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
Among 28 studies testing timolol in Glaucoma — none open to participants now, none under way, none of them phase 3. Timolol · Glaucoma.
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.
1,419 studies on the registry are indexed under Glaucoma; 223 are open to participants now.
This study's enrollment of 35 is below the median of 61 across 964 interventional studies indexed under Glaucoma.
Browse Glaucoma studies →None of the 28 studies testing timolol in Glaucoma is open now.
Timolol: first FDA approval 1978 (TIMOPTIC), first EMA approval 2006. What it is approved for, and how studies give it, is on its page →
Of the 156 Glaucoma studies recruiting now, 114 (73%) set no upper age limit and 9 (6%) stop at 75 or younger; 13 take children under 18; 45 take healthy volunteers.
This study: 18 Years to 90 Years · all sexes · no healthy volunteers.
The full table on the hub →28 studies; the count open now beside each. This study's row is marked.
First in 2000; this study’s year is marked. 1 started in 2017.
Median enrollment 60 across the 28 interventional studies. Of the 24 that completed or were terminated, 8 (33%) have results posted.
10 of 28 have an industry lead sponsor. The 10 most frequent:
Wills Eye is the lead sponsor of 77 studies on the registry; 2 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 10 (83%) have results posted.
38 studies in Glaucoma by Wills Eye: 1 open now, 1 under way, none of them phase 3. Of 35 finished, 17 (49%) have results posted.
Among the 38 studies in Glaucoma by Wills Eye, this one is the 18th largest by enrollment of the 25 interventional ones, is the only one that started in 2017, is one of 3 in phase 4, and was the 37th registered.
Wills Eye’s Glaucoma studies by the year they started, since 2000.
None of the studies under way reaches primary completion within a year.
Among the 28 studies testing timolol in Glaucoma, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Wills Eye’s 38 in Glaucoma:
Nothing recorded among them since 2026-09-25.
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.
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.
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.
Exclusion Criteria:
Other disease, ophthalmic or systemic, that is likely to significantly affect the OCT test in the study eye(s) including:
Timolol maleate 0.5% ophthalmic solution Instillation of one drop in each eye, once.
Drug: Timolol Maleate
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.
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
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)
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)
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)
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)
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)
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)
| Milestone | Timolol | Brimonidine |
|---|---|---|
| Started | 18 | 17 |
| Completed | 16 | 15 |
| Not completed | 2 | 2 |
| Withdrew: Poor quality imaging/scans | 2 | 2 |
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.
| percent change | Brimonidine Group | Timolol Group |
|---|---|---|
| Overall group | -0.51 ± 6.10 | 2.59 ± 6.47 |
| POAG | -0.96 ± 8.069 | 0.96 ± 6.71 |
| NTG | -0.04 ± 6.67 | 4.12 ± 8.11 |
| OHTN | -0.58 ± 4.48 | 2.37 ± 4.77 |
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.
| percent change | Brimonidine Group | Timolol Group |
|---|---|---|
| Overall group | -5.23 ± 10.77 | 0.33 ± 5.11 |
| POAG | -12.55 ± 12.01 | 0.69 ± 7.64 |
| NTG | -4.87 ± 6.35 | 2.76 ± 2.55 |
| OHTN | 1.71 ± 9.68 | -2.92 ± 3.05 |
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.
| percent change | Control B | Brimonidine | Control T | Timolol |
|---|---|---|---|---|
| Overall group | 1.70 ± 6.68 | -0.51 ± 6.10 | -2.05 ± 3.90 | 2.59 ± 6.47 |
| POAG | 2.89 ± 10.73 | -1.62 ± 9.15 | -2.8 ± 4.64 | 0.96 ± 6.71 |
| NTG | 2.02 ± 5.59 | -0.04 ± 6.67 | -3.42 ± 4.01 | 4.12 ± 8.11 |
| OHTN | 0.44 ± 4.89 | -0.58 ± 4.48 | 0.34 ± 2.21 | 2.37 ± 4.77 |
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.
| percent change | Control B | Brimonidine | Control T | Timolol |
|---|---|---|---|---|
| Overall group | 2.35 ± 11.66 | -5.23 ± 10.77 | 1.61 ± 11.10 | 0.33 ± 5.11 |
| POAG | 12.81 ± 15.26 | -14.91 ± 12.45 | -3.65 ± 5.33 | 0.69 ± 7.64 |
| NTG | 0.22 ± 1.95 | -4.87 ± 6.35 | 7.57 ± 16.31 | 2.76 ± 2.55 |
| OHTN | -3.89 ± 9.97 | 1.71 ± 9.68 | -0.26 ± 2.95 | -2.92 ± 3.05 |
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.
| Percent change | Control B | Brimonidine | Control T | Timolol |
|---|---|---|---|---|
| Overall | 1.27 ± 6.95 | 1.08 ± 6.67 | 0.32 ± 4.96 | 0.91 ± 5.45 |
| POAG | 2.22 ± 7.87 | -1.00 ± 6.02 | -2.68 ± 4.37 | 2.65 ± 4.89 |
| NTG | 2.13 ± 7.03 | 2.44 ± 8.21 | 1.70 ± 6.30 | 0.16 ± 7.40 |
| OHTN | -0.34 ± 7.50 | 1.65 ± 7.31 | 1.67 ± 2.66 | 0.08 ± 3.66 |
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.
| percent change | Control B | Brimonidine | Control T | Timolol |
|---|---|---|---|---|
| Overall | 2.69 ± 12.08 | -5.24 ± 10.05 | 1.96 ± 9.08 | -0.69 ± 5.37 |
| POAG | 12.40 ± 14.22 | -13.73 ± 11.02 | -2.38 ± 3.64 | -1.65 ± 7.54 |
| NTG | 0.32 ± 3.42 | -4.17 ± 5.77 | 6.21 ± 13.79 | 2.47 ± 2.65 |
| OHTN | -2.68 ± 13.18 | 0.55 ± 10.65 | 1.21 ± 2.61 | -3.52 ± 4.04 |
Collected over 4 hours. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Timolol | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Brimonidine | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| Age, Categorical(Participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 10 | 10 | 20 |
| >=65 years | 6 | 5 | 11 |
| Sex: Female, Male(Participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| Female | 11 | 10 | 21 |
| Male | 5 | 5 | 10 |
| Ethnicity (NIH/OMB)(Participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 1 |
| Not Hispanic or Latino | 16 | 13 | 29 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Race (NIH/OMB)(Participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 2 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 4 | 7 |
| White | 13 | 8 | 21 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Region of Enrollment(participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| United States | 16 | 15 | 31 |
| Glaucoma type(Participants) | Timolol | Brimonidine | Total |
|---|---|---|---|
| Count of participants | 16 | 15 | 31 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
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.
This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Timolol · Brimonidine
Wills Eye