Plasma Metabolomic Profile May Be a Biomarker for AMD

Age-related macular degeneration (AMD) is the leading cause of blindness in the word; however, the understanding of the disease’s pathogenesis is limited, and there is a lack of accessible and reliable biomarkers for prognosis and diagnosis. Researchers conducted a study to assess and validate plasma metabolomic profiles in patients with AMD and found that patients with AMD have a distinct plasma metabolomic profile compared with patients without AMD, which could signal an easily accessible AMD biomarker. The results of the study were published as part of the American Society of Retina Specialists 2020 Virtual Annual Meeting

This prospective, cross-sectional study was conducted at two sites in Boston, MA, and Coimbra, Portugal. Patients with and without (controls) AMD who were older than 50 years underwent a detailed history, eye exam, color fundus photographs (AMD graded using Age-Related Eye Disease Study classification), and spectral domain-optical coherence tomography. Fasting blood samples were analyzed via ultra-performance liquid chromatography and high-resolution mass spectrometry.

The study included 491 patients: 149 with AMD and 47 controls from Boston, MA, and 242 with AMD and 53 controls from Coimbra, Portugal. After excluding 61 exogenous metabolites, analyses were performed on 544 metabolites.

After controlling for age, body mass index, smoking status, and gender, the meta-analysis identified 69 significantly different metabolites (P<0.05) between patients with and without AMD, 28 of which had statistically significant false discovery rates. Most of the significant metabolites were lipids (35.7%), followed by amino acids (28.6%), nucleotides (21.4%), carbohydrates (7.1%), cofactors and vitamins (3.6%), and peptides (3.6%).

These 28 metabolites belonged to four pathways of significance: purine (P=7.2×10^-4), sphingolipid (P=0.0010), glycerophospholipid (P=0.0037), and nitrogen metabolites (P=0.0404).

“These metabolites could provide insight into disease pathogenesis and be the basis for a precision medicine approach leading to effective therapies for early and intermediate AMD,” the researchers concluded. “Metabolomics offers a potential novel tool for early diagnosis and treatment and may point to new targets for the treatment of macular degeneration.”

Husain D, Lains I, Miller JB, et al. Role of Metabolomics in Age-Related Macular Degeneration. Presented during the ASRS 2020 Virtual Annual Meeting, July 24-26, 2020.