(209 days)
Not Found
No
The description focuses on the physical characteristics of the implant and the clinical trial results, with no mention of AI or ML.
Yes
The device is an implantable system intended to reduce intraocular pressure (IOP) in patients with primary open-angle glaucoma, a condition. The stated indication to "reduce the intraocular pressure (IOP) of the eye" confirms its therapeutic purpose.
No
The device is an implantable system designed to reduce intraocular pressure, explicitly stated as for "treatment." It does not mention any function for diagnosing conditions.
No
The device description clearly states it is an "implantable device" and describes physical components made of titanium, indicating it is a hardware device, not software-only.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is to "reduce the intraocular pressure (IOP) of the eye" by implanting a device. This is a therapeutic intervention performed directly on the patient's body.
- Device Description: The device is an "implantable device" designed to be placed within the eye. IVD devices are used to examine specimens (like blood, urine, or tissue) outside of the body to provide information about a person's health.
- Lack of IVD Characteristics: The description does not mention any components or processes related to analyzing biological samples in vitro.
Therefore, the iStent infinite® Trabecular Micro-Bypass System Model iS3 is a medical device used for treatment, not an in vitro diagnostic device used for diagnosis or monitoring through the analysis of specimens outside the body.
N/A
Intended Use / Indications for Use
The iStent infinite® Trabecular Micro-Bypass System Model iS3 an implantable device intended to reduce the intraocular pressure (IOP) of the eye. It is indicated for use in adult patients with primary open-angle glaucoma in whom previous medical and surgical treatment has failed.
Product codes
KYF
Device Description
The iStent infinite Trabecular Micro-Bypass System Model iS3 is a sterile, single-use injector system that is pre-loaded with three G2-W stents, and is designed to deliver the stents into Schlemm's canal. The G2-W stents are manufactured from implant grade titanium (Ti6Al4V ELI per ASTM F136) and are coated with stearalkonium heparin. An area of reduced outside diameter, midway along the device, is designed to provide retention within the trabecular meshwork, while multiple outlet lateral lumens (4 outflow orifices) are designed to provide an exit route for aqueous from the anterior chamber. The stent has a single piece design, is 360 um in diameter, 360 um in height, and the central inlet and outlet lumen has a diameter of 80 um. The head of the stent has four side outlets that each have a diameter of 50 um.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Angle-based implant
Indicated Patient Age Range
Adult patients
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
A prospective, multi-center, single-arm, open-label, clinical trial was conducted at 14 sites in the US and one OUS site to evaluate the safety and effectiveness of the iStent infinite in adult patients with primary open-angle glaucoma, pseudoexfoliative or pigmentary glaucoma with open angles, and in whom previous medical and surgical treatment has failed. 61 participants were implanted with the iStent infinite and followed post-operatively for 12 months. The two effectiveness endpoints were 1) the proportion of participants achieving a 20% or greater mean diurnal IOP (MDIOP) reduction from baseline at 12 months on the same or fewer number of medication classes and 2) the change from baseline in MDIOP at 12 months. No washout of IOP-lowering medications was performed before implantation. Safety outcomes included adverse events (AEs), surgical complications, best spectacle corrected visual acuity (BSCVA), and ocular findings from slit-lamp biomicroscopy, fundus examination, gonioscopy, pachymetry, and visual field testing.
Effectiveness Results:
- Proportion of Responders at Month 12:
- ITT Population/Worst Postoperative IOP & Last Available Medication Classes: 44/61 (72.1%) (95% CI: 59.2%, 82.9%)
- ITT Population/Failure Assumption: 44/61 (72.1%) (95% CI: 59.2%, 82.9%)
- PP Population: 43/59 (72.9%) (95% CI: 59.7%, 83.6%)
- ITT Population/Exclusion from Cohort: 44/60 (73.3%) (95% CI: 60.3%, 83.9%)
- ITT Population/Multiple Imputation: 73.4% (95% CI: 62.2%, 84.6%)
- 12-Month Diurnal IOP Change from Baseline:
- ITT Population/Worst Postoperative IOP: 61, Mean -5.5 ± 5.24 (-6.9, -4.2)
- PP Population: 59, Mean -5.5 ± 5.29 (-6.9, -4.1)
- ITT Population/Exclusion from Cohort: 60, Mean -5.6 ± 5.27 (-6.9, -4.2)
- ITT Population/Multiple Imputation: 61, Mean -5.5 ± 0.67 (-6.9, -4.2)
Safety Results:
- No intraoperative adverse events (AEs).
