Association of Human Plasma Metabolomics With Delayed Dark Adaptation in Age-Related Macular Degeneration

Abstract

PURPOSE: To assess the association between plasma metabolomic profiles and dark adaptation (DA) in all stages of age-related macular degeneration (AMD). METHODS: 56 AMD patients (14 early-stage AMD, 31 intermediate-stage AMD, 11late-stage AMD) and 19 control patients without any vitreoretinal disease were prospectively recruited from January 2015 to June 2016. Participants underwent profiling for metabolomes in fasting blood and urine samples through the use of mass spectrometry (MS). Nontargeted MS analysis was performed by Metabolon, Inc., using ultrahigh-performance liquid chromatography tandem MS. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. Subjects also obtained DA testing in both eyes with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). Multivariate logistical regressions were performed using various metabolites as predictors for dark adaptation in AMD patients versus controls, while controlling for age. RESULTS: Multivariate logistical regressions between time to dark adapt (continuous variable, truncated at 20 minutes, limit of the test) and 544 general metabolites identified 1 significant metabolite, alpha-tocopherol (AT), as different between AMD patients and control patients. CONCLUSIONS: Participants with AMD may have altered levels of alpha tocopherol compared with controls that could potentially predict ability to dark adapt and supports oxidative stress as a pathogenic mechanism for AMD. CONCLUSIONS: Participants with AMD may have altered levels of alpha tocopherol compared with controls that could potentially predict ability to dark adapt and supports oxidative stress as a pathogenic mechanism for AMD.