Download DIRECTIONS FOR USE/PACKAGE INSERT Glaukos Corporation

that was used to extract the cataract and insert the intraocular lens.
Traverse the
anteriorchamber
chamber
the inserter
and the
position
inserter
tip at
Figure 10a. Approach the stent as shown on right, and press down on the release button
4.The safety and effectiveness of the iStent® Trabecular Micro-Bypass Stent has not been c. c.Traverse
the anterior
withwith
the inserter
and position
inserterthe
tip at
approximately
approximately
the pupillary
Place the
the desired
position
as shown on left.
established as an alternative to the primary treatment of glaucoma with medications. The
the pupillary margin.
Placemargin.
the gonioprism
intogonioprism
the desired into
position
(see Figure
6 for
(see
Figure
6
for
Model
GTS100R).
effectiveness of this device has been demonstrated only in patients with mild to moderate
Model GTS100R).
DIRECTIONS FOR USE TABLE OF CONTENTS
open-angle glaucoma who are currently treated with ocular hypotensive medication and
who are undergoing concurrent cataract surgery for visually significant cataract.
1. DEVICE DESCRIPTION
10. STORAGE REQUIREMENTS
5.The safety and effectiveness of the iStent® Trabecular Micro-Bypass Stent has not been
2. INDICATIONS FOR USE
11. EXPIRATION DATE
established in patients with the following circumstances or conditions which were not
3. CONTRAINDICATIONS
12. RETURN GOODS POLICY
studied in the pivotal trial:
Temporal
Nasal
4. WARNINGS
13. CLINICAL TRIAL RESULTS
• In children
Figure 10b. While holding down the release button (left), position the snorkel of the stent
5. PRECAUTIONS
14. POST-APPROVAL STUDY RESULTS
in the inserter (right).
• In eyes with significant prior trauma
DIRECTIONS FOR USE/PACKAGE INSERT
Direction of feet of
6. ADVERSE
REACTIONS
15. LABELING
Glaukos
Corporation iStent® Trabecular
Micro-Bypass Stent System
•
In
eyes
with
abnormal
anterior
segment
patient
DIRECTIONS FOR USE/PACKAGE INSERT
7. INSTRUCTIONS FOR USE
16. MRI SAFETY INFORMATION
• In eyes with chronic inflammation
Glaukos Corporation iStent® Trabecular Micro-Bypass Stent System
DESCRIPTION
8.DEVICE
ADVERSE
EVENT REPORTING
17. CAUTION
• In glaucoma associated with vascular disorders
®
DEVICE
DESCRIPTION
9.The
HOW
SUPPLIED
iStent Trabecular Micro-Bypass Stent Model GTS100R/L is an intraocular stent that is • In pseudophakic patients with glaucoma
Figure
Figure6.6.
from titanium (Ti6Al4V ELI) and is heparin coated with Duraflo that is • In uveitic glaucoma
1.manufactured
DEVICE DESCRIPTION
The iStent® Trabecular Micro-Bypass Stent Model GTS100R/L is an intraocular stent that is
Gonioscopic
(right
eye)
GonioscopicView
ViewofofApproach
ApproachtotoTrabecular
TrabecularMeshwork
Meshwork
(right
eye)
® from Edwards LifeSciences (note: the porcine source of the heparin is from
purchased
The
iStent
Trabecular
Micro-Bypass
Stent
(Models
GTS100R
and
GTS100L)
is
an
manufactured from titanium (Ti6Al4V ELI) and is heparin coated with Duraflo that is
Figure 10c. Release the release button (left). The stent is now grasped in the inserter (right).
• In patients with prior glaucoma surgery of any type including argon laser trabeculoplasty
animals
raised
only
in
North
America).
The
stent
has
a
single
piece
design,
is
1.0
mm
in
intraocular
stentEdwards
that is manufactured
titanium
(Ti6Al4V
ELI) of
andthe
is heparin
purchased
from
LifeSciencesfrom
(note:
the porcine
source
heparin coated
is from
•
In
patients
with
medicated
intraocular
pressure
greater
than
24
mmHg
d. d.
Locate
length,
mm in height,
with asource).
snorkel The
length of has
0.25a mm,
and
a snorkel
(note:
the0.33
heparin
a porcine
single
piece
design,isbore
is1.0
1.0diameter
mm in of
Locatethe
thetrabecular
trabecularmeshwork,
meshwork,and
andlook
lookfor
forbifurcated
bifurcatedareas
areasbased
basedononasymmetric
asymmetric
animals
raised
only isinfrom
North
America).
The stentstent
has a single
piece
design,
mm
areas
implant location
locationbelow
belowthe
thehorizontal
horizontalmidline
midline
• In patients with unmedicated IOP less than 22 mmHg nor greater than 36 mmHg after
1).
in120µm
length, (Figure
in height, with a snorkel length of 0.25 mm, and a snorkel bore diameter
areasofofpigmentation,
pigmentation, and
and select
select an
an implant
of of
the
length,
0.33 0.33
mm mm
in height,
with a snorkel length of 0.25 mm, and a snorkel bore diameter of
“washout” of medications
of 120µm (Figure 1).
the
meshwork
and
adjacent
to
any
pigmented
areas
(which
could
represent
collector
meshwork
and
adjacent
to
any
pigmented
areas
(which
could
represent
collector
channels).
120µm (Figure 1).
the
tip
of
the
stent
and
the
TM
(Figure
7a).
Insert
the
self-trephining
stent
tip
channels).
Stent Height
Snorkel
• For implantation of more than a single stent
Gently
slide the stent
tip through
the trabecular
meshworkcanal
and into(Figure
Schlemm’s
canalAat slight
the
Snorkel Inside
throughe.the
trabecular
meshwork
and
into Schlemm’s
7b).
(.330 mm)
(.250 mm Long)
• After complications during cataract surgery, including but not limited to, severe corneal e. Gently
nasal position
to 4:00
o’clock position
for the meshwork
right eye; 8and
to 9:00
position
for
slide the(3stent
tip through
the trabecular
into o’clock
Schlemm’s
canal
Diameter (120 µm)
Stent Height
Snorkel
lifting motion
may
be
required
for
Theinferiorly,
stent
be 8inserted
so
that
Snorkel Inside
burn, vitreous removal/vitrectomy required, corneal injuries, or complications requiring
eye),position
with
the(3tiptoof4:00
the insertion.
implant
i.e., towards
the9:00
patient’s
foot:the
atthe
theleft
nasal
o’clockdirected
position
for theshould
right
eye;
to
o’clock
(.330 mm)
(.250 mm Long)
(120 μm)
DiameterRetention
rails are
located
on
back
wall
Schlemm’s
canal
and the
stent
body
istowards
parallel
the placement of an anterior chamber IOL
see
7the
for
aneye),
example
ofTM
Model
insertion
inthe
ainferiorly,
right
eye.
Approach
the totip
theposition
tip Figure
offor
thethe
stent
and
the of
(Figure
7a).
Insert
self-trephining
stent
left
with
the
tip
ofGTS100R
the implant
directed
i.e.,
trabecular
meshwork
atFigure
an
approximate
15º
angle
between
the
tip of (Figure
the stent
and
TM
the iris
plane
(Figures
7c
and
minimal
blood
reflux
is
athein
normal
the
patient’s
foot: see
77d).
forand
anNote:
example
of Model
GTS100R
insertion
a slight
through
the
trabecular
meshwork
into
Schlemm’s
canal
7b).
A
• When implantation has been without concomitant cataract surgery with IOL implantation
Arches
Figures
10a,
To Reacquire
Reacquirean
anImplanted
Implanted
Stent
(Figure
7a).
Insert
self-trephining
stentstent,
tip through
the trabecular
meshwork
and
Retention
Figures
10a,10b
10band
and10c.
10c. Steps
Steps To
Stent
for visually significant cataract
right
eye.
Approach
the
trabecular
atThe
an approximate
15⁰
angle
between
physiological
response
tobethe
placement
ofmeshwork
the
although
this does
not occur
in allthe
lifting
motion
may
required
for
insertion.
stent
should
be
inserted
so into
that
Schlemm’s canal (Figure 7b). A slight lifting motion may be required for insertion. The
Arches
®
are should
located
the back
wall
Schlemm’s
body is parallel
cases.railsstent
6.The safety and effectiveness of the iStent Trabecular Micro-Bypass Stent has not been
Self-Trephining
beon
inserted
so that
the of
rails
are located canal
on the and
backthe
wallstent
of Schlemm’s
canal to8. ADVERSE EVENT REPORTING
established in patients with pseudoexfoliative glaucoma and pigmentary glaucoma,
the and
iristheplane
(Figures
7c toand
7d).
Note:
minimal
blood
reflux
is blood
a normal
Rail
Tip
stent
body
is
parallel
the
iris
plane
(Figures
7c
and
7d).
Note:
minimal
(Only one rail
Adverse events
and/or
potentially sight-threatening complications that may reasonably be
ADVERSE
EVENT
REPORTING
Body (1.00 mm Long) Self-Trephining
because the pivotal trial was not powered to evaluate the outcomes of these groups. The
Schlemm’s
canal
physiological
response
to placement
oftothe
stent, although
this
does not
occur
is visible)
reflux is a normal
physiological
response
placement
of the stent,
although
this does
pg.not
7 in all
regarded as device related must be reported to Glaukos Corporation at:
Tip
Rail
safety and effectiveness of the iStent® has also not been established in patients with other
occur in all cases.
cases.
(Only one rail
Body (1.00 mm Long)
Adverse
and/orNumber:
potentially
sight-threatening
complications that may reasonably be
secondary open-angle glaucomas.
is visible)
U.S. Tollevents
Free Phone
1-800-GLAUKOS
(452-8567)
Figure 1. iStent; front view of right stent GTS100R
15⁰
regarded
as
device
related
must
be
reported
to
Glaukos
Corporation at:
®
Alternate Phone Number: 949-367-9600
Figure 1. iStent ; front view of right stent GTS100R
Schlemm’s canal
Figure 1. iStent; front view of right stent GTS100R
6. ADVERSE REACTIONS
Fax Number:
U.S.
