Retinal Blood Flow and Autoregulation

NCT ID: NCT05344274

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-23
• Study Completion Date: 2027-09-30

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Isocapnic Oxygen

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

Group Type: EXPERIMENTAL

Indocyanine Green Angiography

Intervention Type: DIAGNOSTIC_TEST

Erythrocyte Mediated Angiography with indocyanine green as well as conventional indocyanine green angiography will be conducted to determine retinal blood flow

Isocapnic Oxygen

Intervention Type: BIOLOGICAL

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)

Intervention Type: DIAGNOSTIC_TEST

Investigators will image subjects with OCT as well as AO technology to determine retinal ganglion cell density, vessel density, and vessel flowrates

Interventions

Indocyanine Green Angiography

Erythrocyte Mediated Angiography with indocyanine green as well as conventional indocyanine green angiography will be conducted to determine retinal blood flow

Intervention Type: DIAGNOSTIC_TEST

Isocapnic Oxygen

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.

Intervention Type: BIOLOGICAL

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. age over 18 years

2. open angle in gonioscopy (grade 3 or 4 in Shaffer classification)

3. 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.

Exclusion Criteria

1. corneal abnormalities or other conditions preventing reliable applanation tonometry

2. retinal disease affecting retinal nerve fiber layer thickness such as vitreomacular traction as determined by a glaucoma specialist

3. secondary glaucoma

4. history of prior ocular surgery other than uncomplicated cataract surgery or laser trabeculoplasty

5. inability to safely be off of glaucoma medications for 4 weeks

6. inability to obtain OCT angiography data due to excessive eye motion or inability to fixate

7. unreliable visual fields

8. any history of smoking in the past 6 months

9. cataract greater than lens opacity classification system (LOCS) II Grade≥2

10. diagnosis of diabetes, hypertension, or other known vascular disorder such as vasculitis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 88 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Osamah Saeedi

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Maryland Faculty Physicians, Inc

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Maryland, Baltimore

Baltimore, Maryland, United States

Site Status: RECRUITING

Food and Drug Administration (FDA)

Silver Spring, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Osamah Saeedi, MD, MS

Role: CONTACT

osaeedi@som.umaryland.edu

(410) 328-5929

Other Identifiers

HP-00055126

Identifier Type: -

Identifier Source: org_study_id