Acta Ophthalmologica 2016

Review Article

Primary angle-closure glaucoma: an update

Carrie Wright, Mohammed A. Tawk, Michael Waisbourd and Leslie J. Katz
Wills Eye Hospital, Philadelphia, PA, USA

ABSTRACT. The classication of PACG is often

Primary angle-closure glaucoma is potentially a devastating disease, responsible considered confusing, due to early
for half of glaucoma-related blindness worldwide. Angle closure is characterized by inconsistencies in terminology and
appositional approximation or contact between the iris and trabecular meshwork. nomenclature. These were addressed in
It tends to develop in eyes with shallow anterior chambers, anteriorly positioned or a study by Foster et al. (2002) who
pushed lenses, and angle crowding. Risk of primary angle-closure glaucoma is high standardized the denitions based on
among women, the elderly and the hyperopic, and it is most prevalent in Asia. progression of the disease. Current
Investigation into genetic mechanisms of glaucoma inheritance is underway. American Academy of Ophthalmology
Diagnosis relies on gonioscopy and may be aided by anterior segment optical (AAO) classications follow a similar
framework, as follows (2010) (Table 1).
coherence tomography and ultrasound biomicroscopy. Treatment is designed to
control intraocular pressure while monitoring changes to the angle and optic nerve
head. Treatment typically begins with medical management through pressure- Classication
reducing topical medications. Peripheral iridotomy is often performed to alleviate PACG exists in a spectrum of angle-
pupillary block, while laser iridoplasty has been found eective for mechanisms of closure disorders that includes primary
closure other than pupillary block, such as plateau iris syndrome. Phacoemulsi- angle-closure suspect (PACS), primary
cation, with or without goniosynechialysis, both in eyes with existing cataracts angle closure (PAC) and PACG itself.
and in those with clear lenses, is thus far a viable treatment alternative. Long-term PACS is diagnosed by the presence of
research currently underway will examine its ecacy in cases of angle closure in iridotrabecular contact (ITC) on goni-
early stages of the disease. Endoscopic cyclophotocoagulation is another treatment oscopy. The degree of ITC necessary for
option, which can be combined with cataract surgery. Trabeculectomy remains a PACS diagnosis has often been con-
tested, but most ophthalmologists con-
eective therapy for more advanced cases.
sider the presence of 180 or more of
ITC sucient. According to the AAO
Key words: angle-closure glaucoma argon laser iridoplasty lensectomy peripheral
Preferred Practice Guidelines, 1 in 4
iridotomy phacoemulsication plateau iris primary angle closure pupillary block review
patients with PACS goes on to develop
IOP elevation or peripheral anterior
Acta Ophthalmol. 2016: 94: 217225 synechiae (PAS) over 5 years (2010).
2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
The criteria for PAC include 180 or
doi: 10.1111/aos.12784 more of ITC in conjunction with an
elevated IOP or the presence of PAS.
These may not be secondary to any
Introduction As the name implies, primary other known cause or ocular disease.
Glaucoma is currently the second lead- chronic angle-closure glaucoma is a A diagnosis of PAC becomes PACG
ing cause of blindness worldwide. It type of chronic angle-closure glaucoma in the presence of glaucomatous optic
aects over 60 million people, a num- (CACG), a gradual, often clinically neuropathy. For classication pur-
ber expected to increase to nearly silent, closure of the angle resulting in poses, glaucomatous nerve damage is
80 million by 2020 (Quigley & Broman increased intraocular pressure (IOP) dened as an abnormality in the optic
2006). Primary angle-closure glaucoma and eventual glaucomatous optic nerve disc or retinal nerve bre layer, or a
(PACG) is a type of glaucoma esti- damage. CACG is a broader term that reliably reproducible abnormality of
mated to aect approximately 26% of includes secondary causes for angle- the visual eld.
the glaucoma population; however, closure glaucoma, for example anterior
PACG is responsible for nearly half traction of the peripheral iris due to
the cases of glaucoma-related blindness neovascular membrane formation
Pathogenesis
in the world (Quigley 1996; Quigley & (Tarongoy et al. 2009), which are not In early cases of angle closure, the
Broman 2006). the focus of this review. angle may be only appositionally

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Acta Ophthalmologica 2016
Table 1. Classication of angle-closure disorders.
Primary Angle-closure Suspect (PACS)
Primary Angle-closure (PAC)
Primary Angle-closure Glaucoma (PACG)
ITC, iridotrabecular contact; IOP, intraocular pressure; PAS, peripheral anterior synechiae.
Fig. 1. Double-hump sign as seen on gonios-
copy. Figure reproduced with permission of
Bryn Mawr Communications LLC. Nagori S,
Laroche D. Treating plateau iris. Glaucoma
Today. September/October 2012;10(5):3840.
closed. With time, broad synechiae
form, and the angle closes superiorly
to inferiorly, accompanied by an
increasing intraocular pressure that is
dicult to control. There are several
mechanisms by which PACG can
develop. The appositional obstruction
of the trabecular meshwork by the
peripheral iris can be a consequence
of an abnormal relationship between
the size and position of the structures
of the anterior segment or of the
relative pressure dierential between
the anterior and posterior chambers
of the eye (Lowe & Ritch 1989).
