Spectralis HRA+OCT and variants with OCT Angiography Module

K181594 · Heidelberg Engineering GmbH · OBO · Sep 13, 2018 · Ophthalmic

Device Facts

• Record ID: K181594
• Device Name: Spectralis HRA+OCT and variants with OCT Angiography Module
• Applicant: Heidelberg Engineering GmbH
• Product Code: OBO · Ophthalmic
• Decision Date: Sep 13, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 886.1570
• Device Class: Class 2

Intended Use

The SPECTRALIS is a non-contact ophthalmic diagnostic imaging device. It is intended for: · viewing the posterior segment of the eye, including two- and three-dimensional imaging · cross-sectional imaging (SPECTRALIS HRA+OCT and SPECTRALIS OCT) · fundus imaging · fluorescence imaging (fluorescein angiography, indocyanine green angiography; SPECTRALIS HRA+OCT, SPECTRALIS HRA) · autofluorescence imaging (SPECTRALIS HRA+OCT, SPECTRALIS HRA and SPECTRALIS OCT with BluePeak) · performing measurements of ocular anatomy and ocular lesions. The device is indicated as an aid in the detection and management of various ocular diseases, including: · age-related macular degeneration · macular edema · diabetic retinopathy · retinal and choroidal vascular diseases · glaucoma The device is indicated for viewing geographic atrophy. The SPECTRALIS OCT Angiography Module is indicated as an aid in the visualization of vascular structures of the retina and choroid. The SPECTRALIS HRA+OCT and SPECTRALIS OCT include the following reference databases: · a retinal nerve fiber layer thickness reference database, which is used to quantitatively compare the retinal nerve fiber layer in the human retina to values of Caucasian normal subjects – the classification result being valid only for Caucasian subjects · a reference database for retinal nerve fiber layer thickness and optic nerve head neuroretinal rim parameter measurements, which is used to quantitatively compare the retinal nerve fiber layer and neuroretinal rim in the human retina to values of normal subjects of different races and ethnicities representing the population mix of the USA (Glaucoma Module Premium Edition)

Device Story

Non-contact ophthalmic diagnostic imaging device; combines confocal laser-scanning ophthalmoscope (cSLO) and spectral-domain optical coherence tomographer (SD-OCT). Inputs: infrared, green, blue reflectance light; fluorescein/indocyanine green dyes for angiography; OCT signal for cross-sectional/volume imaging. OCTA functionality uses motion-contrast technique; detects temporal intensity changes from moving erythrocytes; creates contrast between perfused vessels and static tissue. Used in clinics by eye care professionals. Output: 2D/3D images, OCTA flow maps, ocular measurements. Healthcare providers use images to visualize vascular structures, identify pathologies (e.g., microaneurysms, neovascularization), and manage ocular diseases. Benefits: non-invasive visualization of retinal/choroidal vasculature without intravenous dye injection.

Clinical Evidence

Prospective case series, N=79 (32 normal, 47 pathology). Compared SPECTRALIS OCTA to RTVue XR. Endpoints: image quality scores (scale 0-2) and agreement with FA/ICGA reference standard for identifying vascular pathologies (microaneurysms, ischemia, CNV, etc.). Results: SPECTRALIS image quality comparable to RTVue; consensus quality scores ≥1 for all but one image. High agreement with FA/ICGA for PPOI identification (PoA 91.5-100%). No device-related adverse events.

Technological Characteristics

Spectral-domain OCT; 840-920 nm (880 nm avg) superluminescent diode. cSLO uses diode/semiconductor lasers (486-815 nm). Lateral resolution 14 µm; axial resolution 7 µm. OCTA uses motion-contrast technique with 4-7 B-scan repeats. Software-based image processing. Class I laser. Connectivity: networked/standalone. Sterilization: N/A (non-contact).

Indications for Use

Indicated for patients requiring ophthalmic diagnostic imaging of the posterior segment, including those with age-related macular degeneration, macular edema, diabetic retinopathy, retinal/choroidal vascular diseases, glaucoma, or geographic atrophy. OCTA module indicated for visualization of retinal and choroidal vascular structures.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Opto Vue, Inc. RTVue XR OCT Avanti with AngioVue™ Software (K153080)
• SPECTRALIS HRA+OCT and variants (K172649)

Submission Summary (Full Text)

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September 13, 2018

Heidelberg Engineering GmbH % Lena Sattler Consultant Orasi Consulting, LLC. 1655 Forest Drive Medina, OH 44256

Re: K181594

Trade/Device Name: Spectralis HRA+OCT and variants with OCT Angiography Module Regulation Number: 21 CFR 886.1570 Regulation Name: Ophthalmoscope Regulatory Class: Class II Product Code: OBO, MYC Dated: June 15, 2018 Received: June 18, 2018

Dear Lena Sattler:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

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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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

> Sincerely, Bradley S. Cunningham -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) K181594

#### Device Name

SPECTRALIS HRA+OCT and variants with OCT Angiography Module

Indications for Use (Describe)

The SPECTRALIS is a non-contact ophthalmic diagnostic imaging device. It is intended for:

- · viewing the posterior segment of the eye, including two- and three-dimensional imaging
- · cross-sectional imaging (SPECTRALIS HRA+OCT and SPECTRALIS OCT)
- · fundus imaging

· fluorescence imaging (fluorescein angiography, indocyanine green angiography; SPECTRALIS HRA+OCT, SPECTRALIS HRA)

- · autofluorescence imaging (SPECTRALIS HRA+OCT, SPECTRALIS HRA and SPECTRALIS OCT with BluePeak)
- · performing measurements of ocular anatomy and ocular lesions.

