Volume 7, Number 2
Spring, 1998
Neuroprotection:
Help for the Glaucoma Patient?
People with glaucoma do not always retain their vision. In some
cases this is because the glaucoma is far-advanced before it is
detected. Other people do not care for themselves properly and
their glaucoma consequently gets worse. Still others are not cared
for appropriately by their physicians and their glaucoma gets
worse. But somewhere around one third of all those with the commonest
type of glaucoma, idiopathic open-angle glaucoma, get worse even
when they are under the care of skilled physicians and they care
for themselves well. How can that be?
Why, Despite Everything Do Some Glaucoma
Patients Get Worse?
One reason why patients believed to have glaucoma get worse is
because in fact they do not really have glaucoma. Diagnoses cannot
always be made with 100% accuracy, and sometimes a condition can
look like glaucoma but not be glaucoma.
Sometimes a person can have glaucoma and develop another condition
which causes glaucoma-like damage and is not considered because
attention is being paid by the physician and the patient to the
glaucoma that both know the patient has. Because it is not yet
possible to determine just what is the right level of intraocular
pressure that will prevent further damage in a specific patient,
sometimes treatment is too vigorous, and the treatment itself
causes problems. Sometimes the treatment is not vigorous enough,
and the glaucoma gets worse, until it is noted that it is getting
worse, and more vigorous treatment is initiated.
It is also likely that there are some types of glaucoma in which
the optic nerve becomes so damaged that damage continues even
when the intraocular pressure is very low, even as low as 8 mm
Hg.
Isn't There Some More Effective
Way to Keep Glaucoma Patients from Getting Worse?
For all of these reasons, and surely for others as well, some
patients with glaucoma get worse. This is discouraging for everybody.
Consequently, other methods than just lowering intraocular pressure
have been studied to see if it is possible to prevent people with
glaucoma from getting worse.
Neuroprotection
Since the usual reason why people with glaucoma lose vision is
because of damage to the nerve cells (the ganglion cells) that
send electrical impulses from the retina back to the brain it
would make sense to try to protect
these cells from becoming damaged. That is what lowering intraocular
pressure tries to do. But perhaps there are other ways of protecting
the cell. This idea of protecting nerve cells, neuroprotection,
is an old one and was attempted by physicians in the past such
as Bernard Becker at Washington University in St Louis. Recently
the idea has surfaced again, at least partially as a consequence
of many new discoveries in the fields of genetics, neurobiology,
and pharmacology.
But before proceeding further, the reader should know that, to
date, there is no proof that there is any way to protect the nerves
of patients with glaucoma other than lowering the pressure within
the eye. Every other approach, so far, is something that is appropriate
to do in addition to lowering
intraocular pressure the appropriate amount, and not
in place of lowering the intraocular pressure the proper amount.
Why Do Nerve Cells Die?
Cells are factories. They need fuel, they make wastes, they need
instruments to utilize the fuel and dispose of the wastes, and
they must have structural integrity in order to survive. The ganglion
cells of the retina need sugar and oxygen, but they also need
nerve growth factors to sustain them. They can be killed by their
own waste products, such as the acids that result from burning
sugars and fats, the ammonias that result from using protein.
A toxin of special interest in glaucoma is glutamate, a substance
which is essential for cell functioning, but which in excess can
cause the death of the cell. The wall of the cell must be intact,
but must function to let in those things it wants and keep out
those things it does not want. Calcium is needed for the heart
to beat properly, for the bones to develop, but when the cell
membrane breaks down and allows the calcium outside to get inside,
the cell quickly dies. Some substances cause cells to become excited,
and when present in excess, can literally excite the cells to
death. Many different genes control the way these processes occur,
normally or abnormally, and how they are changed and modified
depending upon the environment in which the cell finds itself.
