What is the pathophysiology of primary open-angle glaucoma (POAG)?

Updated: Mar 16, 2020
  • Author: Kristin Schmid Biggerstaff, MD; Chief Editor: Inci Irak Dersu, MD, MPH  more...
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Answer

The exact cause of glaucomatous optic neuropathy is not known, although many risk factors have been identified, to include the following: elevated IOP, family history, race, age older than 40 years, and myopia.

Elevated IOP is the most studied of these risk factors because it is the main clinically treatable risk factor for glaucoma. Multiple theories exist concerning how IOP can be one of the factors that initiates glaucomatous damage in a patient. Two of the major theories include the following: (1) onset of vascular dysfunction causing ischemia to the optic nerve, and (2) mechanical dysfunction via cribriform plate compression of the axons.

In addition to vascular compromise and mechanically impaired axoplasmic flow, contemporary hypotheses of possible pathogenic mechanisms that underlie glaucomatous optic neuropathy include excitotoxic damage from excessive retinal glutamate, deprivation of neuronal growth factors, peroxynitrite toxicity from increased nitric oxide synthase activity, immune-mediated nerve damage, and oxidative stress. The exact role that IOP plays in combination with these other factors and their significance to the initiation and progression of subsequent glaucomatous neuronal damage and cell death over time is still under debate; the precise mechanism is still a hot topic of discussion.


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