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Definition
Detection,
diagnosis and
monitoring
Medications and
their side effects
Glaucoma surgery
The author
DR STUART L GRAHAM,
clinical lecturer, Save Sight
Institute, University of Sydney;
and consultant ophthalmologist,
Eye Associates, Sydney, NSW.
GLAUCOMA
Correction
What is glaucoma?
GLAUCOMA is a progressive optic
neuropathy characterised by the
combination of both changes in the
structure of the optic nerve (disc cupping) and loss of visual field (blind
spots or scotomas).
Raised intraocular pressure (IOP)
is the main cause of this damage, but
it can often occur without elevated
pressure (termed normal-tension
glaucoma). Although visual damage
is not reversible, it can usually be
arrested by treatment with eye drops,
laser or other surgery.
There are two main types of glaucoma — open angle and closed
angle. By far the most common form
is primary open-angle glaucoma
(POAG), which is asymptomatic in
its early stages and is slowly pro-
gressive if not treated.
The diagnosis of POAG is often
late because its detection can be elusive until the disease process is well
advanced. A substantial amount of
vision can be lost before the patient
becomes aware of any defect. This
is why population studies reveal that
up to 50% of glaucoma in the community is undiagnosed.
POAG has an overall incidence of
about 2%, but this increases significantly in the latter decades to up to
8%.
The main risk factors for POAG are
age and family history. Additional systemic associations include diabetes,
hypertension, migraine, Raynaud’s
syndrome and possibly sleep apnoea.
cont’d next page
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‘Chronic kidney disease’
(2 February) advised the use
of gliclazide and glimepiride
as best treatment options for
patients with chronic kidney
disease and diabetes.
However, glimepiride should
be avoided because of the
risk of hypoglycaemia and
the authors recommend
treatment with gliclazide or
glipizide.
P
LIS BS
TE
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How to treat – glaucoma
from previous page
Ocular risks include
myopia, pseudo-exfoliation
syndrome (accumulation of
small white glycoprotein
particles within the eye) and
thin central corneas.
Normal-tension glaucoma
is a subgroup of the openangle glaucomas. It is presumed that patients with this
condition have nerves that
are highly susceptible to
pressure, a vascular pathophysiology or some other
form of neurodegenerative
disease. They still show a
clinical response to lowering
of IOP, so they are treated
as for POAG.
Angle-closure glaucoma is
much less common, but has
a higher incidence in Asian
people. It involves quite a
different mechanism and
presentation. The angle is
the region between the
cornea and the base of the
iris, where the drainage
channels are located (trabecular meshwork).
The angle can obstruct if
the peripheral iris moves forward in susceptible eyes. It
is associated with a sudden
rise in IOP, a painful red eye
with blurring and a middilated pupil. It rapidly proceeds to blindness if not
treated promptly.
Figure 1: Acute angle-closure glaucoma.
Table 1: The two main types of glaucoma
Features
Open angle
Closed angle
Presenting
symptoms
None usually, central vision loss
only in late stages, unrecognised
mid-peripheral field loss progresses
to tunnel vision eventually
Blurring, haloes, pain – deep ache,
redness, headache, vomiting
Signs
Disc cupping, visual field loss,
raised intraocular pressure (IOP)
Mid-dilated non-reacting pupil, very high
IOP, cloudy cornea (figure 1)
Referral
Not urgent — very slow disease process
Emergency — rapid visual loss can follow
Treatment
Control IOP with topical therapy,
laser or surgery
Immediate IOP lowering, topical IV,
urgent laser treatment to open angle
Prognosis
Very good if detected early and
managed well. About 10% still show
slow progression
Good if prompt treatment given, but
many still require treatment and surgery
later
Differential
diagnosis
Exclude optic nerve compression and
tumours if atypical features
Iritis, keratitis, herpes zoster,
ophthalmicus, scleritis
Table 2: Differential diagnosis of other common causes of vision loss
Corticosteroids
Diagnosis
Features
Cataract
Slow onset (years) of visual blurring, glare symptoms, frequent glasses
change, monocular diplopia
Macular degeneration
Slow (or sudden if haemorrhagic) loss of central vision, distortion
(metamorphopsia), central blur or blind spot
Retinal detachment
Flashes, floaters, black curtain partly obstructing view and slowly
progressing from one side across field of view
Optic neuritis
Rapidly increasing vision loss, pain on eye movement
Congenital glaucoma
Migraine (variant episodes) Scintillating lights, expand and migrate across field in minutes, with
scotoma. If both eyes involved, cortical
Iritis
Pain, perilimbal blush, poorly reacting pupil, blurring but vision loss
not a major feature unless severe
The two main types of
glaucoma are compared in
table 1.
There is also a wide range
Corticosteroids — particularly when given as eyedrops, but also
any form of systemic administration such as inhalers — can
induce raised IOP in susceptible people and cause a secondary
open-angle glaucoma. If there is a family history or the patient is
already known to have glaucoma, the IOP should be checked if
therapy is continuing beyond two weeks.
Beware big-eyed babies with blepharospasm: watery eyes may
not be just a blocked tear duct. The high pressure expands the
globe and causes corneal oedema, with pain and tearing. This
is rare, however (1:10,000 births).
tary, uveitic, traumatic, contact lens induced) that through
various mechanisms interfere
with the internal drainage of
of secondary glaucomas,
which are relatively uncommon, caused by various disorders (eg, neovascular, pigmen-
aqueous fluid from the eye.
The differential diagnoses
of glaucoma are listed in
table 2.
How is glaucoma diagnosed?
GLAUCOMA, specifically POAG,
has classically been diagnosed by
testing for raised IOP. However,
we now know that at least onethird of glaucoma patients never
have high pressure, yet they
develop typical disease features (ie,
normal-tension glaucoma).
