Adaptive Optics Retinal Imaging

NCT05370287 | Recruiting FDA Device

• 1 other identifier: 17-062R
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Glaucoma, Primary Open Angle

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

• Retinal ganglion cell (RGC) density

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

  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).

• RGC soma diameter

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

  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).

• 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.

  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).

• 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.

  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).

Study Arms (5)

Glaucoma with oxygen

EXPERIMENTAL

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.

Other: oxygen inhalation; Device: Adaptive optics imaging

Healthy control with oxygen

EXPERIMENTAL

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.

Other: oxygen inhalation; Device: Adaptive optics imaging

Healthy control with stimulation

EXPERIMENTAL

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

Device: Adaptive optics imaging

Glaucoma

EXPERIMENTAL

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

Device: Adaptive optics imaging

Healthy control

EXPERIMENTAL

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

Device: Adaptive optics imaging

Interventions

oxygen inhalation OTHER

Subjects will breath 100% oxygen through a mask.

Glaucoma with oxygen; Healthy control with oxygen

Adaptive optics imaging DEVICE

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

Glaucoma; Glaucoma with oxygen; Healthy control; Healthy control with oxygen; Healthy control with stimulation

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Food and Drug Administration (FDA): lead
• University of Maryland, Baltimore: collaborator

Study Sites (1)

Food and Drug Administration

Silver Spring, Maryland, 20993, United States

RECRUITING

Related Publications (7)

• 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.

  PMID: 30615699 RESULT

• 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.

  PMID: 32551400 RESULT

• 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.

  PMID: 33760041 RESULT

• 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.

  PMID: 35174258 RESULT

• 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.

  PMID: 34605879 RESULT

• 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.

  PMID: 33168747 RESULT

• 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.

  PMID: 31453000 RESULT

MeSH Terms

Conditions

Glaucoma, Open-Angle

Interventions

Oxygen Inhalation Therapy

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Respiratory Therapy; Therapeutics

Study Officials

• Daniel X Hammer, Ph.D.

  Food and Drug Administration (FDA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel X Hammer, Ph.D.

CONTACT

301-796-9320; daniel.hammer@fda.hhs.gov

Zhuolin Liu, Ph.D.

CONTACT

301-796-7914; zhuolin.liu@fda.hhs.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director, Division of Biomedical Physics

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

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: May 11, 2022
• Study Start: January 22, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: For the duration of the study.
• Access Criteria: Available upon request.

Locations

US (1)