Unilateral Bevacizumab for Bilateral Diabetic Macular Edema

This study has been completed.
Sponsor:
Information provided by:
Asociación para Evitar la Ceguera en México
ClinicalTrials.gov Identifier:
NCT00496405
First received: July 3, 2007
Last updated: October 11, 2007
Last verified: October 2007
  Purpose

The endothelial growth factor (VEGF), has been implied in the genesis of diverse Neovascular disease. In the industrialized and developing countries, the main cause of blindness is the diabetic retinopathy. Bevacizumab (Avastin, genentech, Inc., San Francisco, California, the USA) is a drug.In the last years its use "off-label", in ophthalmology field, has become popular. This is due to its proven safeness and effectiveness for the treatment of diverse ocular diseases. A lot has been speculated about the systemic absorption of Bevacizumab. It is for that reason that the objective of this study is the systematic and random revision of the fellows eyes, of the patients programmed for the intravitreal administration of Bevacizumab, with bilateral macular edema. In such a way that the therapeutic value in the fellow eye of bevacizumab can be determined


Condition Intervention Phase
Diabetic Macular Edema
Diabetic Retinopathy
Drug: bevacizumab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: The Role of Unilateral Intravitreal Bevacizumab (Avastin), for the Treatment of Bilateral Diabetic Macular Edema: a Pilot Study.

Resource links provided by NLM:


Further study details as provided by Asociación para Evitar la Ceguera en México:

Primary Outcome Measures:
  • Retinal thickness [ Time Frame: Interventional ]

Secondary Outcome Measures:
  • Best corrected visual acuity

Estimated Enrollment: 13
Study Start Date: April 2007
Study Completion Date: October 2007
  Hide Detailed Description

Detailed Description:

Introduction:

The endothelial growth factor (VEGF), was identified for the first time in the liquid of ascitis in Guinean pigs (6,7). It is a dimeric glycoprotein, naturally expressed in epithelial and tumor cells (1). It's over expression during retinal hypoxia (9), has been implied in the genesis of diverse Neovascular diseases (2,4,8,9,19). The activation of the VEGF pathway promotes endothelial cells growth, increases the growth, migration and survival of the existing vasculature and produces the differentiation and migration of the endothelial mother cells from the bone marrow towards the general circulation (4). It is also a vasculature permeability factor, because it favors the formation of vascular fenestrations, which produces the exit of liquid and protein deposit in the tissue interstice, favoring the formation of macular edema and neovascularisation (3,8-10).

Its activity is mediated by two tyrosine related receptors of high affinity: the VEGFR 1 (FLT-1) and VEGFR 2 (FLT-2) (1,9). The FLT-1 promotes the cellular proliferation whereas the FLT-2 the migration and the interaction between cells and extracellular matrix(4,5,10)

In the industrialized and developing countries, the main cause of blindness is the diabetic retinopathy (9). Followed close in the United States and Europe by Age related Macular Degeneration (10). The most frequent cause of loss of vision in diabetic retinopathy is macular edema (7). Its incidence is between 13.9 to 25.4% (15). It is characterized by the accumulation of intraretinal liquid at level of the outer plexiform and internal nuclear layers, with the subsequent thickening of the macula (13,15). The diabetic macular Edema is associated to high levels of VEGF in the vitreous (7,8,9). At the moment, the gold standard in the treatment of the proliferative retinopathy is the laser photocoagulation(9). The photocoagulation of the macular area for the treatment of diffuse or focal edema, produces a 50% decrease risk of severe visual loss. Nevertheless the long-term prognosis continues being poor (15).

The Optical Coherent Tomography (OCT) is a relative new, noninvasive technique (12,14), based in low frequency interferometry phenomenon. It is able to provide cross-sectional retinal images (11,12,15,17). It has a resolution of 10-15mm. thanks to that, it is also able to quantitatively measure macular thickness (10,12,14,15,17). The measurements obtained with this system are highly reproducible and they correlated with patient visual acuity (7,11,14,16,17,19). It is very useful when evaluating the vitreous-retinal interface and retinal adherences(11). In the macular edema OCT displays low reflectivity images with increase of retinal thickness(11,13). The classification of macular edema by OCT images, proposed by Dr. Otani (16) and modified by Kang (15) consists of 4 types: Type 1, thickening of the fovea with homogenous optical reflectivity in the entire retina. Type 2, thickening of the retina with noticeable diminution of the optical reflectivity in the external layers of the retina. Type 3, thickening of the fovea with accumulation of subfoveal liquid and a defined border of detached retina. Type 3A without foveal traction, 3B with foveal traction (15).

