(267 days)
The 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 provides non-contact, high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the number of endothelial cells, cell density, and cell area is analyzed through the captured images. The captured images and analysis results of the endothelium are used 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 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 built-in thermal printer or captured images can be transferred to a filing system via LAN connection. The Specular Microscope CEM-530 cleared in this 510(k) is identical to the Specular Microscope CEM-530 cleared in K130565 with the addition of a new analysis mode: Center Point Method. All other aspects of the cleared device remain unchanged.
The provided document describes the predicate device and the clinical study conducted for the Nidek Specular Microscope CEM-530. It focuses on demonstrating substantial equivalence to a predicate device (Konan CellChek Plus) rather than establishing novel acceptance criteria for an AI algorithm. Therefore, many of the requested items related to AI-specific acceptance criteria and study methodologies (e.g., sample size for training set, number of experts for ground truth, MRMC study effect size) are not applicable as this submission predates the widespread use and specific regulatory requirements for AI/ML medical devices.
However, based on the information provided, we can infer and or extract the following:
1. A table of acceptance criteria and the reported device performance:
The acceptance criteria are implicitly defined by demonstrating "agreement, accuracy and precision" with the predicate device. The performance data is presented as statistical measures comparing the CEM-530 with the Konan CellCheChek Plus. The key metrics studied are:
- Endothelial Cell Density (CD)
- Coefficient of Variation of Endothelial Cell Area (CV)
- % Hexagonality (% HEX)
Here's a summary derived from the "Device Comparisons" section in Table 2 for "All Subjects - Effectiveness Population":
| Performance Metric | Acceptance Criteria (Implied: Substantially Equivalent to Predicate) | Reported Device Performance (NIDEK CEM-530 vs. Konan CellChek Plus) (All Subjects) |
|---|---|---|
| Endothelial Cell Density (CD) | Agreement with predicate | Mean Difference (SD): 45.7 (104.11) cells/mm²95% LOA: (-162.5, 253.9) |
| Precision (Repeatability and Reproducibility) | Repeatability SD: 48.9Reproducibility SD: 60.9 | |
| Coeff. of Variation (CV) | Agreement with predicate | Mean Difference (SD): -7.6 (3.00)%95% LOA: (-13.6, -1.6) |
| Precision (Repeatability and Reproducibility) | Repeatability SD: 1.5Reproducibility SD: 1.8 | |
| % Hexagonality (% HEX) | Agreement with predicate | Mean Difference (SD): -2.9 (5.90)%95% LOA: (-14.6, 8.9) |
| Precision (Repeatability and Reproducibility) | Repeatability SD: 3.5Reproducibility SD: 4.0 |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Size:
- Agreement Study: 74 subjects (28 non-pathologic young eye, 27 non-pathologic adult eye, 19 pathologic adult eye).
- Precision Study: 47 subjects (15 non-pathologic young eye, 16 non-pathologic adult eye, 16 pathologic adult eye).
- Historical Data (for comparison in precision study): 62 subjects (from CEM-530-US-001 study, for Konan CellChek Plus).
- Data Provenance: The study was a "prospective clinical study." The document does not explicitly state the country of origin, but given the sponsor (Nidek Co., Ltd. Japan) and the contact person (Ora, Inc. Massachusetts), it is likely an international or US-based study.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. The ground truth for this device (a specular microscope) is the "manual measurements" performed by operators using the predicate device, or direct measurements from the Nidek CEM-530 and then compared. This is not an AI-based system where human experts would individually label data for ground truth in the same way. The document refers to "operators" and "machines" performing measurements, implying the ground truth is derived directly from the measurement devices themselves.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
This information is not applicable as the ground truth is established by the device's measurements, not by expert consensus requiring adjudication.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
This was not an MRMC comparative effectiveness study and does not involve AI assistance for human readers. It's a device comparison study evaluating agreement and precision between a new device and a predicate device in performing direct measurements of corneal parameters. Therefore, the effect size of human reader improvement with AI assistance is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device (Specular Microscope CEM-530) itself performs measurements, and the "Center Point Method" is an analysis mode within the device. The study evaluates the performance of this device in a clinical setting. While it's an "algorithm" making measurements, it's not described as a separate AI algorithm being tested in isolation. The study compares the device's performance (including its internal algorithms) against a predicate device. This is primarily a device-to-device comparison study, not a standalone AI algorithm performance study in the contemporary sense.
7. The type of ground truth used:
The ground truth is derived from the measurements obtained from a legally marketed predicate device (Konan CellChek Plus), against which the Nidek Specular Microscope CEM-530's measurements are compared for agreement and precision. This is essentially a "comparator device" ground truth.
