About the Authors

Lai Ling Tan

Lai Ling Tan obtained her MBChB degree from the University of
Edinburgh (UK) in 2007. She is currently an ophthalmology run-
through specialist registrar at Ninewells Hospital, Dundee (UK).
She has research interests in a variety of subjects, including
glaucoma, diabetic retinopathy and automated image analysis.

Roshini Sanders
Roshini Sanders is a consultant ophthalmologist at Queen
Margaret Hospital, Dunfermline (UK). She was Founder Chair of
the Scottish Glaucoma Club and is currently National Clinical Lead
for the Scottish-wide Eyecare Integration IT Project. She has
research interests in clinical and service delivery glaucoma issues.

6 6 © 2013 Future Medicine

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 Chapter 1
Classification

Epidemiology8
Lai Ling Tan &
Aqueous humor dynamics 8 Roshini Sanders
Classification by
This chapter explores the classification of glaucoma by
pathophysiology10
pathophysiology, age of onset and the International
Classification by age Classification of Diseases.
of onset 16
Classification based on
the International
Classification of Diseases 16

doi:10.2217/EBO.12.415

© 2013 Future Medicine 7

Tan & Sanders

Epidemiology
Glaucoma is not a single disease but an umbrella term used to describe
the progressive deterioration of optic nerve head usually, but not always,
accompanied by high intraocular pressure (IOP). Progressive deterioration
of the optic nerve head, termed glaucomatous damage, results in retinal
nerve fiber layer loss and visual field deficit.
Glaucoma is a major cause of irreversible blindness in the world [1]. Globally,
it is estimated that approximately 60 million people have glaucomatous
damage and 8.4 million people who are blind as a result of glaucoma [2,3].
The prevalence of glaucoma is projected to increase with population
growth and the aging of the population, and by 2020 it is expected that
the number of affected people will have risen to 80 million [1]. Even in
developed countries, only half of the people with glaucomatous damage
are aware of the diagnosis [3]. Early detection of glaucoma is crucial as
effective and lifelong treatment for glaucoma prevents significant visual
function loss.
The clear definition of each class of glaucoma is the keystone of
epidemiological research, whether measuring prevalence, studying risk
factors or conducting clinical trials [4]. Classification of glaucoma is
important as it has implications for screening, treatment regimes, prognosis
and surveillance of family members.
This chapter provides a broad overview of glaucoma disease classification
(Figure 1.1). Glaucomatous diseases may be classified by pathophysiology
and age of onset. Additionally, the WHO has an international classification
of glaucomatous disease.

Aqueous humor dynamics

The anterior chamber of the eye is filled with aqueous humor that is
secreted via active transport by the bilayer epithelium of the ciliary
processes of the ciliary body. The aqueous humor that is initially secreted
into the posterior chamber then flows through the pupillary aperture to
fill the anterior chamber of the eye. The flow of aqueous humor provides
nutrition, such as amino acid and glucose, to the avascular tissues, such as
the anterior vitreous, lens, posterior cornea and the trabecular meshwork.
The two principal pathways for drainage of the aqueous humor are the
trabecular meshwork and the uveoscleral pathway. The trabecular
meshwork is a wedge-shaped porous band of tissue that encircles and
bridges the anterior chamber angle. The aqueous humor drains from the
trabecular meshwork into the circular canal of Schlemm, which feeds into
the episcleral veins. The aqueous humor flows out passively via the

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 Figure 1.1. Pathophysiological classification of glaucoma.

Pathophysiological classification of glaucoma

Primary Secondary
Open angle Close angle Open angle Close angle

Congenital Non-congenital AAC IAC CAC Non-iatrogenic Iatrogenic With Without

glaucoma glaucoma pupillary block pupillary block

Pigmentary glaucoma Corticosteroid induced Iris bombe

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Exfoliative glaucoma Secondary to surgery
Lens protein-induced or laser
glaucoma Trauma

Primary juvenile POAG OH Anterior pulling Posterior pushing

glaucoma mechanism mechanism

High pressure Normal pressure Neovascular glaucoma Aqueous misdirection

POAG POAG ICE syndrome glaucoma
PAS Iris/ciliary body tumors
Endothelial posterior Uveal effusion
polymorphus dystrophy Silicon oil/gas implanted
in vitreous cavity

AAC: Acute angle closure; CAC: Chronic angle closure; IAC: Intermittent angle closure; ICE: Iridocorneal endothelial; OH: Ocular hypertension;
PAS: Posterior anterior synechiae; POAG: Primary open-angle glaucoma.

