K Number
K173980
Device Name
Specular Microscope CEM-530
Manufacturer
Date Cleared
2018-03-14

(75 days)

Product Code
Regulation Number
886.1850
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.
Device Description
The NIDEK Specular Microscope CEM-530 which is the subject of this 510(k) is a modification to the NIDEK Specular Microscope CEM-530 cleared in K151706. The only change to the cleared device is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. The NIDEK Specular Microscope CEM-530 provides non-contact. high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the corneal endothelial cell density(CD), the coefficient of variation of corneal endothelial cell area (CV), % hexagonality of cells (%HEX), is analyzed through the captured images. The captured images and analysis results of the endothelium are used to assist in intraocular or corneal surgery, postoperative follow-up, and corneal observation such as for endothelial disorders or the corneal state of patients who wear extended-wear contact lenses. Observation is possible in the central area (visual angle: 5°) and peripheral area (visual angle: 27°) using a periphery capture function as well as in the Center of the cornea. The captured images and analysis results can be printed on the built-in printer or optional video printer, or output to an external device over LAN connection. In addition to the specular microscopy, the corneal thickness can be optically measured in a non-contact method. The CEM-530 has auto-tracking and auto-shooting functions. Results can be printed using the the built-in thermal printer or captured images can be transferred to a filing system via LAN connection.
More Information

No
The summary mentions "automated analysis method" and "auto-cell count algorithm" but does not use terms like AI, ML, or deep learning, nor does it describe characteristics typically associated with AI/ML development like training sets or complex model architectures. The focus is on improving an existing automated method.

No
The device is described as an ophthalmic microscope and camera for examination and measurement of the cornea, intended to assist in surgery, follow-up, and observation of disorders, rather than to treat a condition.

Yes

Explanation: The device is intended for the "examination of the corneal endothelium and for measurement of the thickness of the cornea," and it provides "information such as the corneal endothelial cell density(CD), the coefficient of variation of corneal endothelial cell area (CV), % hexagonality of cells (%HEX), is analyzed through the captured images." This information is used to "assist in intraocular or corneal surgery, postoperative follow-up, and corneal observation such as for endothelial disorders or the corneal state of patients who wear extended-wear contact lenses," which are all diagnostic applications.

No

The device description explicitly states it is a "non-contact ophthalmic microscope, optical pachymeter, and camera," which are hardware components. While the submission focuses on a software modification, the device itself is a physical instrument.

Based on the provided information, the NIDEK Specular Microscope CEM-530 is not an In Vitro Diagnostic (IVD).

Here's why:

  • Intended Use: The intended use clearly states it's for "examination of the corneal endothelium and for measurement of the thickness of the cornea." This is a direct examination of a living tissue within the body, not the analysis of samples taken from the body.
  • Device Description: The description details a non-contact ophthalmic microscope and optical pachymeter. It captures images of the corneal endothelium and measures corneal thickness. These are in-vivo measurements and imaging.
  • Lack of mention of samples: There is no mention of analyzing blood, urine, tissue samples, or any other biological material taken from the patient. The device interacts directly with the patient's eye.
  • Focus on imaging and measurement: The core functions are image capture and measurement of a physical characteristic (thickness) and cellular characteristics (density, variation, hexagonality) in situ.

IVDs are defined as devices intended for use in the examination of specimens derived from the human body to provide information for diagnostic purposes. This device does not fit that definition. It is an ophthalmic diagnostic device used for in-vivo examination.

N/A

Intended Use / Indications for Use

The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.

Product codes

NOE

Device Description

The NIDEK Specular Microscope CEM-530 which is the subject of this 510(k) is a modification to the NIDEK Specular Microscope CEM-530 cleared in K151706. The only change to the cleared device is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. The NIDEK Specular Microscope CEM-530 provides non-contact. high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the corneal endothelial cell density(CD), the coefficient of variation of corneal endothelial cell area (CV), % hexagonality of cells (%HEX), is analyzed through the captured images. The captured images and analysis results of the endothelium are used to assist in intraocular or corneal surgery, postoperative follow-up, and corneal observation such as for endothelial disorders or the corneal state of patients who wear extended-wear contact lenses. Observation is possible in the central area (visual angle: 5°) and peripheral area (visual angle: 27°) using a periphery capture function as well as in the Center of the cornea. The captured images and analysis results can be printed on the built-in printer or optional video printer, or output to an external device over LAN connection. In addition to the specular microscopy, the corneal thickness can be optically measured in a non-contact method. The CEM-530 has auto-tracking and auto-shooting functions. Results can be printed using the the built-in thermal printer or captured images can be transferred to a filing system via LAN connection.

Mentions image processing

Yes

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Optical

Anatomical Site

Cornea/corneal endothelium

Indicated Patient Age Range

The study included subjects aged 18-80 years.

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

The data provided is from a prospective clinical study conducted at one clinical site located in the United States. Endothelial image data captured on the CEM-530 (Ver1.09) in a previous study, CEM-530-US-0002, were imported for auto analysis based on a new auto-cell count algorithm. The study assessed the agreement and precision of the Specular Microscope CEM-530 by comparing results across three machines/operators to those obtained with the predicate device, the Cellchek Plus. Three populations were studied: young (18-28 years of age) and adult (29-80 years of age) healthy subjects and pathologic adult eyes (29-80 years of age).

There were 79 subjects enrolled in the study: 28 in the non-pathologic young eye population, 28 in the non-pathologic adult eye population, and 23 in the pathologic adult eye population. Of those, 74 are included in the effectiveness population (28, 27, and 19, respectively). The agreement population consisted of all 74 subjects (28, 27 and 19, respectively). The precision population included a subset of the effectiveness population, 45 total with 15, 15 and 15 respectively. The pathologic adult subjects consisted of 19 subjects with the following pathologies which qualified them for the subgroup: Guttata (16, 84.2%) and Long Term Fuch's Dystrophy (3, 15.8%).

