Glaucoma treatment trends: a review

Ronan Conlon, MD,* Hady Saheb, MD, MPH, FRCSC,† Iqbal Ike K. Ahmed, MD, FRCSC‡,§,¶
ABSTRACT ●
Glaucoma is one of the most common causes of blindness worldwide, and its prevalence is increasing. The aim of the present review
is to describe the current medical and surgical treatment trends in the management of open-angle glaucoma. There has been an
increase in the availability of glaucoma medications and the use of laser trabeculoplasty over the past decade, with a subsequent
decrease in invasive incisional surgery. In addition, a new class of glaucoma procedures, termed microinvasive glaucoma surgery,
has emerged, which aims to fill the gap between conservative medical management and more invasive surgery.

GLAUCOMA TREATMENT TRENDS: A REVIEW MEDICAL THERAPIES

Glaucoma is the number one cause of irreversible vision
loss and the second leading cause of blindness worldwide.1
Approximately 66.8 million people worldwide are afflicted
with glaucoma. This number is expected to increase to
80 million in 2020 because of both demographic expan-
sion and population aging.2 In Canada, it is estimated
that 2.7% of people over the age of 40 years have
glaucoma and 11% over the age of 80 years.3 Unfortu-
nately, because of the asymptomatic nature of chronic
glaucoma, up to 50% of people in the industrialized
world are unaware of their diagnosis and not receiving
treatment.4,5
Management of glaucoma focuses on lowering intra-
ocular pressure (IOP), which remains the principal proven
method of treatment.6 Target IOP for a particular eye is
established from a number of factors, including pretreat-
ment pressure, risk of progression, optic nerve damage,
and age. It is recommended by the American Academy of
Ophthalmology that initial treatments aim to reduce IOP
in primary open-angle glaucoma (OAG) by 25% from
baseline.7 The aim of the present review is to describe the
current medical and surgical treatment trends in the
management of OAG.
METHODOLOGY
A literature search was conducted with PubMed using
keywords such as OAG, glaucoma treatment trends, laser
trabeculoplasty, nonpenetrating glaucoma surgery, trabe-
culectomy, glaucoma drainage implants (GDIs), and
microinvasive glaucoma surgery. Articles dating back a
maximum of 50 years were included, with a focus on
studies that have influenced current management trends in
OAG. In addition, information from the Canadian
Ophthalmology Society Guidelines was used.
The first approach in the management of OAG is
usually through topical medications. An array of drops can
be used to lower IOP and can be divided into 5 major
classes: prostaglandin analogues, beta-blockers, diuretics,
cholinergic agonists, and alpha agonists.8 Monotherapy
with either prostaglandin analogues or beta-blockers is
most often the first line. Prostaglandin analogues decrease
IOP by reducing outflow resistance, which results in
increased aqueous humor flow through the uveoscleral
pathway.9 Beta-blockers, on the other hand, reduce IOP
by decreasing aqueous formation. The ocular tolerability
of beta-blockers is favourable; however, they may cause
cardiac or respiratory side effects.10
In the past, beta-blockers were the most common first-
line topical medication.11 Prostaglandin analogues have
been shown to reduce IOP more than beta-blockers in
several studies,12–14 with fewer systemic side effects.
During the 1990s, the use of prostaglandin analogues
increased, whereas that of beta-blockers decreased.15
A study conducted in Ontario, Canada, demonstrated
an increase in the usage of glaucoma medications between
1992 and 2004, particularly prostaglandin analogues, with
a subsequent decrease in the number of glaucoma sur-
geries.16 In Ontario, the number of glaucoma medications
dispensed almost doubled between 1992 and 2004. In
addition, the increase in dispensed prostaglandin ana-
logues was strongly correlated (p o 0.001) with a
decreasing number of performed trabeculectomies.16
If monotherapy alone is not effective in controlling
IOP, other drugs with different mechanisms of action can
replace or be added in conjunction with beta-blockers or
prostaglandin analogues. Commonly used second-line
agents include alpha-agonists and topical carbonic anhy-
drase inhibitors.17 A major challenge with adding multiple
drops is compliance. It has been demonstrated that

& 2016 Canadian Ophthalmological Society.

Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcjo.2016.07.013
ISSN 0008-4182/16

CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016 1

Glaucoma treatment trends: a review—Conlon et al.
increasing the number of drop bottles to a patient’s
treatment regimen negatively affects patient adherence.18
To improve patient adherence and reduce exposure to
preservatives, fixed combination therapies have been
developed. A number of fixed-combination glaucoma
drops are currently available. Some examples are Cosopt
(Merck & Co., Inc, Kenilworth, N.Y.), Combigan (Aller-
gan, Irvine, Calif.), Xalacom (Pfizer, New York City, N.
