(see Figure 6 for Model GTS100R).
45-0074 Rev 9 05/24

DIRECTIONS FOR USE/PACKAGE INSERTGlaukos® Corporation iStent® Trabecular Micro-Bypass Stent
SystemDIRECTIONS FOR USE TABLE OF CONTENTS
1. DEVICE DESCRIPTION

10. STORAGE REQUIREMENTS

2. INDICATIONS FOR USE

11. EXPIRATION DATE

3. CONTRAINDICATIONS

12. RETURN GOODS POLICY

4. WARNINGS

13. CLINICAL TRIAL RESULTS

5. PRECAUTIONS RESULTS

14. POST-APPROVAL STUDY RESULTS

DIRECTIONSFOR
USE/PACKAGE
INSERT
DIRECTIONSFOR
USE/PACKAGE
6. ADVERSE REACTIONS
15. LABELING INSERT® ® Trabecular Micro-Bypass Stent System
Glaukos
Corporation
iStentGlaukos
Corporation
iStentTrabecular Micro-Bypass Stent System
7. INSTRUCTIONS FOR USE
16. MRI SAFETY INFORMATION
DEVICEDESCRIPTION
8. ADVERSEEVENT REPORTING
DEVICEDESCRIPTION

17. CAUTION®
9. HOW® SUPPLIED
The
iStentTrabecular Micro-Bypass Stent Model GTS100R/L is an intraocular stent that is

The iStent Trabecular Micro-Bypass Stent Model GTS100R/L is an intraocular stent that is
manufactured
fromtitanium(Ti6Al4V
is heparincoatedDuraflo
1. DEVICE DESCRIPTION
manufactured
fromtitanium(Ti6Al4V
ELI)ELI)
andandis heparincoatedwithwith
Duraflothatthatis ispurchasedfrom
Edwards
LifeSciences(note:
theporcinesourceoftheheparinis from
The iStent®
Trabecular
Micro-Bypass
Stent(Models
GTS100Rand
GTS100L)
is isanfrom
purchasedfrom
Edwards
LifeSciences(note:
theporcinesourceof theheparinintraocular
stent
that
is manufactured
fromtitaniumELI)
andis heparin
animalsraisedinNorth
America).
has
a single
piece
design,is 1.0animalsraisedonlyonlyin NorthAmerica).
TheThestentstenthas(Ti6Al4V
a single
piece
design,is coated
1.0
mmmm
in in
(note:
theheparinfrom
awith
porcinesource).
The
has
a and
singlepiece
design,is of oflength,0.33
mm
inisheight,
a snorkel
lengthofstent
0.25
mm,
a snorkel
bore
diameterlength,0.33
mm
in height,
witha snorkel
length
of
0.25
mm,
and
a snorkel
bore
diameter
1.0 mmin length,
120µm(Figure120µm(Figure1). 1).0.33 mm in height, with a snorkel length of 0.25 mm, and a snorkel
bore diameter of 120µm (Figure 1).

Stent
Height Snorkel
Snorkel
Stent
Heightmm Long)(.330 (.330mm) mm) (.250(.250mm Long)

SnorkelInsideSnorkelInsideDiameter(120(120μm)µm)
Diameter
Retention
Retention
ArchesArchesRail Rail(Only one rail
(Only one rail
is visible)
is visible)

Body
mm Long)Body(1.00(1.00mm Long)

Self-Trephining
Self-Trephining
TipTipFigure1.
iStent;
front
view
of
right
stent
GTS100R
Figure
1. iStent;of right
GTS100R
Figure
1. iStent;
frontfront
viewviewof right
stentstent
GTS100R
The iStent has an “L”-shaped structure with a snorkel (inlet) on the short side which
iStenthasan L-shaped
structurewitha snorkel
on the
short
side
which
resides
TheTheiStenthastheananterior“L”-shaped
structurea openssnorkelon the
short
side
which
resides
residesinchamber,
and withwhichto(inlet)the(inlet)
half-pipe
body
which
residesintheanterior
chamber,
and
which
opens
to
the
half-pipe
body
which
residesinSchlemmsin theanterior
chamber,
and
which
opens
to
the
half-pipe
body
which
residesinSchlemm’sin Schlemm’s canal. The closed side of the body (Figure 1) sits against the inner wall of
canal.
closedsideof thebody(Figure1)closedsitsagainstoftoSchlemmscanal.
canal.
TheTheclosedside
ofretention
thebody(Figuresits
againsttheoftheinner
wallwallof Schlemm’s
canal.
Schlemm’s
canal.
The
arches
on1)
the
side
theinnerbody
serve
securely
retentionarchesontheclosed
side
of
the
body
serve
to
securely
fixatethedevice
TheTheretentionarchesontheclosed
side
of
the
body
serve
to
securely
fixatethedevicefixate the device in Schlemm’s canal. The open half-pipe part of the body (Figure 2) is in in
Schlemms
canal.
The
half-pipeof thebody(Figureis against
the
outer
Schlemm’s
canal.
The
open
half-pipe
partpart
of
the
body
(Figure2) is2)againstthe edges
outer
wall
in in
against the
outer
wall
inopenorder
to accesscollector
channels.
The
rails
are theof wallorder
to accesscollector
channels.
The
theof1,theopen
half-pipe.
Figureorderaccesscollector
channels.
railsrails
the
edges
of theopen
half-pipe.
Figure2 2
thetoopen
half-pipe.
Figure2 showsThea view
ofare
thearestent
inedgesFigurerotated180
degrees,shows
a viewof thestent
in ofFigure1, rotateddegrees,
to display
open
half-pipeshows
a viewof thestentin Figurerotated180180degrees,
to display
the theopen
half-pipeof ofto display
theopen
half-pipe
the1,stent
body.
body.
the thestentstentbody.
RailsRails
Body
Body
(open
half-pipeshown)(open
half-pipeshown)

SnorkelSnorkelSelf-Trephining
Self-Trephining
TipTip2. view
iStent;of openbody(rightstent
GTS100R)
Figure
2. iStent;
view
of
open
stentstentbody(rightstent
GTS100R)
Figure2.Figure
iStent;ofview
open
stent
body
(rightstent
GTS100R)

When
properly
implanted,
iStentisis intended
totocreate
a abypassthroughtrabecularWhenproperly
implanted,
the theiStentis intended
to create
a bypass
throughthe thetrabecularWhenproperly
implanted,
theiStentintendedcreatebypassthroughthemeshwork
to Schlemmscanal
to improve
outflow
throughnaturalphysiologic
meshwork
to Schlemm’s
canal
to improveaqueousoutflow
throughthe thenaturalphysiologic
trabecularmeshworktoSchlemm’s
canaltoaqueousimproveaqueousoutflow
throughthepathway.
The
implant
is provided
to thea pre-loaded
configurationin orderpathway.
implant
isprovidedthesurgeonin ainpre-loaded
configurationin orderto tonaturalThephysiologic
pathway.
Thetoimplant
issurgeon
providedtothe surgeon
in a pre-loaded
allow
preciseinsertion
Schlemms
canal.
The
inserterbeen
designedallow
for forpreciseintointo
Schlemm’s
canal.
The
inserterhas hasbeen
designed
by byconfiguration
ininsertionorder
to allowfor
preciseinsertion
into
Schlemm’s
canal.
The
inserterhas been designed by Glaukos® Corporation to hold the implant and to release theimplant once it has been inserted within Schlemm’s canal. Two model numbers of the
iStent Trabecular Micro-Bypass Stent (GTS100R and GTS100L) are available. The last
digit of these model numbers (R and L) correlates to a right-flow stent and a left-flow pg. 1 pg. 1
stent, respectively. The stents are identical except the body faces opposite directions inorder to facilitate nasal stent placement. Model GTS100L is designed for the left eye, andModel GTS100R is designed for the right eye (Table 1).
The Glaukos iStent Trabecular Micro-Bypass Inserter (Model GTS100i) is also available ina stand-alone configuration; i.e., the Inserter (Model GTS100i) does not have an iStent
Trabecular Micro-Bypass Stent attached to the tip when packaged in this configuration.
The inserter is provided as a single-use, disposable device that is able to reacquire thestent intraocularly should the surgeon determine it is necessary.
TABLE 1
Glaukos Corporation iStent Trabecular Micro-Bypass Stent System
Catalogue # Description
GTS100L
Left-flow iStent attached to disposable inserter, designed for left eye
GTS100R
Right-flow iStent attached to disposable inserter, designed for right eye
GTS100iStand-alone inserter (no stent attached)

