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K Number
K163475
Device Name
iVue
Manufacturer
Optovue, Inc.
Date Cleared
2017-06-09

(179 days)

Product Code
OBO,HLI
Regulation Number
886.1570
Type
Traditional
Panel
Ophthalmic
Reference & Predicate Devices
K121739
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The iVue is a non-contact, high resolution tomographic imaging device. It is intended for in-vivo imaging, axial crosssectional, and three-dimensional imaging and measurement of anterior ocular structures, including retina, retinal nerve fiber layer, ganglion cell complex (GCC), optic disc, corneal epithelia, corneal stroma and anterior chamber of the eye. With the integrated normative database, the iVue is a quantitative tool for the comparison of retina, retinal nerve fiber layer, ganglion cell complex, and optic disc measurements to a database of known normal subjects. The iVue is indicated for use as a device to aid in the diagnosis, documentation, and management of ocular health and diseases in the adult population.

Device Description

The iVue is used to capture, store, display and print spectral domain-optical coherence tomography (SD-OCT) images of the posterior and anterior structure of the eye. The device software includes a Normative Database (NDB), consisting of OCT data from a range of known normal subjects that can be used to compare a new patient's measurements in relation to the normal distribution.

iVue is a computer-controlled ophthalmic imaging system using either a laptop computer or "All-in-One" computer. For laptop systems there are two control box options of 120 or 230 volts. The control box interfaces between the motorized table column and the medical-grade power supply for the computer.

iVue System Key Functional Components:

  • Scanner Head
  • Computer
  • Control Box
  • Joystick and Chinrest Assembly
  • Footswitch (optional)
  • Motorized Table (optional)
  • Cornea Adapter Module
AI/ML Overview

The provided document is a 510(k) Premarket Notification for the Optovue iVue device, seeking clearance for a software modification that allows automated segmentation and measurement of corneal epithelial and stromal layer thickness. The document describes two clinical studies conducted to support the substantial equivalence claim.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state quantitative acceptance criteria in a table format with pass/fail thresholds. Instead, it presents the results of repeatability, reproducibility, and agreement studies, and then concludes whether these results demonstrate "good repeatability and reproducibility" and "good agreement."

Based on the summaries provided, the implicit acceptance criteria seem to be related to achieving clinically acceptable levels of repeatability, reproducibility, and agreement with manual measurements for corneal pachymetry, epithelial thickness, and stromal thickness, across various patient groups.

Table of Implicit Acceptance Criteria and Reported Device Performance:

MetricAcceptance Criteria (Implicit, based on conclusion)Reported Device Performance (Summary)
Repeatability (SD)Demonstrated "good repeatability"Pachymetry:- Normal Group: 1.7 to 7.6 µm (across zones)- Corneal Patients (pooled): 3.3 to 8.6 µm- Subgroups (Contact Lens, Dry Eye, Post-LRS, KCN): Ranged from 1.5 to 13.4 µm (max in Dry Eye S_5_6_Pachy).Epithelial Thickness:- Normal Group: 0.8 to 1.4 µm- Corneal Patients (pooled): 1.2 to 1.9 µm- Subgroups: Ranged from 0.6 to 2.9 µm (max in Dry Eye I_5_6_Epi and IT_5_6_Epi, and Post-LRS C2 Epi)Stromal Thickness:- Normal Group: 1.6 to 7.6 µm- Corneal Patients (pooled): 2.8 to 8.8 µm- Subgroups: Ranged from 1.4 to 13.4 µm (max in Dry Eye S_5_6_Stroma)
Reproducibility (SD)Demonstrated "good reproducibility"Pachymetry:- Normal Group: 2.2 to 7.7 µm- Corneal Patients (pooled): 3.6 to 8.8 µm- Subgroups: Ranged from 1.8 to 13.7 µm (max in Dry Eye S_5_6_Pachy).Epithelial Thickness:- Normal Group: 0.9 to 1.5 µm- Corneal Patients (pooled): 1.2 to 1.9 µm- Subgroups: Ranged from 0.7 to 2.9 µm (max in Dry Eye I_5_6_Epi and IT_5_6_Epi, and Post-LRS C2 Epi)Stromal Thickness:- Normal Group: 2.0 to 7.6 µm- Corneal Patients (pooled): 3.1 to 9.0 µm- Subgroups: Ranged from 1.8 to 13.7 µm (max in Dry Eye S_5_6_Stroma).The report notes: "Repeatability standard deviation was similar to the Reproducibility standard deviation for all study parameters and therefore is not detailed separately in the summary tables below." The tables for each parameter show Reproducibility SD values.
Agreement (Mean of Differences)Demonstrated "good agreement"Mean of differences between software output and manual measurements for all zonal parameters:- Corneal Epithelial Mapping: < 0.7 µm (<1.3% of 54 µm average thickness)- Corneal Stroma Mapping: < 1.9 µm (<0.4% of 490 µm average thickness)- Pachymetry Mapping: < 2.3 µm (<0.4% of 543 µm average thickness)
Agreement (LOA)Demonstrated "good agreement" (within acceptable limits)Limits of Agreement (LOA) between software output and manual measurements for all zonal parameters:- Corneal Epithelial Mapping: (-6.2 to 5.9) µm- Corneal Stroma Mapping: (-9.7 to 10.4) µm- Pachymetry Mapping: (-7.9 to 9.6) µm

2. Sample Sizes and Data Provenance

Study 1: Repeatability and Reproducibility (R&R) of Corneal Epithelial Thickness Mapping

  • Sample Size (Test Set): 59 subjects (from 598 total acquired scans, 527 qualified for final analysis).
    • Normal Subjects: 12 subjects
    • Corneal Patients: 47 subjects (further stratified into 4 subgroups, each with 11-12 subjects: Contact Lens, Dry Eye, Post-Refractive Surgery, Keratoconus).
  • Data Provenance: Not explicitly stated, but clinical studies are generally prospective. The multi-device, multi-operator protocol in Study 1 suggests it was a controlled, prospective collection. Given that Optovue is based in Fremont, CA, and the submission is to the FDA, it is highly probable the data was collected in the USA, although not explicitly stated.

Study 2: Agreement of Corneal Epithelial Thickness Mapping with iVue SD-OCT to Manual Measurement

  • Sample Size (Test Set): 87 study eyes from 87 subjects.
    • Normal Subjects: 17
    • Contact Lens (normal): 16
    • Dry Eye: 18
    • Post-Laser Refractive Surgery: 20
    • Keratoconus: 16
  • Data Provenance: Not explicitly stated, but the mention of "3 study sites" collecting OCT data suggests a prospective clinical study. Again, given the FDA submission, most likely USA.

3. Number of Experts and Qualifications for Ground Truth

  • Study 1 (R&R): Ground truth was based on the iVue software's automated segmentation, with manual edits performed by operators when needed. The document states: "For qualified scans, the operators reviewed the thickness maps for obvious segmentation error and reviewed the individual corneal meridian images to verify segmentation for erroneous maps. Segmentation edit tools were used to perform manual correction and then the epithelial map was reprocessed. Noticeable segmentation errors were manually corrected by the operator and marked for "Manual Correction" in the case report form."

    • The qualifications of these "operators" are not explicitly detailed. It implies they are trained users of the device capable of identifying and correcting segmentation errors, but their specific certifications (e.g., ophthalmologist, optometrist, ophthalmic technician) or years of experience are not mentioned.
    • Number of operators: The study used "device-specific designated operator" for each of the three iVue devices, so a minimum of 3 operators.

  • Study 2 (Agreement): Ground truth was established by manual measurements performed by "3 qualified graders."

