-
FOUR QUESTIONS REGARDING GLAUCOMA
Here are four relevant questions which I believe have never been authoritatively answered.
1. What evidence is there that high IOP causes glaucoma?
2. If there is no evidence that it does -- why try to reduce IOP?
3. What physical, chemical or biological mechanism can explain how high IOP
causes optic nerve degradation?
4. Why don't pearl divers and other free divers all go blind because of the
pressure increase in their eyes when they are under water? (I am under the
impression that any increase in IOP, can't adversely affect any cell within
the eye --
since
everything
within the eye is essentially water-filled
and the pressure would instantly equalize across all cell membranes.)
Please consider the following -- I am an engineer
by
training
and
was diagnosed in 1999 by an ophthalmologist in Santa Barbara as being in danger of developing glaucoma.
I considered the diagnosis to be a mistake that was based on a visit
to
the doctor where he measured my intraocular pressure (IOP) as about 20 mmhg.
The doctor suggested treatment and I refused, based on my suspicion that the
diagnosis was faulty.
I subsequently investigated the subject of "glaucoma" and came to
the general conclusion that glaucoma is often misdiagnosed because there is
little evidence
available as to what causes glaucoma.
Along the way, I was thrown off a glaucoma
listserve email group -- seemingly
because I asked too many pointed questions
that undermined the authority of doctors and "frightened" some young
members of the email group. Robert Ritch, MD (ritch@inx.net) / Professor and
Chief,
Glaucoma Service / the New York Eye and Ear Infirmary / 310 East 14th Street,
New York, NY 10003, was a member of the email group. He was quite helpful when
I first started asking questions, but his patience wore thin over time when
I suggested none of the information he proffered seemed to show that high
IOP actually causes glaucoma. I think the email group was sponsored by The
Glaucoma Foundation. Evidently, the email group has since been abandoned or changed
its name.
I consider the following 7 points to be provable facts:
1. Virtually all ophthalmologists and every glaucoma organization "know" and
teach that glaucoma (progressive deterioration of optic nerve cells) and high
intra-ocular-pressure (IOP) are often, but not always seen together. They say
high IOP is a "risk factor" --- (they never say it is a symptom)
2. Glaucoma is often seen in low IOP individuals.
3. High IOP individuals sometimes do not have glaucoma.
4. I have asked authoritative sources if any tests or data
or evidence prove that high IOP CAUSES glaucoma and that they are not both
byproducts of some
other
factor, like aging. They hedge -- but generally answer, "no".
5. I have investigated the literature and can find
no evidence of a cause and effect relationship. Some authorities have sent
me technical papers
supporting
their theory that high IOP cause glaucoma -- but my reading of these papers
tells me the papers do not show that at all.
6. Virtually all glaucoma treatments (eye drops, laser and
knife surgery) are aimed at reducing IOP.
7. These treatments quite frequently have serious side effects.
Martin R. Carbone.
By the way -- it is now nine years after I was first advised to start treatment to ward off glaucoma. My eyesight is just about the same as it was then. Evidently I have not had significant degradation of the retina. I do have cataracts now, but my current eye doctor adivises against removing them because my sight is too good for the operation to be paid for under Medicare.
Find out more about Glaucoma
A variety of global patient advocacy organizations claim, in ads through Pfizer http://www.pfizeropthalmics.com , that
they can provide a wealth of up-to-date information, support, and resources that will help you to protect your vision.
Write to them and ask them what evidence they have that high Intra Ocular Pressure (IOP) causes glaucoma.
Click on the links below to visit their individual Web sites and learn more about them.
World Glaucoma Association
http://www.globalaigs.org/
World Glaucoma Patient Association
http://aigpo.org/
International Glaucoma Association
http://www.glaucoma-association.com
The Glaucoma Foundation
http://www.glaucomafoundation.org/
Glaucoma Research Foundation
http://glaucoma.org/
Glaucoma Australia
http://www.glaucoma.org.au/
Glaucoma Friends Network
http://www.gfnet.gr.jp
FREQUENTLY ASKED QUESTIONS: GLAUCOMA
I think this authoritative report on frequently asked questions supports my contention that no evidence is available that shows high IOP is a causative factor in the development of glaucoma. Reading of the report therefore supports my conclusion that it is improper to treat high IOP in any manner that is known to cause unpleasant or dangerous side effects (MRC)
Reprinted here in accordance with permission statement shown below in bold.
Copyright, (a) Robert Ritch, MD (ritch@inx.net) / Professor and Chief, Glaucoma
Service / the New York Eye and Ear Infirmary 310 East 14th Street, New York, NY 10003 and (b) Jeffrey Liebmann, MD (liebmann@inx.net)
/ Clinical Associate Professor of Ophthalmology / Associate Director, Glaucoma
Services / The New York Eye and Ear Infirmary
This is the FIFTH posting of this FAQ sheet.
Permission to copy all or part of this work and post to other Websites
is granted provided that the copies are not made or distributed for resale, and provided that the AUTHOR, COPYRIGHT and NO WARRANTY sections
are retained verbatim and displayed as is.
THE AUTHORS PROVIDE NO WARRANTY. THE INFORMATION IS PROVIDED TO ASSIST UNDERSTANDING
OF GLAUCOMA. IT DOES NOT REPLACE AN EYE EXAMINATION AND IS NOT MEANT AS A GUIDELINE
FOR TREATMENT OF ANY INDIVIDUAL PERSON SUFFERING FROM GLAUCOMA.
For additional information about glaucoma, see <<http://www.web-xpress.com/nygri>>, and <<http://www.nyee.edu>>
Your feedback is welcome.
OUTLINE
I. WHAT IS GLAUCOMA?
A. What glaucoma is not
B. What glaucoma is
C. The problem with terminology
II. THE EYE AS A CAMERA
III. HOW GLAUCOMA DEVELOPS
A. Intraocular pressure
B. IOP versus other risk factors
IV. CLASSIFICATION OF THE GLAUCOMAS
V. THE OPEN-ANGLE GLAUCOMAS
A. Primary open-angle glaucoma
B. Pigment dispersion syndrome / Pigmentary glaucoma
C. Exfoliation Syndrome
D. Normal-Tension Glaucoma
E. A diagrammatic overview
VI. ANGLE-CLOSURE GLAUCOMA
A. Acute angle-closure glaucoma
B. Chronic angle-closure glaucoma
VII. GLAUCOMA IN CHILDREN
A. Congenital glaucoma
C. Juvenile primary open-angle glaucoma
D. Sturge-Weber syndrome
E. Aniridia
F. Glaucoma associated with uveitis
VIII. WHO IS AT RISK FOR GLAUCOMA?
IX. DIAGNOSING GLAUCOMA
A. Tonometry
B. Perimetry
C. Ophthalmoscopy
D. Gonioscopy
X. TREATMENT OF GLAUCOMA
A. Eye drops
B. Laser Surgery
1. Open-angle glaucoma
a. Laser trabeculoplasty
2. Angle-closure glaucoma
a. Laser iridotomy
b. Argon laser peripheral iridoplasty
C. Operative Surgery
1. Filtering surgery
2. Glaucoma implants
3. Combined cataract and glaucoma surgery
4. Cyclophotocoagulation
5. Setons
-----------------------------------------------------------------------------
I. WHAT IS GLAUCOMA?
A. What glaucoma is not
Glaucoma is not a single entity. Rather, there are specific conditions that
lead to glaucoma. A specific condition has a defined cause, mode of onset,
pathophysiology, and course. Intervention can potentially occur at a number
of different stages, from prevention, to treatment, to cure, and to reversal
of damage caused by the disease.
Over the last 50 years, what we could call the CENTRAL DOGMA has held sway.
This dogma goes as follows:
1. Glaucoma is a disease caused by elevated intraocular pressure (IOP). The
elevated IOP damages and destroys the axons of the optic nerve, leading to
progressive blindness.
2. Glaucoma can be divided into two broad types - OPEN-ANGLE and ANGLE-CLOSURE.
Each of these, in turn, can be divided into primary and secondary forms. This dogma has played a major role in retarding thinking
and inhibiting new approaches to understanding and therapy of glaucoma, and
it should be discarded.
B. What glaucoma is
Glaucoma is the end result of a variety of diseases, and is analogous to heart
failure or liver failure, each of which can result from a number of different
causes. Glaucoma is a progressive optic neuropathy (a disease of the optic
nerve) characterized by a specific pattern of optic nerve head and visual field
damage. Damage to the visual system in glaucoma is due to the death of the
retinal ganglion cells, the axons of which comprise the optic nerve and carry
the visual impulses from the eye to the brain. Glaucoma represents a final
common pathway resulting from a number of different conditions that can affect the eye, many of which are associated with elevated IOP. It is important
to realize that elevated IOP is not synonymous with glaucoma, but rather is
the most important risk factor we know of for the development and/or progression
of glaucomatous damage.
Other risk factors for glaucomatous damage besides elevated IOP have really
only begun to be explored in the past decade. Much remains to be discovered,
so that new approaches to treatment can be devised. We can refer to these other
risk factors as non-pressure-dependent risk factors, and the damage they cause
as non-IOP-dependent damage. This will described in more detail in Section
III.
The most intensively investigated cause of non-pressure-dependent glaucomatous
damage is the possibility of an insufficient blood supply to the optic nerve
head and adjacent retina. This is presently believed to be a major risk factor
for glaucomatous damage. However, other hemorheologic (flow properties of blood)
abnormalities, such as increased erythrocyte agglutinability (tendency for
red blood cells to stick to each other), decreased erythrocyte deformability
(ability of the red blood cells to change shape so that they can squeeze into
capillaries), increased serum viscosity, or increased platelet aggregability
may also play a role, as may certain cardiovascular conditions, such as atrial
fibrillation.
Other possible risk factors, most of which have been as yet little explored,
include low blood pressure, abnormally low intracranial pressure, autoimmune
phenomena, sleep apnea, sleeping with the pillow or one's knuckles pressed
against the eye, an abnormally hard or soft lamina cribrosa (the stack of platelike "
perforated wafers" through which the optic nerve cells pass through the
eye), inherited or acquired abnormalities of the connective tissue of the lamina cribrosa, primary ganglion cell degeneration, and other as yet
unconsidered possibilities.
