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CompletedNCT03323164Updated Dec 31, 2020Results posted

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

A Phase 4 interventional study of Timolol Maleate and Brimonidine Tartrate in Glaucoma; Drugs, Normal Tension Glaucoma and Primary Open-angle Glaucoma, sponsored by Wills Eye. Completed at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2020-12-31.

Sponsored by Wills Eye · Phase 4, Interventional, and Diagnostic

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Jul 2017, registered Oct 2017).
Phase
Phase 4
Study type
Interventional
Enrollment
35
Allocation
Randomized
Ages
18 Years to 90 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-12

Among 28 studies testing timolol in Glaucoma — none open to participants now, none under way, none of them phase 3. Timolol · Glaucoma.

Enrollment
20th of 28
35 · median 60
Started
2017
the only one that year
Phase 4
13 of 28
none open now
Registered
24th of 28
by date

Among the 28 studies testing timolol in Glaucoma, this one is the 20th largest by enrollment, is the only one that started in 2017, is one of 13 in phase 4, and was the 24th registered.

By phase

28 studies; the count open now beside each. This study's row is marked.

Phase 4this study13 · 0 open
No phase5 · 0 open
Phase 35 · 0 open
Phase 23 · 0 open
Phase 12 · 0 open

By the year they started

First in 2000; this study’s year is marked. 1 started in 2017.

Size and results

Median enrollment 60 across the 28 interventional studies. Of the 24 that completed or were terminated, 8 (33%) have results posted.

Was this useful?
Download CSVWith an account: the 28 studies testing timolol in Glaucoma as a file.
02

Study 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.

Read the 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.

03

Conditions studied

  • Glaucoma; Drugs
  • Normal Tension Glaucoma
  • Primary Open-angle Glaucoma
04

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 4
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
35 participants (actual)

Study arms

  • Active comparator
    Timolol

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

    Drug: Timolol Maleate

  • Active comparator
    Brimonidine

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

    Drug: Brimonidine Tartrate

Interventions

  • Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.

    Also known as: Timolol

  • Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.

    Also known as: Brimonidine

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

  2. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

  3. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

  4. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

  5. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

  6. 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.

    Time frame: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)

07

Results

Posted Dec 31, 2020
Limitations and caveats
Limited sample size in this pilot study.

Participant flow

Participant flow — Overall Study
MilestoneTimololBrimonidine
Started1817
Completed1615
Not completed22
Withdrew: Poor quality imaging/scans22

Outcome measures

PrimaryChanges 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · percent change
Changes in Vessel Density in Treatment Groups Assessed by OCT Angiography
percent changeBrimonidine GroupTimolol Group
Overall group-0.51 ± 6.102.59 ± 6.47
POAG-0.96 ± 8.0690.96 ± 6.71
NTG-0.04 ± 6.674.12 ± 8.11
OHTN-0.58 ± 4.482.37 ± 4.77
PrimaryChanges 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · percent change
Changes in Flow Index in Treatment Groups Assessed by OCT Angiography
percent changeBrimonidine GroupTimolol Group
Overall group-5.23 ± 10.770.33 ± 5.11
POAG-12.55 ± 12.010.69 ± 7.64
NTG-4.87 ± 6.352.76 ± 2.55
OHTN1.71 ± 9.68-2.92 ± 3.05
PrimaryComparison 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · percent change
Comparison of Percent Changes in Peripapillary Vessel Density in Treatment Groups Assessed by OCT Angiography
percent changeControl BBrimonidineControl TTimolol
Overall group1.70 ± 6.68-0.51 ± 6.10-2.05 ± 3.902.59 ± 6.47
POAG2.89 ± 10.73-1.62 ± 9.15-2.8 ± 4.640.96 ± 6.71
NTG2.02 ± 5.59-0.04 ± 6.67-3.42 ± 4.014.12 ± 8.11
OHTN0.44 ± 4.89-0.58 ± 4.480.34 ± 2.212.37 ± 4.77
PrimaryComparison 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · percent change
Comparison of Percent Changes in Peripapillary Flow Index in Treatment Groups Assessed by OCT Angiography
percent changeControl BBrimonidineControl TTimolol
Overall group2.35 ± 11.66-5.23 ± 10.771.61 ± 11.100.33 ± 5.11
POAG12.81 ± 15.26-14.91 ± 12.45-3.65 ± 5.330.69 ± 7.64
NTG0.22 ± 1.95-4.87 ± 6.357.57 ± 16.312.76 ± 2.55
OHTN-3.89 ± 9.971.71 ± 9.68-0.26 ± 2.95-2.92 ± 3.05
PrimaryComparison 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · Percent change
Comparison of Percent Changes in Optic Nerve Head Vessel Density in Treatment Groups Assessed by OCT Angiography
Percent changeControl BBrimonidineControl TTimolol
Overall1.27 ± 6.951.08 ± 6.670.32 ± 4.960.91 ± 5.45
POAG2.22 ± 7.87-1.00 ± 6.02-2.68 ± 4.372.65 ± 4.89
NTG2.13 ± 7.032.44 ± 8.211.70 ± 6.300.16 ± 7.40
OHTN-0.34 ± 7.501.65 ± 7.311.67 ± 2.660.08 ± 3.66
PrimaryComparison 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.