4. The safety and effectiveness of the iStent Trabecular Micro-Bypass Stent has not been
Figure 10a. Approach the stent as shown on right, and press down on the release button
established as an alternative to the primary treatment of glaucoma with medications.
as shown on left.
The effectiveness of this device has been demonstrated only in patients with mild tomoderate open-angle glaucoma who are currently treated with ocular hypotensive
TemporalNasal
medication and who are undergoing concurrent cataract surgery for visuallysignificant cataract.
5. The safety and effectiveness of the iStent Trabecular Micro-Bypass Stent has not been
Direction of feet of
established in patients with the following circumstances or conditions which were
patient
not studied in the pivotal trial:• In children
Figure 10b. While holding down the release button (left), position the snorkel of the stentin the inserter (right).
• In eyes with significant prior trauma
FigureFigure
6.
• In eyes with abnormal anterior segment
6.
Gonioscopic
View of
Approachto Trabecular
Meshwork(right eye)
• In eyes with chronic inflammation
Gonioscopic
View
of Approachto Trabecular
Meshwork(right eye)
• In glaucoma associated with vascular disorders
d. Locate the trabecular meshwork, and look for bifurcated areas based on asymmetric• In pseudophakic patients with glaucoma
d. Locate thetrabecularmeshwork,
lookfor bifurcated
areas
based
on asymmetricareasof pigmentation,
andandselectan implant
location
below
the horizontal
midline ofareas of thepigmentation,
andadjacentselect antoimplant
location areas
below(which
the horizontal
midlinecollectorof• In uveitic glaucoma
meshwork andany pigmented
could represent
the laser
tip of thestentandandtheadjacent
TM (Figure7a). Insert
self-trephiningtip
the meshwork
to any pigmented
areas the(whichcould representstentcollector• In patients with prior glaucoma surgery of any type including argon
channels).
Figure 10c. Release the release button (left). The stent is now grasped in the inserter (right).
trabeculoplasty
through the channels).
trabecularandSchlemm’s
canal(FigureA slightcanale. Gentlymeshworkslide the stent
tip into
throughthe trabecularmeshwork
and7b).
into Schlemm’s• In patients with medicated intraocular pressure greater than 24 mmHg lifting motion
maysliderequired
forthroughinsertion.
The
stent
shouldbe inserted
thattheatbethe(3 tothe4:00
o’clock
position
for andtherighteye; so
8 to
9:00
o’clocke. Gently
thenasalstentpositiontip
trabecularmeshwork
into Schlemm’s
canal• In patients with unmedicated IOP less than 22 mmHg nor greater than 36rails
mmHg
position
for walltheeye),with theposition
tipof thedirectedi.e., towards
are locatedtheposition
backSchlemm’s
canalandtheright
stent
body
paralleltoat theonnasal(3 left
toof4:00
o’clock
forimplanttheeye;
8inferiorly,
tois9:00
o’clock
after “washout” of medications
the
foot:
Figure7 offor(Figure
anexampleof
Model
GTS100R
in a right
the
tip
of
and
the Note:TM
7a).
Insertthe self-trephining
stent tip
positionfor patient’s
the the
left
eye),
with
the
tip
the
implant
directed
inferiorly,i.e.,towards
the iris plane(Figures7c stentand see7d).
minimalblood
refluxisinsertiona normaleye. theApproach
the trabecularmeshwork
anModelapproximate
15º(Figure
angle
theslight• For implantation of more than a single stent
theresponse
patient’s
foot:see Figure
for anexampleinsertion
inalla A
throughtrabecularmeshwork
andalthoughintoatofSchlemm’s
canalphysiologicalto placementof7 thestent,
this GTS100R
does
notoccurbetweenin7b).
tip motionof the stentandtheTM (Figure7a). at
Insertthe stent
self-trephining
stent
tip through• After complications during cataract surgery, including but not limited to,
right
eye.
Approachthetrabecularmeshworkanapproximate
15⁰
angle
betweenliftingmayberequiredfor
insertion.
Theshouldbeinsertedsothat thecases.
Schlemm’s canalslightsevere corneal burn, vitreous removal/vitrectomy required, corneal injuries, orrailstheare trabecularlocated onmeshwork
the back andwall intoof Schlemm’s
canal (Figure
and the 7b).
stent Abodyis liftingparallel tomay (Figures
be required7c
for andinsertion.
stent should
be inserted
so that isthearails
complications requiring the placement of an anterior chamber IOL
the motion
iris plane7d). TheNote:
minimalblood reflux
normalcanal
are located on the backSchlemm’swall of Schlemm’s
canal and the stent body is parallel to the• When implantation has been without concomitant cataract surgery with IOL
physiological response to placement of the stent, although this does notpg.occur
in all7
Figures 10a, 10b and 10c. Steps To Reacquire an Implanted Stent
iris plane (Figures 7c and 7d). Note: minimal blood reflux is a normal physiologicalimplantation for visually significant cataract
Figures 10a, 10b and 10c. Steps To Reacquire an Implanted Stent
cases.
15⁰
response
toplacementofthestent,
although
this
does
not
occur
in
all
cases.
6. The safety and effectiveness of the iStent Trabecular Micro-Bypass Stent has not been
established in patients with pseudoexfoliative glaucoma and pigmentary glaucoma,
Schlemm’s canal
8. ADVERSE EVENT REPORTING
because the pivotal trial was not powered to evaluate the outcomes of these groups.
Adverse events
potentially sight-threatening complications that may reasonably
ADVERSEEVENTand/or
REPORTING
Figure7a
The safety and effectiveness of the iStent has also not been established in patients Figure 7a15⁰
be regarded as device related must be reported to Glaukos Corporation at:
Figure 7b
with other secondary open-angle glaucomas.
U.S. Toll
Free and/or
Phone potentially
Number: 1-800-GLAUKOS(452-8567)
Adverseeventssight-threatening
complications that may reasonably be
regarded
as devicerelatedmust949-367-9600
be reported to Glaukos Corporation at:
Alternate
Phone
Number:
6. ADVERSE REACTIONS
Figure 7a
Figure 7a
Refer to the Pivotal Clinical Trial Results section for the adverse events that occurred in
Fax Number: 949-297-4540
Figure 7b
U.S. Toll Free Phone Number: 1-800-GLAUKOS (452-8567)
the pivotal clinical trial. Additional adverse events that may be reasonably associated
Alternate
Phone
Number: 949-367-9600
9. HOW
SUPPLIED
with the use of the device include but are not limited to the following: anterior chamber
Fax
Number:949-297-4540
Glaukos
iStentTrabecular Micro-Bypass Stent (Models GTS100R and GTS100L):
shallowing, severe, prolonged, or persistent intraocular inflammation, aqueous
The stent is attached to the tip of a single-use inserter, and the system
misdirection, choroidal effusion, choroidal hemorrhage, corneal decompensation,is provided sterile and nonpyrogenic in a blister tray. Each stent system
corneal injury, corneal opacification, cyclodialysis cleft, damage to trabecular meshwork,
HOW
is SUPPLIED
individually serialized, and the serial number is provided on the tray
hyphema, hypopyon, hypotony, hypotony maculopathy, IOL dislocation, iridodialysis, Figure 7c
Figure 7d
lid and unit carton. The device has been sterilized by gamma radiation.
loss of vitreous, perforation of sclera, posterior capsular bag rupture, proliferative
GTS100R/L Stent System:
vitreoretinopathy, pupillary block, pupillary membrane formation, retinal detachment,
TheGlaukos
stent is attachedto the tip Micro-Bypassof a single-useInserter
inserter,(Modeland theGTS100i):
system is provided sterile andiStent Trabecular
Figure 7. Insertion of Stent through Trabecular Meshwork
Figure 7d
Figure 7c
retinal dialysis, retinal flap tears, secondary surgical intervention, including but notnonpyrogenic
in iStenta blister
tray. Eachstent system
is individuallyserialized,is andthe serial
The Glaukos
Trabecular
Micro-Bypass
Inserter(Model GTS100i)
a stand-alone
Figure 7a. Approach trabecular meshwork
limited to glaucoma surgery, stent inadvertently released from inserter in eye, stentinserter; i.e., the Model GTS100i does not have an iStent Trabecular Micro-Bypass Stent
Figures
7b-7d.
Insertion
throughtrabecularmeshwork
into
Schlemm’s
Canal
Figure 7.
7. Insertion
dislocation, stent not retrievable, stent not visible with gonioscopy, stent malfunction,
FigureInsertion ofof Stent
Stent throughthrough TrabecularTrabecularMeshwork
Meshwork
attached to the tip when packaged in this configuration. The inserter (Model GTS100i)
Figure 7a.
and vitreous hemorrhage.
Figure7a. Approach
Approachtrabecular
trabecularmeshwork
meshworkis provided sterile and nonpyrogenic in a blister tray. Each inserter has a lot number
Figures
7b-7d.
Insertion
throughtrabeculartry
meshwork
into
Schlemm’s
Canal
If there is difficultyFigureswith insertion
at the desired
insertingabout
0.5 clock7b-7d. Insertion
through location,
trabecularmeshwork
into
Schlemm’s
Canalwhich is provided on the tray lid and unit carton. The device has been sterilized by
7. INSTRUCTIONS FOR USE
hour inferior (i.e., if the first attempt is at 3:00 in the right eye, move inferiorly to thepg. 10
gamma radiation.
If there is difficulty with insertion at the desired location, try inserting about 0.5 clock
Cataract Surgery
3:30 position; ifIf thefirstattemptis
at insertion
9:00
in theleft
eye,inmove
inferiorly
toinferiorly
theabout
8:30to0.5
there
isinferiordifficultywithat thedesiredlocation,try moveinserting
clock
hour
(i.e.,
ifthefirstattempt
is
at
3:00
the
right
eye,
the
1. Cataract surgery with IOL implantation should be performed first followedbyhour3:30
inferior(i.e.,if if
firstatfor3:00
theeye,right
eye,inferiorly
move inferiorly
10. STORAGE REQUIREMENTS
position).
Continuetomoveinferior
asattempt
neededattempts.
Note:
position;thethefirstattempt
is atis9:00
insubsequent
theinleft
move
to the 8:30to theimplantation of the iStent.
The device should be stored at room temperature in the range of 15-30º C.
3:30position).
position;
if theorfirstattempt
is at 9:00
inpreventthe lefteye,
move
the 8:30
Implanting superior
to the 3:00
9:00
positions
may
the
tip
of inferiorly
thedevicetoNote:
Continuetomoveinferiorasneededforsubsequentattempts.
2. The stent implantations are designed for nasal placement; therefore, surgery is to beposition).
Continuetomoveinferiorasneededforsubsequentattempts.
Note:
Implanting
superior
to
the
3:00
or
9:00
positionsmay
prevent
the
tip
of
the
devicefrom penetrating tissue due to the circular geometry of the eye.
11. EXPIRATION DATE
performed from the temporal side of the head.
Implanting
superior tissue
to thedue
3:00
or circular
9:00 positions
prevent
from penetrating
to thegeometrymayof theeye. the tip of the device
The expiration date on the device package (tray lid) is the sterility expiration date. In
3. If the angle needs to be deepened after cataract surgery for placementf.of the
iStent,Release the stentbypushing
thebyduebuttonontheinserter.
Once
the
stent
in is infrom
penetrating
tissueto thecirculargeometryofthe eye.
f. Release
the stent
pushingthebuttonon the inserter.
Once
the isstent
addition, there is a sterility expiration date that is clearly indicated on the outside of the
an intracameral miotic should be injected.
Schlemm’s canal, gently
tap
the
side
of
the
snorkelwiththeinserter
to
align
the
body
Schlemm’s canal, gently tap the side of the snorkel with the inserter to align the bodyunit carton. Sterility is assured if the tray seal is not punctured or damaged until thef. Release
the stent by pushing the button on the inserter. Once the stent is in
Stent Implantationof the stent in Schlemm’s
canal(Figure canal
8). The
body
stent
will
notwillbenotalignedof the stentin Schlemm’s(Figure8). ofThethebodyof thestent
be aligned
expiration date. This device should not be used past the indicated sterility expiration
Schlemm’s canal, gently tap the side of the snorkel with the inserter to align the body
1. Select the model for implantation (i.e., Model GTS100L or Model GTS100R). within Schlemm’s
withinSchlemm’s
canalwithout
this last step.
date.
canal
without
thislaststep.(Figure
of
the
stent
in
Schlemm’s
canal
8).
The
body
of
the
stent
will
not
be
aligned2. The peel pouch containing the iStent Trabecular Micro-Bypass Stent System should
within Schlemm’s canal without this last step.
be opened onto the sterile field. Caution: Do not use the device if the Tyvek® lid has
12. RETURN GOODS POLICY
Schlemm’s canalbeen opened or the packaging appears damaged. In such cases, the sterility of the
Please contact Glaukos Corporation.
device may be compromised.
Schlemm’s canal
13. PIVOTAL CLINICAL TRIAL RESULTS
3. Grasp the inserter as shown in Figure 3 with your index finger on the release button.
With the release button on the inserter facing up, ensure that the orientation of the
Description of the Randomized Clinical Trial
The study was a prospective, randomized, controlled, open-label, multicenter trial. A
stent on the inserter is appropriate for the desired nasal implantation as shown intotal of 27 sites throughout the U.S. enrolled subjects in the randomized phase of the
Figure 4a for the Model GTS100L and in Figure 4b for the Model GTS100R.
study. A total of 240 eyes of 239 patients meeting the study eligibility criteria wererandomized in a 1:1 fashion to undergo either implantation of the iStent in conjunction
Figure 8. Figure 8.
with cataract surgery (treatment group) or cataract surgery without implantation of the
Figure8.
Release stent andtap sideto align
stentSchlemm’s
canalReleasestentwithand inserter
tap side withinsertertoin
alignstent in Schlemm’s
canal
iStent (control group). Subjects in this randomized population were treated from April
Release stent and tap side with inserter to align stent in Schlemm’s canal13, 2005 through June 28, 2007. All subjects were followed for a period of 2 years. A totalh.
WithdrawAtheviewof theimplanted
withchamber.
the snorkel visible isg. Verifythe
thatinserter.
the inlet ofsnorkelis visible
in thestentanteriorof 117 eyes of 116 subjects were enrolled in the treatment group, and 123 subjects wereg.
Verify that theshown
inletof
the insnorkel
isintheimplanted
anterior stentchamber.
below
Figure9. visibleh.
Withdraw
theinserter.
A
view
of
the
with
the
snorkelvisibleisshowng.
Verify that the inlet of the snorkel is visible in the anterior chamber.
enrolled in the control group. To obtain additional safety information, the study also
below in Figure 9.
included a separate non-randomized arm of patients to undergo iStent implantationin conjunction with cataract surgery. A total of 50 subjects were enrolled in this armof the study (also see additional detail below in the section entitled “Non-Randomized
pg. 8
Cohort”). Study subjects were diagnosed with mild to moderate open-angle glaucoma
FigureFigure3.3.Hand
Handposition
positionon
oninserter
inserterpg. 8(OAG). Pseudoexfoliative and pigmentary glaucoma were acceptable diagnoses.
Figure3.3.Hand
Hand position
position onon
inserterFigureinserter
Nasal
Mild to moderate open-angle glaucoma was defined in the study protocol as:
Temporal
1. Enlarged C:D ratio consistent with glaucoma, but still ≤ 0.8, given the requirement forearly stage glaucomatous disease
Direction of feet of
2. Either visual field defect or nerve abnormalities consistent with glaucoma.
patient