Also, many patients can have
ocular hypertension for years and
never develop the disease. Therefore screening for the disease
cannot rely on raised IOP alone. It
is essential to examine the optic
nerve to see if damage (loss of
nerve fibres) is present.
Clinically the first changes usually occur at the optic disc and it
remains vital that the clinician look
for the characteristic sign of optic
disc cupping. Every doctor should
learn to view the optic disc with
an ophthalmoscope, and anyone
with a large cup, or an asymmetry
between the optic discs of the two
eyes, should be referred for investigation.
Classically, the cup-to-disc ratio
has been used to detect disease, and
a cup greater than 60% of the disc
area (C:D ratio >0.6) is very suspicious of glaucoma (figure 2).
Unfortunately, evaluation of the
C:D ratio is very subjective and suffers from a large amount of interand intra-observer variability. Even
more importantly, the size of the
C:D ratio is directly related to the
size of the optic disc. Large optic
discs have physiologically large
cups and small discs have physiologically small cups.
A final call based on appearance
alone can sometimes be difficult
even for a trained glaucoma subspecialist. Therefore, in such cases
optic disc photographs are used to
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| Australian Doctor | 9 March 2007
Figure 2A: A normal optic disc. The optic cup is the paler area in the centre
and is assessed relative to overall disc size. In this case the cup-to-disc ratio
is 0.4; a ratio >0.6 is suspicious of glaucoma. 2B: Optic disc of a patient with
glaucoma. The darker fundus is due to racial background (Asian). Note the
relatively larger disc overall, with the cup extending out to the inferior rim,
showing loss of nerve fibres. The mottled pigment crescent is a feature of
myopic (short-sighted) eyes.
Figure 3A and 3B: Optic disc haemorrhages — a sign of progressive
glaucoma. There are two small haems on the right (A) and one on the left (B).
These can also occur in hypertension, diabetes and posterior vitreous
detachment. The left disc is notching superiorly, consistent with glaucoma.
A
A
B
B
document the status of the nerve
and to look for subtle future
changes that might suggest progression of the disease.
It is safer to refer someone if they
have a large cup, particularly if
there is a family history of glaucoma, even if this will involve some
false positives. An optic disc haemwww.australiandoctor.com.au
orrhage is also an important sign
(see figure 3).
The other means of detection is to
look for visual field loss. Glaucoma
blind spots (scotomas) tends to be
arc shaped, or ‘arcuate’, which corresponds to the distribution of the
damaged nerve fibres.
Ultimately when superior and
inferior arcuate defects join up, the
patient is left with tunnel vision.
This still remains the gold standard
for diagnosis despite its limitations,
which are discussed below. However, there are also several newer
methods of detecting and monitoring the disease that have recently
been developed.
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Detecting and monitoring glaucoma
Standard ophthalmic tests
IOP measurement (tonometry)
THIS is done by direct contact against the cornea after
application of local anaesthetic, for example, with a
Goldman tonometer, or with
an air-jet non-contact tonometer.
The latter can produce
some falsely high readings on
occasions, but has enabled
optometrists to do mass
screening examinations of the
public and refer when a
patient has raised pressure.
It is now known that the
corneal thickness can affect
the IOP reading, so this is
now also measured with ultrasound (pachymetry) to allow
for any necessary adjustments
to be made.
Figure 4: Standard subjective automated visual field testing and objective visual field testing with
multifocal visual evoked potential (mVEP), both showing scotoma (blind spot), compared with a
normal data base.
SUBJECTIVE VISUAL FIELD – WHITE ON WHITE
OBJECTIVE VISUAL FIELD – MULTIFOCAL VEP
Amplitude deviation
VEP traces
Temporal
area
Nasal
area
Gonioscopy
This involves close examination of the angle region using
a special contact lens containing internal mirrors, to determine whether the patient is at
risk of angle closure. If the
angle is narrow, a laser iridotomy is performed which
helps open the angle configuration and prevent a sudden
attack of closure.
32˚
32˚
P value (%)
≥5.0 <5.0 <2.0 <1.0
276 nV
279 ms
Figure 5: Optic disc imaged with scanning laser ophthalmoscope. Still within normal limits (green
ticks) but the red area on the pixel plot (B) suggests focal change compared with baseline.
A
B
Optic disc photographs
These are used to document
the status of the nerve and to
look for subtle changes in the
future that might suggest progression of the disease. Stereo
photos can provide 3D assessment of the disc structure.
Visual field testing (perimetry)
In white-on-white automated
perimetry the patient is asked
to detect small white-light targets projected into their
peripheral field of view on a
dim white background. The
intensity of the spots is varied
until they are not detected, to
establish the threshold level
for each of the 54 points that
extend out to 24° of eccentricity or more.
It is limited by the fact that
a large proportion (up to
50%) of the nerve fibres can
be lost before an initial defect
is seen and that patients find it
difficult — even stressful —
to perform. The results are
also variable, with a recognised phenomenon of a learning effect: it may take up to
three tests before a meaningful
result is produced.
Air-jet noncontact
tonometry can
produce some
falsely high
readings on
occasions, but
has enabled
optometrists to
do mass
screening
examinations of
the public.
Figure 6: Optic disc imaged with scanning laser polarimeter.
Nerve fibres polarise light: yellow = thicker fibres, blue =
thinner fibres.
Right Nerve Fibre Thickness Map
100%) for detecting moderate to severe losses in glaucoma, making it suitable for
visual field screening, but it is
less suited to monitoring
established defects.
The development of the
new FDT matrix, with a
greater number of smaller targets, improves the ability of
FDT to determine the spatial
extent of visual field defects,
although its sensitivity is
lower.
