 
                    Low Tension Glaucoma

     There comes a time in the education of every
ophthalmologist-to-be, while yet a medical student, or early
in his residency program, when, pleased with his newly
acquired understanding of open angle glaucoma as a disease
caused by elevated intraocular pressure and characterized by
excavation of the optic nerve head and by progressive loss of
the visual field, he is confronted with the description of
yet another disease, which is called glaucoma and yet is not
glaucoma, a shadow of the original, which it belies and
repudiates.  Having just accepted on faith that glaucoma
results from elevated tension, he is now asked to believe
that glaucoma can also develop in the normotensive eye.  He
dares not challenge his preceptors.  Trained by long years of
sitting through lectures to accept the words of the professor
as truth, he has learned that it is safer to insult ones
intelligence than ones teacher.  He marvels at the wisdom
that can reconcile such apparently contradictory definitions,
and being a dutiful pupil, promptly busies himself with
integrating yet another paradox into the thesaurus of his own
memory.  And it is not long until he too firmly believes in
the existence of two entities whose definitions are mutually
exclusive, gives "correct" answers to the examination
questions, and is launched on an illustrious career of
teaching, research and medical practice, based on his
"understanding" of this contradiction and many others like
it.

     It is useful by way of introduction to consider the term
low tension glaucoma as just that, a term, a word whose
primary function, as is the case with all language, is to
serve as a vehicle of communication, an answer that we list
on our examination forms in order to receive passing grades,
a word that we utter in answer to our patient's question
"Doctor, what have I got?"  an ICD-9-CM code that we enter on
the HCFA-1500 request for payment so that our Medicare checks
may be doled out to us.  In what respect, or to what extent a
disease such as "low tension glaucoma" exists in reality, in
nature, in some realm, whatever one chooses call it,
independent of our cognitive conjectures, is a meaningless
question, since that realm of ontologic integrity beyond our
knowledge is by definition a paradise from which we are
excluded.  It serves, like that other paradise of religious
tradition, as a compelling reminder of human inadequacies.
Our task, as always, is the tedious collation of the words by
which we communicate with the reflections of individual
experience, however fragmentary they might be.

     The names that first make us aware of the existence of
diseases, tend also to serve as barriers to our understanding
of them.  Not least in this regard is the name "glaucoma"
itself, The Greek adjective "glaukos" appears to have meant
bluish-green when applied to the ocean, gleaming or flashing
when describing the eyes, so that it is not clear whether
"glaucoma" originally referred to the bluish haze of a dense
corneal scar or merely to the disquieting gleam, unmodulated
by responses to visual stimuli, of the non-seeing eye.
Glaucoma almost certainly did not mean, as a seventeenth
century ophthalmologist once surmised, that the patient was
afflicted with bluish-green vision.  The term "low tension
glaucoma" compounds the etymological disarray, since the
pressures at which it occurs are low only in comparison with
those of the glaucomatous eye, but are otherwise normal.

     The term low tension glaucoma, as is well understood, is
reserved for a disease where in the presence of normal
pressures, there occur disc excavation and field loss
otherwise indistinguishable from that of open angle glaucoma.
Perplexity arises from the circumstance that in glaucoma,
elevated intra-ocular pressure is assumed to be the
indispensable primary cause of disc excavation and field
loss.  In "low tension glaucoma" these processes take place
at normal pressures.  The postulate of "low tension glaucoma"
requires us to assume that a cause other than ocular
hypertension initiates the process of disc destruction, but
as of now, no such cause has been produced.  Until that cause
is identified, not only will the diagnosis and treatment of
low tension glaucoma remain uncertain, but the diagnosis and
treatment of open angle glaucoma will also to some extent be
put in doubt, for the unknown factor responsible for disc
excavation in low tension glaucoma must be assumed to have at
least a potential role in the genesis and progression of open
angle glaucoma as well.

     We must take care not to confuse low tension glaucoma
with a late stage of open angle glaucoma that resembles it.
Here too, when cupping is far advanced, glaucomatous field
loss may progress even though medication or filtering surgery
have reduced the pressure into the statistically normal
range.  The eye may then behave as if it had low tension
glaucoma in that it continues to lose field although the
pressure is normal.  This situation differs from low tension
glaucoma however, in that the initial insult to the optic
nerve *was* caused by pathologically elevated tension, while
in true low tension glaucoma the destruction of the nerve is
assumed to have occurred entirely at statistically normal
intraocular pressures.

     Fundamental to the definition of low tension glaucoma is
the determination of the intraocular pressure, that most
elementary of diagnostic glaucoma procedures whose
difficulties have not been entirely resolved.  When we state
that the intraocular pressure in a given eye is 10 or 15 or
25, we quote the results of but a single measurement.  Even
when the tonometer is precisely calibrated and the technique
of measurement is impeccable, the accuracy of measurement is
limited by the variable tonus of the extraocular muscles, for
when these muscles become abnormally tense in reflex response
to the application of the instrument, the pressure in the eye
will rise transiently, and when the muscles relax it will
fall and overshoot its undisturbed levels.  Thus in a patient
who is unable to relax his extraocular muscles during
tonometry, it may be impossible to obtain an accurate
reading.

