Acta Ophthalmologica 2021

Review Article

Anterior segment imaging in minimally invasive

glaucoma surgery – A systematic review
John Tsia-Chuen Kan,1 Bjorn Kaijun Betzler,2 Sheng Yang Lim2 and Bryan Chin Hou Ang1,3
1
Department of Ophthalmology, Tan Tock Seng Hospital, National Healthcare Group Eye Institute, Singapore, Singapore
2
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3
Department of Ophthalmology, Woodlands Health Campus, National Healthcare Group Eye Institute, Singapore, Singapore

ABSTRACT. recent years as a group of newer

Minimally invasive glaucoma surgery (MIGS) has grown in popularity over the surgical options for glaucoma and has
past decade. This systematic review explores the peri-operative and intraoperative been described as having an ab interno,
application of anterior segment imaging to maximize the efficacy and safety of micro-incisional approach; minimal
MIGS. A review of the PubMed, EMBASE and CINAHL databases was trauma to target tissue with negligible
conducted, with inclusion criteria restricted to MIGS that had received United disruption of normal anatomy and
States Food and Drug Administration (FDA) premarket approval, FDA 510(K) physiology; at least modest efficacy; a
premarket notification, or were listed as a class 1 device exempt from FDA good safety profile; and rapid recovery,
approval or notification. 21 manuscripts from 21 unique studies were identified with minimal impact on patient’s qual-
ity of life (Saheb & Ahmed 2012).
pertaining to MIGS devices including the XEN Gel Stent, Trabectome, iStent
MIGS has grown steadily in popularity
Inject, 1st-generation iStent and the Kahook Dual Blade (KDB). Anterior segment
due to its IOP-lowering efficacy and
imaging modalities included anterior segment optical coherence tomography (AS- superior safety profile compared with
OCT), ultrasound biomicroscopy (UBM), aqueous angiography, OCT volumetric traditional glaucoma surgeries (Minck-
scans and in vivo confocal microscopy. Identification and evaluation of aqueous ler et al. 2005; Minckler et al. 2006;
outflow pathways before and after MIGS have potential for improving patient Francis et al. 2008; Gedde et al. 2012;
preoperative patient selection and postoperative outcomes. Intraoperative imaging Jordan et al. 2013; Fea et al. 2014;
potentially provides the resolution needed for good visualization of angle anatomy Iordanous et al. 2014; Voskanyan et al.
and accurate evaluation of surgical endpoints in angle-based MIGS. Anterior 2014; Arriola-Villalobos et al. 2016;
segment imaging has been used to identify procedural complications, provide Tan & Au 2016; Ansari 2017; Chen &
objective information on implant location in relation to surrounding anatomy, Sng 2017; Kerr et al. 2017; Rahmatne-
assess the post-implantation structural impact of MIGS devices and manage bleb jad et al. 2017; Ahmed et al. 2018;
failure and scarring. Technical difficulties in incorporating imaging modalities into Fingeret & Dickerson 2018; Popovic
the surgical microscope, variable quality of images and optical interference from et al. 2018; Hassan et al. 2019; Hern-
ocular structures or surgical instruments are remaining barriers, which discourage stadt et al. 2019; Le et al. 2019; Sng
et al. 2019; Bartelt-Hofer & Flessa
the widespread clinical use of this technology.
2020; Cubuk & Unsal 2020; Hong
et al. 2020; Ioannidis et al. 2020;
Key words: glaucoma – imaging – minimally invasive glaucoma surgery – systematic review
Kansal et al. 2020; Meier-Gibbons &
Toteberg-Harms 2020; Newman-Casey
Acta Ophthalmol. et al. 2020). It has ignited a paradigm
ª 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd shift in the surgical approach to glau-
doi: 10.1111/aos.14962 coma treatment, filling in the potential
treatment gap between surgery and the
Introduction laser therapy. Traditional filtering sur- conservative options of medications
Glaucoma is the leading cause of irre- gery, such as trabeculectomy and tube and laser therapy.
versible blindness and is projected to shunt surgery, is performed in more With the adoption of these new
further increase in prevalence (Tham advanced or refractory glaucoma given surgical techniques, methods to ensure
et al. 2014). Intraocular pressure (IOP) its associated risks and potentially appropriate preoperative patient selec-
reduction remains the primary target of sight-threatening complications. tion and planning, optimal intraopera-
treatment today and is usually suffi- However, minimally invasive glau- tive device placement as well as
ciently achieved with medication or coma surgery (MIGS) has emerged in effective postoperative management

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Acta Ophthalmologica 2021
and device manipulation, need to be
explored in order to maximize the
efficacy and safety of MIGS.
The use of ocular imaging has been
well established in the management of
glaucoma. While primarily used to aid
diagnosis and monitoring of disease,
improvements in technology and the
emergence of newer imaging modalities
have encouraged greater peri-operative
use today (Binder et al. 2011; Hirn-
schall et al. 2013; Au et al. 2015; Ehlers
et al. 2015; Das et al. 2016; Swami-
nathan & Chang 2017; Ang et al. 2020).
This systematic review aims to
explore the peri-operative application
of anterior segment imaging in MIGS,
by examining and consolidating avail-
able literature. Limitations of current
imaging techniques in relation to
MIGS are discussed. We also explore
potential areas for the further develop-
ment and application of imaging in
MIGS.
Methods
This systematic review was conducted
in accordance with the guidelines stated
in Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analyses
(PRISMA). An electronic search of
the PubMed, EMBASE and CINAHL
databases was performed indepen-
dently by two authors (JK and BB),
from the date of database inception
until 21 April 2020.
We limited our literature search to
MIGS which had received United States
Food and Drug Administration (FDA)
premarket approval, obtained FDA 510
(K) premarket notification, or those
listed as a class 1 device exempt from
FDA approval or notification. These
included MIGS devices and procedures
that (1) increase trabecular outflow such
as the iStent and iStent inject, Hydrus,
trabectome, Trab360 trabeculotomy,
excimer laser trabeculotomy,
gonioscopy-assisted trabeculotomy, ab
interno canaloplasty, Fugo plasma
blade and Kahook dual blade; (2) create
subconjunctival outflow such as the
XEN45 gel stent; and (3) decrease aque-
ous production such as endocyclopho-
tocoagulation. The CyPass Micro-Stent,
which previously received FDA
approval, was recalled due to safety
concerns prior to our literature search
and was not included in this review.
A combination of subject headings
and text words was used as needed to
2
define imaging and minimally invasive
glaucoma surgery (MIGS). We
employed the terms ‘((minimally
AND invasive AND glaucoma AND
surgery) OR istent OR hydrus OR
trabectome OR (trab AND 360) OR
itrack OR visco360 OR (visco AND
360) OR omni360 OR (omni AND
360) OR fugo OR (fugo AND plasma
AND blade) OR kahook OR (kahook
AND dual AND blade) OR xen OR
endocyclophotocoagulation OR (mi-
croprobe laser)) AND ((imaging OR
(optical AND coherence AND tomog-
raphy) OR (ultrasound AND biomi-
croscopy) OR UBM OR (aqueous
AND angiography) OR (ultrasound
AND B-scan) OR (Ultrasound AND
Bscan))’. A secondary search of the
references of all retrieved articles and
review articles was performed to iden-
tify other potentially relevant studies.
The search workflow was designed in
adherence to the Preferred Reporting
Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement
(Fig. 1). The PRISMA checklist is
provided in the Appendix S1.
Initial database query provided 434
unique reports. The identified studies
were assessed independently by three
authors (JK, BB and SY) to determine
eligibility for inclusion in the analysis.
If any discrepancies were identified, a
senior author (BA) was consulted, and
any differences were resolved. Articles
not written in English and those that
did not involve human participants
were excluded from this review. Full-
text articles were assessed for eligibility.
Papers with no reference to anterior
segment imaging in the context of
MIGS, irrelevant study types such as
systematic reviews, and studies that
were conducted in vitro were excluded
from our analysis. We were unable to
obtain the full texts for seven of our
search references, and these were
excluded. There was no limit on min-
imum number of patients required.
Results
After full-text evaluation by the
authors, 21 unique manuscripts were
identified that addressed the applica-
tion of anterior segment imaging in
MIGS. An overview of the included
studies is provided in Table 1.
Of the 21 unique studies included in
our review, 11 were case series, seven
were case reports, two were prospective
studies and one was an observational
study. MIGS that was included was the
XEN (eight of 21 studies), trabectome
(eight of 21 studies), iStent inject (three
of 21 studies), 1st-generation iStent
(one of 21 studies) and the KDB (one
of 21 studies).
The majority of studies examined
AS-OCT use (15 of 21 studies) followed
by UBM (four of 21 studies). The use
of aqueous angiography, OCT volu-
metric scans and in vivo confocal
microscopy was examined in one study
each.
Across the included studies, imaging
was applied mostly postoperatively (19
of 21 studies). Intraoperative (three of
21 studies) and preoperative imaging
(one of 21 studies) were less common.
Trabectome
The trabectome (NeoMedix Corpora-
tion, Tustin, CA) is used in ab interno
trabeculotomy (AbIT), a procedure
which allows direct aqueous outflow
from the anterior chamber into Sch-
lemm’s Canal via mechanical rupture
of the trabecular meshwork (TM). It
has been in use since the early 2000s
and has been used to treat both pri-
mary glaucoma and secondary glau-
coma with good efficacy (Minckler
et al. 2005; Minckler et al. 2006).
Uncommon complications include
reflux of blood into the anterior cham-
ber, injury to the corneal endothelium
and Descemet’s membrane, formation
of peripheral anterior synechiae (PAS),
derangements of IOP such as IOP
spikes or hypotony, ciliolenticular
block and cyclodialysis cleft (Minckler
et al. 2006; Osman & AlMobarak 2015;
Berk et al. 2017; Ahmed et al. 2018). A
total of eight studies have reported the
use of anterior segment imaging in
AbIT and describe the use of imaging
during the intraoperative and postop-
erative phases.
Anterior segment optical coherence tomog-
raphy (AS-OCT)
Intraoperative application. Two studies
examined the use of AS-OCT intraop-
eratively and demonstrated early pro-
mise in improving procedural
visualization and objective assessment
of the desired surgical end point.
Junker et al. reported use of the
LUMERA 700 (Carl Zeiss Meditec
AG, Jena, Germany) microscope with
an integrated spectral-domain iOCT

