Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema, anti-vascular endothelial growth factor
Brief summary
Although multiple studies have suggested that treatment with ranibizumab is safe and efficacious and superior to focal/grid laser alone for patients with center-involved diabetic macular edema (DME), there may be barriers in place to widespread adoption of ranibizumab use given its high cost per dose and the need for multiple treatments over time. Prioritizing resources from a public health policy perspective could be easier if more precise estimates regarding the risks and benefits of other anti-vascular endothelial growth factor (anti-VEGF) therapies were available, especially when the difference in costs could be billions of dollars over just a few years. Thus, there is a clear rationale at this time to explore potential anti-VEGF alternatives to ranibizumab that might prove to be as or more efficacious, might deliver equally lasting or longer-lasting treatment effects, and cost substantially less. Of the potentially available alternative anti-VEGF agents for this trial, bevacizumab and aflibercept are the best candidates for a direct comparison study. Bevacizumab shares the most similar molecular structure, costs far less, and is widely available. Furthermore, there is already preliminary evidence to suggest that it may be efficacious in the treatment of DME and it is already being widely used for this indication. Although aflibercept has a similar cost per unit dose to ranibizumab, it has the potential to decrease treatment burden and associated cost. If results from a comparative trial demonstrate improved efficacy or suggest similar efficacy of bevacizumab or aflibercept over ranibizumab, this information might give clinicians scientific rationale to substitute either one of these drugs for ranibizumab in the treatment of DME, and might thereby have substantial implications for public policy in terms of future estimates of health care dollars and possibly number of treatments necessary for anti-VEGF treatment of diabetic macular disease. Because of its availability and lower cost, bevacizumab is already currently in widespread clinical use for treatment of DME despite the lack of FDA approval for this indication. Thus, a clinical trial that suggested whether bevacizumab could be used as a safe and efficacious alternative to ranibizumab could substantially impact nationwide practice patterns for treatment of DME by either validating the current use of bevacizumab or by demonstrating improved outcomes with ranibizumab or aflibercept treatment for DME. Study Objective The primary objective of the proposed research is to compare the efficacy and safety of (1) intravitreal aflibercept, (2) intravitreal bevacizumab, and (3) intravitreal ranibizumab when given to treat central-involved DME in eyes with visual acuity of 20/32 to 20/320.
Detailed description
A five year follow-up visit is being conducted to gather information on long term outcomes
Interventions
DRUG2.0 mg intravitreal aflibercept
Intravitreal injection of 2.0 mg aflibercept at baseline and up to every 4 weeks using defined retreatment criteria.
DRUG1.25 mg intravitreal bevacizumab
Intravitreal injection of 1.25 mg bevacizumab at baseline and up to every 4 weeks using defined retreatment criteria.
DRUG0.3 mg intravitreal ranibizumab
Intravitreal injection of 0.3 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.
Sponsors
National Eye Institute (NEI)
Genentech, Inc.
Regeneron Pharmaceuticals
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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 (see Procedures Manual for definitions) * At least one eye meets the following study eye criteria: * Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score ≤ 78 (i.e., 20/32 or worse) and ≥ 24 (i.e., 20/320 or better) within eight days of randomization. * On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula. * Diabetic macular edema present on optical coherence tomography (OCT) (central subfield thickness on OCT \>250 µm on Zeiss Stratus or the equivalent on spectral domain OCTs based on gender specific cutoffs), within eight days of randomization. * Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality (for Zeiss Stratus, standard deviation of center point thickness should be ≤ 10% of the center point thickness and signal strength should be ≥ 6) * Media clarity, pupillary dilation, and individual cooperation sufficient for adequate fundus photographs * Able and willing to provide informed consent.
