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

Purpose To evaluate the influence of pharmacologic cholinergic stimulation on segmental aqueous humor outflow (AHO) in living human eyes of brain-dead organ donors. Design A prospective, non-randomized, and interventional study. Subjects Brain-dead organ donors. Methods Aqueous angiography (AA) was performed using intracameral indocyanine green (ICG; 0.4%) in brain-dead organ donors to establish baseline segmental high-flow (HF) 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 FDA-approved acetylcholine (ACh). Repeat AA was then performed using intracameral fluorescein (2%). AA images were acquired using a FLEX Spectralis (Heidelberg Engineering). AHO signal intensity was quantified per quadrant or per eye in a masked fashion and compared across conditions. Main Outcome Measures AA fluorescent patterns, baseline AA signal intensity in various quadrants, change in AA signal intensity after drug treatment or control. Results 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 ± SD). 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. Conclusion 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.