Fig. 1. PRISMA Flow chart.
RESCAN 700 (Carl Zeiss Meditec
AG). This AS-OCT platform allows
the display of OCT and microscope
images concurrently on a touchscreen,
which also allows for an assistant to
control the OCT display. Real-time
OCT images, captured OCT images as
well as the scan marker, can be merged
into the microscopic eyepiece for the
surgeon’s viewing as an overlay, allow-
ing the surgeon to simultaneously
observe the OCT and live operation
site. The study found the quality of
imaging comparable to that of a stan-
dalone AS-OCT and described the
relative ease of acquisition and focus-
ing of retinal and corneal images. In all
their cases, the angle could be visual-
ized and optimal settings were found to
be a short scan length of 3mm in
conjunction with a vertical scan mode.
The iOCT enabled them to easily
determine the success of surgery imme-
diately postoperatively, with objective
evidence of TM removal.
Heindl et al. (2015) reported the use
of another AS-OCT platform, the
iOCT (OptoMedical Technologies,
Luebeck, Germany), mounted onto a
surgical microscope (HS Hi-R NEO
900A NIR; Haag-Streit Surgical
GmbH, Wedel, Germany). The iOCT
was used to determine the position of
the trabectome tip in relation to the
anterior chamber angle, prior to rou-
tine trabeculotomy using only the stan-
dard goniolens without the iOCT
(Fig. 2). The authors found that visu-
alization of the instrument within the
angle was only possible when the
microscope with the overlaid iOCT
was adjusted to a more horizontal
position from the regular position of
60°. They also described the applica-
tion of iOCT in trabecular aspiration
(Trabecular aspirator, Geuder, Heidel-
berg, Germany), both in vivo and in
porcine cadaver eyes (Fig. 3). In this
setting, the use of longer wavelengths
and oblique scanning enabled better
visualization of the angle and trabecu-
lar meshwork as well as imaging of the
spatial relationship between the trabec-
tome tip and the trabecular meshwork.
This may potentially eliminate the need
for intraoperative gonioscopy and
allow for real-time imaging during
removal of the trabecular meshwork.
While both studies were successful in
utilizing the iOCT in trabectome sur-
gery, key limitations were also high-
lighted. While Heindl et al. could
visualize the entire trabectome tip on
iOCT inside the AC (albeit with a mod-
ified surgical position), visualizing the
ACA anatomy itself remained challeng-
ing due to shadowing artefact from the
more superficial layers as well as a
Acta Ophthalmologica 2021
mirroring effect from the ACA. Junker
et al. also faced challenges capturing
good quality images of the ACA and the
trabectome tip for the same reasons and
observed that the overlaying iOCT scan
presented additional challenges to focus-
ing. When iOCT images were overlaid
onto the microscopic eyepiece, this also
caused difficulty in focusing on the area
of interest. Obtaining video recordings
of the surgery was not feasible due to
repeated changes in focus and light
reflectance. An assistant was also usually
required, as handling of the iOCT while
performing surgery remained techni-
cally challenging for the surgeon. Lastly,
the duration of surgery increased due to
additional time required to obtain iOCT
images.
Postoperative application. Postopera-
tively, AS-OCT has been used to
objectively determine the direct effect
of trabectome surgery on the anatomy
of the angle, such as the trabeculotomy
size. Wecker et al. utilized the AS-OCT
to investigate the effect of trabeculo-
tomy opening (TO) size on postopera-
tive IOP after trabectome surgery
(Wecker et al. 2017) (Fig. 4). Swept-
source AS-OCT was used to determine
the extent of the AC angle circumfer-
ence that was open, defined as being
>1/4 of the height of Schlemm’s Canal
on the OCT image. It was determined
3
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Table 1. Summary of included studies

MIGS Imaging Glaucoma

Author, Year Study type Device modality Imaging system Usage Population Intervention subtype

Mastropasqua Prospective case XEN OCTA AngioVue OCTA system Postoperative 43 eyes of 43 patients Six eyes XEN + Phaco POAG
(2020) series (Optovue Inc) Adults in Italy Phacoemulsification PXG
37 eyes XEN only PDG
Figueroa- Case Report XEN AS-OCT Triton Topcon Postoperative 77-year-old female, two eyes Two eyes XEN only POAG
Vercellino Spain
(2019)
Gillmann Prospective case iStent Inject AS-OCT Spectralis OCT (Heidelberg Postoperative 110 eyes of 85 patients 81 eyes XEN + POAG
Acta Ophthalmologica 2021