Exclusion criteria
* Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant. * 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. * 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. * Known allergy to any component of the study drug. * 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. * Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization. * 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. * 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. * Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study. The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye): * Macular edema is considered to be due to a cause other than diabetic macular edema. * An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema. * An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). * An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.). * Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). * History of an anti-VEGF treatment for DME in the past 12 months or history of any other treatment for DME at any time in the past four months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids). * Enrollment will be limited to a maximum of 25% of the planned sample size with any history of anti-VEGF treatment for DME. Once this number of eyes has been enrolled, any history of anti-VEGF treatment for DME will be an exclusion criterion. * History of pan-retinal photocoagulation within four months prior to randomization or anticipated need for pan-retinal photocoagulation in the six months following randomization. * History of anti-VEGF treatment for a disease other than DME in the past 12 months. * History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior four months or anticipated within the next six months following randomization. * History of YAG capsulotomy performed within two months prior to randomization. * Aphakia. * Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year | Baseline to 1-year | Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best. |
| Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69 | Baseline to 1-year | Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best. |
| Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69 | Baseline to 1-year | Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change in Retinal Volume | Baseline to 1-year | Baseline volume values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 459 scans. One-year volume values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 472 scans. When calculating change in volume, measurements taken on the same machine at both visits were not converted, because the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in volume was calculated after converting either the baseline and/or follow-up value from Spectralis or Cirrus to a Stratus equivalent value in 17 eyes. |
| Total Number of Injections Prior to 1 Year | Baseline to 1-year | Only includes participants that completed the 1 year visit |
| Overall Change in Optical Coherence Tomography Central Subfield Thickness | baseline to 1-year | All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes. |
| Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser | Baseline to 1-year | — |
| Total Number of Laser Treatments | between 24 weeks and 1 year | Only includes participants that completed the 1 year visit. |
| Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69 | baseline to 1-year | All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes. |
| Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69 | baseline to 1-year | All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept 2.0 mg intravitreal aflibercept: Intravitreal injection of 2.0 mg aflibercept at baseline and up to every 4 weeks using defined retreatment criteria. | 224 |
| Bevacizumab 1.25 mg intravitreal bevacizumab: Intravitreal injection of 1.25 mg bevacizumab at baseline and up to every 4 weeks using defined retreatment criteria. | 218 |
| Ranibizumab 0.3 mg intravitreal ranibizumab: Intravitreal injection of 0.3 mg ranibizumab at baseline and up to every 4 weeks using defined retreatment criteria. | 218 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 5 | 3 |
| Overall Study | Missed Visit | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 6 | 9 |
Baseline characteristics
| Characteristic | Aflibercept | Total | Ranibizumab | Bevacizumab |
|---|---|---|---|---|
| Age, Customized | 60 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 10 | 60 years STANDARD_DEVIATION 11 | 62 years STANDARD_DEVIATION 10 |
| Diabetes Type Type 1 | 22 participants | 50 participants | 16 participants | 12 participants |
| Diabetes Type Type 2 | 196 participants | 597 participants | 196 participants | 205 participants |
| Diabetes Type Uncertain | 6 participants | 13 participants | 6 participants | 1 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Absent of minimal NPDR | 7 participants | 18 participants | 5 participants | 6 participants |
| Diabetic Retinopathy Severity (ETDRS Level) High risk PDR | 2 participants | 18 participants | 9 participants | 7 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Mild to moderately severe NPDR | 150 participants | 426 participants | 145 participants | 131 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Mild to moderate PDR | 28 participants | 82 participants | 23 participants | 31 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Missing | 3 participants | 12 participants | 2 participants | 7 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Prior PRP; without current PDR | 17 participants | 54 participants | 16 participants | 21 participants |
| Diabetic Retinopathy Severity (ETDRS Level) Severe NPDR | 17 participants | 50 participants | 18 participants | 15 participants |
| Lens Status Phakic | 166 participants | 499 participants | 173 participants | 160 participants |
| Lens Status Pseudophakic | 58 participants | 161 participants | 45 participants | 58 participants |
| OCT Central Subfield | 387 Microns | 387 Microns | 390 Microns | 376 Microns |