Toll Free949-297-4540
Phone Number: 1-800-GLAUKOS (452-8567)
® has an “L”-shaped structure with a snorkel (inlet) on the short side which resides
TheiStent
iStent
The
has an “L”-shaped structure with a snorkel (inlet) on the short side which resides
15⁰ Figure 7a
Refer to the Pivotal Clinical Trial Results section for the adverse events that occurred in the
Alternate Phone Number: 949-367-9600
Figure
7a
theanterior
anterior
chamber,
which
opens
to half-pipe
the half-pipe
in Schlemm’s
ininthe
chamber,
andand
which
opens
to the
body body
whichwhich
residesresides
in Schlemm’s
Figure 7b
Fax
Number:
949-297-4540
9. HOW
SUPPLIED
The iStent has an “L”-shaped structure with a snorkel (inlet) on the short side which resides pivotal clinical trial. Additional adverse events that may be reasonably associated with the use
canal.
closed
side
of the
body
(Figure
1) sits
the inner
wall of
Schlemm’s
canal. canal.
canal.The
The
closed
side
of the
body
(Figure
1) against
sits against
the inner
wall
of Schlemm’s
of the device include but are not limited to the following: anterior chamber shallowing, severe,
®
in the
anterior
chamber,
and
which
opens
to
the
half-pipe
body
which
resides
in
Schlemm’s
Glaukos
iStent
Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L):
The
retention
arches
on
the
closed
side
of
the
body
serve
to
securely
fixate
the
device
in
The retention arches on the closed side of the body serve to securely fixate the device in
prolonged, or persistent intraocular inflammation, aqueous misdirection, choroidal effusion,
Figure 7a
canal.
The
closed
side
of
the
body
(Figure
1)
sits
against
the
inner
wall
of
Schlemm’s
canal.
Figure
7a
Schlemm’s
canal.
open
half-pipe
partpart
of the
body
(Figure
2) is2)against
the outer
wallwall in
The
stent
is
attached
to the tip of a single-use inserter, and the system is provided sterile and
Schlemm’s
canal.The
The
open
half-pipe
of the
body
(Figure
is against
the outer
HOW
SUPPLIED
Figure 7b
Thein retention
archescollector
on the closed side
ofrails
the are
body
to
securely
fixate theFigure
device2 in choroidal hemorrhage, corneal decompensation, corneal injury, corneal opacification,
order to
to access
access
the serve
edges
of the
half-pipe.
nonpyrogenic in a blister tray. Each stent system is individually serialized, and the serial number
order
collectorchannels.
channels.The
The
rails are
the
edges
ofopen
the open
half-pipe. Figure
2
cyclodialysis
cleft,
damage
to
trabecular
meshwork,
hyphema,
hypopyon,
hypotony,
Schlemm’s
canal.
The
openinhalf-pipe
of the
body
(Figure
2) is against
the outer wall
shows
of of
thethe
stent
1,part
rotated
180
degrees,
to display
the open
of in of
is provided on
the tray
lid and unit carton. The device has been sterilized by gamma radiation.
GTS100R/L
Stent
System:
showsa view
a view
stent Figure
in Figure
1, rotated
180 degrees,
to display
the half-pipe
open half-pipe
hypotony maculopathy, IOL dislocation, iridodialysis, loss of vitreous, perforation of sclera,
order
to access
collector channels. The rails are the edges of the open half-pipe. Figure 2
the
body.
The stent is attached
to the tip of a single-use inserter, and the system is provided sterile and
posterior capsular bag rupture, proliferative vitreoretinopathy, pupillary block, pupillary
thestent
stent
body.
®
Glaukos
iStent
Trabecular
Micro-Bypass Inserter (Model GTS100i):
shows a view of the stent in Figure 1, rotated 180 degrees, to display the open half-pipe of membrane formation, retinal detachment, retinal dialysis, retinal flap tears, secondary surgical
nonpyrogenic in a blister tray. Each stent system is individually serialized, and the serial
Rails
®
Body
the stent body.
The
Glaukos
iStent
Trabecular
Micro-Bypass Inserter (Model GTS100i) is a stand-alone
intervention, including but not limited to glaucoma surgery, stent inadvertently released from
(open half-pipe shown)
inserter; i.e., the Model GTS100i does not have an iStent® Trabecular Micro-Bypass Stent
Rails
inserter
in
eye,
stent
dislocation,
stent
not
retrievable,
stent
not
visible
with
gonioscopy,
stent
Body
Figure 7d
Figure 7c
attached to the tip when packaged in this configuration. The inserter (Model GTS100i) is
malfunction, and vitreous hemorrhage.
(open half-pipe shown)
provided sterile and nonpyrogenic in a blister tray. Each inserter has a lot number which is
Snorkel
provided on the tray lid and unit carton. The device has been sterilized by gamma radiation.
Figure
7. Insertion of Stent through TrabecularFigure
Meshwork
7d
pg. 10
Figure 7c
Snorkel
7. INSTRUCTIONS FOR USE
Figure 7a. Approach trabecular meshwork
Self-Trephining
Cataract Surgery
Figure7.7.Insertion
Insertion
of
Stent
Trabecular
Figures 7b-7d. Figure
Insertion
through of
trabecular
meshwork
intoMeshwork
Schlemm’s
10. STORAGE REQUIREMENTS
Stent through
through
Trabecular
Meshwork Canal
Tip
Figure 7a. Approach trabecular meshwork
1.
C
ataract
surgery
with
IOL
implantation
should
be
performed
first
followed
by
implantation
Figure
7a.
Approach
trabecular
meshwork
Self-Trephining
The device should be stored at room temperature in the range of 15-30º C.
Figures 7b-7d. Insertion through trabecular meshwork into Schlemm’s Canal
view
of open
body
(right
stentGTS100R)
GTS100R)
of the iStent®.
Figure 2.Figure
iStent2.®;iStent;
view of
open
stentstent
body
(right
If there is Figures
difficulty
withInsertion
insertion
at the trabecular
desired location,
try into
inserting
aboutCanal
0.5 clock
7b-7d.
through
meshwork
Schlemm’s
Tipstent
2.The stent implantations are designed for nasal placement; therefore, surgery is to hour
be inferior (i.e., if the first attempt is at 3:00 in the right eye, move inferiorly to the 11. EXPIRATION DATE
When properlyFigure
implanted,
iStent
is stent
intended
to create
bypass through the trabecular
2. iStent;the
view
of open
body (right
stent aGTS100R)
If there is difficulty with insertion at the desired location, try inserting about 0.5 clock
®
performed from the temporal side of the head.
When
properly
implanted,
the
iStent
is intended
to create
a bypass
through
the
trabecular
If there
isifdifficulty
insertion
at theindesired
try inserting
aboutthe
0.58:30
clock
meshwork
to
Schlemm’s
canal
to
improve
aqueous
outflow
through
the
natural
physiologic
3:30
position;
the (i.e.,
firstifwith
attempt
is at 9:00
leftlocation,
eye,eye,
move
When properly implanted, the iStent is intended to create a bypass through the trabecular
hour inferior
the first attempt
is at 3:00the
in the
right
moveinferiorly
inferiorly totothe
3:30
The expiration date on the device package (tray lid) is the sterility expiration date. In
®
meshwork
toThe
Schlemm’s
canal
to improve
aqueous
outflow
through the configuration
natural physiologic
pathway.
implant
is
provided
to
the
surgeon
in
a
pre-loaded
in
order
to
hour
inferior
(i.e.,
if move
the firstis
attempt
istheat
3:00
infor
the subsequent
right
eye,tomove
inferiorly
to the addition, there is a sterility expiration date that is clearly indicated on the outside of the
3.If the angle needs to be deepened after cataract surgery for placement of the iStent , position).
an
Continue
to
inferior
as
needed
attempts.
Note:
position;
if
the
first
attempt
at
9:00
in
left
eye,
move
inferiorly
the
8:30
position).
meshwork
to
Schlemm’s
canal
to
improve
aqueous
outflow
through
the
natural
physiologic
pathway.
The
implant
is
provided
to
the
surgeon
in
a
pre-loaded
configuration
in
order
to
allow The
for implant
precise is
insertion
into
canal.
The inserter
has been designed
3:30Continue
position;
iftothethe
first
attempt
is for
atpositions
9:00
in the
leftprevent
eye,Note:
move
inferiorly
to device
the 8:30 unit carton. Sterility is assured if the tray seal is not punctured or damaged until the
to move
inferior
as or
needed
subsequent
attempts.
superior
pathway.
provided
to Schlemm’s
the surgeon
in ainserter
pre-loaded
configuration
order to by intracameral miotic should be injected.
Implanting
superior
3:00
9:00
may
theImplanting
tip of the
allow for
precise insertion
into Schlemm’s
canal. The
has been
designed byin
Glaukos
Glaukos
Corporation
to hold
the Schlemm’s
implant and tocanal.
release the
implant
oncehas
it has
beendesigned
inserted by Stent Implantation
position).
Continue
to
move
inferior
as
needed
for
subsequent
attempts.
to
the
3:00
or
9:00
positions
may
prevent
the
tip
of
the
device
from
penetrating
tissue
dueNote:expiration date. This device should not be used past the indicated sterility expiration date.
allow
for
precise
insertion
into
The
inserter
been
from penetrating tissue due to the circular geometry of the eye.
