The glaucomas are a range of disorders with a characteristic
type of optic nerve damage.
The glaucomas are the second
commonest cause of blindness in the world, and the
commonest cause of irreversible blindness.
The most effective
way of preventing this damage is to lower the intraocular
pressure.
Normally the ciliary body secretes aqueous, which flows into
the posterior chamber and through the pupil into the anterior
chamber.
It leaves the eye through the trabecular meshwork,
flowing into Schlemm’s canal and into episcleral veins.
The
flow and drainage can be obstructed in several ways.
Symptoms and signs
A patient with primary open angle glaucoma (also known as
chronic open angle glaucoma) may not notice any symptoms
until severe visual damage has occurred.
This is because the
rise in intraocular pressure and consequent damage occurs so
slowly that the patient has time to compensate.
In contrast, the
clinical presentation of acute angle closure glaucoma is well
known, as the intraocular pressure rises rapidly and results in
a red, painful eye with disturbance of vision. Raised intraocular pressure
Most patients with raised intraocular pressure (IOP) are
unaware that they have a problem.
Raised IOP is detected most
commonly through screening as part of a routine eye test by an
optometrist.
The IOP is determined by the balance between
aqueous production inside the eye and aqueous drainage out
of the eye through the trabecular meshwork.
Each normal eye makes about 2 µl of aqueous
a minute that is, about 70 litres
during the course of a lifetime.
In a British Caucasian
population, 95% of people have an IOP between 10 and
21 mm Hg, but IOP can drop as low as 0 mm Hg in hypotony
and can exceed 70 mm Hg in some glaucomas.
The rate at which raised IOP causes optic nerve damage
depends on many factors, including the level of IOP and
whether glaucomatous damage is early or advanced.
In general,
raised IOPs in the 20-30 mm Hg range usually cause damage
over several years, but very high IOPs in the 40-50mm Hg
range can cause rapid visual loss and also precipitate
retinovascular occlusion.
Haloes around lights and a cloudy cornea
The cornea is kept transparent by the continuous removal of
fluid by the endothelial cells.
If the pressure rises slowly, this
process takes longer to fail.
When the pressure rises quickly
(acute closed angle glaucoma) the cornea becomes
waterlogged, causing a fall in visual acuity and creating
haloes around lights (like looking at a light through frosted
glass).
Pain
If the rise in pressure is slow, pain is not a feature of
glaucoma until the pressure is extremely high.
Pain is not characteristically a feature of primary open angle
glaucoma.
Visual field loss
Pressure on the nerve fibres and chronic ischaemia at the optic
nerve head cause damage to the retinal nerve fibres and usually
results in characteristic patterns of field loss (arcuate scotoma).
However, this spares central vision initially, and the patient
does not notice the defect.
Sophisticated visual field testing
techniques are required to detect early visual field defects.
The terminal stage of glaucomatous field loss is a severely
contracted field, because only a few fibres from the more richly
innervated macula area survive.
Even at this stage (tunnel
vision) the vision may still be 6/6.
Optic disc changes
The optic disc marks the exit point of the retinal nerve fibres
from the eye. With a sustained rise in IOP the nerve
fibres atrophy, leaving the characteristic sign of chronic
glaucoma the cupped, pale optic disc.
Venous occlusion
Raised IOP can impede blood flow in the low pressure venous
system, increasing the risk of retinal venous occlusion.
Enlargement of the eye
In adults no significant enlargement of the eye is possible
because growth has ceased.
In a young child there may be
enlargement of the eye (buphthalmos or “ox-eye”).
This tends
to occur with raised IOP in children under the age of three
years. These children may also be photophobic and have
watering eyes and cloudy corneas.
Primary open angle glaucoma
Primary open angle glaucoma is the most common form of
glaucoma and is the third most common cause of registration
of blindness in the United Kingdom.
The resistance to outflow
through the trabecular meshwork gradually increases, for
reasons not fully understood, and the pressure in the eye
slowly increases, causing damage to the nerve.
The level
of IOP is the major risk factor for visual loss.
There may be
other damage mechanisms, particularly ischaemia of the optic
nerve head.
Symptoms
Because the visual loss is gradual, patients do not usually
present until severe damage has occurred.
The disease can
be detected by screening high risk groups for the signs
of glaucoma.
At present most patients with primary open
angle glaucoma are detected by optometrists at routine
examinations.
Groups at risk
The prevalence increases with age from 0.02% in the 40-49 age
group to 10% in those aged over 80.
Those with an increased risk include first degree relatives of patients (1 in 10), patients
with ocular hypertension (particularly those with thin corneas,
larger cup to disc ratios and higher IOPs), people with myopia,
and people of African-Caribbean origin (X 5 risk in
Caucasians).
