Volume 11, Number 2
July 2002
How Can We Discover Things That Will Help
Glaucoma Patients?
By George L. Spaeth, MD
Millions of dollars are spent every year on
research in ophthalmology, much related to glaucoma. This research
occurs at many different levels of complexity and with many different
purposes.
New ideas are an important part of research.
But ideas unrealized are of no value. The real challenge of research
is the combination of
- Coming up with an original idea
- Expressing the idea in a way that allows it to be tested
- Testing the idea in a way that is likely to yield a valid
result
- Interpreting the result, incorporating it into what is already
known, and discussing its significance; and
- Letting the world know.
The Idea
Few people can handle all five of these different aspects of research.
Some are veritable “idea trees” waiting for their hypotheses to
be plucked by others, or having them ripen and fall on the ground
to be claimed and utilized by others. Idea people are frequently
brilliantly astute observers who see things that others do not
see.
The Question
On the Glaucoma Service of Wills Eye Hospital ideas for research
frequently come from the glaucoma specialists themselves. For
example, we are all faced with the challenge of correctly diagnosing
glaucoma in individuals seeking our care. Glaucoma is not easy
to diagnose. The days are long gone when it was believed, incorrectly,
that anyone with an eye pressure over 21 mm Hg had glaucoma. It
would certainly be helpful if there were some other objective
characteristic whose presence might accurately and consistently
point to a diagnosis of glaucoma.
Over the years I have noticed that individuals
with an “acquired pit of the optic nerve” (a defect in the normal
continuity of the optic nerve, acquired rather than congenital)
often seem to turn out actually to have glaucoma. This idea or
clinical impression of mine, however, is of little or no use unless
it is true. It must be tested. Research must be done. It is this
process that I would like to review with you.
First, then, the “idea” or question must be
stated clearly. Using our example, we ask, “Are acquired pits
of the optic nerve characteristic of glaucoma?”
The Testing
Next, to determine the answer we must first be as certain as we
can about what kind of data are being tested: 1) people we say
have glaucoma really must have glaucoma, and those we say
do not have glaucoma must really not have glaucoma; 2)
what we call an acquired pit of the optic nerve must
be an acquired pit of the optic nerve, and that when we say
a pit is not present, it must not be present. However,
it is not easy to be certain about these data. It is difficult
to tell, in the early and moderate stages of glaucoma, whether
a person really does have glaucoma, because many people have findings
that resemble glaucoma but are not glaucoma. Additionally, it
is impossible to be sure that a person does not have glaucoma,
because the process of glaucoma may have started but still not
be recognizable.
To complicate matters more, acquired pits do
not come with labels on them. To recognize a pit requires a great
deal of skill, and consequently they are frequently missed in
examinations. On the other hand, the examiner may think he “sees”
a pit that is not actually there.
Bias is also a problem. For example, if the
examiner knows that a patient has glaucoma, and also believes
that acquired pits of the optic nerve are characteristic of glaucoma,
then that examiner tends to interpret changes in the optic nerve
as being characteristic of optic nerve pits. His bias may lead
him incorrectly to think something is a pit when in fact it is
not. We all know that the experience, skill, and bias of the observer
strongly affect the accuracy of the observation that he or she
is making.
The reader might jump to the conclusion that,
given these problems, it is impossible to come up with any accurate
conclusion about a clinical question such as whether an acquired
pit of the optic nerve is characteristic of glaucoma.
Fortunately, there are research techniques that
can be used to mitigate each of these three problems.
• First, consider the problem posed by the
fact that it is often difficult to say whether a person actually
has glaucoma or does not. Here we could establish two different
groups of study patients: in one group will be those who have
glaucoma with a certain probability, and in the other,
again with a certain probability, those who do not have glaucoma.
If these two probabilities are known, they can be compared with
regard to the presence or absence of an acquired pit by using
standard statistical techniques.