Short-wave automated
perimetry or blue/yellow
perimetry
These tests are usually only
available at specialist’s practices or major eye clinics. All
the tests described below are
useful adjuncts to the clinician
but cannot be solely relied on
for diagnosis.
New visual field techniques
Frequency-doubling technology
(FDT)
FDT works by flickering a
coarse pattern of vertical dark
and bright bars at a very high
frequency. This produces the
appearance of twice as many
bars than are physically present. Subjects respond to test
patterns at multiple sites
within the field of view.
The advantages of the FDT
are that it is a compact, transportable test, with tolerance
to refractive errors and rapid
test times. It has good sensitivity and specificity (96-
www.australiandoctor.com.au
scotomas in glaucoma. It may
also be very useful in detecting
and monitoring optic neuritis,
and possibly predicting
patients at higher risk of multiple sclerosis.
The advantages of the
method are that it removes
subject indecision, and
patients find it easier to perform. Limitations are that it
is more technician dependent,
and visual acuity is still important (patients need to focus on
the centre).
New structural tests
Short-wave automated
perimetry (SWAP) is similar
to standard automated
perimetry except that it uses
a blue-light stimulus projected onto a bright-yellow
background. This isolates
the blue cone pathway by
saturating the red and green
cones and simultaneously
suppressing rod activity.
Previous investigations have
established that SWAP is a
more sensitive indicator of
early damage and progression
of field loss than standard
automated perimetry. Clinically it is recommended particularly for younger patients
with early disease or high-risk
suspects.
Objective perimetry —
multifocal visual evoked
potential
New methods available for
detecting glaucoma
The newer methods are specifically designed to detect
change at earlier stages of the
disease or to be less subjective.
Psychophysical tests have been
developed that target smaller
subpopulations of ganglion
cells.
Optic disc and nerve fibre
imaging techniques using
scanning laser ophthalmoscopes or optical coherence
tomography can provide
objective measures of structural change.
Figure 7: Optic cup seen in cross-section, imaged with optical
coherence tomography (OCT).
Because of the variability of
subjective techniques, an
objective measure of the visual
field is valuable (figure 4). The
multifocal visual evoked
potential (mVEP) technique
involves simultaneously
recording visual evoked
potential responses from each
of 58 segments of the visual
field out to 24°, compared
with conventional VEP which
records only a mass signal
dominated by the central field.
The visual stimulus is a
checkerboard pattern of
pseudo-randomly reversing
checks at each of the 58 sites.
The patient is required to look
at a central fixation point.
Four electrodes are placed
over the occipital region to
record responses from the
visual striate cortex.
The mVEP technique is
ideal for patients with unreliable standard perimetry. Clinical studies have shown high
sensitivity (95%) for detecting
Imaging of the optic disc and
retinal nerve fibre layer
The following new technologies document the structure of
the optic nerve head and provide a basis for future comparisons to detect change over
time.
Heidelberg retinal tomography (figure 5). This is a scanning laser ophthalmoscope
that rapidly projects a laser
grid across the disc (1-2 seconds) and records with multiple layers of focal depth. It
then generates a 3D image of
the optic disc surface and surrounding retina.
The scanning laser polarimeter (figure 6). This instrument
provides quantitative assessment of the retinal nerve-fibre
layer, using a polarised laser.
It does not measure optic disc
dimensions or cup size — only
thickness of the retinal nervefibre layer.
Optical coherence tomography (figure 7). This is a noninvasive, non-contact imaging
technique using back-scatterered light that provides crosssectional images of the retina
for evaluating both retinal diseases and glaucoma. It is particularly good for assessing the
macular region in macular
degeneration.
These techniques are easy to
use and have good patient
acceptance. Their main limitation is that, when comparing a
patient’s optic nerve to those
of the general population,
there is such great variability
among normals that we
cannot always be certain that
strangely shaped optic discs or
thin nerves are not just normal
variants. Serial scans over time
are more valuable.
9 March 2007 | Australian Doctor |
25
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How to treat – glaucoma
Medications and their main side effects (table 3)
THE five main groups of therapeutic agents used to treat
glaucoma are beta blockers,
prostaglandin derivatives,
alpha 2 -adrenergic agents,
miotics and carbonic anhydrase inhibitors. All attempt
to lower IOP, some by reducing aqueous production,
others by increasing the escape
of aqueous from the eye.
When drugs are used, the
incidence and severity of systemic side effects can be
reduced by the patient performing digital punctal occlusion with the index finger for
1-2 minutes after drop instillation. This manoeuvre
reduces the amount of the
medication passing down the
nasolacrimal duct to the nasal
mucosa, where drugs are
readily absorbed.
Table 3: Medications used in glaucoma, and their main side effects
Class
Generic/trade names
Side effects
Beta blockers
Timolol (0.25%, 0.5%)
(Nyogel 0.1%, Tenopt, Timoptol,
Timoptol XE, Timoptic),
Levobunolol 0.25% (Betagan),
Betaxolol 0.25%, 0.5% (Betoptic)
Bronchoconstriction, bradycardia,
fatigue, headache, confusion,
depression, nightmares, impotence,
effects on lipids, masking of
hypoglycaemia
Prostaglandin
derivatives
Latanoprost 0.005% (Xalatan),
Travoprost 0.004% (Travatan),
Bimatoprost 0.03% (Lumigan)
Iris colour change to brown,
eyelash growth, periorbital pigment,
hyperaemia, HSV keratitis reactivation
Alpha2 agonists
Aproclonidine 0.5% (Iopidine),
Brimonidine 0.2%, (Alphagan)
Local allergy, fatigue, dry mouth,
blurring
Miotics
Pilocarpine 0.5-6%
Miosis, headache, blurring, reduced
night vision
Topical
Dorzolamide 2 % (Trusopt),
Brinzolamide 1% (Azopt)
Local irritation, metallic taste
Oral
Acetazolamide 250mg (Diamox)
Parasthesiae, malaise, fatigue,
depression, hypokalaemia, metabolic
acidosis, gastrointestinal
disturbances, kidney stones
Carbonic
anhydrase inhibitors
Beta blockers
Timolol 0.25% or 0.5%
(Timoptol, Timoptol XE,
Timoptic, Tenopt, Nyogel
0.1% ) is a non-selective beta
blocker that lowers IOP by
reducing aqueous secretion.