Recently, genetic mutations have been identified
that account for 3-4% of primary open angle glaucomas.
Signs
The eye is white and on superficial examination looks normal.
The best signs for the purpose of detection are the optic disc
changes.
The cup to disc ratio increases as the nerve fibres
atrophy.
Asymmetry of disc cupping is also important, as the
disease often is more advanced in one eye than the other.
Haemorrhages on the optic disc are a poor prognostic sign.
Longer term changes in disc cupping are best detected by serial
photography, and the more recently introduced scanning laser
ophthalmoscope may be able to detect structural changes in
the nerve at an early stage of the disease.
Visual field loss is difficult to pick up clinically without
specialised equipment until considerable damage (loss of up to
50% of the nerve fibres) has occurred.
Computerised field
testing equipment may detect nerve fibre damage earlier,
particularly if certain types of stimuli such as fine motion or
blue on yellow targets are used.
Computer assisted field testing
is also the best method for detecting long term change and
deterioration of visual fields.
The classical signs of glaucoma (field loss and optic disc
cupping) often are seen in patients who have pressures lower
than the statistical upper limit of normal (21 mm Hg).
However, many clinicians now feel that these two glaucomas are
part of the same spectrum of pressure dependent optic
neuropathies, although these patients are sometimes referred
to as having normal tension glaucoma.
For an accurate
measurement of IOP, intraocular pressure phasing, taking
multiple measurements throughout the day is useful, so that
any spikes can be detected.
In normal tension glaucoma there may be a significant
component of vascular associated damage at the optic
nerve head (ischaemia or vasospasm).
Management of
progressive normal tension glaucoma involves lowering IOP.
Drug induced nocturnal hypotension should be considered in
progressive normal tension glaucoma.
Acute angle closure glaucoma
Acute angle closure glaucoma is probably the best known
type of glaucoma, as the presentation is acute and the affected eye becomes red and painful.
In angle closure glaucoma,
apposition of the lens to the back of the iris prevents the
flow of aqueous from the posterior chamber to the anterior
chamber.
This is more likely to occur when the pupil is
semi dilated at night.
Aqueous then collects behind the iris
and pushes it on to the trabecular meshwork, preventing the
drainage of aqueous from the eye, so the IOP rises rapidly.
Symptoms
The eye becomes red and painful because of the rapid rise in
IOP, and there is often vomiting.
Vision is blurred because the
cornea is becoming oedematous; patients may notice haloes
around lights due to the dispersion of light through the
waterlogged cornea.
They may have a history of similar attacks in
the past that were aborted by going to sleep.
During sleep the
pupil constricts and may pull the peripheral iris out of the angle.
Groups at risk
This type of glaucoma usually occurs in longsighted people
(hypermetropes), who tend to have shallow anterior chambers
and shorter axial length eyes.
With increasing age the lens tends
to increase in size and crowd the anterior segment structures in
these eyes. Women have shallower anterior chambers and live
longer and therefore are more at risk of this type of glaucoma.
Signs
Visual acuity is impaired, depending on the degree of corneal
oedema.
The eye is red and tender to touch.
The cornea is hazy
because of oedema, and the pupil is semidilated and fixed to
light.
The attack begins with the pupil in the semidilated
position and the rise in pressure makes the iris ischaemic and
fixed in that position.
On gentle palpation the affected eye feels
much harder than the other.
Patients often are systemically
unwell with nausea, vomiting, and severe pain or headache.
If the patient is seen shortly after an attack has resolved,
none of these signs may be present, hence the importance of
the history.
Management
Emergency treatment is required to preserve the sight of the eye.
If it is not possible to get the patient to hospital immediately,
acetazolamide 500 mg should be given intravenously, and
pilocarpine 4% instilled in the eye to constrict the pupil.
The IOP must first be brought down medically, and a hole
(peripheral iridotomy) subsequently must be made in the
peripheral iris, either with a laser or surgically, in order to restore aqueous flow.
The other eye should be treated similarly,
as a prophylactic measure.
If the treatment is delayed, adhesions may form between
the iris and the cornea (peripheral anterior synechiae) and the
trabecular meshwork itself may be damaged.
A surgical
drainage procedure may then be required.
Angle closure
glaucoma is a very serious condition and even with optimum
management the patient may need multiple surgical
procedures and have impaired vision. Sometimes laser burns
can be made on the iris (iridoplasty) without creating a full
thickness hole in the iris.
This treatment causes the iris to
contract away from the occluded drainage angle.
Other types of glaucoma
If there is inflammation in the eye (anterior uveitis), adhesions
may develop between the lens and iris (posterior synechiae).
These adhesions will block the flow of aqueous between the
posterior and anterior chambers and result in forward
ballooning of the iris and a rise in the IOP.
