Volume 11, Number 1
April 2002
Dr. L. Jay Katz Answers Questions About “Normal-Tension”
Glaucoma
In a recent interview Dr. Katz answered questions
about “normaltension” glaucoma posed by Searchlight Editor, Ken
Parker:
Q: We hear a lot about “normaltension”
or “low-tension” glaucoma. If you tell patients they have this
kind of glaucoma, most broadly, what are you telling them?
Dr. Katz: That their eye pressure is
in a range that typically is seen in the “normal” population of
people without glaucoma. Up to one third of glaucoma patients
in the United States have “normal-pressure” glaucoma. In Japan,
over 50% do. Normal-pressure glaucoma probably encompasses a number
of different disorders that share the common theme of sensitivity
to pressure damage despite having “low” or “normal” pressure.
Q: Many people think that glaucoma is
having an eye pressure higher than normal. How, then, could someone
have glaucoma if his or her pressure was normal or even lower
than normal?
Dr. Katz: Glaucoma is a disease where
the eye pressure, whatever it may be, is high enough to cause
damage to the optic nerve. The level of pressure needed to cause
damage varies considerably among individuals.
Q: Would it be correct, then, to say
that normal-tension glaucoma is a kind of primary open-angle glaucoma?
Dr. Katz: Yes.
Q: Are there any ocular or systemic characteristics
that tend to be associated with normal-tension glaucoma as contrasted
with “ordinary” open-angle glaucoma?
Dr. Katz: It is more common to
see optic nerve hemorrhages with normal- tension glaucoma
[see photo]. These typically indicate impending damage to
the optic nerve. Also, there is usually an association with
vascular problems. For example, migraine and low blood pressure
are frequently seen with normal-tension glaucoma.
Q: Some researchers have talked
about glutamate excitotoxicity in relation to normal-tension
glaucoma? What does that mean?
Dr. Katz: Glutamate is a substance
that is vital to the health of nerve tissue. However, in
high concentrations it literally “excites” nerve cells to
death. For this reason it has been used in animal models
to injure optic nerves. Of interest is the fact that glutamate
has been found at high levels inside the eye of glaucoma
patients as compared with individuals without glaucoma.
Q: Does normal-tension glaucoma
progress differently, in terms of visual field deterioration
or optic nerve damage? |
This photo of the back
of the eye shows a notch, that is, absence of nerve rim,
at the 5:00 o’clock position; and a disc hemorrhage at
the 2:30 o’clock position.
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Dr. Katz: There are more focal, that
is, well-defined (as contrasted with diffuse) areas of damage,
both in the optic nerve and visual field. For example, with this
type of glaucoma there often is a very welldefined area of nerve
tissue loss in the optic nerve, referred to as a “notch” [see
photo]. Also, often there is very dense visual field loss in the
paracentral portion of the visual field called an arcuate scotoma
or blind spot.
Q: Do we have any clues as to why one
person would develop normaltension glaucoma as opposed to “ordinary”
primary open-angle glaucoma? Are the risk factors different? Does
it occur more frequently at a certain age, in men or women? Does
blood pressure play a role?
Dr. Katz: The risk factors appear to
be the same. There may be more of an association with a dip in
blood pressure, for example, when one is asleep. We now have instruments
that can measure blood pressure throughout the night. People for
whom such recordings show dramatic drops in blood pressure or
“nocturnal dips” are thought to be at greater risk for developing
normal- tension glaucoma. In the United States it appears to be
more frequently seen in women, middleaged or older, whereas in
Japan, in contrast, it is more commonly seen in men who are in
their 30's when first diagnosed.
Q: Is the treatment different than that
for primary open-angle glaucoma?
Dr. Katz: No, not yet. However, I am
confident that in the future we will have other kinds of treatment
that will address issues of improving blood flow to the optic
nerve as well as providing neuroprotection to nerve cells without
lowering eye pressure, or as a supplement to pressure-lowering
medications. These treatments would be with medicines or perhaps
even gene therapy.
