GlaucomaPhase 4NCT05344274
Retinal Blood Flow and Autoregulation
A Phase 4 study testing Indocyanine Green Angiography, Isocapnic Oxygen and Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO) in people with Glaucoma, run by University of Maryland, Baltimore at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 88 yearsHealthy volunteers can take part
- Conditions the study is for
- Glaucoma
- What is being tested?
- Indocyanine Green Angiography, Isocapnic Oxygen and Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 4 sitesUnited States
- Study dates
- 23 May 2022to Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 88 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age over 18 years
- open angle in gonioscopy (grade 3 or 4 in Shaffer classification)
- refractive error within the range of +3.00 to -8.00 diopters (4) best-corrected visual acuity 20/25 or better (5) Individuals recruited will be in one of the 3 groups:
- 1) Early Glaucoma as per Hodapp-Anderson-Parrish Criteria (54). Early glaucoma subjects specifically with visual field defects restricted to one side of the horizontal midline will be selected to allow for comparison of rates of progression in both hemifields. Individuals will need to be off of glaucoma medications for four weeks to participate in the study. 2) Pre-perimetric glaucoma defined as the presence of glaucomatous optic nerve damage (e.g., focal notching, rim thinning), RNFL defect, and the absence of a definite glaucomatous visual field defect using standard automated perimetry at the three most recent consecutive examinations. A glaucomatous visual field defect is defined as either 3 or more abnormal points with a P<0.05, of which at least 1 point has a pattern standard deviation (PSD) of P<0.01; or a PSD of P<0.05; or glaucoma hemifield test values outside the normal limits. (55,56) 3) Control group - A subject with no family history of glaucoma who has the following: a) OCT with all four quadrants within the normal range for age-matched controls, b) reliable visual fields with glaucoma hemifield test within normal limits and determined to be normal by a glaucoma specialist, and c) cup-to-disc ratio of 0.4 or lower and asymmetry of the cup to disc ratio no greater than 0.1 as determined by a glaucoma specialist.
- Control subjects will be age matched to the early glaucoma subjects.
Who cannot join
- corneal abnormalities or other conditions preventing reliable applanation tonometry
- retinal disease affecting retinal nerve fiber layer thickness such as vitreomacular traction as determined by a glaucoma specialist
- secondary glaucoma
- history of prior ocular surgery other than uncomplicated cataract surgery or laser trabeculoplasty
- inability to safely be off of glaucoma medications for 4 weeks
- inability to obtain OCT angiography data due to excessive eye motion or inability to fixate
Show all 10Show fewer
- unreliable visual fields
- any history of smoking in the past 6 months
- cataract greater than lens opacity classification system (LOCS) II Grade≥2
- diagnosis of diabetes, hypertension, or other known vascular disorder such as vasculitis
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
University of Maryland Faculty Physicians, Inc
Baltimore, Maryland, 21201
- Recruiting
University of Maryland Medical Center
Baltimore, Maryland, 21201
- Recruiting
University of Maryland, Baltimore
Baltimore, Maryland, 21201
- Recruiting
Food and Drug Administration (FDA)
Silver Spring, Maryland, 20903
About this study
Official title: Direct Measures of Retinal Blood Flow and Autoregulation as Robust Biomarkers for Early Glaucoma
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.
Read the detailed description
There is strong evidence for a vascular component in the development and progression of primary open angle glaucoma (POAG). Specifically, glaucoma is associated with impaired retinal blood flow (RBF) and autoregulation of RBF. Autoregulatory impairment may precede retinal ganglion cell (RGC) loss and has been proposed as a potentially early, reversible biomarker. The rationale underlying this proposal is that highly precise and accurate, direct measures of RBF are necessary to study dynamic changes in RBF and their effect on RGCs. Current methods of quantifying RBF remain limited as the majority of imaging modalities provide indirect, relative measurements of RBF. The investigators will directly measure RBF using two robust direct measures: erythrocyte mediated angiography flowmetry (EMAf) and multimodal adaptive optics (mAO). Both techniques allow for the highly accurate and precise measurement of RBF down to the capillary level in the human eye in vivo. The investigators hypothesize that these direct measures of determining absolute RBF will show impaired autoregulation of microvascular RBF in early glaucoma and that this will correlate with glaucomatous damage. The research program will test this hypothesis through two specific aims. In Specific Aim 1, the investigators will determine the extent of impaired autoregulation associated with early glaucoma and measure its ability to predict further glaucoma damage. In Specific Aim 2, the investigators will determine the relationship of capillary density and RGC density in glaucoma subjects and controls. The investigators predict that early glaucoma subjects will exhibit significant measurable impaired vascular autoregulation as compared to controls and that local changes in these parameters will predict structural glaucomatous deficits.
- Conditions
- Glaucoma
- Being tested
- Indocyanine Green Angiography, Isocapnic Oxygen, Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)
- Keywords
- glaucoma, retinal blood flow, erythrocyte mediated angiography, adaptive optics
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine Green AngiographyDiagnostic test
Erythrocyte Mediated Angiography with indocyanine green as well as conventional indocyanine green angiography will be conducted to determine retinal blood flow
Isocapnic OxygenBiological
Investigators will evaluate retinal blood flow (RBF) in response to oxygen supplementation at a constant level of carbon dioxide (isocapnic hyperoxia) to isolate the vascular autoregulatory response to oxygen.
Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)Diagnostic test
Investigators will image subjects with OCT as well as AO technology to determine retinal ganglion cell density, vessel density, and vessel flowrates
| Study group | Role | What they receive |
|---|---|---|
| Isocapnic Oxygen | Experimental | Investigators will evaluate retinal blood flow in response to oxygen supplementation. Receives: Diagnostic Test: Indocyanine Green Angiography; Biological: Isocapnic Oxygen; Diagnostic Test: Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autoregulation of retinal blood flow
Autoregulation of flow is measured by the percent flow difference in flow between air and oxygen
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start23 May 2022
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Osamah Saeedi, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05344274
- Sponsor's protocol ID
- HP-00055126
- Status last verified
- Nov 2025
- First submitted
- 18 Apr 2022
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Measures of Retinal Blood Flow and Autoregulation as Robust Biomarkers for Early Glaucoma
- ClinicalTrials.gov ID
- NCT05344274
- Acronym / sponsor ID
- HP-00055126
- Conditions
- Glaucoma
- Keywords
- glaucoma, retinal blood flow, erythrocyte mediated angiography, adaptive optics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 23 May 2022 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 25 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
There is strong evidence for a vascular component in the development and progression of primary open angle glaucoma (POAG). Specifically, glaucoma is associated with impaired retinal blood flow (RBF) and autoregulation of RBF. Autoregulatory impairment may precede retinal ganglion cell (RGC) loss and has been proposed as a potentially early, reversible biomarker. The rationale underlying this proposal is that highly precise and accurate, direct measures of RBF are necessary to study dynamic changes in RBF and their effect on RGCs. Current methods of quantifying RBF remain limited as the majority of imaging modalities provide indirect, relative measurements of RBF. The investigators will directly measure RBF using two robust direct measures: erythrocyte mediated angiography flowmetry (EMAf) and multimodal adaptive optics (mAO). Both techniques allow for the highly accurate and precise measurement of RBF down to the capillary level in the human eye in vivo. The investigators hypothesize that these direct measures of determining absolute RBF will show impaired autoregulation of microvascular RBF in early glaucoma and that this will correlate with glaucomatous damage. The research program will test this hypothesis through two specific aims. In Specific Aim 1, the investigators will determine the extent of impaired autoregulation associated with early glaucoma and measure its ability to predict further glaucoma damage. In Specific Aim 2, the investigators will determine the relationship of capillary density and RGC density in glaucoma subjects and controls. The investigators predict that early glaucoma subjects will exhibit significant measurable impaired vascular autoregulation as compared to controls and that local changes in these parameters will predict structural glaucomatous deficits.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Isocapnic Oxygen | Experimental | Diagnostic Test: Indocyanine Green Angiography, Biological: Isocapnic Oxygen, Diagnostic Test: Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)Investigators will evaluate retinal blood flow in response to oxygen supplementation. |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age over 18 years
- open angle in gonioscopy (grade 3 or 4 in Shaffer classification)
- refractive error within the range of +3.00 to -8.00 diopters (4) best-corrected visual acuity 20/25 or better (5) Individuals recruited will be in one of the 3 groups:
- 1) Early Glaucoma as per Hodapp-Anderson-Parrish Criteria (54). Early glaucoma subjects specifically with visual field defects restricted to one side of the horizontal midline will be selected to allow for comparison of rates of progression in both hemifields. Individuals will need to be off of glaucoma medications for four weeks to participate in the study. 2) Pre-perimetric glaucoma defined as the presence of glaucomatous optic nerve damage (e.g., focal notching, rim thinning), RNFL defect, and the absence of a definite glaucomatous visual field defect using standard automated perimetry at the three most recent consecutive examinations. A glaucomatous visual field defect is defined as either 3 or more abnormal points with a P<0.05, of which at least 1 point has a pattern standard deviation (PSD) of P<0.01; or a PSD of P<0.05; or glaucoma hemifield test values outside the normal limits. (55,56) 3) Control group - A subject with no family history of glaucoma who has the following: a) OCT with all four quadrants within the normal range for age-matched controls, b) reliable visual fields with glaucoma hemifield test within normal limits and determined to be normal by a glaucoma specialist, and c) cup-to-disc ratio of 0.4 or lower and asymmetry of the cup to disc ratio no greater than 0.1 as determined by a glaucoma specialist.
- Control subjects will be age matched to the early glaucoma subjects.
Key exclusion criteria (10 listed)
- corneal abnormalities or other conditions preventing reliable applanation tonometry
- retinal disease affecting retinal nerve fiber layer thickness such as vitreomacular traction as determined by a glaucoma specialist
- secondary glaucoma
- history of prior ocular surgery other than uncomplicated cataract surgery or laser trabeculoplasty
- inability to safely be off of glaucoma medications for 4 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indocyanine Green AngiographyErythrocyte Mediated Angiography with indocyanine green as well as conventional indocyanine green angiography will be conducted to determine retinal blood flow | Diagnostic test | Isocapnic Oxygen |
| Isocapnic OxygenInvestigators will evaluate retinal blood flow (RBF) in response to oxygen supplementation at a constant level of carbon dioxide (isocapnic hyperoxia) to isolate the vascular autoregulatory response to oxygen. | Biological | Isocapnic Oxygen |
| Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)Investigators will image subjects with OCT as well as AO technology to determine retinal ganglion cell density, vessel density, and vessel flowrates | Diagnostic test | Isocapnic Oxygen |
Primary outcome
Autoregulation of retinal blood flow
Time frame: 3 years
Autoregulation of flow is measured by the percent flow difference in flow between air and oxygen
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Indocyanine Green Angiography, Isocapnic Oxygen and Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO) in people with Glaucoma, run by University of Maryland, Baltimore at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Osamah Saeedi, MD, MS ((410) 328-5929, osaeedi@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autoregulation of retinal blood flow (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.