Volume 3, Number 1
Summer, 1994
Understanding the Role
of Blood Flow in Glaucoma
by George L. Spaeth, MD
All physicians, including glaucoma specialists, seek to discover
the fundamental causes of an individual's disease. For it is only
when those causes have been identified that the most appropriate
treatment can begin.
Persons with glaucoma have suffered some kind of
tissue damage, frequently to the optic nerve. But knowing that
the cause of glaucoma is optic nerve damage does not provide the
physician nearly enough information. To initiate effective therapy
requires knowing the reason for the tissue damage, so that it
can be prevented or lessened.
Optic Nerve Damage
Let's consider optic nerve damage in a little more detail. The
real questions that must be answered are, first, the general
ones posed to researchers: What is the exact nature of the optic
nerve damage characteristic of glaucoma? and What causes that
damage? Furthermore, the glaucoma specialist must try to answer
questions about individual patients:
What is the exact nature of the optic nerve damage in this individual?
and What specifically has caused that damage?
Of course, knowing the answers to the first questions is crucial
for answering the second and ultimately most important ones. This
means that research is vital for discovering the best treatment
for individuals with glaucoma.
The story of glaucoma research began about 150
years ago, when Helmholtz invented an instrument that allowed
looking inside the eye. For the first time, investigators could
see the inside of eyes diagnosed with the newly-defined condition
known as "glaucoma." What they saw was that the nerve that leads
from the back of the eye into the brain, the optic nerve, was
obviously damaged. Specifically, the surface of the nerve, the
so-called "optic disc," had a bowl-like depression.
Two Theories of Optic Nerve
Damage
Some suggested that the observed depression was
related to the pressure of the aqueous humor, the fluid in the
eye that keeps it firm so that it can serve its purpose as an
optical instrument. It seemed reasonable that if the pressure
of the aqueous on the inside of the eye was too high, it might
directly kill optic nerve cells, leaving the bowl-like depression
now often referred to as "cupping."
This theory continues to be the most popular. And most treatments
for glaucoma aim in one way or another at lowering the pressure
inside the eye.
Even long ago, however, other investigators proposed
that it was not the direct pressure of the aqueous humor on the
optic nerve that damaged it. Rather, they argued, this pressure
is a problem mainly because it squeezes the blood vessels and
thereby reduces the flow of blood to the optic nerve. With insufficient
blood, the cells die, and when the cells die, they disappear,
leaving the characteristic bowl-like depression or cupping.
The Role of Blood Flow in
Optic Nerve Damage
Now, for the first time, technology is helping researchers, including
those at the Glaucoma Service Foundation, understand the major
mechanisms by which the optic nerve becomes damaged in patients
with glaucoma. This is unquestionably one of the most exciting
fields of investigation in all of ophthalmology.
Over the past 20 years, a variety of investigators have performed
extensive studies, some of which have indicated that spasm of
the blood vessels that provide blood to the optic nerve may be
responsible for glaucoma in some patients. Some individuals, such
as those with migraine, are predisposed to this type of spasm.
It has been known for quite a few years that patients with migraine
are predisposed to "low-tension" glaucoma, that is, glaucoma that
has occurred even though the pressure inside the eye is normal
or even lower than normal.
Others have found other specific indications of abnormality of
blood flow in some patients with glaucoma. For example, it is
becoming apparent that blood pressure is an important factor in
determining whether or not optic nerve damage will progress in
a glaucomatous eye.
More recently, Alon Harris, a physiologist at the
University of Indiana specializing in blood-flow studies, working
with one of our ex-Fellows, Louis Cantor, and with George Spaeth
and Bob Sergott, who is in charge of the vascular laboratory at
Wills Eye Hospital, has used a new technology that permits visualization
of the blood vessels of the eye. Based on this technology, Dr.
Harris has presented a number of studies describing changes in
blood flow in the optic nerve in glaucoma and, for the first time,
reported different patterns of blood-flow abnormality in different
types of glaucoma.