Using Drugs to Block the Mechanisms
that Cause Nerve Cells to Die
Blocking these processes can keep cells from dying. For example,
some of the agents used to treat high blood pressure, such as
"Procardia" (nifedipine) or nimodipine stabilize the cell membrane
and prevent excess calcium from entering the cell. These "calcium
channel blockers" have been studied extensively in the field of
glaucoma. Kitazawa, in Japan, is convinced that they can help
prevent damage in some patients with glaucoma, especially those
in whom damage occurs with low pressures. Others, including those
of us at Wills Eye Hospital, are less certain that this is a wise
approach. The calcium channel-blockers have a variety of side
effects, including low blood pressure, which could result in less
blood flowing to the eye, making the glaucoma worse. Additionally,
we have not been able to confirm a beneficial effect.
Protection of nerves would be beneficial in many conditions other
than just glaucoma. However, in general, little benefit has been
demonstrated in these other areas either. Lou Gehrig's disease
(amyotrophic lateral sclerosis) is a rare condition in which there
is gradually loss of function of the nerves that move the muscles;
some individuals with Lou Gehrig's disease have been helped by
being treated with a neuroprotective agent. Other than for this
one condition, however, neuroprotection is more of a promise than
an actuality.
It is quite interesting that two drugs already used in the treatment
of patients with glaucoma have been shown to have a neuroprotective
effect. That is not to say that they have been shown to have a
neuroprotective benefit in glaucoma. But betaxolol (Betoptic)
and brimonidine (Alphagan) in certain experimental cases have
been shown to limit damage to neurons. Additionally, three studies
have suggested that patients with glaucoma who are treated with
betaxolol have more preservation of their visual field than would
be expected on the basis of lowering intraocular pressure alone.
These studies, however, are preliminary and not conclusive.
The Neuroprotection Provided by a
Healthy Life-Style
There are a variety of other approaches to the whole field of
neuroprotection, some of which were hinted at in our earliest
discussion of the relationship between life-style and glaucoma.
It is prudent to live in a way that keeps one's general health
as thriving as possible. Certainly, good general health is neuroprotective.
For example, alcohol is highly toxic to living cells. That is
why alcohol is used as an antiseptic agent to kill bacteria. Sensitivity
to alcohol toxicity varies from person to person. In many individuals
small amounts of alcohol appear to be tolerated without any harmful
biological effect. But for some people, especially those of Asiatic
descent, even minimal amounts of alcohol are damaging; for everybody
large amounts of alcohol are devastating to the well-being of
the body.
Also, for example, marked malnutrition, especially lack of the
B vitamins, causes severe neurologic disease. It does not follow
that taking large amounts of certain nutrients, such as "megadoses"
or vitamin B, is a healthy thing to do. Indeed, excess amounts
of almost all nutrients cause diseases themselves, including large
amounts of some of the B vitamins.
The Take-Home Message
- There is a great deal of interest in the
field of medicine and in the field of glaucoma in finding ways
to protect nerves from becoming damaged.
- The only proven way to prevent progression
of glaucoma damage is to lower intraocular pressure an appropriate
amount in the individual with glaucoma.
- Avoiding known toxic agents and caring
for one's body and spirit are good for one's heart and soul
and probably help with glaucoma also.
- Every drug and every treatment has side
effects, some of which are serious or even fatal, and this includes
"neuroprotective agents" as well.
Therefore, any treatment should be approached with careful consideration
of the known and potential risks and the known and potential benefits.
Neuroprotection may be an important part of treatment for glaucoma
in the future. At the present time, however, treatments alleged
to be "neuroprotective" are mostly "mirrors," reflecting the hope
of the investigator or the desperation of the patient, and they
should be used with full recognition that they are still investigational
and not without problems themselves.
In contrast, being fit physically,
emotionally, and spiritually is probably more likely to be specifically
beneficial to nerves, and, of course, has no negative side effects
at all.
| The Foundation gratefully acknowledges
receipt of a $30,000 grant from the Scholler Foundation to
support the printing and distribution of the Searchlight. |
 At
a special luncheon meeting of the Foundation Board, Dr. Richard
Wilson (left) presents Board of City Trusts President Louis Esposito
a hand-lettered scroll naming the Louis Esposito Professorship
in the Study of Glaucoma.