Q: Has the recognition of normaltension
glaucoma prompted investigators to revise their thinking about
glaucoma in general? Dr. Katz: Yes. It has underscored the importance
of risk factors other than eye pressure, such as blood pressure
and substances such as glutamate.
Q: What kind of research, including your
own, is being done with regard to normal-tension glaucoma?
Dr. Katz: There are two areas of research
pertinent to normal-tension glaucoma. First, we are investigating
agents that actually may protect the optic nerve from damage that
may be independent of lowering eye pressure. There are two large
multi-center trials, the first, in which the Glaucoma Service
is a major center, is testing memantine, an oral medication that
has been used for neurological disorders such as Parkinson’s disease
in Europe. Memantine has no effect on eye pressure at all. It
is currently being used to supplement pressure- lowering medications.
The results of that study are still not available, and the study
is ongoing.
In a second clinical trial a commonly used glaucoma
agent, Alphagan (brimonidine), which is used to lower eye pressure,
is also being evaluated in a multi-center trial in which the Glaucoma
Service is participating (please see Dr. Myers’
article in this issue) with regard to its potential for
neuroprotection above and beyond what it provides by lowering
eye pressure. That study also is ongoing.
These clinical trials will take years before
we will have definitive answers as to whether either of these
agents is beneficial. The reason these take so long is that the
patients enrolled in them are being treated with current therapies
for lowering pressure. We do not feel comfortable placing patients
just on an experimental medication. Furthermore, glaucoma is a
very slowly progressing disease, and measuring change by visual
fields will be necessary over an extended period of time before
there can be differences demonstrated between different groups.
In a second area of research the Glaucoma Research
Center is evaluating the potential of modifying blood flow to
the optic nerve. We now have very sophisticated machinery, such
as the Heidelberg Retinal Flowmetry equipment in our Department.
This is a noninvasive test that can very accurately measure even
capillary or microcirculation in the back of the eye. We are now
studying the effects of glaucoma medications not only in lowering
eye pressure, but also with respect to how they compare in improving
ocular circulation in the vessels that supply blood to the optic
nerve and retina.
Once we have the results from these types of
investigations we will be better able to individualize and supplement
our current therapies for our glaucoma patients, especially those
with normal-tension glaucoma.
Dr. L. Jay Katz (left) with his patient, Jerry Nothman. As is
true for all the Glaucoma Service specialists, Dr. Katz is committed
both to patient care and research. Because the Glaucoma Service
doctors are committed to patient care, they can do better research;
because they are committed to research, they can provide better
patient care.
Photo by Ken Parker
American Glaucoma Society Meeting Features Exciting
Advances
The American Glaucoma Society held its 12th
Annual Meeting February 28th through March 3d in San Juan, Puerto
Rico. Over 300 glaucoma specialists participated. The Wills Eye
Hospital Glaucoma Service has played and continues to play key
roles in the Society: Dr. George Spaeth was the first President;
Dr. Richard Wilson will serve as President beginning in
January 2003. Dr. William Steinmann, Director of the Glaucoma
Service Research Center, as well as a glaucoma patient himself,
kindly offered the following highlights from that meeting:
The recent American Glaucoma Society meeting
in San Juan provided most encouraging evidence to both clinicians
and glaucoma patients such as myself. Of course developments reported
at the meeting also are of great interest to those of us involved
in the cutting- edge research being conducted at the Wills Eye
Hospital Glaucoma Service Research Center.
My excitement stems not only from what was reported
with regard to the treatment of glaucoma but also from new knowledge
presented about screening for, diagnosis of, and the causes of
the disease.
New Medicines
First, I focus on promising new glaucoma medications,
especially ones designed, not to lower eye pressure, but possibly
to protect the optic nerve from damage or help it heal after sustaining
damage from pressure too high for a particular individual’s nerve
to tolerate. Such agents are said to be “neuroprotective.”
Medicines and surgical procedures that lower
pressure undoubtedlywill continue to be central to the treatment
of glaucoma. However, by the time many patients are diagnosed
with glaucoma, “irreversible” damage to the eye already may have
occurred. While current, pressure-lowering treatments can help
prevent further damage in these people, they are of little or
no benefit in reversing damage already done. The preliminary encouraging
results presented at the American Glaucoma Society meeting regarding
the new, potentially neuroprotective, medicines being investigated
at Wills and other important clinical and research centers are
a bright beacon of hope for all glaucoma patients.
