Review Article

Minimally Invasive Surgery, Implantable Sensors, and
Personalized Therapies

Kevin Gillmann, MD, MBBS, FEBOphth, MArch1; Kaweh Mansouri, MD, MPH1,2

1Glaucoma Research Center, Montchoisi Clinic, Swiss Visio, Lausanne, Switzerland
2Department of Ophthalmology, University of Colorado School of Medicine, Denver, CO, USA

ORCID:
Kevin Gillmann: https://orcid.org/0000-0002-7856-6253

Abstract

Glaucoma management has changed dramatically over the last decades, through clinical
advances and technological revolutions. This review discusses the latest innovations
and challenges faced in the field around three major axes: minimally-invasive glaucoma
surgery (MIGS), implantable sensors and injectable therapeutics.
Indeed, the vast number of recently developed MIGS techniques has not only provided
clinicians with a wide range of therapeutic options, but they have also enabled them to
adjust their therapies more finely which may have contributed a more patient-centric
decision-making process. Yet, despite considerable advances in the field, the wide
heterogeneity in clinical trial designs blurs the surgical outcomes, specificities and
indications. Thus, more high-quality data are required to make the choice of a specific
MIGS procedure more than an educated guess. Beyond the scope of MIGS, the potential
of IOP telemetry for self-assessment of IOP-control through implantable sensors is
developing into a real option for clinicians and an empowering opportunity for patients.
Indeed, providing patients with direct feedback enables them to take control and have a
clearer representation of their care, in turn leading to a better control of the disease.
However, there are potential issues with self-monitoring of IOP, such as increased
anxiety levels induced by measured IOP fluctuations and peaks, leading to patients
self-treating during IOP spikes and additional office visits. Furthermore, the advent
of implantable therapeutics may soon provide yet another step towards personalized
glaucoma treatment, by offering not only an efficient alternative to current treatments,
but also a therapeutic option that may better adapt to patients’ lifestyle.
After several decades of relative stagnation through the last century, glaucoma has now
entered what many view as a golden age for the specialty. Like every revolution, this one
brings its fair share of uncertainty, clinical questioning and uneasy periods of adaptation
to ever-changing expectations. Yet, while it is impossible to guess what the landscape of
glaucoma surgery will be like in ten or fifteen years, data suggest a bright outlook both
for patients and clinicians.

Keywords: Glaucoma; MIGS; Quality of Life; Telemetry; Eyemate; Bimatoprost SR

J Ophthalmic Vis Res 2020; 15 (4): 531–546

© 2020 JOURNAL OF OPHTHALMIC AND VISION RESEARCH | PUBLISHED BY KNOWLEDGE E 531

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Innovations in Glaucoma Surgery; Gillmann et al

INTRODUCTION

Glaucoma is a leading cause of irreversible
blindness, and it is estimated that by 2040,
over 110 million people will suffer from
glaucoma globally.[1] To face the increasing
burden of glaucoma, its management has
changed dramatically over the last decades,
through clinical advances and technological
revolutions. Indeed, while the 1990s were the
decade of glaucoma drainage devices (GDD)
and novel topical therapeutic agents, the new
millennium has witnessed an unprecedented
growth in treatment options through the
introduction and integration of minimally
invasive glaucoma surgeries (MIGS), and the
surgical applications of cross-disciplinary
innovations. This review discusses the most
remarkable innovations of the last decade and
explores how they may affect the future of
glaucoma surgery.

METHODS

Multiple literature searches were conducted
in preparation of this review. Searches were
conducted on PubMed and Google Scholar,
using the following keywords. For section A on
MIGS technologies: glaucoma surgery, MIGS,
trabecular bypass, suprachoroidal drainage,
subconjunctival filtration, Trabectome,
Kahook Dual Blade, Trabeculotomy,
Canaloplasty, Hydrus Microstent, iStent,
CyPass, Cyclophotocoagulation, Preserflo,

Correspondence to:

Kaweh Mansouri, MD, MPH. Glaucoma Research Center,
Montchoisi Clinic, Swiss Visio, Lausanne, Switzerland.
E-mail: kwmansouri@gmail.com
Received: 01-05-2020 Accepted: 08-07-2020

