Topical glaucoma therapy is associated with alterations of the ocular surface microbiome

Abstract

Purpose : Preserved topical medications used in the management of glaucoma are associated with ocular surface inflammation. The purpose of this cross-sectional study was to describe the ocular surface microbiome of patients treated with preserved topical ophthalmic medications as compared to that of healthy controls and to determine if microbial community changes were related to measures of ocular surface disease.

Methods : V3-V4 16S rRNA sequencing was conducted on ocular surface swabs collected from both eyes of 17 subjects: 10 patients with asymmetric/unilateral glaucoma using preserved topical glaucoma therapy on only one eye and 7 age-matched, healthy controls with no history of ocular disease or eyedrop use. Air swabs were used as negative controls. Samples were categorized into three groups: patients’ glaucomatous eye treated with eyedrops, patients’ contralateral eye without eyedrops, and healthy control eyes. Comparisons were made for microbial diversity and composition, with differences in composition tested for association with ocular surface disease measures including tear meniscus height (TMH), tear break-up time (TBUT), and Dry Eye Questionnaire scores (DEQ-5). The Columbia University Institutional Review Board approved this study.

Results : Samples obtained from treated and untreated patient eyes both had greater alpha-diversity (Shannon Diversity; Figure 1A, 1C) and distinct microbial composition (Bray Curtis Distance; Figure 1B, 1D) compared to controls. Patient samples had an increased relative abundance of gram-negative organisms dominated by Akkermansia compared to gram-positive commensals in controls (Figure 2). The microbial composition of patient eyes was associated with decreased TMH and TBUT, while metagenomic predictions based on 16S rRNA data suggested increased synthesis of the inflammatory endotoxin lipopolysaccharide.

Conclusions : The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a diverse array of gram-negative bacteria that is significantly different from the predominantly gram-positive microbes detected on healthy control eyes. These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.