(152 days)
No
The document describes algorithms for segmentation and analysis, and mentions a normative database, but does not explicitly state the use of AI or ML. The performance studies focus on repeatability, reproducibility, and comparison to a predicate device, not on the performance of an AI/ML model.
No
The device is described as an imaging and diagnostic tool, supporting diagnosis and monitoring of eye diseases. It does not provide any form of therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states, "It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, macular holes, cystoid macular edema, diabetic retinopathy, age-related macular degeneration, and glaucoma."
No
The device description explicitly states that the CIRRUS photo is a computerized optical instrument that combines a Fundus Camera Main Unit and a spectral domain optical coherence tomographer (SD-OCT) Module, both of which are installed on a single instrument table. This indicates the presence of significant hardware components beyond just software.
Based on the provided information, the CIRRUS photo is not an In Vitro Diagnostic (IVD) device.
Here's why:
- IVD Definition: In Vitro Diagnostic devices are used to examine specimens (like blood, urine, or tissue) taken from the human body to provide information for diagnosis, monitoring, or screening.
- CIRRUS photo Function: The CIRRUS photo is a non-contact imaging device that directly examines the eye in vivo (within the living body). It captures images and performs measurements of ocular structures.
- Intended Use: The intended use clearly states it is for "in vivo viewing, axial cross sectional, and three-dimensional imaging and measurement of posterior ocular structures... as well as imaging of anterior ocular structures and measurement of central corneal thickness." It also uses normative databases for comparison, but this is based on in vivo measurements, not analysis of in vitro specimens.
Therefore, the CIRRUS photo falls under the category of an in vivo diagnostic imaging device, not an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The CIRRUS photo is a non-contact, high resolution tomographic and biomicroscopic imaging device that incorporates a digital camera which is suitable for photographing, displaying and storing the data of the retina and surrounding parts of the eye to be examined under mydriatic and non-mydriatic conditions.
These photographs support the diagnosis and subsequent observation of eye diseases which can be visually monitored and photographically documented. The CIRRUS photo is indicated for in vivo viewing, axial cross sectional, and three-dimensional imaging and measurement of posterior ocular structures, including retinal nerve fiber layer, macula and optic disc as well as imaging of anterior ocular structures and measurement of central corneal thickness.
It also includes a Retinal Nerve Fiber Layer (RNFL), Optic Nerve Head (ONH), and Macular Normative Database which are quantitative tools for the comparison of retinal nerve fiber layer, optic nerve head, and the macula in the human retina to a database of known normal subjects. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, macular holes, cystoid macular edema, diabetic retinopathy, age-related macular degeneration, and glaucoma.
Product codes
OBO, HKI
Device Description
The CIRRUS photo is a computerized optical instrument that combines the diagnostic and imaging capabilities of the Carl Zeiss Meditec VISUCAM PRO NM Digital Camera and the Carl Zeiss Meditec Cirrus HD-OCT Optical Coherence Tomographer Model 4000. The CIRRUS photo was developed to provide both subjective and objective imaging, and to optimize space by combining fundus photography and spectral domain optical coherence tomography, allowing the anterior or posterior segments of the eye to be viewed and photographically documented with the pupil in a non-mydriatic state, within the same instrument. To optimize the workflow, the system applies the same optical beam delivery system for imaging and scanning.
The CIRRUS photo consists of a Fundus Camera Main Unit and a spectral domain optical coherence tomographer (SD-OCT) Module, both of which are installed on a single instrument table. The CIRRUS photo is operated via computer mouse, keyboard and joystick as part of the base of the main unit and an external monitor is mounted on top of the instrument table.
The CIRRUS photo is offered in two models. Model 600 and Model 800. Fundus auto fluorescence is available on both the Model 600 and 800; the Model 800 also offers fluorescein angiography and indocyanine green angiography (ICGA).
CIRRUS photo data can be analyzed using the same Cirrus HD-OCT algorithms and normative database cleared under K111157 (Cirrus HD-OCT software version 6.0), including Advanced Retinal Pigment Epithelium (RPE) Analysis, Guided Progression Analysis (GPA) for Optic Nerve Head (ONH) parameters, and Ganglion Cell Analysis, and the Ganglion Cell Normative Database. As these algorithms and database reside separately on the Cirrus HD-OCT version 6.0 software, the analyses of the CIRRUS photo data are carried out using an external Cirrus Review station.
New Features:
Measurement of Central Corneal Thickness
Advanced Retinal Pigment Epithelium (RPE) Analysis: allows user to examine RPE status in greater detail than Macular Thickness Analysis using two Cirrus algorithms; one to identify and measure areas of sub-RPE illumination (indicating RPE is atrophic), and one to identify and measure elevations in the RPE (associated with drusen).
Guided Progression Analysis (GPA) for Optic Nerve Head Parameters: compares measurements from Optic Disc cube 200 x 200 scan over time and determines if change over time has occurred that exceeds test-retest variability. Analysis includes chronological display of RNFL thickness maps, RNFL change maps, cup and disc boundaries, and thickness graphs (rate of change for average thickness parameters and average cup-to-disc ratio, and RNFL thickness profiles).
Ganglion Cell Analysis (GCA): measures thickness of sum of ganglion cell layer and inner plexiform layer (GCL + IPL) using data from Macular 200 x 200 or Macular 512 x 128 cube scan patterns.
Ganglion Cell Normative Database: derived from an additional analysis of the macula normative database. To establish reference values, scans acquired as part of the Cirrus HD-OCT Macular Thickness normative database were analyzed using a segmentation algorithm that identifies the thickness of the combined ganglion cell plus inner plexiform layers.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Optical Coherence Tomography (OCT), Digital Camera (Fundus Photography)
Anatomical Site
Eye (posterior ocular structures including retina, retinal nerve fiber layer, macula, optic disc; anterior ocular structures including cornea)
Indicated Patient Age Range
19-84 years (for normative database subjects)
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Normal Eyes Study:
Sample Size: 63 normal subjects (30 in Phase 1, 33 in Phase 2)
Data Source: Clinical study. One eye per subject per phase.
Annotation Protocol:
Phase 1 (inter-operator variability): For each subject, three Optic Disc Cube 200x200 scans were taken on one eye, and three Macular Cube 512x128 scans were taken on the fellow eye by each of four operators using one Cirrus HD-OCT Model 4000 and one CIRRUS photo instrument.
Phase 2 (inter-device variability): For each subject, three Optic Disc Cube 200x200 scans were taken on one eye, and three Macular Cube 512x128 scans were taken on the fellow eye from each of the four Cirrus HD-OCT Model 4000 instruments and each of the four CIRRUS photo instruments by one operator.
Diseased Eyes Study:
Sample Size: 77 subjects with glaucoma enrolled, 68 included in analysis.
Data Source: Clinical study.
Annotation Protocol: For each subject, three Macular Cube 512x128 scans and three Macular Cube 200x200 scans were taken on each of three CIRRUS photo instruments by three operators and one Cirrus HD-OCT instrument by one of the three operators.
