Trial Outcomes & Findings for A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin) (NCT NCT00336323)

NCT ID: NCT00336323

Last Updated: 2016-08-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 121 participants
• Primary outcome timeframe: Baseline to 3,6,9, and 12 weeks
• Results posted on: 2016-08-26

Participant Flow

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.

Unless otherwise noted, differences in number of Participants at different visits reflect a missed visit, not a drop-out.

Participant milestones

Measure	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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Overall Study STARTED	19	22	24	22	22
Overall Study 3 Week Visit	18	21	24	22	20
Overall Study 6 Week Visit	18	22	24	22	20
Overall Study 9 Week Visit	18	21	23	21	19
Overall Study 12 Week Visit	19	21	24	22	20
Overall Study 18 Week Visit	19	22	23	21	18
Overall Study 24 Week Visit	18	20	22	22	19
Overall Study COMPLETED	19	21	23	22	19
Overall Study NOT COMPLETED	0	1	1	0	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Laser at Baseline n=19 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 Participants 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 Participants 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	Total n=109 Participants Total of all reporting groups
Hemoglobin A1c	7.0 percent HbA1c n=5 Participants	7.4 percent HbA1c n=7 Participants	7.3 percent HbA1c n=5 Participants	6.7 percent HbA1c n=4 Participants	7.1 percent HbA1c n=21 Participants	6.9 percent HbA1c n=10 Participants
Optical Coherence Tomography (OCT) Central Subfield Thickness	441 microns n=5 Participants	397 microns n=7 Participants	446 microns n=5 Participants	406 microns n=4 Participants	389 microns n=21 Participants	411 microns n=10 Participants
Age, Continuous	64 years n=5 Participants	63 years n=7 Participants	68 years n=5 Participants	60 years n=4 Participants	67 years n=21 Participants	65 years n=10 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	10 Participants n=21 Participants	43 Participants n=10 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	13 Participants n=4 Participants	12 Participants n=21 Participants	66 Participants n=10 Participants
Race/Ethnicity, Customized White	10 participants n=5 Participants	16 participants n=7 Participants	20 participants n=5 Participants	18 participants n=4 Participants	19 participants n=21 Participants	83 participants n=10 Participants
Race/Ethnicity, Customized African-American	7 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	2 participants n=21 Participants	17 participants n=10 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	7 participants n=10 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	0 participants n=21 Participants	1 participants n=10 Participants
Race/Ethnicity, Customized Unknown/ not reported	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	1 participants n=10 Participants
Character of Diabetic Macular Edema (DME) Typical/Predominantly Focal	6 participants n=5 Participants	5 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	4 participants n=21 Participants	20 participants n=10 Participants
Character of Diabetic Macular Edema (DME) Neither Predominantly Focal or Diffuse	4 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	6 participants n=4 Participants	6 participants n=21 Participants	26 participants n=10 Participants
Character of Diabetic Macular Edema (DME) Typical/Predominantly Diffuse	9 participants n=5 Participants	12 participants n=7 Participants	17 participants n=5 Participants	13 participants n=4 Participants	12 participants n=21 Participants	63 participants n=10 Participants
Cystoid Abnormalities on Optical Coherence Tomography (OCT) Yes	18 participants n=5 Participants	22 participants n=7 Participants	24 participants n=5 Participants	21 participants n=4 Participants	21 participants n=21 Participants	106 participants n=10 Participants
Cystoid Abnormalities on Optical Coherence Tomography (OCT) No	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants	3 participants n=10 Participants
Diabetes Type Type 1	1 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	1 participants n=21 Participants	8 participants n=10 Participants
Diabetes Type Type 2	18 participants n=5 Participants	21 participants n=7 Participants	21 participants n=5 Participants	20 participants n=4 Participants	21 participants n=21 Participants	101 participants n=10 Participants
Lens status (clinical examination) Phakic	12 participants n=5 Participants	15 participants n=7 Participants	14 participants n=5 Participants	12 participants n=4 Participants	13 participants n=21 Participants	66 participants n=10 Participants
Lens status (clinical examination) Pseudophakic	7 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	9 participants n=21 Participants	43 participants n=10 Participants
Prior Panretinal Scatter Photocoagulation Yes	3 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants	13 participants n=10 Participants
Prior Panretinal Scatter Photocoagulation No	16 participants n=5 Participants	20 participants n=7 Participants	21 participants n=5 Participants	21 participants n=4 Participants	18 participants n=21 Participants	96 participants n=10 Participants