Side effects include bradycardia, bronchospasm and systemic hypotension.
Timolol should not be used
in patients with heart block
and can cause unrecognised
reduced exercise tolerance in
the elderly. Other side effects
include fatigue, disorientation,
confusion and depression,
headache, nightmares, impotence and masking of hypoglycaemia in patients with diabetes. Nyogel is a gel-based
preparation, allowing a lower
concentration to be used. Levobunolol (0.25%) (Betagan) is
also non-selective and has a
similar profile to Timolol.
Betaxolol (0.25%, 0.5%)
(Betoptic) is a selective beta1adrenergic blocking agent,
which is nearly as effective as
timolol in lowering IOP and
has the advantage of having
little effect on the cardiopulmonary system. It is therefore
safer to use than timolol in
patients with pulmonary disease (but still not totally safe) .
Despite side effects, beta
blockers remain in widespread
use, and timolol is in all four
combination products released
to date (see later).
Prostaglandin derivatives
Latanoprost 0.005% (Xalatan) is a synthetic prostaglandin derived from prostaglandin F2α. It has an
impressive IOP-lowering effect
by increasing outflow through
the uveo-scleral pathway
rather than the trabecular
meshwork. It only requires
once-daily dosage.
It seems to be relatively free
of systemic side effects but can
irreversibly change the colour
of green-brown, yellowbrown and hazel irises to dark
brown in some patients. It
also enhances eyelash growth.
Patients often experience
red eyes after starting therapy,
but in many cases this dimin-
28
Points to note when
using beta blockers
■
Use caution with timolol
and topical beta blockers.
If the patient is already
taking them systemically
they should be avoided.
■
Beta blockers may be the
cause of unexplained
dyspnoea, cough, fatigue,
depression, dizziness.
■
Systemic absorption of
beta blockers (and other
drops) can be reduced by
digital occlusion over the
nasolacrimal sac after
installation.
What about marijuana?
■ Yes it can lower IOP, but
the dose/effects are
variable. Cannabinoid
derivative agents are
being trialled in topical
form.
■ No other herbal or
alternative agents have
been conclusively shown
to be beneficial in
glaucoma. Gingko may
help ocular perfusion.
Coleus potentially could
lower IOP but it is difficult
to get enough delivered
to where it is needed to
the ciliary body.
Acupuncture is not an
effective treatment for
glaucoma.
| Australian Doctor | 9 March 2007
ishes over time. Reactivation
of HSV keratitis has been
reported and, rarely, macular
oedema in patients with previous complicated surgery.
Travoprost 0.004% (Travatan) is a similar synthetic
prostaglandin. Bimatoprost
0.03% (Lumigan) is an alternative prostamide derivative.
Both have a similar mode of
action, efficacy and side effects
to those of latanoprost. The
prostaglandin derivatives are
now the most commonly
prescribed agents for new
patients.
Alpha2-adrenergic agents
These selectively stimulate the
alpha2 receptors in the ciliary
epithelium to reduce the formation of aqueous. The two
drugs available are apraclonidine 0.5% (Iopidine) and brimonidine 0.2% (Alphagan).
They are both very useful
for short-term pressure control, particularly after laser
therapy to prevent pressure
spikes. In longer-term treatment, aproclonidine tends to
lose some efficacy over time
and has a fairly high incidence
of local allergy.
Brimonidine is more alpha2
specific and therefore has less
potential for the alpha1-related
side effects. It is similar to timolol in lowering pressure and
has a dual mode of action,
both decreasing aqueous
inflow and increasing
uveoscleral outflow.
Its side effects mainly relate
to local allergy, the incidence
of which is around 15%, but
feelings of fatigue and lethargy
can also occur. Visual blurring occurs occasionally, and
dry mouth is common.
Dipivefrin 0.1% (Propine)
is a drug that is converted into
adrenaline after absorption
into the eye. Side effects relate
to alpha1 activity and include
conjunctival hyperaemia and
occasional headache and blurring. It is now rarely used.
Carbonic anhydrase
inhibitors
The only orally administered
carbonic anhydrase inhibitor
now used in the treatment of
glaucoma is acetazolamide
(Diamox) 250mg. Acetazolamide can also be administered IV in acute attacks.
Unfortunately, the usefulness of the drug in long-term
therapy is limited by side
effects. Paraesthesiae of the
fingers and toes are a universal side effect. There can
be malaise, fatigue, depression, loss of weight and
decreased libido. This is
often associated with systemic metabolic acidosis.
Other side effects consist of
gastric irritation, abdominal
cramps, diarrhoea and
nausea. Kidney stone formation is another rare complication, related to decreased urinary citrate excretion.
Because the carbonic anhydrase inhibitors belong to the
sulfonamide family of drugs,
they may cause the StevensJohnson syndrome and blood
dyscrasias.
Dorzolamide (Trusopt) 2%
is a carbonic anhydrase
inhibitor that can be used in
drop form (usually three
times daily). It is not as potent
as the oral form but carries
minimal chance of systemic
side effects. It is less effective
than timolol at lowering IOP.
