Proliferative Diabetic Retinopathy
Conditions
Brief summary
Diabetic neovascularization refers to a type of diabetic retinopathy which is worsening by the abnormal growth of blood vessels in the back of the eye, damaging the retina. The usual treatment is a type of laser, called panretinal photocoagulation. One drawback is that the amount of space within the eye for use of this treatment eventually has its limit, and should not be used too near the part of the retina used for detailed vision (the macula). In similar eye disorders, there are certain injectable medications called anti-VEGF treatments which can slow down or stop this abnormal blood vessel growth. This study sought to compare use of ranibizumab versus standard panretinal photocoagulation in treatment of diabetic neovascularization.
Detailed description
The purpose is to compare the efficacy of ranibizumab versus additional panretinal photocoagulation on diabetic neovascularization that is persistent despite previous treatment with panretinal photocoagulation. We hypothesize that ranibizumab intravitreal injections would induce neovascular regression in similar or better fashion than supplemental laser photocoagulation. Consented, enrolled subjects will either receive open-label intravitreal injections of 0.5-mg dose of ranibizumab or additional panretinal photocoagulation (up to 500 300-500 um laser spots) in a ratio of two-to-one (2:1) at the beginning of the study period. ETDRS best-corrected visual acuity, contrast sensitivity, and Optos color photography will be performed at enrollment, at weeks 1, 2, 3 and 4, and at months 2, 3, 4, 5 and 6. The subjects will undergo fluorescein angiography utilizing the Optomap FA (fluorescein angiography) system and optical coherence tomography (OCT) at enrollment, at weeks 2 and 4, and at months 2, 3, 4 and 6. The subjects will be followed for a 6-month period for stabilization, regression, or recurrence of neovascularization. In addition, patients will be evaluated for occurrence of macular edema.
Interventions
DRUGranibizumab
One 0.5 mg intravitreal injection
PROCEDURELaser photocoagulation
panretinal photocoagulation (up to 500 300-500 um laser spots)
Sponsors
Genentech, Inc.
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age 18 years or older Patient related considerations: * Patients with Diabetes Mellitus (Type I or II) are eligible. HgA1c will be evaluated at the beginning of the study, but this value will have no significance in inclusion or exclusion. * Patients will not be pregnant at enrollment and must provide evidence of the use of two types of birth control while enrolled in the study. * Patients will have no known sensitivity to ranibizumab or other anti-VEGF injections. Disease related considerations: * Patients will have diabetic neovascularization as seen on fluorescein angiography that was previously treated with full (at least 1200 laser burns) panretinal photocoagulation and that has persisted at least three months. * There will be no evidence of ocular inflammation at enrollment. * There is no restriction on patient's current medications or concomitant illnesses as long as there is no interference with patient follow-up. Other considerations: * Patients may not be enrolled in another clinical study or observational trial. * There is no limitation on patient's institutional status as long as the patient is able to participate in follow-up.
Exclusion criteria
* Pregnancy (positive pregnancy test) * Uncontrolled glaucoma on three medicines or more to control intraocular pressure * Prior enrollment in the study * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) | Baseline to Week 4; Baseline to Month 4-6 | This is a measurement of how much change in neovascularization has occurred, using the Optomap FA readings to calculate the increase or decrease in surface area of the retina that is affected by neovascularization. |
| The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) | Baseline to Week 4; Baseline to Month 6 | — |
| Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination | Month 6 | — |
| Number of Participants With Occurrence of Adverse Events | Week 1, 2, 4; Month 2, 3, 4, 5, 6 | Patients were randomized to receive IVR vs. additional PRP. Number of participants with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing | 1 month, 6 months | — |
| Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment | 6 month | Complications; including vitreous hemorrhage, iris neovascularization, and tractional retinal detachment were assessed at the 6 month time point and are reported below. |
| Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters | 1 Month; 6 months | — |
Countries
United States
Participant flow
Recruitment details
Subjects will be recruited starting in 2007 and until sufficient subject population is reached. They will be seen in an eye clinic at Rush University Medical Center.
Pre-assignment details
There is no wash-out period. Recruited subjects must be in need of treatment for their PDR, and will be randomized and treated at the baseline visit. There were a total of 8 participants treated.
