Evidence map›Paper›PMID 24836865›Full record

ArticleThe British journal of ophthalmology2014

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture.

Deepika Malik, Mohamed Tarek, Javier Caceres del Carpio, Claudio Ramirez, David Boyer, M Cristina Kenney, Baruch D Kuppermann

Registry-linked trialAbstract read
In one paragraph

Article in The British journal of ophthalmology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02173873 (Ziv-aflibercept in Eyes With Eyes With Retinal Diseases and Poor Vision-phase I), which is not on this map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02173873 phase1unknown statusnot on this map

Ziv-aflibercept in Eyes With Eyes With Retinal Diseases and Poor Vision-phase I

TypeinterventionalSponsorRafic Hariri University HospitalRan2014 to 2016Enrolled100ConditionsAge Related Macular Degeneration, Central Retinal Vein OcclusionArmsziv-aflibercept drug
3 · Its place in the literature

Who cites it

54 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Exploring the efficacy of a novel cannabidiol and bevacizumab combination in non-small cell lung cancer.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Aflibercept for the treatment of pigmentary retinopathy in Kearns-Sayre syndrome?Documenta ophthalmologica. Advances in ophthalmology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal transduction and targeted therapy · 2023
    Review
  16. Article
  17. Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Deepika MalikDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA.ORCID http://orcid.org/0000-0002-3722-6711
Mohamed TarekDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA Department of Ophthalmology, El-Minya University, El-Minya, Egypt.
Javier Caceres del CarpioDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA.
Claudio RamirezDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA.
David BoyerRetina-vitreous Associates Medical Group, Los Angeles, California, USA.
M Cristina KenneyDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA.
Baruch D KuppermannDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, California, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture.

methodsHuman retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death.

resultsCell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses.

conclusionsAt clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses.

Indexed as

Angiogenesis InhibitorsAntibodies, Monoclonal, HumanizedApoptosisBevacizumabCadaverCells, CulturedCell SurvivalHumansMacular DegenerationMaleRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsReference ValuesRetinal Pigment EpitheliumVascular Endothelial Growth Factor AafliberceptAngiogenesis InhibitorsAntibodies, Monoclonal, HumanizedBevacizumabRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVascular Endothelial Growth Factor AAngiogenesisMaculaTreatment Medical

Identifiers

PMID24836865
PMCPMC4033208

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.