Anterior Segment Study (Central Corneal Thickness):
Sample Size: 29 subjects in Phase I, 23 subjects in Phase II.
Data Source: Clinical study.
Annotation Protocol: Three acceptable Anterior Segment Cube 512x128 scans were taken from each device. In Phase I, a single operator obtained scans from three CIRRUS photo instruments and one Cirrus HD-OCT. In Phase II, three operators obtained scans on each of three CIRRUS photo devices; one also obtained scans from Cirrus HD-OCT.
Posterior Segment Studies (Sub-RPE Illumination and RPE Elevation):
Sub-RPE Illumination Study:
Sample Size: 21 subjects with dry AMD and geographic atrophy.
Data Source: Clinical study.
Annotation Protocol: Macular Cube 200 x 200 scans and Macular Cube 512x128 scans were acquired. Operators reviewed and corrected foveal centration and manually edited automated segmentation of increased illumination areas under the RPE.
RPE Elevation Study:
Sample Size: 31 subjects with dry AMD and drusen, 25 and 26 subjects analyzed for 200x200 and 512x128 scans respectively in the RPE elevation study for area and volume.
Data Source: Clinical study.
Annotation Protocol: Macular Cube 200x200 scans and Macular Cube 512x128 scans were acquired.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Testing: Comparability, Repeatability, and Reproducibility
1. Anterior Segment Study: Repeatability and Reproducibility of CIRRUS photo Central Corneal Thickness Measurements and Comparison to CIRRUS HD-OCT.
- Study type: Prospective, multi-phase study.
- Sample size: Phase I: 29 subjects (28 for agreement analysis). Phase II: 23 subjects.
- Key results:
- Equivalence of mean CCT measurements between CIRRUS photo and Cirrus HD-OCT Model 4000.
- Mean difference in CCT: Phase I: 0.89 µm (SD 5.04). Phase II: -1.20 µm (SD 2.28).
- CIRRUS photo showed good repeatability and reproducibility across a large range of values.
- Repeatability SD: 4.49 µm; Repeatability Limit: 12.57 µm; Repeatability COV: 0.8%.
- Reproducibility SD: 5.216 µm; Reproducibility Limit: 14.604 µm; Reproducibility COV: 0.96%.
2. Posterior Segment Studies: Repeatability and Reproducibility of CIRRUS photo Measurements of Area of Increased Illumination Under the RPE and Comparison to CIRRUS HD-OCT.
- Study type: Non-significant risk multiple site study.
- Sample size: 21 subjects with dry AMD and geographic atrophy (19 subjects for 200x200 and 512x128 scan comparisons).
- Key results:
- High level of agreement between CIRRUS photo and Cirrus HD-OCT for sub-RPE illumination area and closest distance to fovea.
- Mean difference in Area of Sub-RPE Illumination: -0.0108 mm² (SD 0.3161) for 200x200 scan; -0.0314 mm² (SD 0.2964) for 512x128 scan.
- Mean difference in Closest Distance to Fovea: 0.01 mm (SD 0.04) for 200x200 scan; 0.02 mm (SD 0.04) for 512x128 scan.
- Repeatability and reproducibility SD and limits of CIRRUS photo were small.
- Area of Sub-RPE Illumination (200x200): Repeatability SD 0.1099 mm², Reproducibility SD 0.1774 mm².
- Area of Sub-RPE Illumination (512x128): Repeatability SD 0.1329 mm², Reproducibility SD 0.2442 mm².
- Closest Distance to Fovea (200x200): Repeatability SD 0.0343 mm, Reproducibility SD 0.0447 mm.
- Closest Distance to Fovea (512x128): Repeatability SD 0.0397 mm, Reproducibility SD 0.0571 mm.
3. Posterior Segment Studies: Repeatability and Reproducibility of CIRRUS photo Measurements of Elevated RPE and Comparison to CIRRUS HD-OCT.
- Study type: Non-significant risk single site study.
- Sample size: 31 subjects with dry AMD and drusen (25 subjects for 200x200 scan, 26 subjects for 512x128 scan).
- Key results:
- High level of agreement between CIRRUS photo and Cirrus HD-OCT for area and volume of RPE elevations.
- Mean differences were very close to zero.
- Reproducibility COV% range: 8.30% to 9.18% for 200x200; 8.46% to 9.07% for 512x128.
- Area of RPE Elevations (3mm Circle, 200x200): Repeatability SD 0.0842, Reproducibility SD 0.1004.
- Volume of RPE Elevations (3mm Circle, 200x200): Repeatability SD 0.0036, Reproducibility SD 0.0047.
4. Repeatability and Reproducibility of CIRRUS photo Ganglion Cell Measurements and Comparison to CIRRUS HD-OCT.
- Study type: Two studies: one for normal eyes, one for diseased eyes.
- Sample size: Normal Eyes Study: 63 normal subjects (33 for inter-device phase). Diseased Eyes Study: 77 subjects with glaucoma (68 included in analysis).
- Key results:
- Mean values of eight thickness parameters were very similar for the two devices.
- Results support incorporation of Cirrus HD-OCT GCA Normative Database into CIRRUS photo with an adjustment based on regression analysis.
- CIRRUS photo showed good repeatability and reproducibility for both normal and diseased eyes. Notably small mean differences in GCA parameters between devices.
- Normal Eyes (Average GCL+IPL Thickness): Mean difference -0.3 µm (SD 0.4), Reproducibility SD 0.8113 µm.