Corporation to hold the implant and to release the implant once it has been inserted within
within Schlemm’s canal. Two model numbers (GTS100L and GTS100R) are available. The
to the circular
geometry
of the
eye.or 9:00 positions may prevent the tip of the device
Implanting
superior
to the
3:00
1. Select the model for implantation (i.e., Model GTS100L or Model GTS100R).
Schlemm’s canal. Two model numbers of the iStent® Trabecular Micro-Bypass Stent
last digit of these model numbers (L and R) correlates to a left-flow stent and a right-flow
f. Release
stent
by tissue
pushing
the
the
inserter.
stent is in 12. RETURN GOODS POLICY
f.the
Release
the stent
by pushing
the
button
onon
the
inserter.
theOnce
stent isthe
in Schlemm’s
from
penetrating
due to
thebutton
circular
geometry
ofOnce
the eye.
®
(GTS100R and GTS100L) are available. The last digit of these model numbers (R and L) pg.2.
1 The peel pouch containing the iStent Trabecular Micro-Bypass Stent System should be
stent. The stents are identical except the body faces opposite directions in order to facilitate
canal,
gently
tap thetap
side
of side
the snorkel
the inserter
the body
of the stent
in
correlates to a right-flow stent and a left-flow stent, respectively. The stents are identical except
Schlemm’s
canal,
gently
the
of thewith
snorkel
with to
thealign
inserter
to align
the body
opened onto the sterile field. Caution: Do not use the device if the Tyvek® lid has been
nasal stent placement. Model GTS100L is designed for the left eye, and Model GTS100R is
f. Release
the stent
by pushing
button
on will
the not
inserter.
Once
the
stent is inPlease contact Glaukos Corporation.
Schlemm’s
canal (Figure
8).(Figure
Thethe
body8).
of the
stent
be aligned
within
Schlemm’s
pg. 1
the
body
faces
opposite
directions
in
order
to
facilitate
nasal
stent
placement.
Model
GTS100L
of
the
stent
in
Schlemm’s
canal
The
body
of
the
stent
will
not
be
aligned
opened
or
the
packaging
appears
damaged.
In
such
cases,
the
sterility
of
the
device
may
designed for the right eye (Table 1).
Schlemm’s
canal,
tap the side of the snorkel with the inserter to align the body
canal without
thisgently
last step.
is designed for the left eye, and Model GTS100R is designed for the right eye (Table 1).
be compromised.
withinofSchlemm’s
without
this (Figure
last step.8). The body of the stent will not be aligned 13. PIVOTAL CLINICAL TRIAL RESULTS
the stent incanal
Schlemm’s
canal
TheGlaukos
Glaukos iStent
iStent®® Trabecular
Trabecular Micro-Bypass
GTS100i
is also
in a
The
Micro-BypassInserter
InserterModel
(Model
GTS100i)
is available
also available
3.Grasp the inserter as shown in Figure 3 with your index finger on the release button. With
®®
Description of the Randomized Clinical Trial
within Schlemm’s canal without this last step.
configuration;
i.e.,i.e.,
ThetheInserter
GTS100i
does
notnot
have
instand-alone
a stand-alone
configuration;
InserterModel
(Model
GTS100i)
does
haveananiStent
iStent
the release button on the inserter facing up, ensure that the orientation of the stent on the
Schlemm’s canal
Trabecular Micro-Bypass
Micro-Bypass Stent
thethe
tip tip
when
packaged
in thisinconfiguration.
The
Trabecular
Stentattached
attachedtoto
when
packaged
this configuration.
The study was a prospective, randomized, controlled, open-label, multicenter trial. A total of
inserter is appropriate for the desired nasal implantation as shown in Figure 4a for the
inserter
is provided
as as
a single-use,
disposable
device
thatthat
is is
able
The
inserter
is provided
a single-use,
disposable
device
abletotoreacquire
reacquirethe
thestent
stent
27 sites throughout the U.S. enrolled subjects in the randomized phase of the study. A total of
Schlemm’s canal
Model GTS100L and in Figure 4b for the Model GTS100R.
intraocularlyshould
shouldthe
the surgeon
surgeon determine
determine itit isis necessary.
intraocularly
necessary.
240 eyes of 239 patients meeting the study eligibility criteria were randomized in a 1:1 fashion
to undergo either implantation of the iStent® in conjunction with cataract surgery (treatment
group) or cataract surgery without implantation of the iStent® (control group). Subjects in this
TABLE
TABLE 11
randomized population were treated from April 13, 2005 through June 28, 2007. All subjects
Glaukos
Micro-BypassStent
StentSystem
System
GlaukosCorporation
Corporation iStent
iStent® Trabecular
Trabecular Micro-Bypass
were followed for a period of 2 years. A total of 117 eyes of 116 subjects were enrolled in the
treatment group, and 123 subjects were enrolled in the control group. To obtain additional
Figure
Figure
8. 8.
safety information, the study also included a separate non-randomized arm of patients to
Catalogue #
Description
stenttap
andside
tap with
side with
inserter
to
stent
Schlemm’s canal
canal
ReleaseRelease
stent and
inserter
to align
stent
ininSchlemm’s
Figure
8. align
undergo iStent® implantation in conjunction with cataract surgery. A total of 50 subjects were
Release
stent
and
tap
side
with
inserter
to
align
stent
in
Schlemm’s
canal
GTS100L
Left-flow iStent attached to disposable inserter,
enrolled in this arm of the study (also see additional detail below in the section entitled “Nong. Verify that the inlet of the snorkel is visible in the anterior chamber.
designed for left eye
Randomized Cohort”). Study subjects were diagnosed with mild to moderate open-angle
g.
Verify
that
the
inlet
of
the
snorkel
is
visible
in
the
anterior
chamber.
h.
Withdraw
the
inserter.
A view
viewofofthetheimplanted
implanted
stent
the snorkel
visible
is
glaucoma (OAG). Pseudoexfoliative and pigmentary glaucoma were acceptable diagnoses.
h.
Withdraw
theinlet
inserter.
A
stent
withwith
thechamber.
snorkel
visible
is shown
g.
Verify
that
the
of
the
snorkel
is
visible
in
the
anterior
GTS100R
Right-flow iStent attached to disposable inserter,
shown
in Figure
9.
belowbelow
in Figure
9.
FigureFigure
3. Hand
on inserter
3. position
Hand position
on inserter
designed for right eye
Mild to moderate open-angle glaucoma was defined in the study protocol as:
Figure3.3.Hand
Hand position
position on
Figure
oninserter
inserter
GTS100i
Stand-alone inserter (no stent attached)
1.Enlarged C:D ratio consistent with glaucoma, but still ≤ 0.8, given the requirement for
pg. 8
pg. 8 early stage glaucomatous disease
2. Either visual field defect or nerve abnormalities consistent with glaucoma.
2. INDICATIONS FOR USE
DIRECTIONS FOR USE/PACKAGE INSERT
Glaukos Corporation iStent® Trabecular Micro-Bypass Stent System
The iStent® Trabecular Micro-Bypass Stent (Models GTS100R and GTS100L) is indicated
for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP)
in adult patients with mild to moderate open-angle glaucoma currently treated with ocular
hypotensive medication.
Temporal
Direction of feet of
patient
3. CONTRAINDICATIONS
The iStent® Trabecular Micro-Bypass Stent is contraindicated under the following
circumstances or conditions:
• I n eyes with primary angle closure glaucoma, or secondary angle-closure glaucoma,
including neovascular glaucoma, because the device would not be expected to work in
such situations
Nasal
FigureFigure
4a.
GTS100L
(top(top
view)
4a. Model
GTS100L
(top
view)
Figure
4a.Model
Model
GTS100L
view)
tip
isis
inferior
andand
points
leftview)
Stent
tip
is inferior
and
points
left
Figure
4a.
Model
GTS100L
(top
Stent
Stent
tip
inferior
points
left
Stent tip is inferior and points left
Figure
4b. 4b.
Model
GTS100R
(top view)
Figure
4b.
Model
GTS100R
(top view)
Figure
Model
GTS100R
(top
view)
Stent
tip
is
inferior
and
points
right
Stent
tip
is inferior
and
points
rightright
Figure
4b.
Model
GTS100R
(top
view)
Stent
tip
is
inferior
and
points
Figure
Figure9.9.
Gonioscopic
stent
(right
eye)
Gonioscopicview
viewofofimplanted
implanted
stent
(right
eye)
Stent tip is inferior and points right
theofend
the procedure,
the following
should
be performed:
7. At 7.
theAt
end
theofprocedure,
the following
should
be performed:
4.Inspect angle with a gonioprism to ensure that a good view is available at the nasal implant
• I n patients with retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any
location.
a.
I
rrigate
the
anterior
chamber
with
balanced
salt
solution
(BSS)
throughthethecorneal
corneal
a. Irrigate the anterior chamber with balanced salt solution
(BSS)
through
other type of condition that may cause elevated episcleral venous pressure
4. Inspect
angle angle
with awith
gonioprism
to ensure
that athat
good
view view
is available
at theatnasal
4. Inspect
a gonioprism
to ensure
a good
is available
the nasal
wound
manually,
or with
automated
irrigation/aspiration
to
removeviscoelastic
viscoelasticand
and
5.
P
lace
a
gonioscope
on
the
cornea
and
reposition
the
surgical
microscope
as
needed
to
wound
manually,
or
with
automated
irrigation/aspiration
to
remove
implant
location.
implant
4. Inspect
anglelocation.
with a gonioprism to ensure that a good view is available at the nasal
4. WARNINGS
refluxed blood.
visualize the trabecular meshwork, through the gonioprism, on the nasal side of the eye.
refluxed
blood.
implant
location. on theoncornea
a gonioscope
andof reposition
the surgical
microscope
needed
5.Focus
Place
theangle
cornea
andeye
reposition
the Look
surgical
microscope
as needed
to b. Inflate the anterior chamber with saline solution as needed to achieve physiologic
1.The following conditions may prohibit sufficient visualization of the angle required for safe 5. Place
on athegonioscope
landmarks in the
the
(Figure
5).
up from
theasiris
root
toto
Inflate
the anterior chamber with saline solution as needed to achieve physiologic
visualize
trabecular
through
theSchwalbe’s
gonioprism,
on(white
the
side
theof
eye.
visualize
the
trabecular
meshwork,
through
thethe
gonioprism,
onnasal
the nasal
the
find the
scleral
spur
(white
Then
for
line
line)
down
from
the
pressure.
and successful stent implantation: corneal haze, corneal opacity, or any other conditions 5. Place
a the
gonioscope
onmeshwork,
theline).
cornea
andlook
reposition
surgical
microscope
asofside
needed
tob.eye.
pressure.
