Brief report
Absence of Histologic Retinal Toxicity of Intravitreal Bevacizumab in a Rabbit Model

https://doi.org/10.1016/j.ajo.2006.03.058Get rights and content

Purpose

To evaluate the retinal toxicity of intravitreal bevacizumab in an animal model.

Design

Animal study.

Methods

Bevacizumab was injected into the vitreous of one eye of each of eight Dutch-belted rabbits; the other eye served as a control. Four rabbits received a dose of 1.25 mg/0.05 ml of bevacizumab intravitreally into one eye, and the other four rabbits were injected with 2.5 mg/0.1 ml of bevacizumab intravitreally into one eye. At one month, the rabbits were killed and both eyes enucleated. The eyes were fixed with paraformaldehyde 2% and examined by light microscopy.

Results

In all injected and control eyes, there was mild vacuolization in the ganglion cell layer, and disruption of photoreceptor outer segments in both treated and control eyes, to the same degree, consistent with autolysis. The optic nerve, retina, and retinal pigment epithelium were otherwise normal by light microscopy with no evidence of toxicity.

Conclusions

Intravitreal bevacizumab at doses of 1.25 mg and 2.5 mg showed no signs of retinal or optic nerve toxicity by light microscopy in this rabbit model.

References (8)

  • P.J. Rosenfeld et al.

    Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration

    Ophthalmic Surg Lasers Imaging

    (2005)
  • R.L. Avery et al.

    Intravitreal bevacizumab (avastin) for neovascular age-related macular degeneration

    Ophthalmology

    (2006)
  • P.J. Rosenfeld et al.

    Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion

    Ophthalmic Surg Lasers Imaging

    (2005)
  • R.F. Spaide et al.

    Intravitreal bevacizumab (avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage

    Retina

    (2006)
There are more references available in the full text version of this article.

Cited by (102)

  • Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study

    2020, Ophthalmology
    Citation Excerpt :

    Although the CATT trial demonstrated that eyes receiving monthly treatment showed a higher incidence of atrophy compared with those being treated with PRN,16 the Alternative Treatments to Inhibit Vascular Endothelial Growth Factor in Patients with Age-Related Choroidal Neovascularization (IVAN) and RIVAL studies found no statistical difference in incidence of atrophy among differing anti-VEGF therapies.34,43 Injections of intravitreal anti-VEGF have been shown to have no association with RPE damage in animal models.44–46 A possible explanation for the inconsistent results reported in the literature is that MA could depend more on specific features of the single neovascular lesions included in the studies or the underlying MA phenotype, rather than on the treatment itself.

  • Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab

    2019, Materials Science and Engineering C
    Citation Excerpt :

    Studies in vivo revealed the absence of ocular toxicity for BEV administrated by intravenous injection. Due to its short half-life and the necessity of frequent intravitreal injection, a method for sustained delivery is required [9–12]. Studies concerning BEV usefulness in the field of ophthalmology as an off-label drug for the treatment of wet AMD have been reported.

  • Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment

    2017, Experimental Eye Research
    Citation Excerpt :

    The concern that bevacizumab might be harmful to the retina has led researchers to evaluate its possible side effects through cell viability assays and the identification of molecules involved in cell death, proliferation and cell reactivity. While several experimental studies have failed to demonstrate any retinal toxicity from intravitreal injections of bevacizumab (Bakri et al., 2006; Feiner et al., 2006; Manzano et al., 2006; Zayit-Soudry et al., 2011), others have described ultrastructural abnormalities, including increased apoptotic activity (Saint-Geniez et al., 2008), increased glial cell reactivity (Fusco et al., 2012), and changes in retinal function (Myers et al.). In addition, newborn rat retinal explants exposed to bevacizumab have been shown to undergo molecular changes such as increased vimentin content, decreased GFAP (Miguel et al., 2012), and decreased neurocan mRNA levels (Krempel et al., 2014), potentially interfering with neuron and glial cell maturation early in the retinal development.

  • Retinal pigment epithelial cell loss assessed by fundus autofluorescence imaging in neovascular age-related macular degeneration

    2013, Ophthalmology
    Citation Excerpt :

    Because VEGF antagonists are the best form of available treatment and consequently all treatable patients are treated with anti-VEGF drugs, the potential that these agents contribute to the development of RPE loss could not be evaluated. In rabbit eyes, intravitreal bevacizumab did not cause any observable damage.36,37 In cell culture, RPE cells exposed to hydrogen peroxide were more likely to die if either VEGF or the VEGF receptor was blocked by antibodies.38

View all citing articles on Scopus

This study was funded by the Research to Prevent Blindness, New York, New York.

View full text