- Diseased Eyes (Average GCL+IPL Thickness): Mean difference -0.3 µm (SD 0.6), Reproducibility SD 0.6413 µm.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Central Corneal Thickness (CCT):
- Repeatability SD: 4.49 microns
- Repeatability Limit: 12.57 microns
- Repeatability COV: 0.008 (0.8%)
- Reproducibility SD: 5.216 microns
- Reproducibility Limit: 14.604 microns
- Reproducibility COV: 0.0096 (0.96%)
Area of Sub-RPE Illumination:
- 200x200 Scan Repeatability SD: 0.1099 mm²
- 200x200 Scan Repeatability Limit: 0.3078 mm²
- 200x200 Scan Repeatability COV%: 1.52%
- 200x200 Scan Reproducibility SD: 0.1774 mm²
- 200x200 Scan Reproducibility Limit: 0.4968 mm²
- 200x200 Scan Reproducibility COV%: 2.45%
- 512x128 Scan Repeatability SD: 0.1329 mm²
- 512x128 Scan Repeatability Limit: 0.3720 mm²
- 512x128 Scan Repeatability COV%: 1.83%
- 512x128 Scan Reproducibility SD: 0.2442 mm²
- 512x128 Scan Reproducibility Limit: 0.6838 mm²
- 512x128 Scan Reproducibility COV%: 3.36%
Closest Distance to Fovea:
- 200x200 Scan Repeatability SD: 0.0343 mm
- 200x200 Scan Repeatability Limit: 0.0961 mm
- 200x200 Scan Reproducibility SD: 0.0447 mm
- 200x200 Scan Reproducibility Limit: 0.1252 mm
- 512x128 Scan Repeatability SD: 0.0397 mm
- 512x128 Scan Repeatability Limit: 0.1113 mm
- 512x128 Scan Reproducibility SD: 0.0571 mm
- 512x128 Scan Reproducibility Limit: 0.1597 mm
Area of RPE Elevations (3 mm Circle):
- 200x200 Scan Repeatability SD: 0.0842
- 200x200 Scan Repeatability Limit: 0.2357
- 200x200 Scan Repeatability COV%: 6.96%
- 200x200 Scan Reproducibility SD: 0.1004
- 200x200 Scan Reproducibility Limit: 0.2812
- 200x200 Scan Reproducibility COV%: 8.30%
- 512x128 Scan Repeatability SD: 0.0808
- 512x128 Scan Repeatability Limit: 0.2262
- 512x128 Scan Repeatability COV%: 6.72%
- 512x128 Scan Reproducibility SD: 0.1069
- 512x128 Scan Reproducibility Limit: 0.2994
- 512x128 Scan Reproducibility COV%: 8.89%
Area of RPE Elevations (5 mm Circle):
- 200x200 Scan Repeatability SD: 0.1165
- 200x200 Scan Repeatability Limit: 0.3262
- 200x200 Scan Repeatability COV%: 6.49%
- 200x200 Scan Reproducibility SD: 0.1553
- 200x200 Scan Reproducibility Limit: 0.4348
- 200x200 Scan Reproducibility COV%: 8.66%
- 512x128 Scan Repeatability SD: 0.1264
- 512x128 Scan Repeatability Limit: 0.3539
- 512x128 Scan Repeatability COV%: 7.03%
- 512x128 Scan Reproducibility SD: 0.1521
- 512x128 Scan Reproducibility Limit: 0.4260
- 512x128 Scan Reproducibility COV%: 8.46%
Volume of RPE Elevations (3 mm Circle):
- 200x200 Scan Repeatability SD: 0.0036
- 200x200 Scan Repeatability Limit: 0.0101
- 200x200 Scan Repeatability COV%: 6.49%
- 200x200 Scan Reproducibility SD: 0.0047
- 200x200 Scan Reproducibility Limit: 0.0131
- 200x200 Scan Reproducibility COV%: 8.45%
- 512x128 Scan Repeatability SD: 0.0035
- 512x128 Scan Repeatability Limit: 0.0097
- 512x128 Scan Repeatability COV%: 7.03%
- 512x128 Scan Reproducibility SD: 0.0045
- 512x128 Scan Reproducibility Limit: 0.0125
- 512x128 Scan Reproducibility COV%: 9.07%
Volume of RPE Elevations (5 mm Circle):
- 200x200 Scan Repeatability SD: 0.0055
- 200x200 Scan Repeatability Limit: 0.0153
- 200x200 Scan Repeatability COV%: 6.78%
- 200x200 Scan Reproducibility SD: 0.0074
- 200x200 Scan Reproducibility Limit: 0.0208
- 200x200 Scan Reproducibility COV%: 9.18%
- 512x128 Scan Repeatability SD: 0.0058
- 512x128 Scan Repeatability Limit: 0.0163
- 512x128 Scan Repeatability COV%: 7.81%
- 512x128 Scan Reproducibility SD: 0.0067
- 512x128 Scan Reproducibility Limit: 0.0188
- 512x128 Scan Reproducibility COV%: 8.99%
Average GCL+IPL Thickness (Normal Eyes):
- Repeatability SD: 0.6103 µm
- Repeatability Limit: 1.7088 µm
- Repeatability COV%: 0.73%
- Reproducibility SD: 0.8113 µm
- Reproducibility Limit: 2.2717 µm
- Reproducibility COV%: 0.97%
Average GCL+IPL Thickness (Diseased Eyes):
- Repeatability SD: 0.5982 µm
- Repeatability Limit: 1.6750 µm
- Repeatability COV%: 0.91%
- Reproducibility SD: 0.6413 µm
- Reproducibility Limit: 1.7955 µm
- Reproducibility COV%: 0.98%
Predicate Device(s)
CIRRUS photo (K112184), Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, Optic Nerve Head and Ganglion Cell Normative Databases (K111157)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 886.1570 Ophthalmoscope.
(a)
Identification. An ophthalmoscope is an AC-powered or battery-powered device containing illumination and viewing optics intended to examine the media (cornea, aqueous, lens, and vitreous) and the retina of the eye.(b)
Classification. Class II (special controls). The device, when it is an AC-powered opthalmoscope, a battery-powered opthalmoscope, or a hand-held ophthalmoscope replacement battery, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.
0
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K133217 MAR 1 9 2014
SECTION 5.
。
. T
510(K) SUMMARY
5. 510(k) Summary
510(k) SUMMARY (per 21 CFR §807.92)
CIRRUS photo
GENERAL INFORMATION
| Applicant: | Carl Zeiss Meditec AG
Goeschwitzer Strasse 51-52
07745 Jena
Germany |
|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Mandy Ambrecht
Staff Regulatory Affairs Specialist
Carl Zeiss Meditec Inc.
5160 Hacienda Drive
Dublin, California 94568
(925) 557-4561 (phone)
(925) 557-4259 (fax) |
| Date Summary Prepared: | March 6, 2014 |
| Classification Name: | Tomography, Optical coherence
Camera, Ophthalmic, AC-powered |
| Product Code and Class: | OBO - Class II
HKI - Class II |
| Classification Number: | 886.1570
886.1120 |
| Trade/Proprietary name: | CIRRUS photo Models 600 and 800 |
| PREDICATE DEVICES | |
| Company:
Device: | Carl Zeiss Meditec AG
CIRRUS photo (K112184) |
| Company:
Device: | Carl Zeiss Meditec, Inc.
Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular,
Optic Nerve Head and Ganglion Cell Normative Databases
(K111157) |
1
INDICATIONS FOR USE
The CIRRUS photo is a non-contact, high resolution tomographic and biomicroscopic imaging device that incorporates a digital camera which is suitable for photographing, displaying and storing the data of the retina and surrounding parts of the eye to be examined under mydriatic and non-mydriatic conditions.
These photographs support the diagnosis and subsequent observation of eye diseases which can be visually monitored and photographically documented. The CIRRUS photo is indicated for in vivo viewing, axial cross sectional, and three-dimensional imaging and measurement of posterior ocular structures, including retinal nerve fiber layer, macula and optic disc as well as imaging of anterior ocular structures and measurement of central corneal thickness.
It also includes a Retinal Nerve Fiber Layer (RNFL), Optic Nerve Head (ONH), and Macular Normative Database which are quantitative tools for the comparison of retinal nerve fiber laver, optic nerve head, and the macula in the human retina to a database of known normal subjects. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, macular holes, cystoid macular edema, diabetic retinopathy, age-related macular degeneration, and glaucoma.