Adhesions may also
develop between the iris and cornea (peripheral anterior
synechiae), covering up the trabecular drainage meshwork.
Inflammatory cells may also block the meshwork.
Topical
steroids may cause a gradual asymptomatic rise in IOP that can
lead to blindness.
(Patients taking topical steroids over a long
period should always be under ophthalmological supervision.)
The growth of new vessels on the iris (rubeosis) occurs both
in diabetic patients and after occlusion of the central retinal
vein resulting from retinal ischaemia.
These vessels also block
the trabecular meshwork causing rubeotic glaucoma, which is
extremely difficult to treat.
The trabecular meshwork itself may have developed
abnormally (congenital glaucoma) or been damaged by trauma
to the eye.
Patients who have had eye injuries have a higher
chance than normal of developing glaucoma later in life. If
there is a bleed in the eye after trauma, the red cells may also
block the trabecular meshwork.
Medical treatment
The main aim of therapy in glaucoma management is
reduction of IOP.
There is now good evidence from multiple
large randomised trials that reducing IOP is effective in
preventing disease progression in ocular hypertension, primary
open angle glaucoma, and even in so-called normal tension
glaucoma.
Target pressures in the low teens are associated with
the lowest progression rates.
Beta blockers ( for example, timolol, levobunolol, carteolol, betaxolol, and
metipranolol)
These reduce the secretion of aqueous and are still the most
commonly prescribed topical treatment.
Contraindications to
their use include a history of lung or heart disease, as the drops
may cause systemic beta blockade.
It is important to be aware that
topical beta blockers can unmask latent and previously
undiagnosed chronic obstructive airway disease in elderly
people.
Systemic effects from eye drops can be reduced by
occlusion of the punctum (finger pressed on the caruncle,
which can be felt as a lump at the inner canthus of the eye) or
shutting the eyes for several minutes after putting in the drops.
This reduces the lacrimal pumping mechanism and stops the
eyedrops running down the lacrimal passages and being
absorbed systemically via the nasal mucosa or by inhalation
directly into the lungs.
This may also enhance ocular
absorption of the drugs.
These drops are usually given twice a day, but long acting forms now available can be given once
a day, either alone or in combination with other drops.
Prostaglandin analogues ( for example, latanoprost,
travoprost, and bimatoprost)
These reduce the IOP by increasing aqueous outflow from the
eye via an alternative drainage route called the uveoscleral
pathway.
It is possible to get reductions in IOP of up to 30–35%
with these drugs.
This ability to achieve larger reductions in
IOP with improved systemic safety profiles has been a major
therapeutic advance in glaucoma.
Systemic side effects are
minimal but an unusual side effect in a few patients with light
irides is a gradual, permanent darkening of the iris.
Patients often notice that their eyelashes increase in length and darken.
For optimum effect, these drops are used once daily (at night).
Sympathomimetic agents
Topical adrenaline, once commonly prescribed, is now rarely
used because of lack of efficacy compared with beta blockers and
adverse effects on the conjunctiva.
A newer generation of agents
that stimulate the alpha receptors of the sympathetic system is now
used for example, brimonidine (used twice a day) or
apraclonidine. Contraindications include cardiovascular disease,
because of the potential systemic sympathomimetic effects.
Parasympathomimetic agents ( for example, pilocarpine)
These constrict the pupil and “pull” on the trabecular
meshwork, increasing the flow of the aqueous out of the eye.
The small pupil may, however, cause visual problems if central
lens opacities are present.
Constriction of the ciliary body
causes accommodation and blurred vision in young patients.
Pilocarpine should not be used if there is inflammation in the
eye, as the pupil may stick to the lens close to the visual axis
(posterior synechiae) and affect vision.
Pilocarpine is usually
administered four times a day but can be used twice daily in
a combined form with a beta blocker, or once at night in a gel
preparation, which reduces side effects.
When patients first
instill pilocarpine they often experience a marked brow ache,
which tends to reduce with longer term use of the drug.
Pilocarpine therapy can increase the risk of retinal detachment.
Carbonic anhydrase inhibitors
These are available as topical (for example, dorzolamide,
brinzolamide) or oral (for example, acetazolamide) agents.
They reduce the secretion of aqueous, and the systemic form,
administered orally, is the most powerful agent for reducing
IOP, although unfortunately it may have side effects, including
nausea, lassitude, paraesthesiae, electrolyte disturbances, and
renal stones.
The topical form has minimal systemic side
effects.
Carbonic anhydrase inhibitors should not be used in
patients with sulphonamide allergy.
Neuroprotective agents
Experimental evidence exists that some neuroprotective agents
may reduce intraocular pressure induced glaucomatous
damage.
