(269 days)
The Cirrus™ HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, Optic Nerve Head and Ganglion Cell Normative Databases is indicated for in-vivo viewing, axial cross-sectional, and three-dimensional imaging and measurement of anterior and posterior ocular structures.
The Cirrus™ HD-OCT is a non-contact, high resolution tomographic and biomicroscopic imaging device. It is indicated for in-vivo viewing, axial cross-sectional, and threedimensional imaging and measurement of anterior and posterior ocular structures, including cornea, retinal nerve fiber layer, ganglion cell plus inner plexiform layer, macula, and optic nerve head. The Cirrus normative databases are quantitative tools for the comparison of retinal nerve fiber layer thickness, macular thickness, ganglion cell plus inner plexiform layer thickness, and optic nerve head measurements to a database of normal subjects. The Cirrus HD-OCT 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.
The Cirrus™ HD-OCT is a computerized instrument that acquires and analyzes crosssectional tomograms of anterior and posterior ocular structures (including cornea, retina, retinal nerve fiber layer, macula, and optic disc). It employs non-invasive, non-contact, low-coherence interferometry to obtain these high-resolution images. Using this noninvasive optical technique, Cirrus HD-OCT produces high-resolution cross-sectional tomograms of the eye without contacting the eye. It also produces images of the retina and layers of the retina from an en face perspective (i.e., as if looking directly in the eye).
The Cirrus HD-OCT is offered in two models, Model 4000 and Model 400. In the Cirrus HD-OCT Model 4000 instrument, the fundus camera is a line scanning ophthalmoscope. The Cirrus HD-OCT Model 400 is similar to the Model 4000 except that it provides the fundus image using the OCT scanner only.
The acquired imaging data can be analyzed to provide thickness and area measurements of regions of interest to the clinician. The system uses acquired data to determine the fovea location or the optic disc location. Measurements can then be oriented using the fovea and/or optic disc locations. The patient's results can be compared to subjects without disease for measurements of RNFL thickness, neuroretinal rim area, average and vertical cup-to-disc area ratio, cup volume, macular thickness and ganglion cell plus inner plexiform layer thickness.
Visit-to-visit comparison of images and measurements is available for the macula. Specifically, change in macular thickness, area and volume of Retinal Pigment Epithelium (RPE) elevations, area of sub-RPE illumination and distance of Sub-RPE illumination to the fovea. Change analysis of multiple visits, up to eight, can be performed for RNFL thickness, neuroretinal rim area, average and vertical cup-to-disc area ratio, cup volume, and macular thickness.
The provided document describes the predicate device and the clinical studies performed to support the substantial equivalence of the "Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL), Macular, Optic Nerve Head and Ganglion Cell Normative Databases" (Cirrus HD-OCT). The clinical evaluation focuses on demonstrating the device's measurement capabilities and the establishment of normative databases.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a pass/fail quantifiable manner for the overall device's performance against a gold standard for disease detection or management. Instead, the studies presented focus on the repeatability and reproducibility of various measurements performed by the device and the comparability of certain automated measurements to expert manual measurements from different imaging modalities.
The tables below summarize the specified repeatability and reproducibility limits (acceptance criteria as per ISO 5725-1 and ISO 5725-6, defined as the upper 95% limit for the difference between repeated results) and the reported performance (SD and limits).