DEVICE DESCRIPTION
The CIRRUS photo is a computerized optical instrument that combines the diagnostic and imaging capabilities of the Carl Zeiss Meditec VISUCAM PRO NM Digital Camera and the Carl Zeiss Meditec Cirrus HD-OCT Optical Coherence Tomographer Model 4000. The CIRRUS photo was developed to provide both subjective and objective imaging, and to optimize space by combining fundus photography and spectral domain optical coherence tomography, allowing the anterior or posterior segments of the eye to be viewed and photographically documented with the pupil in a non-mydriatic state, within the same instrument. To optimize the workflow, the system applies the same optical beam delivery system for imaging and scanning.
The CIRRUS photo consists of a Fundus Camera Main Unit and a spectral domain optical coherence tomographer (SD-OCT) Module, both of which are installed on a single instrument table. The CIRRUS photo is operated via computer mouse, keyboard and joystick as part of the base of the main unit and an external monitor is mounted on top of the instrument table.
The CIRRUS photo is offered in two models. Model 600 and Model 800. Fundus auto fluorescence is available on both the Model 600 and 800; the Model 800 also offers fluorescein angiography and indocyanine green angiography (ICGA).
CIRRUS photo data can be analyzed using the same Cirrus HD-OCT algorithms and normative database cleared under K111157 (Cirrus HD-OCT software version 6.0), including
2
Advanced Retinal Pigment Epithelium (RPE) Analysis, Guided Progression Analysis (GPA) for Optic Nerve Head (ONH) parameters, and Ganglion Cell Analysis, and the Ganglion Cell Normative Database. As these algorithms and database reside separately on the Cirrus HD-OCT version 6.0 software, the analyses of the CIRRUS photo data are carried out using an external Cirrus Review station.
New Features
Measurement of Central Corneal Thickness
In addition to imaging anterior structures, the CIRRUS photo has the capability to measure central corneal thickness.
Advanced Retinal Pigment Epithelium (RPE) Analysis
The Advanced RPE Analysis allows the user to examine the status of the RPE in greater detail than the Macular Thickness Analysis using two Cirrus algorithms: one to identify and measure areas of sub-RPE illumination where the OCT is able to penetrate through to the choroid, indicating that the RPE is atrophic (often associated with geographic atrophy), and one to identify and measure elevations in the RPE (often associated with drusen).
Guided Progression Analysis (GPA) for Optic Nerve Head Parameters
GPA compares measurements from the Optic Disc cube 200 x 200 scan over time and determines if change over time has occurred that exceeds the test-retest variability. The analysis includes a chronological display of RNFL thickness maps, RNFL change maps, cup and disc boundaries, and thickness graphs representing rate of change for average thickness parameters and average cup-to-disc ratio as well as RNFL thickness profiles comparing the current exam to the baseline exams.
Ganglion Cell Analysis (GCA)
The Ganglion Cell Analysis (GCA) measures the thickness of the sum of the ganglion cell laver and inner plexiform layer (GCL + IPL) using data from the Macular 200 x 200 or Macular 512 x 128 cube scan patterns.
Ganglion Cell Normative Database
The CIRRUS Photo Retinal Nerve Fiber Layer (RNFL), Optic Nerve Head (ONH), and Macular Normative Databases were cleared under K112184.
The Cirrus Ganglion Cell normative database [for the Cirrus HD-OCT] was derived from an additional analysis of the macula normative database. To establish reference values, the scans acquired as part of the Cirrus HD-OCT Macular Thickness normative database were analyzed using a segmentation algorithm that identifies the thickness of the combined ganglion cell plus inner plexiform layers.
The database parameters are the same as those used in the original macula normative database. The Ganglion Cell database utilized the same 282 subjects, aged 19-84 years that were deemed representative of a normal population. The data was collected from seven sites. The normative database is age-corrected and has a gender distribution of 133 males, 149
3
females. Ethnicity breakdown of the normative database is as follows: 43% Caucasians, 24% Asians, 18% African American, 12% Hispanic, 1% Indian, and 6% mixed ethnicity.
SUBSTANTIAL EQUIVALENCE
It is the opinion of Carl Zeiss Meditec AG that the CIRRUS photo is substantially equivalent to the CIRRUS photo (K112184) and to the Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, Optic Nerve Head and Ganglion Cell Normative Databases (K111157). The indications for use for the CIRRUS photo is similar to the indications for the predicate devices cited in this application. A technological comparison and clinical testing demonstrate that the CIRRUS photo is functionally equivalent to the predicate devices.
Evaluation performed on the CIRRUS photo supports the expanded indications for use statement and demonstrates that the device is substantially equivalent to the predicate devices and does not raise new questions regarding safety and effectiveness.
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
The CIRRUS photo has very similar indications for use and operating characteristics as the predicate devices. The fundus camera unit of the proposed CIRRUS photo is exactly the same as the predicate CIRRUS photo (K112184) thus it utilizes the same imaging properties and technology as the cleared CIRRUS photo to record morphologic images of the human retina under mydriatic and non-mydriatic conditions, respectively. The SD-OCT Module is the same optical coherence tomography system as in the cleared CIRRUS photo instrument (K112184) and the Cirrus HD-OCT Optical Coherence Tomographer, Model 4000 (K111157).
The CIRRUS photo is therefore substantially equivalent to the predicate devices, i.e., the Carl Zeiss CIRRUS photo (K112184) and the Carl Zeiss Meditec Cirrus HD-OCT, Model 4000 (K11157).
BRIEF SUMMARY OF NON CLINICAL AND CLINICAL TESTS AND RESULTS
The CIRRUS photo has been designed and tested to the applicable standards for electrical and optical safety and verified to established specifications. In addition, clinical testing was conducted.
4
CLINICAL TESTING
Five prospective studies were conducted to determine comparability, repeatability and reproducibility of the measurement data between the CIRRUS photo and Cirrus HD-OCT Model 4000 instruments.
ANTERIOR SEGMENT STUDY
REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO CENTRAL CORNEAL THICKNESS MEASUREMENTS AND COMPARISON TO CIRRUS HD-OCT
A study was conducted to evaluate the equivalence of the mean values of the Central Corneal Thickness (CCT) measurement parameter between the CIRRUS photo and Cirrus HD-OCT, Model 4000 and to determine repeatability and reproducibility of the CIRRUS photo instrument measurements of CCT.
The study inclusion criteria required adult males or females with no known corneal disease or surgery and who were able and willing to make the required study visits, give consent and follow study instructions. In addition, it was required that the subject's study eye have best corrected visual acuity of 20/40 or better and did not have: any previous surgery or laser procedures on the cornea; any corneal abnormality upon slit lamp examination or any abnormality upon examination with a CIRRUS model 4000.
The study exclusion criteria required that the subject's study eye did not have prior refractive or corneal surgery and could not present with known corneal disorders such as keratoconus, corneal leukoma, degenerative diseases, active inflammation, or infections. Subjects with any corneal abnormality upon examination with a slit lamp or a CIRRUS model 4000 were excluded as were subjects who had any known allergy to anesthetic eve drops or whose best corrected visual acuity was worse than 20/40 in the study eye. In addition, blind subjects or those who had low vision and/or severely diseased eyes or who were unable to make the required study visits, give consent or follow study instructions were excluded.
