Specular Microscope CEM-530

{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 {2}------------------------------------------------ # 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) | <span style="font-size:12px">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | |------------------------------------------------------------------------------------| | □ Over-The-Counter Use (21 CFR 801 Subpart C) | CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ ## 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) {4}------------------------------------------------ ## 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 {5}------------------------------------------------ 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 | | | |-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Manufacturer | NIDEK | Konan | | Device Name | CEM-530 | Cellchek Plus | | 510(k) Number | NA | K120264 | | Product Classification | Class II, NQE | Class II, NQE | | Indications for Use | Non-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 Type | Non-contact specular microscope and pachymeter | Non-contact specular microscope and pachymeter | | Capturing Method | Auto capture, auto alignment, auto focus (3D, 2D)/Manual | Auto capture, auto alignment, auto focus(3D)/Manual | | Capture Field | 0.25x 0.55 mm | 0.24 x 0.4 mm | | Fixation Lamp (Central) | 1 point | 1 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 {6}------------------------------------------------ | Camera | Built-in CCD camera | Built-in CCD camera | Built-in CCD image sensing element camera | |---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------| | Flash<br>Illumination for<br>focusing | Cyan LED<br>InfraRed LED | Cyan LED<br>InfraRed LED | Konan Xe tube<br>Konan halogen lamp | | Pachymetry<br>Technology | Optical | Optical | Optical | | Measurement Range<br>Pachymetry | 300 to 1000 microns | 300 to 1000 microns | Unknown | | Accuracy of<br>pachymetry | $\pm$ 10 microns | $\pm$ 10 microns | $\pm$ 10 microns | | Auto Analysis | Yes | Yes | Yes | | Manual Analysis | Yes | Yes | Yes | | Analysis Speed | 2 seconds | 2 seconds | Unknown | | Record (1 patient) | Single mode: 1<br>endothelial image for<br>both right and left eyes<br>Paracentral and<br>Peripheral modes: 15<br>endothelial images for<br>both right and left eyes | Single mode: 1 endothelial<br>image for both right and left<br>eyes<br>Paracentral and Peripheral<br>modes: 15 endothelial<br>images for both right and left<br>eyes | 1 endothelial image for both<br>right and left eyes | | Built-in Printer | Thermal Line Printer<br>with auto cutter | Thermal Line Printer with<br>auto cutter | NA | | External Interface | USB-A: barcode, card<br>reader, LAN for data<br>output, Video output:<br>BNC terminal | USB-A: barcode, card<br>reader, LAN for data output,<br>Video output: BNC terminal | Video output: BNC terminal<br>Input port for mouse and<br>remote control | | Connection to Filing<br>System | Connectable | Connectable | Connectable | | Monitor | 8.4" SVGA color LCD<br>with touch panel | 8.4" SVGA color LCD with<br>touch panel | 19" color LCD monitor | | Input Power | 100 VA | 100 VA | 70 VA | | Dimensions | 291 (W) x 495 (D) x<br>457 (H) mm | 291 (W) x 495 (D) x 457 (H)<br>mm | 334 (W) x 486 (D) x 420 (H)<br>mm | | Weight | 20 Kg | 20 Kg | 20.5 Kg | | Compliance with<br>Safety Standards | AAMI/ANSI ES<br>60601-1<br>IEC 60601-1-2<br>ISO 15004-1<br>ISO 15004-2 | IEC 60601-1<br>IEC 60601-1-2<br>ISO 15004-1<br>ISO 15004-2 | IEC 60601-1<br>IEC 60601-1-2<br>ISO 15004-1<br>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. {7}------------------------------------------------ # 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). {8}------------------------------------------------ | | CD | CV | % HEX | |-----------------------------------------------------------------------------------------------------------------------------------------|----------------------|-------------------|---------------------| | NIDEK