8. The sample size for the training set:
This information is not applicable. The CEM-530 is a medical measurement device, not an AI/ML system that undergoes a separate training phase with a large dataset. The "Center Point Method" is an analysis mode, likely based on established algorithms for image analysis rather than a data-driven machine learning model requiring a "training set" in the common AI sense.
9. How the ground truth for the training set was established:
This information is not applicable as there is no mention of a traditional AI "training set" in the document.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 17, 2016
Nidek Co., Ltd. % Mr. Ryan Bouchard Ora, Inc. 300 Brickstone Square Andover, Massachusetts 01810
Re: K151706
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: NQE Dated: February 4, 2016 Received: February 5, 2016
Dear Mr. 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. 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 (reporting of medical device-related 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.
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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Kesia Alexander
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)
Device Name Specular Microscope CEM-530
Indications for Use (Describe)
The 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 CFR S 807.92.
Date Prepared: March 4, 2016
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 (K130565) 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 provides non-contact, high magnification image capture of the endothelium enabling observation of the size and shape of cells. Information such as the number of endothelial cells, cell density, and cell area is analyzed through the captured images. The captured images and analysis results of the endothelium are used 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 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 built-in thermal printer or captured images can be transferred to a filing system via LAN connection. The Specular Microscope CEM-530 cleared in this 510(k) is identical to the Specular Microscope CEM-530 cleared in K130565 with the addition of a new analysis mode: Center Point Method. All other aspects of the cleared device remain unchanged.
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 K130565. The only difference is the addition of Center Point Method. With Center Point method, the operator touches the center of a cell on the endothelial image with the touch screen pen. A dot is displayed on the endothelial image. Shapes are surrounded by the vertical lines to the lines made by connecting each dot and is recognized as a cell. Connected dots are top of cells and vertical lines are cell walls. Therefore, this discussion will focus primarily on the substantial equivalence to the Konan Cellchek Plus cleared in K120264.
Both the CEM-530 and the Konan Cellchek Plus have a built-in CCD camera. Both the CEM-530 and the Konan Cellchek Plus include an optical pachymeter with an accuracy of ± 10 microns. There were no modifications made to the optical pachymeter in the Specular Microscope CEM-530 compared with the device cleared in K130565.
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Regarding image analysis, both the CEM-530 and the predicate device offer automatic image analysis. The CEM-530, which is the subject of this 510(k), also offers manual analysis of images, as does the Konan predicate device. Clinical performance data is provided which evaluates the precision and agreement of the manual measurements performed by the CEM-530 compared to manual measurements performed with the Konan predicate device. The clinical performance data demonstrates the substantial equivalence of the CEM-530 manual 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 which have been evaluated with non-clinical and clinical performance data. The differences are shown in Table 1.
| SUBSTANTIAL EQUIVALENCE CHART | |||
|---|---|---|---|
| Manufacturer | Nidek | Nidek | Konan |
| Device Name | CEM-530 | CEM-530 | Cellchek Plus |
| 510(k) Number | NA | K130565 | K120264 |
| ProductClassification | Class II, NQE | Class II, NQE | Class II, NQE |
| Indications for Use | Non-contactophthalmic microscope,optical pachymeter, andcamera intended forexamination of thecorneal endotheliumand for measurement ofthe thickness of thecornea. | Non-contact ophthalmicmicroscope, opticalpachymeter, and cameraintended for examination ofthe corneal endothelium andfor measurement of thethickness of the cornea. | Non-contact ophthalmicmicroscope, opticalpachymeter, and cameraintended for examination ofcorneal endothelium and forthe measurement of thethickness of the cornea. |
| Device Type | Non-contact specularmicroscope andpachymeter | Non-contact specularmicroscope and pachymeter | Non-contact specularmicroscope and pachymeter |
| Capturing Method | Auto capture, autoalignment, auto focus(3D, 2D)/Manual | Auto capture, autoalignment, auto focus (3D,2D)/Manual | Auto capture, auto alignment,auto focus(3D)/Manual |
| Capture Field | 0.25x 0.55 mm | 0.25x 0.55 mm | 0.24 x 0.4 mm |
| Fixation Lamp(Central) | 1 point | 1 point | 1 point |
| Fixation Lamp(Paracentral) | 8 points (5 degrees ofvisual angle for eachpoint) | 8 points (5 degrees of visualangle for each point) | 4 points (direction of 12, 2,10 and 6 o'clock) |
| Fixation Lamp(Periphery) | 6 points (27 degrees ofvisual angle fordirection of 12, 2, 10,6, 4 and 8 o'clock) | 6 points (27 degrees of visualangle for direction of 12, 2,10, 6, 4 and 8 o'clock) | |
| Camera | Built-in CCD camera | Built-in CCD camera | Built-in CCD image sensingelement camera |
| Flash | Cyan LED | Cyan LED | Konan Xe tube |
| Illumination for | InfraRed LED | InfraRed LED | Konan halogen lamp |
TABLE 1 SPECULAR MICROSCOPE CEM-530 SUBSTANTIAL EQUIVALENCE CHART
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| focusing | |||
|---|---|---|---|
| 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 | No | Yes |
| Analysis Speed | 2 seconds | 2 seconds | Unknown |
| Record (1 patient) | Single mode: 1 endothelial 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 | IEC 60601-1IEC 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. The pachymetry functionality was evaluated in model eyes and the measurement accuracy of + 10 microns was confirmed.
