Urine Metabolites Associated with Microperimetric Retinal Sensitivity in Age-Related Macular Degeneration

Abstract

Purpose : Best-corrected visual acuity (BCVA) has known limitations in patients with age-related macular degeneration (AMD). Microperimetry can represent an alternative reliable measure. Metabolomics, the comprehensive study of metabolites, has revealed significant insights into the pathogenesis of AMD and can contribute to better understand microperimetry changes in this disease. This study aimed to analyze associations between urine metabolites and microperimetry in AMD patients.

Methods : Prospectively recruited cross-sectional study including patients with AMD and a control group (>50 years). All patients were imaged with color fundus photos for AMD classification. Microperimetry was performed using the MAIA microperimetry system (Centervue, Italy), employing a 37-point full-threshold protocol. Fasting blood and urine samples were used for metabolomic profiling (Metabolon Inc). Multilevel mixed-effects linear models were used to assess associations between urine metabolites and retinal sensitivity. Statistical significance was determined by considering the number of independent tests that accounted for 80% of the variance (ENT80).

Results : We included 151 eyes (42 Control, 18 Early AMD, 73 Intermediate AMD, 18 Advanced AMD). Accounting for multiple comparisons, 8 urine metabolites were significantly associated with mean retinal sensitivity (p< 0.0017). These include 3 lysine metabolites (2-oxoadipate, N6-acetyllysine and 5-hydroxylysine), 1 purine metabolite (urate), 1 leucine, isoleucine, and valine metabolite (ethylmalonate), 1 tryptophan metabolite (3-hydroxyanthranilate), 1 progestin steroid (5alpha-pregnan-3beta,20alpha-diol disulfate), and 1 amino sugar metabolite (erythronate). Two of these metabolites were also found in our previous analysis of plasma metabolites.

Conclusions : To our knowledge, we present the first assessment of associations between urinary metabolites and retinal microperimetry sensitivity in AMD, lending credence to our group’s prior research which highlighted the significance of these pathways in AMD's pathophysiology. The most significant urine metabolites were found in Lysine and Tryptophan pathways. Notably the overlap of our prior findings using plasma and urine metabolites suggest that they might play a role in visual impairment and AMD.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.