DIRECTIONS FOR USE/PACKAGE INSERT

4.

Glaukos®Corporation iStent inject® Trabecular Micro-Bypass System
DIRECTIONS FOR USE TABLE OF CONTENTS
1. DEVICE DESCRIPTION
2. INDICATIONS FOR USE
3. CONTRAINDICATIONS
4. WARNINGS
5. PRECAUTIONS
6. ADVERSE REACTIONS
7. INSTRUCTIONS FOR USE
8. ADVERSE EVENT REPORTING
9. HOW SUPPLIED

10. STORAGE REQUIREMENTS
11. EXPIRATION DATE
12. RETURN GOODS POLICY
13. CLINICAL TRIAL RESULTS
14. POST-APPROVAL STUDY RESULTS
15. LABELING
16. MRI SAFETY INFORMATION
17. CAUTION

1. DEVICE DESCRIPTION
The iStent inject® Trabecular Micro-Bypass System Model G2-M-IS 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 230 μm in
diameter, 360 μm in height, and the central inlet and outlet lumen has a diameter of 80 μm (Figure 1).
The head of the stent has four side outlets that each have a diameter of 50 μm.

5.

Non-clinical testing has demonstrated that the iStent inject is MR Conditional. Please
see the “MRI SAFETY INFORMATION” section at the end of this document on
conditions for safe scanning.

5.
1.

PRECAUTIONSThe surgeon should inform the patient that the stent is MR Conditional (as noted on
their Patient ID card), and if the patient needs to undergo an MRI, they should let theirdoctor know they have an iStent inject stent implanted in their eye.
After the surgery, the surgeon should give the patient the Patient ID card (enclosed
in the iStent inject 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 futurereference. The surgeon should advise the patient that this Patient ID card contains
important information related to the iStent inject and that the card should be shown totheir current and future health care providers.
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 intraocularpressure.
The safety and eﬀectiveness of the iStent inject system has not been established as analternative to the primary treatment of glaucoma with medications. The eﬀectivenessof this device has been demonstrated only in patients with mild to moderate open-angle glaucoma who are undergoing concurrent cataract surgery for visually signiﬁcantcataract.
The safety and eﬀectiveness of the iStent inject system has not been established inpatients with the following circumstances or conditions which were not studied in thepivotal 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 priorto 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 patientswith other secondary open-angle glaucomas.

2.

3.

4.

5.

Figure 1. iStent inject® Stent Dimensions
The iStent inject 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 issymmetrical 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).

Figure 2. iStent inject Model GTS400 Design
6.

Figure 3a. iStent inject G2-M-IS Injector Design

Important Notes:

The iStent inject 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) orwith risk factors for corneal compromise following cataract surgery (e.g., advanced
age, severe nuclear sclerosis).

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 by placing the trocar through the central inlet (Figure 9).
Use the alternative “ﬂush technique” to implant the stent.

e.

After visualization of the trabecular meshwork, the Tyvek® tray lid containing theiStent inject 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.
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.

Figure 9. iStent inject rethreading of stent (left) and ﬂush technique (right)
n. Re-loading can be considered if the surgeon prematurely releases a stent prior to
engaging the trocar with the trabecular 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 thatthe number of stents implanted is less than two (2) before utilizing a second injector.
Perform the following steps:

Figure 3b. iStent inject G2-M-IS Injector Distal End
When properly implanted, the iStent inject stent is intended to create a bypass through thetrabecular meshwork into Schlemm’s canal to improve aqueous outﬂow through the natural
physiologic pathway. The implant is provided in a 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.
2. INDICATIONS FOR USE
The iStent inject Trabecular Micro-Bypass System Model G2-M-IS is indicated for use inconjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adultpatients with mild to moderate primary open-angle glaucoma

Stent Implantationa.
Prepare for gonioscopy by turning the patient head away by approximately 35° andthe scope toward surgeon by approximately 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 the trabecular meshwork, through the gonioprism, on the nasalside of the eye. Focus on the landmarks in the angle of the 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 scleral spur and Schwalbe’s line. Schlemm’s canal isbehind the trabecular meshwork.

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 studyeye• At the Screening visit, a medicated mean (or median) IOP ≤ 24 mmHg on a regimenof 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, and absence of peripheral anterior synechia (PAS), rubeosis orother 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 asfollows:• minimum endothelial cell density as shown in Table 1 below• maximum coeﬃcient of variation (CV) = 0.45

• Irrigate the anterior chamber with balanced salt solution (BSS) through the corneal
wound manually, or with automated irrigation/aspiration to remove viscoelastic andreﬂuxed blood. Repeat as needed until all viscoelastic has been removed.