• Second, we can reduce the problem posed
by the uncertainty as to the ability of an observer to recognize
acquired pits correctly by testing the observer’s ability in
comparison with individuals who are recognized experts in recognizing
acquired pits. The accuracy and reproducibility of that observer
(or, more important, those observers) in recognizing optic pits,
then, can be determined, and this information can then be factored
into the results.
• Finally, the bias of the observers can be
controlled by making sure that they do not have any information
about the patient except the image of the optic nerve under
investigation.
The Interpretation and Incorporation
Now let us assume that a good question has been asked, an appropriate
methodology to try to answer it designed, and that that methodology
has been meticulously followed. Outcome: data. Those data are
not a conclusion but rather just data. The next step is making
sense out of that accumulation of information, acknowledging the
shortcomings of the study design (and there are always some shortcomings),
utilizing appropriate techniques of evaluating likelihood (because
that is all that statistics is), and then relating the data to
the real world.
For example, let us say that our study shows
that an acquired pit of the optic nerve is so characteristic that
when it is observed it means that the person has glaucoma, for
sure! This information, however, may be clinically useless if
an acquired pit of the optic nerve is so difficult to recognize
that very few doctors have the time or knowledge to determine
whether a patient has an acquired pit.
“Merely because somebody finds something
to be ‘true’ does not mean that that finding is useful.”
Or perhaps we find that acquired pits of the
optic nerve occur in only 0.0001% of people with glaucoma. If
that were the case it would not make sense to waste precious time
with a patient looking for an acquired pit of the optic nerve;
there would be many more important things to look for.
The point is that merely because somebody finds
something to be “true” does not mean that that finding is useful.
More generally, it is the researcher’s responsibility to put into
context the significance of his or her findings. Some things are
so obvious that they do not need to be studied. Other things do
not deserve studying. For example, it would not be appropriate
to conduct a research project to determine whether hitting the
eye with a sledgehammer causes it to become damaged. Nor would
it be appropriate to conduct a study to determine whether blue-eyed
individuals with glaucoma are more frequently named Mary or Patricia.
The Telling
The final step in research is telling the world what has been
discovered. For some this is the most difficult part of all. My
files are full of papers in various stages of completion. Believing
that one has answered the question oneself, often the excitement
and urgency abate. The final phase, completing the manuscript,
waiting for the editor’s response, handling the rejection or request
for revision, are tasks that require perseverance and maturity.
For those who make their living from research, the published paper
is the most important part of assuring a continuing income. But,
on the most fundamental level, if the paper is not published,
the research might as well not have been done. No one will benefit.
Conclusion
One reason why research is often best accomplished by teams is
that few investigators have the capability to handle all aspects
of research, from conceiving the idea to sharing the outcome with
the world through the written word. Fortunately for all of us,
the Glaucoma Research Center at Wills is developing just such
a team.
Clinical Fellow Receives
Award
Clinical Fellow Dr. Tara Uhler (left),
Dr. Jeffrey Henderer (center), and Research Fellow Muge
Kesen on the occasion of Dr. Uhler’s receiving a Pharmacia
Corporation Glaucoma Fellow Award for her poster presentation
at the Association for Research in Vision and Ophthalmology
(ARVO) annual meeting in May. The award was given for her
investigation of the factors determining whether persons
identified as glaucoma suspects in screenings go on to see
a doctor for a full examination. “If they do not,” explained
Dr. Henderer, head of the glaucoma screening projects at
Wills, “then the screening process has not fulfilled its
purpose. Dr. Uhler was tireless in contacting patients whose
screening results indicated they might have glaucoma to
find out if they had seen a doctor, and, if not, why not.
Dr. Kesen also has played a critical role in our glaucoma
screening projects.” Pharmacia presents Glaucoma Fellow
Awards to those they judge, on the advice of Dr. Marty Wax,
glaucoma specialist at Washington University in St. Louis,
to have had the best presentations at the ARVO or American
Academy of Ophthalmology annual meetings. Dr. Uhler was
the only recipient of an award for a clinical, as contrasted
with a basic science project.
