The PRIMUS instrument is a non-contact, high resolution tomographic imaging device. It is indicated for in-vivo viewing of axial cross sections and measurement of posterior ocular structures, including retinal nerve fiber layer, macula, and optic disc. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, macular edema, diabetic retinopathy, age-related macular degeneration and glaucoma.

Device Description

The PRIMUS device is an ophthalmic instrument that provides the essential performance and functionality compared to the Carl Zeiss Meditec CIRRUS™ HD-OCT Model 4000 (K11157), with a separate manually-controlled patient interface and simplified analysis features. PRIMUS uses the same SD-OCT technology from the CIRRUS and offers a simplified user interface. In addition, the camera in the PRIMUS instrument operates at a reduced speed to acquire OCT images at comparable resolution in approximately the same amount of time.

The PRIMUS device is a computerized ophthalmologic instrument that acquires and allows visualization of cross-sectional tomograms of the eye using spectral domain optical coherence tomography (SD-OCT). The instrument is designed to scan the eye in a non-contact manner to acquire detailed cross-sectional images of various posterior ocular structures such as the retina and the optic nerve head. Various retinal structures of the eye from the internal limiting membrane to the retinal pigment epithelium (including layers such as the ganglion and retinal nerve fiber) can be imaged.

The PRIMUS instrument is available in one model, Model 200, which has a manually controlled patient interface and separate enclosure with components used in OCT scanning. The operator utilizes a keyboard, monitor and mouse to interface with the computer. Data acquired can be saved to the computer; PDFs of the reports may be saved to a USB-connected storage device.

The principle of operation is identical in that both devices employ a non-invasive, non-contact low-coherence interferometry technique [spectral domain optical coherence tomography (SD-OCT) to generate high-resolution cross-sectional images of internal ocular tissue microstructures by measuring optical reflections from tissue. Both provide cross sectional images of the posterior structures of the eye (i.e., retina, including the ganglion and retinal nerve fiber layers).

The device consists of two main parts: a manually controlled separate patient interface and an imaging engine box. The system is composed of a number of electrical, mechanical, and optical subsystems that are required to facilitate measurements and aid in patient alignment:

Optical head modules
SD-OCT engine modules
Patient module
Support modules

As part of its report driven workflow, at the completion of scan acquisition, PRIMUS presents the pre-ordered report(s) to the user in a sequential manner. The visualization and analysis reports that available in PRIMUS are as follows:

Macular Thickness Analysis (MTA) Based on 512 X 32 Macular Cube Scan
Optic Nerve Head (ONH) & Retinal Nerve Fiber Layer (RNFL) Analysis Based on 128 X 128 ONH & RNFL Cube Scan
HD 5-line Analysis Based on 5 line HD Raster Scan
HD 1-line Analysis Based on 1 line HD Raster Scan

AI/ML Overview

The provided text describes a 510(k) summary for the PRIMUS 200 ophthalmic instrument, focusing on demonstrating its substantial equivalence to a predicate device (Cirrus HD-OCT Model 4000). The information pertains to the device's technical characteristics and performance in clinical evaluation, but it doesn't describe the acceptance criteria and performance against those criteria in a typical AI/ML medical device submission format.

However, based on the provided text, I can infer the "acceptance criteria" are implicitly demonstrating that the performance of the PRIMUS 200 is comparable to the predicate device, with mean differences and limits of agreement falling within acceptable clinical ranges, and showing good repeatability and reproducibility. The study essentially aims to prove that the PRIMUS 200 performs as well as the predicate for the specified measurements.

Here's a breakdown of the requested information based on the provided document:

A table of acceptance criteria and the reported device performance

The document does not explicitly state acceptance criteria in a formal, quantifiable way as you might find for an AI/ML device (e.g., "accuracy > X%" or "sensitivity > Y%"). Instead, the "acceptance criteria" are implied by demonstrating substantial equivalence to the predicate device. This is primarily assessed by comparing the mean differences and limits of agreement between the two devices for various ocular measurements. Good repeatability and reproducibility are also considered.

Since no specific numerical acceptance thresholds are given, the reported device performance is presented as the findings from the comparative effectiveness study:

Implied Acceptance Criteria & Reported Device Performance for PRIMUS 200 vs. CIRRUS 4000

Metric	Implied Acceptance Criterion (relative to predicate)	Reported Device Performance (Mean Differences, PRIMUS 200 - CIRRUS 4000)
Comparative Analysis	Mean differences and 95% Limits of Agreement should demonstrate substantial equivalence (i.e., differences are clinically acceptable and comparable to predicate).	Normal Eyes (N=45): * Macular Thickness: Mean differences range from -4.8 µm (Outer Inferior) to +0.1 µm (Central Subfield). * RNFL Thickness: Mean differences range from -2.8 µm (Inferior) to -1.2 µm (Temporal). * ONH Parameters: Mean differences range from -0.02 mm² (Rim Area, Disc Area) to +0.01 (Average Cup-to-Disc Ratio, Vertical Cup-to-Disc Ratio). Retinal Disease Eyes (N=39): * Macular Thickness: Mean differences range from -6.2 µm (Outer Inferior) to +1.8 µm (Central Subfield). Glaucomatous Eyes (N=43): * RNFL Thickness: Mean differences range from -3.0 µm (Nasal) to +1.2 µm (Temporal). * ONH Parameters: Mean differences range from 0.00 (Rim Area, Average Cup-to-Disc Ratio, Vertical Cup-to-Disc Ratio) to 0.02 mm² (Disc Area). The studies conclude that the mean values of the 19 thickness parameters were very similar between the two devices, demonstrating substantial equivalence.
Repeatability and Reproducibility	Measurements should show good repeatability and reproducibility.	Normal Eyes (N=44): * Repeatability SDs: Macular thickness parameters (0.90% to 1.76% COV), RNFL thickness parameters (2.12% to 5.01% COV), ONH parameters (1.844% to 6.702% COV). * Reproducibility SDs: Macular thickness parameters (1.67% to 2.26% COV), RNFL thickness parameters (2.76% to 5.72% COV), ONH parameters (2.397% to 7.660% COV). Diseased Eyes (N=38 for Macular, N=43 for RNFL/ONH): * Repeatability SDs: Macular thickness parameters (1.14% to 4.02% COV), RNFL thickness parameters (3.02% to 6.10% COV), ONH parameters (1.829% to 8.645% COV). * Reproducibility SDs: Macular thickness parameters (1.59% to 4.52% COV), RNFL thickness parameters (3.89% to 8.36% COV), ONH parameters (2.091% to 8.814% COV). The studies conclude that PRIMUS 200 showed good repeatability and reproducibility for both normal and diseased eyes.

Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Comparative Analysis:
  - Sample Size: 127 subjects (45 normal, 39 retinal disease, 43 glaucoma subjects).
  - Data Provenance: The study was a "prospective study." The country of origin of the data is not specified in the provided text.
- Repeatability and Reproducibility Study:
  - Sample Size: 125 subjects (44 normal, 38 retinal disease, 43 glaucoma subjects).
  - Data Provenance: Not explicitly stated as retrospective or prospective for this specific study, but it follows the comparative analysis which was prospective. Country of origin not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is not an AI/ML device where expert-labeled ground truth for images is typically established. This is a medical device designed for making objective measurements (thickness, area, ratios). The "ground truth" for the comparative analysis is the measurements obtained from the predicate device (Cirrus HD-OCT Model 4000), which is a legally marketed device. The study aims to show that the PRIMUS 200 produces measurements comparable to this established predicate. Experts are involved in operating the devices and potentially interpreting the results, but they are not establishing a subjective "ground truth" for each case in the same way as an image interpretation task.
Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This is not a study assessing diagnostic performance based on subjective interpretations or needing adjudication of disagreeing expert opinions. The study compares quantitative measurements obtained by two different devices.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No. This is not an AI/ML device that assists human readers. It is an imaging device that produces quantitative measurements. The study is a direct comparison of measurements between the proposed device and a predicate device.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, in the sense that the device itself performs the measurements. The "algorithm" here is the device's inherent measurement capability. The clinical evaluation directly compares the measurements generated by the PRIMUS 200 (device only with human operation) to those generated by the predicate device (also device only with human operation). It's a device-to-device comparison for quantitative outputs.
The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" is established by the measurements from the predicate device, the Carl Zeiss Meditec CIRRUS™ HD-OCT Model 4000 (K111157), which is an already cleared device for similar indications. The study's purpose is to demonstrate that the PRIMUS 200 produces measurements that are substantially equivalent to this established device.
The sample size for the training set

Not applicable. This device is not described as an AI/ML device that requires a training set in the conventional sense. Its functionality is based on established optical coherence tomography (OCT) technology and software for measurement rather than a machine learning model trained on a dataset.
How the ground truth for the training set was established

Not applicable, as there is no mention of a machine learning training set or associated ground truth.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 21, 2017

Carl Zeiss Suzhou Co., Ltd. % Dong Hua Sr. Regulatory Affairs Specialist Carl Zeiss Meditec, Inc. 5160 Hacienda Drive Dublin, CA 94568

Re: K163195

Trade/Device Name: PRIMUS Regulation Number: 21 CFR 886.1570 Regulation Name: Ophthalmoscope Regulatory Class: Class II Product Code: OBO Dated: Mav 8. 2017 Received: May 9, 2017

Dear Dong Hua:

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. 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.

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You must comply with all the Act's 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Kesia Alexander

for Malvina B. Eydelman, M.D. Director Division of Ophthalmic and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K163195

Device Name

PRIMUS

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary (Revised)

510(k) SUMMARY (per 21 CFR §807.92)

PRIMUS

GENERAL INFORMATION

Applicant:		Carl Zeiss Suzhou Co., Ltd.Modern Industrial Square 3bNo. 333 Xing Pu Road SipSuzhou, Jiangsu 215126 China+ 86-512-8227-3436 (phone)+ 86-512-6287-1366 (fax)Establishment Registration Number: 3008564898
Contact Person:		Dong HuaSr. Regulatory Affairs SpecialistCarl Zeiss Meditec, Inc.5160 Hacienda DriveDublin, CA 94568(925) 557-4204 Phone(925) 557-4259 FaxE-mail: dong.hua@zeiss.com
Date Prepared:		June 09, 2017
Common Name:		Tomography, Optical Coherence
Classification Name:		Ophthalmoscope
Product Code and Class:		OBO - Class II
Classification Number:		21 CFR 886.1570
Trade/Proprietary Name:		PRIMUS
Model:		200
PREDICATE DEVICE
Company:		Carl Zeiss Meditec, Inc.
Device:	Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, OpticNerve Head and Ganglion Cell Normative Databases (K111157)

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It is the opinion of Carl Zeiss Suzhou Company, Limited that the PRIMUS instrument is substantially equivalent to the predicate Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, Optic Nerve Head and Ganglion Cell Normative Databases Model 4000 (K111157) for the intended use for imaging and measurements of posterior ocular structures. The PRIMUS device is an ophthalmic diagnostic instrument that provides only the essential performance and functionality compared to Cirrus™ HD-OCT, e.g. with a separate manual-controlled patient interface and basic analysis features.

