EM-4000 Specular Microscope

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January 19, 2018 Tomey Corporation % Ryan Bouchard, Official Correspondent Ora, Inc. 300 Brickstone Square Andover, MA 01810 Re: K171313 Trade/Device Name: EM-4000 Specular Microscope Regulation Number: 21 CFR 886.1850 Regulation Name: AC-powered slitlamp biomicroscope Regulatory Class: Class II Product Code: NOE Dated: December 17, 2017 Received: December 19, 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. 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Cunningham -S for Malvina 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) #### K171313 Device Name EM-4000 Specular Microscopy #### Indications for Use (Describe) The EM-4000 Specular Microscope 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) #### 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." Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below. PSC Publishing Services (301) 443-6740 EF {3}------------------------------------------------ ### 510(k) Summary This summary of the 510(k) premarket notification for the Tomey EM-4000 Specular Microscope is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR§807.92. Date Prepared: January 12, 2018 ### SPONSER/ 510(k) OWNER/ MANUFACTURER Tomey Corporation 2-11-33 Noritakeshinmachi Nishi-ku, Nagoya 451-0051 JAPAN #### 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: EM-4000 Specular Microscope 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 Konan Medical, Inc. Cellchek XL (K120264) ### INDICATIONS FOR USE The EM-4000 Specular Microscope 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. {4}------------------------------------------------ ## PRODUCT DESCRIPTION The Tomey EM-4000 Specular Microscope is a non-contact ophthalmic microscope and camera intended for corneal endothelium imaging. Its operating principle is based on the Specular optical principle. This device is used for imaging the corneal endothelium. The EM-4000 analyzes and displays data such as cell number, cell density, coefficient of variation and percent hexagonality. When photographing the corneal endothelium, the equipment performs the alignment and automatically focuses by capturing the reflected light from the patient's eye with the CCD camera. Infrared LEDs are used as the light source for the alignment. Operation with the iovstick also makes it possible to focus manually. The green LED light radiates to the cornea, and the endothelium image is captured with the CCD camera by the reflected light from the cornea. The endothelium images are stored in internal memory. Furthermore, the EM-4000 is able to measure the central corneal thickness. The corneal endothelium is photographed first followed by measuring the central corneal thickness. The infrared LED light for measurement of corneal thickness radiates to the cornea through the objective lens for photographing the cornea, and the central corneal thickness can be calculated by measuring the distance on the optical line sensor between the reflected light from front surface and back surface of cornea. ### SUBSTANTIAL EQUIVALENCE The Tomey EM-4000 Specular Microscope is substantially equivalent to the Konan Medical, Inc. Cellchek XL (K120264). The Tomey EM-4000 Specular Microscope has the same intended use and indications for use, technological characteristics, and principles of operation as the previously cleared predicate device. The Tomey EM-4000 Specular Microscope and the predicate device are both non-contact ophthalmic microscopes, optical pachymeters, and cameras intended for examination of the corneal endothelium and for measurement of the thickness of the cornea. The EM-4000 and the Konan Cellchek XL both utilize the general specular optical principle for imaging endothelial cells and performing pachymetry. The two devices use different light sources for measurement and focusing. However, compliance with ISO 15004-2 is documented. The EM-4000 uses a green LED for measurement and an infrared LED for focusing while the predicate device uses a Xe tube flash lamp for measurement and halogen lamp for focusing. {5}------------------------------------------------ Both devices measure cell number, cell density, coefficient of variation and percent hexagonality. The clinical performance data demonstrates the substantial