Proliferative Diabetic Retinopathy, Vitreous Hemorrhage
Conditions
Keywords
vitreous, hemorrhage, proliferative, diabetic, retinopathy, intravitreal, ranibizumab, Lucentis, saline, vitrectomy
Brief summary
This study is being conducted to determine if intravitreal injections of ranibizumab decrease the proportion of eyes in which vitrectomy is performed compared with saline injections in eyes presenting with vitreous hemorrhage from proliferative diabetic retinopathy.
Detailed description
In mild to moderate cases of vitreous hemorrhage, panretinal photocoagulation (PRP) is performed when possible to achieve regression of new vessels or at least stabilization of the neovascularization with no further growth in order to decrease the probability of subsequent vitreous hemorrhage while spontaneous absorption of the hemorrhage occurs. In cases in which the hemorrhage is too dense to apply PRP, vitrectomy is considered to remove the hemorrhage and provide a clear media for application of PRP (often as endolaser photocoagulation) as well as eliminate extensive neovascularization and relieve traction retinal detachments. Pars plana vitrectomy was introduced in the 1970s as a surgical intervention in diabetes for non-clearing vitreous hemorrhage, traction retinal detachment or very severe proliferative diabetic retinopathy (PDR). The goal of vitrectomy in such eyes is to remove the hemorrhage and provide a clear media for application of PRP (often as endolaser photocoagulation) as well as eliminate extensive neovascularization and relieve traction retinal detachments. Many advances in instrumentation and technique have resulted in a dramatic reduction in complications over the last few decades, but surgical complications remain including the following: neovascular glaucoma, retinal detachment, fibrinoid syndrome, endophthalmitis and hypotony with subsequent phthisis bulbi. Recovery for the subject can take up to 6 weeks. Increased vascular endothelial growth factor (VEGF) levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy, especially PDR. VEGF has been demonstrated to increase vessel permeability by increasing the phosphorylation of tight junction proteins, and has been shown to increase retinal vascular permeability in in vivo models. Anti-VEGF therapy, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of PDR while vitreous hemorrhage clears to facilitate the placement of PRP, potentially avoiding vitrectomy. This study is designed to determine if intravitreal injections of ranibizumab will facilitate clearing of vitreous hemorrhage and avoidance of vitrectomy and its potential complications. Compared with a surgical intervention, use of an intravitreal agent associated with fewer vitrectomies would be preferable because of the reduced costs, reduced time to treatment, reduced intervention time, relatively low risk of side effects, and reduced recovery time. An intravitreal agent also would be a useful alternative for patients who are unwilling to undergo surgery. Furthermore, the study will determine the safety of this medication in the setting of PDR.
Interventions
DRUGRanibizumab
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
DRUGSaline
Saline injection of 0.5mg at baseline, 4 and 8 weeks
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject-level Criteria Inclusion To be eligible, the following inclusion criteria must be met: Age \>= 18 years Diagnosis of diabetes mellitus (type 1 or type 2) At least one eye meets the study eye criteria listed below Able and willing to provide informed consent. Exclusion A subject is not eligible if any of the following
Exclusion criteria
are present: 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). A condition that, in the opinion of the investigator, would preclude subject undergoing elective vitrectomy surgery if indicated during the study. Participation in an investigational trial that involved treatment with any drug within 30 days of randomization that has not received regulatory approval at the time of study entry. Known allergy to any component of the study drug. Blood pressure \> 180/110 (systolic above 180 or diastolic above 110). Myocardial infarction, other 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 4 months prior to randomization. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 months. Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 12 months of the study. Study Eye Criteria The subject must have at least one eye meeting all of the inclusion criteria and none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment or Failure Defined as Vitrectomy | within 112 days of randomization | The cumulative probabilities of vitrectomy by 16 weks (112 days) in each group were computed using the life-table method. The treatment group comparison was made using the log-rank test. Data were censored at the time point of the participant's last completed visit. |
| Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Baseline to 16 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 4, 8 and 12 weeks | Visual acuity was analyzed using a longitudinal mixed regression model adjusting for baseline visual acuity.Unit of measure is based on the E-ETDRS visual acuity letter score scale, 0-97, where 0 = worst and 97 = best. |
| Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 4, 8 and 12 weeks | — |
| Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy | within 112 days of randomization | The proportion of eyes with complete panretinal photocoagulation by 16 weeks in abscence of vitrectomy was computed using the life-table method and treatment groups were compared using the log-rank test. |
| Very Severe Visual Acuity Loss (Defined as <20/800) | 4,8 and 12 weeks | — |
| Severe Visual Acuity Loss (Defined as <20/200) | 4,8 and 12 weeks | — |
| Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 4, 8 and 12 weeks | Optical coherence tomography signal strength was evaluated as a potential indicator of vitreous hemorrhage density in an exploratory analysis. This analysis included only eyes with Optical Coherence Tomography (OCT) signal strength equals to 0 at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks | 125 |
| Saline Injection Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks | 136 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Dropped | 2 | 2 |
| Overall Study | Missed | 2 | 5 |
Baseline characteristics
| Characteristic | Total | Saline Injection | Ranibizumab |
|---|---|---|---|
| Age, Customized | 59 years | 58 years | 61 years |
| Anti-platelet aggregation and anti-coagulant drugs Anti-coagulants | 13 Participants | 6 Participants | 7 Participants |
| Anti-platelet aggregation and anti-coagulant drugs Aspirin | 107 Participants | 57 Participants | 50 Participants |
| Anti-platelet aggregation and anti-coagulant drugs Not Available | 71 Participants | 37 Participants | 34 Participants |
| Anti-platelet aggregation and anti-coagulant drugs NSAIDs | 30 Participants | 15 Participants | 15 Participants |
| Anti-platelet aggregation and anti-coagulant drugs Other anti-platelet aggregation drugs | 40 Participants | 21 Participants | 19 Participants |
| Diabetes Type Type1 | 52 Participants | 31 Participants | 21 Participants |
| Diabetes Type Type 2 | 200 Participants | 99 Participants | 101 Participants |
| Diabetes Type Uncertain | 9 Participants | 6 Participants | 3 Participants |
| Duration of Diabetes (years) | 20 Number | 21 Number | 19 Number |
| Duration of vitreous hemorrhage since first documented on clinical exam 1-3 months | 80 Participants | 39 Participants | 41 Participants |
| Duration of vitreous hemorrhage since first documented on clinical exam < 1month | 141 Participants | 75 Participants | 66 Participants |
| Duration of vitreous hemorrhage since first documented on clinical exam 4-6 months | 18 Participants | 11 Participants | 7 Participants |
| Duration of vitreous hemorrhage since first documented on clinical exam > 6 months | 22 Participants | 11 Participants | 11 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score 23 to 1 letter score - (20/400 to 20/800-3) | 37 Participants | 18 Participants | 19 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score 48 to 24 letter score - (20/125 to 20/320) | 55 Participants | 37 Participants | 18 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score 68 to 49 letter score - (20/50 to 20/100) | 51 Participants | 19 Participants | 32 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score > 69 letter score - (20/40 or better) | 41 Participants | 21 Participants | 20 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score Counting fingers only | 27 Participants | 15 Participants | 12 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score Hand motion only | 39 Participants | 20 Participants | 19 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score Light perception only | 11 Participants | 6 Participants | 5 Participants |
| Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score No light perception | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c | 7.9 Percentage | 8.0 Percentage | 7.7 Percentage |
| Intraocular Pressure | 15 mm Hg | 14 mm Hg | 15 mm Hg |
| Lens Status (on clinical exam) Phakic | 195 Participants | 98 Participants | 97 Participants |
| Lens Status (on clinical exam) Posterior Chamber Intraocular Lens | 66 Participants | 38 Participants | 28 Participants |
| Median Electronic-Early Treatment Diabetic Retinopathy Visual Acuity (letter score) | 31 Units on a scale | 28 Units on a scale | 34 Units on a scale |
| Optical coherence tomography signal strength =0 | 170 Participants | 96 Participants | 74 Participants |
| Optical coherence tomography signal strength > 0 | 88 Participants | 38 Participants | 50 Participants |
| Optical coherence tomography signal strength Missing/not available | 3 Participants | 2 Participants | 1 Participants |
| Pre-Existing Cardiovascular Conditions No | 157 Participants | 76 Participants | 81 Participants |
| Pre-Existing Cardiovascular Conditions Yes | 104 Participants | 60 Participants | 44 Participants |
| Pre-Existing Hypertension No | 39 Participants | 19 Participants | 20 Participants |
| Pre-Existing Hypertension Yes | 222 Participants | 117 Participants | 105 Participants |
| Prior panretinal photocoagulation No | 121 Participants | 58 Participants | 63 Participants |
| Prior panretinal photocoagulation Yes | 140 Participants | 78 Participants | 62 Participants |
| Prior Treatment for Diabetic Macular Edema No | 151 Participants | 79 Participants | 72 Participants |
| Prior Treatment for Diabetic Macular Edema Yes | 110 Participants | 57 Participants | 53 Participants |
| Prior treatment with anti-vascular endothelial growth factor drug for diabetic macular edema No | 233 Participants | 118 Participants | 115 Participants |
