June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Plasma Metabolites Associated with Optical Coherence Tomography (OCT) Features of Age-related Macular Degeneration (AMD)
Author Affiliations & Notes
  • Ines Lains
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Xikun Han
    Harvard University T H Chan School of Public Health, Boston, Massachusetts, United States
  • Joao Quadrado Gil
    Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Coimbra, Portugal
    Associacao para a Investigacao Biomedica e Inovacao em Luz e Imagem, Coimbra, Coimbra, Portugal
  • Joana Providencia
    Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Coimbra, Portugal
    Associacao para a Investigacao Biomedica e Inovacao em Luz e Imagem, Coimbra, Coimbra, Portugal
  • Archana Nigalye
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Rodrigo Alvarez
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Vivian Paraskevi Douglas
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Rachel S Kelly
    Brigham and Women's Hospital, Boston, Massachusetts, United States
  • John B Miller
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Demetrios G. Vavvas
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Ivana K Kim
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Rufino Silva
    Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Coimbra, Portugal
    Associacao para a Investigacao Biomedica e Inovacao em Luz e Imagem, Coimbra, Coimbra, Portugal
  • Jessica Lasky-Su
    Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Joan W Miller
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Deeba Husain
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ines Lains None; Xikun Han None; Joao Gil None; Joana Providencia None; Archana Nigalye None; Rodrigo Alvarez None; Vivian Paraskevi Douglas None; Rachel S Kelly None; John Miller Alcon, Code C (Consultant/Contractor), Allergan, Code C (Consultant/Contractor), Carl Zeiss, Code C (Consultant/Contractor), Sunovion, Code C (Consultant/Contractor), Genentech, Code C (Consultant/Contractor); Demetrios Vavvas Valitor, Code C (Consultant/Contractor), Olix Pharmaceuticals, Code C (Consultant/Contractor), NIH R01EY025362, Code R (Recipient), NIH R21EY0203079, Code R (Recipient), Research to Prevent Blindness, Code R (Recipient), Loeffers Family Foundation, Code R (Recipient), Yeatts Family Foundation, Code R (Recipient), Alcon Research Institute, Code R (Recipient); Ivana Kim Biophytis, Code C (Consultant/Contractor), Castle Biosciences, Code C (Consultant/Contractor), Kodiak Sciences, Code C (Consultant/Contractor), Novartis, Code C (Consultant/Contractor), Allergan, Code R (Recipient); Rufino Silva Allergan, Code C (Consultant/Contractor), Alimera, Code C (Consultant/Contractor), Bayer, Code C (Consultant/Contractor), Novartis, Code C (Consultant/Contractor), Roche, Code C (Consultant/Contractor), Thea, Code C (Consultant/Contractor), Novus Nordisk, Code C (Consultant/Contractor); Jessica Lasky-Su None; Joan Miller Heidelberg Engineering, Code C (Consultant/Contractor), Sunovion, Code C (Consultant/Contractor), KalVista Pharmaceuticals, Code C (Consultant/Contractor), ONL Therapeutics, Code C (Consultant/Contractor), Lowy Medical Research Institute, Code F (Financial Support), ONL, Valeant Pharmaceuticals/ Massachusetts Eye and Ear, Code P (Patent); Deeba Husain Allergan, Code C (Consultant/Contractor), Genentech, Code C (Consultant/Contractor), Omeicos Therapeutics, Code C (Consultant/Contractor), NIH, Code F (Financial Support), Lions VisionGift, Code F (Financial Support), Commonwealth Grant, Code F (Financial Support), Lions International, Code F (Financial Support), Syneos LLC, Code F (Financial Support)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3527. doi:
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      Ines Lains, Xikun Han, Joao Quadrado Gil, Joana Providencia, Archana Nigalye, Rodrigo Alvarez, Vivian Paraskevi Douglas, Rachel S Kelly, John B Miller, Demetrios G. Vavvas, Ivana K Kim, Rufino Silva, Jessica Lasky-Su, Joan W Miller, Deeba Husain; Plasma Metabolites Associated with Optical Coherence Tomography (OCT) Features of Age-related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2022;63(7):3527.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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