INDICATIONS FOR USE (21 CFR §807.92(a)(5))

The PRIMUS instrument is a non-contact, high resolution tomographic and biomicroscopic imaging device. It is indicated for in-vivo viewing of axial cross sections and measurement of posterior ocular structures, including retina, retinal nerve fiber layer, macula, and optic disc. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, macular holes, cystoid macular edema, diabetic retinopathy, age-related macular degeneration and glaucoma.

DEVICE DESCRIPTION SUMMARY (21 CFR §807.92(a)(4))

Device Overview

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nerve fiber layers).

Optical head modules
SD-OCT engine modules
Patient module
Support modules

Macular Thickness Analysis (MTA) Based on 512 X 32 Macular Cube Scan
Optic Nerve Head (ONH) & Retinal Nerve Fiber Layer (RNFL) Analysis Based on 128 X 128 ONH & RNFL Cube Scan
HD 5-line Analysis Based on 5 line HD Raster Scan
HD 1-line Analysis Based on 1 line HD Raster Scan

Description of Software

Software version 2.0 at Release 1 (R1) provides functions of patient management, image acquisition, visualization and analysis capabilities that are categorized into the following groups:

Patient Management and Administration
Acquisition
Analysis

CZSC has implemented a software development process according to IEC 62304. With software version 2.0 at Release 1 (R1), PRIMUS offers automatic retinal thickness measurement and quantitative analysis reports.

Risk Management and General Safety and Effectiveness

The device labeling contains instructions for use and any necessary cautions and warnings to provide for safe and effective use of the device.

Risk management is ensured via a risk analysis, which is used to identify potential hazards and mitigations. These potential hazards are controlled by software means, user instructions, verification of requirements and validation of the clinical workflow to ensure that the product meets its intended uses. To minimize electrical, mechanical and radiation hazards, ZEISS adheres to recognized and established industry practice and relevant international standards.

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Technological Characteristics and Substantial Equivalence (21 CFR §807.92(a)(6)):

It is the opinion of Carl Zeiss Meditec, Incorporated that the proposed device, the PRIMUS 200, is substantially equivalent to the CIRRUS HD-OCT with Software Version 6.0.

The indications for use for the PRIMUS 200 is similar to the indications for the predicate device CIRRUS HD-OCT with Software Version 6.0.

A technological comparison and clinical testing demonstrate that the PRIMUS 200 system is functionally equivalent to the primary predicate CIRRUS HD-OCT (K111157) and does not raise new questions regarding safety and effectiveness.

Summary of Verification and Validation Activity (21 CFR §807.92(b)):

Bench Testing (21 CFR §807.92(b)(1))

Bench testing in the form of Unit, Integration and System Integration testing was performed to evaluate the performance and functionality of the software version 2.0. The System level software verification and regression testing has been performed successfully to meet their previously determined acceptance criteria as stated in the Test Plans.

PRIMUS is designed and tested to applicable standards for electrical and optical safety with established specifications. Performance testing conducted on the PRIMUS instrument was consistent to the intended use claim. The verification testing demonstrates that the device performance complies with specifications and requirements. Results of verification and validation demonstrate safety and effectiveness as the predicate device, tests can be categorized into the following groups:

Device System Verification
Verification According to Harmonized/Recognized Standards
- . Electrical Safety and Electromagnetic Compatibility
- Environmental Simulation .
- . Usability
- Biocompatibility
Software Verification and Validation
Product Validation

Testing to Consensus Standards (21 CFR §807.92(b)(1))

The PRIMUS 200 system has been tested (as needed) to meet the requirements for conformity (where applicable) to multiple industry standards. The R&D evaluation of the relevant testing to consensus standards is documented.

Substantial Equivalence to Predicates (21 CFR §807.92(b)(1))

Verification testing to the system requirements (SRS) for the PRIMUS 200 system and the validation of the intended use is intended to support the claim of substantial equivalence to the following Substantial Equivalence table:

