Konan Specular Microscope XVII

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. March 26, 2020 Konan Medical, Inc. % Alan Donald President Matrix Medical Consulting Inc 8880 Rio San Diego Drive Suite 800 San Diego, California 92108 Re: K191558 Trade/Device Name: Konan Specular Microscope XVII Regulation Number: 21 CFR 886.1850 Regulation Name: AC-Powered Slitlamp Biomicroscope Regulatory Class: Class II Product Code: NQE Dated: February 12, 2020 Received: February 18, 2020 Dear Alan Donald: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's {1}------------------------------------------------ requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems. For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, Elvin Ng Acting Assistant Director DHT1A: Division of Ophthalmic Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ | DEPARTMENT OF HEALTH AND HUMAN SERVICES | | |--------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Food and Drug Administration | | | | Form Approved: OMB No. 0910-0120 | | | Expiration Date: 06/30/2020 | | Indications for Use | | | | See PRA Statement below. | | 510(k) Number (if known) | K191558 | | Device Name | Konan Specular Microscope XVII | | Indications for Use (Describe) | The Konan Specular Microscope XVII, CellChek 20, 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) | | | <label><input checked="checked" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D)</label> | <label><input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C)</label> | 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 FDA 3881 (7/17) | Page 1 of 1 | PSC Publishing Services (301) 443-6740 EF | |----------------------|-------------|-------------------------------------------| |----------------------|-------------|-------------------------------------------| {3}------------------------------------------------ # 510(k) Summary {4}------------------------------------------------ The following 510(k) Summary is being submitted in accordance with the requirements of SMDA 1990 and CFR 807.92. # 510(k) Summary # Submitter Information | A. Company Name: | Konan Medical, Inc. | |---------------------------|-----------------------------------------------------------| | B. Company Address: | 10-29, Miyanishicho, Nishinomiya<br>Hyogo 662-0976, Japan | | C. Company Phone: | +81-798-36-3456 | | D. Company facsimile: | +81-798-26-1028 | | E. Contact Person: | Tatsuya Kasahara | | F. Date Summary Prepared: | March 23, 2020 | # Device Identification | A. Device Trade Name: | Konan Specular Microscope XVII, CellChek 20 | |----------------------------------|---------------------------------------------| | B. Common Name: | Specular Microscope | | C. Classification Name(s): | AC-powered Slit Lamp Biomicroscope | | D. Classification Regulation(s): | 886.1850 | | E. Device Class: | Class 2 | | F. Product Codes: | NQE | | G. Advisory Panel: | Ophthalmic | # Identification of Predicate Device The predicate device is the Konan Specular Microscope XIV, CellChek Plus, which was cleared by FDA under 510(k) number K120264 on April 11, 2012. In addition, the company has utilized the NONCON ROBO PACHY F&A, K062763, as a reference device. {5}------------------------------------------------ # Device Description The Konan Specular Microscope XVII, CellChek 20, is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of corneal endothelium and for measurement of the thickness of the cornea. Cell counting and analysis program are included, and allow for analysis of the images of the cell distribution of the eye. When photographing the corneal endothelium, the device performs the alignment and automatically focuses by capturing the reflected light from patient's eye with the camera. The device permits visual inspection and photography of the corneal endothelium and measurement of the corneal thickness without any object contacting the eye. It features focusing by means of infrared techniques, as well as computer-assisted cell counting and cell analysis capabilities. The computer functions are also used to aid in setting up the various features of the machine and to aid in photography. Photographic images are temporarily stored in the system's memory and can be preserved by using a printer. Both the image of the corneal endothelium and the various computerized control functions are displayed on the touch screen monitor. The parts of the device that come into contact with a patient are the forehead rest and the chin rest. Their material is acrylonitrile butadiene styrene (ABS), the same material used in reference device and one with proven biocompatibility. The function of the software installed in the device is to calculate mainly the cell density, the coefficient of variation of cell area and the percent hexagonality. In the manual methods, Actual identification if the cells and cell boundaries is done by the (physician) user. In the automatic method, the