The Guided Progression Analysis for the Humphrey® Field Analyzer II (HFA II) and Humphrey® Field Analyzer II- i series is a software analysis module that is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, glaucoma. It is also intended to compare change over time and determine if statistically significant change has occurred.

The Carl Zeiss Meditec, Inc. Guided Progression Analysis is a software analysis module for the Humphrey® Field Analyzer II (HFA II) and Humphrey® Field Analyzer II - i series (HFA II - i) that assists practitioners with the detection, measurement, and management of progression of visual field loss. It aids in assessing change over time, including change from baseline and rate of change. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, glaucoma.

Device Description

The Carl Zeiss Meditec, Inc. Guided Progression Analysis (GPA) is a software package for the Humphrey Field Analyzer II and II - i series that is designed to help practitioners identify progressive visual field loss in glaucoma patients. GPA compares the visual field test results of up to 14 follow-up tests to an established baseline over time and determines if there is statistically significant change. The GPA printout highlights any changes from baseline that represent larger than expected clinical variability, and it provides simple plain-language messages such as "Possible Progression" or "Likely Progression" whenever changes show consistent and statistically significant loss. The GPA printout also presents the Visual Field Index (VFI), a global index which reports a measure of the patient's remaining useful vision in the form of a percentage, as well as the VFI Rate of Progression plot which provides a trend analysis of the patient's overall visual field history and indicates a 3-5 year projection of the VFI regression line if the current trend continued.

AI/ML Overview

The provided FDA 510(k) summary for the Guided Progression Analysis (GPA) for the Humphrey® Field Analyzer II and II - i series does not detail specific acceptance criteria in a quantitative table format or a standalone study with a predefined set of performance metrics that the device had to meet. Instead, the submission relies on:

Substantial Equivalence: Demonstrating that the GPA software is functionally equivalent to predicate devices and does not raise new questions regarding safety and effectiveness.
Clinical Literature Review: Citing published research that discusses GPA's development and its successful use in identifying statistically significant visual field progression, particularly referencing its incorporation of metrics from the Early Manifest Glaucoma Trial (EMGT).
Sponsored Study on Test-Retest Variability: A study to quantify perimetric test-retest variability in glaucoma subjects, which was used to establish limits for change at different significance levels based on test-retest variability in glaucomatous visual fields. This allows GPA to indicate when change exceeds normal test-retest variability.

Therefore, a table of explicit acceptance criteria and corresponding reported device performance, in the traditional sense of a validation study with pre-defined thresholds, cannot be directly extracted or constructed from the provided text. The "performance" is described in terms of its ability to identify statistically significant change based on established variability data, rather than specific sensitivity/specificity figures against an external gold standard.

However, I can provide a summary of the information available in the document regarding the study that underpins the device's claims.

Acceptance Criteria and Reported Device Performance

As stated, explicit acceptance criteria (e.g., minimum sensitivity, specificity, or accuracy targets) are not provided in this 510(k) summary. The "performance" is intrinsically linked to its ability to identify changes beyond normal test-retest variability.

Criterion Type	Acceptance Criteria (Not explicitly stated in the document)	Reported Device Performance (as described in the document)
Efficacy in detecting progression	Implicit: Ability to identify statistically significant visual field progression	GPA incorporates visual field progression metrics successfully used in EMGT. It determines if statistically significant change has occurred by comparing follow-up tests to a baseline and highlighting changes that represent larger than expected clinical variability. Provides plain-language messages like "Possible Progression" or "Likely Progression".
Statistical Robustness	Implicit: Ability to distinguish true change from test-retest variability	Results from a sponsored study established limits for change at different significance levels based on test-retest variability in glaucomatous visual fields. GPA indicates when change at a given test location exceeds this test-retest variability.
Aid in management	Implicit: Provides actionable information for clinicians	Presents Visual Field Index (VFI), VFI Rate of Progression plot, and trend analysis with 3-5 year projection to aid in estimating future visual status.

