Optical coherence tomography in multiple sclerosis: A 3‐year prospective multicenter study

Abstract

Objective: To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing-remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS). Methods: Individuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6-monthly thereafter). Results: OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MSassociated optic neuritis--group differences (95% CI) over 3 years: pRNFL: À1.86 (À2.54, À1.17) µm; mGCIPL: À2.03 (À2.78, À1.28) µm (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect

Retinal layer thinning as a biomarker of long-term disability progression in multiple sclerosis

“…18,32 Regarding the latter, aLGCIPL of 0.20 µm and aLpRNFL of 0.52 µm are expected in healthy controls, 26,33,34 which is substantially lower than the mean aLGCIPL and aLpRNFL of 1.0-1.6 and 1.0-1.3 µm observed in this study, respectively. In turn, in comparison to longitudinal data provided by the abovementioned OCTiMS study, 17 aLGCIPL and aLpRNFL in our cohort were slightly higher, which may partly be explained by distinct inclusion criteria and methodological differences.…”

“…While within the OCTiMS trial, no robust association between retinal layer thinning and performance in SDMT could be demonstrated, and a recently published study observed an association between attention and executive function tests and retinal layer thickness. 17,31 Despite some advantages of GCIPL over pRNFL and more pronounced effects in EDSS than in SDMT prognostication, the findings of the present study demonstrate that the prognostic value to predict disability progression still prevails after a long-term follow-up of approximately 6 years. This prognostic potential is based on (1) smaller values of baseline thickness of retinal layers and (2) higher annual thinning rates of retinal layers.…”

“…Eyes with a history of ON more timely distant were excluded from the analysis regarding the prognostic value of baseline thicknesses but not for the analyses of longitudinal layer thinning as further retinal thinning does not differ between eyes with and without a history of ON. 16,17 Eyes suffering ON during the observation period were excluded from the study and only the values of eyes without ON during the observation period were used for calculation of retinal thinning in the analyses. 18 As ON in MS patients may occur subclinical or asymptomatic potentially confounding the prognostic value of retinal thinning, 19 we used new interocular asymmetry compared to the prior OCT with cut-off values of ⩾4 µm for GCIPL and ⩾5 µm for pRNFL, 20,21 to identify subclinical ON.…”

Clinical onset of CNS demyelinating disease after COVID-19 vaccination: denovo disease?

“…This preexisting subclinical disease leads to the fact that firstly in MRI chronic inflammation with demyelination and axonal damage may already be detectable at the time of first clinical onset ( Bjornevik, Munger, and Cortese, 2020 , Borgström et al, 2020 ). Further, cohort analyses using OCT in patients with early MS have consistently shown that retinal neuroaxonal damage is predominantly present at the initial clinical phase of MS and independent of clinical optic nerve involvement compared with matched healthy controls ( Borgström et al, 2020 , Petzold, Balcer, and Calabresi, 2017 , Martinez-Lapiscina, Arnow, and Wilson, 2016 , Paul, Calabresi, and Barkhof, 2021 ). Lastly, it is also known that the presence of CSF-specific OCBS i) has a high positive predictive value for MS and ii) is associated with a significantly increased risk of conversion to MS in patients with a clinically isolated syndrome ( Calabrese et al, 2021 ).…”

Association of Serum Neurofilament Light Chain With Inner Retinal Layer Thinning in Multiple Sclerosis

“…[5][6][7] Optical coherence tomography (OCT) allows the rapid quantification of the thickness of retinal neuroaxonal layers, and studies using OCT have demonstrated that rates of macular ganglion cell + inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thinning are accelerated in people with MS, independently of overt episodes of inflammatory activity involving the anterior visual pathway (i.e., acute optic neuritis [ON]), and are associated with longitudinal brain atrophy. [8][9][10][11] Furthermore, rates of retinal layer thinning are faster in progressive MS, as compared with relapsing-remitting MS (RRMS), with accelerated deeper retinal layer thinning (inner nuclear layer [INL] and outer nuclear layer [ONL]) appearing to be more specific features of progressive MS. 10,12,13 Given the above, OCT-derived retinal measures have been proposed as a biomarker of progressive, diffuse neurodegeneration in MS and assessing associations with sNfL is clearly of significant interest. However, only a few studies have examined this issue and have produced conflicting findings.…”