Seminar

Glaucoma

Anne L Coleman

In 2000 an estimated 66·8 million people worldwide will have glaucoma, 6·7 million of whom will be bilaterally blind
from irreversible optic-nerve damage. Yet even in developed countries with public educational programmes that
target glaucoma, half of the individuals with glaucoma remain undiagnosed. Patients with even mild visual
impairment secondary to glaucoma may have difficulties with mobility, driving, and social interactions. Although
glaucoma may be associated with increased eye pressures, its diagnosis does not rely on a specific level of eye
pressure. Diagnosis of glaucoma often relies on examination of the optic disc and assessment of the visual field.
The two most common types of glaucoma—primary open-angle glaucoma and primary angle-closure glaucoma—have
different risk factors. Although similar medications can be used to treat these two types of glaucoma, the overall
management of patients differs in important ways. Until recently, there were no randomised clinical trials that
showed the effectiveness of lowering eye pressures with medications or surgery in patients with glaucoma. However,
in 1998 a randomised clinical trial showed the benefit of lowering eye pressure in patients with glaucoma who
had eye pressures of 24 mm Hg or less. Because glaucoma is treatable, and because the visual impairment from
glaucoma is irreversible, early detection of the disease is critically important.

Glaucoma is the second leading cause of blindness
worldwide.1,2 In 2000, it is estimated that there will be
66·8 million people with glaucoma and that 6·7 million of
these people will have bilateral blindness secondary
to glaucoma—ie, vision less than 20/400 or 3/60 in the
better eye.2 The blindness caused by glaucoma is
irreversible.
Glaucoma is sometimes called the “silent blinder”,
because many people are unaware that they have the
disease—for example, Tielsch and colleagues3 showed
that 50% of people with glaucoma did not know they had
the disease. Glaucoma can occur in all age groups,
including in infants, but it is most common in elderly
people. Although several eye conditions are variants
of glaucoma, the most common types of glaucoma are
primary open-angle glaucoma (POAG) and primary
angle-closure glaucoma (PACG). Asia accounts for a
disproportionate number of PACG cases, whereas
the prevalence of POAG is more evenly distributed
throughout the world.2
Although PACG and POAG are characterised by
damage to the optic nerve and visual field loss, they
differ in terms of whether the trabecular meshwork is
obstructed by the periphery of the iris. This difference
affects the medical and surgical management of the two
diseases. In PACG the iris obstructs the trabecular
meshwork in the angle of the eye, whereas in POAG the
trabecular meshwork seems to be open and unobstructed
by the iris (figure 1). A procedure known as gonioscopy is
used to differentiate between the two types of glaucoma.
Gonioscopy involves examination of the anterior chamber
with a lens that enables the observer to visualise the angle
between the cornea-sclera and iris. Gonioscopy requires
skill and training and is difficult to use in screening
situations.
Lancet 1999; 354: 1803–10
Glaucoma Division, Department of Ophthalmology, Jules Stein Eye
Institute, University of California, Los Angeles, CA 90095, USA
(Prof A L Coleman MD)
(e-mail: coleman@jsei.ucla.edu)
The loss of peripheral vision, depth perception, and
contrast sensitivity associated with glaucoma can have a
major effect on an individual’s life. Injuries caused by car
crashes and falls are associated with the types of visual
impairments that arise in glaucoma; such injuries can
occur even if a person has excellent central acuity.4,5
Studies indicate that loss of peripheral vision and the use
of medications have the greatest impact on the quality
of life of patients with glaucoma.6–10 Even before the
measurement of a visual disability secondary to
glaucoma, patients with glaucoma complain of a loss of
confidence in themselves, especially when outside of the
home.10 Because populations in developing countries are
ageing, it is likely that the burden of glaucoma will
increase in developed countries.
