Macular Metabolism in Young and Older Adults: A Preliminary Optical Coherence Tomography Biomarker Study

Purpose: To begin to test whether optical coherence tomography (OCT) metabolic biomarkers-established in mouse studies-change with age in ways consistent with published ex vivo findings on macular metabolism in healthy young vs. older adults. Methods: In this cross-sectional study, light-adapted subjects-25 light-adapted participants aged 20-30 years (n = 12) and 70-90 years (n = 13)-without overt ophthalmologic disease were compared. Two OCT metabolic biomarkers were measured: (i) external limiting membrane (ELM) to RPE (ELM-RPE) thickness, which in mice is a proxy for acidosis and retinoid-signaling dysfunction, and (ii) the profile shape aspect ratio of the hyper-reflective band just proximal to the ELM (band 2), which in mice is a proxy for mitochondrial configuration within the photoreceptor inner segments. Retinal laminar thicknesses were also assessed. Results: Older adults, regardless of sex, showed ELM-RPE contraction limited to the fovea and parafovea compared with younger adults. No differences in the profile shape aspect ratio of band 2 were observed in any macular region between the two age groups. Conclusions: As in mouse studies, ELM-RPE thickness and band 2 profile shape behave as independent variables. Central macular ELM-RPE contraction is consistent with subretinal oxidative stress-induced acidosis and impaired retinoid signaling, in line with prior findings of foveal oxidative damage and delayed dark adaptation. A stable band 2 aspect ratio aligns with measurements of a low percentage of mitochondrial abnormalities identified in ex vivo studies. Together, these results support a translational view of OCT metabolic biomarkers and support their application to noninvasive monitoring of outer retinal aging and disease.