Diabetic Traction Retinal Detachment, Proliferative Diabetic Retinopathy, Vitreous Hemorrhage
Conditions
Brief summary
We hypothesized that to reduce the adverse effects of intravitreal bevacizumab on ocular tissue and whole body, intravitreal injection of a low concentration of bevacizumab and conducting vitrectomy shortly after the injection is useful. In the present prospective, double-masked, randomized, controlled study, we aimed to verify the usefulness of intravitreal injection of 0.16 mg/0.05 ml bevacizumab one day before conducting vitrectomy for PDR.
Detailed description
Early postoperative hemorrhage in proliferative diabetic retinopathy (PDR) patients is a major complication. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has reported to reduce vitreous hemorrhage. Recently, numerous reports have shown the efficacy of reducing neovascularization activity before vitrectomy by preoperative intravitreal injection of anti-VEGF agents. When intravitreal bevacizumab (IVB) injection is used as an adjunct therapy, a shortterm effect is needed. Because it is reported some adverse events caused by bevacizumab injection. Hattori et al reported intravitreal injection of 0.16 mg/0.05 ml bevacizumab in PDR patients marked blockage of intravitreal VEGF concentrations in the pilot study. The purpose of this study is to evaluate low dose of intravitreal bevacizumab as a preoperative adjunct therapy reduce the postoperative vitreous hemorrhage. This study involves PDR patients who underwent vitrectomy between May 2012 and August 2013 at Surugadai Hospital of Nihon University. The risks to participants are accompanied by the intravitreal injection of bevacizumab (especially the possibility of endophthalmitis and thromboembolic events). Between June 2012 and August 2013, one investigator (AM) randomized PDR patients with an indication for primary 25-gauge vitrectomy into a sham group and an IVB group. One day after injection, three surgeons except AM conducted the surgeries. Vitreous samples were collected at the start of surgery, and intraoperative and postoperative complications were evaluated.
Interventions
DRUGBevacizumab
0.16 mg/0.05 ml bevacizumab (single injection on 1 day before operation)
PROCEDUREVitrectomy
vitrectomy of 25 gauge system.
DEVICESham injection
Sham injection one day before vitrectomy
Sponsors
Nihon University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of Proliferative Diabetic Retinopathy (PDR) * Indicated for vitrectomy
Exclusion criteria
* History of intraocular surgery, intravitreal injection of drugs or sub-Tenon injection of steroids or retinal photocoagulation within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reoperation | 1 month | Vitreoretinal reoperation due to recurrent vitreous hemorrhage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Vitreous Hemorrhage. | 1 month | Postoperative vitreous hemorrhage that is permitted within 4 weeks after surgery. |
| Vascular Endothelial Growth Factor Concentration in Vitreous | Start of surgery. | Vascular endothelial growth factor concentration in vitreous at the start of vitrectomy. |
| Endolaser Photocoagulation | End of surgery. | Number of intraoperative endolaser photocoagulation. |
| Iatrogenic Retinal Tears | End of surgery. | The number of participants who had intraoperative iatrogenic retinal tears. |
| Surgical Time | End of surgery. | — |
| Intra Operative Hemorrhage | End of the surgery. | Calculate the number of coagulators for the intra operative hemorrhage. |
| Best Corrected Visual Acuity Change | 1 month | Best corrected visual acuity change was calculated by postoperative logMAR visual acuity minus preoperative logMAR visual acuity. The higher values represent a worse outcome. |
| Postoperative Neovascular Glaucoma | Within 1 month after the surgery. | The number of participants with progressive or persistent neovascular glaucoma after surgery. |
| Elevated Intraocular Pressure | Within 1 month after the surgery. | The number of participants with elevated intraocular pressure after surgery. |
| Gas Tamponade | End of surgery. | The number of participants with gas tamponade at the end of the surgery. |
| Silicon Oil Tamponade | End of surgery. | The number of participants with silicon oil tamponade at the end of the surgery. |
| Postoperative Best Corrected Visual Acuity | 1 mouth after surgery. | Best corrected visual acuity was measured using the Landolt ring chart, and the result was converted to logMAR notation for analysis. The minimum of the scale is 2.0 and the maximum of the scale is -0.3. The higher values represent a worse outcome. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab and Vitrectomy 0.16 mg/0.05 ml bevacizumab intravitreal injection one day before surgery and vitrectomy.