Primary open-angle glaucoma
Definition and diagnosis
POAG has an adult onset, is usually bilateral, and has
no noticeable symptoms in most patients until the later
stages of the disease when patients lose their central
vision.11,12 In the USA, POAG has an age-adjusted
prevalence of 1·55%.13 Although POAG has
conventionally been characterised as a disease of raised
eye pressures, it is currently defined as a group of ocular
diseases that may cause characteristic, progressive
changes in the optic nerve head, visual field loss, or
both.11 These changes in the optic nerve head or visual-
field loss are associated with raised eye pressures, but can
occur in individuals whose eye pressures are below the
population mean of 15·5 mm Hg. Thus, the clinical
definition of POAG no longer depends on the eye having
a specific eye-pressure measurement such as 21 mm Hg
or higher.14 Patients with raised eye pressures but no
evidence of glaucomatous optic-nerve damage or visual-
field loss are described as glaucoma suspects or ocular
hypertensives. Although increased eye pressures are no
longer included in the definitions of glaucoma, the
reduction of eye pressures remains the mainstay of POAG
treatment.

THE LANCET • Vol 354 • November 20, 1999 1803

 The characteristic changes been developed to help
in the optic nerve head interpret these data. The
are increased cupping or types of visual-field loss
excavation, notching, or that are characteristic of
thinning of the neuroretinal glaucoma are: nasal-field
rim, disc haemorrhages, loss, superior or inferior
asymmetry of the amount of arcuate-field loss, gen-
optic-nerve cupping between eralised depression, or
the two eyes of the patient, Figure 1: Open-angle glaucoma and angle-closure glaucoma paracentral visual-field loss
Left: eye with open-angle glaucoma in which aqueous humor produced by
and loss of the retinal ciliary body reaches trabecular meshwork but is then blocked from leaving (figure 3).11 The loss of
nerve fibre layer. 11,12
Pallor of eye. central vision before loss of
the optic nerve head that is Right: eye with angle-closure glaucoma in which there is forward bowing of peripheral vision is not
iris and aqueous humor is blocked from reaching trabecular meshwork by
greater than the amount of iris. Flow of the aqueous humor is indicated by the arrows. Reproduced characteristic of glaucoma.
cupping is not regarded as with permission of the American Academy of Ophthalmology. Much effort has been
characteristic of glaucoma. devoted to improving the
The best way to examine speed, accuracy, and
the optic nerve head is at a validity of visual-field
slit lamp with a binocular testing. New visual-field
view, although the optic tests such as the Swedish
nerve head can be assessed interactive test algorithm
adequately with a direct and frequency doubling
ophthalmoscope in a perimetry are reducing the
dilatated pupil. An Figure 2: Optic nerve head amount of time needed
Left: in healthy person there is almost no cup.
impression of the degree of Right: in patient with glaucomatous loss of visual field; there is thinning
to obtain a visual field.
optic-nerve cupping or of the neuroretinal rim and the cup-to-disc ratio vertically is about 07. Improvements in the
excavation can be obtained methods of visual-field
with a direct ophthalmoscope if the centre of the optic testing may help reduce the number of patients who are
nerve head is not in focus when the peripheral surface of undiagnosed.
the nerve is in focus. The size of the cup can be estimated A diagnosis of glaucoma can be made even if neither
with a non-stereoscopic view since the cup has less neural optic-nerve damage nor visual-field loss is present,
tissue than the rim and thus is whiter than the rim. A because a clinician may infer that optic-nerve damage and
standard way to describe the appearance of the optic visual-field loss will occur because of the level of the eye
nerve head is the cup-to-disc ratio, which expresses the pressure. Epidemiological studies show that as eye
size of the cup as a proportion of the size of the optic pressure increases, there is a corresponding increase in
nerve head (figure 2). Eyes with cup-to-disc ratios equal the risk of glaucomatous optic-nerve damage and visual-
to or greater than 0·55 are at increased risk of developing field loss.3 Eye pressures greater than 32 mm Hg
glaucomatous visual field loss compared with eyes with commonly lead to the inference that disease is present.
