DIRECTIONS FOR USE TABLE OF CONTENTS

INDICATIONS FOR USE

3.

CONTRAINDICATIONS4.

WARNINGS

5.

PRECAUTIONS

6.

ADVERSE REACTIONS

7.

INSTRUCTIONS FOR USE

8.

ADVERSE EVENT REPORTING9.

HOW SUPPLIED

10. STORAGE REQUIREMENTS
11. EXPIRATION DATE
12. RETURN GOODS POLICY
13. iSTENT INJECT G2-M-IS SYSTEM - PIVOTAL
CLINICAL TRIAL RESULTS
14. LABELING
15. MRI SAFETY INFORMATION
16. CAUTION

Figure 1. iStent inject W Stent Dimensions
The iStent inject W stent has a rear flange which resides in the anterior chamber, and head that resides in Schlemm’s
canal. The thorax of the stent is retained by the trabecular meshwork. The stent is symmetrical and is designed to be
implanted in the left and right eye (Figure 2). Two preloaded intraocular stents are provided in the injector (Figures
3a & 3b).

6. ADVERSE REACTIONS
Refer to the Pivotal Clinical Trial Results section for the adverse events that occurred in the pivotal clinical trial.
Additional adverse events that may be reasonably associated with the use of the device include but are not limited
to the following: anterior chamber shallowing, severe, prolonged, or persistent intraocular inflammation, aqueous
misdirection, choroidal effusion, choroidal hemorrhage, corneal decompensation, corneal injury, corneal opacification,
cyclodialysis cleft, damage to trabecular meshwork, hyphema, hypopyon, hypotony, hypotony maculopathy,
IOL dislocation, iridodialysis, loss of vitreous, perforation of sclera, posterior capsular bag rupture, proliferative
vitreoretinopathy, pupillary block, pupillary membrane formation, retinal detachment, retinal dialysis, retinal flap
tears, secondary surgical intervention, including but not limited to glaucoma surgery, premature stent release, stentdislocation, stent not retrievable, stent not visible with gonioscopy, over implanted stents that are not visible withgonioscopy, stent malfunction, and vitreous hemorrhage.
7.

INSTRUCTIONS FOR USE

Cataract Surgery
1. Cataract surgery with IOL implantation should be performed first followed by implantation of the iStent inject W.
2. The stent implantations are designed for nasal placement; therefore, it is suggested that surgery is performed fromthe temporal side of the head.
3. An intracameral miotic can be injected to deepen the angle after cataract surgery prior to placement of the iStent
inject W stent.
4. To mitigate difficulty with patient movement or non-compliance, consider using a peri-bulbar or retro-bulbar block.
Figure 2. iStent inject W Model G2-W Stent

Stent Implantationa. Prepare for gonioscopy by turning the patient head away by approximately 35° and the scope toward surgeon byapproximately 35° (70° total).
b. Inspect angle with a gonioprism to ensure that a good view is available at the nasal implant location.
c. Place the gonioprism on the cornea and position the patient and surgical microscope as needed to visualize thetrabecular meshwork, through the gonioprism, on the nasal side of the eye. Focus on the landmarks in the angle ofthe eye (Figures 4a & 4b). Look up from the iris root to find the scleral spur (white line). Then look for Schwalbe’s
line (white line) down from the cornea. The trabecular meshwork (typically a red/brown line) is between the scleralspur and Schwalbe’s line. Schlemm’s canal is behind the trabecular meshwork.

Figure 6. iStent inject W Implant Locationd. Locate the trabecular meshwork and select an implant location (Figure 6). Apply light pressure (or Dimple) onto thetrabecular meshwork with the injector to deliver the stent (Figure 7).

Figure 7. iStent inject W Implant Procedure (left: approach the TM;
center: trocar pierces TM; right: dimple tissue and inject)
e. Center the trocar inside the micro-insertion tube, relax hand and squeeze the stent delivery button with yourindex finger. A single audible click will indicate that the first stent has been delivered from the injector throughthe trabecular meshwork and into Schlemm’s Canal. Look through the micro-insertion tube window during stentimplantation to verify the stent is securely in place within the tissue before withdrawing injector back.
f. Important: Hold the stent delivery button down and carefully withdraw the injector from the stent prior to releasing
your finger from the stent delivery button.
g. Upon release of the stent delivery button, a second audible click will indicate that the next stent is in position andready to deliver.
h. Carefully move the injector at least two clock hours away from the first stent implant. Approach the trabecularmeshwork and repeat steps c - f.
i. After successful implantation of the second stent, carefully withdraw the injector from the implant site, release thestent delivery button and remove the injector from the eye.
j. Confirm proper placement of the two implanted stents, ensuring that each stent flange is visible in the anteriorchamber (shown below in Figure 8).
k. Note: minimal blood reflux is a normal physiological response to placement of the stents, although this does notoccur in all cases.

Figure 8. iStent inject W Implant Sites

Figure 3a. iStent inject W G2-W Injector Design

Figure 4a. iStent inject W Implant Site

Important Notes:
l. If the first stent is under implanted and remains on the trocar, then use an alternative “flush technique” procedure
to re-attempt stent implantation in the nearest available trabecular meshwork tissue (within 1 clock hour away); see
Figure 9.
m. If the first stent is under implanted and does not remain on trocar, this stent can be ‘rethreaded’ onto the trocar byplacing the trocar through the central inlet (Figure 9). Use the alternative “flush technique” to implant the stent.

Figure 4b. iStent inject W Implant Site
d. After visualization of the trabecular meshwork, the Tyvek® tray lid containing the iStent inject W system should be
opened and presented to the user. The device should be handled in the sterile field. Caution: Do not use the device
if the Tyvek lid has been opened or if the packaging appears damaged. In such cases, the sterility of the device may
be compromised.
e. Hold the injector as shown in Figure 5 with your index finger comfortably on the micro insertion sleeve retractor
and within reach of the stent delivery button.

Slit Lamp ExamX

Specular Microscopy

X

IOP via Applanation TonometryX

3. CONTRAINDICATIONS
The iStent inject W Trabecular Micro-Bypass System Model G2-W is contraindicated under the following circumstancesor conditions:• In eyes with angle closure glaucoma.
• In eyes with traumatic, malignant, uveitic, or neovascular glaucoma or discernible congenital anomalies of theanterior chamber (AC) angle• 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 stentimplantation: corneal haze, corneal opacity, or any other conditions that may inhibit the gonioscopic view in theintended implant location.
2. The surgeon should perform a slit lamp gonioscopy examination prior to taking a patient to surgery to exclude
congenital anomalies of the angle, including peripheral anterior synechiae (PAS), rubeosis, and any other angle
abnormalities that could lead to improper placement of the stent and pose a hazard.
3. Patients with peripheral iridotomies are at risk of stent dislocation to the posterior chamber and related sequelae.
4. The iStent inject W is intended for implantation in conjunction with cataract surgery, which may impact corneal
health. Therefore, caution is indicated in eyes with evidence of corneal compromise (e.g., corneal guttae or low
endothelial cell density) or with risk factors for corneal compromise following cataract surgery (e.g., advanced age,severe nuclear sclerosis).
5. Non-clinical testing has demonstrated that the iStent inject W is MR Conditional. Please see the “MRI SAFETYINFORMATION” section at the end of this document on 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 thepatient needs to undergo an MRI, they should let their doctor know they have an iStent inject W stent implanted intheir eye.
2. After the surgery, the surgeon should give the patient the Patient ID card (enclosed in the iStent inject W 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 inject W and that the card should be shown to their current and future health careproviders.
3. The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. If
intraocular pressure is not adequately maintained after surgery, the surgeon should consider an appropriate
additional therapy to reduce intraocular pressure.
4. The safety and effectiveness of the iStent inject W system has not been established as an alternative to the primary
treatment of glaucoma with medications. The effectiveness of this device has been demonstrated only in patients

Figure 5. Hand position on injector
f. Injection of two stents:a. Inject cohesive viscoelastic into the anterior chamber to assist with chamber maintenance.
b. Remove the Tube Protector prior to entering the eye.
c. Place injector through the same temporal corneal incision used to perform cataract surgery, being careful toavoid contact with the cornea and iris in order to minimize sequelae associated with device-cornea touch, stentobstruction and/or iritis. Guide the injector across the anterior chamber, just beyond the pupillary margin, andthen slide back the micro-insertion sleeve retractor (teal colored) to expose the micro insertion tube and trocar.

