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

• ClinicalTrials.gov Identifier: NCT03323164
• Recruitment Status: Completed
• First Posted: October 26, 2017
• Results First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Sponsor: Wills Eye
• Collaborator: Optovue
• Information provided by (Responsible Party): Daniel Lee, MD, Wills Eye

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.

Condition or disease	Intervention/treatment	Phase
Glaucoma; Drugs; Normal Tension Glaucoma; Primary Open-angle Glaucoma	Drug: Timolol Maleate; Drug: Brimonidine Tartrate	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Changes in Peripapillary Blood Flow After Use of Anti-glaucoma Medications: A Prospective, Quantitative OCT Angiography Study
• Actual Study Start Date: July 10, 2017
• Actual Primary Completion Date: December 31, 2018
• Actual Study Completion Date: May 30, 2020

Arms and Interventions

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 Name: 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 Name: Brimonidine

Outcome Measures

Primary Outcome Measures :

1. Changes in Vessel Density in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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.
2. Changes in Flow Index in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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.
3. Comparison of Percent Changes in Peripapillary Vessel Density in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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.
4. Comparison of Percent Changes in Peripapillary Flow Index in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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. Comparison of Percent Changes in Optic Nerve Head Vessel Density in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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.
6. Comparison of Percent Changes in Optic Nerve Head Flow Index in Treatment Groups Assessed by OCT Angiography [ Time Frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Pennsylvania

Glaucoma Research Center - Wills Eye Hospital

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Wills Eye

Optovue

Investigators

• Principal Investigator: Daniel Lee, MD; Wills Eye Hospital

  Study Documents (Full-Text)

Documents provided by Daniel Lee, MD, Wills Eye:

Study Protocol and Statistical Analysis Plan  [PDF] July 7, 2017

More Information

• Responsible Party: Daniel Lee, MD, Principal Investigator, Wills Eye
• ClinicalTrials.gov Identifier: NCT03323164
• Other Study ID Numbers: 17-636E
• First Posted: October 26, 2017
• Results First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Glaucoma; Glaucoma, Open-Angle; Low Tension Glaucoma; Ocular Hypertension; Eye Diseases; Optic Nerve Diseases; Timolol; Brimonidine Tartrate; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists