(75 days)
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.
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.
Here's a summary of the acceptance criteria and study details for the NIDEK Specular Microscope CEM-530, based on the provided text:
1. Table of Acceptance Criteria (Inferred from comparison with predicate) and Reported Device Performance
The acceptance criteria are implicitly defined by demonstrating substantial equivalence to the predicate device, Konan Medical, Inc. Cellchek Plus (K120264). The study aimed to show agreement and precision between the CEM-530's automated analysis and the Konan Cellchek Plus's manual center method. The tables provided present the direct comparisons that demonstrate this.
| Metric (Agreement Study) | Acceptance Criteria (Proxy: Performance of Konan Cellchek Plus) | Reported Device Performance (NIDEK CEM-530 Automated Analysis) - All Subjects (N=74) |
|---|---|---|
| Endothelial Cell Density (CD) | Mean (SD): 2738.6 (412.67) | Mean (SD): 2773.3 (343.10) |
| Mean Difference (CEM-530 vs. Konan) | Implicitly, a small difference and 95% LOA encompassing 0. | 34.7 (157.38) |
| 95% LOA (CEM-530 vs. Konan) | Implicitly, a small range. | (-280.1, 349.4) |
| Correlation (R) | Implicitly, high correlation. | 0.9296 |
| Coefficient of Variation of Endothelial Cell Area (CV) | Mean (SD): 29.6 (4.16) | Mean (SD): 27.4 (4.61) |
| Mean Difference (CEM-530 vs. Konan) | Implicitly, a small difference and 95% LOA encompassing 0. | -2.2 (4.03) |
| 95% LOA (CEM-530 vs. Konan) | Implicitly, a small range. | (-10.3, 5.9) |
| Correlation (R) | Implicitly, high correlation. | 0.5817 |
| % Hexagonality (%HEX) | Mean (SD): 62.6 (7.42) | Mean (SD): 68 (5.16) |
| Mean Difference (CEM-530 vs. Konan) | Implicitly, a small difference and 95% LOA encompassing 0. | 5.4 (8.52) |
| 95% LOA (CEM-530 vs. Konan) | Implicitly, a small range. | (-11.7, 22.4) |
| Correlation (R) | Implicitly, high correlation. | 0.1185 |
| Metric (Precision Study) | Acceptance Criteria (Proxy: Performance of Konan Cellchek Plus) | Reported Device Performance (NIDEK CEM-530 Automated Analysis) - All Subjects (N=45 for CEM-530, N=61 for Konan) |
|---|---|---|
| Endothelial Cell Density (CD) | ||
| Repeatability SD | 62.6 | 74.2 |
| Repeatability SD as % of Mean | 2.4% | 2.7% |
| Reproducibility SD | 95.5 | 83.7 |
| Reproducibility SD as % of Mean | 3.7% | 3.1% |
| Coefficient of Variation of Endothelial Cell Area (CV) | ||
| Repeatability SD | 2.7 | 1.7 |
| Repeatability SD as % of Mean | 8.4% | 6.2% |
| Reproducibility SD | 2.7 | 1.9 |
| Reproducibility SD as % of Mean | 8.5% | 6.8% |
| % Hexagonality (%HEX) | ||
| Repeatability SD | 5.3 | 3.7 |
| Repeatability SD as % of Mean | 8.7% | 5.5% |
| Reproducibility SD | 5.4 | 3.7 |
| Reproducibility SD as % of Mean | 8.9% | 5.5% |
2. Sample Size and Data Provenance
- Test Set (Effectiveness Population): 74 subjects
- Subgroups: 28 non-pathologic young eyes, 27 non-pathologic adult eyes, 19 pathologic adult eyes.
- Precision Population Subset: 45 subjects (15 from each subgroup).
- Data Provenance: Prospective clinical study conducted at one clinical site in the United States.
- Training Set: Not explicitly mentioned in this document for the new auto-cell count algorithm. However, the study states that "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." This implies that the algorithm was trained using data from the prior study.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number of experts used or their specific qualifications for establishing the ground truth of the test set against which the automated CEM-530 was compared.
However, for the agreement study, the CEM-530's automated analysis results were compared against "manual center method measurements performed with the Konan predicate device." This implies that the Konan device's manual measurements served as the comparative 'ground truth' for this specific comparison. It's not stated how many operators performed these manual measurements or their qualifications, but these are inherently human-derived and subject to human variability.
An "Additional Manual Comparison" was conducted by comparing the CEM-530 automated analysis to CEM-530 manual analysis methods across three machines/operators. This indicates that at least 3 operators were involved in generating the manual ground truth for this internal comparison. Their qualifications are not specified beyond being "operators."