    • The qualifications of these "qualified graders" are not specified (e.g., ophthalmologist, ophthalmic technician, years of experience). They used a "2-section caliper tool that was available in the previously cleared iVue software."

4. Adjudication Method for the Test Set

  • Study 1 (R&R): There's no explicit mention of a formal multi-reader adjudication process (e.g., 2+1, 3+1). It states "manual edits were not required in Normal eyes scans, and ranged from 2.8% in Contact Lens sub-group to 17.9% in KCN sub-group...Noticeable segmentation errors were manually corrected by the operator and marked for "Manual Correction"". This suggests correction was done by a single operator per scan if needed, not a consensus or adjudicated process among multiple experts.
  • Study 2 (Agreement): The "agreement to manual measurement of the software was evaluated based on the agreement between the software output and the manual measurements by 3 qualified graders." It appears each grader provided their measurement independently, and then the agreement between the software and their measurements (or a combined representation of their measurements, though "manual measurements" is singular in "agreement to manual measurement") was assessed. It doesn't describe an adjudication process amongst the 3 graders to establish a single ground truth for each case from the graders. The comparison is between the software and the individual manual measurements, then reported collectively.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • No MRMC comparative effectiveness study was done comparing human readers with AI vs. without AI assistance. The study focuses purely on the device's technical measurement performance (repeatability, reproducibility, and agreement with existing manual measurement methods). The iVue is a measurement device, not an AI diagnostic aid in the sense of 'improving human reader performance.'

6. Standalone (Algorithm Only) Performance

  • Yes, standalone performance was evaluated. The core of both clinical studies is the performance of the iVue device's software (algorithm) in segmenting and measuring the corneal layers.
    • In Study 1, it assessed the repeatability and reproducibility of the "modified iVue software" directly.
    • In Study 2, it assessed the "agreement between the software output and the manual measurements." This is a direct evaluation of the algorithm's performance against a human-derived ground truth.

7. Type of Ground Truth Used

  • Study 1 (R&R): The ground truth was the automated segmentation by the iVue software, potentially refined by "operator correction". This is a form of expert-corrected algorithmic output.
  • Study 2 (Agreement): The ground truth was manual measurements performed by "qualified graders" using a digital caliper tool available in the predicate iVue software. This is a form of expert measurement. It's not pathology or outcomes data.

8. Sample Size for the Training Set

  • Not specified in the provided document. The document describes clinical studies for validation and verification of a modified software, not the development or training of the original algorithm. Device approvals like 510(k) often focus on testing the finished product.

9. How the Ground Truth for the Training Set Was Established

  • Not specified in the provided document. As the training set size is not mentioned, neither is the method for establishing its ground truth. This information would typically be found in the algorithm's development and internal validation documentation, not necessarily in a 510(k) summary focused on post-modification performance.

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Public Health Service

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

June 9, 2017

Optovue, Inc. Edward J. Sinclair Vice President, Regulatory and Quality Affairs 2800 Bayview Drive Fremont, CA 94538

Re: K163475

Trade/Device Name: iVue Regulation Number: 21 CFR 886.1570 Regulation Name: Ophthalmoscope Regulatory Class: Class II Product Code: OBO, HLI Dated: May 5, 2017 Received: May 8, 2017

Dear Edward J. Sinclair:

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.

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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 devicerelated 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 contact the Division of Industry and Consumer Education 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. 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 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 Industry and Consumer Education 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.

Denise L. Hampton -S

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)

K163475

Device Name

iVue

Indications for Use (Describe)

The iVue is a non-contact, high resolution tomographic imaging device. It is intended for in-vivo imaging, axial crosssectional, and three-dimensional imaging and measurement of anterior ocular structures, including retina, retinal nerve fiber layer, ganglion cell complex (GCC), optic disc, corneal epithelia, corneal stroma and anterior chamber of the eye. With the integrated normative database, the iVue is a quantitative tool for the comparison of retina, retinal nerve fiber layer, ganglion cell complex, and optic disc measurements to a database of known normal subjects. The iVue is indicated for use as a device to aid in the diagnosis, documentation, and management of ocular health and diseases in the adult population.

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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510(k) SUMMARY

Submitter Information

Company:Optovue, Inc.2800 Bayview DriveFremont, CA 94538Phone: (510) 623-8868Fax: (510) 651-2516Est. Registration No.: 3005950902
Contact Person:Edward J. SinclairVice President, Regulatory and Quality AffairsPhone: (510) 897-1575Fax: (510) 651-2516
Date Prepared:June 8, 2017

Device Name and Classification

Common Name:Optical Coherence Tomography System
Proprietary Name:iVue
Classification Name:Tomography, Optical Coherence
Product Code:OBO, HLI
Regulation Number:21 CFR§ 886.1570
Device Class:II

Predicate Device

Company:Optovue, Inc.
Device:iVue with Normative Database (K121739)

Intended Use

The iVue is an optical coherence tomography system intended for in vivo imaging, axial crosssectional, three-dimensional imaging and measurement of anterior and posterior ocular

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structures. There is no change in the intended use between the predicate i Vue device and the modified i Vue device that is the subject of this submission.

Indications For Use

Optovue has updated the iVue indications for use based on the modified ability of the software to determine the corneal epithelia and stroma layer thickness. The epithelia and stroma have been added to the current list of ocular structures that can be imaged by the iVue device. The complete, updated indication statement is provided below:

The iVue is a non-contact, high resolution tomographic imaging device. It is intended for in vivo imaging, axial cross-sectional, and three-dimensional imaging and measurement of anterior and posterior ocular structures, including retina, retinal nerve fiber layer, ganglion cell complex (GCC), optic disc, cornea, corneal epithelia, corneal stroma and anterior chamber of the eye. With the integrated normative database. the iVue is a quantitative tool for the comparison of retina, retinal nerve fiber layer, ganglion cell complex, and optic disc measurements to a database of known normal subjects. The iVue is indicated for use as a device to aid in the diagnosis, documentation, and management of ocular health and diseases in the adult population.

Device Description

The iVue is used to capture, store, display and print spectral domain-optical coherence tomography (SD-OCT) images of the posterior and anterior structure of the eye. The device software includes a Normative Database (NDB), consisting of OCT data from a range of known normal subjects that can be used to compare a new patient's measurements in relation to the normal distribution.

iVue is a computer-controlled ophthalmic imaging system using either a laptop computer or "All-in-One" computer. For laptop systems there are two control box options of 120 or 230 volts. The control box interfaces between the motorized table column and the medical-grade power supply for the computer.

iVue System Key Functional Components

The iVue system contains the following hardware components:

  • . Scanner Head: the scanner is the main component of the iVue system. It is used to view and scan the patient's eye, collect the OCT signal, and send it to the computer for processing.
  • . Computer: the system computer, either a laptop or All-in-One ("AIO"), which includes the computer and monitor in one unit), is approved for medical use. It supports scanner operation and processes, stores and displays exam data through the application software. The searchable iVue database stores and organizes patient and exam data.
  • . Control Box: the control box supports operation of the scanner and contains the backup hard disk.
  • Joystick and Chinrest Assembly: the joystick moves the scanner left and right, forward and back, and aligns it with the patient's eye to capture the scan.

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  • . Footswitch (optional): the footswitch provides another way to capture scans, including autoadjustment, capture and saving.
  • . Motorized Table (optional): a motorized table is optional. Customers may order the table in two input voltages of 120V or 230V.
  • . Cornea Adapter Module: the cornea lens adapter is attached to the front of the instrument to enable the iVue to image the cornea and anterior chamber of the eye.