New Screening and Diagnostic Tests
A second key area of research well represented
at the meeting were new developments in screening and diagnostic
tests. These tests are used not only to identify those who have
or who are most at risk for developing glaucoma, but also to monitor
the progress of the disease and the success of treatment. Because
such testing provides clinicians ways to detect even the slightest
change in an individual’s glaucoma, treatment can be modified
before more damage occurs. Among the many studies in this area,
including several by Glaucoma Service investigator-clinicians,
was Dr. Spaeth’s Disc Staging System. The pinpointing of the precise
level of damage made possible by the system will allow more accurate,
individualized treatment.
Also at the forefront in this area are instruments
that “read” or measure the back of the eye. Again, the Glaucoma
Service is active in the conduct of this research and the use
of this technology in the daily care of our patients.
Another type of diagnostic test being developed
by Dr. Spaeth and Glaucoma Service Research Fellow the meeting
is designed to determine how actual, everyday physical function
is specifically affected by glaucoma and other eye diseases. Wills
is one of the few institutions in the country pursuing this important
area of research. The potential value of this “Assessment of Function
Related to Vision” test is obvious. Reliable and objective measures
of visual function beyond those afforded by traditional visual
acuity and visual field testing will provide doctors crucial information
to better monitor the effectiveness of treatments in minimizing
patient dysfunction.
The Genetics of Glaucoma
Another focus of the American Glaucoma Society
meeting equally important for us all is the genetic predisposition
of glaucoma. As you probably know, family history is the strongest
predictor or risk factor for glaucoma. If we can identify the
genes that predispose to glaucoma, investigating these apparent
markers will increase our understanding of the causes of glaucoma.
Secondly, knowing these genes will allow us to identify the individuals
most at risk for developing glaucoma. We can then carefully follow
them to identify any disease process at a very early, highly treatable,
stage. Wills Glaucoma Service clinician-investigator Dr. Douglas
Rhee and others here are actively investigating the genetic aspects
of glaucoma, including the establishment of a genetic library
to use for future genetic research projects.
The American Glaucoma Society meeting provided
an exciting forum for those of us involved in the clinical care
of glaucoma patients and the scientific investigation of the disease
to share in the latest developments in glaucoma research. Wills
Eye Hospital clinicians and researchers figured prominently in
the content and conduct of this meeting. We are proud of our accomplishments
and the opportunity to share in the discoveries that will improve
the care and understanding of glaucoma in the broadest sense.
In this light we appreciate greatly the support
received from the contributors to our 2001 Annual Fund listed
in this Searchlight. Those of you who choose to support the cutting-edge
research being conducted on the Glaucoma Service of Wills Eye
Hospital help assure not only yourselves and your families the
latest and most effective care for your eyes. But also, thanks
to meetings such as that of the American Glaucoma Society, your
generosity helps extend these benefits to all glaucoma patients
everywhere.
2001 Gift Report Thank You for Your Wonderful
Support
We are enormously grateful to the many friends
and supporters of the Glaucoma Service Foundation who helped make
2001 the most successful fund-raising year in our history. During
calendar year 2001, more than 1400 individuals, foundations, corporations
and estates donated a total of $528,870 to support the Foundation’s
work.
The tragic events of September 11, 2001 placed
enormous pressure on non-profits not concerned with relief efforts.
Despite this challenge, the Annual Fund continued to grow, with
the total raised of $234,938, up an impressive 11% from last year.
We value every gift, since each contribution—regardless
of its size—reflects confidence in our efforts to better understand
and treat glaucoma. To all of our donors, thank you for your extraordinary
generosity.