The device is indicated as an aid in the detection and management of various ocular diseases, including:

- age-related macular degeneration
- macular edema
- · diabetic retinopathy
- · retinal and choroidal vascular diseases
- glaucoma

The device is indicated for viewing geographic atrophy.

The SPECTRALIS OCT Angiography Module is indicated as an aid in the visualization of vascular structures of the retina and choroid.

The SPECTRALIS HRA+OCT and SPECTRALIS OCT include the following reference databases:

· a retinal nerve fiber layer thickness reference database, which is used to quantitatively compare the retinal nerve fiber layer in the human retina to values of Caucasian normal subjects – the classification result being valid only for Caucasian subjects

· a reference database for retinal nerve fiber layer thickness and optic nerve head neuroretinal rim parameter measurements, which is used to quantitatively compare the retinal nerve fiber layer and neuroretinal rim in the human retina to values of normal subjects of different races and ethnicities representing the population mix of the USA (Glaucoma Module Premium Edition)

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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Image /page/4/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text in a bold, sans-serif font. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". There is a red square to the left of the first line and to the right of the second line.

# 510(K) SUMMARY

Date Prepared

August 31, 2018

## SPONSOR/510(K) OWNER/ MANUFACTURER

Heidelberg Engineering GmbH Max-Jarecki-Strasse 8 69115 Heidelberg, Germany Telephone: Facsimile: Email: Establishment Registration No.:

+49 6221 / 64 63 0 +49 6221 / 64 63 62 [e-mail] 8043762

## OFFICIAL CONTACT PERSON

Lena Sattler Orasi Consulting, LLC. 1655 Forest Dr. Medina, OH 44256 Telephone: Facsimile: E-mail:

[phone] [phone] [e-mail]

## COMMON/USUAL NAME

Optical Coherence Tomography

## PROPRIETARY OR TRADE NAMES

SPECTRALIS HRA+OCT and variants with OCT Angiography Module

## CLASSIFICATION INFORMATION

| Classification Name: | Tomography, Optical Coherence<br>Ophthalmoscope, Laser, Scanning |
|-----------------------|------------------------------------------------------------------|
| Medical Specialty: | Ophthalmic |
| Device Class: | II |
| Classification Panel: | Ophthalmic Device Panel |
| Product Codes: | OBO, MYC |

## PRODUCT CODE: CLASSIFICATION / CFR TITLE

OBO, MYC:

Class II § 21 CFR 886.1570

Heidelberg Engineering GmbH

Traditional 510(k): SPECTRALIS Page 1 of 34

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Image /page/5/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text in a bold, sans-serif font. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". There is a red square to the left of the word "HEIDELBERG" and to the right of the word "ENGINEERING".

## PRIMARY PREDICATE DEVICE

Opto Vue, Inc. RTVue XR OCT Avanti with AngioVue™ Software (K153080), Software Version 2016.1.0

## LEGALLY MARKETED UNMODIFIED PREDICATE DEVICE

Trade/Device Name: Applicant: 510(k) Premarket Notification number: Classification: CFR Title: FDA Product Code(s): Classification Name:

Common Name: Medical Specialty: Classification Panel:

SPECTRALIS HRA+OCT and variants Heidelberg Engineering GmbH K172649 Class II 21 CFR 886.1570 OBO, MYC Tomography, Optical Coherence Ophthalmoscope, Laser, Scanning Optical Coherence Tomography Ophthalmic Ophthalmic Device Panel

## GENERAL DEVICE DESCRIPTION

The Heidelberg Engineering SPECTRALIS HRA+OCT is a non-contact ophthalmic device used to image the anterior and posterior segments of the human eye. The SPECTRALIS HRA+OCT is a combination of a confocal laser-scanning ophthalmoscope (cSLO, the HRA portion) and a spectral-domain optical coherence tomographer (SD-OCT). The confocal laser-scanning part of the device allows for acquisition of reflectance images (with blue, green or infrared light), conventional angiography images (using fluorescein or indocyanine green dye) and autofluorescence images. The different imaging modes can be used either alone or simultaneously. The SD-OCT part of the device acquires cross-sectional and volume images, together with an HRA cSLO image.

A blue laser is used for fluorescein angiography, autofluorescence imaging, and blue reflectance imaging, and two infrared lasers are used for indocyanine green angiography and infrared reflectance imaging. A green laser is used for MultiColor imaging ("composite color images"). MultiColor imaging is the simultaneous acquisition of infrared, green and blue reflectance images that can be viewed separately or as a composite color image. For SD-OCT imaging, an infrared superluminescent diode and a spectral interferometer are used to create the cross-sectional images.

Heidelberg Engineering GmbH

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Image /page/6/Picture/1 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either side. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". The text is in a bold, sans-serif font.

The purpose of this premarket notification [510(k)] is to add OCT Angiography (OCTA) as an optional, add-on functionality to the SPECTRALIS HRA+OCT. Based on OCT imaging, OCTA is a non-invasive method to visualize the retinal and choroidal vasculature without the need for injection of intravenous dyes. The device generates OCTA images from analysis of temporal changes in the intensity of reflected light caused by moving particles, such as erythrocytes flowing through vessels. These changes in the OCT signal are detected by repeatedly capturing OCT images on the retina to allow for the creation of an image contrast between the perfused vessels and the static surrounding tissues.

OCTA volume scans allow for the visualization of en-face images generated from predefined or user-customizable slabs. OCT Angiography is intended for qualitative use only. No quantitative measurements are provided by the OCTA functionality.

Besides the addition of OCT Angiography, the SPECTRALIS device is unchanged. The unmodified device is the predicate device for all functions besides OCT Angiography.