Prior Treatment for Diabetic Macular Edema (DME) in Study Eye None	7 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	5 participants n=4 Participants	7 participants n=21 Participants	34 participants n=10 Participants
Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Focal photocoagulation alone	4 participants n=5 Participants	11 participants n=7 Participants	9 participants n=5 Participants	6 participants n=4 Participants	9 participants n=21 Participants	39 participants n=10 Participants
Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Focal photocoagulation plus other treatment	8 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	11 participants n=4 Participants	6 participants n=21 Participants	31 participants n=10 Participants
Prior Treatment for Diabetic Macular Edema (DME) in Study Eye Other treatment without focal photocoagulation	0 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	5 participants n=10 Participants
Retinopathy Severity Mild nonproliferative diabetic retinopathy (NPDR)	1 participants n=5 Participants	6 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	4 participants n=21 Participants	14 participants n=10 Participants
Retinopathy Severity Moderate NPDR	5 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	15 participants n=10 Participants
Retinopathy Severity Moderately severe NPDR	5 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	8 participants n=4 Participants	9 participants n=21 Participants	36 participants n=10 Participants
Retinopathy Severity Severe NPDR	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants	1 participants n=21 Participants	8 participants n=10 Participants
Retinopathy Severity Mild proliferative diabetic retinopathy (PDR)	4 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	5 participants n=4 Participants	4 participants n=21 Participants	24 participants n=10 Participants
Retinopathy Severity Moderate PDR	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	4 participants n=10 Participants
Retinopathy Severity High Risk PDR	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	2 participants n=10 Participants
Retinopathy Severity Missing	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	0 participants n=21 Participants	6 participants n=10 Participants
Subretinal Fluid on Optical Coherence Tomography (OCT) Definite, center	2 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants	17 participants n=10 Participants
Subretinal Fluid on Optical Coherence Tomography (OCT) Definite, not center	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	3 participants n=10 Participants
Subretinal Fluid on Optical Coherence Tomography (OCT) Questionable	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	0 participants n=21 Participants	3 participants n=10 Participants
Subretinal Fluid on Optical Coherence Tomography (OCT) No evidence	16 participants n=5 Participants	18 participants n=7 Participants	16 participants n=5 Participants	18 participants n=4 Participants	17 participants n=21 Participants	85 participants n=10 Participants
Subretinal Fluid on Optical Coherence Tomography (OCT) Missing	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	1 participants n=10 Participants
Baseline Visual Acuity	64 letter score n=5 Participants	65 letter score n=7 Participants	63 letter score n=5 Participants	64 letter score n=4 Participants	66 letter score n=21 Participants	64 letter score n=10 Participants
Duaration of Diabetes	17 years n=5 Participants	15 years n=7 Participants	18 years n=5 Participants	17 years n=4 Participants	20 years n=21 Participants	17 years n=10 Participants
Optical Coherence Tomography Retinal Volume	8.3 mm^3 n=5 Participants	9.5 mm^3 n=7 Participants	9.1 mm^3 n=5 Participants	8.9 mm^3 n=4 Participants	8.6 mm^3 n=21 Participants	8.6 mm^3 n=10 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Laser at Baseline n=19 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 Participants 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 Participants 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
Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits 3 Weeks	21 microns Interval -62.0 to 79.0	-35 microns Interval -155.0 to 6.0	-86 microns Interval -131.0 to -11.0	-3 microns Interval -49.0 to 7.0	-13 microns Interval -104.0 to 26.0
Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits 6 Weeks	-40 microns Interval -105.0 to 73.0	-35 microns Interval -112.0 to 6.0	-42 microns Interval -127.0 to -10.0	-17 microns Interval -58.0 to 25.0	-20 microns Interval -73.0 to 35.0
Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits 9 Weeks	-53 microns Interval -115.0 to 53.0	-74 microns Interval -113.0 to -31.0	-56 microns Interval -127.0 to -20.0	5 microns Interval -34.0 to 53.0	-48 microns Interval -128.0 to 33.0
Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits 12 Weeks	-40 microns Interval -146.0 to 86.0	-56 microns Interval -120.0 to -6.0	-47 microns Interval -125.0 to -16.0	-5 microns Interval -41.0 to 53.0	-40 microns Interval -103.0 to 33.0