9
Classification
Tan & Sanders

Primar y glaucoma: glaucoma arising trabecular meshwork down a pressure

spontaneously and not associated with, or gradient. Any rise in the episcleral venous
caused by, a previous disease or injury.
pressure will reduce the outflow of
Secondary glaucoma: glaucoma that follows and aqueous humor.
results from an earlier disease or injury.
Approximately 5–10% of the aqueous
Primary open-angle glaucoma: multifactorial optic
neuropathy that is chronic and progressive with a humor drains via the uveoscleral pathway.
characteristic acquired loss of optic nerve fibers in the The aqueous humor flows from the anterior
absence of other known causes of glaucomatous chamber through the connective tissues
disease [102]. It is characterized by open anterior within the ciliary muscle to reach the inner
chamber angle, glaucomatous visual field and/or optic
surface of the sclera. Unlike the trabecular
disc defects [17].
meshwork outflow, the drainage of aqueous
humor via the uveoscleral pathway is
independent of the IOP.
In normal eyes, the IOP is between 10 and 21 mmHg. The IOP is a
consequence of the physiological process of production and drainage of
aqueous humor that is in equilibrium. Any disturbance to the aqueous
pathway described can elevate the IOP. High IOP compromises arterial
blood flow that nourishes the optic nerve head. This results in optic nerve
fiber atrophy and visual field loss.
The pathophysiological classification of glaucoma relates to pathology that
affects the aqueous pathway. This includes obstacles to the normal physical
outflow of aqueous or the failure of aqueous absorption by a malfunctioning
trabecular meshwork.

Classification by pathophysiology
Glaucoma can be broadly divided into primary glaucoma (arising
spontaneously and not associated with or caused by previous disease or
injury) and secondary glaucoma (glaucoma that follows and results from
an earlier disease or injury).
The anterior segment anatomy, specifically the drainage angle, divides the
classification further. In open-angle glaucoma, the drainage angle structures
can be seen on gonioscopy and are not obstructed by the peripheral iris. In
primary angle-closure type, the drainage angle is occludable as it is narrowed
or closed completely by the peripheral iris. The current acceptable definition
used for research studies for an occludable angle is ≥180° of posterior
trabecular meshwork not seen on gonioscopy due to iridotrabecular contact [5].

Primary open-angle glaucoma

Primary open-angle glaucoma is the commonest form of glaucoma and has
an incidence of 3% in those aged above 40 years rising to 5% in those aged

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 Classification

over 80 years [1,6]. In this form of the Primar y angle - closure glaucoma:
disease, the anterior chamber angle is open iridotrabecular contact causing glaucomatous
optic neuropathy. PAS and raised intraocular pressure
but aqueous fluid is not drained efficiently
may be absent at the time of initial examination.
due to a sclerosed trabecular meshwork. It
is a chronic progressive disease that usually
only manifests as visual field deficit at the point when at least 30% of nerve
fibers are lost.
The main risk factors for this disease are elevated IOP, positive family
history, increasing age, high myopia and high hypermetropia and
Afro–Caribbean race [2].These are discussed in detail in a subsequent
chapter. Screening programs in the community for glaucoma are largely
aimed at detection of this form of the disease and treatment instituted
early in the disease process gives patients the best chance of retaining
maximum field of vision.
Normal-pressure glaucoma or low-tension glaucoma accounts for
approximately 10% of open-angle glaucoma. It is characterized by
compromised blood flow to the optic nerve head in the face of IOP being
22 mmHg or less. This disease is associated with small-vessel disease and
has a less predictable course than primary open-angle glaucoma [7]. Key
to classification of this disease is phasing (monitoring of IOP over 24 h) to
pick up spikes in IOP and measurement of corneal thickness, which has a
bearing on absolute IOP measurements.
Juvenile open-angle glaucoma is defined as open-angle glaucoma between
the ages of 2 and 35 years in the absence of other ocular or systemic disease.

Primary angle-closure glaucoma

Primary angle-closure glaucoma (PACG) occurs in eyes where there is
crowding of the anterior segment structures with impediment of flow of
aqueous to the anterior chamber angle. PACG prevalence in the European
population is currently thought to be much higher than previous estimates.
Of those over 40 years of age in European derived populations, 0.4% is
estimated to have PACG [8]. Three-quarters of cases occur in female
subjects. PACG is known to be more common in Chinese people [1].
The main risk factors for this disease are Mongoloid race, increasing age,
female gender, positive family history and high hypermetropia [2].
The acute form of this disease falls into the category of ophthalmic
emergencies necessitating lowering of IOP within hours to prevent acute
visual loss. The chronic form of the disease results in chronically elevated
IOPs with field loss. These forms of glaucoma more often than not require
early laser (yttrium–aluminium–garnet peripheral iridotomy) or surgery

