Essentials of Veterinary Ophthalmology. Kirk N. Gelatt
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2.7 Aqueous humor dynamics formulas.
| I | F in = F at + F uf |
| F = flow (μl/min) | |
| F in = total AH inflow | |
| F at = inflow from active transport | |
| F uf = inflow from ultrafiltration | |
| II | F out = F trab + F uveo |
| F out = total AH outflow | |
| F trab = outflow via the TM | |
| F uveo = outflow via the uveoscleral pathway | |
| III | C total = C trab + C uv + C pseudo |
| C = facility or conductance of flow (μl/min/mmHg) | |
| C total = total AH outflow facility | |
| C trab = facility of outflow via the TM | |
| C uv = facility of outflow via the uveoscleral pathway | |
| C pseudo = pseudofacility | |
| III | At steady state, F = F in = F out |
| IV | F = C trab (P i − P e) (Goldmann equation) |
| P = pressure (mmHg) | |
| P i = IOP | |
| P e = episcleral venous pressure | |
| V | F in = C trab(P i − P e) + F uveo |
| VI | P i = P e + (F in − F uveo)/C trab |
Formulas can be used to describe the formation and drainage of AH (Table 2.7). Episcleral venous pressure or the “backpressure” created by the venous portion of the conventional pathway in the AAP or Schlemm's canal constitutes approximately 50–75% of the resistance (10–12 mmHg) that determines IOP. While minor anatomical variations in the venous system exist between species, results of pressure studies in humans, nonhuman primates, rabbits, and dogs reveal episcleral venous pressure to be between 8 and 12 mmHg. Arteriovenous anastomoses within the episcleral vasculature have been demonstrated in the rabbit, dog, owl monkey, and cynomolgus monkey. These vascular shunts may function in rabbits and dogs, where the episcleral vasculature appears to lack a capillary system, and in the monkey species as an emergency system to elevate IOP after globe perforation or to retrogradely flush the outflow channel. Episcleral venous pressure can be measured by direct cannulation (using very fine glass pipettes) or indirect partial to complete compression schemes (using a string‐gauge system or a fluid‐filled chamber). Results of limited studies indicate that the volume of the anterior chamber directly relates to the rate of aqueous outflow, so that animals with large eyes have faster outflow rates per minute. The resistance to aqueous outflow may be inversely proportional to the facility of outflow (C total).
Regulation of Outflow
Cholinergic agonists such as pilocarpine decrease outflow resistance by contraction of the ciliary muscle and subsequent spreading of the TM. This effect is rapid, such that intravenous administration of pilocarpine to vervet monkeys results in a near‐instantaneous decrease in outflow resistance, suggesting that the effect may be mediated by a structure perfused by arteries. Ciliary muscle disinsertion and removal of the iris in nonhuman primates obliterate this acute response to pilocarpine, suggesting that it is mediated completely by ciliary muscle contraction rather than a direct effect on the TM. The M3 subtype of the muscarinic receptor is strongly expressed in the ciliary muscle and thought to mediate the changes in outflow facility in response to cholinergic agonists. Because the effect of cholinergic agonists on trabecular outflow (increase) is greater than that on uveoscleral outflow (decrease), the net effect is an increase in AH outflow and concomitant decrease in IOP. As expected, cholinergic antagonists, such as atropine, decrease traditional outflow and increase nontraditional outflow by similar mechanisms.
Many other influences on the rate of AH formation and regulation of IOP have been proposed. For example, a center in the feline diencephalon has been found that, when stimulated, causes alterations in the IOP. Central nervous system (CNS) regulation of IOP is poorly understood, however, and hormonal control of AH production may be involved.
Methods to Measure Aqueous Dynamics
Both invasive and noninvasive methods are used to investigate AH dynamics, and normative values have been described in domestic and laboratory animal species (Table 2.8). Invasive studies are more difficult to study in animals as the uveal tissues quickly respond to these “invasions” and can reduce the study objectives, but these early methods were essential and formed the basis for later noninvasive methods. They usually measured the dilution of intracamerally injected substances over short time periods. With the AH volume within the anterior and posterior chambers measured and the amount of dilution of the tracer estimated, the total amount of AH produced per unit of time could be determined. Knowledge of anterior and posterior chamber volumes is critical to determining the rate of AH production (Table 2.9).
Fluorophotometry is a noninvasive method for studying AH flow dynamics, for evaluating ocular pharmaceutical agents used to treat glaucoma, and for determining iris permeability in both normal and disease states. Fluorophotometry of the anterior chamber and vitreous can noninvasively assess the permeability of the BRB in the normal and diseased eye. Fluorophotometry has been used extensively in humans, nonhuman primates, rabbits, cats, dogs, and, most recently, the red‐tailed hawk. This tool can also be used to assess permeability coefficients of the BAB involved in health and disease, determine the effects of selected drugs on the BAB, and mechanisms by which drugs affect the AH dynamics.
Table 2.8 Methods to investigate aqueous humor dynamics.
| I | Techniques to investigate the formation of aqueous humor |
| Cannulation of anterior chamber: constant rate/constant pressure perfusion |