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Study Type: Prospective clinical study (Agreement and Precision studies)
Sample Size:

  • Agreement study: 74 subjects (28 non-pathologic young, 27 non-pathologic adult, 19 pathologic adult)
  • Precision study: 45 subjects (15 non-pathologic young, 15 non-pathologic adult, 15 pathologic adult)
    Key Results:
    Agreement Study (CEM-530 Automated vs. Konan CellChek Plus):
  • All subjects (N=74):
    • CD: Mean Difference (SD) = 34.7 (157.38); 95% LOA = (-280.1, 349.4); Correlation (R) = 0.9296
    • CV: Mean Difference (SD) = -2.2 (4.03); 95% LOA = (-10.3, 5.9); Correlation (R) = 0.5817
    • % HEX: Mean Difference (SD) = 5.4 (8.52); 95% LOA = (-11.7, 22.4); Correlation (R) = 0.1185
  • Non-Pathologic Young Eyes (N=28):
    • CD: Mean Difference (SD) = -25.2 (122.03); 95% LOA = (-269.2, 218.9); Correlation (R) = 0.9131
    • CV: Mean Difference (SD) = -2.7 (3.21); 95% LOA = (-9.1, 3.7); Correlation (R) = 0.4837
    • % HEX: Mean Difference (SD) = 1.6 (5.14); 95% LOA = (-8.6, 11.9); Correlation (R) = 0.3681
  • Non-Pathologic Adult Eyes (N=27):
    • CD: Mean Difference (SD) = 44.3 (146.00); 95% LOA = (-247.7, 336.3); Correlation (R) = 0.9093
    • CV: Mean Difference (SD) = -2.4 (4.77); 95% LOA = (-12.0, 7.1); Correlation (R) = 0.4336
    • % HEX: Mean Difference (SD) = 9.8 (8.64); 95% LOA = (-7.5, 27.1); Correlation (R) = 0.1776
  • Pathologic Adult Eyes (N=19):
    • CD: Mean Difference (SD) = 109.2 (189.07); 95% LOA = (-269.0, 487.3); Correlation (R) = 0.8903
    • CV: Mean Difference (SD) = -1.2 (4.00); 95% LOA = (-9.2, 6.8); Correlation (R) = 0.5779
    • % HEX: Mean Difference (SD) = 4.7 (9.79); 95% LOA = (-14.9, 24.3); Correlation (R) = -0.1454

Precision Study (CEM-530 Automated vs. Konan CellChek Plus):

  • All Subjects (N=45 for CEM-530, N=61 for Konan):
    • CD: CEM-530 Repeatability SD = 74.2 (2.7% of Mean), Reproducibility SD = 83.7 (3.1% of Mean). Konan Repeatability SD = 62.6 (2.4% of Mean), Reproducibility SD = 95.5 (3.7% of Mean).
    • CV: CEM-530 Repeatability SD = 1.7 (6.2% of Mean), Reproducibility SD = 1.9 (6.8% of Mean). Konan Repeatability SD = 2.7 (8.4% of Mean), Reproducibility SD = 2.7 (8.5% of Mean).
    • % HEX: CEM-530 Repeatability SD = 3.7 (5.5% of Mean), Reproducibility SD = 3.7 (5.5% of Mean). Konan Repeatability SD = 5.3 (8.7% of Mean), Reproducibility SD = 5.4 (8.9% of Mean).

Additional Manual Comparison (CEM-530 Automated vs. CEM-530 Manual):

  • All subjects (N=74):
    • CD: Mean Difference (SD) = -11.0 (135.31); Correlation (R) = 0.9626
    • CV: Mean Difference (SD) = 5.4 (4.30); Correlation (R) = 0.4537
    • % HEX: Mean Difference (SD) = 8.2 (8.27); Correlation (R) = 0.1536
  • Precision Study (CEM-530 Automated vs. CEM-530 Manual):
    • All Subjects (N=45 for Automated, N=46 for Manual):
      • CD: Automated Repeatability SD = 74.2 (2.7% of Mean), Manual Repeatability SD = 49.1 (1.8% of Mean).
      • CV: Automated Repeatability SD = 1.7 (6.2% of Mean), Manual Repeatability SD = 1.5 (6.8% of Mean).
      • % HEX: Automated Repeatability SD = 3.7 (5.5% of Mean), Manual Repeatability SD = 3.5 (5.8% of Mean).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Agreement: Mean Difference, Mean Difference as a % of the CellChek reading, 95% LOA (Limits of Agreement), Correlation (R), Deming Regression Intercept (95% CI), Deming Regression Slope (95% CI).
Precision: Repeatability SD, Repeatability SD as a % of the Mean, Repeatability Limit, Repeatability Ratio, Reproducibility SD, Reproducibility SD as a % of the Mean, Reproducibility Limit, Reproducibility Ratio.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

NIDEK Specular Microscope CEM-530 (K151706), Konan Medical, Inc. Cellchek Plus (K120264)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

§ 886.1850 AC-powered slitlamp biomicroscope.

(a)
Identification. An AC-powered slitlamp biomicroscope is an AC-powered device that is a microscope intended for use in eye examination that projects into a patient's eye through a control diaphragm a thin, intense beam of light.(b)
Classification. Class II (special controls). The device, when it is intended only for the visual examination of the anterior segment of the eye, is classified as Group 1 per FDA-recognized consensus standard ANSI Z80.36, does not provide any quantitative output, and is not intended for screening or automated diagnostic indications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.

0

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the seal of the Department of Health & Human Services. To the right of that is the FDA logo, with the letters "FDA" in a blue square. Next to that is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

March 14, 2018

Nidek Co., Ltd. % Ryan Bouchard Official Correspondent Ora, Inc. 300 Brickstone Square Andover, MA 01810

Re: K173980

Trade/Device Name: Specular Microscope CEM-530 Regulation Number: 21 CFR 886.1850 Regulation Name: AC-Powered Slitlamp Biomicroscope Regulatory Class: Class II Product Code: NOE Dated: December 28, 2017 Received: December 29, 2017

Dear Ryan Bouchard:

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.

1

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 devicerelated 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.

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.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Denise L. Hampton -S

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) K173980

Device Name Specular Microscope CEM-530

Indications for Use (Describe)

The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.