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Photo by Christian Habina |
The Glaucoma Service Foundation Has Moved!
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Our new offices, together
with the entire Glaucoma Service, are located on the 11th
floor of the new Wills Eye Hospital. Our mailing address
is:
840 Walnut Street, Suite 1130
Philadelphia, PA 19107
Please note that our phone number has
also changed. You may reach us by calling 215-928-3283.
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View from
the Glaucoma Service patient waiting area on the 11th floor
of the new Wills Eye Hospital. The “old” Wills can be seen
on the left at the corner of 9th and Walnut Sts. The Glaucoma
Service occupies the entire floor, with the Foundation office
at one end, facing Walnut Street, examination rooms in the
center, and the Glaucoma Research Center at the opposite end.
Photo by Ken Parker
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The Role of Glaucoma Patients in Glaucoma
Research
By George Spaeth, MD
No matter how good the research team, no research
would be possible without the cooperation of glaucoma patients
who agree to participate in our studies as well as those who help
us meet the high costs of performing quality research. Those whose
circumstances allow them to do either are bright lights in our
world. After all, discovering new knowledge, the goal of research,
is one of the most important ways to make the world better, better
in every sense — healthier, happier, and more connected. What
are the disadvantages and advantages, from the patient’s point
of view, of participating in a research trial? The disadvantages
may be considerable.
- A research trial will take up the patient’s time and may introduce
significant and perhaps even irritating inconveniences.
- An investigation will almost certainly require standardization
of care, and the best standardized care is never as good as
the best individualized care.
- There is often some risk to the patient involved in a clinical
trial.
- There is always uncertainty as to whether the participation
will be of any benefit whatsoever, not just to the patient but
to anybody.
- Finally, if a study has not been designed properly with appropriate
safeguards the patient may suffer an invasion of privacy or
actual damage.
The advantages of participating in a research
trial are also real:
- The test or treatment being studied may not be available to
anybody else other than those participating in the study.
- Knowing that the institutional review board will review the
research project and would not approve a study which puts patients
at risk unnecessarily, the principal investigator is likely
to design a study in which there may be some very real advantages
to the participants in terms of free tests such as visual field
examinations or optic disc analysis.
- Additionally, it may be important for the research participant
to know that he or she is helping to discover new knowledge
which may be of direct benefit to him or her and should be a
benefit to others in the future.
Patients should be very clear in their
mind that they truly want to participate in a research trial before
they agree to participate. One of the most discouraging aspects
of research from the investigator’s point of view is to have patients
drop out of a study. When that occurs it makes interpretation
of the results of the study extremely difficult, or even impossible.
Did the people who dropped out stop because they were having side
effects? Did they drop out because they felt cured of the basic
problem and thought it was a waste of their time to continue?
If a person drops out of a study because he
is having side effects, the final results would be falsely good,
because this patient, who was not doing so well in the study,
dropped out of the study and therefore his poor results were not
tabulated in the final analysis. If a person drops out of a study
because he believes he is cured, the conclusion would be similarly
incorrect, but in the other direction; that is, if he dropped
out because he felt cured, the truly beneficial effect of the
treatment would not be apparent in the final tabulation of the
results.
If your doctor tells you that you are eligible
to participate in a study, carefully consider the advantages and
disadvantages. If you feel it is right for you, that is a happy
solution for everyone. However, if you do not feel comfortable
agreeing to participate, it is equally important for the sake
of the well-being of the study that you let your doctor know your
feelings.
Clinical Coordinator Fillis
Samuel (left) with glaucoma patient Constance Nicolay. Ms.
Nicolay is participating in a study of the Allergan agent,
memantine, which may prove useful in protecting the optic
nerve from glaucoma damage. |
Clinical Coordinator Sheryl
Wizov (left) with glaucoma patient Mary Holmes. Ms. Holmes
has been participating since 1995 in a major multicenter glaucoma
trial, the Collaborative Initial Glaucoma Treatment Study
(CIGTS).