cup-to-disc ratios of less than 0·55.15 Disc haemorrhages
and notches can be identified easily with careful direct Screening
ophthalmoscopy. Thus, a clinician with a direct One of the challenges of screening people for POAG
ophthalmoscope can at least screen for features of a is the low prevalence of the disease in the general
glaucomatous optic nerve, although the sensitivity and population. Although sensitivity and specificity are the
specificity of classification based on these assessments are traditional criteria used to judge the validity of a test,
59% and 73%, respectively.15 another important factor is the positive-predictive value
There are several instruments currently available for of a screening test, which characterises the fraction of
imaging of optic nerves, such as the Topcon ImageNet positive results that are true positives. If the prevalence
system, the confocal scanning laser ophthalmoscope, the of the disease is small, say 2% or less, there is a fairly
retinal nerve fiber layer analyser, and the optical low ceiling on the number of true positive findings; as a
coherence tomograph. The advantage of these imaging result, a procedure with even a low false-positive rate can
devices is that the computer algorithms used to evaluate actually produce more false-positive results than true
the optic nerve head make the assessment of positive results.16 Since the prevalence of POAG in the
glaucomatous optic-nerve damage more systematic, USA population is reported to be 1·55%, the positive-
although they all require some operator input. The predictive value of an instrument such as the scanning
disadvantages of these devices are that they are expensive, laser polarimeter, which images the nerve fibre layer
they are not portable, and there have been only a limited of the retina, would only be 17·8%, even though the
number of studies on their value in screening settings. procedure has a sensitivity of 96% and a specificity of
The most common way to measure how well the optic 93%.17 Thus, even a test with high sensitivity and
nerve functions is the assessment of the eye’s ability to specificity may have low cost-efficiency in screening for
detect the brightness of small points of light both POAG, because POAG is a rare disease in the general
centrally and peripherally. This type of examination is population. Screening based on eye pressure does not
called visual-field testing and can be done with careful solve this issue, because this type of screening is
manual techniques (static and kinetic) or automatic static associated with only 50% sensitivity and 90% specificity.18
threshold techniques. In the tests of automatic static
11
Other candidate approaches for screening include
thresholds, an individual’s responses are compared with questionnaires about risk factors and visual-field testing.
other individuals of the same age whose visual fields Questionnaires inquiring about risk factors are not,
are within the normal range. Statistical programs have however, very specific. They need to be augmented by

1804 THE LANCET • Vol 354 • November 20, 1999

another screening technique, such as the measurement of
eye pressure or examination of the optic nerve head, both
of which are inadequate when used alone for screening.16
In the Prevent Blindness America Visual Field Screening
Study,19 the Henson visual-field analyser had 100%
specificity in 82 healthy individuals and 97% sensitivity in
39 patients with moderate-to-severe visual-field loss.19 In
line with these findings, the Glaucoma Advisory
Committee of Prevent Blindness America recommends
that screening for POAG should include both eye-
pressure measurements and an approved method to test
visual fields.
Aetiology and risk factors
The aetiology of POAG is unknown. The debate
continues about whether damage to the optic nerve is
caused by eye pressures that are too high, decreased
blood flow to the optic nerve head, or both factors.
Irrespective of what causes the damage, the end result
is that ganglion-cell death in
glaucoma is by apoptosis
(programmed cell death),
because of the lack of trophic
factors.20 In addition,
autoimmune reactions,
increased concentrations of
nitric oxide, and raised
concentrations of glutamate
may contribute to ganglion-
cell death in POAG.21
Several risk factors have
been found to be associated Figure 3: Field of view
with the development of Left: a person without any ocular diseases; notice how clearly the
sidewalk in the foreground is seen.