C. The problem with terminology
The attempt to fit modern concepts into century-old terminology creates confusion
in the minds of physicians and patients alike. Ask 5 glaucoma specialists just
what exactly is primary open-angle glaucoma (POAG) and you may get 5 different
answers. For instance, we use the term POAG to refer to a patient with elevated
IOP and visual field and/or optic nerve damage, while reserving the term "
ocular hypertension" for persons with elevated IOP but no detectable disc
or visual field damage. A better term for the latter group is "
glaucoma suspect," which includes both ocular hypertensives and persons with large cup/disc ratios who may have early normal-tension glaucoma
but still have normal visual fields. Open-angle glaucoma implies visual field
damage, but angle-closure glaucoma does not. Someone with a closed angle and
markedly elevated IOP is deemed to have acute closed-angle (angle-closure)
glaucoma, and one with a mostly closed angle, a normal disc, a normal visual
field, and scar tissue in the angle is called "chronic angle-closure glaucoma." In
some instances we use the term to describe the disc and field damage, in others
the angle damage, and in still others the pressure alone. It is therefore best
to understand the mechanisms of the various entities which lead to glaucoma
and not become bogged down in definitions.
II. THE EYE AS A CAMERA (Figure 1)
The eye captures information about shape,
color, and movement and relays it in the form of nerve impulses to the brain.
The brain processes this information into the "pictures" we see.
The outer, white layer of the eyeball is the sclera, a tough, leathery protective
shell. The front, transparent portion of the shell is the cornea, through which
light enters the eye. The cornea is much like the lens of a camera, providing
the eye with much of its focusing power.
The colored portion of the eye is the iris, which functions like the diaphragm
of a camera. The iris contains muscles which control the size of the pupil,
regulating the amount of light entering the eye. The pupil constricts in bright
light and dilates in dim light, adjusting the amount of light which passes
through the pupil to the retina, which is analogous to the camera's film. The
two layers of cells on the back of the iris are so filled with melanin pigment
that they are black, and are known as the iris pigment epithelium. They prevent
light from passing through the iris anywhere but through the pupil. The difference
between blue and brown irises is the amount of pigment in the front portion
of the iris. The lens behind the iris is also transparent, and adjusts its
shape and thickness to fine focus the image onto the retina. When we read,
the eye accommodates to refocus a near image. The lens enlarges throughout life as it produces new cells. The ability to accommodate decreases
steadily throughout life. Presbyopia occurs when there is not enough accommodative
power remaining to read without glasses, usually in the early 40s. A cataract
is an opacification of the lens, so that vision decreases and cannot be corrected
by changing the power of one's eyeglasses. When the cataract is sufficiently
dense to interfere with one's
activities, surgery becomes necessary.
The lens is held in place by the zonules, which are analogous to the ropes
holding the mat of a trampoline in place. When the eye accommodates, the muscle
holding the zonules against the wall of the eye tightens, loosening the hold
of the zonules on the lens and allowing it to moveslightly forward and increase
in thickness to refocus the image of the close object being looked at on the
retina.
The iris, lens, and zonules play an important role in three common conditions
which lead to glaucoma - pigment dispersion syndrome, exfoliation syndrome, and angle-closure. After passing through the lens, the
light enters the vitreous, a gel-like substance which serves as the shock absorber
for the eye, and then reaches the retina. The retina then delivers the image
to the brain via nerve signals which are sent through the optic nerve to the
brain, which processes these signals into a "picture", or visual
image.
The anterior chamber, or front compartment of the eye, is bounded by the cornea,
iris, pupil, and lens (Figure 2). It is filled with a watery fluid called aqueous
humor, which provides the cornea and the lens with oxygen and vital nutrients.
The aqueous humor also provides the necessary pressure (IOP) to maintain the
shape of the eye. It is secreted into the posterior chamber (the fluid compartment
behind the iris) by the ciliary body, a tiny gland which runs circumferentially
behind
the iris, passes between the iris and the lens into the anterior chamber, and
then flows out through the trabecular meshwork, a tiny sponge-like tissue which
runs circumferentially at the corneal periphery just anterior to the iris.
After passing through the trabecular meshwork, the aqueous humor enters a tiny
circumferential
capillary called Schlemm's canal.
In order to comprehend the
effect of increased IOP, think of the eye as a balloon. When too much air is
blown into a balloon, pressure causes it to pop. But the eye is too strong
to pop. Instead, it gives at the weakest point, which is the site in the sclera
at which the optic nerve leaves the eye. The optic nerve, which carries visual
information to the brain, is made up of over one million nerve cells, and while
each cell is several inches long, it is extremely thin - about one twenty-thousandth of an inch in diameter. Simplistically,
elevated IOP compresses the axons of the nerve cells, causing them to become
damaged and eventually die, resulting in permanent visual loss. Early diagnosis
and treatment can help prevent this from happening.
As a general rule, in the open-angle glaucomas, the eye is anatomically normal,
but blockage or malfunction of the drain of the eye (the trabecular meshwork)
leads to elevated IOP. In normal-tension glaucoma, the major risk factors causing
the glaucoma are not in the trabecular meshwork, but act at the level of the
optic disc. In angle-closure glaucoma, the trabecular meshwork is normal, but
the iris is pushed against it, blocking the flow of fluid (aqueous humor) from
the eye.
The analogy to a sink is a useful one. In a normal eye, the faucet is always
on and the drain is always open. In open-angle glaucoma, the drain gets clogged.
When this happens, aqueous can not leave the eye as fast as it produced, causing
the fluid to back up. Since the eye is a closed compartment, the "sink" can't
overflow. Instead, the backed up fluid causes increased pressure to build up
within the eye. We need to use chemical drain-cleaner (eye drops) to open the
drain or turn down the faucet. If this is insufficient, we can snake the drain
(laser trabeculoplasty), and if that doesn't work, we need to put in new plumbing
(surgery).
In angle-closure glaucoma, the drain is normal, but it's covered by a stopper.
We need to remove the stopper (laser iridotomy or laser iridoplasty) rather
than treat with medications. Open-angle and angle-closure glaucomas are about
as alike as a heart attack and a bullet wound to the heart. The disease mechanisms,
the basic approach to treatment, and the prognosis all differ. And that is
why the terminology is confusing.
III. HOW GLAUCOMA DEVELOPS
A. Intraocular Pressure
Glaucoma has been so intimately connected with the concept of elevated IOP
that a detailed explanation of how these concepts arose, how they have been
used in the management of the disease, and our present concepts of the origin
of glaucomatous damage, which are presently in an active stage of evolution,
is warranted.
The average IOP ranges between 14 and 20 millimeters of mercury (mmHg). A pressure
of 22 is considered to be suspicious and possibly abnormal. However, not all
patients with elevated IOP develop glaucoma-related eye damage. The choice
of 22 mmHg as the dividing line between normal and abnormal was based solely
on statistics. Population studies in the 1950s found an average IOP of about
15.5 mmHg. Two standard deviations from the mean above this was taken as the
upper limit of normal, so that about 2.5% of the population fell above this
line. However, as often happens, what was a conceptual demarcation became established
over a few years into a normal versus disease situation, and It became common
to treat anyone with an IOP of 22 mmHg or more to lower the pressure. By the
late 1960s and early 1970s, it had become evident that only about 10% of people
with an IOP of 22 mmHg or more would develop glaucomatous damage. The higher the IOP, the
greater the chances of developing damage. People with an IOP of 22 mmHg or
more came to be termed ocular hypertensives. Again, this was a working definition,
but later became treated as if it were a separate disease. Ocular hypertension
merely means that a person has an elevated IOP of 22 mmHg or more but no detectable
damage on optic nerve or visual field examination. If a person with ocular
hypertension develops damage, he or she then becomes diagnosed as having glaucoma.
For reasons stated earlier, "
glaucoma suspect" is a better term, and "ocular hypertension" should
be reserved just for dividing patients into different categories for
clinical studies.
Once a sufficient number of nerve cells are destroyed, "blind spots",
or scotomas, begin to form in the field of vision. These scotomas usually develop
first in the peripheral field. Later, the central vision, which we experience
as "seeing", is affected. Once visual loss occurs, it is irreversible
because once the nerve cells are dead, nothing can restore them at the present
time.
B. IOP versus other risk factors
The relationship between IOP as a risk factor and non-pressure-dependent risk
factors in the causation of glaucomatous damage is depicted in Figure 3. The
higher the IOP at which damage develops, the greater the component of pressure-dependent
damage. The lower the IOP at which damage progresses, the greater the contribution
of non-pressure-dependent factors. There is no magic number separating those
with primarily pressure-dependent damage (so-called high-tension glaucoma)
from those with primarily non-pressure-dependent damage (so-called normal-tension
glaucoma). Moreover, the particular IOP at which 50% of damage is due to each
of the risk factor categories can vary from individual to individual or even
in an individual over time.
These non-pressure-dependent factors have been primarily conceived of as causes
of normal-tension (low-tension) glaucoma. However, they are likely to play
a role in high-tension glaucoma as well. Underlying pressure-dependent or non-pressure-dependent
mechanisms of damage may be construed as comprising a spectrum. The higher
the IOP at which damage develops, the greater the component of pressure-dependent
damage. Angle-closure glaucoma, juvenile open-angle glaucoma, and exfoliative
glaucoma fall into this category. The lower the IOP at which damage continues
to progress, the greater the contribution of non-pressure-dependent factors.
A patient who develops glaucomatous damage at an IOP of 14 mmHg most certainly
has a
preponderance of non-pressure-dependent factors.
Looking at glaucomatous damage
in this manner enables us to focus on attempting to ascertain the relative
contribution of pressure-dependent and non-pressure-dependent factors. A patient
presenting with IOP of 40 mmHg obviously needs immediate treatment to lower
the IOP. A patient presenting with maximum IOP of 18 mmHg and glaucoma (i.e., "normal-tension" glaucoma
by definition) may benefit from lowering IOP, but this is done primarily because
we have little other choice of therapy. In the future, this will change. It
is the patient presenting with visual field loss at IOP in the mid-20's that most likely has a multi-mechanism cause of damage. Therefore, whereas lowering
IOP to 20 mmHg (i.e., "normal") will ordinarily suffice
for the patient presenting with IOP of 40 mmHg, at least if the patient does
not have extensive damage), whereas lowering it to 20 mmHg in a patient with
multi-mechanism disease may not be sufficient.