Figure 9. iStent inject W rethreading of stent (top) and flush technique (bottom)
n. Re-loading can be considered if the surgeon prematurely releases a stent prior to engaging the trocar with thetrabecular meshwork.
o. If there is only one stent remaining in the injector, it’s important to use the standard “dimple technique” to implant
the stent after it’s been rethread onto the trocar.
p. There are a total of four positions available on the injector to implant the two stents. After the stent delivery button
has been depressed for the fourth time, the injector will no longer function.
q. In the event that the first injector does not deliver two stents successfully, confirm that the number of stents
implanted is less than two (2) before utilizing a second injector. Perform the following steps:• Inspect the micro-insertion tube under the surgical microscope and verify that at least one stent remains within
the injector; or, verify that at least one stent has been retrieved from the eye.
• To prevent implantation of more than two stents, do not attempt delivery of additional stents with a second
injector above the number verified still within the first injector or retrieved from the eye.
r. At the end of the procedure, the following should be performed:• Irrigate the anterior chamber with balanced salt solution (BSS) through the corneal wound manually, or with
automated irrigation/aspiration to remove viscoelastic and refluxed blood. Repeat as needed until all viscoelastic
has been removed.
• Inflate the anterior chamber with saline solution as needed to achieve physiologic pressure.
• Ensure that the corneal incision is sealed, and place 10-0 nylon suture if needed.
Postoperative Instructions
1. Patients should be managed postoperatively for IOP increases that may occur in the early postoperative period
as a possible sequelae following cataract surgery in patients with glaucoma. Additionally, monitor the patient
postoperatively and consider an appropriate treatment regimen to reduce intraocular pressure if need be.
2. Gonioscopy should be performed to assess the iStent inject W position postoperatively.
3. Ultrasound biomicroscopy (UBM) is a useful adjunctive diagnostic aid in case of poor visualization of stents via
gonioscopy.
4. Variations in gonioscopic visualization and limitations of UBM may prevent localization of a stent. However, in theabsence of clinical sequelae, device adjustment or removal is not recommended.
5. It is highly recommended that Glaukos be contacted prior to post-operative device removal.
Postoperative Retrieval of an Implanted Stent
If the surgeon determines that an instrument is required to recapture a stent after the procedure, micro forceps of the> 65 years

1600 cells/mm2

Procedure
Informed Consent

X

Ocular Medical History

X

Ocular Medication Assessment

X

X

X

X

Medication Assessment

X

X

Manifest Refraction

X

Best Corrected VA (Snellen) with BATXBest Spectacle Corrected VA (ETDRS)

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Day 1

Week
1
Month
1
Month
3
Month
6
Month
111
Month
12
Month
18
Month
231
Month
24
X

24.75

Mean

24.83

Standard Deviation

3.34

3.08

3.28

MedianMinimum
Maximum
P-value1

24.0
20.8
35.8

23.4
20.7
34.3
0.328

23.8
20.7
35.8

Mean (Snellen)

0.234 (20/34)

0.232 (20/34)

0.234 (20/34)

Standard Deviation

0.168

0.161

0.166

X

The counts (n) are the number of subjects reported with the corresponding events. % = n ÷ N x 100%.
There were no cases in which stent implantation was attempted and 0 stents were implanted (i.e., failure to implant 2 stents).

X

X

X

X

Optic Nerve Head Imaging4

X

X

X

X

X

Vertical C/D Ratio

X

X

X

X

X

Median (Snellen)

0.22 (20/33)

0.20 (20/32)

0.22 (20/33)-0.10 (20/16)-0.08 (20/17)-0.10 (20/16)

1.00 (20/200)

1.00 (20/200)

1.00 (20/200)

Postoperative Events

2

2

X
X

X

X

X

X

X

X

X

3

X

3

X

3

X

3

X

3

X

X
X3

Unmedicated IOP atBaseline (mmHg)

BSCVA at Baseline
LogMAR

Visual Field

X

X

X

X

X

Minimum (Snellen)

Pachymetry

X

X

X

X

X

Maximum (Snellen)
P-value1

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

OSDI Questionnaire

X

X

X

X

X

PHQ-9 Questionnaire

X

X

X

X

X

1.

One-month washout visit –subjects on ocular hypotensive medication(s) at Month 11 visit or at Month 23 visit were washed out of medications in study eye forone month.

2.

Gonioscopy was performed unless other changes (e.g., corneal edema) made it too difficult to do so.

3.

UBM was performed if stent visualization was not possible with gonioscopy or if elevated IOP > 30 mmHg at one month or l later.

4.

Optic nerve head imaging was performed at screening and Months 6, 12, 18, and 24 unless certain conditions (e.g., small pupil, dry eye) made it too difficult to doso.

3. Clinical Endpoints
The primary effectiveness endpoint was the proportion of eyes with ≥ 20% decrease in the 24-month medication-freemean diurnal intraocular pressure (DIOP) from baseline.
Subjects were defined as non-responders if they did not achieve the primary effectiveness endpoint, they were missing
the 24-month IOP assessment outcomes, if ocular hypotensive medications were not washed out at the 24-monthvisit, if they underwent an IOP-affecting secondary surgical procedure (e.g., laser trabeculoplasty, trabeculectomy,
shunt or valve placement) prior to the 24-month visit, experienced hypotony (IOP < 6 mmHg) associated with clinicallysignificant findings, experienced no light perception, or if they underwent a procedure to reposition or remove an
iStent inject.
The secondary effectiveness endpoint was diurnal IOP reduction from baseline at Month 24. The diurnal IOP at 24
months for the subjects that did not meet criteria comparable to those listed above for the primary endpoint was
imputed by the baseline IOP.
Each endpoint required a comparison between the iStent inject and Control groups. The primary effectiveness analysis
was performed using the Effectiveness Cohort, comprised of subjects randomized to the iStent inject group who
received 2 stents and subjects randomized to the control group.
With regard to safety, anticipated and unanticipated AEs were reported for all subjects randomized in the study per thetreatment that they actually received. Best Corrected Visual Acuity (BCVA), central corneal pachymetry, slit lamp andfundus exams, gonioscopy and central corneal endothelial cell density (ECD) were also used to assess safety.

