Bevacizumab (Avastin) for the treatment of ocular disease.

University of Wisconsin Department of Ophthalmology and Visual Sciences, Madison, Wisconsin, USA.
Survey of Ophthalmology (Impact Factor: 2.86). 01/2009; 54(3):372-400. DOI: 10.1016/j.survophthal.2009.02.004
Source: PubMed

ABSTRACT The use of intravitreal bevacizumab (Avastin) has greatly expanded since its introduction into ophthalmic care 3 years ago. A PubMed search on 1 August 2008 revealed 51 ocular disease processes that have been treated with bevacizumab. The majority of publications consist of case reports or retrospective case series and their number is increasing quickly. It is important to collate the experiences gained to date to properly inform our clinical decision making and improve the design of future clinical trials. Current studies cannot easily be combined in a meta-analysis given the lack of standardized data and the wide variety of disorders studied in small numbers. This paper will describe the attempted uses of intravitreal bevacizumab and its efficacy for each ocular disease in addition to discussing safety. Comments regarding appropriate use of this treatment are based on our current level of knowledge. It is clear that the initial encouraging results described in this paper warrant further study of intravitreal bevacizumab in larger, controlled, randomized trials.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose:  We have previously shown that photopic cone b-wave implicit time ≥35.0 ms in 30 Hz flicker electroretinography (ERG) predicts ocular neovascularization (NV) in central retinal vein occlusion (CRVO). Here, we evaluate the effects of early panretinal photocoagulation (PRP) in patients with ERG-verified ischaemic CRVO. Methods:  Patients with CRVO, admitted to our department between 2000 and 2008, were classified as having ischaemic or non-ischaemic CRVO based on the ERG-results. In a first group of 71 patients, 18 patients had ischaemic CRVO and were assigned to standard treatment that is regular examinations and PRP as soon as NV was found. In a consecutive group of 65 patients, 18 patients with ischaemic CRVO received early PRP. In this group, ERG was performed on average 6 weeks after the first symptoms of CRVO. The patients underwent PRP as soon as possible after the ERG-examination, and the treatment was completed within one to three sessions. Results:  Twelve patients in the standard treatment group developed neovascular glaucoma during a mean period of 5 months after the CRVO. In the early treatment group, one patient developed subtle iris rubeosis 7 months after PRP. Otherwise, none of the patients showed any signs of ocular NV, and the intraocular pressure remained within normal range, without the necessity of supplementary medication, during a mean follow-up of 41 months. Conclusions:  This study indicates that ocular NV in patients with CRVO can be predicted by photopic 30 Hz flicker ERG and that early PRP in ERG-verified ischaemic CRVO could be suggested as standard treatment.
    Acta ophthalmologica 12/2011; · 2.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Due to its low price, bevacizumab, which binds vascular endothelial growth factor, is currently used off-label for the treatment of over 50 different eye diseases and has been adopted worldwide despite the absence of serious preclinical data. This study examines the effects of intravitreal bevacizumab on monkey eyes with particular focus on choroidal and retinal vessels. Methods: Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab with or without (125)I labeling. The eyes were enucleated between 1 and 14 days after injection and were investigated by electron microscopy, immunocytochemistry, histochemistry or autoradiography. Untreated and phosphate buffered saline (PBS)-injected monkeys were used as controls. Results: Bevacizumab locally accumulated at high concentration within individual blood vessels. It formed electron-dense deposits inside retinal veins and between red and white blood cells, activated thrombocytes and induced retinal vein thrombosis. Retinal cells like Müller cells, astrocytes and microglia were also activated. High amounts of bevacizumab were found in retinal and choroidal vessels which may interfere with blood flow. Conclusions: The deposits on the retinal vein walls may provide a mechanistic basis for the observed retinal blood flow alterations after bevacizumab treatment in patients.
    Expert opinion on biological therapy 11/2012; · 3.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Therapies targeting vascular endothelial growth factor (VEGF) are revolutionizing the treatment of diabetic retinopathy (DR) and diabetic macular edema (DME). In August 2012, ranibizumab, a monoclonal antibody fragment targeting VEGF designed for ocular use, became the first and only U.S. Food and Drug Administration-approved medical therapy for DME and the first approved treatment in over 25 years. This approval was based on strong preclinical data followed by numerous clinical trials that demonstrate an essential role of VEGF in vascular permeability and angiogenesis in both normal physiology and disease pathology. In this Perspective, we will examine the experimental studies and scientific data that aided in the success of the development of therapies targeting VEGF and consider how these approaches may inform the development of future therapeutics for diabetic eye disease. A multipoint model is proposed, based on well-established drug development principles, with the goal of improving the success of clinical drug development. This model suggests that to provide a validated preclinical target, investigators should demonstrate the following: the role of the target in normal physiology, a causal link to disease pathogenesis, correlation to human disease, and the ability to elicit clinically relevant improvements of disease phenotypes in animal models with multiple, chemically diverse interventions. This model will provide a framework to validate the current preclinical targets and identify novel targets to improve drug development success for DR.
    Diabetes 06/2013; 62(6):1808-1815. · 7.90 Impact Factor