Table 1. Repeatability and Reproducibility of Area of Sub-RPE Illumination (Automated Algorithm)
| Scan | Acceptance Criteria (Repeatability Limit, mm²) | Reported Performance (Repeatability Limit, mm²) | Acceptance Criteria (Reproducibility Limit, mm²) | Reported Performance (Reproducibility Limit, mm²) | Reported CVc |
|---|---|---|---|---|---|
| 200x200 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 2.4885 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 2.6460 | 12.5% |
| 512x128 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 2.4313 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 2.8889 | 15.8% |
Table 2. Repeatability and Reproducibility of Closest Distance to Fovea (Automated Algorithm)
| Scan | Acceptance Criteria (Repeatability Limit, mm) | Reported Performance (Repeatability Limit, mm) | Acceptance Criteria (Reproducibility Limit, mm) | Reported Performance (Reproducibility Limit, mm) |
|---|---|---|---|---|
| 200x200 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.2070 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.2133 |
| 512x128 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.3492 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.3520 |
Table 3. Repeatability and Reproducibility of Area of Sub-RPE Illumination (Manually Edited)
| Scan | Acceptance Criteria (Repeatability Limit, mm²) | Reported Performance (Repeatability Limit, mm²) | Acceptance Criteria (Reproducibility Limit, mm²) | Reported Performance (Reproducibility Limit, mm²) | Reported CVc |
|---|---|---|---|---|---|
| 200x200 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.6365 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 1.0705 | 4.3% |
Table 4. Repeatability and Reproducibility of Closest Distance to Fovea (Manually Edited)
| Scan | Acceptance Criteria (Repeatability Limit, mm) | Reported Performance (Repeatability Limit, mm) | Acceptance Criteria (Reproducibility Limit, mm) | Reported Performance (Reproducibility Limit, mm) |
|---|---|---|---|---|
| 200x200 Scan | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.0990 | (Not explicitly stated, but inferred to be the achieved limit based on SD) | 0.1229 |
Table 5. Repeatability and Reproducibility of Area of RPE Elevations
| Circle | Scan | Acceptance Criteria (Repeatability Limit, mm²) | Reported Performance (Repeatability Limit, mm²) | Acceptance Criteria (Reproducibility Limit, mm²) | Reported Performance (Reproducibility Limit, mm²) | Reported CVc |
|---|---|---|---|---|---|---|
| 3 mm Circle | 200x200 Scan | (Not explicitly stated, but inferred) | 0.3626 | (Not explicitly stated, but inferred) | 0.4389 | 10.1% |
| 5 mm Circle | 200x200 Scan | (Not explicitly stated, but inferred) | 0.2834 | (Not explicitly stated, but inferred) | 0.4073 | 4.9% |
| 3 mm Circle | 512x128 Scan | (Not explicitly stated, but inferred) | 0.2343 | (Not explicitly stated, but inferred) | 0.2794 | 7.5% |
| 5 mm Circle | 512x128 Scan | (Not explicitly stated, but inferred) | 0.4304 | (Not explicitly stated, but inferred) | 0.5422 | 9.6% |
Table 6. Repeatability and Reproducibility of Volume of RPE Elevations
| Circle | Scan | Acceptance Criteria (Repeatability Limit, mm³) | Reported Performance (Repeatability Limit, mm³) | Acceptance Criteria (Reproducibility Limit, mm³) | Reported Performance (Reproducibility Limit, mm³) | Reported CVc |
|---|---|---|---|---|---|---|
| 3 mm Circle | 200x200 Scan | (Not explicitly stated, but inferred) | 0.0327 | (Not explicitly stated, but inferred) | 0.0341 | 15.2% |
| 5 mm Circle | 200x200 Scan | (Not explicitly stated, but inferred) | 0.0275 | (Not explicitly stated, but inferred) | 0.0298 | 8.3% |
| 3 mm Circle | 512x128 Scan | (Not explicitly stated, but inferred) | 0.0206 | (Not explicitly stated, but inferred) | 0.0235 | 12.0% |