Focus
on the
landmarks
inmeshwork,
the in
angle
of theof
eye
(Figure
5).
Look
up nasal
from
the
iris
root
toroot to
cornea.
The
trabecular
meshwork
a red/brown
line)
is between
scleral
spur
Focus
on
the landmarks
the(typically
angle
eye (Figure
5).
Look
upthe
from
iris
that may inhibit gonioscopic view in the intended implant location.
visualize
the
trabecular
through
the
gonioprism,
on
the
side
ofthe
the
eye.
c. Ensure that the corneal incision is sealed, and place 10-0 nylon suture if needed.
and
Schwalbe’s
line.
Schlemm’s
canal
behind
thefor
trabecular
meshwork.
find
the
scleral
spur
(white
line).
Then
look
for
Schwalbe’s
(white
line)thedown
fromtoc.
find
the
spur
line).
Then
look
Schwalbe’s
line
(white
line)
down
from
Focus
on
the scleral
landmarks
in(white
the angle
ofis
the
eye
(Figure
5). line
Look
up from
iris root
Ensure that the corneal incision is sealed, and place 10-0 nylon suture if needed.
2.The surgeon should perform gonioscopy prior to taking a patient to surgery to exclude
the
cornea.
The spur
trabecular
meshwork
(typically
red/brown
line)
isline)
between
the
scleral
the cornea.
The(white
trabecular
a red/brown
isline)
between
the
scleral
find
scleral
line).meshwork
Then
look(typically
foraSchwalbe’s
line (white
down
from
congenital anomalies of the angle, peripheral anterior synechiae (PAS), rubeosis, and any
spur
line. Schlemm’s
canal
is behind
the trabecular
meshwork.
spurSchwalbe’s
andThe
Schwalbe’s
line.
Schlemm’s
canal
is
the line)
trabecular
meshwork.
pg. 2 a
the and
cornea.
trabecular
meshwork
(typically
a behind
red/brown
is between
the scleral Postoperative Instructions
other angle abnormalities that could lead to improper placement of the stent and pose
Postoperative
Instructions
1.Patients
should be managed postoperatively for IOP increases that may occur in the early
spur and Schwalbe’s line. Schlemm’s canal is behind the trabecular meshwork.
hazard.
postoperative
period as postoperatively
a possible sequelae
following
cataract
surgery
in in
patients
with
1. Patients
should be managed
for IOP
increases
that may
occur
the early
3.Regarding the Magnetic Resonance (MR) status of the implant, non-clinical testing has
glaucoma.period as a possible sequelae following cataract surgery in patients with
postoperative
®
demonstrated that the iStent Trabecular Micro-Bypass Stent (Models GTS100R and
glaucoma.
GTS100L) is MR Conditional. Please see the “MRI SAFETY INFORMATION” section at
Retrieval of an Implanted Stent
the end of this document for conditions for safe scanning.
If the surgeon determines that another inserter (Model GTS100i) is required to grasp a stent
5. PRECAUTIONS
Retrieval
ofthe
an original
Implanted
Stentfrom the stent system is no longer available or not used), the inserter
(i.e.,
inserter
1.The surgeon should inform the patient that the stent is MR-Conditional (as noted on their
(Model GTS100i) may be used by the surgeon as follows:
If the surgeon determines that another GTS100i inserter is required to grasp a stent (i.e., the
Patient ID card), and if the patient needs to undergo an MRI, they should let their doctor
®
Similar to
the the
initial
implant
procedure,
visualize
the location
the iStent
using a
original1.
inserter
from
stent
system
is no longer
available
or notof used),
the Model
know they have an iStent® implanted in their eye.
GTS100i goniolens.
inserter may be used by the surgeon as follows:
2.After the surgery, the surgeon should give the patient the Patient ID card (enclosed in the
2.Enter
the eye
through
a clear
corneal incision.
1. Similar
to the
initial
implant
procedure,
visualize the location of the iStent using a
iStent® packaging) with the appropriate information filled in, and should advise the patient
Figure 5. iStent® Implant Site
goniolens.
3.Advance to the location of the iStent®, and depress the inserter button to open the inserter
to keep the card in a safe place, e.g., his or her wallet, for future reference. The surgeon
2. Enter the
eye
through
a clear corneal incision.
jaws
(Figure
10a).
should advise the patient that this Patient ID card contains important information related to
3. 6Advance
to the
location
of the
the release
iStent, button,
and depress
the the
inserter
button
to stent
openinthetheinserter
pg.
pg.4.
6 While
holding
down
position
snorkel
of the
inserter
the iStent® and that the card should be shown to their current and future health care providers.
6. Insertion of stent
jaws (Figure
10a).
(Figure
10b),
and
then
release
the
release
button
to
grasp
the
snorkel
of
the stent (Figure
pg. 6
a.Inject viscoelastic into the anterior chamber to assist with chamber maintenance.
3.
The surgeon should monitor the patient postoperatively for proper maintenance of
4. While 10c).
holding
down
the release
stent inin the
Once
the stent
is in the button,
inserter, position
it can thenthe
be snorkel
implantedofasthe
described
Stepinserter
6 above,
intraocular pressure. If intraocular pressure is not adequately maintained after surgery, the
b.Insert the stent (which is attached to the inserter tip) through the temporal incision that was (Figure
andfrom
then the
release
to grasp
theexiting
snorkelthe
ofwound.
the stent (Figure
or10b),
removed
eye. the
Carerelease
shouldbutton
be exercised
when
surgeon should consider an appropriate medication regimen to reduce intraocular pressure.
used to extract the cataract and insert the intraocular lens.
10c). Once the stent is in the inserter, it can then be implanted as described in Step 6
above, or removed from the eye. Care should be exercised when exiting the wound.
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 at clinical examination of moderate to advanced nerve fiber bundle
defects (i.e. Bjerrum scotoma)
In the case of nerve abnormalities consistent with glaucoma, one or more of the following 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 shaped-defect
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 the nerve 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 were required 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 an unmedicated 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 the time of
surgery, with a mean age of 74 years. Most subjects (60%) were female, and the majority
of subjects (71%) were Caucasian. There were equal proportions of right eyes 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. Fifty-eight 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 ocular
hypotensive 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 was compared between the two study
groups.
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
TABLEendpoint
2
18% in favor of the iStent® group on the primary
at 12 months was statistically (p =
IOPand
≤ 21clinically
MMHG significant.
WITHOUT OCULAR HYPOTENSIVE MEDICATIONS AT 12 MONTHS
.004)
Analysis Population and
1
Cataract Surgery
Cataract Surgery
N=116
N=123
P-value1
The ITT population included 117 eyes of 116 subjects randomized to undergo
iStent® implantation. The modified ITT population
Imputation
Method
iStent®
Only
(mITT) included
116 eyes of 116
subjects (excluded 1 eye fromwith
same subject).
1.
(%)
(%)
ABLE
TTABLE
22
mITT
Analysis
68%
50% AT 12 MONTHS
.004
IOPUsing
21Non-Responder
MMH
HGGWITHOUT
WITHOUT O
OCULAR
CULAR H
HYPOTENSIVE
YPOTENSIVE M
MEDICATIONS
EDICATIONS AT
IOP
≤≤ 21
MM
12 MONTHS
Two-sided Z-test.
Cataract Surgery
Surgery Cataract
Cataract Surgery
Surgery
P-value11
Cataract
P-value
with iStent
iStent
Only
with
Only
N=116
N=123 of patients with IOP
The secondary endpoint in the GC-003 pivotalN=116
trial was the proportion
N=123
(%)at 12 months (%)
(%)
(%)
reduced ≥ 20% from baseline without medications
(mITT
using non-responder
mITT Using
Using Non-Responder
Non-Responder
Analysis
68%
50%
.004
®
mITT
Analysis
68%
50%
.004
Analysis Population
Population and
and
Analysis
ImputationMethod
Method
Imputation
analysis).
In theZ-test.
iStent treatment group, 64% of subjects implanted met this endpoint
Two-sided
Z-test.
1.1. Two-sided
compared to 47% in the cataract control group (Table 3). This treatment difference of 17%
wasThe
alsosecondary
statistically
(p = .010)
clinically
significant.
The
secondary
endpoint
in the
theand
GC-003
pivotal
trial was
wasthe
theproportion
proportionof
ofpatients
patientswith
withIOP
IOP
endpoint
in
GC-003
pivotal
trial
was
the
proportion
of
patients
with
IOP
The
secondary
endpoint
reduced
≥ 20%
20% from
from baseline
baseline without
without medications
medicationsat
at12
12months
months(mITT
(mITTusing
usingnon-responder
non-responder
reduced ≥≥
20%
reduced
at
12
months
(mITT
using
non-responder
TABLE
treatment group,
group,
64%3of
of subjects
subjects implanted
implantedmet
metthis
thisendpoint
endpoint
analysis).
In the
the iStent
iStent®®® treatment
analysis). In
In
64%
analysis).
64%
of
subjects
implanted
met
this
endpoint
REDUCTION
≥ in
20%
OCULAR
H(Table
YPOTENSIVE
Mtreatment
EDICATIONS
AT 12of
M
ONTHS
IOP
compared
theWITHOUT
cataract control
control
group
(Table3).
3). This
This
treatmentdifference
difference
of17%
17%
to 47%
47%
in the
group
compared
to
cataract
(Table
3).
This
treatment
difference
of
17%
Population
andand
Cataract
Surgery
Cataract Surgery
P-value1
was also
alsoAnalysis
statistically
(p == .010)
.010)
and clinically
clinically
significant.
significant.
was
statistically
(p
significant.
