing" preservative that converts a mixture of chlorite, chlorate, and chlorine dioxide into oxygen, water, sodium, and chloride ions upon administration. In vivo rabbit studies comparing purite and BAK-preserved formulations show that purite results in significantly less corneal damage and better tolerability.17
Summary of preservatives
While preservatives like purite and polyquad offer reduced ocular toxicity compared to BAK, they may still have some detrimental effects at higher concentrations.17
Therefore, the use of preservative-free formulations, which eliminates the risk of preservative-related toxicity, should be considered whenever possible, especially for patients with sensitive eyes or chronic dry eye conditions.
Inactive ingredients in artificial tears
The inactive ingredients included in an AT are often what provide a drop with its unique properties. To list an ingredient as “active” that does not appear on the FDA-approved monograph requires that the manufacturer submit data on safety and efficacy through either a New Drug Application (NDA) or an Over-the-Counter Monograph Order Request (OMOR).20,21
Therefore, certain ingredients may be listed as “inactive” even though they have biological effects.9 For example, many of the compounds listed as inactive in the US are listed as active in other countries. Such ingredients usually fall into two categories: osmoprotectants and humectants.
Osmoprotectants
Osmoprotectants are agents that protect cells against hyperosmolar-stress-mediated injury that can be seen in DED.22 Corneal epithelial cells are thought to take up the osmoprotectants and facilitate the transfer of water into the cells.23
Some commonly-used osmoprotectants in artificial tears include:22,24
- Trehalose
- Erythritol
- L-carnitine
Another important osmoprotectant is ectoine, a naturally derived bacteria-derived extremolyte found in Optase Allegro (Scope Eyecare). Ectoine stabilizes cell membranes and exerts its protective effect through preferential exclusion, creating a hydration shell or "water shield" that prevents cellular dehydration and inflammation.25,26
Trehalose has been shown to prevent corneal epithelial desiccation.24 Furthermore, another study found that L-carnitine and erythritol, when applied to mouse eyes, significantly decreased corneal staining and expression of TNF-α, IL-17, IL-6, or IL-1β, as well as significantly increased the number of goblet cells.22
Examples of ATs that include either trehalose, erythritol, or L-carnitine include:
- Refresh Optive (Allergan)
- Refresh Optive Advanced (Allergan)
- TheraTears Extra (Akorn)
- Refresh Repair (Allergan)
- Refresh Optive Gel (Allergan)
- Optase Allegro (Scope Eyecare)
Humectants
Humectants are products that facilitate the retention of water.9 Some of the most common humectants in ATs are hyaluronic acid, sodium hyaluronate (SH), and HP guar. Other less-frequently used humectants include flaxseed oil, castor oil, and mineral oil.25
Hyaluronic acid and sodium hyaluronate
Along with acting as a humectant, HA works to help ATs mimic natural tears due to its rheological properties.5 This describes how the fluid flows over the cornea. Natural tears exhibit non-Newtonian behavior. The viscosity remains high between blinks to maintain moisture and becomes less viscous during blinks to reduce shear stress and turbulence.26
HA has this same property; however, not all HA has the same effect. High molecular weight hyaluronic acid (HMWHA) is typically more effective, offering greater viscosity at low shear rates and longer retention on the ocular surface.6
HMWHA has been shown to provide superior symptom relief, better tear film stability, and protection against corneal cell apoptosis and inflammation compared to low molecular weight HA.6 Its cohesive properties enhance retention and ocular surface coverage, while low molecular weight HA tends to be more dispersive.
Sodium hyaluronate is a smaller molecular weight salt derivative of hyaluronic acid. Like hyaluronic acid, it acts as a humectant.5
Examples of ATs that contain HA / SH include:
- iVIZIA Dry Eye Drops (Thea Pharmaceuticals)
- HylaTears Lubricating Eye Drops (Akorn)
- Systane Hydration Preservative-Free Lubricant Eye Drops (Alcon)
- Systane Gel (Alcon)
Hydroxypropyl guar gum (HP guar)
HP guar is a derivative of guar gum, a natural polysaccharide used as a thickening agent in both the food and pharmaceutical industries.25 In artificial tears, HP guar increases viscosity, enhances tear film stability, and mimics the mucin layer by binding to the corneal surface.25,27
Notably, HP guar is pH-sensitive; it remains in a low-viscosity state in the bottle (pH ~7) but undergoes cross-linking and forms a gel upon contact with the ocular surface, where the pH is slightly higher (~7.5).27 This in situ gelation prolongs the retention of demulcents and enhances ocular surface protection.13
HP guar is often combined with demulcents like PEG and PG to synergistically improve lubrication and comfort in dry eye patients.13 Interestingly, HP guar has also been shown to preferentially adhere to dehydrated / damaged cells in the cornea. This forms a protective layer that prevents further injury, which encourages epithelial cell repair and regeneration.28,29,30
Examples of ATs that contain HP guar include:
- The entire Systane family of artificial tears, such as:
- Systane (Alcon)
- Systane Ultra (Alcon)
- Systane Balance (Alcon)
- Systane Gel (Alcon)
- Systane Preservative-Free (Alcon)
- Systane Nighttime (Alcon)
Tips for choosing the best artificial tear for your patients
Selecting the appropriate AT for patients is a critical component of DED management and should be personalized based on the underlying mechanism. Different drops have different mechanisms, and work differently for evaporative dry eye, aqueous-deficient dry eye, or mixed-mechanism dry eye.
