(274 days)
The Specular Microscope SP-1P is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of corneal endothelium and for measurement of the thickness of the cornea.
This instrument is a photographic device dedicated to photograph and record corneal endothelial cells as an electronic image without contacting the eye. The Specular Microscope SP-1P also allows for measuring corneal thickness at the same time as corneal endothelial cells photography. The Specular Microscope SP-1P has functions that permit users to analyze photographed corneal endothelial cells and to calculate the area and form of corneal endothelial cells. It automatically performs alignment, photography and analysis. The Specular Microscope SP-1P contains multiple fixation targets, and allows users to photograph both central and peripheral corneal endothelial cells depending upon which fixation target is used. The Specular Microscope SP-1P has a manual image alignment function which allows the operator to utilize the internal function of the SP-1P to focus on the cornea and obtain the image. The manual image alignment can be utilized in difficult lighting or cases where the subject has a difficult time fixating. The Specular Microscope SP-1P also has a manual editing function which allows the clinician to modify the cells selected on the automatically captured image. Photographed images, images for observation and analysis results are displayed on the color LCD monitor with touch panel. An internal printer allows for printing photographed images and analysis results.
Here's an analysis of the provided text regarding the acceptance criteria and study for the TopCon SP-1P Specular Microscope:
The acceptance criteria are implicitly defined by demonstrating substantial equivalence to the predicate device, Konan Cellchek Plus (K120264), particularly in terms of agreement and precision for key corneal measurements. The study aims to show that the TopCon SP-1P performs similarly to the predicate device across various metrics.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are based on the agreement and precision of four key variables compared to the predicate device. The tables below outline the reported performance relative to the predicate device. The underlying acceptance criterion for each metric is that the TopCon SP-1P measurements should demonstrate substantial equivalence to the Konan CellChek XL (Plus), meaning the differences, LOA intervals, and correlation should indicate a strong agreement and comparable precision.
Agreement Data (Explicitly Stated in "Device Comparisons" section of Table 1)
| Variable | Acceptance Criteria (Implicit for Substantial Equivalence to Predicate) | TopCon SP-1P Reported Performance (vs. Predicate) |
|---|---|---|
| Corneal Endothelial Cell Density (ECD) | Mean difference close to 0, 95% LOA including 0, high correlation (R²) | Mean (SD) difference: 101.3 (145.68) Mean (SD) difference as %: 4.11% (5.908%) 95% LOA: (-190.1, 392.6) (includes 0) Deming Regression R²: 0.9448 |
| Coefficient of Variation (CV) of Endothelial Cell Area | Mean difference close to 0, 95% LOA including 0, high correlation (R²) | Mean (SD) difference: -0.6 (3.47) Mean (SD) difference as %: -1.17% (10.399%) 95% LOA: (-7.5, 6.4) (includes 0) Deming Regression R²: 0.5961 |
| Percent Hexagonality (% 6a) | Mean difference close to 0, 95% LOA including 0, high correlation (R²) | Mean (SD) difference: -5.8 (8.87) Mean (SD) difference as %: -9.25% (14.579%) 95% LOA: (-23.5, 11.9) (includes 0) Deming Regression R²: 0.5197 |
| Central Corneal Thickness (CCT) | Mean difference close to 0, 95% LOA including 0, high correlation (R²) | Mean (SD) difference: -18.2 (15.47) Mean (SD) difference as %: -3.17% (2.663%) 95% LOA: (-49.1, 12.7) (includes 0) Deming Regression R²: 0.9501 |
Precision Data (Repeatability/Reproducibility Ratios, Implicitly aiming for ratios close to 1 or better)
| Variable | Acceptance Criteria (Implicit: ratios close to 1 or better than predicate) | TopCon SP-1P Reported Performance (Ratio SP-1P / Predicate) |
|---|---|---|
| Corneal Endothelial Cell Density (ECD) | Repeatability/Reproducibility ratios around 1, or less than 1 (better) | Repeatability Ratio: 1.1019 Reproducibility Ratio: 1.1148 |
| Coefficient of Variation (CV) | Repeatability/Reproducibility ratios around 1, or less than 1 (better) | Repeatability Ratio: 0.6984 (better) Reproducibility Ratio: 0.6873 (better) |
| Percent Hexagonality (% 6a) | Repeatability/Reproducibility ratios around 1, or less than 1 (better) | Repeatability Ratio: 1.1369 Reproducibility Ratio: 1.1645 |
| Central Corneal Thickness (CCT) | Repeatability/Reproducibility ratios around 1, or less than 1 (better) | Repeatability Ratio: 0.2910 (significantly better) Reproducibility Ratio: 0.3110 (significantly better) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Effectiveness Population): 69 subjects.
