Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema, anti-vascular endothelial growth factor
Brief summary
Both aflibercept and bevacizumab have been shown to improve vision in eyes with DME. In eyes with DME and at least moderate vision loss, both aflibercept and bevacizumab were also shown to be successful in many eyes. However, aflibercept was shown to be more effective at improving vision, on average, at 1 year and at 2 years. Due to the large cost difference between the two drugs, many clinicians and patients are choosing to initiate treatment with bevacizumab and then switch to aflibercept depending on the eye's response to bevacizumab treatment. However, there is no scientific evidence that this treatment strategy is as effective at improving vision as initiating treatment with aflibercept. Patients and clinicians do not know if this approach ultimately has deleterious effects on visual acuity. If starting with aflibercept is not better than starting with bevacizumab and switching to aflibercept if needed, the potential cost savings to future patients and the health care system would be substantial. However, if starting with aflibercept is better, then patients, clinicians, and health care providers can make informed decisions for how to best treat patients with DME and at least moderate vision loss. Study Objectives To compare the efficacy of intravitreous aflibercept with intravitreous bevacizumab + deferred aflibercept if needed in eyes with CI DME and moderate vision loss
Interventions
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
DRUGBevacizumab + 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.
Sponsors
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant-level Criteria Inclusion To be eligible, the following inclusion criteria must be met: 1. Age ≥ 18 years • Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable. 2. Diagnosis of diabetes mellitus (type 1 or type 2) * Any one of the following will be considered to be sufficient evidence that diabetes is present: Current regular use of insulin for the treatment of diabetes Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes Documented diabetes by American Diabetes Association and/or World Health Organization criteria 3. At least one eye meets the study eye criteria listed. 4. Able and willing to provide informed consent. Exclusion An individual is not eligible if any of the following
Exclusion criteria
are present: 5. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant. 6. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control). * Individuals in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled. 7. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied at the time of study entry. • Note: study participants cannot receive another investigational drug while participating in the study. 8. Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine prep). 9. Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110). • If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible. 10. Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study. • These drugs cannot be used during the study. 11. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months. • Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed. 12. Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next two years. Study Eye Criteria The study participant must have at least one eye meeting all of the inclusion criteria and none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Visual Acuity | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increase in E-ETDRS Visual Acuity Letter Score | 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. |
| Decrease in E-ETDRS Visual Acuity Letter Score | 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. |
| Visual Acuity | 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. |
| Optical Coherence Tomography Central Subfield Thickness Change From Baseline | 2 years | 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. |
| Change in Visual Acuity From Baseline | 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. |
| Number of Visits | 2 years | — |
| Number of Injections | 2 years | All study injections were counted, including aflibercept injections received among eyes in the bevacizumab first group. |
| Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria | Baseline to 12 weeks | — |
| Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema | 2 years | 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). |
Countries
United States
Participant flow
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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 | 158 |
| 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 | 158 |
| Bevacizumab-First Group 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. | 154 |
| Bevacizumab-First Group 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. | 154 |
| Total | 624 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 5 |
| Overall Study | Lost to Follow-up | 10 | 11 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Aflibercept- Monotherapy Group | Bevacizumab-First Group | Total |
|---|---|---|---|
| Age, Customized age | 60 years | 61 years | 61 years |
| Central subfield thickness | 478 Microns | 496 Microns | 488 Microns |
| Diabetic retinopathy severity scale Advanced Proliferative diabetic retinopathy Level 81 or 85 | 0 Eyes | 0 Eyes | 0 Eyes |
| Diabetic retinopathy severity scale Diabetic retinopathy absent or questionable; levels 10, 12, 14, or 15 | 0 Eyes | 1 Eyes | 1 Eyes |
| Diabetic retinopathy severity scale High-risk proliferative diabetic retinopathy; level 71 or 75 | 6 Eyes | 7 Eyes | 13 Eyes |
| Diabetic retinopathy severity scale Microaneurysms only; level 20 | 0 Eyes | 2 Eyes | 2 Eyes |
| Diabetic retinopathy severity scale Mild-to-moderate nonproliferative diabetic retinopathy; level 35 or 43 | 58 Eyes | 42 Eyes | 100 Eyes |
| Diabetic retinopathy severity scale Mild-to-moderate proliferative diabetic retinopathy; level 61 or 65 | 15 Eyes | 16 Eyes | 31 Eyes |
| Diabetic retinopathy severity scale Moderately severe to severe nonproliferative diabetic retinopathy; level 47 or 53 | 72 Eyes | 79 Eyes | 151 Eyes |
| Duration of diabetes | 15 years | 14 years | 15 years |
| Glycated hemoglobin | 8.0 Hemoglobin A1c percentage | 8.0 Hemoglobin A1c percentage | 8.0 Hemoglobin A1c percentage |
| Previous anti-VEGF treatment for diabetic macular edema | 25 Eyes | 29 Eyes | 54 Eyes |
| Race/Ethnicity, Customized Asian | 2 Eyes | 2 Eyes | 4 Eyes |
| Race/Ethnicity, Customized Black or African American | 32 Eyes | 26 Eyes | 58 Eyes |
| Race/Ethnicity, Customized Hispanic or Latino | 39 Eyes | 41 Eyes | 80 Eyes |
| Race/Ethnicity, Customized Multiple | 1 Eyes | 1 Eyes | 2 Eyes |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Eyes | 1 Eyes | 2 Eyes |
| Race/Ethnicity, Customized Unknown or not reported | 1 Eyes | 0 Eyes | 1 Eyes |
| Race/Ethnicity, Customized White | 82 Eyes | 83 Eyes | 165 Eyes |
| Sex/Gender, Customized Male | 82 Eyes | 80 Eyes | 162 Eyes |
| Sex/Gender, Customized Women | 76 Eyes | 74 Eyes | 150 Eyes |
| Type of diabetes Type 1 | 7 Eyes | 8 Eyes | 15 Eyes |
| Type of diabetes Type 2 | 151 Eyes | 146 Eyes | 297 Eyes |
| Visual acuity letter score | 61 units on a scale | 60 units on a scale | 60 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 116 | 4 / 112 | 3 / 42 |
| other Total, other adverse events | 100 / 116 | 94 / 112 | 40 / 42 |
| serious Total, serious adverse events | 61 / 116 | 42 / 112 | 18 / 42 |
Outcome results
Primary
Mean Change in Visual Acuity
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.
