Association of Plasma Metabolomics with Microperimetric Retinal Sensitivity in Age-Related Macular Degeneration

Abstract

Purpose : Visual acuity has important limitations in the assessment of visual function in age-related macular degeneration (AMD). Microperimetry, a measure of retinal sensitivity, is an alternative outcome that has been gaining increasing relevance. The large-scale analysis of metabolites, or metabolomics, has been shown to provide important information on AMD pathogenesis. This study aimed to investigate the association between plasma metabolite levels in AMD and average retinal sensitivity using microperimetry.

Methods : Cross-sectional study including patients with AMD. All participants were imaged with color-fundus photographs used for AMD classification (Age-Related Eye Disease Study System). Fasting blood samples were collected and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Retinal sensitivity was assessed via MAIA microperimetry (Centervue, Italy), using a full-threshold 37-point protocol (10 degrees diameter). Associations between metabolite levels and retinal sensitivity were examined using multilevel mixed-effects linear modeling accounting for the inclusion of two eyes of the same patients. Statistical significance was calculated based on the number of independent tests accounting for 80% variance (ENT80).

Results : We included data on 276 eyes with AMD (29 Early AMD, 203 Intermediate AMD, 44 Advanced AMD). 4 metabolites were significantly associated with mean retinal sensitivity. In particular, decreased levels of behenoyl sphingomyelin (P=0.0013) and increased levels of phosphate (P=0.0005), an androgenic steroid (P=0.0008), and a progestin steroid (P=0.00094) were associated with average retinal sensitivity in this cohort. Using a less stringent cut-off at P-Value < 0.01, we found 12 additional significant metabolites, all within the lipid metabolism or amino acid metabolism pathways.

Conclusions : To our knowledge, this is the first report to examine associations between plasma metabolites and microperimetric retinal sensitivity. Our results suggest that metabolites involved in the lipid metabolism and oxidative phosphorylation pathways are significantly associated with decreased retinal sensitivity in AMD patients. This supports our group’s previous suggestions that the lipid metabolism pathways play a major role in AMD pathophysiology, and that oxidative stress is involved in AMD-associated vision loss.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.