glaucoma. The one risk Right: a person with early glaucomatous loss of visual field in the
factor that is closely linked periphery; note the subtle lack of detail and contrast in the periphery of
with glaucoma is eye the image on the right compared with that on the left.
pressure. Support for a
potential causal role of eye pressure for damage to
the optic nerve head is that the higher the eye pressure,
the greater the relative risk of glaucoma.14 In addition,
Quigley and Addicks showed that optic-nerve damage
could be induced in primates after the eye pressure has
been increased secondary to laser damage of the
trabecular meshwork.22 Eyes with asymmetric damage to
the optic nerve usually have higher eye pressures in the
eye with the greater amount of damage.23 Finally, the
Collaborative Normal-Tension Glaucoma Study Group
reported that lowering eye pressure 30% from baseline
was effective in decreasing the rate of visual-field loss.24,25
Demographic risk factors for POAG are African
descent3,26,27 and older age (>70 years).3,26–33 In the
population-based Baltimore Eye Survey in the USA,
African-Americans were four times more likely to
have glaucoma than white people.3 White people and
African-Americans aged 70 years or older were 3·5 and
7·4 times more likely to have glaucoma than white
people and African-Americans aged 40–50 years,
respectively.3
In the Baltimore Eye Survey, first-degree relatives of
patients with POAG had 2·9 times greater odds of having
glaucoma than non-relatives. In a population-based
34
familial aggregation study in Rotterdam, 35 the lifetime risk
of glaucoma was 9·2 times higher in siblings and offspring
of glaucoma patients than in siblings and offspring of
controls. There have been suggestions that diabetes
mellitus, systemic hypertension, migraine headaches, and
THE LANCET • Vol 354 • November 20, 1999
myopia may be risk factors for POAG, but so far, the
evidence is inconclusive.36–46
Genetics
In 1996 and 1997, the first major gene loci for POAG,
GLC1A and GLC1B, were described.47,48 The GLC1A
gene encodes myocilin, the trabecular meshwork-induced
glucocorticoid response protein. GLC1A is located on
chromosome 1; the mechanisms by which mutations in
this gene cause raised eye pressures and damage to the
optic nerve are unknown.48 The GLC1B gene, located on
chromosome 2, is associated with normal-to-moderately
raised eye pressures and optic-nerve damage.47 Several
other genes that increase the risk of POAG have since
been identified. The GLC1C gene, mapped to
chromosome 3, is associated with increased eye pressures
and cup-to-disc ratios greater than or equal to 0·7 or an
abnormal result on a visual-field test.49 The GLC1D gene
on chromosome 8 and the GLC1E gene on chromosome
10 are associated with
mild-to-moderately-raised
eye pressures in individuals
with optic-nerve damage. 50,51
Wirtz and colleagues52
mapped the GLC1F gene
to chromosome 7 and found
this gene was associated
with raised eye pressures or
visual-field loss and a cup-
to-disc ratio of 0·6. The
only so-called glaucoma
gene for which a specific
protein has been identified
is GLC1A. Because POAG
is a heterogeneous disease,
with some individuals
exhibiting features such as
raised eye pressures or optic-nerve cupping and others
without these features, it would not be surprising if more
gene loci were identified in POAG families.
Management
The goal in the treatment of POAG is to prevent further
loss of functional vision during the remainder of a
patient’s life and to avoid an adverse impact on the
patient’s quality of life.11,12 This goal can be difficult to
achieve because the clinician usually does not know when
a patient will die and because many of the interventions
for glaucoma can affect the patient’s quality of life.
Striking an appropriate balance is especially challenging
since the loss of vision from glaucoma also affects the
patient’s quality of life.