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

This summary of the 510(k) premarket notification for the NIDEK Specular Microscope CEM-530 is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR8807.92.

Date Prepared: February 28, 2018

SPONSER/ 510(k) OWNER/ MANUFACTURER

NIDEK CO., LTD. 34-14 Maehama, Hiroishi-cho, Gamagori, Aichi, 443-0038 Japan Telephone: +81-533-67-8901 Facsimile: +81-533-67-6628 E mail: yoneji mizuno(@nidek.co.jp Establishment Registration Number: 8030392

CONTACT PERSON

Ryan Bouchard Ora, Inc. 300 Brickstone Square Andover, MA 01810 Telephone: (978) 332-9574 Facsimile: (978) 689-0020 E-mail: rbouchard@oraclinical.com

NAME OF DEVICE

Trade Name: Specular Microscope CEM-530 Common Name: Specular Microscope

DEVICE CLASSIFICATION/FDA REVIEWING BRANCH

The Ophthalmic Branch has classified AC Powered Slit Lamp Biomicroscopes as Class II devices pursuant to 21 C.F.R. §886.1850.

PRODUCT CODE: CLASSIFICATION / CFR TITLE NQE, 21 CFR 886.1850

PREDICATE DEVICES

NIDEK Specular Microscope CEM-530 (K151706) Konan Medical, Inc. Cellchek Plus (K120264)

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INDICATIONS FOR USE

The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.

PRODUCT DESCRIPTION

The NIDEK Specular Microscope CEM-530 which is the subject of this 510(k) is a modification to the NIDEK Specular Microscope CEM-530 cleared in K151706. The only change to the cleared device is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. The NIDEK Specular Microscope CEM-530 provides non-contact. high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the corneal endothelial cell density(CD), the coefficient of variation of corneal endothelial cell area (CV), % hexagonality of cells (%HEX), is analyzed through the captured images. The captured images and analysis results of the endothelium are used to assist in intraocular or corneal surgery, postoperative follow-up, and corneal observation such as for endothelial disorders or the corneal state of patients who wear extended-wear contact lenses. Observation is possible in the central area (visual angle: 5°) and peripheral area (visual angle: 27°) using a periphery capture function as well as in the Center of the cornea. The captured images and analysis results can be printed on the built-in printer or optional video printer, or output to an external device over LAN connection. In addition to the specular microscopy, the corneal thickness can be optically measured in a non-contact method. The CEM-530 has auto-tracking and auto-shooting functions. Results can be printed using the the built-in thermal printer or captured images can be transferred to a filing system via LAN connection.

SUBSTANTIAL EQUIVALENCE

The Specular Microscope CEM-530 and the predicate devices are all non-contact ophthalmic microscopes, optical pachymeters, and cameras intended for examination of the corneal endothelium and for measurement of the thickness of the cornea. Both the Specular Microscope CEM-530 and the predicate device offer automatic capture features and manual capture modes. The Specular Microscope CEM-530 which is the subject of this 510(k) has identical technological characteristics to the Specular Microscope CEM-530 which was cleared in K151706. The only difference is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. Therefore, this discussion will focus primarily on the substantial equivalence to the Konan Cellcheck Plus cleared in K120264.

Both the Specular Microscope CEM-530 and the Konan Cellchek Plus have a built-in CCD camera. Both the Specular Microscope CEM-530 and the Konan Cellchek Plus include an optical pachymeter with accuracy to ± 10 microns. There were no modifications to the

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optical pachymeter in the Specular Microscope CEM-530 compared with the device cleared in K151706.

Regarding image analysis, both the CEM-530 and the predicate device offer both automatic and manual image analysis. The software of the CEM-530, which is the subject of this 510(k), has been modified to improve the accuracy of the automatic analysis methodology. Clinical performance data is provided which evaluates the precision and agreement of the automated measurements performed by the CEM-530 compared to manual center method measurements performed with the Konan predicate device. The clinical performance data demonstrates the substantial equivalence of the CEM-530 automated mode to the Konan predicate device's manual mode.

Both the CEM-530 and the predicate device comply with applicable electrical safety and light safety standards.

Therefore, in regards to technological characteristics, the Specular Microscope CEM-530 is similar to the Konan but there are some minor differences between the devices.

SUBSTANTIAL EQUIVALENCE CHART
ManufacturerNIDEKKonan
Device NameCEM-530Cellchek Plus
510(k) NumberNAK120264
Product ClassificationClass II, NQEClass II, NQE
Indications for UseNon-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.Non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.
Device TypeNon-contact specular microscope and pachymeterNon-contact specular microscope and pachymeter
Capturing MethodAuto capture, auto alignment, auto focus (3D, 2D)/ManualAuto capture, auto alignment, auto focus(3D)/Manual
Capture Field0.25x 0.55 mm0.24 x 0.4 mm
Fixation Lamp (Central)1 point1 point
Fixation Lamp (Paracentral)8 points (5 degrees of visual angle for each point)4 points (direction of 12, 2, 10 and 6 o'clock)
Fixation Lamp (Periphery)6 points (27 degrees of visual angle for direction of 12, 2, 10, 6, 4 and 8 o'clock)