Photos by Ken
Parker |
Glaucoma Research
Center Actively Recruiting Patients for Studies
The Glaucoma Research Center is actively recruiting
patients for the following studies. If you are interested in participating,
please speak with your doctor to find out if you are eligible.
- A study comparing medication therapy to laser therapy with
the new SLT laser as an early treatment for patients with glaucoma.
Patients should not have been on glaucoma medications for more
than 14 days in their life and have been diagnosed with primary
open-angle glaucoma.
Sponsor: Lumenis
Principle Investigator: Dr. Katz
- A study to test how well the medication Cosopt lowers eye
pressure in glaucoma or ocular hypertension patients. Patients
who have an eye pressure of 30 mm Hg or higher and who have
not been treated in the last 4 weeks are needed.
Sponsor: Merck
Principle Investigator: Dr. Wilson
- A study to evaluate which of the two medication combinations,
Cosopt (Trusopt/Timoptic) or Xalatan/Timoptic, increases blood
flow in the eye more.
Sponsor: Merck
Principle Investigator: Dr. Katz
- A study comparing the safety and efficacy of a Lumigan/Timoptic
combination with each medication by itself in patients with
glaucoma or ocular hypertension.
Sponsor: Allergan
Principle Investigator: Dr. Katz
- A pilot study to learn if there is a genetic basis for angle-closure
glaucoma. We are looking for patients with primary angle-closure
glaucoma who have about 10 blood relatives who would be willing
to come into Wills for genetic testing (a blood test). The relatives
do not have to be diagnosed with or suspected to have glaucoma.
Funding being sought
Principle Investigator: Dr. Spaeth
- A study evaluating how closely eye pressure measurements taken
with an “at home” device (the Proview tonometer) get to those
taken with a standard device used in glaucoma specialists’ offices.
Sponsor: Bausch & Lomb
Principle Investigator: Dr. Moster
- A study investigating if 1) the substance Healon 5 can increase
a patient’s eye pressure after it has fallen to below normal
levels following eye surgery and 2) when used during glaucoma
surgery, its effect on a patient’s long- and short-term eye
pressure.
Sponsor: Pharmacia
Principle Investigator: Dr. Moster
- A study to see how much of the drug Lumigan stays in the eye’s
fluid if Lumigan is given for 21 days prior to cataract surgery.
Glaucoma patients about to undergo cataract surgery or a combined
cataract/glaucoma surgery are needed.
Sponsor: Allergan
Principle Investigator: Dr. Moster
Special Summer Appeal for the Glaucoma Research
Center
By Nancy Petrongolo
As Dr. Spaeth points out in his article on the
role of glaucoma patients in research: “No matter how good the
research team, no research would be possible without (1) the cooperation
of glaucoma patients who agree to participate in our studies as
well as (2) the support of those who help us meet the high costs
of performing quality research.”
This summer, the Foundation is asking folks to consider making
a special, one-time, donation specifically to support the Glaucoma
Research Center of Wills Eye Hospital. Funds are needed to ensure
that the Center’s momentum is maintained and enhanced so that
its maximum potential can be reached as quickly as possible.
The Glaucoma Research Center campaign is directed to donors
who wish to support the research activities of the Glaucoma Service
above and beyond their Annual Fund giving. It is vital that we
continue to receive contributions to the Annual Fund to maintain
and expand our patient and family support groups, community screening
programs, the Searchlight, the Glaucoma Service website,
and our training program for future glaucoma specialists.
Contributions to either the Glaucoma Service Foundation Annual
Fund or the Research Center campaign can be made through our website
by clicking here.
If you wish your donation specifically to go to the Research Center
campaign, please indicate so on the form.
Thank you for your generous support. Stay tuned for news of
the exciting advances your contributions are making possible.