- 21 Non-pathologic young adult (NPY; 18-28 years of age)
- 27 Non-pathologic adult (NPA; 29-80 years of age)
- 21 Pathologic adult (PA; 29-80 years of age)
- Data Provenance:
- Country of Origin: Not explicitly stated, but the submission is to the U.S. FDA, and manufacturers often conduct clinical studies in the country where they seek approval or in international sites that adhere to similar regulatory standards. No specific country is mentioned for the study site.
- Retrospective or Prospective: Prospective, open label, randomized, single-center study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The study compares the TopCon SP-1P results to those obtained with a commercially available predicate device, the CellChek XL (Plus), manufactured by Konan Medical, Inc. This implies the predicate device provides the "ground truth" or a well-established reference for comparison.
- Number of Experts: Not applicable in the sense of independent expert adjudication of images to establish ground truth. The comparison is between automated measurements of two devices. The "ground truth" for the predicate device's measurements (CellChek XL (Plus)) is its established and accepted clinical performance.
- Qualifications of Experts: Not applicable, as no human experts were used to establish ground truth for individual cases in this comparative study. However, the study involved multiple machines/operators: "Machines were tested in three configurations, each with its own operator".
4. Adjudication Method for the Test Set
The adjudication method is not described as a formal consensus among experts. Instead, the study uses the predicate device's measurements as the reference for comparison for agreement. The "Center Method" is mentioned in relation to the predicate device's analysis, but not as an adjudication method for the test set's ground truth.
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
- MRMC Comparative Effectiveness Study: No, this was not an MRMC comparative effectiveness study involving human readers assisting with or without AI. This study compared one automated device (SP-1P) to another (predicate CellChek XL Plus).
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Standalone Performance: Yes, the study evaluates the performance of the TopCon SP-1P, which "automatically performs alignment, photography and analysis." The clinical performance data "evaluates the precision and accuracy of the automatic analysis performed by the Specular Microscope SP-1P compared to the Center Method for the predicate device." While the device has manual editing and manual image alignment functions, the reported clinical performance data specifically relates to the "automatic analysis" mode in comparison to the predicate. This indicates a standalone evaluation of the device's automated capabilities.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for this study is the measurements obtained from a legally marketed predicate device (Konan CellChek XL Plus). The study assesses the agreement and precision of the TopCon SP-1P's measurements relative to the predicate device, rather than against an independent, absolute "gold standard" ground truth like pathology or expert consensus on a per-image basis.
8. The Sample Size for the Training Set
The document does not provide any information about a training set for the device's algorithms. This information is typically proprietary to the manufacturer and not usually disclosed in 510(k) summaries unless directly relevant to a specific AI/ML claim requiring such detail. The device performs "automatic analysis," implying algorithms are used, but their training data is not described.
9. How the Ground Truth for the Training Set Was Established
As no information about a training set is provided, how its ground truth was established is also not described in this document.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 29, 2015
TopCon Corporation c/o Mr. Rvan Bouchard Manager ORA, Inc. 300 Brickstone Square Andover, MA 01810
Re: K142417
Trade/Device Name: TopCon SP-1PSpecular Microscope Regulation Number: 21 CFR 886.1850 Regulation Name: AC-Powered Slitlamp Biomicroscope Regulatory Class: Class II Product Code: NQE Dated: April 20, 2015 Received: April 22, 2015
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
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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.