| Prior treatment with anti-vascular endothelial growth factor drug for diabetic macular edema Yes | 28 Participants | 18 Participants | 10 Participants |
| Race/Ethnicity, Customized African-American | 42 participants | 22 participants | 20 participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 5 participants | 4 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 66 participants | 34 participants | 32 participants |
| Race/Ethnicity, Customized More than one race | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Unknown/not reported | 3 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White | 137 participants | 70 participants | 67 participants |
| Sex: Female, Male Female | 135 Participants | 70 Participants | 65 Participants |
| Sex: Female, Male Male | 126 Participants | 66 Participants | 60 Participants |
| Ultrasound completed to assess eligibility No | 137 Participants | 74 Participants | 63 Participants |
| Ultrasound completed to assess eligibility Yes | 124 Participants | 62 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 125 | 94 / 136 |
| serious Total, serious adverse events | 13 / 125 | 23 / 136 |
Outcome results
Primary
Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)
Time frame: Baseline to 16 weeks
Population: Adverse events for each participants was collected throughout study duration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Recurrent vitreous hemorrhage on clinical exam | 8 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Traction and/or rhegmatogeneous retinal detachment | 10 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Elevated Intraocular Pressure (IOP)/Glaucoma | 16 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Neovascular glaucoma | 1 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Increase of IOP >= 10 mm Hg from baseline | 8 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Endophthalmitis | 0 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | IOP >= 30 mm Hg | 4 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Currently on IOP-lowering medication, not baseline | 13 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Cataract Surgery | 0 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Glaucoma surgery at anytime | 0 participants |
| Ranibizumab | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Angle or iris neovascularization | 1 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Glaucoma surgery at anytime | 0 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Endophthalmitis | 1 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Traction and/or rhegmatogeneous retinal detachment | 11 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Angle or iris neovascularization | 4 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Neovascular glaucoma | 1 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Cataract Surgery | 2 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Recurrent vitreous hemorrhage on clinical exam | 23 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Elevated Intraocular Pressure (IOP)/Glaucoma | 19 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Increase of IOP >= 10 mm Hg from baseline | 11 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | Currently on IOP-lowering medication, not baseline | 14 participants |
| Saline Injection | Safety (Injected-related, Ocular Drug-related and Systemic Drug-related) | IOP >= 30 mm Hg | 4 participants |
p-value: 0.01Fisher Exact
Primary
Treatment or Failure Defined as Vitrectomy
The cumulative probabilities of vitrectomy by 16 weks (112 days) in each group were computed using the life-table method. The treatment group comparison was made using the log-rank test. Data were censored at the time point of the participant's last completed visit.
Time frame: within 112 days of randomization
Population: The primary analysis followed the intent-to-treat principle and included all randomized eyes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab | Treatment or Failure Defined as Vitrectomy | 12 percentage of participants |
| Saline Injection | Treatment or Failure Defined as Vitrectomy | 17 percentage of participants |
Comparison: The cumulative probabilities of vitrectomy by 16 weeks in each group were computed using the life-table method. Treatment group comparisons were performed using the log-rank test. The treatment difference in cumulative probabilities and 95% confidence interval were reported.p-value: 0.3795% CI: [-4, 13]Log Rank
Secondary
Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy
The proportion of eyes with complete panretinal photocoagulation by 16 weeks in abscence of vitrectomy was computed using the life-table method and treatment groups were compared using the log-rank test.
Time frame: within 112 days of randomization
Population: The secondary analysis followed the intent-to-treat principle and included all randomized eyes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab | Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy | 44 percentage of eyes |
| Saline Injection | Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy | 31 percentage of eyes |
p-value: 0.0595% CI: [1.03, 2.3]Log Rank
Secondary
Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength
Optical coherence tomography signal strength was evaluated as a potential indicator of vitreous hemorrhage density in an exploratory analysis. This analysis included only eyes with Optical Coherence Tomography (OCT) signal strength equals to 0 at baseline.