The study was divided into two phases. CCT measurements with the CIRRUS photo and Cirrus HD-OCT, Model 4000, were obtained during both phases. During both phases, three acceptable Anterior Segment Cube 512x128 scans were taken from each device.
Twenty-nine subjects were enrolled in Phase I. A single operator obtained scans from all four devices (three CIRRUS photo instruments and one Cirrus HD-OCT) to determine inter-device variability. Twenty-three subjects were enrolled in Phase II. Three operators obtained scans on each of three CIRRUS photo devices to determine inter-operator variability. One of the three operators also obtained scans from the Cirrus HD-OCT. Phase I and II enrolled different subjects; data from each phase were analyzed separately
Table 1 shows the mean difference in CCT measurements between CIRRUS photo and Cirrus HD-OCT for each phase. Overall. CCT measurements showed equivalence in the measurements between the two instruments in both phases.
5
Tables 2 (Phase I) and 3 (Phase II) show that the mean (of three measurements per subject), standard deviation, and 95% confidence interval of the mean CCT values are equivalent between CIRRUS photo and Cirrus HD-OCT across a large range of values covering more than 100 um.
TABLE 1 MEAN DIFFERENCE IN CENTRAL CORNEAL THICKNESS (CCT) BETWEEN CIRRUS PHOTO AND CIRRUS HD-OCT OPTICAL COHERENCE TOMOGRAPHER, MODEL 4000
| | Cirrus 4000
Mean1 (SD) | CIRRUS
photo Mean1
(SD) | Difference
Mean1,2 (SD) | 95%
Confidence
Interval3 of
Mean
Difference | 95% Limits of
Agreement3 for
Differences
Between
Subject means
[µm]1 |
|----------|---------------------------|-------------------------------|----------------------------|---------------------------------------------------------|-------------------------------------------------------------------------------------|
| Phase I | N = 28 | N = 28 | N = 28 | | |
| CCT [µm] | 546.33
(28.37) | 545.44
(28.07) | 0.89
(5.04) | (-1.06, 2.85) | (-8.98, 10.77) |
| Phase II | N = 23 | N = 23 | N = 23 | | |
| CCT [µm] | 539.30
(30.01) | 540.51
(30.11) | -1.20
(2.28) | (-2.19, -0.22) | (-5.67, 3.27) |
vice phase of the study, 29 subje For the inter-operator phase of the study, 23 subjects were enrolled and qualified for inclusion in the analysis.
1 For each of the two study devices (Cirrus HD-OCT, Model 4000 and CIRRUS photo Unit A), the average value of three measurements from one study eye were calculated (subject mean).
2 Difference = CIRRUS HD-OCT, Model 4000 -- CIRRUS photo.
3 95% Confidence Interval of Mean Difference = Mean ± 1.96 x SE.
95% Limits of Agreement = Mean ± 1.96 x SD.
| | Mean
CCT value
[μm] | 95% Confidence
Interval for
Mean | | Std.
Deviation | Minimum
CCT value
[μm] | Maximum
CCT value
[μm] |
|--------------------------|---------------------------|----------------------------------------|----------------|-------------------|------------------------------|------------------------------|
| | | Lower
Bound | Upper
Bound | | | |
| Cirrus 4000 | 546.33 | 535.33 | 557.34 | 28.37 | 491.33 | 593.00 |
| CIRRUS
photo (Unit A) | 545.44 | 534.56 | 556.32 | 28.07 | 477.67 | 595.33 |
TABLE 2 PHASE I CCT COMPARISON: CIRRUS 4000 AND CIRRUS PHOTO
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| | Mean
CCT value
[μm] | 95% Confidence
Interval for
Mean | | Std.
Deviation | Minimum
CCT value
[μm] | Maximum
CCT value
[μm] |
|--------------------------|---------------------------|----------------------------------------|----------------|-------------------|------------------------------|------------------------------|
| | | Lower
Bound | Upper
Bound | | | |
| Cirrus 4000 | 539.30 | 526.32 | 552.28 | 30.01 | 494.33 | 603.00 |
| CIRRUS
photo (Unit A) | 540.51 | 527.49 | 553.53 | 30.11 | 496.00 | 602.00 |
TABLE 3 PHASE II CCT COMPARISON: CIRRUS 4000 AND CIRRUS PHOTO
Analysis of Variance (ANOVA), a random effects model, was used to estimate repeatability standard deviation and reproducibility standard deviation. Repeatability and reproducibility for the CIRRUS photo are shown in Table 4.
TABLE 4 CIRRUS PHOTO REPEATABILITY AND REPRODUCIBILITY IN MEASURING CENTRAL CORNEAL THICKNESS (CCT)
| | Mean
(N = 51) | Repeatability
(microns) | | Reproducibility
(microns) | | COV3 | |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|----------------------------|--------|------------------------------|--------|---------------------------|-----------------------------|
| | | SD | Limit1 | SD | Limit2 | Based on
Repeatability | Based on
Reproducibility |
| CCT
[µm] | 542.59 | 4.49 | 12.57 | 5.216 | 14.604 | 0.008 (0.8%) | 0.0096 (0.96%) |
| 1 Repeatability SD is the standard deviation under repeatability conditions. Repeatability Limit is the upper 95%
limit for the difference between repeated results under repeatability conditions. Per ISO 5725-1 and ISO 5725-6,
Repeatability Limit = $2.8 \times$ Repeatability SD. | | | | | | | |
| 2 Reproducibility SD is the standard deviation under reproducibility conditions. It was estimated by the square root of the sum of repeatability variance and the variance components of operator, of device and of interaction of operatorsubjects and devicesubjects. | | | | | | | |
| Reproducibility Limit is the upper 95% limit for the difference between repeated results under reproducibility conditions.
Reproducibility Limit = $2.8 \times$ Reproducibility SD. | | | | | | | |
| 3 COV = Coefficient of Variation = SD ÷ Mean.( $\times$ 100). SD is either Repeatability SD or Reproducibility SD. | | | | | | | |
CIRRUS photo showed good repeatability and reproducibility across a large range of values.
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POSTERIOR SEGMENT STUDIES
REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO MEASUREMENTS OF AREA OF INCREASED ILLUMINATION UNDER THE RPE AND COMPARISON TO CIRRUS HD-OCT
A non-significant risk multiple site study was conducted to determine the repeatability and reproducibility of CIRRUS photo measurements of increased illumination areas under the retinal pigment epithelium (RPE), and closest distance to the fovea. Another objective of the study was to evaluate the comparability of CIRRUS photo to Cirrus HD-OCT.
The study inclusion criteria required adult males or females diagnosed to have dry AMD with geographic atrophy who were able and willing to make the required study visits, give consent and follow study instructions and whose geographic atrophy lesions should: not be greater than 5 mm at its widest diameter; not have area smaller than 1.25 mm within the 5 mm circle; not be confluent with peri-papillary atrophy; and not be combined with other lesions such as choroidal neovascularization (CNV).