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/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"
(21CFR 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 Y. Alexander -A
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) K142417
Device Name Specular Microscope SP-1P
Indications for Use (Describe)
The Specular Microscope SP-1P is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of corneal endothelium and for measurement of the thickness of the cornea.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY
Specular Microscope SP-1P
510(k) Owner
Topcon Corporation 75-1 Hasunuma-Cho Itabashi-Ku Tokyo, Japan 174-8580 Phone: (201) 599-5553 Facsimile: (201) 599-5248 Michael Gusel, Manager, Regulatory Affairs and Quality Assurance
Submission Correspondent
Ryan Bouchard Ora, Inc. 300 Brickstone Square Andover, MA 01810 Phone: (978) 685-8900 Facsimile: (978) 689-0020
Date Prepared:May 14, 2015
Trade Name of Device Specular Microscope SP-1P
Common or Usual Name Microscope, specular
Classification Name
AC-powered slitlamp biomicroscope 21 C.F.R. 886.1850 Class II Product Code: NQE
Predicate Device Konan Specular Microscope Xiv Cellchek Plus (K120264)
Device Description
This instrument is a photographic device dedicated to photograph and record corneal endothelial cells as an electronic image without contacting the eye. The Specular Microscope SP-1P also allows for measuring corneal thickness at the same time as corneal endothelial cells photography. The Specular Microscope SP-1P has functions that permit users to analyze photographed corneal endothelial cells and to calculate the area and form of corneal endothelial cells. It automatically performs alignment, photography and analysis. The Specular Microscope SP-1P contains multiple fixation targets, and allows users to photograph both central and peripheral corneal
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endothelial cells depending upon which fixation target is used. The Specular Microscope SP-1P has a manual image alignment function which allows the operator to utilize the internal function of the SP-1P to focus on the cornea and obtain the image. The manual image alignment can be utilized in difficult lighting or cases where the subject has a difficult time fixating. The Specular Microscope SP-1P also has a manual editing function which allows the clinician to modify the cells selected on the automatically captured image. Photographed images, images for observation and analysis results are displayed on the color LCD monitor with touch panel. An internal printer allows for printing photographed images and analysis results.
Indications for Use
The Specular Microscope SP-1P is a non-contact ophthalmic microscope, optical pachymeter, and camera intended for examination of corneal endothelium and for measurement of the thickness of the cornea.
Substantial Equivalence
The Specular Microscope SP-1P is substantially equivalent to the Konan Cellchek Plus cleared in K120264. The intended use for the Specular Microscope SP-1P and the identified predicate device is to examine the cornea of the eye, and to measure corneal endothelium and corneal thickness by optical means. In addition, cell counting and analysis programs included with the device enable the user to analyze images of the cell distribution in the eye. Therefore, the Specular Microscope SP-1P may be found to be substantially equivalent to the predicate device.
The Specular Microscope SP-1P and the predicate device are both non-contact ophthalmic microscopes, optical pachymeters, and cameras intended for examination of the corneal endothelium and for measurement of the thickness of the cornea. Both the Specular Microscope SP-1P and the predicate device offer automatic capture. Both devices have a central and peripheral fixation targets. Both the Specular Microscope SP-1P and the predicate device have a built-in CCD camera. Slight differences in flash, illumination for focusing and fixation lamps were evaluated in terms of light safety and found to meet the requirements of ISO 15004-2.
Both the Specular Microscope SP-1P and the predicate device include an optical pachymeter with an accuracy of ±10 microns.
Regarding image analysis, both the Specular Microscope SP-1P and the predicate device offer automatic image analysis while the predicate device also offers manual analysis of images. Clinical performance data is provided which evaluates the precision and accuracy of the automatic analysis performed by the Specular Microscope SP-1P compared to the Center Method for the predicate device. The clinical performance data demonstrates the substantial equivalence of the Specular Microscope SP-1P automatic measurement mode to the predicate device.
The Specular Microscope SP-1P has the same intended use and indications for use, technological characteristics, and principles of operation as the previously cleared predicate. Performance data is provided which further supports substantial equivalence.
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Performance Data
The Specular Microscope SP-1P has been tested and found in compliance with the following recognized consensus standards:
AAMI ANSI ES 60601-1:2005/(R)2012 and C1:2009/(R)2012 and A2:2010/(R)2012 Medical Electrical Equipment - Part 1: General Requirements for Basic Safety and Essential Performance:
IEC 60601-1-2: 2007 Medical Electrical Equipment - Part 1-2: General Requirements for Basic Safety and Essential Performance: Collateral Standard: Electromagnetic Capability - Requirements and Tests;
ISO 15004-1:2006 Ophthalmic instruments – Fundamental requirements and test methods - Part 1: General requirements applicable to all ophthalmic instruments;
ISO 15004-2:2007 Ophthalmic Instruments – Fundamental requirements and test methods - Part 2: Light hazard protection;
Both the Specular Microscope SP-1P and the predicate device comply with the following consensus standards: 60601-1-2, ISO 15004-1, and ISO 15004 further supporting substantial equivalence.