- Five of 61 participants (8.2%) needed the use of a second injector due to nondeployment of the second or third stent, and there was also head movement in one of these 5 participants.
- No reports of corneal decompensation, choroidal effusion, choroidal hemorrhage, hypotony maculopathy, deep stents ("buried" in the trabecular meshwork) that were not visible at the last three scheduled visits of the study, stent explantation, stent dislocation, or stent repositioning.
- Most common AEs reported were ocular surface disease, substantial increase in IOP vs. baseline, and loss of BSCVA ≥ 2 lines.
- Stent obstruction occurred in two of 61 participants (3.3%).
- Two instances of stent migration occurred in one participant (1.6%).
- Three of 61 participants (4.9%) required secondary surgical intervention (implantation of aqueous shunt) to lower IOP.
Key Metrics
- Proportion of participants achieving a 20% or greater mean diurnal IOP (MDIOP) reduction from baseline at 12 months on the same or fewer number of medication classes.
- Change from baseline in MDIOP at 12 months.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 886.3920 Aqueous shunt.
(a)
Identification. An aqueous shunt is an implantable device intended to reduce intraocular pressure in the anterior chamber of the eye in patients with neovascular glaucoma or with glaucoma when medical and conventional surgical treatments have failed.(b)
Classification. Class II. The special controls for this device are FDA's:(1) “Use of International Standard ISO 10993 ‘Biological Evaluation of Medical Devices—Part I: Evaluation and Testing,’ ”
(2) “510(k) Sterility Review Guidance of 2/12/90 (K90-1),” and
(3) “Aqueous Shunts—510(k) Submissions.”
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 2, 2022
Glaukos Corporation Mr. David Fernquist Vice President Regulatory Affairs 229 Avenida Fabricante San Clemente, California 92672
Re: K220032
Trade/Device Name: iStent infinite Trabecular Micro-Bypass System, Model iS3 Regulation Number: 21 CFR 886.3920 Regulation Name: Aqueous Shunt Regulatory Class: Class II Product Code: KYF Dated: June 21, 2022 Received: June 24, 2022
Dear Mr. David Fernquist:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Anjana Jain, PhD Assistant Director DHT1A: Division of Ophthalmic Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K220032
Device Name iStent infinite® Trabecular Micro-Bypass System Model iS3
Indications for Use (Describe)
The iStent infinite® Trabecular Micro-Bypass System Model iS3 an implantable device intended to reduce the intraocular pressure (IOP) of the eye. It is indicated for use in adult patients with primary open-angle glaucoma in whom previous medical and surgical treatment has failed.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) SUMMARY
This 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92.
| SUBMITTER
I. | Glaukos Corporation
229 Avenida Fabricante
San Clemente, CA 92672 |
|------------------------|---------------------------------------------------------------------------------------------------|
| Contact Person: | David S. Fernquist
Vice President, Regulatory Affairs
Glaukos Corporation
(949) 367-9600 |
| Date Summary Prepared: | August 2, 2022 |
| II.
