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Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
Akiko Hanyuda1,2, Oana A Zeleznik3, Yoshihiko Raita4,5
1Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Metabolites
|July 25, 2025
Summary
Prediagnostic glucose and branched-chain amino acids may reduce exfoliation glaucoma (XFG) risk. Nuclear magnetic resonance (NMR) profiling identified key metabolites linked to XFG etiology, offering insights into this aging-related eye disease.
Area of Science:
- Ophthalmology
- Metabolomics
- Aging Research
Background:
- Exfoliation glaucoma (XFG) is an aging-related eye condition with an unknown cause.
- Previous research utilized liquid chromatography-mass spectrometry (LC-MS) to identify XFG-related metabotypes.
- This study investigates prediagnostic nuclear magnetic resonance (NMR)-based metabolites and their association with XFG risk.
Purpose of the Study:
- To evaluate the relationship between prediagnostic NMR-based metabolites and the risk of developing exfoliation glaucoma (XFG).
- To expand upon prior findings of XFG-related metabotypes identified through LC-MS analysis.
Main Methods:
- Utilized a nested case-control design within three prospective health professional cohorts.
- Analyzed plasma samples collected approximately 11.8 years prior to XFG diagnosis in 217 cases and 217 matched controls.
- Employed the targeted NMR Nightingale platform for plasma metabolite analysis and conditional logistic models with Metabolite Set Enrichment Analysis.
Main Results:
- Higher glucose levels were significantly associated with a reduced risk of XFG (OR = 0.42; 95% CI = 0.26–0.7).
- Inverse associations were observed between XFG risk and lipoprotein subclasses and branched-chain amino acids.
- Conversely, relative lipoprotein lipid concentrations showed an adverse association with XFG risk (FDR < 0.05).
Conclusions:
- NMR profiling suggests that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations are potentially significant factors in the etiology of exfoliation glaucoma.
- These findings contribute to understanding the metabolic underpinnings of XFG and may inform future research directions.