     Of comparable importance are the spontaneous
fluctuations of the intraocular pressure that occur at
several frequencies.  Most obvious is the intraocular pulse,
which can be readily identified because it is synchronous
with the beat of the heart.  Fluctuations, on the other hand,
which have periods of minutes or hours or days cannot be
detected at any given tonometry session, but must be inferred
from sequential readings.  In general we tend to attribute
disproportionate importance to the most recent tonometry
value.  We reason as if we could not trust the antecendent
values, as if somehow our present concern for the patient's
problem reduced the validity of previous observations.  From
a mathematical perspective, any single tonometry value should
concern us only as a sample from a statistical population.
What we really need to know are the statistical parameters of
the pressure as a function of time, the mean, the standard
deviation, the correlation coefficient and the confidence
intervals.  Optimally one would like to see a Fourier
analysis to identify the periodicities that combine to
account for the variations of pressure in the glaucomatous
eye.  Fourier analysis, however, requires a set of
measurements far more closely spaced than is feasible in
clinical practice.

     If these methodological deficiencies in our work are of
no practical consequence, this is the case because the
majority of unselected patients does not have glaucoma, and
because many cases of early open angle glaucoma, if we
discovered them at the inception of the disease, would
require no treatment.  Moreover, undertreatment in the early
stages of the disease becomes apparent only after months or
more likely years have passed.  In general, therapy is
prescribed only when the disease is beyond its initial
stages, and at that point the diseconomies of possible
overtreatment are usually outweighed by the margin of safety
that a potentially lower pressure is likely to entail.  One
would think that our greatest need for exact information
about intraocular pressure would arise when a determination
concerning filtering surgery is to be made, but at that
juncture, paradoxically, the precise behavior of the pressure
seems of less importance, because our decision to operate
rests on an overall assessment of the course of the disease.

     For the definition of the glaucoma, for understanding
its pathophysiology, on the other hand, the arbitrary
acceptance of random pressure measurements is unacceptable
and a more precise description of the intraocular pressure is
indispensable.  Notwithstanding the relative ease of
obtaining a single pressure measurement, it is remarkably
awkward to obtain the numerous tonometries over a protracted
period of time which would be requisite for a sufficient
description of the disease.  This is particularly the case
where, unlike open angle glaucoma, whose initial phase is
characterized by mild elevations of pressure, in low tension
glaucoma the pressure is by definition normal, and the
initial sign of illness is the excavation of the optic nerve
head whose early phases are so extraordinarily difficult to
distinguish.  In order to obtain data on the genesis of low
tension glaucoma one would have to make sequential
measurements of pressure on a large and presumably normal
population, a very small proportion of of whom would
ultimately develop this relatively rare disease.

     As we confront the challenge of searching for the
etiology of low tension glaucoma, be it by laboratory or by
clinical investigation, we do well to remind ourselves that
the phenomena which puzzle us may also be explained in terms
of what we already know about glaucoma.

     Let us suppose for a moment that there were a disorder
characterized by intermittent recurrent pressure elevations.
The less frequently routine tonometry is performed, the more
likely that such tension elevations would go undetected.  It
seems plausible to me, given the sporadic tonometry to which
most of the presumably healthy population is presently
subjected, that such a disorder would frequently be
overlooked.  Suppose further that for one reason or another,
these pressure elevations were self-limited and subsided
spontaneously after a period of time, much as does the
glaucoma that sometimes accompanies iritis, then it is
altogether conceivable that the disc might be surreptitiously
excavated by periods of unrecorded elevated tension.  Later
the compromised disc would prove incapable of tolerating even
a normal pressure, and excavation and field loss would
progress even after the tension had come down to normal.  In
time the patient arrives at the the ophthalmologist's with a
classical case of low tension glaucoma.

     A second plausible explanation of low tension glaucoma
reflects the circumstance that we measure the intraocular
pressure with reference to atmospheric pressure, while the
physiologic effect is exerted, as a brief reflection on
simple anatomic relationships will confirm, against the
pressure that happens to prevail behind the lamina cribrosa,
which is not the pressure of the atmosphere but of the
cerebrospinal fluid in the meningeal sheaths of the optic
nerve.  The occurence of papilledema indicates that the
intracranial pressure is freely transmitted to the optic
nerve.  When the patient is recumbent, intracranial pressure
is normally between 6 and 15 mm Hg.  In the upright position
the pressure at the level of the optic nerves is likely to be
substantially less.  Variations, both normal and
pathological, in the intracranial pressure are well
documented.  A diminution of the intracranial pressure will
increase the pressure gradient across the lamina cribrosa
just as effecively as a heightening of the intraocular
pressure and might well explain the mysterious development of
low tension glaucoma.  Since it is the pressure differential
between the intraocular and intracranial environments which
ultimately determines the fate of the disc, one should at
least consider the possibility that low tension glaucoma
could be a disease where an abnormally high trans-laminar
pressure gradient was caused not by increased intraocular
tension but by an abnormal depression of the intracranial
pressure.

