Retinal Blood Flow Assessment for Glaucoma
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Maryland, Baltimore
Must not be taking: Glaucoma medications
Disqualifiers: Corneal abnormalities, Retinal disease, Secondary glaucoma, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
The purpose of this study is to establish autoregulation of retinal blood flow in arterioles and capillaries as a biomarker for early primary open angle glaucoma.
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 data supports the effectiveness of the treatment Indocyanine Green Angiography and Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO) for glaucoma?
Research shows that Optical Coherence Tomography Angiography (OCT-A) is effective in analyzing retinal blood flow, which is important for understanding and monitoring glaucoma. Additionally, Adaptive Optics (AO) combined with OCT provides high-resolution images of the retina, helping to visualize microscopic structures and potentially detect early glaucomatous changes.12345
Is the retinal imaging technology used in the clinical trial safe for humans?
How does the treatment in the Retinal Blood Flow Assessment for Glaucoma trial differ from other treatments for glaucoma?
This treatment uses optical coherence tomography angiography (OCTA) to non-invasively measure and analyze retinal blood flow, which is unique compared to traditional glaucoma treatments that focus on reducing intraocular pressure through medication, laser, or surgery. OCTA provides detailed insights into blood flow and vessel density, potentially offering a more tailored approach to managing glaucoma progression.19101112
Eligibility Criteria
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
See 6 more
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
See 7 more
Trial Timeline
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
Treatment Details
Interventions
- Indocyanine Green Angiography (Diagnostic Test)
- Isocapnic Oxygen (Gas)
- Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO) (Diagnostic Test)
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Isocapnic OxygenExperimental Treatment3 Interventions
Investigators will evaluate retinal blood flow in response to oxygen supplementation.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland, BaltimoreBaltimore, MD
University of Maryland Faculty Physicians, IncBaltimore, MD
Food and Drug Administration (FDA)Silver Spring, MD
University of Maryland Medical CenterBaltimore, MD
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Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
References
Optical coherence tomography angiography analysis of macular flow density in glaucoma. [2019]Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT-A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients.
Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions. [2022]Adaptive optics-optical coherence tomography (AO-OCT) permits improved imaging of microscopic retinal structures by combining the high lateral resolution of AO with the high axial resolution of OCT, resulting in the narrowest three-dimensional (3D) point-spread function (PSF) of all in vivo retinal imaging techniques. Owing to the high volumetric resolution of AO-OCT systems, it is now possible, for the first time, to acquire images of 3D cellular structures in the living retina. Thus, with AO-OCT, those retinal structures that are not visible with AO or OCT alone (e.g., bundles of retinal nerve fiber layers, 3D mosaic of photoreceptors, 3D structure of microvasculature, and detailed structure of retinal disruptions) can be visualized. Our current AO-OCT instrumentation uses spectrometer-based Fourier-domain OCT technology and two-deformable-mirror-based AO wavefront correction. We describe image processing methods that help to remove motion artifacts observed in volumetric data, followed by innovative data visualization techniques [including two-dimensional (2D) and 3D representations]. Finally, examples of microscopic retinal structures that are acquired with the University of California Davis AO-OCT system are presented.
Optical Coherence Tomography Angiography in Neurodegenerative Diseases: A Review. [2022]Optical coherence tomography angiography (OCT-A) has emerged as a novel, fast, safe and non-invasive imaging technique of analyzing the retinal and choroidal microvasculature in vivo. OCT-A captures multiple sequential B-scans performed repeatedly over a specific retinal area at high speed, thus enabling the composition of a vascular map with areas of contrast change (high flow zones) and areas of steady contrast (slow or no flow zones). It therefore provides unique insight into the exact retinal or choroidal layer and location at which abnormal blood flow develops. OCTA has evolved into a useful tool for understanding a number of retinal pathologies such as diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, vascular occlusions, macular telangiectasia and choroidal neovascular membranes of other causes. OCT-A technology is also increasingly being used in the evaluation of optic disc perfusion and has been suggested as a valuable tool in the early detection of glaucomatous damage and monitoring progression.
High-resolution imaging of diabetic retinopathy lesions using an adaptive optics retinal camera. [2020]Purpose. Adaptive optics (AO) imaging is a promising high-resolution investigation technique in ophthalmology that can bring new information about the pathophysiology of diabetic retinopathy. Material and methods. Seven patients previously diagnosed with diabetic retinopathy were investigated with optical coherence tomography (OCT) scanning, OCT angiography, fundus photo, and AO retinal camera (rtx1TM, Imagine Eyes, Orsay, France). Results. The red lesions on fundus photos appeared on AO imaging as hyporeflective lesions. OCT angiography helped us to differentiate between microaneurysms and hemorrhages. Hard exudates had a heterogeneous granular appearance. Retinal oedema was proved to have a blurring effect on the AO images. In addition to this, cystic spaces were identified to have a hyporeflective demarcation line. Conclusions. AO imaging is offering a fine documentation of retinal lesions and might become an important instrument for early diagnosis of diabetic retinopathy and for explaining its pathophysiological mechanisms. Abbreviations: AO = adaptive optics, AOO = adaptive optics ophthalmoscopy, SS = swept source, OCT =optical coherence tomography, SLO = scanning laser ophthalmoscope.