* Bevacizumab: 0.16 mg/0.05 ml bevacizumab (single injection on 1 day before operation)
* Vitrectomy: vitrectomy of 25 gauge system. | 32 |
| Sham Injection and Vitrectomy Sham injection one day before operation and vitrectomy.
* Sham injection: Sham injection one day before vitrectomy
* Vitrectomy: vitrectomy of 25 gauge system. | 34 |
| Total | 66 |
Baseline characteristics
| Characteristic | Total | Bevacizumab and Vitrectomy | Sham Injection and Vitrectomy |
|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 12.4 | 59.9 years STANDARD_DEVIATION 11.8 | 59.2 years STANDARD_DEVIATION 12.9 |
| HbA1c | 7.8 % STANDARD_DEVIATION 1.6 | 8.0 % STANDARD_DEVIATION 1.7 | 7.6 % STANDARD_DEVIATION 2 |
| Hyperlipidemia No | 54 participants | 27 participants | 27 participants |
| Hyperlipidemia Yes | 12 participants | 5 participants | 7 participants |
| Hypertension No | 36 participants | 18 participants | 18 participants |
| Hypertension Yes | 30 participants | 14 participants | 16 participants |
| Intra Ocular Pressure | 15.0 mm Hg STANDARD_DEVIATION 3.11 | 15.3 mm Hg STANDARD_DEVIATION 2.69 | 14.6 mm Hg STANDARD_DEVIATION 3.42 |
| Lens status phakic | 59 participants | 28 participants | 31 participants |
| Lens status pseudophakic | 7 participants | 4 participants | 3 participants |
| Persistent vitreous hemorrhage | 59 participants | 29 participants | 30 participants |
| Preoperative best corrected visual acuity | 1.11 LogMAR STANDARD_DEVIATION 0.59 | 1.09 LogMAR STANDARD_DEVIATION 0.6 | 1.14 LogMAR STANDARD_DEVIATION 0.58 |
| preoperative Iris neovascularization or neovascular glaucoma | 4 participants | 2 participants | 2 participants |
| Previous panretinal photocoagulation Incomplete | 46 participants | 23 participants | 23 participants |
| Previous panretinal photocoagulation None | 20 participants | 9 participants | 11 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 2 Participants |
| Sex: Female, Male Male | 54 Participants | 22 Participants | 32 Participants |
| Use of anticoagulants No | 51 participants | 25 participants | 26 participants |
| Use of anticoagulants Yes | 15 participants | 7 participants | 8 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 34 |
| serious Total, serious adverse events | 0 / 32 | 0 / 34 |
Outcome results
Primary
Reoperation
Vitreoretinal reoperation due to recurrent vitreous hemorrhage.
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Reoperation | 1 participants |
| Sham Injection and Vitrectomy | Reoperation | 7 participants |
p-value: 0.033Fisher Exact
Secondary
Best Corrected Visual Acuity Change
Best corrected visual acuity change was calculated by postoperative logMAR visual acuity minus preoperative logMAR visual acuity. The higher values represent a worse outcome.
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Best Corrected Visual Acuity Change | -0.63 LogMAR | Standard Deviation 0.61 |
| Sham Injection and Vitrectomy | Best Corrected Visual Acuity Change | -0.73 LogMAR | Standard Deviation 0.8 |
p-value: 0.445Wilcoxon (Mann-Whitney)
Secondary
Elevated Intraocular Pressure
The number of participants with elevated intraocular pressure after surgery.
Time frame: Within 1 month after the surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Elevated Intraocular Pressure | 2 participants |
| Sham Injection and Vitrectomy | Elevated Intraocular Pressure | 6 participants |
p-value: 0.149Fisher Exact
Secondary
Endolaser Photocoagulation
Number of intraoperative endolaser photocoagulation.
