Anterion

K240924 · Heidelberg Engineering GmbH · OBO · Dec 13, 2024 · Ophthalmic

Device Facts

• Record ID: K240924
• Device Name: Anterion
• Applicant: Heidelberg Engineering GmbH
• Product Code: OBO · Ophthalmic
• Decision Date: Dec 13, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 886.1570
• Device Class: Class 2

Intended Use

The ANTERION is a non-contact ophthalmic imaging and analysis device for the eye. It is intended for visualization and measurement of the anterior segment and measurement of the axial length. The analysis covers: - Cornea Thickness - Anterior Segment o Anterior chamber width, depth, volume and angle parameters o Lens Thickness - Axial Length

Device Story

ANTERION is a non-contact ophthalmic imaging device using swept-source optical coherence tomography (SS-OCT) and an infrared (IR) camera. It captures cross-sectional OCT images and en-face IR images of the eye. The device consists of hardware (imager, base, motorized chin rest) and PC-based software (V.1.5) with four licensed apps: Imaging, Cornea, Cataract, and Metrics. Operators (clinicians/technicians) position the patient's eye using a joystick and chin rest. The software processes OCT signals to provide automated measurements of corneal thickness (including epithelial and stromal layers), anterior chamber parameters, lens thickness, and axial length. These measurements assist clinicians in cataract surgery planning and corneal geometry assessment. The device is used in clinical settings; output is viewed via a graphical user interface (VWM module) and integrated with a Medical Image Management and Processing System (MIMPS). The device provides objective biometric data to support clinical decision-making and patient monitoring.

Clinical Evidence

Prospective, randomized clinical study (Protocol B-2020-1) with 115 subjects (32 normal, 82 abnormal cornea). Compared ANTERION to Cirrus HD-OCT 5000. Primary endpoints: repeatability, reproducibility, and agreement of corneal epithelial thickness measurements. ANTERION repeatability SD ranged 0.59-1.59 µm; reproducibility SD ranged 0.59-1.81 µm. Agreement analysis showed ANTERION systematically measured slightly thicker values (mean difference 1.3-5.1 µm) than Cirrus. No adverse events reported.

Technological Characteristics

Swept-source OCT (1310 nm center wavelength) and IR camera. Axial resolution <10 µm; lateral resolution 30-45 µm. Scan patterns: line, volume, arc, radial. A-scan rate: 50,000 Hz. Connectivity: PC-based, requires integration with MIMPS (e.g., HEYEX 2/PACS). Software: V.1.5, modular app-based licensing. Biocompatibility: ISO 10993-1, -5, -10, -18. Electrical safety: IEC 60601-1:2020. Laser safety: IEC 60825-1:2007, ANSI Z80.36:2016.

Indications for Use

Indicated for visualization and measurement of the anterior segment and axial length in patients, including those with normal corneas and those with abnormal corneas (e.g., keratoconus, contact lens wearers, post-keratorefractive surgery, dry eye disease).

Regulatory Classification

Identification

An ophthalmoscope is an AC-powered or battery-powered device containing illumination and viewing optics intended to examine the media (cornea, aqueous, lens, and vitreous) and the retina of the eye.

Special Controls

*Classification.* Class II (special controls). The device, when it is an AC-powered opthalmoscope, a battery-powered opthalmoscope, or a hand-held ophthalmoscope replacement battery, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.

Predicate Devices

• ANTERION (K230897)

Reference Devices

• CIRRUS HD-OCT 5000 (K181534)

Submission Summary (Full Text)

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December 13, 2024

Heidelberg Engineering GmbH % Lena Sattler Consultant Orasi Consulting, LLC. 226 1st Street Bonita Springs, Florida 34134

Re: K240924

Trade/Device Name: Anterion Regulation Number: 21 CFR 886.1570 Regulation Name: Ophthalmoscope Regulatory Class: Class II Product Code: OBO Dated: April 4, 2024 Received: November 5, 2024

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 (the 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 available 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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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

### 2024.12.13 Alexander Beylin -S 12:23:06 -05'00'

for Elvin Ng Assistant Director DHT1A: Division of Ophthalmic Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT, and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

| Submission Number ( <i>if known</i> ) | |
|---------------------------------------|--|
|---------------------------------------|--|

### K240924

Device Name

### ANTERION

Indications for Use (Describe)

| The ANTERION is a non-contact ophthalmic imaging and analysis device for the eye. It is intended |
|--------------------------------------------------------------------------------------------------|
| for visualization and measurement of the anterior segment and measurement of the axial length. |

The analysis covers:

- · Cornea Thickness
- · Anterior Segment

o Anterior chamber width, depth, volume and angle parameters

- o Lens Thickness
- · Axial Length

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/4/Picture/0 description: The image shows the logo for Heidelberg Engineering. The logo consists of two lines of text, with a red square on either side. The first line says "HEIDELBERG" and the second line says "ENGINEERING".

# 510(K) SUMMARY

### Date Prepared

December 10, 2024

### SPONSOR/510(K) OWNER/ MANUFACTURER

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

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

# OFFICIAL CONTACT PERSON

Lena Sattler Orasi Consulting, LLC. 226 1st Street Bonita Springs, FL 34134 Telephone: [phone] Facsimile: [phone] E-mail: [e-mail]

### PROPRIETARY OR TRADE NAMES

### ANTERION

### CLASSIFICATION INFORMATION

| Regulation Number: | 21 CFR 886.1570 |
|-----------------------|--------------------------------------------------|
| Classification name: | Ophthalmoscope,<br>Tomography, Optical Coherence |
| Medical Specialty | Ophthalmic |
| Device Class: | II |
| Classification Panel: | Ophthalmic Device Panel |
| Product Code: | OBO |

# PREDICATE DEVICE

ANTERION (K230897), Heidelberg Engineering GmbH

### REFERENCE DEVICE

CIRRUS HD-OCT 5000 (K181534), Carl Zeiss Meditec Inc.

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Image /page/5/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 of text says "HEIDELBERG", and the second line of text says "ENGINEERING". The text is in a bold, sans-serif font.

# INDICATIONS FOR USE

The ANTERION is a non-contact ophthalmic imaging and analysis device for the eye. It is intended for visualization and measurement of the anterior segment and the measurement of the axial length.

The analysis covers:

- · Cornea Thickness
- · Anterior Segment
- o Anterior chamber width, depth, volume and angle parameters o Lens Thickness
- Axial Length

## GENERAL DEVICE DESCRIPTION

The ANTERION is a diagnostic imaging device for the eye. The technology is based on swept-source optical coherence tomography (SS-OCT) technology. The device itself has two basic component groups:

· ANTERION Hardware (Imager/Base) with integrated forehead/ chin rest: The hardware includes imaging hardware (e.g., laser, LEDs, optics, detectors, hardware for spatial encoding) as well as a touch screen.

• ANTERION Software (V.1.5) (PC): The ANTERION Software includes the main user interface. The software allows for device control, such as selection of examination(s) and imaging parameter(s). The ANTERION software provides an interface for a Medical Image Management and Processing System.

