Glaucoma; DrugsPhase 4NCT03323164
Peripapillary Blood Flow After Use of Anti-glaucoma Medications: An OCT Angiography Study
A Phase 4 study testing Timolol Maleate and Brimonidine Tartrate in people with Glaucoma; Drugs and Normal Tension Glaucoma, run by Wills Eye at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Glaucoma; Drugs, Normal Tension Glaucoma, Primary Open-angle Glaucoma
- What is being tested?
- Timolol Maleate and Brimonidine Tartrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2017to 30 May 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Glaucoma Research Center - Wills Eye Hospital
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
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.
- Being tested
- Timolol Maleate, Brimonidine Tartrate
- Medical subject headings
- Glaucoma, Low Tension Glaucoma, Glaucoma, Open-Angle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol MaleateDrug
Also called Timolol
Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.
Brimonidine TartrateDrug
Also called Brimonidine
Instillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation.
| Study group | Role | What they receive |
|---|---|---|
| Timolol | Active comparator | Timolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once. Receives: Drug: Timolol Maleate |
| Brimonidine | Active comparator | Brimonidine tartrate 0.2% Instillation of one drop in each eye, once. Receives: Drug: Brimonidine Tartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 5.5 hours (3 separate 30 minute OCT Angiography scans with 2 hour post-intervention in between each scan)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2017
- Study start10 Jul 2017
- Primary completion31 Dec 2018
- Study completion30 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glaucoma; DrugsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wills Eye
- Sponsor type
- University, hospital or other
- Collaborators
- Optovue
- Responsible party
- Principal investigator, Daniel Lee, MD, Wills Eye
- Investigators
- Daniel Lee, MD, Principal investigator, Wills Eye Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03323164
- Sponsor's protocol ID
- 17-636E
- Status last verified
- Dec 2020
- First submitted
- 24 Oct 2017
- Last updated
- 31 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Peripapillary Blood Flow After Use of Anti-glaucoma Medications: A Prospective, Quantitative OCT Angiography Study
- ClinicalTrials.gov ID
- NCT03323164
- Acronym / sponsor ID
- 17-636E
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Wills EyeUniversity, hospital or other
- Collaborators
- Optovue
- Study start
- 10 Jul 2017 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 30 May 2020 (actual)
- First posted
- 26 Oct 2017 (actual)
- Results
- Posted 31 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Timolol | Active comparator | Drug: Timolol MaleateTimolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once. |
| Brimonidine | Active comparator | Drug: Brimonidine TartrateBrimonidine tartrate 0.2% Instillation of one drop in each eye, once. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Timolol MaleateAlso: TimololInstillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation. | Drug | Timolol |
| Brimonidine TartrateAlso: BrimonidineInstillation of one drop in each eye, one-time. Obtaining of OCT angiography scans after 2 hours of instillation. | Drug | Brimonidine |
Primary outcome
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Glaucoma; Drugs
Not yet recruitingPhase 4
The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients
Glaucoma, Glaucoma, Open-Angle
Enrolling by invitationObservational study
INTEGRAL Study: A Longitudinal Study of Surgeries and Lasers in Glaucoma: Long-term Results and Success Predictors Analysed From a Large-scale Retrospective and Prospective Glaucoma Register
Glaucoma Open-Angle, Glaucoma Eye
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Lee, MD principal investigator
Wills Eye Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Timolol Maleate and Brimonidine Tartrate in people with Glaucoma; Drugs and Normal Tension Glaucoma, run by Wills Eye at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2020; AzTrials last refreshed its copy on 8 Nov 2026.