DEVICE | |
| Trade Name: | iStent infinite Trabecular Micro-Bypass System Model iS3 |
| Common Name: | Glaucoma Implant |
| Classification Name: | Aqueous shunt (21 CFR 886.3920) |
| Device Class: | Class II (special controls) |
| Device Product Code: | KYF ("Implant, Eye Valve") |
III. PREDICATE DEVICE
- XEN Glaucoma Treatment System (K161457), 21 CFR 886.3920, Product Code KYF
IV. DEVICE DESCRIPTION
The iStent infinite Trabecular Micro-Bypass System Model iS3 is a sterile, single-use injector system that is pre-loaded with three G2-W stents, and is designed to deliver the stents into Schlemm's canal. The G2-W stents are manufactured from implant grade titanium (Ti6Al4V ELI per ASTM F136) and are coated with stearalkonium heparin. An area of reduced outside diameter, midway along the device, is designed to provide retention within the trabecular meshwork, while multiple outlet lateral lumens (4 outflow orifices) are designed to provide an exit route for aqueous from the anterior chamber. The stent has a single piece design, is 360 um in diameter, 360 um in height, and the central inlet and outlet lumen has a diameter of 80 um. The head of the stent has
4
four side outlets that each have a diameter of 50 um.
V. INTENDED USE
The iStent infinite Trabecular Micro-Bypass System Model iS3 has the same intended use as the predicate device and all other devices regulated within the generic type of device known as aqueous shunts in accordance with 21 CFR 886.3920. The iStent infinite is a prescription (Rx) device that is intended to be permanently implanted to reduce intraocular pressure for the management of glaucoma. Both the subject device and predicate device (XEN® Glaucoma Treatment System) have the same intended use for the treatment, namely, "to be permanently implanted to reduce intraocular pressure for the management of glaucoma", as stated above. The iStent infinite will bear the following indications for use statement:
The iStent infinite Trabecular Micro-Bypass System Model iS3 is an implantable device intended to reduce the intraocular pressure (IOP) of the eye. It is indicated for use in adult patients with primary open-angle glaucoma in whom previous medical and surgical treatment has failed.
The indications for use statement for iStent infinite is not substantially different from that of the XEN implant predicate device. The non-substantial difference in the indications for use statement for the iStent infinite vs. the predicate device is that the iStent infinite indication is narrower. Compared to the XEN indications for use statement (shown below), the iStent infinite indications for use statement does not include patients with pseudoexfolative glaucoma or pigmentary glaucoma who have failed maximally tolerated medical therapy. It should be noted that both the pivotal study for XEN and the pivotal study for iStent infinite comprised a substantial majority of primary open-angle glaucoma patients with prior failed surgical intervention and similar baseline characteristics.
The XEN® Glaucoma Treatment System is indicated for the management of refractory glaucomas, including cases where previous surgical treatment has failed, cases of primary open angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy.
VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE SUBJECT DEVICE AND PREDICATE DEVICE
Although the iStent infinite and the XEN do not share identical technological characteristics, those differences do not raise different questions of safety and effectiveness.
5
| Characteristics | Allergan XEN Glaucoma
Treatment System
K161457
PREDICATE DEVICE | iStent infinite
SUBJECT DEVICE |
|--------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | To be permanently implanted to
reduce intraocular pressure for the
management of glaucoma | To be permanently implanted to
reduce intraocular pressure for the
management of glaucoma |
| Regulation
Number/Product
Code | 886.3920, KYF | 886.3920, KYF |
| Indication | The XEN Glaucoma Treatment
System is indicated for the
management of refractory
glaucomas, including cases where
previous surgical treatment has
failed, cases of primary open angle
glaucoma, and pseudoexfoliative or
pigmentary glaucoma with open
angles that are unresponsive to
maximum tolerated medical therapy. | The iStent infinite Trabecular Micro-
Bypass System Model iS3 is an
implantable device intended to
reduce the intraocular pressure (IOP)
of the eye. It is indicated for use in
adult patients with primary open-
angle glaucoma in whom previous
medical and surgical treatment has
failed. |
| Rx or OTC | Rx | Rx |
| Permanent Implant | Yes | Yes |
| Design | Monolithic, round tube design with a
central inlet and outlet lumen | Monolithic round tube design with a
central inlet and outlet lumen |
| Material | Gelatin derived from porcine dermis,
formed into a tube, and then cross-
linked with glutaraldehyde; no
coating | Implant grade titanium (Ti6Al4V
ELI) with a stearalkonium heparin
coating |
| Size (nominal
dimensions) | Dry dimensions:
6 mm length
0.045 mm inner diameter
0.15 mm outside diameter | 0.36 mm length
0.36 mm flange diameter
0.23 mm head diameter
0.08 mm central outlet diameter
0.05 mm flow outlet diameter |
| Sterilization | Terminal gamma ray radiation | Terminal gamma ray radiation |
| Single-Use | Yes | Yes |
| Anatomical site | Angle-based implant | Angle-based implant |
| Mechanism of action | Outflow of aqueous fluid via a
subconjunctival bleb | Outflow of aqueous fluid via
trabecular bypass |
| Method of Insertion | Via a preloaded XEN injector | Via a preloaded injector |
Table 1. Comparison of the iStent infinite System and XEN Glaucoma Treatment System (Predicate Device)
VII. PERFORMANCE DATA
The following performance data were provided in support of the substantial equivalence determination.
6
Bench Testing A.
The nonclinical bench testing conducted on the iStent infinite Trabecular Micro-Bypass System Model iS3 included design verification and functional product testing, sterilization validation, packaging and shelf life testing, and biocompatibility testing. Results of the nonclinical testing demonstrate that theiStent infinite Trabecular Micro-Bypass System Model iS3 functions as intended.
Design Verification and Functional Product Testing:
The iStent infinite Trabecular Micro-Bypass System Model iS3 Stent and injector were evaluated to verify that the design output met the original design input and intent. This testing was based on tests described in ANSI Z80.27, Implantable Glaucoma Devices, the FDA guidance document "Aqueous Shunts - 510(k) Submissions", and the FDA guidance document "Premarket Studies of Implantable Minimally Invasive Glaucoma Surgical (MIGS) Devices". All physical and mechanical testing demonstrated that the stent and injector function as intended.
7
| Table 2. Physical & Mechanical Testing | |
|---|---|
| Test | Results |
| Surface & Edge | |
| Quality | High magnification SEM photos of the G2-W stent demonstrated that the stent |
| had smooth edges and was free from surface defects. | |
| Dimensions | Glaukos has validated that stent production meets tolerances to appropriate |
| statistical levels. | |
| Physical Stability | An in-vivo test to evaluate the physical stability of the titanium stent was |
| performed per ANSI Z80.27 Section 5.5. A total of 10 etched and coated | |
| stents were pulled from a production lot for the validation, inspected, and were | |
| placed into BSS for 14 days at a temperature 35 $\pm$ 2 °C. Visual inspection (at | |
| least 10x) and dimensional measurements were performed at baseline and after | |
| 14 days. The results of the dimensional inspection showed that the four | |
| critical dimension measurements remained the same before and after | |
| incubation. The results of the visual inspection demonstrated that the surface | |
| finish on the incubated stents maintained the same quality as prior to | |
| incubation. The data also show that the coating on the stents remains intact | |
| after incubation. | |
| Pressure/Flow | |
| Characteristics | Numerical modeling, including computational fluid dynamics, was used to |
| evaluate the flow through the stents over physiologically relevant boundary | |
| conditions. The stents were found to have negligible flow resistance. | |