4. Adjudication Method
The document does not specify an adjudication method like 2+1 or 3+1 for resolving discrepancies in ground truth establishment. Given that one of the ground truth comparators was the "manual center method measurements performed with the Konan predicate device" and the other was "CEM-530 manual analysis methods across three machines/operators," it suggests either:
- No formal adjudication process was used, and the direct manual measurements were considered the ground truth.
- If multiple operators performed the manual measurements on the Konan, their agreement would likely be part of the precision analysis but not explicitly an adjudication of a single measurement.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was one done? Yes, in a sense. The study compares the NIDEK CEM-530's automated analysis against the Konan Cellchek Plus's manual method (predicate device) and also against the CEM-530's own manual analysis method. This involves multiple "readers" (automated algorithm vs. human operators) and multiple "cases" (subjects).
- Effect size of human readers improve with AI vs without AI assistance: The study focuses on demonstrating the equivalence of the automated CEM-530 to existing manual methods (Konan) and its own manual methods. It does not provide an effect size for how much human readers improve with AI assistance. Instead, it evaluates the standalone performance of the AI (automated analysis) in comparison to manual benchmarks. The precision ratios (e.g., Repeatability Ratio, Reproducibility Ratio) illustrate how the CEM-530's automated precision compares to the Konan's and its own manual precision, often showing better or comparable precision for the automated method for CV and %Hex, and somewhat higher (less precise) for CD in the CEM-530 auto vs. manual comparison.
6. Standalone Performance Study
Yes, a standalone performance study of the algorithm (automated analysis without human-in-the-loop performance) was done explicitly. The "Agreement study" and "Precision study" sections detail the performance of the NIDEK Specular Microscope CEM-530 using its automated analysis method. These results are then compared to:
- The performance of the predicate device, Konan CellChek Plus (manual center method).
- The performance of the NIDEK CEM-530's own manual analysis method.
7. Type of Ground Truth Used
The ground truth used was human-derived manual measurements / expert consensus. Specifically:
- For the comparison against the predicate, it was "manual center method measurements performed with the Konan predicate device."
- For the internal comparison, it was "CEM-530 manual analysis methods across three machines/operators."
8. Sample Size for the Training Set
The document does not provide the specific sample size for the training set. It mentions that "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." This indicates that a dataset from a prior study (CEM-530-US-0002) was used for training/development of the new algorithm, but the size of that dataset is not specified.
9. How the Ground Truth for the Training Set was Established
The method for establishing ground truth for the training set is not explicitly detailed in the provided text. However, given that the algorithm's purpose is to automate cell counts, it's highly probable that the ground truth for training data would have been established through meticulous manual cell counting and analysis by human experts, similar to how the comparison ground truth was established.
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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.
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You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Denise L. Hampton -S
for Malvina B. Eydelman, M.D. Director Division of Ophthalmic and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173980
Device Name Specular Microscope CEM-530
Indications for Use (Describe)
The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| □ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
This summary of the 510(k) premarket notification for the NIDEK Specular Microscope CEM-530 is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR8807.92.
Date Prepared: February 28, 2018
SPONSER/ 510(k) OWNER/ MANUFACTURER
NIDEK CO., LTD. 34-14 Maehama, Hiroishi-cho, Gamagori, Aichi, 443-0038 Japan Telephone: +81-533-67-8901 Facsimile: +81-533-67-6628 E mail: yoneji mizuno(@nidek.co.jp Establishment Registration Number: 8030392
CONTACT PERSON
Ryan Bouchard Ora, Inc. 300 Brickstone Square Andover, MA 01810 Telephone: (978) 332-9574 Facsimile: (978) 689-0020 E-mail: rbouchard@oraclinical.com
NAME OF DEVICE
Trade Name: Specular Microscope CEM-530 Common Name: Specular Microscope
DEVICE CLASSIFICATION/FDA REVIEWING BRANCH
The Ophthalmic Branch has classified AC Powered Slit Lamp Biomicroscopes as Class II devices pursuant to 21 C.F.R. §886.1850.
PRODUCT CODE: CLASSIFICATION / CFR TITLE NQE, 21 CFR 886.1850
PREDICATE DEVICES
NIDEK Specular Microscope CEM-530 (K151706) Konan Medical, Inc. Cellchek Plus (K120264)
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INDICATIONS FOR USE
The NIDEK Specular Microscope CEM-530 is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of the corneal endothelium and for measurement of the thickness of the cornea.