Access this article online

Website: https://knepublishing.com/index.php/JOVR

DOI: 10.18502/jovr.v15i4.7792

XEN Gel Stent, glaucoma physiology,
aqueous outflow. For section B on intraocular
sensors: IOP variations, 24-hour IOP, dynamic
tonometry, telemetry, intraocular sensor,
Eyemate. For section C on implantable
and injectable therapeutics: glaucoma
pharmacology, prostaglandin, glaucoma
treatment compliance, glaucoma drug
delivery, intracameral implant, bimatoprost
SR, Durysta. Furthermore, references from
the reviewed articles and textbooks were
considered for inclusion within this review,
regardless of their publication date or
language.

RESULTS

a. Minimally Invasive Glaucoma Surgery

The first-line treatment for open-
angle glaucoma has long been topical
pharmaceutical therapies or laser treatments.
Yet, until relatively recently, the only alternative
when these failed was filtering surgery.
With popularization of anti-metabolites
in glaucoma surgery, from the start of
the 1990s, filtering surgery evolved into
highly effective procedures, with a reported
intraocular pressure (IOP) reduction as
high as 50%.[2] However, this evolution
was associated with an increase in severe
adverse events such as chronic hypotony,
bleb leak, or endophthalmitis, with a rate of
late complications in excess of 30% in some
reports.[3] MIGS were designed to bridge
the gap between medical or laser therapies

This is an open access journal, and articles are distributed under the terms of
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How to cite this article: Gillmann K, Mansouri K. Minimally Invasive Surgery,
Implantable Sensors, and Personalized Therapies. J Ophthalmic Vis Res
2020;15:531–546.

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Innovations in Glaucoma Surgery; Gillmann et al

and more invasive filtering surgeries in mild
to moderate glaucoma. By essence, MIGS
are meant to have an extremely favorable
safety profile ensuring prompt postoperative
recovery; however, the amount of IOP
reduction is not as high as traditional filtering
surgery.[4] Through the array of available
techniques, MIGS have not only provided
clinicians with a wider range of therapeutic
options, but they have also enabled them to
adjust their therapies more finely which may
have contributed to a more patient-centric
decision-making process. However, it can be a
bit overwhelming to choose from such a large
armamentarium, especially in the absence of
evidence-based criteria.

Approaches

MIGS are generally classified based on their
anatomical sites of action. Their mechanisms
can focus on: (1) Schlemm’s canal, (2)
Suprachoroidal space, (3) Subconjunctival
space, and (4) Ciliary body. Each class of
MIGS has its own advantages and limitations,
and several different devices or techniques
coexist within most categories. Most of these
options differ in their dimensions, but in
some instances, there may be some more
fundamental technical variations. The main
classes of MIGS are summarized in Figure
1.

Schlemm’s canal: Trabecular meshwork
bypass and Schlemm’s canal dilatation

The trabecular or conventional pathway
is the principal route for aqueous humor
outflow in a physiological condition. Aqueous
percolates through the trabecular meshwork
into Schlemm’s canal, before entering a wide
network of vessels through the collector

channels. In primary open-angle glaucoma,
however, trabecular meshwork outflow
resistance increases, possibly in response
to extracellular matrix changes, the etiology of
which is still mostly unknown.[5, 6] Furthermore,
in the early 1960s, Grant showed how ab
interno 360° removal of the trabecular
meshwork resulted in a 75% reduction of
the total resistance in enucleated eyes at
an IOP of 25 mmHg.[7, 8] Bypassing a site of
increased outflow resistance (often considered
the primary site of resistance) and enhancing
the main physiological outflow pathway are
two of the principles underlying the rationale
of trabecular meshwork bypass or ablation.
This class of MIGS aims to reduce outflow
resistance and IOP by facilitating aqueous
drainage into Schlemm’s canal either by
bypassing the trabecular meshwork via some
stent devices or by merely removing all
or a portion of the trabecular meshwork.
Several variations of stent devices and
trabecular meshwork ablation techniques
exist.

