· 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 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.

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

AI/ML Overview

The provided document details the 510(k) submission for the SPECTRALIS HRA+OCT and variants with OCT Angiography Module (K181594). The primary predicate device for the OCT Angiography module is the RTVue XR OCT Avanti with AngioVue™ Software (K153080).

Here's a breakdown of the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance

The acceptance criteria are not explicitly stated in numerical thresholds in the provided document. Instead, the study aims to demonstrate comparable performance to the predicate device (RTVue XR) in terms of image quality and agreement in identifying vascular pathologies. The reported device performance is presented in various tables comparing the SPECTRALIS with the RTVue XR.

Below is a summary table aggregating some of the reported performance metrics that serve as de facto acceptance criteria based on the comparison to the predicate.

Acceptance Criteria (Implicit - Comparison to RTVue XR)	Reported Device Performance (SPECTRALIS HRA+OCT)
Image Quality (Score ≥ 1, Average or Good)
Percentage of eyes with SPECTRALIS image quality score ≥ RTVue XR (Normal Subjects, Scan Pattern 1)	75.0% (95% CI: 56.6, 88.5)
Percentage of eyes with SPECTRALIS image quality score ≥ RTVue XR (Normal Subjects, Scan Pattern 2)	71.9% (95% CI: 53.3, 86.3)
Percentage of eyes with SPECTRALIS image quality score ≥ RTVue XR (Pathology Subjects, Scan Pattern 1)	93.6% (95% CI: 82.5, 98.7)
Percentage of eyes with SPECTRALIS image quality score ≥ RTVue XR (Pathology Subjects, Scan Pattern 2)	89.4% (95% CI: 76.9, 96.5)
Anatomical Structure Visualization (Score ≥ RTVue XR)
Foveal Avascular Zone (FAZ) visualization (All Subjects, Scan Pattern 1)	95.6% (95% CI: 87.6, 99.1)
Large Vessels (LV) visualization (All Subjects, Scan Pattern 1)	97.5% (95% CI: 91.2, 99.7)
Small Vessels (SV) visualization (All Subjects, Scan Pattern 1)	94.9% (95% CI: 87.5, 98.6)
End Capillaries (EC) visualization (All Subjects, Scan Pattern 1)	89.9% (95% CI: 81.0, 95.5)
Agreement in Vascular Pathology Identification (SPECTRALIS vs. RTVue XR)
Agreement in Microaneurysms identification (All Subjects, Scan Pattern 1)	98.7% (95% CI: 93.1, 100.0)
Agreement in Retinal Vascular Tortuosity identification (All Subjects, Scan Pattern 1)	94.9% (95% CI: 87.5, 98.6)
Agreement in Choroidal Neovascularization identification (All Subjects, Scan Pattern 1)	96.2% (95% CI: 89.3, 99.2)
Agreement in Retinal Ischemia identification (All Subjects, Scan Pattern 1)	91.1% (95% CI: 82.6, 96.4)
Agreement in Retinal Neovascularization identification (All Subjects, Scan Pattern 1)	100.0% (95% CI: 95.4, 100.0)
Agreement in Primary Pathology of Interest (PPOI) identification (All Subjects, Scan Pattern 1)	96.2% (95% CI: 89.3, 99.2)

Note: Scan Pattern 1 refers to SPECTRALIS 10° x 10° and RTVue 3mm x 3mm; Scan Pattern 2 refers to SPECTRALIS 20° x 20° and RTVue 6mm x 6mm.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

Sample Size: A total of 95 participants were enrolled, with 37 in the "Normal" group and 58 in the "Pathology" group. Of these, 79 participants (32 "Normal" and 47 "Pathology") completed the study and were included in the primary analyses.
Data Provenance: The study was conducted at a single clinical site in the United States. It was a prospective, case series study.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

The ground truth for the test set was established by three qualified, masked graders for OCTA image grading and another three qualified, masked graders for FA/ICGA grading. The document does not specify their exact qualifications (e.g., "radiologist with 10 years of experience"), only that they were "qualified."