2. INDICATIONS FOR USE
The iStent Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicatedfor use in conjunction with cataract surgery for the reduction of intraocular pressure(IOP) in adult patients with mild to moderate open-angle glaucoma currently treatedwith ocular hypotensive medication.
3. CONTRAINDICATIONS
The iStent Trabecular Micro-Bypass Stent is contraindicated under the following
circumstances or conditions:• In eyes with primary angle closure glaucoma, or secondary angle-closure glaucoma,
including neovascular glaucoma, because the device would not be expected to workin such situations• In patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or
any other type of condition that may cause elevated episcleral venous pressure
4. WARNINGS
1. The following conditions may prohibit sufficient visualization of the angle required
for safe and successful stent implantation: corneal haze, corneal opacity, or any otherconditions that may inhibit gonioscopic view in the intended implant location.
2. The surgeon should perform gonioscopy prior to taking a patient to surgery to
exclude congenital anomalies of the angle, peripheral anterior synechiae (PAS),
rubeosis, and any other angle abnormalities that could lead to improper placementof the stent and pose a hazard.
3. Regarding the Magnetic Resonance (MR) status of the implant, non-clinical testinghas demonstrated that the iStent Trabecular Micro-Bypass Stent (Models GTS100R
and GTS100L) is MR Conditional. Please see the “MRI SAFETY INFORMATION” section
at the end of this document for conditions for safe scanning.
5. PRECAUTIONS
1. The surgeon should inform the patient that the stent is MR-Conditional (as noted on
their Patient ID card), and if the patient needs to undergo an MRI, they should let theirdoctor know they have an iStent implanted in their eye.
2. After the surgery, the surgeon should give the patient the Patient ID card (enclosed
in the iStent packaging) with the appropriate information filled in, and should advise
the patient to keep the card in a safe place, e.g., his or her wallet, for future reference.
The surgeon should advise the patient that this Patient ID card contains important
information related to the iStent and that the card should be shown to their current
and future health care providers.
3. The surgeon should monitor the patient postoperatively for proper maintenanceof intraocular pressure. If intraocular pressure is not adequately maintained after
surgery, the surgeon should consider an appropriate medication regimen to reduce
intraocular pressure.

Figure 9.
Figure 9.
Gonioscopic view of implanted stent (right eye)
Gonioscopic view of implanted stent (right eye)

7. At the 7.
endAtofthe
theendprocedure,
the following
should beshould
performed:of the procedure,
the following
be performed:a. Irrigate
the anteriorchamberwith balanced
salt solution(BSS)
throughcorneala. Irrigate
the anteriorchamberwith balanced
salt solution(BSS)
throughthethecornealwound manually,
with automatedirrigation/aspiration
to remove
viscoelastic
wound manually,or with orautomated
irrigation/aspiration
to remove
viscoelastic
andrefluxed blood.
Stent tip is inferior and points left
Stent tip is inferior and points rightrefluxedand
blood.
4. Inspect
angle with a gonioprism to ensure thata good view is available at the nasal
b. Inflate the anterior chamber with saline solution as needed to achieve physiologic
implant location.
b. Inflate theanterior chamber with saline solution as needed to achieve physiologic
4.4. 5.Inspect
angle
with
a
gonioprism
toensure
that
a
good
view
is
available
at
the
nasal
Place
a
gonioscopeonthecorneaandreposition
thesurgicalmicroscopeasneededInspect angle with a gonioprism to ensure that a good view is available at the nasal pressure.pressure.
c.
Ensurethat the corneal incision is sealed, and place 10-0 nylon suture if needed.
implant
location.
to visualize
the trabecular meshwork, through the gonioprism, on the nasal side of
implant
location.
4. Inspect
anglewith a gonioprism to ensure that a good view is available at the nasal c. Ensure that the corneal incision is sealed, and place 10-0 nylon suture if needed.
the eye. Focus on the landmarks in the angle of the eye (Figure 5). Look up from
Postoperative Instructions
5.5.implant
Place
Place alocation.
a gonioscopegonioscope onon thethe cornea
cornea andand reposition
reposition thethe surgicalsurgical microscope
microscope asas neededneeded totothe iris root to find the scleral spur (white line). Then look for Schwalbe’s line (white
1. Patients should be managed postoperatively for IOP increases that may occur invisualize
thetrabecularmeshwork,throughthegonioprism,
on
the
nasal
side
of
the
eye.
visualize
thetrabecularmeshwork,throughthegonioprism,
on
the
nasal
side
of
the
eye.
5. Placegonioscopeon cornea.
the cornea
reposition
the surgicalmicroscope
as neededtoline)a downfrom the
Theandtrabecularmeshwork(typicallya red/brownline) Postoperative
Instructions
theearly postoperative period as a possible sequelae following cataract surgery in
Focus
on
the
landmarks
in
the
angle
of
the
eye
(Figure
5).
Look
up
from
the
iris
root
toto
Focus
on
the
landmarks
in
the
angle
of
the
eye
(Figure
5).
Look
up
from
the
iris
root
visualize
the trabecularmeshwork,
the gonioprism,on thenasalis sideof theis between
the scleralspur andthroughSchwalbe’s
line. Schlemm’s
canalbehindtheeye.
patients
with glaucoma.
findscleralspur
findthethethescleralspur (white(whiteline).
line). Then
Thenlook
lookforforSchwalbe’s
Schwalbe’s line
line(white(white line)line)down
down from
from
Focus
on
landmarks
trabecularmeshwork. in the angle of the eye (Figure 5). Look up from the iris root1.to Patients should be managed postoperatively for IOP increases that may occur in the earlythecornea.
The
trabecularmeshwork(typicallyaa red/brownline)
isis betweenthescleralthecornea.
The
trabecularmeshwork(typically
red/brown
line)
betweenthescleralRetrievalofanImplanted
Stent sequelae following cataract surgery in patients withpostoperative
periodas a possible
find the scleral spur (white line). Then look for Schwalbe’s line (white line) down from
spur
and
Schwalbe’s
line.
Schlemm’s
canal
isisbehindthetrabecularmeshwork.
Ifthesurgeondeterminesthat another inserter (Model GTS100i) is required to grasp a
spur
andSchwalbe’s
line.
Schlemm’s
canalbehindthetrabecularmeshwork.
glaucoma.
the cornea. The trabecular meshwork (typically a red/brown line) is between the scleralstent (i.e., the original inserter from the stent system is no longer available or not used),spur and Schwalbe’s line. Schlemm’s canal is behind the trabecular meshwork.
the inserter (Model GTS100i) may be used by the surgeon as follows:
1. Similar to the initial implant procedure, visualize the location of the iStent using a
Retrieval of an Implanted Stent
goniolens.
If the surgeon
determinesthat another
GTS100i
2. Enterthe eye througha clearcornealinserter
incision.is required to grasp a stent (i.e., theoriginal inserter
from
the
stent
systemisnolongeravailable
not used),
Modelthe3. Advance to the location of the iStent, and depress
theor
inserterbuttonthe
to open
GTS100i inserter
mayjaws
be usedby 10a).
the surgeon as follows:
inserter(Figure1. Similar4.toWhilethe initialprocedure,
visualizeposition
the locationof theofiStent
usingholdingimplant
down therelease button,
the snorkel
the stent
in athegoniolens.inserter (Figure 10b), and then release the release button to grasp the snorkel of
2. Enter the eye
a clear10c).
cornealincision.
the throughstent (FigureOnce
the stent is in the inserter, it can then be implanted as
3. Advance tothe locationof 6theiStent,and depress
thetheinserterbuttonto openthe inserter
described
in Step
above,or removed
fromeye. Careshouldbe exercisedwhenjaws (Figure
10a).
exiting the wound.
Figure 5. iStent Implant Site
4. While holding down the release button, position the snorkel of the stent in the inserter(Figure 10b), and then release the release button to grasp the snorkel of the stent (Figure
6. Insertion of stent
10c).
Once the stent is in the inserter, it can then be implanted as described in Step 6
66
a. Inject viscoelastic into the anterior chamber to assist with chamber maintenance. pg.
pg.
b. Insert the stent (which is attached to the inserter tip) through the temporal above, or removed from the eye. Care should be exercised when exiting the wound.
Figure
4a.
Model
view)
Figure4a.
4a.ModelModelGTS100L
GTS100L(top
view)
FigureGTS100L(top
(top
view
Stent
and
pointsleft
Stenttip
tipisisisinferior
inferior
andpointsleft left
Stent
tip
inferior
andpointsFigure 4a. Model GTS100L (top view)

FigureModel
GTS100R
Figure4b.
ModelGTS100R
GTS100R(top(topview)
view)
Figure4b.4b.
Model
(top
view)
Stent
tip
isisinferior
pointsright
Stenttiptipis
inferiorand
andpointsright
Stentinferior
andpointsright
Figure 4b. Model GTS100R (top view)

incision that was used to extract the cataract and insert the intraocular lens.
c. Traverse the anterior chamber with the inserter and position the inserter tip at
approximately the pupillary margin. Place the gonioprism into the desired
position (see Figure 6 for Model GTS100R).

pg. 6

pg. 9

In the case of visual field defect, the following criteria were to be met:
• no severe nasal steps worse than 4 continuous clustered points• no more than 3 clustered points with sensitivity less than 15dB within 15 degrees
from the fixation point
• no
other
evidence
atclinicalexaminationofmoderatetoadvanced
nerve
fiber
bundledefects(i.e.
Bjerrumscotoma)In the case of nerve abnormalities consistent with glaucoma, one or more of thefollowing was acceptable for diagnosis:• segmental loss of neuroretinal rim (notching)• Drance disc hemorrhage (splinter hemorrhage)• nerve fiber layer loss (as observed with an ophthalmoscope)• pseudo pit of the disc• visible laminar dots
• optic nerve abnormalities determined by Heidelberg retina tomograph (HRT)
confocal scanning imaging• findings on polarimetry consistent with early glaucoma such as a wedge shapeddefect connecting to the optic nerve head with values at or below the 5th percentile
as evidenced on the deviation map, any parameter below the 5th percentile, or thenerve fiber indicator (NFI) >35 using GDx• findings on optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL)
thickness outside of the normal range consistent with clinical evaluation of the optic
nerve and RNFL
Subjects with secondary OAG were excluded, except for 4 eyes in the randomized
treatment group and 3 in the randomized control group with pigmentary glaucoma
and 7 eyes in each of the randomized groups with pseudoexfoliative glaucoma in the
study eye based upon the protocol inclusion and exclusion criteria. Subjects wererequired to have best corrected visual acuity of 20/40 or worse with medium Brightness
Acuity Tester, and clinically significant cataract eligible for phacoemulsification, to
qualify for the study. Subjects were required to be on one to three ocular hypotensive
medications, with a medicated IOP of ≤ 24 mmHg at screening evaluation, and with anunmedicated IOP ≥ 22 mmHg and ≤ 36 mmHg at baseline visit, after washout.
Of the 116 subjects in the treatment group, 68% were 70 years of age or older at thetime of surgery, with a mean age of 74 years. Most subjects (60%) were female, andthe majority of subjects (71%) were Caucasian. There were equal proportions of righteyes and left eyes. Similar demographic characteristics were seen in the 123 control
subjects, where 65% were 70 years of age or older with a mean age of 73 years. Fiftyeight percent were female. The majority of subjects (72%) were Caucasian, and there
were equal proportions of right eyes and left eyes.
The primary effectiveness outcome was defined as IOP ≤ 21 mmHg without use of ocularhypotensive medication at 12 months (Intent to Treat (ITT) using Last Observation
Carried Forward (LOCF)). The proportion of subjects with this outcome was compared
between the two study groups. The secondary effectiveness outcome was defined as
IOP reduction from baseline of ≥ 20% without use of ocular hypotensive medication
at 12 months (ITT using LOCF). The proportion of subjects with this outcome wascompared between the two study groups.