Y.), Azarga (Alcon, Fort Worth, Tex.), DuoTrav (Alcon),
and Simbrinza (Alcon).
Another strategy to increase patient compliance is via
injectable sustained release medications. These devices are
designed to release a drug over a prolonged time interval.
A sustained release implant of bimatoprost (Allergan) was
recently developed and is capable of delivering medication
for up to 6 months after a single intracameral injection. In
a phase 2 trial, in which patients received the implant in
1 eye and topical daily bimatoprost in the other, the
efficacy was comparable and the duration of effect was 4–6
months.19
Despite the existence of numerous glaucoma medica-
tions, there is currently no agent that targets the most
common pathogenic cause of increased IOP, impaired
trabecular outflow. Recently, a new class of glaucoma
medications, known as rho kinase inhibitors, has emerged.
They have been shown to increase trabecular outflow by
acting directly on the contractile tone of the trabecular
meshwork.20
AR-13324 (Rhopressa; Aerie Pharmaceuticals, Irvine,
Calif.) is a rho kinase and norepinephrine transporter
inhibitor that is believed to lower IOP by 3 main actions:
reducing aqueous production, increasing trabecular out-
flow, and decreasing episcleral venous pressure. In a recent
phase 2 trial, involving 213 subjects, the efficacy of AR-
13324 was compared to that of latanoprost (Pfizer).21
Mean unmedicated baseline diurnal IOP was 25.8, 25.6,
and 25.5 mm Hg in the AR-13324 0.01%, AR-13324
0.02%, and latanoprost groups, respectively. On day 28, a
total decrease from unmedicated baseline IOP of 5.5, 5.7,
and 6.8 mm Hg was observed. Although AR-13324
0.02% was less effective at lowering IOP by 1 mm Hg,
it had a similar efficacy to latanoprost in a prespecified
patient subgroup that excluded patients with baseline
IOPs of 426 mm Hg.21
Roclatan (Aerie Pharmaceuticals), which is a combina-
tion of Rhopressa and latanoprost, demonstrated superior
IOP-lowering effects compared with latanoprost. In a
phase 2b clinical trial, Roclatan lowered mean diurnal
IOP from 25.1 to 16.5 mm Hg on day 29, which was
about 2 mm Hg greater than that of latanoprost. The most
common complication with Roclatan was hyperemia,
which occurred in approximately 40% of patients and
was scored as mild in the majority.22 Early clinical trials
suggest that rho kinase inhibitors may soon be used more
frequently in the medical management of glaucoma,
although more data are needed.
2 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
There continues to be interest in drugs that may protect
the optic nerve from damage, known as neuroprotection.
Although in theory this would be extremely useful in the
management of OAG, human trials involving memantine
(Namenda; Forest Laboratories, New York, N.Y.) for optic
neuroprotection yielded nonsignificant findings.23 Further
research into the area of neuroprotection needs to be
explored to examine its role, if any, in the management of
glaucoma.
LASER THERAPIES
Medical management does not reduce IOP to target
levels in all patients, and some continue to experience
deterioration of the optic nerve despite maximum medical
therapy. Argon laser trabeculoplasty was introduced as a
treatment modality for OAG by Wise and Witter.24 The
mechanism is not well understood, although it is thought
to be caused by thermal energy directed toward the
trabecular meshwork, which causes focal scarring and
thereby opens space in adjacent structures, or attri-
butable to the inflammation of cytokines and phagocyto-
sis, which induces structural changes with improved
outflow.25
The overall number of laser trabeculoplasty procedures
and bilateral same-day laser treatments increased dramat-
ically in the first half of the 2000s, owing to the advent of
selective laser trabeculoplasty (SLT).26–30 In Ontario,
Canada, the volume of same-day bilateral laser trabeculo-
plasties increased from 15.3 per 1000 with OAG in 2000
to 74.7 in 2013.30 In addition, the number of laser
iridotomies showed a 1.7-fold increase from 2000 to 2012
in Ontario.29
SLT was introduced by Latina et al. in 1998 and is
currently the most widely used and accepted laser therapy
for the treatment of OAG.31–35 SLT is less traumatic than
ALT and uses a frequency-doubled Q-switched Nd:YAG
laser (Selecta 7000; Coherent Medical Group, Santa Clara,
Calif.) to achieve similar results without causing visible
damage to the trabecular meshwork structures. The exact
mechanism by which SLT lowers IOP is not well under-
stood. Minimal structural damage to the trabecular mesh-
work favours theories that SLT acts on a cellular level
without any thermal effects.35,36 This could be either
through phagocytosis of trabecular meshwork debris or by
stimulating growth of the trabecular meshwork to increase
outflow.37,38
In the SLT pilot study by Latina et al., 70% of eyes
achieved an IOP reduction of at least 3 mm Hg at 26
weeks.31 Numerous studies have since followed demon-
strating the effectiveness of SLT. SLT is effective in
reducing IOP Z20% below baseline in 58%–94% of
eyes at 12 months 32,39–41 and 40%–85% at 2 years.35,37,42
The IOP-lowering effect of SLT tends to decrease over
time and the mean survival time (time 50% of eyes fail) is
around 2 years.40,43

SLT is being used earlier in the glaucoma treatment
algorithm, without waiting for maximal medical manage-
ment. It has been compared to medication as a primary
treatment for OAG and has the advantage of not relying
on adherence with glaucoma medications. A meta-analysis
of randomized control studies comparing medication to
SLT showed that there was no statistically significant
difference in IOP reduction or treatment success.44 SLT’s
current role is either as primary treatment or as an adjunct
to medical therapy.
