Plasma Metabolites Associated with Optical Coherence Tomography (OCT) Features of Age-related Macular Degeneration (AMD)

Abstract

Purpose : The most widely used classifications of age-related macular degeneration (AMD) are still based on color fundus photographs (CFP). Yet, OCT is the foundation of real-world clinical assessments of patients with AMD and may better subclassify the wide variety of its phenotypes. While it has been proven that AMD patients have a distinct plasma metabolomic profile compared to controls, all studies to date have used the traditional CFP classification systems. This study examined whether plasma metabolomic profiles are associated with OCT features commonly seen in AMD, a potential step forward towards a more comprehensive classification system for AMD.

Methods : Prospective, cross-sectional study, including subjects with AMD and a control group (> 50 years) from Boston, United States and Coimbra, Portugal. All participants were imaged with CFP, used for AMD staging (AREDS classification), and with spectral-domain OCT (Spectralis, Heidelberg). OCT images were graded by two independent graders for the presence of characteristic AMD features (i.e. presence of classic drusen, subretinal drusenoid deposits, atrophy, among others), according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using non-targeted high resolution mass spectrometry by Metabolon, Inc.). Multilevel mixed regression models were used for analysis, adjusting for sex and age. Analyses were first conducted for each cohort (US and Portugal), with subsequent meta-analysis using a fixed-effect inverse variance method.

Results : We included data on 477 subjects (n= 953 eyes), 381 with AMD and 96 controls, and on 718 named endogenous metabolites. Nine metabolite-OCT associations were identified (p< 0.001). Most associations were seen with amino acids (n=5). In particular, levels of histidine were associated with the presence of hyperreflective foci, ellipsoid zone disruption and extent of classic drusen. The presence of hyperreflective foci was the OCT feature associated with more metabolites (n= 4).

Conclusions : To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Metabolomics may offer a useful biomarker for an improved classification system for this complex disease with many clinical phenotypes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.