software detects the cells and cell boundaries, however, the user is given the opportunity to make corrections. In use, the user interacts with the software by visually placing dots in the center of cells as or by tracing cell boundaries as they appear or on a screen or uses the automatic algorithm. ### Indication for Use The Konan Specular Microscope XVII, CellChek 20, 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. {6}------------------------------------------------ # Technological Characteristics The Konan Specular Microscope XVII, CellChek 20, is technically equivalent to the Konan specular Microscope XIV, CellChek Plus. One of the principal design modifications for the device is that the mechanical unit used for alignment has changed. The mechanical unit of CellChek 20 has only three axes which work for X (right - left) - Y (up - down) - Z (forward - backward) alignment between the optics and a patient's eye. Therefore the patient needs to fixate on a peripheral target to obtain an image of endothelial cells at the peripheral position over the cornea. Another of the principal design modifications for the device is that the data analysis method has changed. The data analysis of CellChek 20 method consists of the Trace method with/without Auto-trace (which does not need to input parameter S, M, L or XL for analysis), the Center method with/without Auto-input (which uses the same algorithm as Auto-trace) and the Flex Center method with/without Auto-input (which uses the same algorithm as Auto-trace). A smaller CPU board (mother board) was implemented, and a new computer program was installed for the mechanical system and the data analysis system of CellChek 20. | Comparative table between CellChek Plus and CellChek 20 | | | | |---------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Model name | CellChek Plus | CellChek 20 | Comparison | | 510(k) No. | K120264 | To Be Assigned by<br>FDA | | | Device name<br>registered | Konan Specular<br>Microscope XIV | Konan Specular<br>Microscope XVII | | | Intended use | The device is a<br>non-contact<br>ophthalmic<br>microscope, optical<br>pachymeter, and<br>camera intended for<br>examination of the<br>corneal endothelium<br>and for measurement<br>of the thickness of the | The device is a<br>non-contact<br>ophthalmic<br>microscope, optical<br>pachymeter, and<br>camera intended for<br>examination of the<br>corneal endothelium<br>and for measurement<br>of the thickness of | Same | | | cornea. | the cornea. | | | Composition | The device is<br>composed of the<br>optical unit, the<br>mechanical unit, the<br>electrical unit and the<br>display. | The device is<br>composed of the<br>optical unit, the<br>mechanical unit and<br>the power unit which<br>includes the electrical<br>unit and the display. | Different on expression.<br>No safety/effectiveness<br>concern. | | Appearance | Image: Slit lamp | Image: Slit lamp | Different.<br>No safety/effectiveness<br>concern. | | Size | 683(H) x 365(W) x<br>451(D) mm | 451(H) x 310(W) x<br>459(D) mm | Different.<br>No safety/effectiveness<br>concern. | | Electric rating | Voltage: 100-230VAC<br>Frequency: 50/60Hz,<br>Power: 150VA | Voltage:<br>100-240VAC<br>Frequency: 50/60Hz<br>Power: 100VA | Almost same<br>No safety/effectiveness<br>concern. | | Class (Electrical<br>Safety) | Class I<br>Type B applied part | Class I<br>Type B applied part | Same | | Operating<br>Principle | The photographing<br>the corneal<br>endothelium, the<br>device performs the<br>alignment and<br>automatically focuses<br>by capturing the<br>reflected light from the<br>patient's eye with the<br>camera. | The photographing<br>the corneal<br>endothelium, the<br>device performs the<br>alignment and<br>automatically<br>focuses by capturing<br>the reflected light<br>from the patient's eye<br>with the camera. | Different on axes.<br>No safety/effectiveness<br>concern. | | | | | | | | The alignment is<br>performed by 5 axes<br>which are X (back and<br>forth), Y (right and<br>left), Z (up and down)<br>θX (horizontal turn)<br>and θY (vertical turn). | The alignment is<br>performed by 3 axes<br>which are X (back<br>and forth), Y (right<br>and left) and Z (up<br>and down). | | | Photographed<br>Area | 0.24 x 0.46 mm² | 0.25 x 0.55 mm² | Almost same.<br>No safety/effectiveness<br>concern. | | Analysis<br>method | CellChek software:<br>Corner method<br>Auto trace method<br>Center method<br>----------<br>Flex Center method<br>---------- | CellChek software:<br>Trace method<br>Auto Trace method<br>Center method<br>Auto Center<br>method<br>F Center method<br>Auto F Center<br>method | Different (Algorithm of<br>Trace method, Center<br>method and F center<br>method has not<br>changed).<br>No safety/effectiveness<br>concern.<br>• Nomenclature was<br>changed "Corner<br>method" to "Trace<br>method" and "Flex<br>Center method" to<br>"F Center method".<br>• The Auto trace<br>method does not<br>need to input<br>parameter S, M, L<br>or XL for analysis.