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Image /page/7/Picture/1 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text in a bold, sans-serif font. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". There is a red square on either side of the text.

## INDICATIONS FOR USE - MODIFIED SPECTRALIS HRA+OCT

The SPECTRALIS is a non-contact ophthalmic diagnostic imaging device. It is intended for:

- viewing the posterior segment of the eye, including two- and three-dimensional . imaging
- cross-sectional imaging (SPECTRALIS HRA+OCT and SPECTRALIS OCT) .
- fundus imaging ●
- . fluorescence imaging (fluorescein angiography, indocyanine green angiography; SPECTRALIS HRA+OCT, SPECTRALIS HRA)
- . autofluorescence imaging (SPECTRALIS HRA+OCT, SPECTRALIS HRA and SPECTRALIS OCT with BluePeak)
- performing measurements of ocular anatomy and ocular lesions. .

The device is indicated as an aid in the detection and management of various ocular diseases, including:

- age-related macular degeneration .
- . macular edema
- . diabetic retinopathy
- retinal and choroidal vascular diseases ●
- . glaucoma

The device is indicated for viewing geographic atrophy.

The SPECTRALIS OCT Angiography Module is indicated as an aid in the visualization of vascular structures of the retina and choroid.

The SPECTRALIS HRA+OCT and SPECTRALIS OCT include the following reference databases:

- a retinal nerve fiber layer thickness reference database, which is used to . quantitatively compare the retinal nerve fiber layer in the human retina to values of Caucasian normal subjects – the classification result being valid only for Caucasian subjects
- a reference database for retinal nerve fiber layer thickness and optic nerve head ● neuroretinal rim parameter measurements, which is used to quantitatively compare the retinal nerve fiber layer and neuroretinal rim in the human retina to values of normal subjects of different races and ethnicities representing the population mix of the USA (Glaucoma Module Premium Edition)

Heidelberg Engineering GmbH

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Image /page/8/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text in a blocky, sans-serif font. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". There is a dark red square to the left of the word "HEIDELBERG" and to the right of the word "ENGINEERING".

## SUBSTANTIAL EQUIVALENCE

The modified SPECTRALIS HRA+OCT and variants with OCT Angiography Module is a device modification to the cleared SPECTRALIS HRA+OCT and variants (K172649) predicate device. Technological characteristics of the device are unchanged except for the modification as stated in the General Device Description. The modified SPECTRALIS has an updated Indications for Use statement, but maintains the same fundamental scientific technology as the unmodified device. The modified SPECTRALIS HRA+OCT and variants measures the same ophthalmic features and parameters as the cleared SPECTRALIS HRA+OCT and variants in K172649. The changes applied to the SPECTRALIS since the clearance in K172649 do not change the intended patient populations, the type of acquired images, or how the SPECTRALIS may be used as an aid to clinical evaluation.

The added OCTA functionality is similar to that of the primary predicate device, RTVue XROCT Avanti with AngioVue software as cleared under K153080.

Non-clinical and clinical performance testing was conducted on the SPECTRALIS HRA+OCT to verify that the device is safe and effective for its intended use and indications for use. The modification to the device does not raise issues of safety and effectiveness. A comparison of technological characteristics and clinical performance testing demonstrate that the SPECTRALIS device is substantially equivalent to the primary predicate device. RTVue XR OCT Avanti with AngioVue software.

The Substantial Equivalence Summary tables below illustrate the comparisons of the modified SPECTRALIS to the predicate devices.

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Image /page/9/Picture/0 description: The image contains the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either side. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING".

### INDICATIONS FOR USE STATEMENT CHART

#### PRIMARY PREDICATE K172649 PREDICATE DEVICE SUBJECT DEVICE K153080 RTVue XR The RTVue XR OCT Avanti The SPECTRALIS is a non-contact The SPECTRALIS is a non-contact with Normative Database is ophthalmic diagnostic imaging ophthalmic diagnostic imaging device. It is an optical coherence device. It is intended for viewing intended for: tomography system indicated the posterior segment of the eye, ● viewing the posterior segment of the for the in vivo imaging and including two- and threeeye, including two- and threemeasurement of the retina, dimensional imaging, crossdimensional imaging sectional imaging (SPECTRALIS retinal nerve fiber layer, and . cross-sectional imaging (SPECTRALIS optic disc as a tool and aid in HRA+OCT and SPECTRALIS HRA+OCT and SPECTRALIS OCT) the diagnosis and management OCT), fundus photography, ● fundus imaging fluorescence imaging (fluorescein of retinal diseases by a . fluorescence imaging (fluorescein clinician. The RTVue XR angiography, indocyanine green angiography, indocyanine green OCT Avanti with Normative angiography; SPECTRALIS angiography; SPECTRALIS Database is also a quantitative HRA+OCT, SPECTRALIS HRA), HRA+OCT, SPECTRALIS HRA) autofluorescence imaging tool for the comparison of ● autofluorescence imaging (SPECTRALIS HRA+OCT, retina, retinal nerve fiber (SPECTRALIS HRA+OCT. layer, and optic disk SPECTRALIS HRA and SPECTRALIS HRA and measurements in the human SPECTRALIS OCT with BluePeak) SPECTRALIS OCT with BluePeak) eye to a database of known and to perform measurements of performing measurements of ocular ● normal subjects. It is intended ocular anatomy and ocular lesions. for use as a diagnostic device anatomy and ocular lesions. The device is indicated as an aid in the The device is indicated as an aid in to aid in the detection and detection and management of various ocular management of ocular the detection and management of diseases, including: diseases. various ocular diseases, including age-related macular degeneration, age-related macular degeneration ● macular edema, diabetic . macular edema retinopathy, retinal and choroidal . diabetic retinopathy vascular diseases, glaucoma, and for . retinal and choroidal vascular diseases viewing geographic atrophy as well glaucoma as changes in the eye that result The device is indicated for viewing from neurodegenerative diseases. geographic atrophy. The RTVue XR OCT Avanti The SPECTRALIS OCT Angiography with AngioVue Software is Module is indicated as an aid in the indicated as an aid in the visualization of vascular structures of the visualization of vascular retina and choroid. structures of the retina and The SPECTRALIS HRA+OCT and choroid. The SPECTRALIS HRA+OCT and SPECTRALIS OCT include the following SPECTRALIS OCT include reference databases: reference databases for retinal nerve a retinal nerve fiber layer thickness . fiber layer thickness and optic nerve reference database, which is used to head neuroretinal rim parameter quantitatively compare the retinal nerve measurements, which are used to fiber layer in the human retina to values quantitatively compare the retinal of Caucasian normal subjects - the nerve fiber layer and neuroretinal classification result being valid only for rim in the human retina to values Caucasian subjects found in normal subjects. ● a reference database for retinal nerve fiber layer thickness and optic nerve head neuroretinal rim parameter measurements, which is used to quantitatively compare the retinal nerve fiber layer and neuroretinal rim in the human retina to values of normal subjects of different races and ethnicities representing the population mix of the USA (Glaucoma Module Premium Edition)

