Disruption of structural brain networks in Primary Open Angle Glaucoma

primary open angle glaucoma (POAG) is one of the most common causes of permanent blindness in the world. recent studies have originated the hypothesis that POAG could be considered as a central nervous system pathology which results in secondary visual involvement. the aim of this study is to assess possible structural whole brain connectivity alterations in POAG by combining multi-shell diffusion weighted imaging, multi-shell multi-tissue probabilistic tractography, graph theoretical measures and a newly designed disruption index, which evaluates the global reorganization of brain networks in group-wise comparisons. we found global differences in structural connectivity between glaucoma patients and controls, as well as in local graph theoretical measures. these changes extended well beyond the primary visual pathway. furthermore, group-wise and subject-wise disruption indices were found to be statistically different between glaucoma patients and controls, with a positive slope. overall, our results support the hypothesis of a whole-brain structural reorganization in glaucoma which is specific to structural connectivity, possibly placing this disease within the recently defined groups of brain disconnection syndrome. clinical relevance—brain measures able to detect early changes in glaucoma can provide novel disease progression tracking strategies which could also be used in e.g. evaluating therapeutic responses, hence empowering clinical trials.