Its side effects include a
metallic taste in the mouth,
local stinging and burning. It
may exacerbate corneal problems. Brinzolamide (Azopt)
1% performs similarly to
Trusopt but has an advantage
of less stinging on installation.
Miotics — pilocarpine
(1%, 2%, 3% and 4%) and
carbachol 3%
Miotics are the oldest treatment group for glaucoma and
work by stimulating cholinergic receptors. This produces
contraction of the ciliary
muscle, which in turn pulls
on the trabecular meshwork
and enhances outflow of
aqueous.
Unfortunately cholinergic
stimulation also contracts the
pupil (miosis) and changes the
www.australiandoctor.com.au
accommodative status of the
lens (induced myopia), which
leads to the common side
effects, including diminished
night vision, permanent
miosis with prolonged use,
reduced visual acuity, and a
generalised constriction of
the visual field.
Frontal headache is a frequent symptom at the start
of therapy but usually
regresses after a few weeks.
Retinal tears and detachment are very rare complications related to ciliary
muscle contraction.
Systemic side effects are
uncommon but include
bradycardia, increased
sweating, diarrhoea, salivation and anxiety, due to
parasympathetic stimulation.
Miotics are cheap and
effective pressure-lowering
drugs but are now used much
less frequently because of
their side effect profile.
Combinations
Combination products use different classes of medication
combined with timolol, which
saves the patient time and
expense and improves compliance. It also reduces the total
exposure to preservatives, and
the washout effects of instilling
drops sequentially.
Available combinations are:
■ Cosopt
(Trusopt plus
Timolol).
■ Xalacom (Xalatan plus
Timolol).
■ Combigan (Alphagan plus
Timolol).
■ DuoTrav (Travatan plus
Timolol).
Drug interactions and
systemic medications
The main risk is that of combining systemic beta blockers
with topical preparations,
increasing the risk of side
effects, especially now there
are several combination
products containing timolol.
Oral Diamox can cause
severe hypokalaemia and
metabolic acidosis, so caution
is required when there is
polypharmacy in the elderly.
Some diuretics and topiramate
(Topamax) have rarely been
reported to cause a secondary
angle closure due to uveal
effusions. SSRI antidepressants
have in a few isolated cases
caused IOP rises.
Many products contain
warnings for use in glaucoma
(eg, anticholinergics, tricyclic
antidepressants). This almost
always refers to patients with
narrow angles, who are at risk
of angle closure, and is not a
factor in POAG patients.
If patients with narrow
angles have had a prophylactic laser iridotomy, it then
becomes safe to prescribe
these drugs. If unsure, check
with the ophthalmologist as
to the type of glaucoma.
Principles of medical
therapy
The initial therapy of glau-
coma is topical. The chosen
drug should be used in its
lowest concentration, as
infrequently as possible, to
achieve the desired effect.
In most cases the initial
medical therapy is with a
prostaglandin derivative or
a beta blocker. If this is ineffective another class of drug
can be tried, or added to the
therapy. Pilocarpine is now
usually reserved for older
patients who are uncontrolled with other medications or cannot take them
because of side effects.
Because of the risk of side
effects, systemic Diamox is
considered mainly for emergency or short-term treatment, or in those in whom
surgery is undesirable or
being deferred.
In general any vascular
risk factors such as diabetes,
hypertension, cholesterol or
carotid artery disease should
also be addressed. The
patient should be encouraged to stop smoking and to
take regular exercise. If
underlying cardiovascular
disease is present, low-dose
aspirin theoretically may
help the ocular circulation.
If the patient is taking systemic antihypertensive medications, care should be
taken that they are not dropping their blood pressure too
low at night (‘dippers’), as
nocturnal hypotension has
been shown to be linked to
progression. The link with
sleep apnoea is still contentious, but could be considered.
Rarely, calcium channel
blockers such as nifedipine
may possibly be of benefit in
certain cases when an underlying vasospastic process is
suspected, but should be
used with caution.
Follow-up evaluation
After initiation of therapy
the patient is seen at 2-4weekly intervals until the
IOP is controlled, and then
at 3-6-monthly intervals.
Unfortunately the actual safe
level of IOP is still unknown,
although in most cases further damage is unlikely if the
IOP has been reduced to the
lower ‘teens’.
An optic nerve head showing minimal damage can tolerate a higher IOP than one
with gross cupping and
advanced visual field loss.
Only stability of the visual
fields and optic disc structure are proof that the IOP is
indeed at a safe level for the
individual.
Myopic (short-sighted)
eyes seem to deteriorate
faster and at lower pressures.
Underlying vascular disease
may also predispose to
damage at relatively lower
pressures. The results of all
large clinical trials suggest
the lower the pressure the
better the chances of stabilising the disease.
AD_HTT_023_030___MAR09_07 2/3/07 4:27 PM Page 29
Glaucoma surgery
Laser therapy
THERE are several possible
applications for the use of
lasers. The most commonly
used laser, the argon laser,
is used for a procedure
known as an argon laser trabeculoplasty. Multiple
microscopic burns are made
in the trabecular meshwork
to enhance the escape of
fluid into the normal
drainage system.
The procedure is suitable
for open-angle glaucoma but
is not suitable for angle-closure glaucoma or secondary
glaucomas when the meshwork is damaged or obstructed, such as traumatic
angle recession, neovascular
(rubeotic), uveitic or angle
closure.
A newer form of laser
procedure termed selective
laser trabeculoplasty has
recently been developed. It
is designed to target the
wavelength of pigment and
to release brief pulses of
energy in the trabecular cells,
without causing collateral
burns or damage.
