Glaucoma overview

Learning objectives
 To understand:
a) The nature of glaucoma.
b) The difference between primary and
secondary glaucoma; open and closed angle
glaucoma.
c) The different symptoms and signs of open
and closed angle glaucoma.
d) The three major forms of glaucoma therapy.
Introduction
 The glaucomas are a group of diseases causing
damage to the optic nerve (optic neuropathy) by
the effects of raised ocular pressure on the optic
nerve head.
 Independent ischaemia of the optic nerve head

may also be important.

 Axon loss results in visual field defects and a

loss of visual acuity if the central visual field is

involved.
Pathophysiology
 The intraocular pressure level is determined by a
balance between production and removal of aqueous
humour . Aqueous is actively secreted into the posterior
chamber by the ciliary processes, by a combination of
active transport and ultrafiltration. It then passes
through the pupil into the anterior chamber and leaves
the eye, predominantly, via the trabecular meshwork,
Schlemm’s canal and the episcleral veins to reach the
bloodstream (the conventional pathway )
Cont…
 A small but important proportion of the aqueous (4%)
drains across the ciliary body into the supra-choroidal
space and is absorbed into the venous circulation (the
uveoscleral pathway ).
 Two theories have been advanced to explain how

elevated intraocular pressure, acting at the nerve head,

damages the optic nerve fibres:
1) Raised intraocular pressure causes mechanical damage
to the axons.
2) Raised intraocular pressure causes ischaemia of the
nerve axons by reducing blood flow at the nerve head.
The pathophysiology of glaucoma is probably
multifactorial and both mechanisms are important.
Diagram of the drainage angle, showing routes taken by aqueous from
production to absorption.
Classification of glaucoma
 The mechanism by which aqueous drainage is
reduced provides a means to classify the
glaucomas. Classifi cation of the primary
glaucomas is based on whether or not the
peripheral iris is:
1) clear of the trabecular meshwork ( open
angle glaucoma);
2) covering the meshwork (closed angle
glaucoma).
Diagram showing the difference between open and closed angle
glaucoma. Outflow resistance is increased in each case. In open angle
glaucoma the obstruction is due to structural changes in the trabecular
meshwork. In closed angle glaucoma the peripheral iris blocks the
meshwork.
Classification of the glaucomas
 Primary glaucoma:
a) Chronic open angle.
b) Acute and chronic closed angle.
 Congenital glaucoma:

a) Primary.
b) Secondary to maternal rubella infection.
c) Secondary to inherited ocular disorders (e.g. aniridia absence of the
iris).
 Secondary glaucoma (causes):

a) Trauma.
b) Ocular surgery.
c) Associated with other ocular disease (e.g. uveitis).
d) Raised episcleral venous pressure.
e) Steroid induced.
Pathogenesis
 Primary open angle glaucoma:
 A special contact lens applied to the cornea (a

gonioscopy lens) provides a view of the iridocorneal

angle with the slit lamp. In open angle glaucoma the
trabecular meshwork appears normal on gonioscopy but
functionally, it offers an increased resistance to the
outflow of aqueous. This results in an elevated ocular
pressure. The causes of outflow obstruction include:
1. thickening of the trabecular lamellae, which reduces
pore size;
2. reduction in the number of lining trabecular cells;