Foundation Board Elects
Five New Trustees
At a special meeting of its
Board of Trustees on April 9th, the Glaucoma Service Foundation
announced the election of five new Trustees:
- James Kim, Chairman of Amkor Electronics
- David Eastburn, Former Chairman,
Federal Reserve Bank of Philadelphia
- Stephen Harmelin, Esq., Partner
in Dilworth, Paxson, Kalish & Kauffman
- Stanley Tuttleman, Investor and
Principal Partner of Tuttson Capital Corporation
- Roffe Wike, Investor Speaking for
the Board, Chairman
S. Stoney Simons said, "With
the addition of these remarkable people to the Board we have taken
a large step forward in strengthening the Foundation's capacity
to advance sophisticated research into the nature and treatment
of glaucoma."
Dr. George Spaeth, Director
of the Glaucoma Service and President of the Foundation noted
that, "Glaucoma is a silent and often undiscovered destroyer of
sight that affects millions of people around the world. The Foundation
is taking dramatic steps in helping us to diagnose, treat and
deal with the disease as a major threat to health, particularly
among seniors."
During the meeting, Dr. L.
Jay Katz of the Glaucoma Service described some of the newest
techniques being used at Wills to treat glaucoma, and Dr. Mon
Harris, noted glaucoma investigator at the University of Indiana,
spoke on current clinical research being conducted on the relationship
between blood flow to the optic nerve and glaucoma.
During the course of the
meeting Dr. Richard Wilson of the Glaucoma Service staff presented
Mr. Louis Esposito, President of the Board of City Trusts, which
oversees Wills Eye Hospital, a hand-lettered scroll announcing
the naming of a new Professorship in Glaucoma Studies for Mr.
Esposito. In accepting the scroll, Mr. Esposito noted, "Wills
has become one of the leading centers in the world for the treatment
of eye disease, and the establishment of the new Clinical Research
Program will rapidly multiply its capabilities." Ophthalmologist-in-Chief
Dr. William Tasman noted that the establishment by the Board at
Wills of four professorships will create an entirely new era of
eye research activity and will significantly increase the already
heavy international patient load at Wills.
| 
Dr. L. Jay Katz (left) of the Glaucoma Service Staff
and real estate developer Mr. Jack Wolgin, glaucoma patient
and friend of the Foundation.
(Photo by Jamie Nicholl)
|
Dr Richard Wilson (left) of the Glaucoma Service
Staff, Board Foundation Chairman S. Stoney Simons (middle),
and Dr Spaeth.
(Photo by Jamie Nicholl)
|
Louis Esposito and his wife Ann with Wills Ophthalmologist-in-Chief
Dr William Tasman (right).
(Photo byJamie Nicholl) |
Education/Screening Project
Initiated
 At
a special meeting sparked by Foundation Trustee Nettie Taylor,
on May 1st in the Wills Eye Auditorium, Foundation President George
Spaeth and Wills ophthalmologists Drs. Walter Harris and Leslie
Brown discussed with African-American clergyman representing five
churches in the Philadelphia area ways of responding to the fact
that the incidence of glaucoma is now seven to eight times higher
in the African American community than in the population.
Dr. Spaeth emphasized the
need for education about the disease
and strategies for early detection among this high-risk population.
Criticizing the typical "doctor knows best" attitude, Dr. Spaeth
urged the clergymen present to help their parishioners learn how
to take responsibility for their own health and well being.
Much of the subsequent discussion
focused on the screening process and on the ways it can be communicated
and enhanced. Dr. Spaeth and his colleagues offered to go anywhere
in the region to speak about glaucoma and to explain the critical
need for early detection. As for the screening process, the consensus
was that this might most effectively be accomplished through the
use of mobile units. It was suggested that this approach might
be tried on an experimental basis at selected locations.
