Proliferative Diabetic Retinopathy, Vitreous Hemorrhage
Conditions
Keywords
Proliferative diabetic retinopathy, vitrectomy, bevacizumab, vitreous hemorrhage
Brief summary
The purpose of this study is to determine the effect of pre- and intra-operative bevacizumab injection on postoperative vitreous hemorrhage after diabetic vitrectomy.
Detailed description
Postoperative vitreous hemorrhage(VH) is a common complication after vitrectomy for proliferative diabetic retinopathy. Persistent or recurrent VH can delay visual rehabilitation and give patients much trouble. There have been efforts to lower the incidence of postoperative VH such as using intraoperative gas tamponade and preoperative bevacizumab injection. Bevacizumab(Avastin) is a potent inhibitor of angiogenesis and has been shown to decrease retinal and iris neovascularization in proliferative diabetic retinopathy. Recently there have been reports showing that preoperative intravitreal bevacizumab (IVB) injection could reduce intraoperative bleeding from abnormal vessels and could make surgery easier and more successful.Our hypothesis is that preoperative bevacizumab injection could reduce postoperative VH by way of decreasing the amount of abnormal vessels and intraoperative injection could also reduce postoperative VH by inhibiting the vessel formation after surgery. To prove our hypothesis, we started the prospective randomized comparative study to determine the effect of pre- and intra-operative IVB injection on postoperative vitreous hemorrhage after diabetic vitrectomy.
Interventions
DRUGBevacizumab
Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml)
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing first vitrectomy for complications of proliferative diabetic retinopathy such as vitreous hemorrhage, tractional fibrovascular membrane proliferation, tractional or combined retinal detachment)
Exclusion criteria
* Follow-up period of less than 6 months * Intraoperative use of long-acting gas or silicone oil * Repeat vitrectomy after first vitrectomy for diseases other than vitreous hemorrhage * Not first vitrectomy * Uncontrolled hypertension * Medical history of abnormal blood coagulation * Time interval between IVB injection and PPV longer than 2 weeks and recent history (within 3 months) of IVB treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrent VH Incidence (Early and Late) | 6 months | Recurrent VH was defined as a new episode of grade 1 or more VH occurring more than 1 week after surgery. Early recurrent VH was VH occurring \<= 4 weeks and late recurrent VH was VH occurring \>4 weeks after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Initial Time of Vitreous Clearing (ITVC) | 6 months | The interval in number of days for VH of grade 1 or more observed at postoperative day 1 to clear-up completely. VH of grade 1 was defined as mild vitreous hemorrhage with visible fundus details, but difficult to evaluate the retinal nerve fiber layer or small vessels. |
| Visual Outcome | 6 months | Best-corrected visual acuity (BCVA) at postoperative 6 months |
| Postoperative Resolution of Neovascularization | 6 months | — |
Countries
South Korea
Participant flow
Recruitment details
Consecutive diabetic patients requiring pars plana vitrectomy (PPV) for complications of diabetic retinopathy at Seoul National University Bundang Hospital were referred to assess eligibility.
Pre-assignment details
If indications for PPV included proliferative diabetic retinopathy (PDR) related complications such as nonclearing vitreous hemorrhage (VH), macula-involving or -threatening tractional retinal detachment (TRD) or fibrovascular proliferation with vitreoretinal adhesions, the patient was enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Preop IVB Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy | 41 |
| Intraop IVB Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy | 43 |
| No IVB Patients will not receive bevacizumab before nor during vitrectomy | 42 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Edophthalmitis after preoperative IVB | 1 | 0 | 0 |
| Overall Study | Injection of intravitreal silicone oil o | 3 | 4 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 3 |
| Overall Study | Non-PDR related VH | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Preop IVB | Intraop IVB | No IVB | Total |
|---|---|---|---|---|
| Age, Continuous | 51.0 years STANDARD_DEVIATION 9.5 | 55.6 years STANDARD_DEVIATION 10.3 | 55.0 years STANDARD_DEVIATION 11.4 | 53.9 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 15 Participants | 20 Participants | 22 Participants | 57 Participants |
| Sex: Female, Male Male | 26 Participants | 23 Participants | 20 Participants | 69 Participants |
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 | 1 / 41 | 3 / 43 | 1 / 42 |
| serious Total, serious adverse events | 0 / 41 | 0 / 43 | 1 / 42 |
Outcome results
Primary
Recurrent VH Incidence (Early and Late)
Recurrent VH was defined as a new episode of grade 1 or more VH occurring more than 1 week after surgery. Early recurrent VH was VH occurring \<= 4 weeks and late recurrent VH was VH occurring \>4 weeks after surgery.
Time frame: 6 months
Population: With study power of 80%, significance level of 0.05, assumption that IVB injection will decrease postoperative VH incidence from 35% to 10%, a sample size of 40 patients for each group was calculated. The ITT approach was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Preop IVB | Recurrent VH Incidence (Early and Late) | Early | 22.2 Percentage of participants |
| Preop IVB | Recurrent VH Incidence (Early and Late) | Late | 11.1 Percentage of participants |
| Intraop IVB | Recurrent VH Incidence (Early and Late) | Early | 10.8 Percentage of participants |
| Intraop IVB | Recurrent VH Incidence (Early and Late) | Late | 16.2 Percentage of participants |
| No IVB | Recurrent VH Incidence (Early and Late) | Early | 32.4 Percentage of participants |
| No IVB | Recurrent VH Incidence (Early and Late) | Late | 14.7 Percentage of participants |
Comparison: With study power of 80%, a significance level of 0.05, and the assumption that IVB injection will decrease postoperative VH incidence from 35% to 10%, a sample size of 40 patients for each group was calculated.p-value: <0.05Chi-squared
Secondary
Initial Time of Vitreous Clearing (ITVC)
The interval in number of days for VH of grade 1 or more observed at postoperative day 1 to clear-up completely. VH of grade 1 was defined as mild vitreous hemorrhage with visible fundus details, but difficult to evaluate the retinal nerve fiber layer or small vessels.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preop IVB | Initial Time of Vitreous Clearing (ITVC) | 26.4 days | Standard Deviation 42.5 |
| Intraop IVB | Initial Time of Vitreous Clearing (ITVC) | 10.3 days | Standard Deviation 8.2 |
| No IVB | Initial Time of Vitreous Clearing (ITVC) | 25.2 days | Standard Deviation 26.1 |
Secondary
Postoperative Resolution of Neovascularization
Time frame: 6 months
Secondary
Visual Outcome
Best-corrected visual acuity (BCVA) at postoperative 6 months
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preop IVB | Visual Outcome | 0.62 logMAR | Standard Deviation 0.58 |
| Intraop IVB | Visual Outcome | 0.68 logMAR | Standard Deviation 0.47 |
| No IVB | Visual Outcome | 0.51 logMAR | Standard Deviation 0.56 |