<br>• "Auto Center<br>method" and "Auto<br>F Center method"<br>were added. They<br>use the same | | Materials of<br>Patient<br>Contacting<br>Parts | PTFE (forehead rest)<br>and ABS resin (chin<br>rest) | ABS resin (forehead<br>rest and chin rest) | algorithm of “Auto<br>Trace method” and<br>the center point of<br>the endothelial cell<br>is calculated as the<br>gravity point of the<br>endothelial cell by<br>“Auto Trace<br>method”.<br><br>Different.<br>No safety/effectiveness<br>concern.<br>Material of<br>forehead rest was<br>changed to the<br>same material of<br>chin rest. | {7}------------------------------------------------ {8}------------------------------------------------ {9}------------------------------------------------ # Summary of Testing - A. Non Clinical Testings The following testing was performed on the Konan Specular Microscope XVII, CellChek 20: - The CellChek 20 device was subjected to electrical safety testing in accordance with ANSI/AAMI ES 60601-1. - The CellChek 20 device was subjected to electromagnetic compatibility (EMC) testing in accordance with IEC 60601-1-2. - The CellChek 20 device was subjected to performance testing in accordance with ISO 15004-1. - The CellChek 20 device was subjected to optical radiation safety testing in accordance with ANSI Z80.36. - The CellChek 20 device was subjected to software validation testing in accordance with IEC 62304. ### Performance Testing - Clinical {10}------------------------------------------------ A prospective clinical study was conducted to assess the agreement, accuracy, and precision of the Konan Specular Microscope XVII, CellChek 20 by comparing the analytical results obtained with the NONCON ROBO PACHY F&A, a reference device, and also the predicate device for the Konan Specular Microscope XIV, CellChek Plus. This clinical performance testing includes the assessment of the agreement, accuracy, and precision of each of the 6 analysis methods, Trace Method, Auto Trace Method, Center Method, Auto Center Method, Flex Center Method, and Auto Flex Center Method of Konan Specular Microscope XVII, CellChek 20 by comparing with Center Method of NONCON ROBO PACHY F&A. The examinees are all of the patients who came to the ophthalmic clinic, which has agreed to cooperate with this study, after the study start date. Some of the ophthalmic staffs basically photographed the right eyes of the examinees with Konan Specular Microscope XVII, CellChek 20 and NONCON ROBO PACHY F&A. However, when their right eyes could not be clearly photographed, the left eyes were photographed. Three analysts analyzed the examinees' images with each of the 6 methods, Center Method, Auto Center Method, Trace Method, Auto Trace Method, Flex Center Method, Auto Flex Center Method, of CellChek 20, and Center Method of F&A. This study protocol pre-described criteria for the agreement limits is that the analysis result of each of the methods of CellChek 20 has a positive correlation with that of Center Method of F&A. The mean (SD) age of the 80 subjects, whose breakdown was 55 females and 25 males, of this study was 65.6 (10.8) years. No adverse events occurred in any examinees during this study. Additionally, no other safety issues of any kinds arose from the subject device and the reference device. The instruments of both of the devices were found to be safe and reliable in the assessment of corneal function. The primary efficiency endpoints are the agreement and precision of the 3 variables, that is, Corneal Endothelial Cell Density, Coefficient of Variation, and Hexagonality (hereinafter mentioned as CD, CV, and HEX, respectively). The discussion on the results of this performance testing is shown as follows. {11}------------------------------------------------ l. Agreement/Accuracy Analysis (Comparison between subject device and reference device) - 1) Cornea Measuring Area: Center Area Analysis Method: Center Method of Subject Device and Reference Device Table 1 Three Corneal Specular Microscopic Variables Assessed with Center Method of Subject Device and Reference Device – Center area | N=80 | CD (/mm²) | CV (%) | HEX (%) | |--------------------------------------------------------------|----------------------|-----------------|-------------------| | NONCON ROBO PACHY F&A (Reference Device) | | | | | Average (SD) | 2717.1 (486.74) | 33.8 (5.12) | 58.1 (7.42) | | Median | 2738.5 | 33.0 | 58.3 | | Min - Max | 849 - 3937 | 25 - 56 | 37 - 77 | | Konan Specular Microscope XVII, CellChek 20 (Subject Device) | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min - Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Device Comparisons | | | | | Average Difference (SD) | 215.6 (151.15) | 0.3 (3.85) | 1.8 (7.27) | | Average Difference (SD) as<br>a % of F&A reading | 7.94% (5.563%) | 0.74% (11.403%) | 3.08% (12.523%) | | 95% LOA | (-86.7, 517.9) | (-7.5, 8.0) | (-12.8, 16.3) | | Correlation (R²) | 0.9193 | 0.5677 | 0.2460 | | Deming Regression<br>Intercept (95% CI) | 107.6 (105.8, 109.4) | 5.5 (3.6, 7.5) | 32.5 (30.6, 34.5) | | Deming Regression Slope<br>(95% CI) | 1.0 (1.0, 1.0) | 0.8 (0.8, 0.9) | 0.5 (0.4, 0.5) | Abbreviations: CD = corneal endothelial cell density; CI = confidence interval; CV = coefficient of variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation The average differences were calculated as (Konan Specular Microscope XVII, CellChek 20) - (NONCON ROBO PACHY F&A). The average differences as a % of NONCON ROBO PACHY F&A reading were calculated by dividing the average differences with the averages of the reference device. The 95% LOA's were calculated as the average differences +/- 2SD's. {12}------------------------------------------------ a) CD Corneal endothelial cell density as measured with the subject device had the average (SD) of 2932.7 (527.83) compared with those of 2717.1 (486.74) for the reference device. The average difference (SD) were 215.6 (151.15). The Deming regression lines had the associated R2 value of 0.9193. b) Coefficient of Variation as measured with the subject device had the average (SD) of 34.0 (5.73) compared with those of 33.8 (5.12) for the reference device. The average difference (SD) were 0.3 (3.85). The Deming regression lines had the associated R2 value of 0.5677. ### c) Percent of Hexagonality as measured with the subject device had the average (SD) of 59.9 (7.05) compared with those of 58.1 (7.42) for the reference device. The average difference (SD) were 1.8 (7.27). The Deming regression lines had the associated R2 value of 0.2460. #### 2) Cornea Measuring Area: Peripheral Area Analysis Method: Center Method of Subject Device and Reference Device | | | Table 2 Three Corneal Specular Microscopic Variables Assessed with Center Method of Subject | | | | | |--|--|---------------------------------------------------------------------------------------------|--|--|--|--| | | | Device and Reference Device – Peripheral Area | | | | | | N=80 | CD (/mm²) | CV (%) | HEX (%) | |--------------------------------------------------------------|-----------------|-----------------|-----------------| | NONCON ROBO PACHY F&A (Reference Device) | | | | | Average (SD) | 2782.4 (464.10) | 33.5 (5.25) | 58.8 (6.98) | | Median | 2825.0 | 32.9 | 59.0 | | Min – Max | 884 - 3802 | 23 - 55 | 34 - 76 | | Konan Specular Microscope XVII, CellChek 20 (Subject Device) | | | | | Average (SD) | 2969.5 (507.65) | 34.4 (6.36) | 59.8 (6.00) | | Median | 3007.5 | 33.7 | 59.9 | | Min – Max | 904 - 4021 | 25 - 61 | 42 - 71 | | Device Comparisons | | | | | Average Difference (SD) | 187.1 (144.61) | 0.8 (4.57) | 1.0 (7.28) | | Average Difference (SD) as<br>a % of F&A reading | 6.72% (5.197%) | 2.46% (13.642%) | 1.67% (12.375%) | {13}------------------------------------------------ 510(k) Summary – Konan Specular Microscope XVII, CellChek 20 | 95% LOA | (-102.1, 476.3) | (-8.3, 10.0) | (-13.6, 15.5) | |-----------------------------------------|-------------------|----------------|-------------------| | Correlation (R2) | 0.9209 | 0.4974 | 0.1439 | | Deming Regression<br>Intercept (95% CI) | 48.8 (46.9, 50.8) | 5.7 (3.8, 7.6) | 40.6 (38.6, 42.6) | | Deming Regression Slope<br>(95% CI) | 1.0 (1.0, 1.1) | 0.9 (0.8, 0.9) | 0.3 (0.3, 0.4) | Abbreviations: CD = corneal endothelial cell density; CI = confidence interval; CV = coefficient of variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation The average differences were calculated as (Konan Specular Microscope XVII, CellChek 20) - (NONCON ROBO PACHY F&A). The average differences as a % of NONCON ROBO PACHY F&A reading were calculated by dividing the average differences with the averages of the reference device. The 95% LOA's were calculated as the average differences +/- 2SD's. #### a) CD Corneal endothelial cell density as measured with the subject device had the average (SD) of 2969.5 (507.65) compared with those of 2782.4 (464.10) for the reference device. The average difference (SD) were 187.1 (144.61). The Deming regression lines had the associated R2 value of 0.9209. # b) Coefficient of Variation as measured with the subject device had the average (SD) of 34.4 (6.36) compared with those of 33.5 (5.25) for the reference device. The average difference (SD) were 0.8 (4.57). The Deming regression lines had the associated R2 value of 0.4974. # c) HEX Percent of Hexagonality as measured with the subject device had the average (SD) of 59.8 (6.00) compared with those of 58.8 (6.98) for the reference device. The average difference (SD) were 1.0 (7.28). The Deming regression lines had the associated R2 value of 0.1439. {14}------------------------------------------------ - II. Agreement/Accuracy Analysis (Comparison between Center Method vs Trace Method, Auto Trance Method, Auto Center Method, Flex Center Method, and Auto Flex Center Method of Subject Device (Konan Specular