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Laser at Baseline n=19 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 Participants 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 Participants 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
Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits 3 Weeks	11 percentage of participants	37 percentage of participants	38 percentage of participants	10 percentage of participants	25 percentage of participants
Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits 6 Weeks	17 percentage of participants	30 percentage of participants	22 percentage of participants	19 percentage of participants	25 percentage of participants
Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits 9 Weeks	19 percentage of participants	38 percentage of participants	22 percentage of participants	10 percentage of participants	37 percentage of participants
Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits 12 Weeks	21 percentage of participants	33 percentage of participants	33 percentage of participants	14 percentage of participants	25 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=19 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 Participants 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 Participants 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
Change in Visual Acuity Letter Score From Baseline Over All All Study Visits 3 Weeks	-2 letters Interval -7.0 to 3.0	5 letters Interval -1.0 to 8.0	6 letters Interval 1.0 to 9.0	2 letters Interval 0.0 to 7.0	0 letters Interval -6.0 to 6.0
Change in Visual Acuity Letter Score From Baseline Over All All Study Visits 6 Weeks	1 letters Interval -6.0 to 6.0	5 letters Interval -2.0 to 12.0	6 letters Interval 2.0 to 11.0	3 letters Interval -2.0 to 6.0	0 letters Interval -4.0 to 6.0
Change in Visual Acuity Letter Score From Baseline Over All All Study Visits 9 Weeks	3 letters Interval -5.0 to 6.0	7 letters Interval 2.0 to 10.0	8 letters Interval 3.0 to 12.0	1 letters Interval -3.0 to 5.0	-2 letters Interval -5.0 to 11.0
Change in Visual Acuity Letter Score From Baseline Over All All Study Visits 12 Weeks	-1 letters Interval -6.0 to 5.0	5 letters Interval 1.0 to 12.0	7 letters Interval 4.0 to 11.0	4 letters Interval -3.0 to 7.0	0 letters Interval -5.0 to 8.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=19 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 Participants 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 Participants 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 Participants 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
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letter improvement at 3 Weeks	1 participants	4 participants	4 participants	2 participants	2 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letters worse at 3 Weeks	1 participants	1 participants	0 participants	1 participants	0 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letter improvement at 6 Weeks	2 participants	7 participants	7 participants	3 participants	3 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letters worse at 6 Weeks	2 participants	0 participants	1 participants	1 participants	4 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letter improvement at 9 Weeks	3 participants	6 participants	9 participants	3 participants	5 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letters worse at 9 Weeks	1 participants	1 participants	0 participants	0 participants	2 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letter improvement at 12 Weeks	3 participants	7 participants	6 participants	2 participants	4 participants
Distribution of Change in Visual Acuity Over All Study Visits ≥ 10 letters worse at 12 Weeks	1 participants	1 participants	0 participants	2 participants	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness <400 microns	-3 microns Interval -49.0 to 13.0	—	—	—	—
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness ≥400 microns	-102 microns Interval -145.0 to -6.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score <65 letters	-35 microns Interval -130.0 to 5.0	—	—	—	—
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score ≥65 letters	-28 microns Interval -102.0 to 13.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline ≤66 years	-45 microns Interval -131.0 to 5.0	—	—	—	—
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline >66 years	-16 microns Interval -107.0 to 6.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender Female	-28 microns Interval -115.0 to 6.0	—	—	—	—
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender Male	-35 microns Interval -105.0 to 5.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval -141.0 to -3.0	—	—	—	—
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 Interval -102.0 to 7.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval -115.0 to 6.0	—	—	—	—
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 Interval -105.0 to 13.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval -67.0 to -2.0	—	—	—	—
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 Interval -32.0 to 20.0	—	—	—	—
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 Interval -139.0 to 5.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline Definite/Questionable	-35 microns Interval -131.0 to 24.0	—	—	—	—
Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline No Evidence	-29 microns Interval -102.0 to 3.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline <400 microns	1 letters Interval -2.0 to 8.0	—	—	—	—
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline ≥400 microns	5 letters Interval 0.0 to 8.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline <65 letters	3 letters Interval 0.0 to 9.0	—	—	—	—
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline ≥65 letters	1 letters Interval -3.0 to 7.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline ≤66 years	4 letters Interval -1.0 to 8.0	—	—	—	—
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline >66 years	2 letters Interval 0.0 to 8.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender Female	3 letters Interval 0.0 to 8.0	—	—	—	—
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender Male	3 letters Interval -1.0 to 7.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval -1.0 to 8.0	—	—	—	—
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 Interval -1.0 to 8.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval 0.0 to 8.0	—	—	—	—
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 Interval -3.0 to 7.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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 Interval 0.0 to 9.0	—	—	—	—
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 Interval -5.0 to 5.0	—	—	—	—
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 Interval 0.0 to 8.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=87 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline Definite/Questionable	6 letters Interval 3.0 to 11.0	—	—	—	—
Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline No Evidence	1 letters Interval -1.0 to 7.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=14 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=22 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=2 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=13 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=10 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=7 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=9 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=2 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=3 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=17 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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 outcome

