Comparing Analyte Concentrations in Paired Tear Fluid and Blood Samples.

Abstract

Purpose: To compare analyte concentrations in paired tear fluid and blood samples, and to evaluate their correlations.

Methods: Studies published between January 1974 and May 2024 and between May 2024 and March 2025, reporting analyte concentrations in tear fluid and blood (including whole blood, serum, or plasma), were identified from a recent scoping review and through searches of MEDLINE and EMBASE, respectively. Two reviewers independently screened studies and extracted relevant data. Concentration data were then pooled using a random-effects model. Comparisons between pooled tear fluid and blood concentrations were performed using Bayesian posterior simulation methods, in which the differences in concentrations were evaluated based on estimated posterior probabilities. Blood-to-tear and tear-to-blood ratios were calculated. A total of 72 significant correlation coefficients from 65 studies were analyzed.

Results: A total of 367 paired tear fluid and blood concentrations for 138 analytes were collected. Based on their functional characteristics, these analytes were divided into nine categories. Most cytokines and neuromodulators exhibited higher concentrations in tear fluid than in blood, while antibodies, drugs, and other proteins or enzymes were generally found at higher concentrations in blood. The highest tear-to-blood ratio was for lactoferrin at 1281-fold, while the highest blood-to-tear ratio was observed for MMP-2 (400-fold). Most analytes (n = 64, 89%) showed positive correlations (r > 0), with the majority (n = 23, 32%) exhibiting strong positive correlations (r > 0.8).

Conclusion: This comprehensive analysis demonstrates that analyte concentrations in paired tear fluid and blood vary according to their functional categories, with cytokines and neuromodulators generally enriched in tear fluid, and antibodies and drugs more abundant in blood. Strong positive correlations between tear fluid and blood concentrations for most analytes support the potential of tear fluid analysis for monitoring systemic physiological and pathological conditions.