| 5 mm Circle | 512x128 Scan | (Not explicitly stated, but inferred) | 0.0245 | (Not explicitly stated, but inferred) | 0.0288 | 11.4% |
Table 7. Cirrus Repeatability and Reproducibility of GCA and ONH Parameters - Normal Subjects
| Parameter | Acceptance Criteria (Repeatability Limit) | Reported Performance (Repeatability Limit) | Acceptance Criteria (Reproducibility Limit) | Reported Performance (Reproducibility Limit) | Reported CVc |
|---|---|---|---|---|---|
| GCA Parameters | |||||
| Average Thickness (µm) | (Not explicitly stated, but inferred) | 1.6348 | (Not explicitly stated, but inferred) | 2.0942 | 0.7% |
| Minimum Thickness (µm) | (Not explicitly stated, but inferred) | 8.0165 | (Not explicitly stated, but inferred) | 8.1018 | 2.5% |
| Temporal-Superior Thickness (µm) | (Not explicitly stated, but inferred) | 2.3502 | (Not explicitly stated, but inferred) | 2.6590 | 1.0% |
| Superior Thickness (µm) | (Not explicitly stated, but inferred) | 2.5522 | (Not explicitly stated, but inferred) | 3.0024 | 1.1% |
| Nasal-Superior Thickness (µm) | (Not explicitly stated, but inferred) | 2.5753 | (Not explicitly stated, but inferred) | 2.9154 | 1.0% |
| Nasal-Inferior Thickness (µm) | (Not explicitly stated, but inferred) | 4.6857 | (Not explicitly stated, but inferred) | 4.8525 | 1.5% |
| Inferior Thickness (µm) | (Not explicitly stated, but inferred) | 2.7894 | (Not explicitly stated, but inferred) | 3.3339 | 1.2% |
| Temporal-Inferior Thickness (µm) | (Not explicitly stated, but inferred) | 2.2948 | (Not explicitly stated, but inferred) | 2.5696 | 1.0% |
| ONH Parameters | |||||
| Cup Disc Ratio | (Not explicitly stated, but inferred) | 0.0380 | (Not explicitly stated, but inferred) | 0.0679 | 5.4% |
| Vertical CD Ratio | (Not explicitly stated, but inferred) | 0.0681 | (Not explicitly stated, but inferred) | 0.0846 | 7.1% |
| Disc Area (mm²) | (Not explicitly stated, but inferred) | 0.1506 | (Not explicitly stated, but inferred) | 0.2637 | 5.4% |
| Rim Area (mm²) | (Not explicitly stated, but inferred) | 0.1177 | (Not explicitly stated, but inferred) | 0.1733 | 4.7% |
| Cup Volume (mm³) | (Not explicitly stated, but inferred) | 0.0181 | (Not explicitly stated, but inferred) | 0.0287 | 7.8% |
Table 8. Repeatability and Visit-to-Visit Variability of ONH Parameters - Glaucomatous Subjects
| Parameter | Acceptance Criteria (Repeatability Limit) | Reported Performance (Repeatability Limit) | Acceptance Criteria (Visit-to-Visit Limit) | Reported Performance (Visit-to-Visit Limit) | Reported CV% |
|---|---|---|---|---|---|
| Disc Area (mm²) | (Not explicitly stated, but inferred) | 0.233 mm² | (Not explicitly stated, but inferred) | 0.233 mm² | 4.4% |
| Rim Area (mm²) | (Not explicitly stated, but inferred) | 0.125 mm² | (Not explicitly stated, but inferred) | 0.125 mm² | 6.6% |
| Average Cup-to-Disc Ratio | (Not explicitly stated, but inferred) | 0.025 | (Not explicitly stated, but inferred) | 0.025 | 1.2% |
| Vertical Cup-to-Disc Ratio | (Not explicitly stated, but inferred) | 0.039 | (Not explicitly stated, but inferred) | 0.042 | 1.9% |
| Cup Volume (mm³) | (Not explicitly stated, but inferred) | 0.089 mm³ | (Not explicitly stated, but inferred) | 0.175 mm³ | 11.7% |
Table 9. Repeatability of GCA Parameters - Glaucomatous Subjects
| GCA Parameters (μm) | Acceptance Criteria (Repeatability Limit) | Reported Performance (Repeatability Limit) | Reported CV% |
|---|---|---|---|
| Overall | |||
| Average GCL + IPL Thickness | (Not explicitly stated, but inferred) | 1.7567 | 1.0% |
| Minimum GCL + IPL Thickness | (Not explicitly stated, but inferred) | 4.2689 | 2.6% |
| Temporal-Superior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 3.4171 | 1.8% |
| Superior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 3.5429 | 1.8% |