However, at present there is no conclusive evidence
that these agents are helpful in glaucoma, but large scale
clinical trials are currently being carried out in this area.
Allergy to glaucoma drops
The main symptoms of drop allergy are intense itching
and irritation of the eyes and eyelids, which are exacerbated
by instillation of the drops.
The characteristic signs of drop
hypersensitivity include red injected eyes, red swollen
eyelids, and ezcema like excoriation of the eyelids and
periocular skin.
The patient may be hypersensitive to the active glaucoma
drug or one of the preservative agents used to stabilise the
preparation (usually benzalkonium chloride).
The diagnostic test for drop hypersensitivity is controlled
cessation of therapy.
Symptoms and signs should rapidly
improve on withdrawal of the topical therapy.
When patients
are on multiple topical agents it can be difficult to isolate the
agent responsible for the allergic reaction.
In cases of allergy to
the preservative agent in the drugs, some topical
drugs used in glaucoma management are available in
preservative free form.
Laser treatment
Laser trabeculoplasty
Argon or diode laser “burns” are applied to the trabecular
meshwork.
How this treatment works is uncertain.
It was
thought to contract one part of the meshwork, so stretching
and opening up adjacent areas, but a more recent hypothesis is
that it rejuvenates the cells in the trabecular meshwork.
This treatment is used only in the types of glaucoma where the
drainage angle is open.
Its effect is relatively short term, so this
treatment is mainly used for more elderly patients.
Laser iridotomy
Peripheral laser iridotomy (PI) can be performed in cases of
angle closure glaucoma with the Nd-YAG laser, which (unlike
argon or diode lasers) actually cuts holes in tissue rather than
just burning.
This procedure can be performed without
incising the eye.
Laser iridoplasty
Argon laser iridoplasty is a useful procedure in some forms of
angle closure glaucoma.
A ring of laser burns is applied to the
peripheral iris, causing contraction of tissue.
This pulls the
peripheral iris away from the drainage angle and helps to
reduce angle occlusion.
Laser ciliary body ablation
Lasers can be used to burn the circular ciliary body that
produces the aqueous humour.
At the correct wavelength the
laser radiation passes through the white sclera and is only
absorbed by the pigmented ciliary body (transcleral ciliary
body cycloablation).
This treatment is now commonly
performed with a diode laser and usually has to be repeated to
maintain lowering of IOP.
Most patients undergoing laser
ciliary body ablation need to continue medical therapy.
Laser
destruction of the ciliary body usually is used only in advanced
refractory glaucomas or where other surgical options are
limited.
Surgical treatment
Surgery was traditionally used only when treatment had
failed to halt the progress of glaucoma, but there is some
evidence that earlier surgical intervention is beneficial for
selected patients.
Iridectomy
Peripheral iridectomy is performed in cases of angle
closure glaucoma, both in the affected eye and prophylactically
in the other eye.
Most of these cases can be treated with the
Nd-YAG laser.
Surgery is reserved for difficult or refractory
cases.
Drainage surgery
When it is not possible to achieve the target IOP with medical
(or laser) therapy in glaucoma, then the next line of
management is surgical.
The most effective glaucoma filtration
procedure is trabeculectomy.
In this procedure a guarded
channel is created, which allows aqueous to flow from the
anterior chamber inside the eye into the sub-Tenon’s and
subconjunctival space (bypassing the blocked trabecular
meshwork).
A drainage “bleb” (aqueous under the conjunctiva
and Tenon’s capsule) can often be seen under the upper lid.
Conjunctivitis in a patient with a drainage bleb should always
be treated promptly, as there is an increased risk of the
infection entering the eye (endophthalmitis).
Possible complications
The main cause of surgical failure is postoperative scarring of
the drainage channel and drainage bleb.
Scarring can be
reduced by using adjuvant antiscarring therapy. Various
antiscarring agents are used, including drugs used in
anticancer therapy.
These are delivered by short applications
during surgery to the drainage bed on a sponge or by
postoperative injections.
The most commonly used drugs
are 5-fluorouracil and mitomycin-c.
Glaucoma filtration procedures do carry some risk and the
patient should be advised of the risk of postoperative cataract
and hypotony (low pressure) and the possibility of a reduction
in postoperative best corrected visual acuity.
Although trabeculectomy remains the gold standard
glaucoma filtration procedure, several alternative filtration
operations also exist.
Non-penetrating deep sclerectomy and
viscocanalostomy have good safety profiles but have tended to
produce less dramatic reductions in IOP in all published trials.
For certain patients with refractory glaucoma, a tube
drainage device may be considered.
A drainage tube is inserted,
connecting the anterior chamber of the eye with a reservoir in
the posterior orbit.
This has a good chance of controlling IOP,
but also has moderately high risk of serious complications.
