Linking Neural and Clinical Measures of Glaucoma with Diffusion Magnetic Resonance Imaging (dMRI)

Purpose To link optic nerve (ON) structural integrity to clinical markers of glaucoma using advanced, semi-automated diffusion weighted imaging (DWI) tractography methods in human glaucoma patients. Methods We characterized optic neuropathy in patients with unilateral advanced-stage glaucoma (n = 6) using probabilistic DWI tractography and compared their results to those in healthy controls (n=6). Results We successfully identified the ONs of glaucoma patients based on DWI in all patients and confirmed that the degree of reduced structural integrity of the ONs determined using DWI correlated with clinical markers of glaucoma severity. Specifically, we found reduced fractional anisotropy (FA), a measure of structural integrity, in the ONs of eyes with advanced, as compared to mild, glaucoma (F(1,10) = 55.474, p < 0.0001). 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 DWI-measures of neural integrity 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 provide semi-automated methods to detect glaucoma-related structural changes using DWI and confirm that they correlate with clinical measures of glaucoma.