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Excerpt
Becker and Neufeld 1 believe that uveoscleral outflow (Fu) is pressure dependent, and propose a modification of the Goldmann equation that is consistent with their thoughts. This modification presumes the existence of a facility of Fu (Cu). The authors believe that this modified equation will be helpful in understanding the mechanism by which prostaglandins (PGs) affect Fu. Many think that PGs reduce intraocular pressure (IOP) by increasing Cu. 2–4
Several studies provide overwhelming evidence that Fu is in fact pressure independent when assessed at normal or high IOPs. 5–8 Several explanations have been offered. 5,8 Despite this relative pressure independence of Fu under normal physiologic conditions, many feel that pharmacological agents, such as PGs or their analogs, can alter Fu by increasing its pressure dependence; i.e., increasing Cu. 2–4
Evidence supporting a PG-induced increase in Cu is virtually nonexistent. Some excellent studies carried out for other purposes only vaguely address the concept of Cu. 9,10 In a single study in cynomolgus monkeys, total outflow facility (Ctot), which includes the sum of trabecular outflow facility (Ctrab), pseudofacility (Cps), and Cu, was determined by a 2-level constant pressure perfusion technique. 10 Ctrab was measured by determining the rate of accumulation of intracamerally infused radioiodinated albumin in the general circulation. It was concluded that Ctot was increased by PGs, but Ctrab was not affected, suggesting that PGs increase Ctot by increasing Cu, without altering Ctrab. 10 However, the publication reported substantial variability of the Ctot measurements with high coefficients of variation. In fact, only 1 of the 3 assessments of Ctot was significant. The 15% to 20% increase in Ctrab was not statistically significant because of the very high coefficient of variation. 10 The questionable increase in Ctot demonstrated in this study may have been partially or totally due to an increase in Cps and perhaps to a mild increase in Ctrab, rather than to an increase in Cu. Overall, a PG-induced increase in Cu was not definitively demonstrated.
In another monkey study that purportedly demonstrated a PG-induced increase in Cu, Fu was assessed at spontaneous IOP (mean of 4 to 5 mm Hg) in 6 monkeys, and at 17 to 18 mm Hg in only 2 monkeys at a similar time interval after the last dose of the PG. 9 Statistical significance of an effect on Cu could not be established because the higher IOP group included only 2 monkeys. Moreover, substantial Cu is expected when assessed at the low spontaneous IOPs 5–7 resulting from the PG therapy in these monkeys.
Although it is an attractive hypothesis, especially when coupled with the PG-induced effects demonstrated in the extracellular matrix of the ciliary muscle, 2,11 neither of these previously discussed studies 9,10 nor any other study that I know of conclusively demonstrates a PG-induced increase in Cu. On the other hand, a single study in cats assessing Fu by invasive tracer techniques at different IOPs demonstrated a very low Cu, which is consistent with previous literature, 5–7 and which was not altered by PG treatment despite a pronounced reduction of IOP and an increase in Fu. 12
The best evidence that PGs reduce IOP by increasing Fu without appreciably increasing Cu is that many studies in a variety of species demonstrate pronounced IOP reductions which cannot be completely accounted for by an effect on Ctot. 13 An effect on Cu would alter Ctot (assuming that Ctrab and Cps are not affected in the opposite direction), which is measured by most of the techniques that we use to assess C.