Summary of the Performance Testing - Clinical
This study is a prospective, open label, randomized, single center study to gather agreement and precision data. This is an open-label study, however, all subject will be randomized to an order of examination on the devices. For non-pathologic subjects, the study eve will be randomly selected if both eyes qualify. For pathologic subjects, the investigator will select the study eye based on presence of qualifying pathology. The clinical study was conducted to assess the accuracy and precision of the Specular Microscope SP-1P by comparing results across three machines/operators to those obtained with a commercially available predicate device, the CellChek XL (Plus), manufactured by Konan Medical, Inc. Machines were tested in three configurations, each with its own operator, in subjects from three eye populations: nonpathologic young adult (NPY; 18-28 years of age) and non-pathologic adult (NPA; 29-80 years of age) subjects and pathologic adult (PA; 29-80 years of age).
A total of 76 subjects were enrolled in the study and comprised the safety population. The effectiveness population comprised 69 subjects. Of the 69 subjects, 21 were in the NPY eye group, 27 were in the NPA eye group and 21 were in the PA eye group. A total of 28 subjects were included in the agreement only cohort and 41 subjects were included in the precision and agreement cohort.
In the effectiveness population, the mean (SD) age was 22.0 (3.06) years for the NPY eye subjects. 52.9 (14.54) years for the NPA eye subjects, and 61.8 (13.71) years for the PA eye
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subjects. The overall mean age of all subjects was 46.2 (20.34) years. There were 46 females and 23 males and the majority of subjects were white, non-Hispanic.
The primary efficacy endpoints are the agreement and precision of the results for the four key variables of Cell Density, Coefficient of Variation, Hexagonality and Central Corneal Thickness. The primary safety endpoint is any adverse events in the study. The discussion of the results by variables for agreement and precision of the measurements with the Topcon SP-1P and the Konan CellChek XL (Plus) follows:
Corneal Endothelial Cell Density
Corneal endothelial cell density as measured with the SP-1P had a mean (SD) of 2737.1 (439.34) compared with 2635.9 (437.48) for the CellChek XL (Plus). The mean (SD) difference was 101.3 (145.68) (Figure 1) with a mean (SD) difference as a percent of the CellChek reading of 4.11% (5.908%).
The 95% LOA intervals included 0 and the Deming regression lines had an associated R-value of 0.9448 (Figure 4).
Bland Altman plots with data as a percentage of the mean are presented in Figure 2. Plots of the device difference by the CellChek XL (Plus) value are presented in Figure 3.
Figure 1: Bland-Altman Plot – Observed Data – Endothelial Cell Density (ECD) – All Subjects – Effectiveness Population
Image /page/6/Figure/7 description: The image is a scatter plot with the title 'Difference' on the y-axis and 'Mean' on the x-axis. The x-axis ranges from 600 to 3400, while the y-axis ranges from -300 to 500. There are three horizontal lines on the plot, one red line at approximately 100 and two green lines at approximately -200 and 400. The data points are scattered across the plot, with a higher concentration between 2400 and 3000 on the x-axis.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Bland-Altman Plot – Data as a Percentage of the Mean – Endothelial Cell Density (ECD) – Figure 2: All Subjects – Effectiveness Population
Image /page/7/Figure/1 description: This image is a scatter plot that shows the difference (% of the mean) on the y-axis and the mean on the x-axis. The x-axis ranges from 600 to 3400, while the y-axis ranges from -25 to 25. There are three horizontal lines on the plot, one at approximately -7, one at approximately 4, and one at approximately 15.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 3: Device Difference by CellChek XL (Plus) Value – Endothelial Cell Density (ECD) – All Subjects – Effectiveness Population
Image /page/8/Figure/1 description: This image is a scatter plot with the title "Konan CELLCHEK PLUS Value" on the x-axis and "Device Difference" on the y-axis. The x-axis ranges from 600 to 3600, while the y-axis ranges from -150 to 500. The scatter plot shows a cluster of data points between x values of 2000 and 3200, with y values ranging from -100 to 450. There is one outlier data point at approximately (700, 40).
Note: The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Image /page/9/Figure/0 description: This image is a scatter plot comparing SP-1P values to Konan CELLCHEK PLUS values. The plot includes a Deming Regression Line and a 45 Degree Line for reference. The axes range from 600 to 3600, with data points scattered along the positive correlation. The Deming Regression Line appears to fit the data points slightly better than the 45 Degree Line.