Comparison of Technological Characteristics with the Predicate Device

The iVue with modified software is substantially equivalent to the iVue predicate device (cleared by FDA in K121739 on January 18, 2013). The intended use, mechanism of action, subassemblies, and key components remain the same. The modified software uses equivalent optical coherence tomography and segmentation technology as the predicate. The iVue device has been updated in the following ways:

    1. A software modification allows automated segmentation of the posterior corneal epithelium boundary to provide the thickness of the epithelial layer. This capability, in conjunction with previously-cleared full cornea thickness measurement (i.e., "pachymetry"), also allows the software to automatically calculate the thickness of the stroma layer. Previously, the thickness of the epithelial and stroma layers could be manually measured using digital calipers in the iVue software. Consequently, the proposed software changes will automate the manual process of measuring the corneal epithelium and stroma layer thickness that could be performed using the previously cleared iVue software and provide color thickness "maps" of those layers.
    1. There were several changes to the iVue device that did not require 510(k) premarket clearance when made. These include changing the Line Scan Camera communication from gigabit Ethernet to USB 3. removal of redundant LCD monitor from the scanner head. addition of an "All-in-One" computer option, support for Windows 7 operating system, updated reports and other minor software changes.

Risk Analysis

The risk management process at Optovue complies with EN ISO 14971:2012 "Medical devices -- Application of risk management to medical devices." As required by this standard, risk analyses are conducted according to defined procedures, using experienced, qualified personnel from multiple functions throughout the organization with prior experience in risk assessment.

The i Vue Hazard Analysis was updated by the same qualified personnel who re-assessed the device with respect to all changes. Potential hazards were mitigated through the device design, software controls and user instructions and any mitigations were subsequently verified and validated. All of the identified hazards were mitigated to an acceptable level of risk. The potential benefits to patients outweigh the low residual risk after modifying the iVue software to enable automated thickness measurement of the corneal epithelia and stroma layers.

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Performance Data

The following performance data were provided in support of the substantial equivalence determination:

Electrical Safety and Electromagnetic Compatibility (EMC) The iVue device has been tested according to IEC 60601-1 and IEC 60601-1-2 standards and was found to meet all requirements.

Software Verification and Validation Testing

Device software was verified and validated to support the indications for use according to IEC 62304:2006 "Medical device software – Software life cycle processes" and FDA's "General Principles of Software Validation: Final Guidance for Industry and FDA Staff." In accordance with the FDA guidance document "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, May 11, 2005," documentation was provided that demonstrates the software changes performed as intended, met acceptance criteria, and did not have a negative impact on product performance, overall product safety, or patient safety.

The software for this device was determined to be a "moderate" level of concern, since a malfunction of, or a latent design flaw in the software device could lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that would likely lead to minor injury. There was no change in the level of concern from the predicate iVue device.

Two clinical studies were performed to evaluate the repeatability and reproducibility and agreement to manual measurement of the iVue pachymetry scan for the corneal thickness (pachymetry), corneal epithelial thickness, and corneal thickness mapping in normal subjects and corneal patients. Overall, the studies showed good repeatability and reproducibility for all study groups, all map zones, and for all 3 parameters evaluated and analyses demonstrating agreement of the automated corneal epithelial thickness segmentation.

Clinical Evaluation

Two clinical studies were conducted to demonstrate substantial equivalence:

1. Clinical Study for Repeatability and Reproducibility (R&R) of Corneal Epithelial Thickness Mapping with iVue SD-OCT

The objective of this clinical study was to evaluate the repeatability and reproducibility of the modified iVue software for the corneal thickness (pachymetry), the epithelial thickness, and the stromal thickness mapping using the ETM 6mm scan in normal subjects and corneal patients based on a crossed-study design and crossed random-effects ANOVA model.

A heterogeneous population of qualified study subjects was evaluated and included a Normal Subjects group (12 subjects), a Corneal Patients group (47 subjects) further stratified into 4 subgroups: Contact Lens (12 subiects). Drv Eve (11 subjects). Post-Refractive Surgerv (LRS) (12 subjects), and Keratoconus (KCN) (12 subjects). The study inclusion criteria required subjects who were 18 years of age or older, able to provide consent, and were

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willing to complete the required examinations. In addition, subjects were qualified based on a history or clinical diagnosis of one or more of the following conditions:

  • . Dry eye patients with no history of refractive surgery
  • Contact lens patients without complications, refractive surgery or dry eye
  • Post-laser refractive surgery patients with 1 month post-surgery without complications ●
  • . Keratoconus patients with a clinical diagnosis of keratoconus in the study eye

The study exclusion criteria excluded those with the inability to complete the required SD-OCT scans (e.g., unable to fixate due to poor vision).

Three iVue devices were used. The same scanning protocol with device-specific designated operator was implemented to scan each qualified subject on 3 different devices, with 3 repeated epithelial thickness scans per device. Based on a crossed-study design, each study subject was imaged with all three iVue/operator pairs, and within each iVue/operator pair, at least three scans were acquired with the operator realigning the instrument on the study eve for each scan acquisition. To ensure realignment for each scan, the operator asked the test subject to sit back after a scan acquisition and then reposition for the next scan.

The evaluated ETM 6 mm scan showed good performance across all study groups in terms of ease of acquisition (no subjects excluded due to inability to perform the scan quality.

Seventy-one out of 598 total acquired scans (11.9%) were excluded from R&R analysis due to the following scan quality issues: decentration of the scan, eyelid artifacts, cropped OCT image, low SSI and motion artifacts. The percentage of disqualified scans was similar across Normal eyes (10.7%) and Corneal Patients eyes (12.1%). The distribution of non-qualifying scans across three different device/operator pairs was also similar: 20/194 (10.3%). 23/199 (11.6%) and 28/205 (13.6%) accordingly for iVue #24220. iVue #20847 and iVue #20779.

Out of 527 scans qualified for final analysis, 40 (7.6%) required manual edits of the segmentation lines. Manual edits were not required in Normal eyes scans, and ranged from 2.8% in Contact Lens sub-group to 17.9% in KCN sub-group, with similar distribution between the 3 iVue devices. For qualified scans, the operators reviewed the thickness maps for obvious segmentation error and reviewed the individual corneal meridian images to verify segmentation for erroneous maps. Segmentation edit tools were used to perform manual correction and then the epithelial map was reprocessed. Noticeable segmentation errors were manually corrected by the operator and marked for "Manual Correction" in the case report form. Scans with manual correction qualified for R&R data analysis.

A total of 59 subjects included in the data analysis had a demographic distribution by ethnicity that was majority Caucasian (40.7%), followed by Asian (25.4%), Hispanic (20.3%), African American (8.5%), and Other/Combined (5.1%). There was fair distribution of gender with 25 (42%) male and 34 (58%) female subjects enrolled.

Age distribution of Normal and Corneal Patient groups and subgroups is listed in table below. Age distribution was similar in Normal vs Corneal Patient group (total).

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Age by CategoryMinMedianMeanMaxSD
Normal1843426315.7
Corneal Patients (total)1840457916.9
Contact Lens Group2036385810.8
Dry Eye Group3062577918.8
Post Laser Refractive Surgery Group3047507818.7
Keratoconus Group1936396314.7

Age distribution for all subjects by enrollment Category.

Corneal Patients Study Group Characterization

Contact Lens Group
All subjects in the Contact Lens group wore soft contact lens regularly for 8 ormore hours per day and for at least 3 months at the time of enrollment. Theduration and the daily wear of contact lens are summarized below.

Contact lens wear data for the Contact Lens study group.

