Biomedical Engineering Reference
In-Depth Information
capture or identification. In one study in dogs compression of both
jugular veins increased IOP estimates by 3.0 mmHg [
40
]. The
Valsalva maneuver, in which the animal exhales against a closed
glottis, can also markedly increase IOP (up to 10.2 mmHg in one
study) [
41
] as can holding a panting dog's mouth closed.
Off-center application
. In one study in humans IOPwas not found to
be different if the central cornea was applanated versus the mid-
peripheral cornea, even though the mid-peripheral cornea was
40
m thicker [
42
]. Of the tonometers most widely used today he
TonoVet is probably the most susceptible to off-center application as
the tonometer probe must remain parallel to the ground to avoid the
effects of gravity on the acceleration and deceleration of the probe tip.
μ
Pharmacologic Pupil Dilation
. Pharmacologic pupil dilation with
tropicamide or other mydriatics has been reported to have a variable
effect on IOP. Some studies suggest pharmacologic pupil dilation
does not alter IOP at all whereas others have found increases of up
to a few mm Hg in normal dogs [
43
], cats [
44
,
45
] and humans
[
46
,
47
]. Although these differences may sometimes achieve statis-
tical significance, and indicate that IOP should be measured prior to
pupil dilation in anti-glaucoma drug efficacy studies, the magnitude
of the increase (if any) is clinically unimportant and in the author's
experience has not resulted in a toxicologically adverse finding for
IOP. Differences between studies showing no effect, and those
showing a mild effect, are likely attributable to differences in the
statistical power between studies to detect a small change in IOP in
many individuals, or the ability of large changes in IOP in few
individuals to skew the data set. In anti-glaucoma drug efficacy
studies it is also important to recognize that topical mydriatics may
alter the pharmacokinetics of the test article by diluting it out,
drying the ocular surface (anticholinergics), or vasconstricting the
conjunctiva vessels (adrenergic agonists). These drugs may also alter
other systemic parameters such as heart rate, blood pressure, and
electrocardiographic tracings which may be a component of a toxic-
ity/tolerability component of the study.
Topical Anesthesia
. Although generally well tolerated, topical pro-
paracaine may transiently markedly reduce tear production (83 % in
beagles in one study) [
48
], alter corneal thickness [
49
], corneal
epithelial cell adhesion and the corneal penetration of topically
applied drugs [
50
]. Recently, tetracaine was demonstrated to result
in a decrease in IOP of 17-29 % for the first 20 min after its
application in normotensive rabbits, and 24-31 % in rabbits with
ocular hypertension induced by water loading [
51
]. Repeated use
of topical anesthesia over a period of hours to a day, as is typical in
many efficacy studies, may result in ocular surface irritation, corneal
epithelial cell drying/sloughing, and fluorescein stain uptake. The
effect of these disruptions of a major barrier to drug penetration is
seldom investigated, but should not be discounted in preclinical