PRODUCT DESCRIPTION
The NIDEK Specular Microscope CEM-530 which is the subject of this 510(k) is a modification to the NIDEK Specular Microscope CEM-530 cleared in K151706. The only change to the cleared device is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. The NIDEK Specular Microscope CEM-530 provides non-contact. high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the corneal endothelial cell density(CD), the coefficient of variation of corneal endothelial cell area (CV), % hexagonality of cells (%HEX), is analyzed through the captured images. The captured images and analysis results of the endothelium are used to assist in intraocular or corneal surgery, postoperative follow-up, and corneal observation such as for endothelial disorders or the corneal state of patients who wear extended-wear contact lenses. Observation is possible in the central area (visual angle: 5°) and peripheral area (visual angle: 27°) using a periphery capture function as well as in the Center of the cornea. The captured images and analysis results can be printed on the built-in printer or optional video printer, or output to an external device over LAN connection. In addition to the specular microscopy, the corneal thickness can be optically measured in a non-contact method. The CEM-530 has auto-tracking and auto-shooting functions. Results can be printed using the the built-in thermal printer or captured images can be transferred to a filing system via LAN connection.
SUBSTANTIAL EQUIVALENCE
The Specular Microscope CEM-530 and the predicate devices are all non-contact ophthalmic microscopes, optical pachymeters, and cameras intended for examination of the corneal endothelium and for measurement of the thickness of the cornea. Both the Specular Microscope CEM-530 and the predicate device offer automatic capture features and manual capture modes. The Specular Microscope CEM-530 which is the subject of this 510(k) has identical technological characteristics to the Specular Microscope CEM-530 which was cleared in K151706. The only difference is to the software which has been revised to improve the accuracy of the automated analysis method. All other aspects of the cleared device remain unchanged. Therefore, this discussion will focus primarily on the substantial equivalence to the Konan Cellcheck Plus cleared in K120264.
Both the Specular Microscope CEM-530 and the Konan Cellchek Plus have a built-in CCD camera. Both the Specular Microscope CEM-530 and the Konan Cellchek Plus include an optical pachymeter with accuracy to ± 10 microns. There were no modifications to the
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optical pachymeter in the Specular Microscope CEM-530 compared with the device cleared in K151706.
Regarding image analysis, both the CEM-530 and the predicate device offer both automatic and manual image analysis. The software of the CEM-530, which is the subject of this 510(k), has been modified to improve the accuracy of the automatic analysis methodology. Clinical performance data is provided which evaluates the precision and agreement of the automated measurements performed by the CEM-530 compared to manual center method measurements performed with the Konan predicate device. The clinical performance data demonstrates the substantial equivalence of the CEM-530 automated mode to the Konan predicate device's manual mode.
Both the CEM-530 and the predicate device comply with applicable electrical safety and light safety standards.
Therefore, in regards to technological characteristics, the Specular Microscope CEM-530 is similar to the Konan but there are some minor differences between the devices.
| SUBSTANTIAL EQUIVALENCE CHART | ||
|---|---|---|
| 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
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| Camera | Built-in CCD camera | Built-in CCD camera | Built-in CCD image sensing element camera |
|---|---|---|---|
| FlashIllumination forfocusing | Cyan LEDInfraRed LED | Cyan LEDInfraRed LED | Konan Xe tubeKonan halogen lamp |
| PachymetryTechnology | Optical | Optical | Optical |
| Measurement RangePachymetry | 300 to 1000 microns | 300 to 1000 microns | Unknown |
| Accuracy ofpachymetry | $\pm$ 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: 1endothelial image forboth right and left eyesParacentral andPeripheral modes: 15endothelial images forboth right and left eyes | Single mode: 1 endothelialimage for both right and lefteyesParacentral and Peripheralmodes: 15 endothelialimages for both right and lefteyes | 1 endothelial image for bothright and left eyes |
| Built-in Printer | Thermal Line Printerwith auto cutter | Thermal Line Printer withauto cutter | NA |
| External Interface | USB-A: barcode, cardreader, LAN for dataoutput, Video output:BNC terminal | USB-A: barcode, cardreader, LAN for data output,Video output: BNC terminal | Video output: BNC terminalInput port for mouse andremote control |
| Connection to FilingSystem | Connectable | Connectable | Connectable |
| Monitor | 8.4" SVGA color LCDwith touch panel | 8.4" SVGA color LCD withtouch panel | 19" color LCD monitor |
| Input Power | 100 VA | 100 VA | 70 VA |
| Dimensions | 291 (W) x 495 (D) x457 (H) mm | 291 (W) x 495 (D) x 457 (H)mm | 334 (W) x 486 (D) x 420 (H)mm |
| Weight | 20 Kg | 20 Kg | 20.5 Kg |
| Compliance withSafety Standards | AAMI/ANSI ES60601-1IEC 60601-1-2ISO 15004-1ISO 15004-2 | IEC 60601-1IEC 60601-1-2ISO 15004-1ISO 15004-2 | IEC 60601-1IEC 60601-1-2ISO 15004-1ISO 15004-2 |
NON-CLINICAL PERFORMANCE SUMMARY
The performance testing conducted using the NIDEK Specular Microscope CEM-530 verified that the device operates as intended. The specifications to which the CEM-530 was verified to are substantially equivalent to the predicate devices and therefore, support a determination of substantial equivalence.