New Date Set for Glaucoma
Conference and Celebration
The Annual Wills Eye Hospital Glaucoma Conference
and special Celebration to mark over 40 years of fellowship training
on the Glaucoma Service of Wills Eye Hospital has been rescheduled
for Friday and Saturday, October 3–4, 2003. Former Glaucoma Service
Fellows from here and around the world, along with other distinguished
glaucoma specialists, will gather in Philadelphia for the one-and-a-half-day
Conference.
The Conference will be followed on Saturday
evening by a special program, including a ballet commissioned
for the occasion through Mr. Meredith Rainey, choreographer and
principal dancer for the Pennsylvania Ballet. The cost of the
ballet will be underwritten by Mr. Jack Wolgin, noted Wills Eye
Hospital benefactor. Thanks to the efforts of long-time Board
member Mr. Stanley Tuttleman and Foundation friend Mr. Ray Perelman,
the Perelman Theater at the Kimmel Center for the Performing Arts
has been reserved for the occasion.
Mrs. Bonnie Carr Long, Chair of the Steering
Committee, along with Committee members Mrs. Ann Ward Spaeth,
Mr. Stanley Tuttleman, Mrs. Sanna Henderer, Mrs. Tina Rhee, Dr.
Laurie Katz, Mrs. Sara Rapuano, Dr. George L. Spaeth, and Mrs.
Nancy Petrongolo have formed the following sub-committees, for
which they are now recruiting volunteers:
- Decorations Committee
- Food Committee
- Printed Materials and Commemorative Items Committee
- Music Committee
- Public Relations Committee
- Program Committee
- Honorary Committee
If you would like more information about the
event or would like to volunteer to serve on a sub-committee,
please contact Foundation Managing Director Nancy Petrongolo at
215-928-3191.
New Research Fellow,
Dr. Sushma Rai
New Research Fellow, Dr. Sushma Rai (left), with
Dr. Richard Wilson. Dr. Rai received her medical and ophthalmological
training in her native India, where she was a practicing ophthalmologist.
Moving to Canada, she spent four years at the University of British
Columbia Eye Care Center as a clinical research assistant, working
on a major multicenter research project studying laser treatment
for neovascularization secondary to age-related macular degeneration.
She worked on two publications in this area, one in the Archives
of Ophthalmology and the other in the American Journal of Ophthalmology.
She has just finished a surgical internship at Maimonides Medical
Center in Brooklyn, NY. While she was there she also worked for
6 months as a Research Fellow at the Lutheran Medical Center.
Photo by Ken Parker
Glaucoma Clinicians’ Research Projects Break
New Ground
The doctors who see patients and perform surgery
on the Glaucoma Service also are intensively involved in glaucoma
research. Because they are committed to patient care, they can
do better research; because they are committed to research, they
can provide better patient care. In each issue of the Searchlight,
as below, we will focus on one of the studies being conducted
by each of the Glaucoma Service faculty.
L. Jay Katz, MD
Medications vs Laser for Newly Diagnosed Glaucoma Patients
Usually, newly diagnosed glaucoma patients are given a variety
of glaucoma medications to treat their eye disease first. Only
after that approach fails will a doctor try using a laser or other
surgical treatment. With this research project, which other hospitals
all over the country are helping us do, we are trying to see if
the usual way of treating glaucoma really is best. We will have
150 open-angle glaucoma patients try medication as a first treatment
for glaucoma and another 150 have a laser procedure with the new
SLT laser. Then we will see which works best. Depending on what
we find, the way glaucoma is typically treated could be significantly
changed.
Douglas J. Rhee, MD
Directed Gene Therapy for Glaucoma
Gene therapy can mean two different things — (1) providing a healthy
copy of a mutated gene or (2) inserting a normal human gene to
treat glaucoma. As of the year 2002, genetic mutations have been
associated with less than 10% of all people with glaucoma. Additionally,
it is not understood how these mutations actually cause glaucoma.