TABLE 1 SPECULAR MICROSCOPE CEM-530 SURSTANTIAL EQUIVALENCE CHART

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CameraBuilt-in CCD cameraBuilt-in CCD cameraBuilt-in CCD image sensing element camera
Flash
Illumination for
focusingCyan LED
InfraRed LEDCyan LED
InfraRed LEDKonan Xe tube
Konan halogen lamp
Pachymetry
TechnologyOpticalOpticalOptical
Measurement Range
Pachymetry300 to 1000 microns300 to 1000 micronsUnknown
Accuracy of
pachymetry$\pm$ 10 microns$\pm$ 10 microns$\pm$ 10 microns
Auto AnalysisYesYesYes
Manual AnalysisYesYesYes
Analysis Speed2 seconds2 secondsUnknown
Record (1 patient)Single mode: 1
endothelial image for
both right and left eyes
Paracentral and
Peripheral modes: 15
endothelial images for
both right and left eyesSingle mode: 1 endothelial
image for both right and left
eyes
Paracentral and Peripheral
modes: 15 endothelial
images for both right and left
eyes1 endothelial image for both
right and left eyes
Built-in PrinterThermal Line Printer
with auto cutterThermal Line Printer with
auto cutterNA
External InterfaceUSB-A: barcode, card
reader, LAN for data
output, Video output:
BNC terminalUSB-A: barcode, card
reader, LAN for data output,
Video output: BNC terminalVideo output: BNC terminal
Input port for mouse and
remote control
Connection to Filing
SystemConnectableConnectableConnectable
Monitor8.4" SVGA color LCD
with touch panel8.4" SVGA color LCD with
touch panel19" color LCD monitor
Input Power100 VA100 VA70 VA
Dimensions291 (W) x 495 (D) x
457 (H) mm291 (W) x 495 (D) x 457 (H)
mm334 (W) x 486 (D) x 420 (H)
mm
Weight20 Kg20 Kg20.5 Kg
Compliance with
Safety StandardsAAMI/ANSI ES
60601-1
IEC 60601-1-2
ISO 15004-1
ISO 15004-2IEC 60601-1
IEC 60601-1-2
ISO 15004-1
ISO 15004-2IEC 60601-1
IEC 60601-1-2
ISO 15004-1
ISO 15004-2

NON-CLINICAL PERFORMANCE SUMMARY

The performance testing conducted using the NIDEK Specular Microscope CEM-530 verified that the device operates as intended. The specifications to which the CEM-530 was verified to are substantially equivalent to the predicate devices and therefore, support a determination of substantial equivalence.

Additionally, the CEM-530 was subjected to electrical safety testing in accordance with AAMI/ANSI ES 60601-1, electromagnetic compatibility (EMC) testing in accordance with IEC 60601-1-2, and optical radiation safety testing in accordance with ISO 15004-1 and ISO 15004-2.

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CLINICAL PERFORMANCE SUMMARY

The data provided below is the second report presenting results from a prospective clinical study conducted at one clinical site located in the United States. Endothelial image data captured on the CEM530(Ver1.09) in the previous study, CEM-530-US-0002 were imported for auto analysis based on a new auto-cell count algorithm. The study was conducted to assess the agreement and precision of the Specular Microscope CEM-530 by comparing results across three machines/operators to those obtained with the predicate device, the Cellchek Plus. Three populations were studied: young (18-28 years of age) and adult (29-80 years of age) healthy subjects and pathologic adult eyes (29-80 years of age).

There were 79 subjects enrolled in the study: 28 in the non-pathologic young eye population, 28 in the non-pathologic adult eye population, and 23 in the pathologic adult eye population. Of those, 74 are included in the effectiveness population (28, 27, and 19, respectively). The agreement population consisted of all 74 subjects (28, 27 and 19, respectively). The precision population included a subset of the effectiveness population, 45 total with 15, 15 and 15 respectively. The pathologic adult subjects consisted of 19 subjects with the following pathologies which qualified them for the subgroup: Guttata (16, 84.2%) and Long Term Fuch's Dystrophy (3, 15.8%). The mean (SD) age of the nonpathologic young population was 22.2 (3.28) years; that of the non-pathologic adult population was 53.0 (13.42) years, and that of the pathologic adult population was 63.9 (12.39) years. All subjects combined had a mean age of 44.1 (20.54) years. The gender distribution of the total population was 27 males (36.5%) and 47 females (63.5%). The gender distribution of the non-pathologic young population was 15 males (53.6%) and 13 females (46.4%); that of the non-pathologic adult population was 8 males (29.6%) and 19 females (70.4%), and that of the pathologic adult population was 4 males (21.1%) and 15 females (78.9%). The majority of subjects were white (66/74 subjects, 89.2%). All of the pathologic adult subjects were white (19/19). The non-pathologic adult were white (21/27), American Indian (1/27), Asian (1/27), African American (1/27) and other (3/27). The nonpathologic young subjects were white (26/28) and other (2/28). With regard to iris color, the highest percentage of subjects had study eyes with brown irides (43.2%), followed by blue irides (28.4%), green irides (6.8%), black irides (1.4%) and gray irides (1.4%).

The result of Agreement study

Table 2 provides a summary of the agreement data for all subjects with the modified automated method while Tables 3, 4 and 5 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).

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CDCV% HEX
NIDEK Specular Microscope CEM-530
N747474
Mean (SD)2773.3 (343.10)27.4 (4.61)68 (5.16)
Median2747.02769.0
Min-Max1941 - 347317 - 4548 - 78
Konan CellChek Plus
N747474
Mean (SD)2738.6 (412.67)29.6 (4.16)62.6 (7.42)
Median2754.529.063.0
Min- Max1757 - 348422 - 4241 - 76
Device Comparisons
Mean Difference (SD)34.7 (157.38)-2.2 (4.03)5.4 (8.52)
Mean Difference (SD) as a % of the CellChek reading1.87% (6.356%)-6.88% (13.326%)10.22%
(16.418%)
95% LOA(-280.1, 349.4)(-10.3, 5.9)(-11.7, 22.4)
Correlation (R)0.92960.58170.1185
Deming Regression Intercept (95% CI)527.5 (324.9, 730.2)-7.8 (-23.8, 8.1)58.3 (38.2, 78.3)
Deming Regression Slope (95% CI)0.8 (0.7, 0.9)1.2 (0.6, 1.7)0.2 (-0.2, 0.5)
For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same

Table 2 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Agreement Analyses - All subjects

configuration are used for the agreement analyses. The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).

The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.