The ANTERION hardware is separated in three parts: the Base (bottom part), the Imager (top part), and the Head Rest (forehead/chin rest).

For examinations, the patient places his/her head in the forehead/chin rest. The Head Rest is mechanically and electronically connected to the Base and controlled via a joystick. Within its stand, a stepper motor with additional mechanic parts and a controller board are placed, allowing the operator to move the motorized chin rest up or down for optimally positioning the patients' eye. An external fixation light is mounted at the forehead rest.

The Base mainly contains the power supply and PC connection of the device. In the Imager, the components for scanning, signal generation, and signal processing are contained.

The operator directly accesses two software modules, which are named AQM (acquisition module) and VWM (viewing module). The AQM allows selecting between examinations. The VWM shows acquired images, parameters, and reports.

The ANTERION device contains two imaging modalities, a scanning optical coherence tomography (OCT) modality and an infrared (IR) camera. The OCT modality allows for cross-sectional imaging and biometry, while the IR camera allows

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for en-face imaging of a patient's eve.

The ANTERION device provides four separate software functionalities (Apps) to acquire various imaging and measurements of the anterior segment of the eye: (1) the Imaging App. (2) the Cornea App. (3) the Cataract App and (4) the Metrics App. The Cornea App provides tomographic data and measurements for the patient´s individual corneal geometry and corneal characteristics. The Cornea App provides tomographic data and parameters, such as corneal curvature and thickness. The Cataract App provides key measurements for cataract surgery planning, such as corneal thickness, anterior chamber depth and axial length. The Metrics App generates OCT images and scan parameters for the anterior chamber such as anterior chamber angle and volume. The four ANTERION Apps are locked/unlocked independently by a license mechanism for each App. The software implementation of these Apps is realized within the AQM and VWM.

The following modification has been applied to the device, subject of this 510(k):

- · Addition of the Epithelial Thickness Module (separate License in the Cornea App) with maps and parameters of the corneal epithelial and stromal thickness.
To function as intended, the ANTERION must be connected to a Medical Image Management and Processing system (MIMPS) with compatible interface. To date, HEYEX 2 / HEYEX PACS is the only available MIMPS with compatible interface.

## COMPARISON OF TECHNOLOGICAL CHARACTERISTICS BETWEEN THE SUBJECT AND THE PREDICATE DEVICE

The predicate ANTERION (K230897) and the subject ANTERION do not share identical technological characteristics. However, the differences in design are marginal and do not raise different questions of safety and effectiveness. The software of both devices, the predicate ANTERION (K230897) and the subject ANTERION, includes all available imaging functions (Imaging App, Cornea App, Cataract App, Metrics App) which are locked/ unlocked independently by a license mechanism for each App. The main difference between both devices is a software modification which provides measurements of the epithelial and stromal thickness in the Cornea App for the subject device. This change, i.e. the addition of the Epithelial Thickness Module, doesn't change the data acquisition process, the intended use/ indications for use or the used imaging technologies (OCT, IR camera) of ANTERION. Regarding the hardware, only maintenance changes regarding assembling processes were implemented for the subject device which have no impact on the technology and performance of the ANTERION.

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| | SUBJECT DEVICE<br>ANTERION | PREDICATE DEVICE<br>ANTERION(K230897) | Same, similar or<br>different |
|------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Intended use/<br>Indications for use | The ANTERION is a non-contact ophthalmic imaging and analysis device for the eye. It is intended for visualization and measurement of the anterior segment and the measurement of the axial length.<br>The analysis covers:<br>• Cornea thickness<br>• Anterior segment<br>o Anterior chamber width, depth, volume, and angle parameters<br>o Lens thickness<br>• Axial Length | The ANTERION is a non-contact ophthalmic imaging and analysis device for the eye. It is intended for visualization and measurement of the anterior segment and the measurement of the axial length.<br>The analysis covers:<br>• Cornea thickness<br>• Anterior segment<br>o Anterior chamber width, depth, volume, and angle parameters<br>o Lens thickness<br>• Axial Length | Same |
| Main Technology | Swept Source OCT<br>Technology | Swept Source OCT<br>Technology | Same |
| Supporting Technologies | Infrared Camera | Infrared Camera | Same |
| OCT center wave length | 1310 nm | 1310 nm | Same |
| OCT axial resolution | <10 µm (tissue) | <10 µm (tissue) | Same |
| OCT lateral resolution | 30 µm, 45 µm | 30 µm, 45 µm | Same |
| Scan length | 5 – 16.5 mm | 5 – 16.5 mm | Same |
| Number of A-Scans per B-Scan | 256; 512; 768; 1024 | 256; 512; 768; 1024 | Same |
| A-scan rate | 50,000 Hz | 50,000 Hz | Same |
| Number of B- Scans | 1-65 | 1-65 | Same |
| Scan Pattern | Line, Volume, Arc, Radial | Line, Volume, Arc, Radial | Same |
| Scan Center | Adjustable | Adjustable | Same |
| Tracking | Available | Available | Same |
| Number of averaged Scans | 1; 2; 4; 8 | 1; 2; 4; 8 | Same |
| IR camera image size (px) | 768 x 576 | 768 x 576 | Same |
| Software Functions | • Imaging App<br>• Cornea App<br>• Cataract App<br>• Metrics App | • Imaging App<br>• Cornea App<br>• Cataract App<br>• Metrics App | Same |
| Main Parameters of<br>Cornea App | Cornea App:<br>• Cornea Curvature<br>• Cornea Thickness<br>- Epithelial Thickness<br>- Stromal Thickness | Cornea App:<br>• Cornea Curvature<br>• Cornea Thickness | Similar,<br>additional<br>measurements in<br>the Cornea App |
| Scan types for corneal<br>thickness parameters | 65 B-Scans<br>(Cornea App) | 65 B-Scans<br>(Cornea App) | Same |
| Dilation of pupil required? | No | No | Same |
| Eye contact required? | No | No | Same |
| Fixation light | Internal, external | Internal, external | Same |
| Working position | Upright sitting position of the patient, using chin rest | Upright sitting position of the patient, using chin rest | Same |
| User Interface | Joystick for user to move and align device, device has GUI (Graphical user interface) for display and analysis of data | Joystick for user to move and align device, device has GUI (Graphical user interface) for display and analysis of data | Same |

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# NON-CLINICAL PERFORMANCE TESTING

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."

Documentation regarding cybersecurity was submitted as recommended by FDA's Guidance for Industry and FDA Staff, "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" and an overall risk assessment regarding security and safety of the device was conducted due to ISO 14971:2019.

Bench verification testing was conducted to demonstrate OCT spatial performance, device sensitivity, depth attenuation and performance of auxiliary functions. The device met all pre-determined acceptance criteria.

