A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)

Sponsor
Jaeb Center for Health Research (Other)
Overall Status
Completed
CT.gov ID
NCT00336323
Collaborator
National Eye Institute (NEI) (NIH)
121
Enrollment
34
Locations
5
Arms
20
Duration (Months)
3.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will provide preliminary data on the dose and dose interval related effects of intravitreally administered Avastin on retinal thickness and visual acuity in subjects with Diabetic Macular Edema (DME) to aid in planning a phase 3 trial.

In addition, this study will provide preliminary data on the safety of intravitreally administered Avastin in subjects with DME.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin.

In a review of three early studies concerning the natural history of diabetic macular edema, Ferris and Patz found that 53% of 135 eyes with diabetic macular edema, presumably all involving the center of the macula, lost two or more lines of visual acuity over a two year period. In the Early Treatment Diabetic Retinopathy Study (ETDRS), 33% of 221 untreated eyes available for follow-up at the 3-year visit, all with edema involving the center of the macula at baseline, had experienced a 15 or more letter decrease in visual acuity score (equivalent to a doubling of the visual angle, e.g., 20/25 to 20/50, and termed "moderate visual loss").

In the ETDRS, focal photocoagulation (direct treatment to microaneurysms and grid treatment to diffuse edema) of eyes with clinically significant macular edema (CSME) reduced the risk of moderate visual loss by approximately 50% (from 24% to 12%, three years after initiation of treatment). Therefore, 12% of treated eyes developed moderate visual loss in spite of treatment. Furthermore, approximately 40% of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months, as did 25% of treated eyes at 36 months.

Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, as demonstrated by the ETDRS, intensive glycemic control, as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) and blood pressure control, as demonstrated by the UKPDS. In the DCCT, intensive glucose control reduced the risk of onset of diabetic macular edema by 23% compared with conventional treatment. Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control, with a 58% risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study.

The frequency of an unsatisfactory outcome with respect to proportion with vision improvement following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. These studies suggest that vitreomacular traction, or the vitreous itself, may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema that have a component of vitreomacular traction contributing to the edema. It also requires a complex surgical intervention with its inherent risks, recovery time, and expense. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and use of intravitreal corticosteroids are under investigation. The use of antibodies targeted at vascular endothelial growth factor (VEGF), such as in the current study, is another treatment modality that has generated considerable interest, and is currently being investigated in phase 3 trials of choroidal neovascularization in age-related macular degeneration (with pegaptanib or ranibizumab) or diabetic macular edema (with pegaptanib).

Increased VEGF levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy. VEGF, also known as vascular permeability factor, has been demonstrated to increase vessel permeability by increasing the phosphorylation of tight junction proteins, and has been shown to increase retinal vascular permeability in in vivo models. Anti-VEGF therapy, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of diabetic macular edema.

Bevacizumab is currently approved for the treatment of metastatic colorectal cancer, and published case reports and widespread clinical use have suggested its efficacy in the treatment of neovascular age-related macular degeneration and macular edema associated with diabetes and central retinal vein occlusion. To date, no evidence of ocular inflammation or other adverse events has been noted in association with intravitreal injection of bevacizumab. However, a study has not been conducted to evaluate its efficacy and safety. In view of the widespread use of bevacizumab, such a study is important to conduct.

From a public health perspective, an intravitreal bevacizumab study is also important to conduct because of the relatively low cost of the bevacizumab drug. As noted earlier, bevacizumab is marketed for systemic use for colon cancer. The dose used in the eye is a fraction of the systemic dose and costs $25 to $50 per dose.

The two doses of bevacizumab being evaluated in this study will be 1.25 mg, which is the dose that has most commonly been used in clinical practice, and 2.5 mg, which has also been used though less commonly. A lower dose than 1.25 mg would create difficulties with dilution and the accuracy of injection of a small volume.

The optimal interval for the bevacizumab doses is not known. Six weeks has been selected for this study as it is not believed that the effect will last longer than this. Retinal thickening and visual acuity will be measured at 3 and 6 weeks to provide the requisite information to judge the duration of effect.

There is expected to be a beneficial cumulative effect of multiple doses. A total of two doses, spaced 6 weeks apart, was selected for the study with the primary outcome 3 weeks after the second dose.

The decision as to whether to proceed to a phase 3 trial will be based on the observation of a substantial reduction in retinal thickening in the bevacizumab-treated eyes compared with the laser-treated eyes and at least a suggestion of benefit on visual acuity, plus a safety profile of minimal risk.

Description: The study involves the enrollment of subjects over 18 years of age with diabetic macular edema. Subjects will have one study eye randomly assigned with equal probability (stratified by visual acuity) to one of 5 treatment groups:

Laser photocoagulation at baseline

1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks

2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks

1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)

1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks

Follow-up includes 10 visits at 4 days, 3 weeks, 6 weeks, 4 days following 6 weeks, 9 weeks, 12 weeks, 18 weeks, 24 weeks, 41 weeks and 70 weeks. At each visit, visual acuity and ocular exams are completed on both eyes, and an OCT is performed on the study eye (except at the 4-day visits).

During the first 12 weeks, no other treatment for DME is given. During weeks 13-24, treatment depends on the response to the treatment given during the first 12 weeks. After 24 weeks, follow-up is for safety and treatment is at the investigator's discretion.

Study Design

Study Type:
Interventional
Actual Enrollment :
121 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)
Study Start Date :
Jun 1, 2006
Actual Primary Completion Date :
Nov 1, 2006
Actual Study Completion Date :
Feb 1, 2008

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: 1

Laser photocoagulation at baseline

Procedure: Laser Photocoagulation
Laser photocoagulation at baseline; If edema present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart

Experimental: 2

1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks

Drug: Bevacizumab
1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Other Names:
  • Avastin
  • anti-VEGF drug
  • Experimental: 3

    2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks

    Drug: Bevacizumab
    2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Other Names:
  • Avastin
  • anti-VEGF drug
  • Experimental: 4

    1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)

    Drug: Bevacizumab
    1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)
    Other Names:
  • Avastin
  • anti-VEGF drug
  • Experimental: 5

    1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks

    Drug: Bevacizumab
    1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Other Names:
  • Avastin
  • anti-VEGF drug
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits [Baseline to 3,6,9, and 12 weeks]

      Change in central subfield retinal thickness from baseline measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading. Negative changes represent a decrease in retinal thickening.

