Alpha-2 adrenergic agonists such as brimonidine and apraclonidine have which mechanism in lowering IOP?

• A. They increase trabecular outflow
• B. They increase aqueous production
• C. They decrease aqueous production and increase uveoscleral outflow
• D. They cause pupil dilation

Answer: (C)

Alpha-2 adrenergic agonists lower IOP mainly by two actions on the anterior chamber. First, they inhibit aqueous humor production at the ciliary body—activation of alpha-2 receptors reduces cyclic AMP signaling in the ciliary epithelium, decreasing secretory activity. Second, they modestly increase outflow via the uveoscleral pathway, likely through relaxation of tissues and changes in the extracellular matrix that enhance fluid drainage through this route. They do not primarily boost trabecular outflow, and they are not agents that cause pupil dilation, so the combination of decreased production with increased uveoscleral outflow best explains their effect.