Diabetic Retinopathy
Conditions
Keywords
diabetic, macular, edema, avastin, bevacizumab, anti-VEGF, retinal thickness, visual acuity, DME
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.
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.
Interventions
PROCEDURELaser 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
DRUGBevacizumab
1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: 4. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant. 5. 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). 6. 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. 7. Known allergy to any component of the study drug. 8. Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110). 9. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months. 10. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization. 11. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization. 12. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 6 months. 13. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Thirty-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 details
Unless otherwise noted, differences in number of Participants at different visits reflect a missed visit, not a drop-out.
Participants by arm
| Arm | Count |
|---|---|
| Laser at Baseline Laser 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 apart | 19 |
| 1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks | 22 |
| 2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks | 24 |
| 1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks) | 22 |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w 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 | 22 |
| Total | 109 |
Baseline characteristics
| Characteristic | Laser at Baseline | 1.25 mg Injection at Baseline and at 6 Weeks | 2.5 mg Injection at Baseline and 6 Weeks | 1.25 mg Injection at Baseline Only | 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64 years | 63 years | 68 years | 60 years | 67 years | 65 years |
| Baseline Visual Acuity | 64 letter score | 65 letter score | 63 letter score | 64 letter score | 66 letter score | 64 letter score |
| Character of Diabetic Macular Edema (DME) Neither Predominantly Focal or Diffuse | 4 participants | 5 participants | 5 participants | 6 participants | 6 participants | 26 participants |
| Character of Diabetic Macular Edema (DME) Typical/Predominantly Diffuse | 9 participants | 12 participants | 17 participants | 13 participants | 12 participants | 63 participants |
| Character of Diabetic Macular Edema (DME) Typical/Predominantly Focal | 6 participants | 5 participants | 2 participants | 3 participants | 4 participants | 20 participants |
| Cystoid Abnormalities on Optical Coherence Tomography (OCT) No | 1 participants | 0 participants | 0 participants | 1 participants | 1 participants | 3 participants |
| Cystoid Abnormalities on Optical Coherence Tomography (OCT) Yes | 18 participants | 22 participants | 24 participants | 21 participants | 21 participants | 106 participants |
| Diabetes Type Type 1 | 1 participants | 1 participants | 3 participants | 2 participants | 1 participants | 8 participants |
| Diabetes Type Type 2 | 18 participants | 21 participants | 21 participants | 20 participants | 21 participants | 101 participants |
| Duaration of Diabetes | 17 years | 15 years | 18 years | 17 years | 20 years | 17 years |
| Hemoglobin A1c | 7.0 percent HbA1c | 7.4 percent HbA1c | 7.3 percent HbA1c | 6.7 percent HbA1c | 7.1 percent HbA1c | 6.9 percent HbA1c |
| Lens status (clinical examination) Phakic | 12 participants | 15 participants | 14 participants | 12 participants | 13 participants | 66 participants |
| Lens status (clinical examination) Pseudophakic | 7 participants | 7 participants | 10 participants | 10 participants | 9 participants | 43 participants |
| Optical Coherence Tomography (OCT) Central Subfield Thickness | 441 microns | 397 microns | 446 microns | 406 microns | 389 microns | 411 microns |
| Optical Coherence Tomography Retinal Volume | 8.3 mm^3 | 9.5 mm^3 | 9.1 mm^3 | 8.9 mm^3 | 8.6 mm^3 | 8.6 mm^3 |
| Prior Panretinal Scatter Photocoagulation No | 16 participants | 20 participants | 21 participants | 21 participants | 18 participants | 96 participants |
| Prior Panretinal Scatter Photocoagulation Yes | 3 participants | 2 participants | 3 participants | 1 participants | 4 participants | 13 participants |
| Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Focal photocoagulation alone | 4 participants | 11 participants | 9 participants | 6 participants | 9 participants | 39 participants |
| Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Focal photocoagulation plus other treatment | 8 participants | 3 participants | 3 participants | 11 participants | 6 participants | 31 participants |
| Prior Treatment for Diabetic Macular Edema (DME) in Study Eye None | 7 participants | 5 participants | 10 participants | 5 participants | 7 participants | 34 participants |
| Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Other treatment without focal photocoagulation | 0 participants | 3 participants | 2 participants | 0 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized African-American | 7 participants | 3 participants | 2 participants | 3 participants | 2 participants | 17 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 2 participants | 2 participants | 0 participants | 1 participants | 7 participants |