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Image /page/10/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either end. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING."

| | TECHNOLOGICAL CHARACTERISTICS COMPARISON TABLE |
|--|------------------------------------------------|
| | |

| | PRIMARY<br>PREDICATE<br>K153080 RTVUE<br>XR | PREDICATE<br>DEVICE K172649<br>SPECTRALIS<br>HRA+OCT | SUBJECT DEVICE | Discussion |
|---------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Device<br>classification<br>name | Optical Coherence<br>Tomographer<br>(OCT) | Optical Coherence<br>Tomographer<br>(OCT) | Optical Coherence<br>Tomographer<br>(OCT) | Same |
| Technology | Spectral Domain<br>OCT | Spectral Domain<br>OCT | Spectral Domain<br>OCT | Same |
| Images of<br>posterior<br>segment of<br>eye | Yes | Yes, using standard,<br>WFO/WFO2, or<br>UWF objective lens | Yes, using standard,<br>WFO/WFO2, or<br>UWF objective lens | Same |
| Images of<br>anterior<br>segment of<br>eye | Yes | With Anterior<br>Segment Module<br>(K113129) | With Anterior<br>Segment Module<br>(K113129) | Same |
| OCT imaging<br>of the<br>anterior and<br>posterior<br>segment | Anterior segment:<br>with CAM (Cornea<br>and Anterior Module) | Anterior segment:<br>With Anterior<br>Segment Module<br>(K113129) | Anterior segment:<br>With Anterior<br>Segment Module<br>(K113129) | Same |
| | Posterior Segment:<br>Yes | Posterior Segment:<br>Yes | Posterior Segment:<br>Yes | |
| OCT<br>Angiography | AngioVue™<br>Software | n/a | OCT Angiography<br>Module;<br>30° OCT/OCTA field<br>of view with standard<br>objective | Similar to the<br>primary predicate |
| Reference<br>Databases | Comparison of retina,<br>retinal nerve fiber<br>layer, and optic disk<br>measurements in the<br>human eye to a<br>database of known<br>normal subjects. | RNFL thickness in<br>reference database for<br>12° circle scans<br>(Caucasian only)<br>(K101223)<br>RNFL thickness in<br>reference database for<br>fixed diameter circle<br>scans, and ONH<br>parameters (BMO-<br>MRW, BMO-MRA)<br>reference database<br>(K152205) | RNFL thickness in<br>reference database for<br>12° circle scans<br>(Caucasian only)<br>(K101223)<br>RNFL thickness in<br>reference database for<br>fixed diameter circle<br>scans, and ONH<br>parameters (BMO-<br>MRW, BMO-MRA)<br>reference database<br>(K152205) | Similar;<br>SPECTRALIS does<br>not include a Retina<br>RDB. |

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## Heidelberg Engineering GmbH

