Imaging for Retinal Dystrophy

(SS-HH-OCT Trial)

Overseen By Ramiro Maldonado, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Refractive error >6 diopters, Glaucoma, Uveitis, Neurologic conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment SS-HH-OCT for retinal dystrophy?

The research shows that handheld swept-source optical coherence tomography (SS-OCT) systems, like SS-HH-OCT, have been used effectively to detect retinal changes in conditions such as Usher syndrome and retinopathy of prematurity. These systems offer a wide field of view and improved scanning efficiency, which can help in evaluating retinal diseases. ^{1 2 3 4 5}

Is the handheld swept-source optical coherence tomography (SS-HH-OCT) safe for use in humans?

The available research does not provide specific safety data for the handheld swept-source optical coherence tomography (SS-HH-OCT) in humans, but it is a non-contact imaging tool, which generally suggests a low risk of harm. ^{2 3 4 6 7}

How does the imaging treatment for retinal dystrophy differ from other treatments?

This treatment uses advanced optical coherence tomography (OCT) technology, which provides high-speed, high-resolution imaging of the retina, allowing for detailed visualization of retinal structures. Unlike traditional treatments that may focus on managing symptoms, this imaging technique helps in early detection and monitoring of retinal changes, potentially before significant vision loss occurs. ^{1 3 5 8 9}

Research Team

Ramiro Maldonado, MD

Principal Investigator

Duke University Eye Center

Eligibility Criteria

This trial is for neonates, infants, and children showing signs of early-onset inherited retinal dystrophies (EORDs). Participants will be included based on their need for clinically-indicated eye exams or procedures related to EORDs. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I am under 9 years old.

My eyes do not have any retinal problems.

I have a genetic condition confirmed by specific gene changes.

Exclusion Criteria

Refractive error higher than 6.00 diopters

I do not have eye conditions like glaucoma or uveitis that could affect study results.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo SS-HH-OCT imaging during clinically-indicated eye examinations or procedures to identify signs of photoreceptor development and degeneration.

Up to 24 months

Visits coincide with clinically-indicated eye examinations

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures, with data collected for future studies.

4 weeks

Treatment Details

Interventions

• SS-HH-OCT

Trial Overview The study is testing the effectiveness of a new high-resolution imaging system called SS-HH-OCT in diagnosing and monitoring retinal dystrophy in young patients. It's an observational study where images are taken during routine eye checks.

Participant Groups

Group I: Group 3 - Control participants Active Control 1 Intervention

10 participants with normal retinal anatomy undergoing anesthesia for strabismus surgery as part of their clinically-indicated care.

Group II: Group 2 - Non-progressive Inherited Retinal Dystrophy (IRD) Active Control 1 Intervention

20 participants with non-progressive IRD (n=20), a subset of IRDs that are less frequently referred to Duke Clinics

Group III: Group 1 - Progressive Inherited retinal dystrophy (IRD) Active Control 1 Intervention

50 participants with progressive IRD; the most common IRD seen at Duke Clinics.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study involving 14 patients with various types of retinal dystrophy and 7 normal controls, high-resolution imaging revealed a significant reduction in both foveal and macular retinal thickness in dystrophy patients compared to controls, indicating structural changes associated with the disease.

Specifically, the outer retinal layer (ORL) thickness was severely decreased by 45% in retinal dystrophy patients, while the inner retinal layer (IRL) showed a smaller, non-significant decrease of 11%, highlighting the more pronounced impact of retinal dystrophy on the outer layers of the retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of Fourier-domain optical coherence tomography of retinal dystrophy patients. Lim, JI., Tan, O., Fawzi, AA., et al.[2022]

A study of 15 patients with cone dystrophy identified four categories of outer retinal changes using spectral-domain optical coherence tomography (SD-OCT), highlighting the varying degrees of structural abnormalities in the retina.

The presence of normal retinal structures in younger patients (category 0) suggests that electrophysiological tests are more effective than imaging for early diagnosis, emphasizing the need for comprehensive assessments in cone dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphologic characteristics of the outer retina in cone dystrophy on spectral-domain optical coherence tomography. Cho, SC., Woo, SJ., Park, KH., et al.[2022]

In a study of 16 pediatric patients with Usher syndrome type 1 (USH1), significant retinal alterations were detected using swept-source optical coherence tomography (SS-OCT), particularly in the outer retinal layers, which may impact visual acuity.

