Macular DiseaseNCT01994174
Effect of Vascular Endothelial Growth Factor Blockers on Aqueous Humor Dynamics
An observational study of Macular Disease, run by University of Nebraska at 2 sites in United States.
Trial summary
The objective of this research is to determine the effects of anti-VEGF drugs (bevacizumab, ranibizumab or aflibercept) on aqueous humor dynamics (AHD) in patients with retinal vascular disease. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Macular Disease
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Dec 2013to 12 Jan 2023
- How long will I take part?
- 4 Weeks
- Phase
- Observational
- Are there results?
- None posted in the registry
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with established diagnosis of retinal vascular diseases (diabetic macular edema, neovascular macular degeneration, presumed ocular histoplasmosis syndrome, high myopia) who require intravitreal injection of anti-VEGF drugs such as bevacizumab, ranibizumab or aflibercept and are likely to need three monthly doses.
Who may be able to join
- Subjects must be at least 19 years of age and older
- Ability to give informed consent and attend the study visits
- Patients with established diagnosis of retinal vascular diseases (diabetic macular edema, neovascular macular degeneration,presumed ocular histoplasmosis syndrome, high myopia) who require intravitreal injection of anti-VEGF drugs such as bevacizumab,ranibizumab or aflibercept and are likely to need three monthly doses.
- Patients who have not received intravitreal injections within 3 months of study entry
- No previous established diagnosis of glaucoma and consequently no previous history of Argon Laser Trabeculoplasty (ALT) or Selective Laser Trabeculoplasty (SLT).
- No previous history of ocular surgery
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- Patients who are not planning on and are unlikely to require an elective ocular surgical or laser procedure within the study duration
- Open angle of the anterior chamber on clinical examination
- Ability to cooperate for aqueous humor dynamic studies
- Contact lenses removed prior to topical fluorescein instillation, and not used until the end of each fluorophotometry session
- Able to participate on site over the multi-visit study period
Who cannot join
- Age less than 18 years of age
- Women who are pregnant or nursing
- Ocular hypertension or glaucoma
- Narrow angle with complete or partial closure (gonioscopy angle <2)
- Any previous surgical or laser procedures
- Secondary glaucoma including pigmentary, exfoliative, uveitic and traumatic glaucomas
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- Any active neovascularization of the iris, angle, disc or retina
- Diagnosis of retinal arterial or vein occlusion
- Chronic or recurrent inflammatory eye disease
- Ocular trauma within the past 6 months
- Ocular infection or ocular inflammation in the past 2 months
- Any abnormality preventing reliable fluorophotometry of either eye,such as corneal scarring or severe dry eye that results in punctuate fluorescein staining of the cornea
- Intraocular surgery within 6 months
- Serious hypersensitivity to any components of the study medications or risk from treatment with glaucoma medications, such as severe asthma or emphysema.
- Use of any glucocorticoid by any route. Subject must be washed out of the glucocorticoid for at least 2 weeks before study entry.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Nebraska Medical Center, Truhlsen Eye Institute
Omaha, Nebraska, 68105
University of Nebraska Medical Center, Department of Ophthalmology and Visual Sciences
Omaha, Nebraska, 68198-5540
About this study
The objective of this research is to determine the effects of anti-VEGF drugs (bevacizumab, ranibizumab or aflibercept) on aqueous humor dynamics (AHD) in patients with retinal vascular disease. The underlying hypothesis is that anti-VEGF drugs increase intraocular pressure (IOP) by increasing aqueous inflow, decreasing uveoscleral outflow or both. The specific aim is to evaluate the changes produced in AHD after 1 baseline and a subsequent 1 monthly injection of anti VEGF agents.
Read the detailed description
Intravitreal injection of different anti-VEGF agents such as bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA, USA) ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA, USA) and aflibercept (Eylea, Regeneron, Tarrytown, NY, USA) has been a widely common practice for treatment of choroidal neovascularization and retinal vascular diseases [1]. Several ocular and systemic adverse events have been reported with the use of anti-VEGF agents [7]. Elevation of intraocular pressure (IOP) is a serious ocular adverse event that may be associated with intravitreal injection of anti-VEGF agents. IOP elevation with anti-VEGF injection may have variable presentation ranging from acute transient post injection elevation to the development of persistent IOP elevation that mandates pressure lowering therapy[8].
