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Adaptive Optics Retinal Imaging

Primary Purpose

Glaucoma, Primary Open Angle

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

oxygen inhalation

Adaptive optics imaging

About this trial

This is an interventional basic science trial for Glaucoma, Primary Open Angle

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Are 21 years of age or older.
Have the ability to cooperate with instructions during adaptive optics imaging (similar to instructions given during a clinical eye exam).
Have the ability to understand and sign an informed consent.
Have been diagnosed with POAG (cohort 2).

Exclusion Criteria:

Are under 21 years of age.
Have a condition which prevents adequate images from being obtained (e.g. unstable fixation or media opacity).
Have visual correction outside of the range +4 diopters (D) to -8 D.
Have a history of adverse reaction to mydriatic drops.
Have a predisposition to (i.e., narrow iridocorneal angle) or any history of acute angle closure glaucoma (AACG).
Have any health conditions that would contraindicate oxygen supplementation, including chronic obstructive pulmonary disease (COPD), emphysema, asthma, or any other obstructive or restrictive lung disease (oxygen challenge participants only).
Have a dependency on oxygen support or a baseline oxygen saturation <95% (oxygen challenge participants only).
Have tested positive for COVID-19 at initial enrollment or have acute or chronic photophobia as a result of contraction.
Are working under the direct supervision of Dr. Hammer.

Sites / Locations

Food and Drug AdministrationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Glaucoma with oxygen

Healthy control with oxygen

Healthy control with stimulation

Glaucoma

Healthy control

Arm Description

Primary open angle glaucoma subjects as well as pre-perimetric glaucoma suspects will be classified by clinical exam by an experienced glaucoma specialist according to the American Academy of Ophthalmology Practice Patterns. Glaucoma subjects and suspects will undergo adaptive optics (AO) imaging of several macular locations. A subset of subjects will undergo oxygen challenge intervention, which involves breathing 100% oxygen through a mask during AO imaging at pre-determined retinal vessel locations.

Age-matched healthy control cohort will undergo the same AO imaging procedures as glaucoma cohort. A subset of subjects will undergo the same oxygen challenge intervention as the glaucoma cohort.

Healthy control subjects will undergo AO imaging at several macular locations while flashes of visible light stimulus are delivered.

Glaucoma subjects and suspects will undergo AO imaging at several macular locations without intervention.

Healthy control subjects will undergo AO imaging at several macular locations without intervention

Outcomes

Primary Outcome Measures

Change in Retinal blood flow (RBF) with oxygen inhalation

RBF [uL/min] will be measured from ensemble RBC velocity [mm/s] measurements from line-scan AOSLO videos and vessel diameter [mm] measurements from average AO-OCT volumes.

Retinal ganglion cell (RGC) density

RGC density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes.

RGC soma diameter

RGC soma diameter will be calculated at specific retinal eccentricities from cells segmented in average AO-OCT volumes.

Retinal pigment epithelium (RPE) cell organelle motility

RPE cell organelle motility will be calculated from the decorrelation time constant for cells segmented from a sequence of AO-OCT volumes.

Photoreceptor (PR) cell function

Photoreceptor cell (cone) function will be measured from phase changes between inner segment - outer segment junction and cone outer segment tip signals in a sequence of AO-OCT volumes collected during visible light stimulation.

Secondary Outcome Measures

Full Information

NCT ID

NCT05370287

First Posted

April 19, 2022

Last Updated

May 6, 2022

Sponsor

Food and Drug Administration (FDA)

Collaborators

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT05370287

Brief Title

Adaptive Optics Retinal Imaging

Official Title

Adaptive Optics Retinal Imaging

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 22, 2018 (Actual)

Primary Completion Date

September 30, 2026 (Anticipated)

Study Completion Date

September 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Food and Drug Administration (FDA)

Collaborators

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of the study is to collect and assess adaptive optics (AO) retinal images from human subjects in support of projects to demonstrate, advance, and enhance clinical use of AO technology.