Shaffer Angle Gradeat Screening

C. Study Population Demographics and Baseline Parameters
The demographics and preoperative characteristics of the study population were as follows:
Table 3. Demographics ITT Population
Parameter

Cataract Surgery with
iStent inject
N = 387

Cataract Surgery Only
N = 118

142/387 (36.7%)

40/118 (33.9%)

182/505 (36.0%)

IV (> 35)

245/387 (63.3%)

78/118 (66.1%)

323/505 (64.0%)

Operative parameters are provided for the iStent inject portion of the procedure (Table 5). In one of the 387 eyes, after
successful cataract extraction and IOL implantation, and subsequent randomization to the iStent inject group, stentimplantation was not attempted as a result of excessive coughing (i.e., 0 stents implanted). Of the 386 eyes that were
implanted with stents, 380 eyes (98.2%) were implanted with 2 stents. Four eyes (1.0%) were implanted with 3 stents
and 2 eyes (<1%) were implanted with 1 stent.
In most eyes (85.5%; n = 331), only a single injector was employed. No associated clinical sequelae were noted in any
cases in which a second injector was used. No difficulties with implantation were reported in the majority of cases(81.4%; n = 315). No associated clinical sequelae were noted in any cases in which stent implantation difficulty wasreported.
Table 5
Operative Parameters — iStent inject Portion of Procedure
ITT Population
N = 387 Subjects
Number
Percent# of Implants
Yes

69
45
98

71
46
86

70
45
98

12/118 (10.2%)
42/118 (35.6%)
52/118 (44.1%)
12/118 (10.2%)

58/505 (11.5%)
193/505 (38.2%)
208/505 (41.2%)
46/505 (9.1%)

54/118 (45.8%)
64/118 (54.2%)

216/505 (42.8%)
289/505 (57.2%)

282/387 (72.9%)

86/118 (72.9%)

368/505 (72.9%)

Hispanic/Latino

24/387 (6.2%)

10/118 (8.5%)

34/505 (6.7%)

Black
Asian
Other

77/387 (19.9%)
3/387 (0.8%)

19/118 (16.1%)
1/118 (0.8%)

96/505 (19.0%)
4/505 (0.8%)

American Indian

1/387 (0.3%)

0/118 (0.0%)

1/505 (0.2%)

East IndianPortuguese
P-value2
OD
OS
P-value2

0/387 (0.0%)
0/387 (0.0%)

1/118 (0.8%)
1/118 (0.8%)

1/505 (0.2%)
1/505 (0.2%)

Intraoperative adverse events duringcataract surgery

64/118 (54.2%)
54/118 (45.8%)

269/505 (53.3%)
236/505 (46.7%)

118/118 (100.0%)505/505 (100.0%)

Prolonged anterior chamber collapse
Significant hyphema (i.e. ≥10% of anteriorchamber)
Vitreous loss
Vitrectomy
Any choroidal hemorrhage
Any choroidal effusion
Significant iris damage
Significant corneal injury
Posterior capsular bag rupture
Significant damage to trabecular meshwork
Capsulorhexis tear
Zonular rupture
Evident zonular weakness or dehiscence
Detached Descemet's membrane
Incomplete phacoemulsification
Complications associated with posteriorchamber IOL implantation
Anterior chamber IOL implantation
Other
Corneal abrasion

Race/ Ethnicity

Study Eye

POAG

Yes

0.164

0.798
162/387 (41.9%)
225/387 (58.1%)
0.459

0.221
205/387 (53.0%)
182/387 (47.0%)
0.834
387/387 (100.0%)

Two-sample t-test
Fisher’s exact test

1
2

Table 4. Preoperative Characteristics
ITT Population
Parameter

Visual Field
Mean Deviation (MD)at Screening (dB)

Corneal Thickness at
Screening (µm)

12
34P-value2
Mean

Cataract Surgery with
iStent inject
N = 387

Cataract Surgery Only
N = 118

Total
N = 505

224/387 (57.9%)
98/387 (25.3%)
63/387 (16.3%)
2/387 (0.5%)

71/118 (60.2%)
30/118 (25.4%)
17/118 (14.4%)
0/118 (0.0%)295/505 (58.4%)
128/505 (25.3%)
80/505 (15.8%)
2/505 (0.4%)

0.943-3.392-3.357-3.384Standard Deviation

3.285

3.143

3.249

MedianMinimum
Maximum
P-value1
Mean

-2.79
-12.58
3.12-3.07-11.672.04-2.89-12.583.12

546.49546.06546.39Standard Deviation

36.16

35.74

36.03

MedianMinimum
Maximum
P-value1

545.0
455.0
620.0

548.5
448.0
620.0

546.0
448.0
620.0

0.915

0.909

Intraoperative Events

Intraoperative adverse events during
iStent inject implantation
Any choroidal hemorrhage
Any choroidal effusion
Prolonged anterior chamber collapse
Significant hyphema (i.e. ≥ 10% of anteriorchamber)
Significant iris damage
Significant corneal injury
Other
1 stent implanted

1.5% (-2.8%, 5.8%)

21 (5.4%)
11 (2.8%)
10 (2.6%)6 (5.0%)4 (3.4%)5 (4.2%)

0.4% (-4.2%, 5.0%)-0.5% (-4.2%, 3.1%)-1.6% (-5.6%, 2.3%)

10 (2.6%)
9 (2.3%)9 (2.3%)9 (2.3%)9 (2.3%)8 (2.1%)5 (4.2%)0 (0.0%)2 (1.7%)2 (1.7%)3 (2.5%)1 (0.8%)-1.6% (-5.6%, 2.3%)
2.3% (0.8%, 3.8%)
0.7% (-2.1%, 3.4%)
0.7% (-2.1%, 3.4%)-0.2% (-3.4%, 3.0%)
1.2% (-0.9%, 3.4%)

8 (2.1%)1 (0.8%)

1.2% (-0.9%, 3.4%)

8 (2.1%)8 (2.1%)4 (1.0%)3 (0.8%)2 (0.5%)1 (0.3%)3 (2.5%)4 (3.4%)3 (2.5%)7 (5.9%)3 (2.5%)3 (2.5%)-0.4% (-3.6%, 2.7%)-1.3% (-4.8%, 2.3%)-1.5% (-4.5%, 1.5%)-5.1% (-9.4%, -0.8%)-2.0% (-4.9%, 0.9%)-2.3% (-5.1%, 0.6%)

1
2
NA

331
55
1

85.5%
14.2%
0.3%

3. The events of “Glaucoma progression requiring secondary surgical intervention’ (4 iStent inject and 1 Cataract) and “Medication
intolerance requiring surgical intervention” (1 iStent inject and 0 Cataract) were included.
4. The events of IOP increase requiring management with oral or intravenous medications or with surgical intervention at ≥ Month 1 and
IOP increase ≥ 10 mmHg vs. baseline IOP occurring at ≥ Month 1 were mutually exclusive. The events of IOP increase requiring surgicalintervention occurring at ≥ Month 1 were also included in the reports of “Secondary Surgical Intervention”.

Yes
No
NA

71
315
1

18.3%
81.4%
0.3%

In addition to the AEs reported in Table 7, events that occurred at a rate of < 2% in both groups included age-related
macular degeneration, chalazion, conjunctivitis, corneal guttata, cystoid macular edema, diplopia, disc hemorrhage,
ectropion, glaucoma progression requiring surgical intervention, lattice degeneration, nerve fiber layer loss, ocular
irritation, optic nerve thinning/cupping, visual field loss ≥ 2.5 dB and vitreous hemorrhage. AEs that occurred at <2% in the iStent inject group included one case (0.3%) each of blepharospasm, branch retinal vein occlusion, corneal
edema ≥ 30 days, corneal striae, eyelash loss, iris atrophy, iris strand, medication intolerance requiring surgicalintervention, ptosis, residual cortex, retinal detachment, retinal tear, and worsening glaucoma; 2 cases (0.5%) each ofanterior basement membrane dystrophy, extraocular papilloma, ocular pain, punctal stenosis, retinal drusen, retinal
hemorrhage and retinal pigment epithelial changes; 3 cases (0.8%) each of peripapillary atrophy, retinal flap tears, retinal
hole and notching; 4 cases (1.0%) of deep stents and transient mild ocular discomfort; 5 cases (1.3%) of subconjunctival
hemorrhage and 7 cases (1.8%) of goniosynechiae. AEs that occurred at < 2% in the control group included 1 case
(0.8%) each of anterior scleritis, central retinal artery occlusion, corneal ulcer, flashes, iris neovascularization and IOL
dislocation; and 2 cases (1.7%) of extraocular trauma.
The study investigators determined for each intraoperative and postoperative ocular AE reported whether an event wasconsidered serious. The proportion of eyes with serious AEs (SAEs) was 0.8% (n=3) in the iStent inject group and 2.5%(n=3) in the control group. iStent inject SAEs comprised 1 case each of mild partial stent obstruction that did not requireintervention, retinal tear requiring laser retinopexy, and glaucoma progression requiring ExPress shunt implantation.
SAEs reported for the control group consisted of 1 case each of blurred vision/visual disturbance; epiretinal membranerequiring vitrectomy with membrane peel, and central retinal artery occlusion and neovascularization requiring panretinal photocoagulation.
A total of 56 AEs reported for 48 iStent inject eyes (12.4%) were determined to be device related including all casesof stent obstruction, deep stents, 3 stents implanted, 1 stent implanted, 2 stents implanted in the same location, andstent implanted in the ciliary body, which accounted for 36 of the 56 device-related AEs. Other AEs determined to be
device-related included 8 cases (2.1%) of intraocular inflammation, 7 cases (1.8%) of goniosynechiae, 3 cases (0.8%) of
intraoperative corneal abrasion, and 1 case (0.3%) each of iris strand and ocular irritation.

