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S. W. Cousins, K. Csaky; Analysis of Potential Toxicity Following Intravitreal Injections of Bevacizumab and Pegaptanib in Nonhuman Primate Eyes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):22.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular endothelial growth factor (VEGF) may serve a neurotrophic or protective function in the retina. We sought to determine if two VEGF inhibitors, intravitreal pegaptanib (Macugen®) and bevacizumab (Avastin®), altered retinal function and anatomy in nonhuman primates using noninvasive imaging, electroretinographic measurements and histology.
Cynomolgus monkeys, age 2-7 years, received bilateral intravitreal injections of bevacizumab 1.25 mg (n=6) or pegaptanib 0.3 mg (n=6) on days 1, 22 (week 4), 43 (week 7), and 64 (week 10) of the study, and were sacrificed at week 14. Exams included ophthalmic examination, color fundus photographs, fluorescein angiography, optical coherence tomography (OCT), scanning laser polarimetry (GDx), Heidelberg retinal tomography (HRT), full field, multifocal and pattern, electroretinography (ERG), visual evoked potentials (VEP), histology, clinical chemistry, and clinical observations.
Baseline characteristics were similar across all animals. No clinical, photographic or angiographic evidence for retinal toxicity was seen in either group. No obvious differences were detected between treatment groups over time on OCT, GDx, and HRT. In terms of electrophysiology, pegaptanib did not affect any of the parameters measured. However, all bevacizumab-treated eyes showed a moderate and sustained reduction from baseline measures in the post-dose scotopic b-wave of the full-field ERG reflecting alterations in rod-driven retinal function. Isolated PERG abnormalities were observed in both eyes of 2 bevacizumab-treated animals, but no changes from baseline were noted in the cone-driven photopic ERG, multifocal ERG, or in the cortical VEP.
No major morphologic or anatomic effects were observed after four doses of pegaptanib or bevacizumab. The clinical significance of the diminished scotopic b-wave in the bevacizumab group is unclear. Results of this study may help to identify potential retinal safety issues that should be investigated further in patients receiving anti-VEGF therapy.
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