Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes standard image processing techniques for OCT Angiography (analysis of temporal changes in intensity) and does not mention any AI/ML algorithms, training data, or performance metrics typically associated with AI/ML.

Therapeutic

No
This device is described as a diagnostic imaging device used to aid in the detection and management of various ocular diseases. It does not provide treatment.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states, "The SPECTRALIS is a non-contact ophthalmic diagnostic imaging device." It also lists various ocular diseases for which the device is indicated as an "aid in the detection and management."

SaMD (Software as a Medical Device)

No

The device description clearly states that the SPECTRALIS is a combination of a confocal laser-scanning ophthalmoscope (cSLO) and a spectral-domain optical coherence tomographer (SD-OCT), both of which are hardware components. The 510(k) is for an add-on software functionality (OCT Angiography) to an existing hardware device.

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an In Vitro Diagnostic (IVD).

Here's why:

IVD Definition: In Vitro Diagnostics are medical devices used to perform tests on samples taken from the human body, such as blood, urine, or tissue, to detect diseases, conditions, or infections.
SPECTRALIS Function: The SPECTRALIS device is described as a non-contact ophthalmic diagnostic imaging device. It directly images the posterior and anterior segments of the eye using various light and imaging technologies. It does not analyze samples taken from the body.
Intended Use: The intended use clearly states it is for "viewing the posterior segment of the eye," "cross-sectional imaging," "fundus imaging," "fluorescence imaging," "autofluorescence imaging," and "performing measurements of ocular anatomy and ocular lesions." These are all direct imaging and measurement functions performed on the eye itself.
Aid in Detection and Management: While the device is indicated as an "aid in the detection and management of various ocular diseases," this is achieved through the visualization and measurement of structures within the eye, not through the analysis of biological samples.

Therefore, the SPECTRALIS device falls under the category of an in vivo diagnostic imaging device, not an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for 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)

Product codes

OBO, MYC

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.

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.

Mentions image processing

Yes

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Optical Coherence Tomography (OCT), Confocal Laser-Scanning Ophthalmoscopy (cSLO)

Anatomical Site

posterior segment of the eye, anterior segment of the human eye, retina, choroid, retinal nerve fiber layer, optic disc, foveal avascular zone, large vessels, small vessels, end capillaries

Indicated Patient Age Range

Not Found

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

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);
1. structural (non-OCTA) OCT imaging;
1. color fundus photography (CFP);
1. 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.

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.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Study Type: Prospective, case series study
Sample Size: 79 participants (32 "Normal," 47 "Pathology")
Key Metrics:
- Image Quality "Response rate": The percentage of eye with SPECTRALIS image quality score (of OCTA images) greater than or equal to that of the RTVue XR.
- Anatomical Structure Score "Response rate": 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).
- Agreement between OCTA images and FA/ICGA images (the defined reference standard) in the ease in identification of the pre-specified PPOI and pertinent vascular pathology.
Key Results:
- Image quality response rates for SPECTRALIS (score ≥ 1) compared to RTVue XR were:
  - Normal Subjects: Scan pattern 1 (10° x 10° vs 3mm x 3mm) 75.0% (95% CI: 56.6, 88.5); Scan pattern 2 (20° x 20° vs 6mm x 6mm) 71.9% (95% CI: 53.3, 86.3).
  - Vascular Pathology Subjects: Scan pattern 1 93.6% (95% CI: 82.5, 98.7); Scan pattern 2 89.4% (95% CI: 76.9, 96.5).
- Inter-grader agreement on image quality scoring for SPECTRALIS ranged from 81% (total) to 84% ("Normal") and 79% ("Pathology") for 10° x 10° scans (same score from 3 graders); and 78% (total) to 72% ("Normal") and 83% ("Pathology") for 20° x 20° scans. RTVue XR showed slightly lower inter-grader agreement.
- Anatomical structure score response rate (SPECTRALIS score ≥ RTVue XR score) ranged from 85.3% to 97.5% across the four key anatomical structures (foveal avascular zone, large vessels, small vessels, end capillaries).
- Agreement in consensus identification of microaneurysms between SPECTRALIS and RTVue showed high percentages of agreement (PoA) ranging from 94.9% to 100.0% across scan patterns and subject groups.
- Agreement in consensus identification of retinal vascular tortuosity showed high PoA ranging from 93.6% to 100.0%.
- Agreement in consensus identification of choroidal neovascularization showed high PoA ranging from 93.6% to 100.0%.
- Agreement in consensus identification of retinal ischemia showed high PoA ranging from 85.1% to 100.0%.
- Agreement in consensus identification of retinal neovascularization showed high PoA ranging from 97.9% to 100.0%.
- Agreement in consensus identification of Primary Pathology of Interest (PPOI) showed high PoA ranging from 91.5% to 100.0%.
- Inter-grader agreement frequencies for identification of microaneurysms were high (92-95% total agreement).
- Inter-grader agreement frequencies for identification of retinal vascular tortuosity were high (95-96% total agreement).
- Inter-grader agreement frequencies for identification of choroidal neovascularization were high (96-99% total agreement).
- Inter-grader agreement frequencies for identification of retinal ischemia were high (94-97% total agreement).
- Inter-grader agreement frequencies for identification of retinal neovascularization were high (97-99% total agreement).
- Inter-grader agreement frequencies for identification of PPOI were high (90-95% total agreement).
- No adverse events related to the OCTA devices were reported.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Image Quality Response rate (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))
Anatomical Structure Score Response rate (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))
Percent of Agreement (PoA) between SPECTRALIS and RTVue for identification of pathologies and PPOI.
Ratio of the percentages of matching with FA/ICGA (SPECTRALIS to RTVue).
Inter-grader agreement (percentage of cases where all three graders determined the same score).