| Race/Ethnicity, Customized Unknown/ not reported | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 10 participants | 16 participants | 20 participants | 18 participants | 19 participants | 83 participants |
| Retinopathy Severity High Risk PDR | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Retinopathy Severity Mild nonproliferative diabetic retinopathy (NPDR) | 1 participants | 6 participants | 3 participants | 0 participants | 4 participants | 14 participants |
| Retinopathy Severity Mild proliferative diabetic retinopathy (PDR) | 4 participants | 5 participants | 6 participants | 5 participants | 4 participants | 24 participants |
| Retinopathy Severity Missing | 1 participants | 1 participants | 2 participants | 2 participants | 0 participants | 6 participants |
| Retinopathy Severity Moderately severe NPDR | 5 participants | 6 participants | 8 participants | 8 participants | 9 participants | 36 participants |
| Retinopathy Severity Moderate NPDR | 5 participants | 3 participants | 1 participants | 3 participants | 3 participants | 15 participants |
| Retinopathy Severity Moderate PDR | 1 participants | 0 participants | 2 participants | 0 participants | 1 participants | 4 participants |
| Retinopathy Severity Severe NPDR | 0 participants | 1 participants | 2 participants | 4 participants | 1 participants | 8 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 9 Participants | 9 Participants | 10 Participants | 43 Participants |
| Sex: Female, Male Male | 10 Participants | 16 Participants | 15 Participants | 13 Participants | 12 Participants | 66 Participants |
| Subretinal Fluid on Optical Coherence Tomography (OCT) Definite, center | 2 participants | 2 participants | 7 participants | 2 participants | 4 participants | 17 participants |
| Subretinal Fluid on Optical Coherence Tomography (OCT) Definite, not center | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 3 participants |
| Subretinal Fluid on Optical Coherence Tomography (OCT) Missing | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Subretinal Fluid on Optical Coherence Tomography (OCT) No evidence | 16 participants | 18 participants | 16 participants | 18 participants | 17 participants | 85 participants |
| Subretinal Fluid on Optical Coherence Tomography (OCT) Questionable | 0 participants | 1 participants | 0 participants | 2 participants | 0 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 19 | 16 / 22 | 19 / 24 | 20 / 22 | 22 / 22 |
| serious Total, serious adverse events | 8 / 19 | 8 / 22 | 6 / 24 | 1 / 22 | 6 / 22 |
Outcome results
Primary
Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits
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.
Time frame: Baseline to 3,6,9, and 12 weeks
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 3 Weeks | 21 microns |
| Laser at Baseline | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 6 Weeks | -40 microns |
| Laser at Baseline | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 9 Weeks | -53 microns |
| Laser at Baseline | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 12 Weeks | -40 microns |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 3 Weeks | -35 microns |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 12 Weeks | -56 microns |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 6 Weeks | -35 microns |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 9 Weeks | -74 microns |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 12 Weeks | -47 microns |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 6 Weeks | -42 microns |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 9 Weeks | -56 microns |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 3 Weeks | -86 microns |
| 1.25 mg Injection at Baseline Only | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 3 Weeks | -3 microns |
| 1.25 mg Injection at Baseline Only | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 6 Weeks | -17 microns |
| 1.25 mg Injection at Baseline Only | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 12 Weeks | -5 microns |
| 1.25 mg Injection at Baseline Only | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 9 Weeks | 5 microns |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 12 Weeks | -40 microns |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 9 Weeks | -48 microns |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 6 Weeks | -20 microns |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits | 3 Weeks | -13 microns |
Comparison: 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 groupp-value: 0.009Least squares regression
Comparison: 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 groupp-value: <0.001Least squares regression
Comparison: 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 visitp-value: 0.66Least squares regression
Comparison: 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 visitp-value: 0.49Least squares regression
Comparison: 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 visitp-value: 0.45Least squares regression
Comparison: 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 visitp-value: 0.9Least squares regression
Primary
Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits
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.