Contact Lens WearMinMedianMeanMaxSD
Duration (years)21111206.3
Hours/Day81112183.6
Dry Eye GroupFor the Dry Eye group, the severity of the dry eye condition for each studysubject was documented using Ocular Surface Disease Index (OSDI) score with a
scale from 0 to 100 (mild to severe) and Tear Break Up Time (TBUT). The
distribution of the OSDI score and TBUT for this group are summarized below.

OSDI Score and Tear Break Up Time (TBUT) distribution of the Dry Eye study group.

Dry EyeMinMedianMeanMaxSD
ODSI Score14.654.548.883.321.5
TBUT (seconds)177103
Post-LRS GroupFor the Post LRS group, the majority (75%) had LASIK procedure versus the PRK procedure (25%), mainly for myopic vision correction (83.3%) and most had the procedure done at least 1 year or more prior to testing (91.7SD of 3.9108 scans%). The summary details are shown in Table below.
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ProcedureTotal% Total
LASIK975
PRK325
CorrectionTotal% Total
Myopic1083.3%
Hyperopic18.3%
Astigmatism18.3%
Duration since procedure
> 1yr1191.7%
> 3mo18.3%

Clinical data for Post LRS study group

KCN GroupThe subjects in the KCN group all had clinical diagnosis of keratoconus. The clinical signs and severity of keratoconus for the study group are summarized in Table 7.5.4a and further details on corneal curvature are summarized in Table 7.5.4b. In addition to one subject had INTACS implant, we identified another subject in the KCN sub-group had PK (penetrating keratoplasty) five years prior to the study visit in the study eye. There were no other surgical treatments in the study eyes. (i.e., Cross linking)
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KCN group distribution by clinical signs and severity

Clinical SignsTotal% Total
Slit lamp exam758.3%
Topographic patterns1191.7%
Slit lamp exam & Topographic patterns650%
Retinoscope reflex216.7%
SeverityTotal% Total
Mild216.7%
Moderate866.7%
Severe*216.7%

Distribution of Steep K and Delta K (difference between Steep K and Flat K) in KCN group.

Corneal CurvatureMinMedianMeanMaxSD
Steep K42.14948.1543.9
Delta K0.62.32.44.31.1

Summary statistical parameters, including the mean, standard deviation (SD), range (minimum and maximum), Repeatability SD, Reproducibility SD, Reproducibility covariance (COV) and Reproducibility Limit for pachymetry, epithelial thickness and stromal thickness for Normal Patients, Corneal Patients, and Corneal Patient study subgroups is provided in the following tables. Repeatability standard deviation was similar to the Reproducibility standard deviation for all study parameters and therefore is not detailed separately in the summary tables below.

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Pachymetry

Normal Group (N scans=108)
MeanSDMinMaxRepeatabilitySDReproducibilitySDCOVLimit*
Zonal Parameters
C_2_Pachy538.119.4506.8588.41.72.20.4%6.0
T_2_5_Pachy546.322.5503.2604.42.82.90.5%8.0
ST_2_5_Pachy564.023.2528.4628.53.73.90.7%10.9
S_2_5_Pachy577.322.4542.1642.64.44.70.8%12.9
SN_2_5_Pachy576.021.3543.4644.15.15.10.9%14.2
N_2_5_Pachy563.021.4532.5630.33.83.80.7%10.6
IN_2_5_Pachy551.620.2520.0607.02.32.70.5%7.4
I_2_5_Pachy544.119.7506.4592.52.12.70.5%7.5
IT_2_5_Pachy540.321.1499.7590.42.12.30.4%6.4
T_5_6_Pachy565.125.0512.9631.23.83.90.7%10.7
ST_5_6_Pachy593.424.8553.7667.65.65.81.0%16.0
S_5_6_Pachy613.923.8573.7685.36.36.81.1%18.7
SN_5_6_Pachy609.123.6570.6685.97.67.71.3%21.3
N_5_6_Pachy589.424.3550.3666.25.25.20.9%14.5
IN_5_6_Pachy573.422.9538.4635.33.73.70.7%10.4
I_5_6_Pachy564.722.1523.2621.03.33.50.6%9.8
IT_5_6_Pachy557.124.0508.5616.43.83.80.7%10.6

Table 1a. Pachymetry measurements - Normal group

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Corneal Patients Group (Pooled) (N scans=419)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Pachy507.549.2389.4678.73.33.60.7%10.0
T_2_5_Pachy521.346.4415.6694.73.83.80.7%10.6
ST_2_5_Pachy541.246.6439.5717.94.74.80.9%13.2
S_2_5_Pachy554.347.2445.1726.25.35.41.0%15.0
SN_2_5_Pachy551.346.1445.1723.05.75.81.0%16.0
N_2_5_Pachy538.044.9439.1704.95.05.21.0%14.4
IN_2_5_Pachy524.746.3430.3687.34.24.50.9%12.6
I_2_5_Pachy513.350.7404.7679.63.33.70.7%10.3
IT_2_5_Pachy510.349.9386.3676.83.53.70.7%10.2
T_5_6_Pachy545.244.3443.6719.95.05.00.9%14.0
ST_5_6_Pachy575.146.8461.1747.76.76.81.2%18.8
S_5_6_Pachy595.648.7478.4757.88.68.81.5%24.4
SN_5_6_Pachy587.646.7482.7759.08.68.81.5%24.4
N_5_6_Pachy568.243.3473.0733.06.56.61.2%18.2
IN_5_6_Pachy553.342.9460.6711.25.25.51.0%15.1
I_5_6_Pachy540.447.7444.2707.95.65.81.1%15.9
IT_5_6_Pachy533.247.0414.2700.25.85.91.1%16.3

