Adaptive Optics Imaging of Outer Retinal Diseases

The objective of the study is to collect adaptive optics (AO) retinal images from human subjects with outer retinal diseases (diseases of the outer retina including photoreceptor, retinal pigment epithelium (RPE), basement membrane or choroidal pathologies) to develop new diagnostic methods, biomarkers, and clinical endpoints.

Study Overview

• Status: Recruiting
• Conditions: Age-Related Macular Degeneration; Retinal Degeneration; Retinitis Pigmentosa; Usher Syndromes; Cone Dystrophy; Rod Dystrophy; Cone Rod Dystrophy; Hydroxychloroquine Retinopathy; Late-Onset Retinal Degeneration; Rod Cone Dystrophy
• Intervention / Treatment: Device: Adaptive optics imaging

Detailed Description

Objective: The objective of the study is to collect adaptive optics (AO) retinal images from human subjects with outer retinal diseases (diseases of the outer retina including photoreceptor, retinal pigment epithelium (RPE), basement membrane or choroidal pathologies) to develop new diagnostic methods, biomarkers, and clinical endpoints.

Study Population: Up to fifty (50) healthy volunteers without eye disease (Cohort 1) and up to fifty (50) affected participants with any type of outer retinal disease (Cohort 2) will be enrolled.

Design: This is a longitudinal study protocol where participants will be imaged with investigational multimodal AO (mAO) retinal imaging systems that include optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) channels over three years. 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 cellular structures will be acquired from several retinal locations using various imaging modes.

Outcome Measures: The primary outcomes for this protocol are development of new diagnostic methods and disease biomarkers, investigation of cellular morphological and functional changes due to various outer retinal diseases, and development of new AO clinical endpoints for novel therapies.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Daniel X Hammer, Ph.D.; Phone Number: 301-796-9320; Email: daniel.hammer@fda.hhs.gov
• Study Contact Backup: Name: Zhuolin Liu, Ph.D.; Phone Number: 301-796-7914; Email: zhuolin.liu@fda.hhs.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20810
      • Recruiting
      • NIH Clinical Center
      • Contact: Catherine Cukras, M.D., Ph.D.; Phone Number: 301-435-5061; Email: cukrasc@nei.nih.gov
    • Silver Spring, Maryland, United States, 20993
      • Recruiting
      • Food and Drug Administration
      • Contact: Daniel X Hammer, Ph.D.; Phone Number: 301-796-9320; Email: daniel.hammer@fda.hhs.gov
      • Contact: Zhuolin Liu, Ph.D.; Phone Number: 301-796-7914; Email: zhuolin.liu@fda.hhs.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All study participants will be recruited from the NIH patient population.

Description

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. (Non-English speaking participants will not be enrolled into the study), and
4. Have been diagnosed with outer retinal disease or condition (Cohort 2).

Exclusion Criteria:

1. Have a condition which prevents adequate images from being obtained (e.g. unstable fixation or media opacity),
2. Have visual correction outside of the range +4 diopters (D) to -8 D,
3. Have a history of adverse reaction to mydriatic drops,
4. Have a predisposition to (i.e., narrow iridocorneal angle) or any history of acute angle closure glaucoma (AACG), or
5. Are working under the direct supervision of Drs. Hammer, Cukras and Liu, or any of the NIH/NEI AIs.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Outer retinal disease; Subjects with outer retinal disease affecting the photoreceptor-retinal pigment epithelium complex will be classified by clinical exam by an experienced retina specialist. Outer retinal disease subjects will undergo adaptive optics (AO) imaging of several macular locations.	Device: Adaptive optics imaging; Adaptive optics scanning laser ophthalmoscopy (AOSLO) and adaptive optics - optical coherence tomography (AO-OCT) retinal imaging
Healthy control; Age-matched healthy control subjects will undergo the same AO imaging procedures as subjects with outer retinal diseases.	Device: Adaptive optics imaging; Adaptive optics scanning laser ophthalmoscopy (AOSLO) and adaptive optics - optical coherence tomography (AO-OCT) retinal imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Photoreceptor (PR) density	PR density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes or average AOSLO frames.	PR density will be calculated once at the AO imaging session in which PRs are the target.
Retinal pigment epithelial (RPE) cell density	RPE cell density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes.	RPE cell density will be calculated once at the AO imaging session in which RPE cells are the target.
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 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 separated by 1-2 weeks.
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 PR cells are stimulated. For the reproducibility portion of the study, PR cell function will be quantified three times separated by 1-2 weeks.

Collaborators and Investigators

• Sponsor: Food and Drug Administration (FDA)
• Collaborators: National Eye Institute (NEI)
• Investigators: Principal Investigator: Daniel X Hammer, Ph.D., Food and Drug Administration (FDA)

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Estimated): April 25, 2024
• Study Completion (Estimated): April 25, 2024

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Ear Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Sensation Disorders; Abnormalities, Multiple; Hearing Disorders; Vision Disorders; Deaf-Blind Disorders; Hearing Loss, Sensorineural; Blindness; Hearing Loss; Deafness; Macular Degeneration; Retinal Diseases; Retinitis; Retinitis Pigmentosa; Cone-Rod Dystrophies; Usher Syndromes; Retinal Degeneration; Cone Dystrophy
• Other Study ID Numbers: 2019-CDRH-074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes