“Genuine error” sees expression of concern for vision loss paper

elsevierA duplicated figure has resulted in an expression of concern for a paper in the American Journal of Pathology on a treatment for ocular neovascularization, which causes vision loss.

According to the notice, the corresponding author, David Shima, now at University College London, brought his concern to the journal. He called it a “genuine error” and stated that all the findings had been reproduced.

Unfortunately, Shima claimed the original data are missing, because the institution that owned the information — Eyetech Research Center — has “since gone through several acquisitions.”

Ocular neovascularization occurs when growth signals in the eye stimulate the creation of many new blood vessels. Over time these blood vessels break, causing bleeding and scarring that limits vision. This is called “wet” macular degeneration.

The scientists found that giving patients drugs to limit two different growth factors at the same time is more effective than one at stopping the progression of AMD. This combination method is in stage three clinical trials, though with different drugs than the authors used here.

The paper, published in 2006, has been cited 130 times, according to Thomson Scientific’s Web of Knowledge. Here’s the EoC for “Inhibition of Platelet-Derived Growth Factor B Signaling Enhances the Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Multiple Models of Ocular Neovascularization”:

It has been brought to our attention that Figure 10B of “Inhibition of Platelet-Derived Growth Factor B Signaling Enhances the Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Multiple Models of Ocular Neovascularization,” by Nobuo Jo, Carolina Mailhos, Meihua Ju, Eunice Cheung, John Bradley, Kazuaki Nishijima, Gregory S. Robinson, Anthony P. Adamis, and David T. Shima (Volume 168, pages 2036–2053 of the June 2006 issue of The American Journal of Pathology) contains data errors, specifically the duplication of fluorescent images between the Prevention (A) and Regression (B) data points. The matter was reviewed by the journal’s Editors.

Corresponding author Dr. Shima brought this matter to the attention of the Editors. Dr. Shima states that “this was a genuine error, and we are confident in the actual quantitative data presented in the figure. Not only have other investigators reproduced combination data[1], we also presented in the article another experiment performed in a distinct set of studies using Gleevec (imatinib) as the PDGF (platelet-derived growth factor) antagonist. Finally, the combination therapy approach has been validated in a Phase 2b proof-of-concept study in neovascular AMD (age-related macular degeneration) patients and is currently in Phase 3 clinical trial (https://clinicaltrials.gov/ct2/home, accession number NCT01940900).”

The authors report that they no longer have access to the original data, which was held by their employer Eyetech Research Center (Lexington, MA); Eyetech Research Center has since gone through several acquisitions.

Reference
1 A. Dong, C. Seidel, D. Snell, S. Ekawardhani, J.K. Ahlskog, M. Baumann, J. Shen, T. Iwase, J. Tian, R. Stevens, S.F. Hackett, M.T. Stumpp, P.A. Campochiaro
Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A Angiogenesis, 17 (2014), pp. 553–562

The notice had been paywalled on Science Direct, but after we reached out to the journal, they made it publicly available and sent us this note:

It is the policy of the Journal that all Corrections, Retractions, and Notes of Concern be freely available. We apologize for the error on the Science Direct platform and have asked the Publisher to release it for free access. The Note of Concern is freely available at http://ajp.amjpathol.org/article/S0002-9440%2814%2900680-4/fulltext and can be viewed there until the Science Direct site is updated.

17 thoughts on ““Genuine error” sees expression of concern for vision loss paper”

  1. So, if we set aside the reasons, and ignore the issue of bias caused by the term “genuine”, can we safely assume that a duplicated figure and no data will lead – at minimum – to an EoC in all (or any?) Elsevier journals? Thus, if we should find a duplicated figure in any Elsevier journal, may we reference this case in a bid to make the editors issue, at least, an EoC for similar cases? Is a duplicated figure equivalent to a duplicated data set, or a duplicated table? Perhaps Elsevier could offer a detailed explanation at RW? By not applying the same rule uniformly across all of its journals, the problem of inconsistency in publishing ethics by this publisher may begin to be focused.