1. In certain cases of stent obstruction, the investigators reported associated findings of transient hyphema (n=8), inferior pigment (n=14)
and/or focal goniosynechiae (n=10). In 8 cases, investigators reported obstruction of both stents. Three cases of stent obstruction weretreated with laser; obstruction resolved in all three cases. Seventeen cases were persistent at Month 24. Of these 17 cases, the primaryeffectiveness endpoint was met in 9 cases despite no treatment with laser.
2. Three subjects in the iStent inject group had chronic iritis defined as anterior cells or flare of grade 1+ or worse persisting for more than
3 months postoperatively that recurs less than three months after discontinuing the initial postoperative steroid regimen.

Safety and Effectiveness Results
1. Safety Results
All safety analyses were performed on the Safety population. Findings are summarized for events occurring
during the intraoperative period through the 24-month post-operative visit. The key safety outcomes for thisstudy are presented below in Tables 6 to 8.
Best Spectacle Corrected Visual Acuity (BSCVA)
Most eyes in both groups achieved BSCVA of 20/40 or better at Month 24, with a slightly higher proportion ofeyes achieving BSCVA of 20/40 or better in the iStent inject arm (98.9%) than in the control group (98.2%).
Adverse Effects that Occurred in the PMA Clinical Study
Intraoperative AEs
A summary of intraoperative AEs is shown in Table 6. Because final study eligibility and randomization totreatment was determined post-cataract surgery, no subjects experiencing a predetermined cataract-surgery
related AE such as posterior capsular rupture, vitreous loss or complications associated with posterior chamber
IOL implantation were randomized. One eye experienced a corneal abrasion during cataract surgery andwas subsequently randomized to the iStent inject group because this was not a clinically significant operativecomplication.
One of the 387 subjects randomized to iStent inject implantation experienced a coughing fit that resulted inincreased positive pressure requiring a corneal suture. Therefore, no attempts to implant stents was made,and this subject was included in the control group of the Safety population. In the 386 iStent inject subjects
implanted, 11 intraoperative AEs were reported during stent implantation (2.8%). Among these cases, there were
4 cases of 3 stents being implanted (1.0%) and two cases of only 1 stent being implanted (0.5%).
Table 6. Intraoperative Ocular Adverse Events in the Study Eye Safety Population

MedianMinimum
Maximum
P-value1< 60
60 to < 70
70 to < 80
≥ 80
P-value2
Male
FemaleP-value2White

5 (4.2%)

There were no cases of iridodialysis and no cases of significant hyphema (≥10% of anterior chamber).

1Reports of use of a second injector and of stent implantation difficulty are not mutually exclusive.
Further, the same reason could be reported for 1 eye in both categories. The most common/notablereasons for use of a second injector include first injector did not deploy 2 stents (5.4%; n = 21), stent
not adequately seated in trabecular meshwork (TM) (5.2%; n = 20), poor visibility (1.3%; n = 5), stentdislodged during I/A (0.3%; n = 1). The most common/notable reasons for stent implantation difficultyinclude injector did not deploy stent (5.9%; n = 23), stent not adequately seated in TM (6.2%; n = 24),
injector initially did not (but did eventually) deploy stent (2.1%; n = 8), poor visibility (1.6%; n = 6); 2
stents implanted in same location (0.3%; n = 1). In these reports of 2nd injector used and/or stentimplantation difficulty, no associated clinical sequelae were noted in any cases.

69.2

22 (5.7%)

68.0%
19.6%
7.5%
4.7%
0.3%

The iStent inject was not attempted for a subject due to coughing fit after randomization.

8.1-0.7% (-8.6%, 7.1%)

263
76
29
18
1

Percent = Number ÷ N x 100%.

70.1

20 (16.8%)
NA

1
2
3
>3
NA

Difficulties with Implantation1

7.7

Difference in %95% CI1

The counts (n) are the number of subjects reported with the corresponding events. % = n ÷ N x 100%.

# of Injector Used1

69.0

Cataract Surgery Only
N = 119
n (%)

1

No

8.2

Ocular surface disease
Stent obstruction, partial or complete, regardlessof how long the obstruction is present1
Any intraocular inflammation (non pre-existing)remaining or arising after the protocol's
specified medication regimen is complete2
Secondary surgical intervention3
Ocular allergies
Loss of BSCVA of 2 line or more (10 letters ormore on ETDRS chart) at or after 3 months
postoperative
Posterior vitreous detachment
Foreign body sensation
Blurred vision/visual disturbance
Extraocular inflammation
Epiretinal membrane
IOP increase ≥ 10 mmHg vs. baseline IOP
occurring at ≥ Month 14
Perioperative ocular pain within 14 days ofsurgery
Vitreous floaters
Corneal abrasion
Corneal opacity
Hyperemia
Non-proliferative diabetic retinopathy
IOP increase requiring management with oral
or intravenous medications or with surgicalintervention at ≥ Month 14

Cataract Surgery with
iStent inject
N = 386n (%)
62 (16.1%)
24 (6.2%)

99.7%
0.5%
98.2%
1.0%
0.3%

2
380
4

# of Attempts

Mean

46/387 (11.9%)
151/387 (39.0%)
156/387 (40.3%)
34/387 (8.8%)

386
1 Stent
2 Stents
3 Stents

Standard Deviation

Age (Years)

Number of
Ocular Hypotensive
Medications at
Screening

0.661

P-value2

Oral medications count as 1 medication. Combination medications count as 2 medications. Two subjects in the Cataract surgery with iStent
inject group took Diamox at Screening.
1
Two-sample t-test
2
Fisher’s exact test

D.
Total
N = 505

0.901

III (25 - 35)

B. Accountability of PMA Cohort
At the time of database lock, of 868 eyes enrolled in the PMA study, 54.7% (475/868) are available for analysis at the
24-month postoperative visit.
Of the 868 eyes enrolled, 41.2% (n = 358) were discontinued prior to surgery, primarily due to failure to meet eligibility
criteria or withdrawal of consent prior to the operative day. An additional 5 eyes (0.6%) were discontinued due tocataract surgery-related complications rendering them ineligible for study randomization. The remaining 58.2% (n =505) eyes were randomized. Upon completion of uncomplicated cataract surgery, 387 eyes were randomized to theiStent inject group, and 118 eyes were randomized to the Control group, in which no additional surgery was planned.
At 24 months postoperatively, 367 eyes in the iStent inject group and 108 Control group eyes completed the study.
The outcomes provided were analyzed according to three (3) separate population cohorts:• The Intent to Treat (ITT) population was defined as all randomized eyes. Eyes were grouped according to theirrandomization assignment (as randomized).
• The Effectiveness Cohort was used for the effectiveness analyses. The Effectiveness Cohort included 380 eyes
randomized to the iStent inject group who were implanted with 2 stents and 118 subjects randomized to thecontrol group.
• The Safety population was defined as all randomized eyes. All subjects in the Safety population were analyzed
according to the treatment they actually received (i.e., 386 subjects who received iStent inject in conjunction withcataract surgery and 119 eyes that underwent cataract surgery only).