Table 3 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Agreement Analyses - Non-
Pathologic Young Eves
CDCV% HEX
NIDEK Specular Microscope CEM-530
N282828
Mean (SD)3005.1 (286.61)24.8 (3.31)68.6 (3.98)
Median3047.025.069.5
Min-Max2502 - 347317 - 3260 - 75
Konan CellChek Plus
N282828
Mean (SD)3030.3 (296.93)27.4 (2.99)67.0 (5.03)
Median3053.527.067.5
Min- Max2398 - 348422 - 3457 - 76
Device Comparisons
Mean Difference (SD)-25.2 (122.03)-2.7 (3.21)1.6 (5.14)
Mean Difference (SD) as a
% of the
CellChek reading-0.72% (4.018%)-9.33% (11.505%)2.86% (7.987%)
95% LOA(-269.2, 218.9)(-9.1, 3.7)(-8.6, 11.9)
Correlation (R)0.91310.48370.3681
Deming Regression Intercept (95% CI)90.0 (-430.4, 610.5)-9.1 (-35.2, 17.0)31.9 (-6.1, 69.9)
Deming Regression Slope
(95% CI)1.0 (0.8, 1.1)1.2 (0.3, 2.2)0.5 (0.0, 1.1)
For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same
configuration are used for the agreement analyses.

The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).

9

The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.

CDCV% HEX
NIDEK Specular Microscope CEM-530
N272727
Mean (SD)2671.7 (302.08)28.6 (4.65)69.1 (4.75)
Median2741.028.070.0
Min-Max2057 - 321922 - 4559 - 78
Konan CellChek Plus XL
N272727
Mean (SD)2627.3 (348.93)31.1 (4.29)59.3 (8.11)
Median2674.031.060.0
Min- Max2033 - 334422 - 4245 - 74
Device Comparisons
Mean Difference (SD)44.3 (146.00)-2.4 (4.77)9.8 (8.64)
Mean Difference (SD) as a % of
the CellChek reading2.08% (5.551%)-7.02% (14.718%)18.58% (18.457%)
95% LOA(-247.7, 336.3)(-12.0, 7.1)(-7.5, 27.1)
Correlation (R)0.90930.43360.1776
Deming Regression Intercept
(95% CI)429.3 (65.1, 793.4)-8.8 (-57.9, 40.2)59.9 (34.3, 85.6)
Deming Regression Slope
(95% CI)0.9 (0.7, 1.0)1.2 (-0.4, 2.8)0.2 (-0.3, 0.6)

Table 4 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Agreement Analyses - Non-Pathologic Adult Eyes

For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.

The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).

The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.

Table 5 CEM-530 Automated Analysis method vs. Konan Cellchek Plus : Agreement Analyses -Pathologic Adult Eyes

CDCV% HEX
NIDEK Specular Microscope CEM-530
N191919
Mean (SD)2576.1 (286.78)29.7 (4.45)65.5 (6.53)
Median2594.02965.0
Min-Max1941 - 313223 - 3948 - 76
Konan CellChek Plus XL
N191919
Mean (SD)2466.9 (392.01)30.8 (4.26)60.8 (6.41)
Median2564.030.061.0
Min- Max1757 - 305824 - 4041 - 68
Device Comparisons
Mean Difference (SD)109.2 (189.07)-1.2 (4.00)4.7 (9.79)
Mean Difference (SD) as a % of the
CellChek reading5.42% (8.445%)-3.05% (13.560%)9.19% (17.755%)
95% LOA(-269.0, 487.3)(-9.2, 6.8)(-14.9, 24.3)
Correlation (R)0.89030.5779-0.1454
Deming Regression Intercept (95% CI)837.1 (321.4, 1352.8)-3.6 (-20.5, 13.4)134.7 (-135.1, 404.6)
Deming Regression Slope
(95% CI)0.7 (0.5, 0.9)1.1 (0.5, 1.6)-1.1 (-5.5, 3.2)

10

For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.

The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).

The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.

The result of Precision study

Table 6 provides a summary of the precision data for all subjects with the modified automated method while Tables 7, 8 and 9 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively). Data from a previous NIDEK study, CEM-530-US-0002, was used as the comparative data with respect to the Konan CellChek Plus results for the precision analysis detailed below. In the evaluation of the suitability of using the historical data it was found that the sample size, age, gender, ethnicity/race, iris color and clinical diagnosis of the pathologic sub group were all similar to allow the usage of the data.

Table 6 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Precision Analyses – All Subjects

| Variable | NIDEK CEM-530
N=45 | Konan CellChek Plus
N=61 |
|---------------------------------------------------------------|-----------------------|-----------------------------|
| Endothelial Cell Density | | |
| Repeatability SD | 74.2 | 62.6 |
| Repeatability SD as a % of the Mean | 2.7% | 2.4% |
| Repeatability Limit | 207.8 | 175.3 |
| Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 1.1855 | --- |
| Reproducibility SD | 83.7 | 95.5 |
| Reproducibility SD as a % of the Mean | 3.1% | 3.7% |
| Reproducibility Limit | 234.3 | 267.5 |
| Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 0.8761 | --- |
| Coefficient of Variation of Endothelial Cell Area
(CV) | | |
| Repeatability SD | 1.7 | 2.7 |
| Repeatability SD as a % of the Mean | 6.2% | 8.4% |
| Repeatability Limit | 4.9 | 7.4 |
| Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 0.6536 | --- |
| Reproducibility SD | 1.9 | 2.7 |
| Reproducibility SD as a % of the Mean | 6.8% | 8.5% |
| Reproducibility Limit | 5.4 | 7.5 |
| Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 0.7183 | --- |
| % Hexagonality | | |
| Repeatability SD | 3.7 | 5.3 |
| Repeatability SD as a % of the Mean | 5.5% | 8.7% |
| Repeatability Limit | 10.5 | 14.9 |
| Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 0.7022 | --- |
| Reproducibility SD | 3.7 | 5.4 |
| Reproducibility SD as a % of the Mean | 5.5% | 8.9% |
| Reproducibility Limit | 10.5 | 15.1 |
| Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus) | 0.6911 | --- |

11

| Variable | NIDEK CEM-530
N=45 | Konan CellChek Plus
N=61 |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------|-----------------------------|
| CellChek Plus) | | |
| N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance
component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation,
which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the
reproducibility standard deviation, which is the square root of the sum of the variance components of operator+device,
operator+device x subject interaction, and residual within subject. | | |