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Device	PRIMUS(Proposed Device K163195)	Cirrus HD-OCT with Retinal Nerve Fiber Layer(RNFL), Macular, Optic Nerve Head andGanglion Cell Normative Database (K111157)[Model: 4000]
		The CirrusTM HD-OCT with Retinal Nerve Fiber
Intended Use	The PRIMUS is used for in-vivoviewing of axial cross-sectionalimaging and measurement ofposterior ocular structures.	Layer (RNFL), Macular, Optic Nerve Head andGanglion Cell Normative Databases is indicatedfor in-vivo viewing, axial cross-sectional, andthree-dimensional imaging and measurementof anterior and posterior ocular structures.
Indication for Use	The PRIMUS instrument is a non-contact, high resolutiontomographic and biomicroscopicimaging device. It is indicated forin-vivo viewing of axial crosssections and measurement ofposterior ocular structures,including retina, retinal nervefiber layer, macula, and opticdisc. It is intended for use as adiagnostic device to aid in thedetection and management ofocular diseases including, but notlimited to, macular holes, cystoidmacular edema, diabeticretinopathy, age-related maculardegeneration and glaucoma	The CirrusTM HD-OCT is a non-contact, highresolution tomographic and biomicroscopicimaging device. It is indicated for in-vivoviewing, axial cross-sectional, and three-dimensional imaging and measurement ofanterior and posterior ocular structures,including cornea, retina, retinal nerve fiberlayer, ganglion cell plus inner plexiform layer,macula, and optic nerve head. The Cirrusnormative databases are quantitative tools forthe comparison of retinal nerve fiber layerthickness, macular thickness, ganglion cell plusinner plexiform layer thickness, and opticnerve head measurements to a database ofnormal subjects. The Cirrus HD-OCT isintended for use as a diagnostic device to aidin the detection and management of oculardiseases including, but not limited to, macularholes, cystoid macular edema, diabeticretinopathy, age-related maculardegeneration, and glaucoma
Device Classification	Optical Coherence Tomography	Optical Coherence Tomography (OCT)
NameGeneric Common Name	(OCT)Optical Coherence Tomography(OCT)	Optical Coherence Tomography (OCT)
Classification ProductCode	OBO	OBO
Class	II	II
Technology	Spectral Domain OCT (SD-OCT)	Spectral Domain OCT (SD-OCT)
OCT Imaging
Methodology	Spectral Domain OCT (SD-OCT)	Spectral Domain OCT (SD-OCT)
Optical Source	Super Luminescent Diode, 840nm	Super Luminescent Diode, 840nm
Optical Power	≤ 725 µW at the cornea	< 725 µW at the cornea
Scan Speed	12,000 (±10%) A-scans per second	27,000 A-scans per second
A-Scan Depth	2.0 mm (in tissue), 1,024 points	2.0 mm (in tissue), 1,024 points
Axial Resolution	5 µm ±1 (in tissue)	5 µm (in tissue)
Transverse Resolution	< 20µm (in tissue, FWHM*)	15 µm (in tissue)

Device	PRIMUS(Proposed Device K163195)	Cirrus HD-OCT with Retinal Nerve Fiber Layer(RNFL), Macular, Optic Nerve Head andGanglion Cell Normative Database (K111157)[Model: 4000]
Scan Pixels	1024 axial x (128-1024) transverse	1024 axial × (200-4096) transverse
Acquisition Time	Up to 2.5 seconds (depending on #of pixels scanned)	Up to 2.9 sec (depending on # of pixelsscanned)
Scan Patterns	5-line raster scan, 1-line HD scan,Macular Cube scan (512x32),ONH/RNFL cube scan (128x128)	Line, circle, cross-hair, raster (a series ofclosely spaced lines), radial scans andcombinations of the above. Includes MacularCube Scan (512x128); ONH/RNFL Cube Scan(200x200); HD 5-line raster; HD Single line scan
Fundus Imaging
Methodology	Confocal Scanning "Laser"Ophthalmoscope (cSLO)	Line Scanning Ophthalmoscope
Optical Source	Super Luminescent Diode (SLD),840nm	Super Luminescent Diode (SLD), 750 nm
Optical Power	≤ 725µW at the cornea	< 1.5 mW at the cornea
Field of View	29 × 21 degrees (W × H)	36 × 30 degrees (W × H)
Frame Rate	Alignment: ≥ 4.0 Hz	> 20 Hz
Transverse Resolution	Alignment : ≤ 80µm (in Tissue)	25 µm (in tissue)
Fixation
Internal Fixation Source	Consistently displayed 525 nm Greencolored LED	LCD (green pixels)
Internal Fixation FocusAdjustment	-23D to +17D (diopters) Focus ofInternal Fixation will changeaccording to different refractiveerror adjustment	-20D to +20D (diopters)
External Fixation Source	Mechanically adjustable arm withblinking LED at the tip	Mechanically adjustable arm with blinkingLED at the tip

Table 1: Substantial Equivalence Table

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Table 1: Substantial Equivalence Table

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CLINICAL EVALUATION

Clinical evaluation performed on the PRIMUS supports the indications for use statement and demonstrates that the device is substantially equivalent to the predicate device and does not raise new questions regarding safety and effectiveness.

A prospective study was conducted to support the indication for use statement for the PRIMUS with software version 2.0 at Release 1 (R1) and to determine comparability of the measurements obtained from both the PRIMUS 200 and the Cirrus HD-OCT Model 4000 instruments. Clinical data was collected and analyzed to determine the repeatability and reproducibility of the measurements of the PRIMUS 200. The study enrolled normal eyes, eyes with retinal disease and glaucoma.

Comparative analysis for the PRIMUS 200 and CIRRUS Model 4000

A study was performed on total 127 subjects, which included 45 normal subjects, 39 retinal disease subjects and 43 glaucoma subjects were analyzed in the study to evaluate equivalence of the means of 19 measurement parameters: retinal nerve fiber layer (RNFL) thickness (5 parameters), optic nerve head (ONH) (5 parameters), and macular thickness (9 parameters) between the PRIMUS 200 and Cirrus HD-OCT Model 4000.

Two study devices, PRIMUS 200 & Cirrus HD-OCT Model 4000 and each measurement parameter, the mean of the available measurements was calculated for each study eye. The difference in each of the 19 measurement parameters between the PRIMUS 200 and Cirrus HD-OCT Model 4000 was calculated for each study eye. The mean difference, the corresponding 95% confidence intervals, and 95% limits of agreement were calculated for each measurement parameter. The comparative analyses utilized on one PRIMUS 200 device, and the results are presented in Tables 2, 3 and 4 for the normal, retinal disease and glaucoma disease eye studies, respectively. Additionally 95% Cls for the lower and upper limits of agreement are provided in Table 2a (normal eyes), Table 3a (retinal disease eyes) and Table 4a (glaucomatous eyes).