Microscope XVII, CellChek 20)) - a) Corneal Measuring Area: Center Area Analysis Method: Center Method vs Trace Method of Subject Device Table 3 Three Corneal Specular Microscopic Variables Assessed with Two Analysis Methods -Center Method vs Trace Method – Center Area | N=80 | CD (/mm²) | CV (%) | HEX (%) | |-----------------------------------------------------------------------------------------------------|----------------------|--------------------|------------------| | Center Method | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min – Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Trace Method | | | | | Average (SD) | 2931.7 (531.31) | 29.5 (7.68) | 57.4 (7.78) | | Median | 2897.5 | 28.5 | 58.4 | | Min – Max | 820 - 4565 | 17 - 52 | 38 - 73 | | Method Comparisons | | | | | Average Difference (SD) | -1.0 (28.00) | -4.5 (4.13) | -2.4 (3.39) | | Average Difference (SD) as<br>a % of Center Method<br>reading | -0.03% (0.955%) | -13.34% (12.132%) | -4.06% (5.671%) | | 95% LOA | (-57.0, 55.0) | (-12.8, 3.7) | (-9.2, 4.4) | | Correlation (R2) | 0.9973 | 0.7215 | 0.8097 | | Deming Regression<br>Intercept (95% CI) | -16.3 (-18.1, -14.5) | -9.2 (-11.3, -7.2) | -2.0 (-4.7, 0.7) | | Deming Regression Slope<br>(95% CI) | 1.0 (1.0, 1.0) | 1.1 (1.1, 1.2) | 1.0 (0.9, 1.0) | | Abbreviations: CD = corneal endothelial cell density; Cl = confidence interval; CV = coefficient of | | | | | variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation | | | | The average differences were calculated as (Trace Method) - (Center Method). The average differences as a % of Center Method reading were calculated by dividing the average differences with the averages of Center Method. The 95% LOA's were calculated as the average differences +/- 2SD's. {15}------------------------------------------------ (i) CD > Corneal endothelial cell density as measured with Trace Method had the average (SD) of 2931.7 (531.31) compared with those of 2932.7 (527.83) for Center Method. The average difference (SD) were -1.0 (28.00). The Deming regression lines had the associated R2 value of 0.9973. - CV (ii) Corneal endothelial cell density as measured with Trace Method had the average (SD) of 29.5 (7.68) compared with those of 34.0 (5.73) for Center Method. The average difference (SD) were -4.5 (4.13). The Deming regression lines had the associated R2 value of 0.7215. - (iii) HEX Corneal endothelial cell density as measured with Trace Method had the average (SD) of 57.4 (7.78) compared with 59.9 (7.05) for those of Center Method. The average difference (SD) were -2.4 (3.39). The Deming regression lines had the associated R2 value of 0.8097. #### b) Cornea Measuring Area: Center Area Analysis Method: Center Method vs Auto Trance Method of Subject Device Table 4 Three Corneal Specular Microscopic Variables Assessed with Two Analysis Methods -Center Method vs Auto Trance Method - Center Area | N=80 | CD (/mm²) | CV (%) | HEX (%) | |----------------------------------------------------|-----------------|-------------------|-----------------| | Center Method | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min – Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Auto Trace Method | | | | | Average (SD) | 2756.1 (430.05) | 19.5 (4.34) | 59.5 (6.51) | | Median | 2816.0 | 19.0 | 60.0 | | Min – Max | 900 - 3475 | 11 - 35 | 38 - 73 | | Device Comparisons | | | | | Average Difference (SD) | -176.6 (213.31) | -14.5 (3.77) | -0.3 (5.80) | | Average Difference (SD) as<br>a % of Center Method | -6.02% (7.273%) | -42.67% (11.065%) | -0.58% (9.695%) | {16}------------------------------------------------ 510(k) Summary – Konan Specular Microscope XVII, CellChek 20 | reading | | | | |---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|-----------------|-------------------| | 95% LOA | (-603.3, 250.0) | (-22.1, -7.0) | (-12.0, 11.3) | | Correlation (R2) | 0.8479 | 0.5682 | 0.4050 | | Deming Regression Intercept (95% CI) | 555.8 (554.2, 557.4) | 0.1 (-1.5, 1.6) | 24.3 (22.1, 26.5) | | Deming Regression Slope (95% CI) | 0.8 (0.7, 0.8) | 0.6 (0.5, 0.6) | 0.6 (0.6, 0.6) | | Abbreviations: CD = corneal endothelial cell density; CI = confidence interval; CV = coefficient of variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation | | | | | The average differences were calculated as (Auto Trace Method) - (Center Method). | | | | | The average differences as a % of Center Method reading were calculated by dividing the average differences with the averages of Center Method. | | | | | The 95% LOA's were calculated as the average differences +/- 2SD's. | | | | #### CD (i) Corneal endothelial cell density as measured with Auto Trace Method had the average (SD) of 2756.1 (430.05) compared with those of 2932.7 (527.83) for Center Method. The average difference (SD) were -176.6 (213.31). The Deming regression lines had the associated R2 value of 0.8479. #### (ii) CV Corneal endothelial cell density