Clinical studies of aqueous humor dynamics are key to understanding the normal physiology of the eye, pathological changes in diseases that affect IOP and mechanisms by which glaucoma treatments work. When it comes to uveoscleral outflow, the problem has always been finding methods that are accurate, reproducible, sensitive to small changes and of course, noninvasive. Ho and a strong team of seven other investigators describe a new in vivo method to assess aqueous humor dynamics in rats that one day may be applicable to spatiotemporal studies of aqueous humor dynamics in humans. Gadolinium (Gd) -enhanced MRI enabled examination of fluid movement through the eye under several experimental conditions that changed IOP. Altered aqueous humor dynamics and ocular tissue permeability changes were monitored over time in a noninvasive manner. The rats were divided into four groups, one group with microbead injections into the anterior chamber to obstruct the trabecular meshwork and increase fluid resistance, and three groups treated with either, timolol, latanoprost or brimonidine, drugs that lower IOP by different mechanisms. Detailed statistical tests were undertaken of the MRI images of the anterior chamber and vitreous cavity that included initial rate of Gd signal increase, peak GD signal enhancement, time to peak, and area under the curve in the Gd signal time courses. The microbead injections increased IOP, and the MRI images showed reduced Gd clearance from the anterior chamber suggesting slowed drainage. The three glaucoma drugs lowered IOP and showed increased Gd clearance from the anterior chamber suggestive of improved drainage (latanoprost) or slowed production (timolol) or possibly both (brimonidine). Additionally, brimonidine affected the Gd signal of untreated fellow eyes indicating systemic effects from topical dosing.
A future study of chronic glaucoma that masks the treatment groups and measures flow rates in microliters per minute will be a gigantic step towards a new, long-awaited research tool for clinical study of aqueous humor dynamics.