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

The document mentions "consensus OCTA image quality score" and "consensus overall anatomical structure score," implying an adjudication method where graders reached a consensus. For image quality scoring, one table shows "total inter-grader agreement on image quality scoring (where the same image quality score was determined by all three graders)." This suggests that when all three agreed, that was the score. For cases where agreement was not total (e.g., "same score from 2 graders"), the document does not explicitly state the adjudication rule (e.g., majority rule or a tie-breaker). For agreement in identification of vascular pathology, the percentages are also based on "consensus identification."

Therefore, it appears a consensus method (likely implicitly 3/3 or majority for 2/x scenarios) was used for grading both image quality and pathology identification, with some tables explicitly reporting instances where all three graders agreed.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Yes, a comparative effectiveness study was done, comparing the SPECTRALIS device (with its new OCTA module) to a legally marketed predicate device, the RTVue XR. However, this was not an MRMC study comparing human readers with AI assistance versus without AI assistance.

Instead, this study compares the performance of two different medical imaging devices (SPECTRALIS OCTA vs. RTVue XR OCTA) in visualizing vascular structures and pathologies. The AI component, if any, is embedded within the OCTA module's acquisition and processing, but the study design is not to assess the improvement of human readers with AI assistance. It evaluates the device's ability to produce images comparable to an existing device and align with a clinical reference standard (FA/ICGA).

Therefore, no effect size for human reader improvement with AI assistance is provided as that was not the objective of this comparative study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The study does not describe a standalone algorithm-only performance evaluation. The data presented is based on the comparison of images generated by the SPECTRALIS OCTA module (which includes its proprietary algorithm for OCTA) with images from the predicate RTVue XR OCTA, and then these images were evaluated by human experts. The focus is on the device's output, not an autonomous diagnostic algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The primary ground truth for the test set was Fluorescein Angiography (FA) and Indocyanine Green Angiography (ICGA) images, which are considered a defined reference standard for visualizing retinal and choroidal vasculature. This was augmented by expert consensus (three qualified, masked graders) for evaluating image quality and ease of identifying vascular structures and pathologies on both OCTA devices, in comparison to the FA/ICGA reference.

8. The sample size for the training set

The document does not provide information on the sample size for the training set. The study described is a clinical performance study for device clearance, focusing on demonstrating substantial equivalence to a predicate device, not on the development or training of algorithms.

9. How the ground truth for the training set was established

Since no information on a training set is provided, how its ground truth was established is not detailed in this document. The study focuses on evaluating the performance of the already developed OCTA module in the SPECTRALIS device.

Summary

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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 (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

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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:

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 CoherenceOphthalmoscope, 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

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.

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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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

	PRIMARYPREDICATEK153080 RTVUEXR	PREDICATEDEVICE K172649SPECTRALISHRA+OCT	SUBJECT DEVICE	Discussion
Deviceclassificationname	Optical CoherenceTomographer(OCT)	Optical CoherenceTomographer(OCT)	Optical CoherenceTomographer(OCT)	Same
Technology	Spectral DomainOCT	Spectral DomainOCT	Spectral DomainOCT	Same
Images ofposteriorsegment ofeye	Yes	Yes, using standard,WFO/WFO2, orUWF objective lens	Yes, using standard,WFO/WFO2, orUWF objective lens	Same
Images ofanteriorsegment ofeye	Yes	With AnteriorSegment Module(K113129)	With AnteriorSegment Module(K113129)	Same
OCT imagingof theanterior andposteriorsegment	Anterior segment:with CAM (Corneaand Anterior Module)	Anterior segment:With AnteriorSegment Module(K113129)	Anterior segment:With AnteriorSegment Module(K113129)	Same
	Posterior Segment:Yes	Posterior Segment:Yes	Posterior Segment:Yes
OCTAngiography	AngioVue™Software	n/a	OCT AngiographyModule;30° OCT/OCTA fieldof view with standardobjective	Similar to theprimary predicate
ReferenceDatabases	Comparison of retina,retinal nerve fiberlayer, and optic diskmeasurements in thehuman eye to adatabase of knownnormal subjects.	RNFL thickness inreference database for12° circle scans(Caucasian only)(K101223)RNFL thickness inreference database forfixed diameter circlescans, and ONHparameters (BMO-MRW, BMO-MRA)reference database(K152205)	RNFL thickness inreference database for12° circle scans(Caucasian only)(K101223)RNFL thickness inreference database forfixed diameter circlescans, and ONHparameters (BMO-MRW, BMO-MRA)reference database(K152205)	Similar;SPECTRALIS doesnot include a RetinaRDB.