Economic modeling shows that SLT alone as a primary
treatment for OAG is cost effective, especially in an aging
population.45 A study conducted in Ontario, Canada,
demonstrated cost savings with SLT over medical therapy
as a primary treatment for OAG over a 6-year period. The
study assumed that SLT was repeated every 2–3 years.
Using the scenario in which SLT is repeated every 2 years,
it produced 6 year cost savings over mono-, bi-, and tri-
drug therapy of $206.45, $1668.64, and $2992.67 per
patient, respectively.46
Although SLT is regarded as less traumatic than ALT,
pressure spikes and transient inflammation may still occur.
Micropulse laser trabeculoplasty (MLT) is a new laser
therapy that uses an 810 nm diode laser Iridex 1Q810
(Iridex Corporation, Mountain View, CA). It delivers
energy in repetitive microsecond pulses followed by an
intermittent period of rest, which reduces the buildup of
thermal energy.47 It has the ability to control thermal
elevation and does not cause observable coagulative
damage to the trabecular meshwork on scanning electron
microscopy.48
Several studies have demonstrated the efficacy of
MLT.49,50 In a prospective interventional case series that
included a total of 20 patients, MLT was successful in 15
patients (75%) with a mean IOP reduction of around
20% at 12 months.49 The preliminary data of another
study comparing MLT with SLT demonstrated compara-
ble results. Twelve eyes underwent MLT and 14 had SLT.
MLT achieved a mean IOP reduction of 3.9 mm Hg,
whereas the reduction in SLT was 2.6 mm Hg. The mean
change in the number glaucoma medications was 0.6 in
the MLT group compared with 0.1 in the SLT group.50
MLT has shown promising results in these early clinical
studies. Larger multicentre studies are currently underway,
which will help define its exact role in the management
of OAG.
Other new laser modalities, including titanium-sapphire
laser trabeculoplasty (TSLT) and pattern scanning trabe-
culoplasty (PLT), are currently being studied. TSLT is a
subtype of laser trabeculoplasty, which uses a SOLX 790
laser (Occulogix, Ont.), emitting near-infrared energy in
pulses ranging from 5 to 10 mls. This laser modality is
thought to allow deeper penetration into the juxtacana-
licular network as well as the inner wall of Schlemm’s
canal.51 PLT uses a 577-nm laser with computer-guided
scanning technology (Topcon Medical Laser Systems,
Glaucoma treatment trends: a review—Conlon et al.
Santa Clara, Calif.) to apply a sequence of pattern laser
spots onto the trabecular meshwork. This laser modality is
thought to achieve a cellular response with less tissue
scarring.51 Initial pilot studies have been able to demon-
strate the IOP-lowering capabilities of both TSLT and
PLT, although larger-scale studies are warranted to deter-
mine their long-term safety and efficacy.52,53
Another laser therapy, known as cyclophotocoagulation,
has been increasingly used among glaucoma surgeons. In
1 study, which examined the glaucoma procedure rates in
the United States, cyclophotocoagulation procedures rose
248%, from 1995 to 2004.26 Cyclophotocoagulation was
first introduced in the early 1970s as a last-line surgery to
lower IOP. During cyclophotocoagulation, a semiconduc-
tor diode laser is used to ablate the ciliary processes. Two
techniques are currently used to perform cyclophotocoa-
gulation: transscleral diode cyclophotocoagulation (TCP)
and endoscopic diode cyclophotocoagulation (ECP). TCP
has traditionally been used as a last resort procedure for
cases of refractory glaucoma. ECP is commonly performed
in conjunction with cataract surgery.54
Previous studies have demonstrated a wide range of IOP
reduction, ranging from 12.3% to 66%, using TCP.55,56
The amount of energy used seems to directly correlate
with treatment success. A meta-analysis performed dem-
onstrated a direct linear correlation between the total
amount of energy applied to the ciliary body and success
rate.57 Although TCP is mainly used in cases of refractory
glaucoma, a growing number studies support the use of
TCP as a primary procedure.55,58–62
ECP is commonly performed in combination with
cataract surgery. Lindfield et al. conducted a retrospective
study in which 56 patients who underwent phacoemulsi-
fication and ECP were reviewed; mean IOP decreased
from 21.5 to 14.4 mm Hg at 24 months postopera-
tively.63 In another study, 626 phacoemulsification and
ECP eyes were compared with a cohort of 81 eyes that
underwent phacoemulsification alone. The combined
group had a mean reduction in IOP of 3.5 mm Hg,
whereas the control group had a mean reduction in IOP of
0.7 mm Hg.64,65
SURGICAL THERAPIES
Trabeculectomy
When medication and laser therapy alone is not
effective in controlling IOP, more invasive incisional
surgery, such as trabeculectomy or GDIs, is indicated.