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. Guide the injector across the anterior chamber, just beyond the pupillary margin, and then slide back the micro-insertion sleeve retractor (teal colored) to expose
the micro insertion tube and trocar.

• 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 theearly postoperative period as a possible sequelae following cataract surgery in patientswith glaucoma. Additionally, monitor the patient postoperatively and consider anappropriate treatment regimen to reduce intraocular pressure if need be.
2. Gonioscopy should be performed to assess the iStent inject 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 the absence 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.

• Subjects 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 orcomplications associated with posterior chamber IOL implantation.

Postoperative Retrieval of an Implanted Stent
If the surgeon determines that an instrument is required to recapture a stent after theprocedure, micro forceps of the surgeon’s choice can be used by the surgeon as follows:1.
2.
Figure 6. iStent inject Implant Locationd. Locate the trabecular meshwork and select an implant location (Figure 6). Applylight pressure (or Dimple) onto the trabecular meshwork with the injector to deliver
the stent (Figure 7).

3.
4.
5.
6.

7.
8.

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:
Figure 7. iStent inject® Implant Procedure (left: approach the TM;
center: trocar pierces TM; right: dimple tissue and injecte. Center the trocar inside the micro-insertion tube, relax hand and squeeze the stentdelivery button with your index ﬁnger. A single audible click will indicate that theﬁrst stent has been delivered from the injector through the trabecular meshwork andinto 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 thenext stent is in position and ready to deliver.
h. Carefully move the injector at least two clock hours away from the ﬁrst stent implant.
Approach the trabecular meshwork and repeat steps 5c-5f.
i. After successful implantation of the second stent, carefully withdraw the injector fromthe implant site, release the stent 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 anterior chamber (shown below in Figure 8).
k. Note: minimal blood reﬂux is a normal physiological response to placement of thestents, although this does not occur in all cases.

• In eyes with angle closure glaucoma.
• In eyes with traumatic, malignant, uveitic, or neovascular glaucoma or discernible congenital anomalies of the anterior 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.

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.
Figure 8. iStent inject Implant Sites• pigmentary or pseudoexfoliative glaucoma• traumatic, uveitic, neovascular, or angle-closure glaucoma; or glaucoma associatedwith vascular disorders• functionally signiﬁcant visual ﬁeld loss
• traumaticrior incisional glaucoma surgery• prior SLT within 90 days prior to screening• prior ALT• prior iridectomy or laser iridotomy• pisual ﬁeld (mean deviation) worse than -12 db• ineligible for ocular hypotensive medication washout period as determined by theinvestigator: a) visual ﬁeld status 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.

U.S. Toll Free Phone Number: 1-800-GLAUKOS (452-8567)
Alternate Phone Number: 949-367-9600
Fax Number: 949-297-4540
9. HOW SUPPLIED
The iStent inject Trabecular Micro-Bypass System is supplied as follows. Two stents arepreloaded within the single-use injector system, and the system is provided sterile andnon-pyrogenic in a Tyvek tray. Each stent system is individually serialized, and the serial
number is provided on the tray lid and unit carton. The device has been sterilized by gamma radiation.
10. STORAGE REQUIREMENTS
The device should be stored at room temperature in the range of 15-30° C.
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.
12. RETURN GOODS POLICY
Please contact Glaukos Corporation.

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 wererandomized 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 databaselock for this report, all available eyes had reached the time point at which the safety andeﬀectiveness endpoints are evaluated, i.e., 24 months postoperative. The database for this
PMA was locked on November 13, 2017.

4. WARNINGS
1. The following conditions may prohibit suﬃcient visualization of the angle required forsafe and successful stent implantation: corneal haze, corneal opacity, or any other conditions that may inhibit the gonioscopic view in the intended implant location.

Subjects were not permitted to enroll in the study if they met any of the following key
exclusion criteria related to glaucoma or IOP:

Prep the patient as one would for stent implantation surgery.
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.
Use cohesive viscoelastic to inﬂate the anterior chamber to create access to the stent’s
location, move the stent away from a delicate structure if loose, and/or protect intraocular tissues.
Use a gonioscope if needed to visualize the location of the stent in the anterior chamber.
Insert a micro forceps device through the corneal incision and grasp the stent in aconvenient and secure manner before removing the stent from the anterior chamber.
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 as needed until all
viscoelastic has been removed.
Inﬂate the anterior chamber with saline solution as needed to achieve normal physiologic pressure.
Ensure that the corneal incision is sealed.

13. 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) G100326 . The aim of the iStent inject Pivotal Trial was to establish areasonable 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 withmild 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.

