Metabolite and Lipid Biomarkers Associated With Intraocular Pressure and Inner Retinal Morphology: 1H NMR Spectroscopy Results From the UK Biobank

PURPOSE: The purpose of this study was to assess metabolites associated with intraocular pressure (IOP) and inner retina structure. METHODS: We cross-sectionally assessed 168 non-fasting plasma metabolites measured by nuclear magnetic resonance (NMR) spectroscopy with IOP (n = 28,195), macular retinal nerve fiber layer thickness (mRNFL; n = 10,584), and macular ganglion cell inner plexiform layer thickness (mGCIPL; n = 10,554) in the UK Biobank. We used multiple linear regression models adjusting for various covariates with probit-transformed metabolite levels as predictors for each outcome. Each estimate represents the difference in outcome variable per standard deviation increase in the probit-transformed metabolite values. We used the number of effective (NEF) tests and false discovery rate (FDR) to adjust for multiple comparisons for metabolites and metabolite classes, respectively. RESULTS: In individual metabolite analysis, multiple amino acids, especially branchedchain amino acids, were associated with lower IOP (-0.12 mm Hg; 95% confidence interval = -0.16 to -0.07; NEF = 2.7E-05). Albumin, 3 hydroxybutyrate, lactate, and several lipids were associated with higher IOP (range = 0.07 to 0.18 mm Hg, NEF = < 0.039). In IOP-adjusted analyses, five HDL-related metabolites were associated with thinner mRNFL (-0.15 microns for all metabolites, NEF = < 0.027), whereas five LDL-related metabolites were associated with thicker mGCIPL (range = 0.17 to 0.20 microns; NEF = < 0.044). In metabolite class analysis, the lipid components of lipoproteins (cholesterol, triglycerides, etc.) were not associated with our outcomes (FDR > 0.2 for all); yet multiple lipoproteins were significantly (FDR < 0.05) associated with all outcomes. CONCLUSIONS: Branched-chain amino acids were associated with lower IOP, HDL metabolites were associated with thinner mRNFL, and LDL metabolites were associated with thicker mGCIPL.

Automated summary

This study assessed the association between metabolites and intraocular pressure (IOP) and inner retina structure. It found that branched-chain amino acids were associated with lower IOP, HDL metabolites were associated with thinner macular retinal nerve fiber layer (mRNFL), and LDL metabolites were associated with thicker macular ganglion cell inner plexiform layer (mGCIPL).