Foundation researchers are actively studying this
latter subject. At the annual meeting of the Association for Research
in Vision and Ophthalmology, the most important annual meeting
for presenting eye research, they showed that lowering the pressure
inside the eye by surgery improved the blood flow in certain patients
with glaucoma. In another paper, they related the amount of damage
to the optic nerve in patients with glaucoma to the amount of
abnormality of blood flow.
The Future
While we now know a fair amount about the relationship between
blood flow in the eye and glaucoma, investigators have a long
way to go. We and others are in an exciting race to come up with
a comprehensive understanding of the various mechanisms by which
the optic nerve becomes damaged in glaucoma.
Once these are known, physicians
will be in a far better position to help each individual patient.
As this new knowledge unfolds, we will see very exciting changes
resulting in significant improvements in patient care.
 Dr.
Alon Harris, from the University of Indiana, during a recent visit
to Wills Eye Hospital, uses new technology in the vascular laboratory
at the Hospital to analyze the blood flow in the eye of a patient
with glaucoma.
(Photograph by Roger Barone)
What Treatment is Best?
[In this article, Dr. George Spaeth, President of the Glaucoma
Service Foundation to Prevent Blindness and Director of the Glaucoma
Service at Wills Eye Hospital presents the third and concluding
part of a discussion of an issue of the utmost importance for
all glaucoma patients and physicians: How to decide what treatment
is best.
The first part concluded with two basic difficulties that each
patient's uniqueness poses in bringing the results of clinical
studies to bear on treatment decisions: studies provide information
about groups, not individuals; and "success" as defined
by a study may not be the same as "success" as defined
by a particular patient.
The second part concluded that in attempting to decide what treatment
is "best," patients must carefully consider the specific
types of side effects associated with medical and surgical (laser
or knife) treatment (established by studies, with all their limitations),
and decide which of these likely or unlikely side effects they
are willing to risk.]
Benefit
The final aspect that must be carefully considered is the benefit
to be expected by the treatment. It is known that the way treatment
at present helps patients with glaucoma is by lowering the pressure
inside the eye, the intraocular pressure. In most people with
glaucoma, eye drops tend to lower the intraocular pressure roughly
around 20% and surgery around 40%. There are indications that
for many people it is necessary to lower the pressure at least
30% to have a beneficial effect.
The pressure-lowering caused by argon laser trabeculoplasty (ALT)
is variable, but tends to add to the effect of drops. This beneficial
effect of ALT on pressure tends in most people not to be permanent,
wearing off in about two years in many individuals; in a few individuals,
the effect of ALT can last five years or more.
Thus, surgery with a knife tends to be more beneficial in terms
of pressure-lowering effect than ALT or eye drops. Roughly speaking,
drops lower pressure adequately in around 1/3 of individuals,
eye drops plus ALT in around 1/2, and surgery in around 3/4.
Risk/Benefit Ratio as Defined by the Patient
As one considers a treatment, one should weigh the degree and
the type of risk, and the degree and type of benefit. These are
compared and then contrasted with what is anticipated if no treatment
is given.
If rapid deterioration seems certain, most individuals will choose
a treatment likely to have a greater immediate benefit, such as
surgery, even though the risk is high. Where the likelihood of
deterioration is low, as in people in whom a diagnosis of glaucoma
is probable but not yet definite, most individuals will choose
an extremely low-risk treatment, even though the potential for
benefit is also low.
Conclusion
By putting all of these factors together and considering each
person's individual unique needs and wants, from the viewpoint
of both health and personality, a treatment plan can be developed
that is prudent and likely to fulfill the needs and accomplish
the goals of the individual person affected. But, clearly, success
is possible only if the patient's needs and goals are clearly
understood by both the patient and the doctor, and if there is
a reasonable probability based on knowledge gained from scientific
studies and the physician's experience that they are achievable.
All of which is to say that when the physician and the patient
are contemplating what treatment is appropriate, it is essential
for both to understand that there is no one treatment that is
going to be best for all individuals. Some treatments certainly
are going to be more likely to be appropriate than others.
For example, using cortisone eye drops for a long period of time
to treat a patient with primary open-angle glaucoma is more likely
to harm a patient than using pilocarpine for the same length of
time. But there are other types of glaucoma in which cortisone
is more likely to help than to harm, and pilocarpine more likely
to harm that to help.
