September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Retinal Toxicity of Intravitreal Injection of Ziv-Aflibercept in albino rabbits
Author Affiliations & Notes
  • Dan Michael Ramon
    Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  • Yonathan Shahar
    Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel
    Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv, Israel
  • Amir Massarweh
    Department of Physiology and Biophysics, Technion-Israel Institute of Technology, Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Irit Mann
    Department of Physiology and Biophysics, Technion-Israel Institute of Technology, Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
  • Ido Perlman
    Department of Physiology and Biophysics, Technion-Israel Institute of Technology, Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
    Rappaport Institute, Haifa, Israel
  • Anat Loewenstein
    Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv, Israel
    Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel
  • Footnotes
    Commercial Relationships   Dan Ramon, None; Yonathan Shahar, None; Amir Massarweh, None; Irit Mann, None; Ido Perlman, None; Anat Loewenstein, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3324. doi:
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      Dan Michael Ramon, Yonathan Shahar, Amir Massarweh, Irit Mann, Ido Perlman, Anat Loewenstein; Retinal Toxicity of Intravitreal Injection of Ziv-Aflibercept in albino rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3324.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Ziv-aflibercept (Zaltrap, Sanofi-aventis U.S. LLC, Bridgewater, NJ), a drug indicated for patients with colon cancer, acts as a soluble receptor that binds to human Vascular Endothelial Growth Factors 1 and 2, and to human Placental Growth Factor. Aflibercept (Eylea, Regeneron Pharmaceuticals, Inc., Tarrytown, NY) the Intravitreal equivalent of ziv-aflibercept, is an FDA approved drug for the treatment of neovascularization in age-related macular degeneration, of macular edema following retinal vein occlusion and of diabetic macular edema. The aim of this study is to evaluate retinal toxicity of ziv-aflibercept.

Methods : A total of 18 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) 4-weeks follow-up (one of these died) and 6 were used for histological and glial fibrillary acidic protein (GFAP) immunocytochemistry during follow-up. ERG responses were recorded 3 days, 1-, 2-, and 4-weeks after injection. The visual evoked potential (VEP) was recorded after 4 weeks. Immunohistochemical and histological studies were performed throughout the follow-up period and after the termination of the follow-up period.

Results : the ERG responses of the experimental eyes did not show any significant difference from the responses of the control eyes, either in amplitude or in pattern, throughout the follow-up period. The flash 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 any signs of structural damage. However, GFAP immunocytochemistry showed activation of retinal Müller cells, indicating mild retinal gliosis.

Conclusions : Ziv-aflibercept was found to be non-toxic to the retina of rabbits based on electrophysiological testing and histologic examination. However, GFAP immunocytochemistry suggests mild retinal stress caused by the drug. Therefore, application of intravitreal ziv-aflibercept in patients needs caution and additional considerations.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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