Imputation Method
with iStent®
mITT Using
Non-Responder
Analysis
PopulationAnalysis
and
Analysis
Population
and
64%
Cataract
Surgery
Cataract
Surgery
with iStent
iStent
with
N=116
N=116
(%)
(%)
64%
64%
Only
ABLE
N=116
N=123
TTABLE
33
(%)
(%)
IOPR
REDUCTION
EDUCTION ≥≥ 20%
20%WITHOUT
WITHOUT O
OCULAR
CULAR H
HYPOTENSIVE
YPOTENSIVE M
MEDICATIONS
EDICATIONS
AT 12
12M
MONTHS
ONTHS
IOP
AT
1
1.
Two-sided Z-test.
ImputationMethod
Method
Imputation
mITT Using
Using
Non-Responder
Analysis
mITT
Non-Responder
Analysis
Safety Results
– Adverse
Events
1. Two-sided Z-test.
1.
Two-sided Z-test.
Cataract47%
Surgery
Cataract
Surgery
Only
Only
N=123
N=123
(%)
(%)
47%
47%
1
.010
P-value
P-value
.010
.010
Intraoperative Complications
Safety Results
Results
Adverse
Events
Safety
Results
Adverse Events
Events
Intraoperative
complications
specifically related to implantation of the iStent are summarized
Safety
––– Adverse
in Table
4
for
the
112
subjects
Intraoperative Complications in whom stent implantation was attempted. These events
Intraoperative
Complications
Intraoperative
Complications
included
iris touch
(n=8), endothelium touch (n=1), intraoperative stent removal
and
®
Intraoperative complications
complicationsspecifically
specifically
related
to implantation
of the
are
Intraoperative
complications
specifically
related
to implantation
implantation
of the
the iStent
iStent
areiStent
summarized
Intraoperative
to
of
are
summarized
replacement
(n=1),
failure
to the
implant
stentrelated
(n=1)
and
stentimplantation
malposition
(n=1).
summarized in Table
4 for
112 subjects
in whom
stent
was
attempted. These
in Table
Table 44 for
for the
the 112
112 subjects
subjects in
in whom
whom stent
stent implantation
implantation was
was attempted.
attempted. These
These events
events
in
events included iris touch (n=8), endothelium touch (n=1), intraoperative stent removal and
included
iris touch
touch
(n=8),
endotheliumwas
touch
(n=1), intraoperative
intraoperative
stent
removal
and
included
iris
(n=8),
endothelium
touch
(n=1),
stent
removal
and
These
data show
that failure
stent
implantation
successful
in
the majority
of cases,
with
only
replacement
(n=1),
to
implant
stent
(n=1)
and
stent
malposition
(n=1).
replacement
(n=1), failure
failure to
to implant
implant stent
stent (n=1)
(n=1) and
and stent
stent malposition
malposition (n=1).
(n=1).
(n=1),
one replacement
report of stent
implantation
not completed
due to
poor visualization
of the angle, and a
These data show that stent implantation was successful in the majority of cases, with only one
lowThese
incidence
of
operative
complications
and
adverse
events.
These
data
show
that stent
stent
implantation
was
successful
in the
the majority
majority
ofangle,
cases,and
with
only
show
that
implantation
in
of
cases,
with
only
report data
of
stent
implantation
not
completedwas
duesuccessful
to poor visualization
of the
a low
one
reportof
ofoperative
stent implantation
implantation
not completed
completed
due
to poor
poor visualization
visualization of
of the
the angle,
angle, and
and aa
incidence
complications
and adversedue
events.
one
report
of
stent
not
to
low incidence
incidence of
of operative
operative complications
complications and
and adverse
adverse events.
events.
low
TABLE 4
OPERATIVE COMPLICATIONS AND ADVERSE EVENTS FROM STENT IMPLANTATION
TABLE
ABLE 44
N = 112T
n (%)
OPERATIVE
PERATIVE
COMPLICATIONS
OMPLICATIONS
AND A
ADVERSE
DVERSE E
EVENTS
VENTS FROM
FROM SSTENT
TENT I8IMPLANTATION
MPLANTATION
Iris touched
by
the device
( 7.1%)
O
C
AND
N == 112
112
N
Endothelium touched
Iris touched
touchedstent
bythe
theremoval
device and replacement
Iris
by
device
Intraoperative
Endothelium
touched
Endothelium
touched
Failure
to implant
stent
Intraoperative
stent removal
removal and
and replacement
replacement
Intraoperative
Stent
malpositionstent
nn1 (%)
((%)
0.9%)
7.1%)
88 ((1 7.1%)
( 0.9%)
0.9%)
11 ((1 0.9%)
( 0.9%)
0.9%)
11 ((1 0.9%)
( 0.9%)
0.9%)
11 (( 0.9%)
0.9%)
11 (( 0.9%)
Failure to
to implant
implant stent
stent
Failure
Stent malposition
malposition
Stent
Postoperative Ocular Adverse Events
A summaryOcular
of postoperative
Postoperative
Adverse ocular
Eventsadverse events reported in the safety population during the
randomized clinical trial is presented below. Anticipated, early postoperative events included
A summary
of
postoperative
ocular
adverse events reported in the safety population during
Postoperative
Ocular
Adverse
Events
Postoperative
Ocular
Events
transient events
suchAdverse
as corneal
edema, trace folds, trace striae, transient hypotony at 5-7
A
summary
of
postoperative
ocular
adverse
events reported
reported
in the
the
safetypostoperative
population
during
the A
randomized
clinical
trial
is
presented
below.
Anticipated,
early
events
summary
of
postoperative
ocular
events
in
safety
population
during
hours, inflammation, epithelial defectadverse
and discomfort
as expected
following
cataract surgery.
the
randomized
clinicalcells
trialand
presented
below.
Anticipated,
early
postoperative
events
the
randomized
clinical
trial
isis presented
below.
Anticipated,
postoperative
Iritis,
anterior chamber
uveitis
were
considered
separate early
and unique
adverse events
event
categories of intraocular anterior 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,
pg. 14
1 anterior chamber +1 cells requiring treatment).
pg.14
14
pg.
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 suffering a stroke. One
subject in the control group had macular traction, macular hole and macular 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 were representative 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 5
POSTOPERATIVE OCULAR ADVERSE EVENTS*
SAFETY POPULATION
Adverse Events
Cataract Surgery
with iStent
N = 116
n (%)
Anticipated early postoperative event
Early postop corneal edema
Early postop anterior chamber cells
Early postop corneal abrasion
Early postop corneal striae
Early postop discomfort
Early postop subconjunctival hemorrhage
Early postop superficial punctate keratitis
Early postop blurry vision
Early postop floaters
Any BCVA loss of at least 1 line at or after the three month visit
Posterior capsular opacification
Stent obstruction by iris, vitreous, fibrous overgrowth,fibrin,
blood, etc.
Blurry vision or visual disturbance
Elevated IOP – other
Stent malposition
Subconjunctival hemorrhage
Epiretinal membrane
Drusen
Iris atrophy
Iritis
Conjunctival irritation due to hypotensive medication
Disc hemorrhage
Elevated IOP requiring treatment with oral or intravenous
medications or with surgical intervention
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
*occurring at ≥ 2% in either group, or other adverse events known to be
or potential risk with stent implantation.
Cataract Surgery
Only
N = 117
n (%)
9(
4(
3(
2(
1(
1(
0(
0(
0(
8(
7(
5(
8%)
3%)
3%)
2%)
1%)
1%)
0%)
0%)
0%)
7%)
6%)
4%)
11 ( 9%)
2 ( 2%)
2 ( 2%)
1 ( 1%)
2 ( 2%)
0 ( 0%)
2 ( 2%)
1 ( 1%)
1 ( 1%)
12 ( 10%)
12 ( 10%)
0 ( 0%)
4(
4(
3(
2(
2(
2(
2(
1(
1(
1(
1(
3%)
3%)
3%)
2%)
2%)
2%)
2%)
1%)
1%)
1%)
1%)
8(
5(
0(
2(
1(
0(
0(
6(
3(
3(
3(
7%)
4%)
0%)
2%)
1%)
0%)
0%)
5%)
3%)
3%)
3%)
1(
1(
1(
1(
1(
1%)
1%)
1%)
1%)
1%)
2(
2(
2(
1(
0(
2%)
2%)
2%)
1%)
0%)
1 ( 1%)
0 ( 0%)
1 ( 1%)
0 ( 0%)
0 ( 0%)
5 ( 4%)
0 ( 0%)
4 ( 3%)
0 ( 0%)
4 ( 3%)
0 ( 0%)
2 ( 2%)
0 ( 0%)
1 ( 1%)
0 ( 0%)
1 ( 1%)
associated with glaucoma procedures
In
reported
in Table
5 (i.e.,
adverse
events
that occurred
at an
In addition
additiontotothe
theadverse
adverseevents
events
reported
in Table
5 (i.e.,
adverse
events
that occurred
incidence
of ≥ 2%
either
adverseadverse
events events
that occurred
at < 2%
bothingroups
at an incidence
of in
≥ 2%
in group),
either group),
that occurred
at in
< 2%
both
included worsening of glaucoma and allergy to cosmetics. Adverse events that occurred at <
2% in the treatment group included age-related macular degeneration, uveitis,
GLAUKOS CORPORATION ISTENT TRABECULAR MICRO-BYPASS STENT
groups included 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, and subjconjunctival 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). Another subject
underwent focal argon laser coagulation for diabetic macular edema. Stent-specific 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 the early 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 and macular edema, and
one subject underwent three separate procedures of wound resuture because of wound leak,
pupilloplasty, and IOL removal and replacement.