    2. Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits [Baseline to 3,6,9, and 12 Weeks]

      Central subfield retinal thickness measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading.

    Secondary Outcome Measures

    1. Change in Visual Acuity Letter Score From Baseline Over All All Study Visits [Baseline to 3,6,9, and 12 weeks]

      Change in visual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; positive change represents an improvement in letter score.

    2. Distribution of Change in Visual Acuity Over All Study Visits [Baseline to 3,6,9, and 12 weeks]

      Visual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; an increase in a letter score by 10 is considered clinically significant.

    Other Outcome Measures

    1. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness [Baseline to 3 Weeks]

      Pooled Bevacizumab groups include the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    2. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score [Baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    3. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline [Baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    4. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender [Baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    5. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline [Baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    6. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks + laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. Retinopathy severity based on investigator discretion on clinical examination.

    7. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    8. Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    9. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    10. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    11. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    12. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    13. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    14. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    15. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    16. Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline [baseline to 3 Weeks]

      Pooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.

    17. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 1.25mg Bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Duration of effect of Bevacizumab was based on additional improvement versus maintained improvement versus worsening within 3 to 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in the DRCR.net paper, Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema.Ophthalmology 2007;114:1520-25.

    18. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had Within a ±11% Change of Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 1.25mg bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The pooled 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    19. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 1.25mg bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The pooled 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    20. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    21. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had Within a ±11% Change in Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    22. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks [3 to 6 Weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    23. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    24. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    25. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    26. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    27. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    28. Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks [3 to 9 weeks]

      The 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    SUBJECT-LEVEL INCLUSION CRITERIA

    To be eligible, the following inclusion criteria (1-3) must be met:
    1. Age >= 18 years

    2. Diagnosis of diabetes mellitus (type 1 or type 2)

    3. Able and willing to provide informed consent.

    EXCLUSION

    A subject is not eligible if any of the following exclusion criteria (4-13) are present:

    1. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.

    2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

    3. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.

    4. Known allergy to any component of the study drug.

    5. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110).

    6. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.

    7. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization.

    8. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization.

    9. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 6 months.

    10. Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 6 months of the study.

    STUDY EYE CRITERIA

    The subject must have one eye meeting all of the inclusion criteria (a-e) and none of the exclusion criteria (f-r) listed below.

    Subjects can have only one study eye. If both eyes are eligible, the study eye will be selected by the investigator and subject.

    The eligibility criteria for a study eye are as follows:

    INCLUSION

    1. Best corrected E-ETDRS visual acuity letter score of >= 24 (i.e., 20/320 or better) and <= 78 (i.e., 20/32 or worse) within 8 days of randomization.

    2. On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.

    3. OCT central subfield >=275 microns within 8 days of randomization.

    4. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.

    5. If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

    EXCLUSION

    The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

    1. Macular edema is considered to be due to a cause other than diabetic macular edema.

    2. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition).

    3. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).

    4. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).

    5. History of treatment for DME at any time in the past 3 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).

    6. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.

    7. Anticipated need for PRP in the 6 months following randomization.

    8. History of prior pars plana vitrectomy.

    9. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization.

    10. History of YAG capsulotomy performed within 2 months prior to randomization.

    11. Aphakia.

    12. Uncontrolled glaucoma (in investigator's judgment).

    13. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

    FELLOW EYE CRITERIA

    The fellow eye must meet the following criteria:
    1. Best corrected E-ETDRS visual acuity letter score >= 19 (i.e., 20/400 or better).

    2. No anti-VEGF treatment within the past 3 months and no expectation of such treatment in next 3 months.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Loma Linda University Health Care, Dept. of OphthalmologyLoma LindaCaliforniaUnited States92354
    2Southern California Desert Retina Consultants, MCPalm SpringsCaliforniaUnited States92262
    3California Retina ConsultantsSanta BarbaraCaliforniaUnited States93103
    4Bay Area Retina AssociatesWalnut CreekCaliforniaUnited States94598
    5Retina Vitreous ConsultantsFt. LauderdaleFloridaUnited States33334
    6Central Florida Retina InstituteLakelandFloridaUnited States33805
    7Southeast Retina Center, P.C.AugustaGeorgiaUnited States30909
    8Illinois Retina AssociatesJolietIllinoisUnited States60435
    9Raj K. Maturi, M.D., P.C.IndianapolisIndianaUnited States46280
    10American Eye InstituteNew AlbanyIndianaUnited States47150
    11Retina and Vitreous Associates of KentuckyLexingtonKentuckyUnited States
    12Paducah Retinal CenterPaducahKentuckyUnited States42001
    13Maine Vitreoretinal ConsultantsBangorMaineUnited States04401
    14Elman Retina Group, P.A.BaltimoreMarylandUnited States21237
    15Retina Consultants of Delmarva, P.A.SalisburyMarylandUnited States21801
    16Ophthalmic Consultants of BostonBostonMassachusettsUnited States02114
    17Joslin Diabetes CenterBostonMassachusettsUnited States02215
    18Retina Center, PAMinneapolisMinnesotaUnited States55404
    19Charlotte Eye, Ear, Nose and Throat Assoc., PACharlotteNorth CarolinaUnited States28210
    20Wake Forest University Eye CenterWinston-SalemNorth CarolinaUnited States27157
    21Retina Associates of Cleveland, Inc.BeachwoodOhioUnited States44122
    22Retina Northwest, PCPortlandOregonUnited States97210
    23Casey Eye InstitutePortlandOregonUnited States97239
    24Penn State College of MedicineHersheyPennsylvaniaUnited States17033
    25Retina ConsultantsProvidenceRhode IslandUnited States02903
    26Palmetto Retina CenterColumbiaSouth CarolinaUnited States29169
    27Carolina Retina CenterColumbiaSouth CarolinaUnited States29223
    28Southeastern Retina Associates, P.C.KnoxvilleTennesseeUnited States37909
    29West Texas Retina Consultants P.A.AbileneTexasUnited States79605
    30Retina Research CenterAustinTexasUnited States78705
    31Texas Retina AssociatesDallasTexasUnited States75231
    32Charles A. Garcia, PA & AssociatesHoustonTexasUnited States77002
    33Texas Retina AssociatesLubbockTexasUnited States79424
    34University of Washington Medical CenterSeattleWashingtonUnited States98195