3. increased extracellular material in the trabecular

meshwork spaces.
Closed angle glaucoma
 This condition occurs in small eyes (i.e. often hypermetropic)
which therefore have shallow anterior chambers. In the normal
eye the point of contact between the pupil margin and the lens
offers a resistance to aqueous flow from the posterior into the
anterior chamber (relative pupil block); there is a pressure drop
between the posterior and anterior chamber. In angle closure
glaucoma, sometimes in response to pupil dilation, when the
peripheral iris may be bunched up in the angle, this resistance is
increased and the increased pressure gradient bows the iris
forward and closes the drainage angle. Aqueous can no longer
drain through the trabecular meshwork and ocular pressure
rises, usually abruptly. This peripheral iris contact ultimately
leads to adhesions, called peripheral anterior synechiae (PAS),
which consolidate the
obstruction
Secondary glaucoma
 In secondary glaucoma, the rise of intraocular pressure
is usually due to trabecular meshwork obstruction. The
trabecular meshwork may be blocked by:
 blood (hyphaema), following blunt trauma;
 inflammatory cells (uveitis );
 pigment from the iris ( pigment dispersion syndrome );
 deposition in the trabecular meshwork of material
produced by the epithelium of the lens, iris and ciliary
body (pseudoexfoliative glaucoma );
 drugs increasing the resistance of the
meshwork( steroid–induced glaucoma).
Secondary glaucoma cont….
 Secondary glaucoma may also result from blunt trauma
to the eye causing damage to the drainage angle (angle
recession ).
 Angle closure may also account for some cases of

secondary glaucoma:
 Abnormal iris blood vessels may obstruct the angle and

cause the iris to adhere to the peripheral cornea, closing

the angle (rubeosis iridis ). This may accompany
proliferative diabetic retinopathy or central retinal vein
occlusion due to the forward diffusion of
vasoproliferative factors such as vascular endothelial
growth factor (VEGF), from the ischaemic retina
 A large choroidal melanoma may push the iris
forward, approximating it to the peripheral cornea
and causing an acute attack of angle closure
glaucoma.
 A cataract may swell, pushing the iris forward and
close the drainage angle.
 Uveitis may cause the iris to adhere to the trabecular
meshwork.
Congenital glaucoma
 This covers a diverse range of disease. It may present at
birth or within the first year. Symptoms and signs include:
 excessive tearing, photophobia and blepharospasm;
 an increased corneal diameter and enlargement of the

globe (buphthalmos ), resulting in progressive myopia;

 a cloudy cornea due to epithelial and stromal oedema;
 splits in Descemet’s membrane.
 Congenital glaucoma is usually treated surgically. An

incision is made into the trabecular meshwork

(goniotomy) to increase aqueous drainage, or a direct
passage between Schlemm’s canal and the anterior
chamber is created ( trabeculotomy ).
CONGENITAL GLAUCOMA
Chronic open angle glaucoma
 Epidemiology:
Chronic open angle glaucoma affects 1 in 200 of the
population over the age of 40, affecting males and
females equally. The prevalence increases with age to
nearly 10% in the over-80 population. There may be
a family history although the mode of inheritance is
often unclear.
Genetics
 First-degree relatives of patients with chronic open angle
glaucoma have up to a 16% chance of developing the
disease themselves. Inheritance of the condition is complex.
Progress has been made with a juvenile form of open angle
glaucoma (presenting at between 3 and 35 years of age)
caused by mutations in the myocillin gene (GLC1A), which
maps to the long arm of chromosome 1.
 A different set of mutations in the same gene may be

associated with some cases of chronic open angle glaucoma

and other genes, such as optineurin (GLC1E) and WD40
repeat36 (GLC1G), may also play a role. The optineurin
gene is predominantly associated with normal tension
glaucoma
History
 The symptoms of glaucoma depend on the rate
at which the intraocular pressure rises.
Chronic open angle glaucoma is associated
with a slow rise in pressure and is
symptomless until the patient becomes aware
of a visual deficit or the diagnosis is made by
chance. Many patients are diagnosed when the
signs of glaucoma are detected by an
optometrist.
Examination
 In patients with chronic open angle glaucoma the eyes are
white and the corneas are clear. Assessment of a glaucoma
suspect requires a full slit-lamp examination and involves:
i. Measurement of ocular pressure with a tonometer.
ii. Measurement of the thickness of the cornea with a
pachymeter.
iii. Examination of the iridocorneal angle by gonioscopy,

