Testing intravitreal toxicity of bevacizumab (Avastin).
ABSTRACT To evaluate the retinal toxicity of varying doses of bevacizumab when injected intravitreally in rabbits. Bevacizumab has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer.
Twelve New Zealand albino rabbits were used for this study and divided into four groups. Four concentrations of bevacizumab were prepared: 500 microg/0.1 mL, 1.0 mg/0.1 mL, 2.5 mg/0.1 mL, and 5.0 mg/0.2 mL. Each concentration was injected intravitreally in one eye of each of three rabbits; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, or toxicity. A baseline electroretinogram (ERG) was performed before the drug treatment and at day 14 before the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity.
Histologic and ERG results in all groups showed no retinal toxicity. However, some inflammatory cells were found in the vitreous at the 5-mg dose.
Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.
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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.
Article: Comparison of intravitreal bevacizumab, intravitreal triamcinolone acetonide, and macular grid augmentation in refractory diffuse diabetic macular edema: A prospective, randomized study.[show abstract] [hide abstract]
ABSTRACT: In spite of laser being the gold standard treatment for Diabetic Macular edema (DME), some patients do not respond to laser. Various treatment modalities are being tried in the management of refractory diffuse DME (DDME). To compare the efficacy of intravitreal bevacizumab (IVB), intravitreal triamcinolone acetonide (IVTA), and macular grid augmentation in the management of refractory DDME. Prospective randomized study in a tertiary eye care center. SIXTY PATIENTS WITH REFRACTORY DDME WERE RANDOMLY ASSIGNED TO THREE GROUPS: Group 1 received IVB (1.25 mg/0.05 ml), Group 2 received IVTA (4 mg/0.1ml), and Group 3 underwent laser augmentation. Primary outcome measures were best corrected visual acuity (BCVA) and central macular thickness (CMT) at the end of 6 months. Analysis was performed using SPSS 14.0 Group 1 and 2 showed significant improvement in mean BCVA from 20/160 at baseline to 20/80 and from 20/125 to 20/63, respectively, at 6 months (P < 0.05). These groups also showed a significant reduction in the mean CMT from 457 ± 151 μ at baseline to 316 ± 136 μ and from 394 ± 61 μ to 261 ± 85 μ, respectively, at 6 months (P < 0.05). Group 3 showed only small improvement in mean BCVA from 20/100 to 20/80 (P = 1.0) while mean CMT increased from 358 ± 89 μ at baseline to 395 ± 127 μ at 6 months (P = 0.191). Eight (40%) eyes in Group 2 had intraocular pressure (IOP) rise and 10 (50%) eyes developed cataract. Both IVB and IVTA may be effective in the treatment of refractory DDME compared with macular grid augmentation. IVTA may be associated with side effects such as IOP rise and cataract formation.Oman Journal of Ophthalmology 09/2012; 5(3):166-70.
Article: Indocyanine green mediated photothrombosis and high dose intravitreal bevacizumab as adjuvant therapy for isolated choroidal metastasis from breast cancer.[show abstract] [hide abstract]
ABSTRACT: To report the effectiveness of indocyanine green mediated photothrombosis (IMP) combined with high dose (4 mg/0.16 ml) intravitreal bevacizumab (IVB) as adjunctive therapy for management of isolated choroidal metastasis from breast cancer. This retrospective interventional case report includes three eyes of two patients with choroidal metastasis from breast cancer. Both patients were submitted to one session of IMP combined with high dose IVB as adjuvant local therapy to systemic chemotherapy. Main outcome measures were tumor response, and fluorescein angiography (FA), optical coherence tomography (OCT), and visual acuity (VA) results. The first patient was a 47-year-old woman who had undergone radical mastectomy, chemotherapy and radiotherapy 7 years earlier and the second patient was a 70-year-old woman managed with chemotherapy and radiotherapy 16 years before presentation. There was no evidence of systemic metastasis in either case and both suffered from gradually blurred vision. The first patient presented with a unilateral choroidal lesion whereas the second case had bilateral unifocal choroidal lesions which was symptomatic in only one eye. Clinical examination, ultrasonography, FA, and OCT revealed accompanying exudative retinal detachment in all three eyes. OCT 3 to 5 weeks after combined therapy demonstrated complete resolution of subretinal fluid and improved VA in two eyes. Combined IMP and high-dose IVB seems to be an effective adjunctive treatment to systemic chemotherapy for management of isolated choroidal metastasis from breast cancer.Journal of ophthalmic & vision research. 10/2012; 7(4):332-40.