Abstract
Purpose :
Flavoprotein fluorescence (FPF) is a non-invasive quantitative biomarker of mitochondrial dysfunction, with higher FPF reflecting increased metabolic stress. We investigated the effect of breathing 100% oxygen (O2) vs. ambient air (21% O2) on FPF intensity, which may differ depending on baseline retinal metabolic state. While greater O2 availability may enhance metabolic function, it may also worsen oxidative stress in disease states associated with baseline mitochondrial dysfunction. Our initial working hypothesis was that 100% O2 would increase FPF intensity compared with 21% O2 in eyes with DR or AMD.
Methods :
We measured FPF intensity in patients with DR (n=7), AMD (n=5), diabetes mellitus (DM) without DR (n=8) and controls (n=3) using the OcuMet Beacon (OcuSciences, Ann Arbor, MI) while breathing 21% O2 and then 100% O2 for 1 minute. Exclusion criteria included glaucoma, retinal disease other than DR or AMD, intraocular inflammation, significant media opacity or pseudophakia. We compared average FPF intensity between groups and between 21% vs. 100% O2 within groups, using generalized estimating equations to account for correlation between eyes.
Results :
Baseline FPF intensity under ambient air conditions was greater in DR, AMD and DM without DR, than controls (95.6, 103.0, 112.9 vs 61.0, p<0.01). In controls, FPF intensity was greater following 100% O2 compared with 21% (67.3 vs 61.0, mean difference 6.3, 95% CI 1.1 to 11.4, p = 0.02). In contrast, DM without DR had lower FPF intensity with 100% O2 (109.7 vs 112.9, difference -3.2, 95% CI -6.2 to -0.3, p = 0.03). There was no significant difference between 100% and 21% O2 in DR or AMD (95.1 vs 95.6, difference -0.5, 95% CI -1.3 to 0.4, p = 0.3; 103.2 vs 103.0, difference 0.2, 95% CI -1.0 to 1.5, p = 0.7).
Conclusions :
Greater FPF intensity in controls following 100% O2 inhalation may indicate that O2 delivery beyond physiologically normal levels increases oxidative stress in healthy retinas. Lower FPF intensity in DM without DR may reflect reversible mitochondrial dysfunction prior to onset of clinically evident retinal disease. More profound and permanent damage to mitochondria in DR and AMD may account for the lack of effect seen in these groups when assessed with a dynamic bioassay. FPF may be useful in detecting subclinical disease prior to permanent structural and functional changes within the retina.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.