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Both plasma and urinary metabolites of the lysine pathway are associated with microperimetric findings in age-related macular degeneration.

Best-corrected visual acuity is the gold standard of retinal function measurement. However, it is not affected until advanced disease due to age-related macular degeneration (AMD). Increasing evidence suggests that microperimetry is a sensitive measure of visual function.

Research has demonstrated the potential of plasma and urine metabolomics to better understand AMD pathogenesis. However, the metabolomic profiles of microperimetric changes in AMD have not been examined. To address this knowledge gap, Deeba Husain, MD, and colleagues analyzed the association between metabolomic profiles and microperimetry in AMD.

They conducted a cross-sectional study, published in Metabolites, of patients with and without AMD. Microperimetry was conducted in both cohorts using the Macular Integrity Assessment (MAIA) system and a 37-point full-threshold testing protocol. Plasma and urine samples were analyzed using ultra-high-performance liquid chromatography–mass spectrometry. Associations between metabolites and retinal sensitivity were evaluated using multilevel mixed-effects linear models.

The study included 363 eyes with 95 controls and 268 patients with AMD (early AMD, n=25; intermediate AMD, n=199; late AMD, n=44). Of these, 151 eyes also had urine data: 42 controls and 109 with AMD. Overall, the mean sensitivity was 25.7. The average age of patients was 68.6 years, and the average BMI was 27.4. The demographic breakdown of ex-smokers to nonsmokers was nearly similar (47.7% and 50.1%, respectively). Among the cohort, 48.2% reported not taking AREDS supplementation, while 51.8% used the supplements.

Impact of Plasma and Urine Lysine Metabolites

The investigators found that both plasma and urinary metabolites of the lysine pathway were associated with the microperimetric findings in the AMD cases, suggesting that this pathway may play a key role in the pathogenesis of the functional changes observed.

In a stratified analysis of plasma metabolites for the AMD group, significant associations were shown by phosphate (β=−11.2; P<0.001) and glutarylcarnitine (C5-DC) in the lysine metabolism sub-pathway (β=3.0; P=0.001).

In urine samples, three metabolites of the lysine pathway were significantly associated with average retinal sensitivity in patients with AMD: 2-oxoadipate (β=−0.7; P<0.001), 5-hydroxylysine (β =−2.3, P<0.001), and N6-acetyllysine (β=−5.7; P<0.001).

“In particular, our findings support that both plasma and urine lysine metabolites are associated with this functional measure in patients with AMD, supporting the role of this pathway in the disease’s pathogenesis,” the investigators concluded, noting that future research focusing on this pathway could help reduce the visual impairments linked to this prevalent blinding condition.