Time frame:
5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Reported as:
Mean · percent change
Comparison of Percent Changes in Optic Nerve Head Flow Index in Treatment Groups Assessed by OCT Angiography
percent changeControl BBrimonidineControl TTimolol
Overall2.69 ± 12.08-5.24 ± 10.051.96 ± 9.08-0.69 ± 5.37
POAG12.40 ± 14.22-13.73 ± 11.02-2.38 ± 3.64-1.65 ± 7.54
NTG0.32 ± 3.42-4.17 ± 5.776.21 ± 13.792.47 ± 2.65
OHTN-2.68 ± 13.180.55 ± 10.651.21 ± 2.61-3.52 ± 4.04

Adverse events

Collected over 4 hours. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Timolol0/16 (0%)0/16 (0%)0/16 (0%)
Brimonidine0/15 (0%)0/15 (0%)0/15 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)TimololBrimonidineTotal
<=18 years000
Between 18 and 65 years101020
>=65 years6511
Sex: Female, Male
Sex: Female, Male(Participants)TimololBrimonidineTotal
Female111021
Male5510
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)TimololBrimonidineTotal
Hispanic or Latino011
Not Hispanic or Latino161329
Unknown or Not Reported011
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TimololBrimonidineTotal
American Indian or Alaska Native000
Asian022
Native Hawaiian or Other Pacific Islander000
Black or African American347
White13821
More than one race000
Unknown or Not Reported011
Region of Enrollment
Region of Enrollment(participants)TimololBrimonidineTotal
United States161531
Glaucoma type
Glaucoma type(Participants)TimololBrimonidineTotal
Count of participants161531
08

Study locations

1 site
  • Glaucoma Research Center - Wills Eye Hospital
    Philadelphia, Pennsylvania 19107, United States
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jul 2017 to primary completion in Dec 2018, 17 months.

Results were first posted in Dec 2020, 2 years after primary completion.

Of 32 non-industry phase 4 interventional studies under Glaucoma, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 45. This study's 17 months is below that.

Counting every sponsor, half of 44 studies reached it within 34 months; a quarter within 11 and three quarters within 66.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 24, 2017
First posted
Oct 26, 2017
StartActual
Jul 10, 2017
Primary completionActual
Dec 31, 2018
CompletionActual
May 30, 2020
Results first posted
Dec 31, 2020
Last update
Dec 31, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 31, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03323164
Lead sponsor
Wills Eye
Collaborators
Optovue
Responsible party
Daniel Lee, MD (Principal Investigator, Wills Eye) — Principal investigator
First posted
Oct 26, 2017
Start date
Jul 10, 2017
Primary completion
Dec 31, 2018
Completion
May 30, 2020
Results posted
Dec 31, 2020
Last update
Dec 31, 2020

Study contacts

Daniel Lee, MD
principal investigator · Wills Eye Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Timolol · Brimonidine

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