Bevacizumab as Adjunctive Treatment to Laser Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Study Overview
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Brief Summary
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This is a prospective, randomized and comparative study is to quantify the functional and structural alterations of the macula in patients with proliferative Diabetic Retinopathy submitted to laser photocoagulation and to evaluate the efficacy of intravitreal bevacizumab as a adjuvant therapy in preventing the adverse events of that procedure. The patients with proliferative Diabetic Retinopathy (DR) with indication of binocular laser photocoagulation will be examined by ophthalmologists who will measure the visual acuity and contrast sensitivity, perform slit lamp examination, fundus examination and optic coherence tomography before and after laser photocoagulation. Laser photocoagulation will be performed in both eyes according Early Treatment Diabetic Retinopathy Study that advocate the realization of 3 episodes of laser photocoagulation in 3 weeks. This comparative study analyses the effect of intravitreal bevacizumab one week before laser photocoagulation and one, three and six months after the randomization visit. The fellow eye will be submitted only to laser photocoagulation and will be considered as control. It is estimated a sample of 30 patients. All procedures, purposes and methods will be explained to all patients.

Detailed Description
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The current gold standard for the treatment of proliferative diabetic retinopathy is panretinal photocoagulation. Therefore this study is designed using both treatments in the same patient: intravitreal Bevacizumab plus panretinal photocoagulation in one eye, compared to panretinal photocoagulation alone in the contralateral eye. These patients had their visual acuity and contrast vision measured and complete ophthalmological examination was performed, including macular slit lamp examination, fluorescein angiography and optical coherence tomography. Patients with similar proliferative diabetic retinopathy without high risk characteristics receive laser therapy in both eyes and intravitreal Bevacizumab injections in one eye. For the Bevacizumab injections, numbing drops, antibiotic drops, and drops to dilate the pupil, and possibly and anesthetic injection, are put in the eye before the medicine is injected into the vitreous. Patients return for follow-up visits 1 day, 1 and 4 weeks after the injection, and then 3 and 6 months. Patients whose condition does not improve may undergo new evaluation.

Official Title
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Structural and Functional Evaluation of the Macula in Patients With Proliferative Diabetic Retinopathy Treated With Panretinal Photocoagulation and Bevacizumab (Avastin ®)

Conditions
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Proliferative Diabetic Retinopathy

Intervention / Treatment
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* Procedure: Panretinal photocoagulation
* Procedure: Procedure: Panretinal Photocoagulation (PRP) Drug: Intravitreous injection of Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Proliferative diabetic retinopathy eyes. Best Corrected-Visual Acuity at baseline > 20/320 in the study eye. Patients with and without diabetic macular edema Type II diabetic subjects as defined by the World Health Organization aged ≥ 18 years. Women must be using effective contraception Ability to provide written informed consent. Indication of panretinal photocoagulation in both eyes Exclusion Criteria: Vitreous hemorrhage or pre-retinal hemorrhage Eyes with prior scatter (panretinal) or focal/grid photocoagulation, within the previous 6 months. Atrophy/scarring/fibrosis/ hard exudates involving the center of the macula. Cataract Any intraocular surgery within 6 months before trial enrollment. Previous vitrectomy. Any of the following underlying systemic diseases: History or evidence of severe cardiac disease or previous thrombus-embolic event

Ages Eligible for Study
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Minimum Age: 18 Years

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: Panretinal photocoagulation<br>Group 1: Panretinal photocoagulation treatment (PRP) at month-0 that can be repeated after month-3. | Procedure: Panretinal photocoagulation<br>* Three episodes of panretinal photocoagulation with one week of interval<br>|
| Experimental: Bevacizumab + Panretinal Photocoagulation (PRP)<br>Group 2: Bevacizumab intravitreous injections plus PRP | Procedure: Procedure: Panretinal Photocoagulation (PRP) Drug: Intravitreous injection of Bevacizumab<br>* Intravitreous injection of Bevacizumab 1 week before and the other at the same day of the third episode of PRP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Macular Evaluation | During this 24 weeks of follow-up the Visual acuity (ETDRS), Contrast vision will be measured at baseline, 4, 12 and finally at 24 week | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural Macular Evaluation | During the 24 weeks of follow-up the following measured will be made: Optical coherence tomography, need of vitrectomy, need panretianal photocoagulation retreatment, adverse events, recurrence of neovascularizaton, need or additional focal and grid macular laser for diabetic macular edema | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proliferative Diabetic Retinopathy, Bevacizumab, Panretinal Photocoagulation