equivalence of the EM-4000 to the Konan predicate device. Both the EM-4000 and the Konan Cellchek XL include an optical pachymeter with an accuracy of + 10 microns. Bench testing comparing the EM-4000 pachymetry functionality to the predicate device is provided. The non-clinical and clinical performance data demonstrated the substantial equivalence of the pachymetry measurements. For the measurements assessed, the Tomey EM-4000 Specular Microscope and predicate device results were found to be substantially equivalent. # NON-CLINICAL PERFORMANCE SUMMARY The performance testing conducted using the EM-4000 verified that the device operates as intended. The pachymetry functionality was evaluated and the measurement accuracy of + 10 microns was confirmed. Additionally, the EM-4000 was subjected to electrical safety testing in accordance with ANSI/AAMI ES60601-1, 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. # CLINICAL PERFORMANCE SUMMARY A prospective clinical study was conducted to assess the agreement, accuracy and precision of the EM-4000 by comparing results across three machines/operators to those obtained with the predicate device, the Konan Cellchek XL. Three populations were studied: young (18-28 years of age) and adult (29-80 vears of age) healthy subjects and pathologic adult eves (29-80 vears of age). There were 70 subjects enrolled in the study: 25 in the non-pathologic voung eye population, 23 in the non-pathologic adult eye population, and 22 in the pathologic adult eye population. Of those, 67 were included in the effectiveness population for the agreement portion of the study for the specular microscope variables. For the central corneal thickness (CCT) variable, 68 subjects were included in the effectiveness population. Of the 70 enrolled subjects, 44 were included in the population for the precision portion of the study: 14 in the non-pathologic young eye population, 15 in the non-pathologic adult eye population, and 15 in the pathologic adult eye population. The agreement and variability of the analysis methods was obtained using a sample that included virtually no eyes with predicate device measurements of {6}------------------------------------------------ Percent Hexagonality <45, Coefficient of Variation >0.40, or Cell Density <1900. Agreement and variability of the analysis methods is not known for eyes with parameters beyond these values. The clinical study results for the device measurements using the Core Method of analysis were based upon the use of a reading center # Endothelial Cell Density For the Core Method, the mean difference for endothelial cell density (CD) was -6.49%. . The mean differences for endothelial cell density are illustrated on the Bland Altman plot (Figure 1). Plots of the device differences by the CellChek XL value are presented (Figure 2). The Deming regression lines showed an associated correlation value of 0.9634 (Figure 3). Table 1 provides a summary of the agreement data for all subjects with the Core Method. #### Figure 1 Bland-Altman Plot - Observed Data - Endothelial Cell Density (CD) -Core Method- All Subjects - Effectiveness Population Image /page/6/Figure/5 description: This image is a scatter plot with the title missing. The x-axis is labeled "Mean" and ranges from 600 to 3600. The y-axis is labeled "Difference" and ranges from -1000 to 400. There are three horizontal lines on the plot, one red and two green, and the data points are clustered in the middle of the plot. Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs). The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). {7}------------------------------------------------ Device Difference by Konan CellChek XL Value – Endothelial Cell Figure 2 Density (CD) – Core Method-All Subjects – Effectiveness Population Image /page/7/Figure/1 description: This image is a scatter plot with the title "Konan CELLCHEK XL Value" on the x-axis and "Device Difference" on the y-axis. The x-axis ranges from 600 to 3600, while the y-axis ranges from -1000 to 400. The data points are clustered between x values of 2000 and 3400, and y values of -500 to 100. The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). #### Deming Regression Plot – Tomey EM-4000 by Konan CellChek XL – Figure 3 Endothelial Cell Density (CD) - Core Method - All Subjects - Effectiveness Population