Table 7 CEM-530 Automated Analysis method vs. Konan Cellchek Plus : Precision Analyses - Non-
Pathologic Young Eve
Pathologic Young Eye
VariableNIDEK CEM-530
N=15Konan CellChek Plus
N= 20
Endothelial Cell Density
Repeatability SD84.959.3
Repeatability SD as a % of the Mean2.9%2.1%
Repeatability Limit237.7166.0
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)1.4320---
Reproducibility SD92.870.2
Reproducibility SD as a % of the Mean3.1%2.5%
Reproducibility Limit259.8196.6
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)1.3218---
Coefficient of Variation of Endothelial Cell Area (CV)
Repeatability SD1.82.6
Repeatability SD as a % of the Mean6.8%8.9%
Repeatability Limit57.4
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.6868---
Reproducibility SD1.92.7
Reproducibility SD as a % of the Mean7.1%9.1%
Reproducibility Limit5.37.6
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.6965---
% Hexagonality
Repeatability SD3.64.2
Repeatability SD as a % of the Mean5.4%6.4%
Repeatability Limit10.111.7
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.8647---
Reproducibility SD3.64.3
Reproducibility SD as a % of the Mean5.4%6.7%
Reproducibility Limit10.112.1
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.8298---
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the

repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the sum of the variance components of operator+device x subject interaction, and residual within subject.

12

Pathologic Adult Eye
VariableNIDEK CEM-530
N=15Konan CellChek Plus
N=22
Endothelial Cell Density
Repeatability SD61.958.9
Repeatability SD as a % of the Mean2.4%2.3%
Repeatability Limit173.4165.0
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)1.0515---
Reproducibility SD76.160.8
Reproducibility SD as a % of the Mean2.9%2.3%
Reproducibility Limit213170.2
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.2517---
Coefficient of Variation of Endothelial Cell Area (CV)
Repeatability SD1.62.3
Repeatability SD as a % of the Mean5.7%7.1%
Repeatability Limit4.56.4
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.6952---
Reproducibility SD1.92.4
Reproducibility SD as a % of the Mean6.9%7.3%
Reproducibility Limit5.46.6
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.8067---
% Hexagonality
Repeatability SD3.84.1
Repeatability SD as a % of the Mean5.5%6.8%
Repeatability Limit10.811.4
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.9400---
Reproducibility SD3.84.6
Reproducibility SD as a % of the Mean5.5%7.7%
Reproducibility Limit10.813.0
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.8299---
VariableNIDEK CEM-530
N=15Konan CellChek Plus
N=19
Endothelial Cell Density
Repeatability SD74.169.8
Repeatability SD as a % of the Mean2.8%3.0%
Repeatability Limit207.4195.4
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)1.0614---
Reproducibility SD81.7141.3
Reproducibility SD as a % of the Mean3.1%6.1%
Reproducibility Limit228.7395.6
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.5781---
Coefficient of Variation of Endothelial Cell Area (CV)
Repeatability SD1.83.1
Repeatability SD as a % of the Mean5.9%9.3%
Repeatability Limit5.18.6
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.5912---
Reproducibility SD2.03.1
Reproducibility SD as a % of the Mean6.6%9.5%
Reproducibility Limit5.68.7
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.6462---
% Hexagonality
Repeatability SD3.87.3
Repeatability SD as a % of the Mean5.6%12.7%
Repeatability Limit10.520.4
Repeatability Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.5154---
Reproducibility SD3.87.3
Reproducibility SD as a % of the Mean5.6%12.7%
Reproducibility Limit10.520.4
Reproducibility Ratio (NIDEK CEM-530/ Konan
CellChek Plus)0.5154---
N represents the total number of subjects in each eye population in the precision and agreement cohort.
If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the
repeatability standard deviation, which is the square root of the residual within subject variance
component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the
square root of the sum of the variance components of operator+device, operator+device x subject
interaction, and residual within subject.

Table 8 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Precision Analyses – Non-Pathologic Adult Eye

N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the sum of the variance components of operator+device x subject interaction, and residual within subject.

13

Table 9 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Precision Analyses – Pathologic Adult Eye

Additional Manual Comparision

An additional comparision was conducted to assess the agreement, accuracy and precision of the Specular Microscope CEM-530 automated analysis compared to the CEM-530 manual analysis methods across three machines/operators. Three populations were studied: young (18-28 years of age) and adult (29-80 years of age) healthy subjects and pathologic

14

adult eyes (29-80 years of age).

The result of Agreement study

Table 10 provides a summary of the agreement data for all subjects while Tables 11, 12 and 13 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).

Table 10 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement
Analyses - All subjects
CDCV% HEX
Nidek Automated CEM-530
N747474
Mean (SD)2773.3 (343.10)27.4 (4.61)68.0 (5.16)
Median2747.027.069.0
Min-Max1941 - 347317 - 4548 - 78
Nidek Manual CEM-530
N747474
Mean (SD)2784.3 (428.52)22.1 (3.36)59.8 (7.30)
Median2795.021.560.0
Min- Max1754 - 363715 - 3541 - 81
Device Comparisons
Mean Difference (SD)-11.0 (135.31)5.4 (4.30)8.2 (8.27)
Mean Difference (SD) as a % of the Nidek
Manual CEM-530 reading0.18% (5.066%)25.71% (21.835%)15.34% (15.544%)
95% LOA(-281.6, 259.6)(-3.2, 14.0)(-8.3, 24.8)
Correlation (R)0.96260.45370.1536
Deming Regression Intercept (95% CI)562.9 (420.9, 704.8)-15.1 (-48.0, 17.7)55.6 (36.0, 75.2)
Deming Regression Slope
(95% CI)0.79 (0.74,0.85)1.9 (0.4, 3.5)0.2 (-0.1, 0.5)

For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.

The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).

The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.

