Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration

Ines Lains, MD, PhD; Xikun Han, PhD; João Gil, MD; Joana Providencia, MD; Archana Nigalye, MD; Rodrigo Alvarez, MD; Vivian Paraskevi Douglas, MD; Kevin Mendez, MSc; Raviv Katz, BSc; Gregory Tsougranis, BSc; Jinglun Li, BSc; Rachel S. Kelly, PhD; Ivana K. Kim, MD; Jessica Lasky-Su, ScD; Rufino Silva, MD, PhD; Joan W. Miller, MD; Liming Liang, PhD; Demetrios Vavvas, MD, PhD; John B. Miller, MD; Deeba Husain, MD

Ophthalmology Science (Jan 2024)

Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration

Ines Lains, MD, PhD,
Xikun Han, PhD,
João Gil, MD,
Joana Providencia, MD,
Archana Nigalye, MD,
Rodrigo Alvarez, MD,
Vivian Paraskevi Douglas, MD,
Kevin Mendez, MSc,
Raviv Katz, BSc,
Gregory Tsougranis, BSc,
Jinglun Li, BSc,
Rachel S. Kelly, PhD,
Ivana K. Kim, MD,
Jessica Lasky-Su, ScD,
Rufino Silva, MD, PhD,
Joan W. Miller, MD,
Liming Liang, PhD,
Demetrios Vavvas, MD, PhD,
John B. Miller, MD,
Deeba Husain, MD

Affiliations

Ines Lains, MD, PhD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Xikun Han, PhD: Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts; Program in Genetic Epidemiology and Statistical Genetics, Harvard T H Chan School of Public Health, Boston, Massachusetts
João Gil, MD: Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
Joana Providencia, MD: Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
Archana Nigalye, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Rodrigo Alvarez, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Vivian Paraskevi Douglas, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Kevin Mendez, MSc: Systems Genetics and Genomics Unit, Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Raviv Katz, BSc: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Gregory Tsougranis, BSc: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Jinglun Li, BSc: Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, Massachusetts
Rachel S. Kelly, PhD: Systems Genetics and Genomics Unit, Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Ivana K. Kim, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Jessica Lasky-Su, ScD: Systems Genetics and Genomics Unit, Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Rufino Silva, MD, PhD: Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal; Clinical Academic Center of Coimbra (CCAC), Coimbra, Portugal
Joan W. Miller, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Liming Liang, PhD: Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, Massachusetts
Demetrios Vavvas, MD, PhD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
John B. Miller, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
Deeba Husain, MD: Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Correspondence: Deeba Husain, MD, Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles St, Boston, MA 02114.

Journal volume & issue: Vol. 4, no. 1
p. 100357

Abstract

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Purpose: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Design: Prospectively designed, cross-sectional study. Participants: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. Methods: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Main Outcome Measures: Plasma metabolite levels associated with OCT features. Results: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. Conclusions: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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