Table 1b. Pachymetry measurement – Corneal Patients pooled group

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Contact Lens Group (N scans=108)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Pachy513.440.0425.5589.01.62.10.4%5.9
T_2_5_Pachy522.740.5432.1597.92.52.80.5%7.6
ST_2_5_Pachy540.142.5444.5630.93.93.90.7%10.7
S_2_5_Pachy553.643.5456.2651.04.74.70.9%13.1
SN_2_5_Pachy551.442.1455.4641.84.74.70.8%12.9
N_2_5_Pachy538.340.3449.3620.23.73.70.7%10.2
IN_2_5_Pachy527.339.0444.9596.32.42.70.5%7.6
I_2_5_Pachy520.139.3436.5588.61.92.90.6%7.9
IT_2_5_Pachy516.839.5430.4586.01.92.70.5%7.6
T_5_6_Pachy541.441.7443.6618.73.73.70.7%10.2
ST_5_6_Pachy569.445.7461.1667.15.45.40.9%14.9
S_5_6_Pachy591.747.9481.7700.77.37.41.2%20.4
SN_5_6_Pachy585.944.7483.5688.27.67.81.3%21.7
N_5_6_Pachy565.341.3473.6652.95.15.10.9%14.2
IN_5_6_Pachy550.238.9467.8620.33.53.70.7%10.2
I_5_6_Pachy541.839.9454.5614.63.44.00.7%11.0
IT_5_6_Pachy534.140.5442.4610.33.54.10.8%11.3
Table 1c. Pachymetry measurements - Contact Lens group)
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Dry Eye Group (N scans=98)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Pachy531.740.6445.6606.03.43.80.7%10.5
T_2_5_Pachy540.336.0469.7600.93.43.50.6%9.6
ST_2_5_Pachy558.338.7485.4640.95.25.20.9%14.5
S_2_5_Pachy573.340.2502.9673.76.87.01.2%19.3
SN_2_5_Pachy570.338.0501.5669.37.47.71.3%21.3
N_2_5_Pachy558.035.6491.8644.85.86.31.1%17.4
IN_2_5_Pachy548.934.2485.9613.04.14.80.9%13.3
I_2_5_Pachy538.041.4436.0590.43.74.00.7%11.2
IT_2_5_Pachy531.844.1418.3588.63.73.70.7%10.3
T_5_6_Pachy557.136.0483.4615.24.44.50.8%12.4
ST_5_6_Pachy588.938.8518.4681.98.88.81.5%24.4
S_5_6_Pachy616.642.0550.0736.313.113.42.2%37.1
SN_5_6_Pachy607.037.6547.3725.011.612.12.0%33.4
N_5_6_Pachy586.732.4531.6680.08.18.41.4%23.3
IN_5_6_Pachy575.029.9522.1634.05.15.51.0%15.3
I_5_6_Pachy559.742.4453.6615.15.15.20.9%14.5
IT_5_6_Pachy546.448.4414.2605.35.45.41.0%14.9
Table 1d. Pachymetry measurements - Dry Eye group
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Post Laser Refractive Surgery Group (N scans=107)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Pachy504.664.5411.8678.71.51.90.4%5.2
T_2_5_Pachy521.360.9435.5694.73.23.40.6%9.3
ST_2_5_Pachy538.663.4439.5717.94.24.20.8%11.7
S_2_5_Pachy552.063.2445.1726.24.54.50.8%12.5
SN_2_5_Pachy548.063.1445.1723.04.94.90.9%13.7
N_2_5_Pachy534.961.6439.1704.94.34.40.8%12.3
IN_2_5_Pachy527.059.9432.0687.33.43.90.7%10.8
I_2_5_Pachy522.058.2433.8679.63.03.50.7%9.7
IT_2_5_Pachy516.857.8433.7676.82.93.20.6%8.8
T_5_6_Pachy548.558.9464.0719.94.95.20.9%14.3
ST_5_6_Pachy577.060.7472.5747.75.75.91.0%16.2
S_5_6_Pachy599.057.7484.3757.86.36.41.1%17.7
SN_5_6_Pachy590.858.7486.1759.07.37.31.2%20.3
N_5_6_Pachy569.158.1473.0733.06.46.41.1%17.7
IN_5_6_Pachy558.456.2460.6711.25.65.81.0%16.2
I_5_6_Pachy553.254.3465.6707.94.64.90.9%13.7
IT_5_6_Pachy543.054.1463.1700.24.75.00.9%13.7

Table 1e. Pachymetry measurements – Post-LRS group

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Keratoconus Group (N scans=106)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Pachy482.132.5389.4522.25.45.51.1%15.1
T_2_5_Pachy502.135.4415.6544.65.35.31.1%14.6
ST_2_5_Pachy529.130.6450.5567.35.55.61.1%15.5
S_2_5_Pachy539.929.3463.3576.54.95.00.9%14.0
SN_2_5_Pachy536.827.3463.6570.05.35.51.0%15.2
N_2_5_Pachy522.327.3453.1563.56.06.11.2%16.9
IN_2_5_Pachy497.231.1430.3548.05.96.11.2%16.9
I_2_5_Pachy474.738.1404.7533.34.24.40.9%12.2
IT_2_5_Pachy477.238.9386.3532.54.84.81.0%13.3
T_5_6_Pachy534.632.8461.1574.76.36.51.2%17.9
ST_5_6_Pachy566.334.6478.6608.76.46.71.2%18.6
S_5_6_Pachy576.636.2478.4623.36.66.61.2%18.4
SN_5_6_Pachy568.433.8482.7616.77.37.61.3%21.0
N_5_6_Pachy553.328.4480.2588.66.06.11.1%17.0
IN_5_6_Pachy531.228.1472.5579.06.36.51.2%17.9
I_5_6_Pachy508.234.9444.2558.98.18.11.6%22.4
IT_5_6_Pachy510.334.6431.5568.48.38.31.6%23.1

Table 1f Pachymetry measurements - KCN group

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Epithelial Thickness

Normal Group (N scans=108)
MeanSDMinMaxRepeatabilitySDReproducibility
SDCOVLimit*
Zonal Parameters
C_2_Epi52.93.447.561.20.90.91.8%2.6
T_2_5_Epi52.23.345.961.21.21.22.3%3.4
ST_2_5_Epi51.72.847.159.81.31.32.5%3.5
S_2_5_Epi52.02.847.359.91.21.22.4%3.4
SN_2_5_Epi52.93.147.661.51.21.22.2%3.3
N_2_5_Epi53.43.047.360.71.11.12.0%3.0
IN_2_5_Epi53.73.647.861.20.90.91.6%2.4
I_2_5_Epi54.03.947.765.31.01.01.8%2.8
IT_2_5_Epi53.23.946.463.41.11.12.1%3.1
T_5_6_Epi52.23.245.259.81.31.32.5%3.6
ST_5_6_Epi50.82.644.860.11.41.52.9%4.0
S_5_6_Epi50.93.043.760.71.31.42.7%3.8
SN_5_6_Epi53.03.446.962.91.21.22.3%3.4
N_5_6_Epi53.62.848.160.81.11.12.0%3.0
IN_5_6_Epi53.83.348.159.81.01.01.8%2.7
I_5_6_Epi54.13.847.966.01.31.32.3%3.5
IT_5_6_Epi53.43.646.762.41.31.32.4%3.6

Table 2a. Epithelial thickness measurements - Normal group.

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Corneal Patients Group (Pooled) (N scans=419)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Epi51.34.638.264.11.21.22.4%3.4
T_2_5_Epi51.34.739.765.21.41.42.7%3.9
ST_2_5_Epi51.74.440.663.11.31.42.7%3.8
S_2_5_Epi51.84.639.163.71.41.42.7%3.8
SN_2_5_Epi52.54.541.863.51.51.52.8%4.1
N_2_5_Epi53.14.243.169.11.41.42.6%3.9
IN_2_5_Epi52.94.141.865.61.41.42.6%3.8
I_2_5_Epi52.24.938.064.91.41.42.7%3.9
IT_2_5_Epi51.45.437.265.81.41.42.7%3.9
T_5_6_Epi51.74.540.665.21.61.73.2%4.6
ST_5_6_Epi51.54.737.964.51.71.73.4%4.8
S_5_6_Epi51.14.836.565.11.71.73.4%4.8
SN_5_6_Epi52.34.641.166.11.61.73.2%4.6
N_5_6_Epi53.44.639.272.81.61.73.1%4.7
IN_5_6_Epi53.74.341.565.91.51.62.9%4.3
I_5_6_Epi53.04.439.166.71.91.93.6%5.3
IT_5_6_Epi52.44.740.972.51.91.93.6%5.3

Table 2b. Epithelial thickness measurements – Corneal Patients pooled group

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Contact Lens Group (N scans=108)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Epi51.03.643.257.80.80.91.8%2.6
T_2_5_Epi50.63.442.356.90.91.12.1%3.0
ST_2_5_Epi50.93.443.757.21.01.12.2%3.0
S_2_5_Epi51.43.445.357.11.11.12.2%3.2
SN_2_5_Epi52.03.246.157.91.11.22.3%3.2
N_2_5_Epi51.92.945.657.60.91.02.0%2.9
IN_2_5_Epi52.02.945.457.00.80.81.6%2.3
I_2_5_Epi52.13.245.258.40.80.91.7%2.5
IT_2_5_Epi51.03.243.857.30.80.91.8%2.6
T_5_6_Epi50.82.943.355.41.11.32.6%3.7
ST_5_6_Epi51.03.344.557.81.61.73.3%4.7
S_5_6_Epi51.23.444.557.41.61.73.3%4.6
SN_5_6_Epi52.53.446.059.31.31.42.7%3.9
N_5_6 Epi52.53.246.860.31.11.32.4%3.5
IN_5_6_Epi52.73.147.260.40.91.01.9%2.7
I_5_6 Epi52.73.346.858.91.01.12.1%3.0
IT_5_6 Epi51.63.244.457.70.91.12.0%2.9