    Sponsors and Collaborators

    • Jaeb Center for Health Research
    • National Eye Institute (NEI)

    Investigators

    • Study Chair: Ingrid U. Scott, M.D., M.P.H., Penn State College of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00336323
    Other Study ID Numbers:
    • NEI-129
    • U10EY018817-03
    • U10EY014229-07
    • U10EY014231-09
    • EY14231, EY14269, EY14229
    First Posted:
    Jun 13, 2006
    Last Update Posted:
    Aug 26, 2016
    Last Verified:
    Aug 1, 2016

    Study Results

    Participant Flow

    Recruitment DetailsThirty-six clinical sites across the United States recruited 121 subjects (109 met criteria for inclusion in the analyses) between June 2006 and August 2006.
    Pre-assignment DetailUnless otherwise noted, differences in number of Participants at different visits reflect a missed visit, not a drop-out.
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Period Title: Overall Study
    STARTED1922242222
    3 Week Visit1821242220
    6 Week Visit1822242220
    9 Week Visit1821232119
    12 Week Visit1921242220
    18 Week Visit1922232118
    24 Week Visit1820222219
    COMPLETED1921232219
    NOT COMPLETED01103

    Baseline Characteristics

    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3wTotal
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeksTotal of all reporting groups
    Overall Participants1922242222109
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    64
    63
    68
    60
    67
    65
    Sex: Female, Male (Count of Participants)
    Female
    9
    47.4%
    6
    27.3%
    9
    37.5%
    9
    40.9%
    10
    45.5%
    43
    39.4%
    Male
    10
    52.6%
    16
    72.7%
    15
    62.5%
    13
    59.1%
    12
    54.5%
    66
    60.6%
    Race/Ethnicity, Customized (participants) [Number]
    White
    10
    52.6%
    16
    72.7%
    20
    83.3%
    18
    81.8%
    19
    86.4%
    83
    76.1%
    African-American
    7
    36.8%
    3
    13.6%
    2
    8.3%
    3
    13.6%
    2
    9.1%
    17
    15.6%
    Hispanic or Latino
    2
    10.5%
    2
    9.1%
    2
    8.3%
    0
    0%
    1
    4.5%
    7
    6.4%
    Asian
    0
    0%
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    1
    0.9%
    Unknown/ not reported
    0
    0%
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    Character of Diabetic Macular Edema (DME) (participants) [Number]
    Typical/Predominantly Focal
    6
    31.6%
    5
    22.7%
    2
    8.3%
    3
    13.6%
    4
    18.2%
    20
    18.3%
    Neither Predominantly Focal or Diffuse
    4
    21.1%
    5
    22.7%
    5
    20.8%
    6
    27.3%
    6
    27.3%
    26
    23.9%
    Typical/Predominantly Diffuse
    9
    47.4%
    12
    54.5%
    17
    70.8%
    13
    59.1%
    12
    54.5%
    63
    57.8%
    Cystoid Abnormalities on Optical Coherence Tomography (OCT) (participants) [Number]
    Yes
    18
    94.7%
    22
    100%
    24
    100%
    21
    95.5%
    21
    95.5%
    106
    97.2%
    No
    1
    5.3%
    0
    0%
    0
    0%
    1
    4.5%
    1
    4.5%
    3
    2.8%
    Diabetes Type (participants) [Number]
    Type 1
    1
    5.3%
    1
    4.5%
    3
    12.5%
    2
    9.1%
    1
    4.5%
    8
    7.3%
    Type 2
    18
    94.7%
    21
    95.5%
    21
    87.5%
    20
    90.9%
    21
    95.5%
    101
    92.7%
    Lens status (clinical examination) (participants) [Number]
    Phakic
    12
    63.2%
    15
    68.2%
    14
    58.3%
    12
    54.5%
    13
    59.1%
    66
    60.6%
    Pseudophakic
    7
    36.8%
    7
    31.8%
    10
    41.7%
    10
    45.5%
    9
    40.9%
    43
    39.4%
    Prior Panretinal Scatter Photocoagulation (participants) [Number]
    Yes
    3
    15.8%
    2
    9.1%
    3
    12.5%
    1
    4.5%
    4
    18.2%
    13
    11.9%
    No
    16
    84.2%
    20
    90.9%
    21
    87.5%
    21
    95.5%
    18
    81.8%
    96
    88.1%
    Prior Treatment for Diabetic Macular Edema (DME) in Study Eye (participants) [Number]
    None
    7
    36.8%
    5
    22.7%
    10
    41.7%
    5
    22.7%
    7
    31.8%
    34
    31.2%
    Focal photocoagulation alone
    4
    21.1%
    11
    50%
    9
    37.5%
    6
    27.3%
    9
    40.9%
    39
    35.8%
    Focal photocoagulation plus other treatment
    8
    42.1%
    3
    13.6%
    3
    12.5%
    11
    50%
    6
    27.3%
    31
    28.4%
    Other treatment without focal photocoagulation
    0
    0%
    3
    13.6%
    2
    8.3%
    0
    0%
    0
    0%
    5
    4.6%
    Retinopathy Severity (participants) [Number]
    Mild nonproliferative diabetic retinopathy (NPDR)
    1
    5.3%
    6
    27.3%
    3
    12.5%
    0
    0%
    4
    18.2%
    14
    12.8%
    Moderate NPDR
    5
    26.3%
    3
    13.6%
    1
    4.2%
    3
    13.6%
    3
    13.6%
    15
    13.8%
    Moderately severe NPDR
    5
    26.3%
    6
    27.3%
    8
    33.3%
    8
    36.4%
    9
    40.9%
    36
    33%
    Severe NPDR
    0
    0%
    1
    4.5%
    2
    8.3%
    4
    18.2%
    1
    4.5%
    8
    7.3%
    Mild proliferative diabetic retinopathy (PDR)
    4
    21.1%
    5
    22.7%
    6
    25%
    5
    22.7%
    4
    18.2%
    24
    22%
    Moderate PDR
    1
    5.3%
    0
    0%
    2
    8.3%
    0
    0%
    1
    4.5%
    4
    3.7%
    High Risk PDR
    2
    10.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.8%
    Missing
    1
    5.3%
    1
    4.5%
    2
    8.3%
    2
    9.1%
    0
    0%
    6
    5.5%
    Subretinal Fluid on Optical Coherence Tomography (OCT) (participants) [Number]
    Definite, center
    2
    10.5%
    2
    9.1%
    7
    29.2%
    2
    9.1%
    4
    18.2%
    17
    15.6%
    Definite, not center
    0
    0%
    1
    4.5%
    1
    4.2%
    0
    0%
    1
    4.5%
    3
    2.8%
    Questionable
    0
    0%
    1
    4.5%
    0
    0%
    2
    9.1%
    0
    0%
    3
    2.8%
    No evidence
    16
    84.2%
    18
    81.8%
    16
    66.7%
    18
    81.8%
    17
    77.3%
    85
    78%
    Missing
    1
    5.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    Baseline Visual Acuity (letter score) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [letter score]
    64
    65
    63
    64
    66
    64
    Duaration of Diabetes (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    17
    15
    18
    17
    20
    17
    Hemoglobin A1c (percent HbA1c) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [percent HbA1c]
    7.0
    7.4
    7.3
    6.7
    7.1
    6.9
    Optical Coherence Tomography (OCT) Central Subfield Thickness (microns) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [microns]
    441
    397
    446
    406
    389
    411
    Optical Coherence Tomography Retinal Volume (mm^3) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mm^3]
    8.3
    9.5
    9.1
    8.9
    8.6
    8.6