TABLE 5 (Continued)
POSTOPERATIVE OCULAR ADVERSE EVENTS*
SAFETY POPULATION
Adverse Events

Efficacy Results – Randomized Trial
Primary and Secondary Efficacy Endpoints
Sixty-eight percent of subjects in the treatment group (combined cataract and iStent
implantation) met the primary endpoint of IOP ≤ 21 mm Hg with no medications at 12
months (mITT1 using non-responder analysis) (Table 2). In comparison, only 50% of
subjects in the control group (cataract surgery only) met the primary endpoint. This
treatment difference of 18% in favor of the iStent group on the primary endpoint at 12
months was statistically (p = .004) and clinically significant.
The ITT population included 117 eyes of 116 subjects randomized to undergo iStent implantation. The modified ITT
population (mITT) included 116 eyes of 116 subjects (excluded 1 eye from same subject).

1

TABLE 2
IOP ≤ 21 MMHG WITHOUT OCULAR HYPOTENSIVE MEDICATIONS AT 12 MONTHS
Analysis Population and
Imputation Method

Cataract Surgery Cataract Surgery P-value1
with iStent
Only
N=116
N=123
(%)
(%)

mITT Using Non-Responder
Analysis

68%

50%

.004

1. Two-sided Z-test.

The secondary endpoint in the GC-003 pivotal trial was the proportion of patients with
IOP reduced ≥ 20% from baseline without medications at 12 months (mITT using nonresponder analysis). In the iStent treatment group, 64% of subjects implanted met thisendpoint compared to 47% in the cataract control group (Table 3). This treatment
difference of 17% was also statistically (p = .010) and clinically significant.
TABLE 3IOP REDUCTION ≥ 20% WITHOUT OCULAR HYPOTENSIVEMEDICATIONS AT 12 MONTHS
Analysis Population and
Imputation Method

Cataract Surgery Cataract Surgery P-value1
with iStent
Only
N=116
N=123
(%)
(%)

mITT Using Non-Responder
Analysis

64%

47%

.010

1. Two-sided Z-test.

Safety Results – Adverse Events
Intraoperative Complications
Intraoperative complications specifically related to implantation of the iStent aresummarized in Table 4 for the 112 subjects in whom stent implantation was attempted.
These events included iris touch (n=8), endothelium touch (n=1), intraoperative stentremoval and replacement (n=1), failure to implant stent (n=1) and stent malposition(n=1).
These data show that stent implantation was successful in the majority of cases, with only
one report of stent implantation not completed due to poor visualization of the angle, and a
low incidence of operative complications and adverse events.
TABLE 4OPERATIVE COMPLICATIONS AND ADVERSE EVENTSFROM STENT IMPLANTATION
N = 112
Iris touched by the device
Endothelium touched
Intraoperative stent removal and replacement
Failure to implant stent
Stent malpositionn (%)
8 ( 7.1%)
1 ( 0.9%)
1 ( 0.9%)
1 ( 0.9%)
1 ( 0.9%)

Postoperative Ocular Adverse Events
A summary of postoperative ocular adverse events reported in the safety population
during the randomized clinical trial is presented below.
Anticipated, early
postoperative events included transient events such as corneal edema, trace folds,
trace striae, transient hypotony at 5-7 hours, inflammation, epithelial defect anddiscomfort as expected following cataract surgery. Iritis, anterior chamber cells anduveitis were considered separate and unique adverse event categories of intraocularanterior segment inflammation. The combined incidence of these events was 2% in
the treatment group (1 iritis, 1 uveitis) vs. 6% in the control group (6 iritis, 1 anteriorchamber +1 cells requiring treatment).
One adverse event in each group was deemed by investigators to be severe. One
subject in the treatment group experienced BCVA loss (“count fingers”) after sufferinga stroke. One subject in the control group had macular traction, macular hole andmacular edema treated with vitrectomy; this subject also had BCVA loss of ≥ 1 line at ≥3 months postoperative.
With the exception of adverse events specifically related to stent malposition or
obstruction, adverse events occurred at a low incidence in both groups and wererepresentative for the elderly, post-cataract surgery population evaluated in this study.
Thus, there were no serious or unanticipated safety concerns related to implantation of
the iStent in conjunction with cataract surgery.
TABLE 5POSTOPERATIVE OCULAR ADVERSE EVENTS*
SAFETY POPULATION
Adverse Events
Cataract Surgery Cataract Surgery
with iStent
Only
N = 116
N = 117n (%)
n (%)
Anticipated early postoperative event
Early postop corneal edema
9 ( 8%)
11 ( 9%)
Early postop anterior chamber cells
4 ( 3%)
2 ( 2%)
Early postop corneal abrasion
3 ( 3%)
2 ( 2%)
Early postop corneal striae
2 ( 2%)
1 ( 1%)
Early postop discomfort
1 ( 1%)
2 ( 2%)
Early postop subconjunctival hemorrhage
1 ( 1%)
0 ( 0%)
Early postop superficial punctate keratitis
0 ( 0%)
2 ( 2%)
Early postop blurry vision0 ( 0%)
1 ( 1%)
Early postop floaters
0 ( 0%)
1 ( 1%)
Any BCVA loss of at least 1 line at or after
8 ( 7%)
12 ( 10%)the three month visit
Posterior capsular opacification
7 ( 6%)
12 ( 10%)
Stent obstruction by iris, vitreous, fibrous
5 ( 4%)
0 ( 0%)
overgrowth, fibrin, blood, etc.
Blurry vision or visual disturbance4 ( 3%)
8 ( 7%)
Elevated IOP – other4 ( 3%)
5 ( 4%)
Stent malposition
3 ( 3%)
0 ( 0%)
Subconjunctival hemorrhage
2 ( 2%)
2 ( 2%)
Epiretinal membrane
2 ( 2%)
1 ( 1%)
Drusen2 ( 2%)
0 ( 0%)
Iris atrophy
2 ( 2%)
0 ( 0%)
Iritis1 ( 1%)
6 ( 5%)
Conjunctival irritation due to hypotensive
1 ( 1%)
3 ( 3%)
medication
Disc hemorrhage
1 ( 1%)
3 ( 3%)

Elevated IOP requiring treatment with oral
or intravenous medications or with surgicalintervention
Allergic conjunctivitis
Dry eye
Macular edema
Cystoid macular edema
Bleeding (vitreous hemorrhage or persistent & non-preexisting hyphema
Corneal edema
Transient hypotony
Mild pain
Foreign body sensation
Posterior vitreous detachment
Rebound inflammation from tapering
steroids
Choroidal detachment
Endophthalmitis

TABLE 9POSTOPERATIVE OCULAR ADVERSE EVENTSNON-RANDOMIZED POPULATION

Cataract Surgery
with iStent
N = 116n (%)
1 ( 1%)

Cataract Surgery
Only
N = 117n (%)
3 ( 3%)

1 ( 1%)
1 ( 1%)
1 ( 1%)
1 ( 1%)
1 ( 1%)

2 ( 2%)
2 ( 2%)
2 ( 2%)
1 ( 1%)
0 ( 0%)

1 ( 1%)
1 ( 1%)
0 ( 0%)
0 ( 0%)
0 ( 0%)
0 ( 0%)

0 ( 0%)
0 ( 0%)
5 ( 4%)
4 ( 3%)
4 ( 3%)
2 ( 2%)

0 ( 0%)
0 ( 0%)

1 ( 1%)
1 ( 1%)*occurring at ≥ 2% in either group, or other adverse events known to be associated with glaucoma procedures or
potential risk with stent implantation.

In addition to the adverse events reported in Table 5 (i.e., adverse events that occurredat an incidence of ≥ 2% in either group), adverse events that occurred at < 2% in bothgroupsincluded worsening of glaucoma and allergy to cosmetics. Adverse events that
occurred at < 2% in the treatment group included age-related macular degeneration,
uveitis, blepharospasm, dysesthesia and/or photophobia, endo pigment, eye splash
injury, eyelid bruise due to fall, metallic particle on iris, mild throbbing pain, periorbital
hematoma due to fall, possible bacterial conjunctivitis, seasonal allergies, andsubjconjunctival hemorrhage secondary to aspirin. Adverse events that occurred at< 2% in the control group included blepharoconjunctivitis, worsening of age-related
macular degeneration, anterior chamber (1+) cells at one month requiring treatment,
burning due to dry eye, carotid artery disease, choroidal tubercle, and conjunctivitis.
Secondary Surgical Interventions
One subject in the treatment group underwent trabeculoplasty (Table 6). Anothersubject underwent focal argon laser coagulation for diabetic macular edema. Stentspecific secondary surgical interventions (Table 6) were reported in 5 randomized
iStent subjects (3 stent repositionings, 1 stent removal and replacement, 1 Nd:YAG laser
iridoplasty) to resolve stent malposition or obstruction observed by investigators in theearly postoperative period.
In the cataract surgery only group, two subjects underwent laser trabeculoplasty, one
subject underwent deep sclerectomy followed by revision and laser sclerostomy five
weeks later, one subject underwent vitrectomy for macular traction, macular hole andmacular edema, and one subject underwent three separate procedures of woundresuture because of wound leak, pupilloplasty, and IOL removal and replacement.
TABLE 6SECONDARY SURGICAL INTERVENTIONS –POSTOPERATIVE OCULAR ADVERSE EVENTSSAFETY POPULATION
Randomized Group
Secondary Surgical Intervention
Cataract Surgery Cataract Surgery
Adverse Eventswith iStent
Only
N = 116
N = 117n (%)
n (%)
Paracentesis1
31 (27%)34 (29%)
Nd:YAG laser capsulotomy
7 ( 6%)
11 ( 9%)Stent repositioning
3 ( 3%)
0 ( 0%)
Punctal cautery/punctal plugs
1 ( 1%)
3 ( 3%)
Trabeculoplasty
1 ( 1%)
2 ( 2%)
Nd:YAG laser iridoplasty for stent
1 ( 1%)
0 ( 0%)
obstruction
Focal argon laser photocoagulation
1 ( 1%)
0 ( 0%)
Stent removal and replacement
1 ( 1%)
0 ( 0%)
Deep sclerectomy/sclerostomy0 ( 0%)
1 ( 1%)
IOL removal and replacement0 ( 0%)
1 ( 1%)LASIK
0 ( 0%)
1 ( 1%)
Pupilloplasty0 ( 0%)
1 ( 1%)
Vitrectomy0 ( 0%)
1 ( 1%)
Wound resuture due to wound leak0 ( 0%)
1 ( 1%)
1. included paracentesis at the 5-7 hr exam