The prevention of loss of vision is mainly achieved by
lowering the eye pressure to a threshold that is deemed to
be safe for the ganglion cells given the current amount of
damage in the optic nerve head (target intraocular
pressure). Individuals with advanced glaucomatous optic-
nerve damage seem to need very low eye pressures
(7–12 mm Hg) to prevent further damage to the optic nerve
and loss of vision.53 Once a patient’s target intraocular
pressure has been achieved, he or she should be
monitored every 3–12 months, although more frequent
monitoring is needed for patients who are monocular or
have advanced bilateral visual-field loss.11 Progressive
glaucomatous damage is determined by changes in the
optic nerve head or in the visual field that are consistent
1805
Panel 1: Glaucoma medications and selected side-effects
Class of drug
Topical cholinergic agonists
Topical b-adrenergic antagonists
Topical adrenergic agonists
Topical or oral inhibitors of
carbonic anhydrase
Prostaglandin analogue
*With echothiophate iodide or demecarium bromide after administration of succinylcholine.
Generic names
Pilocarpine drops and gel,
carbachol, echothiophate iodide,
demecarium bromide
Timolol, levobunolol, carteolol,
metipranolol, betaxolol
Epinephrine, dipiverfrin,
apraclonidine, brimonidine
Topical dorzolamide, brinzolamide, Decrease aqueous production;
oral acetazolamide, methazolamide, duration of action 6–12 h
dichlorphenamide
Latanoprost
Mechanisms and duration of action
Increase aqueous outflow; duration
of action from 6 h to 1 week
Decreased aqueous production;
duration of action 12–36 h
Decreased resistance to aqueous
outflow and decreased aqueous
production; duration of action
8–12 h
Increase aqueous outflow; duration
of action 24–40 h
Selected side-effects
Increased bronchial secretion,
nausea, vomiting, diarrhoea,
increased myopia, eye or brow
pain, decreased vision, apnoea*
Congestive heart failure,
bronchospasm, bradycardia
depression, confusion,
impotence, worsening of
myasthenia gravis, raised
cholesterol
Increased blood pressure,
tachyarrhythmias, tremor
headache, anxiety, conjunctival
injection, pupillary dilation,
allergic reactions
Malaise, anorexia, depression,
paresthesias, serum electrolyte
abnormalities, renal calculi, blood
dyscrasias, allergic reactions,
bitter or sour taste
Increased iris pigmentation,
hypertrichosis, increased
pigmentation of lashes

with the loss of more ganglion cells or axons. Even if
a patient’s eye pressures are at or below the target
intraocular pressure, they need to be monitored because
the target intraocular pressure is only a marker for lack of
progression. Monitoring can be done with visual-field
testing and examination or photographs of the optic nerve
head. The development of new damage in the optic nerve
head or loss of vision on the visual-field test requires
a reassessment of the target intraocular pressure and
further lowering of the eye pressure, if possible.
Topically applied ocular or oral medications are usually
the first step in the management of POAG. Currently
there are five classes of medications that are used to
lower eye pressure: topical cholinergic agonists or
parasympathomimetics, topical b-adrenergic antagonists,
topical adrenergic agonists, topical prostaglandin
analogues, and topical and oral inhibitors of carbonic
anhydrase (panel 1). The clinician must remember that
although most glaucoma medications are applied
topically to the eye, they can cause severe systemic side-
effects and adversely affect a patient’s quality of life.54
When topical medications are prescribed, it is helpful to
inform the patient to close his or her eyes after the
administration of the eye drop for at least 1 min. While
the eyes are closed, the patient can place a finger near the
nose and press against the nasolacrimal duct to help
further reduce systemic absorption of the eye drop
(figure 4).55
The European Glaucoma Society recommends the
following steps in their flow chart on the management of
POAG: medications first, then argon laser trabeculoplasty
if treatment does not lower eye pressure sufficiently, and
finally incisional surgery (trabeculectomy) if argon laser
trabeculoplasty is ineffective.12 This treatment strategy is
similar to the one proposed by the American Academy of
Ophthalmology, although the American Academy of
Ophthalmology recommends that in certain cases either
an initial argon laser trabeculoplasty or an incisional
surgery may be appropriate.11 There has been a shift in
the management of patients with POAG toward more of
a surgical approach because of the findings of several
studies (panel 2).56–61.