(2019) series Engineering AG) Adults in Switzerland Phacoemulsification PXG

19 eyes XEN only
Huang (2019) Prospective case iStent Inject Aqueous Spectralis HRA+OCT Pre- & 14 eyes of 14 patients Combined iStent + POAG
series Angiography (Heidelberg Engineering) Postoperative Adults in USA Phacoemulsification PXG
Lenzhofer Prospective, XEN AS-OCT Visante OCT (Carl Zeiss Postoperative 66 eyes of 54 patients 34 eyes XEN + POAG
(2019a) (1) longitudinal Meditec AG) Adults in Austria Phacoemulsification
clinical study 32 eyes XEN only
Lenzhofer Prospective XEN AS-OCT – Postoperative 78 eyes of 60 patients 42 eyes XEN + POAG
(2019b) (2) single-armed Adults in Austria Phacoemulsification
cohort study 36 eyes XEN only
Mozo- Case Report XEN AS-OCT – Postoperative 78-year-old female 1 eye XEN only POAG
Cuadrado Spain
(2019)
Rigo et al. Retrospective XEN AS-OCT DRI OCT Triton (Topcon Postoperative 16 eyes of 15 patients 15 XEN + Phacoemulsification POAG
(2019) case series Medical Systems, Oakland, Adults in Spain (POAG) PXG
NJ, USA) 1 XEN only (PEXG)
Shue (2019) Case Report KDB UBM – Postoperative 55-year-old male Combined KDB + POAG
USA Phacoemulsification
Teus (2019) Cross-sectional XEN, AS-OCT DRI OCT Triton (Topcon, Postoperative 25 eyes of 25 patients Five eyes XEN + POAG
study Trabectome Madrid, Spain) Adults in Spain Phacoemulsification
five eyes XEN only
12 eyes Trabectome +
Phacoemulsification
three eyes Trabectome only
Gillmann Case Report iStent Inject AS-OCT Spectralis OCT (Heidelberg Postoperative 74-year-old female Combined iStent + POAG
(2018) Engineering AG) Switzerland Phacoemulsification
Yoshikawa Prospective case Trabectome SS-OCT DRI OCT-1 (Topcon, Tokyo, Preoperative 15 eyes of 13 patients Nine eyes Trabectome  POAG
(2018) series volumetric Japan) Adults in Japan Phacoemulsification
scans
Berk (2017) Case Report Trabectome AS-OCT, Visante OCT (Carl Zeiss Postoperative 55-year-old male Repair of a cyclodialysis cleft POAG
UBM Meditec AG) Canada (right eye) created during a
Trabectome procedure
3 years prior.
Fea (2017) Prospective case XEN AS-OCT, RTVue-100 (Optovue, Inc, Postoperative 12 eyes of 11 patients Two eyes XEN + POAG
series IVCM Fremont, CA, USA) Adults in Italy Phacoemulsification
10 eyes XEN only
 Table 1 (Continued)

MIGS Imaging Glaucoma

Author, Year Study type Device modality Imaging system Usage Population Intervention subtype

HRT II/Rostock Cornea

Module (RCM) (Heidelberg
Engineering, Inc)
Junker (2017) Retrospective Trabectome AS-OCT iOCT RESCAN 700 (Carl Zeiss Intra- & Nine patients Trabectome only POAG
case series Meditec AG) Postoperative Adults in Germany PXG
PDG
Olate-Perez Prospective case XEN AS-OCT DRI OCT Triton Swept-Source Postoperative 30 eyes of 18 patients Combined XEN + POAG
(2017) series OCT device (Topcon) Adults in Spain Phacoemulsification
Wecker (2017) Retrospective Trabectome AS-OCT Casia SS-1000 (Tomey, Postoperative 93 eyes of 93 patients 38 eyes Trabectome + POAG
case series Erlangen, Germany) Adults in Germany Phacoemulsification PXG
55 eyes Trabectome only PDG
NTG
Uveitic
Congenital
Trauma-
related
Akil (2016) Prospective case Trabectome AS-OCT SS-1000 CASIA (Tomey Co. Pre- & 38 eyes of 24 patients 20 eyes Trabectome + POAG
series Ltd., Nagoya, Japan) Postoperative Adults in USA Phacoemulsification
(1 month) 18 eyes Trabectome only
Mantravadi Case Report iStent (1st UBM – Postoperative 57-year-old female Combined iStent + POAG
(2016) Gen) USA Phacoemulsification
Heindl (2015) Correspondence Trabectome AS-OCT iOCT (OptoMedical Intraoperative Two eyes of two patients Trabectome only POAG
Technologies) Additional three porcine eyes PXG
for experimental analyzation
of image quality
Adults in Germany
Osman (2015) Case Report Trabectome UBM – Postoperative 33-year-old male Trabectome only JOAG
India

AS-OCT, anterior segment optical coherence tomography; IVCM, in vivo confocal microscopy; JOAG, juvenile open-angle glaucoma; KDB, Kahook Dual Blade; NTG, normal tension glaucoma; OCTA,
optical coherence tomography angiography; PDG, pigment dispersion glaucoma; POAG, primary open-angle glaucoma; PXG, pseudoexfoliation glaucoma; UBM, ultrasound biomicroscopy.
Acta Ophthalmologica 2021

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Acta Ophthalmologica 2021

(B)

(A) (C)

Fig. 2. Intraoperative optical coherence tomography (iOCT) during ab interno trabeculotomy. Courtesy of Heindl et al. (A) Video image. The
trabectome (arrows) is placed within the iridocorneal angle. The horizontal line demonstrates iOCT scanning direction. (B) iOCT image of
iridocorneal angle during placement of the trabectome. Trabecular meshwork is shadowed by scleral tissue, but iris is visible (Co, cornea; CA,
chamber angle; Ir, iris). (C) iOCT section of the trabectome (arrows) within the iridocorneal angle. Iris is not visualized due to the shadowing of the
trabectome.

(B)

(A) (C)

Fig. 3. Intraoperative optical coherence tomography (iOCT) during trabecular aspiration. Courtesy of Heindl et al. (A) Video image. The aspiration
cannula (arrows) is placed within the iridocorneal angle. To maintain intraocular pressure, an irrigation cannula is additionally placed within the
anterior chamber (asterisk). The horizontal line demonstrates iOCT scanning direction. (B) iOCT image of the iridocorneal angle before placement of
the aspiration cannula. Iris and trabecular meshwork are shadowed by scleral tissue (Co, cornea; CA, chamber angle; Ir, iris). (C) iOCT cross section
of aspiration cannula (arrow) within the iridocorneal angle. With a non-parallel scanning direction, the tip of the instrument is difficult to visualize.

(A) (B)

Fig. 4. Anterior segment optical coherence tomography (AS-OCT). Courtesy of and adapted from Wecker et al. (A) Illustration of anterior chamber
depth (ACD) measurement. In their paper, the connecting line between the nasal and temporal angle recess served as baseline. The maximum
perpendicular distance from the baseline to the posterior surface of the cornea was defined as ACD. (B) Representative AS-OCT section showing an
open trabecular meshwork (white arrow).

that a larger TO size had a significant
correlation with deeper ACDs. How-
ever, there was no statistically signifi-
cant effect of TO size on IOP in
patients with chronic open-angle
glaucoma. In a subset of their data
looking at patients with pseudoexfolia-
tive glaucoma, in which trabectome
surgery has been found to be particu-
larly efficacious in previous studies
(Jordan et al. 2013), they noted that
these patients had higher IOP reduc-
tion as compared to POAG patients.
Although their data set was too small
for valid statistical analysis, it was