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SPECIAL THANKS
We are especially grateful to the donors listed below
for their generous support during 2001:
Alpin J. and Alpin W. Cameron Foundation
- For unrestricted support
InSite, Inc. - For support of genetics research
T.J. Kavanaugh Foundation - For unrestricted support
Pharmacia Corporation - For support of a Research
Fellowship and for general support
Mr. Nat C. Robertson - For unrestricted support
Estate of Bernard Schepartz - For unrestricted
support
The Scholler Foundation - For ongoing support of
Searchlight on Glaucoma
Mr. and Mrs. Morris M. Shuster - For ongoing annual
support |
 New
Research Fellow Joins Service
New Glaucoma Service Research Fellow, Dr. Leopoldo
Magacho dos Santos Silva, received his medical degree from the
Federal University of Goiás, in the City of Goiâna, Brazil. He
has already published articles in the Brazilian Archives of Ophthalmology,
Archives of Ophthalmology, and the British Journal of Ophthalmology.
He will be working at the Glaucoma Research Center until at least
the end of August.
Optic Nerve Regeneration
in Animal Models
Jonathan S. Myers, MD
An exciting account
of recent experiments demonstrating optic nerve regeneration after
injury in mice was presented at the weekly Glaucoma Rounds on
January 25th. The speaker, hosted by the Glaucoma Service Foundation,
was Dong Feng Chen, MD, PhD, Assistant Professor in the Program
in Neuroscience and Department of Ophthalmology of Harvard Medical
School and the Schepens Eye Research Institute. Her research has
focused on promoting optic nerve cell survival and regeneration.
Previous research has shown that half of a mouse
optic nerve can be selectively damaged. Normally, following such
an injury, additional damage occurs as the body attempts to clear
the damaged nerve tissue. In mice, as in humans, optic nerves
do not regenerate after such injuries. Certain chemicals have
been shown to reduce the additional damage that can occur after
the original injury. Bcl-2 is a protein which inhibits this damage
and promotes nerve survival.
Dr. Chen and coworkers inserted a human gene
for the protein bcl-2 into mice. These mice produced increased
amounts of bcl-2 within their nerve cells. In mice with the gene
and elevated bcl-2 levels, not only was there reduced damage following
optic nerve injury, but also the nerves actually showed partial
regeneration! This work is a groundbreaking step toward understanding
how to block or to repair damaged optic nerves, perhaps some day
even optic nerve damage caused by glaucoma.
It is too early to apply this promising research
to humans. However, the Glaucoma Service is part of a multicenter
research protocol on the effect of brimonidine on normal-tension
glaucoma as compared to that of timolol. Both brimonidine and
timolol lower intraocular pressure, which helps protect against
glaucoma damage. In some animal models, brimonidine has been shown
to help protect nerve cells separately from pressure reduction,
possibly by increasing production of bcl-2. This low-tension glaucoma
study comparing brimonidine and timolol will help determine if
brimonidine has similar effects in human glaucoma. We hope to
have results in 2–3 years.
Glaucoma Service Research
Accepted for Presentation at National Meeting
All of the seven abstracts
submitted by Glaucoma Service Faculty and Fellows for presentation
at the Annual Meeting of the Association for Research in Vision
and Ophthalmology have been accepted for presentation as posters
at the Ft. Lauderdale meeting, May 5th through the 9th.
- Bleb Needle Revision of Failing Trabeculectomies
with Mitomycin C
Moster M, Natanblut L, Shetty R
- Validation of a New Disc Staging Scale:
The Ability to Detect Change over Time
Bayer A, Altangerel U, Henderer JD, Zwick O, Schwartz L,
Schmidt C, Spaeth, G
- Validity of a New Disc Grading Scale for
Estimating Glaucomatous Damage: Correlation with Visual Field
Damage
Shetty R, Bayer A, Harasymowycz P, Chung J, Henderer JD,
Spaeth G
- Glaucoma Screening at Community Senior
Centers: Follow-up Assessment
Uhler T, Kesen M, Henderer JD, Steinmann W
- Influence of Patient Clinical Data on Cup/Disc
ratio Measurement and Optic Nerve Evaluation for Glaucoma
Kesen M, Henderer JD, Steinmann W, Fontanarosa J, Spaeth
G
- Knowledge of the Chronology of Optic Disc
Stereo-Photographs Influences the Determination of Glaucomatous
Change
Altangerel U, Bayer A, Henderer JD, Zwick O, Spaeth G
- The Prevalence of Clinical Outcome Measures
of Quality of Life and Visual Function in Glaucoma Surgical
Studies
Cox MJ, Kesen M, Steinmann W, Spaeth G
April and May Patient Support Group Meetings
Scheduled
These two meetings will take place on Sunday
afternoons, 1:30–3:00 PM in the Wills Eye Hospital auditorium.
