Antiglaucoma Eye Drops with Preservatives – Higher Likelihood of Glaucoma Surgery?

Introduction

Patients treated for primary open-angle glaucoma or intraocular hypertension often experience ocular surface diseases. This can negatively impact treatment adherence and quality of life. Adverse effects on the ocular surface may be caused by medicinal substances or additives, especially preservatives added to antiglaucoma eye drops to increase shelf life and stability. 

Adverse Effects of Preservatives

There is ongoing debate about the extent to which preservatives contribute to the adverse effects of eye drops on the ocular surface. This particularly pertains to benzalkonium chloride (BAC), which is the most commonly used preservative in glaucoma eye drops. BAC causes tear film instability, loss of goblet cells, metaplasia and apoptosis of conjunctival squamous cells, disruption of the corneal epithelial barrier, and damage to deeper eye tissues. Clinical symptoms vary, including irritation, dry eye, allergies, and subconjunctival fibrosis. Other preservatives, such as SofZia, Purite, or Polyquad, have also been shown to have toxic and inflammatory effects on the ocular surface. The infiltration of preservatives applied to the ocular surface into the eye and their accumulation in deeper layers, such as the trabecular meshwork, can also be harmful when eye drops are used long-term.

Study Methodology and Results

A longitudinal cohort study evaluated data from all patients in France who were first prescribed eye drops for glaucoma treatment between 2008–2015. The authors used data from the French EGB database. A total of 12,454 patients were divided into 3 groups based on their exposure to preservatives: a group using preservative-free eye drops, a mixed group using both preservative-free and preserved eye drops, and a group using only preserved eye drops. 

The median follow-up duration was 4.1 (1.7–6.1) years. During the follow-up, 231 (1.9%) patients underwent glaucoma surgery. The surgery risk for those using only preserved eye drops was nearly 8 times higher compared to patients using preservative-free drops (hazard ratio [HR] 7.97; 95% confidence interval [CI] 3.07–20.67). Patients in the mixed group had a moderate risk, 4 times higher than patients with preservative-free antiglaucoma drops (HR 3.94; 95% CI 1.54–10.05). The association remained significant even after adjusting for treatment duration and the number of concomitantly used antiglaucomatics.

Conclusion

This study was the first to show a connection between exposure to preservatives in antiglaucoma eye drops and the prevalence of subsequent glaucoma surgeries. Its results should be considered in routine prescribing of antiglaucoma eye drops, but future randomized clinical studies are needed to prove a direct connection.

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Source: Chamard C., Larrieu S., Baudouin C. et al. Preservative-free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008–2016. Acta Ophthalmol 2020 Nov; 98 (7): e876–e881, doi: 10.1111/aos.14410.