    Outcome Measures

    1. Primary Outcome
    TitleChange in Central Subfield Retinal Thickness From Baseline Over All Study Visits
    DescriptionChange in central subfield retinal thickness from baseline measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading. Negative changes represent a decrease in retinal thickening.
    Time FrameBaseline to 3,6,9, and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    The primary analysis included per protocol and intent to treat analysis. The intent to treat analysis included all randomized eyes. The last observation carried forward method was used to impute missing data. The per-protocol analysis was performed including only patients who receive treatment as per the protocol and complete the 9-week exam.
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Measure Participants1922242222
    3 Weeks
    21
    -35
    -86
    -3
    -13
    6 Weeks
    -40
    -35
    -42
    -17
    -20
    9 Weeks
    -53
    -74
    -56
    5
    -48
    12 Weeks
    -40
    -56
    -47
    -5
    -40
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline, 1.25 mg Injection at Baseline and at 6 Weeks
    Comments Comparison of central subfield thickness at the 3 week visit between the laser only treatment group to the 1.25 mg injection at baseline and at 6 weeks treatment group
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.009
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of central subfield thickness at the 3 week visit between the laser only treatment group to the 2.5mg injection at baseline and 6 weeks treatment group
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of the reduction in central subfield thickening in the 1.25mg injection at baseline and at 6 weeks treatment group with the 2.5mg injection at baseline and 6 weeks treatment group at the 3 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.66
    CommentsAdjusted for baseline values
    MethodLeast squares regression
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of the reduction in central subfield thickening in the 1.25mg injection at baseline and at 6 weeks treatment group with the 2.5mg injection at baseline and 6 weeks treatment group at the 6 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.49
    CommentsAdjusted for baseline values
    MethodLeast squares regression
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of the reduction in central subfield thickening in the 1.25mg injection at baseline and at 6 weeks treatment group with the 2.5mg injection at baseline and 6 weeks treatment group at the 9 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.45
    CommentsAdjusted for baseline values
    MethodLeast squares regression
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of the reduction in central subfield thickening in the 1.25mg injection at baseline and at 6 weeks treatment group with the 2.5mg injection at baseline and 6 weeks treatment group at the 12 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.90
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    2. Secondary Outcome
    TitleChange in Visual Acuity Letter Score From Baseline Over All All Study Visits
    DescriptionChange in visual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; positive change represents an improvement in letter score.
    Time FrameBaseline to 3,6,9, and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Measure Participants1922242222
    3 Weeks
    -2
    5
    6
    2
    0
    6 Weeks
    1
    5
    6
    3
    0
    9 Weeks
    3
    7
    8
    1
    -2
    12 Weeks
    -1
    5
    7
    4
    0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of improvement in visual acuity between the 1.25mg injection at baseline and at 6 weeks treatment group and the 2.5mg injection at baseline and 6 weeks treatment group at the 3 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.42
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of improvement in visual acuity between the 1.25mg injection at baseline and at 6 weeks treatment group and the 2.5mg injection at baseline and 6 weeks treatment group at the 6 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.67
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of improvement in visual acuity between the 1.25mg injection at baseline and at 6 weeks treatment group and the 2.5mg injection at baseline and 6 weeks treatment group at the 9 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.48
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 1.25 mg Injection at Baseline and at 6 Weeks, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of improvement in visual acuity between the 1.25mg injection at baseline and at 6 weeks treatment group and the 2.5mg injection at baseline and 6 weeks treatment group at the 12 week visit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.82
    Comments
    MethodLeast squares regression
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline, 1.25 mg Injection at Baseline and at 6 Weeks
    Comments Comparison of improvement in visual acuity through the 12 week visit between the laser only treatment group and the 1.25mg injection at baseline and at 6 weeks treatment group
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.01
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline, 2.5 mg Injection at Baseline and 6 Weeks
    Comments Comparison of improvement in visual acuity through the 12 week visit between the laser only treatment group and the 2.5mg injection at baseline and at 6 weeks treatment group
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.003
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    3. Primary Outcome
    TitlePercentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits
    DescriptionCentral subfield retinal thickness measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading.
    Time FrameBaseline to 3,6,9, and 12 Weeks