| | | K181594 |
|--|--|---------|
|--|--|---------|

| | PRIMARY<br>PREDICATE<br>K153080 RTVUE<br>XR | PREDICATE<br>DEVICE K172649<br>SPECTRALIS<br>HRA+OCT | SUBJECT DEVICE | Discussion |
|------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Imaging<br>modes, lights<br>sources and<br>wavelength<br>of light<br>emitted | Live camera:<br>• Near infrared<br>reflectance<br>images: LED, 735<br>nm, | cSLO:<br>• Near infrared<br>reflectance<br>images: diode<br>laser, 815 nm,<br>• Blue light<br>reflectance<br>images: diode<br>laser, 486 nm, or<br>optically pumped<br>semiconductor<br>laser, 488 nm<br>• Green light<br>reflectance<br>images: diode<br>laser, 518 nm<br>• Fluorescein<br>angiography:<br>diode laser, 486<br>nm, or optically<br>pumped<br>semiconductor<br>laser, 488 nm<br>• Indocyanine green<br>angiography:<br>diode laser, 786<br>nm | cSLO:<br>• Near infrared<br>reflectance<br>images: diode<br>laser, 815 nm,<br>• Blue light<br>reflectance<br>images: diode<br>laser, 486 nm, or<br>optically pumped<br>semiconductor<br>laser, 488 nm<br>• Green light<br>reflectance<br>images: diode<br>laser, 518 nm<br>• Fluorescein<br>angiography:<br>diode laser, 486<br>nm, or optically<br>pumped<br>semiconductor<br>laser, 488 nm<br>• Indocyanine green<br>angiography:<br>diode laser, 786<br>nm | Comparable for OCT<br>imaging;<br>Different for fundus<br>imaging:<br>RTVue uses a live<br>camera for fundus<br>imaging;<br>SPECTRALIS uses a<br>cSLO system with<br>several imaging<br>modes |
| | OCT:<br>840 nm ± 10 nm | OCT:<br>superluminescence<br>diode, 840 nm to 920<br>nm (weighted<br>average 880 nm) | OCT:<br>superluminescence<br>diode, 840 nm to 920<br>nm (weighted<br>average 880 nm) | |
| Amount of<br>light<br>irradiated to<br>retina<br>(exposure) | Exposure Power at<br>pupil: less than or<br>equal to 750 μW<br>(Laser Class I) | Low amount, does<br>not exceed Class I<br>laser accessible<br>emission limits | Low amount, does<br>not exceed Class I<br>laser accessible<br>emission limits | Same |
| Lateral<br>optical<br>resolution<br>(OCT) | 15 μm | 14 μm | 14 μm | Comparable |
| Optical depth<br>resolution<br>(OCT) | 5 μm | 7 μm | 7 μm | Comparable |
| | PRIMARY<br>PREDICATE<br>K153080 RTVUE<br>XR | PREDICATE<br>DEVICE K172649<br>SPECTRALIS<br>HRA+OCT | SUBJECT DEVICE | Discussion |
| Fundus<br>imaging field<br>of view | 32° (horizontal) x 22°<br>(vertical) | SO (standard<br>objective):<br>15° x 15° to 30° x<br>30° | SO (standard<br>objective):<br>15° x 15° to 30° x<br>30° | Comparable |
| OCT axial<br>imaging<br>depth | 2 to 3 mm | 1.9 mm | 1.9 mm | RTVue has a slightly<br>higher scanning depth |
| Lateral field<br>of view<br>(OCT) | 2 to 12 mm<br>(approximately 7° to<br>40°) | 10°-30° | 10°-30° | RTVue has a higher<br>range for lateral field<br>of view |
| Digital axial<br>resolution<br>(pixel size<br>OCT) | 3 µm | 3.9 µm | 3.9 µm | Comparable |
| Indications<br>for Use<br>(OCT<br>Angiography<br>part only) | The RTVue XR OCT<br>Avanti with<br>AngioVue Software<br>is indicated as an aid<br>in the visualization of<br>vascular structures of<br>the retina and<br>choroid. | n/a | The SPECTRALIS<br>OCT Angiography<br>Module is indicated<br>as an aid in the<br>visualization of<br>vascular structures of<br>the retina and<br>choroid. | Same Indications for<br>Use for OCT<br>Angiography. |
| OCTA<br>acquisition | Motion-contrast<br>technique | n/a | Motion-contrast<br>technique | Same |
| OCTA<br>algorithm | Split-spectrum<br>amplitude-<br>decorrelation<br>angiography<br>(SSADA);<br>2 repeats of each B-<br>scan | n/a | Proprietary,<br>probabilistic<br>algorithm;<br>4-7 repeats of each B-<br>scan | Same purpose<br>(generation of OCTA<br>flow images), but<br>different<br>mathematical<br>approach. |
| Maximum A-<br>scan rate for<br>OCT and<br>OCTA | 70 kHz | 85 kHz (OCT only) | 85 kHz | Comparable; subject<br>device has slightly<br>faster acquisition rate |
| OCTA<br>Analysis | Visualization of<br>three-dimensional<br>microvasculature | n/a | Visualization of<br>three-dimensional<br>microvasculature | Same as primary<br>predicate. |
| | PRIMARY<br>PREDICATE<br>K153080 RTVUE<br>XR | PREDICATE<br>DEVICE K172649<br>SPECTRALIS<br>HRA+OCT | SUBJECT DEVICE | Discussion |
| Predefined<br>slabs | Superficial (Plexus)<br>Deep (Plexus)<br>Outer Retina<br>Choroid Cap<br>(Capillaries) | n/a | Full image<br>Vitreoretinal<br>Interface<br>Full Retina<br>Superficial Vascular<br>Complex (SVC)<br>Nerve Fiber Layer<br>Vascular Plexus<br>(NFLVP)<br>Superficial Vascular<br>Plexus (SVP)<br>Deep Vascular<br>Complex (DVC)<br>Intermediate<br>Capillary Plexus<br>(ICP)<br>Deep Capillary<br>Plexus (DCP)<br>Avascular Complex<br>(AC)<br>Choriocapillaris (CC)<br>Choroid | Comparable to<br>primary predicate;<br>SPECTRALIS offers<br>more detailed<br>predefined slabs, but<br>both devices cover<br>the full retinal and<br>choroidal vasculature<br>networks |

Image /page/11/Picture/4 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either side. The first line of text reads "HEIDELBERG", and the second line of text reads "ENGINEERING".

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Image /page/14/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either side. The first line says "HEIDELBERG" and the second line says "ENGINEERING".