Detailed Description

Objective: The objective of the study is to collect and assess adaptive optics (AO) retinal images from human subjects in support of projects to demonstrate, advance, and enhance clinical use of AO technology. Study Population: Fifty (50) healthy volunteers without eye disease and thirty (30) subjects with primary open angle glaucoma (POAG) will be enrolled. Design: This is an interventional study protocol where participants will be imaged with investigational multimodal AO retinal imaging systems that include optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) channels. High resolution OCT and SLO videos will be collected while the instruments automatically detect and correct for image distortion caused by ocular aberrations. In general, videos of different retinal structures will be acquired from several retinal locations using various imaging modes. Outcome Measures: The primary outcomes for this protocol are qualitative and quantitative assessment of the AO images and investigation of the cellular morphological and physiological changes due to glaucoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glaucoma, Primary Open Angle

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

One cohort of subjects with clinically diagnosed glaucoma and one cohort of age-matched healthy controls with no evidence of ocular disease

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Glaucoma with oxygen

Arm Type

Experimental

Arm Description

Arm Title

Healthy control with oxygen

Arm Type

Experimental

Arm Description

Age-matched healthy control cohort will undergo the same AO imaging procedures as glaucoma cohort. A subset of subjects will undergo the same oxygen challenge intervention as the glaucoma cohort.

Arm Title

Healthy control with stimulation

Arm Type

Experimental

Arm Description

Healthy control subjects will undergo AO imaging at several macular locations while flashes of visible light stimulus are delivered.

Arm Title

Glaucoma

Arm Type

Experimental

Arm Description

Glaucoma subjects and suspects will undergo AO imaging at several macular locations without intervention.

Arm Title

Healthy control

Arm Type

Experimental

Arm Description

Healthy control subjects will undergo AO imaging at several macular locations without intervention

Intervention Type

Other

Intervention Name(s)

oxygen inhalation

Intervention Description

Subjects will breath 100% oxygen through a mask.

Intervention Type

Device

Intervention Name(s)

Adaptive optics imaging

Intervention Description

Adaptive optics scanning laser ophthalmoscopy (AOSLO) and adaptive optics - optical coherence tomography (AO-OCT) retinal imaging

Primary Outcome Measure Information:

Title

Change in Retinal blood flow (RBF) with oxygen inhalation

Description

RBF [uL/min] will be measured from ensemble RBC velocity [mm/s] measurements from line-scan AOSLO videos and vessel diameter [mm] measurements from average AO-OCT volumes.

Time Frame

RBF will be measured in all subjects twice during a single AO imaging session - once before and once during pure oxygen inhalation. Subjects will be imaged only once; there is no longitudinal component to this outcome measure.

Title

Retinal ganglion cell (RGC) density

Description

RGC density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes.

Time Frame

RGC density will be calculated once at the AO imaging session in which RGCs are the target. For the reproducibility/longitudinal study portion, RGC density will be quantified three times over 1.5 years (visits separated by 6 months).

Title

RGC soma diameter

Description

RGC soma diameter will be calculated at specific retinal eccentricities from cells segmented in average AO-OCT volumes.

Time Frame

RGC diameter will be calculated once at the AO imaging session in which RGCs are the target. For the reproducibility/longitudinal portion of the study, RGC soma diameter will be quantified three times over 1.5 years (visits separated by 6 months).

Title

Retinal pigment epithelium (RPE) cell organelle motility

Description

RPE cell organelle motility will be calculated from the decorrelation time constant for cells segmented from a sequence of AO-OCT volumes.

Time Frame

RPE organelle motility will be calculated once at the AO imaging session in which RPE cells are the target. For the reproducibility portion of the study, RPE organelle motility will be quantified three times over six weeks (visits separated by 2 weeks).

