Prospective Randomized Controlled Study of Intravitreal Injection of Bevacizumab for Proliferative Diabetic Retinopathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective Randomized Controlled Study of Intravitreal Injection of 0.16 mg Bevacizumab One Day Before Surgery for Proliferative Diabetic Retinopathy

Conditions
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Proliferative Diabetic Retinopathy, Diabetic Traction Retinal Detachment, Vitreous Hemorrhage

Intervention / Treatment
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* Drug: Bevacizumab
* Procedure: Vitrectomy
* Device: Sham injection


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bevacizumab injection and vitrectomy<br>0.16 mg/0.05 ml bevacizumab intravitreal injection one day before vitrectomy. | Drug: Bevacizumab<br>* 0.16 mg/0.05 ml bevacizumab (single injection on 1 day before operation)<br>* Other names: Avastin;Procedure: Vitrectomy<br>* vitrectomy of 25 gauge system.<br>|
| Sham Comparator: Sham injection and vitrectomy<br>Sham injection one day before vitrectomy. | Procedure: Vitrectomy<br>* vitrectomy of 25 gauge system.<br>Device: Sham injection<br>* Sham injection one day before vitrectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation | Vitreoretinal reoperation due to recurrent vitreous hemorrhage. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra Operative Hemorrhage | Calculate the number of coagulators for the intra operative hemorrhage. | End of the surgery. | 
| Postoperative Vitreous Hemorrhage. | Postoperative vitreous hemorrhage that is permitted within 4 weeks after surgery. | 1 month | 
| Vascular Endothelial Growth Factor Concentration in Vitreous | Vascular endothelial growth factor concentration in vitreous at the start of vitrectomy. | Start of surgery. | 
| Endolaser Photocoagulation | Number of intraoperative endolaser photocoagulation. | End of surgery. | 
| Iatrogenic Retinal Tears | The number of participants who had intraoperative iatrogenic retinal tears. | End of surgery. | 
| Surgical Time |  | End of surgery. | 
| 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. | 1 mouth after surgery. | 
| 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. | 1 month | 
| Postoperative Neovascular Glaucoma | The number of participants with progressive or persistent neovascular glaucoma after surgery. | Within 1 month after the surgery. | 
| Elevated Intraocular Pressure | The number of participants with elevated intraocular pressure after surgery. | Within 1 month after the surgery. | 
| Gas Tamponade | The number of participants with gas tamponade at the end of the surgery. | End of surgery. | 
| Silicon Oil Tamponade | The number of participants with silicon oil tamponade at the end of the surgery. | End of surgery. |