Optical coherence tomography reflects brain atrophy in multiple sclerosis: A four‐year study

Abstract

Objective The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). Methods Cirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46 months). Three-Tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. Results Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r = 0.45; p<0.001), gray matter (GM; r = 0.37; p<0.001), white matter (WM; r = 0.28; p = 0.007), and thalamic (r = 0.38; p < 0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r = 0.67; p<0.001) than relapsing-remitting MS (RRMS; r = 0.33; p = 0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r = −0.30; p = 0.02) and inner nuclear layer (r = −0.25; p = 0.04) atrophy rates. Interpretation Over time GCIP atrophy appears to mirror whole-brain, and particularly GM, atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials.

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

“…6,17,18 Despite the lack of head-to-head studies directly comparing the efficacy of NAT to other DMTs in RRMS, the overall consensus based on available data and clinical experience is that NAT is one of the most effective RRMS therapies currently available. Considering the potent effects of NAT in reducing CNS inflammation, with the consequential effect of reducing brain atrophy, it is not surprising that NAT could play a similar role in reducing retinal thinning, and in particular GCIP atrophy, which has been shown to mirror global atrophy over time in MS. 8 Indeed, our findings suggest that NAT has Retinal layer thickness changes were analyzed using mixed-effects linear regression adjusting for age at baseline, disease duration at baseline, sex, gap time, and relapse during follow-up, accounting for within-subject intereye correlations and the baseline thickness of the retinal layer of interest, for patients whose gap time was greater than 1 year. a Significant.…”

“…Prior studies demonstrate that OCT-derived ganglion cell 1 inner plexiform layer (GCIP) thickness has superior reliability and reproducibility and correlates better with visual function and disability in MS than peripapillary retinal nerve fiber layer thickness (pRNFL). [8][9][10] Rates of GCIP thinning are accelerated in patients with MS exhibiting inflammatory activity, 11 and correlate strongly with rates of brain, particularly gray matter, atrophy over time. 8 Despite the increasing support for OCT as an outcome for assessing neurodegeneration in MS trials, whether different DMTs differentially affect retinal atrophy in MS remains to be assessed.…”

“…3 Accordingly, the effect of DMTs on MRI-derived estimates of brain atrophy is a common outcome in MS trials. [4][5][6][7] Recent studies reveal that retinal atrophy mirrors brain atrophy over time in MS. 8 However, it remains unclear whether various DMTs differentially affect retinal atrophy, similar to their varying effects upon brain atrophy. Optical coherence tomography (OCT) is a noninvasive, inexpensive, reliable, and reproducible imaging technique that generates high-resolution images of the retina, allowing most individual retinal layers to be discerned and quantified.…”

“…12 pRNFL thickness values were generated by conventional Cirrus HD-OCT software, as described elsewhere. 8 An automated macular segmentation method described in detail elsewhere, 13 with slight modifications of the size of regions from which measurements were derived, was used to compute thicknesses of the GCIP, inner nuclear layer (INL), outer nuclear layer (ONL), and average macular thickness (AMT). The segmentation method uses a validated algorithm 14 that generates thickness measurements by averaging the thickness values within a 535 mm circle centered at the fovea.…”

“…Although both ON history and baseline GCIP thickness influence overall rates of GCIP atrophy, baseline GCIP thickness explains a greater proportion of slope variance in this regard. 8 Therefore, accounting for the baseline retinal layer thickness of interest in regression models may be superior to simply adjusting for ON history.…”