Title

Photoreceptor (PR) cell function

Description

Time Frame

PR function will be calculated once at the AO imaging session in which photoreceptors are stimulated. For the reproducibility portion of the study, PR function will be quantified three times over six weeks (visits separated by 2 weeks).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Are 21 years of age or older. Have the ability to cooperate with instructions during adaptive optics imaging (similar to instructions given during a clinical eye exam). Have the ability to understand and sign an informed consent. Have been diagnosed with POAG (cohort 2). Exclusion Criteria: Are under 21 years of age. Have a condition which prevents adequate images from being obtained (e.g. unstable fixation or media opacity). Have visual correction outside of the range +4 diopters (D) to -8 D. Have a history of adverse reaction to mydriatic drops. Have a predisposition to (i.e., narrow iridocorneal angle) or any history of acute angle closure glaucoma (AACG). Have any health conditions that would contraindicate oxygen supplementation, including chronic obstructive pulmonary disease (COPD), emphysema, asthma, or any other obstructive or restrictive lung disease (oxygen challenge participants only). Have a dependency on oxygen support or a baseline oxygen saturation <95% (oxygen challenge participants only). Have tested positive for COVID-19 at initial enrollment or have acute or chronic photophobia as a result of contraction. Are working under the direct supervision of Dr. Hammer.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel X Hammer, Ph.D.

Phone

301-796-9320

daniel.hammer@fda.hhs.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Zhuolin Liu, Ph.D.

Phone

301-796-7914

zhuolin.liu@fda.hhs.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel X Hammer, Ph.D.

Organizational Affiliation

Food and Drug Administration (FDA)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Food and Drug Administration

City

Silver Spring

State/Province

Maryland

ZIP/Postal Code

20993

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel X Hammer, Ph.D.

Phone

301-796-9320

daniel.hammer@fda.hhs.gov

First Name & Middle Initial & Last Name & Degree

Zhuolin Liu, Ph.D.

Phone

301-796-7914

zhuolin.liu@fda.hhs.gov

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified AO images will be shared with external academic collaborators.

IPD Sharing Time Frame

For the duration of the study.

IPD Sharing Access Criteria

Available upon request.

Citations:

PubMed Identifier

30615699

Citation

Liu Z, Tam J, Saeedi O, Hammer DX. Trans-retinal cellular imaging with multimodal adaptive optics. Biomed Opt Express. 2018 Aug 14;9(9):4246-4262. doi: 10.1364/BOE.9.004246. eCollection 2018 Sep 1.

Results Reference

result

PubMed Identifier

32551400

Citation

Hammer DX, Liu Z, Cava JA, Carroll J, Saeedi O. On the axial location of Gunn's dots. Am J Ophthalmol Case Rep. 2020 Jun 1;19:100757. doi: 10.1016/j.ajoc.2020.100757. eCollection 2020 Sep.

Results Reference

result

PubMed Identifier

33760041

Citation

Liu Z, Saeedi O, Zhang F, Villanueva R, Asanad S, Agrawal A, Hammer DX. Quantification of Retinal Ganglion Cell Morphology in Human Glaucomatous Eyes. Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):34. doi: 10.1167/iovs.62.3.34.

Results Reference

result

PubMed Identifier

35174258

Citation

Soltanian-Zadeh S, Kurokawa K, Liu Z, Zhang F, Saeedi O, Hammer DX, Miller DT, Farsiu S. Weakly supervised individual ganglion cell segmentation from adaptive optics OCT images for glaucomatous damage assessment. Optica. 2021 May 20;8(5):642-651. doi: 10.1364/optica.418274. Epub 2021 May 4.

Results Reference

result

PubMed Identifier

34605879

Citation

Villanueva R, Le C, Liu Z, Zhang F, Magder L, Hammer DX, Saeedi O. Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities. Invest Ophthalmol Vis Sci. 2021 Oct 4;62(13):2. doi: 10.1167/iovs.62.13.2.

Results Reference

result

PubMed Identifier

33168747

Citation

Hammer DX, Agrawal A, Villanueva R, Saeedi O, Liu Z. Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics. Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30661-30669. doi: 10.1073/pnas.2010943117. Epub 2020 Nov 9.

Results Reference

result

PubMed Identifier

31453000

Citation

Liu Z, Kurokawa K, Hammer DX, Miller DT. In vivo measurement of organelle motility in human retinal pigment epithelial cells. Biomed Opt Express. 2019 Jul 19;10(8):4142-4158. doi: 10.1364/BOE.10.004142. eCollection 2019 Aug 1.

Results Reference

result

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Adaptive Optics Retinal Imaging

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