Educating patients on the purpose and limitations of ATs is equally important. While artificial tears can offer quick, symptomatic relief by hydrating the ocular surface and stabilizing the tear film, they are only one part of a comprehensive treatment strategy. If patients feel the need to instill drops more than three to four times per day, stronger therapy may be needed.
Other therapies include prescription anti-inflammatory medications, punctal occlusion, or in-office procedures like radiofrequency (RF) or intense pulsed light (IPL) therapy. Proper patient education not only improves adherence and expectations but also helps prevent the delay of necessary escalated care, ultimately leading to better long-term outcomes in dry eye management.
To learn more about how to use radiofrequency and intense pulsed light therapy for dry eye management, check out Light and Sound: IPL and Radiofrequency for Dry Eye!
Artificial tears for evaporative dry eye / MGD
In MGD, ATs should focus on replenishing the tear film's deficient or dysfunctional lipid layer to reduce evaporation. This means focusing on lipid-based formulations.
Key ingredients could include emollients, such as mineral oils, castor oil, or other oils, often combined with emulsifiers / stabilizers. Some formulations use ingredients like HP guar, which helps stabilize the entire tear film structure.
Examples of ATs with lipid components include:
- Systane Balance (Alcon)
- Systane Complete (Alcon)
- Refresh Optive Mega-3 (AbbVie)
- Soothe XP (Bausch + Lomb)
- Retaine MGD (OcuSoft)
If a patient needs to use drops more than three to four times per day or experiences irritation, it is best to switch to preservative-free versions of lipid-based tears to avoid preservative toxicity.
For overnight lubrication, consider using thicker lubricating ointments or gels specifically designed for nighttime use. These often contain white petrolatum, mineral oil, or lanolin and provide prolonged protection while sleeping.
Artificial tears for aqueous-deficient dry eye
The initial AT choice for ADDE should focus on supplementing the tear film's deficient aqueous volume and improving moisture retention.
Key inactive ingredients to look for include viscosity enhancers and humectants like hyaluronic acid / sodium hyaluronate, carboxymethylcellulose, glycerin, povidone, polyvinyl alcohol, or HP guar. Some may contain osmoprotectants like L-carnitine and erythritol to protect eye surface cells.
Examples of some ATs appropriate for ADDE include:
- Refresh Optive (AbbVie)
- Systane Ultra (Alcon)
- Systane Hydration (Alcon)
- Blink Tears (Johnson & Johnson Vision)
- Oasis Tears (Oasis Medical)
- Refresh Celluvisc (AbbVie)
- iVIZIA Dry Eye Drops (Thea Pharmaceuticals)
Artificial tears in the pipeline
In February 2025, Alcon launched SYSTANE PRO Preservative-Free (PF) in the US market. The formulation includes hyaluronate, nano-sized lipids, and HP guar, positioning it as the longest-lasting dry eye drop within the SYSTANE family.31
Following its initial launch in the US, Alcon intends to expand the availability of SYSTANE PRO PF to additional global markets in 2026.
Want to know more about SYSTANE PRO PF drops? Check out the Glance story Alcon launches Systane Pro PF drops for dry eye!
Key takeaways
- Treat artificial tears with the same care as prescription medications, making specific recommendations based on clinical exam findings and patient symptoms.
- Artificial tear formulations are unique, and they aid in dry eye relief in a multifactorial way.
- Artificial tears should be a component of a dry eye regimen rather than the sole treatment.
- If a patient feels the need to use ATs greater than three to four times per day, additional interventions (e.g., prescription medications, in-office treatments) are likely needed.
- Use of preservative-free AT formulations is preferable whenever possible, as overuse of artificial tears with preservatives can cause further ocular surface irritation and damage.
- Consider the biological activity of both the active and inactive artificial tear ingredients.
