148
D. Cabrera DeBuc et al.
and prognostic biomarkers that can predict clinical progress. In addition, the authors
reported that the outer retina showed no significant differences between the groups
which was in contrast with Somfai et al. earlier report showing significant FD changes
in diabetic patients where, similarly, neurodegeneration was a proposed mechanism
in the background of the observed changes [17]. This could point to the fact of a
different disease mechanism at the level of the photoreceptors.
The observed differences in optical properties in Varga et al. study can be related
both to circulation or inflammatory alterations of the inner retina. There is only little
evidence about the changes in microcirculation of the retina in MS. A recent study by
Wang et al. using OCT angiography showed significantly reduced flow index around
the ONH in eyes after ON compared to healthy controls but no differences were
shown in the parafoveal circulation [146]. Although this may suggest that our observations were most possibly not influenced by alterations in macular microcirculation,
recent results also using hemodynamic information have revealed retinal impaired
microcirculation in the macular region [147–150]. Therefore, further investigation is
needed to better characterize the structure-function relationship in MS. On the other
hand, inflammation may presumably be present also in the retina, possibly supported
by the “inside-out” theory of MS, namely the migration of autoreactive T cells across
the blood-brain barrier from the systemic circulation leading to inflammation [146].
The blood-retina barrier is very like the blood-brain barrier and indeed, the histological study by Green et al. described inflammatory cellular infiltrates surrounding
retinal veins in the connective tissue of the RNFL and GCL in 29% of the relapsing remitting and secondary MS eyes [125]. It should be noted, however, that the
observed inflammation was more localized (i.e. not in all vessels or the entire retina)
than the neurodegeneration observed which makes the direct correlation with our
observed trends questionable in terms of revealing inflammatory alterations present
or not in our study data. However, considering that the inner capillary network lies in
the GCL and the outer capillary network runs from the IPL to the OPL through the
INL, the significant differences observed between the study groups when analyzing
reflectance and texture descriptors of the RNFL and GCL+IPL complex should be
further explored in a larger study and correlated to microvasculature measurements
(e.g. blood flow velocity and perfusion) using advanced optical imaging technologies
[146, 151, 152]. Investigating these two capillary networks in relation to structural,
optical and functional measures may provide a much better insight to determine the
role of the retinal microcirculation (i.e. capillaries, arterioles and venules) in the
increased risk of progression of MS in the presence of vascular comorbidities [153].
Although optical properties of the retinal tissue are not standardized measures for
detecting pathological changes of the retina, in contrast to thickness measurements,
reflectance-based measures are direct measures obtained from OCT images. Therefore, it is expected that these additional properties along with thickness information
could facilitate a better diagnosis of retinal diseases.
D. Cabrera DeBuc et al.
and prognostic biomarkers that can predict clinical progress. In addition, the authors
reported that the outer retina showed no significant differences between the groups
which was in contrast with Somfai et al. earlier report showing significant FD changes
in diabetic patients where, similarly, neurodegeneration was a proposed mechanism
in the background of the observed changes [17]. This could point to the fact of a
different disease mechanism at the level of the photoreceptors.
The observed differences in optical properties in Varga et al. study can be related
both to circulation or inflammatory alterations of the inner retina. There is only little
evidence about the changes in microcirculation of the retina in MS. A recent study by
Wang et al. using OCT angiography showed significantly reduced flow index around
the ONH in eyes after ON compared to healthy controls but no differences were
shown in the parafoveal circulation [146]. Although this may suggest that our observations were most possibly not influenced by alterations in macular microcirculation,
recent results also using hemodynamic information have revealed retinal impaired
microcirculation in the macular region [147–150]. Therefore, further investigation is
needed to better characterize the structure-function relationship in MS. On the other
hand, inflammation may presumably be present also in the retina, possibly supported
by the “inside-out” theory of MS, namely the migration of autoreactive T cells across
the blood-brain barrier from the systemic circulation leading to inflammation [146].
The blood-retina barrier is very like the blood-brain barrier and indeed, the histological study by Green et al. described inflammatory cellular infiltrates surrounding
retinal veins in the connective tissue of the RNFL and GCL in 29% of the relapsing remitting and secondary MS eyes [125]. It should be noted, however, that the
observed inflammation was more localized (i.e. not in all vessels or the entire retina)
than the neurodegeneration observed which makes the direct correlation with our
observed trends questionable in terms of revealing inflammatory alterations present
or not in our study data. However, considering that the inner capillary network lies in
the GCL and the outer capillary network runs from the IPL to the OPL through the
INL, the significant differences observed between the study groups when analyzing
reflectance and texture descriptors of the RNFL and GCL+IPL complex should be
further explored in a larger study and correlated to microvasculature measurements
(e.g. blood flow velocity and perfusion) using advanced optical imaging technologies
[146, 151, 152]. Investigating these two capillary networks in relation to structural,
optical and functional measures may provide a much better insight to determine the
role of the retinal microcirculation (i.e. capillaries, arterioles and venules) in the
increased risk of progression of MS in the presence of vascular comorbidities [153].
Although optical properties of the retinal tissue are not standardized measures for
detecting pathological changes of the retina, in contrast to thickness measurements,
reflectance-based measures are direct measures obtained from OCT images. Therefore, it is expected that these additional properties along with thickness information
could facilitate a better diagnosis of retinal diseases.