Pupillary block and anterior lens move-
ment
The most common aetiology of PAC is
pupillary block, in which inhibition of
aqueous ow causes an increased pres-
sure dierential between the anterior
and posterior compartments of the eye,
leading to iris bowing and appositional
closure of the angle. At baseline, a
pressure dierential of approximately
0.23 mmHg exists between the anterior
and posterior chambers (Heys et al.
2001). This accounts for the normal
outow of aqueous humour from pos-
terior to anterior chamber between the
posterior iris and anterior lens. When
this pressure dierential increases, it
causes anterior bowing of the iris into a
218
180 Elevated IOP or Glaucomatous
of ITC Presence of PAS optic neuropathy
+ dition most common among women
+ +
+ + + with hyperopic refractive error. Kumar
convex form. The convex shape of the
iris brings it into appositional contact
with the trabecular meshwork,
obstructing drainage and potentially
allowing for the formation of PAS
and progression down the path to
PACG. Shallow anterior chambers are
predisposed to pupillary block due to
apposition of the pupil and anterior
lens capsule. Of note, studies demon-
strate that iris thickness can inuence
the pressure dierential between ante-
rior and posterior chambers (Wyatt &
Ghosh 1970; Tarongoy et al. 2009),
suggesting that darker irides may pre-
dispose to pupillary block (Quigley
et al. 2003).
The lens plays a crucial part in the
pathogenesis of PAC, with more ante-
riorly positioned lenses causing greater
degrees of iris convexity (Wyatt &
Ghosh 1970). Movement of the lens
forward, as observed with increasing
age, in phacomorphic glaucoma with
advanced cataract, and in instances of
choroidal expansion, can narrow the
anterior chamber and cause apposi-
tional contact between iris and trabec-
ular meshwork. Choroidal expansion,
seen in malignant glaucoma and sec-
ondary to a wide range of ocular
diseases, is also suspected to occur to
some degree in healthy eyes (Quigley
et al. 2003). A certain degree of phys-
iological expansion of the choroid
occurs in response to changes in arte-
rial and venous pressure, blood vol-
ume, colloid osmotic pressures and
transient variations in IOP. Increasing
choroidal volume may hypothetically
exert pressure on the vitreous and be
conducted forward to the lens, shifting
it more anteriorly in the eye. Loose
zonules, as seen in exfoliation syn-
drome, may also contribute to the
development of PAC via anterior lens
shift.
Angle crowding
Angle crowding refers to the phenom-
enon of angle closure in response to the
compression of the iris between the
trabecular meshwork and another ana-
tomical structure (Tarongoy et al.
2009). This is most frequently seen
with plateau iris conguration, a con-
aged 3050 years, particularly those
et al. estimated that 30% of primary
angle-closure suspect eyes were diag-
nosed with plateau iris on UBM after
laser iridotomy (2008). Plateau iris
conguration occurs in patients with a
large and/or anteriorly positioned
ciliary body that compresses the iris
root forward against the trabecular
meshwork (Pavlin et al. 1992).
Clinically, irides appear at or
slightly convex from pupil to periph-
ery, and the central anterior chamber
depth is relatively normal. However,
gonioscopy reveals that the peripheral
iris takes a sharp turn posteriorly
before inserting into the ciliary body.
This sharp turn can facilitate angle
closure when the pupil is dilated. The
ciliary bodys positioning also prevents
easy movement of the peripheral iris
during indentation gonioscopy. This
causes the iris to assume a sine-shaped
curve, known as the double-hump sign
(Fig. 1), as it curves rst over the
ciliary body and then over the anterior
capsule. The term plateau iris syndrome
refers to the clinical picture of angle
closure despite a patent iridectomy.
This condition may lead to widespread
peripheral anterior synechiae and, with
persistent elevations in IOP, may
progress to PACG.
Epidemiology
Risk factors
Numerous risk factors play a role in
the development of PACG, including
increasing age, female gender, shallow
anterior chamber, short axial length of
the eye in hyperopia, small corneal
diameter, steep corneal curvature, shal-
low limbal chamber depth, and thick,
anteriorly positioned lenses.
Age
The prevalence of relative pupillary
block and PAC, and thus PACG, has
been shown to increase with age. A
recent study of European-derived pop-
ulations reported an age-specic prev-
alence of PACG of 0.02% for those
aged 4049, increasing to 0.95% for
those 70 years and older (Day et al.
2012). Anterior chamber depth and

volume gradually decrease throughout
life. A 1996 analysis of anterior cham-
ber changes demonstrated a depth
decrease of 0.21 mm and volume
decrease of 19 ll over 10 years (Sakai
et al. 1996); in concert, these changes
contribute to angle narrowing and
increase the likelihood of PAS among
the elderly. Lens thickness also con-
tributes to anterior chamber shallowing
(Lee et al. 1984). In younger popula-
tions, PACG is rare and is generally
associated with other ocular abnormal-
ities or plateau iris syndrome (Chang
et al. 2002).
