Dan Ramon1,2, Jonathan Shahar2,3, Amir Massarweh1, Irit Man4, Ido Perlman1, Anat Loewenstein2,3. 1. Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 2. Department of Ophthalmology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 3. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 4. Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Abstract
PURPOSE: To evaluate retinal toxicity of ziv-aflibercept, a drug that had been approved for use for patients with colon cancer. METHODS: Twenty-two albino rabbits were injected intravitreally with 0.1 mL of ziv-aflibercept solution into the experimental eye and 0.1-mL saline into the control eye. Twelve were used for electroretinogram (ERG) at 4-weeks follow-up. An additional 10 rabbits were used for testing penetration of ziv-aflibercept into the retina during follow-up. The visual-evoked potential (VEP) was recorded after 4 weeks of ERG follow-up. Glial fibrillary acidic protein (GFAP) immunocytochemistry and retinal histology were performed after the termination of the follow-up period. RESULTS: The ERG responses of the experimental eyes did not show signs of permanent functional damage. The VEP responses of the experimental eyes were of normal pattern and amplitude, and were similar to those recorded by stimulation of the control eyes. Histologic studies of both experimental and control eyes did not show signs of structural damage. However, GFAP expression was increased in retinal Müller cells of the experimental eyes and not of the control eyes. Retinal penetration of ziv-aflibercept, as indicated by positive antihuman immunoreactivity, was observed 1 day postinjection and was strengthened during the next 7 days. At 14 days postinjection, ziv-aflibercept was not detected. CONCLUSIONS: Ziv-aflibercept was found to be nontoxic to the retina of rabbits based on electrophysiologic testing and histologic examination. However, GFAP immunocytochemistry suggests mild retinal stress caused by the drug. TRANSLATIONAL RELEVANCE: If proven safe, ziv-aflibercept may be a new affordable treatment option in conditions involving neovascularization and macular edema.
PURPOSE: To evaluate retinal toxicity of ziv-aflibercept, a drug that had been approved for use for patients with colon cancer. METHODS: Twenty-two albino rabbits were injected intravitreally with 0.1 mL of ziv-aflibercept solution into the experimental eye and 0.1-mL saline into the control eye. Twelve were used for electroretinogram (ERG) at 4-weeks follow-up. An additional 10 rabbits were used for testing penetration of ziv-aflibercept into the retina during follow-up. The visual-evoked potential (VEP) was recorded after 4 weeks of ERG follow-up. Glial fibrillary acidic protein (GFAP) immunocytochemistry and retinal histology were performed after the termination of the follow-up period. RESULTS: The ERG responses of the experimental eyes did not show signs of permanent functional damage. The VEP responses of the experimental eyes were of normal pattern and amplitude, and were similar to those recorded by stimulation of the control eyes. Histologic studies of both experimental and control eyes did not show signs of structural damage. However, GFAP expression was increased in retinal Müller cells of the experimental eyes and not of the control eyes. Retinal penetration of ziv-aflibercept, as indicated by positive antihuman immunoreactivity, was observed 1 day postinjection and was strengthened during the next 7 days. At 14 days postinjection, ziv-aflibercept was not detected. CONCLUSIONS: Ziv-aflibercept was found to be nontoxic to the retina of rabbits based on electrophysiologic testing and histologic examination. However, GFAP immunocytochemistry suggests mild retinal stress caused by the drug. TRANSLATIONAL RELEVANCE: If proven safe, ziv-aflibercept may be a new affordable treatment option in conditions involving neovascularization and macular edema.
Authors: Jonathan Shahar; Robert L Avery; Gad Heilweil; Adiel Barak; Esther Zemel; Geoffrey P Lewis; Patrick T Johnson; Steven K Fisher; Ido Perlman; Anat Loewenstein Journal: Retina Date: 2006-03 Impact factor: 4.256
Authors: Daniel F Martin; Maureen G Maguire; Stuart L Fine; Gui-shuang Ying; Glenn J Jaffe; Juan E Grunwald; Cynthia Toth; Maryann Redford; Frederick L Ferris Journal: Ophthalmology Date: 2012-05-01 Impact factor: 12.079