SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs) (SS-HH-OCT)

Ultracompact Hand-Held Swept-Source Optical Coherence Tomography (SS-HH-OCT) as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)

The goal of this observational study is to utilize a novel imaging system designed for high-resolution retinal imaging of neonates, infants and children to identify the signs of photoreceptor development and degeneration in children with early-onset inherited retinal dystrophies (EORDs). Participants will have research imaging with SS-HH-OCT at the time of clinically-indicated eye examinations or procedures. The investigators aim to establish the basis for utilization of OCT imaging in earlier diagnosis and disease monitoring in children with EORDs. This work will set data reference standards and IRD endpoints that can be used in clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Retinal Dystrophies
• Intervention / Treatment: Device: SS-HH-OCT

Detailed Description

What photoreceptor degenerative changes take place in children with early-onset inherited retinal dystrophies, and how is photoreceptor development in this patient population affected by genetic defects?

Our novel investigational SS-HH-OCT system features high scanning speed, long laser wavelength, and an ergonomic light-weight handheld design. The investigators hypothesize that imaging with this system will enable us to characterize early-onset retinal dystrophies (EORD)-associated PDCs in young children. To this end, the investigators propose the following specific aims:

Specific Aim 1: Optimize and demonstrate reproducibility of SS-HH-OCT imaging protocols to visualize photoreceptor development and degeneration in children with and without EORDs.

Specific Aim 2: Use SS-HH-OCT parameters to characterize biomarkers of foveal photoreceptor development and degeneration in children with EORDs versus healthy controls.

A total of 80 participants will be enrolled in this study. Participants' age between 0 through 8 years (<9 years).

For children with EORD, successful completion of this study will result in 1) a framework for reproducible OCT imaging; 2) characterization of biomarkers of retinal degeneration; 3) establishment of reference data by genetic variants 4) insights into foveal development. Additionally, this study will set pilot data of structure-function data and timeline of photoreceptor degeneration for future NIH funded studies.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michelle N McCall, MCAPM, BA; Phone Number: (919) 684-0544; Email: michelle.mccall@duke.edu
• Study Contact Backup: Name: Ramiro Maldonado, MD; Phone Number: (919) 684 5631; Email: ramiro.maldonado@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Eye Center
      • Contact: Michelle McCall; Phone Number: 919-684-0544; Email: mccal023@mc.duke.edu
      • Contact: Neeru Sarin; Phone Number: 9196685641; Email: neeru.sarin@duke.edu
      • Sub-Investigator: Cynthia A Toth, MD
      • Sub-Investigator: Mays Dairi, MD
      • Principal Investigator: Ramiro Maldonado, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For all participants:

• Participant's age is between 0 through 8 years (<9 years)
• Parent/legal guardian gives consents for the imaging study
• No ocular media opacities that could preclude imaging
• Refractive error equal or lower than 6 diopters

For EORD participants (Groups 1-2):

Meets clinical and molecular diagnosis of EORD (clinical determined by PI). Molecular diagnosis criteria:

• Autosomal dominant gene: One pathogenic or likely pathogenic variant that meets the clinical phenotype
• Autosomal recessive gene: two pathogenic or likely pathogenic variants in-trans which meet the phenotype.
• X-linked gene: one pathogenic or likely pathogenic variant which meets the phenotype.

For Controls (Group 3): No evidence of retinal pathology

Exclusion Criteria:

For all participants:

• Parent/legal guardian unwilling or unable to provide consent
• Refractive error higher than 6.00 diopters
• Participant has media opacities that preclude imaging
• Any non-IRD ocular condition that confound results interpretation such as glaucoma, uveitis, neurologic conditions affecting the optic nerve, etc.

For EORD participants (Groups 1-2): Does not meet molecular diagnosis criteria

For Controls (Group 3): Any suspicion of IRD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 - Progressive Inherited retinal dystrophy (IRD); 50 participants with progressive IRD; the most common IRD seen at Duke Clinics.	Device: SS-HH-OCT; The investigational swept source OCT systems with handheld UC handpieces used in this study were developed at Duke University. OCT systems are non-contact, in-vivo optical imaging technology. The OCT system creates real-time, non-invasive images of ocular microstructure. OCT devices held above or in front of the eye while the sweeping infrared OCT beam scans across the retina. In contrast to the visible light used in clinical eye examinations, because infrared light is not visible, the participant is not disturbed by the light. OCT imaging allows the capture of hundreds of B-scan (cross-sectional) images in seconds. These B-scans are then stacked to create a volume; the stack may be summed up to create a retinal image. These retinal images are similar to images acquired during retinal photography except that they were captured with infrared light and provide depth information. Each volume and B-scan image can be viewed individually to measure and analyze ocular pathology.; Other Names: Swept-source Handheld Ultracompact Optical Coherence Tomography (HH UC OCT)
Active Comparator: Group 2 - Non-progressive Inherited Retinal Dystrophy (IRD); 20 participants with non-progressive IRD (n=20), a subset of IRDs that are less frequently referred to Duke Clinics	Device: SS-HH-OCT; The investigational swept source OCT systems with handheld UC handpieces used in this study were developed at Duke University. OCT systems are non-contact, in-vivo optical imaging technology. The OCT system creates real-time, non-invasive images of ocular microstructure. OCT devices held above or in front of the eye while the sweeping infrared OCT beam scans across the retina. In contrast to the visible light used in clinical eye examinations, because infrared light is not visible, the participant is not disturbed by the light. OCT imaging allows the capture of hundreds of B-scan (cross-sectional) images in seconds. These B-scans are then stacked to create a volume; the stack may be summed up to create a retinal image. These retinal images are similar to images acquired during retinal photography except that they were captured with infrared light and provide depth information. Each volume and B-scan image can be viewed individually to measure and analyze ocular pathology.; Other Names: Swept-source Handheld Ultracompact Optical Coherence Tomography (HH UC OCT)
Active Comparator: Group 3 - Control participants; 10 participants with normal retinal anatomy undergoing anesthesia for strabismus surgery as part of their clinically-indicated care.	Device: SS-HH-OCT; The investigational swept source OCT systems with handheld UC handpieces used in this study were developed at Duke University. OCT systems are non-contact, in-vivo optical imaging technology. The OCT system creates real-time, non-invasive images of ocular microstructure. OCT devices held above or in front of the eye while the sweeping infrared OCT beam scans across the retina. In contrast to the visible light used in clinical eye examinations, because infrared light is not visible, the participant is not disturbed by the light. OCT imaging allows the capture of hundreds of B-scan (cross-sectional) images in seconds. These B-scans are then stacked to create a volume; the stack may be summed up to create a retinal image. These retinal images are similar to images acquired during retinal photography except that they were captured with infrared light and provide depth information. Each volume and B-scan image can be viewed individually to measure and analyze ocular pathology.; Other Names: Swept-source Handheld Ultracompact Optical Coherence Tomography (HH UC OCT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with abnormal microanatomy as measured by OCT reading	Presence of abnormal retinal microanatomy as measured by OCT reading	Up to 24 months
Thickness of the participants retina at the fovea and surrounding optic nerve as measured by OCT reading	Retinal thickness (microns) at the fovea and surrounding optic nerve	Up to 24 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Ramiro Maldonado, MD, Duke University Eye Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Retinal dystrophy; Inherited retinal dystrophy; Early onset retinal dystrophies (EORDS)
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Retinal Dystrophies
• Other Study ID Numbers: Pro00113941

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No