The Efficacy of Intravitreal Aflibercept Injection in Improvement of Retinal Nonperfusion in Patients With Diabetic Retinopathy
Overview
- Phase
- Phase 2
- Intervention
- Intravitreal Aflibercept injection
- Conditions
- Diabetic Retinopathy
- Sponsor
- Asan Medical Center
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Improvement of retinal nonperfusion
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief 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. 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
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.
Investigators
Young Hee Yoon
Professor
Asan Medical Center
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •A subject who meets any of the following criteria will be excluded from the study.
- •Systemic exclusion criteria
- •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
- •Acute cardiovascular events (acute myocardiac infarction and/or cerebral infarction) within 1 year before Visit 1
- •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
- •Any current or history of retinal diseases that affects visual acuity in the study eye
- •Previous treatment of panretinal photocoagulation
Arms & Interventions
2mg intravitreal aflibercept injection
2mg intravitreal aflibercept (Eylea) injection at baseline, 1M, 2M, 3M, 4M, and 5M
Intervention: Intravitreal Aflibercept injection
Outcomes
Primary Outcomes
Improvement of retinal nonperfusion
Time Frame: 1 year
Mean changes (%) of retinal nonperfusion (Ischemic index) from baseline
Secondary Outcomes
- progression of diabetic retinopathy to proliferative diabetic retinopathy (PDR)(1 year)
- development of diabetic macular edema(1 year)
- Factors associated with the progression of retinal nonperfusion 1 (Functional)(1 year)
- Factors associated with the progression of retinal nonperfusion 2 (Anatomical)(1 year)
- Factors associated with the progression of retinal nonperfusion 3 (Anatomical)(1year)