This concept also makes it easier
to see how susceptibility toglaucomatous damage can change over time. Many
studies have shown that "
ocular hypertensives" convert to glaucoma at a rate of about 1% per year.
But why do they convert? Glaucomatologists have long held that damage builds
up slowly until it finally reaches a great enough extent to be detectable on
ophthalmoscopic or perimetric examination. There is another possibility, just
as likely, that other risk factors for glaucomatous damage may develop even
though IOP remains constant. A patient who is 40 years old and in good physical
condition may be expected to withstand an IOP of 26 mmHg for a long time. However,
as that patient ages, and cardiovascular disease develops, the eye may not
be sufficiently perfused so that it can no longer withstand that IOP of 26
mmHg. Similarly, changes in the lamina cribrosa, supporting nerve cells (e.g.,
astrocytes), systemic blood pressure abnormalities, development of diabetes,
etc., may compromise the status of the optic nerve.
IV. CLASSIFICATION OF THE GLAUCOMAS
Epidemiologically, glaucoma affects people of all ages in every population
in the world, so that an estimated 65 million people worldwide have it. In
dividing up glaucoma, there are 5 common entities which comprise the greatest
proportion of the affected populations. Each of these is more or less common
among certain populations. Each of these is described in more detail below.
In addition, there are many other conditions which can lead to glaucoma, some of which are hereditary, and others acquired. POAG has been called the
most common "form" of glaucoma. It is a diagnosis of exclusion, in
that the diagnosis is made when nothing else is visible, such as pigment, exfoliation,
or inflammation, to which to attribute the glaucoma. It is the most common
because patients with elevated IOP but no visible damage (glaucoma suspects,
ocular hypertension) are included in the category. POAG is most common among
persons of African descent, who are affected about 4-5 times as commonly as
Caucasians. Myopes are also more commonly affected.
Normal-tension glaucoma, until recently called low-tension glaucoma and thought
to be rare, is now realized to be quite common. In Japan, it is more common
than high-tension glaucoma.
Pigment dispersion syndrome (pigmentary glaucoma) is an autosomal dominant
condition which may affect about 2.5% of the Caucasian population. It is rare
in other populations. This is about 20-30 times as common as previously believed,
the reason being that many people with mild involvement never have eye examinations
or are not diagnosed. It typically appears in the 20s and 30s, ages not usually
thought of as being susceptible to glaucoma.
Exfoliation syndrome occurs worldwide and increases in prevalence with age
(incidence is the number of new cases appearing in a given amount of time; prevalence is the percentage of cases existing in an examined population).
It occurs in about 10% of the population over age 50 and its frequency varies
from one population to another. People with exfoliation syndrome have about
6 times the chance of developing glaucoma compared to those who do not.
Angle-closure glaucoma also occurs worldwide but is most common in Orientals.
The highest rate in the world occurs in Eskimos.
Farsighted people are more
likely to develop angle-closure. This is really a different category of disease
from the other four entitiesabove.
*
The following paragraphs have been taken from Chapter 32, Classification of
the Glaucomas, from The Glaucomas, 2d edition, edited by R Ritch, MB Shields,
and T Krupin, CV Mosby Co, St Louis,1996, with permission.
The Stages of Glaucoma
One way to think of the glaucomas is in five stages: 1) an initial sequence
of events, which cause 2) alterations in the aqueous outflow system, which
result in 3) elevated IOP, which leads to 4) atrophy of the optic nerve and
5) progressive loss of the visual field. This scheme, however, implies that
elevated IOP is the only contributing factor, which we know is not true. To
be complete, we should include IOP-independent causative factors, such as vascular
and structural alterations of the optic nerve head, which may also contribute
in some cases to the mechanism of glaucomatous optic
neuropathy. In normal-tension glaucoma, for example, pressure-independent mechanisms
may be the main, if not sole, cause of the optic nerve damage.
The fact is, however, that an IOP which is too high for the eye in question
is the principal causative factor in the vast majority of the glaucomas. Furthermore,
it is the only factor for which we currently have effective treatment measures.
For these reasons, we will focus primarily on the pressure-related portion
of the five-part pathway as we consider new classifications for the glaucomas.
However, as continued studies lead to a better understanding of the pressure-independent
mechanisms of glaucomatous optic atrophy, this knowledge will influence not
only the classification of the glaucomas, but also our approach to managing
many of the conditions.
Stage 1 includes the series of events that initiate pathologic alterations
in a previously normal aqueous outflow system.
Stage 2 begins with the first
detectable change in the system, which eventually leads to aqueous outflow
obstruction and elevated IOP. These two stages distinguish the various clinical
forms of glaucoma and, therefore, provide the most logical basis for classifying
the glaucomas. The last three stages represent a more or less common pathway,
although variations may be seen within the clinical forms of glaucoma.
Stage
3 (elevated IOP) differs somewhat among the glaucomas according to the rate
of onset, magnitude, and chronicity of the pressure elevation. These clinical
variations in the IOP may influence the variable nature of the of optic neuropathy
(Stage 4) and the subsequent visual field loss
(Stage 5), although variations
in the latter two stages are also most likely a result of the pressure-independent
mechanisms of glaucomatous optic atrophy.
The fundamental question of how we define glaucoma must be addressed. One school
of thought is that the diagnosis should be reserved for those patients with
documented visual field and/or optic nerve loss, since all individuals with
elevated IOP do not develop damage. If we were to carry this thought to its
extremes, what diagnosis would we someday give to a person who has only a defective
gene (i.e., Stage 1) that is known to be associated with a certain form of
glaucoma? Although we lack the information at the present time to answer that
question, it is most likely that, for any glaucoma, only a certain percentage of patients with Stages 1, 2 or 3 will develop glaucomatous
optic neuropathy (Stage 4). For each form of glaucoma, therefore, we will have
to consider the potential risk for progression from one stage to the next,
and the risk/benefit ratio of a specific treatment, before deciding whether
to intervene at a particular stage.
Treatment Based on Initial Events
Possibly the most important of the recent advances in glaucoma research have
come in our understanding of the series of events that start the five-stage
process toward eventual blindness. These observations provide the potential
for early diagnosis and treatment of the initial events before they lead
to outflow obstruction. Appropriate treatment at this stage would not only
reduce the risk of eventual IOP elevation and subsequent visual loss, but
would also spare our patients the side effects and complications that are
currently associated with the medical and surgical management of elevated
IOP.
This treatment concept, has been referred to as "early glaucoma intervention," is
already possible for some forms of glaucoma. One example is neovascular glaucoma,
in which at least part of the initial series of events (Stage 1) typically
include a retinal vascular disorder, decreased oxygen supply to the retina,
stimulation of new blood vessel formation, and new blood vessels on the iris.
The mechanism of aqueous outflow obstruction (Stage 2) begins with neovascular
changes in the anterior chamber angle and progresses through formation of a
fibrovascular membrane which obstructs aqueous outflow and eventually contracts to close the angle, causing further outflow
obstruction.
Another glaucoma in which we are very close to applying the concept of early
glaucoma intervention is pigmentary glaucoma. We have learned that the initial
events (Stage 1) in this condition include a specific configuration of the
anterior ocular segment, posterior bowing of the peripheral iris, and rubbing
of iris pigment epithelium against packets of lens zonules with the subsequent
release and dispersion of pigment granules. We have also learned that the mechanism
(Stage 2) by which these initial events lead to outflow obstruction includes
clogging of the intertrabecular spaces with the pigment granules and eventual loss of trabecular endothelial cells with collapse
of the trabecular collagen beams. More recently we have learned that a pressure
differential between the anterior and posterior chambers is responsible for
the posterior iris bowing in many eyes with pigment dispersion and that this
can be relieved by a laser iridotomy. Therefore, if we were able to identify
patients with the pigment dispersion syndrome before the development of irreversible
outflow obstruction, we might be able to prevent IOP elevation with a prophylactic
iridotomy. Before this treatment strategy can be recommended, however, we need
diagnostic measures to predict which patients with the pigment dispersion syndrome
have a sufficient risk
of developing IOP elevation to justify the prophylactic iridotomy, and we need
long-term trials to prove that the iridotomy will prevent the eventual IOP
elevation.
The two glaucomas cited above have traditionally been classified as secondary
glaucomas. One example of how arbitrary our division of primary and secondary
glaucomas has been occurs with the pupillary block form of "primary" angle-closure
glaucoma. In this condition we have a reasonable understanding of the initial
events (Stage 1) which include a specific configuration of the anterior ocular
segment, mid-dilation of the pupil, functional pupillary block, and a pressure
differential between the anterior and posterior chambers. The mechanism of
outflow obstruction (Stage 2) is also known to involve closure of the anterior
chamber angle due to forward bowing of the peripheral iris. In addition we
have an excellent treatment in the laser iridotomy. All we lack before the
concept of early glaucoma intervention can be applied to this glaucoma is a
test that will predict which patients in the high risk population have a high
enough chance of developing angle closure to justify a prophylactic iridotomy.
These three examples of how the concept of early glaucoma intervention will
someday be applied to both "primary and secondary" glaucomas are
provided to emphasize the importance of understanding the initial events of
all the glaucomas. It follows, therefore, that the ideal classification scheme
for the glaucomas should be based on these initial events. At the present time,
however, it is not possible to fully develop such a classification, due to
our incomplete understanding of the initial events for all the glaucomas. The
largest gap in our knowledge has to do with that group of glaucomas that we have called POAG. Despite the fact that more research has been focused on these
conditions than any other group of glaucomas, our understanding of both the
initial events and the mechanisms of aqueous outflow obstruction remains remarkably
limited. We are beginning, however, to see glimpses of what the future may
hold through continued research in cellular and molecular biology, and some
day we will have an understanding of genetic defects for many of the glaucomas.
This knowledge will not only provide a means of early diagnosis of the initial
events, but also a rationale for treatment before these events lead to outflow
obstruction.