X

X

17.5
9.0
26.0

18.0
11.0
24.0
0.997
24.50

X

X

Medical History/ Demographics

17.5
9.0
26.0

X

1 (0.3%)4 (1.0%)3 (0.8%)1 (0.3%)X

GenderSubjects able and willing to provide written informed consent and to attend scheduled follow-up exams for two
years postoperatively (and up to five years postoperatively as part of a post-approval study)
Enrollment in the iStent inject Pivotal Trial was limited to subjects who did not undergo complications of cataract
surgery such as posterior capsular rupture, vitreous loss or complications associated with posterior chamber IOL
implantation.
Subjects were not permitted to enroll in the study if they met any of the following key exclusion criteria related toglaucoma or IOP:
• pigmentary or pseudoexfoliative glaucoma• traumatic, uveitic, neovascular, or angle-closure glaucoma; or glaucoma associated with vascular disorders• functionally significant visual field loss
• prior incisional glaucoma surgery• prior SLT within 90 days prior to screening• prior ALT• prior iridectomy or laser iridotomy• visual field (mean deviation) worse than -12 db• ineligible for ocular hypotensive medication washout period as determined by the investigator: a) visual fieldstatus would be placed at risk by washout period or b) unmedicated IOP after washout would be expected to
exceed 36 mmHg
• clinically significant corneal dystrophy, active inflammation or surgery that may interfere with IOP measurement
reliability• elevated episcleral venous pressure such as associated with active thyroid orbitopathy or cavernous sinus fistula• use of systemic medications that could cause an increase in IOP
2. Follow-up Schedule
All subjects were scheduled to return for follow-up examinations at defined intervals through 24 months. Table 2
shows the schedule of events and procedures at each protocol-required visit.
Table 2. Schedule of Events and Procedures

X

MedianMinimum
Maximum
P-value1

2 stents implanted in same location
3 stents implanted
Corneal abrasion
Stent implanted in ciliary body

X

X

1800 cells/mm2

X

2.94

X

Clinical Assessment of Nerve
Abnormality

VFQ-25 Questionnaire

56 to 65 years

X

X

X

X

2000 cells/mm2

X

X

17.54

2.78

Difference in %95% CI1

X

Subjective Assessment

46 to 55 years

X

X

17.54

2.99

Cataract Surgery Only
N = 119n (%)

X

11. EXPIRATION DATEThe expiration date on the device package (Tyvek tray lid) is the sterility expiration date. In addition, there is a sterility
expiration date that is clearly indicated on the outside of the unit carton. Sterility is assured if the tray seal is not
punctured or damaged before the expiration date. This device should not be used past the indicated sterility expiration
date.

2200 cells/mm2

X

X

X

17.54

Cataract Surgery with
iStent inject
N = 386
n (%)

X

X

45 years

X

X

X

Mean
Standard Deviation

Intraoperative Events

X

Adverse Event Assessment

Minimum endothelial cell density

X

X

Total
N = 505

X

X

Age at time of enrollment

X

X

Cataract Surgery Only
N = 118

X

X

Surgical Data

1. Clinical Inclusion and Exclusion Criteria
Enrollment in the iStent inject Pivotal Trial was limited to subjects who met the following key preoperative inclusion
criteria:• Male or female, 45 years of age or older• Diagnosis of mild to moderate primary open-angle glaucoma in the designated study eye• At the Screening visit, a medicated mean (or median) IOP ≤ 24 mmHg on a regimen of 1 – 3 medications• At the Baseline visit, following medication washout, an unmedicated mean diurnal IOP > 21 mmHg and ≤ 36
mmHg, which also had to be ≥ 3.0 mmHg higher than the medicated IOP measured at the Screening Visit, in the
study eye.
• Gonioscopy confirming normal open angle in the designated study eye as defined by Shaffer grade ≥ 3, andabsence of peripheral anterior synechia (PAS), rubeosis or other angle abnormalities that could impair proper
placement of stent• Clinically significant age-related cataract eligible for phacoemulsification and BCVA 20/40 or worse with medium
Brightness Acuity Meter (BAT)• Ability to provide an adequate, interpretable visual field• Corneal endothelial cell criteria based on images taken prior to Operative visit as follows:• minimum endothelial cell density as shown in Table 1 below• maximum coefficient of variation (CV) = 0.45

X

Ultrasound Biomicroscopic (UBM)
Imaging

10. STORAGE REQUIREMENTS
The device should be stored at room temperature in the range of 15-30˚ C.

A. Study Design
The iStent inject Pivotal Trial (Protocol GC-008) was a prospective, randomized, comparative, multicenter investigation
conducted in the United States, in which a total of 505 eyes from 40 sites were randomized in a 3:1 fashion to undergo
either implantation of the iStent inject after uncomplicated cataract surgery (iStent inject group) or to undergo cataract
surgery without implantation of the iStent inject (Control group). A total of 387 eyes were randomized to the iStent
inject group and 118 eyes were randomized to the Control group. The study was initiated in September 2011 under IDE
G100326. At the time of the database lock for this report, all available eyes had reached the time point at which thesafety and effectiveness endpoints are evaluated, i.e., 24 months postoperative. The database for this PMA was locked
on November 13, 2017.
The subjects and Medical Monitor were masked to treatment assignments. Each IOP measurement was to be performed
using Goldmann applanation by two observers, one of whom was masked to the treatment group assignment.
There were two (2) hypotheses for the primary effectiveness endpoint defined as ≥ 20% reduction in medication-free
diurnal IOP at Month 24. The first hypothesis was that a larger proportion of eyes who received the iStent inject would
meet the primary effectiveness endpoint than those who received cataract surgery alone. The second hypothesis wasthat the 24-month IOP response rate of the iStent inject group would be better than 50%. This hypothesis was to betested if the observed Cataract surgery-only response rate was greater than 35%.
The sample size calculation was based on the hypothesis testing for effectiveness, and evaluation for safety. For
effectiveness, the sample size was estimated to be at least 376 eyes (282 iStent inject and 94 control) for the first set of
hypotheses, and 274 iStent inject eyes for the second set of hypotheses. For safety, a sample size of 300 iStent inject eyes
at 24 months is sufficient to detect safety events occurring at a rate of 1% or greater. With allowance for up to 10% losses
per year to follow-up at two years, at least 370 iStent inject eyes and 123 control eyes were to be randomized. Therefore,
the sample size was set at 500 randomized eyes (375 iStent inject and 125 control).
The study included a medical monitor, data safety monitoring board (DSMB), and specular microscopy reading center.

X

Medicated IOP at
Screening (mmHg)

X

X

1
The iStent inject implants were implanted using an injector that is slightly different from the commercially available injector. Minor changes were made to some of the
IDE injector components and to the manufacturing process to improve manufacturability and to accommodate production scale-up. Validation testing was performed
to demonstrate that injector functionality was not altered. Clinical testing is not available for the modified injector.

X

X

Randomization

13. iSTENT INJECT G2-M-IS SYSTEM - PIVOTAL CLINICAL TRIAL RESULTS
The safety and effectiveness of the iStent inject System was assessed through a clinical trial, known as the iStent inject
Pivotal Trial (Protocol GC-008) under Investigational Device Exemption (IDE) G1003261 . The aim of the iStent inject
Pivotal Trial was to establish a reasonable assurance of safety and effectiveness of the iStent inject for use in conjunction
with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate primary
open-angle glaucoma (OAG). Data from this clinical study were the primary basis for the PMA approval decision. Key
safety and effectiveness information derived from the pivotal study are summarized below.