Therefore, I am concentrating on delivering normal human genes
into various cells in the eye to prevent damage from glaucoma,
thereby potentially helping all people with glaucoma. Although
the technology to deliver genes to many tissues in the eye has
been available for over a decade, no one has yet been able to
selectively target only those parts of the eye involved in glaucoma.
The goals of my gene therapy project are (1) to test my novel
systems to selectively deliver genes, and (2) to test various
candidate genes for insertion that could be used not only to treat
glaucoma, but also to help us understand what causes glaucoma.
If successful, gene therapy would have the advantage of using
the body to treat itself and potentially cure individuals in which
a genetic defect has caused their glaucoma.
Richard Wilson, MD
Creating an Internet Network of Wills ex-Residents and ex-Fellows
to Greatly Expand the Scope of Studies that Can Be Accomplished
under the Direction of the Wills Glaucoma Service
Most of our patients come to the Glaucoma Service on multiple
medications. This makes it difficult to study the effects of any
one medication in and of itself. The internet presents an opportunity
to unite the vast number of Wills ex-residents and exfellows,
who are much more likely to have patients at an earlier stage
of the disease. In this project, study design and protocol, inclusion
and exclusion criteria, as well as all the forms required will
be made accessible on the internet. Standardized forms submitted
over the internet will allow information on study patients to
be collected from many offices across the country, allowing a
much more effective study of medications than otherwise would
be possible. And the more we know about medications used to treat
glaucoma, the more effective treatment is likely to be.
Jonathan Myers, MD
Comparing Three Different Ways of Determining Whether a Patient’s
Visual Field Has Gotten Worse
Visual field analysis is the primary measure of visual function
in the monitoring of glaucoma. The Visual Field Progression Study
is a prospective study comparing the ability of clinicians to
determine whether a patient’s visual field has gotten worse or
not, using three different commonly used software sets to view
the same data for a series of 40 patients. Visual field progression
is an important clinical indicator of the need for more intensive
therapy. The more accurately doctors can determine the extent
and rate of visual field deterioration, the more effective treatment
is likely to be.
Jeffrey Henderer, MD
Screening to Identify Glaucoma in the Community and to Ensure
Appropriate Follow-up for Those Who Have Signs Indicating They
May Have the Disease
Glaucoma tends to affect certain groups more than others. It is
more common in the elderly. Persons with a family history are
at a higher risk as well. African-Americans are three to four
times as likely to develop the disease as whites. It also affects
these individuals at an earlier age. To compound matters, African-Americans
are less likely to receive care for their glaucoma. This screening
program will be designed both to identify glaucoma in the community
and to cover the costs of a follow-up eye exam. This new program
will expand the Glaucoma Service’s current screenings, improve
the system that reminds patients to have a follow-up exam, schedule
patients at Wills Eye Hospital if they have no doctor, and provide
for transportation and exam costs by the staff at Wills Eye Hospital.
Marlene Moster, MD
Determining How Effective a New Device Allowing Patients to Measure
Their Own Intraocular Pressure Is
A new device, the Proview Eye Pressure Monitor (Bausch & Lomb
Surgical), allows patients to monitor their intraocular pressure
between doctor visits. This study will compare Proview readings
with those using the standard office measuring device, the Goldmann
tonometer. Also to be investigated is whether just being able
to monitor IOP at home or at the office reduces anxieties patients
might have about their glaucoma.
George L. Spaeth, MD
Using Genetic Information to Determine the Need in Certain Patients
for Earlier, Aggressive Treatment with Safer, More Effective Ways
to Combat Visual Loss
Some patients have a severe form of primary open-angle glaucoma
which continues to deteriorate despite available treatments. Genetic
mapping techniques have been used to look for markers in 189 patients
who were seen for at least 10 years on the Glaucoma Service of
Wills Eye Hospital. The purpose was to identify a predisposition
to this severe form of glaucoma. Children, grandchildren, and
future family members of patients with advanced glaucoma and those
in highrisk groups stand to benefit from earlier, aggressive treatment
with safer, more effective ways of combating visual loss.
