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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
Sponsored by
Food and Drug Administration (FDA)
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

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

Exclusion Criteria:

  1. Are under 21 years of age.
  2. Have a condition which prevents adequate images from being obtained (e.g. unstable fixation or media opacity).
  3. Have visual correction outside of the range +4 diopters (D) to -8 D.
  4. Have a history of adverse reaction to mydriatic drops.
  5. Have a predisposition to (i.e., narrow iridocorneal angle) or any history of acute angle closure glaucoma (AACG).
  6. 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).
  7. Have a dependency on oxygen support or a baseline oxygen saturation <95% (oxygen challenge participants only).
  8. Have tested positive for COVID-19 at initial enrollment or have acute or chronic photophobia as a result of contraction.
  9. 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

Experimental

Experimental

Experimental

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

First Posted
April 19, 2022
Last Updated
May 6, 2022
Sponsor
Food and Drug Administration (FDA)
Collaborators
University of Maryland, Baltimore
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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
No
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.
No
Data Monitoring Committee
No

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
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.
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
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.
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
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
Email
daniel.hammer@fda.hhs.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Zhuolin Liu, Ph.D.
Phone
301-796-7914
Email
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
Email
daniel.hammer@fda.hhs.gov
First Name & Middle Initial & Last Name & Degree
Zhuolin Liu, Ph.D.
Phone
301-796-7914
Email
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

Learn more about this trial

Adaptive Optics Retinal Imaging

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