Figure 4: Deming Regression Plot – Topcon SP-1P by CellChek XL (Plus) – Endothelial Cell Density (ECD) – All Subjects – Effectiveness Population
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Coefficient of Variation of Endothelial Cell Area
The coefficient of variation of endothelial cell area as measured with the SP-1P had a mean (SD) of 30.5 (3.66) compared with 31.0 (4.04) for the CellChek XL (Plus). The mean (SD) difference was -0.6 (3.47) (Figure 5) with a mean (SD) difference as a percent of the CellChek reading of -1.17% (10.399%).
The 95% LOA intervals included 0 and the Deming regression lines had an associated R" value of 0.5961 (Figure 8).
Bland Altman plots with data as a percentage of the mean are presented in Figure 6. Plots of the device difference by the CellChek XL (Plus) value are presented in Figure 7.
Image /page/10/Figure/4 description: The image is a title for a figure. The title reads "Figure 5 Bland-Altman Plot – Observed Data – Coefficient of Variation Endothelial Cell Area (CV) – All Subjects – Effectiveness Population." This title indicates that the figure is a Bland-Altman plot, which is a type of scatter plot used to compare two methods of measurement. The data being plotted is the coefficient of variation of endothelial cell area, and the data is from all subjects in the effectiveness population.
Image /page/10/Figure/5 description: This image is a scatter plot with the title "Difference" on the y-axis and "Mean" on the x-axis. The x-axis ranges from 20 to 44, while the y-axis ranges from -15 to 15. There are two horizontal green lines at approximately y=6 and y=-7, and a horizontal red line at y=0. The scatter plot contains blue asterisk data points.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 6 Bland-Altman Plot – Data as a Percentage of the Mean – Coefficient of Variation Endothelial Cell Area (CV) – All Subjects – Effectiveness Population
Image /page/11/Figure/1 description: This image is a scatter plot that shows the difference (% of the mean) on the y-axis and the mean on the x-axis. The x-axis ranges from 20 to 44, while the y-axis ranges from -40 to 40. There are two horizontal green lines at approximately 20 and -23, and a horizontal red line at approximately 0.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 7 Device Difference by CellChek XL (Plus) Value – Coefficient of Variation Endothelial Cell Area (CV) – All Subjects – Effectiveness Population
Image /page/12/Figure/1 description: This image is a scatter plot with the title "Konan CELLCHEK PLUS Value" on the x-axis and "Device Difference" on the y-axis. The x-axis ranges from 20 to 48, while the y-axis ranges from -14 to 8. The scatter plot shows a negative correlation between the two variables, with the points clustered more densely between x values of 27 and 33.
Note: The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 8 Deming Regression Plot – Topcon SP-1P by CellChek XL (Plus) – Coefficient of Variation Endothelial Cell Area (CV) – All Subjects – Effectiveness Population
Image /page/13/Figure/1 description: This image is a scatter plot that compares SP-1P values to Konan CELLCHEK PLUS values. The x-axis represents the Konan CELLCHEK PLUS values, ranging from 10 to 60, while the y-axis represents the SP-1P values, also ranging from 10 to 60. The plot includes a Deming Regression Line and a 45 Degree Line, which are used to analyze the relationship between the two variables. The data points are clustered between x values of 25 and 40.
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Percent Hexagonality
Percent hexagonality as measured with the SP-1P had a mean (SD) of 55.1 (10.06) compared with 60.9 (7.41) for the CellChek XL (Plus). The mean (SD) difference was -5.8 (8.87) (Figure 9) with a mean (SD) difference as a percent of the CellChek reading of -9.25% (14.579%).
The 95% LOA intervals included 0 and the Deming regression lines had an associated R2 value was 0.5197 (Figure 12).
Bland Altman plots with data as a percentage of the mean are presented in Figure 10. Plots of the device difference by the CellChek XL (Plus) value are presented in Figure 11.
