On the other hand, there are minor differences between our findings and theirs. For example, they observed a greater prominence of the OLM in their region A, a region with an otherwise approximately normal retina. In general, this was not apparent in the scans we analyzed. However, probably the biggest difference between our framework and theirs concerns the thickness of the INL. In their framework, as the retina progressed from normal (their region A) to severe field loss, the INL thickened to a level above normal limits, while the ONL decreased to the point where it was no longer detectable.
1 In our study, in general the INL had approximately normal thickness throughout the transition from normal to severely affected retina. Even in the three patients who showed an apparent thickening of the INL in the temporal retina, this thickening was not region specific (
Fig. 5B). On the other hand, it is clear that an INL thickening can occur in both humans (cf.
Figs. 5 and
6B in Aleman et al.)
2 and animals (cf. Fig. 7 in Aleman et al.).
2 Thus, we must ask why is it not more common in our results. There are at least three possible reasons. First, although we take the Jacobson et al.
1 framework as our starting point, in fairness they make no claims about the frequencies of their different regions, including the thickening of the INL layer, across patients. Second, most of the INL thickening they have reported occurred beyond 4 mm from the foveal center, while our transition zones are within 3 mm. Thus, our framework needs testing in patients with transition zones beyond the central 3 mm, where the INL thickening may be more common. Finally, as they
1,2,15 point out, a thickening of the hyporeflective layer identified as the INL may represent intermingled INL and residual ONL nuclei, as can be seen in the animal model work of this group.
2 In particular, we defined the INL as the thickness between border 3 (IPL/INL) and border 4 (INL/OPL). This is illustrated in
Figure 6A, which shows a peripheral portion of the normal scan from
Figure 1B. A similar portion of the scan from the patient in
Figure 2 is shown in
Figure 6B and again in
Figure 6C, but expanded and without segmentation lines in this case. When the INL/OPL is no longer discernable, as shown by the dark green arrows in
Figures 6B and
6C, we do not measure a thickness for the INL. That is, because we define the INL as the difference between borders 3 and 4, if border 4 is missing, as in
Figure 6B, then we do not report an INL thickness. On the other hand, the Jacobson et al.
1 framework defines the INL and ONL as the two hyporeflective regions between the RPE and vitreal borders. Thus, when the border between them is no longer present, then the single layer would be considered the INL. We find that, in the more affected regions, the INL/OPL
4 and the IS/OS
6 borders, as well as the OLM,
5 become indistinct. Because the entire region between our border 7 (OS/RPE) and our border 3 (IPL/INL) can appear hyporeflective, by the Jacobson et al. definition this is a thick INL, although as mentioned above they point out that this could also be an intermingling of INL with residual ONL. Thus, it remains an open question as to the conditions under which the INL is normal versus when it is thicker due to a remodeling.