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Ellipsoid Zone Reflectivity: Exploring its Potential as a Novel Non-Invasive Biomarker for Assessing Mitochondrial
I Kleerekooper1,2,3, D V Verschueren1,2,3,4,5,6, S A Trip2,4
1Department of Brain Repair and Rehabilitation, Moorfields Eye Hospital NHS Foundation Trust, UCL, London, UK.
Neuro-Ophthalmology (Aeolus Press)
|November 25, 2024
Summary
Optical coherence tomography (OCT) can reliably measure ellipsoid zone (EZ) reflectivity, a marker of mitochondrial function. This reflectivity is reduced in neuroinflammatory and mitochondrial optic neuropathies, suggesting its potential as a diagnostic biomarker.
Area of Science:
- Ophthalmology
- Neuroscience
- Biomarker Discovery
Background:
- The ellipsoid zone (EZ) in optical coherence tomography (OCT) scans shows high intensity due to light-scattering mitochondria.
- EZ reflectivity is a potential indicator of mitochondrial function and health.
- Developing reliable methods to quantify EZ reflectivity is crucial for its use as a biomarker.
Purpose of the Study:
- To develop a reliable tool for quantifying relative EZ reflectivity from OCT scans.
- To investigate the potential of EZ reflectivity as a biomarker in optic neuritis (ON), primary progressive optic neuropathy (PPON), chronic progressive external ophthalmoplegia (CPEO), and dominant optic atrophy (DOA).
- To assess the test-retest reliability and diagnostic value of EZ reflectivity in various optic neuropathies.
Main Methods:
- Developed and validated an analysis tool to extract relative EZ reflectivity, normalized to the retinal pigment epithelium (RPE) and outer nuclear layer (ONL).
- Analyzed OCT scans from 12 healthy controls and 66 patients with ON, PPON, CPEO, or DOA.
- Assessed reliability using intraclass correlation coefficients (ICC) and analyzed group differences using multivariable linear regression.
Main Results:
- EZ reflectivity (EZ/RPE20% and EZ/ONL ratios) demonstrated good test-retest reliability (ICCs 0.76 and 0.63, respectively).
- Significantly lower EZ/RPE20% and EZ/ONL ratios were observed in patients with CPEO, DOA, PPON, and ON compared to healthy controls.
- These reductions suggest impaired mitochondrial function in these neuroinflammatory and mitochondrial optic neuropathies.
Conclusions:
- EZ reflectivity can be reliably quantified using OCT scans.
- Reduced EZ reflectivity is associated with neuroinflammatory and mitochondrial optic neuropathies.
- EZ reflectivity shows promise as a non-invasive, in-vivo biomarker for mitochondrial health in the retina.