Sample size used for the test set and the data provenance:
- Sample Size: 363 qualified glaucoma subjects.
- Data Provenance: Data was collected across a worldwide nine-site study. It is not specified if it was retrospective or prospective, but the description ("Each subject was tested four times within one month") suggests a prospective data collection for the purpose of establishing test-retest variability.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense of defining disease progression. The study focused on quantifying perimetric test-retest variability in glaucoma subjects. The "ground truth" or reference for this study was the inherent variability of visual field measurements themselves, not an expert-determined clinical diagnosis of progression.
Adjudication method for the test set:
- Adjudication methods (like 2+1 or 3+1) are typically used when experts are determining a ground truth for a diagnostic outcome. Since the study focused on quantifying test-retest variability rather than an expert-adjudicated ground truth for progression, no adjudication method is described or implied in the provided text.
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:
- No MRMC comparative effectiveness study is described in this 510(k) summary. The device, Guided Progression Analysis (GPA), is a software analysis module designed to assist practitioners, but its performance is described in terms of its algorithmic output based on statistical analysis of visual field data, not human reader performance with or without AI (in this case, "AI" refers to the GPA algorithm). The summary indicates that "the results allow HFA GPA to indicate when the change... exceeds the test-retest variability," which implies the software's direct output.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the core study mentioned (quantifying perimetric test-retest variability) and the subsequent development of GPA to use this data to identify statistically significant changes represent a standalone algorithmic function. The GPA software, without human intervention in its analysis, compares visual field test results to a baseline and determines statistical significance of changes, providing messages like "Possible Progression" or "Likely Progression." This is an algorithm-only function based on statistical rules derived from the variability study.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" used for the development and validation of the statistical thresholds within GPA was data on perimetric test-retest variability. This means the system's ability to declare "progression" is benchmarked against the statistically expected noise and fluctuations in visual field measurements in glaucoma patients, as determined by the sponsored study. It is not an expert consensus on true progression, pathology, or long-term outcomes data, although the underlying clinical effectiveness of detecting visual field progression is supported by reference to studies like EMGT.
The sample size for the training set:
- The document references the Early Manifest Glaucoma Trial (EMGT) literature (citations 3 and 4) as providing the "visual field progression metrics successfully used" in GPA. The EMGT study design document (cited as "Ophthalmology 1999; 106:2144-2153") would contain details about its sample size, which served as a foundational dataset for the conceptual framework of progression analysis incorporated into GPA. However, a specific "training set" sample size for the development of this particular software version (GPA for HFA II) is not explicitly stated in the document beyond the reference to EMGT and the "363 qualified glaucoma subjects" used for the test-retest variability study. The 363 subjects constituted a dataset for establishing variability limits, which are essentially statistical parameters used by the algorithm. It is unclear if these 363 subjects' data was used for training a machine learning model vs. establishing statistical thresholds.
How the ground truth for the training set was established:
- Given the reliance on EMGT, the "ground truth" for the principles of progression analysis would have been established within the EMGT, likely through clinical outcomes and expert evaluation of visual field series over time in relation to glaucoma diagnosis and treatment. For the test-retest variability study (the 363 subjects), the "ground truth" was derived from repeated measurements from the same subjects to quantify the inherent variability, rather than a clinical ground truth of progression. The document does not describe a machine learning-style training set with an explicitly adjudicated ground truth for progression; instead, it highlights the incorporation of established clinical knowledge and statistical principles from previous large-scale studies.

Summary

{0}------------------------------------------------

K69.3213

MAR 1 2 2010

5. 510(K) SUMMARY

510(k) SUMMARY Guided Progression Analysis (GPA) for the Humphrey® Fleld Analyzer II and II - i series

GENERAL INFORMATION

Manufacturer:

Carl Zeiss Meditec Inc. 5160 Hacienda Drive Dublin, California 94568 (925) 557-4616 (phone) (925) 557-4259 (fax) ----Est. Reg. No. 2918630

Contact Person:

Judith A. Brimacombe, MA Director, Regulatory/Clinical Affairs Carl Zeiss Meditec Inc. 5160 Hacienda Drive Dublin, California 94568 (925) 557-4616 (phone) (925) 557-4259 (fax)

Classification name:

Classification:

Perimeter

HPT

Class I (according to 21 CFR 886.1605)

Product Code:

Trade/Proprietary name: Guided Progression Analysis (GPA) for the Humphrey® Field Analyzer II and Humphrey® Field Analyzer II - i series

PREDICATE DEVICES

Company: Device:

Carl Zeiss Meditec, Inc. Humphrey® Field Analyzer II (K954167)

Company: Device:

Carl Zeiss Meditec, Inc. Cirrus™ HD-OCT with Retinal Nerve Fiber Layer and Macular Normative Databases (K083291)

{1}------------------------------------------------

INTENDED USE

INDICATIONS FOR USE

DEVICE DESCRIPTION

SUBSTANTIAL EQUIVALENCE

The Guided Progression Analysis for the Humphrey® Field Analyzer II (HFA II) and Humphrey Field Analyzer II- i series is substantially equivalent to the Humphrey® Field Analyzer II and Guided Progression Analysis for the Cirrus HD-OCT with Retinal Nerve Fiber Layer (RNFL) and Macular Normative Databases. The

{2}------------------------------------------------

indications for use for the Guided Progression Analysis for the Humphrey® Field Analyzer II and Humphrey® Field Analyzer II- i series are similar to the indications for the predicate devices cited in this application. A technological comparison demonstrates that the Guided Progression Analysis for the Humphrey® Field Analyzer II (HFA II) and Humphrey® Field Analyzer II- i series is functionally equivalent to the predicate devices.

Evaluation of published literature on Guided Progression Analysis for the Humphrey® Field Analyzer II and Humphrey® Field Analyzer II- i series supports the indications for use statement, and demonstrates that the device is substantially equivalent to the predicate devices and does not raise new questions regarding safety and effectiveness.

