Adaptive Optics Retinal Imaging

Glaucoma, Primary Open Angle Clinical Trial

Official title:

Adaptive Optics Retinal Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05370287
• Other study ID #: 17-062R
• Status: Recruiting
• Phase: N/A
• Start date: January 22, 2018
• Est. completion date: September 30, 2026

Study information

• Verified date: December 2023
• Source: Food and Drug Administration (FDA)
• Contact: Daniel X Hammer, Ph.D.
• Phone: 301-796-9320
• Email: daniel.hammer[@]fda.hhs.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glaucoma, Open-Angle
• Glaucoma, Primary Open Angle

Intervention

Other:
• oxygen inhalation
Subjects will breath 100% oxygen through a mask.

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

Locations

Country	Name	City	State
United States	Food and Drug Administration	Silver Spring	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Food and Drug Administration (FDA)	University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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).
Primary	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).
Primary	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).
Primary	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).