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Peripapillary Blood Flow After Use of Anti-glaucoma Medications: An OCT Angiography Study

Primary Purpose

Glaucoma; Drugs, Normal Tension Glaucoma, Primary Open-angle Glaucoma

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Timolol Maleate
Brimonidine Tartrate
Sponsored by
Wills Eye
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Glaucoma; Drugs

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of ocular hypertension, primary open angle glaucoma, or normal tension glaucoma in the study eye(s)
  • Age 18-90
  • Best corrected visual acuity of 20/60 or better

Exclusion Criteria:

  • Current use of either brimonidine or timolol
  • Other disease, ophthalmic or systemic, that is likely to significantly affect the OCT test in the study eye(s) including:

    • More than moderate grade cataract that significantly reducing OCTA scan signal level
    • Macular degeneration other than mild drusen or pigmentary changes
    • Diabetic retinopathy other than mild background non proliferative retinopathy
    • Prior or current macular edema
    • Prior laser treatment to the retina
    • Prior retinal detachment
    • Prior central serous retinopathy
    • Prior retinal vein or artery occlusion
    • Prior inflammatory retinopathy or choroidopathy
    • Keratoconus or other corneal ectasia
    • Corneal scarring in central 4 mm
    • Prior penetrating keratoplasty
    • Ischemic optic neuropathy
    • Dementia beyond early/mild memory loss
    • History of cerebrovascular accident
    • History of severe carotid stenosis
    • History of previous ocular surgery other than non-complicated cataract extraction

Sites / Locations

  • Glaucoma Research Center - Wills Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Timolol

Brimonidine

Arm Description

Timolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once.

Brimonidine tartrate 0.2% Instillation of one drop in each eye, once.

Outcomes

Primary Outcome Measures

Changes in Vessel Density in Treatment Groups Assessed by OCT Angiography
Percent change in peripapillary vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm with the use of topical brimonidine or timolol eye drops to lower eye pressure.
Changes in Flow Index in Treatment Groups Assessed by OCT Angiography
Percent change in peripapillary Flow Index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm with the use of topical brimonidine or timolol eye drops to lower eye pressure.
Comparison of Percent Changes in Peripapillary Vessel Density in Treatment Groups Assessed by OCT Angiography
Comparison of the percent change in peripapillary vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in vessel density after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in vessel density after using topical brimonidine or timolol drops to lower eye pressure.
Comparison of Percent Changes in Peripapillary Flow Index in Treatment Groups Assessed by OCT Angiography
Comparison of the percent change in peripapillary flow index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in flow index after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in flow index after using topical brimonidine or timolol drops to lower eye pressure.
Comparison of Percent Changes in Optic Nerve Head Vessel Density in Treatment Groups Assessed by OCT Angiography
Comparison of the percent change in optic nerve head vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in vessel density after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in vessel density after using topical brimonidine or timolol drops to lower eye pressure.
Comparison of Percent Changes in Optic Nerve Head Flow Index in Treatment Groups Assessed by OCT Angiography
Comparison of the percent change in Optic Nerve Head Flow Index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in flow index after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in flow index after using topical brimonidine or timolol drops to lower eye pressure.

Secondary Outcome Measures

Full Information

First Posted
October 24, 2017
Last Updated
December 4, 2020
Sponsor
Wills Eye
Collaborators
Optovue
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1. Study Identification

Unique Protocol Identification Number
NCT03323164
Brief Title
Peripapillary Blood Flow After Use of Anti-glaucoma Medications: An OCT Angiography Study
Official Title
Changes in Peripapillary Blood Flow After Use of Anti-glaucoma Medications: A Prospective, Quantitative OCT Angiography Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
July 10, 2017 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
May 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wills Eye
Collaborators
Optovue