Tests for electrical safety (IEC 60601-1:2020) and electromagnetic compatibility (IEC 60601-1- 2:2020 and IEC TR 60601-4-2: 2016) were performed with ANTERION and passed the relevant requirements of the applied standards.

Laser safety testing for the light sources used in ANTERION was submitted in the previous ANTERION 510(k) K230897 and showed that the requirements according to FDA recognized standards IEC-60825- 1:2007 and ANSI Z80.36:2016 were fulfilled. The test results are still valid for the subject ANTERION.

Biocompatibility of the device was previously demonstrated by cytotoxicity testing, skin sensitization testing and chemical analysis according to ISO 10993-5:2009, ISO 10993-10:2021 and ISO 10993-18:2005, respectively, and supported by biocompatibility assessment according to 10993-1:2018. The test results remain valid for the subject ANTERION.

### CLINICAL PERFORMANCE TESTING

B-2020-1 was a prospective, randomized precision and agreement clinical study conducted at one diverse clinical site, located in the United States. In the study, the investigational ANTERION device (Cornea App with Epithelial Thickness Module) was compared with Cirrus HD-OCT 5000 with Anterior Segment Premier Module (K181534). For Protocol B-2020-1, eligible participants age 22 or older were assigned to one of two groups: eyes with normal cornea (Group A), eyes with abnormal cornea (Group B). Participants in the eyes with abnormal cornea population had at least one eye with at least one of the following: keratoconus, contact lens wearer, status postkeratorefractive surgery and/or dry eye disease. One eye of each study subject was enrolled. Eyes enrolled in the study that met all inclusion criteria and did not meet any exclusion criteria were assigned to the corresponding subject population and subgroup. Any enrolled subject that did not meet inclusion/exclusion criteria was screen failed. A baseline eye examination that

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included manifest refraction, slit-lamp biomicroscopy, assessment of bestcorrected visual acuity (BCVA), OSDI score, Keratograph, tonometry was performed to verify eligibility. One eye per participant was randomly selected as the study eye. Three ANTERION and three CIRRUS 5000 HD-OCT devices were used. These six instruments were paired with three operators to form three device-operator configurations. All participants were imaged repeatedly on all three configurations. Three replicates per acquisition type, per configuration were obtained from each participant. The order of imaging by configuration and device order within configuration were randomized. Image quality was assessed by the operator after each acquisition. Image quality assessment of CIRRUS images were performed consistent with the CIRRUS instructions for use. Repeatability and reproducibility of measurements were estimated using a two-way, random-effects analysis of variance (ANOVA) model. Agreement was characterized using Bland-Altman and Deming regression analyses.

The analysis population of this study included 115 subjects: thirty-two (32) in the Normal Cornea population and eighty-two (82) in the Abnormal Cornea population which include; twenty-five (25) in the Keratoconus subgroup, twenty (20) in the Contact Lens Wearer subgroup, eighteen (18) in the Status Post-Keratorefractive Surgery subgroup, and nineteen (19) in the Dry Eye Disease subgroup. One eye was not allocated to a group before screen failure. Data from 32 Group A participants and 81 Group B participants were included in the precision analyses, respectively. Data from 32 Group A and 80 Group B participants were included in the agreement analyses, respectively. The mean age in the safety population was 46.3 ± 15.7 years overall (mean 41.6±15.4 years in Group A, 48.2±15.5 years in Group B). 63.2% (72/114) were women (62.5% [20/32] Group A, 63.4% [52/82] Group B). 91.2% (104/114) were Caucasian (93.8% [30/32] in Group A, 90.2% [74/82] in Group B), 6.1% (7/114) were Black/African American (6.3% [2/32] Group A, 6.1% [5/82] Group B), 4.4% (5/114) were Asian (9.4% [3/32] Group A, 2.4% [2/82] Group B). 11.4% (13/114) were Hispanic/Latino (12.5% [4/32] Group A, 11.0% [9/82] Group B). Demographics are similar for the Precision Analysis Population and the Agreement Analysis Population. There were no adverse events related to this study.

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The following quantitative parameters were evaluated:

- Corneal Epithelial Thickness 0-2mm ring
- Average Thickness
- Corneal Epithelial Thickness 2-5mm ring
- Average Thickness .
- . Average Thickness Nasal Sector
- . Average Thickness Superior Sector
- Average Thickness SuperiorNasal Sector
- Average Thickness SuperiorTemporal Sector
- . Average Thickness Temporal Sector
- . Average Thickness InferiorTemporal Sector
- Average Thickness Inferior Sector
- . Average Thickness InferiorNasal Sector
- Corneal Epithelial Thickness 5-7mm ring
- Average Thickness ●
- Average Thickness Nasal Sector •
- . Average Thickness Superior Sector
- Average Thickness SuperiorNasal Sector
- . Average Thickness SuperiorTemporal Sector
- . Average Thickness Temporal Sector
- . Average Thickness InferiorTemporal Sector
- . Average Thickness InferiorSector
- . Average Thickness InferiorNasal Sector
- Minimum Thickness from 7mm zone [um]
- Maximum Thickness from 7mm zone [µm]
- Corneal Epithelial Average Thickness 2-4mm ring
- Corneal Epithelial Average Thickness 4-6mm ring
- Corneal Epithelial Average Thickness 6-7mm ring
- Corneal Epithelial Mean Average Thickness from 7mm zone [um]
- Corneal Epithelial Superior Thickness 2-7 mm
- Corneal Epithelial Inferior Thickness 2-7 mm

Rates of acquisition acceptability, as determined by the investigator/operator, were higher for ANTERION Cornea App acquisitions (83.0%) than Cirrus Pachymetry Scans (66.3%) for all eyes. These acceptance rates were similar between the Normal Cornea Eyes and Abnormal Cornea Eyes populations, for both devices.

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ANTERION precision results are presented in the tables below:

Table 1 below provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Normal Cornea Eyes Population.

Table 1 Repeatability and Reproducibility of ANTERION Precision Analysis Population of Normal Cornea Eyes