The mean values of the 19 thickness parameters were very similar between the two devices. The results of the study parameters demonstrate substantial equivalence between the PRIMUS 200 and Cirrus HD-OCT Model 4000.

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Table 2: Mean difference in macular thickness, RNFL thickness and ONH measurements between PRIMUS 200 and CIRRUS 4000 (Normal eyes)

	Primus 200Mean (SD)	Cirrus 4000Mean (SD)	DifferenceMean (SD)	95%ConfidenceInterval ofMeanDifference	95% Limits ofAgreement forDifferencesBetweenSubject Means
	Macular Thickness Parameters (N=45)
Central Subfield (µm)	236.1 (19.87)	236.0 (20.77)	0.1 (5.36)	(-1.5, 1.7)	(-10.4, 10.6)
Inner Nasal (µm)	315.1 (17.16)	316.2 (18.14)	-1.1 (6.74)	(-3.1, 0.9)	(-14.3, 12.1)
Inner Superior (µm)	311.9 (16.11)	315.6 (16.47)	-3.8 (6.30)	(-5.6, -2.0)	(-16.1, 8.5)
Inner Temporal (µm)	299.4 (16.59)	301.5 (16.49)	-2.1 (6.25)	(-3.9, -0.3)	(-14.3, 10.2)
Inner Inferior (μm)	309.6 (16.80)	312.4 (16.96)	-2.8 (6.44)	(-4.7, -0.9)	(-15.4, 9.8)
Outer Nasal (μm)	291.0 (13.47)	293.9 (14.08)	-3.0 (4.96)	(-4.4, -1.6)	(-12.7, 6.7)
Outer Superior (µm)	273.5 (11.67)	274.1 (10.37)	-0.6 (6.71)	(-2.6, 1.4)	(-13.8, 12.6)
Outer Temporal (µm)	252.7 (12.81)	255.6 (12.02)	-2.9 (5.11)	(-4.4, -1.4)	(-12.9, 7.1)
Outer Inferior (µm)	258.0 (12.18)	262.8 (13.37)	-4.8 (3.78)	(-5.9, -3.7)	(-12.2, 2.6)
RNFL Thickness Parameters (N=45)
Average RNFLThickness (µm)	90.6 (10.03)	92.8 (10.00)	-2.3 (4.05)	(-3.5, -1.1)	(-10.2, 5.6)
Temporal (µm)	58.4 (6.11)	59.7 (8.65)	-1.2 (5.49)	(-2.8, 0.4)	(-12.0, 9.6)
Superior (µm)	115.5 (16.88)	118.0 (16.64)	-2.5 (7.41)	(-4.7, -0.3)	(-17.0, 12.0)
Nasal (µm)	71.7 (9.86)	74.2 (10.93)	-2.5 (5.06)	(-4.0, -1.0)	(-12.4, 7.4)
Inferior (µm)	116.6 (17.20)	119.5 (16.31)	-2.8 (7.14)	(-4.9, -0.7)	(-16.8, 11.2)
ONH Parameters (N=45)
Rim Area (mm²)	1.29 (0.194)	1.31 (0.184)	-0.02 (0.057)	(-0.04, 0.00)	(-0.13, 0.09)
Disc Area (mm²)	1.94 (0.337)	1.96 (0.341)	-0.02 (0.089)	(-0.05, 0.01)	(-0.19, 0.15)
Average Cup-to-DiscRatio	0.54 (0.143)	0.53 (0.148)	0.01 (0.026)	(0.00, 0.02)	(-0.04, 0.06)
Vertical Cup-to-DiscRatio	0.52 (0.138)	0.51 (0.145)	0.01 (0.031)	(0.00, 0.02)	(-0.05, 0.07)
Cup Volume (mm³)	0.21 (0.149)	0.20 (0.148)	0.00 (0.018)	(-0.01, 0.01)	(-0.04, 0.04)

95% Confidence Interval of Mean Difference = mean ± 1.96 x SE.

95% Limits of Agreement = mean ± 1.96 x SD.

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Table 2a: 95% Limits of Agreement for Difference between PRIMUS 200 and CIRRUS 4000 Means, 95% Cls for the Limits of Agreement (Normal eyes)