| Nasal-Superior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 2.3013 | 1.2% |
| Nasal-Inferior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 3.1371 | 1.7% |
| Inferior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 2.9593 | 1.7% |
| Temporal-Inferior GCL + IPL Thickness | (Not explicitly stated, but inferred) | 3.4049 | 2.0% |
| Mild Glaucoma | |||
| Average GCL + IPL Thickness | (Not explicitly stated, but inferred) | 1.4277 | 0.7% |
| ... (specific metrics provided for Mild, Moderate, and Severe Glaucoma in the document) | ... | ... | ... |
Summary of Studies Demonstrating Acceptance:
The studies listed above (Advanced RPE Analysis Study, measurements of Elevated RPE, Repeatability and Reproducibility studies) and the establishment of the normative databases serve as the proof that the device meets its intended use and demonstrates substantial equivalence. The "acceptance criteria" appear to be the demonstrated repeatability and reproducibility limits themselves, calculated according to ISO 5725-1 and ISO 5725-6 standards, or the statistical comparability (e.g., paired t-test showing no significant difference, good correlation R+) in the case of the RPE illumination comparison.
2. Sample Sizes used for the Test Set and Data Provenance:
- Advanced RPE Analysis Study (Areas of Increased Illumination):
- Test Set Sample Size: 52 eyes from 52 subjects.
- Data Provenance: Not explicitly stated (e.g., country of origin), but it was a "non-significant risk clinical study" with "Four sites participated in the clinical data collection." The study was conducted on subjects evaluated for dry AMD with geographic atrophy. The study compares Cirrus HD-OCT automated measurements to FAF images (an existing, accepted modality). This implies a prospective data collection for this comparison.
- Advanced RPE Analysis Study (Measurements of Elevated RPE):
- Test Set Sample Size: 70 eyes from 70 subjects were considered; the number included in final analysis is not explicitly stated but implies a similar number after qualification.
- Data Provenance: Not explicitly stated (e.g., country of origin), but "Three sites participated in the clinical data collection." Subjects were 50 years or older with dry age-related macular degeneration (AMD) with macular drusen. This implies a prospective data collection for this comparison.
- Measurements of Area of Increased Illumination Under the RPE Repeatability and Reproducibility:
- Test Set Sample Size: Phase 1: 49 eyes of 37 subjects. Phase 2: 53 eyes of 39 subjects.
- Data Provenance: "Single-site clinical study." The subjects had dry AMD with geographic atrophy. This suggests prospective data collection.
- Measurements of Elevated RPE Repeatability and Reproducibility:
- Test Set Sample Size: Phase 1: 26 eyes of 23 subjects. Phase 2: 24 eyes of 21 subjects.
- Data Provenance: "Single-site clinical study." The subjects had dry AMD with macular drusen. This suggests prospective data collection.
- Optic Nerve Head and Ganglion Cell Analysis Repeatability and Reproducibility (Normal Subjects):
- Test Set Sample Size: 63 normal subjects.
- Data Provenance: Not explicitly stated (e.g., multi-site, country). This suggests prospective data collection.
- Optic Nerve Head Parameters Repeatability and Visit-to-Visit Variability (Glaucomatous Subjects):
- Test Set Sample Size: 55 glaucomatous subjects.
- Data Provenance: Not explicitly stated (e.g., multi-site, country). This suggests prospective data collection.
- GCA Parameters Repeatability (Glaucomatous Subjects):
- Test Set Sample Size: 119 subjects with glaucoma enrolled; 94 subjects with two qualified scans each were included in the analysis.
- Data Provenance: "clinical study conducted at four sites." Not explicitly stated (e.g., country). This suggests prospective data collection.