Image /page/7/Figure/4 description: This image is a scatter plot that compares Tomey Value and Konan CELLCHEK XL. The x-axis represents Konan CELLCHEK XL, ranging from 600 to 3600, while the y-axis represents Tomey Value, ranging from 400 to 3600. The plot includes a Deming Regression Line and a 45 Degree Line, which are used to analyze the relationship between the two variables. The data points are clustered along the lines, indicating a positive correlation between Tomey Value and Konan CELLCHEK XL. {8}------------------------------------------------ | | CD | CV | % HEX | CCT | | | |--------------------------------------------|---------------------------|--------------------|--------------------|-----------------------|--|--| | Tomey Specular Microscope EM-4000 | | | | | | | | N | 67 | 67 | 67 | 68 | | | | Mean (SD) | 2504.6<br>(443.68) | 31.8 (3.83) | 60.3 (6.54) | 542.1 (41.88) | | | | Median | 2604.0 | 31.0 | 60.0 | 543.5 | | | | Min-Max | 650-3161 | 24-42 | 41-77 | 416 - 644 | | | | Konan CellChek XL | | | | | | | | N | 67 | 67 | 67 | 67 | | | | Mean (SD) | 2674.3<br>(454.08) | 31.5 (4.18) | 60.8 (8.61) | 559.9 (42.25) | | | | Median | 2778.0 | 32.0 | 60.0 | 560.5 | | | | Min- Max | 990-3472 | 21-40 | 33-80 | 441 - 677 | | | | Device Comparisons | | | | | | | | Mean Difference (SD) | -169.7<br>(121.95) | 0.3 (3.49) | -0.4 (7.38) | -17.8 (22.57) | | | | Mean Difference (SD) as a | -6.49%<br>(5.648%) | 1.65%<br>(11.304%) | 0.70%<br>(15.091%) | -3.11%<br>(3.995%) | | | | 95% LOA | (-413.6, 74.2) | (-6.7, 7.3) | (-15.2, 14.3) | (-62.9, 27.4) | | | | Correlation (R) | 0.9634 | 0.6226 | 0.5549 | 0.8561 | | | | Deming<br>Regression<br>Intercept (95% CI) | -106.1<br>(-387.7, 175.4) | 4.4 (-4.0, 12.8) | 22.9 (2.5, 43.3) | 66.9<br>(-3.8, 137.6) | | | | Deming Regression Slope<br>(95% CI) | 1.0 (0.9, 1.1) | 0.9 (0.6, 1.1) | 0.6 (0.3, 0.9) | 1.0 (0.9, 1.1) | | | Core Method: Corneal Specular Microscopic Variables Assessed with Table 1 the Two Devices – All Configurations – All Subjects – Effectiveness Population Abbreviations: CD = endothelial cell density; CI = confidence interval; CV = coefficient of variation of endothelial cell area; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation 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 (Tomey Specular Microscope EM-4000) - (Konan CellChek XL). The mean differences as a % of the CellChek reading are calculated for each subject first and then summarized. # Coefficient of Variation (CV) of Endothelial Cell Area For the Core Method, for all configurations and all subjects, the Tomey EM-4000 mean (SD) difference, as illustrated on the Bland Altman plots (Figure 4) was 1.65% (SD 11.304%). Plots of the device difference by the CellChek XL value are presented in (Figure 5). The Deming regression lines showed an associated value of 0.6226 (Figure 6). {9}------------------------------------------------ Bland-Altman Plot – Observed Data – Coefficient of Variation Figure 4 Endothelial Cell Area (CV) - Core Method - All Subjects - Effectiveness Population Image /page/9/Figure/1 description: This image is a scatter plot with the title 'Difference' on the y-axis and 'Mean' on the x-axis. The x-axis ranges from 20 to 48, while the y-axis ranges from -10 to 25. There are two horizontal green lines at approximately y=7 and y=-7, and a horizontal red line at y=0. The scatter plot contains numerous blue data points. Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs). The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). #### Device Difference by Konan CellChek XL Value - Coefficient of Figure 5 Variation Endothelial Cell Area (CV) - Core Method - All Subjects - Effectiveness Population Image /page/9/Figure/4 description: This image is a scatter plot with the title "Device Difference" on the y-axis and "Konan CELLCHEK XL Value" on the x-axis. The x-axis ranges from 20 to 44, while the y-axis ranges from -10 to 25. The data points are scattered across the plot, showing the relationship between the two variables. Most of the data points are between 24 and 40 on the x axis. The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). {10}------------------------------------------------ Deming Regression Plot - Tomey EM-4000 by Konan CellChek XL -Figure 6 Coefficient of Variation Endothelial Cell Area (CV) - Core Method - All