Trial Outcomes & Findings for DRCR.Net Aflibercept vs. Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME (NCT NCT03321513)

Last Updated: 2024-04-25

Results Overview

Area under the curve mean change in the electronic early treatment diabetic retinopathy study visual acuity. Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, \<20/800), with higher scores indicating better vision. The data presented are the best-corrected visual acuity in the study eye after protocol-defined refraction. The primary outcome was the time-averaged change in the visual-acuity letter score over a period of 104 weeks. The score was derived by calculating the area under the curve (AUC) over the 104-week period for the change in visual acuity from baseline and dividing by the length of follow-up.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

270 participants

Primary outcome timeframe

2 years

Results posted on

2024-04-25

Participant Flow

Participants with both eyes enrolled had one eye in each group (N = 42). Participants could have had 1 (unilateral) or each eye (bilateral) assigned to each group. "Unilateral: "Aflibercept- Monotherapy Group" only (116 participants), "Bevacizumab-First Group" only (112 participants); Bilateral: 42 participants

Unit of analysis: Eyes

Participant milestones

Participant milestones
Measure	Aflibercept- Monotherapy Group 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Overall Study STARTED	158 158	154 154
Overall Study COMPLETED	132 132	128 128
Overall Study NOT COMPLETED	26 26	26 26

Reasons for withdrawal

Reasons for withdrawal
Measure	Aflibercept- Monotherapy Group 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Overall Study Death	11	5
Overall Study Withdrawal by Subject	5	10
Overall Study Lost to Follow-up	10	11

Baseline Characteristics

84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Mean Change in Visual Acuity	15 Letter Score Standard Deviation 8.5	14 Letter Score Standard Deviation 8.8

SECONDARY outcome

Timeframe: 2 years

Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, \<20/800), with higher scores indicating better vision.

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Change in Visual Acuity From Baseline	14.7 Letter Score Standard Deviation 14.5	15.9 Letter Score Standard Deviation 12.4

SECONDARY outcome

Timeframe: 2 years

Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, \<20/800), with higher scores indicating better vision.

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Increase in E-ETDRS Visual Acuity Letter Score 10 or more letters	101 Eyes	98 Eyes
Increase in E-ETDRS Visual Acuity Letter Score 15 or more letters	70 Eyes	74 Eyes

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Decrease in E-ETDRS Visual Acuity Letter Score 15 or more letters	9 Eyes	5 Eyes
Decrease in E-ETDRS Visual Acuity Letter Score 10 or more letters	8 Eyes	4 Eyes

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Visual Acuity 20/20 or better	29 Eyes	28 Eyes
Visual Acuity 20/40 or worse	96 Eyes	95 Eyes
Visual Acuity 20/200 or worse	6 Eyes	2 Eyes

SECONDARY outcome

Timeframe: 2 years

Population: The analysis included only eyes for which baseline data on the central subfield thickness were available.

Measurements made on the Cirrus device were converted to equivalent scores as would be assessed on the Spectralis device with the use of the following formula: Spectralis score = 40.78 + 0.95 × Cirrus score.

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=126 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=127 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Optical Coherence Tomography Central Subfield Thickness Change From Baseline	-192 microns Standard Deviation 143	-198 microns Standard Deviation 160

SECONDARY outcome

Timeframe: 2 years

Population: The analysis included only eyes for which baseline data on the central subfield thickness were available.

Optical coherence tomography (OCT) central subfield thickness equivalents for measurements obtained on Spectral domain OCT machines were 320 μm for men and 305 μm for women on the Spectralis device (Heidelberg) and were 305 μm and 290 μm, respectively on the Cirrus OCT measurement device (Zeiss).

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=126 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=127 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema	76 Eyes	70 Eyes

SECONDARY outcome

Timeframe: 2 years

Population: This analysis was limited to patients with one study eye who completed 2 years of follow-up.

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=98 Participants 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=94 Participants 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Visits	22.0 visits Standard Deviation 3.6	22.5 visits Standard Deviation 3.4

SECONDARY outcome

Timeframe: 2 years

Population: Limited to eyes that completed the 2-year visit or any later common visit.

All study injections were counted, including aflibercept injections received among eyes in the bevacizumab first group.

