Investigation of inter- and intra-day variability of tear fluid in terms of flow rate, protein concentration and protein composition

Aim: The aim of this study was to determine the intra- and inter-day variability of tear flow rate, tear protein concentration and tear protein composition for biomarker studies 1.
Methods: The study was performed by non-invasive collection of tear fluid from 18 healthy volunteers who repeated the Schirmer's tests at four different time points over a period of two days. The flow rate of the tears fluid was quantified using Schirmer test strips. Tear proteins were extracted from test strips and protein concentration determined. Tear protein composition was analysed by DIA-based mass spectrometry. Subjects underwent a comprehensive neurological and ophthalmological examination to exclude the possibility of health impairment.
Results: The results showed that sampling tear fluid from either the right or left eye had no effect on tear flow rate or protein concentration in individual subjects. In addition, protein concentration was found to be independent of tear volume. A comparison between study days revealed significant differences in tear flow rate and protein concentration. Mass spectrometric analysis of the tear fluid revealed eleven proteins that were differentially regulated between the two examination days.
Conclusions: Our results provide evidence for diurnal variations in tear flow rate, tear proteome concentration and composition in healthy subjects. This suggests that diurnal variations should be taken into account when investigating tear biomarkers.

Guntermann, A. et al. Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition. Invest Ophthalmol Vis Sci 64, 13 (2023). https://doi.org/10.1167/iovs.64.13.13