Cholinergic Improvement of Low-Flow Segmental Aqueous Humor Outflow in Humans

To evaluate the influence of pharmacologic cholinergic stimulation on segmental aqueous humor outflow (AHO) in living human eyes of brain-dead organ donors.

A prospective, nonrandomized, and interventional study.

Brain-dead organ donors.

Aqueous angiography (AA) was performed using intracameral indocyanine green (ICG; 0.4%) in brain-dead organ donors to establish baseline segmental high-flow and low-flow (LF) AHO regions. The eyes were then treated using intracameral balanced salt solution (BSS; n = 5) or Miochol-E (n = 7; 10 mg/ml), which is US Food and Drug Administration-approved acetylcholine. Repeat AA was then performed using intracameral fluorescein (2%). Aqueous angiography images were acquired using a FLEX Spectralis (Heidelberg Engineering). Aqueous humor outflow signal intensity was quantified per quadrant or per eye in a masked fashion and compared across conditions.

Aqueous angiography fluorescent patterns, baseline AA signal intensity in various quadrants, and change in AA signal intensity after drug treatment or control.

All eyes received initial baseline ICG AA. Segmental AHO was seen qualitatively and quantitatively across all quadrants (temporal: 18.4 ± 10.0; superior: 25.6 ± 16.5; nasal: 49.9 ± 28.6; and inferior: 25.9 ± 13.2 arbitrary units [AU], mean ± standard deviation). Consistent with prior reports, the greatest AHO was seen nasally (temporal vs nasal, P < 0.001; superior vs. nasal, P = 0.012; and inferior vs nasal, P = 0.013). After BSS treatment, fluorescein AA showed very similar patterns to baseline ICG AA. After Miochol-E treatment, fluorescein AA showed qualitative AHO improvement in some baseline LF regions. After drug treatment, Miochol-E-treated eyes showed a greater quantitative increase in fluorescence intensity per quadrant (25.9 ± 31.7 AU; P < 0.001) and per eye (25.9 ± 22.9; P = 0.024) compared to the BSS control condition.

Cholinergic stimulation enhances AHO in segmental regions as opposed to circumferentially around the limbus. In particular, focal improvement in baseline LF regions was observed, implying a segmental response to drug treatment. Understanding the biological and physiological basis underlying this responsiveness may lead to new pharmacological and surgical glaucoma treatments.

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