Implementation of the program
is expected some time in the Fall.
Dr. Myers Describes Current Foundation Research
At the final meeting of the season of the Glaucoma
Patient Support Group on Sunday, May 17th, Dr. Jonathan Myers
of the Glaucoma Service staff and Assistant Director of Research
for the Foundation in addition to speaking about the training
ophthalmologists receive, spoke about current research being done
on the Service.
Dr. Myers explained that patients have crucial
roles to play in these efforts. He noted that patients should
tell their doctors about things they notice (for example, longer
eyelashes on a new medicine), participate themselves and encourage
others to participate in studies, and even suggest ideas for research
projects. He also encouraged them to support the Foundation's
research through donations. The following are representative of
both completed and ongoing studies.
Drug Studies
Three relative new drugs, already familiar to many glaucoma patients
taking eye drops to lower their intraocular pressure to levels
required to minimize damage to the optic nerve are Alphagan, Trusopt
and Xalatan (pronounced ZAL a tan). The following are representative
of Foundation studies of these three medications:
Background: Both
Alphagan and Trusopt have been shown to further lower intraocular
pressure when added to the schedule of patients already taking a
beta-blocker (for example, Timoptic or Betagan).
Question: Which
one, Alphagan or Trusopt, is more effective in this regard?
Answer: Regardless
of whether Alphagan or Trusopt was added, 10% to 20% additional
reduction in pressure was achieved.
(The same question is being asked with regard to
Alphagan and Xalatan in an ongoing study.)
Background: Xalatan
is in a class of pressure-lowering drugs known as prostaglandins,
some of which have been demonstrated to affect blood flow. Altering
blood flow to the retina could be undesirable in glaucoma patients,
because it could deprive optic nerve cells in the retina of needed
nourishment.
Question: Does
Xalatan have any effect on blood flow to the retina?
Answer: Xalatan
had no effect on blood flow to the retina.
Background: Both
Alphagan and Timoptic lower eye pressure, but Alphagan has been
shown to protect optic nerves in rats in some way other than by
lowering pressure.
Question: Does
Alphagan protect patients with low-tension glaucoma better than
Timoptic?
Answer: Ongoing.
Alternative Medicines
Background: Alternative
medicines in general are being used by more and more people. Any
disease, such as glaucoma, for which there is no cure invites patients
to perform their own research in the sense that they are eager to
see if something the doctor did not prescribe might help.
Question: What
percentage of glaucoma patients are trying alternative medications
such as bilberry, gingko, or marijuana to treat their condition?
Results: Ongoing.
One thousand patients are being surveyed anonymously.
Glaucoma and Near-Sightedness
Question: Does
the fact that a person is near-sighted have any effect on that person's
optic nerve? Does the amount of refractive error affect the course
of glaucoma?
Answer: The optic
nerves of near-sighted people appear to have different patterns
of optic nerve damage than those with 20/20 vision, and this fact
should be taken into account in making treatment decisions.
Neuroprotective Drugs
Background: In
his article in this newsletter Dr. Spaeth discusses neuroprotective
drugs.
Question: Can
the neuroprotective drug memantine keep the optic nerve cells of
glaucoma patients from dying?
Answer: This study
is ongoing.
Complications of Glaucoma Surgery
Background: Sometimes
the blister or bleb created by glaucoma surgeons to allow the fluid
in the eye to flow out of the eye more easily and thereby reduce
intraocular pressure develops a leak.
Question: Can
these leaks be closed using transplanted conjunctival tissue?
Answer: Such transplants
were found effective in aiding leak closure.
In Appreciation
The Foundation deeply appreciates the
many gifts received from friends and relatives in memory
of Dr Spaeth's long-time patient, Mr. Daniel M. Layman,
who passed away April 12, 1998.
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