AzTrials
AzTrials

Diabetic RetinopathyPhase 2NCT03006081

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

A Phase 2 study testing Intravitreal Aflibercept injection in people with Diabetic Retinopathy, run by Asan Medical Center at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Retinopathy
What is being tested?
Intravitreal Aflibercept injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteSouth Korea
Study dates
14 Apr 2016to 30 Aug 2018
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A subject must meet the following criteria to be eligible for inclusion in the study:
  • Adults ≥ 18 years with type 1 or 2 diabetes mellitus
  • Patients diagnosed as nonproliferative diabetic retinopathy with retinal nonperfusion (Ischemic index >20%) Severe nonproliferative diabetic retinopathy - Early proliferative diabetic retinopathy
  • Willing and able to comply with clinic visits and study-related procedures
  • Provide a signed informed consent form

Who cannot join

  • A subject who meets any of the following criteria will be excluded from the study.
  • Systemic exclusion criteria 1. Renal failure requiring hemodialysis or peritoneal dialysis within 6 months prior to baseline or anticipated need for hemodialysis, peritoneal dialysis at any time during the study 2. Acute cardiovascular events (acute myocardiac infarction and/or cerebral infarction) within 1 year before Visit 1 3. Blood HbA1c level greater than 12% at Visit 0
  • Ocular exclusion criteria
  • <!-- -->
  • 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
  • Presence of rubeosis (neovascularization of the iris or the angle) in the study eye
Show all 20Show fewer
  • Any current or history of retinal diseases that affects visual acuity in the study eye
  • Previous treatment of panretinal photocoagulation
  • Previous treatment with anti-VEGF in study eye within 6 months before Visit 1
  • Previous treatment with intraocular or periocular corticosteroids in the study eye within 6 months before Visit 1
  • Previous history of intraocular surgery other than cataract surgery in the study eye
  • Cataract surgery within 3 months before Visit 1 in the study eye
  • Yttrium-aluminium-garnet (YAG) capsulotomy in the study eye within 1 month before Visit 1
  • Aphakia in the study eye
  • 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
  • Presence of a visually significant cataract in the study eye
  • BCVA score < 34 letters in the fellow eye
  • Hypersensitivity to aflibercept
  • Ocular or periocular infection
  • Active intraocular inflammation

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan medical center

    Seoul, Seoul, 05505

Other trials in South Korea

About this study

Official title: The Efficacy of Intravitreal Aflibercept Injection in Improvement of Retinal Nonperfusion in Patients With Diabetic Retinopathy

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.

Read the detailed description

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.

Being tested
Intravitreal Aflibercept injection
Keywords
Retinal nonperfusion, Aflibercept
Medical subject headings
Diabetic Retinopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intravitreal Aflibercept injectionDrug

    Also called Eylea

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

Study groups in NCT03006081
Study groupRoleWhat they receive
2mg intravitreal aflibercept injectionExperimental2mg intravitreal aflibercept (Eylea) injection at baseline, 1M, 2M, 3M, 4M, and 5M
Receives: Drug: Intravitreal Aflibercept injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Improvement of retinal nonperfusion

    Mean changes (%) of retinal nonperfusion (Ischemic index) from baseline

    Measured: 1 year

Secondary outcomes (5)

  1. progression of diabetic retinopathy to proliferative diabetic retinopathy (PDR)

    Number of patients who receive rescue treatment due to PDR and time to rescue treatment due to PDR

    Measured: 1 year

  2. development of diabetic macular edema

    Number of patients who receive rescue treatment due to DME and time to rescue treatment due to DME

    Measured: 1 year

  3. Factors associated with the progression of retinal nonperfusion 1 (Functional)

    • Visual acuity parameters: Mean changes of BCVA from baseline at every 3 month visit The proportion of subjects with gaining / losing ≥ 15letters or more in BCVA

    Measured: 1 year

  4. Factors associated with the progression of retinal nonperfusion 2 (Anatomical)

    • Optical coherence tomography (OCT) parameters: Mean changes of Central Retinal Thickness (CRT) from baseline at every 3 month visit Mean changes of Central Retinal Volume from baseline at every 3 month visit Mean change subfoveal choroidal thickness (SFChT) from baseline at every 3 month visit

    Measured: 1 year

  5. Factors associated with the progression of retinal nonperfusion 3 (Anatomical)

    • Fluorescein angiography (FA) parameters: Baselinenonperfusion area(Ischemic index) at posterior and peripheral retina Baseline degree of vascular leakage at posterior and peripheral retina

    Measured: 1year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2016 (estimated)
  2. Study start14 Apr 2016
  3. Primary completion30 Aug 2018
  4. Study completion30 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03006081
Sponsor's protocol ID
FLOW_001
Status last verified
Dec 2018
First submitted
5 Dec 2016
Last updated
2 Dec 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • 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.

    PubMed 26350546

  • 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.

    PubMed 24768239

  • 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.

    PubMed 25704318

  • 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.

    PubMed 33077475

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Intravitreal Aflibercept injection in people with Diabetic Retinopathy, run by Asan Medical Center at 1 site in South Korea.

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 5 inclusion and 20 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: finished, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Improvement of retinal nonperfusion (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03006081, which also lists 4 linked publications.

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 2 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in