6

postulated that a larger TO size may
correlate with a greater reduction in
IOP.
The AS-OCT has also been shown to
objectively determine changes in ante-
rior chamber anatomy. Akil et al. mea-
sured various anterior chamber
parameters pre- and postoperatively
after trabectome surgery using swept-
source AS-OCT in open-angle glau-
coma patients, including the angle
opening distance at 500 lm
(AOD500) and 750 lm (AOD700)
from the scleral spur, trabecular-iris
space area at 500 mm2 (TISA500) and
750 mm2 (TISA750), angle recess area
at 500 mm2 (ARA500) and 750 mm2
(ARA750), trabecular-iris angle (TIA),
anterior chamber depth (ACD), width
(ACW) and volume (ACV). Pre- and
postoperative measurements were com-
pared to explore differences after AbIT
with and without concurrent cataract
surgery. Despite the observable short-
term differences in the evaluated
parameters and IOP reduction, there
was no analysis to correlate these
factors. The authors suggested follow-
up with serial AS-OCTs over time in
both open- and closed-angle glaucoma
patients to determine the utility of AS-
OCT in the longer-term follow-up of
post-trabectome patients.
The feasibility and reliability of
using AS-OCT to assess ACA anatomy
are well established. Only a short
duration is required for the scan, there
is good repeatability, excellent intra-
and intergrader reproducibility, and
anatomical structures can be identified
easily – especially the trabecular cleft
which may not be apparent clinically
on gonioscopy. No contact with the
patient is required to acquire images,
hence making the AS-OCT also suit-
able for use in the immediate postop-
erative phase with minimal risk of
wound dehiscence or ocular infection.
The AS-OCT may also be used to
confirm findings resulting from opera-
tive complications, such as cyclodialy-
sis cleft causing hypotony, as described
by Berk et al. (2017) Limitations of AS-
OCT include shadowing artefacts and
the difficulty in identifying structures
such as the scleral spur.
The use of swept-source OCT volu-
metric scans to evaluate aqueous
humour outflow (AHO) pathways has
been reported, with the functional
evaluation of AHO pathways and their
effect on anatomical structure an area
with potential for further investigation.
The technique imaging the AHO path-
ways from Schlemm’s Canal through
to the episcleral venous plexus with
swept-source OCT was first described
by Uji et al. (2016). Volume scanning
with swept-source OCT was first per-
formed at the nasal and corneal limbus,
with resultant scan images converted
into en face images (at the level of the
conjunctival epithelium) using in-built
software. Based on these en face
images, the scleral vasculature maps
at three different depths (superficial,
intermediate and deep layer networks)
were constructed by using the motion
contrast enhancement technique on the
basis that vessels were detected as dark,
moving objects against the brighter
sclera (Uji et al. 2016). Yoshikawa
et al. (2018) utilized this same tech-
nique in patients undergoing trabec-
tome surgery to obtain preoperative
and postoperative images of the AHO
pathways (Figs 5 and 6). The authors
found that the SS-OCT provided an
easily reproducible, non-invasive and
convenient method of assessing the
AHO. Identical AHO pathways could
be identified in the same patient both
before surgery and after surgery in
about 80% of subjects. In comparison,
the use of the AS-OCT to identify the
AHO pathway is usually achieved by
identifying the intrascleral lumen which
has been found to localize to angio-
graphically positive signals in primate
eyes (Huang et al. 2017). However, the
relationship between functional AHO
pathways and identification of the
intrascleral lumen needs to be further
clarified as it remains unclear how the
function of the AHO pathway affects
the size of the lumen and vice versa. It
was noted that there were no significant
quantitative or qualitative morpholog-
ical changes after trabeculectomy sur-
gery although IOP reduction was
achieved. This may be because postop-
erative changes in the AHO may have
been too minute to be noticeable on the
OCT volumetric scans. Techniques
with increased sensitivity and refine-
ment could yield more useful informa-
tion which may aid clinicians in
targeting surgical sites and assessing
postoperative direct outcomes.
Ultrasound Biomicroscopy (UBM)
Postoperative application. The UBM has
been used to detect postoperative com-
plications after trabectome surgery.
Acta Ophthalmologica 2021
The UBM may be used to confirm the
presence of a cyclodialysis cleft, as seen
in the case report by Berk et al. (2017),
in which the cleft had also been
detected on AS-OCT. Osman et al.
also reported the use of the 35 MHz
UBM in identifying a 360-degree cilio-
choroidal effusion in a patient who
presented with persistent hypotony fol-
lowing trabectome surgery. The under-
lying cyclodialysis cleft was only
visualized with an 80 MHz UBM.
Kahook Dual Blade (KDB)
The KDB was introduced in 2015
(Greenwood et al. 2017) and, like the
trabectome, is used in AbIT to achieve
complete removal of trabecular tissue,
with no implantable device. However,
in contrast to the trabectome, the KDB
is a single-use, non-electronic device. A
sharp distal tip is used to enter Sch-
lemm’s Canal through the TM, which
is lifted by a ramp to facilitate cutting
by two parallel blades. The KDB
exhibits a promising efficacy and safety
profile and is clinically indicated in
patients with mild-to-severe glaucoma.
The most common complication is
intraoperative blood reflux from col-
lector channels, which have been
shown to resolve spontaneously
(Greenwood et al. 2017). Other com-
plications include postoperative IOP
spike and posterior capsule opacifica-
tion (Greenwood et al. 2017). Postop-
erative hypotony is rare and has not
been reported elsewhere in the litera-
ture apart from the single case report
including in our review.
Ultrasound Biomicroscopy (UBM)
Postoperative application. Like its use in
patients undergoing trabectome sur-
gery, ultrasound biomicroscopy
(UBM) has been used to support
cyclodialysis cleft elucidation after
combined KDB and phacoemulsifica-
tion surgery as described in a case
report by Shue et al. (2019). A 55-year-
old man with POAG underwent KDB
surgery and was found to have IOP of
4 mmHg on the first postoperative day.
While postoperative best corrective
visual acuity (BCVA) was normal at
the outset, he developed macula
changes and his BCVA OD dropped
to 20/40. However, the lack of overt
intraoperative complications, reason-
able postoperative BCVA and the
presence of 360° iridotrabecular
7
Acta Ophthalmologica 2021

(A1) (B1)

(A2) (B2)

Fig. 5. Illustration of objective measurement of the post-trabecular aqueous outflow pathway. Courtesy of Yoshikawa et al. Preoperative and
postoperative reconstructed B-scan images of the same post-trabecular aqueous outflow pathway are shown in A1 and A2, respectively. The outflow
pathways (red arrowhead) were measured from Schlemm’s canal (yellow arrowhead) to the episcleral veins (B1, B2). The measured area (yellow area)
increased postoperatively from 5338 to 5714 pixels.

(A) (B) (C) (D) (E) (F)

(G) (H) (I) (J) (K) (L)

Fig. 6. Representative images of the aqueous humour outflow pathway before and after surgery. Courtesy of Yoshikawa et al. The temporal limbus
of a 32-year-old woman who received trabectome surgery in her left eye. Preoperative images (A–F) and postoperative images (G–L) are shown
contrastively. (A, G) Merged images of the vasculature maps from three scleral layers in different colours: (B,H) Superficial layer in red; (C,I)
intermediate layer in green; (D, J) deep layer in blue. (E,K) The identified aqueous outflow (yellow line) delineated on the enface image. (F,L)
Reconstructed B-scan obtained by re-slicing the volume scan data along the identified aqueous outflow pathway in the x-y plane. Post-trabecular
aqueous outflow pathway width seems to increase postoperatively.

contact on gonioscopy that obscured
cleft visualization led to a low initial
clinical suspicion of the cleft. There is
also a paucity of literature describing
cyclodialysis clefts resulting from KDB
goniotomy. UBM revealed moderate
anterior chamber depth with irido-
corneal touch peripherally and the
presence of supraciliary fluid at the site
of goniotomy. This prompted Shue and
colleagues to undertake diagnostic
anterior chamber reformation with vis-
coelastic, to confirm the presence of a
cyclodialysis cleft which was then
treated with argon laser photocoagula-
tion. The utility of UBM to identify the
supraciliary effusion seen in cyclodial-
ysis clefts provides a useful supportive
tool to evaluating this as a cause of
postoperative hypotony.
iStent and iStent Inject
The iStent Trabecular Micro-Bypass
(Glaukos Corporation, Laguna Hills,
CA, USA) was given FDA approval in
June 2012 for use in conjunction with