Additionally, the CEM-530 was subjected to electrical safety testing in accordance with AAMI/ANSI ES 60601-1, electromagnetic compatibility (EMC) testing in accordance with IEC 60601-1-2, and optical radiation safety testing in accordance with ISO 15004-1 and ISO 15004-2.
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CLINICAL PERFORMANCE SUMMARY
The data provided below is the second report presenting results from a prospective clinical study conducted at one clinical site located in the United States. Endothelial image data captured on the CEM530(Ver1.09) in the previous study, CEM-530-US-0002 were imported for auto analysis based on a new auto-cell count algorithm. The study was conducted to assess the agreement and precision of the Specular Microscope CEM-530 by comparing results across three machines/operators to those obtained with the predicate device, the Cellchek Plus. Three populations were studied: young (18-28 years of age) and adult (29-80 years of age) healthy subjects and pathologic adult eyes (29-80 years of age).
There were 79 subjects enrolled in the study: 28 in the non-pathologic young eye population, 28 in the non-pathologic adult eye population, and 23 in the pathologic adult eye population. Of those, 74 are included in the effectiveness population (28, 27, and 19, respectively). The agreement population consisted of all 74 subjects (28, 27 and 19, respectively). The precision population included a subset of the effectiveness population, 45 total with 15, 15 and 15 respectively. The pathologic adult subjects consisted of 19 subjects with the following pathologies which qualified them for the subgroup: Guttata (16, 84.2%) and Long Term Fuch's Dystrophy (3, 15.8%). The mean (SD) age of the nonpathologic young population was 22.2 (3.28) years; that of the non-pathologic adult population was 53.0 (13.42) years, and that of the pathologic adult population was 63.9 (12.39) years. All subjects combined had a mean age of 44.1 (20.54) years. The gender distribution of the total population was 27 males (36.5%) and 47 females (63.5%). The gender distribution of the non-pathologic young population was 15 males (53.6%) and 13 females (46.4%); that of the non-pathologic adult population was 8 males (29.6%) and 19 females (70.4%), and that of the pathologic adult population was 4 males (21.1%) and 15 females (78.9%). The majority of subjects were white (66/74 subjects, 89.2%). All of the pathologic adult subjects were white (19/19). The non-pathologic adult were white (21/27), American Indian (1/27), Asian (1/27), African American (1/27) and other (3/27). The nonpathologic young subjects were white (26/28) and other (2/28). With regard to iris color, the highest percentage of subjects had study eyes with brown irides (43.2%), followed by blue irides (28.4%), green irides (6.8%), black irides (1.4%) and gray irides (1.4%).
The result of Agreement study
Table 2 provides a summary of the agreement data for all subjects with the modified automated method while Tables 3, 4 and 5 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).
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| 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%(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% of theCellChek 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(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 sameconfiguration are used for the agreement analyses. |
The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).
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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 % ofthe 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(95% CI) | 429.3 (65.1, 793.4) | -8.8 (-57.9, 40.2) | 59.9 (34.3, 85.6) |
| Deming Regression Slope(95% CI) | 0.9 (0.7, 1.0) | 1.2 (-0.4, 2.8) | 0.2 (-0.3, 0.6) |
Table 4 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Agreement Analyses - Non-Pathologic Adult Eyes
For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.
The mean differences are calculated as (NIDEK Specular Microscope CEM-530) - (Konan CellChek Plus).
The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.
