Why Recommending Preservative-Free Matters in Chronic Dry Eye Management

Key Takeaways:

• Common preservatives like benzalkonium chloride (BAK) can damage the corneal surface and worsen inflammation, particularly with frequent, long-term use.
• Patients with moderate-to-severe CDE who use artificial tears more than 4 times daily should switch to preservative-free options to avoid cumulative irritation.
• Eliminating preservatives reduces side effects like stinging and burning, making it a more effective strategy for long-term ocular surface healing and comfort.

Chronic dry eye (CDE) remains one of the most common reasons for eye clinic visits, affecting millions of people in the United States. Artificial tears are a frontline therapy for managing symptoms.^1,2

Most multi-dose eye drops require a preservative to maintain sterility. The most common of these is benzalkonium chloride (BAK). While effective as an antimicrobial, BAK also presents a significant clinical consideration for people with CDE.²

This is especially true for patients who require frequent, long-term dosing. For these individuals, the preservative itself may contribute to ocular surface disease (OSD).^3,4

What the research shows

Benzalkonium chloride is a powerful antiseptic. This property, which makes it an effective antimicrobial, also allows it to disrupt the ocular surface. Research shows that BAK can be toxic to the corneal and conjunctival epithelium.^2-4

Prolonged exposure to BAK can:^2-4

• Disrupt the tear film’s lipid layer
• Reduce the viability of epithelial cells
• Compromise the epithelial barrier function
• Cause infiltration of inflammatory cells

This creates a cycle of iatrogenic damage. The very treatment intended to relieve CDE symptoms may, in fact, worsen the underlying inflammation and irritation of the ocular surface.^3,4

Why dosing frequency is a critical factor

The toxic effects of BAK are dose-dependent. For a patient with mild, occasional symptoms who uses preserved drops infrequently (less than 4 times per day), the risk may be low.^3-5

The clinical picture changes dramatically for people with moderate-to-severe chronic dry eye. These patients often rely on artificial tears far more frequently. This cumulative, long-term exposure significantly increases the risk of preservative-induced toxicity. For these frequent users, the preservative is a constant irritant that can prevent the ocular surface from healing.^3-5

The clinical benefit of preservative-free formulations

The primary benefit of preservative-free (PF) formulations is clear: They eliminate the source of preservative-induced toxicity. By removing BAK, clinicians can help reduce the chemical load on an already compromised ocular surface.^3,4

This switch often leads to improved patient-reported outcomes, including a reduction in:^3,4

• Burning
• Stinging
• General irritation

While some studies comparing PF and preserved drops show similar efficacy in improving tear film stability, the key advantage of PF is avoiding harm. Studies note that preservative-free formulations appear more effective at decreasing ocular inflammation in patients with CDE. This makes them the ideal choice for patients with sensitive eyes, those on multiple ocular medicines, and anyone using drops more than 4 to 6 times daily.^3,4

Empowering the patient conversation

Many patients are not aware of the difference between preserved and preservative-free drops. This provides a key educational opportunity for clinicians. When recommending a switch, the explanation can be simple:

“The eye drops you are using now contain a preservative to keep the bottle sterile. Because you need to use them often for your chronic dry eye, we find that this preservative can sometimes irritate the surface of the eye. This may be contributing to your discomfort. I am recommending we switch to a preservative-free version. These are gentler on the eye and are much safer for the frequent, long-term use you need.”

This empowers the patient to understand why the change is being made, moving the focus from "all drops are the same" to a specific, targeted therapeutic choice.⁵

Navigating OTC preservative-free options

A robust market of over-the-counter (OTC) preservative-free options is available. These formulations maintain sterility through innovative packaging rather than chemical additives.⁵

The most common format is the single-use, disposable vial. These are ideal for eliminating contamination risk and are often recommended for post-surgical patients or those with severe sensitivities.⁵

More recently, multi-dose preservative-free (MDPF) bottles have become available. These bottles use special tips with filters and 1-way valves to keep the solution sterile for weeks after opening. This technology offers the convenience of a multi-dose bottle with the safety of a PF formulation.⁵

Several over-the-counter products, such as the Refresh® line, offer a wide range of preservative-free options. These include formulations for various CDE severities, from standard lubricating drops to thicker gels, available in both single-use vials and MDPF bottles. Data shows that Refresh is the number one doctor-recommended preservative-free brand.⁶

Making the best recommendation

While preserved artificial tears are appropriate for many people with mild or occasional dry eye, they pose a clear risk to patients with chronic CDE who require frequent dosing. The cumulative toxicity of preservatives like BAK can perpetuate inflammation and irritation.^3-5

By evaluating a patient’s dosing frequency and ocular surface health, clinicians can make a targeted recommendation. Switching frequent users to a preservative-free formulation is a clinically sound strategy to improve tolerability, reduce iatrogenic harm, and better manage chronic dry eye.^3-5