June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Effects of intravitreally injected ranibizumab and aflibercept on retina and choroid of monkey eyes
Author Affiliations & Notes
  • Ulrich Schraermeyer
    Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tubingen, Germany
  • Sylvie Julien
    Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Tubingen, Germany
  • Footnotes
    Commercial Relationships Ulrich Schraermeyer, Novartis Pharma AG (F), Novartis Pharma AG (R), Acucela (C); Sylvie Julien, Novartis Pharma AG (F), Novartis Pharma AG (R)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2180. doi:
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    • Get Citation

      Ulrich Schraermeyer, Sylvie Julien; Effects of intravitreally injected ranibizumab and aflibercept on retina and choroid of monkey eyes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2180.

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

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Abstract
 
Purpose
 

Because there is evidence that the Fc domain of anti-VEGF drugs may cause unexpected effects in retinal and choroidal vessels, the effects of intravitreal ranibizumab and aflibercept on monkey eyes were investigated.

 
Methods
 

Four Cynomolgus monkeys were intravitreally injected with 0.5mg ranibizumab (Lucentis®) and another four with 2mg aflibercept (Eylea®). All eyes underwent fluorescein angiography (FA) and OCT before injection as well as before sacrifice (1 or 7 days post-injection). Three untreated monkeys and one injected with aflibercept vehicle served as controls. The eyes were inspected by light and electron microscopy and the choriocapillaris lumen width was measured by morphometry.

 
Results
 

Neither FA nor OCT showed any effects of drug treatment. Focal thrombocyte activation, fibrin formation and microparticles were seen in choroidal vessels 24 hours after injection of either drug, but more often with ranibizumab. Hemolysis in the choriocapillaris was observed in all eyes even vehicle-injected. In aflibercept-treated eyes swelling of endothelial cells was observed and individual RPE cells were completely filled with hemoglobin indicating cell death (Fig.1b). Deposits on the endothelial cells of choroidal vessels were denser after treatment with aflibercept compared to ranibizumab or control. The choriocapillaris lumen width was significantly reduced after treatment with either drug. After aflibercept, individual capillaries collapsed completely (Fig.1a).

 
Conclusions
 

OCT and FA are not suitable to detect microangiopathy. Both drugs reduced similarly the choriocapillaris lumen. The cause of hemolysis is not clear, as it can also be induced by fluorescein. After aflibercept treatment, microangiophathy (Fig.1a) and RPE cell death (Fig.1b) were observed. The dense material attached on choroidal vessel walls indicates protein complex formation as observed after bevacizumab treatment1. Whether these results are related to aflibercept’s Fc domain or to other characteristics of the molecule remain to be investigated. 1 Schraermeyer & Julien (2012) 10.1517/14712598.2012.748741 [doi]

 
 
Fig.1a: After aflibercept treatment endothelial cells (arrow) show microangiopathy and the lumen (asterisk) of the choriocapillaris is completely collapsed. Fig.1b: A dead RPE cell with damaged mitochondriae (arrowhead) is filled with hemoglobin (asterisk) after aflibercept treatment. B = Bruch’s membrane
 
Fig.1a: After aflibercept treatment endothelial cells (arrow) show microangiopathy and the lumen (asterisk) of the choriocapillaris is completely collapsed. Fig.1b: A dead RPE cell with damaged mitochondriae (arrowhead) is filled with hemoglobin (asterisk) after aflibercept treatment. B = Bruch’s membrane
 
Keywords: 503 drug toxicity/drug effects • 412 age-related macular degeneration • 452 choroid  
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