If medications, argon laser trabeculoplasty, and
trabeculectomies are ineffective in lowering a patient’s
eye pressure, then the placement of drainage devices or
ciliodestructive procedures are recommended. In certain
cases, drainage devices or ciliodestructive procedures may
be done instead of an initial trabeculectomy, because of
the high likelihood of a trabeculectomy failing.62
Because patients with POAG can continue to have loss
of vision despite reductions of eye pressure, the role of
neuroprotection in the management of POAG warrants
consideration. Two clinical trials showed a beneficial
effect in normal-tension glaucoma with calcium-channel
blockers.63,64 In a retrospective case-control study, patients
with normal-tension glaucoma who were taking calcium-
channel blockers had less progressive loss of visual
field than those who were not taking calcium-channel
blockers.63 Prospective, randomised clinical trials of the
effectiveness of calcium-channel blockers in POAG have
not yet been completed. Other neuroprotective agents,
such as glutamate blockers, antioxidants, inhibitors of
nitric-oxide synthase, antiapoptosis agents, and heat-
shock proteins are under investigation.65
There has been much public attention on marijuana
as a possible treatment of glaucoma. Inhalation of
marijuana does lower eye pressures.66 Because it is
Figure 4: Patient closing eyes with nasolacrimal occlusion (A)
and oblique flashlight test (B)
A: These two manoeuvers help decrease the systemic absorption of
topical eye medications.
B: Note how penlight is held parallel to the iris so that illumination of the
iris can be assessed.
Published with permission of the American Academy of Ophthalmology.

1806 THE LANCET • Vol 354 • November 20, 1999

thought that sustained lowering of eye pressure is likely
to confer greater benefit, the amount of marijuana
smoke needed to produce clinical benefits may be
associated with substantial side-effects, and thus,
marijuana is not recommended as a treatment for
glaucoma.
Primary angle-closure glaucoma
Diagnosis and epidemiology
Patients with PACG may present with acute raised eye
pressures, a mid-dilated pupil, a red eye, or nausea and
vomiting, whereas in other cases they may have no
complaints or may complain of a non-specific headache,
eye pain, or halos around lights.67 The diagnosis of PACG
requires an assessment of the anterior chamber angle to
find out if the trabecular meshwork is blocked by the
peripheral iris. If a skilled observer, slit-lamp, and
gonioscopy lens are not available, a presumptive diagnosis
of PACG may be made with the oblique flashlight test. In
this test, a penlight or flashlight is held off to the side and
parallel to the iris of the eye with the beam shining across
the anterior chamber. If the whole iris is illuminated, the
angle is judged to be open. If a shadow is cast on the iris
near the nose, then the angle is deemed to be narrow or
closed (figure 4). The sensitivity and specificity of this
test in a rural population of Taiwanese Chinese was 80%
and 69%, respectively.68
In PACG one of the mechanisms for the obstruction of
the trabecular meshwork by the iris is pupillary block or
the inability of the aqueous humor to leave the posterior
chamber behind the iris, because of the apposition of the
iris to the lens of the eye. This inability of aqueous humor
to flow around the lens of the eye results in a pressure