Gene linkage studies are progressing at a rapid pace. We have already obtained
significant information regarding the genetic defects in autosomal dominant juvenile open-angle glaucoma, primary congenital glaucoma,
pigment dispersion syndrome, Axenfeld-Rieger syndrome some rare diseases which cause glaucoma in infants and children. As knowledge of
the initial events becomes available for an ever increasing number of the glaucomas,
we may eventually be able to develop a complete classification scheme, based
on these initial events. Until continued research provides the answers to these
gaps in our knowledge, however, we can only partially develop this classification.
* * * * * *
V. THE OPEN-ANGLE GLAUCOMAS
A. Primary open-angle glaucoma
This is the most "common" glaucoma affecting Caucasians and persons
of African ancestry. Its incidence increases with age. POAG has no symptoms
- IOP slowly rises and the disease often goes undetected - for which reason
it has been termed the "sneak thief of sight". It is painless and
the patient often does not realize that he or she is slowly losing vision until
the later stages of the disease. However, by the time the vision is impaired,
the damage is irreversible.
The term "primary open-angle glaucoma" is a misnomer. It implies
that there is a single disease with a specific abnormality causing the disease
(an abnormality which has yet to be discovered). In actuality, a patient is
diagnosed as having POAG when we can't see anything on slit-lamp examination
which would lead to its being calledsomething else. In other words, it is a
diagnosis of exclusion (in medical terms, a "wastebasket" diagnosis
is a group of disorders which we have not figured out how to identify and separate).
A better term would be "idiopathic" open-angle glaucoma, indicating
that we don't know what causes it. However, the term POAG has been in use for
so long, we will continue to use it here for now. In POAG, there is no visible
abnormality of the trabecular meshwork. It is believed that something is wrong
with the ability of the cells in the trabecular meshwork to carry out their
normal function, or there may be fewer cells present, as a natural result of
aging. POAG is a chronic disease which is presently incurable. However, it can be slowed or arrested by treatment. Since there are no symptoms,
many patients find it difficult to understand why lifelong
treatment with expensive drugs is necessary, especially when these drugs are
often bothersome to take and have a variety of side effects.
B. Pigment Dispersion
Syndrome/Pigmentary Glaucoma
Pigment dispersion syndrome (PDS) is a hereditary condition (autosomal dominant
- so that 50% of children and siblings and one parent have the disease) affecting
primarily Caucasians (95%). We have seen it in patients from as far east as
India and as far south as Ethiopia. The prevalence of PDS has been greatly
underestimated and it is often not diagnosed on eye examination because of
a low index of suspicion. The gene may be present in over 2% of the Caucasian
population. Not everyone with the gene appears to develop the syndrome. It
is most common in myopes (nearsighted persons) and quite rare in hyperopes
(farsighted persons). About 10% of people carrying the gene develop glaucoma,
which usually develops between ages 20 and 40. Pigmentary glaucoma is the most
common glaucoma in persons under age 40. The more nearsighted one is, the earlier
the glaucoma develops. For unknown reasons, men develop glaucoma 2-3 times
as often as women (perhaps a protective effect of progesterone?). It most often
begins in the 20s and 30s, which makes it particularly threatening to a lifetime
of normal vision. Because most people with PDS are younger, they don't get
checked for glaucoma routinely, and it is all too common for the diagnosis
to be made after one eye has become blind or lost significant vision. Younger
people with glaucoma may complain of blurred vision and worsening vision and
still not have their pressures checked or visual fields performed because they
are told they are too young to have glaucoma.
The anatomy of the eye plays a key role in the development of pigmentary glaucoma.
The normal iris is flat, like a frisbee. In PDS, the iris drops downward before
angling centrally, so that it looks like a pie pan. This causes the pigment
layer of the iris to rub against the zonules when the pupil constricts and
dilates during focusing. This rubbing action ruptures the cells of the iris
pigment epithelium, releasing pigment particles into the aqueous humor. The
pigment is deposited throughout the anterior segment, including the trabecular
meshwork, which becomes densely clogged with pigment,
visible on examination.
Sudden pigment release at the time of pupillary dilation or after bouncing-type
exercise, such as jogging or basketball, may produce sudden and marked rises
in IOP by overloading the trabecular meshwork. Exercise-induced pigment liberation
may be prevented by pretreatment with pilocarpine.
Pigment release tapers off after age 40. We think this is due to the development
of relative pupillary block secondary to gradual lens enlargement, eliminating
the contact between the iris and the zonules, and also to presbyopia. The ideal
primary treatment for pigmentary glaucoma would be not to just lower IOP, but
to eliminate contact between the iris and zonules, preventing further pigment release.
Miotic (cholinergic) drugs, such as pilocarpine, produce both pupillary constriction
and an increase in aqueous outflow and should be in principle the drug of choice
with which to initiate therapy. However, their side effects are most prominent
in younger patients, who are the ones who have pigmentary glaucoma. These include
accommodative spasm, induced myopia, and difficulty with functioning both in
work-related situations and activities such as sports and driving, particularly
at night. Fortunately, a slow-release form, pilocarpine Ocuserts, are well
tolerated by younger individuals.
We have had great success with pilocarpine Ocuserts in patients with pigmentary
glaucoma. They immobilize the pupil without causing extreme miosis. In most
cases, the pupil is about 3 mm in diameter, allowing more normal functioning.
The IOP-lowering effect is irregular on the 6th and 7th days, and we have patients
change them every 5 days. Unless patients are already taking 4% pilocarpine,
we initiate treatment with P-20 Ocuserts (2% equivalent) and suggest that the
patient begin it in one eye only for 2 weeks until getting used to it and becoming
comfortable. Patients are shown an instructional video and then further instructed
on insertion and removal by a technician. They are also told to expect to have
it fall out during sleep or in the shower for a while, but that eventually
it will remain in place.
With this encouragement, acceptance and success have been high. Because of
the association of retinal detachment with PDS (about 6-7% lifetime chance),
a thorough peripheral retinal evaluation should be performed before starting
treatment with miotics. Lattice degeneration, a peripheral retinal thinning,
which predisposes to retinal detachment, is more common in patients with PDS
than in normals with similar refractive errors. The success of laser iridotomy
in eliminating contact between the iris and zonules offers new possibilities,
both in treatment and in our understanding of the mechanism. In pigment dispersion
syndrome, the area of contact between the iris and lens is greater than normal,
so that the iris drapes over the lens, preventing aqueous humor from equilibrating
between the posterior and anterior chambers. Aqueous humor produced in the
posterior chamber flows normally to the anterior chamber, but cannot flow back,
resulting in a higher pressure in the anterior chamber than in the posterior
chamber, and pushing the iris against the zonules. This has been termed "reverse pupillary block",
to distinguish it from the analogous situation, pupillary block, which
occurs in angle-closure glaucoma. Iridotomy creates an additional pathway,
just as in angle-closure glaucoma, allowing for aqueous equilibration and flattening the contour of the iris.
Who should undergo laser iridotomy? Ostensibly, by preventing pigment liberation
from the iris, the trabecular meshwork would have time to clear itself of pigment
already deposited and reduce or eliminate further deposition. Therefore, patients
should still be in the pigment liberation stage, which is suggested by the
liberation of visible pigment into the anterior chamber after dilation of the
pupil with special eye drops. Patients who have uncontrolled glaucoma and are
facing surgery are also poor candidates for laser iridotomy, since perhaps
years are required to achieve functional reconstitution of the trabecular meshwork.
We have restricted iridotomy to patients under age 45 who have elevated IOP
with no damage or early glaucomatous damage. Clinical trials are needed to determine whether Ocuserts or iridotomy can normalize
IOP in eyes with glaucomatous damage, prevent glaucomatous damage in eyes with elevated IOP, and prevent elevated IOP in normotensive
eyes. Since perhaps as few as 10% of people with PDS go on to develop glaucoma,
and since laser iridotomy itself destroys iris cells and releases a large amount
of pigment and debris, which can further compromise the trabecular meshwork,
we do not presently advocate treating eyes of people with PDS and normal IOPs.
For a more complete, illustrated discussion of PDS and pigmentary glaucoma,
see http://www.web-xpress.com/nygri.
C. Exfoliation Syndrome (Figure 4)
Exfoliation syndrome (XFS) is the most common identifiable cause of glaucoma
worldwide. We estimate that it accounts for about 25% of all glaucoma, or about
16 million affected people. About 25% of people with XFS have elevated IOP
or glaucoma, so that perhaps 60 million people worldwide have XFS. The diagnosis
is very often missed, and the patients considered to have POAG. XFS is found
in every race and ethnic group in the world. The reported prevalence (how common
it is) rates have varied widely, reflecting a combination of true differences
due to racial, ethnic, or other yet-to-be-defined reasons, age of the population
group examined, the clinical criteria for making the diagnosis, the ability
of the examiner to detect earlier stages of the disease, and the thoroughness
of examination. In particular, many cases of XFS go undetected because of failure
to dilate the pupil or to examine the lens by the slit-lamp after dilation,
and because of a low index of suspicion on the part of the examiner.
Glaucoma resulting from XFS, or exfoliative glaucoma, has a worse prognosis
than POAG, and the clinical course is more severe. The average IOP is higher
at the time of detection of exfoliative glaucoma than it is in POAG, while
optic nerve and visual field defects are more severe at the time of presentation
and progress more rapidly. It responds less well to medical therapy than does
POAG and treatment failure occurs more commonly. The proportion of patients
with XFS shows a steady increase when measured in groups of patients with open-angle
glaucoma without optic nerve damage, in those with damage, in those undergoing
surgery, and in those with end-stage glaucoma.
XFS is characterized by the buildup of white material on the anterior lens
surface in three distinct zones. There is a thin central disc of material deposited
on the lens surface, a peripheral granular zone, which may consist of more
than one layer, and a clear zone separating these two areas. The appearance
is reminiscent of sugar-coated cereal. The material is rubbed off the lens
by movement of the iris and at the same time, pigment is rubbed off the iris.
Both pigment and exfoliation material clog the trabecular meshwork, leading
to elevated IOP, sometimes to very high levels (e.g., over 50 mmHg).
American ophthalmologists have traditionally put little emphasis on making
a diagnosis of XFS, since treatment was regarded as the same as that for POAG.