| Structural Integrity | A study was undertaken to evaluate the stress levels during the highest |
| anticipated load conditions for the stent by Finite Element Analysis (FEA). | |
| Based on the modeling data, it was determined that the safety factors at the | |
| lowest and highest implant velocities were 41x and 14x, respectively. The | |
| results confirm that the stent will maintain its structural integrity after | |
| implantation with the velocity range seen clinically. | |
| Insertion Testing | As part of the shelf life testing for the iS3 injector, functional testing was |
| performed at baseline and after 1 year of aging to demonstrate that all specified | |
| requirements were met e.g. stent delivery, stent singulation, stent implantation | |
| and trocar penetration in synthetic tissue. All tested injectors successfully | |
| passed all predetermined acceptance criteria for stent delivery. | |
| Stability of Coating | Stability of the stearalkonium heparin coating on the stent was demonstrated |
| for the shelf life period of the finished, sterile device. | |
| MRI Compatibility | Non-clinical testing has demonstrated that the iStent infinite Trabecular Micro- |
| Bypass System (Model iS3) is MR Conditional. A patient with this device can | |
| be safely scanned in an MR system meeting conditions specified in the IFU | |
| and patient implant card. | |
| Corrosion Resistance | Glaukos submitted samples that were representative of the finished, sterile |
| titanium stent to a contract laboratory for electrochemical evaluation in | |
| accordance with ASTM (American Society For Testing and Materials) F2129- | |
| 15, Standard Test Method for Conducting Cyclic Potentiodynamic Polarization | |
| Measurements to Determine the Corrosion Susceptibility of Small Implant | |
| Devices". The test lab concluded that test samples displayed acceptable | |
| corrosion resistance to pitting and crevice corrosion in the ASTM F2129 test in | |
| the received condition. |
Sterilization Validation:
The gamma irradiation sterilization method was validated using the VDmx 35 method described in ISO 11137-1:2015 and ISO 11137-2:2015. Validation results demonstrate that a minimum
8
exposure dose of 25 kGy has been substantiated for the routine sterilization of the iStent infinite Trabecular Micro-Bypass System Model iS3 to provide a 10-6 sterility assurance level (SAL).
Bacterial Endotoxin
Endotoxin Limulus amebocyte lysate (LAL) testing has been performed as recommended in the FDA guidance document "Endotoxin Testing Recommendations for Single-Use Intraocular Ophthalmic Devices."
Packaging and Shelf Life Testing:
The iStent infinite Trabecular Micro-Bypass System Model iS3 is labeled with an expiration date of 1 year. The shelf life study evaluated the functional performance of the G2-W Stent and the iS3 injector, as well as the packaging integrity of the tray sealed with the Tyvek lid. Additional testing was completed to evaluate the impact of environmental conditioning and distribution factors. Test results confirm that the G2-W Stent and the iS3 injector meet their functional requirements and the sterile barrier (package integrity) remains intact after simulated distributionand aging. This testing provides the justification for the 1-year shelf life and the maintenance of the sterile barrier.
Biocompatibility Testing
The biocompatibility testing outlined in the tables below (Table 4) was performed on the stent (or representative samples of the finished device) and the patient-contacting portion of the injector in accordance with the relevant parts of International Organization for Standardization (ISO) standard 10993. All testing demonstrated that the device materials have an acceptable biocompatibility profile. With respect to physico-chemical testing of the stent, there is an extensive history of titanium use in medical devices. Therefore, tests for extraction in aqueous and organic solvents and for hydrolytic stability were not performed on the device, since they were considered unnecessary. In addition, the device's titanium material contains no monomers and is not subject to hydrolytic degradation.