  2. I must admit that I found that the description of this EoC a bit confusing. The statement “The scientists found that giving patients drugs to limit two different growth factors at the same time is more effective than one at stopping the progression of AMD. This combination method is in stage three clinical trials, though with different drugs than the authors used here” seems to be a bit out of context. It implies that the data in the article comes from a clinical trial when it comes from animal models.
    There is also a scientific error in the following statement “Dr. Shima states that “this was a genuine error, and we are confident in the actual quantitative data presented in the figure. Not only have other investigators reproduced combination data, we also presented in the article another experiment performed in a distinct set of studies using Gleevec (imatinib) as the PDGF (platelet-derived growth factor) antagonist.” Gleevec is not a PDGF antagonist. It is a PDGF RECEPTOR antagonist.

    With respect to the duplication, it wasn’t just a simple duplication but a duplication with a slightly different magnification. That difference in magnification might be reflected in the graph below the images.

  3. Now I have looked at the Note of Concern closely it seems that I have a concern about the quality of the Note of Concern.

    My web broswer lost the superscripted 1 after the word “data”. Sorry about that.

    In addition, the statement “Finally, the combination therapy approach has been validated in a Phase 2b proof-of-concept study in neovascular AMD (age-related macular degeneration) patients” doesn’t have a citation. This seems to refer to Fovista (based on the CT.gov entry). I don’t think that the Fovista Phase 2b data have been published yet but I might be wrong.

  4. Am J Pathol. 2002 Dec;161(6):2229-40.
    Constitutive nuclear factor-kappaB activity is crucial for human retinoblastoma cell viability.
    Poulaki V1, Mitsiades CS, Joussen AM, Lappas A, Kirchhof B, Mitsiades N.
    Author information
    1Retina Research and Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 325 Cambridge Street, Boston, MA 02114, USA.

    Figure 3.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850903/figure/f3/

    Please see: https://pubpeer.com/publications/12466137

    http://i.imgur.com/POtsT34.jpg

  5. Penultimate author of paper which is topic of post, AP Adamis.

    J Clin Invest. 2002 Mar;109(6):805-15.
    Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF.
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    Author information
    1Laboratory of Surgical Research, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    Please see: https://pubpeer.com/publications/11901189

    Especially:

    Figure 1.
    http://i.imgur.com/QVQG3ca.jpg

    and figure 4a.
    http://i.imgur.com/MIVDsps.jpg

  6. Ppenultimate author of paper which is topic of post, AP Adamis.

    Am J Pathol. 2004 Aug;165(2):457-69.
    Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy.
    Poulaki V1, Joussen AM, Mitsiades N, Mitsiades CS, Iliaki EF, Adamis AP.
    Author information
    1Retina Research Institute, Massachusetts Eye and Ear Infirmary, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

    Please see: https://pubpeer.com/publications/15277220

    http://i.imgur.com/mMCDJnU.jpg

  7. Invest Ophthalmol Vis Sci. 2003 May;44(5):2184-91.
    Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo.
    Koizumi K1, Poulaki V, Doehmen S, Welsandt G, Radetzky S, Lappas A, Kociok N, Kirchhof B, Joussen AM.
    Author information
    1Department of Vitreoretinal Surgery, Center for Ophthalmology, and Center for Molecular Medicine, University of Cologne, Cologne, Germany.

    https://pubpeer.com/publications/12714660

    Figure 8A.
    http://i.imgur.com/4qUiWrK.jpg

  8. Mol Vis. 2009 Jul 25;15:1418-28.
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    Author information
    1Department of Ophthalmology, Heinrich Heine University, Duesseldorf, Germany.

    https://pubpeer.com/publications/B4E26E4DFBD539DA7E9F9B755327A2#fb24898

    Please compare 30 KD control band figure 6A Mol Vis 15,1418
    with 30 KD anti-TNF band figure 8A Invest Ophthalmol Vis Sci 44,2184.

    http://i.imgur.com/mhwiAOE.jpg

    For reference.
    Invest Ophthalmol Vis Sci 44,2184.
    https://pubpeer.com/publications/12714660

  9. FASEB J. 2007 Jul;21(9):2113-23. Epub 2007 Mar 30.
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    Poulaki V1, Iliaki E, Mitsiades N, Mitsiades CS, Paulus YN, Bula DV, Gragoudas ES, Miller JW.
    Author information
    1Angiogenesis/Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St., Boston, MA 02114, USA.