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Heidelberg Engineering GmbH

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

	PRIMARYPREDICATEK153080 RTVUEXR	PREDICATEDEVICE K172649SPECTRALISHRA+OCT	SUBJECT DEVICE	Discussion
Imagingmodes, lightssources andwavelengthof lightemitted	Live camera:• Near infraredreflectanceimages: LED, 735nm,	cSLO:• Near infraredreflectanceimages: diodelaser, 815 nm,• Blue lightreflectanceimages: diodelaser, 486 nm, oroptically pumpedsemiconductorlaser, 488 nm• Green lightreflectanceimages: diodelaser, 518 nm• Fluoresceinangiography:diode laser, 486nm, or opticallypumpedsemiconductorlaser, 488 nm• Indocyanine greenangiography:diode laser, 786nm	cSLO:• Near infraredreflectanceimages: diodelaser, 815 nm,• Blue lightreflectanceimages: diodelaser, 486 nm, oroptically pumpedsemiconductorlaser, 488 nm• Green lightreflectanceimages: diodelaser, 518 nm• Fluoresceinangiography:diode laser, 486nm, or opticallypumpedsemiconductorlaser, 488 nm• Indocyanine greenangiography:diode laser, 786nm	Comparable for OCTimaging;Different for fundusimaging:RTVue uses a livecamera for fundusimaging;SPECTRALIS uses acSLO system withseveral imagingmodes
	OCT:840 nm ± 10 nm	OCT:superluminescencediode, 840 nm to 920nm (weightedaverage 880 nm)	OCT:superluminescencediode, 840 nm to 920nm (weightedaverage 880 nm)
Amount oflightirradiated toretina(exposure)	Exposure Power atpupil: less than orequal to 750 μW(Laser Class I)	Low amount, doesnot exceed Class Ilaser accessibleemission limits	Low amount, doesnot exceed Class Ilaser accessibleemission limits	Same
Lateralopticalresolution(OCT)	15 μm	14 μm	14 μm	Comparable
Optical depthresolution(OCT)	5 μm	7 μm	7 μm	Comparable
	PRIMARYPREDICATEK153080 RTVUEXR	PREDICATEDEVICE K172649SPECTRALISHRA+OCT	SUBJECT DEVICE	Discussion
Fundusimaging fieldof view	32° (horizontal) x 22°(vertical)	SO (standardobjective):15° x 15° to 30° x30°	SO (standardobjective):15° x 15° to 30° x30°	Comparable
OCT axialimagingdepth	2 to 3 mm	1.9 mm	1.9 mm	RTVue has a slightlyhigher scanning depth
Lateral fieldof view(OCT)	2 to 12 mm(approximately 7° to40°)	10°-30°	10°-30°	RTVue has a higherrange for lateral fieldof view
Digital axialresolution(pixel sizeOCT)	3 µm	3.9 µm	3.9 µm	Comparable
Indicationsfor Use(OCTAngiographypart only)	The RTVue XR OCTAvanti withAngioVue Softwareis indicated as an aidin the visualization ofvascular structures ofthe retina andchoroid.	n/a	The SPECTRALISOCT AngiographyModule is indicatedas an aid in thevisualization ofvascular structures ofthe retina andchoroid.	Same Indications forUse for OCTAngiography.
OCTAacquisition	Motion-contrasttechnique	n/a	Motion-contrasttechnique	Same
OCTAalgorithm	Split-spectrumamplitude-decorrelationangiography(SSADA);2 repeats of each B-scan	n/a	Proprietary,probabilisticalgorithm;4-7 repeats of each B-scan	Same purpose(generation of OCTAflow images), butdifferentmathematicalapproach.
Maximum A-scan rate forOCT andOCTA	70 kHz	85 kHz (OCT only)	85 kHz	Comparable; subjectdevice has slightlyfaster acquisition rate
OCTAAnalysis	Visualization ofthree-dimensionalmicrovasculature	n/a	Visualization ofthree-dimensionalmicrovasculature	Same as primarypredicate.
	PRIMARYPREDICATEK153080 RTVUEXR	PREDICATEDEVICE K172649SPECTRALISHRA+OCT	SUBJECT DEVICE	Discussion
Predefinedslabs	Superficial (Plexus)Deep (Plexus)Outer RetinaChoroid Cap(Capillaries)	n/a	Full imageVitreoretinalInterfaceFull RetinaSuperficial VascularComplex (SVC)Nerve Fiber LayerVascular Plexus(NFLVP)Superficial VascularPlexus (SVP)Deep VascularComplex (DVC)IntermediateCapillary Plexus(ICP)Deep CapillaryPlexus (DCP)Avascular Complex(AC)Choriocapillaris (CC)Choroid	Comparable toprimary predicate;SPECTRALIS offersmore detailedpredefined slabs, butboth devices coverthe full retinal andchoroidal vasculaturenetworks