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Tan & Sanders

(lens extraction) and are less amenable to long-term topical antiglaucoma

medications.
In 2002, the International Society for Geographical and Epidemiological
Ophthalmology formed an international consensus panel that subsequently
published definitions for PACG, which are now widely used in research [4].
PACG is divided into three different stages:
n Primary angle-closure suspect: two or more quadrants of iridotrabecular

contact normal IOP, no posterior anterior synechiae (PAS), and no

evidence of glaucomatous optic neuropathy;
n Primary angle closure: iridotrabecular contact with evidence of past
attacks of angle closure, such as PAS, glaucomflecken, pigmentation of
the angle and/or raised IOP. No evidence of glaucomatous optic
neuropathy;
n PACG: iridotrabecular contact causing glaucomatous optic neuropathy.
PAS and raised IOP may be absent at the time of initial examination.

Secondary open-angle glaucoma

Pre-existing ophthalmic conditions, diseases, interventions and treatments
may result in secondary glaucoma. The secondary glaucomas arise as a result
of abnormalities at the pre-trabecular, trabecular and post-trabecular sites.
Pigmentary glaucoma results from melanin granules released from the iris
that block the trabecular meshwork, thus preventing the absorption of
aqueous fluid. Pseudoexfoliation glaucoma is the consequence of fibrillar
protein material released from basement membranes that clog up the
trabecular meshwork. Any inflammatory conditions of the eye such as
primary or secondary uveitis result in white cells obstructing the trabecular
meshwork with resultant raised IOP. Phacolytic glaucoma occurs when a
mature cataract spontaneously discharges lens proteins through an intact
lens capsule and into the anterior chamber, resulting in inflammation of
the anterior segment and subsequent glaucoma. Ghost cell glaucoma
results from ghost red blood cells (abnormal rigid blood cells) that persist
in the eye most commonly after vitreous hemorrhage.
Any form of ophthalmic surgery if complicated or prolonged with
resultant hemorrhage or inflammation has the potential to precipitate
glaucoma. This is seen in particular with complex cataract, corneal and
vitreoretinal surgery. The latter in particular on occasion requires the
introduction of silicone oil or perfluorocarbon gases into the vitreous
cavity resulting in a form of secondary glaucoma that requires challenging
treatment options.

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 Classification

Approximately one in 20 of the Western population is a steroid responder,

where their IOP increases in response to steroid exposure. Steroid
responsiveness in children occurs more frequently, more severely and more
rapidly than that reported in adults [9]. The pathophysiology for this process
is that steroids react with glucocorticoid receptors in the eye and cause
raised IOP. These steroids may be used systemically, as local eye drops or
as intraocular injections. Even when used in small concentrations, such as
in nasal sprays or topical skin creams, steroids have the potential to cause
glaucoma in susceptible individuals.
Trauma to the eye can result in damage to the trabecular meshwork causing
angle recession, which may result in glaucoma in the long term.

Secondary angle-closure glaucoma

Secondary angle-closure glaucoma without pupillary block is divided into
two classes [10]. The anterior ‘pulling’ mechanism describes the iris and/
or a membrane that is progressively pulled forward to occlude the
chamber angle. Disease states that may cause this include new vessel
growth in the eye as a result of central retinal vein occlusion or diabetic
retinopathy resulting in neovascular glaucoma. Peripheral anterior
synechiae are adhesions between the base of the iris and trabecular
meshwork. They result from ocular inflammation, thus resulting in
glaucoma. Iridocorneal endothelial syndrome is a developmental

Table 1.1. Glaucoma classification by age of onset.

Age of onset Features
Congenital Onset from birth. It is usually bilateral but each eye could be affected to different
degrees. Family history may be present although sporadic cases occur.
It is usually related to developmental abnormalities. Trabeculodysgenesis is
common. High intraocular pressure that results from poor draining of aqueous
humor distends the sclera and enlarges the globe.
Congenital glaucoma has been associated with mutations in the CYP1B1 gene
which codes for a molecule in the anterior eye tissues [12].
Surgical treatment is almost always necessary.
Infantile Glaucoma that is not present at birth but develops before 2 years of age. The
intraocular pressure is normal at birth but gradually increase over time.
Juvenile Onset after the 2nd year of life to the 35th year of life. Family history may be
present.
Genes associated with primary juvenile glaucoma have been indentified on
chromosome 1 (1q21–q31) and MYOC [13,14].
Adult Onset after the 35th year of life. There are usually no identifiable structural
abnormalities in the chamber angle. Patients are often asymptomatic until field
loss is advanced.

