Effect of Vascular Endothelial Growth Factor Blockers on Aqueous Humor Dynamics
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Uveoscleral outflow changes
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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.
结局指标
主要结局
Uveoscleral outflow changes
时间窗: 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.
次要结局
未报告次要终点