Additionally, the CEM-530 was subjected to electrical safety testing in accordance with IEC 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
A prospective clinical study was conducted to assess the agreement, accuracy and precision of the Specular Microscope CEM-530 Center Point Method 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, 47 total with 15, 16 and 16 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 non-pathologic 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 Center Point Method while Tables 3, 4 and 5 provide the same data by subgroup (non-pathologic young eyes, nonpathologic adult eyes, pathologic adult eyes, respectively).
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| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Specular Microscope 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 |
| 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) | 45.7 (104.11) | -7.6 (3.00) | -2.9 (5.90) |
| Mean Difference (SD) as a % of theCellChek reading | 1.71% (3.976%) | -25.20% (8.391%) | -4.07% (9.662%) |
| 95% LOA | (-162.5, 253.9) | (-13.6, -1.6) | (-14.6, 8.9) |
| Correlation (R2) | 0.9701 | 0.7019 | 0.6791 |
| Deming Regression Intercept (95% CI) | -62.9 (-224.4, 98.6) | 0.1 (-6.4, 6.7) | -1.3 (-20.2, 17.5) |
| Deming Regression Slope(95% CI) | 1.0 (1.0, 1.1) | 0.7 (0.5, 1.0) | 1.0 (0.7, 1.3) |
Table 2 Center Point Method: Four Corneal Specular Microscopic Variables Assessed with the Two Devices - All Configurations - All Subjects - Effectiveness Population
Table 3 Center Point Method: Corneal Specular Microscopic Variables – All Configurations – Non-Pathologic Young Eyes - Effectiveness Population
| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Specular Microscope 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 |
| Konan CellChek Plus XL | |||
| 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) | 39.2 (93.37) | -7.2 (2.94) | -4.0 (5.31) |
| Mean Difference (SD)as a % of theCellChek reading | 1.19% (3.069%) | -25.59%, (8.660%) | -5.79% (7.933%) |
| 95% LOA | (-147.5, 226.0) | (-13.1, -1.3) | (-14.6, 6.7) |
| Correlation (R2) | 0.9695 | 0.3398 | 0.5841 |
| Deming Regression Intercept (95% CI) | -482.7 (-892.1, -73.4) | 11.4 (-0.8, 23.5) | -35.9 (-82.1, 10.3) |
| Deming Regression Slope(95% CI) | 1.2 (1.0, 1.3) | 0.3 (-0.1, 0.8) | 1.5 (0.8, 2.2) |
| 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 XL).
The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.
Table 4 Center Point Method: Corneal Specular Microscopic Variables - All Configurations - Non-Pathologic Adult Eyes – Effectiveness Population
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| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Specular Microscope 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 |
| 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) | 51.3 (100.35) | -7.8 (3.04) | -2.2 (6.10) |
| Mean Difference (SD) as a % ofthe CellChek reading | 1.82% (3.753%) | -24.70% (7.780%) | -2.94% (10.324%) |
| 95% LOA | (-149.4, 252.0) | (-13.9, -1.7) | (-14.4, 10.0) |
| Correlation (R2) | 0.9697 | 0.7075 | 0.6750 |
| DemingRegressionIntercept(95% CI) | -278.5 (-566.9, 9.9) | 2.0 (-13.1, 17.1) | 12.7 (-7.5, 32.9) |
| Deming Regression Slope(95% CI) | 1.1 (1.0, 1.2) | 0.7 (0.2, 1.2) | 0.7 (0.4, 1.1) |
| For subjects in the Precision and Agreement cohort, the measurements from the first acceptable images from each machine within the same |
configuration are used for the agreement analyses.
The mean differences are calculated as (Nidek Specular Microscope CEM-530) - (Konan CellChek Plus XL).