9
| Test | Purpose | Acceptance
Criteria | Results |
|---------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------|---------|
| Cytotoxicity: | | | |
| ISO Inhibition Of Cell
Growth | To determine the potential biological reactivity of a
mammalian cell culture (L929) in response to the test
article extract | Cell growth
inhibition S. typhimurium and E. coli respectively | No mutagenic
changes | Pass |
| Mouse Bone Marrow
Micronucleus Study | To determine the ability of the test article and/or its
metabolites to induce micronuclei in maturing
erythrocytes of mice | No toxicity or
mutagenic
effects | Pass |
| In Vitro Chromosomal
Aberration Study | To determine the ability of the test article to induce
chromosome aberrations, structural or numerical, in
CHO cells in the presence or absence of an
exogenous mammalian activation system | No
chromosomal
aberrations
induced | Pass |
| Other: | | | |
| Intraocular Irritation
Study in the Rabbit | To evaluate the potential of the test article extract to
cause intraocular irritation or toxicity following an
intracameral injection in rabbits | No evidence of
irritation | Pass |
| Guinea Pig Kligman
Maximization Test | To evaluate the allergenic potential or sensitizing
capacity of the test article | No evidence of
delayed dermal
contact
sensitization | Pass |
| Muscle Implantation
in the Rabbit (2, 4, and
13 Weeks) | To evaluate the test article for local tissue responses
and the potential to induce local toxic effects after
implantation | No significant
reaction | Pass |
| Acute Systemic
Toxicity in the Mouse | To evaluate the test article extracts for potential toxic
effects following a single-dose systemic injection in
mice | No evidence of
systemic
toxicity | Pass |
| USP Material-
Mediated Rabbit
Pyrogen Study | To determine the potential presence of chemical
pyrogens in extracts of the test article | Non-pyrogenic | Pass |
| Test | Purpose | Acceptance
Criteria | Results |
| Cytotoxicity: | | | |
| ISO Medium Eluate
Method Test (1x CMEM
Extract) | To determine the biological reactivity of a mammalian
cell culture (L929) in response to the test article extract | No cell lysis or
toxicity | Pass |
| ISO Agar Diffusion Test
(Solid Sample) | To determine the biological reactivity of a mammalian
monolayer cell culture (L929) in response to the test
article | No cell lysis or
toxicity | Pass |
| Other: | | | |
| Intraocular Irritation
Test (Phosphate
Balanced Saline Extract) | To evaluate the potential of the test article extract to
cause intraocular irritation or toxicity following an
intracameral injection in rabbits | No evidence of
irritation | Pass |
| Guinea Pig Kligman
Maximization Test
(Saline & Vegetable Oil
Extracts) | To evaluate the allergenic potential or sensitizing
capacity of the test article | No evidence of
delayed dermal
contact
sensitization | Pass |
| Rabbit Intracutaneous
Reactivity/Irritation Test
(Saline & Vegetable Oil
Extracts) | To evaluate the test article for potential irritation effects
as a result of an intracutaneous injection in New Zealand
White rabbits | Non-irritating | Pass |
| Acute Systemic Toxicity
in the Mouse (Saline &
Vegetable Oil Extracts) | To evaluate the test article extracts for potential toxic
effects following a single-dose systemic injection in mice | No evidence of
systemic toxicity | Pass |
| Rabbit (Material-
Mediated) Pyrogen Test
(Normal Saline Extract) | To determine the potential presence of chemical pyrogens
in extracts of the injector test article using the ISO Rabbit
Pyrogen Test (Material Mediated) procedure. | Non-pyrogenic | Pass |
Table 3. Biocompatibility Testing - Stent
10
| Table 4. Biocompatibility Testing - Injector | |||
|---|---|---|---|
| -- | ---------------------------------------------- | -- | -- |
B. Clinical Performance Testing
A prospective, multi-center, single-arm, open-label, clinical trial was conducted at 14 sites in the US and one OUS site to evaluate the safety and effectiveness of the iStent infinite in adult patients with primary open-angle glaucoma, pseudoexfoliative or pigmentary glaucoma with open angles, and in whom previous medical and surgical treatment has failed. 61 participants were implanted with the iStent infinite and followed post-operatively for 12 months. The two effectiveness endpoints were 1) the proportion of participants achieving a 20% or greater mean diurnal IOP (MDIOP) reduction from baseline at 12 months on the same or fewer number of medication classes and 2) the change from baseline in MDIOP at 12 months. No washout of IOP-lowering medications was performed before implantation. Safety outcomes included adverse events (AEs), surgical complications, best spectacle corrected visual acuity (BSCVA), and ocular findings from slit-lamp biomicroscopy, fundus examination, gonioscopy, pachymetry, and visual field testing.