Patients with previously existing glaucoma may have a higher rate of persistent IOP elevation associated with intravitreal injection of anti-VEGF agents. Good et al, reported the rate of persistent IOP elevation after intravitreal anti-VEGF to be 33% in glaucoma patients versus 3.1% in eyes without previous diagnosis of glaucoma [9]. Tseng et al, reported 25 eyes with sustained elevation of IOP after serial intravitreal injections of anti-VEGF agents (mean = 20injections). All the 25 eyes were normotensive prior to the study and 23 of them were not previously diagnosed with glaucoma[10].
Multicenter clinical trials that studied the intravitreal injection of anti-VEGF agents, such as MARINA and ANCHOR for ranibizumab, VISION for pegaptanib and PACORES for bevacizumab, did not show sustained IOP elevation with the intravitreal injection of the study agents [12-15]. However, a subgroup analysis of the data of MARINA and ANCHOR trials showed at least 6 mm Hg increase of IOP from baseline in 2.1% of eyes in MARINA trial and 3.6% of eyes in ANCHOR trial [16]. A retrospective chart review of 207 patients over a 6-months follow up period after serial intravitreal injections of anti-VEGF reported an IOP elevation greater than 5 mm Hg in 2 consecutive visits compared to baseline in 11.6% of the treated eyes versus 5.3% in control eyes [17].
The pathophysiology of the reported IOP elevation associated with intravitreal injection of anti-VEGF is unknown. Anti-VEGF compounds might increase aqueous humor inflow by the breakdown of the blood-aqueous barrier or reduce uveoscleral outflow by the ciliary body vasculature. These potential changes could translate into elevated IOP and glaucoma.
- Conditions
- Macular Disease
- Keywords
- vascular, retina, Anti-VEGF, Aqueous humor dynamics
- Medical subject headings
- Macular Degeneration
What is being measured
The primary outcome is the main question the study is designed to answer.
Uveoscleral outflow changes
The uveoscleral outflow changes will be assess at baseline prior to any anti-VEGF treatment and after the 3rd intravitreal treatment has been done.
Measured: 1-2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study start20 Dec 2013
- Primary completion12 Jan 2023
- Study completion12 Jan 2023
Why it stopped: Limited resources; IRB approval was not maintained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Macular DiseaseStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
- Target duration
- 4 Weeks
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vikas Gulati, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994174
- Sponsor's protocol ID
- 0583-13-FB
- Status last verified
- Oct 2023
- First submitted
- 19 Nov 2013
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vascular Endothelial Growth Factor Blockers on Aqueous Humor Dynamics
- ClinicalTrials.gov ID
- NCT01994174
- Acronym / sponsor ID
- 0583-13-FB
- Conditions
- Macular Disease
- Keywords
- vascular, retina, Anti-VEGF, Aqueous humor dynamics
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Limited resources; IRB approval was not maintained
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 20 Dec 2013 (actual)
- Primary completion
- 12 Jan 2023 (actual)
- Study completion
- 12 Jan 2023 (actual)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this research is to determine the effects of anti-VEGF drugs (bevacizumab, ranibizumab or aflibercept) on aqueous humor dynamics (AHD) in patients with retinal vascular disease. The underlying hypothesis is that anti-VEGF drugs increase intraocular pressure (IOP) by increasing aqueous inflow, decreasing uveoscleral outflow or both. The specific aim is to evaluate the changes produced in AHD after 1 baseline and a subsequent 1 monthly injection of anti VEGF agents.
