Intravitreal Aflibercept for Submacular Hemorrhage

Study Overview
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Brief Summary
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The prognosis of exudative age-related macular degeneration (AMD) accompanied by submacular hemorrhage is generally poor. A recently developed anti-VEGF agent eyeliaTM is also a useful treatment option for exudative AMD. However, one major limitation of VIEW study was that lack of data regarding eyes with submacular hemorrhage. The purpose of the present study was to evaluate the efficacy of Eylea in submacular hemorrhage secondary to exudative AMD.

Detailed Description
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The prognosis of exudative age-related macular degeneration (AMD) accompanied by submacular hemorrhage is generally poor. Although anti-vascular endothelial growth factor (VEGF) has been demonstrated excellent efficacy in the treatment of exudative AMD, eyes with submacular hemorrhage were excluded from the previous well-known clinical trials. The exclusion of these patients may probably be determined by some concerns suggesting possible poor prognosis in these patients. Firstly, it was well known that subretinal hemorrhage itself induces retinal damage and degeneration. Secondly, it was not certain whether the drug penetrates through hemorrhage and stabilize to the underlying lesion or not. As a result, the efficacy in submacular hemorrhage could not be demonstrated in these clinical trials. The efficacy of anti-VEGF therapy in eyes with submacular hemorrhage has recently been spotlighted. Several reports demonstrated significant improvement in visual acuity after anti-VEGF monotherapy, including LucentisTM, AvastinTM, or both, in eyes with exudative AMD with submacular hemorrhage. Although histopathologic evidence using animal model has not been presented, results of these clinical studies suggest that anti-VEGF may penetrates the hemorrhage and stabilize the underlying lesion. Recently, a large prospective clinical trial that evaluated the efficacy of anti-VEGF therapy in this condition showed favorable outcome. Result of this study may be published in a near future A recently developed anti-VEGF agent eyeliaTM is also a useful treatment option for exudative AMD. The result of VIEW study clearly demonstrated that this new agent has comparable efficacy to LucentisTM using less frequent injection schedule. However, one major limitation of VIEW study was that lack of data regarding eyes with submacular hemorrhage. Investigators carefully reviewed the study protocol of VIEW study and found that lesions composed of >50% blood were excluded. In addition, investigators could not aware any report in English literature that evaluated the efficacy of eyeliaTM in exudative AMD with submacular hemorrhage. It took almost 8 years to demonstrate the efficacy of two previously available anti-VEGF agents (LucentisTM and AvastinTM) in eyes with submacular hemorrhage. Investigators believe that a prospective study evaluating the efficacy of eyeliaTM in exudative AMD with submacular hemorrhage may help to achieve a consensus that eyeliaTM is also a useful treatment for submacular hemorrhage within a relatively short time. The purpose of the present study was to evaluate the efficacy of Eylea in submacular hemorrhage secondary to exudative AMD.

Official Title
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Efficacy of Intravitreal Aflibercept Monotherapy for Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration: A Prospective Clinical Trial

Conditions
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Exudative Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Vascular endothelial growth factor trap-eye


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 years of older Newly diagnosed, treatment-naïve exudative AMD Fovea-involving submacular hemorrhage greater than 1 disc areas at diagnosis Exclusion Criteria: History of previous treatment for neovascular AMD Greater than 15 disc diameter areas of hemorrhage extent History of vitreoretinal surgery History of glaucoma surgery, such as trabeculectomy or glaucoma implant surgery History of ocular steroid injection therapy within 1 month History of cataract surgery within 3 months Aphakia or anterior chamber intraocular lens implantation Spherical equivalents greater than -6.0 diopters evidence of other retinal disorders that may affect visual function including diabetic retinopathy, hypertensive retinopathy, epiretinal membrane, macular hole, and microaneurysm severe media opacity uncontrolled systemic disorders, including hypertension or diabetes mellitus history of major systemic vascular events, such as myocardial infarction and stroke hypersensitivity to aflibercept ocular or periocular infection active intraocular inflammation

Ages Eligible for Study
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Minimum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Eyes with submacular hemorrhage secondary to exudative age-related macular degeneration and were treated with vascular endothelial growth factor trap-eye. | Drug: Vascular endothelial growth factor trap-eye<br>* Intravitreal injection of vascular endothelial growth factor trap-eye During the first 3 months, 3 monthly injections are performed After 3 serial injections, additional injections are performed once per 2 months until 48 weeks after the initial injection.<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Early Treatment of Diabetic Retinopathy Study visual acuity Score | Increase or decrease in the Early Treatment of Diabetic Retinopathy Study letter score | Changes from baseline in visual acuity at 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who exhibited 15 letters or greater change in visual acuity | Changes in visual acuity of 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or greater | 56 weeks | 
| Changes in central macular thickness | Changes in central macular thickness (1 mm diameter centered at the centered at the fovea which is measured by optical coherence tomography) | Changes from baseline in central macular thickness at 56 weeks | 
| Duration of complete hemorrahge resolution | Duration between the first injection and the complete hemorrhage resolution | 56 weeks | 
| Incidence of recurrence of submacular hemorrhage or fluid | New development or increase in the amount of hemorrhage or fluid | 56 weeks | 
| Leakage on angiography | Leakage on angiography | 56 week |