Retinal Blood Flow Assessment for Glaucoma

Recruiting at 3 trial locations

Overseen By Osamah Saeedi, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Must not be taking: Glaucoma medications

Disqualifiers: Corneal abnormalities, Retinal disease, Secondary glaucoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how retinal blood flow can help detect early glaucoma, a condition that damages the optic nerve and can lead to vision loss. Researchers will use special imaging techniques, including Indocyanine Green Angiography (a type of dye-based imaging) and Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO), to observe blood movement in the eyes of individuals at various stages of glaucoma. The trial involves administering Isocapnic Oxygen (a controlled oxygen therapy) and using advanced eye scans to track changes. It suits those with early signs of glaucoma, noticeable changes in the optic nerve, or healthy eyes with no family history of the condition. Participants should not have diabetes, high blood pressure, or other eye diseases. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

Will I have to stop taking my current medications?

If you have early glaucoma, you will need to stop taking your glaucoma medications for four weeks before participating in the study. If you cannot safely stop these medications, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that isocapnic oxygen, one of the treatments in this trial, is generally safe for people. Studies have examined its effects on breathing and exercise. Although these studies do not specifically address glaucoma, they have not identified any major safety issues.

This trial is in a late stage, indicating that the treatment has likely already demonstrated safety. Earlier studies typically identify and resolve significant safety concerns. Based on past research, isocapnic oxygen appears to be well-tolerated by people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this trial?

Unlike the standard treatments for glaucoma that primarily focus on lowering intraocular pressure, the use of Isocapnic Oxygen in this trial targets retinal blood flow. Researchers are excited about this approach because it offers a different mechanism by enhancing oxygen delivery to the retina, potentially preserving vision more effectively. This method could address the underlying vascular issues associated with glaucoma, offering hope for more comprehensive management of the condition.

What evidence suggests that this trial's treatments could be effective for glaucoma?

Research shows that Isocapnic Oxygen, which participants in this trial may receive, affects blood circulation. Studies have found it helps maintain steady oxygen levels by balancing blood gases. While most research focuses on general benefits for blood flow and breathing, there is interest in its impact on eye blood flow, particularly for conditions like glaucoma. By improving blood flow, it might help protect the eyes from glaucoma-related damage. However, evidence of its effectiveness specifically for glaucoma is still developing. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early or pre-perimetric glaucoma, and a control group without glaucoma. Participants must not have had ocular surgery (except cataract surgery/laser trabeculoplasty), no diabetes/hypertension/vascular disorders, no retinal diseases affecting the nerve layer, non-smokers for at least 6 months, and able to be off glaucoma meds for four weeks.

Inclusion Criteria

Open angle in gonioscopy (grade 3 or 4 in Shaffer classification)

Individuals recruited will be in one of the 3 groups:

Best-corrected visual acuity 20/25 or better

Exclusion Criteria

I have been diagnosed with secondary glaucoma.

Inability to safely be off of glaucoma medications for 4 weeks

Any history of smoking in the past 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessment of retinal blood flow and autoregulation using EMAf and mAO techniques

1-2 weeks

Treatment

Participants receive isocapnic oxygen to evaluate retinal blood flow response

3 years

Follow-up

Participants are monitored for changes in retinal blood flow and autoregulation over time

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Indocyanine Green Angiography
• Isocapnic Oxygen
• Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)

Trial Overview

The study tests how well blood flow in the retina adjusts itself in people with early-stage open-angle glaucoma using Indocyanine Green Angiography, Isocapnic Oxygen inhalation, and advanced imaging techniques like OCT and AO to potentially identify new biomarkers.

How Is the Trial Designed?

Group I: Isocapnic Oxygen Experimental Treatment 3 Interventions

Investigators will evaluate retinal blood flow in response to oxygen supplementation.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study involving 30 glaucoma patients and 21 healthy individuals, it was found that glaucoma patients have significantly reduced macular flow density in both the superficial and deep retinal plexus, indicating potential vascular changes associated with the disease.

The reduced flow density in glaucoma patients was independent of retinal thickness and nerve fiber layer measurements, suggesting that alterations in ocular blood flow may play a critical role in glaucoma development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical coherence tomography angiography analysis of macular flow density in glaucoma. Kromer, R., Glusa, P., Framme, C., et al.[2019]

Adaptive optics-optical coherence tomography (AO-OCT) provides unprecedented imaging of microscopic retinal structures, allowing visualization of details like retinal nerve fiber layers and photoreceptor mosaics that were previously undetectable.

The advanced AO-OCT system combines high lateral and axial resolution, enabling the acquisition of 3D cellular structures in the living retina, which enhances our understanding of retinal health and disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions. Zawadzki, RJ., Choi, SS., Jones, SM., et al.[2022]

In a study involving 58 patients with normal tension glaucoma and 44 healthy subjects, retinal blood flow (RBF) measurements using Doppler OCT were found to be significantly reduced in both damaged and normal hemispheres of glaucoma eyes, indicating potential for early detection.