Predicate Device(s)

K153080, K172649

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 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.

Summary

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the U.S. Food & Drug Administration. The Department of Health & Human Services logo is on the left and consists of a stylized human figure. The FDA logo is on the right and consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

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.

1

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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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

2

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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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 Christoph.Schoess@HeidelbergEngineering.com 8043762

OFFICIAL CONTACT PERSON

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

(440) 554-3706 (866) 904-4315 lena@orasiconsulting.com

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

11

Heidelberg Engineering GmbH

		K181594
--	--	---------

| | PRIMARY
PREDICATE
K153080 RTVUE
XR | PREDICATE
DEVICE K172649
SPECTRALIS
HRA+OCT | SUBJECT DEVICE | Discussion |
|------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Imaging
modes, lights
sources and
wavelength
of light
emitted | Live camera:
• Near infrared
reflectance
images: LED, 735
nm, | cSLO:
• Near infrared
reflectance
images: diode
laser, 815 nm,
• Blue light
reflectance
images: diode
laser, 486 nm, or
optically pumped
semiconductor
laser, 488 nm
• Green light
reflectance
images: diode
laser, 518 nm
• Fluorescein
angiography:
diode laser, 486
nm, or optically
pumped
semiconductor
laser, 488 nm
• Indocyanine green
angiography:
diode laser, 786
nm | cSLO:
• Near infrared
reflectance
images: diode
laser, 815 nm,
• Blue light
reflectance
images: diode
laser, 486 nm, or
optically pumped
semiconductor
laser, 488 nm
• Green light
reflectance
images: diode
laser, 518 nm
• Fluorescein
angiography:
diode laser, 486
nm, or optically
pumped
semiconductor
laser, 488 nm
• Indocyanine green
angiography:
diode laser, 786
nm | Comparable for OCT
imaging;
Different for fundus
imaging:
RTVue uses a live
camera for fundus
imaging;
SPECTRALIS uses a
cSLO system with
several imaging
modes |
| | OCT:
840 nm ± 10 nm | OCT:
superluminescence
diode, 840 nm to 920
nm (weighted
average 880 nm) | OCT:
superluminescence
diode, 840 nm to 920
nm (weighted
average 880 nm) | |
| Amount of
light
irradiated to
retina
(exposure) | Exposure Power at
pupil: less than or
equal to 750 μW
(Laser Class I) | Low amount, does
not exceed Class I
laser accessible
emission limits | Low amount, does
not exceed Class I
laser accessible
emission limits | Same |
| Lateral
optical
resolution
(OCT) | 15 μm | 14 μm | 14 μm | Comparable |
| Optical depth
resolution
(OCT) | 5 μm | 7 μm | 7 μm | Comparable |
| | PRIMARY
PREDICATE
K153080 RTVUE
XR | PREDICATE
DEVICE K172649
SPECTRALIS
HRA+OCT | SUBJECT DEVICE | Discussion |
| Fundus
imaging field
of view | 32° (horizontal) x 22°
(vertical) | SO (standard
objective):
15° x 15° to 30° x
30° | SO (standard
objective):
15° x 15° to 30° x
30° | Comparable |
| OCT axial
imaging
depth | 2 to 3 mm | 1.9 mm | 1.9 mm | RTVue has a slightly
higher scanning depth |
| Lateral field
of view
(OCT) | 2 to 12 mm
(approximately 7° to
40°) | 10°-30° | 10°-30° | RTVue has a higher
range for lateral field
of view |
| Digital axial
resolution
(pixel size
OCT) | 3 µm | 3.9 µm | 3.9 µm | Comparable |
| Indications
for Use
(OCT
Angiography
part only) | The RTVue XR OCT
Avanti with
AngioVue Software
is indicated as an aid
in the visualization of
vascular structures of
the retina and
choroid. | n/a | The SPECTRALIS
OCT Angiography
Module is indicated
as an aid in the
visualization of
vascular structures of
the retina and
choroid. | Same Indications for
Use for OCT
Angiography. |
| OCTA
acquisition | Motion-contrast
technique | n/a | Motion-contrast
technique | Same |
| OCTA
algorithm | Split-spectrum
amplitude-
decorrelation
angiography
(SSADA);
2 repeats of each B-
scan | n/a | Proprietary,
probabilistic
algorithm;
4-7 repeats of each B-
scan | Same purpose
(generation of OCTA
flow images), but
different
mathematical
approach. |
| Maximum A-
scan rate for
OCT and
OCTA | 70 kHz | 85 kHz (OCT only) | 85 kHz | Comparable; subject
device has slightly
faster acquisition rate |
| OCTA
Analysis | Visualization of
three-dimensional
microvasculature | n/a | Visualization of
three-dimensional
microvasculature | Same as primary
predicate. |
| | PRIMARY
PREDICATE
K153080 RTVUE
XR | PREDICATE
DEVICE K172649
SPECTRALIS
HRA+OCT | SUBJECT DEVICE | Discussion |
| Predefined
slabs | Superficial (Plexus)
Deep (Plexus)
Outer Retina
Choroid Cap
(Capillaries) | n/a | Full image
Vitreoretinal
Interface
Full Retina
Superficial Vascular
Complex (SVC)
Nerve Fiber Layer
Vascular Plexus
(NFLVP)
Superficial Vascular
Plexus (SVP)
Deep Vascular
Complex (DVC)
Intermediate
Capillary Plexus
(ICP)
Deep Capillary
Plexus (DCP)
Avascular Complex
(AC)
Choriocapillaris (CC)
Choroid | Comparable to
primary predicate;
SPECTRALIS offers
more detailed
predefined slabs, but
both devices cover
the full retinal and
choroidal vasculature
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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13

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

15

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."

16

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);
1. structural (non-OCTA) OCT imaging;
1. color fundus photography (CFP);
1. 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".

1. 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.

1. 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
(N=32) | Pathology
(N=47) | Total
(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

20

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
(N=32) | Pathology
(N=47) | Total
(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
--	--	--	-------------------------------------------------------	--	--

21

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

| (95% CI) |
|-----------------------------|------ | RTVue Score¹, n (%) | 0 | All Subjects | | Scan pattern 1² (N=68) | | 0 | 0 (0) | 1 | 0 (0) | 2 | 0 (0) | Total | 0 (0) | Scan pattern 2² (N=75) | | 0 | 1 (1) | 1 | 3 (4) | 2 | 1 (1) | Total | 5 (7) | Normal Subjects | | Scan pattern 1² (N=32) | | 0 | 0 (0) | 1 | 0 (0) | 2 | 0 (0) | Total | 0 (0) | Scan pattern 2² (N=32) | | 0 | 0 (0) | 1 | 0 (0) | 2 | 0 (0) | Total | 0 (0) | Vascular Pathology Subjects | | Scan pattern 1² (N=36) | | 0 | 0 (0) | 1 | 0 (0) | 2 | 0 (0) | Total | 0 (0) | Scan pattern 2² (N=43) | | 0 | 1 (2) | 1 | 3 (7) | 2 | 1 (2) | Total | 5 (12) | SPECTRALIS Score¹ | | | | Response Rate (%)³
-------------|---------|----------|----------|--------------------------------|
| 1 | 2 | Total | |
| | | | |
| | | | 95.6 (87.6, 99.1) |
| 0 (0) | 0 (0) | 0 (0) | |
| 12 (18) | 2 (3) | 14 (21) | |
| 3 (4) | 51 (75) | 54 (79) | |
| 15 (22) | 53 (78) | 68 | |
| | | | 85.3 (75.3, 92.4) |
| 0 (0) | 0 (0) | 1 (1) | |
| 14 (19) | 11 (15) | 28 (37) | |
| 7 (9) | 38 (51) | 46 (61) | |
| 21 (28) | 49 (65) | 75 | |
| | | | |
| | | | 100.0 (89.1, 100.0) |
| 0 (0) | 0 (0) | 0 (0) | |
| 0 (0) | 0 (0) | 0 (0) | |
| 0 (0) | 32 (100) | 32 (100) | |
| 0 (0) | 32 (100) | 32 | |
| | | | 96.9 (83.8, 99.9) |
| 0 (0) | 0 (0) | 0 (0) | |
| 1 (3) | 3 (9) | 4 (13) | |
| 1 (3) | 27 (84) | 28 (88) | |
| 2 (6) | 30 (94) | 32 | |
| | | | |
| | | | 91.7 (77.5, 98.2) |
| 0 (0) | 0 (0) | 0 (0) | |
| 12 (33) | 2 (6) | 14 (39) | |
| 3 (8) | 19 (53) | 22 (61) | |
| 15 (42) | 21 (58) | 36 | |
| | | | 76.7 (61.4, 88.2) |
| 0 (0) | 0 (0) | 1 (2) | |
| 13 (30) | 8 (19) | 24 (56) | |
| 6 (14) | 11 (26) | 18 (42) | |
| 19 (44) | 19 (45) | 43 | |

Number of subjects with OCTA image quality scores from either device. The anatomical structure score for a poor quality OCTA image is assigned to 0.

1 Score: 0=Unable to be distinguished; 1=Difficult; 2=Easy

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

22

Image /page/22/Picture/0 description: The image contains 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".

TABLE 5: COMPARISON OF CONSENSUS VISUALIZATION OF LARGE VESSELS BETWEEN SPECTRALIS AND RTVUE

| RTVue Score1, n (%) | SPECTRALIS Score1 | | | Total | Response Rate (%)3
(95% CI) |
|------------------------------------|-------------------|-------|----------|----------|--------------------------------|
| All Subjects | | | | | |
| Scan pattern 12 (N=79) | | | | | 97.5 (91.2, 99.7) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 1 (1) | 0 (0) | 1 (1) | |
| 2 | 0 (0) | 2 (3) | 76 (96) | 78 (99) | |
| Total | 0 (0) | 3 (4) | 76 (96) | 79 | |
| Scan pattern 22 (N=79) | | | | | 97.5 (91.2, 99.7) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 1 (1) | 0 (0) | 0 (0) | 1 (1) | |
| 2 | 0 (0) | 1 (1) | 77 (97) | 78 (99) | |
| Total | 1 (1) | 1 (1) | 77 (97) | 79 | |
| 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) | |
| 2 | 0 (0) | 0 (0) | 32 (100) | 32 (100) | |
| Total | 0 (0) | 0 (0) | 32 (100) | 32 | |
| Scan pattern 22 (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) | |
| 2 | 0 (0) | 0 (0) | 32 (100) | 32 (100) | |
| Total | 0 (0) | 0 (0) | 32 (100) | 32 | |
| Vascular Pathology Subjects | | | | | |
| Scan pattern 12 (N=47) | | | | | 95.7 (85.5, 99.5) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 1 (2) | 0 (0) | 1 (2) | |
| 2 | 0 (0) | 2 (4) | 44 (94) | 46 (98) | |
| Total | 0 (0) | 3 (6) | 44 (94) | 47 | |
| Scan pattern 22 (N=47) | | | | | 95.7 (85.5, 99.5) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 1 (2) | 0 (0) | 0 (0) | 1 (2) | |
| 2 | 0 (0) | 1 (2) | 45 (96) | 46 (98) | |
| Total | 1 (2) | 1 (2) | 45 (96) | 47 | |

Number of subjects with OCTA image quality scores from either device. The anatomical structure score for a poor quality OCTA image is assigned to 0.