Time frame: Baseline to 3,6,9, and 12 Weeks
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 3 Weeks | 11 percentage of participants |
| Laser at Baseline | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 6 Weeks | 17 percentage of participants |
| Laser at Baseline | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 9 Weeks | 19 percentage of participants |
| Laser at Baseline | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 12 Weeks | 21 percentage of participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 3 Weeks | 37 percentage of participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 12 Weeks | 33 percentage of participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 6 Weeks | 30 percentage of participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 9 Weeks | 38 percentage of participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 12 Weeks | 33 percentage of participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 6 Weeks | 22 percentage of participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 9 Weeks | 22 percentage of participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 3 Weeks | 38 percentage of participants |
| 1.25 mg Injection at Baseline Only | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 3 Weeks | 10 percentage of participants |
| 1.25 mg Injection at Baseline Only | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 6 Weeks | 19 percentage of participants |
| 1.25 mg Injection at Baseline Only | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 12 Weeks | 14 percentage of participants |
| 1.25 mg Injection at Baseline Only | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 9 Weeks | 10 percentage of participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 12 Weeks | 25 percentage of participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 9 Weeks | 37 percentage of participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 6 Weeks | 25 percentage of participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits | 3 Weeks | 25 percentage of participants |
Secondary
Change in Visual Acuity Letter Score From Baseline Over All All Study Visits
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.
Time frame: Baseline to 3,6,9, and 12 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 3 Weeks | -2 letters |
| Laser at Baseline | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 6 Weeks | 1 letters |
| Laser at Baseline | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 9 Weeks | 3 letters |
| Laser at Baseline | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 12 Weeks | -1 letters |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 3 Weeks | 5 letters |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 12 Weeks | 5 letters |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 6 Weeks | 5 letters |
| 1.25 mg Injection at Baseline and at 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 9 Weeks | 7 letters |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 12 Weeks | 7 letters |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 6 Weeks | 6 letters |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 9 Weeks | 8 letters |
| 2.5 mg Injection at Baseline and 6 Weeks | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 3 Weeks | 6 letters |
| 1.25 mg Injection at Baseline Only | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 3 Weeks | 2 letters |
| 1.25 mg Injection at Baseline Only | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 6 Weeks | 3 letters |
| 1.25 mg Injection at Baseline Only | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 12 Weeks | 4 letters |
| 1.25 mg Injection at Baseline Only | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 9 Weeks | 1 letters |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 12 Weeks | 0 letters |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 9 Weeks | -2 letters |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 6 Weeks | 0 letters |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Change in Visual Acuity Letter Score From Baseline Over All All Study Visits | 3 Weeks | 0 letters |
Comparison: 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 visitp-value: 0.42Least squares regression
Comparison: 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 visitp-value: 0.67Least squares regression
Comparison: 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 visitp-value: 0.48Least squares regression
Comparison: 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 visitp-value: 0.82Least squares regression
Comparison: 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 groupp-value: 0.01Least squares regression
Comparison: 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 groupp-value: 0.003Least squares regression
Secondary
Distribution of Change in Visual Acuity Over All Study Visits
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.
Time frame: Baseline to 3,6,9, and 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 12 Weeks | 3 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 12 Weeks | 1 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 6 Weeks | 2 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 6 Weeks | 2 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 9 Weeks | 3 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 3 Weeks | 1 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 9 Weeks | 1 participants |
| Laser at Baseline | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 3 Weeks | 1 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 9 Weeks | 1 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 6 Weeks | 0 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 12 Weeks | 1 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 12 Weeks | 7 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 6 Weeks | 7 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 3 Weeks | 1 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 9 Weeks | 6 participants |
| 1.25 mg Injection at Baseline and at 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 3 Weeks | 4 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 9 Weeks | 9 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 12 Weeks | 6 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 3 Weeks | 4 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 12 Weeks | 0 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 3 Weeks | 0 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 6 Weeks | 1 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 9 Weeks | 0 participants |
| 2.5 mg Injection at Baseline and 6 Weeks | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 6 Weeks | 7 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 12 Weeks | 2 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 3 Weeks | 1 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 6 Weeks | 3 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 6 Weeks | 1 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 3 Weeks | 2 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 9 Weeks | 3 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 12 Weeks | 2 participants |
| 1.25 mg Injection at Baseline Only | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 9 Weeks | 0 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 6 Weeks | 4 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 3 Weeks | 2 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 3 Weeks | 0 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 6 Weeks | 3 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 12 Weeks | 2 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 9 Weeks | 5 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letters worse at 9 Weeks | 2 participants |
| 1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w | Distribution of Change in Visual Acuity Over All Study Visits | ≥ 10 letter improvement at 12 Weeks | 4 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 0 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 4 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 3 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 0 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 2 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 0 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 1 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 6 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 2 participants |
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 3 Weeks to 6 Weeks | 1 Participants |
| Laser at Baseline | 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 | Within ± 11% Change from 3 Weeks to 6 Weeks | 11 Participants |
| Laser at Baseline | 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 | >11% Increased Change from 3 Weeks to 6 Weeks | 2 Participants |
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 3 Weeks to 6 Weeks | 1 Participants |
| Laser at Baseline | 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 | Within ± 11% Change from 3 Weeks to 6 Weeks | 1 Participants |
| Laser at Baseline | 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 | >11% Increased Change from 3 Weeks to 6 Weeks | 0 Participants |
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 3 Weeks to 6 Weeks | 2 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 3 Weeks to 6 Weeks | 16 participants |
| Laser at Baseline | 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 | >11% Increased Change from 3 Weeks to 6 Weeks | 4 participants |
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 3 Weeks to 6 Weeks | 0 Participants |
| Laser at Baseline | 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 | Within ± 11% Change from 3 Weeks to 6 Weeks | 9 Participants |
| Laser at Baseline | 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 | >11% Increased Change from 3 Weeks to 6 Weeks | 4 Participants |
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
Population: 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.
