OCT Variability Prevents Their Use as Robust Biomarkers in Multiple Sclerosis

Abstract

Objective: To evaluate the agreement between the peripapillary retinal nerve fiber layer (pRNFL) and foveal thickness (FT) measurements among three different spectral domainoptical coherence tomography (SD-OCT) instruments in a sample of multiple sclerosis (MS) patients and a healthy age-matched control group. Methods: An observational cross-sectional study with three groups: healthy subjects and MS patients w/w a previous clinical diagnosis of optic neuritis (ON) was conducted. The pRNFL and FT were measured using three different SD-OCT instruments (OCT PRIMUS 200 and OCT CIRRUS 500 SD-OCT [Carl Zeiss Meditec] and OCT 3D 2000 [Topcon]). Results: Twenty eyes from 10 healthy subjects matched in age with MS patients without a previous history of eye disease and 62 MS eyes from 31 MS patients (29 eyes without history of ON and 33 eyes with history of ON) were enrolled. Healthy subjects and MS patients without ON did not show differences between the pRNFL and FT thickness (P>0.99) with any of the instruments. However, MS eyes with a previous episode of ON showed thinner pRNFL and FT (P<0.01). PRIMUS and CIRRUS OCT showed better agreement of the pRNLF and FT in both healthy and MS eyes. However, 3D OCT showed less agreement in the pRNFL measurement with CIRRUS in both healthy and MS eyes. Interpretation: Although OCT is a valuable technology to improve MS patient assessment, differences between devices must be taken into account. It is necessary to create an international group that standardizes the measurement conditions and above all that provides reference bases for normal subjects.

A multi-regression approach to improve optical coherence tomography diagnostic accuracy in multiple sclerosis patients without previous optic neuritis

“…While some studies have shown a thinning in pRNFL thickness in MS patients without a history of optic neuritis ( Albrecht et al, 2012 , Gonzalez-Lopez et al, 2014 , Para-Prieto et al, 2021 , Parisi et al, 1999 , Syc et al, 2012 ), others have not found a significant difference between MS patients and controls ( Behbehani et al, 2016 , Knier et al, 2016 , Oberwahrenbrock et al, 2013 ). Most of these studies have adjusted for the age when comparing the pRNFL measurements between MS and controls.…”

“…Significant thinning of mGCIPL in non-optic neuritis eyes of MS patients is now firmly established ( Petzold et al, 2017 ). However, previous MS studies showed pRNFL thickness diagnostic sensitivity to be significantly variable, especially when considering non-optic neuritis eyes ( Albrecht et al, 2012 , Behbehani et al, 2016 , Gonzalez-Lopez et al, 2014 , Knier et al, 2016 , Oberwahrenbrock et al, 2013 , Para-Prieto et al, 2021 , Parisi et al, 1999 , Syc et al, 2012 ). A previous study reported the capacity of pRNFL thickness in assessing MS was lower as compared to mGCIPL ( Gonzalez-Lopez et al, 2014 ).…”

“…The poorer accuracy of pRNFL may be related to the wide variability of pRNFL. Indeed, interindividual variability is often wider for pRNFL parameter compared to mGCIPL ( Para-Prieto et al, 2021 ). A broad range of pRNFL measurements creates difficulties in establishing an absolute diagnostic cutoff with good sensitivity and specificity.…”