3. Number of Experts used to Establish the Ground Truth for the Test Set and Qualifications:
- Advanced RPE Analysis Study (Areas of Increased Illumination): Ground truth was established by "expert manual measurements of areas of hypofluorescence typical of geographic atrophy in fundus autofluorescence (FAF) images." The number and specific qualifications of these experts are not specified in the document.
- Advanced RPE Analysis Study (Measurements of Elevated RPE): Ground truth was established by "manually drawn by experts designated as drusen on color fundus photographs (CFPs)." The number and specific qualifications of these experts are not specified in the document.
- For repeatability and reproducibility studies, the ground truth is implicitly the repeated measurements themselves by the device, as the studies aim to quantify the variation within the device's measurements, not compare them against an external gold standard by human experts for classifications.
4. Adjudication Method:
- For the studies comparing automated measurements to expert manual measurements (e.g., Advanced RPE Analysis), the adjudication method is not explicitly stated. It mentions "expert manual measurements" and "manually drawn by experts," implying these were used as reference, but how inconsistencies between experts (if there were multiple) were resolved is not detailed.
- For the repeatability and reproducibility studies, adjudication doesn't apply in the traditional sense, as these studies focus on the intrinsic variation of the device's measurements.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, and if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No MRMC comparative effectiveness study was described where human readers' performance with and without AI assistance was evaluated. The studies primarily focus on the device's measurement accuracy, repeatability, and reproducibility, and the establishment of normative databases. The comparison for RPE illumination detection was between the device's automated measurements and expert manual measurements from a different imaging modality, not an AI-assisted human vs. human-alone scenario.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the comparability studies for Advanced RPE Analysis (Areas of Increased Illumination and Elevated RPE) assess the device's "automated measurements" (automated algorithm) against expert manual measurements from other imaging modalities. These can be considered standalone performance assessments of specific algorithms within the device.
- Similarly, all the repeatability and reproducibility studies for various parameters (GCA, ONH, RPE illumination, RPE elevations) assess the intrinsic performance of the device's measurement algorithms in a standalone manner, quantifying their consistency.
7. The Type of Ground Truth Used:
- Advanced RPE Analysis Study (Areas of Increased Illumination): Ground truth was "expert manual measurements of areas of hypofluorescence typical of geographic atrophy in fundus autofluorescence (FAF) images." This is a form of expert consensus/manual delineation using another imaging modality.
- Advanced RPE Analysis Study (Measurements of Elevated RPE): Ground truth was "manually drawn by experts designated as drusen on color fundus photographs (CFPs)." This is also a form of expert consensus/manual delineation using another imaging modality.
- Normative Databases (RNFL, Macular, Optic Nerve Head, Ganglion Cell): The ground truth for these databases is implicitly the classification of subjects as "normal" based on clinical criteria (not specified in detail, but implied by the selection of normal subjects). The measurements are then statistically analyzed to establish reference values.
- For repeatability and reproducibility studies, the ground truth is the repeated measurements, not an external gold standard.
8. The Sample Size for the Training Set:
The document doesn't explicitly mention "training sets" as it would for a typical machine learning algorithm development (e.g., deep learning). The device is likely based on established image processing algorithms.
- The normative databases serve a similar function to a reference set, providing "normal" ranges for comparison in diagnosis.
- Optic Nerve Head Normative Database: Derived from a "post-hoc analysis" of 282 eyes from 284 subjects (aged 19-84 years) included in a previous RNFL normative database (K083291).
- Ganglion Cell Normative Database: Utilized the "same 282 subjects, aged 19-84 years that were deemed representative of a normal population" as the original macula normative database (K083291).
9. How the Ground Truth for the Training Set was Established:
- For the normative databases, the "ground truth" for inclusion was that the subjects were considered "normal." The document states the subjects (n=282) were "deemed representative of a normal population." However, the specific criteria or methods (e.g., expert clinical review, exclusion criteria) used to define and confirm these subjects as "normal" are not detailed in this summary. The data were collected from "seven sites."
§ 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.