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Mean Change in Visual Acuity | 15 Letter Score | Standard Deviation 8.5 |
| Bevacizumab-First Group | Mean Change in Visual Acuity | 14 Letter Score | Standard Deviation 8.8 |
Secondary
Change in Visual Acuity From Baseline
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.
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Change in Visual Acuity From Baseline | 14.7 Letter Score | Standard Deviation 14.5 |
| Bevacizumab-First Group | Change in Visual Acuity From Baseline | 15.9 Letter Score | Standard Deviation 12.4 |
Secondary
Decrease in E-ETDRS Visual Acuity Letter Score
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.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Decrease in E-ETDRS Visual Acuity Letter Score | 15 or more letters | 9 Eyes |
| Aflibercept- Monotherapy Group | Decrease in E-ETDRS Visual Acuity Letter Score | 10 or more letters | 8 Eyes |
| Bevacizumab-First Group | Decrease in E-ETDRS Visual Acuity Letter Score | 15 or more letters | 5 Eyes |
| Bevacizumab-First Group | Decrease in E-ETDRS Visual Acuity Letter Score | 10 or more letters | 4 Eyes |
Secondary
Increase in E-ETDRS Visual Acuity Letter Score
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.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Increase in E-ETDRS Visual Acuity Letter Score | 15 or more letters | 70 Eyes |
| Aflibercept- Monotherapy Group | Increase in E-ETDRS Visual Acuity Letter Score | 10 or more letters | 101 Eyes |
| Bevacizumab-First Group | Increase in E-ETDRS Visual Acuity Letter Score | 15 or more letters | 74 Eyes |
| Bevacizumab-First Group | Increase in E-ETDRS Visual Acuity Letter Score | 10 or more letters | 98 Eyes |
Secondary
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria
Time frame: Baseline to 52 weeks
Population: Eyes that did not meet the switch criteria were censored at the last completed visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept- Monotherapy Group | Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria | 88 Eyes |
Secondary
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria
Time frame: Baseline to 104 weeks
Population: Eyes that did not meet the switch criteria were censored at the last completed visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept- Monotherapy Group | Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria | 100 Eyes |
Secondary
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria
Time frame: Baseline to 12 weeks
Population: Eyes that did not meet the switch criteria were censored at the last completed visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept- Monotherapy Group | Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria | 16 Eyes |
Secondary
Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria
Time frame: Baseline to 24 weeks
Population: Eyes that did not meet the switch criteria were censored at the last completed visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept- Monotherapy Group | Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria | 57 Eyes |
Secondary
Number of Injections
All study injections were counted, including aflibercept injections received among eyes in the bevacizumab first group.
Time frame: 2 years
Population: Limited to eyes that completed the 2-year visit or any later common visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Number of Injections | 14.6 injections | Standard Deviation 4.1 |
| Bevacizumab-First Group | Number of Injections | 16.1 injections | Standard Deviation 4.1 |
Secondary
Number of Visits
Time frame: 2 years
Population: This analysis was limited to patients with one study eye who completed 2 years of follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Number of Visits | 22.0 visits | Standard Deviation 3.6 |
| Bevacizumab-First Group | Number of Visits | 22.5 visits | Standard Deviation 3.4 |
Secondary
Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema
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).
Time frame: 2 years
Population: The analysis included only eyes for which baseline data on the central subfield thickness were available.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Aflibercept- Monotherapy Group | Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema | 76 Eyes |
| Bevacizumab-First Group | Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema | 70 Eyes |
Secondary
Optical Coherence Tomography Central Subfield Thickness Change From Baseline
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.
Time frame: 2 years
Population: The analysis included only eyes for which baseline data on the central subfield thickness were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Optical Coherence Tomography Central Subfield Thickness Change From Baseline | -192 microns | Standard Deviation 143 |
| Bevacizumab-First Group | Optical Coherence Tomography Central Subfield Thickness Change From Baseline | -198 microns | Standard Deviation 160 |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Aflibercept- Monotherapy Group | Visual Acuity | 20/40 or worse | 96 Eyes |
| Aflibercept- Monotherapy Group | Visual Acuity | 20/200 or worse | 6 Eyes |
| Aflibercept- Monotherapy Group | Visual Acuity | 20/20 or better | 29 Eyes |
| Bevacizumab-First Group | Visual Acuity | 20/20 or better | 28 Eyes |
| Bevacizumab-First Group | Visual Acuity | 20/40 or worse | 95 Eyes |
| Bevacizumab-First Group | Visual Acuity | 20/200 or worse | 2 Eyes |