Thickness mapping of individual retinal layers and sectors by Spectralis Spectral Domain‐optical Coherence Tomography in Autosomal Dominant Optic Atrophy (2019)

We read with great interest the paper by Corajevic et al. (2018) entitled ‘Thickness mapping of individual retinal layers and sectors by Spectralis Spectral Domain (SD)-optical coherence tomography in Autosomal Dominant Optic Atrophy’. In their manuscript, the authors corroborated the results of our study involving a smaller sample of 11 Autosomal Dominant Optic Atrophy (ADOA) patients from five independent families harbouring distinct pathogenic variants in the OPA1 gene (Cesareo et al. 2017). In our work, retinal automatic segmentation was confirmed in each patient by an experienced operator and no degree of manual correction was necessary. This was mostly due to the particular attention dedicated in obtaining high-quality optical coherence tomography (OCT) scans, with signal quality >25 in mostly young patients with transparent optic media and presenting only minor refraction defects. We believe that manual correction of the segmentation is necessary in some cases, but it may introduce an important operator-related bias. Our aim was to evaluate a significantly larger retinal area as compared to that measured by the Early Treatment Diabetic Retinopathy Study grid. As such, the posterior pole scan may contain more information useful for the morpho-functional analysis. For this reason, we developed a fundus perimetry pattern which accurately matched the retinal posterior pole OCT scan, to obtain a better topographic correlation between structural and functional results. In addition to the standard automated perimetry (SAP) evaluation, we used fundus perimetry. This technique allows automated follow-up analogous to the SD-OCT, which is topographically more accurate than SAP. Both SD-OCT and fundus perimetry are landmark-based methods that use eye-tracking technology, bringing two main advantages: firstly, allowing structural evaluation of a significant amount of functionally important retinal layers, beyond the papillo-macular bundle alone, as illustrated in the discussion section of our paper (Cesareo et al. 2017); secondly, reducing a significant amount of noise and fluctuation, intrinsic to the SAP examination. Our main findings included a significant reduction of the ganglion cell layer thickness in the whole posterior pole. Furthermore, our data allowed us to construct a morpho-functional matrix that we consider useful in the investigation of the natural history of ADOA in our patients. Lastly, we described a slight but significant thickening of the outer plexiform layer and outer nuclear layer (ONL). We therefore hypothesized that this finding was due to reactive gliosis (or possible reactive hypertrophy of the Müller cells) spanning the entire retinal thickness. This is consistent with the finding of hyperreflective dots in 4 of 11 ADOA patients at the level of the parafoveal ONL. Another possible explanation of such diverse findings may lie in the different genetic background (i.e. different mutations) observed in our patients and/or in, yet unknown, modifier factors governing phenotypic variability in ADOA.