The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.
| Table 5 Center Point Method: Corneal Specular Microscopic Variables – All Configurations – | |
|---|---|
| Pathologic Adult Eves - Effectiveness Population | |
| CD | CV | % HEX | |
|---|---|---|---|
| Nidek Specular Microscope 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 |
| 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) | 47.3 (127.36) | -7.8 (3.11) | -2.1 (6.47) |
| Mean Difference (SD) as a % of theCellChek reading | 2.32% (5.367%) | -25.34% (9.218%) | -3.15% (11.085%) |
| 95% LOA | (-207.5, 302.0) | (-14.1, -1.6) | (-15.0, 10.8) |
| Correlation (R2) | 0.9472 | 0.7237 | 0.6134 |
| Deming Regression Intercept (95% CI) | 318.7 (-127.8, 765.3) | -6.4 (-23.1, 10.4) | -27.7 (-176.4, 121.0) |
| Deming Regression Slope(95% CI) | 0.9 (0.7, 1.1) | 1.0 (0.4, 1.5) | 1.4 (-1.0, 3.8) |
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 XL).
The mean differences as a % of the CELLCHEK reading are calculated for each subject first and then summarized.
The result of Precision study
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Table 6 provides a summary of the precision data for all subjects with the Center Point Method while Tables 7, 8 and 9 provide the same data by subgroup (non-pathologic young eyes, nonpathologic adult eyes, pathologic adult eyes, respectively). Data from a previous Nidek study, CEM-530-US-001, was used as the comparative data with respect to the Konan Cell Chek 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 Center Point Method: Precision Analyses – All Subjects – Effectiveness Population
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| Variable | NIDEK CEM-530N=47 | Konan CellChek PlusN=62 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 48.9 | 62.4 |
| Repeatability SD as a % of the Mean | 1.8% | 2.4% |
| Repeatability Limit | 136.8 | 174.8 |
| Repeatability Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.7829 | --- |
| Reproducibility SD | 60.9 | 95.2 |
| Reproducibility SD as a % of the Mean | 2.2% | 3.7% |
| Reproducibility Limit | 170.4 | 266.7 |
| Reproducibility Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.6391 | --- |
| Coefficient of Variation of Endothelial CellArea (CV) | ||
| Repeatability SD | 1.5 | 2.7 |
| Repeatability SD as a % of the Mean | 6.7% | 8.5% |
| Repeatability Limit | 4.1 | 7.5 |
| Repeatability Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.5521 | --- |
| Reproducibility SD | 1.8 | 2.7 |
| Reproducibility SD as a % of the Mean | 8.4% | 8.6% |
| Reproducibility Limit | 5.1 | 7.6 |
| Reproducibility Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.6778 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.5 | 5.4 |
| Repeatability SD as a % of the Mean | 5.8% | 8.8% |
| Repeatability Limit | 9.9 | 15.0 |
| Repeatability Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.6586 | --- |
| Reproducibility SD | 4.0 | 5.4 |
| Reproducibility SD as a % of the Mean | 6.5% | 8.9% |
| Reproducibility Limit | 11.1 | 15.2 |
| Reproducibility Ratio (NIDEK CEM-530/Konan CellChek Plus XL) | 0.7267 | --- |
| 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, |
Center Point Method: Precision Analyses – Non-Pathologic Young Eye Table 7 — Effectiveness Population
operator+device x subject interaction, and residual within subject.
