Retinal Segmentation to Demonstrate Hyperplasia in Ataxia of Charlevoix-Saguenay: Critique on Study Methodology and Results

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. ^2–4 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