Table 2c. Epithelial thickness measurements – Contact Lens group

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Dry Eye Group (N scans=98)
MeanSDMinMaxRepeatabilitySDReproducibility
SDCOVLimit*
Zonal Parameters
C_2_Epi51.73.443.660.01.61.63.2%4.6
T_2_5_Epi50.53.342.758.61.91.93.9%5.4
ST_2_5_Epi49.94.340.659.81.81.83.6%5.0
S_2_5_Epi50.05.539.163.72.02.04.1%5.7
SN_2_5_Epi51.15.241.863.52.42.44.7%6.7
N_2_5_Epi52.14.743.769.12.12.24.3%6.1
IN_2_5_Epi52.64.641.865.62.22.24.2%6.1
I_2_5_Epi52.74.440.964.92.42.44.5%6.5
IT_2_5_Epi52.14.042.265.32.22.24.1%6.0
T_5_6_Epi50.24.242.964.62.02.14.1%5.8
ST_5_6_Epi49.15.237.960.11.92.04.1%5.5
S_5_6_Epi49.36.936.565.12.02.14.2%5.8
SN_5_6_Epi50.96.341.166.12.42.44.7%6.6
N_5_6_Epi52.86.443.772.82.52.54.8%7.0
IN_5_6_Epi52.55.041.565.72.52.54.7%6.8
I_5_6_Epi52.45.139.166.72.92.95.5%8.0
IT_5_6_Epi52.45.441.772.52.62.64.9%7.2
Table 2d. Epithelial thickness measurements - Dry Eye group
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Post Laser Refractive Surgery Group (N scans=107)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Epi54.04.642.864.10.60.71.2%1.9
T_2_5_Epi54.14.743.665.21.01.12.0%3.0
ST_2_5_Epi53.24.445.263.10.91.01.8%2.7
S_2_5_Epi52.94.544.162.20.80.81.5%2.2
SN_2_5_Epi53.44.145.661.40.70.71.4%2.1
N_2_5_Epi54.43.847.062.20.70.81.5%2.3
IN_2_5_Epi55.23.748.162.80.80.81.5%2.4
I_2_5_Epi56.13.747.363.30.80.91.5%2.4
IT_2_5_Epi55.54.844.565.80.91.01.7%2.7
T_5_6_Epi52.44.241.462.11.41.53.0%4.3
ST_5_6_Epi51.43.642.459.21.41.63.1%4.3
S_5_6_Epi51.53.742.758.01.11.22.3%3.3
SN_5_6_Epi53.03.843.558.31.01.12.0%3.0
N_5_6_Epi54.03.246.159.91.11.12.1%3.1
IN_5_6_Epi54.73.846.662.41.11.22.2%3.3
I_5_6_Epi54.93.945.263.21.41.62.9%4.4
IT_5_6_Epi54.64.240.965.51.41.62.9%4.4

Table 2e. Epithelial thickness measurements – Post-LRS group

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Keratoconus Group (N scans=106)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Epi48.64.838.258.41.41.53.0%4.1
T_2_5_Epi49.85.639.761.11.31.42.7%3.8
ST_2_5_Epi52.64.444.361.71.51.52.9%4.3
S_2_5_Epi52.74.545.161.81.31.32.4%3.6
SN_2_5_Epi53.35.044.262.21.21.22.3%3.5
N_2_5_Epi53.94.943.161.71.21.32.3%3.5
IN_2_5_Epi51.84.243.963.21.31.32.5%3.6
I_2_5_Epi48.14.638.055.81.11.22.4%3.2
IT_2_5_Epi47.05.537.258.41.21.32.7%3.5
T_5_6 Epi53.45.740.665.21.71.73.2%4.7
ST_5_6_Epi54.34.943.764.51.61.73.1%4.7
S_5_6_Epi52.14.442.160.81.81.93.6%5.2
SN_5_6 Epi52.74.541.263.81.51.63.1%4.5
N_5_6 Epi54.44.739.262.71.41.63.0%4.4
IN_5_6_Epi54.74.746.265.91.11.22.2%3.4
I_5_6_Epi51.84.642.561.21.71.73.2%4.6
IT_5_6 Epi51.15.142.762.42.12.14.1%5.8
Table 2f. Epithelial thickness measurements - KCN group)
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Stromal Thickness

Normal Group (N scans=108)
MeanSDMinMaxRepeatabilitySDReproducibility
Zonal ParametersSDCOVLimit*
C_2_Stroma485.220.0449.8539.51.62.00.4%5.4
T_2_5_Stroma494.123.1450.8555.72.42.60.5%7.1
ST_2_5_Stroma512.423.6475.9579.13.43.70.7%10.3
S_2_5_Stroma525.322.9490.9594.14.24.60.9%12.7
SN_2_5_Stroma523.221.9491.2593.84.94.90.9%13.7
N_2_5_Stroma509.621.8476.7578.93.63.60.7%10.0
IN_2_5_Stroma497.920.5463.8556.72.12.50.5%7.0
I_2_5_Stroma490.120.1450.4542.51.92.50.5%6.9
IT_2_5_Stroma487.221.7444.3540.91.92.10.4%5.8
T_5_6_Stroma512.925.4461.2581.93.63.70.7%10.2
ST_5_6_Stroma542.625.0503.9618.65.45.71.0%15.7
S_5_6_Stroma563.024.1524.2634.26.26.71.2%18.5
SN_5_6_Stroma556.024.2519.8634.57.67.61.4%21.1
N_5_6_Stroma535.724.5498.2614.05.15.10.9%14.1
IN_5_6_Stroma519.623.0482.6583.73.43.50.7%9.7
I_5_6_Stroma510.522.4468.4570.43.23.30.7%9.3
IT_5_6_Stroma503.724.3451.0567.03.63.60.7%10.1

