Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma

Study Overview
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Brief Summary
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This 52 week study will assess the use of intravitreal aflibercept injections in patients with neovascular glaucoma (NVG) compared to standard of care panretinal photocoagulation. The investigators hypothesize that the neovascularization of the iris and angle present in neovascular glaucoma will resolve more quickly in eye treated with intravitreal aflibercept injection alone and result in increased comfort and preservation of visual field as compared to current standard of care utilizing pan-retinal photocoagulation. The advantages to intravitreal aflibercept injection use could include resolution of NVI/NVA (neovascularization of the iris/neovascularization of the angle) leading to quicker pain relief and quicker lowering of IOP (intraocular pressure).

Detailed Description
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The two arms of this study will compare current common practice (initial intravitreal anti-VEGF (vascular endothelial growth factor) to study treatment (VEGF) injection only) for 52 weeks. This single center study will consist of 20 patients with NVG. Patients will be randomized to: Group A: A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks. or Group B: 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks. Clinical assessment will include pain assessment (Universal Pain Scale), best corrected visual acuity (ETDRS), ophthalmic examination, anterior segment assessment including number of clock-hours of NVI/NVA, gonioscopy, anterior segment photography, visual field test (Humphrey SITA- Standard 24-2), optic nerve OCT (Zeiss Cirrus Optic Disc Cube 200x200), macular OCT (Cube scan 512 x 128 and 5 Line Raster), fluorescein angiography (initial iris phase followed by standard retinal angiography), and concurrent medical/ocular medications. Qualitative assessment of neovascularization will be made by the investigator based on comparison to baseline angiography.

Official Title
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Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma

Conditions
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Neovascular Glaucoma

Intervention / Treatment
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* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of neovascular glaucoma (Stage I-II) Individuals who are ages 21-90 years old; male or female of any race Presence of neovascularization of the iris and/or angle At least 90 degrees of unzipped anterior chamber angle as noted by gonioscopy. (a zipped angle is the term used for a drainage angle that is slowly closing due to scar tissue from the neovascularization process) Visual acuity of light perception or better in the study eye Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Exclusion Criteria: Use of intravitreal anti-VEGF agents in the study eye in the past 3 months. Full PRP in the study eye Prior vitrectomy in the study eye Prior trabeculectomy or other filtration surgery in the study eye Active ocular or periocular infection in the study eye Ocular conditions (Cataract or vitreous hemorrhage) that might require surgery in next 12 months Allergy to fluorescein dye Any past use of systemic anti-VEGF medication Myocardial infarction within 6 months prior to study enrollment Stroke within 6 months prior to study enrollment Pregnant or breast-feeding women Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aflibercept with Laser<br>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks | Drug: Aflibercept<br>* Details covered in arm description<br>* Other names: Eylea;|
| Experimental: Aflibercept<br>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks. | Drug: Aflibercept<br>* Details covered in arm description<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the incidence of adverse events | 2 year | 
| Severity of Adverse Events | Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the severity of adverse events | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate and Extent of Resolution of Neovascularization | Compare between Groups A and B the Rate and extent of resolution of neovascularization in patients with NVG Stages 1 & 2. | 1 year | 
| Intraocular Pressure (mmHg) at Baseline | Intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B | Baseline | 
| Intraocular Pressure (mmHg) at Week 52 | Mean intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B | Week 52 | 
| Number of Patients Losing > 5 Letters on Visual Acuity in Each Group A and Group B | Comparison between patients, groups A and B, that lost > 5 letters on visual acuity | Baseline to Week 52 | 
| Number of Patients in Each, Group A and Group B, Gaining > 5 Letters on Visual Acuity | Comparison of patients in each, group A and group B, that gained > 5 letters on visual acuity | Baseline to Week 52 | 
| Visual Acuity at Baseline | Comparison of visual acuity between groups A and B | Baseline | 
| Visual Acuity at Week 52 | Comparison of visual acuity at Week 52 between groups A and B | Week 52 | 
| Comparison of the Visual Field Between Groups | Comparison of the Visual field s measured by HVF 24-2 SITA Standards between groups A and B | 1 year | 
| Measure of the Optical Coherence Tomography(OCT) Outcomes | Evaluation of the Optical Coherence Tomography(OCT) outcomes (average retinal nerve fiber layer(RNFL) and central macular thickness), Compared between groups A and B. | Baseline to Week 52 | 
| Number of Patients With Need for Surgical Intervention | Comparison between groups A and B and the need for surgical intervention in both arms during the follow-up period | 1 year | 
| Number of Participants With Need for Additional IOP Lowering Medications | Comparison between groups A and B for the need of additional IOP lowering medications | 1 year | 
| Extent of Resolution of Neovascularization Between Groups | Comparison of groups A and B and the extent of resolution of neovascularization in patients with NVG Stages 1 & 2 | 1 year | 
| Evaluation of the Average Retinal Nerve Fiber Layer (RNFL) | Comparison between groups A and B of the average retinal nerve fiber layer (RNFL) as measured by Optical Coherence Tomography (OCT) | 1 year |