Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: Intravitreous Anti-Vascular Endothelial Growth Factor Treatment for Prevention of Vision Threatening Diabetic Retinopathy in Eyes at High Risk
Brief Summary: Multiple studies have implicated vascular endothelial growth factor VEGF as a major causative factor in human eye diseases characterized by neovascularization including proliferative diabetic retinopathy (PDR) and vascular permeability including diabetic macular edema (DME). While there is strong evidence that PDR outcomes are markedly reduced in eyes that are treated with monthly anti-VEGF therapy (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus: RIDE/RISE) and moderately reduced in eyes that received fairly frequent dosing during the 1st year of treatment (Diabetic Retinopathy Clinical Research Network protocol I), it is unknown whether or not an earlier but less frequent dosing regimen would result in similar, favorable anatomic outcomes, and whether favorable anatomic outcomes subsequently would result in favorable visual acuity outcomes.

If this study demonstrates that intravitreous aflibercept treatment is effective and safe for reducing the onset of PDR or center involved- DME (CI-DME) in eyes that are at high risk for these complications, a new strategy to prevent vision threatening complications of diabetes will be available for patients. The application of intravitreous aflibercept earlier in the course of disease (i.e., at the time when an eye has baseline severe non-proliferative diabetic retinopathy) could help to reduce future potential treatment burden in patients, at the same time resulting in similar or better long-term visual outcomes, if PDR and DME are prevented.

The primary objectives of this protocol are to 1) determine the efficacy and safety of intravitreous aflibercept injections versus sham injections (observation) for prevention of PDR or CI-DME in eyes at high risk for development of these complications and 2) compare long-term visual outcomes in eyes that receive anti-VEGF therapy early in the course of disease with those that are observed initially, and treated only if high-risk PDR or CI-DME with vision loss develops.

Secondary objectives include:

* Comparing other visual acuity outcomes between treatment groups, such as proportion of eyes with at least 10 or at least 15 letter loss from baseline, or gain or loss of at least 5 letters at the consecutive study visit just before and at the 2- or 4-year visit
* Comparing optical coherence tomography (OCT) outcomes, such as mean change in OCT central subfield thickness and volume from baseline
* Comparing proportion of eyes with at least 2 and 3-step worsening or improvement of diabetic retinopathy severity level (scale for individual eyes) by central reading center from baseline
* Comparing associated treatment and follow-up exam costs between treatment groups
* Comparing safety outcomes between treatment groups


Options:
A: Arm Label: Dosing regimen 1; Type: EXPERIMENTAL; Interventions: Drug: Intravitreal aflibercept injection [IAI] | Arm Label: Dosing regimen 2; Type: EXPERIMENTAL; Interventions: Drug: Intravitreal aflibercept injection [IAI] | Arm Label: Dosing regimen 3; Type: SHAM_COMPARATOR; Interventions: Drug: Sham | Intervention Type: DRUG; Name: Intravitreal aflibercept injection [IAI]; Assigned to Arm(s): Dosing regimen 1, Dosing regimen 2 | Intervention Type: DRUG; Name: Sham; Assigned to Arm(s): Dosing regimen 3
B: Arm Label: Glycemia Trial: intensive control; Type: EXPERIMENTAL; Interventions: Drug: Anti-hyperglycemic Agents | Arm Label: Glycemia Trial: standard control; Type: ACTIVE_COMPARATOR; Interventions: Drug: Anti-hyperglycemic Agents | Arm Label: BP Trial: intensive control; Type: EXPERIMENTAL; Interventions: Drug: Anti-hypertensive Agents | Arm Label: BP Trial: standard control; Type: ACTIVE_COMPARATOR; Interventions: Drug: Anti-hypertensive Agents | Arm Label: Lipid Trial: fenofibrate; Type: EXPERIMENTAL; Interventions: Drug: Blinded fenofibrate or placebo plus simvastatin | Arm Label: Lipid Trial: placebo; Type: PLACEBO_COMPARATOR; Interventions: Drug: Blinded fenofibrate or placebo plus simvastatin | Intervention Type: DRUG; Name: Anti-hyperglycemic Agents; Assigned to Arm(s): Glycemia Trial: intensive control, Glycemia Trial: standard control | Intervention Type: DRUG; Name: Anti-hypertensive Agents; Assigned to Arm(s): BP Trial: intensive control, BP Trial: standard control | Intervention Type: DRUG; Name: Blinded fenofibrate or placebo plus simvastatin; Assigned to Arm(s): Lipid Trial: fenofibrate, Lipid Trial: placebo
C: Arm Label: Anti-VEGF+Deferred PRP; Type: EXPERIMENTAL; Interventions: Drug: 0.5-mg Ranibizumab, Other: Deferred panretinal photocoagulation | Arm Label: Prompt PRP; Type: ACTIVE_COMPARATOR; Interventions: Other: Prompt Panretinal Photocoagulation | Intervention Type: OTHER; Name: Prompt Panretinal Photocoagulation; Assigned to Arm(s): Prompt PRP | Intervention Type: DRUG; Name: 0.5-mg Ranibizumab; Assigned to Arm(s): Anti-VEGF+Deferred PRP | Intervention Type: OTHER; Name: Deferred panretinal photocoagulation; Assigned to Arm(s): Anti-VEGF+Deferred PRP
D: Arm Label: Observation (Prompt Sham); Type: SHAM_COMPARATOR; Interventions: Procedure: Prompt Sham, Procedure: Deferred laser, Drug: Deferred aflibercept | Arm Label: Prompt aflibercept; Type: EXPERIMENTAL; Interventions: Drug: Prompt aflibercept, Procedure: Deferred laser, Drug: Deferred aflibercept | Intervention Type: PROCEDURE; Name: Prompt Sham; Assigned to Arm(s): Observation (Prompt Sham) | Intervention Type: DRUG; Name: Prompt aflibercept; Assigned to Arm(s): Prompt aflibercept | Intervention Type: PROCEDURE; Name: Deferred laser; Assigned to Arm(s): Observation (Prompt Sham), Prompt aflibercept | Intervention Type: DRUG; Name: Deferred aflibercept; Assigned to Arm(s): Observation (Prompt Sham), Prompt aflibercept

Answer: D