Table 5 CEM-530 Automated Analysis method vs. Konan Cellchek Plus : Agreement Analyses -Pathologic Adult Eyes
| 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 theCellChek 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(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-530N=45 | Konan CellChek PlusN=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/ KonanCellChek 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/ KonanCellChek Plus) | 0.8761 | --- |
| Coefficient of Variation of Endothelial Cell Area(CV) | ||
| Repeatability SD | 1.7 | 2.7 |
| Repeatability SD as a % of the Mean | 6.2% | 8.4% |
| Repeatability Limit | 4.9 | 7.4 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek Plus) | 0.6911 | --- |
{11}------------------------------------------------
| Variable | NIDEK CEM-530N=45 | Konan CellChek PlusN=61 |
|---|---|---|
| CellChek Plus) | ||
| N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variancecomponent 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 thereproducibility standard deviation, which is the square root of the sum of the variance components of operator+device,operator+device x subject interaction, and residual within subject. |
| Table 7 CEM-530 Automated Analysis method vs. Konan Cellchek Plus : Precision Analyses - Non- | |
|---|---|
| Pathologic Young Eve |
| Pathologic Young Eye | ||
|---|---|---|
| Variable | NIDEK CEM-530N=15 | Konan CellChek PlusN= 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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-530N=15 | Konan CellChek PlusN=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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek 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/ KonanCellChek Plus) | 0.8299 | --- |
| Variable | NIDEK CEM-530N=15 | Konan CellChek PlusN=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/ KonanCellChek Plus) | 1.0614 | --- |
| Reproducibility SD | 81.7 | 141.3 |
| Reproducibility SD as a % of the Mean | 3.1% | 6.1% |
| Reproducibility Limit | 228.7 | 395.6 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus) | 0.5781 | --- |
| Coefficient of Variation of Endothelial Cell Area (CV) | ||
| Repeatability SD | 1.8 | 3.1 |
| Repeatability SD as a % of the Mean | 5.9% | 9.3% |
| Repeatability Limit | 5.1 | 8.6 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus) | 0.5912 | --- |
| Reproducibility SD | 2.0 | 3.1 |
| Reproducibility SD as a % of the Mean | 6.6% | 9.5% |
| Reproducibility Limit | 5.6 | 8.7 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus) | 0.6462 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.8 | 7.3 |
| Repeatability SD as a % of the Mean | 5.6% | 12.7% |
| Repeatability Limit | 10.5 | 20.4 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus) | 0.5154 | --- |
| Reproducibility SD | 3.8 | 7.3 |
| Reproducibility SD as a % of the Mean | 5.6% | 12.7% |
| Reproducibility Limit | 10.5 | 20.4 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus) | 0.5154 | --- |
| N represents the total number of subjects in each eye population in the precision and agreement cohort. | ||
| If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times therepeatability standard deviation, which is the square root of the residual within subject variancecomponent. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is thesquare root of the sum of the variance components of operator+device, operator+device x subjectinteraction, and residual within subject. |
Table 8 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Precision Analyses – Non-Pathologic Adult Eye
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the sum of the variance components of operator+device x subject interaction, and residual within subject.
{13}------------------------------------------------
Table 9 CEM-530 Automated Analysis method vs. Konan Cellchek Plus: Precision Analyses – Pathologic Adult Eye
Additional Manual Comparision
An additional comparision was conducted to assess the agreement, accuracy and precision of the Specular Microscope CEM-530 automated analysis compared to the CEM-530 manual analysis methods across three machines/operators. Three populations were studied: young (18-28 years of age) and adult (29-80 years of age) healthy subjects and pathologic
{14}------------------------------------------------
adult eyes (29-80 years of age).
The result of Agreement study
Table 10 provides a summary of the agreement data for all subjects while Tables 11, 12 and 13 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).
| Table 10 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement |
|---|
| Analyses - All subjects |
| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Automated CEM-530 | |||
| N | 74 | 74 | 74 |
| Mean (SD) | 2773.3 (343.10) | 27.4 (4.61) | 68.0 (5.16) |
| Median | 2747.0 | 27.0 | 69.0 |
| Min-Max | 1941 - 3473 | 17 - 45 | 48 - 78 |
| Nidek Manual CEM-530 | |||
| N | 74 | 74 | 74 |
| Mean (SD) | 2784.3 (428.52) | 22.1 (3.36) | 59.8 (7.30) |
| Median | 2795.0 | 21.5 | 60.0 |
| Min- Max | 1754 - 3637 | 15 - 35 | 41 - 81 |
| Device Comparisons | |||
| Mean Difference (SD) | -11.0 (135.31) | 5.4 (4.30) | 8.2 (8.27) |
| Mean Difference (SD) as a % of the NidekManual CEM-530 reading | 0.18% (5.066%) | 25.71% (21.835%) | 15.34% (15.544%) |
| 95% LOA | (-281.6, 259.6) | (-3.2, 14.0) | (-8.3, 24.8) |
| Correlation (R) | 0.9626 | 0.4537 | 0.1536 |
| Deming Regression Intercept (95% CI) | 562.9 (420.9, 704.8) | -15.1 (-48.0, 17.7) | 55.6 (36.0, 75.2) |
| Deming Regression Slope(95% CI) | 0.79 (0.74,0.85) | 1.9 (0.4, 3.5) | 0.2 (-0.1, 0.5) |
For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.