TABLE 6
SECONDARY SURGICAL INTERVENTIONS – POSTOPERATIVE OCULAR ADVERSE EVENTS
SAFETY POPULATION
Secondary Surgical Intervention
Adverse Events
Paracentesis1
Nd:YAG laser capsulotomy
Stent repositioning
Punctal cautery/punctal plugs
Trabeculoplasty
Nd:YAG laser iridoplasty for stent
obstruction
Focal argon laser photocoagulation
Stent removal and replacement
Deep sclerectomy/sclerostomy
IOL removal and replacement
LASIK
Pupilloplasty
Vitrectomy
Wound resuture due to wound leak
1. included paracentesis at the 5-7 hr exam
Randomized Group
Cataract Surgery
Cataract Surgery
with iStent
Only
N = 116
N = 117
n (%)
n (%)
31 (27%)
34 (29%)
7 ( 6%)
11 ( 9%)
3 ( 3%)
0 ( 0%)
1 ( 1%)
3 ( 3%)
1 ( 1%)
2 ( 2%)
1 ( 1%)
0 ( 0%)
1(
1(
0(
0(
0(
0(
0(
0(
1%)
1%)
0%)
0%)
0%)
0%)
0%)
0%)
0(
0(
1(
1(
1(
1(
1(
1(
0%)
0%)
1%)
1%)
1%)
1%)
1%)
1%)
Non-Randomized Cohort
Non-Randomized
Cohort
As described earlier,
a non-randomized arm of the study was performed. A total of 50
AsNon-Randomized
described
earlier,Cohort
aatnon-randomized
arm of the study
was
A total of
50
subjects
were enrolled
10 sites in the non-randomized
phase
of performed.
the study subsequent
to the
subjects
were
enrolled
10of
sites
the arm
non-randomized
phase
of the study
subsequent
the
As described
aat
non-randomized
of thepopulation.
study was
performed.
A total
of in
50 subjects
completion
of earlier,
enrollment
theinrandomized
Subjects
enrolled
this tononcompletion
of
of non-randomized
the randomized
population.
Subjects
in this nonwere enrolled
atenrollment
10underwent
sites in the
phase
the study
subsequent
to thesurgery.
completion
randomized
phase
iStent
implantation
inofconjunction
with enrolled
cataract
The
randomized
phase
underwent
iStent
implantation
in was
conjunction
with
cataract
surgery.
The
of enrollment
of
the
randomized
population.
Subjects
enrolled
in this
non-randomized
phase
purpose
of this
non-randomized
phase
of
the
study
to
collect
safety
data
on
additional
®
underwent
iStent
implantation
in
conjunction
with
cataract
surgery.
The
purpose
of
this
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
non-randomized
phase of and
the study
was to collect
safety
on additional
subjects. The
subjects.
The criteria.
randomized
non-randomized
phases
of data
the study
used identical
and exclusion
Both phases
used the same
standardized
procedures,
applied inclusion
the same
randomized
and
non-randomized
phases
of the
study
used identical
inclusionapplied
and exclusion
and
exclusion
criteria.
Both
phases
used in
the
same
standardized
procedures,
the
same
surgical
techniques,
and
placed
the
stent
the
same
anatomical
location.
Of
the 50surgical
subjects
criteria.
Both
phases
used
the
same
standardized
procedures,
applied
the
same
surgical
techniques,
and
placed
the
stent
in
the
same
anatomical
location.
Of
the
50
subjects
enrolled,
46 and
wereplaced
implanted
with
thesame
iStent,
2 subjects
withdrew
surgery
and 2
techniques,
the stent
in the
anatomical
location.
Of thebefore
50 subjects
enrolled,
enrolled,
46 were
with
the iStent,
2 subjects
withdrew
before
surgery
and 2
subjects
exitedimplanted
afterthe
surgery
iStent
implantation.
Preoperative
46 werewere
implanted
with
iStent®following
, 2 subjectsunsuccessful
withdrew before
surgery
and 2 subjects
were
subjects
were
exited
after
surgery
following
unsuccessful
iStent
implantation.
Preoperative
®
parameters
in
the
non-randomized
population
were
similar
to
those
in
the
randomized
exited afterinsurgery
following unsuccessful
iStentwere
implantation.
parameters
in
parameters
the non-randomized
population
similar toPreoperative
those in the
randomized
population.
the non-randomized population were similar to those in the randomized population.
population.
Results of the 46 subjects successfully implanted with the iStent (the Non-Randomized
® (the Non-Randomized
Results
implanted
with
theiStent
iStent
Resultsofofthe
the 46
46 subjects
subjects
successfully
with
the
(the Non-Randomized
Population)
are
presented
in successfully
Tables 7- 10.implanted
Forty-four
subjects
completed
follow-up through
Population)
are
ininTables
10. the
Forty-four
subjects
completed
follow-up
through
Population)
are
presented
Tables 7710.
Forty-four
subjects
completed
follow-up
Month
24, and
2presented
subjects terminated
from
study prior
to Month
24. There
were through
no
stents
Month
24,
and
2
subjects
terminated
from
the
prior
to
Month
24.
There
were
no
stents
Month
24,
and
2
subjects
terminated
from
study
prior
to
Month
24.
There
were
no
stents
removed or replaced during the 24-month follow-up period.
removedororreplaced
replacedduring
duringthe
the24-month
24-monthfollow-up
follow-up period.
removed
TABLE 7
TABLE 7
IOP ≤ 21 MMHG WITHOUT OCULAR HYPOTENSIVE MEDICATIONS
IOP ≤ 21 MMHG WITHOUT OCULAR HYPOTENSIVE MEDICATIONS
IOP REDUCTION ≥ 20% WITHOUT OCULAR HYPOTENSIVE MEDICATIONS
≥ 20%
WITHOUT OCULAR HYPOTENSIVE MEDICATIONS
IOP REDUCTION
NON-R
ANDOMIZED POPULATION AT 12 MONTHS
NON-R
ANDOMIZED POPULATION AT 12 MONTHS
Non-Randomized Cataract
Surgery
IOP ≤ 21 mmHg
IOP Reduction ≥ 20%
Non-Randomized
with iStentCataract
(N = 46)Surgery
with iStent (N = 46)
ITT using Non-Responder Analysis
ITT using Non-Responder Analysis
IOP
≤ 21 mmHg
without
Ocular
Hypotensive
without Medications
Ocular Hypotensive
Medications
(%)
(%)
78%
78%
IOP Reduction
≥ 20%
without
Ocular Hypotensive
without Medications
Ocular Hypotensive
Medications
(%)
(%)
72%
pg. 18
72%
TABLE 8
TABLE
8
FROM STENT IMPLANTATION
OPERATIVE COMPLICATIONS
OPERATIVE C
OMPLICATIONS FROM STENT IMPLANTATION
SUBJECTS
WITH ISTENT IMPLANT
WITH
STENT(NIMPLANT
SUBJECTS
Non-Randomized Cataract
Surgery
withIiStent
= 46)
n (%)
Non-Randomized Cataract Surgery with iStent (N = 46)
Iris damage*
Iris damage*
Stent
malposition*
Stent
Ocularmalposition*
pain during insertion
Ocular
pain during
insertion
Iris touched
by the device
Iris
touched
by the device
Endothelial touch
Endothelial
touch collapse
Anterior chamber
Anterior
* same eyechamber collapse
n
1(
1
1 ((
1
1 ((
1
3 ((
3
1 ((
1
1 ((
1(
(%)
2.2%)
2.2%)
2.2%)
2.2%)
2.2%)
2.2%)
6.5%)
6.5%)
2.2%)
2.2%)
2.2%)
2.2%)
TABLE 9
POSTOPERATIVE OCULAR ADVERSE EVENTS
NON-RANDOMIZED POPULATION
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
Uveitis
Vitreous 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
T ABLE 11
A LL S IGHT -T HREATENING A DVERSE E VENTS
(D ATA FROM GC-003 AND GTS100-PAS)
Cataract Surgery
with iStent
N = 46
n (%)
2(
2(
1(
1(
1(
1(
1(
4(
4(
3(
4%)
4%)
2%)
2%)
2%)
2%)
2%)
9%)
9%)
7%)
2(
2(
2(
2(
2(
4%)
4%)
4%)
4%)
4%)
2(
1(
1(
1(
1(
1(
1(
1(
1(
1(
1(
1(
1(
1(
0(
4%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
2%)
0%)
0(
0(
0(
0(
0%)
0%)
0%)
0%)
Adverse Event
TABLE 10
SECONDARY SURGICAL INTERVENTIONS – POSTOPERATIVE OCULAR ADVERSE EVENTS
NON-RANDOMIZED POPULATION
Secondary Surgical Intervention
Adverse Events
Paracentesis1
Nd:YAG laser capsulotomy
Nd:YAG laser for stent obstruction
Iris reposition
1.included paracentesis at the 5-7 hr. exam
Non-Randomized
Cataract Surgery
with iStent
N = 46
n (%)
12 ( 26%)
7 ( 15%)
1 ( 2%)
1 ( 2%)
pg. 20
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 sightthreatening adverse events, after 5 years of implantation, that was higher than the rate of
sight-threatening adverse events that occurs after cataract surgery alone, by more than a noninferiority margin of 5%.
pg. 19
pg. 19
Randomized
Cataract Surgery Only
N = 122
n of Subjects
n of
with Event (%)
Events
2 (2%)
4
7 (6%)
7
Epiretinal membrane
Loss of BCVA of 3 lines or more vs. baseline at
any time postoperatively
Age related macular degeneration or worsening of
9 (6%)
10
7 (6%)
7
age related macular degeneration
Worsening of glaucoma
4 (3%)
4
2 (2%)
2
4 (3%)
5
3 (2%)
3
IOP increase requiring management with oral or
intravenous medications or surgical intervention
(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 or surgical intervention
Macular edema
1 (<1%)
1
2 (2%)
2
Any other event that could lead to significant
2 (1%)
2
1 (<1%)
1
1
vision loss, if not appropriately treated
Iris atrophy
2 (1%)
2
0 (0%)
0
Retinal detachment
2 (1%)
2
0 (0%)
0
2
2
Significant corneal complications including edema,
2 (1%)
2
0 (0%)
0
opacification, decompensation
Uveitis
2 (1%)
3
0 (0%)
0
Corneal 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 retinopathy
0 (0%)
0
1 (<1%)
1
Segmental loss of neuroretinal rim
0 (0%)
0
1 (<1%)
1
Any choroidal hemorrhage
0 (0%)
0
0 (0%)
0
Aqueous misdirection
0 (0%)
0
0 (0%)
0
Any2
36 (23%)
56
28 (23%)
41
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.