	95% Limits ofAgreement forDifferences BetweenSubject Means	95% ConfidenceInterval for LowerLimit of Agreement	95% ConfidenceInterval for UpperLimit of Agreement
Macular Thickness Parameters (N = 45)
Central Subfield (µm)	(-10.4, 10.6)	(-13.1, -7.7)	(7.9, 13.3)
Inner Nasal (μm)	(-14.3, 12.1)	(-17.7, -10.9)	(8.7, 15.5)
Inner Superior (µm)	(-16.1, 8.5)	(-19.3, -12.9)	(5.3, 11.7)
Inner Temporal (µm)	(-14.3, 10.2)	(-17.5, -11.1)	(7.0, 13.4)
Inner Inferior (µm)	(-15.4, 9.8)	(-18.7, -12.1)	(6.5, 13.1)
Outer Nasal (μm)	(-12.7, 6.7)	(-15.2, -10.2)	(4.2, 9.2)
Outer Superior (µm)	(-13.8, 12.6)	(-17.2, -10.4)	(9.2, 16.0)
Outer Temporal (µm)	(-12.9, 7.1)	(-15.5, -10.3)	(4.5, 9.7)
Outer Inferior (μm)	(-12.2, 2.6)	(-14.1, -10.3)	(0.7, 4.5)
RNFL Parameter (N = 45)
Average RNFL Thickness (μm)	(-10.2, 5.6)	(-12.2, -8.2)	(3.6, 7.6)
Temporal (µm)	(-12.0, 9.6)	(-14.8, -9.2)	(6.8, 12.4)
Superior (µm)	(-17.0, 12.0)	(-20.7, -13.3)	(8.3, 15.7)
Nasal (µm)	(-12.4, 7.4)	(-15.0, -9.8)	(4.8, 10.0)
Inferior (µm)	(-16.8, 11.2)	(-20.4, -13.2)	(7.6, 14.8)
ONH Parameters (N = 45)
Rim Area (mm²)	(-0.13, 0.09)	(-0.16, -0.10)	(0.06, 0.12)
Disc Area (mm²)	(-0.19, 0.15)	(-0.24, -0.14)	(0.10, 0.20)
Average Cup-to-Disc Ratio	(-0.04, 0.06)	(-0.05, -0.03)	(0.05, 0.07)
Vertical Cup-to-Disc Ratio	(-0.05, 0.07)	(-0.07, -0.03)	(0.05, 0.09)
Cup Volume (mm³)	(-0.04, 0.04)	(-0.05, -0.03)	(0.03, 0.05)

95% Limits of Agreement = mean ± 1.96 x SD.

95% Confidence Interval of (Lower/Upper) Limit of Agreement = (Lower/Upper) Limit ± 1.96 x V3*SE.

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	Primus 200Mean (SD)	Cirrus 4000Mean (SD)	DifferenceMean (SD)	95%ConfidenceInterval ofMeanDifference	95% Limits ofAgreement forDifferencesBetween SubjectMeans
Macular Thickness Parameters (N=39)
Central Subfield (µm)	308.8 (113.31)	307.0 (114.32)	1.8 (22.06)	(-5.1, 8.7)	(-41.4, 45.0)
Inner Nasal (µm)	353.2 (71.61)	354.2 (67.90)	-0.9 (12.28)	(-4.8, 3.0)	(-25.0, 23.2)
Inner Superior (µm)	349.8 (71.23)	352.0 (70.01)	-2.2 (16.04)	(-7.2, 2.8)	(-33.6, 29.2)
Inner Temporal (µm)	346.5 (85.67)	348.8 (87.22)	-2.3 (15.13)	(-7.0, 2.4)	(-32.0, 27.4)
Inner Inferior (µm)	353.2 (81.13)	356.3 (82.62)	-3.1 (14.72)	(-7.7, 1.5)	(-32.0, 25.8)
Outer Nasal (µm)	322.6 (53.88)	324.5 (54.96)	-1.9 (7.22)	(-4.2, 0.4)	(-16.1, 12.3)
Outer Superior (µm)	311.6 (70.11)	309.9 (72.34)	1.7 (10.69)	(-1.7, 5.1)	(-19.3, 22.7)
Outer Temporal (µm)	289.3 (67.34)	291.9 (65.99)	-2.6 (11.64)	(-6.3, 1.1)	(-25.4, 20.2)
Outer Inferior (µm)	296.0 (70.34)	302.2 (70.65)	-6.2 (9.34)	(-9.1, -3.3)	(-24.5, 12.1)

Table 3: Mean difference in macular thickness measurements between PRIMUS 200 and CIRRUS 4000 (Retinal disease eyes)

95% Confidence Interval of Mean Difference = mean ± 1.96 x SE. 95% Limits of Agreement = mean ± 1.96 x SD.

Table 3a: 95% Limits of Agreement for Difference between PRIMUS 200 and CIRRUS 4000 Means of Macular Thickness Measurements, 95% Cls for the Limits of Agreement (Retinal disease eyes)

	95% Limits ofAgreement forDifferencesBetween SubjectMeans	95% ConfidenceInterval for LowerLimit ofAgreement	95% ConfidenceInterval for UpperLimit of Agreement
Macular Thickness Parameters (N = 39)
Central Subfield (µm)	(-41.4, 45.0)	(-53.4, -29.4)	(33.0, 57.0)
Inner Nasal (µm)	(-25.0, 23.2)	(-31.7, -18.3)	(16.5, 29.9)
Inner Superior (µm)	(-33.6, 29.2)	(-42.3, -24.9)	(20.5, 37.9)
Inner Temporal (µm)	(-32.0, 27.4)	(-40.2, -23.8)	(19.2, 35.6)
Inner Inferior (µm)	(-32.0, 25.8)	(-40.0, -24.0)	(17.8, 33.8)
Outer Nasal (µm)	(-16.1, 12.3)	(-20.0, -12.2)	(8.4, 16.2)
Outer Superior (µm)	(-19.3, 22.7)	(-25.1, -13.5)	(16.9, 28.5)
Outer Temporal (µm)	(-25.4, 20.2)	(-31.7, -19.1)	(13.9, 26.5)
Outer Inferior (µm)	(-24.5, 12.1)	(-29.6, -19.4)	(7.0, 17.2)

95% Limits of Agreement = mean ± 1.96 x SD.

95% Confidence Interval of (Lower/Upper) Limit of Agreement = (Lower/Upper) Limit ± 1.96 x V3*SE.