Non-Randomized Cohort
As described earlier, a non-randomized arm of the study was performed. A total of 50
subjects were enrolled at 10 sites in the non-randomized phase of the study subsequent
to the completion of enrollment of the randomized population. Subjects enrolled inthis non-randomized phase underwent iStent implantation in conjunction with cataract
surgery. The purpose of this non-randomized phase of the study was to collect safety
data on additional subjects. The randomized and non-randomized phases of the study
used identical inclusion and exclusion criteria. Both phases used the same standardized
procedures, applied the same surgical techniques, and placed the stent in the sameanatomical location. Of the 50 subjects enrolled, 46 were implanted with the iStent,
2 subjects withdrew before surgery and 2 subjects were exited after surgery following
unsuccessful iStent implantation. Preoperative parameters in the non-randomized
population were similar to those in the randomized population.
Results of the 46 subjects successfully implanted with the iStent (the Non-Randomized
Population) are presented in Tables 7- 10. Forty-four subjects completed follow-up
through Month 24, and 2 subjects terminated from the study prior to Month 24. There
were no stents removed or replaced during the 24-month follow-up period.
TABLE 7
IOP ≤ 21 MMHG WITHOUT OCULAR HYPOTENSIVE MEDICATIONSIOP REDUCTION ≥ 20% WITHOUT OCULAR HYPOTENSIVE MEDICATIONSNON-RANDOMIZED POPULATION AT 12 MONTHS
Non-Randomized Cataract
Surgery with iStent (N = 46)

IOP ≤ 21 mmHg
without OcularHypotensive
Medications (%)

IOP Reduction≥ 20% without
Ocular Hypotensive
Medications (%)

ITT using Non-Responder Analysis

78%

72%

TABLE 8OPERATIVE COMPLICATIONS FROM STENT IMPLANTATIONSUBJECTS WITH ISTENT IMPLANT
Non-Randomized Cataract Surgery with iStent (N = 46)n (%)
Iris damage*1 ( 2.2%)
Stent malposition*
1 ( 2.2%)
Ocular pain during insertion
1 ( 2.2%)
Iris touched by the device
3 ( 6.5%)
Endothelial touch
1 ( 2.2%)
Anterior chamber collapse
1 ( 2.2%)* same eye
Note: Two subjects were discontinued before surgery, and two did not have successful stent implantation. Thesefour subjects are not in the populations of subjects with an iStent implant and were excluded from calculations in
the table.

Cataract Surgery
with iStent
N = 46n (%)

Adverse Events
Anticipated early postoperative event
Early postop anterior chamber cells
Early postop corneal edema
Early postop anterior chamber inflammation
Early postop corneal abrasion
Early postop corneal erosion
Early postop corneal striae
Early postop pain
Epiretinal membrane
Posterior capsular opacification
Any BCVA loss of at least 1 line at or after the three month visit
Blepharitis
Blurry vision or visual disturbance
Posterior vitreous detachment
Stent malposition
Stent obstruction by iris, vitreous, fibrous overgrowth, fibrin,blood, etc.
Vitreous floaters
Age related macular degeneration
Allergic conjunctivitis
Blepharoconjunctivitis
Cystoid macular edema
Elevated IOP – other
Iris incarceration
Keratitis
Periorbital swelling
Unwanted eyelid sensation
UveitisVitreous condensations
Worsening of age related macular degeneration
Worsening of glaucoma
Bleeding (vitreous hemorrhage or persistent & non-preexisting
hyphema)
Corneal edema
Transient hypotony
Choroidal detachment
Endophthalmitis

2 ( 4%)
2 ( 4%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
4 ( 9%)
4 ( 9%)
3 ( 7%)
2 ( 4%)
2 ( 4%)
2 ( 4%)
2 ( 4%)
2 ( 4%)
2 ( 4%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
1 ( 2%)
0 ( 0%)
0 ( 0%)
0 ( 0%)
0 ( 0%)
0 ( 0%)TABLE 10SECONDARY SURGICAL INTERVENTIONS –POSTOPERATIVE OCULAR ADVERSE EVENTSNON-RANDOMIZED POPULATION
Secondary Surgical Intervention
Adverse Events
Paracentesis1
Nd:YAG laser capsulotomy
Nd:YAG laser for stent obstruction
Iris reposition

Non-Randomized
Cataract Surgery
with iStent
N = 46n (%)
12 ( 26%)
7 ( 15%)
1 ( 2%)
1 ( 2%)

1.included paracentesis at the 5-7 hr. exam

14. POST-APPROVAL STUDY RESULTS
Study Objective
In accordance with the PMA conditions of approval, a post-approval study was
conducted. Following approval by FDA on March 5, 2013 of the study protocol entitled“GTS100-Post Approval Study (PAS)”, the study was initiated. The goal of this study was
to demonstrate that use of this device in conjunction with cataract surgery did not
result in a rate of sight-threatening adverse events, after 5 years of implantation, thatwas higher than the rate of sight-threatening adverse events that occurs after cataract
surgery alone, by more than a non-inferiority margin of 5%.
Study Design
This was an extended follow-up study involving subjects previously enrolled in Glaukos
Study GC-003. Extended follow-up was planned in subjects eligible to participate in thisfollow-up study. Subjects were to be followed for five years postoperatively (one final
visit was conducted on those subjects who were past the five year post-operative timepoint). Please note that no postoperative specular microscopy was performed, because
preoperative specular microscopy was not performed in the pivotal trial.
Study Population
The study included subjects previously enrolled in Glaukos Study GC-003 who would
be able and willing to participate in this extended follow-up study. The study excluded
subjects previously enrolled in Glaukos Study GC-003 who would not be able or willingto participate in this extended follow-up study, as well as patients not previously
enrolled in Glaukos Study GC-003.
Study Endpoint
The primary endpoint was the occurrence of sight-threatening adverse events. Sightthreatening adverse events included events such as BCVA loss ≥ 3 lines vs. baseline,
endophthalmitis, corneal decompensation, retinal detachment, severe choroidal
hemorrhage, severe choroidal detachment and aqueous misdirection.
Total Number of Enrolled Study Sites and Subjects; Length of Follow-Up
The first subject had enrolled in Pivotal Trial GC-003 in 2005, and the final subject had
enrolled in February, 2008. The final subject exited Study GC-003 on March 18, 2010.
At the time the study protocol was approved by FDA in March of 2013, all eligible
subjects had passed the Month 60 visit window. Overall, the time from surgery to
the final GTS100-PAS visit was 6.6 years in the overall iStent + cataract surgery group(pooled randomized phase and non-randomized cohort subjects) and 6.8 years in the
randomized cataract surgery group.
Of the 27 original study sites participating in Pivotal Trial GC-003, 25 sites participatedin this post-approval study. Of the 279 subjects (162 overall iStent + cataract surgery
subjects plus 117 cataract surgery only subjects), a total of 255 subjects (148 overall
iStent + cataract surgery subjects plus 107 cataract surgery only subjects) had
completed follow-up through 2 years in Study GC-003 and were eligible for enrollment.
Of these, 108 subjects (73 iStent + cataract surgery subjects and 35 cataract surgery only
subjects) were enrolled in the post-approval study. The reasons for 108 of 255 subjects
enrolled were due to the extended length of time between final subject exit from Study
GC-003 (March 18, 2010) and approval by FDA of the post-approval extended follow-up
study 3 years later, by which time many of the exited subjects in this elderly population
had either expired or were no longer available or willing to participate in a clinical study.
To this point, the average age at time of enrollment was 78 (SD 8.0) years in the overall
iStent + cataract surgery group and 75 (SD 8.4 years) in the cataract surgery only group.
Final Safety Findings – All Sight-Threatening Adverse Events from Pivotal Trial andPost-Approval Study
Table 11 presents all sight-threatening adverse events reported from both Pivotal Trial
GC-003 and Study GTS100-PAS for the overall iStent + cataract surgery group and therandomized cataract surgery only group.

1. Advanced open angle glaucoma and advanced optic atrophy were reported for 1 subject in the iStent group.
Choroidal neovascularization was reported for 1 subject in the iStent group and 1 subject in the control group.
2. Two subjects with pre-existing Fuchs’ dystrophy prior to iStent + cataract surgery reported with corneal
decompensation. (A third iStent subject with pre-existing Fuchs’ dystrophy did not report with corneal
decompensation.) The two subjects underwent Descemet’s stripping endothelial keratoplasty 4 and 5 years,
respectively, after their iStent surgery (also refer to Table 13). Both subjects experienced worsening of the disease in
their fellow eyes as well, and one subject underwent penetrating keratoplasty in their fellow eye. The investigators
considered these events “definitely unrelated” to iStent.
One of the investigators statues the adverse event was®
GLAUKOSISTENT TRABECULAR MICRO-BYPASS STENT“typical chronicevolutionC
ofORPORATION
Fuchs’ corneal dystrophy”.
3. Number of subjects reported with any adverse events. Subjects could report with more than one adverse event.

Rate of Sight-Threatening Adverse Events from Pivotal Trial and Post-Approval
Study
Rate of Sight-Threatening Adverse Events from Pivotal Trial and Post-Approval Study
Figure11presents
presentsthethe
KM
curvesinvolvingsight-threatening
adversethe
Figure 11
KM
curvesinvolvingsight-threatening
adverseevents events
for the foroveralloverall+ cataract
group
the cataract
only group.
theiStent +iStent
cataract
surgerysurgery
group andtheandcataract
surgery surgery
only group.
Due toDue
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small
denominators
6 years,
the KM comparisonsanalyses comparisonswereatperformed
denominators
beyond 6beyond
years, theKM analyses
were performed
6 years. At at
5
theAtrateof sight-threatening
AEs was 28.5% AEs
for the+ overallcataract iStent
surgery+
6years,years.
5 years,
the rate of sight-threatening
wasoverall
28.5%iStent
for thegroup andsurgery
42.8% groupin the cataract
surgery
onlygroup.surgery
At 6 years,
rate ofcataract
and 42.8%
in thecataract
onlythegroup.
Atsight-threatening
6 years, the rateAEs
was 29.9% for the
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surgerygroup
and 45.7%in thecataractofsight-threatening
AEsoverall
was 29.9%
the overall
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surgerygroupandsurgeryinonly
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the p-value
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thegroup,cataract
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comparison
surgerygroup
and+cataract
surgery
onlygroup,
againstsurgery
a non-inferiority
marginof 5%,
theoveralliStentcataract
surgerygroup
andandcataract
only group,
and against
0.011, indicatingthat ofthe5%,
overallcataract surgery
group
was not
inferior
to theawas
non-inferiority
marginwasiStent
0.011,+indicatingthat theoveralliStent+ cataract
cataract groupsurgery was
onlynotgroup.
In toaddition,the p-valueof only
the logrank Intestaddition,
was 0.317,
surgeryinferior
the cataract
surgerygroup.
theconfirming
thatlog
the ranksight-threatening
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over 6 yearsthat
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statistically different
betweenp-valueof thetest was 0.317,
rateover 6the overall
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surgery
only+group.
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was not
statisticallybetweenthe overall
iStentcataract surgery groupand cataract surgery only group.
FIGURE
11
FIGURE 11

Postoperative Ocular Adverse Events
Table 12 presents all postoperative ocular adverse events reported from Study GTS100PAS for the overall iStent + cataract surgery group and the randomized cataract surgery
only group. Table 13 summarizes ocular surgeries from Study GTS100-PAS.
TABLE 12POSTOPERATIVE OCULAR ADVERSE EVENTS FOR STUDY EYES
Page 25 of 31
GTS100-PAS

Adverse EventAge related macular degeneration
or worsening of age related maculardegeneration
Amaurosis fugax

OverallRandomized
Cataract Surgery with
Cataract Surgery Only
iStentN = 35
N = 73n of Subjects
n of
n of Subjects
n ofwith Event (%) Events with Event (%) Events
6 (8%)

7

6 (17%)