For further information, please call 215-503-2986.
April 21: Dr. L. Jay Katz
“Update on Neuroprotection”
May 19: Dr. Jonathan Myers
“Glaucoma Research: At Wills and Around the World”
Dr. Werner “Chats” About Visual Field Testing
On January 30 Dr. Elliot Werner, a glaucoma specialist
at Wills, and the glaucoma chat group (on the Glaucoma Service
website, www.willsglaucoma.org) discussed “Understanding Visual
Fields.” Here are some excerpts from the Chat Highlights prepared
by Norma Devine, Editor of the Highlights for the website.
Moderator: Doctor, is there a typical pattern of loss
of visual field in a glaucoma patient? If so, where is it?
Dr. Werner: Typically, glaucoma patients develop loss
of visual field in the paracentral area. That is, between about
5 degrees and 20 degrees from the center.
P: What area of the visual field is involved first?
Dr. Werner: Most often that’s superiorly, above the center,
and more often on the nasal, or inside, part.
P: Should someone with good visual fields for ten years,
but high intraocular pressure, worry about glaucoma or do something
about it?
Dr. Werner: I wouldn’t worry a lot. Developing glaucoma
damage is a risk, but the risk is fairly low.
P: Dr. Werner: Does the vision loss from a cataract show
up differently on the field than the loss from the glaucoma? In
other words, is it easy to tell the difference in a person who
has both?
Dr. Werner: Yes, the visual field defects are quite different
and can usually be distinguished, but it requires clinical examination
as well.
P: I have been advised to start with a different eye
at every testing, but my left eye is much worse than my right.
Should I not always start with the worst eye?
Dr. Werner: There is a fatigue effect with perimetry,
so it is a good idea to alternate eyes.
P: I have a visual field test tomorrow. Any tips?
Dr. Werner: Don’t worry. Just look straight ahead and
push the button when you see the light. The machine will accurately
measure your visual field if you do that.
P: You can hold the button down to stop the test if you
need to rest.
P: The last visual field test I took was with a new glaucoma
specialist. I was so anxious to have a good test, I was exhausted
and dizzy afterward. Did I overdo my intensity in trying to see
as many lights as possible?
Dr. Werner: Yes. There are no right or wrong answers.
Just relax, breathe normally and push the button when you’re sure
you see the light. If you’re not sure, it’s best not to push.
P: I have been told to push the button if I think I see
the light. There are many times, especially as the test goes on
and I am tired, that I click, probably because I think it is about
time and I am not sure. I’m afraid I’d really have a poor test
if I only indicated when I was sure.
Dr. Werner: Generally, patients who push the button because
they think they should do not give reliable results. It is best
to be sure you see the light even if some time goes by and you
don’t see anything. Patients need to receive detailed and easily
understood instructions.
P: Does the test start with brightest light at each spot
and then progressively dim to the point that the patient can no
longer detect the light at each individual spot?
Dr. Werner: No. The machine presents dim and bright lights
in a random sequence to come to the brightness that the patient
is just able to perceive—called the threshold.
P: Would you please explain about testing the blind spot
at the beginning of the test and sometimes during the test?
Dr. Werner: The blind spot is tested several times during
the test to be sure the patient is not moving his or her eye around
too much. The blind spot should be in the same place all the time
and the machine “knows” that.
P: The visual field test has gotten shorter over the
years. Any chance that it may get shorter still?
Dr. Werner: Yes. In fact, in a few years we may have
objective visual field testing that does not require any response
from the patient. There are some very exciting techniques in development
right now.
P: How long should a normal test take?
Dr. Werner: A normal test with the new SITA program takes
between 5 and 8 minutes per eye.
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