Figure 9Bland-Altman Plot – Observed Data – % Hexagonality (% 6a) – All Subjects – Effectiveness Population
Image /page/14/Figure/5 description: This image is a scatter plot with the title "Bland-Altman plot". The x-axis is labeled "Mean" and ranges from 20 to 80. The y-axis is labeled "Difference" and ranges from -40 to 20. There are three horizontal lines on the plot, one at approximately -23, one at approximately -5, and one at approximately 12.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Bland-Altman Plot – Data as a Percentage of the Mean – % Hexagonality (% 6a) – All Figure 10 Subjects – Effectiveness Population
Image /page/15/Figure/1 description: This image is a scatter plot that shows the difference (% of the mean) on the y-axis and the mean on the x-axis. The x-axis ranges from 20 to 80, while the y-axis ranges from -70 to 50. There are three horizontal lines on the plot, one at approximately y=23, one at approximately y=-10, and one at approximately y=-45.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs)
The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Device Difference by CellChek XL (Plus) Value – % Hexagonality (% 6a) – All Subjects – Figure 11 Effectiveness Population
Image /page/16/Figure/1 description: This scatter plot shows the relationship between the Konan CELLCHEK PLUS Value and Device Difference. The x-axis represents the Konan CELLCHEK PLUS Value, ranging from 40 to 80. The y-axis represents the Device Difference, ranging from -35 to 20. The data points are scattered across the plot, with a concentration between 55 and 65 on the x-axis and between -10 and 10 on the y-axis.
Note: The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 12 Deming Regression Plot – Topcon SP-1P by CellChek XL (Plus) – % Hexagonality (% 6a) – All Subjects – Effectiveness Population
Image /page/17/Figure/1 description: This image is a scatter plot that compares SP-1P value and Konan CELLCHEK PLUS. The x-axis represents the Konan CELLCHEK PLUS, ranging from 40 to 80, while the y-axis represents the SP-1P value, ranging from 10 to 110. The plot includes a Deming Regression Line and a 45 Degree Line, along with scattered data points.
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Central Corneal Thickness
Central corneal thickness as measured with the SP-1P had a mean (SD) of 535.5 (39.39) compared with 553.7 (46.83) for the CellChek XL (Plus). The mean (SD) difference was -18.2 (15.47) (Figure 13) with a mean (SD) difference as a percent of the CellChek reading of -3.17% (2.663%).
The 95 % LOA intervals included 0 and the Deming regression lines had an associated R value was 0.9501 (Figure 16).
Bland Altman plots with data as a percentage of the mean are presented in Figure 14. Plots of the device difference by the CellChek XL (Plus) value are presented in Figure 15.
Image /page/18/Figure/4 description: This image contains the title of a Bland-Altman Plot that shows observed data for central corneal thickness (CCT) for all subjects. The title also indicates that the data is from the effectiveness population. The figure number is 13.
Image /page/18/Figure/5 description: The image is a scatter plot with the title 'Difference' on the y-axis and 'Mean' on the x-axis. The x-axis ranges from 450 to 700, while the y-axis ranges from -70 to 50. The scatter plot shows a cluster of blue star data points, with a red horizontal line at approximately -18 and two green horizontal lines at approximately 13 and -50.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Figure 14 Bland-Altman Plot – Data as a Percentage of the Mean – Central Corneal Thickness (CCT) – All Subjects – Effectiveness Population
Image /page/19/Figure/1 description: This image is a scatter plot that shows the difference (% of the mean) on the y-axis and the mean on the x-axis. The x-axis ranges from 450 to 700, while the y-axis ranges from -20 to 20. There are three horizontal lines on the plot, one at approximately -9, one at approximately -3, and one at approximately 2. The data points are scattered around the horizontal lines.
Note: The red line is the mean and the green lines are the Limits of Agreement (LOAs) The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Device Difference by CellChek XL (Plus) Value – Central Corneal Thickness (CCT) – All Figure 15 Subjects – Effectiveness Population
Image /page/20/Figure/1 description: This scatter plot shows the relationship between the Konan CELLCHEK PLUS Value and Device Difference. The x-axis represents the Konan CELLCHEK PLUS Value, ranging from 450 to 750, while the y-axis represents the Device Difference, ranging from -60 to 30. The plot displays a cluster of data points, with most points concentrated between 500 and 600 on the x-axis and between -30 and 0 on the y-axis. There appears to be a slight negative correlation, as the Device Difference tends to decrease as the Konan CELLCHEK PLUS Value increases.
Note: The differences are calculated as (Topcon SP-1P) – (Konan CellChek XL [Plus])
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Deming Regression Plot – Topcon SP-1P by CellChek XL (Plus) – Central Corneal Thickness Figure 16 (CCT) – All Subjects – Effectiveness Population
Image /page/21/Figure/1 description: This image is a scatter plot that compares SP-1P values to Konan CELLCHEK PLUS values. The x-axis represents the Konan CELLCHEK PLUS values, ranging from 450 to 750, while the y-axis represents the SP-1P values, also ranging from 450 to 750. The plot includes a Deming Regression Line and a 45 Degree Line, which are used to analyze the relationship between the two sets of values. The data points are clustered around the lines, indicating a positive correlation between SP-1P and Konan CELLCHEK PLUS values.
