Vascular and autonomic dysregulation in primary open-angle glaucoma

The purpose of this review is to discuss whether vascular dysfunction and autonomic dysfunction are related to primary open-angle glaucoma stratified by the intraocular pressure (IOP) level.

Patients with primary open angle glaucoma (POAG) across the spectrum of IOP exhibit a variety of ocular and nonocular vascular abnormalities. Interestingly, common genetic variation in nitric oxide synthase 3 (NOS3) and the caveolin 1/caveolin 2 (CAV1/CAV2) genomic regions, which code for proteins involved in setting vascular tone, are associated with POAG. These markers seem to stratify with POAG subtypes stratified by sex or pattern of initial visual field loss and not by IOP level. Overall, it is clear that there is also cardiovascular autonomic dysfunction in high-tension glaucoma and normal-tension glaucoma but it is unclear if this dysfunction is more common in normal-tension glaucoma compared with high-tension glaucoma.

Overall, POAG is likely a heterogeneous disease but stratifying cases by IOP level associated with initial optic nerve damage may be less useful than using other endophenotype approaches. Embracing the evidence suggesting systemic endothelial and autonomic dysfunction are operative in POAG will help us move beyond an IOP-centric view of the disease and facilitate 'tearing down the wall' that divides treating physicians and a better understanding of POAG pathogenesis.