Participants by arm
| Arm | Count |
|---|---|
| 1 - Ranibizumab Intravitreal injection of 0.5-mg dose of ranibizumab | 6 |
| 2 - Additional PRP Treatment Additional panretinal photocoagulation (up to 500 300-500 um laser spots) | 2 |
| Total | 8 |
Baseline characteristics
| Characteristic | 2 - Additional PRP Treatment | 1 - Ranibizumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 6 Participants | 7 Participants |
| Age, Continuous | 67 years | 57 years | 59 years |
| Region of Enrollment United States | 2 participants | 6 participants | 8 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 0 / 6 | 2 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 |
Outcome results
Primary
Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination
Time frame: Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 - Ranibizumab | Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination | 0 number of events |
| 2 - Additional PRP Treatment | Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination | 1 number of events |
Primary
Number of Participants With Occurrence of Adverse Events
Patients were randomized to receive IVR vs. additional PRP. Number of participants with adverse events.
Time frame: Week 1, 2, 4; Month 2, 3, 4, 5, 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 - Ranibizumab | Number of Participants With Occurrence of Adverse Events | 0 Participants |
| 2 - Additional PRP Treatment | Number of Participants With Occurrence of Adverse Events | 2 Participants |
Primary
The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography)
Time frame: Baseline to Week 4; Baseline to Month 6
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1 - Ranibizumab | The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) | Change from Baseline to Week 4 | -2.4 percentage of change (mean) |
| 1 - Ranibizumab | The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) | Change from baseline to Month 6 | 54.1 percentage of change (mean) |
| 2 - Additional PRP Treatment | The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) | Change from Baseline to Week 4 | -8.4 percentage of change (mean) |
| 2 - Additional PRP Treatment | The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) | Change from baseline to Month 6 | -2.1 percentage of change (mean) |
Primary
The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography)
This is a measurement of how much change in neovascularization has occurred, using the Optomap FA readings to calculate the increase or decrease in surface area of the retina that is affected by neovascularization.
Time frame: Baseline to Week 4; Baseline to Month 4-6
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1 - Ranibizumab | The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) | Change at Week 4 from baseline | -83.8 percentage of change in area (mean) |
| 1 - Ranibizumab | The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) | Change at Month 4-6 from baseline | 11.3 percentage of change in area (mean) |
| 2 - Additional PRP Treatment | The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) | Change at Week 4 from baseline | 52.6 percentage of change in area (mean) |
| 2 - Additional PRP Treatment | The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) | Change at Month 4-6 from baseline | 55.4 percentage of change in area (mean) |
Secondary
Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters
Time frame: 1 Month; 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 - Ranibizumab | Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters | Week 4 | 2 lines of vision gained | Standard Deviation 1 |
| 1 - Ranibizumab | Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters | Month 6 | 3 lines of vision gained | Standard Deviation 1.5 |
| 2 - Additional PRP Treatment | Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters | Week 4 | 0 lines of vision gained | Standard Deviation 1 |
| 2 - Additional PRP Treatment | Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Lines Gained on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters | Month 6 | 2 lines of vision gained | Standard Deviation 1.5 |
Secondary
Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment
Complications; including vitreous hemorrhage, iris neovascularization, and tractional retinal detachment were assessed at the 6 month time point and are reported below.
Time frame: 6 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 - Ranibizumab | Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment | 0 number of PDR complications |
| 2 - Additional PRP Treatment | Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment | 1 number of PDR complications |
Secondary
Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing
Time frame: 1 month, 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 - Ranibizumab | Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing | Percentage of Participants with Lines gained in BCVA at 1 mos | 50.0 percentage of participants |
| 1 - Ranibizumab | Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing | Percentage of Participants with Lines gained in BCVA at 6 mos | 75.0 percentage of participants |
| 2 - Additional PRP Treatment | Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing | Percentage of Participants with Lines gained in BCVA at 1 mos | 0 percentage of participants |
| 2 - Additional PRP Treatment | Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing | Percentage of Participants with Lines gained in BCVA at 6 mos | 33.33 percentage of participants |