as measured with Auto Trace Method had the average (SD) of 19.5 (4.34) compared with those of 34.0 (5.73) for Center Method. The average difference (SD) were -14.5 (3.77). The Deming regression lines had the associated R2 value of 0.5682. - HEX (iii) Corneal endothelial cell density as measured with Auto Trace Method had the average (SD) of 59.5 (6.51) compared with those of 59.9 (7.05) for Center Method. The average difference (SD) were -0.3 (5.80). The Deming regression lines had the associated R2 value of 0.4050. {17}------------------------------------------------ #### c) Cornea Measuring Area: Center Area Analysis Method: Center Method vs Auto Center Method of Subject Device Table 5 Three Corneal Specular Microscopic Variables Assessed with Two Analysis Method -Center Method vs Auto Center Method – Center Area | N=80 | CD (/mm²) | CV (%) | HEX (%) | |---------------------------------------------------------------|----------------------|----------------|-------------------| | Center Method | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min - Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Auto Center Method | | | | | Average (SD) | 2777.7 (433.55) | 34.3 (5.83) | 59.8 (6.96) | | Median | 2828.0 | 34.5 | 60.0 | | Min - Max | 921 - 3434 | 24 - 55 | 36 - 71 | | Device Comparisons | | | | | Average Difference (SD) | -155.0 (210.98) | 0.3 (3.39) | -0.1 (4.67) | | Average Difference (SD) as<br>a % of Center Method<br>reading | -5.29% (7.194%) | 0.75% (9.966%) | -0.16% (7.796%) | | 95% LOA | (-577.0, 266.9) | (-6.5, 7.0) | (-9.4, 9.2) | | Correlation (R2) | 0.8504 | 0.6854 | 0.6055 | | Deming Regression<br>Intercept (95% CI) | 556.3 (554.7, 557.9) | 5.6 (3.9, 7.4) | 13.8 (11.4, 16.2) | | Deming Regression Slope<br>(95% CI) | 0.8 (0.8, 0.8) | 0.8 (0.8, 0.9) | 0.8 (0.7, 0.8) | The average differences as a % of Center Method reading were calculated by dividing the average differences with the averages of Center Method. The 95% LOA's were calculated as the average differences +/- 2SD's. {18}------------------------------------------------ CD (i) > Corneal endothelial cell density as measured with Auto Center Method had the average (SD) of 2777.7 (433.55) compared with those of 2932.7 (527.83) for Center Method. The average difference (SD) were -155.0 (210.98). The Deming regression lines had the associated R2 value of 0.8504. - CV (ii) Corneal endothelial cell density as measured with Auto Center Method had the average (SD) of 34.3 (5.83) compared with those of 34.0 (5.73) for Center Method. The average difference (SD) were 0.3 (3.39). The Deming regression lines had the associated R2 value of 0.6854. - (iii) HEX Corneal endothelial cell density as measured with Auto Center Method had the average (SD) of 59.8 (6.96) compared with those of 59.9 (7.05) for Center Method. The average difference (SD) were -0.1 (4.67). The Deming regression lines had the associated R2 value of 0.6055. #### d) Cornea Measuring Area: Center Area Analysis Method: Center Method vs Flex Center Method of Subject Device | Table 6 Three Corneal Specular Microscopic Variables Assessed with Two Analysis Method - | | | |------------------------------------------------------------------------------------------|--|--| | Center Method vs Flex Center Method – Center Area | | | | N=80 | CD (/mm²) | CV (%) | HEX (%) | |----------------------------------------------------|-----------------|----------------|----------------| | Center Method | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min – Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Flex Center Method | | | | | Average (SD) | 2917.8 (531.26) | 36.0 (5.80) | 59.9 (5.91) | | Median | 2899.2 | 35.0 | 60.2 | | Min – Max | 822 - 4524 | 26 - 57 | 48 - 74 | | Device Comparisons | | | | | Average Difference (SD) | -14.9 (28.88) | 2.0 (1.74) | 0.1 (3.47) | | Average Difference (SD) as<br>a % of Center Method | -0.51% (0.985%) | 5.85% (5.106%) | 0.09% (5.798%) | {19}------------------------------------------------ 510(k) Summary – Konan Specular Microscope XVII, CellChek 20 | reading | | | | |------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|----------------|-------------------| | 95% LOA | (-72.6, 42.9) | (-1.5, 5.5) | (-6.9, 7.0) | | Correlation (R2) | 0.9971 | 0.9114 | 0.7587 | | Deming Regression<br>Intercept (95% CI) | -29.6 (-31.4, -27.8) | 3.1 (1.3, 5.0) | 16.2 (13.9, 18.6) | | Deming Regression Slope<br>(95% CI) | 1.0 (1.0, 1.0) | 1.0 (0.9, 1.0) | 0.7 (0.7, 0.8) | | Abbreviations: CD = corneal endothelial cell density; CI = confidence interval; CV = coefficient of<br>variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation | | | | | The average differences were calculated as (Flex Center Method) - (Center Method). | | | | The average differences as a % of Center Method reading were calculated by dividing the average differences with the averages of Center Method. The 95% LOA's were calculated as the average