Linking neural and clinical measures of glaucoma with diffusion magnetic resonance imaging (dMRI)

Purpose To 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. Methods We 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). Results We 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, R-2 = 0.66), retinal nerve fiber layer thickness (RNFL) predicted ON FA (F(1,10) = 11.477, p < 0.01, R-2 = 0.63) and ON FA predicted perceptual deficits (visual field index [VFI]) (F(1,10) = 15.308, p < 0.005, R-2 = 0.52). Conclusion We describe semi-automated methods to detect glaucoma-related structural changes using dMRI and confirm that they correlate with clinical measures of glaucoma.