| Eye Population<br>Parameter (µm) | # of<br>Eyes | # of<br>Scans | Intercept | Repeatability | | | Reproducibility | | |
|----------------------------------|--------------|---------------|-----------|---------------|-------|------|-----------------|-------|------|
| | | | | SD | Limit | CV% | SD | Limit | CV% |
| Normal Cornea Eyes | | | | | | | | | |
| 0-2 mm Ring Average | 32 | 285 | 50.79 | 0.72 | 2.02 | 1.42 | 0.99 | 2.77 | 1.94 |
| 2-5 mm Ring Average | 32 | 285 | 50.00 | 0.59 | 1.66 | 1.18 | 0.86 | 2.42 | 1.73 |
| 2-5 mm Ring Nasal | 32 | 285 | 50.52 | 0.96 | 2.68 | 1.89 | 1.09 | 3.07 | 2.17 |
| 2-5 mm Ring Superior Nasal | 32 | 285 | 50.00 | 0.80 | 2.23 | 1.59 | 1.03 | 2.88 | 2.06 |
| 2-5 mm Ring Superior | 32 | 285 | 48.90 | 0.81 | 2.26 | 1.65 | 0.97 | 2.71 | 1.98 |
| 2-5 mm Ring Superior Temporal | 32 | 285 | 48.58 | 0.79 | 2.22 | 1.63 | 0.97 | 2.72 | 2.00 |
| 2-5 mm Ring Temporal | 32 | 285 | 48.93 | 0.75 | 2.10 | 1.53 | 0.97 | 2.73 | 1.99 |
| 2-5 mm Ring Inferior Temporal | 32 | 285 | 50.45 | 0.88 | 2.48 | 1.75 | 1.25 | 3.51 | 2.48 |
| 2-5 mm Ring Inferior | 32 | 285 | 51.42 | 0.76 | 2.13 | 1.48 | 1.06 | 2.96 | 2.05 |
| 2-5 mm Ring Inferior Nasal | 32 | 285 | 51.14 | 0.88 | 2.48 | 1.73 | 1.09 | 3.05 | 2.13 |
| 5-7 mm Ring Average | 32 | 285 | 49.95 | 0.60 | 1.68 | 1.20 | 0.80 | 2.25 | 1.61 |
| 5-7 mm Ring Nasal | 32 | 285 | 50.81 | 0.88 | 2.47 | 1.74 | 1.03 | 2.90 | 2.04 |
| 5-7 mm Ring Superior Nasal | 32 | 285 | 50.45 | 0.89 | 2.49 | 1.76 | 1.13 | 3.16 | 2.23 |
| 5-7 mm Ring Superior | 32 | 285 | 48.01 | 0.98 | 2.73 | 2.03 | 1.11 | 3.10 | 2.31 |
| 5-7 mm Ring Superior Temporal | 32 | 285 | 48.17 | 0.95 | 2.66 | 1.98 | 1.17 | 3.27 | 2.42 |
| 5-7 mm Ring Temporal | 32 | 285 | 48.91 | 0.95 | 2.67 | 1.95 | 1.10 | 3.08 | 2.25 |
| 5-7 mm Ring Inferior Temporal | 32 | 285 | 50.84 | 1.09 | 3.05 | 2.14 | 1.38 | 3.87 | 2.72 |
| 5-7 mm Ring Inferior | 32 | 285 | 51.25 | 0.95 | 2.66 | 1.85 | 1.18 | 3.31 | 2.31 |
| 5-7 mm Ring Inferior Nasal | 32 | 285 | 50.79 | 1.02 | 2.87 | 2.02 | 1.20 | 3.37 | 2.37 |
| 7 mm Zone Minimum | 32 | 285 | 42.24 | 1.73 | 4.84 | 4.09 | 1.78 | 4.98 | 4.21 |
| 7 mm Zone Maximum | 32 | 285 | 57.74 | 1.73 | 4.84 | 2.99 | 1.78 | 4.97 | 3.08 |
| 2-4 mm Ring Average | 32 | 285 | 49.96 | 0.63 | 1.77 | 1.27 | 0.86 | 2.42 | 1.73 |
| 4-6 mm Ring Average | 32 | 285 | 50.01 | 0.60 | 1.67 | 1.19 | 0.85 | 2.39 | 1.70 |
| 6-7 mm Ring Average | 32 | 283 | 49.87 | 0.67 | 1.88 | 1.34 | 0.87 | 2.43 | 1.74 |
| 7 mm Zone Average | 32 | 285 | 50.00 | 0.58 | 1.63 | 1.16 | 0.84 | 2.34 | 1.67 |
| 2-7 mm Ring Superior | 32 | 285 | 49.19 | 0.62 | 1.75 | 1.27 | 0.86 | 2.42 | 1.76 |
| 2-7 mm Ring Inferior | 32 | 285 | 50.72 | 0.66 | 1.85 | 1.31 | 0.90 | 2.53 | 1.78 |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator device pairs for a total of 9 scans for each study eye). In the study, 31 Normal Cornea population study eyes had 3 acceptable scans from each of the 3 operator'device pairs, and one study eye had 6 acceptable scans (one pair did not have any acceptable scans). Therefore, a total of 9 × 31 + 6 × 1 = 285 scans were included in the analysis for all parameters, except for 6-7 mm Ring Average which had missing values for two acceptable scans (i.e., 285 - 2 = 283).

Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance Repeatability limit = 2.8 × Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility CV% = (Reproducibility SD)/Intercept × 100%.

{12}------------------------------------------------

Table 2 below provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Abnormal Cornea Eyes Population.

Table 2 Repeatability and Reproducibility of ANTERION Precision Analysis Population of Abnormal Cornea Eyes