Demographics and Preoperative Characteristics
61 participants were implanted. The mean age of participants was 71.7 years (median 71.0, range 49 to 88) and there were 28 men (28/61 or 45.9%) and 33 women (33/61 or 54.1%). 37 of 61 (60.7%) participants were White, 15 of 61 (24.6%) were Black, six of 61 (9.8%) were Asian: race
11
was not reported for three of 61 (4.9%) subjects. 11 of 61 participants (18.0%) had ethnicity reported as Hispanic or Latino. 55 participants (90.1%) were diagnosed with primary open angle glaucoma (POAG), three (4.9%) had pseudoexfoliative glaucoma, and three (4.9%) had pigmentary glaucoma. All 61 participants had undergone prior filtering or cilioablative glaucoma procedures. Preoperatively, the mean visual field mean deviation (MD) score was -15.1 (SD 8.56) dB (median -13.7 dB, range -31.82 to -1.79 dB). The mean baseline medicated MDIOP was 23.5±2.82 mm Hg (median 22.7 mm Hg, range 20-35 mm Hg). At baseline, participants were using a mean of 3.0 (± 0.9) ocular hypotensive medications, with 19 of 61 (31.1%) on two or fewer medications and 42 of 61 (68.9%) on three or more medications.
Effectiveness Results
Tables 5 and 6 summarize the primary effectiveness analyses based on 12-month diurnal IOP data.
| Analysis Population/Imputation Method for Missing Data | iStent infinite
n/N (%)
(95% CI)
N= 61 |
|--------------------------------------------------------------------------------|-------------------------------------------------|
| ITT Population/Worst Postoperative IOP & Last Available
Medication Classes1 | 44/61 (72.1%)
(59.2%, 82.9%) |
| ITT Population/Failure Assumption2 | 44/61 (72.1%)
(59.2%, 82.9%) |
| PP Population | 43/59 (72.9%)
(59.7%, 83.6%) |
| ITT Population/Exclusion from Cohort3 | 44/60 (73.3%)
(60.3%, 83.9%) |
| ITT Population/Multiple Imputation4 | 73.4%
(62.2%, 84.6%) |
Table 5. Analyses of Responder Effectiveness Endpoint Proportion of Responders at Month 12
Participants with hypotony (IOP = 10 mmHg vs. baseline IOP¹ | 5 (8.2%) |
| IOP increase requiring oral medication¹ | 2 (3.3%) |
| IOP increase requiring surgical intervention¹ | 3 (4.9%) |
| Increase in C/D ratio of > 0.3 units on ophthalmoscopic examination | 0 (0.0%) |
| Intraocular inflammation arising after the protocol's specified medication regimen
is complete | 1 (1.6%) |
| Intraocular inflammation following tube shunt surgery | 2 (3.3%) |
| Iridodialysis | 0 (0.0%) |
| Lens/IOL dislocation | 0 (0.0%) |
| Loss of best spectacle corrected visual acuity (BSCVA) of 2 lines or more | 7 (11.5%) |
| 30 days² | 6 (9.8%) |
| Loss of eye | 0 (0.0%) |
| Macular edema | 2 (3.3%) |
| Macular puckering | 0 (0.0%) |
| Nd:YAG capsulotomy | 0 (0.0%) |
| Needling procedure | NA |
| iStent infinite N = 61 | |
| | Number (Percent) of
Subjects with Event |
| Postoperative Adverse Event | |
| Ocular hypotensive medication intolerance | 3 (4.9%) |
| Ocular pain | 1 (1.6%) |
| Ocular surface disease | 7 (11.5%) |
| Perioperative inflammation | 4 (6.6%) |
| Posterior vitreous detachment | 1 (1.6%) |
| Proliferative vitreoretinopathy | 0 (0.0%) |
| Ptosis | 0 (0.0%) |
| Pupillary block | 0 (0.0%) |
| Retinal detachment | 0 (0.0%) |
| Retinal dialysis | 0 (0.0%) |
| Retinal flap tears | 0 (0.0%) |
| Secondary surgical intervention | 3 (4.9%) |
| Significant corneal complications including opacification and decompensation | 0 (0.0%) |
| Significant corneal edema | 0 (0.0%) |
| Significant corneal injury | 0 (0.0%) |
