Adaptive Optics Imaging of Outer Retinal Diseases

Recruiting

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

• Registration Number: NCT05355415
• Lead Sponsor: Food and Drug Administration (FDA)

Brief Summary

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.

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 Timeline

• Study Start: 2021-08-27
• Study First Submitted: 2022-04-19
• Study First Submitted QC: 2022-04-25
• Study First Posted: 2022-05-02
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Primary Completion: 2026-08-27
• Study Completion: 2026-08-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Outer retinal disease	Adaptive optics imaging	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.
Healthy control	Adaptive optics imaging	Age-matched healthy control subjects will undergo the same AO imaging procedures as subjects with outer retinal diseases.

Primary Outcome Measures

Name	Time	Method
PR cell function	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.	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.
Photoreceptor (PR) density	PR density will be calculated once at the AO imaging session in which PRs are the target.	PR density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes or average AOSLO frames.
Retinal pigment epithelial (RPE) cell density	RPE cell density will be calculated once at the AO imaging session in which RPE cells are the target.	RPE cell density will be calculated at specific retinal eccentricities from cells counted in average AO-OCT volumes.
RPE cell organelle motility	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.	RPE cell organelle motility will be calculated from the decorrelation time constant for cells segmented from a sequence of AO-OCT volumes.

Trial Locations

Locations (2)

NIH Clinical Center; 🇺🇸 Bethesda, Maryland, United States

Food and Drug Administration; 🇺🇸 Silver Spring, Maryland, United States