Developments in recent years make it much more important to make a correct
diagnosis. XFS is now khown to be an ocular manifestation of a systemic condition,
seen physically only in the eye because of its easy visibility and the fact
that it causes glaucoma. Differences in the approach and response to various
treatments are beginning to be recognized. Finally, XFS develops prior to its
clinically visible appearance on the lens surface, and other signs can serve
as a tip-off to diagnosis. Recently, XFS has been associated with stroke, angina,
and myocardial infarction. It is only a lack of attention that is holding back
major strides in the elucidation of the fundamental nature of this condition.
XFS can cause both open-angle glaucoma and angle-closure glaucoma, often producing
both in the same person. The chance of developing glaucoma is about six times
as high in people with XFS compared to the general population. It often appears
in one eye long before the other, for unknown reasons. In anyone over age 50
with unilateral glaucoma, XFS should be the presumptive diagnosis in the absence
of another obvious cause. XFS can be detected before glaucoma develops, and
people with it should be observed regularly for the onset of elevated IOP or
narrowing of the angle.
It is theoretically logical that miotics (e.g., pilocarpine) could be the drug
of choice in XFS with glaucoma. Beta-adrenergic blocking agents, although reducing
aqueous secretion, decrease th amount of aqueous flow through the meshwork,
which could be detrimental to clearing of pigment, and could decrease the volume
of the posterior chamber, perhaps increasing the degree of contact between
the iris and the lens, and the amount of pigment rubbed off the iris. Miotics,
in addition to increasing aqueous outflow, could help to prevent the progression
of the disease by reducing pupillary
movement.
Argon laser trabeculoplasty is initially highly successful, producing a greater
average drop in IOP in eyes with XFS than in eyes with POAG. In XFS, however,
sudden late rises in IOP may occur after a year or more of good control. Presumably,
this is due to continued liberation of iris pigment causing further blockage
of the trabecular meshwork. Continued use of pilocarpine after ALT may theoretically
prevent this. Retreatment may be successful in some eyes.
The results of trabeculectomy are comparable to those in POAG. There do not
appear to be any unusual complications. Complications of cataract surgery,
however, are 6 to 10 times more common in patients with XFS. These include
poor dilation of the pupil at the time of surgery, rupture of the lens capsule,
tearing of the zonules, and loss of vitreous fluid during the operation. Eyes
with XFS also have more postoperative inflammation and more problems with shifting
of the position of intraocular lenses as time goes by.
D. Normal-Tension Glaucoma (Low-Tension Glaucoma)
Normal-tension glaucoma has
been defined as open-angle glaucoma in a person in whom the IOP never goes
above 22 mmHg. For a long time, this was thought to be a rare disease. It is
now being realized that the number of persons with normal-tension glaucoma
has been vastly underestimated. In Japan, for instance, twice as many people
have normal-tension glaucoma as high-tension glaucoma. Paramount in the clinical
evaluation of individuals with normal-tension glaucoma is a careful history
with attention to the presence of a family history of glaucoma, vasospastic
symptoms such as Raynaud's phenomenon or migraine headache, or history of hypotension
or significant blood loss. The chronicity and pattern of visual loss (e.g.,
darkening or blurring of acuity) is critical. Patients with non-glaucomatous
cupping may report a history of ocular trauma, ocular pain (particularly associated
with eye movements) or prior episodes of visual loss, concurrent neurologic
symptoms (such as headache or cranial arteritis symptomatology), or history
of syphilis. In addition, it is important to inquire about a history of prior
corticosteroid use which may suggest previous intraocular pressure elevation.
The terms high-tension and normal-tension glaucoma are misleading. The problem
has resulted from artificial definitions, such as 22 mmHg as a cutoff. There
is no real cutoff point. People can have a pressure component to their damage
and they can have non-pressure-dependent mechanisms of damage. The proportion
of sensitivity to each may vary from individual to individual. Both IOP and
other mechanisms of damage are "risk factors" for glaucomatous damage.
The higher the IOP, the greater the risk of pressure-induced damage. The worse
the vascular supply to the optic nerve, the greater the risk of damage on this
basis. When more than one risk factor is present, they are presumably additive.
People with no other risk factors and a pressure of 25 mmHg may never develop
damage. People with IOP of 25 mmHg and several other risk factors may be easily
susceptible to damage. There is no hard and fast rule.
E. A Diagrammatic Overview
In figure 5, glaucoma represents the state of optic nerve damage, whether mild
or extensive. Increased IOP is merely a proximate step leading to the damage.
But that elevated IOP is caused by dysfunction of the trabecular meshwork,
which in turn has specific causes (X, Y, Z) representing different diseases
which act by specific mechanisms. For example, X could be autosomal dominant
juvenile open-angle glaucoma (JOAG), for which the gene has recently been identified
as producing a protein which affects the "stickiness" of the fluid
pathways in the trabecular meshwork. Y could be pigment dispersion syndrome, in which the iris rubs against the zonules which hold
the lens in place, causing disruption of the pigmented cells in the back of
the iris and releasing pigment which clogs the trabecular meshwork. C could
represent uveitis, in which inflammation gradually kills off the cells of the
trabecular meshwork.
It is easy to see that waiting until damage has occurred to start treating
IOP is like locking the barn door after 3/4 of the horse is out. The only approach
to glaucoma has been to lower IOP. Common sense suggests that if we can treat
PRIOR to elevation of IOP, we can prevent the damage to the meshwork which
causes the elevated IOP which causes the damage (sort of like "The House
That Jack Built". Nevertheless, relatively little attention has been paid
to preventing elevated IOP. At the present time, we can't replace the gene
or modulate TIGR protein activity for JOAG, but that will come. We can't replace
the gene for pigment dispersion, but we can prevent pupillary movement, leading
to reversal of the disease. Increasing discoveries regarding inflammation and
the immune system will lead to improved treatments of uveitis. What is important
now is to try to prevent the development of glaucoma in newer ways than just
lowering IOP.
VI. ANGLE-CLOSURE GLAUCOMA
Angle-closure glaucoma affects nearly half a million people in the United States.
In China and surrounding countries, it is more common than open-angle glaucoma.
There is a tendency for this disease to be inherited. It is more common in
hyperopes (far-sighted people). Within the category of angle-closure, the terminology
is inconsistently used. Some use "angle-closure," others "closed-angle," and
still others "narrow angle." The latter is particularly misleading,
since it can describe a patient with POAG and narrow angles or one with actual
angle-closure.
In people with a tendency to angle-closure glaucoma, the anterior chamber is
smaller than average. As mentioned earlier, the trabecular meshwork is situated
in the angle formed where the cornea and the iris meet. In most people, this
angle is about 45 degrees. The narrower the angle, the closer the iris is to
the trabecular meshwork. As we age, the lens routinely grows larger. The ability
of aqueous humor to pass between the iris and lens on its way to the anterior
chamber becomes decreased, causing fluid pressure to build up behind the iris,
further narrowing the angle. If the pressure becomes sufficiently high, the iris is forced against the trabecular meshwork, blocking
drainage, similar to putting a stopper over the drain of a sink. When this
space becomes completely blocked, an angle-closure glaucoma attack (acute glaucoma)
results.
A. Acute angle-closure glaucoma
Unlike POAG, in which IOP increases slowly, in acute angle-closure, it increases
suddenly. This sudden rise in pressure can occur within a matter of hours and
become very painful. If the pressure rises high enough, the pain may become
so intense that it can cause nausea and vomiting. The eye becomes red, the
cornea swells and clouds, and the patient may see haloes around lights and
experience blurred vision.
If the attack goes untreated, scarring of the trabecular meshwork may occur
and result in permanent glaucoma, which is much more difficult to control.
Cataracts may also develop. Damage to the optic nerve may occur quickly and
cause permanently impaired vision. Many of these sudden "attacks" occur
in darkened rooms, such as movie theaters, which cause the pupil to dilate.
Acute stress is another predisposing condition. When the pupil dilates, the
contact between the lens and the iris is maximized. This further narrows the
angle and may trigger an attack. A variety of drugs can also cause dilation
of the pupil and lead to an attack of glaucoma. These include anti-depressants,
cold medications, antihistamines, and some medications to treat nausea.
Acute glaucoma attacks are not always full blown. Sometimes a patient may have
a series of minor attacks. A slight blurring of vision and haloes (rainbow-colored
rings around lights) may be experienced, but without pain or redness. These
attacks may end when the patient enters a well lit room or goes to sleep-two
situations which naturally cause the pupil to constrict, thereby allowing the
angle to open spontaneously.
An acute attack is an emergency condition. If the pressure is not relieved
within a few hours, vision can be permanently lost. An acute attack may be
stopped with a combination of drops which constrict the pupil, and drugs that
help reduce aqueous production. When IOP has dropped to a safe level, laser
iridotomy is the treatment of choice. This is an outpatient procedure in which
a laser beam is used to make a small opening in the iris, allowing aqueous
to pass directly from the posterior chamber to the anterior chamber. Since
it is common for the other eye also to have a narrow angle, laser iridotomy
on the unaffected eye is done as a preventative measure. Routine examination
using a technique called gonioscopy can predict one's chances of developing
angle-closure. A special lens which contains a mirror is placed lightly on
the front of the eye and the width of the angle examined visually. Patients
with narrow angles can be warned of early symptoms, so that they can seek immediate
treatment.
B. Chronic angle-closure glaucoma
Not all people with angle-closure experience an acute attack. Many develop
what is called chronic angle-closure glaucoma. In this case, the iris gradually
closes over the drain, causing no overt symptoms. When this occurs, scars slowly
form between the iris and the drain and the IOP will not rise until there is
a significant amount of scar tissue formed-enough to cover the drainage area.
If the patient is treated with medication, such as pilocarpine, an acute attack
may be prevented, but the chronic form of the disease may still develop.
VII. GLAUCOMA IN CHILDREN
The number of younger people with glaucoma has been vastly underestimated in
the past. In fact, it was more common than not a generation ago not to bother
checking IOP in people under the age of 35 because it was thought glaucoma
was exceedingly rare in this age group. We know now that it is not, and we
know that glaucomatous damage ordinarily takes a long time to develop. Someone
with symptomatic damage detected at age 45 might have had elevated IOP for
20 years. Glaucoma does increase in frequency with age. Those glaocmas that
increase iln frequency with age are primarily POAG, exfoliation syndrome, non-pressure-dependent
mechanisms of damage, and angle-closure. Pigmentary glaucoma, as mentioned,
develops in the 20s and 30s. Juvenile open-angle glaucoma, often hereditary,
is probably second in frequency to pigmentary glaucoma. Glaucoma in childhood (under age 18) is much less common and is often associated with specific syndromes.
We will describe the more common of these here.
A. Congenital Glaucoma
Congenital, or infantile, glaucoma, occurs in about 1 in 10,000 births. It
is defined as glaucoma appearing between birth and ages 3 to 4. Up to this
age, the eye wall is distensible, so that the eye can noticeably and progressively
enlarge when IOP is elevated. It may occur without other findings (primary
congenital glaucoma), associated with other syndromes, or after injury, congenital
cataract extraction, or inflammation. Primary congenital glaucoma is due to failure of development or abnormal development of the trabecular meshwork.
Most cases of primary congenital glaucoma are sporadic in occurrence. In the
approximately 10% in which a hereditary pattern is evident, it is believed
to be usually autosomal recessive.
Congenital glaucoma is usually detected by the parents when the eye is noted
to enlarge or the cornea becomes hazy. When the cornea stretches, breaks occur
in the inner corneal lining, or endothelium, which pumps water out of the cornea
to maintain its transparency. When breaks occur, aqueous humor enters the cornea,
causing it to swell, a hazy, frosted glass appearance. The baby is sensitive
to light and tearing may be present. As the cornea
stretches, ruptures allow more aqueous into the corneal stroma and epithelium,
causing a sudden increase in edema and haze and an increase of tearing and
avoidance of bright light. The infant may become irritable to the point of
burying its head in a pillow to avoid lights.
Treatment is surgical and often successful, although more than one operation
may be necessary. Goniotomy and trabeculotomy are operations designed to incise
the trabecular meshwork to help it to function. If these are unsuccessful,
then filtering surgery as performed in adults becomes necessary. The prognosis
is worse if the glaucoma is present at birth.
Advances in our understanding of the genetics of glaucoma are progressing at
a rapid pace. There are at least 3 different chromosomes which can contain
abnormal genes causing congenital glaucoma. The one best characterized to date
is a gene on chromosome 2 which codes for a protein called cytochrome P4501B1,
one of a series of enzymes involved in oxygen metabolism (mono-oxygenases).
B. Juvenile primary open-angle glaucoma.
By definition, glaucoma developing between ages 4 and 10 are called late congenital
glaucoma, or developmental glaucoma. Primary open-angle glaucoma, because thought
rare in younger patients, was considered a disease affecting people from age
35 on. Thus, POAG developing the span between ages 10 and 35 came to be termed,
by convention, juvenile primary open-angle glaucoma. About 35% of people with
this disease are high myopes (very nearsighted), and 85% total are nearsighted.
Juvenile POAG is strongly hereditary and often autosomal dominant, meaning
that only a single copy of the gene from one parent can cause disease, so that
50% of the offspring of an affected parent are affected. The first glaucoma
gene characterized, in 1996, was one responsible for autosomal dominant juvenile
POAG, and since that time, numerous mutations in this gene have been found
in several large families with hereditary glaucoma. This gene produces a "sticky" protein,
TIGR, or myocilin, which makes the trabecular meshwork less permeable to aqueous
humor leaving the eye. Its concentration may increase in susceptible individuals
when they are treated with steroids. Mutations in this gene are also responsible
for about 3% of POAG in older age groups. Several other genes on other chromosomes are under
active investigation for their ability to cause either juvenile or adult-onset
POAG or both.
C. Sturge-Weber syndrome (Figure 6)
Sturge-Weber syndrome is relatively common and everyone has known someone at
one time or another with a port-wine stain on the face. When the port-wine
stain affects the forehead and upper lid, glaucoma occurs about 2/3 of the
time. It can occur at birth or infancy, but more commonly develops between
ages 9 and 16. For some reason, this has not been well known, and many children
are only detected after they have suffered severe damage. Sturge-Weber Syndrome
is a common cause of blindness from glaucoma in childhood. Most of this blindness
could be prevented through timely diagnosis and appropriate treatment.
Ocular manifestations of Sturge-Weber syndrome occur in infancy and early childhood.
The hallmark of the condition is a facial birthmark (port wine stain), which
is unilateral in 90% of affected children, and involves the region of distribution
of the first and second divisions of the trigeminal (fifth) nerve. The first
division corresponds to the forehead and upper eyelid. The second division
corresponds to the cheek and lower eyelid. The third division corresponds to
the jaw.
Vascular malformations may affect the eyelids, sclera, conjunctiva, and iris.
When the upper lid is involved, the eye is also usually involved. The iris
may appear darker than that in the opposite eye. Vascular malformations of
the choroid, the spongy vascular tissue which lies between the retina and the
sclera, in about 40% of affected eyes. They are easily overlooked in younger
patients and grows slowly. One third of patients with Sturge-Weber syndrome
have increased IOP. This is characteristically on the same side as the vascular
malformation, although glaucoma can sometimes occur
bilaterally. Glaucoma can occur at various stages in life, but most commonly
occurs in infancy and childhood.
Glaucoma may be present at birth or develop in the first few years of life.
This is called congenital glaucoma. Congenital glaucoma results from developmental
abnormalities that result in malfunction of the tissue which drains fluid from
the eye. It is usually detected by the parents. The most characteristic signs
of congenital glaucoma are enlargement of the eye, a hazy cornea, tearing,
and photophobia (the baby tries to hide its head from bright light). All babies
with Sturge-Weber syndrome should have IOP measured in infancy and, if normal,
once a year thereafter. After the age of three or four, the eye wall becomes
thicker and does not enlarge when the IOP rises, and it is necessary to measure
IOP in order to determine the presence or absence of glaucoma.
The development of glaucoma during childhood and adolescence is also common.
These children usually have a vascular malformation of the sclera, which causes
elevated pressure in the veins which drain the eye. This, in turn, causes IOP
to rise, with subsequent damage to the drainage system of the eye. Medical
treatment (eye drops) may control this type of glaucoma. If medical treatment
fails, surgical intervention becomes necessary. Laser treatment for the glaucoma
is ineffective. With early diagnosis, and appropriate treatment geared to the
type of glaucoma and the findings from examination of the eye, the glaucoma
can often be controlled and vision preserved.
E. Aniridia (Figure 7)
Aniridia is a hereditary condition uniformly associated with iris abnormalities.
This development condition is rare, occurring in approximately 1 in 50,000
live births. Typically, the iris appears as a small rudimentary stump associated
with a large pupil. Aniridia may be associated with congenital glaucoma, but
glaucoma most commonly develops in childhood or adolescence. Other abnormalities
include cataract, failure of the macula (the area of the retina responsible
for sharp central vision) to develop, nystagmus (uncontrolled movements of
the eyeball), and corneal vascularization.
Three genetic types of aniridia have been recognized. About 85% of patients
have isolated, autosomal dominant aniridia (not associated with other systemic
manifestations). About 13% have autosomal dominant aniridia associated with
Wilms' tumor, genitourinary anomalies, and mental retardation (WAGR), while
2% have autosomal recessive aniridia associated with cerebellar ataxia and
mental retardation. The aniridia gene, now called the PAX6 gene, has been established
as the only genetic locus for aniridia and is located on chromosome number
11.
Treatment of congenital glaucoma is the same as for primary congenital glaucoma.
Long-term treatment of childhood glaucoma is difficult, complicated, and often
frustrating, but is constantly improving.
F. Glaucoma Associated with Uveitis
Uveitis is a nonspecific term referring to inflammation of the choroid, ciliary
body, and or iris. It may be due to local, systemic, exogenous or endogenous
causes. Although some forms of uveitis may be classified into clinical entities,
most are nonspecific and can be broadly described as being only anterior or
posterior, granulomatous or nongranulomatous. Anterior uveitis is also termed
iritis or iridocyclitis. Glaucoma is a frequent complication of uveitis. IOP
may be low in eyes with anterior uveitis because of a decrease in aqueous humor
formation ("secretory hypotony"). However, uveitis may also lead
to acute or chronic, open-angle or angle-closure glaucoma. Elevated IOP may
be caused by active inflammation, insufficient antiinflammatory therapy, excessive
corticosteroid use, or insufficient glaucoma therapy. The chronic and recurrent
nature of the inflammation may lead to death of the trabecular cells which
control the exit of aqueous humor, and which do not replenish themselves.
Medical treatment of glaucoma associated with active uveitis is directed toward
controlling inflammation and preventing its damaging effects on outflow pathways,
as well as controlling IOP. Dilating the pupil and decreasing the inflammation
help to minimize damage and scarring of intraocular tissues and visual loss.
If medical therapy fails, surgery may become necessary. When angle-closure
occurs, laser iridotomy is indicated. Argon laser trabeculoplasty is contraindicated
in open-angle glaucoma associated with uveitis because it fails in virtually
all cases, causes increased inflammation, and destroys a certain percentage
of the remaining viable trabecular cells. Filtration surgery in eyes with uveitis
has a lower success rate and higher complication rate than in eyes without
uveitis.
VIII. WHO IS AT RISK FOR GLAUCOMA?
Since glaucoma is produced by many different conditions, it occurs at all ages
and in all races. However, some people are at greater risk than others.
A. People over age 45. While glaucoma can develop in younger patients, it occurs
more frequently with age.
B. People with a family history of glaucoma. This applies particularly to people
with pigmentary glaucoma, which is strongly inherited. Juvenile POAG is also
commonly inherited. A number of rare types are genetic. Adult onset POAG and
exfoliation syndrome may have some hereditary tendency, but data is tenuous.
C. Myopes are more prone to develop open-angle glaucoma. Hyperopes are more
prone to develop angle-closure glaucoma.
D. There is no glaucoma exclusive to any race or ethnic group. However, there
are some rough epidemiological rules. Persons of African descent are more prone
to develop POAG, by a ratio to about
4:1 compared to Caucasians. Pigmentary glaucoma occurs almost exclusively in
Caucasians. Angle-closure is more common than open-angle glaucoma in Asians.
Everyone can develop exfoliation syndrome, but it appears to be most common
in those of European descent.
IX. DIAGNOSING GLAUCOMA
A variety of diagnostic tools aid in determining the presence, absence, or
predisposition to glaucoma.
