Specific and non-linear effects of glaucoma on optic radiation tissue properties

Changes in sensory input with aging and disease affect brain tissue properties. To establish the link between glaucoma, the most prevalent cause of irreversible blindness, and changes in major brain connections, we characterized white matter tissue properties in diffusion MRI measurements in a large sample of subjects with glaucoma (N=905; age 49-80) and healthy controls (N=5,292; age 45-80) from the UK Biobank. Confounds due to group differences were mitigated by matching a sub-sample of controls to glaucoma subjects. A convolutional neural network (CNN) accurately classified whether a subject has glaucoma using information from the primary visual connection to cortex (the optic radiations, OR), but not from non-visual brain connections. On the other hand, regularized linear regression could not classify glaucoma, and the CNN did not generalize to classification of age-group or of age-related macular degeneration. This suggests a unique non-linear signature of glaucoma in OR tissue properties. ### Competing Interest Statement Dr. A. Lee reports grants from Santen, personal fees from Genentech, personal fees from US FDA, personal fees from Johnson and Johnson, grants from Carl Zeiss Meditec, personal fees from Topcon, personal fees from Gyroscope, non-financial support from Microsoft, grants from Regeneron, outside the submitted work; This article does not reflect the views of the US FDA.