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Table 4: Mean difference in RNFL thickness and ONH measurements between PRIMUS 200 and CIRRUS 4000 (Glaucomatous eyes)

	Primus 200Mean (SD)	Cirrus 4000Mean (SD)	DifferenceMean (SD)	95%ConfidenceInterval ofMeanDifference	95% Limits ofAgreement forDifferencesBetween SubjectMeans
	RNFL Parameters (N=43)
Average RNFL Thickness (µm)	71.0 (15.00)	72.3 (15.78)	-1.4 (3.34)	(-2.4, -0.4)	(-7.9, 5.1)
Temporal (µm)	55.5 (11.51)	54.3 (9.72)	1.2 (7.62)	(-1.1, 3.5)	(-13.7, 16.1)
Superior (μm)	85.2 (25.96)	87.4 (25.51)	-2.1 (6.50)	(-4.0, -0.2)	(-14.8, 10.6)
Nasal (µm)	61.8 (9.16)	64.8 (12.94)	-3.0 (6.44)	(-4.9, -1.1)	(-15.6, 9.6)
Inferior (µm)	81.6 (26.11)	82.8 (26.17)	-1.2 (5.80)	(-2.9, 0.53)	(-12.6, 10.2)
ONH Parameters (N=43)
Rim Area (mm²)	0.83 (0.301)	0.82 (0.300)	0.00 (0.074)	(-0.02, 0.02)	(-0.15, 0.15)
Disc Area (mm²)	2.07 (0.367)	2.05 (0.345)	0.02 (0.110)	(-0.01, 0.05)	(-0.20, 0.24)
Average Cup-to-Disc Ratio	0.77 (0.106)	0.76 (0.107)	0.00 (0.022)	(-0.01, 0.01)	(-0.04, 0.04)
Vertical Cup-to-Disc Ratio	0.76 (0.097)	0.75 (0.103)	0.00 (0.037)	(-0.01, 0.01)	(-0.07, 0.07)
Cup Volume (mm³)	0.60 (0.333)	0.59 (0.335)	0.01 (0.044)	(0.00, 0.02)	(-0.08, 0.10)

95% Confidence Interval of Mean Difference = mean ± 1.96 x SE.

95% Limits of Agreement = mean ± 1.96 x SD.

Table 4a: 95% Limits of Agreement for Difference between PRIMUS 200 and CIRRUS 4000 Means of RNFL thickness and ONH Measurements, 95% Cls for the Limits of Agreement (Glaucomatous eyes)

	95% Limits ofAgreement forDifferences BetweenSubject Means	95% ConfidenceInterval for LowerLimit of Agreement	95% ConfidenceInterval for UpperLimit of Agreement
RNFL Parameter ( N = 43)
Average RNFL Thickness (µm)	(-7.9, 5.1)	(-9.6, -6.2)	(3.4, 6.8)
Temporal (µm)	(-13.7, 16.1)	(-17.6, -9.8)	(12.2, 20.0)
Superior (µm)	(-14.8, 10.6)	(-18.2, -11.4)	(7.2, 14.0)
Nasal (µm)	(-15.6, 9.6)	(-18.9, -12.3)	(6.3, 12.9)
Inferior (µm)	(-12.6, 10.2)	(-15.6, -9.6)	(7.2, 13.2)
ONH Parameters (N = 43)
Rim Area (mm²)	(-0.15, 0.15)	(-0.19, -0.11)	(0.11, 0.19)
Disc Area (mm²)	(-0.20, 0.24)	(-0.26, -0.14)	(0.18, 0.30)
Average Cup-to-Disc Ratio	(-0.04, 0.04)	(-0.05, -0.03)	(0.03, 0.05)
Vertical Cup-to-Disc Ratio	(-0.07, 0.07)	(-0.09, -0.05)	(0.05, 0.09)
Cup Volume (mm³)	(-0.08, 0.10)	(-0.10, -0.06)	(0.08, 0.12)

95% Limits of Agreement = mean ± 1.96 x SD.

95% Confidence Interval of (Lower/Upper) Limit of Agreement = (Lower/Upper) Limit ± 1.96 x √ 3 *SE.

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Repeatability and Reproducibility Study on the PRIMUS 200

A study was performed to determine the repeatability and reproducibility of the measurements of the PRIMUS 200 by analyzing 125 subjects, which included 44 normal subjects, 38 retinal disease subjects and 43 glaucoma subjects.

Analysis of variance (ANOVA) with the mixed-effects model was used for the inter-device/operator variability, repeatability SD, the repeatability % COV, and interaction between subject and device/operator variability of each measurement parameter. Since each operator was assigned to a single PRIMUS 200 device, the inter-operator and inter-device variability were not estimated separately. The repeatability and reproducibility standard deviation (SD) and limits for the PRIMUS 200 are shown in Tables 4 and 5. PRIMUS 200 showed good repeatability and reproducibility for both normal and diseased eyes.