The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).
The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.
| Table 11 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement | ||
|---|---|---|
| Analyses - Non-Pathologic Young Eves | ||
| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Automated 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 |
| Nidek Manual CEM-530 | |||
| N | 28 | 28 | 28 |
| Mean (SD) | 3069.5 (346.41) | 20.3 (1.90) | 63.0 (6.33) |
| Median | 3104.0 | 21.0 | 63.0 |
| Min- Max | 2437 - 3637 | 15 - 24 | 52 - 81 |
| Device Comparisons | |||
| Mean Difference (SD) | -64.4 (118.86) | 4.5 (3.14) | 5.6 (6.63) |
| Mean Difference (SD) as a % of the NidekManual CEM-530 reading | --1.86% (3.609%) | 22.72% (15.797%) | 9.76% (10.871%) |
| 95% LOA | (-302.1, 173.3) | (-1.8, 10.8) | (-7.7, 18.9) |
{15}------------------------------------------------
| Correlation (R) | 0.9469 | 0.3703 | 0.2384 |
|---|---|---|---|
| Deming Regression Intercept (95% CI) | 492.0 (153.8, 830.3) | -45.0 (-213.2, 123.1) | 53.9 (23.9, 83.8) |
| Deming Regression Slope(95% CI) | 0.8 (0.7, 0.9) | 3.4 (-4.8, 11.7) | 0.2 (-0.2, 0.7) |
For subjects in the Precision and Agreements from the first acceptable images from each machine within the same configuration are used for the agreement analyses.
The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).
The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.
Table 12 CEM-530Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement Analyses – Non-Pathologic Adult Eyes
| Analyses - Non Pathologic Adult Eyes | |||
|---|---|---|---|
| CD | CV | % HEX | |
| Nidek Automated 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 |
| Nidek Manual CEM-530 | |||
| N | 27 | 27 | 27 |
| Mean (SD) | 2678.6 (391.33) | 23.3 (3.27) | 57.1 (6.66) |
| Median | 2772.0 | 23.0 | 56.0 |
| Min- Max | 1956 - 3399 | 19 - 35 | 47 - 73 |
| Device Comparisons | |||
| Mean Difference (SD) | -6.9 (130.19) | 5.4 (5.06) | 12.0 (7.31) |
| Mean Difference (SD) as a % of the Nidek | 0.29% (4.908%) | 24.61% (24.465%) | 22.37% (14.963%) |
| Manual CEM-530 reading | |||
| 95% LOA | (-267.3, 253.5) | (-4.8, 15.5) | (-2.6, 26.6) |
| Correlation (R) | 0.9620 | 0.2193 | 0.2134 |
| Deming Regression Intercept (95% CI) | 624.5 (461.5, 787.4) | -54.5 (-277.1, 168.2) | 52.9 (9.8, 95.9) |
| Deming Regression Slope(95% CI) | 0.76(0.71,0.82) | 3.6 (-6.2, 13.4) | 0.3 (-0.5, 1.0) |
| For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the sameconfiguration are used for the agreement analyses. |
The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).
The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.
| Table 13 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Agreement |
|---|
| Analyses - Pathologic Adult Eyes |
| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Automated CEM-530 | |||
| N | 19 | 19 | 19 |
| Mean (SD) | 2576.1 (286.78) | 29.7 (4.45) | 65.5 (6.53) |
| Median | 2594.0 | 29.0 | 65.0 |
| Min-Max | 1941 - 3132 | 23 - 39 | 48 - 76 |
| Nidek Manual CEM-530 | |||
| N | 19 | 19 | 19 |
| Mean (SD) | 2514.2 (351.02) | 23.0 (4.11) | 58.7 (7.96) |
| Median | 2522.0 | 22.0 | 60.0 |
| Min- Max | 1754 - 3078 | 17 - 33 | 41 - 71 |
| Device Comparisons | |||
| Mean Difference (SD) | 61.9 (136.03) | 6.7 (4.49) | 6.8 (9.99) |
{16}------------------------------------------------
K173980 510(K) Summary
| Mean Difference (SD) as a % of the NidekManual CEM-530 reading | 3.01% (5.902%) | 31.66% (25.329%) | 13.57% (18.797%) |
|---|---|---|---|
| 95% LOA | (-210.2, 334.0) | (-2.3, 15.7) | (-13.2, 26.8) |
| Correlation (R) | 0.9286 | 0.4529 | 0.0605 |
| Deming Regression Intercept (95% CI) | 553.2 (171.3, 935.2) | 2.3 (-35.1, 39.7) | 56.8 (-38.4, 152.1) |
| Deming Regression Slope(95% CI) | 0.8 (0.6, 1.0) | 1.2 (-0.5, 2.9) | 0.1 (-1.4, 1.7) |
| For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same |
For subjects in the Precision and Agreement cohort, the measurements from first acceptable images from each machine within the the configuration are used for the agreement analyses.
