 
                           20060206.00

                 What causes Open Angle Glaucoma ?

     For some years now, I have intended to make explicit and to
record my understanding of the mechanism by which open angle
glaucoma develops. Inasmuch as I have had no occasion to
corroborate my thoughts with the results of laboratory studies.
my description is vulnerable to disparagement as arm-chair
physiology by those who presume to maintain a rigid distinction
between theory and facts.  They however who understand Goethe's
"Das Hoechste waere zu begreifen, dass alles Faktische schon
Theorie ist."  (Wahlverwandschaften) (The most profound insight
might be to understand that every fact is theory already.)  may
recognize that prevailing theories of glaucoma causation are
based on purported "facts" that have been accepted, not because
they reflect observable phenomena, but because they are in accord
with traditional teaching.

     That traditional teaching holds that the aqueous humor is
produced by the epithelium of the ciliary processes, flows
thought the zonules, around the lens, beneath the posterior
surface of the iris, through the pupil into the anterior chamber;
and hence into and through the trabecular meshwork.  It is
postulated, furthermore, that the trabecular meshwork constitutes
the site of major resistance to the outflow of aqueous in the
healthy eye, and that it is an increase in the flow resistance of
the meshwork that explains the pathological elevations of
intraocular pressure that characterize glaucoma.

     The classical teaching holds that having passed through the
trabecular meshwork, the aqueous drains through the sclera via
emissary channels of minimal resistance and thence into the
capillary bed of the subconjunctival space.  In addition to the
historical studies, never repeated in recent memory, by which the
existence of these emissary veins was purportedly proved, it is
stated that their existence can be simply confirmed by the common
slitlamp examination of the periorbital conjunctiva of the
healthy eye.

     My theory has its origin in the circumstance that I myself,
though I have tried many times, have never been able to convince
myself that any of the vessels that I am able to observe with the
slit lamp are in fact emissary veins carrying acellular aqueous
rather than ordinary lymphatic vessels. Consequently, I entertain
the hypothesis that the emissary veins visible under the
conjunctiva are an instance of the emperor's new clothes, as
these were described by Hans Christian Andersen.

     However that may be, there has in recent years developed
agreement that a certain substantial fraction of the aqueous
humor does not pass through the sclera through emissary veins,
but streams back into the ciliary body and/or into the
suprachoroidal space and ultimately into the choroid itself.
It is this (hypothetical) drainage of a substantial fraction of
aqueous into, and its absorption from the choroid which seems to
me to open up new and potentially highly productive theories
concerning the pathophysiological etiology of open angle
glaucoma.

     The necessity of a pressure gradient across the retina to
maintain its apposition to Bruch's membrane has long been
recognized as an explanation for rhegmatogenous retinal
detachment.  A break or a hole in the retina breaks the vacuum
which hold the retina in place and leads to an accumulation of
fluid in the subretinal space and thus to retinal detachment.
That this pressure gradient is ultimately the result of the
choroidal circulation is demonstrated by the rhegmatogenous
retinal detachment in the absence of retinal hole or tear that
occurs invariably within a few hours after the cessation of blood
flow at the time of death.

     If, as I believe, it is plausible and a matter of general
agreement, that a substantial portion of the aqueous drains into
the choroidal tissues to be absorbed by the choroidal
circulation, then it is logical to postulate that the same
pressure differential which causes the retina to apply to the
choroid will also serve to pull aqueous through the trabecular
meshwork.  Then glaucoma may be explained as the failure of the
mechanism which accounts in the healthy eye for the relative
vacuum of the intrachoroidal space.

     I suppose one could invent various biochemical and
biophysical hypotheses to explain the mechanism by which
choroidal blood flow is responsible for the pressure gradient
across the retina, but the most obvious of such mechanisms is the
Bernoulli effect that results from large quantities of blood
flowing from a region of high pressure inside the globe to the
low pressure environment of the vortex veins.  Such a decrease in
pressure would necessarily be accompanied by an acceleration of
flow and a concomintant constriction of the affected blood vessel
that reduces its cross section.

     There is, in addition to the difference between upstream and
downstream pressures determining the velocity of flow, yet a
third factor that enters into the equation, namely the compliance
of the walls themselves, It is a pathological change, and the
pharmacologic modification of this compliance which would explain
both the etiology of glaucoma and its dramatic and otherwise
unexplained response to vasoactive drugs.  In this model, the
development of open angle glaucoma might be explained by the
relaxation and subsequent dilation of the upstream choroidal
vasculature; or by a tightening and subsequent constriction of
the downstream chroidal vasculature. Similarly the effectiveness
of vasoactive drugs, such a pilocarpine, epinephrine,
brimonidine, timolol and clonidine might result from a
constriction of the upstream chroidal vascular bed or a dilation
of the downstream choroidal vascular bed.  This, it seems to me,
is an eminently persuasive explanation for open angle glaucoma
and the relative effectiveness of its pharmacologic treatment.


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Copyright 2006, Ernst Jochen Meyer
