Does the Artificial Tear We Prescribe Matter?

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11 min read

Welcome to Interventional Mindset! In this video, Drs. Preeya K. Gupta and Mark Milner discuss the value of preservative-free multi-dose artificial tears.

In this installment of Interventional Mindset, Drs. Preeya K. Gupta and Mark Milner discuss how to counsel patients on selecting the appropriate over-the-counter (OTC) artificial tear for their dry eye symptoms and developments in multi-dose preservative-free formulas.

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Advising patients on artificial tear selection

Among the most common first-line therapies, OTC artificial tears can improve lubrication and provide relief for dry eye patients. With current pharmaceutical technologies, there is now a multitude of eye drops available to patients at the pharmacy or local big-box drugstore. To prevent patients from feeling overwhelmed or confused by the wide selection of artificial tears, it’s vital that clinicians provide specific instructions and recommendations.
When providing recommendations to dry eye patients, Dr. Milner always tells patients—especially those with more than mild dry eye, including any form of keratitis—to avoid artificial tears with vasoconstrictors such as tetrahydrozoline or naphazoline.

When to prescribe preservative-free artificial tears to patients

Preservatives, such as benzalkonium chloride (BAK), have been proven to negatively impact the ocular surface through epithelial toxicity, inflammation, and irritation.1 Patients with dry eye oftentimes have existing inflammation, adding further irritation to this already stressed ocular surface environment resulting in increased rates of adverse events and allergies to the preservation system.
In particular, clinicians must prioritize minimizing the amount of irritation and inflammation on the ocular surface of glaucoma patients, as symptoms of ocular surface disease can exacerbate noncompliance in this patient population.

International Task Force recommendations for artificial tears

Additionally, using the International Task Force (ITF) classification system for stratifying dry eye patients,2 Dr. Milner prescribes preservative-free artificial tears to patients with moderate to severe dry eye disease (DED). For patients with mild symptoms, he recommends trying preserved artificial tears initially, and if irritation or side effects are observed, switching to a preservative-free formula.
Interestingly, Dr. Milner noted that the ITF did not discourage the overall use of preserved artificial tears because they recognize that artificial tears make up a billion-dollar industry, making it unrealistic to expect that patients will never use them. Instead, the ITF recommended that preserved tears only be used on patients with mild dry eye.

Commonly-used molecules in artificial tears

Developments in artificial tear technology have allowed for formulations to be specifically designed with dry eye in mind to provide more than lubrication. To simultaneously treat the various root causes of dry eye, Dr. Milner prefers prescribing patients eye drops with multiple mechanisms of action to alleviate dryness.

Four mechanisms of action used in artificial tears to treat dry eye:

  1. Counteracting hypertonicity: Clinicians can use hypotonic drops to treat patients with an inflamed eye and tear film hyperosmolarity.
  2. Increasing the oily layer: For patients with dry eye caused by meibomian gland dysfunction (MGD), using an oily tear aids in preventing tear film evaporation.
  3. Increasing retention time: Enhanced viscous lubricants, such as carboxymethylcellulose and glycerin, help with improving retention time and potentially tear viscosity.
  4. Compatible solutes: Also called osmoprotection, this is a new approach to treating dry eye with artificial tears. A hypertonic tear layer causes water to egress from the cell, and in response, the cell retains salt, which ultimately causes damage to the epithelial cells. This causes cell desiccation and death, and damage to the ocular surface.
    1. To prevent this, a compatible solute is inserted into the cell, which improves the water retention of epithelial cells and limits desiccation.
In addition, hyaluronic acid (HA) is another molecule that is new to artificial tear formulations in the United States, although it has been used internationally for decades. HA is considered a hyper lubricant that helps to reduce shearing stress on the ocular surface and increases tear viscosity.

Patient selection for artificial tears

The best way to treat a dry eye patient is to thoroughly understand their ocular physiology and symptoms gleaned from the patient history. For example, if a patient presents to the clinic with dry eye symptoms, before prescribing a drop, it’s important to run basic diagnostic tests to narrow down the root cause. An MGD patient will greatly benefit from using oil-based tears because they are efficacious in improving the oil layer to prevent tear evaporation.
The one caveat to this is cyclosporine-based formulations because they require an oil emulsion to stabilize the compound. For this reason, it is difficult for generic versions of cyclosporine drops to replicate the branded “recipe” because there are few vehicles that can stabilize the molecule. Based on his clinical experience, Dr. Milner recommends to patients who use oil emulsion tears not to instill them 10 minutes prior to or after using a cyclosporine-based artificial tear because it is unknown whether it could potentially dilute the cyclosporine.
Lastly, clinicians need to keep in mind that the patients’ personal preferences heavily influence which artificial tear they choose to use long-term. To account for this, Dr. Milner recommended having samples on hand and allowing patients to use these to determine which drop best treats their symptoms and improves their quality of life.
Similarly, Dr. Gupta mentioned that she offers patients samples and coupons with an image of the vial on it. That way, when patients go to the eye drop aisle, they know exactly which one to choose.