Timeframe: 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.

Outcome measures

Measure	Laser at Baseline n=2 Participants 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	1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	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
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	—	—	—	—
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	—	—	—	—
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	—	—	—	—

Adverse Events

Laser at Baseline

Serious events: 8 serious events

Other events: 14 other events

Deaths: 0 deaths

1.25 mg Injection at Baseline and at 6 Weeks

Serious events: 8 serious events

Other events: 16 other events

Deaths: 0 deaths

2.5 mg Injection at Baseline and 6 Weeks

Serious events: 6 serious events

Other events: 19 other events

Deaths: 0 deaths

1.25 mg Injection at Baseline Only

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w

Serious events: 6 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Laser at Baseline n=19 participants at risk 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 participants at risk 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 participants at risk 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 participants at risk 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 participants at risk 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
Blood and lymphatic system disorders Anemia	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Skin and subcutaneous tissue disorders Bacterial skin infection	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Musculoskeletal and connective tissue disorders Cellulitis	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Vascular disorders Cerebrovascular accident	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Chest pain	0.00% 0/19	4.5% 1/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Hepatobiliary disorders Cholelithiasis	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Congestive cardiac failure	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders Death	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Delerium	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders Endophthalmitis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Gastrointestinal disorders Gastroenteritis	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Glaucoma	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Musculoskeletal and connective tissue disorders Hip fracture	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Hyperglycaemia	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Hypoglycaemia	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Endocrine disorders Inadequate control of diabetes mellitus	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Intraventricular haemorrhage	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Infections and infestations Localised infection	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Metastatic lung cancer	0.00% 0/19	4.5% 1/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Cardiac disorders Myocardial infarction	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	13.6% 3/22
Gastrointestinal disorders Pancreatic carcinoma	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Vascular disorders Peripheral vascular disorder	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Respiratory, thoracic and mediastinal disorders Pneumonia	10.5% 2/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Renal and urinary disorders Renal failure	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Renal and urinary disorders Renal impairment	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Skin and subcutaneous tissue disorders Skin ulcer or skin lesion	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Syncope	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Vitrectomy	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Gastrointestinal disorders Vomiting	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22