Subjects -Effectiveness Population Image /page/10/Figure/1 description: This image is a scatter plot that compares Tomey values to Konan CELLCHEK XL values. The x-axis represents the Konan CELLCHEK XL values, ranging from 10 to 60, while the y-axis represents the Tomey values, ranging from 10 to 70. The plot includes a Deming Regression Line and a 45 Degree Line, which are used to analyze the relationship between the two sets of values. The data points are clustered between 25 and 40 on the x-axis and 25 and 45 on the y-axis. ## Percent Hexagonality For the Core Method, for all configurations and all subjects, the Tomey EM-4000 mean (SD) % HEX compared to the CellChek XL was 0.70% (SD 15.091%). Bland Altman plots with data as a percentage of the mean are presented in Figure 7. Plots of the device difference by the CellChek XL value are presented in Figure 8. The Deming regression lines showed an associated correlation value of 0.5549 (Figure 9). {11}------------------------------------------------ Figure 7 Bland-Altman Plot – Observed Data – % Hexagonality (HEX) – Core Method - All Subjects - Effectiveness Population Image /page/11/Figure/1 description: The image is a scatter plot with two axes labeled "Mean" and "Difference". The x-axis, "Mean", ranges from 30 to 80, while the y-axis, "Difference", ranges from -50 to 30. A red horizontal line is at y=0, and two green horizontal lines are at approximately y=14 and y=-14. The scatter plot shows a cluster of points mostly between x=50 and x=70, with a few outliers. Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs). The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). Device Difference by CellChek XL Value – % Hexagonality – Core Figure 8 Method - All Subjects - Effectiveness Population Image /page/11/Figure/4 description: This image is a scatter plot with the x-axis labeled "Konan CELLCHEK XL Value" ranging from 30 to 90, and the y-axis labeled "Device Difference" ranging from -50 to 30. The data points are clustered, showing a negative correlation between the two variables. As the Konan CELLCHEK XL Value increases, the Device Difference tends to decrease. The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL). {12}------------------------------------------------ Deming Regression Plot - Tomey EM-4000 by Konan CellChek XL -Figure 9 % Hexagonality (HEX) - Core Method - All Subjects - Effectiveness Population Image /page/12/Figure/1 description: This image is a scatter plot comparing "Tomey Value" and "Konan CELLCHEK XL". The x-axis represents "Konan CELLCHEK XL" with values ranging from 30 to 90, while the y-axis represents "Tomey Value" with values ranging from 10 to 110. The plot includes two lines: a blue line labeled "Deming Regression Line" and a red dashed line labeled "45 Degree Line", along with scattered blue points representing the data. ### Central Corneal Thickness For the Core Method, for all configurations and all subjects, the Tomey EM-4000 mean (SD) CCT compared to the CellChek XL was -3.11% (SD 3.995%). Bland Altman plots with data as a percentage of the mean are presented in Figure 10. Plots of the device difference by the CellChek XL value are presented in Figure 11. The Deming regression lines showed an associated correlation value of 0.8561 (Figure 12). {13}------------------------------------------------ Bland-Altman Plot -- Observable Data -- Central Corneal Thickness (CCT) --Figure 10 Core Method – All Subjects – Effectiveness Population Image /page/13/Figure/1 description: This image is a scatter plot with the title "Difference" on the y-axis and "Mean" on the x-axis. The x-axis ranges from 400 to 700, while the y-axis ranges from -70 to 50. There are three horizontal lines on the plot at approximately -65, -18, and 28. Note: The red line is the mean and the green lines are the LOAs. The differences are calculated as (Tomey EM-4000) – (Konan CellChek XL) Device Difference by CellCheck XL Value – Central Corneal Thickness (CCT) Figure 11 - Core Method - All Subject - Effectiveness Population. Image /page/13/Figure/4 description: This image is a scatter plot with the title "Device Difference" on the y-axis and "Konan CELLCHEK XL Value" on the x-axis. The x-axis ranges from 400 to 750, while the y-axis ranges from -70 to 40. The scatter plot shows a cluster of blue points, indicating the