Using iVIZIA artificial tears to treat dry eye

Innovations in preservative-free formulas have resulted in multi-dose preservative-free vials as well as decreased costs, which greatly improved on previous formulas that were relatively inaccessible to patients due to the financial burden and the need for single-use vials.
Dr. Gupta’s favorite preservative-free tear for patients with lipid deficiencies and MGD-related dry eye symptoms is Systane COMPLETE, which features lipid-stabilizing molecules.
However, for patients who need increased tear volume and viscosity due to an aqueous deficiency or mixed-mechanism disease, she prescribes preservative-free iVIZIA artificial tears.

iVIZIA eye drops and gel* have a multi-action formula with three active ingredients:

  1. Povidone 0.5% (active ingredient): Helps with bioprotection and the regeneration of goblet cells to prevent apoptosis. Also, increases tear viscosity and retention time on the ocular surface.3
  2. Trehalose 3%: A disaccharide that acts as a compatible solute for improved water retention in epithelial cells, potentially decreasing inflammation, and regulating cellular osmosis.4
  3. Hyaluronic acid 0.15%: Increases tear film stability and improves lubrication by preventing goblet cell and corneal epithelial apoptosis.5
*The gel formulation contains carbomer for increased tear viscosity and retention time on the ocular surface.
Patient feedback about iVIZIA has been overwhelmingly positive at Dr. Milner’s clinic, and one patient even told Dr. Milner that he has discontinued the use of cyclosporine, saying he no longer needed it since the new drop was so effective.
Dr. Gupta highlighted that point because the iVIZIA bottle is a more malleable material compared to other vials,6 where she has gotten feedback from arthritic patients that it is easier to hold and squeeze.

How do multi-dose preservative-free artificial tears prevent microbial growth?

Recent recalls of EzriCare and Delsam Pharma artificial tears occurred because they were contaminated with a rare and multi-drug-resistant strain of Pseudomonas aeruginosa, amongst other pathogens. With this top of mind, clinicians need to feel comfortable prescribing artificial tears that carry enhanced sterility safeguards for patient use.
To prevent contamination, iVIZIA features a one-way valve that blocks airflow into the vial and a 0.2-micron filter in the bottle that blocks the fluid and bacteria on the ocular surface from entering the vial.


Accompanying the paradigm shift is a much-needed call to action for the ophthalmic community to go beyond treating dry eye with a “one size fits all” lubricant. With the advent of advanced artificial tear formulations, clinicians can reach for targeted dry eye treatments based on specific symptoms reported by the patient and uncovered during the examination.
To prevent the patient from becoming overwhelmed at the pharmacy or drugstore, Dr. Gupta recommends that clinicians stay up-to-date on innovations in artificial tears, brush up on the mechanism of action of two or three favorite artificial tears, and pick a patient profile to match to these drops. This process provides clinicians with a primary suggestion when counseling patients on selecting the appropriate artificial tear.
Preservative-free artificial tear formulations—such as iVizia sterile eye drops and gels—are a key ingredient (pun intended) to increasing dry eye patient satisfaction by improving ocular surface health. With these recent technological advancements, it has become more affordable and accessible to patients, which is a win for all those who suffer from dry eye.
Preeya K. Gupta, MD
About Preeya K. Gupta, MD

Dr. Gupta earned her medical degree at Northwestern University’s Feinberg School of Medicine in Chicago, and graduated with Alpha Omega Alpha honors. She fulfilled her residency in ophthalmology at Duke University Eye Center in Durham, North Carolina, where she earned the K. Alexander Dastgheib Surgical Excellence Award, and then completed a fellowship in Cornea and Refractive Surgery at Minnesota Eye Consultants in Minneapolis. She served on the faculty at Duke University Eye Center in Durham, North Carolina as a Tenured Associate Professor of Ophthalmology from 2011-2021.

Dr. Gupta has authored many articles in the peer-reviewed literature and serves as an invited reviewer to journals such as Ophthalmology, American Journal of Ophthalmology, and Journal of Refractive Surgery. She has also written several book chapters about corneal disease and ophthalmic surgery, as well as served as an editor of the well-known series, Curbside Consultation in Cataract Surgery. She also holds several editorial board positions.

Dr. Gupta serves as an elected member of the American Society of Cataract and Refractive Surgery (ASCRS) Refractive Surgery clinical committee, and is also is the Past-President of the Vanguard Ophthalmology Society. She gives presentations both nationally and internationally, and has been awarded the National Millennial Eye Outstanding Female in Ophthalmology Award, American Academy of Ophthalmology (AAO) Achievement Award, and selected to the Ophthalmologist Power List.

Preeya K. Gupta, MD
Mark S. Milner, MD
About Mark S. Milner, MD

Dr. Mark Milner is the director of cornea at Goldman Eye in Palm Beach Gardens, Florida, and an associate clinical professor of ophthalmology at Yale School of Medicine.

Mark S. Milner, MD
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