Detailed description
Intravitreal injection of different anti-VEGF agents such as bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA, USA) ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA, USA) and aflibercept (Eylea, Regeneron, Tarrytown, NY, USA) has been a widely common practice for treatment of choroidal neovascularization and retinal vascular diseases [1]. Several ocular and systemic adverse events have been reported with the use of anti-VEGF agents [7]. Elevation of intraocular pressure (IOP) is a serious ocular adverse event that may be associated with intravitreal injection of anti-VEGF agents. IOP elevation with anti-VEGF injection may have variable presentation ranging from acute transient post injection elevation to the development of persistent IOP elevation that mandates pressure lowering therapy[8].
Patients with previously existing glaucoma may have a higher rate of persistent IOP elevation associated with intravitreal injection of anti-VEGF agents. Good et al, reported the rate of persistent IOP elevation after intravitreal anti-VEGF to be 33% in glaucoma patients versus 3.1% in eyes without previous diagnosis of glaucoma [9]. Tseng et al, reported 25 eyes with sustained elevation of IOP after serial intravitreal injections of anti-VEGF agents (mean = 20injections). All the 25 eyes were normotensive prior to the study and 23 of them were not previously diagnosed with glaucoma[10].
Multicenter clinical trials that studied the intravitreal injection of anti-VEGF agents, such as MARINA and ANCHOR for ranibizumab, VISION for pegaptanib and PACORES for bevacizumab, did not show sustained IOP elevation with the intravitreal injection of the study agents [12-15]. However, a subgroup analysis of the data of MARINA and ANCHOR trials showed at least 6 mm Hg increase of IOP from baseline in 2.1% of eyes in MARINA trial and 3.6% of eyes in ANCHOR trial [16]. A retrospective chart review of 207 patients over a 6-months follow up period after serial intravitreal injections of anti-VEGF reported an IOP elevation greater than 5 mm Hg in 2 consecutive visits compared to baseline in 11.6% of the treated eyes versus 5.3% in control eyes [17].
The pathophysiology of the reported IOP elevation associated with intravitreal injection of anti-VEGF is unknown. Anti-VEGF compounds might increase aqueous humor inflow by the breakdown of the blood-aqueous barrier or reduce uveoscleral outflow by the ciliary body vasculature. These potential changes could translate into elevated IOP and glaucoma.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 4 Weeks
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with established diagnosis of retinal vascular diseases (diabetic macular edema, neovascular macular degeneration, presumed ocular histoplasmosis syndrome, high myopia) who require intravitreal injection of anti-VEGF drugs such as bevacizumab, ranibizumab or aflibercept and are likely to need three monthly doses.
Key inclusion criteria (11 listed)
- Subjects must be at least 19 years of age and older
- Ability to give informed consent and attend the study visits
- Patients with established diagnosis of retinal vascular diseases (diabetic macular edema, neovascular macular degeneration,presumed ocular histoplasmosis syndrome, high myopia) who require intravitreal injection of anti-VEGF drugs such as bevacizumab,ranibizumab or aflibercept and are likely to need three monthly doses.
- Patients who have not received intravitreal injections within 3 months of study entry
- No previous established diagnosis of glaucoma and consequently no previous history of Argon Laser Trabeculoplasty (ALT) or Selective Laser Trabeculoplasty (SLT).
Key exclusion criteria (15 listed)
- Age less than 18 years of age
- Women who are pregnant or nursing
- Ocular hypertension or glaucoma
- Narrow angle with complete or partial closure (gonioscopy angle <2)
- Any previous surgical or laser procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Uveoscleral outflow changes
Time frame: 1-2 months
The uveoscleral outflow changes will be assess at baseline prior to any anti-VEGF treatment and after the 3rd intravitreal treatment has been done.
Results and safety
The study was stopped early (reason given: Limited resources; IRB approval was not maintained). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
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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.
Vikas Gulati, MD principal investigator
University of Nebraska
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Macular Disease, run by University of Nebraska at 2 sites 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 11 inclusion and 15 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: stopped early, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
Are results available for this study?
The study was stopped early (reason given: Limited resources; IRB approval was not maintained). Results are not available in the source record.
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?
Uveoscleral outflow changes (time frame: 1-2 months). 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 6 Oct 2023.