The exclusion criteria required that subjects did not have a history of retinal surgery, laser photocoagulation, and/or radiation therapy to the eye; evidence of other retinal diseases of the eve, including wet AMD, diabetic retinopathy, diabetic macular edema, significant vitreomacular traction, or sub-retinal scarring; or thick media opacity or inability to fixate that precluded obtaining acceptable scans.
The evaluations were performed after foveal location was reviewed and corrected, and after manual edits to the automated segmentation algorithm were entered by the operators (when necessary and consistent with the instructions provided in the labeling). Twenty one enrolled subjects with dry AMD and geographic atrophy (GA) had at least one eye that qualified for inclusion in data analysis. The mean age of the included subjects was 79.8 years with a range of 61 to 90 years.
Subiects were examined on three CIRRUS photo instruments by three operators: each operator was assigned to a specific CIRRUS photo device; one of the three operators also obtained scans using one Cirrus HD-OCT. The operators acquired three Macular Cube 200 x 200 scans and three Macular Cube 512x128 scans on each subject from each of the four devices.
After all scans had been acquired, each operator reviewed the scans to ensure that they were centered on the fovea or corrected the foveal centration if required. In addition, the operators reviewed the segmentation of the increased illumination areas under the RPE made automatically by the advanced RPE algorithm and manually edited the segmentation as needed. Each operator was responsible for reviewing and editing the scans they acquired.
Table 5 presents the agreement between CIRRUS photo and Cirrus HD-OCT based on the first acceptable scan. The difference in measurements is very close to zero for both the area of sub-RPE illumination and the closest distance to the fovea parameters, which shows a high level of agreement between the two devices.
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TABLE 5 AGREEMENT BETWEEN CIRRUS HD-OCT AND CIRRUS PHOTO MEASUREMENTS OF AREA OF SUB-RPE ILLUMINATION AND CLOSEST DISTANCE TO THE FOVEA
| Parameter | Cirrus
HD-OCT | Mean (SD), 95% CI
CIRRUS
photo | Difference | 95% Limits of Agreement (LOA) | |
|----------------------------------------------|------------------|--------------------------------------|-------------------|-------------------------------|-----------------------|
| | | | | Lower Limit
95% CI | Upper Limit
95% CI |
| 200x200 Scan (N = 19 Subjects) | | | | | |
| Area of Sub-
RPE
Illumination
(mm²) | 7.1474 (4.3979) | 7.1582 (4.3342) | -0.0108 (0.3161) | -0.6430 | 0.6215 |
| | (5.0276, 9.2671) | (5.0691, 9.2472) | (-0.1632, 0.1416) | (-0.9070, -0.3791) | (0.3576, 0.8854) |
| Closest Distance
to Fovea (mm) | 0.07 (0.09) | 0.06 (0.10) | 0.01 (0.04) | -0.08 | 0.09 |
| | (0.02, 0.11) | (0.02, 0.11) | (-0.01, 0.02) | (-0.11, -0.04) | (0.05, 0.12) |
| 512x128 Scan (N = 19 Subjects) | | | | | |
| Area of Sub-
RPE
Illumination
(mm²) | 7.1368 (4.3948) | 7.1682 (4.3328) | -0.0314 (0.2964) | -0.6242 | 0.5614 |
| | (5.0186, 9.2551) | (5.0799, 9.2566) | (-0.1742, 0.1115) | (-0.8716, -0.3767) | (0.3140, 0.8089) |
| Closest Distance
to Fovea (mm) | 0.13 (0.25) | 0.11 (0.25) | 0.02 (0.04) | -0.06 | 0.09 |
| | (0.01, 0.25) | (-0.01, 0.23) | (-0.00, 0.03) | (-0.09, -0.03) | (0.06, 0.12) |
For each of study eve, the first scan of the corresponding scan type (200x200 or 512x128) of the device (Cirus HD-OCT or CIRRUS photo) taken by Operator A was used for the agreement analysis. Difference = Cirrus HD-OCT - CIRRUS photo.
Tables 6 and 7 present the repeatability and the reproducibility standard deviation (SD) and limits of the CIRRUS photo for the sub-RPE illumination area measurements (Table 6) and the closest distance to the fovea (Table 7) for both 200x200 and 512x128 scans. Overall, the repeatability and reproducibility SD and limits of CIRRUS photo were small.
| TABLE 6 |
|---|
| REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO |
| MEASUREMENTS OF AREA OF SUB-RPE ILLUMINATION |
| Repeatabilitya | Reproducibilityb | |||||
|---|---|---|---|---|---|---|
| Parameter | SD (mm2) | Limit | ||||
| (mm2) | COV% | SD (mm2) | Limit | |||
| (mm2) | COV% | |||||
| 200x200 Scan | 0.1099 | 0.3078 | 1.52% | 0.1774 | 0.4968 | 2.45% |
| 512x128 Scan | 0.1329 | 0.3720 | 1.83% | 0.2442 | 0.6838 | 3.36% |
Repeatability Limit is the upper 95% limit for the difference between repeated results. a Per ISO 5725-1 and ISO 5725-6. Repeatability Limit = 2.8 x Repeatability SD. Repeatability COV% = Repeatability SD = |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation. Reproducibility Limit is the upper 95% limit calculated for the difference between individual b
measurements using different operators and instruments. Per ISO 5725-1 and ISO 5725-6, Reproducibility Limit = 2.8 x Reproducibility SD.
- Reproducibility COV% = Reproducibility SD = |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation.
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TABLE 7 REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO MEASUREMENTS OF CLOSEST DISTANCE TO THE FOVEA
| Parameter | Repeatabilitya | Reproducibilityb | ||
|---|---|---|---|---|
| SD (mm) | Limit (mm) | SD (mm) | Limit (mm) | |
| 200x200 Scan | 0.0343 | 0.0961 | 0.0447 | 0.1252 |
| 512x128 Scan | 0.0397 | 0.1113 | 0.0571 | 0.1597 |
Repeatability Limit is the upper 95% limit for the difference between ಡಿ repeated results. Per ISO 5725-1 and ISO 5725-6, Repeatability Limit = 2.8 x Repeatability SD.
Reproducibility Limit is the upper 95% limit calculated for the difference b between individual measurements using different opcrators and instruments. Per ISO 5725-1 and ISO 5725-6, Reproducibility Limit = 2.8 x Reproducibility SD.
REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO MEASUREMENTS OF ELEVATED RPE AND COMPARISON TO CIRRUS HD-OCT
A non-significant risk single site study was conducted to determine the repeatability and reproducibility of the CIRRUS photo measurements of RPE elevation and its comparability to Cirrus HD-OCT.
The study inclusion criteria required adult males or females diagnosed to have dry AMD with macular drusen who were able and willing to make the required study visits, give consent and follow study instructions and whose drusen volume was at least 0.02 mm3 in the central 3 mm circle, determined by a screening scan acquired with Cirrus HD-OCT 6.0.
