Topical Glaucoma Therapy Is Associated With Alterations of the Ocular Surface Microbiome

Abstract

Purpose To investigate the ocular surface microbiome of patients with unilateral or asymmetric glaucoma being treated with topical ophthalmic medications in one eye and to determine whether 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 topical glaucoma therapy on only one eye and seven age-matched, healthy controls with no history of ocular disease or eyedrop use. 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, tear break-up time, and Dry Eye Questionnaire. Results Samples obtained from the patients’ treated and untreated eyes both had significantly greater alpha-diversity and relative abundance of gram-negative organisms compared to healthy controls. The microbial composition of patient eyes was associated with decreased tear meniscus height and tear break-up time, whereas metagenomic predictions, based on 16S rRNA data, suggested increased synthesis of lipopolysaccharide. Conclusions The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a highly 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.

Perturbations of the ocular surface microbiome and their effect on host immune function

“…The ocular surface microbiome of patient eyes receiving topical medications was dominated by Akkermansia (11.8%), Faecalibacterium (6.3%), Lachnospiraceae (5.9%), Komagataeibacter (4.8%), Finegoldia (4.6%), Corynebacterium (3.9%), and Blautia (3.6%). This was different from the more typical commensals of the healthy control eye samples, Corynebacterium (71.7%), Cutibacterium (5.4%), and Blautia (4.4%) [38 ▪ ]. Metagenome inference analysis suggested that the ocular surface microbes of patients using drops were more capable of lipopolysaccharide synthesis whereas the microbes of healthy controls had capacity for reducing inflammation.…”

“…It is not fully understood why contact lens wearers have an altered microbiome; however, chronic exposure to peroxide-based preservative solutions that bathe the lenses when not in use may play role. In patients using preserved topical glaucoma medications [38 ▪ ], the ocular surface microbiome was likely altered by chronic daily exposure to the detergent BAK, with a resultant microbial composition capable of increased synthesis of lipopolysaccharide, a pro-inflammatory endotoxin. The effect of topical medications and contact lenses on the ocular surface microbiome warrants further study to determine how local immune function may be affected by these disrupted microbiomes.…”

Dry Eye Disease Symptoms Among Glaucoma Patients at a Portuguese Hospital

“…Benzalkonium chloride (BAK) is one of the most commonly used preservatives in IOP-lowering medications because it has antimicrobial properties through its action as a detergent that disrupts bacterial cell walls and prevents the growth of pathogenic bacteria in eyedrop containers [ 3 , 4 , 9 ]. However, it is associated with a disruption of the corneal surface with corneal epithelial punctate erosion and shorter tear breakup time and may also cause alterations in the microorganisms of the ocular surface which can in turn lead to inflammation [ 3 , 9 , 10 ]. Other preservatives such as Polyquad, Purite, and sofZia seem to have less toxic effects [ 2 , 11 ].…”

Usability of an Eye Drop Delivery Aid for Single-Dose Instillation: Results from a Market Research Study

“…There is evidence to suggest that the healthy ocular surface harbors a stable composition of organisms that, when disrupted (such as with ocular trauma or contamination), can predispose patients to developing ocular surface infection or inflammation. 5 The ocular microbiota includes all types of microorganisms, both commensal and pathogenic, living on or in the eye, which can regulate, defend, or provoke and perpetuate the development of chronic eye diseases. 6 Therefore, proper eye drop instillation remains important.…”