The combination of retinal nerve fiber layer thickness (RNFLT) and RBF measurements improved diagnostic accuracy for glaucoma, achieving an area under the curve (AUC) of 0.987 in damaged hemispheres, suggesting that integrating these methods could enhance glaucoma diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glaucoma Diagnostic Performance of Retinal Blood Flow Measurement With Doppler Optical Coherence Tomography. Abe, T., Yoshioka, T., Song, Y., et al.[2022]

Optical coherence tomography angiography (OCTA) is a reliable noninvasive technique for measuring blood perfusion in the optic nerve head (ONH), showing high repeatability and reproducibility in healthy volunteers across multiple visits.

In a study involving 10 healthy eyes scanned three times, ONH perfusion measurements demonstrated low variability (coefficient of variation ≤5.2%) and strong interobserver agreement (intraclass correlation coefficient ≤0.966), indicating that OCTA can be a valuable tool in clinical ophthalmic assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography. Chen, CL., Bojikian, KD., Xin, C., et al.[2022]

Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that effectively visualizes retinal blood vessels and can detect changes in blood flow associated with glaucoma, showing reduced vessel density and loss of choriocapillaris in affected areas.

OCTA measurements correlate well with functional and structural changes in glaucoma, making it a valuable tool for diagnosing the disease, monitoring its progression, and assessing the risk of faster deterioration in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical Coherence Tomography Angiography in Glaucoma. Rao, HL., Pradhan, ZS., Suh, MH., et al.[2022]

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]

Optical coherence tomography angiography (OCT-A) is a fast, safe, and non-invasive imaging technique that provides detailed vascular maps of the retina and choroid, helping to identify abnormal blood flow in various retinal diseases.

OCT-A has shown promise in correlating with the severity of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease, although it has limitations like a narrow field of view and potential motion artifacts, indicating a need for further research to address these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical Coherence Tomography Angiography in Neurodegenerative Diseases: A Review. Tsokolas, G., Tsaousis, KT., Diakonis, VF., et al.[2022]

Intraocular pressure reduction is crucial for managing glaucoma, a leading cause of irreversible blindness, and requires tailored treatments based on disease severity and progression.

Optical coherence tomography angiography is emerging as a valuable non-invasive tool for assessing retinal capillary perfusion, which may improve understanding of the relationship between retinal health and visual field sensitivity in glaucoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical coherence tomography angiography in glaucoma: analysis of the vessel density-visual field sensitivity relationship. Holló, G.[2020]

The integration of adaptive optics (AO) with optical coherence tomography (OCT) has significantly enhanced imaging capabilities, allowing for ultrahigh 3D resolution (3 × 3 × 3 μm³) and much faster imaging speeds, making it ideal for detailed cellular imaging in the retina.

AO-OCT has enabled the visualization of cellular structures in the retina that were previously only observable through histology, providing valuable insights into conditions affecting retinal health, as demonstrated in studies measuring retinal nerve fiber layers and foveal capillaries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive optics and the eye (super resolution OCT). Miller, DT., Kocaoglu, OP., Wang, Q., et al.[2022]

The combination of Fourier-domain optical coherence tomography (FD-OCT) with adaptive optics (AO) significantly enhances the imaging quality of retinal structures, achieving a lateral resolution of approximately 4 μm and maintaining an axial resolution of about 6 μm.

This advanced AO-OCT system allows for detailed three-dimensional visualization of retinal features, including microscopic blood vessels and cone photoreceptor mosaics, which could improve diagnostic capabilities in ophthalmology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. Zawadzki, RJ., Jones, SM., Olivier, SS., et al.[2022]

This review discusses various advanced imaging techniques used to study ocular blood flow, which is important for understanding vascular dysfunction related to diseases like glaucoma.

By highlighting the strengths and limitations of these imaging methods, the review aims to help physicians better interpret research findings and their implications for ocular health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring and interpreting ocular blood flow and metabolism in glaucoma. Harris, A., Kagemann, L., Ehrlich, R., et al.[2016]

The study introduced ultrahigh-resolution adaptive optics-optical coherence tomography (UHR-AO-OCT) for detailed in vivo imaging of retinal structures, enhancing visualization of the macula and optic nerve head.

New visualization techniques were developed to improve data interpretation, including co-registering AO-OCT images with fundus photography and creating large field of view high-resolution volumes, which could aid in better understanding retinal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular resolution volumetric in vivo retinal imaging with adaptive optics-optical coherence tomography. Zawadzki, RJ., Choi, SS., Fuller, AR., et al.[2021]

Citations

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This study showed that the deoxygenation of the intercostal muscles decreased after eight weeks of RMT independent of the type of training.

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Isocapnic hyperpnea training improves performance in competitive male runners ... The improvements cannot be ascribed to improved blood oxygen delivery to muscle ...

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The Proof, Is In The Science: Respiratory Muscle Training

They found that isocapnic respiratory training increased subjects ability to control high output breathing patterns by over 200% compared to traditional types ...