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 /firmware	PREDICATE DEVICEK172649Final version#	SUBJECT DEVICEK181594Final version#	Description of changes
SPECTRALISProduct Familysoftware	6.6	6.9	Addition of OCT Angiography
Software Level ofConcern (LOC)	Moderate	Moderate	Unchanged
Software & firmware changes
General ProductRequirements (GPR)	1.10	1.12	1. OCT Angiography2. New Glaucoma Overview Report
SPECTRALISSystem	1.10	1.12	1. OCTA image acquisition2. OCTA image review3. Hardware requirements updated for OCTAacquisition
Heidelberg EyeExplorer (HX)	1.9	1.10	1. Display of GTIN number in the software2. Performance improvements
Acquisition Module(AQM)	6.5	6.9	1. OCT Angiography Acquisition Mode / UIchanges2. OCT Angiography Processing3. Licensing Mechanism (Activation Codes)4. Memory Handling5. FLEX mount support (not available in theUSA)
Viewing Module(VWM)	6.6	6.9	1. New analysis tab: Display OCT Angio2. New analysis tab: OCT Angiography3. New licensing mechanism4. Scan planning tool support for OCTA5. Configuration of printouts6. New printouts: Glaucoma OverviewReport, 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);
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

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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(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
--	--	--	-------------------------------------------------------	--	--

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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(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)
2	0 (0)	0 (0)	32 (100)	32 (100)
Total	0 (0)	0 (0)	32 (100)	32
Scan pattern 2² (N=32)					96.9 (83.8, 99.9)
0	0 (0)	0 (0)	0 (0)	0 (0)
1	0 (0)	1 (3)	3 (9)	4 (13)
2	0 (0)	1 (3)	27 (84)	28 (88)
Total	0 (0)	2 (6)	30 (94)	32
Vascular Pathology Subjects
Scan pattern 1² (N=36)					91.7 (77.5, 98.2)
0	0 (0)	0 (0)	0 (0)	0 (0)
1	0 (0)	12 (33)	2 (6)	14 (39)
2	0 (0)	3 (8)	19 (53)	22 (61)
Total	0 (0)	15 (42)	21 (58)	36
Scan pattern 2² (N=43)					76.7 (61.4, 88.2)
0	1 (2)	0 (0)	0 (0)	1 (2)
1	3 (7)	13 (30)	8 (19)	24 (56)
2	1 (2)	6 (14)	11 (26)	18 (42)
Total	5 (12)	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

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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

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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

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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

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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)
VascularPathologySubjects
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

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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	NotMatch²	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)	VascularPathologySubjects	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)
VascularPathologySubjects
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

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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
		NotMatch2				NotMatch2
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)
VascularPathologySubjects
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.

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

SPECTRALIS10° x 10°	RTVue 3mm x 3mm			SPECTRALIS20° 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)
VascularPathologySubjects				VascularPathologySubjects
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	NotMatch2	Total		Match1	NotMatch2	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)
VascularPathologySubjects
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.

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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	NotMatch²	Total	20° x 20°	Match¹	NotMatch²	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)
VascularPathologySubjects
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