gradient between the posterior and anterior chambers of
the eye. This pressure gradient causes a forward bowing
of the peripheral iris that then obstructs the trabescular
meshwork (figure 1).67 Another mechanism is called
creeping angle closure69 and involves the development of
peripheral anterior synechiae, even when there is a patent
peripheral iridotomy.70

Panel 2: Randomised clinical trials of management of patient with POAG or suspected glaucoma
Trial name Study population Treatment groups Length of Findings
(number of patients) follow-up
Scottish Glaucoma Trial58 Patients with open-angle glaucoma, (1) Medicine first 4·6 years Less deterioration of visual fields
eye pressure >25 mm Hg (n=116) (2) Trabeculectomy first in trabeculectomy-first group than
in medicine-first group
Moorfields Primary Treatment Patients with open-angle glaucoma, (1) Medicine first >5 years Less deterioration of visual fields
Trial59 eye pressures Ä24 mm Hg (n=168) (2) Laser trabeculoplasty in trabeculectomy group than in
first medicine and laser groups
(3) Trabeculectomy first
Glaucoma Laser Trial56 Patients with open-angle glaucoma, (1) Medicine first 9 years Less deterioration in optic nerve
eye pressures Ä22 mm Hg (n=271) (2) Laser trabeculoplasty and visual field in laser-
first trabeculoplasty-first group than
medicine-first group
Fluorouracil Filtering Surgery Glaucoma patients who had had (1) Trabeculectomy with 5 years 5-year cumulative probability of
Study60 intraocular surgery (n=213) 5-fluorouracil success was 48% in
(2) Trabeculectomy 5-fluorouracil group and 21% in
without 5-fluorouracil control group
(control)
Trabeculectomy with Patients with open-angle glaucoma (1) Trabeculectomy with 10 months 73% of patients in 5-fluorouracil
intraoperative 5-fluorouracil in Ghana (n=85) intraoperative group and 93% in the mitomycin
vs mitomycin C61 5-fluorouracil C group had eye pressures
(2) Trabeculectomy with <21 mm Hg
with intraoperative
mitomycin C
Collaborative Normal Tension Patients with normal-tension (1) Reduction of eye >5 years Visual-field progression more
Glaucoma Study24,25 glaucoma with damage and eye pressure Ä30% below common in untreated group than
pressures of ¶24 mm Hg (n=230) baseline level treated group when analysis
(2) No reduction of controlled for presence of
eye pressure cataracts
Advanced Glaucoma Patients with open-angle glaucoma (1) ATT 7 years Deterioration in visual field is
Intervention Study57 on maximum medical therapy (2) TAT less in black patients in ATT
(n=591) group and in white patients in
TAT group
Early Manifest Glaucoma Swedish residents with early (1) Betaxolol and laser >4 years Trial continuing
Trial84 glaucomatous visual field defects trabeculoplasty
(n=255) (2) No treatment
Collaborative Initial Glaucoma Open-angle glaucoma patients, eye (1) Medicine >5 years Trial continuing
Treatment Study85 pressures Ä20 mm Hg or higher (2) Trabeculectomy
(n=607)
Ocular Hypertension Ocular hypertensives with eye (1) Medicine >5 years Trial continuing
Treatment Study86 pressures 24–32 mm Hg (n=1637) (2) No treatment
ATT=argon laser trabeculoplasty followed by trabeculectomy if the argon laser trabeculoplasty fails and trabeculectomy again if the first trabeculectomy fails.
TAT=trabeculectomy followed by argon laser trabeculoplasty if the trabeculectomy fails and then another trabeculectomy if the argon laser trabeculoplasty fails.

