The Efficacy of Intravitreal Aflibercept Injection in Improvement of Retinal Nonperfusion in Diabetic Retinopathy

NCT ID: NCT03006081

Last Updated: 2016-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2018-06-30

Brief Summary

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Retinal nonperfusion drives vision-threatening complications such as pathological neovascularization, which can lead to neovascular glaucoma, vitreous hemorrhage, or tractional retinal detachments and macular edema in diabetic retinopathy. Thus, decreasing nonperfusion area with aid of anti-VEGF agents might be a useful way to prevent deteriorating course of diabetic retinopathy. The main purpose of this study is to determine the efficacy of intravitreal aflibercept injection in improvement of retinal nonperfusion and identify associated factors in patients with nonproliferative diabetic retinopathy with moderate retinal nonperfusion.

Detailed Description

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Retinal nonperfusion drives vision-threatening complications such as pathological neovascularization, which can lead to neovascular glaucoma, vitreous hemorrhage, or tractional retinal detachments and macular edema in various retinal vascular diseases including diabetic retinopathy and retinal vein occlusion. Silva et al revealed that retinal nonperfusion area was correlated highly with diabetic retinopathy severity in their recent paper. It should be clarified that retinal nonperfusion is not synonymous with retinal ischemia, which implies tissue hypoxia, but is a useful surrogate.

Retinal nonperfusion has known to be associated with the production of vascular endothelial factor (VEGF). Recently, Campochiaro et al reported that neutralization of VEGF using ranibizumab improved macular edema and reversed the worsening of retinal nonperfusion in patients with retinal vein occlusion and diabetic macular edema. The precise mechanism for improved perfusion in the VEGF treated eye is uncertain. The authors suggested that VEGF exacerbates retinal ischemia by increasing leukostasis, and intravitreal anti-VEGF agents may break the feedback loop, allowing reperfusion to occur. There might be a portion of circulation that is closed but not permanently, and this reversible closure is modulated by VEGF.

The study by Campochiaro et al, however, was limited in that they reviewed retinal nonperfusion within a template consisting of the Early Treatment Diabetic Retinopathy subfields mainly confined to posterior pole of the fundus. Wide-field retinal imaging is an imaging technique that allows a view of almost 200° of the fundus in a single image. It has been well shown that wide-field scans allow the detection of peripheral pathology that may be missed on 75 degrees of achieved by montaging the Early Treatment Diabetic Retinopathy Study 7-standard fields.

To investigators knowledge, there has been no previous study evaluating the longitudinal change of retinal nonperfusion after aflibercept treatment in a larger area of the retina by taking advantage of the 200° field of view in diabetic retinopathy. The main purpose of this study is to determine the efficacy of intravitreal aflibercept injection in improvement of retinal nonperfusion and identify associated factors in patients with nonproliferative diabetic retinopathy with moderate retinal nonperfusion.

Conditions

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Diabetic Retinopathy

Keywords

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Retinal nonperfusion Aflibercept

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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2mg intravitreal aflibercept injection

2mg intravitreal aflibercept (Eylea) injection at baseline, 1M, 2M, 3M, 4M, and 5M

Group Type EXPERIMENTAL

Intravitreal Aflibercept injection

Intervention Type DRUG

Six number of injections at baseline, 1M, 2M, 3M, 4M, and 5M

Interventions

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Intravitreal Aflibercept injection

Six number of injections at baseline, 1M, 2M, 3M, 4M, and 5M

Intervention Type DRUG

Other Intervention Names

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Eylea

Eligibility Criteria

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Inclusion Criteria

* A subject must meet the following criteria to be eligible for inclusion in the study:

1. Adults ≥ 18 years with type 1 or 2 diabetes mellitus
2. Patients diagnosed as nonproliferative diabetic retinopathy with retinal nonperfusion (Ischemic index \>20%) Severe nonproliferative diabetic retinopathy - Early proliferative diabetic retinopathy
3. Willing and able to comply with clinic visits and study-related procedures
4. Provide a signed informed consent form

Exclusion Criteria

* A subject who meets any of the following criteria will be excluded from the study.


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1. Diabetic macular edema involving the center of the macula (Defined as the area of the center subfield of OCT, Heidelberg Spectralis: ≥305 in women; ≥320 in men) in the study eye
2. Presence of rubeosis (neovascularization of the iris or the angle) in the study eye
3. Any current or history of retinal diseases that affects visual acuity in the study eye
4. Previous treatment of panretinal photocoagulation
5. Previous treatment with anti-VEGF in study eye within 6 months before Visit 1
6. Previous treatment with intraocular or periocular corticosteroids in the study eye within 6 months before Visit 1
7. Previous history of intraocular surgery other than cataract surgery in the study eye
8. Cataract surgery within 3 months before Visit 1 in the study eye
9. Yttrium-aluminium-garnet (YAG) capsulotomy in the study eye within 1 month before Visit 1
10. Aphakia in the study eye
11. Elevated intraocular pressure (≥ 22 mmHg) in spite of using topical IOP lowering agents at Visit 1 or a diagnosis of glaucoma (Visual field defect corresponding to glaucomatous optic neuropathy) in the study eye
12. Presence of a visually significant cataract in the study eye
13. BCVA score \< 34 letters in the fellow eye
14. Hypersensitivity to aflibercept
15. Ocular or periocular infection
16. Active intraocular inflammation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Asan Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Young Hee Yoon

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Young Hee Yoon

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

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Asan medical center

Olympicro 43 Gil 88, Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Yoon Jeon Kim, MD

Role: CONTACT

Phone: 82-2-3010-3680

Email: [email protected]

Facility Contacts

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Young Hee Yoon, MD

Role: primary

References

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Silva PS, Dela Cruz AJ, Ledesma MG, van Hemert J, Radwan A, Cavallerano JD, Aiello LM, Sun JK, Aiello LP. Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography. Ophthalmology. 2015 Dec;122(12):2465-72. doi: 10.1016/j.ophtha.2015.07.034. Epub 2015 Sep 6.

Reference Type BACKGROUND
PMID: 26350546 (View on PubMed)

Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014 Sep;121(9):1783-9. doi: 10.1016/j.ophtha.2014.03.021. Epub 2014 Apr 24.

Reference Type BACKGROUND
PMID: 24768239 (View on PubMed)

Silva PS, Cavallerano JD, Haddad NM, Kwak H, Dyer KH, Omar AF, Shikari H, Aiello LM, Sun JK, Aiello LP. Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years. Ophthalmology. 2015 May;122(5):949-56. doi: 10.1016/j.ophtha.2015.01.008. Epub 2015 Feb 19.

Reference Type BACKGROUND
PMID: 25704318 (View on PubMed)

Kim YJ, Yeo JH, Son G, Kang H, Sung YS, Lee JY, Kim JG, Yoon YH. Efficacy of intravitreal AFlibercept injection For Improvement of retinal Nonperfusion In diabeTic retinopathY (AFFINITY study). BMJ Open Diabetes Res Care. 2020 Oct;8(1):e001616. doi: 10.1136/bmjdrc-2020-001616.

Reference Type DERIVED
PMID: 33077475 (View on PubMed)

Other Identifiers

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FLOW_001

Identifier Type: -

Identifier Source: org_study_id