Overall, there has been a reduction in the number of
glaucoma surgeries performed in Canada, United States,
the Netherlands, Australia, England, Scotland, and
Wales.16,26,27,66–71 This decrease can be attributed to the
introduction of improved glaucoma pharmacotherapy in
the 1990s. In 1 study, which examined the glaucoma
surgical procedure rates in Canada, a 29% decrease in the
number of trabeculectomies performed was observed
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016 3
Glaucoma treatment trends: a review—Conlon et al.
Table 1—Overview of 3 landmark tube studies: Tube versus Trabeculectomy (TVT), Ahmed Baerveldt comparison (ABC), Ahmed
versus Baerveldt (AVB)
TVT.85
Comparison Patients who had previous trabeculectomy and/ Patients with previous intraocular surgery or
groups or cataract extraction and uncontrolled
glaucoma (IOP Z18 on maximal medical
therapy) were randomized to either tube shunt surgery was planned were randomized to
surgery (350 mm2 Baerveld glaucoma implant) implantation of the Ahmed FP7 glaucoma valve
or trabeculectomy with mitomycin C
Criteria for Prospectively defined as IOP 421 mm Hg or
failure less than 20% reduction below baseline on
2 consecutive follow-up visits after 3 months,
IOP r5 mm Hg on 2 consecutive follow-up
visits after 3 months, reoperation for glaucoma, reoperation for glaucoma, loss of light
or loss of light perception
Proportion of The cumulative probability of failure was 29.8% The cumulative probability of failure during
success in the tube group and 46.9% in the
trabeculectomy group at 5 years
postoperatively
between 1995 and 2004.27 In another study, conducted in
the United States, a 53% decrease in trabeculectomies was
observed between 1995 and 2004.26
Not only has there been a reduction in the number of
glaucoma surgeries performed, there has also been a
decrease in the number of surgeons performing incisional
glaucoma surgery.72 In a study conducted in Ontario,
Canada, a 47% decline in the percentage of ophthalmol-
ogists performing incisional glaucoma surgery between
1995 and 2010 was observed (from 35% in 1995 to 19%
in 2010). At the same time, the proportion of incisional
glaucoma surgery provided by glaucoma surgeons has
more than doubled. A likely explanation for this trend is
the expansion in glaucoma fellowship training opportuni-
ties, providing general ophthalmologists with easier access
to a subspecialist.72
Although trabeculectomy remains the “gold standard”
for glaucoma surgery,73–75 it is accompanied by high rates
of both short- and long-term complications. In the early
postoperative period these complications include choroidal
effusions, hypotony, shallow anterior chambers, and
hyphema.76–81 Long-term complications are often bleb
related and include leakage, blebitis, and endophthalmitis.
Glaucoma Drainage Implants
In recent years, there has been an increased interest in
GDIs.26,29,72 Traditionally, GDIs were used in more
refractory glaucoma, although they have been gaining
favour, even in cases of nonrefractory glaucoma. In 1 study,
which examined the glaucoma surgical procedure rates in
the United States, a 184% increase in the use of GDIs,
from 2728 in 1995 to 7744 in 2004, was observed.
Surveys of the membership of the American Glaucoma
Society performed in 1996, 2002, and 2008 have also
shown a significant increase in the use of GDIs compared
with trabeculectomy.82–84
The shift in practice pattern toward increased use of
GDIs even in cases of nonrefractory glaucoma was
4 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
ABC.116 AVB.117
Patients with uncontrolled or high-risk
refractory glaucoma and IOP Z18 mm Hg in glaucoma refractory to maximal medical
whom glaucoma drainage implant (GDI) therapy were randomized to an Ahmed FP7
glaucoma valve or an Baerveldt-350 implant.