6

0 (0%)0

1 (3%)1

TABLE 12 (Continued)
POSTOPERATIVE OCULAR ADVERSE EVENTS FOR STUDY EYESGTS100-PAS

Adverse Event

Anterior ischemic optic neuropathy
Any intraocular inflammation (non preexisting) remaining or arising after the
protocol’s specified medication regimen
is complete (1+ cells or flare will not be
considered an AE unless persisting >=1month postoperative)
Any other event that could lead to significant
vision loss, if not appropriately treated1
Bleeding (vitreous hemorrhage or persistent& non-preexisting hyphema)
Blepharitis
Blurry vision or visual disturbanceBranch retinal vein occlusion
Brow ache
Chalazion
Conjunctival hyperemia
Conjunctival irritation due to hypotensive
medication
Conjunctivitis
Corneal abrasion
Corneal graft edema
Cotton wool spot
Cystoid macular edema
Deep stents (“buried” in the trabecularmeshwork) that are not visible
Dermatochalasis
Dot hemorrhage
DrusenDry eye
Ectropion
Elevated IOP
Epiphora
Epiretinal membrane
Episcleritis
Floppy eyelid syndrome
Foreign body sensation
Fuch's dystrophy
Glaucoma progression
Goniosynechiae
Hollenhurst plaqueHyperemia
IOP increase >= 10 mmHg vs. baseline IOP
occurring at any visit
IOP increase requiring management withoral or intravenous medications or withsurgical intervention (Note: IOP treated withoral medication at the 6 hour visit is not an
Adverse Event)Implicated meibomian glands
Increased cup to disc ratio
Lacrimal stenosis
Lid edema
Loss of best corrected visual acuity (BCVA)of 3 lines or more vs. baseline at any time
postoperatively
Loss of best spectacle corrected visualacuity (BSCVA) of 2 lines or more (logMAR
scale; 10 letters or more on ETDRS chart)
postoperative as compared to baseline
or best recorded visual acuity measured
at any visit postoperative (NOTE: a lossof BSCVA in conjunction with posterior
capsular opacification, followed by Nd:YAG
capsulotomy and improvement of BSCVA, is
NOT considered an adverse event)Macular hemorrhage
Macular scar
Meibomian cyst
Meibomitis
Nerve fiber layer loss
Nonproliferative diabetic retinopathy
Notched lids
Ocular irritation/itching
Ocular migraine
Ocular pain
Optic TIA
Pain
Papilloma
Periorbital redness
Periorbital swelling
Peripapillary scarring
Photophobia
Pigmentary macular fibrosis
Posterior capsular opacification
Posterior vitreous detachment
Postoperative discomfort (NOTE:
postoperative discomfort up to andincluding the Week 1 postoperative exam is
NOT considered an adverse event)Ptosis
Punctal eversion
Retinal detachment
Retinal flap tears
Retinal pigment epithelial changes
Scotoma
Secondary surgical intervention
Significant corneal complications including
edema, opacification, decompensation(NOTE: a classification of mild or moderate
corneal edema up to and including Week 1
postoperative is NOT considered an adverse
event)
Stent8/25/2015
malposition
Aida Flores
1:09 PM
StentFont:Bold
obstruction (i.e., positive visualization
Formatted:
of lumen obstruction), partial or complete,Unknown
regardlessof how long the obstruction is
Field CodeChangedpresent
Aida Flores
8/25/2015 1:09 PM
Stye Font:Bold
Formatted:
Subconjunctival hemorrhage
Unknown
Field CodeChangedTelangiectasia
Aida Flores
8/25/2015 1:09 PM
Trichiasis
Formatted:
VisualFont:Bold
field defectVitreous floaters
Vitreous in anterior chamber
Vitreous syneresis
Watery eyes
Any3OverallRandomized
Cataract Surgery with
Cataract Surgery Only
iStentN = 35
N = 73n of Subjects
n of
n of Subjects
n ofwith Event (%) Events with Event (%) Events
0 (0%)0
1 (3%)1

1 (1%)1

0 (0%)0

2 (3%)2

1 (3%)1

1 (1%)1

0 (0%)0

6 (8%)
4 (5%)
1 (1%)
1 (1%)
0 (0%)
1 (1%)

6
5
1
1
0
1

4 (11%)
0 (0%)
0 (0%)
0 (0%)
1 (3%)
0 (0%)

6
0
0
0
1
0

1 (1%)1

1 (3%)1

2 (3%)
0 (0%)
1 (1%)
0 (0%)
2 (3%)

301
02

1 (3%)
1 (3%)
0 (0%)
1 (3%)
0 (0%)

110
102 (3%)2

0 (0%)0

4 (5%)
0 (0%)
1 (1%)
18 (25%)
1 (1%)
1 (1%)
2 (3%)
3 (4%)
0 (0%)
1 (1%)
3 (4%)
1 (1%)
2 (3%)
2 (3%)
1 (1%)
1 (1%)

4
0
1
18
1
1
2
3
0
1
3
1
2
2
1
1

2 (6%)
1 (3%)
1 (3%)
7 (20%)
0 (0%)
2 (6%)
0 (0%)
1 (3%)
1 (3%)
0 (0%)
2 (6%)
0 (0%)
1 (3%)
0 (0%)
0 (0%)
0 (0%)

2
1
1
8
0
2
0
2
1
0
2
0
1
0
0
0

2 (3%)2

0 (0%)0

4 (5%)5

3 (9%)3

1 (1%)
4 (5%)
1 (1%)
0 (0%)

14
1
0

0 (0%)
0 (0%)
0 (0%)
1 (3%)

0001

1 (1%)1

2 (6%)

2

17 (23%)17

7 (20%)7

1 (1%)
0 (0%)
1 (1%)
1 (1%)
0 (0%)
4 (5%)
1 (1%)
4 (5%)
1 (1%)
1 (1%)
1 (1%)
2 (3%)
3 (4%)
1 (1%)
1 (1%)
1 (1%)
2 (3%)
1 (1%)
18 (25%)8 (11%)

1
0
1
1
0
4
1
5
1
1
1
2
3
1
1
1
2
1
18
8

0 (0%)
1 (3%)
0 (0%)
0 (0%)
1 (3%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
1 (3%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
9 (26%)
3 (9%)

0
1
0
0
1
0
0
0
0
1
0
0
0
0
0
0
0
0
10
3

1 (1%)1

0 (0%)0

4 (5%)
2 (3%)
2 (3%)
1 (1%)
1 (1%)
2 (3%)
1 (1%)

4
2
2
1
1
2
1

2 (6%)
0 (0%)
0 (0%)
0 (0%)
1 (3%)
3 (9%)
0 (0%)

2
0
0
0
1
3
0

22 (3%)22

0 (0%)0

1 (1%)1

0 (0%)0

1 (1%)1

0 (0%)00 (0%)
2 (3%)
1 (1%)
3 (4%)
8 (11%)
8 (11%)
0 (0%)
1 (1%)
1 (1%)

0
2
1
3
8
9
0
1
1

1 (3%)
0 (0%)
0 (0%)
0 (0%)
1 (3%)
3 (9%)
1 (3%)
1 (3%)
1 (3%)

1
0
0
0
1
4
1
1
1

60 (82%)202

28 (80%)84

1. Advanced open angle glaucoma and advanced optic atrophy were reported for 1 subject in the iStent group.
Choroidal neovascularization was reported for 1 subject in the iStent group and 1 subject in the control group.
2. Two subjects with pre-existing Fuchs’ dystrophy prior to iStent + cataract surgery reported with corneal
decompensation. (A third iStent subject with pre-existing Fuchs’ dystrophy did not report with corneal
decompensation.) The two subjects underwent Descemet’s stripping endothelial keratoplasty 4 and 5 years,
respectively, after their iStent surgery (also refer to Table 13). Both subjects experienced worsening of the disease in
their fellow eyes as well, and one subject underwent penetrating keratoplasty in their fellow eye. The investigators
considered these events “definitely unrelated” to iStent. One of the investigators statues the adverse event was“typical chronic evolution of Fuchs’ corneal dystrophy”.
3. Number of subjects reported with any adverse events. Subjects could report with more than one adverse event.

TABLE 13
OCULAR SURGERIES AFTER GC-003 STUDY
GTS-100 PAS
OverallRandomized
Cataract Surgery with Cataract Surgery Only
iStentAdverse Event
N = 35
N = 73n of Subjects
n of
n of Subjects
n ofwith Event (%) Events with Event (%) Events
Nd:YAG laser capsulotomy
13 (18%)13
11 (31%)
11
Selective laser trabeculoplasty
1 (1%)1
3 (9%)
3
Blepharoplasty
2 (3%)2
0 (0%)
0
Descemet’s stripping
endothelial keratoplasty (treat
pre-existing Fuch’s dystrophy
21 (3%)21
0 (0%)
0prior to stent + cataract
surgery)
Basal cell carcinoma excision/
1 (1%)2
0 (0%)
0
lid reconstruction
Dacryocystorhinostomy/
1 (1%)2
0 (0%)
0lacrimal irrigation
Retinal tear repair (laser
photocoagulation, retinal
1 (1%)2
0 (0%)
0buckle)Laser iridoplasty
1 (1%)1
0 (0%)
0
Trabeculectomy
1 (1%)1
0 (0%)
0
Any choroidal hemorrhage
0 (0%)00 (0%)
0
Aqueous misdirection
0 (0%)00 (0%)
0
1. Two subjects with pre-existing Fuchs’ dystrophy prior to iStent + cataract surgery reported with corneal
decompensation. (A third iStent subject with pre-existing Fuchs’ dystrophy did not report with corneal
decompensation.) The two subjects underwent Descemet’s stripping endothelial keratoplasty 4 and 5 years,
respectively, after their iStent surgery. Both subjects experienced worsening of the disease in their fellow eyes as
well, and one subject underwent penetrating keratoplasty in their fellow eye. The investigators considered these
events “definitely unrelated” to iStent. One of the investigators statues the adverse event was “typical chronicevolution of Fuchs’ corneal dystrophy”.

Study Strength and Weaknesses
The main reason for the large number of potentially available subjects who did notenroll or complete the study is the 5+ year gap between subjects exiting Study GC003 and the date of final approval by FDA of the protocol for this extended follow-up
study. Many of the surviving patients in this elderly population had increased healthissues or age-related reasons for not enrolling in the follow-up study. There were more
subjects in the overall iStent + cataract surgery group than the cataract surgery only
group, because the non-randomized cohort of iStent + cataract surgery subjects had
been added to the randomized iStent + cataract surgery group.
Importantly, there were no unanticipated adverse device effects (UADE) identified
during the study, which extended to greater than 6 years after iStent implantation +cataract surgery.
GTS100-Post Approval Study 2 (GTS100-PAS2)
Study Objective
In accordance with the PMA conditions of approval, a post-approval study was
conducted. The GTS100-PAS2 protocol was approved by the FDA on March 8, 2013,
and the updated protocol was approved by the FDA on May 13, 2016. The goal of thisstudy was to demonstrate that use of the iStent Trabecular Micro-Bypass Stent Model
GTS100 in conjunction with cataract surgery did not result in a rate of sight-threatening
adverse events, within 3 years of implantation, that was higher than the rate of sightthreatening adverse events that occurs after cataract surgery alone, by more than a
non-inferiority margin of 5%.
Study Design
In this prospective, multicenter, post-approval study, 183 subjects with mild tomoderate open-angle glaucoma currently treated with ocular hypotensive medicationand scheduled to undergo cataract surgery underwent iStent implantation duringcataract surgery and 276 subjects underwent cataract surgery only.
Study Population/Data Source
In the GTS100-PAS2 initial study design, subjects with mild to moderate open-angle
glaucoma currently treated with ocular hypotensive medication and scheduled toundergo cataract surgery were randomized/assigned to iStent + cataract surgery
or cataract surgery only. The revised study design allowed 1) enrollment of iStent+ cataract surgery subjects and 2) use of data from other trials to comprise a control
group of subjects who underwent cataract surgery.