Figure 4a. iStent inject Implant Site

1. Clinical Inclusion and Exclusion Criteriar. At the end of the procedure, the following should be performed:

3. CONTRAINDICATIONS
The iStent inject Trabecular Micro-Bypass System Model G2-M-IS is contraindicated under
the following circumstances or conditions:3. Patients with peripheral iridotomies are at risk of stent dislocation to the posterior chamber and related sequelae.

The study included a medical monitor, data safety monitoring board (DSMB), and specular
microscopy reading center.

• 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.

7. INSTRUCTIONS FOR USE
Cataract Surgery
1.
Cataract surgery with IOL implantation should be performed ﬁrst followed by implantation of the iStent inject.
2.
The stent implantations are designed for nasal placement; therefore, it is suggested
that surgery is performed from the 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 stent.
4.
To mitigate diﬃculty with patient movement or non-compliance, consider using aperi-bulbar or retro-bulbar block.

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.

• Inspect the micro-insertion tube under the surgical microscope and verify that atleast one stent remains within the injector; or, verify that at least one stent has been
retrieved from the eye.

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.

6.
ADVERSE REACTIONS
Refer to the Pivotal Clinical Trial Results section for the adverse events that occurred in thepivotal clinical trial. Additional adverse events that may be reasonably associated with theuse 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, pupillarymembrane formation, retinal detachment, retinal dialysis, retinal ﬂap tears, secondary surgical intervention, including but not limited to glaucoma surgery, premature stent release,stent dislocation, stent not retrievable, stent not visible with gonioscopy, over implanted
stents that are not visible with gonioscopy, stent malfunction, and vitreous hemorrhage.

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 eﬀectivenessendpoint than those who received cataract surgery alone. The second hypothesis was thatthe 24-month IOP response rate of the iStent inject group would be better than 50%. Thishypothesis was to be tested if the observed Cataract surgery-only response rate was greaterthan 35%.
The sample size calculation was based on the hypothesis testing for eﬀectiveness, andevaluation 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 injecteyes 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 injecteyes and 123 control eyes were to be randomized. Therefore, the sample size was set at 500
randomized eyes (375 iStent inject and 125 control).

Figure 4b. iStent inject Implant Sited.

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.

\

3. Clinical Endpoints
The primary eﬀectiveness endpoint was the proportion of eyes with ≥ 20% decrease in
the 24-month medication-free mean 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 ocularhypotensive medications were not washed out at the 24-month visit, 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 clinically signiﬁcant 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Corneal Endothelial Cell Density

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.

There was little diﬀerence in endothelial cell loss (ECL) between the iStent inject andControl groups. Results were consistent 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.

Each endpoint required a comparison between the iStent inject and Control groups. The
primary eﬀectiveness analysis was performed using the Eﬀectiveness Cohort, comprisedof subjects randomized to the iStent inject group who received 2 stents and subjects
randomized to the control group.

A similar proportion of eyes in each group (10.4% in the iStent inject group and 9.5% in thecontrol group) experienced ECL > 30% at 24 months postoperatively.

With regard to safety, anticipated and unanticipated AEs were reported for all subjects
randomized in the study per the treatment that they actually received. Best Corrected
Visual Acuity (BCVA), central corneal pachymetry, slit lamp and fundus exams, gonioscopy and central corneal endothelial cell density (ECD) were also used to assess safety.

2. Eﬀectiveness Results
Results from the primary and secondary endpoints are shown in Table 9. The primary effectiveness endpoint was met, with 75.8% (288/380) in the iStent inject group and 61.9%(73/118) in the Control group achieving a clinically signiﬁcant (≥ 20%) reduction in
medication-free diurnal IOP from baseline at 24 months. This diﬀerence between groups
was statistically signiﬁcant (p=0.003).

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 operativeday. An additional 5 eyes (0.6%) were discontinued due to cataract 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 the iStent inject group, and 118 eyes were randomized to theControl 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 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 from baseline to 24 months was 7.0 mmHg (SD4.0) in the iStent inject group compared to 5.4 mmHg (SD 3.7) in the control group (p<0.001).

The outcomes provided were analyzed according to three (3) separate population
cohorts:

The demographics and preoperative characteristics of the study population were as
follows:

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 (SD3.4) 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% as compared with baseline in the absence of IOP-aﬀecting surgery
during the study), 84% of subjects in the iStent inject group (243/288) and 67% ofsubjects in the Control Group (49/73) were not using ocular hypotensive medication at
23 months.
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 withclinically 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.
4. Based on mean observed unmedicated IOP values from only those subjects with unmedicated IOP and without SSIs
or other events (including loss of light perception or hypotony (IOP < 6 mmHg) associated with clinically signiﬁcant
ﬁndings).

