August 2014
Volume 55, Issue 8
Free
Letters to the Editor  |   August 2014
Retinal Segmentation to Demonstrate Hyperplasia in Ataxia of Charlevoix-Saguenay: Critique on Study Methodology and Results
Author Affiliations & Notes
  • Philipp Albrecht
    Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany;
  • Lisanne Balk
    Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands; and
  • Axel Petzold
    Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands; and
  • 3 Charité - Universitätsmedizin Berlin, NeuroCure Clinical Research Center and Department of Neurology, Berlin, Germany. E-mail: phil.albrecht@gmail.com  
Investigative Ophthalmology & Visual Science August 2014, Vol.55, 4728. doi:10.1167/iovs.14-14876
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      Philipp Albrecht, Lisanne Balk, Timm Oberwahrenbrock, Axel Petzold, Friedemann Paul; Retinal Segmentation to Demonstrate Hyperplasia in Ataxia of Charlevoix-Saguenay: Critique on Study Methodology and Results. Invest. Ophthalmol. Vis. Sci. 2014;55(8):4728. doi: 10.1167/iovs.14-14876.

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

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With great interest we read the recent article by Garcia-Martin and colleagues 1 on the retinal segmentation of optical coherence tomography (OCT) scans from patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay. We were impressed by the thorough ophthalmological and radiological workup of these patients with genetic confirmation of this rare disease. Therefore, it comes as a surprise that the quantitative results of the automated segmentation and the qualitative description of some of the retinal layers in the figures do not correspond to the retinal anatomy. While a realistic thickness of 90 μm for controls was presented for the routine assessment of the peripapillary retinal nerve fiber layer (Fig. 2), neither the results section nor the tables reported values within this expected range. Instead, unitless data were presented with unrealistic values for single layer thickness ranging from 4.19 to 7.81, with a supposed total retinal thickness of 62.6 in controls. Published data on paramacular retinal thickness from control subjects are around 320 μm and around 8 mm3 for retinal volume. 24 More confusingly, the reported thickness values of the different layers relative to each other did not correspond to retinal anatomy. For example, the highest values were reported for the retinal pigment epithelium, which is impossible because anatomically, this is one of the thinnest retinal layers. Furthermore, how do the authors propose to be able to measure the thickness of a cellular monolayer, the inner limiting membrane, with values exceeding most of the other retinal layers? 
In addition to these methodological errors, the authors incorrectly labelled the retinal layers in Figure 3, where the nerve fiber layer is indicated while the segmentation lines encompass the ganglion cell layer and the ganglion cell layer is indicated while the lines segment the inner plexiform layer. 
There are exciting times ahead for the application of retinal OCT in neurodegenerative disease 5 and a rigorous, quality-controlled approach (e.g., using the OSCAR-IB criteria) will be needed to establish the technique as a potential outcome measure for clinical trials. 6  
References
Garcia-Martin E Pablo LE Gazulla J Retinal segmentation as noninvasive technique to demonstrate hyperplasia in ataxia of Charlevoix-Saguenay. Invest Ophthalmol Vis Sci . 2013; 54: 7137–7142. [CrossRef] [PubMed]
Albrecht P Müller AK Ringelstein M Retinal neurodegeneration in Wilson's disease revealed by spectral domain optical coherence tomography. PLoS One . 2012; 7: e49825. [CrossRef] [PubMed]
Balk L Tewarie P Killestein J Polman C Uitdehaag B Petzold A. Disease course heterogeneity and OCT in multiple sclerosis [ published online ahead of print January 8, 2014]. Mult Scler .
Oberwahrenbrock T Schippling S Ringelstein M Retinal damage in multiple sclerosis disease subtypes measured by high-resolution optical coherence tomography. Mult Scler Int . 2012; 2012: 530305.
Kersten HM Roxburgh RH Danesh-Meyer HV. Ophthalmic manifestations of inherited neurodegenerative disorders. Nat Rev Neurol . 2014; 10: 349–362. [CrossRef] [PubMed]
Tewarie P Balk L Costello F The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One . 2012; 7 : e34823.
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