TABLE 14 (Continued)
ALL SIGHT-THREATENING ADVERSE EVENTS (SORTED ALPHABETICALLY)
GTS100-PAS2
Cataract Surgery with
Cataract Surgery Only
iStentN = 276
N = 183
Adverse Event
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event
Hypotony (IOP < 6 mmHg)
at one month postoperative00 (0.0%)4
2 (0.7%)or later
IOL dislocation00 (0.0%)1
1 (0.4%)
IOP increase >= 10 mmHg
vs. baseline IOP occurring
2
2 (1.1%)4
3 (1.1%)>= Month 1
IOP increase requiring oral
22 (1.1%)13
10 (3.6%)
medication
IOP increase requiring
secondary surgical33 (1.6%)7
6 (2.2%)intervention
Iris atrophy00 (0.0%)1
1 (0.4%)Iris neovascularization00 (0.0%)1
1 (0.4%)
Juxtafoveal telangiectasia
00 (0.0%)1
1 (0.4%)
Loss of BSCVA of 3 lines
1 (0.5%)or more compared tobaseline or best recorded
144 (1.4%)visual acuity at any time
postoperatively persisting attime of study exit
Macular edema
5
4 (2.2%)3
3 (1.1%)
Nerve fiber layer loss
00 (0.0%)22 (0.7%)
Optic nerve thinning/
0 (0.0%)01
1 (0.4%)
cupping
Peripapillary atrophy1
1 (0.5%)00 (0.0%)Retained crystalline lens
1 (0.5%)100 (0.0%)fragments
Retinal detachment2
1 (0.5%)1
1 (0.4%)Retinal flap tears
1
1 (0.5%)1
1 (0.4%)Retinal hemorrhage
1
1 (0.5%)00 (0.0%)4 (2.2%)Retinal pigment epithelial
40
0 (0.0%)changes0 (0.0%)
Segmental loss of02
2 (0.7%)
neuroretinal rim (notching)Significant corneal
0 (0.0%)complications including
01
1 (0.4%)edema, opacification,
decompensation
1 (0.5%)Significant hyphema (i.e.,
100 (0.0%)>= 10% of anterior chamber)
Visual field loss >=2.5 dB
2
2 (1.1%)4
3 (1.1%)
Vitreous hemorrhage
00 (0.0%)22 (0.7%)
Wound dehiscence00 (0.0%)1
1 (0.4%)51
39 (21.3%)
95
59 (21.4%)
Any1
1 Number of subjects reported with any adverse events. Subjects could report with more than one adverse event.

Rate of Sight-Threatening Adverse Events
Figure 12 presents the KM curves involving sight-threatening adverse events for the
iStent + cataract surgery group and the cataract surgery only group. Due to the small
denominators beyond 3 years, the KM analyses comparisons were performed at 3 years.
At 3 years, the rate of sight-threatening AEs was 22% for the iStent + cataract surgery
group and 24% in cataract only group. and the one-sided p-value for the comparison
between the overall iStent + cataract surgery group and cataract surgery only group,
and against a non-inferiority margin of 5%, was 0.0409 indicating that the iStent +cataract surgery group is not inferior to the cataract only group. In addition, the p-valueof the log rank test was 0.7231 confirming that the sight-threatening AE rate over 3
years is not statistically different between the iStent + cataract surgery group andcataract surgery only group.

Study Endpoint
The primary endpoint was the occurrence of sight-threatening adverse events. Sightthreatening adverse events included events such as BCVA loss ≥ 3 lines, endophthalmitis,
corneal decompensation, retinal detachment, severe choroidal hemorrhage, severechoroidal detachment and aqueous misdirection.
Total Number of Enrolled Study Sites and Subjects, Length of Follow-Up, Followup Rates
In the GTS100-PAS2 study, a total of 357 subjects were enrolled with 207 subjects at
23 sites assigned to either iStent + cataract surgery (n=183) or cataract surgery only
(n=24). The final subject was enrolled on April 23, 2018. A total of 252 cataract surgery
only subjects were enrolled at 46 sites in other trials. Subjects were followed through 3
years postoperatively.
In the iStent + cataract surgery group of 183 subjects, follow-up rates were 97.8% at
Month 12, 87.8% at Month 24, and 86.5% at Month 36.
In the cataract surgery only group of 276 subjects, follow-up rates were 97.4% at Month12, 92.9% at Month 24, and 86.0% at Month 36.
Final Safety Findings - Sight Threatening Adverse Events
Table 14 presents all sight-threatening adverse events reported for the iStent + cataract
surgery group and cataract surgery only group.
TABLE 14ALL SIGHT-THREATENING ADVERSE EVENTS (SORTED ALPHABETICALLY)
GTS100-PAS2
Cataract Surgery with
Cataract Surgery Only
iStentN = 276
N = 183
Adverse Event
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event
Age related maculardegeneration or worsening
22 (1.1%)44 (1.4%)of age related maculardegeneration
Anterior scleritis
00 (0.0%)1
1 (0.4%)
Any intraocularinflammation (non preexisting) remaining or
11
11 (6.0%)13
11 (4.0%)
arising after the protocol's
specified medication
regimen is complete
Blot macular hemorrhage
1
1 (0.5%)00 (0.0%)Central retinal artery00 (0.0%)1
1 (0.4%)
occlusion
Corneal opacity00 (0.0%)33 (1.1%)
Corneal ulcer0
0 (0.0%)1
1 (0.4%)
Cotton wool spots
1
1 (0.5%)00 (0.0%)Diabetic retinopathy
00 (0.0%)33 (1.1%)Disc hemorrhage
1
1 (0.5%)8
7 (2.5%)
Epiretinal membrane
55 (2.7%)44 (1.4%)Glaucoma progression
requiring secondary surgical33 (1.6%)3
3 (1.1%)intervention
Hypertensive retinopathy
1
1 (0.5%)00 (0.0%)FIGURE 12
Kaplan-Meier Plot for Sight-Threatening AE
GTS100-PAS2
0.4

S ight-Threate ning AE Probability

TABLE 11
ALL SIGHT-THREATENING ADVERSE EVENTS(DATA FROM GC-003 AND GTS100-PAS)
Overall Cataract Surgery
Randomized
with iStent
Cataract Surgery Only
N = 157
N = 122
Adverse Eventn of Subjects
n of
n of Subjects
n ofwith Event (%) Events with Event (%) Events
Epiretinal membrane
9 (6%)
92 (2%)
4
Loss of BCVA of 3 lines ormore vs. baseline at any
2 (1%)2
7 (6%)
7time postoperatively
Age related maculardegeneration or worsening
9 (6%)10
7 (6%)
7of age related maculardegeneration
Worsening of glaucoma
4 (3%)4
2 (2%)
2
IOP increase requiring
management with oral or
intravenous medications
or surgical intervention
4 (3%)5
3 (2%)
3(IOP treated with oral
medication at 6 hour visit is
not an Adverse Event)Cystoid macular edema
4 (3%)
4
1 (<1%)
1
Increased cup to disc ratio
4 (3%)
4
0 (0%)
0
Disc hemorrhage
1 (<1%)1
3 (2%)
3
Elevated IOP requiring
treatment with oral or
1 (<1%)1
3 (2%)
6
intravenous medications orsurgical intervention
Macular edema
1 (<1%)1
2 (2%)
2
Any other event that could
lead to significant vision
2 (1%)
2
1 (<1%)
1
loss, if not appropriately
treated1
Iris atrophy
2 (1%)2
0 (0%)
0
Retinal detachment
2 (1%)2
0 (0%)
0Significant corneal
complications including22
0 (0%)0
22 (1%)
edema, opacification,
decompensation
Uveitis2 (1%)
3
0 (0%)
0Corneal edema
1 (<1%)1
0 (0%)
0
Eye splash injury
1 (<1%)1
0 (0%)
0
Metallic particle on iris
1 (<1%)1
0 (0%)
0
Retinal flap tears
1 (<1%)1
0 (0%)
0
Choroidal detachment
0 (0%)
0
1 (<1%)
1
Endophthalmitis
0 (0%)
0
1 (<1%)
1
Macular hole
0 (0%)
0
1 (<1%)
1
Proliferative diabetic
0 (0%)
0
1 (<1%)
1
retinopathy
Segmental loss of
0 (0%)
0
1 (<1%)
1
neuroretinal rim
Any choroidal hemorrhage
0 (0%)00 (0%)
0
Aqueous misdirection
0 (0%)00 (0%)0Any3
36 (23%)56
28 (23%)41

C ENSORE D

0.3

0.2

0.1

0.0
C ataract Surgery wi th One
G TS 10 0 Stent

156

132

44

C ataract Surgery On ly

224

162

47

0

500

1000

1500

Event or last day from operation

Postoperative Ocular Adverse Events
Table 15 presents all postoperative ocular adverse events and Table 16 presents
secondary surgical interventions from Study GTS100-PAS2 for the iStent + cataract
surgery group and the cataract surgery only group.
TABLE 15POSTOPERATIVE OCULAR ADVERSE EVENTS FOR STUDY EYES(SORTED ALPHABETICALLY)
GTS100-PAS2
Cataract Surgery with
Cataract Surgery Only
iStentN = 276
N = 183
Adverse Event
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event
Postoperative events
211
97 (53.0%)
277
124 (44.9%)
Age related maculardegeneration or worsening
22 (1.1%)44 (1.4%)of age related maculardegeneration
Anterior basement00 (0.0%)1
1 (0.4%)
membrane dystrophy
Anterior scleritis
00 (0.0%)1
1 (0.4%)
Any intraocularinflammation (non preexisting) remaining or
11
11 (6.0%)13
11 (4.0%)
arising after the protocol's
specified medication
regimen is complete
Arcus senilis
1
1 (0.5%)00 (0.0%)TABLE 15 (Continued)
POSTOPERATIVE OCULAR ADVERSE EVENTS FOR STUDY EYES(SORTED ALPHABETICALLY) GTS100-PAS2

Adverse Event

Blot macular hemorrhage
Blurry vision or visual
disturbanceCapsular phimosis
Central retinal artery
occlusion
Conjunctival chemosis
Conjunctival concretion
Conjunctival melanosis
Conjunctivitis
Conjunctivochalasis
Corneal abrasion
Corneal folds
Corneal opacity
Corneal pigmentation
Corneal scar
Corneal ulcer
Cotton wool spots
Dermatochalasis
Diabetic retinopathy
Diplopia
Disc hemorrhage
Disorder of lacrimal system
Dry eye
Ectropion
Epiretinal membrane
Evident zonular weakness ordehiscence
Extraocular papilloma
Extraocular trauma
Eyelid abnormality
Foreign body sensation
Glaucoma progression
requiring secondary surgicalintervention
Goniosynechiae
Guttata
Hyperemia
Hypertensive retinopathy
Hypotony (IOP < 6 mmHg)
at one month postoperativeor later
IOL dislocation
IOP increase >= 10 mmHg
vs. baseline IOP occurring>= Month 1
IOP increase requiring oral
medication
IOP increase requiring
secondary surgicalintervention
Infiltrate on suture
Iris atrophy
Iris neovascularization
Juxtafoveal telangiectasia
Loss of BSCVA of 2 lines ormore and less than 3 lines
compared to baseline orbest recorded visual acuityat any time postoperatively
Loss of BSCVA of 2 lines ormore and less than 3 lines
compared to baseline orbest recorded visual acuityat any time postoperatively
persisting at time of study
exit
Loss of BSCVA of 3 lines
or more compared tobaseline or best recorded
visual acuity at any time
postoperatively
Loss of BSCVA of 3 lines
or more compared tobaseline or best recorded
visual acuity at any time
postoperatively persisting attime of study exit
Macular edema
Nerve fiber layer loss
Non-glaucomatous retinal
abnormalities
Ocular allergies
Ocular hypotensive
medication intolerance
Ocular irritation
Ocular migraine
Optic nerve thinning/
cupping
Pain (Chronic pain in
the study eye present
greater than 3 months
postoperative)
Periorbital swelling
Peripapillary atrophy
Peripheral microcystic
corneal edema
Peripheral retinal pigment
epithelium detachment
Posterior vitreous
detachment
PtosisRetained crystalline lensfragments
Retinal detachment
Retinal flap tears
Retinal hemorrhage
Retinal pigment epithelialchangesCataract Surgery with
Cataract Surgery Only
iStentN = 276
N = 183
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event1
1 (0.5%)00 (0.0%)7