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=132 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=128 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Injections	14.6 injections Standard Deviation 4.1	16.1 injections Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Eyes that did not meet the switch criteria were censored at the last completed visit

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=154 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria	16 Eyes	—

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Population: Eyes that did not meet the switch criteria were censored at the last completed visit

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=154 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria	57 Eyes	—

SECONDARY outcome

Timeframe: Baseline to 52 weeks

Population: Eyes that did not meet the switch criteria were censored at the last completed visit

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=154 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria	88 Eyes	—

SECONDARY outcome

Timeframe: Baseline to 104 weeks

Population: Eyes that did not meet the switch criteria were censored at the last completed visit

Outcome measures

Outcome measures
Measure	Aflibercept- Monotherapy Group n=154 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria	100 Eyes	—

Adverse Events

Unilateral Aflibercept- Monotherapy Group

Serious events: 61 serious events

Other events: 100 other events

Deaths: 10 deaths

Unilateral Bevacizumab-First Group

Serious events: 42 serious events

Other events: 94 other events

Deaths: 4 deaths

Bilateral Participants

Serious events: 18 serious events

Other events: 40 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Adam Glassman

JAEB CENTER FOR HEALTH RESEARCH

Phone: 8139758690

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Aflibercept- Monotherapy Group n=158 Eyes 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique	Bevacizumab-First Group n=154 Eyes 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria. 1.25 mg intravitreous bevacizumab was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, and only if protocol-specified criteria were met, eyes in this group stopped bevacizumab therapy and started aflibercept therapy. Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique.	Total n=312 Eyes Total of all reporting groups
Age, Customized age	60 years n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	61 years n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	61 years n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Sex/Gender, Customized Women	76 Eyes n=158 Eyes	74 Eyes n=154 Eyes	150 Eyes n=312 Eyes
Sex/Gender, Customized Male	82 Eyes n=158 Eyes	80 Eyes n=154 Eyes	162 Eyes n=312 Eyes
Race/Ethnicity, Customized White	82 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	83 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	165 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Black or African American	32 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	26 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	58 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Hispanic or Latino	39 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	41 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	80 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Asian	2 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	2 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	4 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	1 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	2 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Multiple	1 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	1 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	2 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Race/Ethnicity, Customized Unknown or not reported	1 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	0 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	1 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Type of diabetes Type 1	7 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	8 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	15 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Type of diabetes Type 2	151 Eyes n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	146 Eyes n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	297 Eyes n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Duration of diabetes	15 years n=158 Eyes	14 years n=154 Eyes	15 years n=312 Eyes
Glycated hemoglobin	8.0 Hemoglobin A1c percentage n=148 Eyes • Data on the glycated hemoglobin level were unavailable for 10 eyes in each trial group.	8.0 Hemoglobin A1c percentage n=144 Eyes • Data on the glycated hemoglobin level were unavailable for 10 eyes in each trial group.	8.0 Hemoglobin A1c percentage n=292 Eyes • Data on the glycated hemoglobin level were unavailable for 10 eyes in each trial group.
Visual acuity letter score	61 units on a scale n=158 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	60 units on a scale n=154 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	60 units on a scale n=312 Eyes • 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Central subfield thickness	478 Microns n=156 Eyes • Data were unavailable for two eyes in the aflibercept-monotherapy group; a optical coherence tomography reading center confirmed the presence of diabetic macular edema in these eyes. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	496 Microns n=154 Eyes • Data were unavailable for two eyes in the aflibercept-monotherapy group; a optical coherence tomography reading center confirmed the presence of diabetic macular edema in these eyes. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	488 Microns n=310 Eyes • Data were unavailable for two eyes in the aflibercept-monotherapy group; a optical coherence tomography reading center confirmed the presence of diabetic macular edema in these eyes. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Diabetic retinopathy absent or questionable; levels 10, 12, 14, or 15	0 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	1 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	1 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Microaneurysms only; level 20	0 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	2 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	2 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Mild-to-moderate nonproliferative diabetic retinopathy; level 35 or 43	58 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	42 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	100 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Moderately severe to severe nonproliferative diabetic retinopathy; level 47 or 53	72 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	79 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	151 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Mild-to-moderate proliferative diabetic retinopathy; level 61 or 65	15 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	16 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	31 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale High-risk proliferative diabetic retinopathy; level 71 or 75	6 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	7 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	13 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Diabetic retinopathy severity scale Advanced Proliferative diabetic retinopathy Level 81 or 85	0 Eyes n=151 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	0 Eyes n=147 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).	0 Eyes n=298 Eyes • Data were not available for one eye in the bevacizumab-first group. Eyes could not be graded for seven eyes in the aflibercept-monotherapy group and for six eyes in the bevacizumab-first group. Percentages are based on the numbers of eyes with gradable severity of diabetic retinopathy at baseline. 84 eyes were enrolled with from 42 participants with two study eyes (i.e., one eye in each treatment group).
Previous anti-VEGF treatment for diabetic macular edema	25 Eyes n=158 Eyes	29 Eyes n=154 Eyes	54 Eyes n=312 Eyes