Other Pre-specified
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
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.
Time frame: 3 to 6 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 3 Weeks to 6 Weeks | 0 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 3 Weeks to 6 Weeks | 9 participants |
| Laser at Baseline | 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 | >11% Increased Change from 3 Weeks to 6 Weeks | 1 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 0 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 2 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 1 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 2 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 14 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 1 participants |
Other Pre-specified
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
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.
Time frame: 3 to 9 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Laser at Baseline | 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 | >11% Decreased Change from 9 Weeks to 12 Weeks | 1 participants |
| Laser at Baseline | 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 | Within ± 11% Change from 9 Weeks to 12 Weeks | 1 participants |
| Laser at Baseline | 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 | >11% Increased Change from 9 Weeks to 12 Weeks | 0 participants |
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline
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.
Time frame: Baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline | ≤66 years | -45 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline | >66 years | -16 microns |
Comparison: 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.p-value: 0.44Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness
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.
Time frame: Baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness | <400 microns | -3 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness | ≥400 microns | -102 microns |
Comparison: 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.p-value: <0.0001Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score
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.
Time frame: Baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score | <65 letters | -35 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score | ≥65 letters | -28 microns |
Comparison: 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.p-value: 0.31Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Neither Predominantly Focal or Diffuse | -8 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Typical/Predominantly Diffuse | -82 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Typical/Predominantly Focal | -13 microns |
Comparison: 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.p-value: 0.93Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender
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.
Time frame: Baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender | Male | -35 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender | Female | -28 microns |
Comparison: 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.p-value: 0.55Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline
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.
Time frame: Baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline | No | -40 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline | Yes | -29 microns |
Comparison: 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.p-value: 0.16Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline | Proliferative diabetic retinopathy or severe NPDR | -31 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline | <Severe nonproliferative diabetic retinopathy | -31 microns |
Comparison: 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.p-value: 0.53Least squares regression
Other Pre-specified
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline | Definite/Questionable | -35 microns |
| Laser at Baseline | Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline | No Evidence | -29 microns |
Comparison: 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.p-value: 0.52Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline | ≤66 years | 4 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline | >66 years | 2 letters |
Comparison: 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.p-value: 0.23Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline | <400 microns | 1 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline | ≥400 microns | 5 letters |
Comparison: 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.p-value: 0.22Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Typical/Predominantly Focal | 7 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Neither Predominantly Focal or Diffuse | 0 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline | Typical/Predominantly Diffuse | 3 letters |
Comparison: 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.p-value: 0.45Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender | Female | 3 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender | Male | 3 letters |
Comparison: 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.p-value: 0.37Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema | No | 5 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema | Yes | 2 letters |
Comparison: 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.p-value: 0.04Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline | <Severe nonproliferative diabetic retinopathy | 3 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline | Proliferative diabetic retinopathy or severe NPDR | 1 letters |
Comparison: 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.p-value: 0.38Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline | Definite/Questionable | 6 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline | No Evidence | 1 letters |
Comparison: 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.p-value: 0.06Least squares regression
Other Pre-specified
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline
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.
Time frame: baseline to 3 Weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline | <65 letters | 3 letters |
| Laser at Baseline | Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline | ≥65 letters | 1 letters |
Comparison: 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.p-value: 0.006Least squares regression