Score: 0=Unable to be distinguished; 1=Difficult; 2=Easy 1

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

23

Image /page/23/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".

TABLE 6: COMPARISON OF CONSENSUS VISUALIZATION OF SMALL VESSELS BETWEEN SPECTRALIS AND RTVUE

| RTVue Score1, n (%) | SPECTRALIS Score1 | | | Total | Response Rate (%)3
(95% CI) |
|-----------------------------|-------------------|---------|----------|----------|--------------------------------|
| All Subjects | | | | | |
| Scan pattern 12 (N=79) | | | | | 94.9 (87.5, 98.6) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 6 (8) | 3 (4) | 9 (11) | |
| 2 | 0 (0) | 4 (5) | 66 (84) | 70 (89) | |
| Total | 0 (0) | 10 (13) | 69 (87) | 79 | |
| Scan pattern 22 (N=79) | | | | | 88.6 (79.5, 94.7) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 1 (1) | 2 (3) | 4 (5) | 7 (9) | |
| 2 | 0 (0) | 8 (10) | 64 (81) | 72 (91) | |
| Total | 1 (1) | 10 (13) | 68 (86) | 79 | |
| 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) | |
| 2 | 0 (0) | 0 (0) | 32 (100) | 32 (100) | |
| Total | 0 (0) | 0 (0) | 32 (100) | 32 | |
| Scan pattern 22 (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) | |
| 2 | 0 (0) | 0 (0) | 32 (100) | 32 (100) | |
| Total | 0 (0) | 0 (0) | 32 (100) | 32 | |
| Vascular Pathology Subjects | | | | | |
| Scan pattern 12 (N=47) | | | | | 91.5 (79.6, 97.6) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 0 (0) | 6 (13) | 3 (6) | 9 (19) | |
| 2 | 0 (0) | 4 (9) | 34 (72) | 38 (81) | |
| Total | 0 (0) | 10 (21) | 37 (79) | 47 | |
| Scan pattern 22 (N=47) | | | | | 80.9 (66.7, 90.9) |
| 0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1 | 1 (2) | 2 (4) | 4 (9) | 7 (15) | |
| 2 | 0 (0) | 8 (17) | 32 (68) | 40 (85) | |
| Total | 1 (2) | 10 (21) | 36 (77) | 47 | |

Number of subjects with OCTA image quality scores from either device. The anatomical structure score for a poor quality OCTA image is assigned to 0.

Score: 0=Unable to be distinguished; 1=Difficult; 2=Easy 1

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

24

Image /page/24/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 end. The top line reads "HEIDELBERG" and the bottom line reads "ENGINEERING".

TABLE 7: COMPARISON OF CONSENSUS VISUALIZATION OF END CAPILLARIES BETWEEN SPECTRALIS AND RTVUE

		SPECTRALIS Score¹	Response Rate (%)³
RTVue Score¹, n (%)	0	1	2	Total	(95% CI)
All Subjects
Scan pattern 1² (N=79)					89.9 (81.0, 95.5)
0	0 (0)	0 (0)	0 (0)	0 (0)
1	1 (1)	19 (24)	5 (6)	25 (32)
2	0 (0)	7 (9)	47 (59)	54 (68)
Total	1 (1)	26 (33)	52 (66)	79
Scan pattern 2² (N=79)					92.4 (84.2, 97.2)
0	1 (1)	0 (0)	0 (0)	1 (1)
1	0 (0)	26 (33)	22 (28)	48 (61)
2	0 (0)	6 (8)	24 (30)	30 (38)
Total	1 (1)	32 (41)	46 (58)	79
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)
2	0 (0)	0 (0)	32 (100)	32 (100)
Total	0 (0)	0 (0)	32 (100)	32
Scan pattern 2² (N=32)					90.6 (75.0, 98.0)
0	0 (0)	0 (0)	0 (0)	0 (0)
1	0 (0)	0 (0)	11 (34)	11 (34)
2	0 (0)	3 (9)	18 (56)	21 (66)
Total	0 (0)	3 (9)	29 (91)	32
Vascular Pathology Subjects
Scan pattern 1² (N=47)					83.0 (69.2, 92.4)
0	0 (0)	0 (0)	0 (0)	0 (0)
1	1 (2)	19 (40)	5 (11)	25 (53)
2	0 (0)	7 (15)	15 (32)	22 (47)
Total	1 (2)	26 (55)	20 (43)	47
Scan pattern 2² (N=47)					93.6 (82.5, 98.7)
0	1 (2)	0 (0)	0 (0)	1 (2)
1	0 (0)	26 (55)	11 (23)	37 (79)
2	0 (0)	3 (6)	6 (13)	9 (19)
Total	1 (2)	29 (62)	17 (36)	47

Number of subjects with OCTA image quality scores from either device. The anatomical structure score for a poor quality OCTA image is assigned to 0.

Score: 0=Unable to be distinguished; 1=Difficult; 2=Easy 1

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

25

The agreement in identification of vascular pathology and the PPOI between SPECTRALIS OCTA images and RTVue OCTA images is summarized in Table 8 through Table 13.