A. Tonometry.
From a practical standpoint, a "normal" IOP is one that does not
result in glaucomatous optic nerve head damage. Because not all eyes respond
similarly to a particular IOP level, a normal pressure cannot be represented
as a specific measurement. Therefore, the most that we can expect is to determine
their relative chance of developing glaucoma at different pressure levels given
the knowledge of the distribution of IOP in general populations and in populations
of individuals with glaucomatous damage
The tonometer measures IOP. In applanation tonometry, the eye is anesthetized
with drops and, at the slit lamp, a plastic prism is lightly placed on the
cornea. A strain gauge determines IOP. In air tonometry, which is less accurate,
a
puff of air is sent onto the cornea to take the measurement. Since this instrument
does not come in direct contact with the cornea, no anesthetic eye drops are
required.
B. Perimetry
Testing the visual field is the best way of determining if vision is being
lost due to glaucoma. At the present time, almost all visual field testing
is done using computerized automated perimetry. The patient sits facing a computerized
screen and asked to press a button whenever a flash of light appears. If the
flash of light falls into a scotoma, it is not seen, and this registers on
the printout as a blind spot. Sequential visual fields in a glaucoma patient
can be used to determine whether the disease is stable or progressing
C. Ophthalmoscopy
The optic nerve can be seen directly by the examiner using an instrument called
an ophthalmoscope. The color and appearance of the disc can indicate whether
or not damage from glaucoma is present and how extensive it is.
D. Gonioscopy
In this test, a mirrored lens is placed on the cornea, allowing the examiner
to view the angle directly. Narrow angles and angle-closure can be detected.
This test should be performed routinely on any initial complete eye examination
and patients with narrow angles should be gonioscoped at routine intervals
to inspect for further narrowing or capability of closure.
X. TREATMENT OF GLAUCOMA
Glaucoma can be treated with eye drops, pills, laser surgery, eye operations,
or a combination of methods. The whole purpose of treatment is to prevent further
loss of vision. LOSS OF VISION IN GLAUCOMA IS IRREVERSIBLE. Bringing the pressure
under control will not restore lost vision, but only prevent further vision
from being lost. Keeping the IOP under control is the key to preventing loss
of vision from glaucoma. New approaches are being developed for the treatment
of normal-tension glaucoma [section under development]. In order to prevent
further visual loss from glaucoma, the IOP must be constantly controlled. This
requires taking medications chronically. If a drop is given four times a day,
it is because the effect of the drop only lasts about 6 hours. Drops given
twice a day have a "duration of action" of about 12 hours. Proper
taking of drops and use of punctal occlusion will result in more of the drop
getting into the eye and less into the blood stream, resulting in more effective
treatment. Punctal occlusion and proper drop instillation are very important.
One of the most difficult problems faced by glaucoma patients is that of having
to take medications which may have both ocular and systemic side effects to
control a disease which is usually painless and has no symptoms. Understanding
the necessity for the medication often helps to reduce the severity of a side
effect, since it is often magnified by anxiety.
A side effect is any action produced by a drug beyond the intended one of lowering
IOP. Some patients have no side effects whatsoever, while others find them
too severe to tolerate. Why a drug causes side effects in some persons and
not others or why the same side effect of the same drug is severe in one person
and mild in another are poorly understood.
Quality of life is important. We sometimes have to make the decision to perform
laser or surgery, even if the pressure can be controlled, if the side effects
of the medications necessary for control are intolerable. It is up to the patient
to participate in and ultimately make the decision in such a situation. What
one should not do is skip taking the medications and lose vision because of
side effects. One should also not be afraid to mention any side effects one
might have or attribute to the drugs, since it is not one's fault that the
drugs cause them.
All drops may cause some burning or stinging when instilled. Often, this effect
is due not to the drug but to the antibacterial preservatives in the solution.
It is rarely intolerable and can be used to advantage, since it lets the patient
know that the drop got into the eye. Many patients don't think a drop is really
medicine if it doesn't cause a little irritation.
A. Eye drops
Miotics (cholinergic agents) are drops which help to open the spaces in the
trabecular meshwork and increase the rate of fluid flow out of the eye. The
most common is pilocarpine. Carbachol is somewhat stronger and echothiophate
(Phospholine(r)) is stronger still but has a tendency to cause cataracts and
is only used in patients who have already had cataracts removed.
Epinephrine also lowers intraocular pressure by increasing the rate of fluid
flow out of the eye. Dipivefrin (Propine(r)) is converted to epinephrine once
inside the eye.
Beta-adrenergic blocking agents, or beta-blockers, decrease the rate at which
fluid flows into the eye. Timolol (Timoptic(r)) and levobunolol (Betagan(r))
appear to have a slightly greater pressure-lowering effect than betaxolol (Betoptic(r)),
but the latter is safer in patients with pulmonary disease, such as asthma
or emphysema, and may have less of an effect on blood pressure. Oral beta-blockers
are commonly used for hypertension and angina and in
these situations, also lower IOP.
Carbonic anhydrase inhibitors (CAI) reduce fluid flow into the eye by inhibiting
the enzyme which interconverts water and carbon dioxide to hydrogen and bicarbonate
ions. For over 40 years, only pills were available. These consisted of acetazolamide
(Diamox(r)), methazolamide (Neptazane(r)) and chlorpropamide (Daranide(r)).
Although well tolerated by many patients, they were also associated with many
serious side effects (see below), including fatalities. In 1995, the first
CAI eye drop, dorzolamide (Trusopt(r)) became available. Brinzolamide (Azopt)
was released in 1998. Although side effects may still occur in some patients,
they have been greatly reduced overall.
Alpha agonists reduce aqueous humor production and increase aqueous outflow.
Uveoscleral outflow normally accounts for about 10% of the outflow from the
eye. The rest is handled by the trabecular meshwork. However, when the meshwork
is damaged by glaucoma, uveoscleral outflow becomes more important. Apraclonidine
(Iopidine(r)) and brimonidine (Alphagan(r)) are presently marketed. Brimonidine
has a significantly higher relative selectivity for the alpha-2 receptors,
while apraclonidine has mixed alpha-1 and alpha-2 stimulatory activity.
Prostaglandins act to increase the rate of outflow of aqueous humor not through
the trabecular meshwork, but by another pathway called uveoscleral outflow.
Latanoprost (Xalatan(r)), the agent most recently brought to market in the
U.S., represents a new class of compounds which should prove additive with
all other antiglaucoma drugs.
B. Common Side Effects of Antiglaucoma Drugs
One should not become neurotic when reading a list of possible side effects
of a drug, such as the package insert. You may not get any side effects at
all. If you do, it may only be a minor bother. Serious side effects are rare.
If they weren't, we wouldn't be using the drugs in the first place. Sometimes,
the only way to prove a side effect, particularly subjective ones such as anxiety,
depression, or vivid dreams, is due to the medication is to stop using it,
wait for
the reaction to go away, and try it again. This is known as retesting. If you
think you have an unusual reaction to a drug, mention it to your physician
or post it on the Internet. A good place for this is alt.support.glaucoma.
If you retest yourself twice and prove the side effect related to the drug
and it is an unusual one, contact us by e-mail. We can then forward it to the
National Registry of Ocular Drug-Induced Side Effects. Remember that all drops
may cause burning and stinging and that any drug may produce a rash. If you
have a definite allergic reaction to a drug, you should stop using it. Miotics
may cause periorbital pain, browache, and pain inside the eye. This often disappears
after a few days of taking the drop. Blurred vision and extreme nearsightedness
are most common in younger patients, who often cannot tolerate these drops.
Because miotics reduce the size of the pupil and prevent it from dilating normally
in the dark, many patients complain of dim vision, particularly at night or
when going into a dark room. Systemic side effects are rare with pilocarpine,
more common with carbachol, and not unusual with echothiophate. These include
stuffy nose, sweating, increased salivation, and occasional gastrointestinal
problems. Rare side effects include retinal detachment, mostly on circumstantial
evidence. Patients with high myopia and pigment dispersion are more prone to
both retinal detachment and glaucoma.
PILOCARPINE GEL is applied at bedtime and may be substituted for drops in many
patients. In addition to the convenience of not having to use drops four times
a day, the effect on the pupil is often less. Ocuserts are pilocarpine membranes
worn under the lids and changed every 5 days. These cause less blurring of
vision and are especially useful in younger patients. Epinephrine and dipivefrin
frequently cause burning on instillation. A red eye is common and is an effect
not of the drop initially, which whitens the eye by constricting blood vessels,
but of the rebound effect when it wears off. The most common problem is development
of an allergic reaction, which may occur after years of use. Epinephrine may
cause palpitations, elevated blood pressure, tremor, headache, and anxiety.
Dipivefrin has a much lower rate of systemic side effects.
Beta-blockers cause few ocular side effects. A few patients have complained
of blurring of vision. This is more common when beta-blockers and epinephrine
are used together, because this combination dilates the pupil. The most common
systemic side effects include exacerbation of pulmonary disease, difficulty
breathing, slowing of the pulse, and decreased blood pressure. More recently,
central nervous system side effects have been reported. these include memory
loss, dizziness, fatigue, weakness, decreased exercise tolerance, anxiety,
hallucinations, insomnia, and impotence.
Carbonic anhydrase inhibitors commonly cause side effects. The most common
are urinary frequency and tingling in the fingers and toes. These are often
transient and disappear after a few days. Kidney stones may occur, but are
also common without their use. Most glaucoma specialists use them unless a
patient has had or develops a kidney stone or only has one kidney. A rare but
serious side effect is aplastic anemia. Rashes are not uncommon. Potassium
loss may occur when these drugs are taken simultaneously with digitalis, steroids,
or chlorothiazide diuretics.
Depression, fatigue, and lethargy are common side effects and are often not
realized by the patient or by close family. These side effects may not appear
immediately but develop gradually. Since many patients with glaucoma are elderly,
these side effects are attributed to getting older. Patients and their families
should be on the alert for these side effects and, when suspected, the drug
can be stopped for a short time for verification. Other common side effects
are gastrointestinal upset, metallic taste to carbonated beverages, impotence,
and weight loss. Sequels cause less side effects than tablets.
The use of topical CAIs has markedly reduced the frequency and severity of
these side effects. With chronic use, some 20% of patients develop a topical
allergy, with conjunctival redness and itching, redness, and scaling of the
lower eyelids.
