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

Changes in Peripapillary Blood Flow After Use of Anti-glaucoma Medications: A Prospective, Quantitative OCT Angiography Study

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.

Study Overview

• Status: Completed
• Conditions: Primary Open-angle Glaucoma; Normal Tension Glaucoma; Glaucoma; Drugs
• Intervention / Treatment: Drug: Timolol Maleate; Drug: Brimonidine Tartrate

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Glaucoma Research Center - Wills Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Timolol; Timolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once.	Drug: Timolol Maleate; Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.; Other Names: Timolol
ACTIVE_COMPARATOR: Brimonidine; Brimonidine tartrate 0.2% Instillation of one drop in each eye, once.	Drug: Brimonidine Tartrate; Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.; Other Names: Brimonidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
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.	5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

Collaborators and Investigators

• Sponsor: Wills Eye
• Collaborators: Optovue

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 10, 2017
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): May 30, 2020

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (ACTUAL): October 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Optic Nerve Diseases; Glaucoma; Glaucoma, Open-Angle; Low Tension Glaucoma; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Timolol; Brimonidine Tartrate
• Other Study ID Numbers: 17-636E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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