| Eye Population | # of | # of | | Repeatability | | | Reproducibility | | |
|-------------------------------|------|-------|-----------|---------------|-------|------|-----------------|-------|------|
| Parameter (µm) | Eyes | Scans | Intercept | SD | Limit | CV% | SD | Limit | CV% |
| Abnormal Cornea Eyes | | | | | | | | | |
| 0-2 mm Ring Average | 81 | 725 | 50.75 | 0.74 | 2.07 | 1.46 | 1.14 | 3.19 | 2.24 |
| 2-5 mm Ring Average | 81 | 725 | 50.64 | 0.68 | 1.90 | 1.34 | 0.99 | 2.77 | 1.96 |
| 2-5 mm Ring Nasal | 81 | 725 | 51.03 | 0.87 | 2.43 | 1.70 | 1.13 | 3.16 | 2.21 |
| 2-5 mm Ring Superior Nasal | 81 | 725 | 50.42 | 0.84 | 2.34 | 1.66 | 1.13 | 3.16 | 2.24 |
| 2-5 mm Ring Superior | 81 | 725 | 49.65 | 0.90 | 2.52 | 1.82 | 1.27 | 3.56 | 2.56 |
| 2-5 mm Ring Superior Temporal | 81 | 725 | 49.81 | 0.89 | 2.49 | 1.79 | 1.11 | 3.11 | 2.23 |
| 2-5 mm Ring Temporal | 81 | 725 | 49.82 | 0.92 | 2.59 | 1.85 | 1.16 | 3.23 | 2.32 |
| 2-5 mm Ring Inferior Temporal | 81 | 725 | 50.81 | 0.86 | 2.42 | 1.70 | 1.13 | 3.16 | 2.22 |
| 2-5 mm Ring Inferior | 81 | 725 | 51.74 | 0.91 | 2.54 | 1.75 | 1.28 | 3.57 | 2.47 |
| 2-5 mm Ring Inferior Nasal | 81 | 725 | 51.86 | 0.99 | 2.77 | 1.91 | 1.33 | 3.71 | 2.56 |
| 5-7 mm Ring Average | 81 | 725 | 50.40 | 0.72 | 2.02 | 1.43 | 0.95 | 2.66 | 1.89 |
| 5-7 mm Ring Nasal | 81 | 725 | 50.79 | 0.97 | 2.71 | 1.91 | 1.28 | 3.59 | 2.53 |
| 5-7 mm Ring Superior Nasal | 81 | 725 | 50.07 | 0.99 | 2.78 | 1.98 | 1.27 | 3.56 | 2.54 |
| 5-7 mm Ring Superior | 81 | 725 | 48.48 | 1.09 | 3.04 | 2.24 | 1.37 | 3.83 | 2.82 |
| 5-7 mm Ring Superior Temporal | 81 | 725 | 49.13 | 1.14 | 3.18 | 2.31 | 1.29 | 3.62 | 2.63 |
| 5-7 mm Ring Temporal | 81 | 725 | 50.04 | 0.99 | 2.78 | 1.98 | 1.19 | 3.33 | 2.37 |
| 5-7 mm Ring Inferior Temporal | 81 | 725 | 51.55 | 1.20 | 3.37 | 2.34 | 1.39 | 3.89 | 2.70 |
| 5-7 mm Ring Inferior | 81 | 725 | 51.61 | 1.19 | 3.33 | 2.31 | 1.40 | 3.92 | 2.71 |
| 5-7 mm Ring Inferior Nasal | 81 | 725 | 51.39 | 1.18 | 3.31 | 2.30 | 1.47 | 4.13 | 2.87 |
| 7 mm Zone Minimum | 81 | 725 | 39.98 | 1.72 | 4.81 | 4.30 | 1.82 | 5.10 | 4.56 |
| 7 mm Zone Maximum | 81 | 725 | 60.60 | 1.93 | 5.39 | 3.18 | 2.18 | 6.11 | 3.60 |
| 2-4 mm Ring Average | 81 | 725 | 50.50 | 0.69 | 1.92 | 1.36 | 1.00 | 2.81 | 1.99 |
| 4-6 mm Ring Average | 81 | 725 | 50.70 | 0.70 | 1.95 | 1.37 | 0.98 | 2.74 | 1.93 |
| 6-7 mm Ring Average | 81 | 716 | 50.20 | 0.76 | 2.13 | 1.51 | 0.97 | 2.72 | 1.94 |
| 7 mm Zone Average | 81 | 725 | 50.56 | 0.66 | 1.86 | 1.31 | 0.94 | 2.62 | 1.85 |
| 2-7 mm Ring Superior | 81 | 725 | 49.76 | 0.72 | 2.02 | 1.45 | 0.95 | 2.67 | 1.92 |
| 2-7 mm Ring Inferior | 81 | 725 | 51.26 | 0.75 | 2.09 | 1.46 | 1.02 | 2.85 | 1.99 |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator/device pairs for a total of 9 scans for each study eye). In the study, 79 Abnormal Cornea population study eyes (22 Keratoconus, 20 Contact Lens Wearer, 18 Post-Keratorefractive Surgery, and 19 Dry Eye Disease) had 3 acceptable scans from each of the 3 operator/device pairs; 1 Keratoconus eye had 6 acceptable scans (one operator/device pair did not have any acceptable scans), and 1 Keratoconus eye had 8 acceptable scans. Therefore, a total of 9 × 79 + 6 × 1 = 725 scans were included in the analysis for all parameters, except for 6-7 mm Ring Average which had missing values for 9 acceptable scans (6 Keratoconus, 2 Contact Lens Wearer, and 1 Dry Eye Disease; i.e., 725 - 9 = 716).

Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance Repeatability limit = 2.8 × Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility SDV(Intercept × 100%.

{13}------------------------------------------------

Table 3 provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Keratoconus Eyes subgroup.

### Table 3 Repeatability and Reproducibility of ANTERION Corneal Epithelial Thickness Measurements Precision Analysis Population of Keratoconus Eyes

| Eye Population | # of | # of | | Repeatability | | | Reproducibility | | | |
|-------------------------------|------|-------|-----------|---------------|-------|------|-----------------|-------|------|--|
| Parameter (µm) | Eyes | Scans | Intercept | SD | Limit | CV% | SD | Limit | CV% | |
| Keratoconus Eyes | | | | | | | | | | |
| 0-2 mm Ring Average | 24 | 212 | 48.18 | 0.86 | 2.42 | 1.79 | 1.36 | 3.82 | 2.83 | |
| 2-5 mm Ring Average | 24 | 212 | 49.15 | 0.82 | 2.30 | 1.67 | 1.22 | 3.42 | 2.48 | |
| 2-5 mm Ring Nasal | 24 | 212 | 50.41 | 1.06 | 2.98 | 2.11 | 1.33 | 3.72 | 2.64 | |
| 2-5 mm Ring Superior Nasal | 24 | 212 | 50.16 | 1.01 | 2.81 | 2.00 | 1.44 | 4.05 | 2.88 | |
| 2-5 mm Ring Superior | 24 | 212 | 49.63 | 1.11 | 3.12 | 2.25 | 1.76 | 4.93 | 3.55 | |
| 2-5 mm Ring Superior Temporal | 24 | 212 | 49.70 | 1.13 | 3.15 | 2.26 | 1.43 | 3.99 | 2.87 | |
| 2-5 mm Ring Temporal | 24 | 212 | 47.08 | 1.21 | 3.39 | 2.57 | 1.54 | 4.32 | 3.27 | |
| 2-5 mm Ring Inferior Temporal | 24 | 212 | 46.78 | 1.08 | 3.02 | 2.30 | 1.38 | 3.85 | 2.94 | |
| 2-5 mm Ring Inferior | 24 | 212 | 48.86 | 1.09 | 3.07 | 2.24 | 1.53 | 4.28 | 3.13 | |
| 2-5 mm Ring Inferior Nasal | 24 | 212 | 50.53 | 1.06 | 2.98 | 2.10 | 1.44 | 4.04 | 2.86 | |
| 5-7 mm Ring Average | 24 | 212 | 49.79 | 0.85 | 2.37 | 1.70 | 1.08 | 3.03 | 2.17 | |
| 5-7 mm Ring Nasal | 24 | 212 | 49.98 | 1.07 | 2.98 | 2.13 | 1.39 | 3.89 | 2.78 | |
| 5-7 mm Ring Superior Nasal | 24 | 212 | 49.40 | 1.20 | 3.35 | 2.42 | 1.53 | 4.27 | 3.09 | |
| 5-7 mm Ring Superior | 24 | 212 | 48.86 | 1.25 | 3.51 | 2.57 | 1.76 | 4.92 | 3.59 | |
| 5-7 mm Ring Superior Temporal | 24 | 212 | 50.01 | 1.47 | 4.12 | 2.94 | 1.69 | 4.73 | 3.38 | |
| 5-7 mm Ring Temporal | 24 | 212 | 49.08 | 1.14 | 3.20 | 2.33 | 1.47 | 4.13 | 3.00 | |
| 5-7 mm Ring Inferior Temporal | 24 | 212 | 49.37 | 1.59 | 4.46 | 3.23 | 1.81 | 5.07 | 3.67 | |
| 5-7 mm Ring Inferior | 24 | 212 | 50.52 | 1.52 | 4.25 | 3.01 | 1.63 | 4.57 | 3.23 | |
| 5-7 mm Ring Inferior Nasal | 24 | 212 | 50.99 | 1.20 | 3.37 | 2.36 | 1.38 | 3.86 | 2.71 | |
| 7 mm Zone Minimum | 24 | 212 | 34.68 | 2.03 | 5.68 | 5.85 | 2.12 | 5.93 | 6.10 | |
| 7 mm Zone Maximum | 24 | 212 | 64.82 | 2.32 | 6.50 | 3.58 | 2.48 | 6.94 | 3.82 | |
| 2-4 mm Ring Average | 24 | 212 | 48.65 | 0.79 | 2.20 | 1.62 | 1.21 | 3.38 | 2.48 | |
| 4-6 mm Ring Average | 24 | 212 | 49.93 | 0.82 | 2.31 | 1.65 | 1.14 | 3.19 | 2.28 | |
| 6-7 mm Ring Average | 24 | 206 | 49.56 | 0.86 | 2.42 | 1.74 | 1.03 | 2.87 | 2.07 | |
| 7 mm Zone Average | 24 | 212 | 49.43 | 0.80 | 2.24 | 1.62 | 1.11 | 3.12 | 2.25 | |
| 2-7 mm Ring Superior | 24 | 212 | 49.52 | 0.90 | 2.51 | 1.81 | 1.21 | 3.39 | 2.44 | |
| 2-7 mm Ring Inferior | 24 | 212 | 49.45 | 0.83 | 2.32 | 1.67 | 1.12 | 3.13 | 2.26 | |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator device pairs for a total of 9 scans for each study eye). In the study, 22 Keratoconus population study eves had 3 acceptable scans from each of the 3 operator/device pairs, one study eye had 6 acceptable scans (one operator/device pair did not have any acceptable scans) and one study eye had 8 acceptable scans. Therefore, a total of 9 × 22 + 6 × 1 + 8 × 1 = 212 scans were included in the analysis for all parameters, except for 6-7 mm Ring Average which had missing values for 6 acceptable scans (i.e., 212 - 6 = 206).

Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance Repeatability limit = 2.8 × Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility SDV(Intercept × 100%.

{14}------------------------------------------------

Table 4 below provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Contact Lens Wearer subgroup.

Table 4 Repeatability and Reproducibility of ANTERION Corneal Epithelial Thickness Measurements Precision Analysis Population of Contact Lens Wearer

| Eye Population<br>Parameter (μm) | # of<br>Eyes | # of<br>Scans | Intercept | SD | Repeatability<br>Limit | CV% | SD | Reproducibility<br>Limit | CV% |
|----------------------------------|--------------|---------------|-----------|------|------------------------|------|------|--------------------------|------|
| Contact Lens Wearer | | | | | | | | | |
| 0-2 mm Ring Average | 20 | 180 | 50.06 | 0.79 | 2.21 | 1.58 | 1.07 | 3.01 | 2.15 |
| 2-5 mm Ring Average | 20 | 180 | 49.67 | 0.71 | 1.99 | 1.43 | 1.04 | 2.92 | 2.10 |
| 2-5 mm Ring Nasal | 20 | 180 | 50.02 | 0.89 | 2.49 | 1.78 | 1.26 | 3.52 | 2.52 |
| 2-5 mm Ring Superior Nasal | 20 | 180 | 49.14 | 0.80 | 2.25 | 1.63 | 1.11 | 3.12 | 2.27 |
| 2-5 mm Ring Superior | 20 | 180 | 48.17 | 0.95 | 2.66 | 1.97 | 1.15 | 3.23 | 2.39 |
| 2-5 mm Ring Superior Temporal | 20 | 180 | 48.09 | 0.83 | 2.32 | 1.73 | 1.02 | 2.85 | 2.11 |
| 2-5 mm Ring Temporal | 20 | 180 | 49.06 | 0.85 | 2.38 | 1.73 | 1.04 | 2.91 | 2.12 |
| 2-5 mm Ring Inferior Temporal | 20 | 180 | 50.63 | 0.87 | 2.44 | 1.72 | 1.09 | 3.04 | 2.14 |
| 2-5 mm Ring Inferior | 20 | 180 | 51.32 | 0.92 | 2.59 | 1.80 | 1.31 | 3.65 | 2.54 |
| 2-5 mm Ring Inferior Nasal | 20 | 180 | 50.99 | 1.10 | 3.07 | 2.15 | 1.55 | 4.34 | 3.04 |
| 5-7 mm Ring Average | 20 | 180 | 50.24 | 0.79 | 2.21 | 1.57 | 1.08 | 3.01 | 2.14 |
| 5-7 mm Ring Nasal | 20 | 180 | 50.77 | 0.97 | 2.71 | 1.91 | 1.45 | 4.06 | 2.86 |
| 5-7 mm Ring Superior Nasal | 20 | 180 | 49.77 | 1.02 | 2.85 | 2.05 | 1.33 | 3.73 | 2.68 |
| 5-7 mm Ring Superior | 20 | 180 | 48.17 | 1.18 | 3.31 | 2.46 | 1.34 | 3.76 | 2.79 |
| 5-7 mm Ring Superior Temporal | 20 | 180 | 48.47 | 0.99 | 2.77 | 2.04 | 1.13 | 3.17 | 2.34 |
| 5-7 mm Ring Temporal | 20 | 180 | 49.80 | 1.02 | 2.85 | 2.04 | 1.12 | 3.14 | 2.25 |
| 5-7 mm Ring Inferior Temporal | 20 | 180 | 51.61 | 1.04 | 2.91 | 2.01 | 1.18 | 3.31 | 2.29 |
| 5-7 mm Ring Inferior | 20 | 180 | 51.91 | 1.20 | 3.37 | 2.32 | 1.54 | 4.31 | 2.96 |
| 5-7 mm Ring Inferior Nasal | 20 | 180 | 51.37 | 1.23 | 3.45 | 2.40 | 1.78 | 4.99 | 3.47 |
| 7 mm Zone Minimum | 20 | 180 | 43.23 | 1.55 | 4.33 | 3.58 | 1.74 | 4.86 | 4.01 |
| 7 mm Zone Maximum | 20 | 180 | 57.68 | 1.96 | 5.49 | 3.40 | 2.37 | 6.63 | 4.11 |
| 2-4 mm Ring Average | 20 | 180 | 49.58 | 0.79 | 2.20 | 1.58 | 1.05 | 2.95 | 2.12 |
| 4-6 mm Ring Average | 20 | 180 | 49.92 | 0.77 | 2.16 | 1.54 | 1.08 | 3.03 | 2.17 |
| 6-7 mm Ring Average | 20 | 178 | 50.44 | 0.88 | 2.48 | 1.75 | 1.14 | 3.20 | 2.27 |
| 7 mm Zone Average | 20 | 180 | 49.99 | 0.74 | 2.08 | 1.48 | 1.04 | 2.91 | 2.08 |
| 2-7 mm Ring Superior | 20 | 180 | 48.91 | 0.80 | 2.23 | 1.63 | 0.99 | 2.78 | 2.03 |
| 2-7 mm Ring Inferior | 20 | 180 | 51.01 | 0.82 | 2.29 | 1.60 | 1.17 | 3.27 | 2.29 |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator device pairs for a total of 9 scans for each study eye). In the study, all 20 Contact Lens Wearer population study eyes had 3 acceptable scans from each of the 3 operator/device pairs. Therefore, a total of 9 × 20 = 180 scans were included in the analysis for all parameters, except for 6-7 mm Ring Average which had missing values from two acceptable scans (i.e., 180 - 2 = 178).

Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance Repeatability limit = 2.8 × Repeatability CV% = (Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility CV% = (Reproducibility SD)/Intercept × 100%.

{15}------------------------------------------------

Table 5 below provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Post Keratorefractive Surgery Eyes subgroup.

Table 5 Repeatability and Reproducibility of ANTERION Corneal Epithelial Thickness Measurements Precision Analysis Population of Post Keratorefractive Surgery Eyes

| Eye Population | # of | # of | Intercept | SD | Repeatability | | Reproducibility | | |
|-------------------------------|------|-------|-----------|------|---------------|------|-----------------|-------|------|
| Parameter (µm) | Eyes | Scans | | | Limit | CV% | SD | Limit | CV% |
| Post Keratorefractive Surgery | | | | | | | | | |
| 0-2 mm Ring Average | 18 | 162 | 55.02 | 0.67 | 1.87 | 1.21 | 1.04 | 2.90 | 1.88 |
| 2-5 mm Ring Average | 18 | 162 | 54.10 | 0.59 | 1.66 | 1.10 | 0.93 | 2.62 | 1.73 |
| 2-5 mm Ring Nasal | 18 | 162 | 53.73 | 0.80 | 2.24 | 1.49 | 1.03 | 2.89 | 1.92 |
| 2-5 mm Ring Superior Nasal | 18 | 162 | 53.10 | 0.76 | 2.12 | 1.43 | 1.00 | 2.79 | 1.88 |
| 2-5 mm Ring Superior | 18 | 162 | 52.52 | 0.73 | 2.04 | 1.39 | 1.00 | 2.80 | 1.90 |
| 2-5 mm Ring Superior Temporal | 18 | 162 | 53.19 | 0.70 | 1.97 | 1.32 | 0.93 | 2.61 | 1.75 |
| 2-5 mm Ring Temporal | 18 | 162 | 54.49 | 0.70 | 1.97 | 1.29 | 0.96 | 2.68 | 1.76 |
| 2-5 mm Ring Inferior Temporal | 18 | 162 | 55.65 | 0.70 | 1.96 | 1.25 | 1.15 | 3.21 | 2.06 |
| 2-5 mm Ring Inferior | 18 | 162 | 55.30 | 0.81 | 2.26 | 1.46 | 1.26 | 3.53 | 2.28 |
| 2-5 mm Ring Inferior Nasal | 18 | 162 | 54.84 | 1.06 | 2.98 | 1.94 | 1.33 | 3.73 | 2.43 |
| 5-7 mm Ring Average | 18 | 162 | 51.81 | 0.61 | 1.72 | 1.18 | 0.91 | 2.55 | 1.76 |
| 5-7 mm Ring Nasal | 18 | 162 | 51.90 | 1.05 | 2.93 | 2.01 | 1.29 | 3.61 | 2.49 |
| 5-7 mm Ring Superior Nasal | 18 | 162 | 51.36 | 0.94 | 2.62 | 1.82 | 1.21 | 3.38 | 2.35 |
| 5-7 mm Ring Superior | 18 | 162 | 49.90 | 0.98 | 2.76 | 1.97 | 1.22 | 3.42 | 2.45 |
| 5-7 mm Ring Superior Temporal | 18 | 162 | 50.56 | 0.97 | 2.71 | 1.92 | 1.09 | 3.06 | 2.16 |
| 5-7 mm Ring Temporal | 18 | 162 | 51.88 | 0.83 | 2.32 | 1.60 | 1.03 | 2.89 | 1.99 |
| 5-7 mm Ring Inferior Temporal | 18 | 162 | 53.27 | 0.96 | 2.69 | 1.80 | 1.20 | 3.35 | 2.25 |
| 5-7 mm Ring Inferior | 18 | 162 | 52.75 | 0.96 | 2.68 | 1.81 | 1.25 | 3.51 | 2.38 |
| 5-7 mm Ring Inferior Nasal | 18 | 162 | 52.50 | 1.46 | 4.07 | 2.77 | 1.72 | 4.80 | 3.27 |
| 7 mm Zone Minimum | 18 | 162 | 41.75 | 1.63 | 4.56 | 3.90 | 1.68 | 4.71 | 4.03 |
| 7 mm Zone Maximum | 18 | 162 | 60.77 | 1.71 | 4.78 | 2.81 | 1.98 | 5.54 | 3.26 |
| 2-4 mm Ring Average | 18 | 162 | 54.34 | 0.62 | 1.75 | 1.15 | 1.00 | 2.79 | 1.83 |
| 4-6 mm Ring Average | 18 | 162 | 53.12 | 0.61 | 1.70 | 1.15 | 0.95 | 2.67 | 1.80 |
| 6-7 mm Ring Average | 18 | 162 | 51.06 | 0.67 | 1.88 | 1.31 | 0.98 | 2.74 | 1.92 |
| 7 mm Zone Average | 18 | 162 | 53.07 | 0.55 | 1.54 | 1.04 | 0.88 | 2.45 | 1.65 |
| 2-7 mm Ring Superior | 18 | 162 | 51.99 | 0.57 | 1.59 | 1.09 | 0.82 | 2.30 | 1.58 |
| 2-7 mm Ring Inferior | 18 | 162 | 53.78 | 0.76 | 2.12 | 1.41 | 1.05 | 2.95 | 1.96 |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator device pairs for a total of 9 scans for each study eye). In the study, all 18 Post Keratorefractive Surgery population study eyes had 3 acceptable scans from each of the 3 operator/device pairs. Therefore, a total of 9 × 18 = 162 scans were included in the analysis for all parameters. Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance

Repeatability limit = 2.8 × Repeatability CV% = (Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility SDV(Intercept × 100%.

{16}------------------------------------------------

Table 6 below provides the results of the repeatability and reproducibility analyses for the ANTERION for corneal epithelial thickness measurements for the Dry Eye Disease subgroup.