Specular Microscope CEM-530 | | | | | N | 74 | 74 | 74 | | Mean (SD) | 2773.3 (343.10) | 27.4 (4.61) | 68 (5.16) | | Median | 2747.0 | 27 | 69.0 | | Min-Max | 1941 - 3473 | 17 - 45 | 48 - 78 | | Konan CellChek Plus | | | | | N | 74 | 74 | 74 | | Mean (SD) | 2738.6 (412.67) | 29.6 (4.16) | 62.6 (7.42) | | Median | 2754.5 | 29.0 | 63.0 | | Min- Max | 1757 - 3484 | 22 - 42 | 41 - 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 reading | 1.87% (6.356%) | -6.88% (13.326%) | 10.22%<br>(16.418%) | | 95% LOA | (-280.1, 349.4) | (-10.3, 5.9) | (-11.7, 22.4) | | Correlation (R) | 0.9296 | 0.5817 | 0.1185 | | 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 | | | | | | | CD | CV | % HEX | | | NIDEK Specular Microscope CEM-530 | | | | | | N | 28 | 28 | 28 | | | Mean (SD) | 3005.1 (286.61) | 24.8 (3.31) | 68.6 (3.98) | | | Median | 3047.0 | 25.0 | 69.5 | | | Min-Max | 2502 - 3473 | 17 - 32 | 60 - 75 | | | Konan CellChek Plus | | | | | | N | 28 | 28 | 28 | | | Mean (SD) | 3030.3 (296.93) | 27.4 (2.99) | 67.0 (5.03) | | | Median | 3053.5 | 27.0 | 67.5 | | | Min- Max | 2398 - 3484 | 22 - 34 | 57 - 76 | | | Device Comparisons | | | | | | Mean Difference (SD) | -25.2 (122.03) | -2.7 (3.21) | 1.6 (5.14) | | | Mean Difference (SD) as a<br>% of the<br>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) | 0.9131 | 0.4837 | 0.3681 | | | 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<br>(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<br>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. | | CD | CV | % HEX | |--------------------------------------------------------|---------------------|--------------------|-------------------| | NIDEK Specular Microscope CEM-530 | | | | | N | 27 | 27 | 27 | | Mean (SD) | 2671.7 (302.08) | 28.6 (4.65) | 69.1 (4.75) | | Median | 2741.0 | 28.0 | 70.0 | | Min-Max | 2057 - 3219 | 22 - 45 | 59 - 78 | | Konan CellChek Plus XL | | | | | N | 27 | 27 | 27 | | Mean (SD) | 2627.3 (348.93) | 31.1 (4.29) | 59.3 (8.11) | | Median | 2674.0 | 31.0 | 60.0 | | Min- Max | 2033 - 3344 | 22 - 42 | 45 - 74 | | Device Comparisons | | | | | Mean Difference (SD) | 44.3 (146.00) | -2.4 (4.77) | 9.8 (8.64) | | Mean Difference (SD) as a % of<br>the CellChek reading | 2.08% (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) | 0.9093 | 0.4336 | 0.1776 | | Deming Regression Intercept<br>(95% CI) | 429.3 (65.1, 793.4) | -8.8 (-57.9, 40.2) | 59.9 (34.3, 85.6) | | Deming Regression Slope<br>(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 | | CD | CV | % HEX | |--------------------------------------------------------|-----------------------|--------------------|-----------------------| | NIDEK Specular Microscope CEM-530 | | | | | N | 19 | 19 | 19 | | Mean (SD) | 2576.1 (286.78) | 29.7 (4.45) | 65.5 (6.53) | | Median | 2594.0 | 29 | 65.0 | | Min-Max | 1941 - 3132 | 23 - 39 | 48 - 76 | | Konan CellChek Plus XL | | | | | N | 19 | 19 | 19 | | Mean (SD) | 2466.9 (392.01) | 30.8 (4.26) | 60.8 (6.41) | | Median | 2564.0 | 30.0 | 61.0 | | Min- Max | 1757 - 3058 | 24 - 40 | 41 - 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<br>CellChek reading | 5.42% (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) | 0.8903 | 0.5779 | -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<br>(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<br>N=45 | Konan CellChek Plus<br>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<br>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<br>CellChek Plus) | 0.8761 | --- | | Coefficient of Variation of Endothelial Cell Area<br>(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<br>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<br>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<br>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<br>CellChek Plus) | 0.6911 | --- | {11}------------------------------------------------ | Variable | NIDEK CEM-530<br>N=45 | Konan CellChek Plus<br>N=61 | |--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------|-----------------------------| | CellChek Plus) | | | | N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance<br>component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation,<br>which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the<br>reproducibility standard deviation, which is the square root of the sum of the variance components of operator+device,<br>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 | | | |----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------|------------------------------| | Variable | NIDEK CEM-530<br>N=15 | Konan CellChek Plus<br>N= 20 | | Endothelial Cell Density | | | | Repeatability SD | 84.9 | 59.3 | | Repeatability SD as a % of the Mean | 2.9% | 2.1% | | Repeatability Limit | 237.7 | 166.0 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 1.4320 | --- | | Reproducibility SD | 92.8 | 70.2 | | Reproducibility SD as a % of the Mean | 3.1% | 2.5% | | Reproducibility Limit | 259.8 | 196.6 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 1.3218 | --- | | Coefficient of Variation of Endothelial Cell Area (CV) | | | | Repeatability SD | 1.8 | 2.6 | | Repeatability SD as a % of the Mean | 6.8% | 8.9% | | Repeatability Limit | 5 | 7.4 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.6868 | --- | | Reproducibility SD | 1.9 | 2.7 | | Reproducibility SD as a % of the Mean | 7.1% | 9.1% | | Reproducibility Limit | 5.3 | 7.6 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.6965 | --- | | % Hexagonality | | | | Repeatability SD | 3.6 | 4.2 | | Repeatability SD as a % of the Mean | 5.4% | 6.4% | | Repeatability Limit | 10.1 | 11.7 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.8647 | --- | | Reproducibility SD | 3.6 | 4.3 | | Reproducibility SD as a % of the Mean | 5.4% | 6.7% | | Reproducibility Limit | 10.1 | 12.1 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>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 | | | |------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------|-----------------------------| | Variable | NIDEK CEM-530<br>N=15 | Konan CellChek Plus<br>N=22 | | Endothelial Cell Density | | | | Repeatability SD | 61.9 | 58.9 | | Repeatability SD as a % of the Mean | 2.4% | 2.3% | | Repeatability Limit | 173.4 | 165.0 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 1.0515 | --- | | Reproducibility SD | 76.1 | 60.8 | | Reproducibility SD as a % of the Mean | 2.9% | 2.3% | | Reproducibility Limit | 213 | 170.2 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.2517 | --- | | Coefficient of Variation of Endothelial Cell Area (CV) | | | | Repeatability SD | 1.6 | 2.3 | | Repeatability SD as a % of the Mean | 5.7% | 7.1% | | Repeatability Limit | 4.5 | 6.4 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.6952 | --- | | Reproducibility SD | 1.9 | 2.4 | | Reproducibility SD as a % of the Mean | 6.9% | 7.3% | | Reproducibility Limit | 5.4 | 6.6 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.8067 | --- | | % Hexagonality | | | | Repeatability SD | 3.8 | 4.1 | | Repeatability SD as a % of the Mean | 5.5% | 6.8% | | Repeatability Limit | 10.8 | 11.4 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.9400 | --- | | Reproducibility SD | 3.8 | 4.6 | | Reproducibility SD as a % of the Mean | 5.5% | 7.7% | | Reproducibility Limit | 10.8 | 13.0 | | Reproducibility Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 0.8299 | --- | | Variable | NIDEK CEM-530<br>N=15 | Konan CellChek Plus<br>N=19 | | Endothelial Cell Density | | | | Repeatability SD | 74.1 | 69.8 | | Repeatability SD as a % of the Mean | 2.8% | 3.0% | | Repeatability Limit | 207.4 | 195.4 | | Repeatability Ratio (NIDEK CEM-530/ Konan<br>CellChek Plus) | 1.0614 | --- | | Reproducibility SD…