4. Oversight

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

5. Study Description

Brief Summary
This study evaluates the possible acute changes in peripapillary blood flow after instillation of antiglaucoma medications in patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG), or ocular hypertension (OHTN) using Optical Coherence Tomography (OCT) angiography.
Detailed Description
Reduction of intraocular pressure (IOP) with topical antihypertensive medications is the mainstay of initial treatment in patients with OHTN, POAG, and NTG. Many patients, however, continue to experience disease progression despite IOP reduction. Alternative mechanisms of neurodegeneration, including vascular dysregulation and structural susceptibility of the lamina cribrosa, have been proposed as important mechanisms in progression, particularly in cases of NTG. Prior studies have also found decreased calculated mean ocular perfusion with the use of timolol compared to other antiglaucoma medications in patients with normal tension glaucoma. Visual field deterioration has also been shown to be associated with systemic nocturnal arterial hypotension in patients with NTG, POAG, and after anterior ischemic optic neuropathy. The use of ophthalmic topical beta-blockers has been shown to lower nocturnal diastolic blood pressure and heart rate. Thus, topical beta blockers are often avoided in the treatment of NTG due to the potential risk of reduced optic nerve head perfusion Studies evaluating optic nerve head (ONH) perfusion are limited. Earlier studies evaluated indirect measurements, such as calculated mean ocular perfusion pressure or systemic hypotension, as indications of optic nerve hypoperfusion. Direct measurements of ocular perfusion have been attempted using retrobulbar color Doppler imaging, which demonstrated decreased short posterior ciliary artery flow velocity in patients with glaucomatous visual field progression. This technique, however, has yielded inconsistent results in other studies, and is only capable of detecting gross changes to ocular blood flow. Optical Coherence Tomography Angiography (OCTA) is a novel technique first introduced in 2014 using a custom swept-source OCT system.No studies currently exist to evaluate the effects of antiglaucoma medications on peripapillary blood flow using OCTA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma; Drugs, Normal Tension Glaucoma, Primary Open-angle Glaucoma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Timolol
Arm Type
Active Comparator
Arm Description
Timolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once.
Arm Title
Brimonidine
Arm Type
Active Comparator
Arm Description
Brimonidine tartrate 0.2% Instillation of one drop in each eye, once.
Intervention Type
Drug
Intervention Name(s)
Timolol Maleate
Other Intervention Name(s)
Timolol
Intervention Description
Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.
Intervention Type
Drug
Intervention Name(s)
Brimonidine Tartrate
Other Intervention Name(s)
Brimonidine
Intervention Description
Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.
Primary Outcome Measure Information:
Title
Changes in Vessel Density in Treatment Groups Assessed by OCT Angiography
Description
Percent change in peripapillary vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm with the use of topical brimonidine or timolol eye drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Title
Changes in Flow Index in Treatment Groups Assessed by OCT Angiography
Description
Percent change in peripapillary Flow Index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm with the use of topical brimonidine or timolol eye drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Title
Comparison of Percent Changes in Peripapillary Vessel Density in Treatment Groups Assessed by OCT Angiography
Description
Comparison of the percent change in peripapillary vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in vessel density after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in vessel density after using topical brimonidine or timolol drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Title
Comparison of Percent Changes in Peripapillary Flow Index in Treatment Groups Assessed by OCT Angiography
Description
Comparison of the percent change in peripapillary flow index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in flow index after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in flow index after using topical brimonidine or timolol drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Title
Comparison of Percent Changes in Optic Nerve Head Vessel Density in Treatment Groups Assessed by OCT Angiography
Description
Comparison of the percent change in optic nerve head vessel density detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in vessel density after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in vessel density after using topical brimonidine or timolol drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Title
Comparison of Percent Changes in Optic Nerve Head Flow Index in Treatment Groups Assessed by OCT Angiography
Description
Comparison of the percent change in Optic Nerve Head Flow Index detected by OCT (optical coherence tomography) Angiography using spectrum amplitude decorrelation angiography (SSADA) algorithm before and after the use of topical brimonidine or timolol eye drops to lower eye pressure. The Control groups represent the percent changes in flow index after using artificial tears. The medicine groups (Brimonidine/Timolol) represents the percent changes in flow index after using topical brimonidine or timolol drops to lower eye pressure.
Time Frame
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of ocular hypertension, primary open angle glaucoma, or normal tension glaucoma in the study eye(s) Age 18-90 Best corrected visual acuity of 20/60 or better Exclusion Criteria: Current use of either brimonidine or timolol Other disease, ophthalmic or systemic, that is likely to significantly affect the OCT test in the study eye(s) including: More than moderate grade cataract that significantly reducing OCTA scan signal level Macular degeneration other than mild drusen or pigmentary changes Diabetic retinopathy other than mild background non proliferative retinopathy Prior or current macular edema Prior laser treatment to the retina Prior retinal detachment Prior central serous retinopathy Prior retinal vein or artery occlusion Prior inflammatory retinopathy or choroidopathy Keratoconus or other corneal ectasia Corneal scarring in central 4 mm Prior penetrating keratoplasty Ischemic optic neuropathy Dementia beyond early/mild memory loss History of cerebrovascular accident History of severe carotid stenosis History of previous ocular surgery other than non-complicated cataract extraction
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Lee, MD
Organizational Affiliation
Wills Eye Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Glaucoma Research Center - Wills Eye Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Peripapillary Blood Flow After Use of Anti-glaucoma Medications: An OCT Angiography Study

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