Gender
Risk of PACG among women is
approximately 3 times higher than in
men (Foster et al. 1996, 2000; Quigley
& Broman 2006). This, too, is likely the
result of anatomical and mechanical
dierences between male and female
eyes. Okabe studied 1169 eyes of par-
ticipants diagnosed with PACG and
found that certain measurements,
including anterior chamber depth and
axial length, were much lower in
women, while angle width in women
was signicantly narrower than in men
across all age groups (1991). Prevalence
among women is also a function of
relative life spans, as PACG is primar-
ily a disease of the elderly, and women
tend to outlive men.
Ethnicity
Worldwide, the prevalence of PACG is
highest in China. Of the 15 million
people estimated to have ACG in 2010,
47.5% were located in China, and
projections suggest that 20 million Chi-
nese will have ACG by the year 2020
(Quigley & Broman 2006). An esti-
mated 1.7 million Chinese persons are
bilaterally blind from glaucoma, and
the majority (91%) of that blindness is
attributable to PACG (Foster & John-
son 2001). Numbers are similarly high
86.5% throughout Asia (Quigley &
Broman 2006). Prevalence diers
among Asian groups, with Mongolians
demonstrating the highest prevalence
of PAGC at 1.4% (Foster et al. 1996).
Asians have a notably higher preva-
lence of PACG (0.61%) (Dandona
et al. 2000; Foster et al. 2000; Yamam-
oto et al. 2005) than either Caucasians
(0.090.4%) (Bonomi et al. 1998; Day
et al. 2012) or Africans (0.5%) (Rot-
chford & Johnson 2002). Within indi-
vidual ethnic groups, prevalence of
PACG was highest by far among the
Inuit population, at 2.65% (Arkell
et al. 1987).
Refractive error
Small, hyperopic eyes are most at risk
for developing PACG; the condition is
rare in myopes, although it has been
noted more frequently in those with a
spherical equivalent of -6 dioptres
(Mitchell et al. 1999; Barkana et al.
2006; He et al. 2006). As mentioned
above, patients with PACG have a
shorter axial length, shallower anterior
chamber depth and diameter, and a
thicker, more anteriorly positioned lens
(Fontana & Brubaker 1980; Lee et al.
1984; Marchini et al. 1998).
Family history and genetic predisposition
Although most cases of PACG are
sporadic, recent research among Asian
populations has indicated a hereditary
element to the disease. In a 2014 study
of prevalence of angle closure among
siblings, 57.9% of siblings with one
family member aected by PACG were
categorized along the angle-closure
spectrum themselves, with 14.7% dem-
onstrating full PACG (Yazdani et al.
2014). A broader study of rst-degree
relatives of PAC and PACG patients
conducted in Singapore found that
32.1% had narrow angles, with overall
heritability of narrow angles calculated
at 57.95. Siblings of PACG and PAC
patients, in particular, were more than
7 times more likely to have narrow
angles than the general population
(Amerasinghe et al. 2011). A similar
study in India examined the risk of
narrow angles in siblings of PACS and/
or PACG patients. The study found
that odds of developing narrow angles
were nearly 14 times greater among
these siblings than in the general pop-
ulation, with a greater than 1 in 3 risk
of angle closure (Kavitha et al. 2014).
Though imperfectly understood, the
familial connection is clear, and sib-
lings may benet from PACG screen-
ing.
The genetic causes that underlie
angle-closure glaucoma are still being
elucidated. An extensive genomewide
association study published in 2012
identied three genomic loci that pre-
dispose patients to PACG: rs11024102
on PLEKHA7, rs3753841 on
COL11A1 and rs1015213 on chromo-
some 8q (Vithana et al. 2012). The
precise mechanism of pathology arising
Acta Ophthalmologica 2016
from aberrant gene loci is still
unknown. PLEKHA7 is known to
regulate tight junctions; it is theorized
that a deciency at this locus might
disrupt uid dynamics in the eye.
COL11A1 generally encodes collagen;
the studys authors proposed that this
might manifest in scleral matrix anom-
alies or alteration of trabecular mesh-
work cells that could contribute to
PACG development. Additional analy-
sis determined that these polymor-
phisms did not impact axial length or
anterior chamber depth (Nongpiur
et al. 2013); further research may yet
clarify the functional insult contribut-
ing to the development of acute dis-
ease. The clinical implications of the
presence of these polymorphisms were
recently investigated in a paper by Wei
et al., who found no signicant associ-
ation between the alleles and the clin-
ical features of glaucoma in the
patients whose genotype contained
them. No particular allele was found
to be associated with phenotypically
higher IOP, disease severity or disease
progression; the presence of these loci
appeared to increase susceptibility only
(2014).
