Is primary open-angle glaucoma an ocular manifestation of systemic disease?

Primary open-angle glaucoma is currently characterized by a pattern of progressive retinal ganglion cell loss that stems from a complex underlying pathophysiology that remains poorly elucidated. The roles of blood flow and intraocular pressure (IOP) in glaucoma pathogenesis have been extensively studied. Further, it has been established that lowering IOP can slow the progression of glaucoma. In addition, a number of influential factors have emerged and gained momentum over the years. Increasing evidence implicates the contributions of low cerebrospinal fluid pressure, autoimmunity, neurodegeneration, and impaired autoregulation towards glaucoma pathophysiology. We aggregate and explore these different camps of thought that have garnered attention over the last few decades, and, in doing so, aim to challenge the long-standing view of glaucoma as a primary disease of the eye. A shift in our perspective towards understanding glaucoma as an ocular manifestation of systemic dysregulation may lead ultimately to better clinical management of the disease.