The mean differences are calculated as (Nidek Automated CEM-530) - (Nidek Manual CEM-530).
The mean differences as a % of the Nidek Manual CEM-530 reading are calculated for each subject first and then summarized.
The result of Precision study
Table 14 provides a summary of the precison data for all subjects while Tables 15, 16 and 17 provide the same data by subgroup (non-pathologic young eyes, non-pathologic adult eyes, pathologic adult eyes, respectively).
Table 14 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses - All Subjects
| Variable | NIDEK AutomatedCEM-530N= 45 | Nidek ManualCEM-530N= 46 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 74.2 | 49.1 |
| Repeatability SD as a % of the Mean | 2.7% | 1.8% |
| Repeatability Limit | 207.8 | 137.6 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.5109 | --- |
| Reproducibility SD | 83.7 | 61.3 |
| Reproducibility SD as a % of the Mean | 3.1% | 2.3% |
| Reproducibility Limit | 234.3 | 171.8 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.3643 | --- |
| Coefficient of Variation of Endothelial Cell Area(CV) | ||
| Repeatability SD | 1.7 | 1.5 |
| Repeatability SD as a % of the Mean | 6.2% | 6.8% |
| Repeatability Limit | 4.9 | 4.2 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1694 | --- |
| Reproducibility SD | 1.9 | 1.9 |
| Reproducibility SD as a % of the Mean | 6.8% | 8.4% |
| Reproducibility Limit | 5.4 | 5.2 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.0417 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.7 | 3.5 |
| Repeatability SD as a % of the Mean | 5.5% | 5.8% |
| Repeatability Limit | 10.5 | 9.9 |
{17}------------------------------------------------
| Variable | NIDEK AutomatedCEM-530 | Nidek ManualCEM-530 |
|---|---|---|
| N= 45 | N= 46 | |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.0559 | --- |
| Reproducibility SD | 3.7 | 4.0 |
| Reproducibility SD as a % of the Mean | 5.5% | 6.5% |
| Reproducibility Limit | 10.5 | 11.1 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 0.9422 | --- |
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.
Table 15 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses – Non-Pathologic Young Eye
| Variable | NIDEK AutomatedCEM-530N= 15 | Nidek ManualCEM-530N=15 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 84.9 | 46.0 |
| Repeatability SD as a % of the Mean | 2.9% | 1.5% |
| Repeatability Limit | 237.7 | 128.8 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.8459 | --- |
| Reproducibility SD | 92.8 | 51.9 |
| Reproducibility SD as a % of the Mean | 3.1% | 1.7% |
| Reproducibility Limit | 259.8 | 145.4 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.7874 | --- |
| Coefficient of Variation of Endothelial Cell Area(CV) | ||
| Repeatability SD | 1.8 | 1.3 |
| Repeatability SD as a % of the Mean | 6.8% | 6.4% |
| Repeatability Limit | 5.0 | 3.5 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.4289 | --- |
| Reproducibility SD | 1.9 | 1.5 |
| Reproducibility SD as a % of the Mean | 7.1% | 7.5% |
| Reproducibility Limit | 5.3 | 4.2 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.2629 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.6 | 3.1 |
| Repeatability SD as a % of the Mean | 5.4% | 4.8% |
| Repeatability Limit | 10.1 | 8.6 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1700 | --- |
{18}------------------------------------------------
| Variable | NIDEK AutomatedCEM-530 | Nidek ManualCEM-530 |
|---|---|---|
| N=15 | N=15 | |
| NIDEK Manual CEM-530) | ||
| Reproducibility SD | 3.6 | 3.8 |
| Reproducibility SD as a % of the Mean | 5.4% | 5.8% |
| Reproducibility Limit | 10.1 | 10.6 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 0.9532 | --- |
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.
