Abstract
PurposeTo link optic nerve (ON) structural properties to clinical markers of glaucoma using advanced, semi-automated diffusion magnetic resonance imaging (dMRI) tractography in human glaucoma patients.MethodsWe characterized optic neuropathy in patients with unilateral advanced-stage glaucoma (n = 6) using probabilistic dMRI tractography and compared their results to those in healthy controls (n = 6).ResultsWe successfully identified the ONs of glaucoma patients based on dMRI in all patients and confirmed that dMRI measures of the ONs correlated with clinical markers of glaucoma severity. Specifically, we found reduced fractional anisotropy (FA) in the ONs of eyes with advanced, as compared to mild, glaucoma (F(1,10) = 55.474, p < 0.0001, FDR < 0.0005). Furthermore, by comparing the ratios of ON FA in glaucoma patients to those of healthy controls (n = 6), we determined that this difference was beyond that expected from normal anatomical variation (F(1,9) = 20.276, p < 0. 005). Finally, we linked the dMRI measures of ON FA to standard clinical glaucoma measures. ON vertical cup-to-disc ratio (vCD) predicted ON FA (F(1,10) = 11.061, p < 0.01, R2 = 0.66), retinal nerve fiber layer thickness (RNFL) predicted ON FA (F(1,10) = 11.477, p < 0.01, R2 = 0.63) and ON FA predicted perceptual deficits (visual field index [VFI]) (F(1,10) = 15.308, p < 0.005, R2 = 0.52).ConclusionWe describe semi-automated methods to detect glaucoma-related structural changes using dMRI and confirm that they correlate with clinical measures of glaucoma.
Highlights
Vision loss is a major cause of disability worldwide that is common among the elderly, conferring a greater risk of injury and diminished quality of life [1,2]
We successfully identified the optic nerve (ON) of glaucoma patients based on diffusion magnetic resonance imaging (dMRI) in all patients and confirmed that dMRI measures of the ONs correlated with clinical markers of glaucoma severity
By comparing the ratios of ON fractional anisotropy (FA) in glaucoma patients to those of healthy controls (n = 6), we determined that this difference was beyond that expected from normal anatomical variation (F(1,9) = 20.276, p < 0
Summary
We identified strong correlations between vCD and RNFL (F(1,10) = 229.17, p = 3.20e-8, R2 = 0.98), vCD and VFI (F(1,10) = 15.662, p = 0.0027, R2 = 0.64), and RNFL and VFI (F(1,10) = 24.228, p = 0.00060, R2 = 0.76) (Fig 3) These measures quantify the anticipated correlations between clinical measures of structural and functional glaucomatous optic nerve damage in our patient sample. To more precisely characterize the nature of these within-subject effects, we compared the FA ratios of advanced/mild ONs in glaucoma patients to non-dominant/dominant ONs in controls. We found a significant difference between the ON FA ratios of glaucoma patients compared to controls in a LME model including group and age as fixed factors (F(1,9) = 20.276, p = 0.0015) (Fig 5). DMRI measures of FA in the optic nerve reliably linked the retinal and perceptual deficits observed in our patient sample
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