However, recent studies have suggested
that contrary to the common belief that the
main site of glaucoma resistance lies within the
juxtacanalicular trabeculum, the IOP elevation
observed in primary open-angle glaucoma is
more accurately caused by a combination
of three equally determinant factors: (1)
loss of permeability of the entire thickness
of the trabecular meshwork, (2) collapse
of Schlemm’s canal, and (3) downstream
resistance, notably with the closing of collector
channel entrances.[11–13] This was further
supported by the finding that Schlemm’s canal
dilatation was positively correlated with the
magnitude of IOP reduction.[9] It was, therefore,
hypothesized that Schlemm’s canal increased
volume is associated with the stretching of
its walls, which in turn causes the opening

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Figure 1. Illustration of the different classes of minimally invasive glaucoma surgery, their anatomical relationship with the ocular
structures (top), and examples of implants and techniques available in each category.

of pressure-dependent collector channels,
leading to aqueous outflow.[10] Based on these
observations, another subcategory of MIGS
specifically targets Schlemm’s canal, with
the aim of restoring a healthy Schlemm’s
canal function and opening closed collecting
channels. Two approaches were used to dilate

Schlemm’s canal: the mechanical dilatation
using a temporary or resorbable medium
and the use of a permanent implantable
scaffold.
Despite theoretically different approaches,

these two subcategories of MIGS are,
in effect, physiologically related. Indeed,

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Innovations in Glaucoma Surgery; Gillmann et al

Figure 2. Eyemate intraocular sensor (top) and a size comparison with a eurocent coin.

while the latter group directly targets
Schlemm’s canal to cause its dilatation
with aqueous humor and restore distal
outflow capacity, studies have shown that
the former group, while merely bypassing
the trabecular meshwork, produces a similar
effect. Indeed, it has been reported that
the magnitude of IOP reduction following
trabecular meshwork bypass implantation
was directly correlated to the dilatation of
Schlemm’s canal.[11] Furthermore, aqueous
angiography techniques have shown
that, beyond their effects on Schlemm’s
canal, trabecular bypass devices could
increase collector channel outflow.[12] The
limitation of both approaches is that they
do not address any resistance that may be

distal to the collector channels’ openings.
Therefore, there is a floor effect to IOP
reduction depending on distal outflow
resistance.

Aqueous angiography: The road to
personalized surgery

The role of distal outflow resistance in IOP
reduction indicates the importance of targeting
collector channels with MIGS. It was reported
that trabeculotomies performed in the nasal
hemisphere, where the concentration of
collector channels is denser, increases
the outflow more than trabeculotomies
performed in the temporal hemisphere,[13]

but more recent research suggests a more

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Figure 3. Intraoperative aqueous angiography showing the collector channels (arrows). S, Superior; N, Nasal

nuanced reality. Huang et al have designed
a new imaging technique allowing collector
channel visualization using intraoperative
aqueous angiography. Their first report
suggested that targeting an area deprived
of collector channel outflow could recruit
new, previously closed, channels.[14] Figure
2 shows collector channels identified with
aqueous angiography. It could therefore be
speculated that locating collector channels
prior to MIGS or filtering surgery may
result in a more targeted treatment. In
the absence of dedicated comparative
studies, however, the question remains
controversial and most MIGS procedure
continue to be performed supero-nasally,
both for practical reasons and to target more
collector channels.

Suprachoroidal space: Suprachoroidal shunts

The physiological proportion of aqueous
humor draining through the suprachoroidal
space is subject to debate due to the lack of
techniques available to measure uveoscleral
flow, but estimates range between 4% and
60%.[15, 16] It is, however, accepted that aging
is responsible for a marked reduction in
uveoscleral outflow.[17] This outflow pathway
is created by a combination of relative ciliary
body permeability, which is believed to be
the site of main resistance in the uveoscleral
pathway,[18] and the existence of a hydrostatic
pressure gradient through the anterior
chamber, the supraciliary space, and the
suprachoroidal space.[19] Such a negative
gradient is believed to be produced by

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Figure 4. Bimatoprost SR injector (A) and the bimatoprost implant, compared with the size of a dime and a eurocent coin (B).

the rapid absorption of aqueous from the
suprachoroidal space into the large and
dense choroidal vasculature.[20, 21] Another
characteristic of the uveoscleral pathway is
that it is relatively pressure-independent and
was shown to have a constant effect between
4 and 35 mmHg.[22]

