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Making artificial tears less artificial

Optometry Times JournalOctober digital edition 2022
Volume 14
Issue 10

Preservative-free eye drops offer benefits for ocular health.

A patient consults you for relief from dry, scratchy eyes, and you recommend artificial tears. Weeks later, the patient presents with worsened redness and irritation.

What went wrong? If you are an optometrist who treats dry eye complaints as frequently as I do, you can probably predict the answer: The patient used a store-brand OTC formulation that included preservatives.

Artificial tears stabilized by preservatives have been around for decades and work well in some patients. The challenge is that the antimicrobial activity that so effectively keeps eye drops bacteria free can also cause conjunctival and corneal irritation in the very patients these solutions are designed to help. In particular, numerous studies have demonstrated an association between eye irritation and benzalkonium chlorides, a type of preservative widely used in store-brand dry eye drops.1,2

In recent years, I’ve avoided this problem by directing patients toward options that minimize exposure to preservatives: preservative-free artificial tears. Current estimates are that preservative-free solutions represent more than 40% of the global market for artificial tears.3 Now offered in the United States by several companies, these OTC products are often conveniently packaged in multiuse bottles rather than individual-dose vials.

They can fill the needs of patients with a variety of conditions that cause eye discomfort, either taken alone or as an adjunct to other treatments. These drops can be beneficial to patients in the following situations:

» Environmentally induced eye dryness arising from movement between moist and dry environments, such as outdoor settings and air-conditioned buildings, or from staring at computer screens for extended periods without breaks. Preservative-free artificial tears can help by safely supplementing the natural lubrication of the ocular surface.

It is critically important to be specific about the exact artificial tear you want your patient to use.

» Temporary discomfort or vision problems while wearing contact lenses, often due to long daily wear schedules or use in dry environments. Preservative-free artificial tears are appropriate as needed in these cases to remoisturize the lenses, which will add comfort for the patient and restabilize vision. This is a critical consideration for those who wear multifocal lenses. Preservative-free artificial tears can be particularly helpful to those who wear specialty lenses, including scleral lenses. Added to the bowl of these lenses, artificial tears can help rehabilitate a cornea that is desiccated. Preservative-free drops are crucial for this purpose, because any preservatives in the bowl of a scleral lens during daily wear should be avoided.

» Epithelial basement membrane dystrophy, which puts patients at risk of recurrent corneal erosion. Keeping the ocular surface moisture rich is critical in promoting the best possible optical functionality in these individuals.

» Postsurgical rehabilitation following laser in situ keratomileusis (LASIK), cataract surgery, or other ocular surgeries. In the critical 2 weeks after surgery, patients tend to benefit from increased lubrication of the ocular surface to promote a healthy, healing cornea.

Available options

Fortunately, the preservative-free dry eye options available on drugstore shelves are multiplying. Those that come in multiuse bottles include products containing such ingredients as propylene glycol, 0.6% (Systane; Alcon); hyaluronic acid (Biotrue Multi-Purpose Solution; Bausch + Lomb); carboxymethylcellulose sodium, 0.5%, and glycerin, 0.9% (Refresh Relieva; Allergan); and povidone (iVIZIA; Théa Pharma Inc).

Although these products share a commitment to being preservative free, they have varying active ingredients4—meaning they use different forms of mechanisms to treat patients with dry eye.

Many feature combinations of ingredients such as the lubricating agent hyaluronic acid, a naturally occurring glycosaminoglycan polysaccharide and tear-film component that binds 1000 times its weight in water, protecting the corneal epithelium with prolonged residence time and favorable rheologic properties5-7; glycerin, which eases irritation, lubricates, and moisturizes; propylene glycol and/or polyethylene glycol, which moisturize and form a protective layer over the ocular surface; and hydroxypropyl guar and/or carboxymethylcellulose sodium, which increase an eye drop’s viscosity.

In early 2022, a preservative-free therapeutic advancement to our dry eye armamentarium (iVIZIA) was introduced in the US that combines trehalose with hyaluronic acid and povidone to deliver lubrication with longer-lasting relief5,8 to patients with any type of dry eye, including those who wear contact lenses.

Figure 1. A 42-year-old patient presented with inferior corneal staining but negative InflammaDry (Quidel) test readings upon examination.  Figure 2. Between 3 and 4 weeks following treatment of a new-generation artificial tear containing hyaluronic acid, trehalose, and povidone, the patient’s tear film had stabilized and fully resolved her corneal staining and focusing problems.   (Images courtesy of Mile Brujic, OD, FAAO)

Figure 1. A 42-year-old patient presented with inferior corneal staining but negative InflammaDry (Quidel) test readings upon examination.