## KEY SOFTWARE DIFFERENCES BETWEEN THE MODIFIED AND UNMODIFIED SPECTRALIS HRA+OCT

| Software /<br>firmware | PREDICATE DEVICE<br>K172649<br>Final version# | SUBJECT DEVICE<br>K181594<br>Final version# | Description of changes |
|------------------------------------------|-----------------------------------------------|---------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| SPECTRALIS<br>Product Family<br>software | 6.6 | 6.9 | Addition of OCT Angiography |
| Software Level of<br>Concern (LOC) | Moderate | Moderate | Unchanged |
| Software & firmware changes | | | |
| General Product<br>Requirements (GPR) | 1.10 | 1.12 | 1. OCT Angiography<br>2. New Glaucoma Overview Report |
| SPECTRALIS<br>System | 1.10 | 1.12 | 1. OCTA image acquisition<br>2. OCTA image review<br>3. Hardware requirements updated for OCTA<br>acquisition |
| Heidelberg Eye<br>Explorer (HX) | 1.9 | 1.10 | 1. Display of GTIN number in the software<br>2. Performance improvements |
| Acquisition Module<br>(AQM) | 6.5 | 6.9 | 1. OCT Angiography Acquisition Mode / UI<br>changes<br>2. OCT Angiography Processing<br>3. Licensing Mechanism (Activation Codes)<br>4. Memory Handling<br>5. FLEX mount support (not available in the<br>USA) |
| Viewing Module<br>(VWM) | 6.6 | 6.9 | 1. New analysis tab: Display OCT Angio<br>2. New analysis tab: OCT Angiography<br>3. New licensing mechanism<br>4. Scan planning tool support for OCTA<br>5. Configuration of printouts<br>6. New printouts: Glaucoma Overview<br>Report, OCTA Overview Report |
| OCT Firmware | 1.5 | 1.6 | 1. Support for OCTA volume scans |

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# DESIGN CONTROL

Heidelberg Engineering designed and developed the modified SPECTRALIS per the company's Design Control procedure, which complies with the FDA Quality System Regulations CFR Part 820 and ISO 13485:2016. The Design Control procedure also incorporates Risk Management procedures, which comply with ISO 14971:2007.

Risk assessment was conducted on the modified SPECTRALIS, and the impact of the design modifications were assessed on the predicate 510(k) cleared device.

The modified SPECTRALIS is manufactured and tested in the exact manner as the predicate 510(k) cleared device.

Heidelberg Engineering performed bench testing, and software verification and validation, to confirm that the modified SPECTRALIS HRA+OCT functions as intended, and that the addition of OCT Angiography does not interfere with existing SPECTRALIS functionality.

# NON-CLINICAL PERFORMANCE TESTING

The modified SPECTRALIS was evaluated according to the requirements of FDA recognized consensus standards ISO 14971, Medical Devices - Application of Risk Management to Medical Devices and AAMI / ANSI / IEC 62304:2006 Medical Device Software - Software Life Cycle Processes and was found to meet the requirements of the applicable parts.

Laser safety testing, biocompatibility, electromagnetic compatibility, and electrical safety testing was conducted on the previously cleared SPECTRALIS HRA+OCT device. Since there were no hardware changes for the addition of OCT Angiography, these performance and safety tests were not required to be repeated for this change.

Software documentation was provided, and software verification and validation was conducted as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."

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# CLINICAL PERFORMANCE TESTING

A prospective, case series study was conducted at a single clinical site in the United States to compare the clinical performance of the OCTA functionality between the SPECTRALIS and the RTVue XR devices. 79 participants age 22 or older meeting eligibility criteria in at least one eye were enrolled into a single study cohort with two sub-groups, the "Normal group" (without ocular pathology) and the "Pathology group" (those with retinal vascular pathologies affecting different anatomic depths throughout the retina and choroid). One eye of each participant was selected to be the study eye, (randomly determined when both eyes were eligible). After completion of a baseline clinical evaluation, eligible participants underwent the following imaging:

- 1. OCTA imaging with the Spectralis (HR10 and HS20 scan patterns) and the RTVue XR (AngioRetina 3.0 mm and 6.0 mm scan patterns);
- 2. structural (non-OCTA) OCT imaging;
- 3. color fundus photography (CFP);
- 4. fluorescein angiography (FA) and, when clinically indicated, indocyanine green angiography (ICGA).

"Normal group" participants were randomized to having OCTA imaging performed before dilation or after dilation. All "Pathology group" participants underwent dilated OCTA imaging unless the location of relevant pathology was already known. For those included into the "Pathology group," the investigator determined a "primary pathology of interest" (PPOI) and corresponding "region of interest" (ROI) to which reading center (RC) grading is directed. Device operators were instructed to image only the designated ROI, and were masked to the determined PPOI. Up to three reattempts were allowed when the proper ROI was not acquired. The clinical site reviewed the imaging and selected the first acceptable OCTA image set from each OCTA device; any manual segmentation correction was performed by the clinical site at the investigator's discretion. Acquired images were submitted to an independent RC (two sets of three qualified, masked graders, one set for OCTA image grading, one set for FA/ICGA grading) for evaluation of image quality and clinically relevant content.

The following endpoints were evaluated:

- 1) "Response rate":
- The percentage of eye with SPECTRALIS image quality score (of OCTA । images) greater than or equal to that of the RTVue XR; scoring is based on a scale (0 = poor, 1 = average, 2 = good).
- -The percentage of eye with SPECTRALIS anatomical structure score greater than or equal to that of the RTVue XR for clinically relevant vascular structures (foveal avascular zone, large vessels, small vessels, end capillaries); scoring is based on a scale (0 = unable to distinguish, 1 = difficult, 2 = easy).

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Image /page/17/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of the words "HEIDELBERG" on the top line and "ENGINEERING" on the bottom line. There is a red square to the left of the word "HEIDELBERG" and to the right of the word "ENGINEERING".