Table 16 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses - Non-Pathologic Adult Eye
| Variable | NIDEK AutomatedCEM-530N= 15 | Nidek ManualCEM-530N= 15 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 61.9 | 48.3 |
| Repeatability SD as a % of the Mean | 2.4% | 1.8% |
| Repeatability Limit | 173.4 | 135.1 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.2835 | --- |
| Reproducibility SD | 76.1 | 58.2 |
| Reproducibility SD as a % of the Mean | 2.9% | 2.2% |
| Reproducibility Limit | 213.0 | 163.0 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.3072 | --- |
| Coefficient of Variation of Endothelial Cell Area(CV) | ||
| Repeatability SD | 1.6 | 1.4 |
| Repeatability SD as a % of the Mean | 5.7% | 6.3% |
| Repeatability Limit | 4.5 | 4.0 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1209 | --- |
| Reproducibility SD | 1.9 | 1.7 |
| Reproducibility SD as a % of the Mean | 6.9% | 7.6% |
| Reproducibility Limit | 5.4 | 4.8 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1174 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.8 | 3.1 |
| Repeatability SD as a % of the Mean | 5.5% | 5.3% |
| Repeatability Limit | 10.8 | 8.7 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.2387 | --- |
{19}------------------------------------------------
| Variable | NIDEK AutomatedCEM-530N= 15 | Nidek ManualCEM-530N= 15 |
|---|---|---|
| NIDEK Manual CEM-530) | ||
| Reproducibility SD | 3.8 | 3.5 |
| Reproducibility SD as a % of the Mean | 5.5% | 5.9% |
| Reproducibility Limit | 10.8 | 9.7 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1117 | --- |
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator-device, operator+device x subject interaction, and residual within subject.
Table 17 CEM-530 Automated Analysis Method vs CEM-530 Manual Analysis Method: Precision Analyses – Pathologic Adult Eye
| Variable | NIDEK AutomatedCEM-530N=15 | Nidek ManualCEM-530N=16 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 74.1 | 52.7 |
| Repeatability SD as a % of the Mean | 2.8% | 2.1% |
| Repeatability Limit | 207.4 | 147.4 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.4065 | --- |
| Reproducibility SD | 81.7 | 72.4 |
| Reproducibility SD as a % of the Mean | 3.1% | 2.9% |
| Reproducibility Limit | 228.7 | 202.7 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.1283 | --- |
| Coefficient of Variation of Endothelial Cell Area(CV) | ||
| Repeatability SD | 1.8 | 1.7 |
| Repeatability SD as a % of the Mean | 5.9% | 7.3% |
| Repeatability Limit | 5.1 | 4.8 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 1.0508 | --- |
| Reproducibility SD | 2.0 | 2.3 |
| Reproducibility SD as a % of the Mean | 6.6% | 9.8% |
| Reproducibility Limit | 5.6 | 6.4 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 0.8800 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.8 | 4.3 |
| Repeatability SD as a % of the Mean | 5.6% | 7.3% |
| Repeatability Limit | 10.5 | 11.9 |
| Repeatability Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 0.8844 | --- |
{20}------------------------------------------------
| Variable | NIDEK AutomatedCEM-530 | Nidek ManualCEM-530 |
|---|---|---|
| N=15 | N=16 | |
| Reproducibility SD | 3.8 | 4.6 |
| Reproducibility SD as a % of the Mean | 5.6% | 7.9% |
| Reproducibility Limit | 10.5 | 12.9 |
| Reproducibility Ratio (NIDEK Auto CEM-530/NIDEK Manual CEM-530) | 0.8161 | --- |
N represents the total number of subjects in each eye population in the precision and agreement cohort. If any variance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability standard deviation, which is the square root of the residual within subject variance component. The reproducibility limit is 2.8 times the reproducibility standard deviation, which is the square root of the variance components of operator+device, operator+device x subject interaction, and residual within subject.
CONCLUSIONS
The NIDEK Specular Microscope CEM-530 has the same intended use and indications for use, technological characteristics, and principles of operation as the previously cleared predicate. The minor differences between the subject device and the predicate device have been assessed in a human clinical trial which found agreement and precision between the two devices. Therefore, the NIDEK Specular Microscope CEM-530 is as safe and effective as its predicate device, and thus, substantially equivalent.
§ 886.1850 AC-powered slitlamp biomicroscope.
(a)
Identification. An AC-powered slitlamp biomicroscope is an AC-powered device that is a microscope intended for use in eye examination that projects into a patient's eye through a control diaphragm a thin, intense beam of light.(b)
Classification. Class II (special controls). The device, when it is intended only for the visual examination of the anterior segment of the eye, is classified as Group 1 per FDA-recognized consensus standard ANSI Z80.36, does not provide any quantitative output, and is not intended for screening or automated diagnostic indications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.