Abstract
Purpose :
Patients with age-related macular degeneration (AMD) and across different severity stages have been shown to have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible and more accessible alternative to plasma biomarkers. However, to our knowledge, no studies have evaluated urinary mass spectrometry (MS) metabolomics in AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group.
Methods :
We conducted a prospectively designed, multicenter, cross-sectional study including patients with AMD and a control group (>50 years old). At our two study sites – Boston, US and Coimbra, Portugal – participants had a complete ophthalmological exam and were imaged with color fundus photographs for AMD classification and staging (AREDS classification scheme). At the same visit, fasting urine samples were collected, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography – Mass Spectrometry, Metabolon, Inc). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for age, gender, body mass index and use of AREDS supplementation.
Results :
We included 484 participants, 389 with AMD (89 early, 201 intermediate and 99 late AMD) and 95 controls. Six urinary metabolites differed significantly (p< 0.01) across the severity stages of AMD (early, intermediate and late stage) with pathway analysis revealing an enrichment of sphingolipid metabolism. Of note, two of the metabolites (sphingosine and phosphoethanolamine) have been previously shown by our group to also differ in the plasma of patients with AMD compared to controls and all across AMD severity stages.
Conclusions :
This is the first investigation of urine metabolomics using Mass Spectrometry in AMD. We identified some differences across stages of disease that support our previous findings using plasma, supporting the potential of these metabolites as biomarkers for this common, blinding disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.