Table 11 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement
Analyses - Non-Pathologic Young Eves
CDCV% HEX
Nidek Automated CEM-530
N282828
Mean (SD)3005.1 (286.61)24.8 (3.31)68.6 (3.98)
Median3047.025.069.5
Min-Max2502 - 347317 - 3260 - 75
Nidek Manual CEM-530
N282828
Mean (SD)3069.5 (346.41)20.3 (1.90)63.0 (6.33)
Median3104.021.063.0
Min- Max2437 - 363715 - 2452 - 81
Device Comparisons
Mean Difference (SD)-64.4 (118.86)4.5 (3.14)5.6 (6.63)
Mean Difference (SD) as a % of the Nidek
Manual CEM-530 reading--1.86% (3.609%)22.72% (15.797%)9.76% (10.871%)
95% LOA(-302.1, 173.3)(-1.8, 10.8)(-7.7, 18.9)

15

Correlation (R)0.94690.37030.2384
Deming Regression Intercept (95% CI)492.0 (153.8, 830.3)-45.0 (-213.2, 123.1)53.9 (23.9, 83.8)
Deming Regression Slope
(95% CI)0.8 (0.7, 0.9)3.4 (-4.8, 11.7)0.2 (-0.2, 0.7)

For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.

The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).

The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.

Table 12 CEM-530Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement Analyses – Non-Pathologic Adult Eyes

Analyses - Non Pathologic Adult Eyes
CDCV% HEX
Nidek Automated CEM-530
N272727
Mean (SD)2671.7 (302.08)28.6 (4.65)69.1 (4.75)
Median2741.028.070.0
Min-Max2057 - 321922 - 4559 - 78
Nidek Manual CEM-530
N272727
Mean (SD)2678.6 (391.33)23.3 (3.27)57.1 (6.66)
Median2772.023.056.0
Min- Max1956 - 339919 - 3547 - 73
Device Comparisons
Mean Difference (SD)-6.9 (130.19)5.4 (5.06)12.0 (7.31)
Mean Difference (SD) as a % of the Nidek0.29% (4.908%)24.61% (24.465%)22.37% (14.963%)
Manual CEM-530 reading
95% LOA(-267.3, 253.5)(-4.8, 15.5)(-2.6, 26.6)
Correlation (R)0.96200.21930.2134
Deming Regression Intercept (95% CI)624.5 (461.5, 787.4)-54.5 (-277.1, 168.2)52.9 (9.8, 95.9)
Deming Regression Slope
(95% CI)0.76(0.71,0.82)3.6 (-6.2, 13.4)0.3 (-0.5, 1.0)
For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same
configuration are used for the agreement analyses.

The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).

The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.

Table 13 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement
Analyses - Pathologic Adult Eyes
CDCV% HEX
Nidek Automated CEM-530
N191919
Mean (SD)2576.1 (286.78)29.7 (4.45)65.5 (6.53)
Median2594.029.065.0
Min-Max1941 - 313223 - 3948 - 76
Nidek Manual CEM-530
N191919
Mean (SD)2514.2 (351.02)23.0 (4.11)58.7 (7.96)
Median2522.022.060.0
Min- Max1754 - 307817 - 3341 - 71
Device Comparisons
Mean Difference (SD)61.9 (136.03)6.7 (4.49)6.8 (9.99)

16

K173980 510(K) Summary

| Mean Difference (SD) as a % of the Nidek

Manual CEM-530 reading3.01% (5.902%)31.66% (25.329%)13.57% (18.797%)
95% LOA(-210.2, 334.0)(-2.3, 15.7)(-13.2, 26.8)
Correlation (R)0.92860.45290.0605
Deming Regression Intercept (95% CI)553.2 (171.3, 935.2)2.3 (-35.1, 39.7)56.8 (-38.4, 152.1)
Deming Regression Slope
(95% CI)0.8 (0.6, 1.0)1.2 (-0.5, 2.9)0.1 (-1.4, 1.7)
For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same

For subjects in the Precision and Agreement cohort, the measurements from first acceptable images from each machine within the the configuration are used for the agreement analyses.

The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).

The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.

The result of Precision study

Table 14 provides a summary of the precison data for all subjects while Tables 15, 16 and 17 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).

Table 14 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses - All Subjects

| Variable | NIDEK Automated
CEM-530
N= 45 | Nidek Manual
CEM-530
N= 46 |
|---------------------------------------------------------------------|-------------------------------------|----------------------------------|
| Endothelial Cell Density | | |
| Repeatability SD | 74.2 | 49.1 |
| Repeatability SD as a % of the Mean | 2.7% | 1.8% |
| Repeatability Limit | 207.8 | 137.6 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.5109 | --- |
| Reproducibility SD | 83.7 | 61.3 |
| Reproducibility SD as a % of the Mean | 3.1% | 2.3% |
| Reproducibility Limit | 234.3 | 171.8 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.3643 | --- |
| Coefficient of Variation of Endothelial Cell Area
(CV) | | |
| Repeatability SD | 1.7 | 1.5 |
| Repeatability SD as a % of the Mean | 6.2% | 6.8% |
| Repeatability Limit | 4.9 | 4.2 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1694 | --- |
| Reproducibility SD | 1.9 | 1.9 |
| Reproducibility SD as a % of the Mean | 6.8% | 8.4% |
| Reproducibility Limit | 5.4 | 5.2 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.0417 | --- |
| % Hexagonality | | |
| Repeatability SD | 3.7 | 3.5 |
| Repeatability SD as a % of the Mean | 5.5% | 5.8% |
| Repeatability Limit | 10.5 | 9.9 |

17

| Variable | NIDEK Automated
CEM-530 | Nidek Manual
CEM-530 |
|---------------------------------------------------------------------|----------------------------|-------------------------|
| | N= 45 | N= 46 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.0559 | --- |
| Reproducibility SD | 3.7 | 4.0 |
| Reproducibility SD as a % of the Mean | 5.5% | 6.5% |
| Reproducibility Limit | 10.5 | 11.1 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 0.9422 | --- |

N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.