The most common abnormalities included disruptions in the external limiting membrane and ellipsoid zone of photoreceptors, with these disruptions being independently associated with decreased best-corrected visual acuity (BCVA), highlighting the importance of monitoring photoreceptor health in USH1 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal findings in pediatric patients with Usher syndrome Type 1 due to mutations in MYO7A gene. Subirà, O., Català-Mora, J., Díaz-Cascajosa, J., et al.[2022]

The handheld swept-source optical coherence tomography (OCT) system features a groundbreaking 105° field of view (FOV), the widest achieved in portable non-contact retinal imaging, which enhances the ability to visualize retinal diseases.

This system's spiral scanning pattern improves scanning efficiency and allows for real-time visualization, making it particularly useful for evaluating conditions like retinopathy of prematurity that affect the peripheral retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

105° field of view non-contact handheld swept-source optical coherence tomography. Ni, S., Nguyen, TP., Ng, R., et al.[2023]

A new prototype retinal swept-source OCT system was developed with a long working distance of 350 mm, making it suitable for imaging young and autistic children who may be uncomfortable with traditional imaging methods.

The system uses a compact 2f retinal scanning configuration, which reduces the number of optical elements and overall size, allowing for effective imaging in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long working distance OCT with a compact 2f retinal scanning configuration for pediatric imaging. Carrasco-Zevallos, OM., Qian, R., Gahm, N., et al.[2022]

High-resolution spectral-domain optical coherence tomography (HR-SD-OCT) is an effective tool for monitoring photoreceptor degeneration in live mouse models, allowing for precise measurement of retinal layer thickness and photoreceptor vitality.

The technique enables real-time visualization and assessment of subretinal injections, ensuring accurate delivery of therapeutic agents like adeno-associated virus (AAV) or nanoparticles, which is crucial for evaluating their efficacy and potential toxicity in preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research. Butler, MC., Sullivan, JM.[2020]

Fourier domain optical coherence tomography (FD OCT) effectively allows for noninvasive imaging of retinal structures in Rs1h-knockout mice, a model for X-linked juvenile retinoschisis, enabling the identification of retinal layers and measurement of their thickness.

The study revealed significant retinal degeneration, with approximately 30% loss of the outer nuclear layer (ONL) by 2 months of age in Rs1h-knockout mice, highlighting the potential of FD OCT for monitoring retinal health and disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo imaging of the mouse model of X-linked juvenile retinoschisis with fourier domain optical coherence tomography. Xu, J., Molday, LL., Molday, RS., et al.[2022]

The newly developed handheld swept source optical coherence tomography (SS-OCT) device offers high-speed imaging at 350 kHz with 10 µm axial resolution, making it effective for capturing detailed retinal images in just 1.4 seconds.

This technology not only allows for early detection of retinal diseases but also expands the potential for use in various settings beyond traditional clinics, such as pediatrics and military medicine, enhancing accessibility to eye care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror. Lu, CD., Kraus, MF., Potsaid, B., et al.[2022]

Ultrahigh resolution optical coherence tomography (UHR OCT) effectively visualizes intraretinal changes in macular dystrophies, revealing significant differences in photoreceptor layer integrity between adult-onset foveomacular vitelliform dystrophy (AOFVD) and Stargardt's disease (SD).

Patients with AOFVD showed mostly intact photoreceptor layers and a central foveal thickness of 142 micrometers, while those with SD exhibited significant degeneration and a reduced central foveal thickness of 94 micrometers, indicating the potential of UHR OCT for monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrahigh resolution optical coherence tomography in macular dystrophy. Wirtitsch, MG., Ergun, E., Hermann, B., et al.[2007]

References

1. United States pubmed.ncbi.nlm.nih.gov

A pilot study of Fourier-domain optical coherence tomography of retinal dystrophy patients. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Morphologic characteristics of the outer retina in cone dystrophy on spectral-domain optical coherence tomography. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Retinal findings in pediatric patients with Usher syndrome Type 1 due to mutations in MYO7A gene. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

105° field of view non-contact handheld swept-source optical coherence tomography. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Long working distance OCT with a compact 2f retinal scanning configuration for pediatric imaging. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

In vivo imaging of the mouse model of X-linked juvenile retinoschisis with fourier domain optical coherence tomography. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Ultrahigh resolution optical coherence tomography in macular dystrophy. [2007]