X

Cataract Surgery with
iStent inject
N = 387

Dilated Fundus Exam

Gonioscopy (all subjects)

9. HOW SUPPLIED
The iStent inject W Trabecular Micro-Bypass System is supplied as follows. Two stents are preloaded within the
single-use injector system, and the system is provided sterile and non-pyrogenic in a Tyvek tray. Each stent system isindividually serialized, and the serial number is provided on the tray lid and unit carton. The device has been sterilized
by gamma radiation.

12. RETURN GOODS POLICY
Please contact Glaukos Corporation.

6 Hr
XParameter

Postoperative AEs
There were no unanticipated adverse events. There were no reports of flat AC with lens cornea touch, shallow AC withiridocorneal apposition, shallow AC with peripheral iridocorneal apposition, wound dehiscence, endophthalmitis,
corneal decompensation, choroidal hemorrhage or effusion,, aqueous misdirection, cyclodialysis, hypotony at one
month postoperative or later, hypotony maculopathy, atrophy/phthisis, cup-to-disc (CD) ratio increase of ≥ 0.3, lossof light perception or stent dislocation. Moreover, no cases of pupillary block or hypopyon were reported during thestudy.
A lower proportion of subjects in the iStent inject group experienced postoperative ocular AEs than in the Control
group (54.1% of subjects [n = 209] in the iStent inject group and 62.2% of subjects [n = 74] in the Control group).
A list of the more common AEs (occurring at a rate of 2% or greater) and the associated rates are provided in Table 7.
Anterior segment inflammation, which was generally mild, was reported in 5.7% of iStent inject subjects and 4.2% ofControl subjects.
Table 7. Postoperative Ocular Adverse Events Occurring at 2% or Greater in the Study Eye Safety Population

Diurnal IOP via Applanation Tonometry•

2. INDICATIONS FOR USE
The iStent inject W Trabecular Micro-Bypass System Model G2-W is indicated for use in conjunction with cataract surgery
for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate primary open-angle glaucoma.

Operative

Pinhole VA

Table 1. Minimum Endothelial Cell Density at Screening

Figure 3b. iStent inject W G2-W Injector Distal End
When properly implanted, the iStent inject W stent is intended to create a bypass through the trabecular meshwork
into Schlemm’s canal to improve aqueous outflow through the natural physiologic pathway. The implant is provided ina pre-loaded configuration allowing for precise implantation into Schlemm’s canal. The injector has been designed by
Glaukos® Corporation to hold two stents to be implanted one at a time into Schlemm’s canal.
Data from the clinical study of the Model G2-M-IS system, a prior iteration of the iStent inject W Model G2-W System,
was used to support the safety and effectiveness of the G2-W system (see Section 13, “iStent inject G2-M-IS System –Pivotal Clinical Trial Results”, below). The G2-W stents include a wider proximal end in the anterior chamber of 360 µm,
rather than 230 µm for Model G2-M-IS.

Baseline

Screening

Procedure

8. ADVERSE EVENT REPORTING
Adverse events and/or potentially sight-threatening complications that may reasonably be regarded as device related
must be reported to Glaukos Corporation at:
U.S. Toll Free Phone Number: 1-800-GLAUKOS (452-8567)
Alternate Phone Number: 949-367-9600
Fax Number: 949-297-4540

Week
1
Month
1
Month
3
Month
6
Month
111
Month
12
Month
18
Month
231
Month
24

2.

Day 1

DEVICE DESCRIPTION

6 Hr

1.

surgeon’s choice can be used by the surgeon as follows:
1. Prep the patient as one would for stent implantation surgery.
2. Re-open the eye at the preferred location in order to reach the stent. A clear corneal incision measuring approximately
1.5 mm in length is recommended.
3. Use cohesive viscoelastic to inflate the anterior chamber to create access to the stent’s location, move the stent awayfrom a delicate structure if loose, and/or protect intraocular tissues.
4. Use a gonioscope if needed to visualize the location of the stent in the anterior chamber.
5. Insert a micro forceps device through the corneal incision and grasp the stent in a convenient and secure manner
before removing the stent from the anterior chamber.
6. Irrigate the anterior chamber with balanced salt solution (BSS) through the corneal wound to remove all viscoelastic.
Press down on the posterior edge of the incision as needed to facilitate complete removal of viscoelastic. Repeat asneeded until all viscoelastic has been removed.
7. Inflate the anterior chamber with saline solution as needed to achieve normal physiologic pressure.
8. Ensure that the corneal incision is sealed.

Operative

Instructions for Use

with mild to moderate open-angle glaucoma who are undergoing concurrent cataract surgery for visually significant
cataract.
5. The safety and effectiveness of the iStent inject W system has not been established in patients with the following
circumstances or conditions which were not studied in the pivotal trial:• In children• In eyes with significant prior trauma• In eyes with abnormal anterior segment• In eyes with chronic inflammation• In glaucoma associated with vascular disorders• In pseudophakic patients with glaucoma• In uveitic glaucoma• In eyes with prior incisional glaucoma surgery or cilioablative procedures• In eyes with prior laser trabeculoplasty (LT) with selective LT within 90 days prior to screening or prior argon laser
trabeculoplasty (ALT) at any time
• In patients with medicated intraocular pressure greater than 24 mmHg
• In patients with unmedicated IOP less than 21 mmHg nor greater than 36 mmHg after “washout” of medications• For implantation of more or less than two stents• After complications during cataract surgery, including but not limited to, severe corneal burn, vitreous removal/
vitrectomy required, corneal injuries, or complications requiring the placement of an anterior chamber IOL• When implantation has been without concomitant cataract surgery with IOL implantation for visually significant
cataract• In patients with pseudoexfoliative glaucoma or pigmentary glaucoma, or in patients with other secondary openangle glaucomas.
6. The stent is comprised of implant grade titanium (Ti6-Al-4V-ELI) with a stearalkonium heparin coating. The total
amount of heparin is estimated to be less than 0.9 microgram per stent, or approximately 0.01 to 0.02 units.
7. The surgeon should be careful to avoid contact with the cornea and iris during stent implantation in order tominimize sequelae associated with device-cornea touch, stent obstruction and/or iritis.

Baseline

Glaukos® Corporation iStent inject® W
Trabecular Micro-Bypass System

1. DEVICE DESCRIPTION
The iStent inject® W Trabecular Micro-Bypass System Model G2-W contains two preloaded intraocular stents that are
manufactured from titanium (Ti6Al4V ELI) and are coated with stearalkonium heparin (note: the heparin is from a
porcine source). The stent has a single piece design, is 360 µm in diameter, 360 µm in height, and the central inlet andoutlet lumen has a diameter of 80 µm (Figure 1). The head of the stent has four side outlets that each have a diameterof 50 µm.

Screening

45-0244 Rev. 1 06/20

being visualized intraoperatively and/or at an earlier postoperative exam. . Among these cases, there were no associated clinical sequelae or secondary surgeries
to modify device positioning, none experienced an endothelial cell loss >30% at 24 months or posterior segment sequelae, and three of the four eyes met the
primary effectiveness endpoint.