It is therefore theoretically
much safer, and clinical trials
show that it provides at least
equivalent efficacy if not better
results than traditional laser.
It is presumed new cells repopulate the meshwork after the
procedure. The procedure can
potentially be repeated, unlike
argon laser trabeculoplasty,
which it has replaced in my
clinical practice.
A second type of treatment is the peripheral laser
iridotomy, which uses the
laser to create a channel
through the iris. Either argon
laser or Nd YAG laser can
be used for this. The purpose
of the channel is to prevent
or treat angle-closure glaucoma.
Aqueous collecting in the
posterior chamber can pass
directly through the iridotomy to the anterior chamber, allowing the peripheral
iris to move backwards,
minimising pupil block.
Pupil block occurs when
the margin of the pupil sits
snugly back against the
convex anterior lens surface
and slows the flow of aqueous through to the anterior
chamber. This causes the
peripheral iris to bulge for-
as these, success rates are as
low as 50% for routine trabeculectomy, unless antiscarring agents are used.
During the last two
decades, anti-metabolites
have been commonly used in
conjunction with glaucoma
filtration surgery to reduce
scarring. Postoperative 5-fluorouracil (5-FU) has been
used since the mid-1980s. It
was found to increase the
success of filtration surgery
in high-risk eyes.
More recently, mitomycinC and 5-FU are being used
intra-operatively during glaucoma filtration surgery, and
have demonstrated increased
surgical success rates.
ward and obstruct the meshwork by direct contact.
If the angle-closure attack
is already established, a
peripheral laser iridotomy is
an effective emergency treatment that saves the patient
from conventional surgery.
It usually does not serve to
lower the pressure on its
own in open-angle glaucoma.
Occasionally it is necessary to perform both peripheral laser iridotomy and
argon or selective laser trabeculoplasty if a patient is at
risk of both forms of glaucoma, but they are usually
done at separate sessions.
Laser therapy is performed
on site at either the specialists’ rooms or the hospital
clinic. It is done as a day
procedure and the patient
can walk out afterwards.
The procedures are virtually
painless, so they do not
require any anaesthetic other
than topical for placing a
special contact lens.
Apart from some initial
blurring for a few hours,
vision quickly returns to
normal. Each treatment only
takes a few minutes to perform.
When does laser treatment
become necessary?
In POAG, laser trabeculoplasty is usually used as a
second-line treatment when
eye drops have either not
provided sufficient effect on
their own, or are not well
tolerated because of side
effects.
Laser can also be used as a
first-line treatment if the
ophthalmologist and patient
prefer this approach. Occasionally the laser treatment
lowers the IOP enough to
allow the patient to reduce
the number of eye drops
being used.
Argon or selective laser
trabeculoplasty can lower
IOP by up to one-third in
most patients (about 70%
will show a response).
However, the magnitude of
the reduction achieved
varies greatly between individuals and is impossible to
predict.
The duration of effect
ranges from months to many
years (up to 10 years). Most
studies claim that about
75% of patients will achieve
a lowering of pressure, with
the remainder unchanged.
Peripheral iridotomies usually remain open for life, and
only occasionally close spontaneously.
Filtration surgery
In general, filtration surgery
should be considered in
cases of uncontrolled glaucoma despite maximally tolerated medical therapy and
laser therapy. The aim of
glaucoma filtration surgery
is to create a new route of
escape for the aqueous fluid,
from the anterior chamber
directly to the subconjunctival space. From there the
fluid will be reabsorbed via
the episcleral venous system
and returned to the bloodstream.
Trabeculectomy
This is the most common
surgical procedure performed for glaucoma. It can
be done in isolation or
together with cataract
extraction and lens implant
(a combined procedure). A
two-thirds-thickness scleral
trapdoor is dissected, and a
deep block of sclera is
excised to enter the anterior
chamber.
A peripheral iridectomy is
performed. The scleral flap
is repositioned and resutured
with 10/0 nylon. The conjunctiva is closed over the
top, but aqueous filters
through the trapdoor and
this lifts the conjunctiva up
into a bubble or ‘bleb’ at the
site of filtration, from where
it is reabsorbed by conjunctival vessels.
Some serious complications can occur at the time
of surgery (such as expulsive
haemorrhage) or later,
including changes in refraction, hyphema, shallow anterior chamber or hypotony,
wound leaks, endophthalmitis, cataract (late, around 3050%), conjunctival scarring
and bleb failure.
The success rate of filtration surgery in glaucoma is
about 80-90%. Success is
defined as lowering the pressure into the normal range
(<20mmHg). The results are
less favourable in young
patients, black patients, eyes
with uveitis or neovascular
glaucoma and in people with
any previous ocular surgery.
In high-risk groups such
Author’s case study
Slowly progressing ocular
hypertension in an older
woman
A 58-YEAR-old woman presented in 1986 with a family history of glaucoma in her mother.
She had IOPs of R 22mmHg
and L 26mmHg. She had
normal-appearing optic discs,
with cup-to-disc ratios of 0.5 in
both, and normal visual fields.
There were no other systemic or
ocular risk factors.
She was diagnosed with ocular
hypertension, and her management plan was annual observation. She remained stable with
an IOP range of 18-24mmHg
for the next 10 years.
Her left optic disc then started
to thin at the superior pole. She
started treatment with timolol,
and IOP was maintained in the
17-20mmHg range (inside the
normal limits of 10-20mmHg).
However, her visual field defect
progressed and further notching
of the optic disc was detected.
Corneal thickness revealed
thin corneas, at R 478µm and L
480µm. True IOP was therefore
several points higher than suspected, and pressure not as well
controlled as thought.
