Abstract
We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US (n = 185) and Coimbra, Portugal (n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography—Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly (p < 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD.
Highlights
Age-related macular degeneration (AMD) is one of the leading causes of irreversible adult blindness in the world, [1] and poses a tremendous socioeconomic burden related to an aging population [2]
We present a cross-sectional study evaluating associations between urinary metabolomic profiles assessed by mass spectrometry and age-related macular degeneration (AMD)
Two of the urinary metabolites identified have been previously shown by our group to differ in the plasma of patients of AMD compared to controls and across severity stages [18]
Summary
Age-related macular degeneration (AMD) is one of the leading causes of irreversible adult blindness in the world, [1] and poses a tremendous socioeconomic burden related to an aging population [2]. In its early and intermediate stages, AMD is mostly asymptomatic, and individuals are frequently unaware of their diagnosis except if they have a dilated eye exam. Some patients progress to the blinding forms of the disease, choroidal neovascularization (neovascular form) or geographic atrophy [3,4]. Even though AMD progression can be predicted based on retinal appearance by a dilated ophthalmic examination, the utility of this prediction is limited. Even wet AMD can go undetected by patients for a long time, especially if they have preserved vision in the fellow eye, with previous reports describing a mean duration of symptom onset to assessment of 2 months [5].
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