7 (3.8%)6

3 (1.1%)1

1 (0.5%)00 (0.0%)00 (0.0%)1

1 (0.4%)

1
1
1
3
1
1
1
0
2
0
1
1
10
0
0
1
0
43
0
5

1 (0.5%)1 (0.5%)1 (0.5%)3 (1.6%)
1 (0.5%)1 (0.5%)1 (0.5%)0 (0.0%)2 (1.1%)0 (0.0%)1 (0.5%)1 (0.5%)10 (5.5%)
0 (0.0%)0 (0.0%)1 (0.5%)0 (0.0%)32 (17.5%)
0 (0.0%)5 (2.7%)

0
0
0
2
1
5
1
3
0
1
1
0
3
3
3
8
1
52
3
4

0 (0.0%)0 (0.0%)0 (0.0%)2 (0.7%)1 (0.4%)5 (1.8%)1 (0.4%)3 (1.1%)0 (0.0%)1 (0.4%)1 (0.4%)0 (0.0%)3 (1.1%)3 (1.1%)3 (1.1%)7 (2.5%)1 (0.4%)41 (14.9%)
3 (1.1%)4 (1.4%)1

1 (0.5%)00 (0.0%)000
50 (0.0%)0 (0.0%)0 (0.0%)5 (2.7%)12
1
6

1 (0.4%)2 (0.7%)1 (0.4%)6 (2.2%)3

3 (1.6%)3

3 (1.1%)2
15
12 (1.1%)1 (0.5%)4 (2.2%)1 (0.5%)52
13
0

5 (1.8%)2 (0.7%)
11 (4.0%)0 (0.0%)00 (0.0%)4

2 (0.7%)00 (0.0%)1

1 (0.4%)22 (1.1%)4

3 (1.1%)2

2 (1.1%)13

10 (3.6%)

3

3 (1.6%)7

6 (2.2%)000
00 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)111
1

1 (0.4%)1 (0.4%)1 (0.4%)1 (0.4%)20

17 (9.3%)

77 (2.5%)Adverse Event

Segmental loss ofneuroretinal rim (notching)Significant corneal
complications including
edema, opacification,
decompensation
Stent obstruction (i.e.,
positive visualization oflumen obstruction), partial
or complete, regardless of
how long the obstruction ispresent (specify)
Stye
Subconjunctival
hemorrhage
Transient ocular pain
Unwanted eyelid sensation
Visual field loss < 2.5 dB
Visual field loss >=2.5 dB
Vitreous floaters
Vitreous hemorrhage
Vitreous syneresis
Wound dehiscence

1 (0.5%)1

1 (0.4%)22 (1.1%)33 (1.1%)1

1 (0.5%)44 (1.4%)5
0

4 (2.2%)0 (0.0%)3
23 (1.1%)2 (0.7%)3

3 (1.6%)1

1 (0.4%)7

6 (3.3%)13

12 (4.3%)

22 (1.1%)65 (1.8%)010 (0.0%)1 (0.5%)10

1 (0.4%)0 (0.0%)00 (0.0%)1

1 (0.4%)22 (1.1%)00 (0.0%)010 (0.0%)1 (0.5%)30

3 (1.1%)0 (0.0%)1

1 (0.5%)00 (0.0%)1

1 (0.5%)00 (0.0%)1414 (7.7%)

12

12 (4.3%)

22 (1.1%)00 (0.0%)1

1 (0.5%)00 (0.0%)2
1
1

1 (0.5%)1 (0.5%)1 (0.5%)1
1
0

1 (0.4%)1 (0.4%)0 (0.0%)44 (2.2%)00 (0.0%)

SymbolCataract Surgery with
Cataract Surgery Only
iStentN = 276
N = 183
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event0
0

0 (0.0%)0 (0.0%)2
12 (0.7%)1 (0.4%)yyyy-mm-dd

66 (3.3%)

NA

NA

5

5 (2.7%)44 (1.4%)22 (1.1%)44 (1.4%)

1
0
1
2
2
0
0
0

1 (0.5%)0 (0.0%)1 (0.5%)2 (1.1%)2 (1.1%)0 (0.0%)0 (0.0%)0 (0.0%)

8
2
1
4
5
2
1
1

6 (2.2%)1 (0.4%)1 (0.4%)3 (1.1%)5 (1.8%)2 (0.7%)1 (0.4%)1 (0.4%)

NA=Not applicable

TABLE 16
SECONDARY SURGICAL INTERVENTIONS (SORTED ALPHABETICALLY)
GTS-100 PAS2
Cataract Surgery with
Cataract Surgery Only
iStentN = 276
N=
183
Secondary SurgicalIntervention
Number Number (%) of Number Number (%) ofof
Subjects withofSubjects with
Reports
Event
Reports
Event
Overall15
11 (6.0%)15
14 (5.1%)
Focal laser for juxtafoveal00 (0.0%)1
1 (0.4%)
telangiectasia
Focal laser for macular1
1 (0.5%)00 (0.0%)edema
IOL repositioning
00 (0.0%)1
1 (0.4%)Laser for stent obstruction
1
1 (0.5%)00 (0.0%)Laser retinopexy42 (1.1%)1
1 (0.4%)
Panretinal photocoagulation00 (0.0%)1
1 (0.4%)
Selective laser
6
6 (3.3%)6
6 (2.2%)trabeculoplasty
Trabeculectomy with/
00 (0.0%)44 (1.4%)
without Express shunt
Vitrectomy3
2 (1.1%)00 (0.0%)Vitrectomy with membrane00 (0.0%)1
1 (0.4%)peel
Stent Visibility
Stents were visible via gonioscopy in the vast majority of eyes at each exam. Stents
were visible via gonioscopy at Month 36 in all but 2 eyes (Table 17). In both cases ofstents not visible via gonioscopy at Month 36, stents had been identified via ultrasoundbiomicroscopic imaging (UBM) at multiple exams in the vicinity of the Month 36 visit.
In summary, stents were visible in all eyes through approximately 3 months before
postoperative evaluation Month 36 via either gonioscopy or UBM, and in 99.3% of eyes(all but 1 eye as described in footnote 4 of Table 17 below) at Month 36.
Table 17
Gonioscopy Examination - Stent Visibility
Cataract Surgery with GTS100 Stent Implanted During Surgery
Safety PopulationDay
Week Month Month Month Month Month Month Month Month Month
1
1
1
3
6
12
18
23
24
30
36
# and % Visible 180/181 177/178 177/179 178/180 176/178 175/177 173/175 164/167 162/164 155/157 147/149 151/153= Yes(99.4%) (99.4%) (98.9%) (98.9%) (98.9%) (98.9%) (98.9%) (98.2%) (98.8%) (98.7%) (98.7%) (98.7%)# and % Visible
1/181
1/178
2/179
2/180
2/178
2/177
2/175
3/167
2/164
2/157
2/149
2/153
= No
(0.6%)(0.6%) (1.1%) (1.1%) (1.1%) (1.1%) (1.1%) (1.8%) (1.2%) (1.3%) (1.3%) (1.3%)
Not Reported
0
3
0
0
0
0
0
0
0
0
0
0
Gonioscopy Stent Visibility in Subjects with at Least One Report of Visible = No
Subject ID1
A
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
B2
C3
Yes
Yes
No
No
No
No
No
No
No
No
No
No
Yes
ND
No
No
No
No
No
No
No
No
No
No
D4
N = number of records with available gonioscopy data.
Not Reported = number of eyes returned for the visit but the gonioscopy was not done.
ND = returned for the visit but the gonioscopy was not done.
1. Subjects numbered A-D to protect actual subject numbers
2. Stent not visible at operative exam and at Day 1 due to hyphema
3. Stent visualized via UBMs performed 1 day prior to the Month 1 visit, 1 month after the Month 12 visit, and at
the Month 24 and Month 36 visits.
4. Stent visualized via UBMs performed approximately 6 weeks postoperatively, six weeks after the Month 24 visit,
and approximately three months before the Month 36 visit.”
Subject

1

15. LABELINGThe following symbols are used on the device packaging.

TABLE 15 (Continued)
POSTOPERATIVE OCULAR ADVERSE EVENTS FOR STUDY EYES(SORTED ALPHABETICALLY) GTS100-PAS2

Operative

Study Strength and Weaknesses
The original study design was a prospective, randomized, concurrently controlled,parallel group, multicenter study. Due to challenges with enrollment, the protocol wasamended to prospectively enroll only subjects with iStent implantation in conjunction
with cataract surgery and to use data from other studies in order to have a sufficientnumber of cataract only subjects. In the other studies, subjects were initially consented
to study participation for 24 Months. Therefore, these subjects in the cataract only
group had to reconsent to be assessed at the Month 36 visit, and not all subjects agreed
to participate. There were more subjects in the cataract surgery only group than the
iStent + cataract group.
Importantly, there were no UADEs identified during the study, which extended togreater than 3 years after iStent implantation + cataract surgery.

Definition
Catalogue/Model
NumberSymbol30˚C
15˚C

Definition
Temperature Storage
Requirements

Serial Number(for the stent)

CE Marking

Lot Number

MR Conditional

Do not re-use

For prescription use
only

Use By(year-month-day)Consult Instructions
For Use.

Do not use if package
is damaged.
Sterilized by Gamma
Irradiation

Manufacturer
Authorized European
Representative

16. MRI SAFETY INFORMATION

Non-clinical testing has demonstrated that the iStent Trabecular Micro-Bypass Stent(Models GTS100R and GTS100L) is MR Conditional. A patient with this device can besafely scanned in an MR system meeting the following conditions:∙ Static magnetic field of 3 T or less
∙ Maximum spatial gradient magnetic field of 4,000 gauss/cm (40 T/m)
∙ Maximum MR system reported, whole body averaged specific absorption rate
(SAR of 4 W/kg (First Level Controlled Operating Mode)
Under the scan conditions defined above, the iStent Trabecular Micro-Bypass Stent(Models GTS100R and GTS100L) is not expected to produce a clinically significant
temperature rise after 15 minutes of continuous scanning.
In non-clinical testing, the image artifact caused by the device extends less than 15mm from the device when imaged with a gradient echo pulse sequence and a 3.0 T
MRI system.
17. CAUTION
Federal law restricts this device to sale by, or on the order of, a physician.
Physician training by certified Glaukos personnel is required prior to use of this device.
Training consists of three main parts:• Didactic session• Simulated implantation of iStent• Supervised iStent implantation of clinical cases until implantation proficiency isdemonstrated

Manufacturer:
Glaukos Corporation
229 Avenida Fabricante
San Clemente, CA 92672 U.S.A
Tel: 949.367.9600, Fax: 949.367.9984
www.glaukos.com
Toll-Free: 1-800-GLAUKOS (452-8567)
Glaukos® and iStent® are registered trademarks of Glaukos Corporation.
Tyvek® is a registered trademark of DuPont USA.

To:

GLAUKOS CORP

Date:

Part No: 45-0074 REV 3
Phone (951) 296-0300
FAX (951) 296-0306

06/04/24

Env. ID: G6198 (4RF)

Reference:

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