| Significant damage to trabecular meshwork | 0 (0.0%) |
| Significant hyphema (i.e, >= 10% of anterior chamber) | 2 (3.3%) |
| Significant iris damage | 0 (0.0%) |
| Stent dislocation | 0 (0.0%) |
| Stent explant | 0 (0.0%) |
| Stent migration3 | 1 (1.6%) |
| Stent obstruction4 | 2 (3.3%) |
| Stent-cornea touch | 0 (0.0%) |
| Stye | 1 (1.6%) |
| Subconjunctival hemorrhage | 1 (1.6%) |
| Toxic Anterior Segment Syndrome (TASS) | 0 (0.0%) |
| Transient hypotony | 1 (1.6%) |
| Visual field loss = 2.5 dB | 4 (6.6%) |
| Vitreous hemorrhage | 0 (0.0%) |
| Vitreous loss | 0 (0.0%) |
| Wound leak/dehiscence | 0 (0.0%) |
| Wound repair | 0 (0.0%) |
Table 7. Postoperative Ocular Adverse Events in the Study Eye (Sorted Alphabetically)
14
-
- A total of 8 eyes (8/61 or 13.1%) experienced 12 AEs of increased IOP (consisting of elevated IOP, IOP increase > 10 mmHz vs. baseline IOP, IOP increase requiring oral medication and IOP increase requiring surgical intervention). The 4 eyes with more than one AE of increased IOP are as follows:
- One eye had an AE of IOP increase >= 10 mmHg vs. baseline IOP and an AE of IOP increase requiring secondary surgical intervention
- · One eye had an AE of IOP increase requiring oral medication and an AE of IOP increase requiring surgical intervention
- · One eye had an AE of elevated IOP and an AE of IOP increase requiring secondary surgical intervention
- · One eye had 2 AES of IOP increase >= 10 mmHg vs. baseline IOP
-
- Includes persistent BSCVA loss
-
- One subject was reported with 2 events of stent migration. The visualization was impaired during implantation of the 1:00 and 4:30 stents due to corneal arcus, striae and external location-marking dye. The stent reported as implanted at 1:00 was identified in the 1:00 position via UBM ("imbedded deep beyond iris insertion"), and the stent reported as implanted at 4:30 was identified in the 7:30 position via both gonioscopy and UBM.
-
- The 2 AEs of stent obstruction involved obstruction of 2 stents each. The investigators reported associated findings of significant hyphema in 1 case and pre-existing and postoperative focal goniosynechiae in both cases. One case of stent obstruction resolved following treatment with pilocarpine, and 1 case was not treated and was ongoing at Month 12. Both subjects experienced Month 12 MDIOP reduction on the same medication regimen as preoperative.
15
VIII. CONCLUSIONS
The iStent infinite Trabecular Micro-Bypass System Model iS3 has the same intended use as the legally marketed predicate device identified in this 510(k) notification and all other aqueous shunts regulated by FDA under 21 CFR § 886.3920. The indications for use statement differs from those for the predicate device, however, the differences do not alter the intended use of the device.
The iStent infinite Trabecular Micro-Bypass System Model iS3 technological characteristics differ from the predicate device, however, the differences do not raise new or different questions of safety or effectiveness. Results of the nonclinical testing demonstrate that the iStent infinite Trabecular Micro-Bypass System Model iS3 functions as intended. Results of clinical performance testing support a favorable safety and effectiveness profile that supports a determination of substantial equivalence. The non-clinical and clinical performance testing demonstrate that the device is as safe, as effective, and performs as well as or better than the legally marketed device predicate.