- 2) Agreement between OCTA images and FA/ICGA images (the defined reference standard) in the ease in identification of the following:
- The pre-specified PPOI; -
- Pertinent vascular pathology (microaneurysms, retinal vascular tortuosity, choroidal neovascularization, retinal ischemia, retinal neovascularization, other types).

This endpoint was evaluated based on the analysis of the boxed area of the FA/ICGA images that best represented the area scanned by each device's respective OCTA scan pattern.

- 3) The frequency and nature of adverse events.
A total of 95 participants were enrolled, 37 "Normal," 58 "Pathology." 32 "Normal" and 47 "Pathology" participants completed the study; the rest were discontinued as screen failures. The primary analyses were based on data from these 79 participants. The median age in the "Normal" and "Pathology" sub-groups are 36.5 and 68, respectively (range, 24-77 "Normal," 27-90 "Pathology"). The proportion of women was 75% and 49% in the "Normal" and "Pathology" sub-groups, respectively. The majority (86%) of the entire cohort was racially white. In the "Normal" sub-group, the mean O values (a signal strength indicator) were 41.5±2.7 (range 37-46) for the HR10 scan pattern and 38.6±2.6 (range 33-43) for the HS20 scan pattern; in the "Pathology" sub-group, the mean Q values were 35.8±3.4 (range 28-42) and 34.3±2.9 (range 26-39) for the HR10 and HS20 scan patterns, respectively. The RTVue SSI values in the "Normal" sub-group were 75.0±7.1 (range 57-89) and 70.5±7.3 (range 52-84) for the AngioRetina 3.0 mm and 6.0 mm scan patterns, respectively. In the "Pathology" subgroup, the RTVue SSI values were 61.4±10.3 (range 41-84) and 56.9±9.6 (range 37-75) for the AngioRetina 3.0 mm and 6.0 mm scan patterns, respectively. The distribution of vascular pathologies in the "Pathology" sub-group is shown in Table 1.

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Image /page/18/Picture/1 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text in a stylized, blocky font. The first line reads "HEIDELBERG" and the second line reads "ENGINEERING". There is a maroon square to the left of the first line and to the right of the second line.

| | Normal<br>(N=32) | Pathology<br>(N=47) | Total<br>(N=79) |
|----------------------------------------|------------------|---------------------|-----------------|
| Primary vascular pathology of interest | | | |
| None | 32 (100) | 0 (0) | 32 (41) |
| Retinal ischemia | 0 (0) | 8 (17) | 8 (10) |
| Microaneurysms | 0 (0) | 18 (38) | 18 (23) |
| Choroidal neovascularization | 0 (0) | 14 (30) | 14 (18) |
| Retinal neovascularization | 0 (0) | 1 (2) | 1 (1) |
| Retinal vascular tortuosity | 0 (0) | 3 (6) | 3 (4) |
| Other | 0 (0) | 3 (6) | 3 (4) |
| Vascular pathology1 | | | |
| None | 32 (100) | 0 (0) | 32 (41) |
| Retinal ischemia | 0 (0) | 16 (34) | 16 (20) |
| Microaneurysms | 0 (0) | 22 (47) | 22 (28) |
| Choroidal neovascularization | 0 (0) | 14 (30) | 14 (18) |
| Retinal neovascularization | 0 (0) | 3 (6) | 3 (4) |
| Retinal vascular tortuosity | 0 (0) | 10 (21) | 10 (13) |
| Other | 0 (0) | 3 (6) | 3 (4) |
| 1Eyes may have more than 1 pathology. | | | |

### TABLE 1: VASCULAR PATHOLOGY OF STUDY EYES

SPECTRALIS OCTA images rejection frequencies for the HR10 scan pattern were 5% and 15% in the "Normal" and "Pathology" sub-groups, respectively, and 14% and 9% for the HS20 scan pattern. RTVue OCTA image rejection frequencies for the AngioRetina 3.0 mm scan pattern were 3% and 12% in the "Normal" and "Pathology" sub-groups, respectively, and 3% and 18% for the AngioRetina 6.0 mm scan pattern. Manual segmentation correction frequencies for the HR10 scan pattern were 16% and 52% in the "Normal" and "Pathology" sub-groups, respectively, and 38% for the HS20 scan pattern. Manual segmentation correction frequencies for the AngioRetina 3.0 mm scan pattern were 47% and 52% in the "Normal" and "Pathology" sub-groups, respectively, and 22% and 38% for the AngioRetina 6.0 mm scan pattern.

For image quality assessment for each OCTA device and scan pattern, all but one image were graded as average or good (score ≥ 1) by the graders. The consensus OCTA image quality score response rates are summarized in Table 2.

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Image /page/19/Picture/1 description: The image contains the logo for Heidelberg Engineering. The logo consists of two lines of text, with a square on either side. The first line says "HEIDELBERG" and the second line says "ENGINEERING."