Support Group Meetings
Please call the Foundation Office in early September
for a schedule of next season’s Glaucoma Patient Support Group
meetings: 215-928-3283.
Blood Flow to the Optic Nerve: An Important
Risk Factor for Glaucoma
By Richard P. Wilson, MD
At this point, our knowledge concerning the cause
of glaucoma is fairly rudimentary, and many questions concerning
the mechanism of injury in glaucoma remain to be answered.
Intraocular Pressure is not the Sole, or
in Some Cases Even the Chief Factor in Producing Glaucoma Damage
We have an abundant evidence of this:
- Abnormally high intraocular pressure is ten times more common
than glaucoma damage.
- Approximately 1 out of 6 patients with glaucoma damage never
has elevated intraocular pressures, even on repeated testing.
- Although women have only a slightly higher intraocular pressure
than men, on average, as they age, they suffer a rate of “normal-tension”
glaucoma twice that of males.
- The intraocular pressure is approximately equal in African-Americans
and Caucasians, but African- Americans have three to four times
the prevalence of glaucoma.
- In Japan, although the incidence of glaucoma damage increases
with age at about the same rate as it does in America or Europe,
the intraocular pressure diminishes with advancing age.
- One study showed the presence and progression of glaucoma
damage was only weakly related to the level of intraocular pressure.
- Patients with advanced glaucoma tend to slowly worsen no matter
what interventions are applied unless the intraocular pressure
is reduced to the single digits.
Clearly, something more than elevated intraocular pressure is
required to cause glaucoma damage.
Blood Flow is also a Major Risk Factor for Glaucoma
There is abundant evidence that blood flow is the second major
risk factor in glaucoma after elevated intraocular pressure. This
evidence includes:
- The fact that intraocular pressure is only slightly related
to the level of systemic blood pressure. High blood pressure,
hypertension, seems to be protective against glaucoma damage
in young patients but is a risk factor in older patients.
- The fact that “perfusion pressure,” the pressure pushing blood
through an organ, in this case the eye, is the best predictor
for looking at the risk of developing glaucoma. When the perfusion
pressure as evidenced by the diastolic blood pressure (the lower
number) is on the low side, the risk of developing glaucoma
is six times higher than normal.
- The strong association between glaucoma damage and low blood
pressure. The majority of individuals, healthy or otherwise,
have a drop in their blood pressure during sleep, especially
in the midnight to 3:00 a.m. time interval. Glaucoma patients
with the greatest blood pressure dips at night show an increased
risk of progressive visual field loss.
Other studies have shown that a drop in blood pressure during the
night will reduce blood flow through the small arteries that supply
the optic nerve. Twenty-four-hour blood pressure monitoring with
an ambulatory monitor may well reveal large dips in systemic blood
pressure. Patients who may have blood pressures of 175/134 in the
afternoon can be down to 92/44 in the early morning hours. Such
a drop seriously weakens the resistance of the optic nerve to glaucoma
damage.
- Arteriosclerosis, or hardening of the arterial vessel walls,
seems to be a much less significant risk factor for glaucoma.
One study has shown that it increases the sensitivity of the
patient to intraocular pressure but there is little evidence
in the literature that arteriosclerosis is a major risk factor
for glaucomatous damage.
Autoregulation is the ability of an organ to regulate
its own blood supply to meet its functional needs. Abnormal spasms
or narrowing of the vessel going to an organ is one form of defective
autoregulation. Spasms in vessels leading to an organ would abnormally
limit the supply of blood to the organ. This would be especially
damaging if the vasospasm occurred at a time of increased use
and requirement for oxygen and nutrients. Vasospasm would
be one type of disregulation. Another type of disregulation
would be if the vessels going to an organ like the eye did not
dilate at a time when the organ was quite active and had increased
requirements for oxygen and nutrients.