8

cataract surgery, with the purpose of
reducing IOP in adult patients with
mild-to-moderate OAG. It has a
second-generation counterpart – the
iStent Inject (Glaukos Corporation),
which was FDA approved in June
2015, for reducing IOP in adult mild-
to-moderate POAG patients undergo-
ing concomitant cataract surgery
(Samuelson et al. 2019).
Both devices are made of heparin-
coated, non-ferromagnetic titanium,
meant for ab interno implantation into
Schlemm’s Canal (Saheb & Ahmed
2012). While the iStent Trabecular
Micro-Bypass creates a unidirectional
outflow via a sideways cannula with
three retention arches, the iStent Inject
creates a multidirectional outflow via
four perpendicular holes (Pillunat et al.
2017). Both devices have demonstrated
favourable safety and efficacy profiles.
Potential adverse events include stent
obstruction by iris tissue, hyphema,
posterior capsule opacification and
stent malposition, including under-
and over-implantation (Fea et al.
2014; Voskanyan et al. 2014; Arriola-
Villalobos et al. 2016; Popovic et al.
2018).
Our search identified five studies
describing the use of anterior segment
imaging with the iStent class of devices
(Table 1).
Aqueous angiography
With aqueous angiography, it is possi-
ble to demonstrate the effect of iStent
Inject implantation on aqueous out-
flow pathways in the immediate post-
operative period. In a study by Huang
et al., indocyanine green aqueous
angiography was used to establish
baseline angiographic AHO patterns
in the nasal hemisphere of the eye prior
to commencing iStent Inject implanta-
tion in the operating room (Huang
et al. 2019). After tracer introduction,
infrared and angiographic images were
captured by the Spectralis HRA+OCT
(Heidelberg Engineering GmbH, Hei-
delberg, Germany), mechanically sup-
ported by the Spectralis FLEX Module
(Heidelberg Engineering GmbH). The
images were acquired immediately pos-
terior to the limbus, near Schlemm’s
Canal, with the subject looking in
different directions. Once the two
iStent Inject implants were embedded
in the TM, fluorescein aqueous angiog-
raphy was used to document outflow
immediately after implantation, before
transitioning into cataract surgery.
Indocyanine green (preimplantation/
baseline) and fluorescein (postimplan-
tation) angiographic patterns were
compared up until 1-minute past signal
initiation. The time to the first signal
shows from baseline angiography sig-
nificantly decreased after device
implantation. Post-implantation signal
intensity ratios were also 11.2-fold
greater than baseline signal intensity
ratios. Angiographic improvement and
IOP reduction were documented in all
patients with no reported complica-
tions. However, the exact correlation
between these two parameters was not
established.
The authors also observed variation
in angiographic response after trabec-
ular meshwork bypass. Areas with low
signal preoperatively that subsequently
had iStents implanted were found to
demonstrate new signal postoperatively
(termed ‘new recruitment’) (Fig. 7).
Within the same eyes, iStents
implanted adjacent to regions with
prior angiographic signal demonstrated
brighter and earlier signal postopera-
tively (‘earlier recruitment’). Other
patients demonstrated the lack of
‘new recruitment’ but the presence of
‘earlier recruitment’, within the same
eye. The authors postulated that each
site was independent of another due to
the observation of different types of
responses within the same eye and that
other factors apart from distal AHO
pathway regulation may contribute to
these observations.
The main limitation of this proce-
dure is that follow-up aqueous
angiography is difficult to justify since
there is often no clinical indication for
further invasive ocular procedures. It
may be more feasible to utilize the
AS-OCT instead to evaluate angio-
graphically altered regions – tracer-
based imaging may provide better
functional assessment of aqueous out-
flow dynamics compared with sole
structural evaluation (Li et al. 2013).
Real-time measurement of aqueous
humour dynamics also remains chal-
lenging due to intraoperative time
limitations and the need to avoid
unnecessarily compromising visual
outcomes (Huang et al. 2019). Inflam-
matory stimuli during and after sur-
gery may also influence both the
intracameral and episcleral venous
pressures, confounding findings on
aqueous angiography.
Acta Ophthalmologica 2021
AS-OCT
The AS-OCT has been employed for
the iStent Inject to determine the pre-
cise location of the implants postoper-
atively (Gillmann et al. 2019), to
analyse the effects of implantation on
the structures of the iridocorneal angle
after surgery (Gillmann et al. 2018;
Gillmann et al. 2019) and to correlate
the placement of the device to postop-
erative IOP-lowering outcomes (Gill-
mann et al. 2019).
Gillmann et al. (2019) performed
AS-OCT imaging (Spectralis OCT;
Heidelberg Engineering AG) with
radial sections passing through the
implants and additional sections
500 lm temporally beside each
implant. The iStent Inject was clearly
identifiable as a  360 lm long hyper-
reflective hollow device within the TM,
with the central lumen and side holes
appearing as areas of decreased reflec-
tivity (Fig. 8A). However, substantial
OCT signal loss was noted to occur
within the shadow of the iStent Inject,
impairing visualization of the area on
the posterior side of the implant (Gill-
mann et al. 2019). The amount of
iStent Inject extrusion into the AC
was measured to assess whether over-
or under-implantation occurred. In this
study, all the scans clearly showed
normal angle structures post-iStent
Inject implantation and visualized
92% of implants (versus 88% with
gonioscopy) (Gillmann et al. 2019).
The authors postulated that the
remaining 8% of implants which were
not visible on the AS-OCT were hugely
displaced and lodged within the ciliary
sulcus. The inadvertent burying, or
over-implantation, of the iStent Inject
within the trabecular tissue is not
uncommon (Popovic et al. 2018) and
may have clinical implications as bur-
ied iStent Inject implants are associated
with higher postoperative IOPs (Gill-
mann et al. 2019). The AS-OCT may
be used to verify the precise location of
seemingly well-positioned iStent Inject
implants on gonioscopy but with para-
doxically poor filtration.
In a separate paper, Gillmann et al.
(2018) quantitatively assessed, via AS-
OCT, the dilation of Schlemm’s Canal
post-iStent Inject implantation and
postulated that this anatomical change
may contribute to the postoperative
IOP-lowering effect. Under AS-OCT,
Schlemm’s Canal appears as a hypore-
flective ellipsoid area behind the TM
9
Acta Ophthalmologica 2021

Fig. 7. Sequential aqueous angiography in glaucoma patients with trabecular meshwork bypass (TMB) in initially low outflow regions showing new
angiographic patterns. Courtesy of Huang et al. (A-H) The first patient. (I–P) The second patient. (A–D and I–L) First, indocyanine green (ICG)
aqueous angiography was performed. (D, L) Second, TMB was conducted (blue arrows). (E–H and M–P) Third, fluorescein (FL) aqueous
angiography was performed immediately after TMB. (B, F) In the first patient, black arrows point out conjunctival pigment on the cornea that
blocked fluorescence transmission. This location serves as a reference point across all images for that eye. (D, L) Red arrows point out nasal regions of
the eye without initial ICG signal. (H, P) Green arrows point out regions of new fluorescein angiographic signal after TMB. (C) This image serves as
an example of how to calculate an angiographic signal intensity ratio. A 75 9 75-pixel region of interest was placed postlimbal near the region of
TMB (white boxes). For each region of interest, the signal intensity was normalized by dividing it by the signal in a region of known background away
from the proposed areas of TMB (yellow box). This allowed for the assessment of signal intensity in any image, internally normalized to the settings
on the Spectralis. A ratio of 1 would imply that the signal intensity in that region of interest was no different than the background. s = seconds after
signal initiation.