    Outcome Measure Data

    Analysis Population Description
    The primary analysis included per protocol and intent to treat analysis. The intent to treat analysis included all randomized eyes. The last observation carried forward method was used to impute missing data. The per-protocol analysis was performed including only patients who receive treatment as per the protocol and complete the 9-week exam.
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Measure Participants1922242222
    3 Weeks
    11
    57.9%
    37
    168.2%
    38
    158.3%
    10
    45.5%
    25
    113.6%
    6 Weeks
    17
    89.5%
    30
    136.4%
    22
    91.7%
    19
    86.4%
    25
    113.6%
    9 Weeks
    19
    100%
    38
    172.7%
    22
    91.7%
    10
    45.5%
    37
    168.2%
    12 Weeks
    21
    110.5%
    33
    150%
    33
    137.5%
    14
    63.6%
    25
    113.6%
    4. Secondary Outcome
    TitleDistribution of Change in Visual Acuity Over All Study Visits
    DescriptionVisual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; an increase in a letter score by 10 is considered clinically significant.
    Time FrameBaseline to 3,6,9, and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    Measure Participants1922242222
    ≥ 10 letter improvement at 3 Weeks
    1
    5.3%
    4
    18.2%
    4
    16.7%
    2
    9.1%
    2
    9.1%
    ≥ 10 letters worse at 3 Weeks
    1
    5.3%
    1
    4.5%
    0
    0%
    1
    4.5%
    0
    0%
    ≥ 10 letter improvement at 6 Weeks
    2
    10.5%
    7
    31.8%
    7
    29.2%
    3
    13.6%
    3
    13.6%
    ≥ 10 letters worse at 6 Weeks
    2
    10.5%
    0
    0%
    1
    4.2%
    1
    4.5%
    4
    18.2%
    ≥ 10 letter improvement at 9 Weeks
    3
    15.8%
    6
    27.3%
    9
    37.5%
    3
    13.6%
    5
    22.7%
    ≥ 10 letters worse at 9 Weeks
    1
    5.3%
    1
    4.5%
    0
    0%
    0
    0%
    2
    9.1%
    ≥ 10 letter improvement at 12 Weeks
    3
    15.8%
    7
    31.8%
    6
    25%
    2
    9.1%
    4
    18.2%
    ≥ 10 letters worse at 12 Weeks
    1
    5.3%
    1
    4.5%
    0
    0%
    2
    9.1%
    2
    9.1%
    5. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness
    DescriptionPooled Bevacizumab groups include the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time FrameBaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <400 microns
    -3
    ≥400 microns
    -102
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had baseline central subfield thickness of <400 microns compared to those that had baseline central subfield thickness of ≥400 microns. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    6. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time FrameBaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <65 letters
    -35
    ≥65 letters
    -28
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had baseline visual acuity letter score that was <65 letters compared to those that had baseline visual acuity letter score that was ≥65 letters. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.31
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline score
    7. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time FrameBaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    ≤66 years
    -45
    >66 years
    -16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between those that were ≤66 years old compared to those that were >66 years old at baseline. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.44
    Comments
    MethodLeast squares regression
    Comments
    8. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time FrameBaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Female
    -28
    Male
    -35
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between females and males. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.55
    Comments
    MethodLeast squares regression
    Comments
    9. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time FrameBaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    No
    -40
    Yes
    -29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had no history of treatment for diabetic macular edema compared to those that had history or treatment for diabetic macular edema. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.16
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    10. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline
    DescriptionPooled Bevacizumab group includes treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks + laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. Retinopathy severity based on investigator discretion on clinical examination.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <Severe nonproliferative diabetic retinopathy
    -31
    Proliferative diabetic retinopathy or severe NPDR
    -31
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had baseline retinopathy severity that was <severe nonproliferative diabetic retinopathy (NPDR) compared to those that had baseline retinopathy severity that was proliferative diabetic retinopathy or severe NPDR. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.53
    Comments
    MethodLeast squares regression
    Comments
    11. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Typical/Predominantly Focal
    -13
    Neither Predominantly Focal or Diffuse
    -8
    Typical/Predominantly Diffuse
    -82
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had baseline clinical diabetic macular edema characterized as typical/predominantly focal, neither predominantly focal or diffuse, or typical/predominantly diffuse. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.93
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    12. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. Negative values represent a reduction in central subfield thickness. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Definite/Questionable
    -35
    No Evidence
    -29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of central subfield thickness (microns) change from baseline to the 3 week visit between eyes that had baseline subretinal fluid that was definite/questionable compared to eyes that had no evidence of subretinal fluid at baseline. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.52
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    13. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <400 microns
    1
    ≥400 microns
    5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that had baseline central subfield thickness of <400 microns compared to eyes that had baseline central subfield thickness of ≥400 microns. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.22
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    14. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <65 letters
    3
    ≥65 letters
