Abstract
Purpose :
To evaluate the long-term retinal toxicity after repeated intravitreal injections of a humanized anti-human VEGF-A monoclonal antibody (PRO-169) versus ranibizumab in New Zealand white (NZW) rabbit eyes.
Methods :
NZW Rabbits were injected intravitreally with PRO-169 (n=12), 1.25 mg/0.05ml or ranibizumab (n=12), 0.5 mg/0.05ml into the right eye, whereas the left eye of each rabbit was the control. Three consecutive injections were administered at 30-days intervals. An electroretinogram (ERG) was recorded 30 days after each injection. The dark-adapted ERG b-wave, was fitted to a Naka Rushton-type hyperbolic function (Eq. 1) to drive the maximum b-wave amplitude (Vmax) and the semi saturation constant (σ). Clinical examination was conducted, including intraocular pressure determination and eye fundus exploration before and after injections. Eyes were enucleated and prepared for histopathologic assesment.
Results :
ERGs of the experimental and control eyes in PRO-169 and ranibizumab groups were similar in amplitude and pattern throughout the follow-up period. ERG changes were considered significant if the follow-up differences in amplitude (b-waves) were over 20% inferior in the PRO-169 group when compared to the positive control group(ranibizumab). Both groups only showed a decrease in amplitude at day 60 (after 2nd injection) of 32.3% for PRO-169 and 12.7% in ranibizumab when compared to day 30 (p=0.386). There was no significant decrease in amplitude in both groups at day 90 when compared to day 60 (p=0.386), or to the baseline (p=0.564). No significant differences in retinal function were found between the experimental and control eyes at any time point in both treatments, expressed in Vmax and σ values (p 〉0.05). Clinical examination found no alterations. The histopathologic studies showed similar results in both groups.
Conclusions :
Our study did not find evidence of retinal toxicity from a repeated intravitreal injection of PRO-169 or ranibizumab (Lucentis®) in rabbits. These findings support intravitreal PRO-169 as a safe candidate to be considered as a future alternative for the treatment of diabetic macular edema.
This is a 2020 ARVO Annual Meeting abstract.