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Tan & Sanders

abnormality whereby the anterior chamber angles develop in an

abnormal fashion thus narrowing the anterior chamber angle. Endothelial
posterior polymorphous dystrophy develops in adulthood with swelling
of the posterior corneal surface resulting in narrowing of the anterior
chamber angle.
The posterior ‘pushing’ mechanism describes the iris and ciliary body
that are pushed forward to occlude the chamber angle. This may occur
when substances such as oil and gas are introduced into the vitreous
cavity in the treatment of retinal detachments and macular hole surgery.
Aqueous misdirection occurs when aqueous is directed posteriorly into
the vitreous cavity, thus causing increased posterior pressure and occlu-
sion of the base of the iris, thus causing secondary angle closure. Tumors
of the iris and ciliary body may also occlude the angle in a similar fashion.
Uveal effusion syndrome can occur following ocular surgery or in ocular

Box 1.1. Hoskins’ anatomic classification of the developmental glaucomas.

I. Isolated trabeculodysgenesis: malformation of trabecular meshwork in absence of
iris or corneal anomalies
A. Flat iris insertion
ƒƒ
−− 1. Anterior insertion
−− 2. Posterior insertion
−− 3. Mixed insertion
B. Concave (wrap around) iris insertion
ƒƒ
C. Unclassified
ƒƒ
II. Iridotrabeculodysgenesis: trabeculodysgenesis with iris anomalies
A. Anterior stromal defects of the iris
ƒƒ
−− 1. Hypoplasia
−− 2. Hyperplasia
B. Anomalous iris vessels
ƒƒ
−− 1. Persistence of tunica vasculosa lentis
−− 2. Anomalous superficial vessels
C. Structural anomalies
ƒƒ
−− 1. Holes
−− 2. Colobomas
−− 3. Aniridia
III. Corneotrabeculodysgenesis: usually associated with iris anomalies
A. Peripheral
ƒƒ
B. Midperipheral
ƒƒ
C. Central
ƒƒ
D. Corneal size
ƒƒ

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 Classification

inflammation states causing pronounced swelling of the ciliary body and

angle-closure glaucoma.
There are also external ocular causes that cause a rise in episcleral venous
pressure and impede the outflow of aqueous fluid in addition to causing
an element of angle-closure glaucoma. Examples of these are orbital
cellulitis, orbital pseudotumor, thyroid eye disease and vascular conditions,
such as cavernous sinus thrombosis and superior vena cava obstruction.

Table 1.2. Block H40–H42 of the International Classification of

Diseases: glaucoma.
Code Disease
H40.0 Glaucoma suspect
Ocular hypertension
H40.1 Primary open-angle glaucoma
Glaucoma (primary) (residual stage):
– Capsular with pseudoexfoliation of lens
– Chronic simple
– Low-tension
– Pigmentary
H40.2 Primary angle-closure glaucoma
Angle-closure glaucoma (primary) (residual stage):
– Acute
– Chronic
– Intermittent
H40.3 Glaucoma secondary to eye trauma
H40.4 Glaucoma secondary to eye inflammation
H40.5 Glaucoma secondary to other eye disorders
H40.6 Glaucoma secondary to drugs
H40.8 Other glaucoma
H40.9 Glaucoma, unspecified
H42 Glaucoma in diseases classified elsewhere
H42.0 Glaucoma in endocrine, nutritional and metabolic diseases
Glaucoma in:
– Amyloidosis
– Lowe’s syndrome
H42.8 Glaucoma in other diseases classified elsewhere
Glaucoma in onchocerciasis
Excluding: absolute glaucoma (H44.5), congenital glaucoma (Q15.0), traumatic glaucoma
due to birth injury (P15.3).

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Tan & Sanders

Classification by age of onset

Although the chances of developing glaucoma increase with age, it can
occur at any age. Glaucoma can also be classified by age of onset. The
features of this classification are described in Table 1.1 [11].
In congenital and infantile glaucoma, the identification of anatomic defects
seen at the time of examination can be useful in determining appropriate
therapy and prognostic factors [15]. Box 1.1 shows the Hoskins’ anatomic
classification of glaucoma [16].

Classification based on the International Classification of Diseases

The WHO produced the International Classification of Diseases (ICD-10) as
the standard diagnostic tool for epidemiology, health management and
clinical purposes [101]. Block H40 to H42 within Chapter VII in the ICD-10
describes glaucoma diseases (Table 1.2).

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organi-
zation or entity with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript. This includes employment, con-
sultancies, honoraria, stock ownership or options, expert testimony, grants or
patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Summary.

Each class of glaucoma has its own initial therapeutic approach, late complications and
ƒƒ
prognosis.
Pathophysiological classification allows the institution of appropriate therapy for each class of
ƒƒ
disease.

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