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Simon R Bababeygy, Deepika Malik, Javier Caceres del Carpio, David S Boyer, Cristina M Kenney, Baruch Kuppermann; Safety Profile of Anti-VEGF Agents on Retinal Pigment Epithelium Cells: In Vitro Cell Viability. Invest. Ophthalmol. Vis. Sci. 2014;55(13):596.
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© ARVO (1962-2015); The Authors (2016-present)
While the advent of anti-VEGF drugs ranibizumab, bevacizumab, and aflibercept have revolutionized the treatment of wet AMD, differences in molecular structure of these drugs may have variable effects on enzymatic activity and metabolic processes in retinal cells, and may cause mild occult toxicity despite their significant benefit. This study was designed to compare the safety profiles of anti-VEGF drugs ranibizumab, bevacizumab, aflibercept, and ziv-aflibercept on retinal pigment epithelium cells in culture by assessing cell viability post drug exposure.
Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 hours to one of four anti-VEGF drugs at 1/2X, 1X, 2X or 10X clinical doses. Cell viability using the trypan blue dye exclusion assay was performed to evaluate the amount of overall cell death post drug exposure for each drug.
Ranibizumab was found to be safe at all doses of treatment including the highest dose, 10X the clinical dose. There was no statistically significant difference between control and all ranibizumab doses tested from 1/2X to 10X clinical dose. Cell viability of ARPE-19 cells treated with 10X dose of bevacizumab, aflibercept and ziv-aflibercept showed a statistically significant decrease to 82.38 + 1.5% (p=0.0002), 82.62 + 1.7% (p=0.0001) and 77.25 + 2.1% (p<0.0001), respectively compared to control (normalized to 100%). There were no statistically significant differences on ARPE-19 cells between at 1/2X, 1X and 2X anti-VEGF treated cells compared to control/untreated cells.
At clinical equivalent doses, none of the four anti-VEGF drugs tested exhibited significant decreases in cell viability on ARPE-19 cells in culture. However, at supranormal doses 10X the clinical dose, only ranibizumab showed no significant decrease in RPE cell viability. At 10X the clinical dose, bevacizumab, aflibercept, and ziv-aflibercept all showed significant decreases in RPE cell viability. This study suggests that ranibizumab may have the broadest safety profile of all four studied anti-VEGF drugs tested on RPE cells in culture.
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