Numerous other studies have exam-
ined genetic determinants for the risk
factors referenced above. Nair et al.
demonstrated an association between
alterations in serine protease PRSS56
and a decreased axial length in the
mouse model, contributing to the
development of increased IOP, angle
closure and choroidal expansion, pre-
sumably secondary to alterations in
extracellular matrix processing during
development (2011). Mutations of this
protease also contributed to decreased
axial length in humans with posterior
microphthalmia. Other avenues of
enquiry include research into the mem-
brane-type frizzled-related protein
(MFRP), another factor responsible
for determining axial length and depth
of the anterior chamber, observed in
eyes with nanophthalmos (Liu & All-
ingham 2011) and into single nucleo-
tide polymorphisms (SNPs) in
metalloproteinases responsible for
extracellular matrix formation (Shastry
2013). Still more genetic studies have
shown an association between PACG
and endothelial nitric oxide synthase
polymorphisms in Australian, Nepa-
lese and Pakistani populations (Ayub
et al. 2010; Awadalla et al. 2013). Fur-
ther research will hopefully clarify the
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Acta Ophthalmologica 2016

Using the four-mirror lens, the clini-

cian gently indents the central cornea;
this displaces the aqueous from the
centre to the periphery of the anterior
chamber, mechanically deepening the
angle and enabling better visualization
of angle structures (Fig. 2) (Shields
1998). Dynamic indentation gonios-
copy also aides in determining the
extent of PAS (Fig. 3A) and may
dierentiate plateau iris conguration
from pupillary block. Corneal indenta-
tion during gonioscopy results in pos-
terior movement of the mid-peripheral
iris in eyes with pupillary block,
whereas in plateau iris conguration,
the ciliary process prevents movement
and a sine-shaped curve of the iris
surface can be seen at the slit lamp
(Shields 1998).

Clinical estimation
Several techniques exist for the evalu-
ation of anterior chamber depth at the
slit lamp to identify patients at risk of
angle closure. One traditional assess-
ment method is Van Hericks tech-
nique, which measures limbal chamber
depth. This technique is performed by
Fig. 2. Anatomically narrow angle. Top panel: Prior to indentation gonioscopy, most angle
osetting the light beam of the slit
structures are not visible, apart from the anterior portion of Schwalbes line (barely seen). The iris lamp by 60 from its central axis to
curvature is anteriorly bowed. Bottom panel: Following indentation gonioscopy, the iris attens create a thin column of light which is
and angle structures are revealed. (From top to bottom: Schwalbes line, non-pigmented then directed at the temporal limbus.
trabecular meshwork, pigmented trabecular meshwork and scleral spur. The ciliary body band is The observer compares the corneal
barely seen). thickness to the depth of the anterior
chamber, which is visualized as a black
space between the light reexes on the
cornea and iris (Fig. 4). Based on the
ratio of limbal depth to corneal thick-
ness, the observer grades the likelihood
of angle closure on a scale from 1 to 4
(Table 2), with 1 indicating complete
closure and 4 indicating completely
open angles (Van Herick et al. 1969;
Gispets et al. 2014). Gonioscopy is
recommended at grade 1 and below.
A second means of assessment is
(A) (B)
Smiths method. In this technique, the
Fig. 3. Peripheral anterior synechiae as seen on gonioscopic (A) and OCT (B) imaging.
angle between the slit beam and micro-
Figure adapted with permission of Elsevier (Lai et al. 2013). scope is set to 60, and the light beam is
oriented horizontally. The physician
directs a horizontal beam of light from
link between known genetic loci and in particular is an essential technique the slit lamp across the cornea, forming
phenotypic expression of narrowed for assessing PAS and appositional two images of the slit beam upon the
angles. angle closure. The technique relies on patients eye: one image is in focus on
the use of a four-mirror Zeiss, Sussman the cornea, and the second is out of
or Posner lens rather than the standard focus across the lens and iris. The
Diagnosis Goldmann lens. These lenses have an physician then adjusts the slit length
Gonioscopy area of contact smaller than the cornea control knob until these two images
Gonioscopy remains the most impor- to enable the ease of indentation, and appear to touch end-to-end (Smith
tant diagnostic method for assessing unlike the Goldmann lens, they require 1979). The length of the slit beam with
angle closure. Indentation gonioscopy no coupling medium for a clear view. the two images in contact is multiplied

220

Fig. 4. Semi-objective measurement, through
image analysis, of the width of the peripheral
corneal thickness (PCT, solid line rectangle)
and the peripheral anterior angle depth
(PACD, broken line rectangle). This image
was awarded a grade 3. Figure reproduced
with permission of John Wiley & Sons, Inc.
(Gispets et al. 2014), 2013 The Authors and
Optometrists Association Australia.
Table 2. Van Herick grading scale.
Limbal depth relative
Grade to corneal thickness
4 corneal thickness
3 corneal thickness
2 corneal thickness
1 < corneal thickness
Narrow Slit
Grade is determined by comparing limbal
anterior chamber depth to the thickness of
the cornea (Van Herick et al. 1969). Gonio-
scopic evaluation is recommended at grade 1
or below.
by a constant, commonly 1.4 or 1.31, to
obtain a value for ACD in millimetres.
Both of these techniques are imprecise
one study estimated that Van Her-
icks method often overestimated grade
while Smiths often overestimated
ACD (Eperjesi & Holden 2010) but
they provide a sense of a patients risk
for angle closure without requiring
gonioscopy.