| Variable | NIDEK CEM-530 | Konan CellChek Plus |
|---|---|---|
| ---------- | --------------- | --------------------- |
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| N=15 | XLN= 20 | |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 46.0 | 59.3 |
| Repeatability SD as a % of the Mean | 1.5% | 2.1% |
| Repeatability Limit | 128.8 | 166.0 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7758 | --- |
| Reproducibility SD | 51.9 | 70.2 |
| Reproducibility SD as a % of the Mean | 1.7% | 2.5% |
| Reproducibility Limit | 145.4 | 196.6 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7395 | --- |
| Coefficient of Variation of Endothelial Cell Area (CV) | ||
| Repeatability SD | 1.3 | 2.6 |
| Repeatability SD as a % of the Mean | 6.4% | 8.9% |
| Repeatability Limit | 3.5 | 7.4 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.4806 | --- |
| Reproducibility SD | 1.5 | 2.7 |
| Reproducibility SD as a % of the Mean | 7.5% | 9.1% |
| Reproducibility Limit | 4.2 | 7.6 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.5515 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.1 | 4.2 |
| Repeatability SD as a % of the Mean | 4.8% | 6.4% |
| Repeatability Limit | 8.6 | 11.7 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7391 | --- |
| Reproducibility SD | 3.8 | 4.3 |
| Reproducibility SD as a % of the Mean | 5.8% | 6.7% |
| Reproducibility Limit | 10.6 | 12.1 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.8705 | --- |
| 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 variance components of operator+device,operator+device x subject interaction, and residual within subject. |
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Table 8 Center Point Method: Precision Analyses – Non-Pathologic Adult Eye – Effectiveness Population
| Variable | NIDEK CEM-530N=16 | Konan CellChek PlusXLN=22 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 47.6 | 58.9 |
| Repeatability SD as a % of the Mean | 1.8% | 2.3% |
| Repeatability Limit | 133.1 | 165.0 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.8072 | --- |
| Reproducibility SD | 56.9 | 60.8 |
| Reproducibility SD as a % of the Mean | 2.2% | 2.3% |
| Reproducibility Limit | 159.4 | 170.2 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.9364 | --- |
| Coefficient of Variation of Endothelial Cell Area (CV) | ||
| Repeatability SD | 1.4 | 2.3 |
| Repeatability SD as a % of the Mean | 6.2% | 7.1% |
| Repeatability Limit | 3.9 | 6.4 |
| Repeatability Ratio (NIDEK CEM-530/KonanCellChek Plus XL) | 0.6125 | --- |
| Reproducibility SD | 1.7 | 2.4 |
| Reproducibility SD as a % of the Mean | 7.4% | 7.3% |
| Reproducibility Limit | 4.7 | 6.6 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7056 | --- |
| % Hexagonality | ||
| Repeatability SD | 3.1 | 4.1 |
| Repeatability SD as a % of the Mean | 5.3% | 6.8% |
| Repeatability Limit | 8.6 | 11.4 |
| Repeatability Ratio (NIDEK CEM-530/KonanCellChek Plus XL) | 0.7557 | --- |
| Reproducibility SD | 3.4 | 4.6 |
| Reproducibility SD as a % of the Mean | 5.9% | 7.7% |
| Reproducibility Limit | 9.7 | 13.0 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7449 | --- |
| 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 variance components of operator+device,operator+device x subject interaction, and residual within subject. |
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| Variable | NIDEK530N=16 | CEM-Konan CellChek PlusXLN=20 |
|---|---|---|
| Endothelial Cell Density | ||
| Repeatability SD | 52.7 | 68.9 |
| Repeatability SD as a % of the Mean | 2.1% | 3.0% |
| Repeatability Limit | 147.4 | 192.9 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7641 | --- |
| Reproducibility SD | 72.4 | 138.8 |
| Reproducibility SD as a % of the Mean | 2.9% | 6.1% |
| Reproducibility Limit | 202.7 | 388.6 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.5218 | --- |
| Coefficient of Variation of Endothelial Cell Area (CV) | ||
| Repeatability SD | 1.7 | 3.1 |
| Repeatability SD as a % of the Mean | 7.3% | 9.4% |
| Repeatability Limit | 4.8 | 8.7 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.5561 | --- |
| Reproducibility SD | 2.3 | 3.2 |
| Reproducibility SD as a % of the Mean | 9.8% | 9.7% |
| Reproducibility Limit | 6.4 | 8.9 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.7236 | --- |
| % Hexagonality | ||
| Repeatability SD | 4.3 | 7.3 |
| Repeatability SD as a % of the Mean | 7.3% | 12.6% |
| Repeatability Limit | 11.9 | 20.4 |
| Repeatability Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.5837 | --- |
| Reproducibility SD | 4.6 | 7.3 |
| Reproducibility SD as a % of the Mean | 7.9% | 12.6% |
| Reproducibility Limit | 12.9 | 20.4 |
| Reproducibility Ratio (NIDEK CEM-530/ KonanCellChek Plus XL) | 0.6326 | --- |
| N represents the total number of subjects in each eye population in the precision and agreement cohort. If anyvariance component was negative, it was reported as 0. The repeatability limit is 2.8 times the repeatability |
Center Point Method: Precision Analyses - Pathologic Adult Eye -Table 9 Effectiveness Population
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.
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Overall, within eye/subject variability was acceptable, and similar for both machines. The precision of the two devices was assessed with repeatability and reproducibility measures: the first within a given subject and the second within and among configurations. With regard to overall precision, using the Center Point Method, the largest component of variation was the subject to subject variation. The CEM-530 machine was less variable than the Cellchek Plus machine for endothelial cell density and % Hexagonality. The CEM-530 was also less variable than the Cellchek Plus machine for the coefficient of variation.
In summary, the agreement and precision of the Specular Microscope CEM-530 Center Point Method were found to be substantially equivalent to the Konan CellChek Plus center method.
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, accuracy 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.