iv. Exclusion of other ocular disease that may be a cause of

a secondary
glaucoma.
v. Examination of the optic disc and determination of
whether it is pathologically cupped.
Symptoms and signs of chronic
open angle glaucoma
 Symptomless in its early stages.
 A white eye and clear cornea.
 Raised intraocular pressure.
 Visual field defect.
 Cupped optic disc.
Treatment
 Treatment is aimed at reducing intraocular pressure.
The level to which the pressure must be lowered
varies from patient to patient and is that which
minimizes further glaucomatous visual loss. This
requires careful monitoring in the outpatient clinic.
Three modalities of treatment are available:
1. medical treatment;
2. laser treatment;
3. surgical treatment.
Medical treatment
 Topical drugs commonly used in the treatment of
glaucoma.
 In chronic open angle glaucoma the prostaglandin

analogues are becoming the first-line treatment.

 They act by increasing the passage of aqueous through

the uveoscleral pathway.

 Topical adrenergic beta-blockers may further reduce

the pressure by suppressing aqueous secretion.

Laser trabeculoplasty
 This involves placing a series of laser burns
(50 μm wide) in the trabecular meshwork, to
improve aqueous outflow. Whilst effective
initially, the intraocular pressure may slowly
increase. In the UK there is an increasing
tendency toproceed to early drainage surgery.
Surgical t reatment
 Drainage surgery ( trabeculectomy ) relies on the
creation of a fistula between the anterior chamber and
the subconjunctival space. Aqueous humour leaves the
anterior chamber, via a bleb of conjunctiva, into the
subconjunctival space. The operation usually achieves
a substantial reduction in intraocular pressure. It is
performed increasingly early in the treatment of
glaucoma.
Complications of surgery include
 shallowing of the anterior chamber in the immediate
postoperative period risking damage to the lens and
cornea;
i. intraocular infection;
ii. possibly accelerated cataract development;
iii. failure to reduce intraocular pressure adequately.
iv. an excessively low pressure (hypotony) which may
cause macular oedema.
Trabeculectomy / surgical

(a) Diagram showing a section through a

trabeculectomy. An incision is (b) The appearance of a
made in the conjunctiva, which is dissected
and reflected to expose bare sclera.
trabeculectomy bleb
Primary angle closure glaucoma
 Epidemiology:
Primary angle closure glaucoma affects 1 in 1000
subjects over 40 years old, with females more
commonly affected than males. Patients with angle
closure glaucoma are likely to be long - sighted,
because the long - sighted eye is small and the
structures of the anterior chamber are more crowded.
 Examination:

On examination visual acuity is reduced, the eye red,

the cornea cloudy and the pupil oval, fixed and dilated.
History
 In acute angle closure glaucoma, there is an abrupt
increase in pressure and the eye becomes
photophobic and very painful due to ischaemic tissue
damage. There is watering of the eye and loss of
vision. The patient may be systemically unwell with
nausea and referred abdominal pain, symptoms which
may take them to a general casualty department.
Intermittent primary angle closure glaucoma occurs
when an acute attack spontaneously resolves. The
patient may complain of pain, blurring of vision and
seeing coloured rainbows around lights.
Treatment
 The acute and dramatic rise in pressure seen in
angle closure glaucoma must be urgently
countered to prevent permanent damage to the
vision. Acetazolamide is administered
intravenously and subsequently orally,
together with topical pilocarpine and beta -
blockers. Pilocarpine constricts the pupil and
draws the peripheral iris out of the angle; the
acetazolamide and beta-blocker reduce
aqueous secretion and the pressure gradient
across the iris.
Prognosis of the glaucomas
 The goal of treatment in glaucoma is to stop or reduce
the rate of visual damage. It may be that control of
intraocular pressure alone is not the only factor that
needs to be addressed in the management of glaucoma.
The possible role of optic nerve ischaemia has been
discussed, and there is interest in developing
neuroprotective drugs. Reducing intraocular pressure is
thus currently the mainstay of treatment. Some patients
will continue to develop visual loss despite a large
decrease in intraocular pressure.