SPECTRALIS	RTVue 3mm x 3mm			SPECTRALIS	RTVue 6mm x 6mm
10° x 10°	Match1	Not Match2	Total	20° x 20°	Match1	Not Match2	Total
All Subjects
Match1	71 (90)	1 (1)	72 (91)	Match1	71 (90)	3 (4)	74 (94)
Not Match2	0 (0)	7 (9)	7 (9)	Not Match2	1 (1)	4 (5)	5 (6)
Total	71 (90)	8 (10)	79	Total	72 (91)	7 (9)	79
PoA (95% CI)3	98.7 (93.1, 100.0)			PoA (95% CI)3	94.9 (87.5, 98.6)
Ratio (95% CI)4	1.014 (0.987,
1.042)			Ratio (95% CI)4	1.028 (0.974,
1.084)
Normal Subjects
Match1	29 (91)	0 (0)	29 (91)	Match1	29 (91)	1 (3)	30 (94)
Not Match2	0 (0)	3 (9)	3 (9)	Not Match2	0 (0)	2 (6)	2 (6)
Total	29 (91)	3 (9)	32	Total	29 (91)	3 (9)	32
PoA (95% CI)3	100.0 (89.1, 100.0)			PoA (95% CI)3	96.9 (83.8, 99.9)
Ratio (95% CI)4	1.000 (1.000,
1.000)			Ratio (95% CI)4	1.034 (0.968,
1.106)
Vascular
Pathology
Subjects
Match1	42 (89)	1 (2)	43 (91)	Match1	42 (89)	2 (4)	44 (94)
Not Match2	0 (0)	4 (9)	4 (9)	Not Match2	1 (2)	2 (4)	3 (6)
Total	42 (89)	5 (11)	47	Total	43 (91)	4 (9)	47
PoA (95% CI)3	97.9 (88.7, 99.9)			PoA (95% CI)3	93.6 (82.5, 98.7)
Ratio (95% CI)4	1.024 (0.978,
1.072)			Ratio (95% CI)4	1.023 (0.946,
1.106)

TABLE 8: AGREEMENT IN CONSENSUS IDENTIFICATION OF MICROANEURYSMS BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF FA/ICGA

1 Between the FA/ICGA image and the OCTA image from a device, the pathology is present in both images or is absent from both images.

Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from വ the other image, or at least one image is ungradable.

PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method. ന

Ratio of the percentages of matching with FA/ICGA (SPECTRALIS to RTVue). 95% confidence interval is estimated by a 4 log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

26

TABLE 9: AGREEMENT IN CONSENSUS IDENTIFICATION OF RETINAL VASCULAR TORTUOSITY BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF FA/ICGA

SPECTRALIS		RTVue 3mm x 3mm		SPECTRALIS	RTVue 6mm x 6mm
10° x 10°	Match¹	Not
Match²	Total	20° x 20°	Match¹		Total
All Subjects
Match¹	66 (84)	4 (5)	70 (89)	Match¹	72 (91)	1 (1)	73 (92)
Not Match²	0 (0)	9 (11)	9 (11)	Not Match²	1 (1)	5 (6)	6 (8)
Total	66 (84)	13 (16)	79	Total	73 (92)	6 (8)	79
PoA (95% CI)³	94.9 (87.5, 98.6)			PoA (95% CI)³	97.5 (91.2, 99.7)			Ratio (95% CI)⁴	1.061 (1.001,
1.124)			Ratio (95% CI)⁴	1.000 (0.963,
1.039)			Normal Subjects								Match¹	31 (97)	1 (3)	32 (100)	Match¹	32 (100)	0 (0)	32 (100)	Not Match²	0 (0)	0 (0)	0 (0)	Not Match²	0 (0)	0 (0)	0 (0)	Total	31 (97)	1 (3)	32	Total	32 (100)	0 (0)	32	PoA (95% CI)³	96.9 (83.8, 99.9)		PoA (95% CI)³	100.0 (89.1, 100.0)		Ratio (95% CI)⁴	1.032 (NE)	Ratio (95% CI)⁴	1.000 (NE)	Vascular
Pathology
Subjects								Match¹	35 (74)	3 (6)	38 (81)	Match¹	40 (85)	1 (2)	41 (87)	Not Match²	0 (0)	9 (19)	9 (19)	Not Match²	1 (2)	5 (11)	6 (13)	Total	35 (74)	12 (26)	47	Total	41 (87)	6 (13)	47	PoA (95% CI)³	93.6 (82.5, 98.7)			PoA (95% CI)³	95.7 (85.5, 99.5)		Ratio (95% CI)⁴	1.086 (0.989,
1.192)			Ratio (95% CI)⁴	1.000 (0.935,
1.070)
PoA (95% CI)³	94.9 (87.5, 98.6)			PoA (95% CI)³	97.5 (91.2, 99.7)
Ratio (95% CI)⁴	1.061 (1.001,
1.124)			Ratio (95% CI)⁴	1.000 (0.963,
1.039)
Normal Subjects
Match¹	31 (97)	1 (3)	32 (100)	Match¹	32 (100)	0 (0)	32 (100)
Not Match²	0 (0)	0 (0)	0 (0)	Not Match²	0 (0)	0 (0)	0 (0)
Total	31 (97)	1 (3)	32	Total	32 (100)	0 (0)	32
PoA (95% CI)³	96.9 (83.8, 99.9)			PoA (95% CI)³	100.0 (89.1, 100.0)
Ratio (95% CI)⁴	1.032 (NE)			Ratio (95% CI)⁴	1.000 (NE)
Vascular
Pathology
Subjects
Match¹	35 (74)	3 (6)	38 (81)	Match¹	40 (85)	1 (2)	41 (87)
Not Match²	0 (0)	9 (19)	9 (19)	Not Match²	1 (2)	5 (11)	6 (13)
Total	35 (74)	12 (26)	47	Total	41 (87)	6 (13)	47
PoA (95% CI)³	93.6 (82.5, 98.7)			PoA (95% CI)³	95.7 (85.5, 99.5)
Ratio (95% CI)⁴	1.086 (0.989,
1.192)			Ratio (95% CI)⁴	1.000 (0.935,
1.070)

1 Between the FA/CGA image and the OCTA image from a device, the pathology is present in both images or is absent from both images.