These last two characteristics suggest
that exploiting uveoscleral pathway may
theoretically make up for some of the
conventional pathway limitations: the risk
of distal resistance and the floor effect.
However, devices targeting this pathway
can be expected to have a whole different
risk profile to trabecular bypass devices.
Indeed, the potentially greater outflow
capacity of this approach could, in theory,
be associated with higher risks of hypotony
and choroidal detachment, especially in
patients with a long history of prostaglandin
therapy. While the cases are too rare to
warrant for a prospective study, there have
been anecdotal cases suggesting that
patients who were chronically treated with
prostaglandins may be at a higher risk of
developing choroidal pathologies.[28–31] This
may be related to the effect of prostaglandins,

reducing collagens within the uveoscleral
pathway.[23] Furthermore, from a practical point
of view, the suprachoroidal space may be
less readily accessible and visualizable by a
surgeon than the trabeculum.
While there is no commercially available

MIGS relying on suprachoroidal drainage,
some new devices are under development
and sound clinical data is available on a
previously commercialized device. Therefore,
we will discuss the case of this device, some
characteristics of which may be comparable to
future devices of the same category.

Subconjunctival space: Subconjunctival
filtration

Contrary to the trabecular and the uveoscleral
approaches, subconjunctival filtration does not
seek to enhance or increase a physiological
pathway. Instead, it relies on the creation
of an artificial canal between the anterior
chamber and the subconjunctival space,
typically through a stent. This process
results in an iatrogenic filtration bleb from
which aqueous humor diffuses into the
surrounding subconjunctival tissue and is

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Innovations in Glaucoma Surgery; Gillmann et al

eventually reabsorbed into subconjunctival
capillaries.[24]

The idea of subconjunctival filtration
is not new and stems from the anterior
sclerectomy technique designed by De
Wecker in 1858.[25] While modern-day
trabeculectomies and deep sclerectomies
have considerably refined the technique,
the use of the subconjunctival pathway has
survived. Like trabeculectomy, the success
of subconjunctival MIGS procedure depends
on the persistence of a healthy filtering
bleb. Therefore, these MIGS share many
similarities with filtering surgeries, in terms
of risks and advantages. One of the main
advantages of subconjunctival filtration is
precisely that it does not impact any of
the physiological outflow pathways, and as
such, preserves any remaining physiological
filtration. Another significant advantage of
these techniques is that they do not rely on
episcleral venous pressure or suprachoroidal
pressure gradients to achieve filtration.
Instead, their filtration capacity is only
dependent on the outflow resistances of
the stent and the subconjunctival space.
Therefore, they can potentially achieve lower
IOPs than physiological approaches.
The outflow resistance of the

subconjunctival space, however, is very
much patient dependent and can be difficult
to predict. A significant factor recognized to
influence resistance is conjunctival scarring
and fibrosis, which results in the failure of
filtering surgery.[26] The pathophysiology
of fibrosis is complex, but growth factors
and cytokines expressed in inflammatory
cells are clear culprits.[27] This is particularly
problematic in glaucoma patients when
inflammation is exacerbated through four
mechanisms: (1) the predisposition of patients
to conjunctival fibrosis through long-term use

of topical prostaglandins or toxic preservative,
both of which were associated with local
inflammation,[28, 29] (2) the surgical procedure
itself, (3) subconjunctival flow, by itself,
constitutes a persistent mechanical stress to
local tissue, which was shown to translate into
pro-inflammatory biochemical signals,[39–41]

and (4) the mere presence of aqueous humor
in the subconjunctival space, where it is not
naturally present, was shown to promote
tissue fibrosis. Some components, particularly
TGF-b and VEGF-A, present at increased
levels in the aqueous humor of glaucoma
patients are believed to be responsible for
subconjunctival fibrosis.[30, 31] While both
VEGF antagonists and Rho-kinase inhibitors
were suspected to be beneficial in the
context of bleb surgery, they have so far
failed to demonstrate clear superiority or
to translate into clinical practice,[32, 33] and,
to date, the clinical recommendations with
regards to inflammation mediation are the
preoperative washout from pro-inflammatory
topical medications and the prolonged
postoperative use of topical steroids.
This point, however, remains the major
impediment to sustainable subconjunctival
filtration. With this regard, MIGS may have
a role to play in reducing the amount of
inflammation caused by subconjunctival
procedures.

