Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-related Macular Degeneration

Abstract

Purpose : Metabolomics can provide unique insights into the understanding of the pathophysiology of multifactorial diseases. We and others have shown that plasma metabolomic profiles vary between patients with age related macular degeneration (AMD) and controls and across stages of AMD. However, to our knowledge, no longitudinal studies have assessed how metabolomic profiles relate to AMD progression. This work aimed to analyze the association between plasma metabolomic profiles and progression of AMD over a three-year period.

Methods : Prospective longitudinal study including patients with AMD and a control group (>50 years old). At baseline and three years later (± 3 months), all included participants (both eyes) were imaged with color fundus photographs (CFP) for AMD grading and fasting plasma samples were collected. Eyes were considered to have AMD progression if at three-years their AMD stage was more advanced than the baseline stage grading with the AREDS classification scheme using CFP. Metabolomic profiling was performed using Ultrahigh Performance Liquid chromatography – Mass Spectrometry. Multilevel mixed models (i.e. considering inclusion of two eyes of the same patient), accounting for age, body mass index, smoking and gender were used for analysis, using as outcome progression of AMD (yes/no).

Results : We included data on 196 eyes (n= 98 patients), 13% (n= 26) of them with progression at the three-years follow-up. After quality control, a total of 645 plasma endogenous metabolites were considered for analysis. Among the baseline plasma metabolites, 3 (N-palmitoyl-sphingosine, methylsuccinate and N,N-dimethylalanine) were significantly associated with three-year AMD progression (p<= 0.009). When evaluating the association between changes in plasma metabolites (between baseline and 3 years) with progression of AMD, 10 significant associations were seen (p<= 0.009).

Conclusions : Baseline metabolites and changes in metabolomic profiles were associated with clinical progression of AMD at 3 years. In particular, lipid and amino acid metabolites appear to be among the relevant metabolites linked to AMD progression. This work contributes to our understanding of AMD progression and to the development of future biomarkers to monitor and potential therapeutics for this blinding disease.

This is a 2021 ARVO Annual Meeting abstract.