Other adverse events

Measure	Laser at Baseline n=19 participants at risk 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	1.25 mg Injection at Baseline and at 6 Weeks n=22 participants at risk 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks	2.5 mg Injection at Baseline and 6 Weeks n=24 participants at risk 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks	1.25 mg Injection at Baseline Only n=22 participants at risk 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)	1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w n=22 participants at risk 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
General disorders Abdominal pain	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Blood and lymphatic system disorders Anemia	5.3% 1/19	4.5% 1/22	4.2% 1/24	4.5% 1/22	4.5% 1/22
Eye disorders Angle Closure Glaucoma	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Anorexia	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders Anterior chamber cell	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders Anterior chamber flare	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders Back injury	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders Blepharitis	5.3% 1/19	9.1% 2/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Bronchitis	10.5% 2/19	4.5% 1/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Eye disorders Cataract nuclear	0.00% 0/19	9.1% 2/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Vascular disorders Cerebrovascular accident	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders Conjunctival hemorrhage	0.00% 0/19	22.7% 5/22	4.2% 1/24	27.3% 6/22	13.6% 3/22
Endocrine disorders Diabetes mellitus	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders Diabetic Retinopathy	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders Diabetic retinal edema	0.00% 0/19	22.7% 5/22	12.5% 3/24	9.1% 2/22	4.5% 1/22
Eye disorders Diplopia	0.00% 0/19	9.1% 2/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Gastrointestinal disorders Duodenitis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders Eye irritation	0.00% 0/19	4.5% 1/22	0.00% 0/24	9.1% 2/22	4.5% 1/22
Eye disorders Eye pain	10.5% 2/19	18.2% 4/22	20.8% 5/24	13.6% 3/22	22.7% 5/22
Eye disorders Foreign body sensation in eyes	5.3% 1/19	0.00% 0/22	8.3% 2/24	0.00% 0/22	9.1% 2/22
Gastrointestinal disorders Gastroenteritis viral	0.00% 0/19	9.1% 2/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders Glaucoma	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Injury, poisoning and procedural complications Head injury	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders Headache	5.3% 1/19	9.1% 2/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Blood and lymphatic system disorders Hypercholesterolemia	5.3% 1/19	9.1% 2/22	0.00% 0/24	9.1% 2/22	0.00% 0/22
Vascular disorders Hypertension	10.5% 2/19	9.1% 2/22	8.3% 2/24	4.5% 1/22	4.5% 1/22
Eye disorders Increased intraocular pressure	0.00% 0/19	4.5% 1/22	12.5% 3/24	13.6% 3/22	9.1% 2/22
Respiratory, thoracic and mediastinal disorders Influenza	0.00% 0/19	0.00% 0/22	4.2% 1/24	9.1% 2/22	4.5% 1/22
Eye disorders Lacrimation increased	5.3% 1/19	13.6% 3/22	8.3% 2/24	9.1% 2/22	4.5% 1/22
Infections and infestations Localised infection	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	5.3% 1/19	0.00% 0/22	12.5% 3/24	0.00% 0/22	0.00% 0/22
Eye disorders Ocular hyperaemia	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	9.1% 2/22
General disorders Osteomyelitis	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Vascular disorders Peripheral vascular disease	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders Tooth abcess	0.00% 0/19	9.1% 2/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders Vision blurred	26.3% 5/19	27.3% 6/22	20.8% 5/24	22.7% 5/22	22.7% 5/22
Eye disorders Visual acuity reduced	10.5% 2/19	18.2% 4/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders Visual disturbance	0.00% 0/19	0.00% 0/22	16.7% 4/24	9.1% 2/22	4.5% 1/22
Eye disorders Vitreous floaters	0.00% 0/19	31.8% 7/22	33.3% 8/24	4.5% 1/22	13.6% 3/22
Eye disorders Vitreous hemorrhage	0.00% 0/19	4.5% 1/22	20.8% 5/24	13.6% 3/22	9.1% 2/22
General disorders anxiety	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
General disorders arthralgia	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders asbestosis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Nervous system disorders autonomic nervous system imbalance	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders back pain	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders benign breast neoplasm	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders blister	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders blood creatine increased	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Blood and lymphatic system disorders blood glucose decreased	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Blood and lymphatic system disorders blood potassium increased	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders breast cancer	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders cataract	5.3% 1/19	4.5% 1/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Eye disorders cataract cortical	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders cataract operation	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Eye disorders cataract operation complication	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders cataract subcapsular	5.3% 1/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
General disorders caugh	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders chalazion	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Cardiac disorders chest pain	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Cardiac disorders chronic obstructive pulmonary disease	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders colon cancer	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders conjunctivitis	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders conjunctivitis allergic	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders conjunctivitis viral	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders constipation	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders corneal abrasion	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders corneal oedema	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Ear and labyrinth disorders deafness	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Vascular disorders deep vein thrombosis	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Psychiatric disorders depression	5.3% 1/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Skin and subcutaneous tissue disorders dermatitis allergic	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Skin and subcutaneous tissue disorders dermatitis contact	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	4.5% 1/22
