aqueous humor dynamics include aqueous flow, outflow facility, uveoscleral outflow, and episcleral venous pressure. Multiple methods are available to assess these components. Interpretation of data collected by these methods requires an understanding of the inherent assumptions and limitations of each method applicable to the species of animal under investigation. Despite the inevitable problems associated with each method, invaluable information has been collected regarding normal circadian rhythms and interspecies diVerences in aqueous humor dynamics. Additionally, studies of animal models of spontaneous and induced glaucoma have enhanced our understanding of human glaucoma and facilitated the design of improved pharmacological treatments and surgical procedures. This chapter describes the various methods to assess aqueous humor dynamics and summarizes findings from the animal species that have contributed the most to our understand of aqueous humor dynamics.

II.COMPONENTS OF AQUEOUS HUMOR DYNAMICS AND MEASUREMENT TECHNIQUES

The major components of aqueous humor dynamics include the production rate of aqueous humor, resistance to outflow through the trabecular meshwork, rate of outflow from the anterior chamber angle other than through the trabecular meshwork (most commonly termed uveoscleral outflow, although other descriptive names exist), and the pressure in the aqueous humor collection vessels (episcleral venous pressure).

The original Goldmann equation described the relationship between the IOP and the components of aqueous humor dynamics as they were understood half a century ago:

where IOP is intraocular pressure, Fp is the rate of aqueous humor production and drainage, Ctrab is the facility of outflow through the trabecular meshwork, and Pv is the pressure in the vessels that drain the aqueous humor from the trabecular meshwork (episcleral veins). In the early studies describing the relationship between IOP and components of aqueous humor dynamics, it was believed that the aqueous humor secreted by the ciliary processes entered the anterior chamber and drained exclusively through the trabecular meshwork. Tracer originally injected into the anterior chamber that was occasionally observed in the uvea was thought to be inconsequential. Since the original equation was written, the importance of

uveoscleral outflow has become more apparent and the Goldmann equation was changed accordingly. In a steady state, aqueous humor production (Fp) is the sum of aqueous humor drainage through the two outflow pathways: trabecular (Ftrab) and uveoscleral (Fu).

Ftrab is pressure dependent, that is, as IOP increases, fluid flow through the trabecular meshwork increases. Ftrab can be rewritten as the product

of the facility of trabecular outflow (Ctrab) and the pressure diVerence across the trabecular meshwork (IOP Pv). Hence, trabecular outflow is described as given below:

Subs titution ofEq. (3)into Eq. (2)yiel ds:

Assessment of aqueous humor dynamics requires the evaluation of each of these variables. Studies of aqueous humor dynamics in mice, rats, rabbits, cats, dogs, and monkeys are summarized in Tables I through VI. Clinical studies of aqueous humor dynamics are described in Chapter 8.

A. Intraocular Pressure

The health of the eye and normal visual function require a firm control of the IOP. When the IOP deviates from a narrow healthy range for an extended period of time, irreversible damage may occur to the optic nerve and retina, resulting in permanent vision loss. Transient changes in the IOP occur by seemingly benign daily activities including blinking, wearing a tight necktie, stooping, a valsalva maneuver, or a bowel movement. Eyelid pressure, tension on extraocular muscles, arterial and venous blood pressure, and gravity are additional factors that aVect the IOP. Intraocular pressure under steady state conditions occurs at a time when aqueous humor inflow and outflow are equal and the pressure in the eye is relatively stable. Normal values of steady state IOP in research animals are surprisingly similar among species, 15–17 mmHg in mice and rats (Tables I and II), 10–25 mmHg in rabbits (Table III), 14–25 mmHg in cats (Table IV), 9–26 mmHg in dogs (Table V), and 14–23 mmHg in monkeys (Table VI). Acute measurements of the IOP are made indirectly by tonometry and directly by manometry. Continuous IOP measurements over a period of weeks to months are made by telemetry.

Reported are mean values from untreated or vehicle treated control groups standard errors or standard deviations as provided in the original papers.

C, outflow facility measured by two level constant pressure perfusion method; Fa, aqueous flow measured by afluorophotometry, baqueous humor sampling method, cconfocal microscopy; Fu, uveoscleral outflow calculated from the modified Goldmann equation; IOP, intraocular pressure measured by manometry; Pev, episcleral venous pressure measured by the intracameral microneedle method, d2,2,2 tribromoethanol.

TABLE II

Aqueous Humor Dynamics in Rats

Reported are mean values from untreated or vehicle treated control groups standard errors or standard deviations as provided in the original papers.

C, outflow facility measured by the two level constant pressure perfusion method; Fa, aqueous flow measured by the aqueous humor sampling method; IOP, intraocular pressure measured by aTono Pen, bmanometry.

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TABLE IV

Aqueous Humor Dynamics in Cats

Values are means standard error or standard deviation (when available) as provided in original publications. The selected articles are those published since 1980 that reported one or more values of aqueous humor dynamics in healthy untreated or vehicle treated cats.

C, outflow facility measured by atonography, btwo level constant pressure perfusion method; Fa, aqueous flow measured by can aqueous humor sampling method, dfluorophotometry, emathematical calculation; Fu, uveoscleral outflow measured by fintracameral tracer method, gmathematical calculation; IOP, intraocular pressure measured by pneumatonometry; Pev, episcleral venous pressure measured by venomanometry.