Alpha-agonists are chemically related to systemic medications for the treatment
of hypertension, and systemic side effects of these medications are unusual.
Ocular allergy develops in a high percentage of patients using apraclonidine
on a prolonged basis; allergic reactions appear to be less with brimonidine.
Patients who develop an allergy to apraclonidine can be switched to brimonidine.
The most common side effects are slight elevation of the upper lid, dry mouth,
dry nose, and mild sedation. Some patients may develop dizziness. Prostaglandin
analogues stimulate the uveoscleral pathway for aqueous outflow, and can be potent pressure-reduction medications. Although
ocular injection and irritation may occur, these drugs are extremely
well-tolerated and require only once daily dosing. A darkening of iris color
occurs in approximately 5% of eyes with use of latanoprost for several months
or more due to an increase in the production of melanin in the melanocytes
of the iris. Pure brown eyes and pure blue eyes are not effected. Hazel, green,
and golden-brown eyes are. Increased eyelash growth is not uncommon (and a
patent for hair growth has been granted). Since the drug is new, other side
effects are only beginning to be reported and have not been proven yet. Conjunctival
redness is common. Flareups of uveitis and macular edema, facial burning or
rash, and uterine bleeding in postmenopausal women are possibilities.
B. Laser surgery
Laser surgery is been used as treatment for a wide variety of glaucomas. The
ability of light to penetrate the transparent structures of the eye (cornea
and lens) allows it to have its desired affect on the targeted tissue. This
is different from most other sites in the body, where penetration of light
is blocked by the skin or thick outer tissues. Numerous different types of
lasers are used in eye surgery for various purposes. These include argon, krypton, neodymium-YAG, diode, and excimer lasers.
1. OPEN-ANGLE GLAUCOMA.
a. Laser Trabeculoplasty
In eyes with open-angle glaucoma, the laser energy is applied directly to the
damaged drain, or trabecular meshwork. Argon laser trabeculoplasty (ALT) was
first used as an intermediate step between drugs and surgery, but is now being
used earlier in the disease process. ALT is most successful in eyes which do
not have active inflammation. Its success increases with the age of the patient
(except in pigmentary glaucoma) and the amount of pigment on the trabecular
meshwork. Of the three most common forms of open-angle glaucoma, primary or
chronic open-angle glaucoma, pigmentary glaucoma, and exfoliative glaucoma, the effect of ALT is greatest in the latter. In general,
ALT is more effective in older individuals, except in pigmentary glaucoma,
where younger patients tend to have a better pressure-lowering response. ALT
works less well in eyes with a history of prior surgery, such as cataract or
angle-closure glaucoma following laser iridotomy (see below). It may be useful
in normal-tension glaucoma. ALT produces borderline or poor results in most
other open-angle glaucomas. Aside from pigmentary glaucoma or other glaucomas
with pigmentation of the trabecular meshwork, we do not feel that it should be performed in patients under age 40, as it is usually ineffective
and may worsen the condition. It should also not be performed in eyes with
active uveitis, neovascular glaucoma, iridocorneal endothelial syndrome, aniridia,
or other childhood glaucomas.
The entire procedure takes less than ten minutes, is painless, and is performed
on an outpatient basis. A single drop of anesthetic is administered beforehand.
Most doctors also pretreat with a drop of apraclonidine (Iopidine), which decreases
the likelihood of a postoperative rise in pressure. The laser beam is focused
on the trabecular meshwork and 50 to 100 burns over 180° to 360° placed
on the meshwork. Many surgeons divide the treatment into two sessions of 180° treatment
each, in order to gauge its effectiveness and limit complications. If IOP comes
under control after the first treatment, the second may be postponed until the effect of the first treatment wears off.
One to three hours after the surgery the pressure in the eye is rechecked.
Follow-up varies from 1 day to 1 week, and depends upon the type and status
of the glaucoma. The final effect is often not attained for 4-6 weeks. Complications
are infrequent and usually transient and include of pressure and mild inflammation.
Contrary to what some people think, the laser does not burn a hole through
the eye. Instead, the heat causes some areas of the trabecular meshwork to
shrink, theoretically resulting in adjacent areas stretching open and permitting
aqueous humor to drain more easily. It is also possible that the laser stimulates
DNA synthesis, promoting regrowth of trabecular cells.
The timing of laser trabeculoplasty remains controversial. In the 1980s, it
was first used as an intermediate step between drugs and surgery, but is now
being used earlier in the disease process. A long-term study performed by the
National Eye Institute/National Institutes of Health (USA) has confirmed the
clinical impression that, at the very least, laser trabeculoplasty is a safe
and effective method of lowering IOP.
The effectiveness of laser trabeculoplasty varies from individual to individual
and usually cannot be predicted. The average reduction in eye pressure is approximately
11 mmHg in exfoliative glaucoma and 7 mmHg in POAG and younger patients with
pigmentary glaucoma. On the other hand, if the target pressure is 16 mm Hg,
and the starting pressure is 35 mm Hg, the likelihood of achieving the target
pressure with ALT is low. Unfortunately, virtually all patients who undergo
ALT will either need to continue their eye drops or require them later on.
The duration of the effect is also variable. Some individuals appear to respond
only transiently, while others can maintain good control for years.
2. ANGLE-CLOSURE GLAUCOMA.
1. Laser Iridotomy
Blockage of aqueous flow between the posterior and anterior chambers in relative
pupillary block (the most common cause of angle-closure glaucoma) can be relieved
with a procedure called laser iridotomy. This surgery, which can be performed
with the argon or Nd-YAG lasers, creates a hole in the iris to allow free passage
of aqueous. In angle-closure glaucoma, the blockage of fluid flow may cause
an acute attack of glaucoma and very high IOP, pain, and loss of vision. Laser
iridotomy can successfully eliminate the chance of acute or chronic angle-closure
glaucoma in most eyes. A series of high quality images of the living eye depicting the anatomy before and after laser
iridotomy can be found at the Ocular Imaging Center, information for patients.
This link can be accessed through The Glaucoma Home Page at www.web-xpress.com/gany.
Laser iridotomy is also being evaluated as
a possible therapy for reverse pupillary block in pigment dispersion syndrome
and pigmentary glaucoma, although this remains under investigation. The procedure for laser iridotomy and potential for complications are described
above. The procedure is ambulatory, generally pain-free, and takes approximately
10 minutes to perform.
2. Argon Laser Peripheral Iridoplasty (ALPI)
Under certain circumstances, laser iridotomy may fail to open a closed angle.
If the angle is not permanently closed with scar tissue, ALPI may help to open
the angle. This is particularly useful in less common forms of angle-closure,
such as plateau iris syndrome or lens-related angle-closure. The procedure
consist of applying the laser to contract and mechanically pull the iris out
of the drain. Other uses include acute attacks of angle-closure in which laser
iridotomy cannot be performed or is ineffective or continued angle-closure
despite a patent laser iridotomy is present.
C. Operative Surgery
1. Filtering Surgery
Operative surgery for glaucoma falls into 2 general categories reflecting the
mechanism by which the surgery lowers the pressure. Since the problem in most
glaucomas is that the drain does not function properly, the most commonly performed
type of surgery involves creation of a new drainage structure for aqueous to
leave the eye. The most common operation of this type is called trabeculectomy.
In trabeculectomy, the surgeon fashions a new drain in the region of the trabecular
meshwork (the damaged drain) and the sclera (which is the white covering of
the eye). Fluid production within the eye is allowed to continue normally, and pressure reduction is achieved by allowing
the fluid to exit the eye through the new drain. With the advent of microsurgery
and the use of the antiscarring drugs 5-fluorouracil (also known as 5-FU) and
mitomycin C, these procedure have become much more effective at lowering pressure,
preserving vision, and preventing complications. Techniques such as releasable
sutures and laser suture lysis allow for a more gradual reduction of IOP after
surgery and often avoid periods of prolonged low pressure, which can be a major
source of complications during the first few weeks after surgery. Long term
complication of this type of surgery include the possibility that cataract
formation might accelerate andfailure of the filtering operation months or
years later. Since this procedure is performed in an operating room, it typically
takes longer (about 30-45 minutes) and involves more frequent follow-up care
by the surgeon. Most patients are seen frequently (once or twice per week)
for the first 4-6 weeks following the surgery, during which time the pressure
is monitored and the healing process monitored. Postoperative drops can often
be eliminated during this time.
2. Glaucoma Implants
Upon occasion, because of abnormal eye anatomy or history of previous eye surgery,
it is not possible for the surgeon to build a new drain from the tissue present
within the eye. Under these circumstances, an artificial drainage tube, made
of plastic, may be inserted into the eye to act as a new drain. Although the
modern form of glaucoma drainage tube implant surgery was first developed in
the1960s, advances in implant design during the 1980s and 1990s have made this
procedure safer.
3. Combined cataract and glaucoma surgery
Since glaucoma often occurs in older individuals, the presence of a hazy lens,
or cataract, is common during the preoperative examination. Although the correction
of vision loss due to cataract requires surgery, the good news is that cataract
surgery can successfully reverse the vision loss associated with the cataract,
although the glaucoma damage will still be present. In this situation, the
presence of coexisting cataract and glaucoma can be addressed by combined cataract
surgery and glaucoma filtering surgery, most often with good results for both.
The success of the glaucoma surgery in this instance is aided by the use of
the antiscarring medication mitomycin C, which has been a huge advance for
glaucoma surgeons and their patients requiring combined cataract and glaucoma
surgery.
4. Cyclodestruction
As mentioned earlier, in the above forms of glaucoma surgery the surgeon creates
or implants a new drain for fluid to exit the eye and fluid production is allowed
to continue. In cyclodestruction, the gland that produces the fluid, the ciliary
body, is partially destroyed to decrease the amount of fluid produced in the
eye. This is analogous to turning down the faucet in an overflowing sink. Unfortunately,
the functioning of the eye depends upon the production of fluid, and cyclodestruction can cause a change in the composition of the
fluid. Fortunately, the development of new laser technologies have made his
procedure safer and less uncomfortable than in the past. Most physicians, however,
reserve this surgery for eyes which have failed filtering surgery or those
which are so badly damaged that the prognosis for the retention of vision is
grim.
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