Figure 2. Between 3 and 4 weeks following treatment of a new-generation artificial tear containing hyaluronic acid, trehalose, and povidone, the patient’s tear film had stabilized and fully resolved her corneal staining and focusing problems.

(Images courtesy of Mile Brujic, OD, FAAO)

Trehalose is a disaccharide demonstrated to provide ocular bioprotection, osmoprotection, and rehydration.9-12

Povidone is a viscosity-enhancing agent beneficial to the ocular surface that provides moisturizing and lubricating properties.

Patient case

I have had excellent results in recommending these advanced artificial tear formulations to patients.

One example involved a woman aged 42 years who complained of blurry vision while working at her computer for 8 hours a day. Examination showed inferior corneal staining but negative InflammaDry (Quidel) test readings (see Figure 1). I asked the patient to rest her eyes by breaking every 20 minutes to look across the room, and requested that she hydrate her ocular surface with a new-generation artificial tear that contains hyaluronic acid, trehalose, and povidone. Between 3 and 4 weeks later, her tear film had stabilized, fully resolving her corneal staining and focusing problems (see Figure 2).

Preservative-free eye drops are experiencing a successful transition from individual-dose vials to multidose bottles because of new technologies in bottle design. These bottles for preservative-free formulations use a special filter to keep the solutions sterile.

Patients should be educated about the appropriate way to use these bottles in order to optimize their use. Various designs provide different drop mechanisms for patients and patients should always be educated on appropriate use of eye drops.


Advances in the delivery of preservative-free artificial tears will be certain to improve patient outcomes and adherence. It is critically important to be specific about the exact artificial tear you want your patient to use. Stressing the importance of not only the brand but of a preservative-free solution and offering samples or coupons when possible are crucial steps in optimizing adherence.

Mile Brujic, OD, FAAO,  is a partner of Premier Vision Group in Bowling Green, Ohio. mile.brujic75@gmail.com

These simple but effective strategies can help patients achieve better ocular health and comfort by providing advanced lubricants to the ocular surface in a multidose bottle without preservatives. With all we know about today’s preservative-free artificial tears, gentle yet effective treatment should be an option for every patient who has dry eyes.

1. Meloni M, Balzaretti S, Ceriotti L. Medical devices biocompatibility assessment on HCE: evidences of delayed cytotoxicity of preserved compared to preservative free eye drops. Regul Toxicol Pharmacol. 2019;106:81-89. doi:10.1016/j.yrtph.2019.04.022
2. Aronson JK. Benzalkonium chloride. In: Aronson JK, ed. Meyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. 16th ed. Elsevier; 2016:843-844.
3. Alcon announces launch of Systane Complete Preservative-Free Lubricant Eye Drops in Europe. Alcon. January 12, 2022. Accessed August 29, 2022. https://www.alcon.com/media-release/alcon-announces-launch-systane-complete-preservative-free-lubricant-eye-drops-europe
4. Larson T. Artificial tears: a primer. The University of Iowa. November 23, 2016. Accessed August 29, 2022. https://webeye.ophth.uiowa.edu/eyeforum/tutorials/Artificial-Tears.htm
5. Jones L, Downie LE, Korb D, et al. TFOS DEWS II management and therapy report. Ocul Surf. 2017;15(3):575-628. doi:10.1016/j.jtos.2017.05.006
6. Pisárčik M, Bakoš D, Čeppan M. Non-Newtonian properties of hyaluronic acid aqueous solution. Colloids Surf A Physicochem Eng Asp. 1995;97(3):197-202. doi:10.1016/0927-7757(95)03097-W
7. Rah MJ. A review of hyaluronan and its ophthalmic applications. Optometry. 2011;82(1):38-43. doi:10.1016/j.optm.2010.08.003
8. Ophthalmic Drug Products for Over-the-Counter Human Use, 21 CFR Part 349 (1988). Accessed August 29, 2022. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-349
9. Chen W, Zhang X, Liu M, et al. Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis. Exp Eye Res. 2009;89(3):311-318. doi:10.1016/j.exer.2009.03.015
10. Aragona P, Colosi P, Rania L, et al. Protective effects of trehalose on the corneal epithelial cells. ScientificWorldJournal. 2014;2014:717835. doi:10.1155/2014/717835
11. Chiambaretta F, Doan S, Labetoulle M, et al; HA-trehalose Study Group. A randomized, controlled study of the efficacy and safety of a new eyedrop formulation for moderate to severe dry eye syndrome. Eur J Ophthalmol. 2017;27(1):1-9. doi:10.5301/ejo.5000836
12. Liu Z, Chen D, Chen X, et al. Trehalose induces autophagy against inflammation by activating TFEB signaling pathway in human corneal epithelial cells exposed to hyperosmotic stress. Invest Ophthalmol Vis Sci. 2020;61(10):26. doi:10.1167/iovs.61.10.26
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