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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how adaptive optics imaging, which provides highly detailed pictures of the eye, can aid in understanding and treating glaucoma. Researchers are testing this imaging on different groups: healthy individuals, those with glaucoma, and those considered suspects for glaucoma. Some participants will also undergo an oxygen challenge, which involves breathing pure oxygen during the imaging. Individuals diagnosed with primary open-angle glaucoma or considered potential glaucoma cases might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance glaucoma diagnosis and treatment.

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 prior data suggests that adaptive optics imaging is safe for humans?

Research has shown that adaptive optics imaging is safe for people. This technology corrects vision errors to produce detailed images of the retina, the light-sensitive part of the eye. Studies have found that it achieves this without harming the eye.

Breathing pure oxygen, a part of the trial, has been safely used in medical treatments for many years. While very high oxygen levels can sometimes affect the eyes or lungs, this typically occurs only at much higher pressures than those used in this trial.

Overall, both adaptive optics imaging and the oxygen test have been well-tolerated in the past, with no major safety concerns reported in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about adaptive optics (AO) imaging for glaucoma because it offers a new way to visualize the eye's macular region with unprecedented detail. Unlike traditional imaging techniques, AO imaging can detect minute changes in retinal structure, potentially identifying glaucoma damage earlier. By incorporating oxygen challenges or light stimulation in some tests, this method might reveal how different conditions affect retinal health. These insights could lead to earlier diagnosis and better-targeted treatments, sparking significant interest in the medical community.

What evidence suggests that adaptive optics imaging is effective for glaucoma?

Studies have shown that adaptive optics (AO) imaging provides very clear pictures of the eye's retina. This technology helps doctors see tiny details in the eye that are usually hard to spot. Research indicates that AO offers a better view of the blood vessels in the retina, which could be important for understanding glaucoma. In this trial, some participants with glaucoma will undergo AO imaging while breathing pure oxygen, potentially offering more insight. Some studies suggest that oxygen can change blood flow in the eye, which might aid in studying and managing glaucoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel X Hammer, Ph.D.

Principal Investigator

Food and Drug Administration (FDA)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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]

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]

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]

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]

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]

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]

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]

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]

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 (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]

Citations

1. trialx.com trialx.com/clinical-trials/listings/265778/adaptive-optics-retinal-imaging-2/

Adaptive Optics Retinal Imaging | Clinical Research Trial ... The objective of the study is to collect and assess adaptive optics (AO) retinal images from human subjects in support of projects to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10817033/

Is Primary Open-Angle Glaucoma a Vascular Disease ... Adaptive optics (AO) is a new technology that enables the analysis of retinal vasculature at the cellular level in vivo. The purpose of this ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05355415

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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05370287

NCT05370287 | Adaptive Optics Retinal Imaging Outcome Measures: The primary outcomes for this protocol are qualitative and quantitative assessment of the AO images and investigation of the cellular ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4031042/

Adaptive Optics Retinal Imaging – Clinical Opportunities and ... Adaptive optics (AO) is a technique to compensate for the eye's aberrations and provide nearly diffraction-limited resolution.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2949889924000400

Adaptive optics imaging in ophthalmology This technology, adapted into ophthalmology, corrects for the eye's optical aberrations, providing extraordinarily detailed images of the retina at a cellular ...

7. nature.com nature.com/articles/s41467-024-54687-z

Ultrafast adaptive optics for imaging the living human eye We develop an ultrafast ophthalmic AO system that increases AO bandwidth by ~30× and improves aberration power rejection magnitude by 500×.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0039625723001297

Adaptive optics imaging in inherited retinal diseases This scoping review systematically identifies and summarizes clinical studies evaluating AO imaging in IRDs.