®
GLAUKOS
CORPORATION
TENT Tunrelated”
RABECULAR
MICRO
STENT statues the
The investigators
considered
these eventsIS“definitely
to iStent.
One -B
of YPASS
the investigators
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.
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
Figure 11 presents the KM curves involving sight-threatening adverse events for the overall
Figure+11cataract
presentssurgery
the KMgroup
curvesand
involving
sight-threatening
adverse
iStent
the cataract
surgery only
group.events
Duefor
to the
theoverall
small
iStent® + cataract
surgery
group
and analyses
the cataract
surgery were
only performed
group. Due
the small
denominators
beyond
6 years,
the KM
comparisons
at 6toyears.
At 5
Page 24 of
31
denominators
6 years, the KM
comparisons
were performed
at 6 years.
At 5
years,
the rate beyond
of sight-threatening
AEsanalyses
was 28.5%
for the overall
iStent® + cataract
surgery
years,and
the 42.8%
rate of in
sight-threatening
AEs was
overall
cataract surgery
group
the cataract surgery
only 28.5%
group. for
Atthe
6 years,
theiStent
rate of+sight-threatening
groupwas
and29.9%
42.8%for
in the
group.
At 6 years,
of sight-threatening
AEs
the cataract
overall surgery
iStent®+only
cataract
surgery
group the
andrate
45.7%
in the cataract
AEs was
29.9%
forand
the the
overall
iStent
+ cataract
surgery
groupthe
and
45.7%iStent
in the
cataract
surgery
only
group,
p-value
for the
comparison
between
overall
+ cataract
®
surgery group
only group,
and thesurgery
p-value only
for the
comparison
between
the overall iStent
+ cataract
surgery
and cataract
group,
and against
a non-inferiority
margin
of 5%,
surgery
group
and cataract
surgery
group,
and against
a non-inferiority
was
0.011,
indicating
that the
overallonly
iStent
+® cataract
surgery
group was not margin
inferiorofto 5%,
the
was 0.011,
indicating
the overall
iStent the+ cataract
group
wastest
notwas
inferior
to
cataract
surgery
only that
group.
In addition,
p-value surgery
of the log
rank
0.317,
the cataractthat
surgery
only group. Inrate
addition,
p-value
of statistically
the log rankdifferent
test was
0.317,
confirming
the sight-threatening
over 6 the
years
was not
between
confirming
that the
sight-threatening
rate over
6 years surgery
was notonly
statistically
the
overall iStent
+ cataract
surgery group
and cataract
group. different between
the overall iStent® + cataract surgery group and cataract surgery only group.
FIGURE 11
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 this followup 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 time-point). Please
note that no postoperative specular microscopy was performed, because preoperativespecular
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 willing to 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. Sight-threatening
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.
*Note:
sameTwo
eye subjects were discontinued before surgery, and two did not have successful stent implantation.
Note:
werenot
discontinued
before surgery,
andwith
twoan
didiStent
not have
successful
stent
implantation.
These Two
four subjects are
in the populations
of subjects
implant
and were
excluded
from
These
four subjects
are not in the populations of subjects with an iStent implant and were excluded from
calculations
in the table.
calculations in the table.
Overall Cataract Surgery
with iStent®
N = 157
n of Subjects
n of
with Event (%) Events
9 (6%)
9
2 (1%)
2
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.
pg. 21
Of the 27 original study sites participating in Pivotal Trial GC-003, 25 sites participated
in 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 GC003 (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 and
Post-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 the
randomized cataract surgery only group.
Postoperative Ocular Adverse Events
Table 12 presents all postoperative ocular adverse events reported from Study GTS100-PAS
for the overall iStent + cataract surgery group and the randomized cataract surgery only group.
Table 13 summarizes ocular surgeries from Study GTS100-PAS.
Page 25 of 31
GLAUKOS CORPORATION ISTENT TRABECULAR MICRO-BYPASS STENT
T ABLE 12
P OSTOPERATIVE O CULAR A DVERSE E VENTS
GTS100-PAS
Adverse Event
FOR
TABLE 13
OCULAR SURGERIES AFTER GC-003 STUDY
GTS-100 PAS
S TUDY E YES
Overall
Cataract Surgery with
iStent®
N = 73
n of Subjects
n of
with Event (%) Events
6 (8%)
7
Overall
Randomized
Cataract Surgery with Cataract Surgery Only
iStent®
N = 73
N = 35
n of Subjects
n of
n of Subjects
n of
with Event (%) Events with Event (%) Events
13 (18%)
13
11 (31%)
11
1 (1%)
1
3 (9%)
3
2 (3%)
2
0 (0%)
0
1
1
2 (3%)
2
0 (0%)
0
Randomized
Cataract Surgery Only
N = 35
n of Subjects
n of
with Event (%) Events
6 (17%)
6
Adverse Event
Nd:YAG laser capsulotomy
Age related macular degeneration or worsening of age
Selective laser trabeculoplasty
related macular degeneration
Blepharoplasty
Amaurosis fugax
0 (0%)
0
1 (3%)
1
Descemet’s stripping endothelial keratoplasty (treat preAnterior ischemic optic neuropathy
0 (0%)
0
1 (3%)
1
existing Fuch’s dystrophy prior to stent + cataract surgery)
Any intraocular inflammation (non pre-existing)
1 (1%)
1
0 (0%)
0
Basal cell carcinoma excision/lid reconstruction
1 (1%)
2
0 (0%)
0
remaining or arising after the protocol’s specified
Dacryocystorhinostomy/lacrimal irrigation
1 (1%)
2
0 (0%)
0
medication regimen is complete (1+ cells or flare will
Retinal tear repair (laser photocoagulation, retinal buckle)
1 (1%)
2
0 (0%)
0
not be considered an AE unless persisting >=1 month
Laser iridoplasty
1 (1%)
1
0 (0%)
0
postoperative)
Trabeculectomy
1 (1%)
1
0 (0%)
0
Any other event that could lead to significant vision
2 (3%)
2
1 (3%)
1
Any choroidal hemorrhage
0 (0%)
0
0 (0%)
0
loss, if not appropriately treated1
Aqueous misdirection
0 (0%)
0
0 (0%)
0
Bleeding (vitreous hemorrhage or persistent & non1 (1%)
1
0 (0%)
0
1. Two subjects with pre-existing Fuchs’ dystrophy prior to iStent + cataract surgery reported with corneal
preexisting hyphema)
decompensation. (A third iStent subject with pre-existing Fuchs’ dystrophy did not report with corneal
Blepharitis
6 (8%)
6
4 (11%)
6
decompensation.) The two subjects underwent Descemet’s stripping endothelial keratoplasty 4 and 5 years,
Blurry vision or visual disturbance
4 (5%)
5
0 (0%)
0
respectively, after their iStent surgery. Both subjects experienced worsening of the disease in their fellow eyes as
Branch retinal vein occlusion
1 (1%)
1
0 (0%)
0
Brow ache
1 (1%)
1
0 (0%)
0
well, and one subject underwent penetrating keratoplasty in their fellow eye. The investigators considered these
Chalazion
0 (0%)
0
1 (3%)
1
events “definitely unrelated” to iStent. One of the investigators statues the adverse event was “typical chronic
Conjunctival hyperemia
1 (1%)
1
0 (0%)
0
evolution of Fuchs’ corneal dystrophy”.
Conjunctival irritation due to hypotensive medication
1 (1%)
1
1 (3%)
1
Conjunctivitis
2 (3%)
3
1 (3%)
1
Corneal abrasion
0 (0%)
0
1 (3%)
1
Study Strength and Weaknesses
Study Strength and Weaknesses
Corneal graft edema
1 (1%)
1
0 (0%)
0
The
availablesubjects
subjectswho
whodid
didnot
notenroll
enrolloror
Cotton wool spot
0 (0%)
0
1 (3%)
1
Themain
mainreason
reasonfor
forthe
the large
large number
number of
of potentially
potentially available
®
GLAUKOS
MICRO
TENT
Cystoid macular
edema CORPORATION ISTENT TRABECULAR
2 (3%)
2 -BYPASS0S(0%)
0
complete
the 5+
5+ year
yeargap
gapbetween
betweensubjects
subjects
exiting
Study
GC-003
the date
completethe
thestudy
study is
is the
exiting
Study
GC-003
and and
the date
of
Deep stents (“buried” in the trabecular meshwork) that
2 (3%)
2
0 (0%)
0
offinal
finalapproval
approvalbybyFDA
FDAofofthe
theprotocol
protocolfor
forthis
thisextended
extendedfollow-up
follow-upstudy.
study.Many
Manyofofthe
the
are not visible
Aida
Flores 8/25/2015
PM elderly
surviving
patients1:09
this
elderly population
population had
surviving
patients
ininthis
had increased
increasedhealth
healthissues
issuesororage-related
age-relatedreasons
reasons
T ABLE 12 ( CONTINUED
Dermatochalasis
4 (5%) )
4
2 (6%)
2
Formatted:
Font:Bold in the follow-up study. There were more
fornot
notenrolling
enrolling
Dot hemorrhage
(0%)
1
P OSTOPERATIVE O CULAR A DVERSE0 E
VENTS FOR0 S TUDY 1E(3%)
YES
for
in the follow-up study. There were more subjects in the overall
overall iStent
iStent®+ +
Unknown
Drusen
1 (1%)
1
1 (3%)
1
cataract
surgery group
group than
than the
the cataract
cataract surgery
surgery only
GTS100-PAS
cataract
surgery
only group,
group, because
becausethe
thenon-randomized
non-randomized
Field
Code
Changed
Dry eye
18 (25%)
18
7 (20%)
cohortofofiStent
iStent® +
+ cataract
cataract surgery
surgery subjects
subjects had
Overall
Randomized 8
cohort
had been
been added
added to
to the
the randomized
randomized iStent
iStent®+ +
Aida
Flores 8/25/2015 1:09
PM
Ectropion
1 (1%) Surgery with
1
0 (0%)Surgery Only
0
Cataract
Cataract
cataract
surgery group.