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

• The Intent to Treat (ITT) population was deﬁned as all randomized eyes. Eyes weregrouped according to their randomization 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 implantedwith 2 stents and 118 subjects randomized to the control 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 with cataract surgery and 119 eyesthat underwent cataract surgery only).
C. Study Population Demographics and Baseline Parameters

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%).

D. 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 this study 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 of eyes 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 andrandomization to treatment 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 wererandomized. One eye experienced a corneal abrasion during cataract surgery and was
subsequently randomized to the iStent inject group because this was not a clinicallysigniﬁcant operative complication.
One of the 387 subjects randomized to iStent inject implantation experienced a coughing
ﬁt that resulted in increased positive pressure requiring a corneal suture. Therefore, noattempts to implant stents was made, and this subject was included in the control groupof 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%).

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 andvitreous 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 surgical intervention, ptosis, residual cortex, retinal detachment, retinal
tear, and worsening glaucoma; 2 cases (0.5%) each of anterior 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 stents2
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

Additional detail regarding the reasons patients did not achieve the primary endpoint(IOP non-responders) is shown in Table 10.

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 was considered serious. The proportion of eyes withserious AEs (SAEs) was 0.8% (n=3) in the iStent inject group and 2.5% (n=3) inthe control group. iStent inject SAEs comprised 1 case each of mild partial stent obstruction that did not require intervention, retinal tear requiring laser retinopexy, andglaucoma progression requiring ExPress shunt implantation. SAEs reported for thecontrol group consisted of 1 case each of blurred vision/visual disturbance; epiretinal
membrane requiring vitrectomy with membrane peel, and central retinal artery occlusion and neovascularization requiring pan-retinal photocoagulation.
A total of 56 AEs reported for 48 iStent inject eyes (12.4%) were determined to be
device related including all cases of stent obstruction, deep stents, 3 stents implanted,
1 stent implanted, 2 stents implanted in the same location, and stent 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, and1 case (0.3%) each of iris strand and ocular irritation.
2. In each of the four eyes with “deep stents,” there was a single stent per eye that was unable to bevisualized by either gonioscopy or UBM at the last 3 visits, despite 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 toachieve 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 bothgroups are shown in Table 8.

3. Summary of Supplemental Clinical Information
A. For the pivotal trial of the iStent inject, the Ocular Surface Disease Index (OSDI©)
was self-administered by 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 100with 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
group involving 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 tocollect these data has not been validated, and therefore the true rates of these symptoms
may diﬀer from those presented in the Table 11.

15. MRI SAFETY INFORMATION

Non-clinical testing has demonstrated that the iStent inject Trabecular Micro-Bypass System
Model G2-M-IS 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 (SARof 4 W/kg
Under the scan conditions deﬁned above, the iStent inject Trabecular Micro-Bypass System
Model G2-M-IS is not expected to produce a clinically signiﬁcant temperature rise after 15
minutes of continuous scanning.
In non-clinical testing, the image artifact caused by the device extends less than 15 mmfrom the device when imaged with a gradient echo pulse sequence and a 3.0 T MRI system.
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 main parts:

In most eyes (85.5%; n = 331), only a single injector was employed. No associated clinicalsequelae were noted in any cases in which a second injector was used. No diﬃculties withimplantation were reported in the majority of cases (81.4%; n = 315). No associated clinicalsequelae were noted in any cases in which stent implantation diﬃculty was reported.

Postoperative AEs
There were no unanticipated adverse events. There were no reports of ﬂat AC with lenscornea touch, shallow AC with iridoc traumatic orneal 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, loss of light perception or stent dislocation. Moreover, nocases of pupillary block or hypopyon were reported during the study.
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 associatedrates are provided in Table 7. Anterior segment inﬂammation, which was generally
mild, was reported in 5.7% of iStent inject subjects and 4.2% of Control subjects.

Other Operative/Postoperative Observations
Reporting of other ocular observations was at the study investigator’s discretion. Similar
data may not be reported for every 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 wereboth stents not visible on the operative day. The other ocular observations that werereported 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 were visualized 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.

Manufacturer:
Glaukos Corporation
229 Avenida Fabricante
San Clemente, CA 92672
Tel: 949.367.9600, Fax: 949.367.9984
www.glaukos.com
Toll-Free: 1-800-GLAUKOS (452-8567)
Glaukos® and iStent inject® are registered trademarks of Glaukos Corporation.
Tyvek® is a registered trademark of DuPont USA.
45-0176 Rev 1 06/18

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, stent implantation 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.

• Didactic session• Simulated implantation of iStent inject• Supervised iStent inject implantation of clinical cases until implantation proﬁcien
cy is demonstrated