| Prior Anti-VEGF for DME | 24 participants | 84 participants | 29 participants | 31 participants |
| Prior Coronary Artery Disease | 22 participants | 83 participants | 34 participants | 27 participants |
| Prior Focal/Grid Laser for DME | 80 participants | 244 participants | 80 participants | 84 participants |
| Prior Hypertension | 177 participants | 533 participants | 175 participants | 181 participants |
| Prior Myocardial Infarction | 13 participants | 43 participants | 16 participants | 14 participants |
| Prior other treatment for DME | 14 participants | 37 participants | 11 participants | 12 participants |
| Prior PRP | 32 participants | 107 participants | 35 participants | 40 participants |
| Prior Stroke | 8 participants | 31 participants | 10 participants | 13 participants |
| Prior Transient Ischemic attacks | 6 participants | 24 participants | 10 participants | 8 participants |
| Race/Ethnicity, Customized American Indian/Alaskin Native | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 8 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Black/African American | 32 participants | 105 participants | 36 participants | 37 participants |
| Race/Ethnicity, Customized Hispanic | 37 participants | 103 participants | 30 participants | 36 participants |
| Race/Ethnicity, Customized More than one race | 4 participants | 6 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander | 2 participants | 4 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Unknown/not reported | 1 participants | 3 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 145 participants | 430 participants | 146 participants | 139 participants |
| Sex/Gender, Customized Men | 114 participants | 353 participants | 124 participants | 115 participants |
| Sex/Gender, Customized Women | 110 participants | 307 participants | 94 participants | 103 participants |
| Visual Acuity Letter Score | 69 units on a scale | 69 units on a scale | 68 units on a scale | 69 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 | — / — | — / — | — / — |
| other Total, other adverse events | 152 / 224 | 151 / 218 | 144 / 218 |
| serious Total, serious adverse events | 61 / 224 | 46 / 218 | 57 / 218 |
Outcome results
Primary
Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69
Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Time frame: Baseline to 1-year
Population: Visual acuity change truncated to +/- 3SD (-22 and +44) to minimize the effects of outliers for 6 eyes in the aflibercept group (4 on the positive end, 2 on the negative end) and 2 eyes in the bevacizumab group (both on the negative end).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69 | 18.9 units on a scale | Standard Deviation 11.5 |
| Bevacizumab | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69 | 11.8 units on a scale | Standard Deviation 12 |
| Ranibizumab | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69 | 14.2 units on a scale | Standard Deviation 10.6 |
Comparison: Aflibercept vs. Bevacizumabp-value: 0.00195% CI: [2.9, 10.1]ANCOVA
Comparison: Aflibercept vs. Ranibizumabp-value: 0.003195% CI: [1.4, 8]ANCOVA
Comparison: Ranibizumab vs Bevacizumabp-value: 0.2195% CI: [-1.1, 4.8]ANCOVA
Primary
Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69
Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Time frame: Baseline to 1-year
Population: Visual acuity change truncated to +/- 3SD (-22 and +44) to minimize the effects of outliers for 6 eyes in the aflibercept group (4 on the positive end, 2 on the negative end) and 2 eyes in the bevacizumab group (both on the negative end).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69 | 8.0 units on a scale | Standard Deviation 7.6 |
| Bevacizumab | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69 | 7.5 units on a scale | Standard Deviation 7.4 |
| Ranibizumab | Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69 | 8.3 units on a scale | Standard Deviation 6.8 |
Comparison: Aflibercept vs Bevacizumabp-value: 0.6995% CI: [-1.3, 2.7]ANCOVA
Comparison: Aflibercept vs Ranibizumabp-value: 0.6995% CI: [-2.3, 1.5]ANCOVA
Comparison: Ranibizumab vs Bevacizumabp-value: 0.6995% CI: [-0.9, 3.1]ANCOVA
Primary
Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year
Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Time frame: Baseline to 1-year
Population: Visual acuity change truncated to +/- 3SD (-22 and +44) to minimize the effects of outliers for 6 eyes in the aflibercept group (4 on the positive end, 2 on the negative end) and 2 eyes in the bevacizumab group (both on the negative end).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year | 13.3 units on a scale | Standard Deviation 11.1 |
| Bevacizumab | Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year | 9.7 units on a scale | Standard Deviation 10.1 |
| Ranibizumab | Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year | 11.2 units on a scale | Standard Deviation 9.4 |
Comparison: Aflibercept vs. Bevacizumabp-value: <0.00195% CI: [1.4, 5.7]ANCOVA
Comparison: Aflibercept vs. Ranibizumabp-value: 0.03495% CI: [0.1, 4.2]ANCOVA
Comparison: Ranibizumab vs. Bevacizumabp-value: 0.1295% CI: [-0.4, 3.2]ANCOVA
Secondary
Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69
All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes.
Time frame: baseline to 1-year
Population: In addition to participants missing the 1-year visit, 3 in the aflibercept group, 3 in the bevacizumab group, and 5 in the ranibizumab group had 1-year visits but unusable OCT data to compute change due to the scan being missing or ungradable at either baseline or 1 year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69 | -210 microns | Standard Deviation 151 |
| Bevacizumab | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69 | -135 microns | Standard Deviation 152 |
| Ranibizumab | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69 | -176 microns | Standard Deviation 151 |
Secondary
Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69
All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes.