Further risks common to all bleb-creating
procedures include bleb dysesthesia,
bleb leaks, blebitis, and bleb-related
endophthalmitis. These complications can
be common and some authors have reported
rates of bleb interventions in excess of 50%
following XEN implantations.[34] Hypotony is
another inherent risk of bypassing physiologic
outflow pathway, but this risk can theoretically
be mediated by the adjustment of devices’
internal dimensions to create specific levels

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Innovations in Glaucoma Surgery; Gillmann et al

of outflow resistance.[35] Finally, contrary
to traditional filtration surgery, prospective
studies and occasional case reports have
highlighted a risk of stent displacement and
occlusion, which are inherent to the placement
of an artificial stent.[36, 37]

Ciliary body: Reduction of aqueous humor
production

The ciliary body is site of aqueous production.
Reducing aqueous humor production is a
logical alternative to enhancing aqueous
outflow to lower IOP. Cyclophotocoagulation
consists of using a laser to selectively deliver
thermal energy to the pigmented tissues of
the ciliary body and induce tissue coagulative
necrosis.[38] Historically, the technique that
emerged in the 1930s as cyclodiathermy has
long been exclusively indicated for refractory
glaucoma and painful blind eyes. This was
mostly due to the relatively high risk of intense
and chronic postoperative inflammation,
pain, hypotony, vision loss, and phthisis.[39, 40]

However, recent innovations have allowed
for more targeted treatments and less
collateral tissue necrosis, leading to reduced
complication rates and better safety profiles.
This has led to cyclophotocoagulation’s
gradual acceptance for the treatment of
milder forms of glaucoma, and to some
surgeons considering it a MIGS. The main
theory underlying this change in practice is
that the rates and severity of complications
following cyclophotocoagulation are directly
related to the total amount of energy
used during the procedure.[41] However,
despite a clear reduction in the rates of
complications over the last decades, the risk
of permanent visual loss to a sighted eye
remains non-negligible,[42, 43] and a recent
Cochrane review concluded that there

was still insufficient evidence to conclude
positively on the effectiveness and safety
of cyclophotocoagulation in non-refractory
glaucoma.[44]

Furthermore, it has been speculated
that the significant perilimbal conjunctival
inflammation and scarring produced by
transscleral cyclophotocoagulation could
affect the outcome of subsequent filtering
surgeries, casting further doubt over the
indications of this type of treatment as an
initial procedure.

b. Intraocular sensors

With such an array of techniques designed
specifically to lower IOP, pressure control has
become the key element of surgical outcomes
and the cornerstone of glaucoma care as
a whole. Innovation, however, has been
slower when it comes to IOP measurement
techniques, and the gold standard technique
has essentially remained the same since 1950,
when Goldmann applanation tonometery
(GAT) was introduced.[45] GAT relies on the
Imbert-Fick principle to estimate IOP based
on the force that is required to flatten the
3.06 mm diameter area corresponding to
the tip of the Goldmann prism. Yet, this
technique is widely regarded as imperfect
and studies have pointed out its flaws both
in terms of design and concept. Not only is
GAT relatively imprecise, its instant nature
also fails to reflect the complexity of real-life
IOP variations.[58–60] Indeed, over the last
decades, there has been ample evidence that
individuals’ IOP are far from being static and
fluctuate widely over the course of 24 hours
and through the year, and even suggestions
that IOP variations may play a significant role
in glaucoma progression regardless of their
absolute values.[61–66]

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Eyemate

While several companies are actively working
on IOP-monitoring sensor prototypes, the
German company Implandata introduced
the first implantable continuous monitoring
device. It was CE-certified in 2017 for use in
primary open-angle glaucoma patients, and is
composed of three devices: the implantable
sensor (or wireless intraocular transducer
[WIT]), the handheld reader unit, and the
wireless module.[67–69] The sensor itself is
implanted in the ciliary sulcus during routine
cataract surgery and is designed to stay in
the patient’s eye indefinitely. To offer options
to patients regardless of their lens status
or anterior chamber pathologies, another
suprachoroidal approach was developed and
is currently being assessed. Figure 3 shows a
picture of the Eyemate sensor.