    1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that had a baseline visual acuity letter score of <65 letters compared to eyes that had baseline visual acuity letter score of ≥65 letters. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.006
    Comments
    MethodLeast squares regression
    CommentsAdjusted for baseline values
    15. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    ≤66 years
    4
    >66 years
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that were ≤66 years old at baseline compared to eyes that were >66 years old at baseline. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.23
    Comments
    MethodLeast squares regression
    Comments
    16. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Female
    3
    Male
    3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between females and males. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.37
    Comments
    MethodLeast squares regression
    Comments
    17. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    No
    5
    Yes
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that did not have a prior history of treatment for diabetic macular edema compared to eyes that did have a prior history of treatment for diabetic macular edema. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.04
    Comments
    MethodLeast squares regression
    Comments
    18. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    <Severe nonproliferative diabetic retinopathy
    3
    Proliferative diabetic retinopathy or severe NPDR
    1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that had a baseline retinopathy severity of <severe nonproliferative diabetic retinopathy (NPDR) compared to eyes that had baseline retinopathy severity of proliferative diabetic retinopathy or severe NPDR. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.38
    Comments
    MethodLeast squares regression
    Comments
    19. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Typical/Predominantly Focal
    7
    Neither Predominantly Focal or Diffuse
    0
    Typical/Predominantly Diffuse
    3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that had a baseline clinical diabetic macular edema (DME) characterization of typical/predominantly focal compared to neither predominantly focal or diffuse characterization at baseline and compared to typical/predominantly diffuse characterization at baseline. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.45
    Comments
    MethodLeast squares regression
    Comments
    20. Other Pre-specified Outcome
    TitleChange in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline
    DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks, 2.5mg at baseline and at 6 weeks, 1.25mg at baseline only, and 1.25mg at baseline and 6 weeks plus laser at 3 weeks. The 4 bevacizumab groups (N=87) were pooled to compare differences in response at 3 weeks among subgroups of interest. The pooled Bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure. Positive values represent an improvement in letter score.
    Time Framebaseline to 3 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled Bevacizumab Groups
    Arm/Group DescriptionPooled Bevacizumab group includes the following treatment groups: 1.25mg at baseline and at 6 weeks; 2.5mg at baseline and at 6 weeks; 1.25mg at baseline only; and 1.25mg at baseline and 6 weeks plus laser at 3 weeks.
    Measure Participants87
    Definite/Questionable
    6
    No Evidence
    1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Laser at Baseline
    Comments Comparison of change in visual acuity letter score from baseline to the 3 week visit between eyes that had a baseline subretinal fluid presence that was definite/questionable compared to eyes that there was no evidence of subretinal fluid at baseline. Eyes included all of those from the pooled Bevacizumab group.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.06
    Comments
    MethodLeast squares regression
    Comments
    21. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 1.25mg Bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Duration of effect of Bevacizumab was based on additional improvement versus maintained improvement versus worsening within 3 to 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in the DRCR.net paper, Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema.Ophthalmology 2007;114:1520-25.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled 1.25mg Initial Bevacizumab Injection Groups
    Arm/Group DescriptionThe following are the treatment groups included in the Pooled 1.25mg Bevacizumab Groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only
    Measure Participants14
    >11% Decreased Change from 3 Weeks to 6 Weeks
    1
    5.3%
    Within ± 11% Change from 3 Weeks to 6 Weeks
    11
    57.9%
    >11% Increased Change from 3 Weeks to 6 Weeks
    2
    10.5%
    22. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had Within a ±11% Change of Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 1.25mg bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The pooled 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled 1.25mg Initial Bevacizumab Injection Groups
    Arm/Group DescriptionThe following are the treatment groups included in the Pooled 1.25mg Bevacizumab Groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only
    Measure Participants22
    >11% Decreased Change from 3 Weeks to 6 Weeks
    2
    10.5%
    Within ± 11% Change from 3 Weeks to 6 Weeks
    16
    84.2%
    >11% Increased Change from 3 Weeks to 6 Weeks
    4
    21.1%
    23. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 1.25mg bevacizumab groups include the following treatment groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The pooled 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePooled 1.25mg Initial Bevacizumab Injection Groups
    Arm/Group DescriptionThe following are the treatment groups included in the Pooled 1.25mg Bevacizumab Groups: 1.25mg at baseline and 6 weeks; and 1.25mg at baseline only
    Measure Participants2
    >11% Decreased Change from 3 Weeks to 6 Weeks
    1
    5.3%
    Within ± 11% Change from 3 Weeks to 6 Weeks
    1
    5.3%
    >11% Increased Change from 3 Weeks to 6 Weeks
    0
    0%
    24. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants13
    >11% Decreased Change from 3 Weeks to 6 Weeks
    0
    0%
    Within ± 11% Change from 3 Weeks to 6 Weeks
    9
    47.4%
    >11% Increased Change from 3 Weeks to 6 Weeks
    4
    21.1%
    25. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had Within a ±11% Change in Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants10
    >11% Decreased Change from 3 Weeks to 6 Weeks
    0
    0%
    Within ± 11% Change from 3 Weeks to 6 Weeks
    9
    47.4%
    >11% Increased Change from 3 Weeks to 6 Weeks
    1
    5.3%
    26. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 6 Weeks