OCT
Anterior segment OCT uses the reec-
tion of light to provide high-resolution
images of the anterior segment of the
eye. The main limitation of OCT in the
context of PACG is its inability to
provide information on structures pos-
terior to the iris. This prevents the
physician from distinguishing plateau
iris, ciliary body cysts, tumours or
ciliary eusions that may be contribut-
ing to a narrow angle. However, OCT,
as a non-contact technique, creates less
patient discomfort than UBM and
depends less on technician skill.
Advances in OCT suggest that this
technique may soon become more
valuable in assessing the extent and
progression of PAS (Fig. 3B). A prom-
ising report by Lai et al. (2013) on
swept-source OCT demonstrated that
newer models of OCT can provide
reproducible, quantiable information
on the area of PAS in patient eyes
across 360 degrees. By varying lighting
conditions, it was also possible to
dierentiate appositional from synechi-
al closure. OCT, however, remains less
reliable than diagnostic assessment via
gonioscopy. A recent study by Hu
et al. assessed accuracy and consis-
tency of Visante and Cirrus OCT
measurements at detecting the presence
of angle closure, as compared with
gonioscopy performed by three inde-
pendent examiners. Results did not
support the use of OCT in patients
with angle closure, reporting only slight
to fair agreement between OCT-diag-
nosed and gonioscopically detected
angle closure, and demonstrating less
consistency between OCT machines
than among clinician examiners (Hu
et al. 2014). As technology continues
to improve, OCT may become a more
prevalent method for quantication
and circumferential assessment of the
angle in the development and progres-
sion of PAC; however, it currently is
not as reliable as gonioscopy.
UBM
Ultrasound biomicroscopy (UBM)
shows the position of the ciliary body
and processes, as well as the structures
anterior and posterior to the iris root.
UBM has a resolution of 40 microns
and a penetration depth of 4 mm
(Schacknow & Samples 2010). It shows
the zonular threads of the lens but not
retrolenticular details. Examination
can be dicult and dependent on
operator skill and may cause some
discomfort to the patient.
Treatment
The principle behind PACG manage-
ment is to control IOP while monitor-
ing changes to the angle and optic
nerve head. Often, this is accomplished
by revising the angle conguration
through laser/surgical intervention.
Medical management
Initial IOP control is attempted
through the use of topical glaucoma
Acta Ophthalmologica 2016
medications. Although aqueous sup-
pressants are usually the treatment of
choice, prostaglandin analogues were
recently found eective in lowering
IOP in PACG, even in the presence of
360 of PAS (Netland 2008).
Parasympathomimetics, also known
as miotics due to their action on the
pupil, were the earliest drugs used in
glaucoma treatment, introduced in the
late 1800s (Shields 1998). They remain
in use today for angle-closure glau-
coma. Miotics act to contract both the
ciliary muscle and the pupillary sphinc-
ter. As the ciliary muscle contracts, it
places traction on the scleral spur,
altering the conguration of the trabec-
ular meshwork and allowing for
improved aqueous outow. Meanwhile,
contraction of the pupillary sphincter
thins the iris and mechanically pulls it
away from the drainage structures of
the anterior chamber angle. The end
result is improved outow and relief of
pupillary block (Shields 1998; Rao et al.
2013a,b). Miotics are also particularly
useful in the treatment of plateau iris
syndrome, as they help to prevent the
acute angle-closure crises often precip-
itated by pupillary dilation. (Pavlin
et al. 1992). Of the miotic agents, pilo-
carpine is the most frequently used and
extensively studied; often, it is used in
combination with the beta-blocker
Timolol, and it can also be combined
with carbonic anhydrase inhibitors or
alpha-agonists. Potential side-eects of
pilocarpine include ciliary muscle
spasm, browache, induced myopia from
anterior chamber shallowing, dimness
of vision due to miosis, and retinal
detachment, as well as systemic musca-
rinic eects such as glandular stimula-
tion and contraction of smooth muscle
(Shields 1998).
Laser peripheral iridotomy (LPI)
The current standard for initial treat-
ment in PACG is LPI, which alleviates
pupillary block by reducing the pres-
sure dierence across the iris. The
decreased pressure dierence permits
the angle to open; the iris attens and
the ciliary body shifts to a slightly more
posterior position (He et al. 2007).
Several studies have examined the
rate of progression from angle-closure
suspect to PAC or PACG among
patients undergoing LPI, with varying
results. One such study among Asian
populations demonstrated no progres-
sion from PACS to PAC or PACG over
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Acta Ophthalmologica 2016
an average 4-year follow-up, a remark-
able improvement given the estimated
rate of progression in untreated eyes,
which varies from 19 to 35% depending
on the populations studied (Pandav
et al. 2007; Peng et al. 2011). A subse-
quent study in a Vietnamese population
showed less favourable results, with a
rate of 2226% of PACS suspects pro-
gressing to either PAC or PACG over
10 years (Peng et al. 2011).