and 320 lm anterior to the angle
(Fig. 8B) (Gillmann et al. 2018). Sch-
lemm’s Canal diameter is estimated to
be approximately 121 lm (Irshad et al.
2010). This case report demonstrated
marked dilation of Schlemm’s Canal
along most of the angle circumference
after iStent Inject implantation, reach-
ing 390 lm at the widest point. While
part of the dilatory effect on Schlemm’s
Canal in eyes undergoing combined
iStent Inject and cataract surgery may
be attributed to the phacoemulsifica-
tion procedure itself (Zhao et al. 2016),
a greater extent of dilation has been
recorded in eyes undergoing combined
surgery compared with standalone cat-
aract surgery, suggesting that iStent
Inject implantation does cause Sch-
lemm’s Canal dilation.
The authors proposed that the iStent
Inject may have a dual IOP-lowering
mechanism – reducing aqueous outflow
resistance via a bypass of the trabecular
meshwork (as intended) as well as
inducing dilation of Schlemm’s Canal,
as also observed following canaloplasty
procedures (Kuerten et al. 2018). The
IOP-lowering outcomes of iStent Inject
implantation may be correlated with

10
 Acta Ophthalmologica 2021

b
b

c
(B)

d
(A)

Fig. 8. (A) Typical appearance of an iStent inject device on anterior segment optical coherence tomography (AS-OCT). Courtesy of Gillmann et al.
The central lumen and side holes on either side of the head are clearly identifiable. Position and depth of implantation within the angle varies widely;
some devices protrude (a–c) and others appear buried within the trabeculum (d). (B) Appearance of Schlemm canal on AS-OCT. The Schlemm canal
(arrows) has the appearance of a hyporeflective ellipsoid area lying immediately behind the trabecular meshwork. Its dimensions are highly variable
from markedly dilated (a) to barely visible (c) or not visible at all.

the degree of device protrusion into the
anterior chamber as well as postoper-
ative Schlemm’s Canal dimensions,
both of which can be quantified by
the AS-OCT.
UBM
Postoperative application. The UBM
may be used postoperatively to locate
misplaced iStent Trabecular Micro-
Bypass implants. In a case report by
Mantravadi et al., the stent was lost
during implantation as it was being
repositioned after the inadvertent
occurrence of localized iridodialysis.
Intraoperatively, they were unable to
locate the misplaced stent. On the first
postoperative day, the implant still
could not be visualized with gonio-
scopy and was suspected to have
migrated into the supraciliary space.
UBM confirmed this suspicion, with
the stent being successfully detected in
the superciliary space, posterior to the
ciliary body. No intervention was per-
formed in view of the patient’s clinical
stability, and no adverse events were
reported.
XEN45 Gel Stent
To date, the XEN45 Gel Stent remains
the only commercially available FDA-
approved MIGS that lowers IOP
through the creation of a filtration bleb,
similar to trabeculectomy surgery
(Chatzara et al. 2019). XEN45 Gel Stent
implantation allows the creation of a
filtration channel through the ab interno
approach with minimal disruption of
underlying lymphatics and drainage
systems. This shortens surgical time,
minimizes damage to surrounding tis-
sues and theoretically decreases the risk
of bleeding, scarring and subsequent
bleb failure (Gedde et al. 2009; Saheb &
Ahmed 2012). Complications include
ptosis, hyphema, hypotony with or
without choroidal effusions, cystoid
macular oedema, as well as implant
blockage, exposure or malposition
(Sng et al. 2019; Hong et al. 2020).
Challenges in XEN45 Gel Stent
implantation include precise placement
and positioning of the stent intraoper-
atively, as well as optimal postopera-
tive bleb assessment and management,
necessary to minimize bleb fibrosis and
scarring (Skuta & Parrish 1987; Fea
et al. 2017; Olate-P
erez et al. 2017;
Vera et al. 2019). Various imaging
modalities have therefore been
explored to enhance postoperative bleb
management. A total of 9 studies,
detailing the use of AS-OCT, anterior
segment OCT angiography and in vivo
confocal microscopy, were identified in
our search for the use of imaging in
XEN45 Gel Stent implantation surgery
(Table 1).
AS-OCT
Postoperative application. Anterior seg-
ment imaging has been used to objec-
tively assess bleb morphology and to
evaluate structure–function correlation
in blebs. Fea et al. utilized the AS-OCT
to evaluate the maximal height of the

11
Acta Ophthalmologica 2021

bleb, total area of hyporeflective cystic
spaces, bleb-wall reflectivity and bleb-
wall thickness, up to 1 year after
surgery. Considering their study sub-
jects as a whole, there was no change in
the measured parameters and morphol-
ogy of the bleb over 1 year, indicating
that any morphologic changes that
occurred after surgery probably did
not progress beyond postoperative
month 1, which was when the first
AS-OCT images were acquired in their
study. However, when comparison was
made between functioning (‘success’)
compared with non-functioning
(‘failure’) blebs, the authors found that
functioning blebs had significantly
greater bleb height and cystic spaces
at 3 and 6 months, as well as signifi-
cantly lower wall reflectivity at all
timepoints during their study. The
correlation between higher bleb-wall
reflectivity and non-functioning blebs
has also been previously reported by
Ciancaglini et al (2008) and Addicks
et al. (1983), and the authors proposed
that the density of the bleb connective
tissue may hence determine postopera-
tive functionality of the bleb.
Mastropasqua et al. (2020) also
reported AS-OCT findings while
assessing the differences between
‘success’ and ‘failure’ groups in terms
of bleb-wall cyst-like structure area
(BCSA), bleb-wall cyst-like structure
density (BCSD) and bleb-wall thick-
ness (BT) after approximately
7.5 months after surgery.
Utilizing a combination of the
above-mentioned parameters, Len-
zhofer et al. (2019a,2019b) classified
XEN45 blebs into four different mor-
phologies – uniform, subconjunctival
separation, microcystic multiform and
multiple internal layers (Fig. 9). The
presence of microcystic multiform mor-
phology was attributed to bleb encap-
sulation by the authors and its
appearance at 3 months was a predic-
tor for surgical failure at 12 months. A
uniform bleb morphology was associ-
ated with higher mean IOP at 1 week
and 3 months compared with other
morphologies, and its presence at
9 months was predictive for surgical
failure at 12 months. The subconjunc-
tival separation morphology appears as
a diffuse distribution of fluid with small
intrableb cysts seen and may suggest
less fibrosis and consequently a lower
outflow resistance of the bleb. This
morphology was associated with lower
mean IOP over the first year postoper-
atively and may demonstrate OCT
characteristics of a well-functioning
early bleb. Olate-Perez et al. also
described the use of AS-OCT in corre-
lating bleb morphology and reflectivity
with function. The authors found that
cystic morphology with low reflectivity
was associated with a higher incidence
of functional blebs and postulated that
bleb morphology may predict bleb
functionality.
AS-OCT has been used to compare
differences in bleb morphology
between trabeculectomy and XEN45
gel stent surgery. Teus et al. compared
the bleb morphologies among healthy
eyes, eyes with successfully functioning
blebs after trabeculectomy and eyes
that underwent XEN surgery, on AS-
OCT. The authors found that the
height of XEN45 blebs was signifi-
cantly lower than trabeculectomy
blebs, with the absence of subepithelial
fibrosis in XEN45 blebs compared with
its presence in 40% of trabeculectomy
blebs. XEN blebs appeared morpho-
logically more similar to healthy con-
junctiva, and this was attributed to the
relative greater restriction to flow in the
XEN45 gel stent, as governed by the
Hagen–Poiseuille equation.
Additionally, AS-OCT has also been
used to detect intraluminal stent

Fig. 9. Bleb morphology in anterior segment optical coherence tomography (AS-OCT) after XEN Glaucoma Gel Stent Implantation. Courtesy of
Lenhzofer et al. Bleb morphology in AS-OCT was classified into four groups. (1) Uniform (top left and top right): No fluid-filled hyporeflective spaces
in the subconjunctival space. (2) Subconjunctival separation (middle left and middle right): multiple small spaces in more superficial layers. (3)
Microcystic multiform (bottom left): multiple cystic hyporeflective areas in deep layer separated by thin septae, which are highlighted with arrows;
their thicker bleb wall makes the bleb appear encapsulated in AS-OCT. (4) Multiple internal layer (bottom right): Hyporeflective spaces in deep and
superficial layers of conjunctiva with channels of fluid parallel to the surface of the sclera, highlighted by arrowheads.

