Dear Mr. Kotik,
.PP
.na
I was pleased to receive your letter 
and the copy of Dr. Langham's paper
because I have been thinking about the ocular pulse
for some months and welcome the chance
to write to you about it.
In time I expect to work my way through some of the literature
but meanwhile I don't want to keep you waiting for an answer,
so, without further preparation,
I thought I should let you know how the
very interesting and obscure issues which you raise look to me.
.PP
To represent the eye and its vasculature,
permit me to suggest a very crude model:
I imagine two concentric cylinders of adjustable elasticity.
The outer cylinder representing the eye itself
contains a compressible fluid
and is sealed both to the outside
and to the inner cylinder which traverses it.
The inner cylinder representing the vasculature
is perfused from an external source
with pulses of a non-compressible fluid.
Let the inner cylinder be fitted with two valves,
adjustable both in their resistance
and in their axial position.
One is located upstream at the entrance of the vessel
to the eye, the other is located downstream at the exit
of the vessel from the eye.
Initially both valves are open.
.PP
Under these circumstances,
as pulses of blood flow through the intraocular vessels
these vessels will expand,
the intraocular contents will be compressed,
and the wall of the eye will stretch.
The term "ocular pulse" then may refer either to the 
transient increase in intraocular pressure
brought about by the intermittent pulsating blood flow,
or it may refer to the transient distention of the wall of the eye.
In a myopic eye of large volume, with thin, more elastic sclera,
I would expect the volume expansion to be relatively greater 
and the pressure pulse to be somewhat smaller.
For this reason I think the ocular pressure pulse
in the myopic eye is not necessarily comparable
to the ocular pressure pulse in the emmetropic
or hyperopic eye.
.PP
As one begins to close the upstream valve,
increasing the inflow resistance,
I would expect the ocular pulse to diminish
with decreasing blood flow
until, when the circulation was cut off, it disappeared.
If, on the other hand, with the upstream valve open,
one gradually closes the downstream valve,
the blood flow will similarly decrease,
but the ocular pulse increases until,
at the point where flow is completely arrested,
given a sufficiently elastic blood vessel wall,
the intraocular pulsation becomes equal to
the intravascular pulsation.
.PP
One may consider also a third situation,
where the downstream valve is fully open and
the upstream valve is partially closed.
If one now moves the upstream valve in the downstream
direction, the foregoing considerations suggest
that the ocular pulse will increase,
and assuming that the function we are observing is
mathematically continuous,
one should be able to find a point on the axis of the inner cylinder
where the pulse amplitude regains its initial magnitude.
At this point, I would suspect that pulse amplitude
would be relatively independent of blood flow.
This point, I surmise, represents an inflection on the function curve
which relates pulse amplitude to volume flow through the vessel.
.PP
In the case of the eye, because of the circumstance that
the tissues to be perfused are inherently at intraocular pressure
there must be a significant flow resistance
distal to the capillary network.
Therefore it is possible
that instead of the positive correlation
between pulse amplitude and blood flow which Dr. Langham postulates,
the relationship might in fact be inverse,
with low pulse amplitude indicative of increased minute volume.
.PP
The second question which your letter raises
concerns the sensitivity of the glaucomatous eye to
a decrease in blood flow.
We see in the course of time hundreds of patients with glaucoma,
many of whom are elderly,
and some of whom have severe circulatory impairment,
yet it is unusual in my experience
to find the onset of the circulatory disorder
to coincide with a deterioration of the visual field.
Impairment of the carotid circulation,
which is unfortunately a common disorder,
is consistently found not to precipitate 
any glaucoma-like disease. 1)
.FS 1)
1) Carotid insufficiency does, in some instances, lead to 
intraocular neovascularization,
and this neovascularization may produce a very severe glaucoma.
The pathophysiology of this neovascular glaucoma, however,
appears radically different from that of open angle glaucoma
which is in issue.}
.FE
.PP
Your third question concerns the effect of timolol on the
intraocular circulation.
It is well established that timolol can produce constriction
of vessels caudal to the carotid biforcation,
but laboratory data suggest that cephalad to that point,
in the brain and presumably also in the eyes,
timolol has a dilating effect.
In any event, I consider these inferences too tenuous
to have any bearing on the decision to use or not to use timolol
in the clinical treatment of glaucoma.
I have numerous patients whose visual field has apparently
been protected by timolol for many years;
and I would be unwilling to forego the use of it
on the basis of purely speculative contraindications.
.PP
Furthermore, one should not lose sight of the fact that
other topical medications used in glaucoma treatment,
specifically pilocarpine and most especially
choline esterase inhibitors such as demecarium and
echothiophate, produce profound alterations in the
vascular tissues of the eye which are identifiable at
surgery months and perhaps years after the
medication has been discontinued.
I would think than in any patient who had been
on one of these drugs in conjunction with timolol,
the pharmacologic alteration of the vasculature
could not be assigned to either medication alone.
I have not yet had occasion to review
the pharmacology of clonidine.
.PP
To my mind, therefore, it would seem unwise
for any patient with advanced glaucoma 
who has been given timolol by his physician to curtail
its use on the basis of considerations
which at this juncture are necessarily theoretical.
But I am open-minded, and if, after reviewing the literature
I change my mind, I will let you know.
.PP
Please forgive me if I again repeat my disclaimer
to the effect that I never presume give advice to patients
whom I have not personally examined.
One does, in the practice of medicine,
customarily give opinions to ones colleagues 
about actual or hypothetical cases,
and it is as such, as someone concerned with the
science of ophthalmology that I have written to you.
Your attempt to cope with your very difficult problem
by making yourself literally expert in the field
has my profound respect and admiration.
If you wished,
I should be happy to sit down and talk with you
about any of these interesting and difficult issues,
and I thank you for having given me the opportunity
to consider them in the perspective of your concerns.