Neurodegeneration of multiple sclerosis (MS) can be measured with optic coherence tomography (OCT), as thinning of peripapillary retinal nerve fiber layer (pRNFL), or as reduced total macula volume (TMV). The macula scan can be further segmented into the ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), which are plausible markers for neuronal loss, dendritic loss, or ongoing inflammation. Unlike traditional method yields only several averaged values of the whole image, voxel-based morphometry (VBM) can visualize and compare the whole macula map, therefore it can be more sensitive in detecting focal lesions.
Here we applied VBM to macula OCT in different types of MS and compare the results with traditional parameters such as pRNFL or TMV.
Three groups of patients with CIS (N=12, 2 male, age=32±12 years, disease duration = 0.9±1.3 years), RRMS (N=9, 6 male, age=32±8 years, disease duration = 1.2±1.2 years), PPMS (N=14, 11 male, age=44±9 years, disease duration = 2.5±1.3 years) and eighteen healthy subjects (4M, age = 29±5 y) were enrolled. Eyes with histories of optic neuritis were excluded. Peripapillary and Macula volume scans were performed and segmented with Heidelberg Spectralis OCT. The segmented thickness maps of RNFL, GCL, IPL, and INL were registered to generate group maps with VBM. total macula volume(TMV) and peripapillary thickness (pRNFL) were compared with healthy with independent t-test, while voxel-wise t-tests were performed between patients and healthy maps with correction of false discovery rate(FDR).
No group difference was found in pRNFL, while the PPMS group showed significantly lower TMV of RNFL, GCL, and IPL. On the other hand, the voxel-wise comparison showed significant differences in all patients’ groups compared with healthy, while the lesion loads in RNFL and GCL showed a gradient increases from CIS to RRMS to PPMS. In the MS groups, the significant atrophy of IPL and thickening in INL co-localized at parafovea, while in CIS group the IPL atrophy located in nasal macula while the INL thickening still located at parafovea.
Our results suggest that applying VBM in macula OCT can increase the detection sensitivity of neurodegeneration in MS patients than traditional measures such as pRNFL or TMV. Also, Common neurodegenerative patterns were found in RNFL and GCL and the lesion load increases with disability, while the difference of IPL and INL differs between MS and CIS cohort and can be a potential biomarker for predicting converters.