Latanoprost was added to her
treatment to achieve lower target
pressure in her left eye, aiming
for <14mmHg. A subsequent
disc haemorrhage in the right
eye suggested that glaucoma was
active in this eye also and so
needed tighter control.
www.australiandoctor.com.au
Implant tubes (Molteno,
Baerveldt and Ahmed)
Tube implants consist of a
domed plate attached to a
tube that allows free flow to
the implant from the anterior
chamber. In this way the fistula is maintained and a reliable, more posteriorly located
bleb is formed. Molteno
implants are used in cases for
which previous surgery has
been unsuccessful, or when
standard surgery is not likely
to be effective.
When to refer
All patients with POAG and
a family history of glaucoma
should have a baseline check
by age 40, and earlier if
there are several family
members involved, or the
age of onset was relatively
young. They should then
have a routine check every
four years.
If there are additional risk
factors such as myopia,
hypertension, diabetes, Raynaud’s syndrome, migraine
or known ocular risk factors
(such as pseudo-exfoliation),
the frequency of checks
should be increased appropriately, for example, every
1-2 years.
Any patient with angleclosure glaucoma and a
painful red eye needs immediate referral, particularly if
the pupil is reacting poorly.
Intermittent angle-closure
attacks can produce episodes
of pain and blurring (with
or without haloes), without
redness, so beware of this on
history.
Further reading
Mitchell P, et al. Prevalence
of open-angle glaucoma in
Australia: the Blue
Mountains Eye Study.
Ophthalmology 1996;
103:1661-69.
Kass MA, et al. The Ocular
Hypertension Treatment
Study. Archives of
Ophthalmology 2002;
120:701-13.
Graham SL. Are vascular
factors involved in
glaucomatous damage?
Australian and New
Zealand Journal of
Ophthalmology 1999;
27:354-56.
Graham SL, et al. Clinical
application of the multifocal
VEP in glaucoma. Archives
of Ophthalmology 2005;
123:729-39.
Fraser C, et al. Multifocal
VEP latency analysis —
predicting progression to
multiple sclerosis. Archives
of Neurology 2006; 63:84750.
Online resources
Glaucoma Australia is a
very active patient-support
group with online patient
information, regular
newsletters and
educational meetings for
patients:
www.glaucoma.org.au
■ Eye Associates (patient
information on common
eye disorders):
www.eyeassociates.com.
au
■ Save Sight Institute
(services and research):
www.eye.usyd.edu.au
■ Royal Australian and
New Zealand College of
Ophthalmology:
www.ranzco.edu
■
Proprietary statement
Dr Graham is a consultant
for ObjectiVision Pty Ltd.
9 March 2007 | Australian Doctor |
29
AD_HTT_023_030___MAR09_07 2/3/07 4:28 PM Page 30
How to treat – glaucoma
GP’s contribution
DR PHILIP LYE
Sutherland, NSW
Case study
JEAN, an 80-year-old Australian woman, has had
glaucoma for many years.
Over the last few years she
had been treated with
betaxolol (Betoptic, Betoquin) and brimonidine
(Alphagan, Enidin). I saw
her when her usual GP was
on holidays.
She complained of
headaches, pain behind her
eyes, fatigue and worsening
anxiety. Her blood pressure
was 200/90mmHg and I
increased her antihypertensive medications.
I was not able to refer
Jean to her usual ophthalmologist and requested the
local optometrist measure
her IOP, which showed
readings of 22-23mmHg in
both eyes. She was also
noted to be developing a
right cataract, so I added
pilocarpine drops. Unfortunately, she did not improve
and she also had nausea and
worsening confusion.
When her ophthalmologist
returned to work, her ocular
pressures were 16mmHg in
both eyes. Several months
later her pressures were still
in the high teens, and he
stopped all the above eye
drops and changed her to
dorzolamide-timolol drops
(Cosopt).
Unfortunately, Jean still
has intermittent headaches
and pains behind her eyes.
Her ocular pressures are in
the mid-teens, her blood
pressure is now just under
control and her pulse rate is
about 50bpm.
She is also taking ramipril,
irbesartan, metoprolol and
hydrochlorothiazide for her
hypertension. For anxiety
and depression she takes
oxazepam and doxepin.
Questions for the author
Could Jean’s glaucoma treatment account for some of
her symptoms? If so, what
other medications should we
try?
Beta blockers and brimonidine can both cause
headaches and fatigue. This
ing to bradycardia and can
also cause depression.
General questions for the
author
could be exacerbated
because she is also using systemic metoprolol. Cosopt
still contains a beta blocker,
and pilocarpine can cause
headaches by ciliary muscle
contraction.
You should consider using
one of the prostaglandin
derivatives (if not already
tried) dorzolamide or brinzolamide; otherwise laser
treatment would be the next
choice.
How often should her ocular
pressures be checked if we
How to Treat Quiz
Could she be having adverse
drug interactions?
Yes, definitely, with the
other agents she is taking.
Timolol could be contribut-
about every five years
❏ c) If she develops POAG, early and
continued treatment can prevent progression
in 90% of cases
❏ d) Having hypertension increases her risk of
POAG
2. Which TWO features are characteristic of
POAG?
❏ a) Loss of visual field
❏ b) Universal elevation of intraocular pressure
(IOP)
❏ c) Optic disc cupping
❏ d) Rapid progression if untreated
4. Janice is referred to an ophthalmologist
for assessment. Which TWO statements
about the diagnosis of POAG are correct?
