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Published on: November 16, 2021
Quantification of Mitochondrial Stress in Nonarteritic Anterior Ischemic Optic Neuropathy Using Flavoprotein
Rishita Rama Pujari1, Yulan Ren, Jamie Zhang
1Department of Ophthalmology (RRP, YR, JZ, AA, HW, YJL), Stanford University School of Medicine, Stanford, California; OcuSciences (CR), Inc., Ann Arbor, Michigan; and Department of Neurology and Neurosciences (YJL), Stanford University School of Medicine, Stanford, California.
Background:
Nonarteritic anterior ischemic optic neuropathy (NAION) or optic nerve stroke is the most common acute optic neuropathy in patients older than 50 years and results in severe vision loss. Endogenous flavoprotein fluorescence (FPF) imaging is a novel imaging modality to quantify axonal mitochondrial stress in the living central nervous system. We investigated the evolution of optic disc and macular FPF, and other ophthalmic measurements in the first 6 months after NAION onset.
Methods:
We retrospectively analyzed 10 patients (15 eyes) with acute NAION and performed serial assessments of visual function, optic disc FPF, macular FPF, and spectral-domain optical coherence tomography for 6 months. Longitudinal trends in optic disc FPF and peripapillary retinal nerve fiber layer (pRNFL) were modeled using generalized additive models with random effects to account for repeated measures. Linear mixed-effects models were used to assess changes from baseline to the 2-4 and 5-7-month follow-up periods.
Results:
In the acute phase (<45 days), pRNFL thickness was elevated, consistent with optic disc edema, while optic disc FPF values were within the normal range. Over time, optic disc FPF increased, and pRNFL thickness decreased, with relative stabilization after approximately 3 months, whereas visual acuity remained stable. Linear mixed-effects analysis of eyes with baseline imaging ≤45 days and follow-up at 2-4 months (5 eyes) and/or 5-7 months (6 eyes) demonstrated a significant increase in optic disc FPF (Δ = 5.77 dB, P < 0.001) and a significant decrease in pRNFL thickness by 2-4 months (Δ = -153.02 µm, P < 0.001), with no significant changes from the 2-4-month to the 5-7-month period.
Conclusions:
Optic disc FPF is normal in acute NAION because of masking by optic disc edema. As optic disc edema resolves, optic disc FPF score increases, reaching a plateau at around 3 months after onset, consistent with increased axonal metabolic stress.