ଠ Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from the other image, or at least one image is ungradable.

3 PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method.

4 Ratio of the percentages of matching with FA/CGA (SPECTRALIS to RTVue). 95% confidence interval is estimated by a log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

27

Image /page/27/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.

TABLE 10: AGREEMENT IN CONSENSUS IDENTIFICATION OF CHOROIDAL NEOVASCULARIZATION BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF FA/ICGA

SPECTRALIS	RTVue 3mm x 3mm			SPECTRALIS	RTVue 6mm x 6mm
		Not
Match2				Not
Match2
10° x 10°	Match1		Total	20° x 20°	Match1		Total
All Subjects
Match1	71 (90)	3 (4)	74 (94)	Match1	72 (91)	0 (0)	72 (91)
Not Match2	0 (0)	5 (6)	5 (6)	Not Match2	1 (1)	6 (8)	7 (9)
Total	71 (90)	8 (10)	79	Total	73 (92)	6 (8)	79
PoA (95% CI)3	96.2 (89.3, 99.2)			PoA (95% CI)3	98.7 (93.1, 100.0)
Ratio (95% CI)4	1.042 (0.995,
1.092)			Ratio (95% CI)4	0.986 (0.960,
1.013)
Normal Subjects
Match1	32 (100)	0 (0)	32 (100)	Match1	32 (100)	0 (0)	32 (100)
Not Match2	0 (0)	0 (0)	0 (0)	Not Match2	0 (0)	0 (0)	0 (0)
Total	32 (100)	0 (0)	32	Total	32 (100)	0 (0)	32
PoA (95% CI)3	100.0 (89.1, 100.0)			PoA (95% CI)3	100.0 (89.1, 100.0)
Ratio (95% CI)4	1.000 (NE)			Ratio (95% CI)4	1.000 (NE)
Vascular
Pathology
Subjects
Match1	39 (83)	3 (6)	42 (89)	Match1	40 (85)	0 (0)	40 (85)
Not Match2	0 (0)	5 (11)	5 (11)	Not Match2	1 (2)	6 (13)	7 (15)
Total	39 (83)	8 (17)	47	Total	41 (87)	6 (13)	47
PoA (95% CI)3	93.6 (82.5, 98.7)			PoA (95% CI)3	97.9 (88.7, 99.9)
Ratio (95% CI)4	1.077 (0.990,
1.171)			Ratio (95% CI)4	0.976 (0.930,
1.024)

1 Between the FA/ICGA image and the OCTA image from a device, the pathology is present in both images or is absent from both images.

ଥ Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from the other image, or at least one image is ungradable.

ന PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method.

Ratio of the percentages of matching with FA/ICGA (SPECTRALIS to RTVue). 95% confidence interval is estimated by a 4 log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

28

TABLE 11: AGREEMENT IN CONSENSUS IDENTIFICATION OF RETINAL ISCHEMIA BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF FA/ICGA

| SPECTRALIS
10° x 10° | RTVue 3mm x 3mm | | | SPECTRALIS
20° x 20° | RTVue 6mm x 6mm | | |
|-----------------------------------|----------------------|------------|----------|-----------------------------------|----------------------|------------|----------|
| | Match1 | Not Match2 | Total | | Match1 | Not Match2 | Total |
| All Subjects | 62 (78) | 4 (5) | 66 (84) | All Subjects | 65 (82) | 3 (4) | 68 (86) |
| Not Match2 | 3 (4) | 10 (13) | 13 (16) | Not Match2 | 1 (1) | 10 (13) | 11 (14) |
| Total | 65 (82) | 14 (18) | 79 | Total | 66 (84) | 13 (16) | 79 |
| PoA (95% CI)3 | 91.1 (82.6, 96.4) | | | PoA (95% CI)3 | 94.9 (87.5, 98.6) | | |
| Ratio (95% CI)4 | 1.015 (0.938, 1.099) | | | Ratio (95% CI)4 | 1.030 (0.972, 1.092) | | |
| Normal Subjects | | | | Normal Subjects | | | |
| Match1 | 32 (100) | 0 (0) | 32 (100) | Match1 | 32 (100) | 0 (0) | 32 (100) |
| Not Match2 | 0 (0) | 0 (0) | 0 (0) | Not Match2 | 0 (0) | 0 (0) | 0 (0) |
| Total | 32 (100) | 0 (0) | 32 | Total | 32 (100) | 0 (0) | 32 |
| PoA (95% CI)3 | 100.0 (89.1, 100.0) | | | PoA (95% CI)3 | 100.0 (89.1, 100.0) | | |
| Ratio (95% CI)4 | 1.000 (NE) | | | Ratio (95% CI)4 | 1.000 (NE) | | |
| Vascular
Pathology
Subjects | | | | Vascular
Pathology
Subjects | | | |
| Match1 | 30 (64) | 4 (9) | 34 (72) | Match1 | 33 (70) | 3 (6) | 36 (77) |
| Not Match2 | 3 (6) | 10 (21) | 13 (28) | Not Match2 | 1 (2) | 10 (21) | 11 (23) |
| Total | 33 (70) | 14 (30) | 47 | Total | 34 (72) | 13 (28) | 47 |
| PoA (95% CI)3 | 85.1 (71.7, 93.8) | | | PoA (95% CI)3 | 91.5 (79.6, 97.6) | | |
| Ratio (95% CI)4 | 1.030 (0.883, 1.203) | | | Ratio (95% CI)4 | 1.059 (0.947, 1.184) | | |

1 Between the FA/CGA image and the OCTA image from a device, the pathology is present in both images or is absent from both images.

