Abstract
Purpose: :
To study drug safety and possible side-effects of three different VEGF blocking substances (bevacizumab, ranibizumab and pegaptanib), after intra-vitreal administration to the rabbit eye, evaluating retinal function with ERG and mfERG.
Methods: :
48 rabbits of mixed strain (6 months of age, bodyweight 3 kg) were randomized into four groups (n=12).The rabbits were examined with full-field ERG and with mfERG 2- 3 weeks before drug exposal. The rabbits were then injected intra-vitreally with bevacizumab (50 uL, 25mg/ml), ranibizumab (50 uL, 10mg/ml), pegaptanib (90 uL, 0.3mg) and a balanced saline solution (BSS) (50 uL, 9mg/ml), respectively. ERG was assessed at 1 week and at 8 weeks post injection. MfERG was assessed at 2 weeks and at 9 weeks post injection.
Results: :
Two subjects in the ranibizumab group were excluded (one died spontaneously 5 days post injection and one was euthanized because of endophthalmitis in the injected eye). There was no significant difference in ERG responses in the four groups prior to injection of anti-VEGF, while all three groups injected with antiVEGF showed a significant reduction of amplitudes of the dark adapted rod response, at some time point after injection (bevacizumab and pegaptanib at both 1 and 8 weeks, ranibizumab only at 8 weeks). Bevacizumab affected also significantly the dark adapted cone response to the single flash red stimulation (both 1 week and 8 weeks post injection), pegaptanib only after 8 weeks, and ranibizumab at neither time point. Repeated measurement analysis revealed that the observed increase in rod response amplitudes over time in the BSS injected group (possibly representing a retinal maturation), was absent in all of the anti-VEGF injected groups, which demonstrated similar rod amplitudes prior to- and at 8 weeks post injection. MfERG responses were unaffected by anti-VEGF at all time points.
Keywords: vascular endothelial growth factor • electroretinography: non-clinical