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.
"Pegaptanib is an aptamer engineered to bind specifically to VEGF165, the isoform primarily responsible for pathological ocular angiogenesis (Ng et al., 2006). Bevacizumab is a humanized monoclonal antibody to VEGF inhibiting VEGF-receptor interaction (Gunther and Altaweel, 2009). Ranibizumab is a recombinant humanized fraction of anti-VEGF antibody that binds to all VEGF isoforms (Rosenfeld et al., 2006). "
[Show abstract][Hide abstract] ABSTRACT: Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly. Despite the presence of effective therapy in many cases, these diseases are still a significant health burden. Anti-VEGF biologics are the standard of care, but may cause ocular or systemic side effects after intraocular administration and patients may be refractory. Many anti-angiogenic compounds inhibit tumor growth and metastasis alone or in combination therapy, but a more select subset of them has been tested in the context of ocular neovascular diseases. Here, we review the promise of natural products as anti-angiogenic agents, with a specific focus on retinal and choroidal neovascularization. The multifunctional curcumin and the chalcone isoliquiritigenin have demonstrated promising anti-angiogenic effects in mouse models of DR and choroidal neovascularization (CNV) respectively. The homoisoflavanone cremastranone and the flavonoid deguelin have been shown to inhibit ocular neovascularization in more than one disease model. The isoflavone genistein and the flavone apigenin on the other hand are showing potential in the prevention of retinal and choroidal angiogenesis with long-term administration. Many other products with anti-angiogenic potential in vitro such as the lactone withaferin A, the flavonol quercetin, and the stilbenoid combretastatin A4 are awaiting investigation in different ocular disease-relevant animal models. These natural products may serve as lead compounds for the design of more specific, efficacious, and affordable drugs with minimal side effects.
Experimental Eye Research 10/2014; 129. DOI:10.1016/j.exer.2014.10.002 · 2.71 Impact Factor
"Intravitreal injection of bevacizumab, a monoclonal antibody which targets VEGF, has been shown to provide stability or improvement in eyes with DME . Ocular adverse effects of intravitreal bevacizumab (IVB) include bacterial endophthalmitis, tractional retinal detachment, uveitis, rhegmatogenous retinal detachment, and vitreous hemorrhage . We report 2 eyes of a patient which developed vitreomacular traction (VMT) and increased DME after IVB injection. "
[Show abstract][Hide abstract] ABSTRACT: To report 2 eyes of a patient which developed vitreomacular traction (VMT) 1 month after intravitreal bevacizumab (IVB) injection.
A 45-year-old female with bilateral diffuse diabetic macular edema (DME) received bilateral IVB.
Her initial visual acuity (VA) was 0.15 and 0.2 in OD and OS, respectively. Central foveal thickness (CFT) was 568 and 662 µm in OD and OS, respectively, without any sign of VMT. Both eyes responded well initially but developed VMT at 1 month. This time, intravitreal triamcinolone (IVTA) injection was performed. One month after IVTA injection, VMT was released and CFT decreased to 163 and 181 µm in OD and OS, respectively. Six months after IVTA injection, CFT was 163 and 153 µm, and VA was 0.7 and 0.9 in OD and OS, respectively.
In eyes with DME and attached posterior vitreous, VMT may develop after IVB injection and increase edema. IVTA injection might be an option to release VMT before considering vitrectomy.
Case Reports in Ophthalmology 01/2013; 4(1):7-10. DOI:10.1159/000342873
"Bevacizumab (Avastin; Genentech Inc., San Francisco, CA, USA) is a complete, humanized monoclonal antibody directed against all isoforms of vascular endothelial growth factor (VEGF). Bevacizumab was originally developed as a treatment for metastatic colorectal cancer , and it has been successfully applied off-label for intravitreal treatment of VEGF-mediated ocular diseases such as choroidal neovascular disorder, central retinal vein occlusion, proliferative diabetic retinopathy, and pseudophakic cystoid macular edema . Recently, bevacizumab has been introduced as a new therapeutic strategy for many other ocular disorders, such as recurrent pterygium, neovascularization caused by chemical burns, viral infections of the cornea and bleb survival after glaucoma surgery [3-7]. "
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the myotoxicity of bevacizumab on extraocular muscles in a rabbit model.
Thirty New Zealand white rabbits were used for this study. The animals were evenly divided into two groups. In the first group, 15 rabbits were treated with intramuscular injections of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal saline solution (0.05 mL) in the left superior rectus muscle. In the second group, 15 rabbits were treated with subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each group were sacrificed at one day, two weeks and four weeks after the injections. Extraocular muscle samples were prepared for light microscopic (LM) and electron microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD-11b immunohistochemistry, and global muscle change was investigated using hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson trichrome stains, and ultrastructural changes were observed on EM.
We observed no significant inflammatory cell infiltration, muscle necrosis or fibrotic change in treated and control eyes. EM findings revealed no significant damage to muscle or vascular tissue after bevacizumab injection.
We found no signs of extraocular muscle toxicity after LM and EM intramuscular and subconjunctival bevacizumab injections in a rabbit model.
Korean Journal of Ophthalmology 08/2012; 26(4):290-6. DOI:10.3341/kjo.2012.26.4.290
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