Technically, the WIT consists of eight
miniature pressure sensor cells, a temperature
sensor, an identification encoder, an analog-
to-digital encoder, and a telemetry unit into
a single microelectromechanical system
(MEMS). The MEMS is attached to a gold
circular antenna and the entire device is
encapsulated in implantation-grade silicone.
It weighs 0.1 g and comes in three sizes with
a varying external diameter of 11.3 mm, 11.7
mm, or 12.1 mm, in order to accommodate
varying sulcus diameter. It has an internal
diameter of 7 mm and an overall thickness
of 0.5 mm, while the thickness at the sensor
area is 0.9 mm. Each MEMS pressure sensor
cell is made of two miniature parallel plates: a
thin flexible plate that indents with changes in
IOP and a thicker rigid base plate integrated
with an A/D converter for the digitalized
pressure information. With changes in IOP,
the thin plate is mechanically defected. As
the distance between the two plates varies, a

corresponding analogue signal is generated
and then converted to a digital signal that is
transmitted externally by radiofrequency.[46]

The handheld reader unit, that resembles
a television remote control, receives the
digital data and visually displays the IOP
values on its LED display. The reader and
the intraocular transponder unit must be
within 5 cm of each other before a button
is pressed on the reader to activate the
electromagnetic coupling sequence and the
two units can correspond with each other.
This is all the cooperation required from the
patient. The sensor does not require a battery.
The handheld reader is battery powered
and supplies the WIT externally through
electromagnetic inductive coupling at the time
of communication. The sensor can conduct up
to 10 IOP measurements per second and there
are a range of settings that allow for automatic
monitoring at variable intervals. The base unit
can store up to 3000 IOP measurements,
and additional memory modules can be
added to the reader device. The wireless
module can be installed to automatically
download all measured data to a cloud-
based server, allowing the clinical provider
easy and instantaneous access to the data.
The ophthalmologist receives the patient’s
IOP measurements and can easily create a
tension profile, detect dips and peaks during
diurnal and nocturnal IOP fluctuations, and
recognize situations that require adjustments
of the therapy.
In 2011, the ARGOS-01 study investigated the

safety of the Eyemate and the accuracy of its
IOP measurements. Six patients with POAG
underwent cataract surgery and ciliary sulcus
placement of the sensor. The IOP sensor
was well tolerated by all the patients, despite
four of them developing self-limited sterile
anterior chamber inflammation. No difference

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Innovations in Glaucoma Surgery; Gillmann et al

in endothelial cell count and central corneal
thickness was observed after 12 months in
any of the patients. All patients were able
to perform self-tonometry as instructed, and
telemetric IOP values correlated well with
GAT measurement, except for one patient
who recorded negative values throughout the
study.[47]

Since the original study, other reports
illustrated how close self-monitoring could
detect non-symptomatic IOP variations that
would otherwise go unnoticed. Abnormal
self-measurements can prompt the patients to
obtain more IOP measurements and search
for repetitive patterns. In a published case
report by Rüfer et al, a patient even found a
rare connection between the administration of
his dorzolamide eyedrops and the subsequent
IOP rises before he received any medical
input.[48] This suggests that placing the patient
in charge and providing them with the means
to easily and accurately self-monitor could
improve glaucoma care by detecting IOP
aberrations earlier and eliciting causative
factors with more ease. The increased
frequency of IOP measurement associated
with the democratization of such sensors is
likely to lead to an increased incidence of
abnormal pressure readings. While this may
represent crucial information on a patient’s
individual IOP control, more research will be
needed to determine the clinical relevance of
every fluctuation captured through continuous
monitoring.