Serious adverse events
Measure	Unilateral Aflibercept- Monotherapy Group n=116 participants at risk 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique.	Unilateral Bevacizumab-First Group n=112 participants at risk 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique. For participants who switched from Bevacizumab to Aflibercept, all randomized eyes are included in the safety analysis and analyzed according to treatment assignment at randomization, regardless of the treatment actually received.	Bilateral Participants n=42 participants at risk Participants with one eye enrolled in each arm of the study. For participants who switched from Bevacizumab to Aflibercept, all randomized eyes are included in the safety analysis and analyzed according to treatment assignment at randomization, regardless of the treatment actually received. Ocular adverse events specific to each treatment are reported as footnotes.
Nervous system disorders Dizziness	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Anemia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	7.1% 3/42 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Anemia of chronic disease	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Enlargement of lymph nodes	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders AFib	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Angina pectoris	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Cardiac arrest	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Cardiogenic shock	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Congenital heart disease NOS	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Congestive heart failure	7.8% 9/116 • Number of events 11 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	9.5% 4/42 • Number of events 4 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Coronary artery disease	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Heart block first degree	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Heart failure	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Myocardial infarction	3.4% 4/116 • Number of events 4 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.7% 3/112 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Tachycardia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Diabetes	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Diabetic ketoacidosis	0.86% 1/116 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Hyperglycemia	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Nervous system disorders Fainting	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Hypoglycemia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Worsening of diabetes	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Double vision	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Endophthalmitis	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Penetrating eye injury	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Rhegmatogenous retinal detachment	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Vision decreased	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Vitreous hemorrhage	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Abdominal pain	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Constipation	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Diabetic gastroparesis	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 13 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Enterocolitis	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Gastritis	1.7% 2/116 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Gastro intestinal bleeding	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Gastroenteritis	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Gastrointestinal motility disorder	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Indigestion	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Irritable bowel syndrome	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Nausea	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Gastrointestinal disorders Stomach pain	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.

Other adverse events
Measure	Unilateral Aflibercept- Monotherapy Group n=116 participants at risk 2.0 mg intravitreous aflibercept intravitreous aflibercept: Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema. Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert. Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using sterile technique.	Unilateral Bevacizumab-First Group n=112 participants at risk 1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria Bevacizumab + Deferred Aflibercept Group: Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma. Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc. Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used. The injection will be performed using a sterile technique. For participants who switched from Bevacizumab to Aflibercept, all randomized eyes are included in the safety analysis and analyzed according to treatment assignment at randomization, regardless of the treatment actually received.	Bilateral Participants n=42 participants at risk Participants with one eye enrolled in each arm of the study. For participants who switched from Bevacizumab to Aflibercept, all randomized eyes are included in the safety analysis and analyzed according to treatment assignment at randomization, regardless of the treatment actually received. Ocular adverse events specific to each treatment are reported as footnotes.
Blood and lymphatic system disorders Anemia	5.2% 6/116 • Number of events 6 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	5.4% 6/112 • Number of events 6 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	7.1% 3/42 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Anemia of chronic disease	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Lymphangitis	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Thrombocytopenia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Blood and lymphatic system disorders Thrombocytosis	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Atrial fibrillation	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Bundle branch block	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Cardiac arrhythmia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Cardiomyopathy	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Congestive heart failure	1.7% 2/116 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	3.6% 4/112 • Number of events 4 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Coronary artery disease	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Heart block first degree	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Heart failure	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Ischemic cardiomyopathy	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Mitral regurgitation	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Premature ventricular contractions	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Cardiac disorders Tricuspid regurgitation	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Ear and labyrinth disorders Ear infection	1.7% 2/116 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Ear and labyrinth disorders Otitis media acute	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Diabetes	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Diabetes mellitus poor control	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.7% 3/112 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Hyperglycemia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Hypoglycemia	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Hypothyroidism	2.6% 3/116 • Number of events 3 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Loss of control of blood sugar	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Endocrine disorders Worsening of diabetes	6.0% 7/116 • Number of events 7 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	4.5% 5/112 • Number of events 5 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	4.8% 2/42 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Abnormal vision	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Age-related macular degeneration	0.00% 0/116 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Anatomical narrow angle borderline glaucoma	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Anterior chamber cell	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Arcus senilis	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Blepharitis (eyelid irritation)	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Blurred vision	3.4% 4/116 • Number of events 4 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	6.2% 7/112 • Number of events 9 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Blurry vision	2.6% 3/116 • Number of events 4 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	1.8% 2/112 • Number of events 2 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	2.4% 1/42 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Borderline glaucoma (glaucoma suspect)	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.89% 1/112 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Branch retinal artery occlusion	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.
Eye disorders Burning eyes	0.86% 1/116 • Number of events 1 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/112 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.	0.00% 0/42 • 2 Years To get the total number of participant/eyes in each treatment group add the unilateral and bilateral participants together: Unilateral Aflibercept monotherapy = 116 Total Aflibercept monotherapy = unilateral Aflibercept monotherapy + bilateral = 116 + 42 = 158 Unilateral Bevacizumab first = 112 total Bevacizumab first = unilateral Bevacizumab first + bilateral = 112 + 42 = 154.