Aqueous humor circulates into the anterior chamber and out through the chamber's angle (Figure 1). It supplies nutrients to the avascular ocular tissues and removes their waste products while simultaneously maintaining IOP and the shape of the globe. This keeps the eye healthy and enables clear vision.
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Figure 1. Fluid movement into and out of the anterior segment of the eye. Fluid flows from the posterior chamber into the anterior chamber and then drains out through either the trabecular or uveoscleral outflow pathways.
The modified Goldmann equation describes the relationship among four variables of aqueous humor dynamics (AHD) that define IOP: IOP = (AHF - Fu)/C + EVP (Figure 2). AHF (µL/min) is the rate at which aqueous humor flows from the posterior chamber into the anterior chamber. C (µL/min/mm Hg) is the facility of outflow of aqueous humor from the anterior chamber angle. Fu (µL/min) is uveoscleral outflow, also referred to as unconventional outflow. EVP (mm Hg) is the episcleral venous pressure. Clearly, pathologic changes in AHD can adversely affect IOP, as happens in glaucoma, and the AHD variables can be altered by pharmacologic treatment, laser therapy, or device implantation to restore IOP to a healthy physiologic range.
Figure 2. A modified Goldmann equation representing four variables that determine IOP. The boxes list conditions in the categories of general, disease, and treatment, which affect the given variable. Abbreviations: AHF = aqueous humor flow; C = outflow facility; EVP = episcleral venous pressure; Fu = uveoscleral outflow; IOP = intraocular pressure.
The Eye Dynamics and Engineering Network (EDEN) Consortium is conducting a prospective study to gather data on demographics, systemic factors, ocular biometrics, AHD variables, ultrasound biomicroscopy imaging, and genetics that could improve clinicians’ understanding of the mechanisms underlying patients’ varied responses to IOP-lowering drugs.1 The mechanisms can be further studied as potential biomarkers to help determine the most appropriate treatment and time to intervene for each individual. This could, in turn, improve patient care and reduce health care costs.
CURRENT METHODS
Noninvasive methods for measuring AHD in humans have been in use for decades and have changed very little. Despite their well-known limitations and assumptions,2 these methods remain the best options available for studying AHD and IOP regulation. Table 1 summarizes the methods used by the EDEN Consortium to assess AHD in human volunteers.
Data from more than 130 patients have been collected over several years. Some key findings are summarized in Table 2.
The EDEN Consortium is working on several projects to improve measurements of AHD, as summarized in Table 3. These include ultrasound biomicroscopy imaging to observe uveoscleral drainage, tonometry with the iCare Home (Icare USA) to capture real-world IOP patterns, video capture of episcleral and aqueous veins to allow visualization and quantitation of fluid flow, and newer statistical methods to model IOP variance.
CONCLUSION
Work by the EDEN Consortium is providing detailed information on AHD and IOP variance in a large cohort of healthy individuals and patients with elevated IOP. Variance in the parameters of AHD is being examined to explain the lack of IOP response to timolol and latanoprost observed in a subset of patients.
Author acknowledgments: Figure 1 was drawn by Sophie Williams and Alivia Blackburn, graphic and marketing designers at The Ohio State University. Support was provided by R01 EY022124 (S.M.), P30 EY032857 (S.M.), and New Chair Challenge Grant from Research to Prevent Blindness (S.M.).
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7. Kolli A, Toris CB, Reed DM, et al. The effects of topical timolol and latanoprost on calculated ocular perfusion pressure in nonglaucomatous volunteers. J Ocul Pharmacol Ther. 2021;37(10):565-574.
8. Kazemi A, McLaren JW, Trese MGJ, et al. Effect of timolol on aqueous humor outflow facility in healthy human eyes. Am J Ophthalmol. 2019;202:126-132.
9. Kazemi A, McLaren JW, Lin SC, et al. Comparison of aqueous outflow facility measurement by pneumatonography and digital Schiøtz tonography. Invest Ophthalmol Vis Sci. 2017;58(1):204-210.
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11. Moroi SE, Reed DM, Sanders DS, et al. Precision medicine to prevent glaucoma-related blindness. Curr Opin Ophthalmol. 2019;30(3):187-198.
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