CLINICAL EVALUATION

Clinical data on GPA has been collected by various researchers and is reported in the clinical literature.12 A review of the clinical literature that discusses the relevant studies related to the development of GPA for analysis of visual field progression has been included in this Premarket Notification. GPA incorporated the visual field progression metrics successfully used in the Early Manifest Glaucoma Trial (EMGT), 34 in which pattern deviation maps were used to identify statistically significant visual field progression.

Carl Zeiss Meditec. Inc. sponsored a study to quantify perimetric test-retest variability in glaucoma subjects having a wide range of visual field loss. A total of 363 qualified glaucoma subjects were enrolled across a worldwide nine-site study. Each subject was tested four times within one month. The results of this study, which used the three threshold testing algorithms available on the Humphrey Field Analyzer (SITA Standard, SITA Fast, and Full Threshold), established the limits for change at different significance levels based on test-retest variability in glaucomatous visual fields. The results allow HFA GPA to indicate when the change for a given patient at a given test location exceeds the test-retest variability for the region.

1 Amalish-Montel F, Casas-Llera P, Mudoz-Negrete FJ, Rebolleda G. Performance of glaucoma progression analysis software in a glaucoma population. Graefes Arch Clin Exp Ophthalmol 2009;247:391-397.

2 Casas-Llera P, Rebolleda G, Muñoz-Negree FJ, Amalich-Montiel F, Pérez-López M, Femández-Buenaga R. Visual field index rate and event-based glaucoma progression analysis: Companison in a glaucoma population. Br. J. Ophthalmol. published online 16 June 2009.

3 Leske CM, Heijl A, Hyman L, Bengtson B for the Early Manifest Glaucoma Trial Croup. Early Manifest Glaucoma Trial - Design and baseline data. Ophthalmology 1999; 106:2144-2153.

4 Heil A, Leske CM, Bengtson B, Hussen B, Hussein M for the Early Manifest Glaucoma Trial Group. Reduction of intraccular pressure and glaucona progression - results from the Early Manifest Glaucoma Trial. Arch Ophhalmol. 2002; 120: 268-1279.

{3}------------------------------------------------

GPA was further refined to include the visual field index (VFI) described by Bengtsson and Heijl.5 This index utilizes data from the pattern deviation probability maps and is incorporated into the new VFI graphical analysis in the GPA software. Linear regression analysis was used to determine the rate of change in VFI. For a visual field series with sufficient follow-up data, the linear regression line is extended into the future to aid the clinician in estimating a patient's future visual status, should previously observed progression rates continue into the future.

SUMMARY

As described in this 510(k) Summary, all testing deemed necessary was conducted on the Guided Progression Analysis for the Humphrey® Field Analyzer II (HFA II) and Humphrey® Field Analyzer II- i series to ensure that the device is substantially equivalent to the predicate devices, and safe and effective when used in accordance with its Instructions for Use.

5 B. Beagsson and A. Heiji. A visual field index for cakulation of glaucoma rate of progression; Am J Ophthalmol, Feb 2002; 145(2): 343-53.

{4}------------------------------------------------

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

MAR 1 2 2010

Carl Zeiss Meditec, Inc. c/o Ms. Judith A. Brimacombe, M.A. Director, Clinical and Regulatory Affairs 5160 Hacienda Drive Dublin, CA 94568

Re: K093213

Trade/Device Name: Guided Progression Analysis (GPA) for the Humphrey® Field Analyser II and Humphrey® Field Analyser II - i series

Regulation Number: 21 CFR 886.1605 Regulation Name: Perimeter Regulatory Class: Class II Product Code: HPT Dated: February 5, 2010 Received: February 12, 2010

Dear Ms. Brimacombe:

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. 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.

{5}------------------------------------------------

Page 2 - Ms. Judith A. Brimacombe, M.A.

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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Kesia Alexander for

Malvina B. Eydelman, M.D. Director Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{6}------------------------------------------------

510(k) Number (if known): K093213

Device Name:

Guided Progression Analysis (GPA) for the Humphrey® Field Analyzer II and Humphrey® Field Analyzer II ~ i series

Indications for Use:

The Carl Zeiss Meditec, Inc. Guided Progression Analysis is a software analysis module for the Humphrey Field Analyzer II (HFA II) and Humphrey® Field Analyzer II- i series (HFA II - i) that assists practitioners with the detection, measurement, and management of progression of visual field loss. It aids in assessing change over time, including change from baseline and rate of change. It is intended for use as a diagnostic device to aid in the detection and management of ocular diseases including, but not limited to, glaucoma,

Prescription Use _x (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page of

Bruce Drum

(Division Sign-Off) Division of Ophthalmic, Neurological and Ear, Nose and Throat De nees

510(k) Number K093213

Regulation Number and Section

§ 886.1605 Perimeter.

(a)
Identification. A perimeter is an AC-powered or manual device intended to determine the extent of the peripheral visual field of a patient. The device projects light on various points of a curved surface, and the patient indicates whether he or she sees the light.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter, subject to the limitations in § 886.9. The device is also exempt from the current good manufacturing practice requirements of the quality system regulation in part 820 of this chapter, with the exception of § 820.180, with respect to general requirements concerning records, and § 820.198, with respect to complaint files.