Research is still ongoing as to the
preventative value of LPI. Of particu-
lar note, the Zhongshan Angle Closure
Prevention (ZAP) trial currently under-
way aims to clarify the value of LPI as
a preventative measure in PACS sus-
pects. The trial compares LPI versus no
treatment across 870 patients with
PACS diagnoses, with monitoring over
3 years for signs of increased IOP,
formation of synechiae, and instances
of acute angle closure (Jiang et al.
2010). Its results should oer valuable
insight into the specic benet of LPI
in limiting PACG progression.
Specic analysis of anterior chamber
anatomy pre- and postprocedure
revealed an average increase in angle
recess depth of 75% among patients
with PACS after LPI, although
approximately 60% of treated eyes
had persistent appositional closure on
UBM. Across studies, disease progres-
sion post-LPI is greater in eyes with a
higher degree of PAS, iridotrabecular
contact in more than one quadrant and
more signicantly elevated IOP prep-
rocedure. Accordingly, these are the
eyes most likely to need subsequent
treatment (He et al. 2007; Pandav et al.
2007; Peng et al. 2011; Rao et al.
2013a,b). Overall, although it seems
LPI favourably alters the course of
disease progression, many eyes half
or more of those already diagnosed
with PAC/PACG (Peng et al. 2011;
Rao et al. 2013a,b) require further
medical or surgical intervention post-
LPI. The best benet is appreciated at
earlier stages of the disease.
Cataract surgery was a signicant
factor in PACS eyes that did not
progress to PAC or PACG (Peng et al.
2011). Please see below for further
discussion of the role of cataract extrac-
tion in managing primary angle closure.
Argon laser peripheral iridoplasty (ALPI)
Argon laser peripheral iridoplasty
applies surface photocoagulation burns
to the peripheral iris to contract the iris
222
stroma, mechanically pulling the iris
away from the trabecular meshwork to
open the anterior chamber angle. The
technique may be used alone, as an
adjunct with LPI, or after LPI to assist
in opening of the angle and minimizing
PAS. ALPI has been shown to be
particularly eective for forms of angle
closure due to mechanisms other than
pupillary block, such as plateau iris,
phacomorphic glaucoma, and posterior
segment processes (Ritch et al. 2004,
2007; Lee et al. 2011). In one study,
87% of plateau iris eyes treated with
ALPI had open angles at the end of
long-term follow-up (mean 79 months)
after a single treatment, with no need
for future ltration surgery (Ritch
et al. 2004). However, ALPI seems to
carry some small risk for Urrets-Zav-
alia syndrome, a condition wherein a
patient develops a xed, dilated pupil
unresponsive to miotic agents follow-
ing a surgical ocular procedure. Espana
et al. (2007) reported eight patients
who developed the syndrome following
ALPI, although these patients lacked
other typical syndrome features of iris
atrophy and increased IOP and recov-
ered normal pupillary function over the
course of a year without treatment.
In spite of its utility in plateau iris
syndrome, ALPI oers less benet when
applied to angle-closure suspects. Stud-
ies comparing LPI alone to LPI with
ALPI have demonstrated more or less
equivalent long-term IOP, although
LPI/ALPI has had greater eect than
LPI alone in deepening the mid-periph-
eral anterior chamber and reducing the
degree of PAS (Sun et al. 2010; Lee
et al. 2011). The current consensus view
is that APLI alone is of limited use
outside of the acute setting, where it may
be used to break the attacks of acute
angle closure (Ng et al. 2012).
Lens extraction
In recent years, a series of studies has
highlighted the eectiveness of phaco-
emulsication and intraocular lens
implantation, long considered a valid
treatment for phacomorphic glaucoma
(Shams & Foster 2012), in treating
PACG. Results have been promising,
with most studies demonstrating that
extraction has been benecial in low-
ering IOP and reducing reliance on
glaucoma medication postoperatively.
A 2009 review by Tarongoy et al.
analysed 22 studies over 19882007,
examining the impact of lensectomy on
PACS, PAC and PACG, mostly con-
ducted on eyes with visually signicant
cataracts. Early studies showed that
more than 65% of patients undergoing
lens extraction and IOL placement dem-
onstrated normal IOP postoperatively
without the need for glaucoma medica-
tion. Others showed that lens extraction
decreased the degree of PAS in the eye
through an unknown mechanism. Cur-
rent theories include errors in gonios-
copy presurgery and the possibility of
viscoelastic material exerting positive
pressure to free the trabecular mesh-
work during surgery (Tarongoy et al.
2009).
Research has been consistent in
demonstrating the most pronounced
improvement in IOP in patients who
have highest baseline IOP (Tarongoy
et al. 2009; Liu et al. 2011; Shams &
Foster 2012). A 2012 study of PAC/
cataract patients by Shams and Foster
reported an average post phacoemulsi-
cation decrease in IOP of 3 mmHg,
but noted that lens extraction had a
signicantly greater impact on eyes in
more advanced stages of disease. Aver-
age increase in angle width in the
Tarongoy study was 20, while the
extent of PAS decreased by 48 and
number of glaucoma medications in
use dropped by one (2009). A 2011
paper examined the pre-operative vari-
ables that contributed to long-term
IOP control post-phacoemulsication,
and found that both pre-operative IOP
and, surprisingly, anterior chamber
depth were positively associated with
postoperative IOP values (Liu et al.).
