Effects of Carboxymethylcellulose Artificial Tears on Ocular Surface Microbiome Diversity and Composition, A Randomized Controlled Trial

Abstract

Purpose Carboxymethylcellulose is an artificial tear ingredient known to decrease gut microbiome diversity when ingested. This study examines the effect of carboxymethylcellulose on ocular surface microbiome diversity and composition. Methods Healthy adult participants without significant ophthalmic disease or concurrent carboxymethylcellulose artificial tear use were allocated randomly to take carboxymethylcellulose or control polyethylene glycol artificial tears for seven days. Conjunctival swabs were collected before and after artificial tear treatment. This trial is registered at clinicaltrials.gov (NCT05292755). Primary outcomes included abundance of bacterial taxa and microbiome diversity as measured by the Chao-1 richness estimate, Shannon's phylogenetic diversity index, and UniFrac analysis. Secondary outcomes included Ocular Surface Disease Index scores and artificial tear compliance. Results Of the 80 enrolled participants, 66 completed the trial. Neither intervention affected Chao-1 richness (analysis of variance [ANOVA], P = 0.231) or Shannon's diversity index (ANOVA, P = 0.224). Microbiome samples did not separate by time point (permutation multivariate analysis of variance [PERMANOVA], P = 0.223) or intervention group (PERMANOVA, P = 0.668). LEfSe taxonomic analysis revealed that carboxymethylcellulose depleted several taxa including Bacteroides and Lachnoclostridium , but enriched Enterobacteriaceae , Citrobacter , and Gordonia . Both interventions decreased OSDI scores (Wilcoxon signed rank test, P < 0.05), but there was no significant difference between interventions (Mann-Whitney U , P = 0.54). Conclusions Carboxymethylcellulose artificial tears increased Actinobacteriota but decreased Bacteroides and Firmicutes bacteria. Carboxymethylcellulose artificial tears do not affect ocular surface microbiome diversity and are not significantly more effective than polyethylene glycol artificial tears for dry eye treatment. Translational Relevance The 16S microbiome analysis has revealed small changes in the ocular surface microbiome associated with artificial tear use.

Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma

“…A randomized trial comparing Carboxymethylcellulose to Polyethylene Glycol artificial tears found specific changes at genus level, including an increase in Bacteroidota and Actinobacteriota with Carboxymethylcellulose treatment [ 58 ]. However, overall diversity of the OSM was not significantly altered by these interventions.…”

Assessing the Effects of 0.3% Carboxymethylcellulose Tear Substitute Treatment on Symptoms and Signs of Dry Eye Disease in Elderly Population: A Prospective Longitudinal Study

“…Although the mechanism of action of CMC is not yet fully understood, it has been shown that its high micro-viscosity allows it to bind to human corneal epithelial cells [12], improving the ocular protection index for at least 20 min after instillation [21]. In addition, CMC also reduces the enrichment of Firmicutes bacteria [22], which have been associated with MGD and, therefore, a reduced LLT [22,23]. This is consistent with our results, which seem to be higher than those reported by the aforementioned studies that used 0.5% CMC tear substitute treatment.…”

“…CMC mimics the muco-mimetic properties of natural mucin found in the tear film, thus aiding in moisture retention and corneal epithelium healing [12,21]. In addition, CMC may also reduce the enrichment of Firmicutes bacteria, which is associated with MGD [22,23]. Recent innovations, such as preservative-free CMC tear substitutes, have expanded the scope of its application, significantly reducing the toxic effects commonly associated with preservatives in ophthalmic solutions [19].…”