     As for the development of nerve fiber bundle defects in
the visual field, it is well understood that although they
are seen most commonly in glaucoma, their occurrence is by no
means limited to that disease.  The configuration of these
scotomata reflects the disposition of fibers within the optic
nerve, and any lesion from the chiasm to the disc that
impairs the nerve function may be responsible for them.  This
is particularly true of arteriolar vascular lesions such as
are thought to account for ischemic optic neuropathy.  The
apperance in an older person of a nerve fiber bundle defect
in the presence of a flat optic nerve head and in the absence
of elevated intraocular pressure is usually ascribed to
vascular disease.

     Inasmuch as intraocular pressure is normal by
definition, and the field defects are relatively non-
specific, it is the development of nerve head excavation in
association with scotomata that is the sine qua non of low
tension glaucoma.  The excavation seen in low tension
glaucoma is more likely to be shallow, with the formation of
a sharp rim, and with the associated sharp bending of the
vessels as they descend from the level of the retina to the
floor of the shallow cup.  As opposed to open angle glaucoma,
the excavation is more likely to be asymmetrical, reaching
the edge of the disc in one meridian while elsewhere a
substantial rim of tissue remains intact.  This picture of
partial atrophy of the disc is not uncommon in the elderly,
although in the absence of elevated tension it seldom leads
to field loss, and thus does not fulfill the criteria of low
tension glaucoma.

     It is important to distinguish low tension glaucoma as
it appears in the second half of life from a very different
constellation of symptoms that is not uncommonly seen in
children and adolescents.  These young patients are found to
have large deep excavations with baring of the lamina
cribrosa, so that on first glance on fears to have detected a
case of advanced juvenile glaucoma.  But when one looks again
one is reassured by seeing a pink, albeit thin rim of nerve
fibers descending into the depths of the cup.  No field
defect is demonstrable, and on checking the pressure one
notes with relief that it is on the low rather than the high
side of normal.  These young patients do not have and do not
develop glaucoma.  The sieve-like openings in the lamina
cribrosa which are so clearly visible, associated with an
unusually low intraocular pressure, suggest that perhaps in
some patients the lamina cribrosa might not be impervious to
fluid after all and that it might be worthwhile to study the
hydrodynamic behavior of that tissue, particularly in the
juvenile eye, without any preconceptions about its
permeability.

     Like many decisions in the therapy of glaucoma, the
question of how to treat low tension glaucoma is fraught with
difficulties.  These problems reflect in part the obscurities
of diagnosis.  Patients in the age group in which the disease
is prevalent not infrequently have a benign atrophy of the
optic nerve head which, in the absence of field loss, cannot
be distinguished from the early stages of low tension
glaucoma.  They are prone to vasculopathies that can mimic
glaucomatous field defects.  We may be confident that our
usual armamentarium of anti-glaucoma medications will be
helpful in reducing a pressure of, for example, 34 mm Hg, but
it is much less certain how large a pressure reduction can be
achieved if the tension is no more than 12 or 13 mm Hg. to
begin with.  Even more important is the question in what
proportion of eyes which are losing field, for example, at 13
mm Hg.  reduction of pressure to 10 or even 8 mm Hg.  will be
effective in preserving the vision.  At best we  have  only
anecdotal data, and more often than not we proceed with
treatment the basis of ill-defined hunches and theories.

     The problem receives its most poignant formulation when
one is confronted with a patient in whom medication is
ineffective in lowering an intraocular pressure which is
statistically normal, but at which visual field continues to
be lost.  Shall we then stand by like helpless spectators to
the race between blindness and death, or shall we assert our
prerogatives of intervention, and, in the vernacular of our
trade, "filter the patient", knowing full well that although
if he is fortunate, we will save his sight, our well-
intentioned attempt to do so may set in motion a series of
events from which he could rapidly lose what little vision he
has.  The litany of complications of filtering surgery is
well-known.  The chamber goes flat and the choroid separates,
the macula becomes edematous, a cataract forms, the lens is
extracted, and then, if the patient is unfortunate the
filtering bleb is lost, and a lengthy therapeutic effort will
have been counterproductive.

     Here if anywhere, it is necessary that the patient make
the decision that determines his fate.  For while he has the
right to the benefit of every technical procedure that modern
ophthalmology has to offer, he must also have the right to
reject that technology, especially when it is fraught with
such grave risks.  The patient who refuses surgery under
those circumstances denies the surgeon the opportunity of
demonstrating his technical virtuosity, but at the same time
gives the physician the chance to care for him nonetheless,
and thereby to prove himself, what in the end is just as
important, a kind and understanding and compassionate human
being.


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Copyright 2006, Ernst Jochen Meyer