(AGV) or the Baerveldt 101–350 glaucoma
implant (BGI)
Defined as IOP Z21 mm Hg or less than a 20% Defined as any of the following: IOP outside
reduction below baseline on 2 consecutive target range (5–18 mm Hg, with Z20%
study visits after 3 months, IOP r5 mm Hg on reduction from baseline) for 2 consecutive
2 consecutive study visits after 3 months, visits after 3 months, vision-threatening
complications, de novo glaucoma
perception, or removal of the implant for any procedures, or loss of light perception
reason
The cumulative probability of failure at 3 years
5 years of follow-up was 44.7% in the AGV was 51% in the AGV group and 34% in the
group and 39.4% in the BGI group BGI group
validated by the results of the Tube versus Trabeculectomy
(TVT) Study (Table 1).85 In this study, patients who had
previous trabeculectomy and/or cataract extraction and
uncontrolled glaucoma (with IOP Z18) were randomized
to either tube shunt surgery (350 mm2 Baerveld glaucoma
implant) or trabeculectomy with mitomycin C (Mutamy-
cin; Bristol-Myers Squibb, New York City, N.Y.). It was
found that patients who underwent tube shunt surgery
had a higher success rate compared with trabeculectomy
during 5 years of follow-up. The cumulative probability of
failure was 29.8% in the tube group and 46.9% in the
trabeculectomy group at 5 years postoperatively.85 Pre-
viously reported data also demonstrated a higher failure
rate with trabeculectomy with mitomycin C at both 1 and
3 years.86,87
The trabeculectomy failure rate in the TVT study was
similar to other studies88–99; however, the failure rate of
tube shunts was lower than previously reported.100–109 A
probable explanation for this difference is that the TVT
study enrolled eyes at lower risk of failure than eyes that
have traditionally underwent tube shunt surgery. It is
important to note that the TVT study included only
patients who had a previous failed trabeculectomy or
cataract extraction. The goal of the study was not to
compare 2 surgical techniques on previously unoperated
eyes. Currently, there is a primary TVT study underway
that will address this question.
All GDIs share a similar design and consist of a tube
that is used to divert aqueous humor from the anterior
chamber of the eye to an external reservoir. The devices
differ with respect to the presence or absence of valves,
size, and composition of the end plate. Two of the most
commonly used GDIs are the Ahmed valve (New World
Medical, Inc, Rancho Cucamonga, Calif.) and Baerveldt
implant (Abbott Medical Optics, Inc, Santa Ana, Calif.).
The Ahmed implant has a venturi-based flow restrictor,
designed to reduce postoperative hypotony, although it
has been associated with high rates of encapsulation and
inadequate IOP reduction.107,110–113 The Baerveldt

implant is nonvalved and requires intraoperative mechan-
ical flow restriction to allow adequate time for a capsule to
form. Aqueous drainage begins only after the flow
restriction reverses, usually 4–6 weeks postoperatively.
This delay in aqueous drainage has been reported to cause
early postoperative IOP volatility.114,115
The Ahmed Baerveldt Comparison (ABC) was a pro-
spective, randomized study initiated to compare the safety
and efficacy of the Ahmed FP7 glaucoma valve (AGV) and
the Baerveldt 101–350 glaucoma implant (BGI)
(Table 1).116 Patients with refractory glaucoma and an
IOP Z18 in whom GDI surgery was planned were
enrolled in the study and randomly assigned to implanta-
tion of an AGV or BGI. The primary outcome in the ABC
study was cumulative failure rate. The probability of
failure at 5 years was 44.7% in the AGV group compared
with 39.4% in the BGI group (p ¼ 0.65), although the
reasons for failure were different. Failure with the AGV
was mainly attributable to high IOP end points, whereas
failure with the BGI was most often related to safety end
points (hypotony, loss of light perception, and implant
explantation).116
At 5 years, mean IOP decreased from baseline averages
of 31 to 32 mm Hg to 14.7 mm Hg in the AGV group
and 12.7 mm Hg in the BGI group (p ¼ 0.015).
Although the BGI decreased IOP to a greater extent in
the long-term, AGV decreased IOP more in the early
postoperative period compared with the BGI. In addition,
the BGI group required fewer adjunctive medications at
5 years (2.2 in the AGV group vs 1.8 in the BGI
group).116
The results of the ABC study were supported by a
similar study, the Ahmed versus Baerveldt Study (AVB),
which also compared the AGV to BGI (Table 1).117
Again, lower failure rates and a reduction in the need for
glaucoma medications were observed with the BGI,
although there were more vision-threatening complica-
tions and hypotony in the BGI group.117
The ABC and AVB studies do not demonstrate
superiority of 1 GDI. Other important considerations,
such as individual patient characteristics and surgeon
experience, are critical in selecting an implant. For
example, if the surgeon’s goal is to lower pressure as much
as possible to prevent progression, it may be more
advantageous to use a BGI. On the other hand, if the
target pressure is higher and the goal is to obtain an IOP
within normal limits, the AGV may be more suitable given
its superior safety profile. After 5 years of follow-up more
reoperations for implant-related complications occurred in
the BGI group in the ABC study.118
Nonpenetrating Glaucoma Surgery
Nonpenetrating glaucoma surgery (NPGS), such as
deep sclerectomy (DS) and viscocanalostomy (VC),
were popularized in the 1990s as an alternative to
Glaucoma treatment trends: a review—Conlon et al.
