PRESERVATIVES are ubiquitous throughout eye care. They are seen in both prescription and over-the-counter topical ophthalmic drops, contact lens disinfection solutions, and in-office pharmacologic drops. It is challenging to diagnose patients who have ocular irritation, as most presentations are multifactorial and complicated by underlying ocular surface disease. For eyecare practitioners, being aware of the various preservatives and preservative-based systems used in ophthalmic products is key in pinpointing which specific products can exacerbate signs and symptoms.

Preservatives are used in topical ophthalmic products to maintain sterility and increase the life of the product (Goldstein et al, 2022). The most common preservative in eyecare products is benzalkonium chloride (BAK), which is used in almost 70% of ophthalmic topical medications and is effective against gram-positive and gram-negative bacteria, as well as fungi (Goldstein et al, 2022; Walsh and Jones, 2019).

BAK-related ocular irritation occurs due to the effect on the ocular surface at the cellular level. BAK has been shown to cause corneal epithelial cell injury, conjunctival goblet cell loss, and delayed corneal wound healing, and may induce corneal epithelial cell apoptosis, just to name a few of its drawbacks (Goldstein et al, 2022) (Figure 1). These cellular reactions clinically manifest as punctate staining, eye pain, increased tear breakup time, conjunctival staining, discomfort, and tearing (Goldstein et al, 2022).

BAK is the most widely used and studied preservative, but other preservatives have been developed to reduce the negative effects on the ocular surface (Table 1). Advances in eye drop delivery have been made to avoid preservatives getting to the ocular surface at all. These include oxidizing agents, which cause the preservative to break into nontoxic components once they land on the ocular surface, or multidose preservative-free bottles that contain special valves or membranes to keep the preservative in the bottle and prevent it from touching the ocular surface (Walsh and Jones, 2019). Of course, preservative-free artificial tears in single dose vials are best for the ocular surface, but these products cost significantly more than their preserved counterparts (Pucker, 2020), and there can be compliance issues with discarding the vials.

When patients present with ocular surface dryness, especially when they are wearing contact lenses, practitioners typically recommend the use of contact lens rewetting drops or artificial tears (off label) to aid in symptom control. Many patients are not aware of the wide array of artificial tear and contact lens rewetting drops available on the market and the differences between them in terms of ingredients, viscosity, and preservative content.

Patients typically only apply topical drops when they become symptomatic (Uchino et al, 2022), but research has shown that applying drops prior to symptoms, especially for contact lens wearers, can result in less ocular surface staining and hyperemia (Michaud and Frenette, 2012).

TAKEAWAY POINTS

• Be familiar with unique preservatives and bottle designs that can help avoid ocular surface irritation.

• Be intentional and specific when recommending drops, taking into account the patient’s ocular surface status and any specific preservative reactions in the past.

• Advise patients on applying topical lubricants consistently prior to the onset of symptoms.

• Teach patients how to apply drops to avoid bottle or vial contamination and how to dispose of vials properly.

REFERENCES

1. Goldstein MH, Silva FQ, Blender N, Tran T, Vantipalli S. Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond). 2022 Feb;36:361-368. 

2. Walsh K, Jones L. The use of preservatives in dry eye drops. Clin Ophthalmol. 2019 Aug 1;13:1409-1425.

3. Pucker AD. A Review of the Compatibility of Topical Artificial Tears and Rewetting Drops with Contact Lenses. Cont Lens Anterior Eye. 2020 Oct;43:426-432.

4. Uchino M, Yokoi N, Shimazaki J, Hori Y, Tsubota K; On Behalf Of The Japan Dry Eye Society. Adherence to Eye Drops Usage in Dry Eye Patients and Reasons for Non-Compliance: A Web-Based Survey. J Clin Med. 2022 Jan 12;11:367.

5. Michaud L, Frenette B. Evaluation of Sodium Hyaluronate Lubricating Drops Used before Insertion of Contact Lenses on Symptomatology, Severity, and Intensity of Ocular Dryness. ISRN Ophthalmol. 2012 Sep 2;2012:762784.