differences +/- 2SD's. #### CD (i) Corneal endothelial cell density as measured with Flex Center Method had the average (SD) of 2917.8 (531.26) compared with those of 2932.7 (527.83) for Center Method. The average difference (SD) were -14.9 (28.88). The Deming regression lines had the associated R2 value of 0.9971. #### (ii) CV Corneal endothelial cell density as measured with Flex Center Method had the average (SD) of 36.0 (5.80) compared with those of those of 34.0 (5.73) for Center Method. The average difference (SD) were 2.0 (1.74). The Deming regression lines had the associated R2 value of 0.9114. - HEX (iii) Corneal endothelial cell density as measured with Flex Center Method had the average (SD) of 59.9 (5.91) compared with those of 59.9 (7.05) for Center Method. The average difference (SD) were 0.1 (3.47). The Deming regression lines had the associated R2 value of 0.7587. {20}------------------------------------------------ #### Cornea Measuring Area: Center Area e) Analysis Method: Center Method vs Auto Flex Center Method of Subject Device | Table 7 Three Corneal Specular Microscopic Variables Assessed with Two Analysis Method - | | | | | |------------------------------------------------------------------------------------------|--|--|--|--| | Center Method vs Auto Flex Center Method – Center Area | | | | | | N=80 | CD (/mm²) | CV (%) | HEX (%) | |-----------------------------------------------------------------------------------------------------|----------------------|-----------------|-------------------| | Center Method | | | | | Average (SD) | 2932.7 (527.83) | 34.0 (5.73) | 59.9 (7.05) | | Median | 2915.9 | 33.2 | 59.9 | | Min – Max | 816 - 4532 | 25 - 52 | 40 - 74 | | Auto Flex Center Method | | | | | Average (SD) | 2760.8 (433.37) | 35.1 (5.84) | 59.6 (6.83) | | Median | 2835.0 | 35.0 | 60.0 | | Min – Max | 905 - 3415 | 24 - 58 | 38 - 70 | | Device Comparisons | | | | | Average Difference (SD) | -172.0 (212.44) | 1.1 (3.60) | -0.3 (5.59) | | Average Difference (SD) as<br>a % of Center Method<br>reading | -5.86% (7.244%) | 3.21% (10.586%) | -0.47% (9.342%) | | 95% LOA | (-596.9, 252.9) | (-6.1, 8.3) | (-11.5, 10.9) | | Correlation ( $R^2$ ) | 0.8480 | 0.6499 | 0.4564 | | Deming Regression<br>Intercept (95% CI) | 543.5 (541.9, 545.0) | 7.2 (5.4, 8.9) | 20.4 (18.1, 22.7) | | Deming Regression Slope<br>(95% CI) | 0.8 (0.8, 0.8) | 0.8 (0.8, 0.9) | 0.7 (0.6, 0.7) | | Abbreviations: CD = corneal endothelial cell density; Cl = confidence interval; CV = coefficient of | | | | | variation; HEX = hexagonality; LOA = limits of agreement; SD = standard deviation | | | | | The average differences were calculated as (Auto Flex Center Method) - (Center Method). | | | | | The average differences as a % of Center Method reading were calculated by dividing the average | | | | differences with the averages of Center Method. The 95% LOA's were calculated as the average differences +/- 2SD's. {21}------------------------------------------------ CD (i) > Corneal endothelial cell density as measured with Auto Flex Center had the average (SD) of 2760.8 (433.37) compared with those of 2932.7 (527.83) for Center Method. The average difference (SD) were -172.0 (212.44). The Deming regression lines had the associated R2 value of 0.8480. - CV (ii) Corneal endothelial cell density as measured with Auto Flex Center had the average (SD) of 35.1 (5.84) compared with those of 34.0 (5.73) for Center Method. The average difference (SD) were 1.1 (3.60). The Deming regression lines had the associated R2 value of 0.6499. - (iii) HEX Corneal endothelial cell density as measured with Auto Flex Center had the average (SD) of 59.6 (6.83) compared with those of 59.9 (7.05) for Center Method. The average difference (SD) were -0.3 (5.59). The Deming regression lines had the associated R2 value of 0.4564. - III. Precision Analysis - Cornea Measuring Area: Center Area 1) Analysis Method: Center Method of Subject Device vs Center Method of Reference Device Table 8 Precision Analyses for Center Method of Subject Device vs Center Method of Reference Device - Center Area | Variable | Konan Specular<br>Microscope XVII,<br>CellChek 20<br>(Subject Device)<br>Center Method | NONCON ROBO<br>PACHY F&A<br>(Reference Device)<br>Center Method | |-----------------------------------------|----------------------------------------------------------------------------------------|-----------------------------------------------------------------| | CD | | | | Repeatability SD | 9.1 | 9.8 | | Repeatability SD as a% of the Average | 0.3% | 0.4% | | Repeatability limit | 25.5 | 27.4 | | Repeatability Ratio (CellChek 20/F&A) | 0.9286 | ----- | | Reproducibility SD | 53.2 | 99.3 | | Reproducibility SD as a% of the Average | 1.8% | 3.8% | | Reproducibility limit | 149.0 | 278.