The exclusion criteria required that subjects did not have a history of retinal surgery, laser photocoagulation, and/or radiation therapy to the eye; evidence of other retinal diseases of the eve, including wet AMD, choroidal neovascularization (CNV), diabetic retinopathy, diabetic macular edema, or significant vitreomacular traction; or thick media opacity or inability to fixate that precluded obtaining acceptable scans.
Thirty one enrolled subjects with dry AMD and drusen had at least one eye that qualified for inclusion in data analysis. The mean age of the included subjects was 80.1 years with a range of 55 to 89 years.
Each subject was scanned on three CIRRUS photo devices and one Cirrus HD-OCT device. Three operators, each assigned to a specific CIRRUS photo device, performed the study scans. One of the three operators was assigned to perform the Cirrus HD-OCT study scans as well. The operators acquired three Macular Cube 200x200 scans and three Macular Cube 512x128 scans on each subject from each of the four devices.
Table 8 presents the agreement between CIRRUS photo and Cirrus HD-OCT for the area and volume of RPE elevations within the 3 and 5 mm circles as measured by the automated algorithm based on the first acceptable scan. For both scan types (200x200 and 512x128), the
10
mean differences (= Cirrus HD-OCT – CIRRUS photo) are all zero or very close to zero which indicates a high level of agreement between CIRRUS photo and Cirrus HD-OCT measurements.
| MEASUREMENTS OF AREA AND VOLUME OF RPE ELEVATION | ||||||
|---|---|---|---|---|---|---|
| Mean (SD), 95% CI | 95% Limits of Agreement (LOA) | |||||
| Cirrus | ||||||
| HD-OCT | CIRRUS | |||||
| photo | Difference | Lower Limit | ||||
| 95% Cl | Upper Limit | |||||
| 95% CI | ||||||
| 200x200 Scan (N = 25 Subjects) | ||||||
| Area of RPE Elevation | ||||||
| 3 mm | 1.188 (0.698) | 1.228 (0.717) | -0.040 (0.141) | -0.323 | 0.243 | |
| Circle | (0.900, 1.476) | (0.932, 1.524) | (-0.098, 0.018) | (-0.424, -0.222) | (0.142, 0.344) | |
| 5 mm | 1.784 (1.052) | 1.800 (1.045) | -0.016 (0.212) | -0.439 | 0.407 | |
| Circle | (1.350, 2.218) | (1.369, 2.231) | (-0.103, 0.071) | (-0.590, -0.288) | (0.256, 0.558) | |
| Volume of RPE Elevation | ||||||
| 3 mm | 0.0542 (0.0440) | 0.0566 (0.0468) | -0.0024 (0.0062) | -0.0148 | 0.0100 | |
| Circle | (0.0360, 0.0723) | (0.0372, 0.0759) | (-0.0050, 0.0002) | (-0.0193, -0.0104) | (0.0056, 0.0145) | |
| 5 mm | 0.0799 (0.0593) | 0.0817 (0.0611) | -0.0018 (0.0098) | -0.0213 | 0.0177 | |
| Circle | (0.0554, 0.1044) | (0.0565, 0.1069) | (-0.0058, 0.0022) | (-0.0283, -0.0144) | (0.0108, 0.0247) | |
| 512x128 Scan (N = 26 Subjects) | ||||||
| Area of RPE Elevation | ||||||
| 3 mm | 1.192 (0.534) | 1.196 (0.531) | -0.004 (0.173) | -0.350 | 0.342 | |
| Circle | (0.977, 1.408) | (0.982, 1.411) | (-0.074, 0.066) | (-0.471, -0.229) | (0.221, 0.464) | |
| 5 mm | 1.785 (1.038) | 1.777 (1.010) | 0.008 (0.258) | -0.507 | 0.523 | |
| Circle | (1.365, 2.204) | (1.369, 2.185) | (-0.096, 0.112) | (-0.688, -0.327) | (0.343, 0.703) | |
| Volume of RPE Elevation | ||||||
| 3 mm | 0.0491 (0.0240) | 0.0489 (0.0254) | 0.0002 (0.0077) | -0.0153 | 0.0157 | |
| Circle | (0.0394, 0.0588) | (0.0386, 0.0591) | (-0.0029, 0.0034) | (-0.0207, -0.0098) | (0.0103, 0.0211) | |
| 5 mm | 0.0753 (0.0519) | 0.0740 (0.0500) | 0.0013 (0.0134) | -0.0255 | 0.0282 | |
| Circle | (0.0544, 0.0963) | (0.0538, 0.0942) | (-0.0041, 0.0068) | (-0.0348, -0.0161) | (0.0188, 0.0375) |
TABLE 8 AGREEMENT BETWEEN CIRRUS HD-OCT AND CIRRUS PHOTO
For each of study eye, the first scan of the corresponding scan type (200x200 or 512x128) of the device (Cirrus HD-OCT or CIRRUS photo) taken by Operator A was used for the agreement analysis. Difference = Cirrus HD-OCT - CIRRUS photo.
Tables 9 and 10 present the repeatability and the reproducibility standard deviation (SD) and limits of CIRRUS photo for the area (Table 9) and volume (Table 10) of the RPE elevations for both 200 x 200 and 512 x 128 scan types within the 3 and 5 mm circles.
For CIRRUS photo, the reproducibility coefficient of variation in percentage (COV%) were similar between the 200 x 200 scan type (ranged from 8.30% to 9.18%) and the 512 x 128 scan type (8.46% to 9.07%).
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TABLE 9
CIRRUS PHOTO RPE ELEVATION REPEATABILITY AND REPRODUCIBILITY AREA OF RPE ELEVATIONS
| Repeatabilitya | Reproducibilityb | |||||
|---|---|---|---|---|---|---|
| SD | Limit | COV% | SD | Limit | COV% | |
| 200x200 Scan | ||||||
| Area of RPE Elevation | ||||||
| 3 mm Circle | 0.0842 | 0.2357 | 6.96% | 0.1004 | 0.2812 | 8.30% |
| 5 mm Circle | 0.1165 | 0.3262 | 6.49% | 0.1553 | 0.4348 | 8.66% |
| 512x128 Scan | ||||||
| Area of RPE Elevation | ||||||
| 3 mm Circle | 0.0808 | 0.2262 | 6.72% | 0.1069 | 0.2994 | 8.89% |
| 5 mm Circle | 0.1264 | 0.3539 | 7.03% | 0.1521 | 0.4260 | 8.46% |
Repeatability Limit is the upper 95% limit for the difference between repeated results. Per a ISO 5725-1 and ISO 5725-6, Repeatability Limit = 2.8 x Repeatability SD. Repeatability COV% = Repeatability SD = |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation.
Reproducibility Limit is the upper 95% limit calculated for the difference between b individual measurements using different operators and instruments. Per ISO 5725-1 and 1SO 5725-6, Reproducibility Limit = 2.8 x Reproducibility SD. Reproducibility COV% = Reproducibility SD = |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation.