12

obstruction postoperatively. Rigo et al.
(2019) demonstrated the use of AS-
OCT in detecting obstruction of
XEN45 gel stents by connective tissue,
which were not visible on slit-lamp
photography. The imaging characteris-
tics (reflectiveness of material) further
allowed the authors to postulate the
origin of the connective tissue – as from
the anterior chamber or from out-
growth of episcleral fibrous tissue.
AS-OCT may also be used to deter-
mine stent positioning, which may be
correlated with surgical outcomes. Len-
zhofer et al. (2019a,2019b) described
the use of AS-OCT (Visante OCT;
Zeiss, Germany) in determining the
effect of outer stent position on post-
operative reduction in IOP and number
of IOP-lowering medications. Layers of
implantation were classified as intra-
and subtenon, or intraconjunctival,
depending on the location of the outer
lumen as observed on the AS-OCT.
The authors found that deeper implant
position in the intra- and subtenon
group was associated with higher IOP-
lowering efficacy and lower needling
rates. There was a significantly greater
IOP reduction in the intra- and sub-
tenon group compared with the intra-
conjunctival group at week 1, week 2,
month 1 and month 12. At 6 months,
while there was no difference in IOP
reduction between both groups, the
number of IOP-lowering medication
was significantly lower for the intra-
and subtenon groups compared with
the intraconjunctival group. Further-
more, the needling rate was signifi-
cantly lower in the intra- and subtenon
groups compared with the intracon-
junctival group, at 12 months. Overall,
the intra- and subtenon groups showed
higher qualified success at 12 months.
Mozo et al. also described the use of
AS-OCT to confirm the presence in a
single patient of a short XEN segment
that had gone unnoticed intraopera-
tively and was observed on follow-up
in clinic after surgery.
In vivo confocal microscopy (IVCM)
Postoperative applications. IVCM has
been used to examine postoperative
bleb changes in XEN45 gel stent
implantation surgery. Utilizing the
IVCM HRT II/Rostock Cornea Mod-
ule (RCM; Heidelberg Engineering,
Inc, Franklin, MA, USA), Fea et al.
observed that preoperatively, micro-
cysts were already seen in the
superonasal conjunctiva. As optically
clear structures that were round or oval
shaped, they were scattered in distribu-
tion with no signs of clustering and
were surrounded by a hyper-reflective
wall. Postoperatively, microcysts
appeared to be of heterogeneous
shapes and sizes, their distribution
became more clustered, and the sur-
rounding wall exhibited low reflectiv-
ity. There was a significant
postoperative increase in both mean
microcyst area and mean microcyst
density, from preoperatively to
12 months after surgery. The authors
attributed these findings to progressive
aqueous percolation after stent implan-
tation. In addition, the mean subep-
ithelial connective tissue density
(SCTD) decreased significantly from
preoperatively to 6 months but
increased by 12 months postopera-
tively. This was attributed to a slower
manifestation of tissue rearrangement
in the deeper layers. Of the above
parameters, only the SCTD was signif-
icantly different between the ‘success’
and ‘failure’ groups with a greater
SCTD found in the ‘failure’ group,
suggesting the presence of new or
increased alternative aqueous humour
outflow induced by the stent implanta-
tion. This was noted to be contrary to
findings by Ciancalini et al., who pre-
viously reported that all IVCM param-
eters correlated well with bleb
functionality following trabeculectomy
surgery (Ciancaglini et al. 2008).
AS-OCT angiography (AS-OCTA)
Postoperative application. The AS-
OCTA may enable the surgeon to predict
surgical success through the measure-
ment of bleb angiographic parameters
after XEN45 gel stent implantation.
Overall, less vascularized blebs have
been shown to be correlated with lower
IOP values after filtering surgery
(Hayek et al. 2019; Seo et al.,
2019a,2019b). Histological studies
(Picht & Grehn 1998; Sacu et al.
2003; Messmer et al. 2006) have also
demonstrated that less vascularized
blebs are less inflamed and less prone
to fibrosis due to the reduced supply of
fibroblast-stimulating cytokines. The
inflammatory response has been linked
to trauma and the degree of postoper-
ative inflammation, as well as to the
preoperative state of the conjunctiva,
episcleral and integrity of the blood-
aqueous barrier.
Acta Ophthalmologica 2021
Mastropasqua et al (2020) reported
the use of the AS-OCTA (AngioVue
OCTA system; Optovue Inc., Fremont,
CA, USA) in the measurement of
vessel displacement areas (VDAs),
major vessel displacement area
(MVDA), non-flow whole area
(NFWA) and bleb-wall vessel density
(BVD) (Fig. 10). VDAs were defined as
flow-void areas in the whole OCTA
image, delimited by flow vessel signals,
whose size had to be at least one-third
of a single quadrant of the colour-
coded angiographic map. MVDAs
were defined as the largest flow-void
area in the whole OCTA image.
NFWAs were defined as the sum of
each VDA, including the MDVA. BVD
was defined as the percentage area
occupied by vessels in the whole
3 9 3 mm OCTA image. The authors
demonstrated that VDAs were found
in all successful blebs but only in
28.4% of failed blebs. Significantly
higher NFWA, VDAs and MVDAs
were found in the ‘success’ population
(Fig. 11). Conversely, lower mean (SD)
BVDs were found in the ‘success’
population at 46.19 (3.82) versus
54.15 (4.40).
Hence, the AS-OCTA may allow for
the early assessment of bleb vascularity
– which is associated with bleb dys-
function – while changes remain clini-
cally undetectable. This is supported by
Seo et al who reported a good corre-
lation between OCTA colour and
brightness densities of the bleb-wall,
with bleb vascularity after trabeculec-
tomy. Early detection of vascularity by
OCTA can allow for targeted interven-
tion or increased follow-up frequency
for eyes, which are at higher risk of
failure.
Discussion
This systematic review summarizes
how imaging has been explored for
use in all three preoperative, intraop-
erative and postoperative stages of
MIGS.
The minimally invasive nature and
fine surgical precision required in
MIGS have provided an impetus for
surgeons to explore intraoperative
imaging as an aid to maximize surgical
success. Outcomes of angle-based
MIGS depend on good visualization
of angle anatomy and accurate evalu-
ation of surgical end points. Even
minute variations in implantation
13
Acta Ophthalmologica 2021

(A) (C) (E)

(B)
(D) (F)

Fig. 10. Angiographic and structural scans of a functioning filtration bleb. Courtesy of Mastropasqua et al. (A) Vessel density perfusion map
(warmer colour corresponding to greater flow) showing numerous and confluent vessel displacement areas (VDAs) (asterisks) and the major vessel
displacement area (MVDA) (arrowhead). (B) Slit-lamp biomicroscopy of the XEN gel stent-related filtration bleb. (C) En face optical coherence
tomography (OCT) angiogram showing a rarefied bleb-wall vascularity. (D) Co-registered structural B-scan showing the blood flow signals (in red)
within the bleb wall. (E) En face OCT bleb-wall image highlighting the XEN gel stent (arrows). (F) Co-registered structural B-scan, showing intra-
bleb-wall hyporeflective cysts (arrowhead) along with a microcyst (asterisk) inside the typical ‘double-layer’ hyper-reflective signal of the XEN gel
stent (red arrow).