Bevacizumab (Avastin, genentech , Inc., San Francisco, California, the USA) is a drug, approved by the FDA for the treatment of the metastatic colorectal cancer(2). It consists of a humanized monoclonal antibody that binds all active forms of VEGF (3,18,19), blocking the activity of its two receptors (4). In the last years its use "off-label", in ophthalmology field, has become popular. This is due to its proven safeness and effectiveness for the treatment of diverse ocular diseases (2-4,7,20). Within the ophthalmic pathologies that have been treated successfully with the Intravitreal administration of Bevacizumab, we can mention different Neovascular pathologies (diabetic Retinopathy (9,18), age related macular degeneration(2,4,18)) and pathologies that alter the vascular permeability (macular edema (4,7), Central and branch retinal vein occlusion (3,8,20), central serous choroidopathy). In all of them , treatment responses is characterized by an improvement of the visual acuity, decrease of macular thickness and improvement of the angiographic patterns (8,10). The potential complications of the use of Bevacizumab are the severe thromboembolic event, arterial hypertension (18), epistaxis, proteinuria,hemoptysis, alteration in wound healing and gastrointestinal bleed (4,10).

Exposition of the Problem:

A lot has been speculated about the systemic absorption of Bevacizumab. In a study at the Bascom Palmer Eye Institute, doctors Rosenfeld, Puliafito et al demonstrated the effectiveness of the systemic application of Bevacizumab for the treatment of the age related macular degeneration applying dose of 5mg/Kg. thus Demonstrating, the passage of the molecule from the systemic circulation to specific tissue in both eyes(10). Recently, doctor Bakri and her team at Mayo Clinic in Rochester, Minnesota, establish that a small portion of intravitreal bevacizumab is able to pass to the systemic circulation (1.6% of the injected dose) obtaining detectable concentrations in the vitreous of the fellow eye (11.17ng/ml) at week number 4 after the treatment (21). In the same way, we have cases in our hospital, reported like anecdotal cases, of Bevacizumab application in one eye and improvement of the base pathology in the fellow eye.

It is for that reason that the objective of this study is the systematic and random revision of the fellows eyes, of the patients programmed for the intravitreal administration of Bevacizumab, with bilateral macular edema. In such a way that the therapeutic value of the small concentrations reached in the vitreous of the fellow eye of bevacizumab can be determined.

  Eligibility

Ages Eligible for Study:   30 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient greater of 30 years old, with bilateral diffuse diabetic macular edema, with any degree of diabetic retinopathy that has been programmed for Bevacizumab intravitreal administration in one of both eyes.
  • Bilateral macular Thickening, measured by OCT of 225mm or bigger.
  • Pupil dilatation greater than 5mm.
  • Patient with no previous treatment for diabetic macular edema.

Exclusion Criteria:

  • Focal diabetic macular edema or macular edema of different etiology, besides diabetes. (uveitis, pseudophakic patients, vitreous-retinal traction, CRVO, BRVO, CSC).
  • Macular edema 3B patter, measured by OCT, according to the macular edema classification.
  • Medical history of severe thromboembolic events, uncontrolled arterial hypertension, transitory ischemic attacks, cardiac stroke, acute cerebral vascular event.
  • Pregnant women or breast feeding women
  • Know allergy to Bevacizumab
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496405

Locations
Mexico
Asociación para Evitar la Ceguera en Mexico
Mexico, DF, Mexico, 04030
Sponsors and Collaborators
Asociación para Evitar la Ceguera en México
Investigators
Principal Investigator: Raul Velez-Montoya, MD Asociación para Evitar la Ceguera en Mexico
  More Information

No publications provided by Asociación para Evitar la Ceguera en México

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00496405     History of Changes
Other Study ID Numbers: APEC
Study First Received: July 3, 2007
Last Updated: October 11, 2007
Health Authority: Mexico: Ministry of Health

Keywords provided by Asociación para Evitar la Ceguera en México:
Vascular endothelial growth factor.
Retinal Thickness
Diabetic Macular Edema
Optical Coherent Tomography

Additional relevant MeSH terms:
Diabetic Retinopathy
Edema
Macular Edema
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endocrine System Diseases
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Signs and Symptoms
Vascular Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014