Table 6 Repeatability and Reproducibility of ANTERION Corneal Epithelial Thickness Measurements Precision Analysis Population of Dry Eye Disease

| Eye Population<br>Parameter (µm) | # of<br>Eyes | # of<br>Scans | Intercept | Repeatability | | | Reproducibility | | |
|----------------------------------|--------------|---------------|-----------|---------------|-------|------|-----------------|-------|------|
| | | | | SD | Limit | CV% | SD | Limit | CV% |
| Dry Eye Disease | | | | | | | | | |
| 0-2 mm Ring Average | 19 | 171 | 50.68 | 0.56 | 1.56 | 1.10 | 0.98 | 2.74 | 1.93 |
| 2-5 mm Ring Average | 19 | 171 | 50.27 | 0.50 | 1.40 | 1.00 | 0.59 | 1.64 | 1.17 |
| 2-5 mm Ring Nasal | 19 | 171 | 50.34 | 0.60 | 1.67 | 1.19 | 0.73 | 2.05 | 1.45 |
| 2-5 mm Ring Superior Nasal | 19 | 171 | 49.54 | 0.70 | 1.95 | 1.41 | 0.75 | 2.11 | 1.52 |
| 2-5 mm Ring Superior | 19 | 171 | 48.53 | 0.68 | 1.89 | 1.39 | 0.83 | 2.32 | 1.71 |
| 2-5 mm Ring Superior Temporal | 19 | 171 | 48.56 | 0.77 | 2.16 | 1.59 | 0.90 | 2.51 | 1.85 |
| 2-5 mm Ring Temporal | 19 | 171 | 49.67 | 0.75 | 2.11 | 1.52 | 0.84 | 2.36 | 1.69 |
| 2-5 mm Ring Inferior Temporal | 19 | 171 | 51.51 | 0.68 | 1.92 | 1.33 | 0.76 | 2.12 | 1.47 |
| 2-5 mm Ring Inferior | 19 | 171 | 52.43 | 0.69 | 1.93 | 1.31 | 0.84 | 2.36 | 1.61 |
| 2-5 mm Ring Inferior Nasal | 19 | 171 | 51.63 | 0.65 | 1.83 | 1.27 | 0.80 | 2.25 | 1.56 |
| 5-7 mm Ring Average | 19 | 171 | 50.01 | 0.55 | 1.53 | 1.09 | 0.61 | 1.72 | 1.23 |
| 5-7 mm Ring Nasal | 19 | 171 | 50.77 | 0.74 | 2.06 | 1.45 | 0.89 | 2.49 | 1.75 |
| 5-7 mm Ring Superior Nasal | 19 | 171 | 49.98 | 0.69 | 1.93 | 1.38 | 0.85 | 2.38 | 1.70 |
| 5-7 mm Ring Superior | 19 | 171 | 46.99 | 0.81 | 2.27 | 1.72 | 0.90 | 2.52 | 1.92 |
| 5-7 mm Ring Superior Temporal | 19 | 171 | 47.36 | 0.93 | 2.60 | 1.96 | 1.04 | 2.92 | 2.20 |
| 5-7 mm Ring Temporal | 19 | 171 | 49.75 | 0.90 | 2.52 | 1.81 | 0.98 | 2.75 | 1.98 |
| 5-7 mm Ring Inferior Temporal | 19 | 171 | 52.60 | 1.00 | 2.80 | 1.90 | 1.14 | 3.20 | 2.17 |
| 5-7 mm Ring Inferior | 19 | 171 | 51.58 | 0.87 | 2.43 | 1.68 | 1.01 | 2.83 | 1.96 |
| 5-7 mm Ring Inferior Nasal | 19 | 171 | 50.85 | 0.73 | 2.04 | 1.43 | 0.85 | 2.37 | 1.67 |
| 7 mm Zone Minimum | 19 | 171 | 41.61 | 1.55 | 4.33 | 3.72 | 1.64 | 4.60 | 3.95 |
| 7 mm Zone Maximum | 19 | 171 | 58.17 | 1.49 | 4.17 | 2.56 | 1.72 | 4.82 | 2.96 |
| 2-4 mm Ring Average | 19 | 171 | 50.18 | 0.45 | 1.27 | 0.90 | 0.61 | 1.70 | 1.21 |
| 4-6 mm Ring Average | 19 | 171 | 50.18 | 0.49 | 1.37 | 0.98 | 0.60 | 1.69 | 1.20 |
| 6-7 mm Ring Average | 19 | 170 | 49.96 | 0.54 | 1.51 | 1.08 | 0.66 | 1.84 | 1.31 |
| 7 mm Zone Average | 19 | 171 | 50.22 | 0.46 | 1.28 | 0.91 | 0.56 | 1.57 | 1.12 |
| 2-7 mm Ring Superior | 19 | 171 | 48.85 | 0.50 | 1.40 | 1.03 | 0.60 | 1.69 | 1.24 |
| 2-7 mm Ring Inferior | 19 | 171 | 51.43 | 0.52 | 1.45 | 1.01 | 0.59 | 1.66 | 1.15 |

All statistics are estimated (REML) from two-way random-effect ANOVA model with random effects operator/device, eye and interaction between operator/device and eye. Per study protocol, each operator had a maximum number of 9 attempts to acquire 3 acceptable scans (i.e., theoretically, 3 repeated scans from each of the 3 operator/device pairs for a total of 9 scans for each study eye). In the study, all 19 Dry Eye Disease population study eyes had 3 acceptable scans from each of the 3

operator/device pairs. Therefore, a total of 9 × 19 = 171 scans were included in the analysis for all parameters, except for 6-7 mm Ring Average which had missing values for one acceptable scan (i.e., 171 - 1 = 170).

Reproducibility SD = Square root of the operator/device variance, the interaction variance and the residual variance Repeatability limit = 2.8 × Repeatability CV% = (Repeatability SD)/Intercept × 100%.

Reproducibility limit = 2.8 × Reproducibility SD. Reproducibility CV% = (Reproducibility SD)/Intercept × 100%.

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Agreement results are presented in the figures below:

In the figures below, the summary of Limit of Agreement (LoA) and the corresponding 95% CIs of the lower LoA and upper LoA are shown for Normal Cornea Eyes (Figure 1) and Abnormal Cornea Eyes (Figure 2) populations, as well as stratified into the subgroups Keratoconus Eyes (Figure 3), Contact Lens Wearer (Figure 4), Post- Keratorefractive Surgery Eyes (Figure 5) and Dry Eye Disease (Figure 6). Note that the difference between ANTERION and Cirrus is calculated as ANTERION - Cirrus, where positive differences indicate that ANTERION measures thicker and negative differences indicate that ANTERION measures thinner.

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Figure 1 Summary of Limit of Agreement of Corneal Epithelial Thickness Measurements Between ANTERION and Cirrus, Agreement Analysis Population of Normal Cornea Eyes

| Parameter<br>(μm) | Mean<br>Bias | Limit of<br>Agreement<br>(LoA) | 95% CI of<br>Lower Limit<br>of LoA | 95% CI of<br>Upper Limit<br>of LoA | |
|-------------------|--------------|--------------------------------|------------------------------------|---------…