Time frame: 4, 8 and 12 weeks
Population: This analysis followed the intent-to-treat principle
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 4 week results | 40 percentage of eyes |
| Ranibizumab | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 8 week results | 46 percentage of eyes |
| Ranibizumab | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 12 week results | 51 percentage of eyes |
| Saline Injection | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 4 week results | 28 percentage of eyes |
| Saline Injection | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 8 week results | 38 percentage of eyes |
| Saline Injection | Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength | 12 week results | 52 percentage of eyes |
Comparison: Signal strength was analyzed as a composite outcome defined as OCT signal strength \> = and no vitrectomy vs. OCT signal strength = 0.p-value: 0.87GLM with GEE method
Secondary
Severe Visual Acuity Loss (Defined as <20/200)
Time frame: 4,8 and 12 weeks
Population: Participant with a completed 4,8 and 12 week visit and an available visual acuity measurement were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Severe Visual Acuity Loss (Defined as <20/200) | 4 week results | 38 percentage of participants |
| Ranibizumab | Severe Visual Acuity Loss (Defined as <20/200) | 8 week results | 30 percentage of participants |
| Ranibizumab | Severe Visual Acuity Loss (Defined as <20/200) | 12 week results | 20 percentage of participants |
| Saline Injection | Severe Visual Acuity Loss (Defined as <20/200) | 4 week results | 38 percentage of participants |
| Saline Injection | Severe Visual Acuity Loss (Defined as <20/200) | 8 week results | 35 percentage of participants |
| Saline Injection | Severe Visual Acuity Loss (Defined as <20/200) | 12 week results | 27 percentage of participants |
p-value: 0.023Fisher Exact
Secondary
Very Severe Visual Acuity Loss (Defined as <20/800)
Time frame: 4,8 and 12 weeks
Population: Participants with a completed 4, 8 and 12 week visit respectively and an available visual acuity measurement were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Very Severe Visual Acuity Loss (Defined as <20/800) | 8 week results | 16 percentage of participants |
| Ranibizumab | Very Severe Visual Acuity Loss (Defined as <20/800) | 4 week results | 20 percentage of participants |
| Ranibizumab | Very Severe Visual Acuity Loss (Defined as <20/800) | 12 week results | 11 percentage of participants |
| Saline Injection | Very Severe Visual Acuity Loss (Defined as <20/800) | 4 week results | 25 percentage of participants |
| Saline Injection | Very Severe Visual Acuity Loss (Defined as <20/800) | 8 week results | 19 percentage of participants |
| Saline Injection | Very Severe Visual Acuity Loss (Defined as <20/800) | 12 week results | 16 percentage of participants |
p-value: 0.27Fisher Exact
Secondary
Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status
Visual acuity was analyzed using a longitudinal mixed regression model adjusting for baseline visual acuity.Unit of measure is based on the E-ETDRS visual acuity letter score scale, 0-97, where 0 = worst and 97 = best.
Time frame: 4, 8 and 12 weeks
Population: Number of participants with a complete 4 week visit, 8 and 12 week respectively and an available visual acuity measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 4 week results | 45 letter scores | Standard Deviation 30 |
| Ranibizumab | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 8 week results | 51 letter scores | Standard Deviation 30 |
| Ranibizumab | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 12 week results | 57 letter scores | Standard Deviation 27 |
| Saline Injection | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 4 week results | 42 letter scores | Standard Deviation 31 |
| Saline Injection | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 8 week results | 47 letter scores | Standard Deviation 31 |
| Saline Injection | Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status | 12 week results | 49 letter scores | Standard Deviation 29 |
p-value: 0.04Mixed Models Analysis
Secondary
Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit
Time frame: 4, 8 and 12 weeks
Population: This analysis followed the intent-to-treat principle. It includes all randomized eyes with a completed 4, 8 and 12 week visit respectively and an available visual acuity measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 4 week results | 29 percentage of participants |
| Ranibizumab | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 8 week results | 36 percentage of participants |
| Ranibizumab | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 12 week results | 45 percentage of participants |
| Saline Injection | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 4 week results | 29 percentage of participants |
| Saline Injection | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 8 week results | 33 percentage of participants |
| Saline Injection | Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit | 12 week results | 33 percentage of participants |