    Outcome Measure Data

    Analysis Population Description
    There were no participants with a change in central subfield thickness from 3 to 6 weeks in this treatment group that had a >11% increase in change of central subfield thickness from baseline to 3 weeks.
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants0
    27. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title1.25 mg Injection at Baseline and at 6 Weeks
    Arm/Group Description1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants7
    >11% Decreased Change from 9 Weeks to 12 Weeks
    0
    0%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    4
    21.1%
    >11% Increased Change from 9 Weeks to 12 Weeks
    3
    15.8%
    28. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title1.25 mg Injection at Baseline and at 6 Weeks
    Arm/Group Description1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants9
    >11% Decreased Change from 9 Weeks to 12 Weeks
    1
    5.3%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    6
    31.6%
    >11% Increased Change from 9 Weeks to 12 Weeks
    2
    10.5%
    29. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 1.25mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 1.25mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title1.25 mg Injection at Baseline and at 6 Weeks
    Arm/Group Description1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants2
    >11% Decreased Change from 9 Weeks to 12 Weeks
    0
    0%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    2
    10.5%
    >11% Increased Change from 9 Weeks to 12 Weeks
    0
    0%
    30. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants3
    >11% Decreased Change from 9 Weeks to 12 Weeks
    0
    0%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    2
    10.5%
    >11% Increased Change from 9 Weeks to 12 Weeks
    1
    5.3%
    31. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants17
    >11% Decreased Change from 9 Weeks to 12 Weeks
    2
    10.5%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    14
    73.7%
    >11% Increased Change from 9 Weeks to 12 Weeks
    1
    5.3%
    32. Other Pre-specified Outcome
    TitleChange in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks
    DescriptionThe 2.5mg bevacizumab treatment group received an injection at both baseline and at 6 weeks. Change in central subfield thickness was categorized according to whether it exceeded 11%, the reliability limit for real change determined in another Diabetic Retinopathy Clinical Research Network study 16. The 2.5mg bevacizumab treatment group will be the only group/arm that has values, all other treatment groups/arms will have a null value for this outcome measure.
    Time Frame3 to 9 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title2.5 mg Injection at Baseline and 6 Weeks
    Arm/Group Description2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
    Measure Participants2
    >11% Decreased Change from 9 Weeks to 12 Weeks
    1
    5.3%
    Within ± 11% Change from 9 Weeks to 12 Weeks
    1
    5.3%
    >11% Increased Change from 9 Weeks to 12 Weeks
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleLaser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Arm/Group DescriptionLaser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
    All Cause Mortality
    Laser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Laser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total8/19 (42.1%) 8/22 (36.4%) 6/24 (25%) 1/22 (4.5%) 6/22 (27.3%)
    Blood and lymphatic system disorders
    Anemia1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Cardiac disorders
    Arteriosclerosis coronary artery0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Chest pain0/19 (0%) 1/22 (4.5%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    Congestive cardiac failure1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Hyperglycaemia0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Hypoglycaemia1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Intraventricular haemorrhage1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Myocardial infarction0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 3/22 (13.6%)
    Endocrine disorders
    Inadequate control of diabetes mellitus1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Gastrointestinal disorders
    Gastroenteritis1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Pancreatic carcinoma0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Vomiting0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    General disorders
    Death1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Delerium0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Endophthalmitis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Glaucoma0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Syncope0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Vitrectomy0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Hepatobiliary disorders
    Cholelithiasis0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Infections and infestations
    Localised infection0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Musculoskeletal and connective tissue disorders
    Cellulitis1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Hip fracture0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Renal and urinary disorders
    Renal failure0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Renal impairment0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Metastatic lung cancer0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Pneumonia2/19 (10.5%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Skin and subcutaneous tissue disorders
    Bacterial skin infection1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Skin ulcer or skin lesion1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Vascular disorders
    Cerebrovascular accident1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Peripheral vascular disorder1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Other (Not Including Serious) Adverse Events
    Laser at Baseline1.25 mg Injection at Baseline and at 6 Weeks2.5 mg Injection at Baseline and 6 Weeks1.25 mg Injection at Baseline Only1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total14/19 (73.7%) 16/22 (72.7%) 19/24 (79.2%) 20/22 (90.9%) 22/22 (100%)
    Blood and lymphatic system disorders
    Anemia1/19 (5.3%) 1/22 (4.5%) 1/24 (4.2%) 1/22 (4.5%) 1/22 (4.5%)
    Hypercholesterolemia1/19 (5.3%) 2/22 (9.1%) 0/24 (0%) 2/22 (9.1%) 0/22 (0%)
    blood glucose decreased0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    blood potassium increased0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    haemoglobin decreased1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    hyperkalaemia1/19 (5.3%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    hypoglycaemia0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    leukocytosis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Cardiac disorders
    chest pain0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    chronic obstructive pulmonary disease1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    heart rate irregular0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    Ear and labyrinth disorders
    deafness1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Endocrine disorders
    Diabetes mellitus0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    diabetes mellitus inadequate control0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Eye disorders
    Angle Closure Glaucoma0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Anterior chamber cell0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Anterior chamber flare0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Blepharitis1/19 (5.3%) 2/22 (9.1%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    Cataract nuclear0/19 (0%) 2/22 (9.1%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Conjunctival hemorrhage0/19 (0%) 5/22 (22.7%) 1/24 (4.2%) 6/22 (27.3%) 3/22 (13.6%)
    Diabetic Retinopathy0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Diabetic retinal edema0/19 (0%) 5/22 (22.7%) 3/24 (12.5%) 2/22 (9.1%) 1/22 (4.5%)
    Diplopia0/19 (0%) 2/22 (9.1%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    Eye irritation0/19 (0%) 1/22 (4.5%) 0/24 (0%) 2/22 (9.1%) 1/22 (4.5%)
    Eye pain2/19 (10.5%) 4/22 (18.2%) 5/24 (20.8%) 3/22 (13.6%) 5/22 (22.7%)
    Foreign body sensation in eyes1/19 (5.3%) 0/22 (0%) 2/24 (8.3%) 0/22 (0%) 2/22 (9.1%)
    Glaucoma0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Increased intraocular pressure0/19 (0%) 1/22 (4.5%) 3/24 (12.5%) 3/22 (13.6%) 2/22 (9.1%)
    Lacrimation increased1/19 (5.3%) 3/22 (13.6%) 2/24 (8.3%) 2/22 (9.1%) 1/22 (4.5%)
    Ocular hyperaemia1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 2/22 (9.1%)
    Vision blurred5/19 (26.3%) 6/22 (27.3%) 5/24 (20.8%) 5/22 (22.7%) 5/22 (22.7%)
    Visual acuity reduced2/19 (10.5%) 4/22 (18.2%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    Visual disturbance0/19 (0%) 0/22 (0%) 4/24 (16.7%) 2/22 (9.1%) 1/22 (4.5%)
    Vitreous floaters0/19 (0%) 7/22 (31.8%) 8/24 (33.3%) 1/22 (4.5%) 3/22 (13.6%)
    Vitreous hemorrhage0/19 (0%) 1/22 (4.5%) 5/24 (20.8%) 3/22 (13.6%) 2/22 (9.1%)