Secondary Surgical Interventions
Secondary ocular surgeries during the course of the study, some of which were to achieve further IOP reduction,
occurred in 5.4% of iStent inject group subjects (n = 21) and 5.0% (n = 6) of subjects in the control group. Secondary
surgeries reported in both groups are shown in Table 8.
Table 8. Surgical Interventions in the Study Eye Safety Population
Secondary Surgical Intervention

Cataract Surgery Only
N = 119n (%)

IOL exchange1

Cataract Surgery
with iStent inject
N = 386n (%)
22 Reports from
21 subjects
5.4%
1 (0.3%)Difference in %95% CI1

IOL repositioning

0 (0.0%)1 (0.8%)Laser for stent obstruction2

3 (0.8%)NA

Laser retinopexy

6 (1.6%)0 (0.0%)1.6% (0.3%, 2.8%)

Cataract Surgery with
iStent inject
N = 386n (%)

Cataract Surgery Only
N = 119n (%)

1 Reports from
1 subjects
0.3%
0 (0.0%)0 Reports from0 subjects
0.0%
0 (0.0%)0.0% (0.0%, 0.0%)

0 (0.0%)0 (0.0%)0.0% (0.0%, 0.0%)

Panretinal photocoagulation

0 (0.0%)1 (0.8%)-0.8% (-2.5%, 0.8%)

0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)
0.0% (0.0%, 0.0%)

Posterior vitreolysis

2 (0.5%)0 (0.0%)0.5% (-0.2%, 1.2%)

Removal of residual cortex

1 (0.3%)0 (0.0%)0.3% (-0.2%, 0.8%)

Selective laser trabeculoplasty

2 (0.5%)3 (2.5%)-2.0% (-4.9%, 0.9%)

0 (0.0%)0 (0.0%)0.0% (0.0%, 0.0%)

0 (0.0%)0 (0.0%)0.0% (0.0%, 0.0%)

1 (0.3%)
11 Reports from
11 subjects
2.8%
0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0.3% (-0.2%, 0.8%)

NANA

0 (0.0%)0 (0.0%)0 (0.0%)2 (0.5%)Difference in %95% CI1

2In each of the four eyes with “deep stents,” there was a single stent per eye that was unable to be visualized by either gonioscopy or UBM at the last 3 visits, despite

0.3%(-0.2%, 0.8%)

Overall

7 Reports from
6 subjects
5.0%
0 (0.0%)0.4% (-4.2%, 5.0%)
0.3% (-0.2%, 0.8%)-0.8% (-2.5%, 0.8%)

Trabeculectomy/Express Shunt

4 (1.0%)1 (0.8%)0.2% (-1.7%, 2.1%)

Vitrectomy3

1 (0.3%)0 (0.0%)0.3% (-0.2%, 0.8%)

Vitrectomy with membrane peel

1 (0.3%)1 (0.8%)-0.6% (-2.3%, 1.1%)

The counts (n) are the number of subjects reported with the corresponding events. % = n ÷ N x 100%.
All SSIs, regardless of reason, were included.
There were no cases of free-floating stents leading to sequelae in the posterior segment.
1
The reason for IOL exchange was dysphotopsia despite good spherical/astigmatic refractive outcome. The dysphotopsia resolved
following exchange of the original spheric acrylic IOL with an aspheric silicone IOL of equivalent refractive power.
2
Stent obstruction was treated with argon laser iridoplasty in 2 cases and Nd:YAG laser membranectomy in 1 case.
3
The reason for vitrectomy was retinal detachment repair.

Other Operative/Postoperative Observations
Reporting of other ocular observations was at the study investigator’s discretion. Similar data may not be reported forevery subject, or consistently within the course of a given subject’s study participation. Consequently, no conclusions
regarding the overall frequency of these findings can be drawn from the incidence rates noted. In no cases were bothstents not visible on the operative day. The other ocular observations that were reported operatively included, but were
not limited to: 1 implanted stent not visible on the operative day (3.6%; n = 14). In 12 of these 14 eyes, stents werevisualized postoperatively. In the remaining 2 cases, non-visible stents were detected via ultrasound biomicroscopy(UBM) prior to Month 24 with minimal associated clinical sequelae besides “deep stent” as an adverse event (AE). The
other ocular observations that were reported postoperatively included, but were not limited to: goniosynechiae (7.7%;
n = 30); microhyphema (3.9%; n = 15); and corneal endothelial pigment (0.8%; n = 3). Early IOP increase ≥ 10 mmHg (i.e.
prior to Month 1) or IOP increase < 10 mmHg was reported in 2.6% (n = 10) eyes in the iStent inject group and 5.0% (n= 6) eyes in the Control group.

Corneal Endothelial Cell Density
There was little difference in endothelial cell loss (ECL) between the iStent inject and Control groups. Results wereconsistent with previous reports of cataract surgery-related ECL. The mean percent change in ECD from baseline to 24
months was -13.1% (SD 12.4; 95% CI -14.4%, -11.8%) for the iStent inject group and -12.3% (SD 12.7%; 95% CI -14.8%,-9.8%) for the control group.
A similar proportion of eyes in each group (10.4% in the iStent inject group and 9.5% in the control group) experienced
ECL > 30% at 24 months postoperatively.
2.

Effectiveness Results
Results from the primary and secondary endpoints are shown in Table 9. The primary effectiveness endpoint wasmet, with 75.8% (288/380) in the iStent inject group and 61.9% (73/118) in the Control group achieving a clinicallysignificant (≥ 20%) reduction in medication-free diurnal IOP from baseline at 24 months. This difference between
groups was statistically significant (p=0.003).
The secondary endpoint, a clinically significant mean change in medication-free diurnal IOP from baseline at
24-month postoperative examination, was met. The mean reduction in medication-free mean diurnal IOP frombaseline to 24 months was 7.0 mmHg (SD 4.0) in the iStent inject group compared to 5.4 mmHg (SD 3.7) in thecontrol group (p <0.001).
Table 9. Primary and Secondary Effectiveness Results
Effectiveness Endpoint(Evaluated at 24 Months
Postoperatively)

Cataract Surgery with
iStent inject
N = 380

Cataract Surgery Only
N = 118

Difference(iStent inject vs. control)

P-valuefor difference

Proportion of subjects withmedication-free DIOP reduction≥ 20% from baseline
Medication-free mean DIOP
(mmHg) change from baseline1

75.8%

61.9%

13.9%

0.0032-7.0-5.4< 0.0013

2. One-sided Fisher’s exact test with a significance level of 0.025.
3. One-sided two-sample t-test with a significance level of 0.025.

Additional detail regarding the reasons patients did not achieve the primary endpoint (IOP non-responders) is shownin Table 10.
Table 10. Non-Responder Categories at 24 Months Effectiveness Cohort
Cataract Surgery
with iStent inject
N = 380n/N (%)
92 (24.2%)

Total Non-Responders

Cataract Surgery Only
N = 118n/N (%)
45 (38.1%)

Non-Responders: 24-month unmedicated diurnal IOP reduction from baseline < 20%

56 (14.7%)

26 (22.0%)

Non-Responders for reasons other than IOP reduction1

36 (9.5%)

19 (16.1%)

Secondary glaucoma surgery

5 (1.3%)3 (2.5%)

Other IOP-affecting secondary surgery3

0 (0.0%)0 (0.0%)

Stent reposition or removal

0 (0.0%)0 (0.0%)Loss of light perception

0 (0.0%)0 (0.0%)

Clinically significant hypotony

0 (0.0%)0 (0.0%)4 (3.4%)2

Did not complete medication washout – Safety concerns

12 (3.2%)

Did not complete medication washout – Instructions not provided/followed⁴

0 (0.0%)2 (1.7%)

Missing 24-month diurnal IOP data⁴

19 (5.0%)

10 (8.5%)Death

4 (1.1%)6 (5.1%)

Investigator’s decision

1 (0.3%)0 (0.0%)

Lost contact

8 (2.1%)2 (1.7%)

Subject’s decision

6 (1.6%)

Definition

SymbolConsult instructions For use

Serial Number (for the stent)

Manufacturer

Lot Number

Sterilized by Gamma Irradiation

Do not reuse

For prescription use only
30˚C

yyyy-mm-dd

Definition

Catalogue/Model Number

Use-by date (year-month-day)
15˚C

Do not use if package is damaged

Temperature Storage
Requirement
MR Conditional

2 (1.7%)

1M
n (%)

Cataract Surgery Only
Total Number of Subjects = 119
6M
12M
n (%)
n (%)

16. 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 mainparts:• Didactic session• Simulated implantation of iStent inject W• Supervised iStent inject W implantation of clinical cases until implantation proficiency is demonstrated

Patented: Patent info: www.glaukos.com/patents
Glaukos® and iStent inject® W are registered trademarks of Glaukos Corporation.
Tyvek® is a registered trademark of DuPont USA.