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Table 1 provides a summary of the agreement data for all subjects in tabular format as a summary.
| Table 1 - Four Corneal Specular Microscopic Variables Assessed with the Two Devices – All Configurations - |
|---|
| – All Subjects – Effectiveness Population |
| ECD | CV | % 6a | CCT | |
|---|---|---|---|---|
| Topcon SP-1P | ||||
| N | 69 | 69 | 69 | 69 |
| 2737.1 | 30.5 | 55.1 | 535.5 | |
| Mean (SD) | (439.34) | (3.66) | (10.06) | (39.39) |
| Median | 2772.0 | 30.0 | 56.0 | 537.0 |
| Min-Max | 700-3413 | 23-40 | 31-79 | 466-669 |
| Konan CellChek XL (Plus) | ||||
| N | 69 | 69 | 69 | 69 |
| 2635.9 | 31.0 | 60.9 | 553.7 | |
| Mean (SD) | (437.48) | (4.04) | (7.41) | (46.83) |
| Median | 2681.0 | 31.0 | 61.0 | 558.0 |
| Min- Max | 662-3413 | 23-47 | 42-78 | 461-706 |
| Device Comparisons | ||||
| Mean Difference (SD) | 101.3 | -0.6 | -5.8 | -18.2 |
| (145.68) | (3.47) | (8.87) | (15.47) | |
| Mean Difference (SD) as a % | 4.11% | -1.17% | -9.25% | -3.17% |
| of the CellChek reading | (5.908%) | (10.399%) | (14.579%) | (2.663%) |
| 95% LOA | (-190.1, 392.6) | (-7.5, 6.4) | (-23.5, 11.9) | (-49.1, 12.7) |
| Correlation (R²) | 0.9448 | 0.5961 | 0.5197 | 0.9501 |
| Deming Regression | 89.4 | 4.2 | -52.2 | 73.9 |
| Intercept (95% CI) | (-100.9, 279.7) | (-9.0, 17.4) | (-95.8, -8.6) | (41.7, 106.2) |
| Deming Regression Slope | 1.0 | 0.5 | 1.8 | 0.8 |
| (95% CI) | (0.9, 1.1) | (0.4, 0.7) | (1.1, 2.5) | (0.7, 0.9) |
| 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 (Topcon SP-1P) - (Konan CellChek XL [Plus]). |
The mean differences as a % of the CELLCHECK reading are calculated for each subject first and then summarized.
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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. Table 2 shows the repeatability and reproducibility data for each of the 4 variables in all subjects.
Table 2 Repeatability/Reproducibility Ratios by Measurement and Subject Population for All Configurations
| All Subjects | Pathologic Adult | Non PathologicAdult | Non PathologicYoung | |
|---|---|---|---|---|
| Parameter | ||||
| ECD | 1.1019/1.1148 | 1.5159/1.4140 | 0.9016/0.9263 | 1.0641/1.1957 |
| CV | 0.6984/0.6873 | 0.8343/0.7698 | 0.6416/0.5967 | 0.5884/0.7094 |
| % 6a | 1.1369/1.1645 | 1.4190/1.3395 | 1.1226/1.1371 | 0.8849/1.0102 |
| CCT | 0.2910/0.3110 | 0.2727/0.3197 | 0.2858/0.3075 | 0.3219/0.3036 |
| The repeatability ratios = Topcon SP-1P/CellChek XL (Plus) | ||||
| NA= not applicable |
Table 3 summarizes the precision analyses for all subjects.