relationship between the two variables. The points are concentrated between x values of 500 and 600. The differences are calculated as (Tomey EM-4000) - (Konan CellChek XL) {14}------------------------------------------------ Figure 12 Deming Regression Plot – Tomey EM-4000 by Konan CellChek XL – Central Corneal Thickness (CCT) – Core Method – All Subjects – Effectiveness Population Image /page/14/Figure/1 description: This image is a scatter plot comparing Tomey Value and Konan CELLCHEK XL. The x-axis represents Konan CELLCHEK XL, ranging from 400 to 750, while the y-axis represents Tomey Value, also ranging from 400 to 750. The plot includes a Deming Regression Line and a 45 Degree Line, providing a visual comparison between the two measurement methods. Table 2 Core Method: Precision Analyses - All Subjects - Effectiveness Population | Variable | Tomey EM-4000<br>N=44 | Konan CellChek<br>N=44 | |-------------------------------------------------------------|-----------------------|------------------------| | Endothelial Cell Density | | | | Repeatability SD | 49.9 | 65.9 | | Repeatability SD as a % of the Mean | 2.0% | 2.5% | | Repeatability Limit | 139.6 | 184.4 | | Repeatability Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.7570 | -- | | Reproducibility SD | 54.6 | 72.7 | | Reproducibility SD as a % of the Mean | 2.2% | 2.8% | | Reproducibility Limit | 152.9 | 203.4 | | Reproducibility Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.7514 | -- | | Variable | Tomey EM-4000<br>N=44 | Konan CellChek<br>N=44 | | Coefficient of Variation of Endothelial Cell<br>Area (CV) | | | | Repeatability SD | 2.0 | 2.2 | | Repeatability SD as a % of the Mean | 6.1% | 7.1% | | Repeatability Limit | 5.5 | 6.1 | | Repeatability Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.8925 | --- | | Reproducibility SD | 2.1 | 2.3 | | Reproducibility SD as a % of the Mean | 6.5% | 7.4% | | Reproducibility Limit | 5.8 | 6.4 | | Reproducibility Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.9062 | --- | | % Hexagonality | | | | Repeatability SD | 3.6 | 4.3 | | Repeatability SD as a % of the Mean | 5.9% | 6.8% | | Repeatability Limit | 10.1 | 11.9 | | Repeatability Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.8449 | --- | | Reproducibility SD | 4.0 | 4.3 | | Reproducibility SD as a % of the Mean | 6.5% | 6.9% | | Reproducibility Limit | 11.2 | 12.0 | | Reproducibility Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.9271 | --- | | Central Corneal Thickness (CCT) | | | | Repeatability SD | 5.9 | 17.7 | | Repeatability SD as a % of the Mean | 1.1% | 3.1% | | Repeatability Limit | 16.4 | 49.7 | | Repeatability Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.3298 | --- | | Reproducibility SD | 7.6 | 26.6 | | Reproducibility SD as a % of the Mean | 1.4% | 4.7% | | Reproducibility Limit | 21.4 | 74.4 | | Reproducibility Ratio (TOMEY EM-4000/<br>Konan CellChek XL) | 0.2874 | --- | {15}------------------------------------------------ Abbreviations: SD = standard deviation 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. Overall, within eye/subject variability results were reasonably similar for both machines for the parameters measured, as seen in Table 2. The precision of the two devices was assessed with repeatability and reproducibility measures: the first within a given subject and the second {16}------------------------------------------------ within and among configurations. With regard to overall precision, using the core method, the largest component of variation was the subject to subject variation. The EM-4000 machine was slightly less variable than the CellChek XL machine for all variables: CD, CV, %HEX and CCT. In summary, for the parameters measured the agreement and precision results of the Tomey EM-4000 core method and the Konan CellChek XL center method were found to be substantially equivalent. ## CONCLUSIONS The Tomey EM-4000 has the same intended use and indications for use, technological characteristics, and principles of operation as the previously cleared predicate. The differences between the subject device and the predicate device have been assessed in a human clinical trial which found agreement, accuracy and precision between the two devices. Therefore, the Tomey EM-4000 and the predicate device were determined to be substantially equivalent.