Eyedrops Change Surface Microbiota

Download PDF

Benzalkonium chloride (BAK) is the most frequently found preservative in eyedrops. Now researchers report a possible link between preservatives, which are intended to prevent growth of pathogenic bacteria in medication bottles, and microbial changes that may put the ocular surface at greater risk for inflammation.¹

For this study, the researchers evaluated the impact of topical glaucoma medications. “We found that glaucoma patients taking IOP-lowering drops [with preservatives] had an altered ocular surface microbiome compared to age-matched subjects without a history of glaucoma or use of eyedrops,” said Bryan J. Winn, MD, at the University of California, San Francisco. “These glaucoma patients had fewer of the normal commensal bacteria that we think are important for maintaining ocular surface homeostasis.”

MICROBIAL COMPOSITION. Treated eyes had a highly diverse array of microbes on their ocular surface, including Bifidobacterium.

Comparing three groups. For this study, the researchers conducted ribosomal RNA sequencing on ocular surface swabs collected from both eyes of 17 participants. Ten patients had asymmetric/unilateral glaucoma and were being treated with a variety of topical eyedrops containing BAK on one eye. Seven age-matched healthy controls had no history of ocular disease or eyedrop use.

The samples were categorized into three groups: 1) patients’ glaucomatous eyes treated with eyedrops (n = 10), 2) a control group of the patients’ contralateral untreated eyes (n = 10), and 3) a secondary control group of healthy eyes (n = 14). The researchers compared microbial diversity and composition, with differences tested for association with ocular surface disease measures.

Effect on the microbiota. The microbial composition of treated eyes was distinct from that found in healthy controls. Specifically, treated eyes had a highly diverse array of bacteria that was significantly different from the less diverse microbes found on the eyes of healthy controls.

In an unexpected finding, ocular surface changes occurred in both treated and contralateral untreated glaucomatous eyes. This may indicate that the ocular surface microbiome is a “bilateral microbial niche,” Dr. Winn said. In other words, changes or perturbations that occur in one eye may have bilateral effects.

Other findings. In other findings, treated eyes were found to have decreased tear meniscus height and tear break-up time. In addition, results of genome inference analysis suggested that the ocular surface microbes of treated eyes had a greater capacity for inducing inflammation than those of healthy controls.

Is BAK to blame? Patients were treated with a variety of eyedrop formulations, yet all eyes exhibited similar changes to the ocular microbiome. In addition, neither the duration nor the frequency of glaucoma therapy was associated with differences in ocular bacterial diversity or microbiome composition. “These findings suggest that an ingredient common to all drops, and not the active medication ingredient, may be responsible for inducing the changes to the microbiota,” Dr. Winn said.

Follow-up study. Are the findings relevant to other drops with preservatives, such as those recommended for dry eye? “That is one of our concerns and is an avenue we are investigating,” Dr. Winn said. “The greatest number of drops used, including those available over the counter, are for the treatment of dry eye. If preservatives disturb ocular surface homeostasis via microbiome alterations, it may lend even more support for using nonpreserved alternatives.”

Dr. Winn added, “We think the most plausible explanation for our findings is that a constant application of a detergent-like preservative to the ocular surface alters the ocular surface microbiome, but prospective studies are needed to confirm this.”

—Miriam Karmel

___________________________

1 Chang CJ et al. Invest Ophthalmol Vis Sci. 2022;23(9):32.

___________________________

Relevant financial disclosures: Dr. Winn—Columbia University: P.

For full disclosures and the disclosure key, see below.

• Acute Macular Neuroretinopathy and COVID-19

• OCT Centers: Role in Glaucoma Screening?

• Emergency Visits After Cataract Surgery