Metabolomic Profile Of Cataract Patients With And Without Dry Eye Disease

The aim of this paper was to investigate and compare alterations in the metabolomic profile of tear fluid obtained from age-related cataract patients, with or without Dry Eye Disease (DED), to look for metabolomic signatures that could help us identify DED cases. Improved understanding of specific biomarkers in DED may enhance diagnosis and treatment. Moreover, better comprehension of underlying metabolic pathways may suggest new therapeutic targets.

The results of the metabolomic analyses is a part of a larger prospective randomized interventional study of DED and cataract surgery conducted from August 2020 to January 2022 at iFocus Eyeclinic in Haugesund, Norway. All patients were recruited from a single cataract clinic. 

218 patients scheduled for cataract surgery were examined for DED in one randomly selected eye and questioned regarding symptoms and risk factors. Patients were diagnosed with DED if they fulfilled the DEWS II criteria. 81 patients were randomly selected for metabolomic analysis from both dry eye positive (DED+) and negative (DED-) groups prior to cataract surgery. Tear film was collected using Schirmer-1 strips, and analyzed using a newly developed method aimed at low-volume Schirmer samples and possible combined omics (such as lipidomic and metabolomic analysis) approach. Metabolomic data was compared using a global LC-MS method.

All samples were successfully analyzed using global LC-MC method, with an average of 2625 features, including 1718 in positive and 897 in negative ionization mode. Samples were compared using Principal Component Analysis (PCA) and Volcano plots to look for overall global differences as well as specific metabolites of interest. A lack of spontaneous clustering was observed on PCA plots for either the DED+ or DED- groups, indicating no overall global similarities in each group. However, volcano plots displayed a general negative shift, implying that patients with DED have lower overall metabolic activity, rather than just a deficiency of specific metabolites. Moreover, several metabolites of interest were discovered.

Untargeted metabolomic analysis of tear samples is crucial with regards to research regarding biochemical activity and state of cells/tissues – making it ideal for the discovery of active biomarkers. Although no overall global difference was observed on the PCA plots, a general trend of reduced metabolomic activity of the DED group was shown. Moreover, several metabolites of interest were discovered, which may aid the development of future therapeutic targets.