THE LANCET • Vol 354 • November 20, 1999 1807


People of Eskimo,71 Chinese,72,73 or Asian Indian74
descent are at increased risk of PACG. In Wales in the
UK the prevalence of PACG in people older than 40
years was 0·09% and the prevalence of POAG was
0·5%,75 whereas the prevalence of PACG in Alaskan
Eskimos was 2·6% in people older than 40 years.76 In
a Chinese population, the prevalence was 1·37% for
PACG, compared with 0·11% for POAG,72 and in
an Asian Indian population, the prevalence of PACG in
individuals age 30–60 years was 4·33% versus 0·41%
for POAG.74 Patients with PACG, especially Chinese and
Asian Indians, may not have acutely increased eye
pressures and symptoms because of chronic, creeping
angle closure.74,77
Additional risk factors for PACG include a family
history of the disease, age of 30 years or older, female sex,
and hypermetropic eyes. First-degree relatives of Eskimos
with PACG have a 3·5 time greater risk of developing
PACG than the Eskimo population in general.78 In white
people, the prevalence of PACG in first-degree relatives
ranges from 1 to 12%.79 Although there have been formal
recommendations to start screening for PACG at age 40,
studies from India 74 and China80 indicate that screening at
age 30 years or older would be more appropriate. The
prevalence of PACG peaks in individuals aged 50–69
years.79 Women are reported to be at increased risk of
PACG if they are white,75 Eskimo,81 or Chinese.72 In the
Asian Indian population, there was not a significant
difference in the prevalence of PACG between men
and women.74 White people who have hypermetropic eyes
are at increased risk of PACG.82 This increased risk is
consistent with the finding that patients with PACG have
shallower anterior chambers and smaller-sized globes
than individuals who do not have PACG. Lowe82 has
postulated that these smaller, more-crowded eyes are
predisposed to the blockage of the trabecular meshwork
by the peripheral iris.
Management
Medications for PACG are similar to those used in
POAG (panel 1). In the management of an acute attack
of PACG, treatment with miotics, a-adrenergic agonists,
b-adrenergic blockers, inhibitors of carbonic anhydrase,
and systemic hyperosmotic agents may be used to help
lower the eye pressure and arrest the attack. However,
the primary management of PACG is the placement of
a laser iridotomy or opening in the peripheral iris. This
hole will effectively eliminate the forward bowing of
the iris and obstruction of the trabecular meshwork by
the iris.67
The presence of a patent iridotomy does not mean
that the patient does not need further follow-up or
medications. Additional concerns include permanent
synechiae of the iris to the trabecular meshwork before the
iridotomy, undetected trabecular damage from temporary
apposition of the iris to the trabecular meshwork, and the
possibility of creeping angle closure. Some patients need
chronic medications to lower the eye pressure despite
the presence of a patent iridotomy. The medications used
are similar to those used in the treatment of POAG. In
patients with chronic PACG who do not respond to
medications, the next step is trabeculectomy with or
without antimetabolites or drainage devices. Argon laser
trabeculoplasty is contraindicated in these eyes if there is
more than 90 degrees of angle closure.67
1808
Health-related quality of life
Health-related quality of life encompasses a patient’s
ability to engage in activities of daily living such as self-
care, driving, and working and his or her perception of
well-being. Assessments of health-related quality of life
include questions about the symptoms of disease that are
apt to be of greatest importance to patients. In addition,
such questionnaires are useful in assessing the effects of
alternative treatments. Patients with POAG have lower
scores than population-based norms on generic measures
of quality of life such as the medical outcomes study
short-form-36 questionnaire.6,7 The scores of individuals
with POAG are similar to the scores of people with well-
controlled systemic hypertension or diabetes mellitus.83
Visual-field loss is associated with lower scores on quality-
of-life surveys that target vision such as the national eye
institute visual functioning questionnaire (NEI-VFQ) and
the visual functioning 14 questionnaire, especially when
visual-field loss afflicts the eye with better visual acuity.8,9
Thus, glaucoma does have a substantial impact on
health-related quality of life.
Conclusion
If current trends prevail, the worldwide prevalences of
POAG and PACG will continue to increase. Attempts to
reduce substantially the visual impairment and blindness
associated with glaucoma will need more aggressive
detection, so that more people with glaucoma are aware
that they have this disease. Also needed is more careful
management of POAG and PACG that incorporates
lessons learned from current research. Because of the
health, social, and economic consequences of blindness,
the burden of POAG and PACG falls not only on
patients and their physicians, but also on society. Thus,
disease-control strategies need to go beyond the simple
suggestion that primary care physicians screen routinely
for the disease. Broader public information campaigns
might highlight the need for periodic eye examinations,
especially among individuals with a family history of the
disease or other risk factors for glaucoma.
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