	PRIMUS 200
Parameter	Repeatability			Reproducibility
	SD	Limit	COV %	SD	Limit	COV %
Macular Thickness Parameters (N = 44)
Central Subfield ( $μm$ )	3.02	8.46	1.29	4.63	12.96	1.97
Inner Nasal ( $μm$ )	2.81	7.87	0.90	5.52	15.46	1.77
Inner Superior ( $μm$ )	3.30	9.24	1.07	5.53	15.48	1.79
Inner Temporal ( $μm$ )	2.79	7.81	0.94	5.21	14.59	1.75
Inner Inferior ( $μm$ )	3.01	8.43	0.98	5.14	14.39	1.67
Outer Nasal ( $μm$ )	2.73	7.64	0.94	4.75	13.30	1.64
Outer Superior ( $μm$ )	4.82	13.50	1.76	6.18	17.30	2.26
Outer Temporal ( $μm$ )	3.03	8.48	1.20	4.98	13.94	1.97
Outer Inferior ( $μm$ )	3.20	8.96	1.25	4.63	12.95	1.80
RNFL Thickness Parameters (N = 44)
Avg. RNFL Thickness ( $μm$ )	1.93	5.40	2.12	2.51	7.03	2.76
Temporal ( $μm$ )	2.96	8.29	5.01	3.38	9.46	5.72
Superior ( $μm$ )	3.64	10.19	3.14	5.15	14.42	4.44
Nasal ( $μm$ )	3.35	9.38	4.57	3.91	10.95	5.33
Inferior ( $μm$ )	3.79	10.61	3.29	5.38	15.06	4.66
ONH Parameters (N = 44)
Rim Area ( $mm²$ )	0.037	0.104	2.839	0.048	0.134	3.683
Disc Area ( $mm²$ )	0.058	0.162	2.957	0.072	0.202	3.671
Average CD Ratio	0.010	0.028	1.844	0.013	0.036	2.397
Vertical Cup-to-Disc Ratio	0.017	0.048	3.308	0.019	0.053	3.698
Cup Volume ( $mm³$ )	0.014	0.039	6.702	0.016	0.045	7.660

Table 5: PRIMUS 200 repeatability and reproducibility in measuring macular thickness and ONH parameters (Normal eyes)

Per ISO 5725-1 and ISO 5725-6, Repeatability Limit = 2.8 × Repeatability SD.

Reproducibility SD is the standard deviation under reproducibility conditions. It was estimated by the square root of the sum of repeatability variance and the variance components of operator, operatorsubjects, device and devicesubjects.

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Reproducibility Limit is the upper 95 % limit for the difference between repeated results under reproducibility conditions.

Reproducibility Limit = 2.8 ×reproducibility SD.

COV = Coefficient of Variation = SD 🇿🇿ean. 🇿🇿00. SD is either Repeatability SD or Reproducibility SD.

Table 6: PRIMUS 200 repeatability and reproducibility in measuring macular thickness and ONH parameters (Diseased eyes)

	PRIMUS 200
Parameter	Repeatability			Reproducibility
	SD	Limit	COV %	SD	Limit	COV %
	Macular Thickness Parameters (N = 38)
Central Subfield (µm)	12.31	34.47	4.02	13.84	38.75	4.52
Inner Nasal (µm)	5.37	15.04	1.54	6.46	18.09	1.85
Inner Superior (µm)	7.05	19.74	2.04	8.42	23.58	2.43
Inner Temporal (µm)	7.22	20.22	2.10	9.40	26.32	2.73
Inner Inferior (μm)	4.48	12.54	1.28	6.88	19.26	1.96
Outer Nasal (μm)	3.66	10.25	1.14	5.10	14.28	1.59
Outer Superior (µm)	4.16	11.65	1.34	5.08	14.22	1.64
Outer Temporal (µm)	4.73	13.24	1.63	7.69	21.53	2.65
Outer Inferior (µm)	4.35	12.18	1.47	5.17	14.48	1.75
	RNFL Thickness Parameters (N = 43)
Avg. RNFL Thickness (μm)	2.12	5.94	3.02	2.73	7.64	3.89
Temporal (µm)	3.34	9.35	6.10	4.58	12.82	8.36
Superior (μm)	4.67	13.08	5.56	5.74	16.07	6.83
Nasal (μm)	3.47	9.72	5.57	4.19	11.73	6.72
Inferior (µm)	4.47	12.52	5.60	5.39	15.09	6.75
ONH Parameters (N = 43)
Rim Area (mm²)	0.050	0.140	6.028	0.055	0.154	6.631
Disc Area (mm²)	0.098	0.274	4.733	0.105	0.294	5.072
Average CD Ratio	0.014	0.039	1.829	0.016	0.045	2.091
Vertical Cup-to-DiscRatio	0.024	0.067	3.173	0.025	0.070	3.305
Cup Volume (mm³)	0.051	0.143	8.645	0.052	0.146	8.814

Per ISO 5725-1 and ISO 5725-6, Repeatability Limit = 2.8 × Repeatability SD. Reproducibility SD is the standard deviation under reproducibility conditions. It was estimated by the square root of the sum of repeatability variance and the variance components of operator, operatorsubjects, device and devicesubjects. Reproducibility Limit is the upper 95 % limit for the difference between repeated results under reproducibility conditions.

Reproducibility Limit = 2.8 × Reproducibility SD.

COV = Coefficient of Variation = SD ÷ Mean. × 100. SD is either Repeatability SD or Reproducibility SD.

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510(k) Summary (21 CFR §807.92(c))

As described in this 510(k) Summary, all testing deemed necessary was conducted on the PRIMUS 200 with Software Version 2.0 to ensure that the device is safe and effective for its intended use when used in accordance with its Instructions for Use and substantially equivalent to, and performs as well as, the predicate device

Regulation Number and Section

§ 886.1570 Ophthalmoscope.

(a)
Identification. An ophthalmoscope is an AC-powered or battery-powered device containing illumination and viewing optics intended to examine the media (cornea, aqueous, lens, and vitreous) and the retina of the eye.(b)
Classification. Class II (special controls). The device, when it is an AC-powered opthalmoscope, a battery-powered opthalmoscope, or a hand-held ophthalmoscope replacement battery, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.