    Please see: https://pubpeer.com/publications/17400913

    and http://i.imgur.com/fjkE5o3.jpg

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    Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.
    Peter Carmeliet1, Yin-Shan Ng2, Dieter Nuyens1, Gregor Theilmeier1, Koen Brusselmans1, Ivo Cornelissen1, Elisabeth Ehler3, Vijay V. Kakkar4, Ingeborg Stalmans1, Virginie Mattot1, Jean-Claude Perriard3, Mieke Dewerchin1, Willem Flameng5, Andras Nagy6, Florea Lupu4, Lieve Moons1, Désiré Collen1, Patricia A. D’Amore2 & David T. Shima2, 7
    1 The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven , Leuven, B-3000, Belgium
    2 Schepens Eye Research Institute, Harvard Medical School , Boston, Massachusetts 02115, USA
    3 Institute for Cell Biology, Swiss Federal Institute of Technology, Zürich, CH-8093, Switzerland
    4 Vascular Biology Laboratory, Weston Experimental Research Center, Thrombosis Research Institute, London SW3 6LR , UK
    5 Laboratory of Experimental Cardiac Surgery, KU Leuven, Leuven, B-3000, Belgium
    6 Samuel Lunenfeld Institute, Mount Sinai Hospital, Toronto, ON M5 1X5, Canada
    7 Cell Biology, Imperial Cancer Research Fund, London WC2A 3PX, UK

    Please see:
    https://pubpeer.com/publications/4BED94B956B79DEAE38C6799022E6A#fb25112

    Figure 2k.
    http://i.imgur.com/zsRGNDO.jpg

    Figure 3g.
    http://i.imgur.com/c6me8Aj.jpg

  11. EMBO Mol Med. 2012 Sep;4(9):980-91. doi: 10.1002/emmm.201101084. Epub 2012 Aug 20.
    2 comments on PubPeer
    β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment.
    Jun Cai1,†, Xiaoping Qi1,†, Norbert Kociok2, Sergej Skosyrski2, Alonso Emilio1, Qing Ruan1, Song Han3, Li Liu4, Zhijuan Chen1, Catherine Bowes Rickman5, Todd Golde6, Maria B. Grant4, Paul Saftig7, Lutgarde Serneels8,9, Bart de Strooper8,9, Antonia M. Joussen2 and Michael E. Boulton (meboulton@ufl.edu) *,1
    1Department of Anatomy & Cell Biology, University of Florida, Gainesville, FL, USA
    2Department of Ophthalmology, Charité Universitätsmedizin Berlin, Berlin, Germany
    3Department of Surgery, University of Florida, Gainesville, FL, USA
    4Department of Pharmacology & Therapeutics, University of Florida, Gainesville, FL, USA
    5Department of Ophthalmology & of Cell Biology, Duke University Medical Center, Durham, NC, USA
    6Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA
    7Biochemical Institute, Christian‐Albrecht’s University, Kiel, Germany
    8Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, Leuven, Belgium
    9VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium

    Please see Pubpeer comments.

    https://pubpeer.com/publications/5CBF05BEBE80EDE91A70B48DF3358F

  12. Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5182-8.
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    Author information

    1Department of Ophthalmology, University of Cologne, 50924 Koeln, Germany.

    Please see Pubpeer comments.

    https://pubpeer.com/publications/14638715

  13. Exp Eye Res. 2010 Feb;90(2):244-53. doi: 10.1016/j.exer.2009.10.012. Epub 2009 Oct 28.
    Retinal localization of the glutamate receptor GluR2 and GluR2-regulating proteins in diabetic rats.
    Semkova I1, Huemmeke M, Ho MS, Merkl B, Abari E, Paulsson M, Joussen AM, Plomann M.
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    1Department of Ophthalmology, University of Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.

    https://pubpeer.com/publications/79F9C96BFFC8C414CD19020B7AB37E#fb25238

    http://i.imgur.com/9IKUtzz.jpg

  14. Am J Pathol. 2002 May;160(5):1683-93.
    Suppression of diabetic retinopathy with angiopoietin-1.
    Joussen AM1, Poulaki V, Tsujikawa A, Qin W, Qaum T, Xu Q, Moromizato Y, Bursell SE, Wiegand SJ, Rudge J, Ioffe E, Yancopoulos GD, Adamis AP.
    Author information
    1Laboratory for Surgical Research, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    Please see Pubpeer comment:

    https://pubpeer.com/publications/3CF916E5F93F1A99EA8B2B6241456D#fb25824

    http://ajp.amjpathol.org/cms/attachment/2000643919/2001376442/gr1_lrg.jpg

    http://imgur.com/GP4TiyA

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