Time frame: baseline to 1-year
Population: In addition to participants missing the 1-year visit, 3 in the aflibercept group, 3 in the bevacizumab group, and 5 in the ranibizumab group had 1-year visits but unusable OCT data to compute change due to the scan being missing or ungradable at either baseline or 1 year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69 | -129 microns | Standard Deviation 110 |
| Bevacizumab | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69 | -67 microns | Standard Deviation 65 |
| Ranibizumab | Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69 | -119 microns | Standard Deviation 109 |
Secondary
Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser
Time frame: Baseline to 1-year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aflibercept | Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser | 2 Eyes |
| Bevacizumab | Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser | 4 Eyes |
| Ranibizumab | Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser | 1 Eyes |
Secondary
Overall Change in Optical Coherence Tomography Central Subfield Thickness
All baseline and 1-year optical coherence tomography (OCT) scans were graded by Duke Reading Center. In addition, a random sample of OCT images from other visits and images for which the investigator believed central grading was needed also were graded by Duke Reading Center. Baseline CSF values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 583 scans. One-year CSF values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 604 scans. When calculating change in CSF thickness, measurements taken on the same machine at both visits were not converted, since the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in CSF thickness was calculated after converting either the baseline and/or follow-up thickness value from Spectralis or Cirrus to a Stratus equivalent value in 26 eyes.
Time frame: baseline to 1-year
Population: In addition to participants missing the 1-year visit, 3 in the aflibercept group, 3 in the bevacizumab group, and 5 in the ranibizumab group had 1-year visits but unusable OCT data to compute change due to the scan being missing or ungradable at either baseline or 1 year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Overall Change in Optical Coherence Tomography Central Subfield Thickness | -169 microns | Standard Deviation 138 |
| Bevacizumab | Overall Change in Optical Coherence Tomography Central Subfield Thickness | -101 microns | Standard Deviation 121 |
| Ranibizumab | Overall Change in Optical Coherence Tomography Central Subfield Thickness | -147 microns | Standard Deviation 137 |
Comparison: Aflibercept vs Bevacizumabp-value: <0.00195% CI: [-91.1, -48.6]ANCOVA
Comparison: Aflibercept vs Ranibizumabp-value: 0.03695% CI: [-36, -1.2]ANCOVA
Comparison: Ranibizumab vs Bevacizumabp-value: <0.00195% CI: [-71.2, -31.3]ANCOVA
Secondary
Overall Change in Retinal Volume
Baseline volume values were converted from the thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 459 scans. One-year volume values were converted from a thickness value measured on a Spectralis or Cirrus OCT machine to a Stratus equivalent value for 472 scans. When calculating change in volume, measurements taken on the same machine at both visits were not converted, because the conversion equation slope is nearly 1 and the constant difference does not affect the change calculation. Therefore, change in volume was calculated after converting either the baseline and/or follow-up value from Spectralis or Cirrus to a Stratus equivalent value in 17 eyes.
Time frame: Baseline to 1-year
Population: In addition to participants missing the 1-year visit, 46 in the aflibercept group, 53 in the bevacizumab group, and 44 in the ranibizumab group had 1-year visits but unusable OCT data to compute change due to the scan being missing or ungradable at either baseline or 1 year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Overall Change in Retinal Volume | -1.7 mm^3 | Standard Deviation 1.6 |
| Bevacizumab | Overall Change in Retinal Volume | -1.0 mm^3 | Standard Deviation 1.2 |
| Ranibizumab | Overall Change in Retinal Volume | -1.7 mm^3 | Standard Deviation 1.5 |
Secondary
Total Number of Injections Prior to 1 Year
Only includes participants that completed the 1 year visit
Time frame: Baseline to 1-year
Population: Seven study eyes received 1 injection and 2 eyes received 2 injections of 0.5 mg of ranibizumab prior to the FDA approving a 0.3 mg dosage of ranibizumab for diabetic macular edema treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Total Number of Injections Prior to 1 Year | 9.2 Injections | Standard Deviation 2 |
| Bevacizumab | Total Number of Injections Prior to 1 Year | 9.7 Injections | Standard Deviation 2.3 |
| Ranibizumab | Total Number of Injections Prior to 1 Year | 9.4 Injections | Standard Deviation 2.1 |
Secondary
Total Number of Laser Treatments
Only includes participants that completed the 1 year visit.
Time frame: between 24 weeks and 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aflibercept | Total Number of Laser Treatments | 1 | 57 participants |
| Aflibercept | Total Number of Laser Treatments | 0 | 132 participants |
| Aflibercept | Total Number of Laser Treatments | 2 | 19 participants |
| Bevacizumab | Total Number of Laser Treatments | 1 | 85 participants |
| Bevacizumab | Total Number of Laser Treatments | 0 | 91 participants |
| Bevacizumab | Total Number of Laser Treatments | 2 | 30 participants |
| Ranibizumab | Total Number of Laser Treatments | 0 | 111 participants |
| Ranibizumab | Total Number of Laser Treatments | 2 | 18 participants |
| Ranibizumab | Total Number of Laser Treatments | 1 | 77 participants |