In the case of anterior chamber depth,
this was thought to be due to the fact
that the lens plays less of a role in angle
closure in eyes with suciently deep
anterior chambers, while those with
shallower chambers are more greatly
impacted by lens removal. The need for
glaucoma medications was also
observed to drop initially, but subse-
quently rise over 4 years. The long-
term clinical course of PACG post-
lens-extraction has yet to be explored.
Lens extraction appears to compare
favourably to current standard treat-
ments for PACG, functioning both
alone and in combination with other
therapies. One comparison of phaco-
emulsication and trabeculectomy
demonstrated comparable long-term
IOP control between the methods;
trabeculectomy patients relied less on
glaucoma medications postsurgically

but had an increased rate of postoper-
ative complications (Liu et al. 2011).
Another showed improved IOP in the
trabeculectomy group but noted that
60% of trabeculectomy patients subse-
quently required cataract extraction
(Tarongoy et al. 2009; Tham et al.
2013).
The Shams and Foster study
observed that IOP reduction after lens
extraction was comparable in patients
with and without prior LPI (2012).
Studies of acute angle closure have also
compared the benet of cataract extrac-
tion versus LPI as a primary treatment;
they found that patients who underwent
phacoemulsication had consistently
lower IOP values than those undergoing
LPI, with a mean IOP of
12.6  1.9 mmHg versus 15  3.4
mmHg, respectively (Lam et al. 2008;
Husain et al. 2012). Over 18 months,
46.7% of patients who underwent LPI
had a rise in IOP, compared to 3.2% in
the phaco group, and phacoemulsica-
tion had both a lower rate of IOP
increase and fewer intraoperative com-
plications than LPI over 2 years.
The above results have favoured cases
of advanced disease and have often been
conducted in eyes with clinically signif-
icant cataracts. It is unclear whether or
not early phacoemulsication and IOL
implantation will be benecial for
patients with mild cases of PACG. Lim-
ited research exists on the subject of clear
lens extraction in PACG treatment, but
an ongoing study by the Eectiveness in
Angle-closure Glaucoma of Lens
Extraction (EAGLE) study group is
currently investigating this question
(Azuara-Blanco et al. 2011).
Goniosynechialysis (GSL) with/without
lens extraction
Goniosynechialysis is a surgical tech-
nique performed to strip peripheral
anterior synechiae (PAS) from the
trabecular surface and provide the
aqueous with renewed access to the
trabecular meshwork. When PAS has
been present for less than a year, the
success rate of GSL is approximately
80%. Irreversible damage to the mesh-
work may occur in areas of synechial
closure, with proliferation of iris or
brous tissue into the intertrabecular
space. This may explain the diminished
eectiveness of GSL in eyes with
longer durations of angle closure.
Complications of GSL include cataract
progression, corneal injury via endo-
thelial cell loss, exudation of brin and
minor haemorrhage (Tanihara et al.
1992).
Combining GSL with lens extraction
and phacoemulsication provides
noticeable visual improvement postsur-
gery, and it has been shown to be more
eective than GSL alone in controlling
IOP, with studies ranging from 85 to
100% success in maintaining normal
IOP and avoiding follow-up proce-
dures (Harasymowycz et al. 2005; Ka-
meda et al. 2013). Removal of the lens
may also decrease the possibility of
recurrent angle closure. This surgery
has been found eective in patients
with pupillary block or plateau iris who
are unresponsive to other treatments. It
is eective in increasing anterior cham-
ber depth in addition to lowering IOP
in patients with plateau iris syndrome
(Harasymowycz et al. 2005; Ng &
Morgan 2012). Risk factors for surgical
failure in GSL/phaco include youth,
presumably due to a brisk inamma-
tory response, lower pre-operative IOP,
as higher IOP is more likely to have
been treated with prior surgery, and
failure to perform follow-up LPI,
which helps to prevent reclosure
(Kameda et al. 2013).
Trabeculectomy
Trabeculectomy, a mainstay of glau-
coma treatment for decades, has been
shown to have reliable long-term
results in managing IOP; one study
tracking patients over 20 years
reported an overall 79% success rate
in controlling IOP across all glaucoma
subtypes (Bevin et al. 2008). However,
any aqueous-draining procedure in an
eye with a shallow anterior chamber
and a chronic closed angle has the
potential for postoperative complica-
tions. Trabeculectomy in chronic angle
closure is associated with a risk of
ltration failure, shallowing of the
anterior chamber, malignant glau-
coma/aqueous misdirection, choroidal
detachment, hyphema, endophthalm-
itis and/or cataract progression (Bevin
et al. 2008; Ng & Morgan 2012; Tham
et al. 2013). The same study reported
14% of failure among eyes with angle
closure, and 30% of all patients studied
required additional postoperative
intraocular procedures.