| Table 3 Precision Analyses -All Subjects-Effectiveness Population | ||
|---|---|---|
| Variable | Topcon SpecularMicroscope SP-1PN=41 | Konan CellChek XL (Plus)N=41 |
|---|---|---|
| ECD | ||
| Repeatability SD | 70.7 | 64.1 |
| Repeatability SD as a % of the Mean | 2.5% | 2.4% |
| Repeatability Limit | 197.9 | 179.6 |
| Repeatability Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 1.1019 | -- |
| Reproducibility SD | 76.6 | 68.8 |
| Reproducibility SD as a % of the Mean | 2.7% | 2.5% |
| Reproducibility Limit | 214.6 | 192.5 |
| Reproducibility Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 1.1148 | -- |
| CV | ||
| Repeatability SD | 1.6 | 2.3 |
| Repeatability SD as a % of the Mean | 5.3% | 7.2% |
| Repeatability Limit | 4.4 | 6.3 |
| Repeatability Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 0.6984 | -- |
| Reproducibility SD | 1.7 | 2.4 |
| Reproducibility SD as a % of the Mean | 5.5% | 7.7% |
| Reproducibility Limit | 4.6 | 6.7 |
| Reproducibility Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 0.6873 | -- |
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| Variable | Topcon SpecularMicroscope SP-1PN=41 | Konan CellChek XL (Plus)N=41 |
|---|---|---|
| % 6a | ||
| Repeatability SD | 4.9 | 4.3 |
| Repeatability SD as a % of the Mean | 8.4% | 7.0% |
| Repeatability Limit | 13.7 | 12.1 |
| Repeatability Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 1.1369 | -- |
| Reproducibility SD | 5.2 | 4.5 |
| Reproducibility SD as a % of the Mean | 9.0% | 7.3% |
| Reproducibility Limit | 14.7 | 12.6 |
| Reproducibility Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 1.1645 | -- |
| CCT | ||
| Repeatability SD | 3.4 | 11.8 |
| Repeatability SD as a % of the Mean | 0.6% | 2.1% |
| Repeatability Limit | 9.6 | 33.0 |
| Repeatability Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 0.2910 | -- |
| Reproducibility SD | 3.9 | 12.6 |
| Reproducibility SD as a % of the Mean | 0.7% | 2.3% |
| Reproducibility Limit | 11.0 | 35.3 |
| Reproducibility Ratio [Specular MicroscopeSP-1P/CellChek XL (Plus)] | 0.3110 | -- |
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.
Source: Table 14.2.2
Non-Evaluable Images
There were 20 subjects on the SP-1P machine that recorded Non-evaluable results and 4 subjects on the CellChek Plus. A breakdown can be seen in Table 4.
Table 4 Non-Evaluable Results
| Non-PathologicYoung(N=23) | Non-PathologicAdult(N=27) | PathologicAdult(N=26) | All Subjects(N=76) | |
|---|---|---|---|---|
| Total Non-Evaluable | ||||
| SP-1P | 6 (26.1%) | 2 (7.4%) | 12 (46.2%) | 20 (26.3%) |
| CellChek Plus | 1 (4.3%) | 0 (0.0%) | 3 (11.5%) | 4 (5.3%) |
| Insufficient Number ofCells |
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| SP-1P | 0 (0.0%) | 1 (3.7%) | 0 (0.0%) | 1 (1.3%) |
|---|---|---|---|---|
| CellChek Plus | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Insufficient Quality | ||||
| SP-1P | 6 (26.1%) | 1 (3.7%) | 12 (46.2%) | 19 (25.0%) |
| CellChek Plus | 1 (4.3%) | 0 (0.0%) | 3 (11.5%) | 4 (5.3%) |
| Fair Quality | ||||
| SP-1P | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| CellChek Plus | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Poor Quality | ||||
| SP-1P | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| CellChek Plus | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Impossible Quality | ||||
| SP-1P | 6 (26.1%) | 1 (3.7%) | 12 (46.2%) | 19 (25.0%) |
| CellChek Plus | 1 (4.3%) | 0 (0.0%) | 3 (11.5%) | 4 (5.3%) |
The high numbers of non-evaluable eves in the Table 4 is an artifact of the study design and not indicative of the clinical utility of the SP-1P. Any eye that did not have a full dataset available was considered non-evaluable. Subjects participating in the Agreement/Precision Group required 18 acceptable total images and subjects in the Agreement Only Group required 2 acceptable images. Therefore, all subjects that did not meet the minimum number of acceptable images were included in the Non-Evaluable table.
There were 6 times that no images with numerical values were collected for the SP-1P and 4 times for the CellChek. In the cases where no numerical calculation was provided the raw images were available for clinical usability.
There were no AEs in this study in any subject. No safety issues of any kind arose during this study, regardless of the device used. Both instruments were found to be safe and reliable in the assessments of corneal function in all of the eye populations evaluated (NPY, NPA, and PA).
Conclusions
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. Repeatability was comparable for ECD, CV and % 6a between the two machines while the SP-1P was better for CCT.
In summary, the agreement and precision of the Topcon SP-1P was found to be substantially equivalent to the Konan CellChek XL (Plus).
§ 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.