Adaptive optics and the eye (super resolution OCT). [2022]The combination of adaptive optics (AO) and optical coherence tomography (OCT) was first reported 8 years ago and has undergone tremendous technological advances since then. The technical benefits of adding AO to OCT (increased lateral resolution, smaller speckle, and enhanced sensitivity) increase the imaging capability of OCT in ways that make it well suited for three-dimensional (3D) cellular imaging in the retina. Today, AO-OCT systems provide ultrahigh 3D resolution (3 × 3 × 3 μm³) and ultrahigh speed (up to an order of magnitude faster than commercial OCT). AO-OCT systems have been used to capture volume images of retinal structures, previously only visible with histology, and are being used for studying clinical conditions. Here, we present representative examples of cellular structures that can be visualized with AO-OCT. We overview three studies from our laboratory that used ultrahigh-resolution AO-OCT to measure the cross-sectional profiles of individual bundles in the retinal nerve fiber layer; the diameters of foveal capillaries that define the terminal rim of the foveal avascular zone; and the spacing and length of individual cone photoreceptor outer segments as close as 0.5° from the fovea center.
Cellular resolution volumetric in vivo retinal imaging with adaptive optics-optical coherence tomography. [2021]Ultrahigh-resolution adaptive optics-optical coherence tomography (UHR-AO-OCT) instrumentation allowing monochromatic and chromatic aberration correction was used for volumetric in vivo retinal imaging of various retinal structures including the macula and optic nerve head (ONH). Novel visualization methods that simplify AO-OCT data viewing are presented, and include co-registration of AO-OCT volumes with fundus photography and stitching of multiple AO-OCT sub-volumes to create a large field of view (FOV) high-resolution volume. Additionally, we explored the utility of Interactive Science Publishing by linking all presented AO-OCT datasets with the OSA ISP software.
Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. [2022]We have combined Fourier-domain optical coherence tomography (FD-OCT) with a closed-loop adaptive optics (AO) system using a Hartmann-Shack wavefront sensor and a bimorph deformable mirror. The adaptive optics system measures and corrects the wavefront aberration of the human eye for improved lateral resolution (~4 μm) of retinal images, while maintaining the high axial resolution (~6 μm) of stand alone OCT. The AO-OCT instrument enables the three-dimensional (3D) visualization of different retinal structures in vivo with high 3D resolution (4×4×6 μm). Using this system, we have demonstrated the ability to image microscopic blood vessels and the cone photoreceptor mosaic.
Optical Coherence Tomography Angiography in Glaucoma. [2022]Optical coherence tomography angiography (OCTA) is a relatively new, noninvasive, dye-free imaging modality that provides a qualitative and quantitative assessment of the vasculature in the retina and optic nerve head. OCTA also enables visualization of the choriocapillaris, but only in areas of parapapillary atrophy. With OCTA, the movement of red blood cells is used as a contrast to delineate blood vessels from static tissues. The features seen with OCTA in eyes with glaucoma are reduction in the superficial vessel density in the peripapillary and macular areas, and complete loss of choriocapillaris in localized regions of parapapillary atrophy (called deep-layer microvascular dropout). These OCTA changes correlate well topographically with the functional changes seen on visual field examination and structural changes seen on optical coherence tomography (OCT) (ie, parapapillary retinal nerve fiber layer changes and inner retinal layer thickness changes at macula). The OCTA measurements also have acceptable test-retest variability and well differentiate glaucomatous from normal eyes. OCTA measurements can be affected by various subject-related, eye-related, and disease-related factors. Vessel density reduction on OCTA reaches a base level (floor) at a more advanced disease stage than the structural changes on OCT and therefore has the potential to monitor progression in eyes with advanced glaucomatous damage. OCTA also adds information about glaucoma patients at risk of faster progression. OCTA, therefore, complements visual field and OCT examinations to diagnose glaucoma, detect progression, and assess risk of progression.
Measuring and interpreting ocular blood flow and metabolism in glaucoma. [2016]There is a growing body of evidence suggesting that vascular dysfunction is related to several prominent ophthalmic diseases, including glaucoma. The vast majority of studies providing data on ocular circulation and disease pathophysiology use a relatively small number of complicated ocular blood flow imaging techniques. Although these imaging technologies are not commonly used in clinical settings, understanding the medical literature characterizing ocular blood flow requires familiarity with their methodology and function. This review highlights the imaging technologies most commonly used to investigate ocular blood flow, including color Doppler imaging, confocal scanning laser ophthalmoscopic angiography with fluorescein and indocyanine green dye, Canon laser blood flowmetry, scanning laser Doppler flowmetry, and retinal photographic oximetry. Each imaging technique's ability to define vascular function and reveal pathology is discussed as are limitations inherent to each technology. The ultimate goal of this review is to provide the physician with a clinically relevant foundation for differentiating the various ocular blood flow outcome measures often presented in the literature and determine how they are related to ocular health and disease.
Glaucoma Diagnostic Performance of Retinal Blood Flow Measurement With Doppler Optical Coherence Tomography. [2022]The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes.
Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography. [2022]Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.
Optical coherence tomography angiography in glaucoma: analysis of the vessel density-visual field sensitivity relationship. [2020]Glaucoma, a well-defined group of progressive optic neuropathies is one of the leading causes of irreversible blindness worldwide. In order to stop or slow down the progression of glaucomatous vision deterioration, intraocular pressure reduction by medical, laser or surgical treatment is needed. To ensure that treatment is efficient and tailored to the actual needs both cross sectional evaluation of disease severity and measurement of rate of progression are essential. Currently staging and progression are investigated with visual field and retinal thickness measurements. Perimetry, however, is influenced by several biological factors which are not related to glaucoma, and the use of retinal thinning is limited by floor effect. Therefore, clinical application of optical retinal coherence tomography angiography, a new and rapidly developing non-invasive measurement of the capillary perfusion in the various retinal layers, respectively, is now in the focus of clinical glaucoma research. This comprehensive review summarizes the current knowledge on one of the most important research areas in optical coherence tomography angiography in glaucoma, the relationship between retinal capillary perfusion and the spatially corresponding visual field threshold sensitivity.