c. Implantable and injectable therapeutics

Despite all these innovations, the most
common first-line treatment for open angle
glaucoma remains pharmacological, and often
consists of a topical prostaglandin analog
(PGA). Numerous studies have confirmed

their potential to achieve substantial IOP
reductions for up to 48 hours, providing
both diurnal and nocturnal effect, contrary
to topical beta-blockers that were proven to
be somewhat inefficient at night. This class
of medications act by primarily increasing
uveoscleral outflow and, to some extent,
enhancing trabecular outflow. While PGA
is a generally well-tolerated medication, a
number of side effects are commonly reported,
including cystoid macular edema, excessive
eyelash growth, iris pigmentation, allergic
reactions, and conjunctival hyperhemia and
scarring. The latter of which was associated
with increased risk of surgical failure in
subsequent filtering procedures. Beyond
these adverse effects, topical PGA suffer the
same problems as all self-administered topical
medications.[49]

There is ample data, both self-reported and
from pharmacies, indicating that adherence
with topical anti-glaucoma treatments is
generally poor. Indeed, American studies have
estimated that as many as 27% of all prescribed
medications are simply not purchased by the
patients, and nearly half of all glaucoma
patients miss over 25% of their treatment
doses.[74–76] Unsurprisingly, poor compliance
is associated with worse IOP control and
disease progression. In addition, even when
topical medications are administered, patients’
instillation techniques can be poor and lead
to a further decrease in treatment efficacy.
To remedy these universal issues inherent
to self-administered eye drops, several drug
delivery approaches are being developed and
will soon become available to the glaucoma
specialists. They include options as varied as
drug-eluting contact lenses or periocular rings,
topical nebulizers releasing microdroplets of
the active ingredient directly on the surface of
the cornea, or subconjunctival injections. One

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Innovations in Glaucoma Surgery; Gillmann et al

of them, an intracameral bimatoprost-releasing
implant, has already reached stage 3 clinical
trials and is showing promising results.[50]

It consists of a biodegradable matrix
designed to be injected into the anterior
chamber, where it gradually releases 15 μg of
sustained-release bimatoprost over a period of
up to six months. Figure 4 shows the implant.
In recent studies, the efficacy of the implant
was comparable to that of daily instillation of
the topical medication, with no observable
side effects.[51] This mode of administration
presents several clear advantages. Firstly,
with patients only having to attend a bi-annual
appointment to receive their treatments, it
would considerably reduce the potential for
missed doses compared to topical therapies.
Secondly, the seemingly reduced contact and
effect of bimatoprost on ocular surface may
decrease the prevalence of long-term side
effects and the negative impact of prolonged
treatments on subsequent filtering surgeries.
Thirdly, and interestingly, contrary to topical
instillation, no ceiling effect was identified for
intracamerular instillation of bimatoprost. It has
been speculated that it may be due to a direct
lowering effect of intraocular bimatoprost
on episcleral venous pressure. Finally, after
several intracameral injections, the IOP-
lowering effect of the treatment appeared
to persist considerably longer than the six-
month lifespan of the implant, leading to
prolonged periods of treatment free reduced
IOP.[52] The advent of implantable or injectable
therapeutics may soon provide yet another
step in the glaucoma treatment ladder.

Opinion

The traditional landscape of glaucoma
management has changed dramatically over
the last decade, with the development of

a large array of novel surgical techniques.
While a surge in attention, investment and
innovation and, eventually, treatment options
foretells a bright future for the sub-specialty,
at a clinical level, it raises the questions
of patient-centered treatment choices and
evidence-based decisions. Indeed, one of the
advantages of such a heterogenous range of
surgical options is the chance to tailor therapy
in an individualized manner. High quality data
are required to make this choice more than an
educated guess. To provide some objective
criteria in the assessment of glaucoma surgery,
and to guide innovation, the “10-10-10 Goal”
was set. According to these criteria, the ideal
surgical technique would take less than 10 min
to perform, be able to consistently achieve
IOPs below 10 mmHg, and last >10 years
without any significant complications.