Table 3a. Stromal thickness measurements - Normal group

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Corneal Patients Group (Pooled) (N scans=419)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Stroma456.249.7351.2630.52.83.10.7%8.5
T_2_5_Stroma470.046.8375.9646.23.53.60.8%9.9
ST_2_5_Stroma489.548.2387.3671.94.74.81.0%13.3
S_2_5_Stroma502.549.2392.3682.15.35.41.1%14.9
SN_2_5_Stroma498.848.0391.2677.45.65.61.1%15.6
N_2_5_Stroma484.946.7383.3656.94.74.81.0%13.4
IN_2_5_Stroma471.847.3372.6637.93.84.10.9%11.3
I_2_5_Stroma461.050.2361.5628.13.03.30.7%9.1
IT_2_5_Stroma458.949.5349.1627.43.23.30.7%9.1
T_5_6_Stroma493.445.2389.7672.04.85.01.0%13.9
ST_5_6_Stroma523.648.5407.4703.46.87.01.3%19.3
S_5_6_Stroma544.550.9425.5715.18.89.01.7%25.0
SN_5_6_Stroma535.348.4425.4714.48.68.91.7%24.6
N_5_6_Stroma514.845.0415.0686.66.46.41.2%17.8
IN_5_6_Stroma499.644.5400.3662.55.25.31.1%14.8
I_5_6_Stroma487.547.9397.3653.55.45.51.1%15.3
IT_5_6_Stroma480.847.5355.8649.55.25.31.1%14.7
Table 3b. Stromal thickness measurements - Corneal Patients pooled group
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Contact Lens Group (N scans=108)RepeatabilityReproducibility
MeanSDMinMaxSDSDCOVLimit*
Zonal Parameters
C_2_Stroma462.538.8373.9532.51.41.80.4%4.9
T_2_5_Stroma472.139.6378.6542.32.22.40.5%6.6
ST_2_5_Stroma489.241.8391.1573.83.53.60.7%9.9
S_2_5_Stroma502.143.3400.6594.04.44.40.9%12.3
SN_2_5_Stroma499.542.2399.9586.74.34.40.9%12.2
N_2_5_Stroma486.440.2394.2565.83.53.50.7%9.7
IN_2_5_Stroma475.338.6389.9541.12.32.60.5%7.1
I_2_5_Stroma468.038.4382.4531.71.92.60.6%7.3
IT_2_5_Stroma465.838.5376.6530.51.82.50.5%7.0
T_5_6_Stroma490.641.3389.7563.93.33.40.7%9.3
ST_5_6_Stroma518.445.2407.4610.25.35.31.0%14.8
S_5_6_Stroma540.647.7427.3645.47.17.41.4%20.5
SN_5_6_Stroma533.445.3425.4633.37.47.91.5%21.8
N_5_6_Stroma512.841.9415.0598.54.85.11.0%14.1
IN_5_6_Stroma497.539.3409.1565.43.53.60.7%10.0
I_5_6_Stroma489.139.9397.5558.73.43.80.8%10.6
IT_5_6_Stroma482.540.2385.9555.43.33.80.8%10.4
Table 3c. Stromal thickness measurements - Contact Lens group
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Dry Eye Group (N scans=98)
MinMaxRepeatabilitySDReproducibility
MeanSDSDCOVLimit*
Zonal Parameters
C_2_Stroma480.042.2390.9560.33.03.40.7%9.5
T_2_5_Stroma489.837.9414.6555.23.23.20.7%9.0
ST_2_5_Stroma508.441.4430.4600.35.25.21.0%14.4
S_2_5_Stroma523.343.5448.1633.46.86.91.3%19.0
SN_2_5_Stroma519.240.9449.0627.57.27.41.4%20.4
N_2_5_Stroma506.038.5433.2597.75.45.81.1%16.1
IN_2_5_Stroma496.437.0425.1565.93.54.30.9%11.8
I_2_5_Stroma485.443.8378.5543.43.03.30.7%9.1
IT_2_5_Stroma479.746.7358.3540.03.13.10.7%8.7
T_5_6_Stroma506.938.7426.7569.04.24.20.8%11.7
ST_5_6_Stroma539.842.2460.8641.68.68.61.6%23.8
S_5_6_Stroma567.346.5496.5697.513.413.72.4%38.0
SN_5_6_Stroma556.141.1493.4683.911.511.92.1%33.0
N_5_6_Stroma533.935.5470.6632.47.67.81.5%21.5
IN_5_6_Stroma522.532.7470.2586.04.95.21.0%14.5
I_5_6_Stroma507.345.1398.2569.75.05.11.0%14.0
IT_5_6_Stroma494.052.3355.8557.85.15.11.0%14.1
Table 3d. Stromal thickness measurements - Dry Eye group
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Post Laser Refractive Surgery Group (N scans=107)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Stroma450.666.9355.5630.51.51.80.4%5.0
T_2_5_Stroma467.263.0380.3646.23.53.70.8%10.4
ST_2_5_Stroma485.465.5387.3671.94.14.20.9%11.7
S_2_5_Stroma499.165.5392.3682.14.94.91.0%13.6
SN_2_5_Stroma494.665.1391.2677.45.05.01.0%13.9
N_2_5_Stroma480.563.4383.3656.93.94.00.8%11.2
IN_2_5_Stroma471.861.9372.6637.93.33.70.8%10.2
I_2_5_Stroma465.960.1372.4628.12.93.30.7%9.3
IT_2_5_Stroma461.360.1373.6627.43.03.20.7%8.8
T_5_6_Stroma496.159.4415.2672.05.55.91.2%16.4
ST_5_6_Stroma525.662.1422.0703.46.46.61.3%18.4
S_5_6_Stroma547.560.1428.1715.16.66.71.2%18.5
SN_5_6_Stroma537.760.2431.3714.47.57.51.4%20.7
N_5_6_Stroma515.159.4418.1686.66.86.81.3%18.9
IN_5_6_Stroma503.758.2400.3662.56.06.21.2%17.2
I_5_6_Stroma498.455.1402.8653.55.05.41.1%14.9
IT_5_6_Stroma488.455.2404.7649.54.85.11.0%14.2

Table 3e. Stromal thickness measurements – Post-LRS group

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Keratoconus Group (N scans=106)
MeanSDMinMaxRepeatabilityReproducibility
SDSDCOVLimit*
Zonal Parameters
C_2_Stroma433.531.6351.2471.94.44.41.0%12.3
T_2_5_Stroma452.433.4375.9486.64.54.61.0%12.7
ST_2_5_Stroma476.532.2398.4520.05.65.71.2%15.8
S_2_5_Stroma487.231.7406.8530.15.05.11.1%14.2
SN_2_5_Stroma483.529.9404.3521.75.35.41.1%15.1
N_2_5_Stroma468.429.8395.4513.05.45.51.2%15.4
IN_2_5_Stroma445.431.1378.9498.55.25.41.2%15.0
I_2_5_Stroma426.635.6361.5479.83.73.80.9%10.6
IT_2_5_Stroma430.235.7349.1477.44.14.11.0%11.5
T_5_6_Stroma481.233.1406.4521.25.86.01.2%16.6
ST_5_6_Stroma512.036.4423.1563.96.77.11.4%19.8
S_5_6_Stroma524.537.8425.5576.46.76.91.3%19.0
SN_5_6_Stroma515.734.5426.8565.07.37.81.5%21.7
N_5_6_Stroma498.930.7421.8533.45.75.91.2%16.5
IN_5_6_Stroma476.528.9411.9523.75.85.91.2%16.5
I_5_6_Stroma456.433.1397.3503.57.37.31.6%20.1
IT_5_6_Stroma459.232.4386.4511.76.96.91.5%19.1
Table 3f. Stromal thickness measurements - KCN groupे
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  • Reproducibility Limit is the 95% limit for the difference between measurements under the reproducibility conditions. Reproducibility Limit = 2.8 x Reproducibility SD per ISO 5725-1 and ISO 5725-6.

Summary

Overall, the study showed good repeatability and reproducibility for all study groups, all map zones, and for all 3 parameters evaluated - corneal pachymetry, corneal epithelial, and corneal stromal thickness.

2. Clinical Study for Agreement of Corneal Epithelial Thickness Mapping with iVue SD-OCT to Manual Measurement

The objective of this clinical study was to evaluate the agreement to manual measurement of the iVue with modified software with the participation of 3 study sites, each with one iVue instrument for the OCT data collection. The agreement to manual measurement of the software was evaluated based on the agreement between the software output and the manual measurements by 3 qualified graders. The manual measurements were performed with a 2section caliper tool that was available in the previously cleared iVue software.

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The agreement was assessed based on the combined group of 87 study eyes of 87 subjects, consisting of 17 normal subjects, 16 contact lens normal subjects, 18 dry eye subjects, 20 post-laser refractive surgery subjects, and 16 keratoconus subjects. No patients in the agreement study keratoconus subgroup had prior surgery.