Time frame: End of surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Endolaser Photocoagulation | 1260 photocoagulation | Standard Deviation 686 |
| Sham Injection and Vitrectomy | Endolaser Photocoagulation | 1335 photocoagulation | Standard Deviation 663 |
p-value: 0.667Wilcoxon (Mann-Whitney)
Secondary
Gas Tamponade
The number of participants with gas tamponade at the end of the surgery.
Time frame: End of surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Gas Tamponade | 23 participants |
| Sham Injection and Vitrectomy | Gas Tamponade | 24 participants |
p-value: 0.67Fisher Exact
Secondary
Iatrogenic Retinal Tears
The number of participants who had intraoperative iatrogenic retinal tears.
Time frame: End of surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Iatrogenic Retinal Tears | 5 participants |
| Sham Injection and Vitrectomy | Iatrogenic Retinal Tears | 5 participants |
p-value: 0.593Fisher Exact
Secondary
Intra Operative Hemorrhage
Calculate the number of coagulators for the intra operative hemorrhage.
Time frame: End of the surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Intra Operative Hemorrhage | 0.63 coagulators | Standard Deviation 1 |
| Sham Injection and Vitrectomy | Intra Operative Hemorrhage | 1.3 coagulators | Standard Deviation 1.4 |
p-value: 0.025Wilcoxon (Mann-Whitney)
Secondary
Postoperative Best Corrected Visual Acuity
Best corrected visual acuity was measured using the Landolt ring chart, and the result was converted to logMAR notation for analysis. The minimum of the scale is 2.0 and the maximum of the scale is -0.3. The higher values represent a worse outcome.
Time frame: 1 mouth after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Postoperative Best Corrected Visual Acuity | 0.46 LogMAR | Standard Deviation 0.54 |
| Sham Injection and Vitrectomy | Postoperative Best Corrected Visual Acuity | 0.43 LogMAR | Standard Deviation 0.48 |
p-value: 0.929Wilcoxon (Mann-Whitney)
Secondary
Postoperative Neovascular Glaucoma
The number of participants with progressive or persistent neovascular glaucoma after surgery.
Time frame: Within 1 month after the surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Postoperative Neovascular Glaucoma | 0 participants |
| Sham Injection and Vitrectomy | Postoperative Neovascular Glaucoma | 3 participants |
p-value: 0.131Chi-squared
Secondary
Postoperative Vitreous Hemorrhage.
Postoperative vitreous hemorrhage that is permitted within 4 weeks after surgery.
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Postoperative Vitreous Hemorrhage. | 3 participants |
| Sham Injection and Vitrectomy | Postoperative Vitreous Hemorrhage. | 13 participants |
p-value: 0.006Chi-squared
Secondary
Silicon Oil Tamponade
The number of participants with silicon oil tamponade at the end of the surgery.
Time frame: End of surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Vitrectomy | Silicon Oil Tamponade | 4 participants |
| Sham Injection and Vitrectomy | Silicon Oil Tamponade | 6 participants |
p-value: 0.378Chi-squared
Secondary
Surgical Time
Time frame: End of surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Surgical Time | 49 minutes | Standard Deviation 20 |
| Sham Injection and Vitrectomy | Surgical Time | 56 minutes | Standard Deviation 27 |
p-value: 0.298Wilcoxon (Mann-Whitney)
Secondary
Vascular Endothelial Growth Factor Concentration in Vitreous
Vascular endothelial growth factor concentration in vitreous at the start of vitrectomy.
Time frame: Start of surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab and Vitrectomy | Vascular Endothelial Growth Factor Concentration in Vitreous | 25.0 μg/ml | Standard Deviation 13.6 |
| Sham Injection and Vitrectomy | Vascular Endothelial Growth Factor Concentration in Vitreous | 1315 μg/ml | Standard Deviation 1153 |
p-value: <0.0001Wilcoxon (Mann-Whitney)