With procedures typically taking between 15
and 30 min to perform, MIGS have managed
to significantly reduce surgical times. While
this represents a 50% reduction from most
traditional filtering procedure or glaucoma
drainage device implantations, MIGS are yet
to provide us with a simple enough procedure
to be consistently carried out in <10 min by
the average glaucoma surgeon. In terms of
IOP reduction potential, considering that the
average candidate for MIGS surgery has a
preoperative IOP in the 20–25 mmHg range, it
would require a 50–60% reduction to achieve
postoperative pressures under the 10-mmHg
threshold. In the literature, only rarely did
some MIGS provide IOP reduction of 50% or
more. Furthermore, the few incidences of IOP
reductions >50% could not be replicated, and
the same surgical techniques showed more
modest effects in alternative studies. It does,
however, appear that the sub-conjunctival
approach is more likely than other categories
of MIGS to achieve IOPs in the low-teens.

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Innovations in Glaucoma Surgery; Gillmann et al

But in this context of intense innovation, new
technologies will likely appear and reshuffle
the cards in the years to come, including
new devices offering variations on existing
techniques, or all-new approaches such as
drug-coated devices or ocular surface shunts.
Finally, it is, at present, difficult to assess the
sustainability of MIGS efficiencies. Since most
MIGS have been commercially available for <5
years, there is a general lack of long-term data
in the field, but knowledge is slowly accruing.
This aim of longevity, however, should prompt
us to design sound clinical trials early on, in
order to obtain not only extensive, but also
reliable long-term data.

Overall, reviews confirm the efficiency
of most MIGS compared to standalone
phacoemulsification, and the reported rates
of complications also compare favorably
with traditional filtering surgeries. But to be
clinically advisable, a procedure needs not
only be safe, but also to prove its non-inferiority
to commonly accepted alternatives. However,
there are only few studies comparing different
MIGS techniques, especially considering
the vast and growing number of procedures
available nowadays, and even fewer assessing
MIGS against topical medications. More
comparative data, especially with gold
standard therapies and common practice
options could be extremely relevant for
ophthalmologists and healthcare authorities,
allowing to ascertain the best therapeutic
option for the patients, and potentially
reducing the medication burden and its
associated costs. But considerably more
evidence will be needed to achieve this
level of certainty. Indeed, current evidence,
while non-negligible, is still mostly limited to
non-randomized studies and uncontrolled
retrospective comparisons with few quality
randomized controlled trials. This leads to

significant variability in studies’ results and a
blurring of the outcomes, and further highlights
the need for carefully designed randomized
controlled trials.
Beyond the scope of MIGS, the potential

of IOP telemetry for self-assessment of
IOP control through implantable sensors is
developing into a real option for clinicians
and an empowering opportunity for
patients. Indeed, providing patients with
direct feedback enables them to take
control and have a clearer representation
of their care, in turn leading to a better
control of the disease.[68] Building on the
reports that patients’ adherence increases
shortly before their medical appointments,
continuous measurements may provide
patients with an incentive for better adherence
to treatment, and clinicians with a more
accurate representation of out-of-clinic
IOPs. It also might remove an element
of self-deception where brief periods of
adherence suffice to reassure both patients
and treating clinicians.[53] This paves the way
for personalized glaucoma care, in which the
actual effect of lifestyle and treatments can be
self-monitored by the patients and therapeutic
decisions can be made accordingly in real
time before there is further optic nerve
injury.
Patients are increasingly demanding an

equal role in clinical decision-making. Many
no longer accept the paternalistic model
of medical care in which doctors decide
and patients comply. However, there are
potential issues with self-monitoring of IOP,
such as increased anxiety levels induced by
measured IOP fluctuations and peaks, leading
to patients self-treating during IOP spikes
and additional office visits. The availability of
continual IOP monitoring will be a challenge to
the current glaucoma management paradigm,

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Innovations in Glaucoma Surgery; Gillmann et al

which, however, has the important potential to
improve patient health outcomes.
After several decades of relative stagnation

through the last century, glaucoma has now
entered what many view as a golden age
for the specialty. Like every revolution, this
one brings its fair share of uncertainty, clinical
questioning, and uneasy periods of adaptation
to ever-changing expectations. Yet, while it is
impossible to guess what the landscape of
glaucoma surgery will be like in 10 or 15 years,
data suggest a bright outlook both for patients
and clinicians.

Financial Support and Sponsorship

This review has been supported in part by
the Swiss Glaucoma Research Foundation,
Lausanne, Switzerland.

Conflicts of Interest

There are no conflicts of interest.

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