Correlation between systemic branched-chain amino acid metabolism and tear fluid inflammation with visual quality of life in patients with dry eye disease
- 1Department of Ophthalmology, The First Affiliated Hospital of Soochow University
- 2Department of Ophthalmology, The Fourth Affiliated Hospital of Soochow University
Abstract
Background: Dry eye disease (DED) is a common multifactorial ocular surface disorder characterized by tear film instability, inflammation, and visual impairment, with rising global prevalence affecting quality of life. While inflammation is central to DED pathophysiology, the role of systemic metabolic dysregulation in modulating local ocular surface inflammation remains unclear. This study investigates the correlation between systemic branched-chain amino acid (BCAA) metabolism and tear inflammatory markers as well as visual-related quality of life (VR-QOL) in DED patients.
Methods: This retrospective study enrolled 111 DED patients and 64 healthy controls from a single center (2022–2024). In the pilot phase, tear samples from 26 DED and 22 controls underwent untargeted metabolomics using UPLC-MS to identify differential metabolites and pathways. In the serum-based sequential exploratory phase, serum BCAA levels (leucine, valine, ILE) were measured in 85 DED patients (stratified by severity) and 42 controls. Tear inflammatory factors (IL-1β, IL-6, IL-8, hs-CRP, TNF-α) were quantified by ELISA/immunofluorescence. Pearson correlation analyzed associations between serum BCAAs and ocular surface sign parameters (Schirmer’s test, corneal staining), and inflammatory markers. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the apparent discriminative ability of serum BCAAs for suboptimal visual quality of life in patients with dry eye disease (DED).
Results: Untargeted metabolomics revealed 15 significantly altered tear metabolites in DED (8 upregulated, 7 downregulated). Enrichment analysis revealed a suggestive trend toward enrichment of the BCAA biosynthesis pathway (Raw P = 0.016; after Benjamini–Hochberg correction, FDR Q = 0.058, which did not meet the significance threshold of Q < 0.05.). In this study, pathways with raw P < 0.05 but corrected Q ≥ 0.05 were defined as exhibiting a “suggestive enrichment trend” and were not considered as definitive conclusions, warranting further targeted validation. Serum levels of leucine, valine, and ILE were significantly elevated in both mild-to-moderate and severe DED groups versus controls (all P<0.05), but did not differ by severity. Positive correlations were found between each BCAA and specific tear inflammatory factors (IL-1β, hs-CRP, TNF-α; r=0.35–0.66, all P<0.05), while no significant associations emerged with IL-6, IL-8, or clinical signs. ROC analysis revealed notable associations between serum BCAAs and poor VR-QOL, with AUCs of 0.916 (leucine), 0.837 (valine), and 0.886 (ILE). These exploratory findings suggest a potential link between BCAA levels and vision-related quality of life, but do not establish clinical utility as biomarkers.
Conclusions: Untargeted tear metabolomics in a small cohort revealed BCAA-related metabolic alterations in DED. Sequential exploratory analysis of an independent large-sample serum cohort further demonstrated that elevated serum Leu, Val, and ILE, which correlated positively with tear IL-1β, hs-CRP, and TNF-α at the population level. These findings provide exploratory evidence linking serum BCAAs to DED. However, given the use of two distinct matrices without paired sampling and the control group sample size n = 42 during the serum association exploratory phase being modestly lower than the predetermined goal—potentially compromising the statistical power of some tests—the results only support population-level cross-biofluid associations and do not confirm individual-level coupling.
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BibTeX
@article{wang2026correlation,
title = {{Correlation between systemic branched-chain amino acid metabolism and tear fluid inflammation with visual quality of life in patients with dry eye disease}},
author = {Yingming Wang and Lijuan Que and Zhengtai Sun and Lei Zhong and Xiaofeng Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1817802},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1817802/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Correlation between systemic branched-chain amino acid metabolism and tear fluid inflammation with visual quality of life in patients with dry eye disease
AU - Yingming Wang
AU - Lijuan Que
AU - Zhengtai Sun
AU - Lei Zhong
AU - Xiaofeng Zhang
PY - 2026
DA - 2026/10/16
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1817802
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1817802/full
AB - Background: Dry eye disease (DED) is a common multifactorial ocular surface disorder characterized by tear film instability, inflammation, and visual impairment, with rising global prevalence affecting quality of life. While inflammation is central to DED pathophysiology, the role of systemic metabolic dysregulation in modulating local ocular surface inflammation remains unclear. This study investigates the correlation between systemic branched-chain amino acid (BCAA) metabolism and tear inflammatory markers as well as visual-related quality of life (VR-QOL) in DED patients. Methods: This retrospective study enrolled 111 DED patients and 64 healthy controls from a single center (2022–2024). In the pilot phase, tear samples from 26 DED and 22 controls underwent untargeted metabolomics using UPLC-MS to identify differential metabolites and pathways. In the serum-based sequential exploratory phase, serum BCAA levels (leucine, valine, ILE) were measured in 85 DED patients (stratified by severity) and 42 controls. Tear inflammatory factors (IL-1β, IL-6, IL-8, hs-CRP, TNF-α) were quantified by ELISA/immunofluorescence. Pearson correlation analyzed associations between serum BCAAs and ocular surface sign parameters (Schirmer’s test, corneal staining), and inflammatory markers. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the apparent discriminative ability of serum BCAAs for suboptimal visual quality of life in patients with dry eye disease (DED). Results: Untargeted metabolomics revealed 15 significantly altered tear metabolites in DED (8 upregulated, 7 downregulated). Enrichment analysis revealed a suggestive trend toward enrichment of the BCAA biosynthesis pathway (Raw P = 0.016; after Benjamini–Hochberg correction, FDR Q = 0.058, which did not meet the significance threshold of Q < 0.05.). In this study, pathways with raw P < 0.05 but corrected Q ≥ 0.05 were defined as exhibiting a “suggestive enrichment trend” and were not considered as definitive conclusions, warranting further targeted validation. Serum levels of leucine, valine, and ILE were significantly elevated in both mild-to-moderate and severe DED groups versus controls (all P<0.05), but did not differ by severity. Positive correlations were found between each BCAA and specific tear inflammatory factors (IL-1β, hs-CRP, TNF-α; r=0.35–0.66, all P<0.05), while no significant associations emerged with IL-6, IL-8, or clinical signs. ROC analysis revealed notable associations between serum BCAAs and poor VR-QOL, with AUCs of 0.916 (leucine), 0.837 (valine), and 0.886 (ILE). These exploratory findings suggest a potential link between BCAA levels and vision-related quality of life, but do not establish clinical utility as biomarkers. Conclusions: Untargeted tear metabolomics in a small cohort revealed BCAA-related metabolic alterations in DED. Sequential exploratory analysis of an independent large-sample serum cohort further demonstrated that elevated serum Leu, Val, and ILE, which correlated positively with tear IL-1β, hs-CRP, and TNF-α at the population level. These findings provide exploratory evidence linking serum BCAAs to DED. However, given the use of two distinct matrices without paired sampling and the control group sample size n = 42 during the serum association exploratory phase being modestly lower than the predetermined goal—potentially compromising the statistical power of some tests—the results only support population-level cross-biofluid associations and do not confirm individual-level coupling.
SN - 1664-3224
ER -