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.5358 | ----- | | CV | | | | Repeatability SD | 0.4 | 0.6 | {22}------------------------------------------------ | 310(k) Summary - Konan Specular Microscope XVII, CellChek 20 | | | |--------------------------------------------------------------|--------|-------| | Repeatability SD as a% of the Average | 1.2% | 1.8% | | Repeatability limit | 1.1 | 1.7 | | Repeatability Ratio (CellChek 20/F&A) | 0.6667 | ----- | | Reproducibility SD | 0.9 | 3.2 | | Reproducibility SD as a% of the Average | 2.7% | 9.1% | | Reproducibility limit | 2.5 | 9.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.2813 | ----- | | HEX | | | | Repeatability SD | 0.8 | 1.2 | | Repeatability SD as a% of the Average | 1.3% | 2.1% | | Repeatability limit | 2.2 | 3.4 | | Repeatability Ratio (CellChek 20/F&A) | 0.6667 | ----- | | Reproducibility SD | 1.3 | 2.2 | | Reproducibility SD as a% of the Average | 2.2% | 3.8% | | Reproducibility limit | 3.6 | 6.2 | | Reproducibility Ratio (CellChek 20/F&A) | 0.5909 | ----- | 510(k) Summary – Konan Specular Microscope XVII. CellChek 20 The repeatability limit was 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. #### Cornea Measuring Area: Center Area 2) Analysis Method: Trace Method of Subject Device vs Center Method of Reference Device Table 9 Precision Analyses for Trace Method of Subject Device vs Center Method of Reference Device – Center Area | Variable | Konan Specular<br>Microscope XVII,<br>CellChek 20<br>(Subject Device)<br>Trace Method | NONCON ROBO<br>PACHY F&A<br>(Reference Device)<br>Center Method | |-----------------------------------------|---------------------------------------------------------------------------------------|-----------------------------------------------------------------| | CD | | | | Repeatability SD | 12.1 | 9.8 | | Repeatability SD as a% of the Average | 0.4% | 0.4% | | Repeatability limit | 33.9 | 27.4 | | Repeatability Ratio (CellChek 20/F&A) | 1.2347 | ------- | | Reproducibility SD | 38.6 | 99.3 | | Reproducibility SD as a% of the Average | 1.3% | 3.8% | | Reproducibility limit | 108.1 | 278.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.3887 | ------- | | CV | | | {23}------------------------------------------------ | Repeatability SD | 0.9 | 0.6 | |-----------------------------------------|--------|-------| | Repeatability SD as a% of the Average | 3.1% | 1.8% | | Repeatability limit | 2.5 | 1.7 | | Repeatability Ratio (CellChek 20/F&A) | 1.5000 | ----- | | Reproducibility SD | 2.8 | 3.2 | | Reproducibility SD as a% of the Average | 8.9% | 9.1% | | Reproducibility limit | 7.8 | 9.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.8750 | ----- | | HEX | | | | Repeatability SD | 0.6 | 1.2 | | Repeatability SD as a% of the Average | 1.0% | 2.1% | | Repeatability limit | 1.7 | 3.4 | | Repeatability Ratio (CellChek 20/F&A) | 0.5000 | ----- | | Reproducibility SD | 1.7 | 2.2 | | Reproducibility SD as a% of the Average | 3.0% | 3.8% | | Reproducibility limit | 4.8 | 6.2 | | Reproducibility Ratio (CellChek 20/F&A) | 0.7727 | ----- | 510(k) Summary – Konan Specular Microscope XVII, CellChek 20 The repeatability limit was 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. - Cornea Measuring Area: Center Area 3) Analysis Method: Auto Trace Method of Subject Device vs Center Method of Reference Device Table 10 Precision Analyses for Auto Trace Method of Subject Device vs Center Method of Reference Device – Center Area | Variable | Konan Specular<br>Microscope XVII,<br>CellChek 20<br>(Subject Device)<br>Auto Trace Method | NONCON ROBO<br>PACHY F&A<br>(Reference Device)<br>Center Method | |-----------------------------------------|--------------------------------------------------------------------------------------------|-----------------------------------------------------------------| | CD | | | | Repeatability SD | 0.0 | 9.8 | | Repeatability SD as a% of the Average | 0.0% | 0.4% | | Repeatability limit | 0.0 | 27.4 | | Repeatability Ratio (CellChek 20/F&A) | 0.0000 | ----- | | Reproducibility SD | 22.4 | 99.3 | | Reproducibility SD as a% of the Average | 0.8% | 3.8% | | Reproducibility limit | 62.7 | 278.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.2256 | ----- | {24}------------------------------------------------ | CV | | | |-----------------------------------------|--------|-------| | Repeatability SD | 0.0 | 0.6 | | Repeatability SD as a% of the Average | 0.0% | 1.8% | | Repeatability limit | 0.0 | 1.7 | | Repeatability Ratio (CellChek 20/F&A) | 0.0000 | ----- | | Reproducibility SD | 0.7 | 3.2 | | Reproducibility SD as a% of the Average | 3.6% | 9.1% | | Reproducibility limit | 2.0 | 9.0 | | Reproducibility Ratio (CellChek 20/F&A) | 0.2188 | ----- | | HEX | | | | Repeatability SD | 0.0 | 1.2 | | Repeatability SD as a% of the Average | 0.0% | 2.1% | | Repeatability limit | 0.0 | 3.4 | | Repeatability Ratio (CellChek 20/F&A) | 0.0000 | ----- | | Reproducibility SD | 1.4 | 2.2 | | Reproducibility SD as a% of the Average | 2.4% | 3.8% | | Reproducibility limit…