Cyclophotocoagulation
In 1950, Bietti introduced cyclocryo-
therapy, which uses a probe at 80C
Acta Ophthalmologica 2016
to destroy the ciliary body epithelium,
stroma and vasculature. This results in
reduced production of aqueous
humour and subsequent lowering of
IOP. The clinical usefulness of cyclo-
cryodestruction is limited by its com-
plications, which include hypotony,
phthisis, hyphema, choroidal detach-
ment and retinal detachment. More
recently, diode lasers have been imple-
mented for cycloablation; these oer
greater penetration into the tissues and
improved absorption (Bloom et al.
2013). They also oer a better safety
prole, although risk remains for hyp-
otony, vision loss, corneal oedema,
pupil atony or distortion, and cystoid
macular oedema (Lai et al. 2003,
2005).
Over recent decades, trans-scleral
diode laser cyclophotocoagulation
(TSCPC) using the G-probe has been
used as a treatment option, mostly for
patients with end-stage glaucoma. The
success rates of cyclodestruction vary
among procedures and types of glau-
coma. Diode TSCPC has a reported
eectiveness of 92.3% in controlling
IOP to less than 21 mmHg over 2 years
in patients with refractory glaucoma
but the study also noted that all patients
required postprocedural IOP-lowering
medications to achieve this goal (Lai
et al. 2005). A recent comparison of
laser cyclodestruction versus tube sur-
gery found that the latter was more
eective than cyclodestruction in lower-
ing IOP. Cyclodestruction had a lower
rate of complications and did not
require the hospital stay associated with
tube surgery (Bloom et al. 2013). Due to
the risk prole and eectiveness versus
other techniques, TSCPC is typically
used only in patients refractory to med-
ical management and ltration surgery.
Endoscopic cyclophotocoagulation
(ECP) is another promising technique,
which uses a bre-optic cable to deliver
laser energy to the ciliary processes
using a video monitor. This procedure
may be benecial for patients with
PACG or plateau iris, either in combi-
nation with cataract surgery or as a
separate procedure. Unlike the other
ciliodestructive procedures, ECP may
change the plateau conguration and
open the angle.
Conclusions
Primary angle-closure glaucoma is a
signicant cause of blindness
223
Acta Ophthalmologica 2016
worldwide. Although this subtype is
present in only 26% of the glaucoma
population, it is responsible for half the
cases of glaucoma-related blindness.
The predominant mechanism of
angle-closure glaucoma is pupillary
block, with anterior lens movement as
a strong contributing factor, often due
to age, cataractous changes or poster-
ior segment changes.
Treatment for primary angle-closure
glaucoma typically begins with IOP-
lowering topical medications, including
aqueous suppressants and prostaglan-
dins. Procedural intervention begins
with peripheral iridotomy, which may
have a favourable impact upon disease
progression, particularly during early
stages, decreasing rates of progression
to 016% from the 1935% rate of
untreated eyes. LPI performed at later
stages of the disease tends to require
further medical or surgical interven-
tion, such as trabeculectomy or gonio-
synechialysis.
In recent years, lens extraction has
become a promising surgical interven-
tion for reducing IOP and decreasing
the degree of PAS in the eye, with 65%
of patients with PAC and cataracts
exhibiting normal IOP post-phaco-
emulsication without requiring medi-
cation. Lens extraction compares to
other interventions, including LPI, tra-
beculectomy and goniosynechialysis.
Goniosynechialysis with lens extraction
has been shown to have greater impact
on IOP than goniosynechialysis alone.
Trabeculectomy remains eective in
refractory cases.
The bulk of research into lens extrac-
tion has focused on eyes with existing
cataracts. The EAGLE study group is
currently investigating clear lens extrac-
tion as an intervention in earlier stages
of angle closure. If proven eective and
safe, this technique could dramatically
impact treatment and the course of
glaucoma progression.
Method of literature
search
Research team at Wills Eye searched
the PubMed database for 1980 through
2013, using the following terms: pri-
mary angle-closure, angle-closure glau-
coma, pupillary block, plateau iris,
peripheral iridotomy, argon laser iri-
doplasty, phacoemulsification, lensecto-
my, goniosynechialysis, trabeculectomy
224
and diode cyclophotocoagulation. We
included articles cited in the reference
lists in all languages. We excluded
articles focusing on acute angle closure
or other types of glaucoma.
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Received on October 8th, 2014.
Accepted on May 11th, 2015.
Correspondence:
L. Jay Katz, MD
Director
Glaucoma Service, Wills Eye Hospital
840 Walnut Street
Philadelphia, PA
USA
Tel: 215 285 8148
Fax: 215 928 3903
Email: ljkatz@willseye.org
L. Jay Katz MD has previously received grant/research
support from Allergan, Aerie Pharm., Merck, Bausch
& Research Support Lomb; consulting fee from Aller-
gan, Alcon, Glaukos, Aerie Pharm. Bausch & Lomb,
Sucampo, Inotek Sensimed AG; honoraria from Aller-
gan, Alcon, Merck and Lumenis; and stock from Glau-
kos, Mati Therapeutics, Aerie Pharm.
225
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