TABLE 10
CIRRUS PHOTO RPE ELEVATION REPEATABILITY AND REPRODUCIBILITY VOLUME OF RPE ELEVATIONS
| Repeatabilitya | Reproducibilityb | |||||
|---|---|---|---|---|---|---|
| SD | Limit | COV% | SD | Limit | COV% | |
| 200x200 Scan | ||||||
| Volume of RPE Elevation | ||||||
| 3 mm Circle | 0.0036 | 0.0101 | 6.49% | 0.0047 | 0.0131 | 8.45% |
| 5 mm Circle | 0.0055 | 0.0153 | 6.78% | 0.0074 | 0.0208 | 9.18% |
| 512x128 Scan | ||||||
| Volume of RPE Elevation | ||||||
| 3 mm Circle | 0.0035 | 0.0097 | 7.03% | 0.0045 | 0.0125 | 9.07% |
| 5 mm Circle | 0.0058 | 0.0163 | 7.81% | 0.0067 | 0.0188 | 8.99% |
Repeatability Limit is the upper 95% limit for the difference between repeated results. Per ಡಿ 1SO 5725-1 and ISO 5725-6, Repeatability Limit = 2.8 x Repeatability SD. Repeatability COV% = Repeatability SD + |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation.
Reproducibility Limit is the upper 95% limit calculated for the difference between b individual measurements using different operators and instruments. Per ISO 5725-1 and 1SO 5725-6. Reproducibility Limit = 2.8 x Reproducibility SD. Reproducibility COV% = Reproducibility SD = |mean| x 100%. The mean was the estimated general mean in the random ANOVA model for the R&R calculation.
12
REPEATABILITY AND REPRODUCIBILITY OF CIRRUS PHOTO GANGLION CELL MEASUREMENTS AND COMPARISON TO CIRRUS HD-OCT
Two studies were conducted to determine comparability of the measurements obtained from the CIRRUS photo and the Cirrus HD-OCT Model 4000 instruments, and to determine the repeatability and reproducibility of the ganglion cell analysis (GCA) parameters. One study enrolled normal eyes and one study enrolled eyes with glaucoma.
NORMAL EYES STUDY
Sixtv-three normal subjects were enrolled in a study to evaluate the equivalence of the means of eight ganglion cell (GCA) measurement parameters between the CIRRUS photo and Cirrus HD-OCT Model 4000.
The study inclusion criteria required adult males or females who had no known macular disease or glaucoma with best spectacle corrected visual acuity of 20/40 or better in both eyes and who were able and willing to make the required study visits, give consent and follow study instructions in English.
The exclusion criteria required that subjects did not present with active inflammation or infections in either eve and that their best spectacle corrected visual acuity was not worse than 20/40 in either eve. Subjects who were unable to make the required study visits or to give consent or follow study instructions were excluded.
The study was divided into two phases. Thirty subjects were enrolled in Phase 1 that evaluated inter-operator variability. For each subject, three Optic Disc Cube 200x200 scans were taken on one eye, and three Macular Cube 512x128 scans were taken on the fellow eye by each of four operators using one Cirrus HD-OCT Model 4000 and one CIRRUS photo instrument. Thirtythree subjects were enrolled in Phase 2 that evaluated inter-device variability. For each subject, three Optic Disc Cube 200x200 scans were taken on one eye, and three Macular Cube 512x128 scans were taken on the fellow eye from each of the four Cirrus HD-OCT Model 4000 instruments and each of the four CIRRUS photo instruments by one operator. Subjects could not participate in both phases. The mean age of the included subjects was 43.5, with a range from 28 to 66 years.
DISEASED EYES STUDY
Seventy-seven subjects with glaucoma were enrolled in a study to evaluate the equivalence of eight GCA measurement parameters between the CIRRUS photo and Cirrus HD-OCT Model 4000.
The study inclusion criteria required adult males or females who had been diagnosed with glaucoma and who had Humphrev Field Analyzer visual field results within the past one year. Subjects were also required to be able and willing to make the required study visit(s), give consent and follow study instructions as well as to be able to maintain fixation necessary for the study scans.
13
Visual field results were used to classify the subjects with glaucoma into three categories using the mean deviation (MD): mild (MD > -6 dB or better); moderate (MD -3.00 D cylinder or who had any active infection of anterior or posterior segments were excluded.
For each subject, three Macular Cube 512x128 scans and three Macular Cube 200x200 scans were taken on each of three CIRRUS photo instruments by three operators and one Cirrus HD-OCT instrument by one of the three operators.
Sixty-eight subjects were included in the analysis of which 37 were categorized as mild glaucoma, 16 as moderate, 13 as severe, and 2 as end stage glaucoma. The mean age of the included subjects was 67.4 years, with a range from 40 to 93 years.
DATA ANALYSIS
For each of the two study devices and each measurement parameter, the mean of the available measurements was calculated for each study eye. The difference in each of the eight GCA measurement parameters between the CIRRUS photo and Cirrus HD-OCT Model 4000 were calculated for each study eye. The mean difference, the corresponding 95% confidence intervals, and 95% limits of agreement were calculated for each measurement parameter. As the interoperator phase utilized only one device, only the results for the inter-device phase are presented in Table 11.
The mean values of the eight thickness parameters were very similar for the two devices. The results of these two studies support the incorporation of the GCA normative database established with the Cirrus HD-OCT Model 4000 instrument into the CIRRUS photo instrument with an adjustment based on regression analysis.
Additionally, analysis of variance (ANOVA) with random effect models was used to evaluate the repeatability, inter-device variability and inter-operator variability of each measurement parameter for the CIRRUS photo. The repeatability standard deviation (SD) and limits for the CIRRUS photo are shown in Tables 12 and 13 for the normal and diseased eyes studies, respectively. CIRRUS photo showed good repeatability and reproducibility for both normal and diseased eyes.
GCA NORMATIVE DATABASE AND LIMITS
In order to support transference of the Cirrus HD-OCT GCA Normative Database, studies were conducted with both normal and diseased eves to demonstrate that the measurements obtained
14
from the CIRRUS photo instrument were comparable to the same data obtained using the Cirrus HD-OCT. The Cirrus HD-OCT GCA Normative Database was adjusted for the CIRRUS Photo (adjusted CIRRUS photo Normative Database) using regression analysis based on the data from these studies. Then, the CIRRUS photo GCA normative limits were established based on the adiusted CIRRUS photo Normative Database.
The Cirrus GCA normative database [for the Cirrus HD-OCT] was developed utilizing 282 subjects aged 19-84. Gender distribution was 133 males, and 149 females. Ethnicity breakdown was as follows: 43% Caucasians, 24% Asians, 18% African American, 12% Hispanic, 1% Indian, and 6% mixed ethnicity.
Results revealed that the mean difference in the average ganglion cell plus inner plexiform layer (GCL + IPL) thickness between any two race groups is within 4.3 um. Subjects of European descent have thinner GCL + IPL thickness on average, while subjects of Hispanic and Chinese descent have thicker ganglion cell plus inner plexiform layer thickness (p