depth of angle-based devices have been
shown to influence postoperative effi-
cacy – intraoperative imaging may be
able to provide the resolution needed
to achieve this level of surgical preci-
sion (Heindl et al. 2015; Junker et al.
2017). Ablative or excisional angle-
based procedures may have better out-
comes with clear surgical endpoints,
which may be better defined with
intraoperative imaging (Wecker et al.
2017; Gillmann et al. 2019). Current
FDA-approved subconjunctival MIGS
involves the use of stents which, with
their microlumens, also demand
greater placement precision to ensure
good outcomes. iOCT has been
described previously in the PIONEER
(Ehlers et al. 2014) and DISCOVER
(Ehlers et al. 2018) studies, with the
vast majority of iOCT utilization in
these instances being in corneal trans-
plantation. The real-time visual feed-
back provided by iOCT was found to
aid surgical decision making and tech-
nique, as well as provide information
on endothelial graft orientation and
positioning. Intraoperative imaging
may also serve as an invaluable teach-
ing tool for observers and novice sur-
geons. These key benefits are relevant
and translatable to MIGS where pre-
cise manoeuvring and implant place-
ment are crucial to success. However,
while intraoperative imaging technol-
ogy has seen significant advancements
in recent years, remaining challenges
discourage the widespread clinical use
of this technology. These include tech-
nical difficulties in incorporating imag-
ing modalities into the surgical
microscope, variable quality of images
and optical interference from ocular
structures or surgical instruments
(Heindl et al. 2015; Ehlers et al. 2017;
Junker et al. 2017).
With increasing confidence and
familiarity with MIGS, there is grow-
ing interest in improving patient selec-
tion and in better predicting treatment
response. AHO pathways and the dis-
tal outflow resistance are postulated to
limit the efficacy of angle-based MIGS
and this has been corroborated by
imaging studies (Hann et al. 2011;
Wecker et al. 2017). The potential of
imaging to define the structure, func-
tion and distribution of collector chan-
nels and AHO pathways in individual
eyes as well as the effect of TM bypass
device implantation on these AHO
pathways is an area for further
research. Once better understood, this
information may allow a more targeted
approach to the placement of angle-
based MIGS devices, which may yield
more predictable and efficacious post-
operative outcomes (Huang et al.
2019). Imaging studies in subconjunc-
tival MIGS have established correla-
tions between preoperative structural
and functional conjunctival character-
istics with postoperative outcomes.
This understanding may be used to
improve the predictability of subcon-
junctival MIGS.
This use of imaging to elucidate
structure–function relationships may

14
 Acta Ophthalmologica 2021

(A) (C) (E)

(B) (D) (F)

Fig. 11. Angiographic and structural scans of a failed filtration bleb. Courtesy of Mastropasqua et al. (A) Vessel density perfusion map (warmer
colour corresponding to greater flow) showing scattered vessel displacement areas (VDAs) (asterisk), without evidence of the major vessel
displacement area (MVDA). (B) Slit-lamp biomicroscopy of the XEN gel stent-related filtration bleb. (C) En face optical coherence tomography
(OCT) angiogram showing a dense bleb vascularity. (D) Co-registered structural B-scan showing numerous and wider blood flow signals (in red)
within the bleb wall. (E) En face OCT bleb-wall image highlighting the XEN gel stent (arrows). (F) Co-registered structural B-scan, showing only one
isolated bleb-wall hyporeflective cyst (asterisk) contained inside the hyper-reflective signal of the XEN gel stent (arrow).

deepen our understanding of the mech-
anisms of action of MIGS and provide
corroborative outcome measures of
efficacy postoperatively. While angle-
based devices such as the iStent were
postulated to function via simple
bypass of the TM, AS-OCT studies
now demonstrate the possible addi-
tional effect of Schlemm Canal dilation
in reducing IOP (Gillmann et al. 2019).
The AS-OCT has also revealed signif-
icant changes in anterior chamber
anatomy after trabectome surgery.
Further studies may be useful in exam-
ining the correlation of these anatom-
ical changes to long-term IOP
reduction. More advanced AS-OCT
modalities such as the 3D-micro-CT
and SD-OCT have also been used to
evaluate distal outflow pathways and
may be potential imaging modalities
for future studies evaluating correla-
tions between anatomical changes and
clinical outcomes (Kagemann et al.
2010; Hann et al. 2011; Li et al. 2017).
Overall, anterior segment imaging in
MIGS appears to be applied most in
the postoperative phase. It has been
used to identify procedural
complications, provide objective infor-
mation of implant location in relation
to surrounding anatomy and assess the
postimplantation structural impact of
MIGS devices. Imaging has been
shown to have a critical role in locating
misplaced MIGS devices, which is
often challenging clinically due to the
size and location of these implants. An
in vitro study not included in our
review compared the utilization of
three imaging modalities – the UBM,
AS-OCT and B-scan ultrasonography
– to locate two intentionally misplaced
iStent implants in human cadaveric
eyes. This study reported that UBM
may be most useful in locating iStent
implants in the anterior or posterior
chamber, while the AS-OCT may be
used for stent detection in the anterior
chamber (Ichhpujani et al. 2010). Being
easily accessible, these imaging options
are likely to be clinically useful in
locating missing MIGS implants. In
addition, imaging may be used to
confirm the occurrence of other
MIGS-related complications – the
UBM and AS-OCT have been used to
diagnose cyclodialysis clefts after both
trabectome and KDB surgeries (Berk
et al. 2017; Shue et al. 2019).
Imaging may play an important role
in the postoperative diagnosis and
management of bleb failure and scar-
ring after subconjunctival MIGS.
Imaging studies have characterized
the process of bleb scarring and con-
solidation, through parameters such as
bleb height, area of cystic spaces, bleb-
wall reflectivity and thickness (Fea
et al. 2017; Lenzhofer et al.
(2019a,2019b); Teus et al. 2019). Infor-
mation on these bleb parameters may
be used to further establish correlations
in postoperative structure–function
outcomes. AS-OCT may further iden-
tify the pathophysiology of failure –
demonstrating obstruction of subcon-
junctival stent tip by fibrotic tissue,
encapsulation or diffuse subconjuncti-
val scarring. This may allow a more
targeted approach to postoperative
bleb management and needling. In
addition, imaging may minimize the
risk of inadvertent stent truncation and
damage during needling of XEN45
blebs, particularly when there is poor
visualization during the procedure due

15
Acta Ophthalmologica 2021
to significant encapsulation or subcon-
junctival haemorrhage.
This review aims to be comprehen-
sive but nonetheless faces certain lim-
itations. Due to the heterogeneity of
the data collected, no meta-analysis
could be performed to pool the results
of the studies. The expansive spectrum
and various definitions of ‘MIGS’
necessitated that we focused our review
on only FDA-approved MIGS. The
use of imaging in other ‘MIGS’ proce-
dures may be instructive and translat-
able; however, they were not included
for the purposes of this paper.
Conclusion
Barriers to the widespread adoption of
imaging in MIGS continue to exist,
given the still exploratory nature of
many studies as well as limitations in
feasibility and cost. However, this sys-
tematic review summarizes current lit-
erature and demonstrates the clear
potential of imaging in all pre-, intra-
and postoperative phases, in both
angle-based and subconjunctival
MIGS. With the continued, rapid
development of both MIGS and oph-
thalmic imaging, it is imperative that
surgeons continue to explore ways to
integrate both technologies, to opti-
mize their surgical outcomes and suc-
cess of MIGS.
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Appendix S1. Acta Prisma checklist.