Formatted:
Font:Boldgroup.
cataract surgery
Elevated IOP
1 (1%)
1
2 (6%)
2LABELING
iStent®
N = 73
N = 35
Epiphora
2 (3%)
2
0 (0%)
0
Unknown
Importantly,there
therewere
wereno
nounanticipated
unanticipated adverse
adverse device
Importantly,
deviceeffects
effects(UADE)
(UADE)identified
identifiedduring
duringthe
the
n of3Subjects
n of
n of1Subjects
n of
Epiretinal membraneAdverse Event
(4%)
3
(3%)
2
Field Code Changed
study,which
whichextended
extended
to greater
greater
thandevice
66 years
iStent
+ cataract
surgery.
®
arePMto
used
on the
packaging.
study,
than
years after
after
iStentimplantation
implantation
+ cataract
surgery.
with 0Event
with 1Event
Episcleritis
(0%) (%) Events
0
(3%) (%) Events
1The following
Aida
Floressymbols
8/25/2015 1:09
Aida eyelid
Floressyndrome
8/25/2015 1:09 PM
Floppy
1 (1%)
1
0 (0%)
0
Formatted: Font:Bold
Foreign
body sensation
3 (4%)
3
2 (6%)
2LABELING
Formatted:
Font:Bold
Symbol
Definition
15.LABELING
LABELING
Fuch's
dystrophy
1
(1%)
1
0
(0%)
0
Unknown
15.
Glaucoma
progression
2 (3%)
2
1 (3%)
1
Field Code
Changed
The
following
symbols
are
used
on
the
device
packaging.
The
on the
the device
devicepackaging.
packaging.
Goniosynechiae
2 (3%)
2
0 (0%)
0
Thefollowing
followingsymbols
symbols are
are used
used on
Page 26 of 31
Aida Flores 8/25/2015 1:09 PM
Hollenhurst plaque
1 (1%)
1
0 (0%)
0
Formatted:
Font:Bold
Hyperemia
1 (1%)
1
0 (0%)
0
Symbol
Definition
Symbol
Definition
Unknown
IOP
increase >= 10 mmHg vs. baseline IOP occurring at
2 (3%)
2
0 (0%)
0
anyField
visit Code Changed
Catalogue/Model
IOP
increase
management
4 (5%)
5
3 (9%)
3
Aida
Floresrequiring
8/25/2015
1:09 PM with oral or
Number
intravenous
medications
Formatted:
Font:Boldor with surgical intervention
Serial Number
(Note: IOP treated with oral medication at the 6 hour
Page (for
29 ofthe
31 stent)
visit is not an Adverse Event)
Implicated meibomian glands
1 (1%)
1
0 (0%)
0
Increased cup to disc ratio
4 (5%)
4
0 (0%)
0
Lacrimal stenosis
1 (1%)
1
0 (0%)
0
Lid edema
0 (0%)
0
1 (3%)
1
Loss of best corrected visual acuity (BCVA) of 3 lines
1 (1%)
1
2 (6%)
2
or more vs. baseline at any time postoperatively
Loss of best spectacle corrected visual acuity (BSCVA)
17 (23%)
17
7 (20%)
7
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 loss of BSCVA in conjunction
with posterior capsular opacification, followed by
Nd:YAG capsulotomy and improvement of BSCVA, is
NOT considered an adverse event)
Macular hemorrhage
1 (1%)
1
0 (0%)
0
Macular scar
0 (0%)
0
1 (3%)
1
Meibomian cyst
1 (1%)
1
0 (0%)
0
®
MICRO
TENT
Meibomitis GLAUKOS CORPORATION ISTENT TRABECULAR
1 (1%)
1 -BYPASS0S(0%)
0
Nerve fiber layer loss
0 (0%)
0
1 (3%)
1
Nonproliferative diabetic retinopathy
4 (5%)
4
0 (0%)
0
T ABLE 12 ( CONTINUED
Notched lids
1 (1%) )
1
0 (0%)
0
P OSTOPERATIVE O CULAR A DVERSE4 E
VENTS FOR5 S TUDY 0E(0%)
YES
Ocular irritation/itching
(5%)
0
Ocular migraine
1 (1%)
1
0 (0%)
0
GTS100-PAS
Ocular pain
1 (1%)
1
1 Randomized
(3%)
1
Overall
Optic TIA
1 (1%) Surgery with
1
0 (0%)Surgery Only
0
Cataract
Cataract
iStent®
Pain
2 (3%)
2
0 (0%)
0
N = 73
N = 35
Papilloma
3 (4%)
3
0 (0%)
0
Adverse
Event
n
of
Subjects
n
of
n
of
Subjects
n
of
Periorbital redness
1 (1%)
1
0 (0%)
0
with
Event
(%)
Events
with
Event
(%)
Events
Periorbital swelling
1 (1%)
1
0 (0%)
0
Peripapillary scarring
1 (1%)
1
0 (0%)
0
Photophobia
2 (3%)
2
0 (0%)
0
Pigmentary macular fibrosis
1 (1%)
1
0 (0%)
0
Posterior capsular opacification
18 (25%)
18
9 (26%)
10
Posterior vitreous detachment
8 (11%)
8
3 (9%)
3
Postoperative discomfort (NOTE: postoperative
1 (1%)
1
0 (0%)
0
Page 27 of 31
discomfort up to and including the Week 1 postoperative
exam is NOT considered an adverse event)
Ptosis
4 (5%)
4
2 (6%)
2
Punctal eversion
2 (3%)
2
0 (0%)
0
Retinal detachment
2 (3%)
2
0 (0%)
0
Retinal flap tears
1 (1%)
1
0 (0%)
0
Aida Flores
8/25/2015
PM
Retinal
pigment
epithelial1:09
changes
1 (1%)
1
1 (3%)
1
Formatted: Font:Bold
Scotoma
2 (3%)
2
3 (9%)
3
Secondary
1 (1%)
1
0 (0%)
0
Unknown surgical intervention
2
2
Significant
corneal
complications including edema,
2 (3%)
2
0 (0%)
0
Field Code
Changed
opacification,
decompensation
(NOTE: a classification
Aida Flores 8/25/2015
1:09 PM
of mild or moderate corneal edema up to and including
Formatted: Font:Bold
Week 1 postoperative is NOT considered an adverse
Unknown
event)
Fieldmalposition
Code Changed
Stent
1 (1%)
1
0 (0%)
0
Stent
(i.e., positive
visualization of lumen
1 (1%)
1
0 (0%)
0
Aidaobstruction
Flores 8/25/2015
1:09 PM
obstruction),
or complete, regardless of how long
Formatted:partial
Font:Bold
the obstruction is present
Stye
0 (0%)
0
1 (3%)
1
Subconjunctival hemorrhage
2 (3%)
2
0 (0%)
0
Telangiectasia
1 (1%)
1
0 (0%)
0
Trichiasis
3 (4%)
3
0 (0%)
0
Visual field defect
8 (11%)
8
1 (3%)
1
Vitreous floaters
8 (11%)
9
3 (9%)
4
Vitreous in anterior chamber
0 (0%)
0
1 (3%)
1
Vitreous syneresis
1 (1%)
1
1 (3%)
1
Watery eyes
1 (1%)
1
1 (3%)
1
Any3
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.
Page 28 of 31
A
F
U
F
A
F
U
F
A
F
Catalogue/Model
Number
Lot Number (for the
Serial
Numberassembly)
inserter/stent
(for the stent)
For single use only; do not
resterilize
Lot Number (for the
inserter/stent assembly)
Use By (year-month)
For single use only; do not
resterilize
Sterilized by Gamma
Irradiation
Use By (year-month)
CE Marking Authorization
Sterilized by Gamma
Irradiation
yyyy-mm
yyyy-mm
0086
For
prescription
use only
CE Marking
Authorization
Aida Flores 8/25/2015 1:09 PM
Formatted: Font:Bold 0086
For prescription use only
Unknown
Field Code Changed
30°C
Aida Flores 8/25/2015 1:09 PM
Formatted: Font:Bold
Unknown
Field Code Changed
Room temperature storage
requirement
15°C
30°C
Aida Flores 8/25/2015 1:09 PM
Formatted: Font:Bold
MR Conditional
Room temperature storage
requirement
15°C
MR Conditional
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 be
safely scanned in an MR system meeting the following conditions:
• Static magnetic field of 3T 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.
Aida Flores 8/25/2015 1:09 PM
Formatted: Font:Bold
In non-clinical testing, the image artifact caused by the device extends less than 15 mm from
with a gradient echo pulse sequence and a 3.0 T MRI system.
Unknown
the device
when imaged
Field
Code Changed
Aida
8/25/2015 1:09 PM
17. Flores
CAUTION
Formatted: Font:Bold
Federal law restricts
Unknown
Field Code Changed
this device to sale by, or on the order of, a physician.
Aida Flores 8/25/2015 1:09 PM
PhysicianFont:Bold
training is required
Formatted:
prior to use of the device, and consists of three main parts:
• Webinar
• Didactic session with Glaukos surgical representative
• Observation of surgical cases by Glaukos representative until implantation proficiency is
demonstrated
Manufacturer:
Glaukos Corporation
26051 Merit Circle #103
Laguna Hills, CA 92653
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
45-0074 rev 5
pg.
pg.