Our study presents first data on RNFL measures in HSP patients in order to target the question whether RNFL loss can be observed unspecifically in any form of neurodegenerative disorder and whether the distribution pattern within the retina is specific for single disease entities as previously suggested
]. Interestingly, some studies investigating RNFL in different neurodegenerative diseases claimed specific patterns of RNFL loss for the different disease entities even though there are still controversial findings to report on: E.g. in idiopathic Parkinson’s disease (PD), one study showed the RNFL to be significantly reduced in the (inferior-) temporal sector
], other studies revealed statistically significant decrease of global RNFL
] or reduced inner retinal thickness (RNFL, ganglion cell and inner plexiform layer) in both inferior and superior macular fields
], while another study did not detect any statistically significant difference in measurements of retinal thickness at all
]. According to the limited amount of published data available regarding RNFL in degenerative ataxias, patients with spinocerebellar ataxias type SCA1, SCA2 and SCA3 showed decreased RNFL thickness, whereas a reduced macular thickness was found in patients with SCA 1, 3 and 6 but not SCA2
]. OCT-measurements in MSA patients showed significant reduction of RNFL in nasal quadrants compared to healthy controls
]. In contrast, patients suffering from Alzheimer’s disease featured significant RNFL decrease in the superior quadrant in one study
] while all quadrants were reported affected in another study
]. Final evidence of specific reduction patterns for each underlying neurodegenerative disorder has not yet been yielded, but most available data seem to confirm the notion that neurodegenerative/-inflammatory disorders such as AD, PD, MSA, some SCAs and MS are associated with a significant loss of retinal nerve fibres. While these observations have been gathered using different generations of OCT devices of varying axial resolution, signal to noise ratio and methods of artifact reduction, new studies from latest generation OCT devices further substantiate previous findings of significant morphological differences on a retinal level in patients with neurodegenerative/-inflammatory disorders
In this study, HSP patients, in contrast to patients with other neurodegenerative disorders showed only a tendency towards global thinning of RNFL, but no statistically significant changes. RNFL thickness (global as well as within different sectors) did not correlate with clinical severity, duration of disease or age. This is in line with the current notion of molecular pathogenesis of HSP as a length dependent axonal degeneration, which widely restricts the degenerative process to neuronal fibre tracts with the longest axons e.g. corticospinal tracts, dorsal column and peripheral nerves of the lower limbs. Even though molecular mechanisms responsible for the assumed axonal degeneration in HSP are only partially understood, our findings fit into this concept. Here we show, that retinal ganglion cell axons forming the retinal nerve fibre layer are not affected by the degenerative process in pure HSP. This finding for the first time can bring up scientific data that discards the assumption of RNFL loss being an unspecific surrogate marker for all forms of neurodegeneration.
In contrast, patients with complex forms of HSP where the disease spreads beyond the long fibre tracts presented significant thinning of RNFL especially in temporal and temporal inferior sectors. These changes reached significance despite the small number of individuals with complex HSP included in this study. However, these changes were not statistically significant after correction for multiple comparisons and need to be reproduced in a larger cohort of patients with complex HSP. This may also help to depict genotype specific effects. So far we found patients with mutations in the nuclear-encoded mitochondrial AAA metalloproteinase paraplegin causing SPG7
] to present with retinal changes. Interestingly, within the small group of SPG7-patients abnormal thinning of RNFL was restricted to the two patients with complex phenotypes.
As mitochondrial defects are thought to play a crucial role in the pathogenesis of SPG7 and affection of retinal ganglion cells as well as optical atrophy are a common feature of other mitochondriopathies
] it would be interesting to see whether thinning of the RNFL is a common feature in other mitochondriopathies. Our observation suggests that underlying mitochondrial pathology and a complex phenotype in HSP may predispose for developing optical atrophy. Further stratification of this risk potential is clearly needed in a bigger cohort of SPG7-patients but personal communication (Alexandra Dürr) suggests that RNFL is indeed frequently altered in SPG7. It would be of interest to learn whether patients with SPG31, another rare subform of HSP with mitochondrial dysfunction
] also present RNFL loss like SPG7.