Table 15 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses – Non-Pathologic Young Eye

| Variable | NIDEK Automated
CEM-530
N= 15 | Nidek Manual
CEM-530
N=15 |
|---------------------------------------------------------------------|-------------------------------------|---------------------------------|
| Endothelial Cell Density | | |
| Repeatability SD | 84.9 | 46.0 |
| Repeatability SD as a % of the Mean | 2.9% | 1.5% |
| Repeatability Limit | 237.7 | 128.8 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.8459 | --- |
| Reproducibility SD | 92.8 | 51.9 |
| Reproducibility SD as a % of the Mean | 3.1% | 1.7% |
| Reproducibility Limit | 259.8 | 145.4 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.7874 | --- |
| Coefficient of Variation of Endothelial Cell Area
(CV) | | |
| Repeatability SD | 1.8 | 1.3 |
| Repeatability SD as a % of the Mean | 6.8% | 6.4% |
| Repeatability Limit | 5.0 | 3.5 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.4289 | --- |
| Reproducibility SD | 1.9 | 1.5 |
| Reproducibility SD as a % of the Mean | 7.1% | 7.5% |
| Reproducibility Limit | 5.3 | 4.2 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.2629 | --- |
| % Hexagonality | | |
| Repeatability SD | 3.6 | 3.1 |
| Repeatability SD as a % of the Mean | 5.4% | 4.8% |
| Repeatability Limit | 10.1 | 8.6 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1700 | --- |

18

| Variable | NIDEK Automated
CEM-530 | Nidek Manual
CEM-530 |
|---------------------------------------------------------------------|----------------------------|-------------------------|
| | N=15 | N=15 |
| NIDEK Manual CEM-530) | | |
| Reproducibility SD | 3.6 | 3.8 |
| Reproducibility SD as a % of the Mean | 5.4% | 5.8% |
| Reproducibility Limit | 10.1 | 10.6 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 0.9532 | --- |

N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.

Table 16 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses - Non-Pathologic Adult Eye

| Variable | NIDEK Automated
CEM-530
N= 15 | Nidek Manual
CEM-530
N= 15 |
|---------------------------------------------------------------------|-------------------------------------|----------------------------------|
| Endothelial Cell Density | | |
| Repeatability SD | 61.9 | 48.3 |
| Repeatability SD as a % of the Mean | 2.4% | 1.8% |
| Repeatability Limit | 173.4 | 135.1 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.2835 | --- |
| Reproducibility SD | 76.1 | 58.2 |
| Reproducibility SD as a % of the Mean | 2.9% | 2.2% |
| Reproducibility Limit | 213.0 | 163.0 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.3072 | --- |
| Coefficient of Variation of Endothelial Cell Area
(CV) | | |
| Repeatability SD | 1.6 | 1.4 |
| Repeatability SD as a % of the Mean | 5.7% | 6.3% |
| Repeatability Limit | 4.5 | 4.0 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1209 | --- |
| Reproducibility SD | 1.9 | 1.7 |
| Reproducibility SD as a % of the Mean | 6.9% | 7.6% |
| Reproducibility Limit | 5.4 | 4.8 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1174 | --- |
| % Hexagonality | | |
| Repeatability SD | 3.8 | 3.1 |
| Repeatability SD as a % of the Mean | 5.5% | 5.3% |
| Repeatability Limit | 10.8 | 8.7 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.2387 | --- |

19

| Variable | NIDEK Automated
CEM-530
N= 15 | Nidek Manual
CEM-530
N= 15 |
|---------------------------------------------------------------------|-------------------------------------|----------------------------------|
| NIDEK Manual CEM-530) | | |
| Reproducibility SD | 3.8 | 3.5 |
| Reproducibility SD as a % of the Mean | 5.5% | 5.9% |
| Reproducibility Limit | 10.8 | 9.7 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1117 | --- |

N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.

Table 17 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses – Pathologic Adult Eye

| Variable | NIDEK Automated
CEM-530
N=15 | Nidek Manual
CEM-530
N=16 |
|---------------------------------------------------------------------|------------------------------------|---------------------------------|
| Endothelial Cell Density | | |
| Repeatability SD | 74.1 | 52.7 |
| Repeatability SD as a % of the Mean | 2.8% | 2.1% |
| Repeatability Limit | 207.4 | 147.4 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.4065 | --- |
| Reproducibility SD | 81.7 | 72.4 |
| Reproducibility SD as a % of the Mean | 3.1% | 2.9% |
| Reproducibility Limit | 228.7 | 202.7 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.1283 | --- |
| Coefficient of Variation of Endothelial Cell Area
(CV) | | |
| Repeatability SD | 1.8 | 1.7 |
| Repeatability SD as a % of the Mean | 5.9% | 7.3% |
| Repeatability Limit | 5.1 | 4.8 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 1.0508 | --- |
| Reproducibility SD | 2.0 | 2.3 |
| Reproducibility SD as a % of the Mean | 6.6% | 9.8% |
| Reproducibility Limit | 5.6 | 6.4 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 0.8800 | --- |
| % Hexagonality | | |
| Repeatability SD | 3.8 | 4.3 |
| Repeatability SD as a % of the Mean | 5.6% | 7.3% |
| Repeatability Limit | 10.5 | 11.9 |
| Repeatability Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 0.8844 | --- |

20

| Variable | NIDEK Automated
CEM-530 | Nidek Manual
CEM-530 |
|---------------------------------------------------------------------|----------------------------|-------------------------|
| | N=15 | N=16 |
| Reproducibility SD | 3.8 | 4.6 |
| Reproducibility SD as a % of the Mean | 5.6% | 7.9% |
| Reproducibility Limit | 10.5 | 12.9 |
| Reproducibility Ratio (NIDEK Auto CEM-530/
NIDEK Manual CEM-530) | 0.8161 | --- |

N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator+device, operator+device x subject interaction, and residual within subject.

CONCLUSIONS

The NIDEK Specular Microscope CEM-530 has the same intended use and indications for use, technological characteristics, and principles of operation as the previously cleared predicate. The minor differences between the subject device and the predicate device have been assessed in a human clinical trial which found agreement and precision between the two devices. Therefore, the NIDEK Specular Microscope CEM-530 is as safe and effective as its predicate device, and thus, substantially equivalent.