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Aqueous Humor Dynamics

A Dysfunctional Drain Increases Eye Pressure

In normal eyes, intraocular pressure (IOP) is maintained by a balance between two opposing dynamics, as shown in the diagram below1-3:

  1. The rate of production of aqueous humor in the eye, primarily by ciliary bodies1-3
  2. The resistance to aqueous humor outflow through the conventional trabecular pathway and the uveoscleral pathway1-3

Degenerative anatomical changes to the trabecular meshwork (TM) increases the resistance to outflow of aqueous humor through the trabecular pathway, the primary drain for aqueous outflow. This increased resistance to TM outflow is thought to be the primary cause of increased IOP, which is the only modifiable risk factor for glaucoma.1,4-6

No commonly prescribed class of IOP-lowering drugs have been shown to primarily target the diseased tissue of the TM to increase outflow.3,7

1. Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: a review. Open Ophthalmol J. 2010;4:52-59. 2. Crawley L, Zamir SM, Cordeiro MF, Guo L. Clinical options for the reduction of elevated intraocular pressure. Ophthalmol Eye Dis. 2012;4:43-64. 3. McLaren NC, Moroi SE. Clinical implications of pharmacogenetics for glaucoma therapeutics. Pharmacogenomics J. 2003;3:197-201. 4. Kopczynski CC, Epstein DL. Emerging trabecular outflow drugs. J Ocul Pharmacol Ther. 2014;30(2-3):85-87. 5. Sacca SC, Pulliero A, Izzoti A. The Dysfunction of the Trabecular Meshwork During Glaucoma Course. J Cell Physiol. 2015;230:510-525. 6. Sihota R, Goyal A, Kaur J, Gupta V, Nag TC. Scanning electron microscopy of the trabecular meshwork: Understanding the pathogenesis of primary angle closure glaucoma. Indian J Ophthalmol. 2012;60(3):183-188. 7. Malihi M, Sit AJ. Aqueous humor dynamics and implications for clinical practice. Int Ophthalmol Clin. 2011;51(3):119-139.