ଠ Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from the other image, or at least one image is ungradable.

3 PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method.

4 Ratio of the percentages of matching with FA/CGA (SPECTRALIS to RTVue). 95% confidence interval by a log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

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Image /page/29/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 top line reads "HEIDELBERG" and the bottom line reads "ENGINEERING". There is a red square to the left of the word "HEIDELBERG" and to the right of the word "ENGINEERING".

		TABLE 12: AGREEMENT IN CONSENSUS IDENTIFICATION OF RETINAL
NEOVASCULARIZATION BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF
		FA/ICGA

SPECTRALIS	RTVue 3mm x 3mm			SPECTRALIS	RTVue 6mm x 6mm
	Match1	Not
Match2	Total		Match1	Not
Match2	Total
10° x 10°				20° x 20°
All Subjects
Match1	77 (97)	0 (0)	77 (97)	Match1	75 (95)	0 (0)	75 (95)
Not Match2	0 (0)	2 (3)	2 (3)	Not Match2	1 (1)	3 (4)	4 (5)
Total	77 (97)	2 (3)	79	Total	76 (96)	3 (4)	79
PoA (95% CI)3	100.0 (95.4, 100.0)			PoA (95% CI)3	98.7 (93.1, 100.0)
Ratio (95% CI)4	1.000 (1.000,
1.000)			Ratio (95% CI)4	0.987 (0.962,
1.013)
Normal Subjects
Match1	32 (100)	0 (0)	32 (100)	Match1	32 (100)	0 (0)	32 (100)
Not Match2	0 (0)	0 (0)	0 (0)	Not Match2	0 (0)	0 (0)	0 (0)
Total	32 (100)	0 (0)	32	Total	32 (100)	0 (0)	32
PoA (95% CI)3	100.0 (89.1, 100.0)			PoA (95% CI)3	100.0 (89.1, 100.0)
Ratio (95% CI)4	1.000 (NE)			Ratio (95% CI)4	1.000 (NE)
Vascular
Pathology
Subjects
Match1	45 (96)	0 (0)	45 (96)	Match1	43 (91)	0 (0)	43 (91)
Not Match2	0 (0)	2 (4)	2 (4)	Not Match2	1 (2)	3 (6)	4 (9)
Total	45 (96)	2 (4)	47	Total	44 (94)	3 (6)	47
PoA (95% CI)3	100.0 (92.5, 100.0)			PoA (95% CI)3	97.9 (88.7, 99.9)
Ratio (95% CI)4	1.000 (1.000,
1.000)			Ratio (95% CI)4	0.977 (0.934,
1.022)

Between the FA/CGA image and the OCTA image from a device, the pathology is present in both images or is absent from 1 both images.

2 Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from the other image, or at least one image is ungradable.

3 PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method.

4 Ratio of the percentages of matching with FA/CGA (SPECTRALIS to RTVue). 95% confidence interval is estimated by a log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

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TABLE 13: AGREEMENT IN CONSENSUS IDENTIFICATION OF PRIMARY PATHOLOGY OF INTEREST (PPOI) BETWEEN SPECTRALIS AND RTVUE USING BOXED AREA OF FA/ICGA

SPECTRALIS	RTVue 3mm x 3mm			SPECTRALIS	RTVue 6mm x 6mm
10° x 10°	Match¹	Not
Match²	Total	20° x 20°	Match¹	Not
Match²	Total
All Subjects
Match¹	65 (82)	3 (4)	68 (86)	Match¹	64 (81)	4 (5)	68 (86)
Not Match²	0 (0)	11 (14)	11 (14)	Not Match²	1 (1)	10 (13)	11 (14)
Total	65 (82)	14 (18)	79	Total	65 (82)	14 (18)	79
PoA (95% CI)³	96.2 (89.3, 99.2)			PoA (95% CI)³	93.7 (85.8, 97.9)
Ratio (95% CI)⁴	1.046 (0.994,
1.101)			Ratio (95% CI)⁴	1.046 (0.979,
1.117)
Normal Subjects
Match¹	29 (91)	0 (0)	29 (91)	Match¹	29 (91)	1 (3)	30 (94)
Not Match²	0 (0)	3 (9)	3 (9)	Not Match²	0 (0)	2 (6)	2 (6)
Total	29 (91)	3 (9)	32	Total	29 (91)	3 (9)	32
PoA (95% CI)³	100.0 (89.1, 100.0)			PoA (95% CI)³	96.9 (83.8, 99.9)
Ratio (95% CI)⁴	1.000 (1.000,
1.000)			Ratio (95% CI)⁴	1.034 (0.968,
1.106)
Vascular
Pathology
Subjects
Match¹	36 (77)	3 (6)	39 (83)	Match¹	35 (74)	3 (6)	38 (81)
Not Match²	0 (0)	8 (17)	8 (17)	Not Match²	1 (2)	8 (17)	9 (19)
Total	36 (77)	11 (23)	47	Total	36 (77)	11 (23)	47
PoA (95% CI)³	93.6 (82.5, 98.7)			PoA (95% CI)³	91.5 (79.6, 97.6)
Ratio (95% CI)⁴	1.083 (0.989,
1.186)			Ratio (95% CI)⁴	1.056 (0.949,
1.174)

Between the FA/ICGA image and the OCTA image from a device, the pathology is present in both images or is absent from 1 both images.