The i Vue scan was easy to acquire. Of the 88 subjects met the enrollment criteria, only one dry eye subject was disqualified due to poor image quality. Good image quality was obtained in 75 of the 88 subjects on the first scan and therefore didn't require additional scans, another 12 subjects required 1 or 2 additional scans to yield a good quality image, and only one subject was excluded due to poor image quality.

The automatic segmentation algorithm worked well in 78 scans (90%) out of 87 total study scans and no manual editing was performed for these scans. For the 9 scans which required manual editing, 5 were from the keratoconus sub-group.

The ethnic distribution was largely Caucasian (48.9%), followed by Asian and Hispanic at 23.9% and 15.9% respectively. Majority of the subjects enrolled in the study were female. The study eyes consisted of 44 right eyes and 44 left eyes from the 88 qualified subjects.

Age DistributionMinMedianMeanMaxSD
Entire Group233438.67312.6
Normal253233.56610.4
Contact Lens253035.25811.1
Dry Eye245146.57315.3
Post Laser Refractive Surgery233838.8568.9
Keratoconus253438.06211.7

Age distribution of the combined group and each sub-group are provided in the table below, covering a wide age range.

Table: Age distribution by entire study group and by sub-groups.

Of the 16 subjects in the Contact Lens sub-group, 15 subjects wore soft contact lens and 1 subject wore hard contact lens. All subjects wore contact lens regularly for 8 or more hours per day and for at least one year at the time of enrollment. The duration and the daily wear of contact lens are summarized in table below.

Contact Lens WearMinMedianMeanMaxSD
Duration (yr)11011206.07
Hours/Day81212.6162.06

Table: Contact lens wear data for the Contact Lens sub-group.

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For the 18 subjects in the Dry Eye group, the severity of the dry eye condition for each study subject was documented using Ocular Surface Disease Index (OSDI) score with a scale from 0 to 100 (mild to severe) and Tear Break Up Time (TBUT). The distribution of the OSDI score and TBUT for the dry eye subjects are summarized in table below.

Dry EyeMinMedianMeanMaxSD
OSDI score6.320.822.240.95.28
TBUT14.84.671.83

Table: OSDI Score and Tear Break Up Time (TBUT) distribution of the Dry Eye sub-group.

For the 20 subjects in the Post LRS group, the majority (75%) had LASIK procedure versus the PRK procedure (25%), mainly for myopic vision correction (83.3%) and most had the procedure done at least 1 year or more prior to testing (83.3%). The summary details are shown in the table below.

ProcedureTotal% Total (n=20)
LASIK1575.0%
PRK525.0%
Correction
Myopic1365.0%
Hyperopic420.0%
Astigmatism00.0%
Mixed*315.0%
Duration since procedure
> 1yr1680.0%
> 3mo420.0%
> 1mo00.0%

Table: Summary of the Post LRS sub-group. * Mixed represented procedures either combining myopic correction with astigmatism correction or hyperopic correction with astigmatism correction.

The 16 subjects in the KCN sub-group all had clinical diagnosis of keratoconus. The clinical signs are provided in Table a, severity of keratoconus for the KCN subjects are summarized in Table b, and details on corneal curvature are summarized in Table c.

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Subject IDSeverityslit lampthinningslit lampprotrusionslit lampmunsonslit lampvogtslit lampfleisherslit lamprizuttitopo bow-tietoposteeptopoclaw
DS-10moderate11
DS-12mild11
DS-21moderate111
DS-29moderate1111
DS-31severe111
DS-32moderate111
DS-34severe111
DS-36moderate111
DS-37mild11
MP-08severe1
MP-14moderate1
MP-19moderate11
MP-25mild1
MP-28severe1
MP-31moderate1
K1. SHmoderate1

Table a. KCN subjects diagnosis by clinical signs.

SeverityTotal% Total (n=16)
Mild318.8%
Moderate956.3%
Severe425.0%

Table b. KCN group distribution by severity

CornealCurvatureMinMedianMeanMaxSD
Steep K41.8047.7649.6570.806.47
Delta K0.362.673.308.332.17

Table c. Distribution of Steep K and Delta K (difference between Steep K and Flat K) of the KCN sub-group.

As summarized in Table 4A, the mean of differences between the software output and the manual measurements for all zonal parameters is less than 0.7 µm (<1.3% of average epithelial thickness of 54 um) for corneal epithelial mapping, less than 1.9 µm (<0.4% of average stroma thickness of 490 µm) for corneal stroma mapping, and less than 2.3 µm (<0.4% of average corneal thickness of 543 um) for pachymetry mapping. The overall difference between the software output and the manual measurements is negligible.

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Mean ofDifferences (μm)(N = 87)EpithelialStromaPachymetry
2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone
mean0.20.40.50.30.70.7
min-0.4-0.1-0.3-1.2-0.8-0.2-1.6-0.6-0.2
max0.30.71.91.22.31.3

Table 4A. Summary of the mean of differences by measurement zone and by corneal map type.

As summarized in Tables 4B and 4C, the limits of agreement between the software output and the manual measurements for all zonal parameters are within the range of (-6.2 ~ 5.9) um for corneal epithelial mapping, within the range of (-9.7 ~ 10.4) um for corneal stroma mapping, and within the range of (-7.9 ~ 9.6) um for pachymetry mapping, indicating good agreement between the 2 methods.

Table 4B. Summary of the LOA lower bound by measurement zone and by corneal map type.

LOALower Bound(μm)(N = 87)EpithelialStromaPachymetry
2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone
mean-4.0-4.8-4.4-7.2-3.0-4.5
min-3.4-4.4-6.2-4.7-5.7-9.7-3.5-4.5-7.9
max-3.7-4.3-3.6-5.5-2.2-2.0

Table 4C. Summary of the LOA upper bound by measurement zone and by corneal map type.

LOAUpper Bound(µm)(N = 87 subjects)EpithelialStromaPachymetry
2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone2 mmzone2 to 5mmzone5 to 6mmzone
mean2.64.45.62.45.57.90.34.55.9
min4.15.23.55.72.53.8
max4.75.97.510.46.79.6

In summary, the study demonstrated good agreement between the i Vue with modified software and the manual measurements.

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Limits of Agreement

The limits of agreement of the corneal thickness mapping between the software output and manual measurements are provided for the Combined Group, and, for additional information, also for the 5 sub-groups (Normal, Contact Lens, Dry Eye, Post-LRS, and KCN) respectively.

The Bland-Altman plots for the agreement between software output and manual measurement are provided for the Combined Group and the 5 sub-groups. The Bland-Altman plot is a scatter plot of the difference between the software-based and manual methods, using manual measurements as reference as represented by the horizontal axis. Reference lines were added to the plot including that at mean differences and the upper and lower limits of agreement (LOA).

Deming regression analysis and Scatter plots for the corneal epithelial thickness between the software output and the manual measurements are provided for the Combined Group and the 5 sub-groups. Deming regression analysis on corneal epithelial thickness for the Combined Group is also provided, including intercept, confidence intervals (CI) of intercept, slope, and confidence intervals (CI) of slope.

Conclusions From Data

The conclusions drawn from the non-clinical verification tests (software, electrical safety, and EMC) and validated by clinical studies demonstrate that the iVue subject device with modified software is as safe and as effective as the legally marketed iVue predicate device.

§ 886.1570 Ophthalmoscope.

(a)
Identification. An ophthalmoscope is an AC-powered or battery-powered device containing illumination and viewing optics intended to examine the media (cornea, aqueous, lens, and vitreous) and the retina of the eye.(b)
Classification. Class II (special controls). The device, when it is an AC-powered opthalmoscope, a battery-powered opthalmoscope, or a hand-held ophthalmoscope replacement battery, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 886.9.