trabeculectomy, with fewer complications.119 The main
difference between NPGS and trabeculectomy is that the
procedures involve the creation of a filtration membrane
(the Trabeculo-Descemet’s membrane) rather than a
sclerostomy.
Most studies agree that NPGS has a lower complication
rate than trabeculectomy,120–125 although their efficacy in
terms of lowering IOP remains a subject of debate. Some
studies suggest that NPGS techniques have comparable
IOP-lowering capabilities as the standard trabeculec-
tomy,124,126 whereas others suggest that NPGS is inferior
at lowering IOP.122–132 Randomized prospective studies
have found success rates of DS and trabeculectomy to be
similar.133–136 Cillino et al. found no significant difference
in outcomes between the 2 techniques, but concluded that
trabeculectomy was more suitable with patients with
higher IOPs.136 A meta-analysis of 10 randomized control
trials comparing trabeculectomy and VC concluded that
trabeculectomy had a greater pressure-lowering effect than
VC, but a higher risk profile.137 In 1 prospective random-
ized study of 50 eyes, 42% of patients in the trabeculec-
tomy group had a successful outcome compared with 21%
in the VC group.125
The main benefit of using NPGS is its increased safety
profile. The avoidance of full-thickness penetration and its
potential for sudden hypotony is an enticing option for
patients at high risk for complications with trabeculec-
tomy. One of the main limitations to their widespread use
is their surgical difficulty.
Microinvasive Glaucoma Surgery
Recently, a new class of glaucoma procedures, termed
“microinvasive glaucoma surgery” (MIGS), has emerged.
MIGS procedures are used earlier in the glaucoma treat-
ment algorithm and aim to fill the gap between medi-
cation and more invasive surgeries such as trabeculectomy
or GDIs. Many MIGS procedures are performed in
conjunction with cataract surgery, where the patient has
already accepted the risks of intraocular surgery. In
contrast with more invasive glaucoma surgeries, MIGS
procedures use an ab interno approach and are relatively
low risk.
MIGS procedures target 3 main outflow channels:
Schlemm’s canal through trabecular outflow; the supra-
choroidal space via the uveoscleral pathway; and the
subconjunctival space, by creating an alternative outflow
pathway for aqueous humor (Table 2). In general, MIGS
procedures share 5 important features: ab interno
approach, minimal trauma, ability to lower IOP,
extremely high safety profile, and rapid recovery.138 The
definition of MIGS is subject to debate, and was initially
termed minimally invasive glaucoma surgery (Ahmed I.K.,
personal communication, 2016). It is the opinion of the
authors that the term micro is more representative of
MIGS, as it truly differentiates MIGS from other
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016 5
Glaucoma treatment trends: a review—Conlon et al.
Table 2—Classification of microinvasive glaucoma surgery
(MIGS) devices by outflow channel
Outflow channel MIGS device
Schlemm’s canal iStent (Glaukos Corporation, Laguna Hills, Calif.)
iStent inject (Glaukos Corporation)
Hydrus (Ivantis, Irvine, Calif.)
Trabectome (Neomedix, Inc, Tustin, Calif.)
Suprachoroidal space iStent supra (Glaukos Corporation)
CyPass (Transcend Medical, Menlo Park, Calif.)
Subconjunctival space Xen Gel Stent (Allergan, Irvine, Calif.)
minimally invasive procedures in nonophthalmic special-
ties.139 Either way, MIGS is understood as per the above
definition.
The iStent (Glaukos Corporation, Laguna Hills, Calif.)
is one of the most widely used and studied MIGS devices.
The microstent is manufactured from heparin-coated
titanium and can be implanted into Schlemm’s canal
using a preloaded inserter.140 A randomized clinical trial of
240 OAG eyes compared cataract surgery alone to iStent
implantation and cataract surgery combined. The primary
outcome measure was the percent of patients who
achieved an IOP r21 mm Hg without the use of ocular
hypotensive medications. Seventy-two percent of partic-
ipants achieved an unmedicated IOP of r21 in the
combined surgery group versus 50% in the cataract
surgery group at 1 year, with no substantial differences
in adverse events.140 After 2 years, a 61% success rate was
observed in the combined surgery group versus 50% in the
cataract surgery group.141
Preliminary evidence suggests that the implantation of
multiple iStents may be advantageous. Belovay et al.142
demonstrated a significant reduction in IOP and glaucoma
medications with the use of 2–3 iStents. Mean preoper-
ative IOP decreased from 18 mm Hg to 14.4 mm Hg at
1 year postoperatively (p o 0.001). In addition, mean
topical hypotensive medications decreased from 2.7 to
0.7 at 1 year (p o 0.001).142
A second-generation iStent, known as iStent inject
(Glaukos Corporation), was recently developed. The
device is smaller and designed for more direct implanta-
tion in Schlemm’s canal. In addition, the device is a 2-
stent system.143 Voskanyan et al. evaluated the safety and
efficacy of the device on 99 patients with OAG. Partic-
ipants enrolled in the study were on at least 2 topical
ocular hypotensive medications and required additional
IOP lowering. Mean preoperative IOP decreased from
26.3 mm Hg (after medication washout) to 15.7 mm Hg
at 1 year postoperatively. In addition, 65% of participants
were medication-free at 1 year.144 Fea et al. conducted a
randomized study comparing the iStent inject to ocular
hypotensive agents and found the device to be at least as
effective as medications in controlling IOP in patients
with OAG, with an excellent safety profile.145
A third-generation iStent (iStent supra), made of
heparin-coated polyethersulfone and a titanium sleeve,
was recently developed. The device is designed for
6 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
implantation in the suprachoroidal space. Clinical trials
are currently underway. Auffarth and Kretz implanted the
device in 80 eyes with mild to moderate OAG uncon-
trolled on 2 topical medications and demonstrated a
significant reduction in IOP and medication burden at
18 postoperatively as well as a favourable safety profile.146
The Hydrus (Ivantis, Irvine, Calif.) is another MIGS
device that targets Schlemm’s canal to increase aqueous
outflow. The device is an 8-mm-long nitinol (nickel–
titanium alloy) Schlemm’s canal scaffold with 3 open-
ings.147 It is implanted through the trabecular meshwork
using a manual inserter. A preclinical study was able to
demonstrate the long-term biocompatibility of the device
in animal models.148 Randomized controlled trials are
underway, and the results have been promising. Pfeiffer
et al. compared the efficacy of the microstent in con-
junction with cataract surgery to cataract surgery alone in
patients with OAG. The proportion of patients achieving
a 20% reduction in IOP was significantly higher in the
Hydrus plus cataract surgery group at 24 months post-
operatively (80% vs 46%; p ¼ 0.008). In addition, the
proportion of patients using no hypotensive medication at
24 months was significantly higher in the Hydrus plus
cataract surgery group (73% vs 38%; p ¼ 0.008), and
adverse event frequency was similar in the 2 groups.149
The Trabectome (Neomedix, Inc, Tustin, Calif.) is an
instrument that uses microelectrocautery to ablate a strip
of tissue from the trabecular meshwork, leaving the inner
wall of Schlemm’s canal intact to preserve collector
channel drainage. Studies have demonstrated an acceptable
safety profile.150,151 In 2010, a study that compared 539
Trabectome and 290 combined cataract surgery and
Trabectome procedures revealed a 1-year success rate
(IOP r21) of 64.9% in the Trabectome group and
86.9% in the combined procedure group.150 Francis and
Winarko prospectively compared eyes undergoing cataract
and Trabectome surgery to eyes undergoing cataract and
trabeculectomy surgery. A decrease in IOP from 22.1 to
15.4 mm Hg was observed in the cataract and Trabectome
surgery group, and a reduction in IOP from 23.0 to 11.0
mm Hg was seen in the cataract and trabeculectomy
surgery group. Although the IOP-lowering effect was
greater in the cataract and trabeculectomy surgery group,
a higher rate of postoperative complications was
observed.151 Another study demonstrated that a previously
failed Trabectome procedure does not negatively impact
the outcomes of a subsequent trabeculectomy.152 This
study highlights an important feature of the majority of
MIGS devices; conventional glaucoma surgery can be
performed if necessary.
Another MIGS pathway to decrease IOP is via the
suprachoroidal space. The CyPass implant (Transcend
Medical, Menlo Park, Calif.) is a suprachoroidal shunt
made of a polyamide material. The device can be inserted
ab interno into the suprachoroidal space using a manual
inserter.138 Early clinical studies have shown that

implantation of the device at the time of cataract surgery
or as a standalone procedure leads to significant reduction
in IOP and glaucoma medications.153,154 Hoeh et al.
reported their initial surgical experience with the micro-
stent when combined with cataract surgery. Two analysis
cohorts were prespecified based on medicated IOP: Z21
mm Hg (cohort 1, n ¼ 65) or o21 mm Hg (cohort 2,
n ¼ 102). At 1 year, cohort 1 showed a 35% decrease in
mean IOP and a 49% reduction in glaucoma medication
usage. Cohort 2 had a 75% reduction in mean medication
use, while maintaining an IOP o21 mm Hg.153 Garcia-
Feijoo et al. evaluated the efficacy of the device in patients
refractory to topical medications. Patients with OAG and
uncontrolled medicated IOPs of 421 were enrolled.
Baseline IOP was reduced from 24.5 to 16.4 mm Hg
(p o 0.0001) at 12 months. In addition, the mean
number of medications was reduced from 2.2 to 1.4
(p ¼ 0.002). No secondary surgery was performed in 83%
(53/64) of patients, precluding them for more invasive
glaucoma surgery.154
The XEN Gel Stent (Allergan) targets the subconjunc-
tival space for aqueous drainage via an ab interno
approach. The device is 6 mm in length and is composed
of cross-linked gelatin. It is designed to swell at the time of
implantation to secure the device in place. Initial results
suggest that, when combined with antimetabolites, IOP-
lowering effects are similar to that of trabeculectomy,
although the risks may be slightly higher than typical
MIGS procedures.155,156 In a recent prospective, non-
randomized study, mean IOP decreased from 20.8 mm
Hg preoperatively to 14.4 mm Hg at 6 months and 13.1
mm Hg at 12 months. In addition, glaucoma medications
decreased from 2.7 to 0.9 at 12 months.155 Another study
demonstrated similar results, with a mean preoperative
IOP decreasing from 22.7 to 13.4 mm Hg at 12 months
and glaucoma medication usage decreasing by 64%.156
Long-term data are still needed to assess the devices
sustained IOP-lowering effect.
RELATIONSHIP WITH OPTOMETRISTS
Not only has the medical and surgical management of
glaucoma evolved, but also so has the role of optometrists,
as the scope of their practice expands. In 2008, the
membership of the Canadian Glaucoma Society (CGS)
created a committee to develop a model of interprofes-
sional collaboration between optometrists and ophthal-
mologists in the care of glaucoma patients and glaucoma
suspects. A general principle of this model is that
ophthalmologists should evaluate patients early in the
course of their disease.157
According to the model set forth by the CGS, glaucoma
suspects with low/moderate risk can initially be assessed by
optometrists and do not require referral to an ophthalmol-
ogist. High-risk glaucoma suspects can also be monitored
by optometrists, with periodic consultation to an
Glaucoma treatment trends: a review—Conlon et al.
ophthalmologist (every 3–4 years). Stable early glaucoma
patients should be referred to an ophthalmologist in a
timely fashion. Once stable, these patients can be returned
to the optometrist for monitoring, although they should
be reassessed by an ophthalmologist at least every 2–3
years. Patients with moderate and advanced disease should
primarily be managed by an ophthalmologist.157
CONCLUSIONS
Glaucoma remains one of the most common causes of
blindness worldwide and with the aging population there
is an increasing prevalence.158 The present review outlines
the treatment trends in the early management of glaucoma
(which involves topical medications or laser therapy),
NPGS, invasive glaucoma surgeries, and the newer MIGS
procedures. Overall, there has been an increase in the use
of topical medications and laser trabeculoplasty, and a
decrease in invasive incisional glaucoma surgery. Fewer
ophthalmologists are performing incisional glaucoma sur-
gery (more restricted to fellowship-trained glaucoma sub-
specialists), while general ophthalmologists have increased
responsibility for clinical care and laser therapy.159 In
addition, there has been increased use of and reliance on
optic nerve imaging and reduction in visual field testing.
Previously, there was a gap between conservative medical
management and more invasive glaucoma surgery. The
newer MIGS procedures aim to fill this gap and early
studies have demonstrated their ability to lower IOP with
minimal risk in patients with mild to moderate glaucoma.
More data and longer follow-up are still needed to
determine their exact role in the glaucoma treatment
algorithm.
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Footnotes and Disclosure:
The authors have no proprietary or commercial interest in any
materials discussed in this article.
From the *University of Ottawa, Ottawa, Ont; †McGill Uni-
versity, Montreal, Que.; ‡University of Toronto, Toronto, Ont.;
§Trillium Health Partners, Mississauga, Ont.; ¶Prism Eye
Institute, Mississauga, Ont.
Originally received Feb. 8, 2016. Final revision May. 19, 2016.
Accepted Jul. 28, 2016.
Correspondence to Hady Saheb, MD, MPH, FRCSC, McGill
University Health Center Research Institute, 5252 de Maison-
neuve, Montreal, Que. H4A 3S5; hady.saheb@mcgill.ca
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016 11