2 Between the FA/ICGA image and the OCTA image from a device, the pathology is present in one image and is absent from the other image, or at least one image is ungradable.

3 PoA = Percent of agreement between SPECTRALIS and RTVue. 95% confidence interval is calculated by exact method.

4 Ratio of the percentages of matching with FA/ICGA (SPECTRALIS to RTVue). 95% confidence interval is estimated by a log-linear regression with device as a single covariate using generalized estimating equation. NE = Not evaluable

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Image /page/31/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 says "HEIDELBERG" and the second line says "ENGINEERING."

Total inter-grader agreement frequencies are summarized in Table 14 through Table 19 and range from 94-100% in the "Normal" sub-group and 87-98% in the "Pathology" sub-group.

	SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	31 (97)	44 (94)	75 (95)	31 (97)	42 (89)	73 (92)
95% CI2	83.8,
99.9	82.5, 98.7	87.5,
98.6	83.8,
99.9	76.9, 96.5	84.2,
97.2
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	41 (87)	73 (92)	32 (100)	42 (89)	74 (94)
95% CI2	89.1,
100.0	74.3, 95.2	84.2,
97.2	89.1,
100.0	76.9, 96.5	85.8,
97.9

TABLE 14: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF MICROANEURYSMS

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

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	SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)		Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	43 (91)	75 (95)	31 (97)	44 (94)	75 (95)
95% CI2	89.1,
100.0	79.6, 97.6	87.5,
98.6		83.8,
99.9	82.5, 98.7	87.5,
98.6
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	44 (94)	76 (96)	32 (100)	46 (98)	78 (99)
95% CI2	89.1,
100.0	82.5, 98.7	89.3,
99.2		89.1,
100.0	88.7, 99.9	93.1,
100.0

TABLE 15: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF RETINAL VASCULAR TORTUOSITY

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

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		SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	44 (94)	76 (96)	32 (100)	45 (96)	77 (97)
95% CI2	89.1,
100.0	82.5, 98.7	89.3,
99.2	89.1,
100.0	85.5, 99.5	91.2,
99.7
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	46 (98)	78 (99)	32 (100)	46 (98)	78 (99)
95% CI2	89.1,
100.0	88.7, 99.9	93.1,
100.0	89.1,
100.0	88.7, 99.9	93.1,
100.0

TABLE 16: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF CHOROIDAL NEOVASCULARIZATION

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

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		SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	45 (96)	77 (97)	30 (94)	44 (94)	74 (94)
95% CI2	89.1,
100.0	85.5, 99.5	91.2,
99.7	79.2,
99.2	82.5, 98.7	85.8,
97.9
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	43 (91)	75 (95)	32 (100)	44 (94)	76 (96)
95% CI2	89.1,
100.0	79.6, 97.6	87.5,
98.6	89.1,
100.0	82.5, 98.7	89.3,
99.2

TABLE 17: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF RETINAL ISCHEMIA

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

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		SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	46 (98)	78 (99)	32 (100)	46 (98)	78 (99)
95% CI2	89.1,
100.0	88.7, 99.9	93.1,
100.0	89.1,
100.0	88.7, 99.9	93.1,
100.0
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	45 (96)	77 (97)	32 (100)	46 (98)	78 (99)
95% CI2	89.1,
100.0	85.5, 99.5	91.2,
99.7	89.1,
100.0	88.7, 99.9	93.1,
100.0

TABLE 18: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF RETINAL NEOVASCULARIZATION

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

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	SPECTRALIS			RTVue
	Normal
(N=32)	Pathology
(N=47)	Total
(N=79)		Normal
(N=32)	Pathology
(N=47)	Total
(N=79)
Scan pattern 11
Number of subjects	32	47	79	32	47	79
Total Agreement	31 (97)	44 (94)	75 (95)	30 (94)	41 (87)	71 (90)
95% CI2	83.8,
99.9	82.5, 98.7	87.5,
98.6		79.2,
99.2	74.3, 95.2	81.0,
95.5
Scan pattern 21
Number of subjects	32	47	79	32	47	79
Total Agreement	32 (100)	43 (91)	75 (95)	32 (100)	42 (89)	74 (94)
95% CI2	89.1,
100.0	79.6, 97.6	87.5,
98.6		89.1,
100.0	76.9, 96.5	85.8,
97.9

TABLE 19: INTER-GRADER AGREEMENT IN OCTA IDENTIFICATION OF PRIMARY PATHOLOGY OF INTEREST (PPOI)

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

2 95% confidence interval is calculated by exact method.

There were two adverse events that occurred during the course of the study. Both of the adverse events were directly associated with the fluorescein angiography imaging. Neither of these two events was considered related to the study devices. There were no adverse events related to the OCTA devices.

The results of this case series study demonstrate that the SPECTRALIS HRA+OCT generates OCTA images of similar quality as those of the RTVue XR and that these images can allow for visualization of key anatomical vascular structures and vascular pathologies of the retina and choroid.

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CONCLUSION

Comparison of technological characteristics and evaluation of non-clinical and clinical performance testing show that the modifications to the SPECTRALIS HRA+OCT and variants with OCT Angiography Module do not introduce any new potential safety risk and the device is as safe and effective as the predicate devices, therefore supporting a determination of substantial equivalence.