❏ a) An IOP >20mmHg is considered abnormal
❏ b) For exclusion of glaucoma patients need
fundoscopy as well as IOP measurement
❏ c) On field testing, blind spots are usually
circular in shape
❏ d) Gonioscopy is used to measure IOP
3. Janice, 48, presents for a repeat
prescription for her antihypertensive
medication. She wears glasses for distant
vision and has had no problems with her
vision. She has not seen her optometrist for
many years. Janice mentions that her mother
uses eye drops for POAG. What information
would you discuss with Janice (choose TWO)?
❏ a) As Janice has no visual symptoms she is
unlikely to have glaucoma
❏ b) She should be screened for glaucoma
5. Thomas, 67, has just been diagnosed with
POAG and his ophthalmologist wishes to
start him on medical therapy. When choosing
therapy which TWO statements about
medication side effects are correct?
❏ a) Timolol should not be used if Thomas has a
history of asthma
❏ b) A disadvantage of latanoprost is the need
to use it three times daily
❏ c) Reactivation of HSV keratitis is a potential
problem with latanoprost
Have formulas been developed to calculate risk of
glaucoma by factoring in
these risk factors?
The Ocular Hypertension
Treatment Study findings
(see Further reading) have
been used to produce a risk
calculator for ocular hypertension that can be used by
ophthalmologists, but this
What pressures are considered unacceptably high, so
that patients should be seen
as soon as possible by an
ophthalmologist?
There is no definite cutoff, but certainly IOPs
>30mmHg should be treated
as relatively urgent, as there
is an increased risk of a vascular occlusion in this scenario.
I would like a very simple
section on how to read a
RNFL report and perimetry
report. Copies of these are
now routinely sent to me by
the ophthalmologist and I
have no idea what I am
reading! Is there a simple
explanation available?
Unfortunately there is no
simple approach, as all the
tests use different printouts
and statistical analyses. Perimetric and imaging tests all
use a probability plot compared with normative values,
so any point at the p<0.01
level is highly significant,
(but not diagnostic or specific for glaucoma). Interpret
with caution!
INSTRUCTIONS
Complete this quiz to earn 2 CPD points and/or 1 PDP point by marking the correct answer(s) with
an X on this form. Fill in your contact details and return to us by fax or free post.
FAX BACK
Photocopy form
and fax to
(02) 9422 2844
Glaucoma — 9 March 2007
1. Which TWO statements about primary
open-angle glaucoma (POAG) are correct?
❏ a) Long-sighted people are at greater risk of
this condition
❏ b) Family history and age are the most
significant risk factors
❏ c) Visual losses can be restored by treatment
❏ d) Incidence in older people is up to 8%
are titrating dosage of glaucoma medications?
If the pressures are not
dangerously high or the
optic disc not badly damaged, we usually wait 3-6
weeks to check, depending
on the class of drug being
used. Prostaglandins can
take six weeks to reach
stable effects.
The RACGP does not recommend routine screening
for glaucoma using tonometry or visual field tests. However, GPs play an essential
role in identifying patients at
higher risk for glaucoma and
referring them to an ophthalmologist for testing.
Patients with increased risk
include those aged over 60
or with a family history of
glaucoma, or with high
myopia >8 diopters, diabetes
or history of long-term
steroid use. Would it be reasonable to recommend a
glaucoma check at the 4549 year check up if patients
have the above risk factors?
Yes.
requires corneal thickness
measurement and visual field
values.
FREE POST
How to Treat quiz
Reply Paid 60416
Chatswood DC NSW 2067
❏ d) About one-third of patients using
brimonidine will develop local allergy side
effects
6. Thomas has been started on timolol drops.
Which THREE side effects should you warn
him about?
❏ a) Impotence
❏ b) Fatigue
❏ c) Dry mouth
❏ d) Nightmares
7. Jim, 79, is using several different eye drops
for his POAG — trusopt-timolol combined
drops (Cosopt), bimatoprost and pilocarpine.
He complains of reduced night vision, a
metallic taste in his mouth, headache and
tiredness. Which THREE associations of
medications and side effects are correct?
❏ a) Trusopt-timolol and metallic taste
❏ b) Pilocarpine and reduced night vision
❏ c) Bimatoprost and headache
❏ d) Trusopt-timolol and fatigue
8. Jim is tired of constantly using eye drops
and putting up with side effects. He asks
about the possibility of surgery to treat his
glaucoma. Which TWO pieces of advice do
ONLINE
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for immediate feedback
you give Jim?
❏ a) A peripheral laser iridotomy would be the
most suitable procedure for Jim
❏ b) He has about a 70% chance of
improvement in his IOP with argon or
selective laser trabeculoplasty
❏ c) Having laser treatment will allow Jim
to be free of using eye drops
❏ d) He will probably only need a topical
anaesthetic if he has laser surgery
9. Which TWO statements about
angle-closure glaucoma are correct?
❏ a) The angle is the region between the iris and
the lens
❏ b) It is more common in Caucasian people
❏ c) It usually presents with a painful red eye
with a mid-dilated pupil that does not react
to light
❏ d) Patients may report seeing haloes and
have a headache and vomiting
10. Which TWO medications can cause
secondary glaucoma?
❏ a) Corticosteroid eye drops
❏ b) Beta blockers
❏ c) SSRI antidepressants
❏ d) Salbutamol
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HOW TO TREAT Editor: Dr Marcela Cox
Co-ordinator: Julian McAllan
Quiz: Dr Marcela Cox
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Your CPD activity will be updated on your RACGP records every January, April, July and October.
NEXT WEEK The next How to Treat looks at community-acquired pneumonia. The author is Professor Nigel Stocks, professor and head, discipline of general practice; director, primary health care research
evaluation and development program; director, Australian sentinel practices research network, school of population health and clinical practice; and assistant dean (student), medical school faculty of health
sciences, University of Adelaide, Australia.
30
| Australian Doctor | 9 March 2007
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