Tear Global Metabolomic Differences in Pre-Operative Cataract Patients With and Without Dry Eye Disease

Curr Eye Res. 2025 Mar 6:1-11. doi: 10.1080/02713683.2025.2472369. Online ahead of print.

Abstract

Purpose: The primary aim of this article was to investigate differences in the metabolomic profile of tear fluid obtained from pre-operative cataract patients, with or without dry eye disease. The objective was to look for metabolomic signatures that might discriminate between the two groups.

Methods: A total of 222 patients were enrolled in the study. Eighty-one were randomly selected for metabolomic analysis from both dry eye positive and dry eye negative groups, categorized prior to cataract surgery. Tear film was collected using Schirmer-1 strips and analyzed using an optimized method developed for low-volume Schirmer samples and allowing for repeated analyses, including other -omics approaches at a later stage. Metabolomic data were collected using a global liquid chromatography-mass spectrometry method. Samples were compared using principal component analysis and volcano plots to look for overall global differences as well as group-specific metabolic signatures.

Results: All samples were analyzed with a high number of features identified. No group-specific clustering was observed in principal component analysis for the dry eye positive or dry eye negative groups. However, volcano plots revealed that a majority of the metabolomic features had lower concentration in the dry eye positive group compared to the dry eye negative group. Four of these features had a Log2-fold change ≤ -1 and p value ≤.05. These warrant further study.

Conclusion: Although no overall global difference was observed on the principal component analysis plots, a general trend of lower metabolite concentrations in the dry eye disease group was shown. Moreover, several metabolites of interest were discovered with significantly different signal intensities between the groups. These metabolites may aid future diagnostics and serve as possible biomarkers and therapeutic targets for dry eye disease in pre-operative cataract patients.

Keywords: Dry eye disease; cataract; metabolomics; ocular surface; tear film.