    cataract1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    cataract cortical0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    cataract operation0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    cataract operation complication0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    cataract subcapsular1/19 (5.3%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    conjunctivitis0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    conjunctivitis allergic0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    conjunctivitis viral0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    corneal abrasion0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    corneal oedema0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    desemets membrane disorder0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    dry eye0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    eye inflammation0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    eye pruritus0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 1/22 (4.5%) 1/22 (4.5%)
    eyelid oedema0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 0/22 (0%) 1/22 (4.5%)
    eyelid pain1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    eyelid ptsosis1/19 (5.3%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    foreign body in eye0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    injection site irritaion0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    keratoconjunctivitis sicca1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    macular oedema1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 1/22 (4.5%)
    maculopathy1/19 (5.3%) 1/22 (4.5%) 2/24 (8.3%) 1/22 (4.5%) 0/22 (0%)
    oedema peripheral1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    optic nerve cupping1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    periorbital haematoma1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    photophobia0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    photopsia0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 1/22 (4.5%) 0/22 (0%)
    posterior capsule opacification0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    pterygium0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    punctate keratitis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    retinal degeneration0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    retinal detachment0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    retinal exudates0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    retinal laser coagulation0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    retinal neovascularisation0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    retinal oedema1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    retinal telagiectasia0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    vitrectomy0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    vitreous degeneration0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    vitreous detachment0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    vitreous opacities0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Gastrointestinal disorders
    Duodenitis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Gastroenteritis viral0/19 (0%) 2/22 (9.1%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    gastroenteritis0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    gastrooespohageal reflux disease1/19 (5.3%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    General disorders
    Abdominal pain0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Anorexia0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Back injury0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Headache1/19 (5.3%) 2/22 (9.1%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    Osteomyelitis1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Tooth abcess0/19 (0%) 2/22 (9.1%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    anxiety0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    arthralgia0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    asbestosis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    back pain0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    benign breast neoplasm0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    blister0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    blood creatine increased0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    breast cancer0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    caugh0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    chalazion0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    colon cancer0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    constipation1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    dizziness0/19 (0%) 0/22 (0%) 1/24 (4.2%) 1/22 (4.5%) 1/22 (4.5%)
    epistaxis0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    fall0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    haematochezia0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    herpes zoster1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    insomnia0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    intervertebral disc protrusion1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    joint dislocation1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    localised infection1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    nasopharyngitis1/19 (5.3%) 0/22 (0%) 3/24 (12.5%) 0/22 (0%) 0/22 (0%)
    nausea0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 0/22 (0%) 1/22 (4.5%)
    pain in extremity0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    pharyngolaryngeal pain0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    protein urine present1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    pruritus0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    reading disorder0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    respiratory tract congestion0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    rhinitis allergic0/19 (0%) 1/22 (4.5%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    sinusitis0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    swollen tongue0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    upper respiratory tract infection0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Infections and infestations
    Localised infection1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Injury, poisoning and procedural complications
    Head injury1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Musculoskeletal and connective tissue disorders
    rheumatoid arthritis0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    prostate cancer0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    skin cancer1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Nervous system disorders
    autonomic nervous system imbalance0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    nerve injury1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    trigeminal neuralgia0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Psychiatric disorders
    depression1/19 (5.3%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    Renal and urinary disorders
    renal failure1/19 (5.3%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    renal failure chronic1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    urinary incontinence1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    urinary tract infection0/19 (0%) 1/22 (4.5%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchitis2/19 (10.5%) 1/22 (4.5%) 0/24 (0%) 1/22 (4.5%) 1/22 (4.5%)
    Influenza0/19 (0%) 0/22 (0%) 1/24 (4.2%) 2/22 (9.1%) 1/22 (4.5%)
    Nasopharyngitis1/19 (5.3%) 0/22 (0%) 3/24 (12.5%) 0/22 (0%) 0/22 (0%)
    Pneumonia0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    Skin and subcutaneous tissue disorders
    Skin ulcer0/19 (0%) 0/22 (0%) 0/24 (0%) 1/22 (4.5%) 0/22 (0%)
    dermatitis allergic0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    dermatitis contact1/19 (5.3%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 1/22 (4.5%)
    fungal skin infection0/19 (0%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 1/22 (4.5%)
    peritonitis0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    rash0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    skin lesion excision0/19 (0%) 0/22 (0%) 1/24 (4.2%) 0/22 (0%) 0/22 (0%)
    Vascular disorders
    Cerebrovascular accident1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    Hypertension2/19 (10.5%) 2/22 (9.1%) 2/24 (8.3%) 1/22 (4.5%) 1/22 (4.5%)
    Peripheral vascular disease1/19 (5.3%) 0/22 (0%) 0/24 (0%) 0/22 (0%) 0/22 (0%)
    deep vein thrombosis0/19 (0%) 1/22 (4.5%) 0/24 (0%) 0/22 (0%) 0/22 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleName/Official Title: Adam Glassman, M.S., Director
    OrganizationJaeb Center for Health Research, Diabetic Retinopathy Clinical Research Network
    Phone(813) 975-8690
    Emaildrcrnet@jaeb.org
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00336323
    Other Study ID Numbers:
    • NEI-129
    • U10EY018817-03
    • U10EY014229-07
    • U10EY014231-09
    • EY14231, EY14269, EY14229
    First Posted:
    Jun 13, 2006
    Last Update Posted:
    Aug 26, 2016
    Last Verified:
    Aug 1, 2016