Eye disorders desemets membrane disorder	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Endocrine disorders diabetes mellitus inadequate control	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders dizziness	0.00% 0/19	0.00% 0/22	4.2% 1/24	4.5% 1/22	4.5% 1/22
Eye disorders dry eye	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
General disorders epistaxis	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders eye inflammation	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders eye pruritus	0.00% 0/19	4.5% 1/22	4.2% 1/24	4.5% 1/22	4.5% 1/22
Eye disorders eyelid oedema	0.00% 0/19	4.5% 1/22	4.2% 1/24	0.00% 0/22	4.5% 1/22
Eye disorders eyelid pain	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders eyelid ptsosis	5.3% 1/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders fall	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders foreign body in eye	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Skin and subcutaneous tissue disorders fungal skin infection	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Gastrointestinal disorders gastroenteritis	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Gastrointestinal disorders gastrooespohageal reflux disease	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders haematochezia	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Blood and lymphatic system disorders haemoglobin decreased	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Cardiac disorders heart rate irregular	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders herpes zoster	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Blood and lymphatic system disorders hyperkalaemia	5.3% 1/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Blood and lymphatic system disorders hypoglycaemia	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Eye disorders injection site irritaion	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders insomnia	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders intervertebral disc protrusion	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders joint dislocation	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders keratoconjunctivitis sicca	5.3% 1/19	4.5% 1/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Blood and lymphatic system disorders leukocytosis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
General disorders localised infection	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders macular oedema	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	4.5% 1/22
Eye disorders maculopathy	5.3% 1/19	4.5% 1/22	8.3% 2/24	4.5% 1/22	0.00% 0/22
General disorders nasopharyngitis	5.3% 1/19	0.00% 0/22	12.5% 3/24	0.00% 0/22	0.00% 0/22
General disorders nausea	0.00% 0/19	4.5% 1/22	4.2% 1/24	0.00% 0/22	4.5% 1/22
Nervous system disorders nerve injury	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders oedema peripheral	5.3% 1/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders optic nerve cupping	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders pain in extremity	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Eye disorders periorbital haematoma	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Skin and subcutaneous tissue disorders peritonitis	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders pharyngolaryngeal pain	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders photophobia	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders photopsia	0.00% 0/19	4.5% 1/22	4.2% 1/24	4.5% 1/22	0.00% 0/22
Eye disorders posterior capsule opacification	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	4.5% 1/22
Neoplasms benign, malignant and unspecified (incl cysts and polyps) prostate cancer	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders protein urine present	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders pruritus	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders pterygium	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders punctate keratitis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Skin and subcutaneous tissue disorders rash	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders reading disorder	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Renal and urinary disorders renal failure	5.3% 1/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Renal and urinary disorders renal failure chronic	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders respiratory tract congestion	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders retinal degeneration	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders retinal detachment	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders retinal exudates	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders retinal laser coagulation	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders retinal neovascularisation	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders retinal oedema	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Eye disorders retinal telagiectasia	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Musculoskeletal and connective tissue disorders rheumatoid arthritis	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders rhinitis allergic	0.00% 0/19	4.5% 1/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
General disorders sinusitis	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Neoplasms benign, malignant and unspecified (incl cysts and polyps) skin cancer	5.3% 1/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Skin and subcutaneous tissue disorders skin lesion excision	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
General disorders swollen tongue	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Nervous system disorders trigeminal neuralgia	0.00% 0/19	4.5% 1/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
General disorders upper respiratory tract infection	0.00% 0/19	4.5% 1/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Renal and urinary disorders urinary incontinence	5.3% 1/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	0.00% 0/22
Renal and urinary disorders urinary tract infection	0.00% 0/19	4.5% 1/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders vitrectomy	0.00% 0/19	0.00% 0/22	4.2% 1/24	0.00% 0/22	0.00% 0/22
Eye disorders vitreous degeneration	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22
Eye disorders vitreous detachment	0.00% 0/19	0.00% 0/22	0.00% 0/24	4.5% 1/22	0.00% 0/22
Eye disorders vitreous opacities	0.00% 0/19	0.00% 0/22	0.00% 0/24	0.00% 0/22	4.5% 1/22

Additional Information

Name/Official Title: Adam Glassman, M.S., Director

Jaeb Center for Health Research, Diabetic Retinopathy Clinical Research Network

Phone: (813) 975-8690

Email: drcrnet@jaeb.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place