Intravitreal Bevacizumab and Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA)

Study Overview
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Brief Summary
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Intravitreal triamcinolone has been effective for central macular thickness reduction and concomitant visual acuity improvement in patients with diabetic macular edema (DME). VEGF is a very effective inducer of permeability, being 50.000 times more potent than histamine, and may exert its effect on retinal vascular permeability by altering tight-junctions proteins, such as occluding and VE-cadherin. Based on these principles, there is a rationale for anti-VEGF agents treatment of increased retinal capillary permeability conditions, such as diabetic macular edema. Therefore, the purpose of this study is to evaluate the effects of intravitreal bevacizumab and intravitreal triamcinolone associated to laser photocoagulation for diabetic macular edema.

Detailed Description
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Macular edema is a leading cause of decreased visual acuity in patients with diabetic retinopathy1,2. Laser photocoagulation is the standard of care treatment for diabetic macular edema, based on ETDRS and recent clinical trials findings3,4. However, because visual acuity improvement post-laser is observed infrequently, and because of the frequent recurrence or persistence of DME (refractory DME) after appropriate laser treatment, particularly in eyes presenting with angiographically diffuse macular edema5-9, there is a need for alternative treatments for the management of DME. In addition, for some patients with significant cataract, precise visualization of posterior pole structures may not be possible, so that pharmacological therapy with intravitreal agents may be preferable over laser treatment. Recent studies have shown promising results of pharmacological therapies for Diabetic macular edema. Triamcinolone has shown similar results when compared to ranibizumab and deferred focal/grid LASER in pseudophakic eyes (DRCRnet, prompt versus deferred). Ranibizumab associated with deferred LASER or as monotherapy has also shown promising results (RISE and RIDE). However, there are several concerns regarding long-term intravitreal injections therapies that include economic feasibility for the public health system, risk of endophthalmitis and patient acceptability. For these reasons, the present study decided to check associations between LASER and drug therapy, in an attempt to improve focal/grid laser outcomes with reduced number of intravitreal injections.

Official Title
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Intravitreal Bevacizumab and Intravitreal Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Procedure: Laser photocoagulation
* Drug: Intravitreal triamcinolone
* Drug: Intravitreal bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically significant DME - by biomicroscopic evaluation with generalized breakdown of the inner blood-retina barrier with diffuse fluorescein leakage involving the foveal center and most of the macular area on fluorescein angiography Snellen logarithm of minimum angle of 20/40 or worse Central macular thickness greater than 275 µm on optical coherence tomography (OCT) Exclusion Criteria: Glycosylated hemoglobin rate above 10% History of glaucoma or ocular hypertension Systemic corticoid therapy History of thromboembolic event (including myocardial infarction or cerebral vascular accident) Major surgery within the prior 6 months or planned within the next 28 days Uncontrolled hypertension Severe systemic disease Any condition affecting documentation or follow-up

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Laser Group<br>Focal / grid Laser photocoagulation in diabetic macular edema | Procedure: Laser photocoagulation<br>* Focal / grid photocoagulation for diabetic macular edema according to ETDRS guidelines<br>|
| Experimental: Triamcinolone group<br>Intravitreal triamcinolone associated to laser photocoagulation for diabetic macular edema | Drug: Intravitreal triamcinolone<br>* Intravitreal preservative-free triamcinolone (4mg) associated to focal photocoagulation for diabetic macular edema on baseline; Re-treatment at weeks 20 and 40 if CMT>275um<br>* Other names: Triancinolona (Ophthalmos);|
| Experimental: Bevacizumab group<br>Intravitreal Bevacizumab associated to laser photocoagulation for diabetic macular edema | Drug: Intravitreal bevacizumab<br>* Intravitreal bevacizumab (1.5mg) associated to focal photocoagulation for diabetic macular edema at baseline; Re-treatment at weeks 20 and 40 if CMT>275um<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual acuity |  | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macular Mapping Test |  | One Year | 
| Multifocal Electroretinogram |  | One Year | 
| Central Macular Thickness |  | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, Diabetes, Intravitreal, Macular edema, triamcinolone, VEGF