- There is a large body of research that links vascular disregulation
to glaucoma damage. Nocturnal dips in blood pressure are associated
with reductions in the velocity of blood going into the eye
in glaucoma patients but not in normal controls. This suggests
that glaucoma patients suffer from vascular disregulation at
night.
- Patients with “normal-tension” glaucoma have a much increased
rate of migraine headaches compared to the normal population.
Migraines represent a spasm of vessels in the brain. There seems
to be an extension of these spasms to the vessels supplying
blood flow to the eye. Breathing carbon dioxide can improve
the visual fields of some patients by theoretically counteracting
vasospasm and will normalize blood flow to the optic nerve.
This suggests that the vascular defects causing glaucoma damage
may be reversible.
- On the other hand, patients with narrowing of the carotid
artery leading to the front half of the head and, therefore,
the eye have low perfusion pressure to the eye but do not seem
to have an increased risk of glaucoma. Also the majority of
patients with vasospastic disease do not develop glaucoma.
These findings suggest that risk factors beyond vasospasm must
be necessary to produce glaucoma damage. For example, someone
with vasospasm may also need to have nocturnal hypotension in
order to develop glaucoma damage, or someone with carotid stenosis
may also need elevated intraocular pressure to develop glaucoma.
The combination of two or more risk factors would dramatically
increase the chance for glaucoma damage.
Conclusion
I have included here only some of the more basic findings suggesting
a strong link between blood flow to the optic nerve and glaucoma
damage. This new knowledge clearly advances our understanding
of the causes of glaucoma. Still, as is so often the case in scientific
investigation, the more we discover, the more we realize remains
to be learned. The more we learn about the causes of glaucoma,
here at our own Glaucoma Research Center and around the world,
the better we glaucoma specialists will be able to help glaucoma
patients everywhere.
Tips For Glaucoma Patients From Glaucoma Patients
Radio Shack Dual-Memory Timer/Clock
Dr. Katz’s patient, Ms. Flora Grossman, recommends this little
gadget as an aid in taking glaucoma medications. One timer can
be set to remind you that it is time to take your medication.
The other timer can be used to time the interval between taking
two different drops or the couple of minutes or so needed for
punctal occlusion (closing the eye while putting pressure on the
inner corner of the eye against the nose; this will close the
tear duct and both maximize the drops’ absorption into the eye
and minimize their absorption into the rest of the body). The
Radio Shack Dual- Memory Timer/Clock (catalog number 63-899) is
available from Radio Shack stores for $16.99.
Eye Drop Delivery Aid
Dr. Henderer’s patient, Edna M. Harris, reports that Upsher-Smith
Laboratories’ “Eye Drop Delivery Aid” is making putting her eye
drops in “quite easy and effortless.” She explained, “I sit in
a rocking chair, tilt my head back and squeeze the Aid. The drop
falls right into the eye; no mirror is needed.” According to the
manufacturer, “The Eye Drop Delivery Aid fits securely and comfortably
around your eye and helps your hand squeeze the bottle.” The Aid,
which costs about $10, can be ordered by your pharmacy if they
do not have it in stock.
New Board Members Announced
Three new members joined the Glaucoma Service
Foundation Board at the May 13th semi-annual Board meeting. Mr.
Hyman Lovitz has been in general private practice for 40 years,
having founded the law firm of Lovitz and Gold, P.C., specializing
in employment and discrimination law. He is a member of the Board
of Managers of the Associated Alumni of Central High School of
Philadelphia as well as past President of the organization. Other
new Board members announced at the meeting include Judge Phyllis
Beck, Associate Judge of the Superior Court of Pennsylvania, and
active in many community organizations, including the Free Library
of Philadelphia and the Independence Foundation, and Mr. Thomas
Henderer (photo not available), father of Glaucoma Service staff
physician Dr. Jeffrey Henderer, a lawyer specializing in estate
planning, wills and trusts for Wilmington Trust in Wilmington,
Delaware.
Mr. Hyman Lovitz
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Judge Phyllis Beck
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