Finally, all treatments must be advised by the physician and
followed by the patient with the full understanding that the advice
may be wrong. "Wrong" in the sense that that particular
patient does not respond in the desired and expected way.
This conclusion will be disappointing to patients accustomed
to thinking that medicine is a science with guaranteed results
and that physicians are unerring superhumans who use that knowledge
to cure disease. Indeed, this very attitude can only impede a
patient's receiving the "best" treatment.
One thing is clear, however. The more knowledge we have, the
better will be the chance that all patients will receive the "best"
treatment. That is why the Glaucoma Service Foundation to Prevent
Blindness exists.
Capital Campaign Launched
The research entity of the Foundation, comprised typically of
three full-time investigators, three part-time investigators,
and a research director operate at an astonishingly high level
for such a relatively small group. Currently, 13 investigations
are under way, ranging from blood-flow studies, to the effects
of antifibrotic agents in glaucoma filtration surgery, to work
with image analysis of the optic disc. New areas of interest are
being evaluated constantly.
Thanks to the generosity of
many, many contributors, the Glaucoma Service Foundation is now
ready to advance to a new level.
To take this step forward
will require funding on a much larger scale. While annual contributions
will continue to be absolutely essential, the Foundation's Board
has decided to launch a capital campaign.
We have chosen to pursue a
strategy of building from the top down, that is, hiring a research
professor of sufficient stature and experience that he or she
would bring with him or her funding at least partially sufficient
to cover his or her expenses as well as those required for support
personnel.
This plan is immensely strengthened
by the fact that a candidate already has expressed interest in
this position. Alon Harris, MD, currently at the University of
Indiana, has truly remarkable characteristics, perfect for the
Glaucoma Service.
Trained in physiology, he
has an intense interest in developing new knowledge relating to
the vascular mechanisms of the eye. For example, he already has
demonstrated that different types of glaucoma respond differently
to the acidity of the blood. This gives us a clue for the first
time as to who should be treated with agents to affect blood flow
to the optic nerve, so that, in the future the treatment of glaucoma
will have a rational basis not only for lowering intraocular pressure
but for selecting which patients need to have their blood flow
altered.
Because of the variety of
factors involved, we cannot say precisely the amount of funds
required to bring Dr. Harris to the Glaucoma Service. However,
an endowment fund in the range of one million dollars would probably
be adequate.
Achievement of the Foundation's
long-term goals will require additional endowment funds sufficient
to generate approximately $425,000 a year to pay the salaries
of the Research Director, three research fellows, a statistician,
a part-time person to oversee management of grants, a part-time
fundraising person, a part-time editor (and production costs)
for the "Searchlight," and rental of additional space.
New Glaucoma
Research Fellows at Wills
Dr. Annette Terebuh
(left), who joined the Glaucoma Service staff last year
after having served as a clinical/research Fellow here,
discusses a new project with researchers Silvana Araujo
(middle) and Kun Jin Yang (right). Dr. Araujo, from Brazil,
is nearing the end of her productive tenure. Dr. Yang has
just arrived from Korea, where he most recently served as
Assistant Professor of Ophthalmology at Chonnam University
Hospital. |
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Dr.
Louis Schwartz (right), long time member of the Glaucoma Service
staff, points out features of state-of-the-art laser equipment
to new clinical/research Fellow, Dr. Mark Lesk (left). Dr.
Lesk, who recieved his medical degree from McGill University
in Montreal, comes to us having just completed his residency
in ophthalmology at the University of Montreal. Our other
two new clinical/research fellows are Dr. Scott Stoller, who
has just completed his residency at the Albany Medical College;
and Dr. Patirck Tiedeken, who has come to us after extensive
practice in plastic, orbital, and neuro-ophthalmological surgery
to pursue his interest in glaucoma.
(Photographs by Jamie Nicholl)
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You can help support the research
and education activities of the Glaucoma Service Foundation to
Prevent Blindness. To make a donation to our Annual Fund click
here.
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