Schirmer Strips in Tear Metabolomics of Dry Eye Disease: Pre-analytical and Analytical Considerations

Dry eye disease (DED) is a prevalent ocular surface condition characterized by tear film instability and inflammation, significantly impacting patients' quality of life. While the Schirmer test remains a key diagnostic tool, Schirmer strips are increasingly used for tear fluid collection in metabolomics studies aimed at, e.g. identifying biomarkers for DED. However, both pre-analytical and analytical variables inherent to Schirmer strip use can compromise data integrity and hamper reproducibility.

For this review, the PubMed database and Google Scholar were searched for published human studies in English relevant to pre-analytical and analytical aspects of tear metabolomics, especially from dry eye patients, when tear samples were collected with Schirmer strips.

This article discusses the critical pre-analytical factors, including variability in Schirmer strip materials, tear sampling techniques, storage conditions, and potential contamination, that influence metabolomic data quality. Analytical considerations are also examined, with particular focus on volume-adjusted extraction protocols that address tear volume variability.

We conclude that standardized guidelines for Schirmer strip use, covering material selection, sampling protocols, storage, and extraction, are urgently needed to advance tear metabolomics as a reliable clinical and research tool. Future research should focus on validating these recommendations in multi-center studies, exploring inter-individual variability, and developing innovative analytical workflows to optimize metabolite recovery and quantification. Such efforts will enhance the translational potential of tear metabolomics, paving the way for biomarker discovery and improved management of DED.