Summary of Supplemental Clinical Information
A. For the pivotal trial of the iStent inject, the Ocular Surface Disease Index (OSDI©) was self-administeredby study subjects.
The OSDI questionnaire contains 12 questions involving ocular symptoms,
vision-related function and environmental triggers experienced by the subject during the past
week, and is assessed on a scale of 0 to 100 with higher scores representing greater disability.
Table 11 summarizes the change in OSDI subscales and overall score from baseline. The mean improvements
at 24 months from baseline were slightly higher in the iStent inject group compared to the control groupinvolving ocular symptoms (-16.41 vs. -10.69) and vision-related function (-22.60 vs. -18.56) and similar
involving environmental triggers (-7.41 vs. -7.70). The mean improvement in OSDI overall score at 24 months
was also higher in the iStent inject group compared to the control group (-16.25 vs. -12.38). The questionnaire
used to collect these data has not been validated, and therefore the true rates of these symptoms may differ
from those presented in the Table 11.
Table 11
Change in OSDI Questionnaire Sub-Scale Score from Baseline Safety Population

Cataract Surgery with iStent inject
Total Number of Subjects = 386
1M
6M
12M
24M
Statistics
n (%)
n (%)
n (%)
n (%)
Ocular Symptoms (Q1, Q2, Q3)
N
382
376
367
361
Mean
-11.87-15.04-16.93-16.41
SD
22.39
21.23
19.96
21.13
Median
-10.0
-15.0
-15.0
-15.0
Min
-100
-100
-90.0
-100
Max
75.0
50.0
33.8
60.0
Not Reported
2135Vision-Related Function (Q4, Q5, Q6, Q7, Q8, Q9)
N
379
374
363
359
Mean
-16.07-21.46-22.82-22.60
SD
29.80
27.93
28.22
27.30
Median
-12.5
-18.8
-18.8
-18.8
Min
-93.8
-100
-100
-100
Max
100.0
77.1
62.5
62.5
Not Reported
53
77
Environmental Triggers (Q10, Q11, Q12)
N
370
367
358
353
Mean
-5.20
-7.27
-7.83
-7.41
SD
21.52
20.70
21.65
22.61
Median
0.0
0.0
0.0
0.0
Min
-83.3
-100
-100
-100
Max
100.0
58.3
75.0
66.7
Not Reported
14
10
12
13
Overall Composite Score
N
382
376
367
361
Mean
-11.87-15.44-16.66-16.25
SD
20.29
19.39
19.38
19.73
Median
-10.4
-12.5
-13.3
-12.5
Min
-93.8
-93.8
-95.8
-100
Max
72.9
37.5
31.3
45.8
Not Reported
2135Non-clinical testing has demonstrated that the iStent inject W Trabecular Micro-Bypass System Model G2-W is MR
Conditional. A patient with this device can be safely 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
Under the scan conditions defined above, the iStent inject W Trabecular Micro-Bypass System Model G2-W is notexpected 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 15 mm from the device when imaged
with a gradient echo pulse sequence and a 3.0 T MRI system.

Manufacturer:
Glaukos Corporation
229 Avenida Fabricante
San Clemente, CA 92672 U.S.A.
Tel: +1.949.367.9600, Fax: +1.949.367.9984
www.glaukos.com
Toll-Free: 1-800-GLAUKOS (452-8567)

n = number of eyes with the corresponding responses. % = n ÷N x 100%.
1 Subjects were included in the primary category of ‘’Non-Responders for reasons other than IOP reduction”.
2 Secondary glaucoma surgeries include trabeculectomy, and laser trabeculoplasty.
3 Other IOP-affecting secondary surgeries.
4 The outcomes of these subjects were imputed for the 24-month analysis.
There were 2 subjects on oral medication at 23 months and both subjects underwent washout. Hence, although any subjects on oral
medication at 24 months would have been considered non-responders due to the potential to confound the endpoint analysis, there wereno subjects in this category.

24M
n (%)

117
-6.41
20.53
-5.0
-55.0
80.0
2

118
-10.55
18.45
-10.0
-60.0
40.0
0

115
-11.53
17.16
-10.0
-75.0
35.0
1

109
-10.69
17.74
-10.0
-65.0
35.0
0

117
-14.08
29.94
-6.3
-100
87.5
2

118
-17.32
27.49
-12.5
-100
75.0
0

115
-20.92
27.66
-16.7
-100
37.5
1

109
-18.56
28.92
-12.5
-100
68.8
0

114
-4.61
21.95
0.0
-75.0
66.7
5

116
-7.26
21.61
0.0
-100
41.7
2

113
-7.82
21.60
0.0
-100
33.3
3

106
-7.70
20.66
0.0
-75.0
75.0
3

117
-8.48
20.02
-6.2
-60.4
70.8
2

118
-11.91
18.01
-10.4
-66.7
37.5
0

115
-13.60
17.18
-10.7
-64.6
17.6
1

109
-12.38
18.38
-10.4
-62.5
56.3
0

Each sub-scale is a summarization of some specific questions to the OSDI.
3. Based on proportional analysis using a non-responder imputation for missing data. Subjects without Month 24 medication-free diurnal
IOP, or with IOP-related SSIs, loss of light perception or hypotony (IOP < 6 mmHg) associated with clinically significant findings prior
to 24 months were treated as non-responders. iStent inject subjects with stent reposition or removal prior to 24 months were treatedas non-responders.

B. In the iStent inject pivotal trial, at 24 months, the proportion of subjects with medication-free diurnal IOP ≤18 mmHg was 63.2% in the treatment group and 50.0% in the control group (difference 13.2%; 95% CI 2.9%,
23.4%).3
C. In the iStent inject pivotal trial, mean observed unmedicated IOP was higher at baseline and lower at 24 months
in the iStent inject group. IOP at baseline was 24.8 (SD 3.4) mmHg in the iStent inject group and 24.5 (SD 3.1)mmHg in the control group. Unmedicated IOP at 24 months was 17.1 mmHg (SD 3.6) at 24 months in the iStent
inject group and 17.8 mmHg (SD 3.5) in the control group4.
D. Of the subjects who were responders (e.g., 24-month unmedicated mean DIOP was reduced by ≥20% ascompared with baseline in the absence of IOP-affecting surgery during the study), 84% of subjects in the iStent
inject group (243/288) and 67% of subjects in the Control Group (49/73) were not using ocular hypotensive
medication at 23 months.
Based on mean observed unmedicated IOP values from only those subjects with unmedicated IOP and without SSIs or other events (including loss of lightperception or hypotony (IOP < 6 mmHg) associated with clinically significant findings).

4

Symbol

15. MRI SAFETY INFORMATION

Subjects without Month 24 medication-free diurnal IOP, or with IOP-related SSIs, loss of light perception or hypotony (IOP < 6 mmHg)
associated with clinically significant findings prior to 24 months were treated as non-responders. iStent inject subjects with stent reposition
or removal prior to 24 months were treated as non-responders.
1. The 24-month diurnal IOP values were subtracted from baseline diurnal IOP in all subjects, except for the non-responders describedabove. For the non-responders described above, the baseline diurnal IOP values were used for the 24-month diurnal IOP values (i.e., achange of 0 mmHg was used).

3.

14. LABELING
Not all symbols may be included in the labeling of this product.