| | SPECTRALIS Score1 | | | | Response Rate (%)3 |
|-----------------------------|-------------------|---------|---------|---------|--------------------|
| RTVue Score1, n (%) | 0 | 1 | 2 | Total | (95% CI) |
| Normal Subjects | | | | | |
| Scan pattern 12 (N=32) | | | | | 75.0 (56.6, 88.5) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 3 (9) | 2 (6) | 5 (16) | |
| 2 | 0 (0) | 8 (25) | 19 (59) | 27 (84) | |
| Total | 0 (0) | 11 (34) | 21 (66) | 32 | |
| Scan pattern 22 (N=32) | | | | | 71.9 (53.3, 86.3) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 3 (9) | 6 (19) | 9 (28) | |
| 2 | 0 (0) | 9 (28) | 14 (44) | 23 (72) | |
| Total | 0 (0) | 12 (38) | 20 (63) | 32 | |
| Vascular Pathology Subjects | | | | | |
| Scan pattern 12 (N=47) | | | | | 93.6 (82.5, 98.7) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 32 (68) | 3 (6) | 35 (74) | |
| 2 | 0 (0) | 3 (6) | 9 (19) | 12 (26) | |
| Total | 0 (0) | 35 (74) | 12 (26) | 47 | |
| Scan pattern 22 (N=47) | | | | | 89.4 (76.9, 96.5) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 1 (2) | 29 (62) | 8 (17) | 38 (81) | |
| 2 | 0 (0) | 4 (9) | 5 (11) | 9 (19) | |
| Total | 1 (2) | 33 (70) | 13 (28) | 47 | |

#### TABLE 2: COMPARISON OF CONSENSUS OCTA IMAGE QUALITY BETWEEN SPECTRALIS AND RTVUE FOR NORMAL SUBJECTS AND VASCULAR PATHOLOGY SUBJECTS

√ = Number of subjects with image quality scores from both devices

Score: 0=Poor; 1=Average; 2=Good

Scan pattern 1: SPECTRALIS 10° x 10° and RTVue 3mm x 3mm; Scan pattern 2: SPECTRALIS 20° x 20° and RTVue 6mm x 6mm

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Total inter-grader agreement on image quality scoring (where the same image quality score was determined by all three graders for an OCTA image) is summarized in Table 3.

| | Normal<br>(N=32) | Pathology<br>(N=47) | Total<br>(N=79) |
|---------------------------------|------------------|---------------------|-----------------|
| SPECTRALIS 10° x 10° | | | |
| Number of subjects | 32 | 47 | 79 |
| Same score from 3 graders | 27 (84) | 37 (79) | 64 (81) |
| 95% CI1 | 67.2, 94.7 | 64.3, 89.3 | 70.6, 89.0 |
| Same score from 2 graders | 5 (16) | 10 (21) | 15 (19) |
| Different scores from 3 graders | 0 (0) | 0 (0) | 0 (0) |
| RTVue 3mm x 3mm | | | |
| Number of subjects | 32 | 47 | 79 |
| Same score from 3 graders | 25 (78) | 28 (60) | 53 (67) |
| 95% CI1 | 60.0, 90.7 | 44.3, 73.6 | 55.6, 77.3 |
| Same score from 2 graders | 7 (22) | 19 (40) | 26 (33) |
| Different scores from 3 graders | 0 (0) | 0 (0) | 0 (0) |
| SPECTRALIS 20° x 20° | | | |
| Number of subjects | 32 | 47 | 79 |
| Same score from 3 graders | 23 (72) | 39 (83) | 62 (78) |
| 95% CI1 | 53.3, 86.3 | 69.2, 92.4 | 67.8, 86.9 |
| Same score from 2 graders | 9 (28) | 8 (17) | 17 (22) |
| Different scores from 3 graders | 0 (0) | 0 (0) | 0 (0) |
| RTVue 6mm x 6mm | | | |
| Number of subjects | 32 | 47 | 79 |
| Same score from 3 graders | 23 (72) | 30 (64) | 53 (67) |
| 95% CI1 | 53.3, 86.3 | 48.5, 77.3 | 55.6, 77.3 |
| Same score from 2 graders | 9 (28) | 17 (36) | 26 (33) |
| Different scores from 3 graders | 0 (0) | 0 (0) | 0 (0) |
| 1 Exact 95% confidence interval | | | |

| | | | TABLE 3: INTER-GRADER AGREEMENT IN OCTA IMAGE QUALITY | | |
|--|--|--|-------------------------------------------------------|--|--|
|--|--|--|-------------------------------------------------------|--|--|

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The consensus overall anatomical structure score response rate (percentage of eyes with SPECTRALIS anatomical structure score greater than or equal to RTVue anatomical structure score) ranged from 85.3% to 97.5% for the four key anatomical structures [Table 4: foveal avascular zone (FAZ), Table 5: large vessels (LV), Table 6: small vessels (SV), and Table 7: end capillaries (EC)].

| TABLE 4: COMPARISON OF CONSENSUS VISUALIZATION OF FOVEAL AVASCULAR ZONE | | | | |
|--------------------------------------------------------------------------|-------------------------------------|--|--|--|
| | BORDER BETWEEN SPECTRALIS AND RTVUE | | | |

| | SPECTRALIS Score¹ | | | | Response Rate (%)³<br>(95% CI) |
|-----------------------------|-------------------|---------|----------|----------|--------------------------------|
| RTVue Score¹, n (%) | 0 | 1 | 2 | Total | |
| All Subjects | | | | | |
| Scan pattern 1² (N=68) | | | | | 95.6 (87.6, 99.1) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 12 (18) | 2 (3) | 14 (21) | |
| 2 | 0 (0) | 3 (4) | 51 (75) | 54 (79) | |
| Total | 0 (0) | 15 (22) | 53 (78) | 68 | |
| Scan pattern 2² (N=75) | | | | | 85.3 (75.3, 92.4) |
| 0 | 1 (1) | 0 (0) | 0 (0) | 1 (1) | |
| 1 | 3 (4) | 14 (19) | 11 (15) | 28 (37) | |
| 2 | 1 (1) | 7 (9) | 38 (51) | 46 (61) | |
| Total | 5 (7) | 21 (28) | 49 (65) | 75 | |
| Normal Subjects | | | | | |
| Scan pattern 1² (N=32) | | | | | 100.0 (89.1, 100.0) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |…