Adaptive Optics Imaging for Glaucoma

Overseen By Daniel X Hammer, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Food and Drug Administration (FDA)

Disqualifiers: Acute angle closure glaucoma, COPD, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Adaptive Optics Imaging for Glaucoma?

Adaptive Optics Imaging is a high-resolution technique that has been shown to provide detailed images of the retina, helping in the early diagnosis and understanding of retinal diseases like diabetic retinopathy and glaucoma. It allows for the visualization of retinal microstructures, which can be crucial for monitoring disease progression and evaluating treatment effects. ^{1 2 3 4 5}

Is Adaptive Optics Imaging safe for humans?

Adaptive Optics Imaging is generally considered safe for humans, as it is used in retinal imaging to visualize eye structures without causing harm. However, some studies have noted that light exposure during imaging can cause changes in the retina, but these are below published safety limits. ^{4 6 7 8 9}

How is the treatment Adaptive Optics Imaging different from other treatments for glaucoma?

Adaptive Optics Imaging is unique because it allows for high-resolution visualization of the retina, enabling direct observation of individual cells and structures like photoreceptors and nerve fibers, which can help in the early detection and understanding of glaucoma-related changes. ^{1 4 10 11 12}

Research Team

Daniel X Hammer, Ph.D.

Principal Investigator

Food and Drug Administration (FDA)

Eligibility Criteria

This trial is for adults over 21 with open-angle glaucoma who can follow eye exam instructions and consent to the study. It's not for those under 21, with vision correction outside +4 to -8 diopters, oxygen dependency, or certain lung diseases like COPD.

Inclusion Criteria

I have been diagnosed with primary open-angle glaucoma.

I can follow instructions during an eye exam.

Have the ability to understand and sign an informed consent

Exclusion Criteria

I do not have lung conditions like COPD, emphysema, or asthma that would prevent me from using supplemental oxygen.

I am younger than 21 years old.

Have a history of adverse reaction to mydriatic drops

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Session

Participants undergo adaptive optics (AO) retinal imaging at several macular locations using investigational multimodal AO retinal imaging systems.

1 session

1 visit (in-person)

Reproducibility Study

For reproducibility, RPE organelle motility and PR function are quantified three times over six weeks.

6 weeks

3 visits (in-person, every 2 weeks)

Longitudinal Study

RGC soma diameter and RGC density are quantified three times over 1.5 years to assess changes over time.

1.5 years

3 visits (in-person, every 6 months)

Follow-up

Participants are monitored for safety and effectiveness after imaging sessions.

4 weeks

Treatment Details

Interventions

• Adaptive Optics Imaging
• Oxygen Inhalation

Trial Overview The study tests adaptive optics retinal imaging technology on people with glaucoma. Participants will undergo AO imaging possibly combined with oxygen inhalation to assess enhancements in clinical use of AO tech.

Participant Groups

Group I: Healthy control with stimulation Experimental Treatment 1 Intervention

Healthy control subjects will undergo AO imaging at several macular locations while flashes of visible light stimulus are delivered.

Group II: Healthy control with oxygen Experimental Treatment 2 Interventions

Age-matched healthy control cohort will undergo the same AO imaging procedures as glaucoma cohort. A subset of subjects will undergo the same oxygen challenge intervention as the glaucoma cohort.

Group III: Healthy control Experimental Treatment 1 Intervention

Healthy control subjects will undergo AO imaging at several macular locations without intervention

Group IV: Glaucoma with oxygen Experimental Treatment 2 Interventions

Primary open angle glaucoma subjects as well as pre-perimetric glaucoma suspects will be classified by clinical exam by an experienced glaucoma specialist according to the American Academy of Ophthalmology Practice Patterns. Glaucoma subjects and suspects will undergo adaptive optics (AO) imaging of several macular locations. A subset of subjects will undergo oxygen challenge intervention, which involves breathing 100% oxygen through a mask during AO imaging at pre-determined retinal vessel locations.

Group V: Glaucoma Experimental Treatment 1 Intervention

Glaucoma subjects and suspects will undergo AO imaging at several macular locations without intervention.

Adaptive Optics Imaging is already approved in European Union, China, Japan for the following indications:

Approved in European Union as Adaptive Optics Imaging for:

• Retinal imaging for diagnostic purposes

Approved in China as Adaptive Optics Imaging for:

• Retinal imaging for diagnostic purposes

Approved in Japan as Adaptive Optics Imaging for:

• Retinal imaging for diagnostic purposes

Who Is Running the Clinical Trial?

Food and Drug Administration (FDA)

Lead Sponsor

Trials

184

Recruited

1,553,000+

University of Maryland, Baltimore

Collaborator

Trials

729

Recruited

540,000+

Findings from Research

Adaptive optics (AO) technology enhances retinal imaging by correcting distortions in light waves, allowing for detailed assessment of photoreceptor cells and other retinal structures in both healthy and diseased eyes.

The transition of AO from a research tool to a diagnostic instrument is underway, with potential for improved diagnosis of retinal diseases and glaucoma, although challenges like imaging quality and cost remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal imaging using adaptive optics technology. Kozak, I.[2021]

Adaptive optics (AO) imaging provides high-resolution details of retinal lesions in diabetic retinopathy, revealing features like hyporeflective lesions that correlate with red lesions seen in fundus photos.

The combination of AO imaging with OCT angiography allows for better differentiation of retinal conditions, such as identifying microaneurysms versus hemorrhages, which could enhance early diagnosis and understanding of diabetic retinopathy's mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution imaging of diabetic retinopathy lesions using an adaptive optics retinal camera. Cristescu, IE., Ochinciuc, R., Balta, F., et al.[2020]

Adaptive optics significantly enhances retinal imaging by providing excellent lateral resolution, allowing for detailed visualization of photoreceptors, blood vessels, and the optic nerve head.

A comprehensive review identified 261 publications and 389 conference abstracts, highlighting the growing importance of adaptive optics in ophthalmology for studying cellular-level details in the retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics imaging of the retina. Battu, R., Dabir, S., Khanna, A., et al.[2021]

Adaptive optics (AO) enhances retinal imaging by allowing direct visualization of photoreceptor cells and other microstructures, which is crucial for detecting early pathological changes in retinal diseases.

AO technology is being applied in clinical research for common causes of blindness, such as diabetic retinopathy and age-related macular degeneration, potentially improving diagnosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics technology for high-resolution retinal imaging. Lombardo, M., Serrao, S., Devaney, N., et al.[2022]

Adaptive Optics (AO) retinal imaging allows for detailed, non-invasive observation of retinal structures at the cellular level, enabling large-scale studies and monitoring of individual retinas over time without the need for invasive histology.

AO imaging is safe and well-tolerated by patients, making it a promising tool for clinical trials to monitor retinal diseases and therapeutic interventions, especially when combined with other imaging techniques like OCT and fluorescence imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics imaging of the human retina. Burns, SA., Elsner, AE., Sapoznik, KA., et al.[2023]

Higher retinal radiant exposures (RREs) of 1600 and 3200 J/cm² caused significant disruption of the retinal pigment epithelium (RPE) and reduced rhodopsin density in macaques, indicating potential functional impairment.

Interestingly, exposure to the lowest RRE of 400 J/cm² resulted in an increase in apparent rhodopsin density, suggesting that not all light exposures below safety limits lead to functional loss, despite RPE disruption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rod photopigment kinetics after photodisruption of the retinal pigment epithelium. Masella, BD., Hunter, JJ., Williams, DR.[2021]

An automatic algorithm for adaptive optics retinal imaging allows for effective imaging even when the subject's pupil is not perfectly round or stable, improving accessibility for various subjects.

Testing on a model eye and five human subjects demonstrated that using a larger exit pupil than the subject's actual pupil does not compromise image quality, enhancing the flexibility of retinal imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics retinal imaging with automatic detection of the pupil and its boundary in real time using Shack-Hartmann images. de Castro, A., Sawides, L., Qi, X., et al.[2018]

Exposure to 568-nm light at levels 2 to 150 times higher than routine imaging caused immediate decreases in autofluorescence of retinal pigment epithelial (RPE) cells, indicating potential retinal damage.

The study suggests that retinal damage is linked to the total average power of light exposure, regardless of the delivery method, highlighting the need for a re-evaluation of laser safety standards for visible light exposure to the retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium. Morgan, JI., Hunter, JJ., Masella, B., et al.[2021]

The adaptive optics scanning laser ophthalmoscope (AOSLO) demonstrated high precision in measuring visual sensitivity across the retina, with successful stimulus delivery to targeted locations in 90.1% of trials, indicating its efficacy for detailed retinal function testing.

Visual sensitivity was found to decrease with eccentricity from the fovea, and the AOSLO allowed for longitudinal tracking of retinal function, making it a valuable tool for studying photoreceptor health in retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics scanning laser ophthalmoscope-based microperimetry. Tuten, WS., Tiruveedhula, P., Roorda, A.[2022]

Adaptive optics (AO) imaging can significantly enhance the quality of retinal nerve fiber layer (RNFL) images, which is crucial for early detection of glaucoma, a leading cause of preventable blindness.

The development of specific image processing techniques improves the reliability of analyzing RNFL fiber texture, allowing for better assessment of neuroretinal pathologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images. Ramaswamy, G., Lombardo, M., Devaney, N.[2022]

Adaptive optics (AO) imaging systems enable the direct visualization of individual photoreceptor cells and other retinal structures, overcoming the limitations of traditional imaging methods due to optical aberrations.

This technology has significantly advanced our understanding of retinal health and diseases, providing clearer insights into the structure and function of the retina, which can improve clinical diagnosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics retinal imaging: emerging clinical applications. Godara, P., Dubis, AM., Roorda, A., et al.[2022]

Using adaptive optics scanning light ophthalmoscope (AO-SLO) imaging, researchers identified distinct patterns of retinal nerve fiber (RNF) damage in glaucoma patients, revealing details that standard optical coherence tomography (OCT) could not detect.

The study involved seven glaucoma patients and highlighted that AO-SLO could differentiate between normal and abnormal RNF bundles, suggesting its potential for monitoring disease progression and improving clinical management of glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma. Chen, MF., Chui, TY., Alhadeff, P., et al.[2022]

References

1. India pubmed.ncbi.nlm.nih.gov

Retinal imaging using adaptive optics technology. [2021]

2. Romania pubmed.ncbi.nlm.nih.gov

High-resolution imaging of diabetic retinopathy lesions using an adaptive optics retinal camera. [2020]

3. India pubmed.ncbi.nlm.nih.gov

Adaptive optics imaging of the retina. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adaptive optics technology for high-resolution retinal imaging. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Adaptive optics imaging of the human retina. [2023]

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

Rod photopigment kinetics after photodisruption of the retinal pigment epithelium. [2021]

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

Adaptive optics retinal imaging with automatic detection of the pupil and its boundary in real time using Shack-Hartmann images. [2018]

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

Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium. [2021]

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

Adaptive optics scanning laser ophthalmoscope-based microperimetry. [2022]

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

Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images. [2022]

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

Adaptive optics retinal imaging: emerging clinical applications. [2022]

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

Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma. [2022]