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Retinal Blood Flow and Autoregulation

Primary Purpose

Glaucoma

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Indocyanine Green Angiography
Isocapnic Oxygen
Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Glaucoma focused on measuring glaucoma, retinal blood flow, erythrocyte mediated angiography, adaptive optics

Eligibility Criteria

18 Years - 88 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Maryland Faculty Physicians, IncRecruiting
  • University of Maryland Medical CenterRecruiting
  • University of Maryland, BaltimoreRecruiting
  • Food and Drug Administration (FDA)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Isocapnic Oxygen

Arm Description

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

Outcomes

Primary Outcome Measures

Autoregulation of retinal blood flow
Autoregulation of flow is measured by the percent flow difference in flow between air and oxygen

Secondary Outcome Measures

Full Information

First Posted
April 18, 2022
Last Updated
April 30, 2023
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT05344274
Brief Title
Retinal Blood Flow and Autoregulation
Official Title
Direct Measures of Retinal Blood Flow and Autoregulation as Robust Biomarkers for Early Glaucoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2022 (Actual)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma
Keywords
glaucoma, retinal blood flow, erythrocyte mediated angiography, adaptive optics

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Isocapnic Oxygen
Arm Type
Experimental
Arm Description
Investigators will evaluate retinal blood flow in response to oxygen supplementation.
Intervention Type
Diagnostic Test
Intervention Name(s)
Indocyanine Green Angiography
Intervention Description
Erythrocyte Mediated Angiography with indocyanine green as well as conventional indocyanine green angiography will be conducted to determine retinal blood flow
Intervention Type
Biological
Intervention Name(s)
Isocapnic Oxygen
Intervention Description
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
Diagnostic Test
Intervention Name(s)
Ocular Imaging with Optical Coherence Tomography (OCT) and Adaptive Optics (AO)
Intervention Description
Investigators will image subjects with OCT as well as AO technology to determine retinal ganglion cell density, vessel density, and vessel flowrates
Primary Outcome Measure Information:
Title
Autoregulation of retinal blood flow
Description
Autoregulation of flow is measured by the percent flow difference in flow between air and oxygen
Time Frame
3 years

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
88 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Osamah Saeedi, MD, MS
Phone
(410) 328-5929
Email
osaeedi@som.umaryland.edu
Facility Information:
Facility Name
University of Maryland Faculty Physicians, Inc
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Maryland, Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Food and Drug Administration (FDA)
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20903
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

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Retinal Blood Flow and Autoregulation

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