scholarly journals Longitudinal optical coherence tomography study of optic atrophy in secondary progressive multiple sclerosis: Results from a clinical trial cohort

2017 ◽  
Vol 25 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Kimberly M Winges ◽  
Charles F Murchison ◽  
Dennis N Bourdette ◽  
Rebecca I Spain
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Optical Coherence Tomography ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Progressive Multiple Sclerosis ◽  
Optical Coherence ◽  
Whole Brain ◽  
Secondary Progressive ◽  
Sd Oct

Background: Limited prospective information exists regarding spectral-domain optical coherence tomography (SD-OCT) in secondary progressive multiple sclerosis (SPMS). Objective: Document cross-sectional and longitudinal retinal nerve fiber layer (RNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) features of an SPMS clinical trial cohort. Methods: Prospective, observational study using a 2-year randomized placebo-controlled SPMS trial cohort with yearly SD-OCT testing. Post hoc analysis determined influences of optic neuritis (ON), disease duration, and baseline SD-OCT on annualized atrophy rates and on correlations between OCT and brain atrophy. Results: Mean RNFL and GCIPL values of patients ( n = 47, mean age = 59 years, mean disease duration = 30 years) were significantly lower among eyes with prior ON than those without (no history of ON (NON)). Annualized RNFL (−0.31 µm/year) and GCIPL (−0.29 µm/year) atrophy rates did not differ between ON and NON eyes. Baseline RNFL thickness >75 µm was associated with greater annualized RNFL atrophy (−0.85 µm/year). Neither RNFL nor GCIPL atrophy correlated with whole-brain atrophy. Conclusion: This study suggests that eyes with and without ON history may be pooled for atrophy analysis in SPMS clinical trials using SD-OCT. Low baseline RNFL, small retinal atrophy rates, and lack of correlation with whole-brain atrophy in this population are important trial design considerations.

Retinal Optical Coherence Tomography Metrics Are Unchanged in Verubecestat Alzheimer’s Disease Clinical Trial but Correlate with Baseline Regional Brain Atrophy

2021 ◽  
Vol 79 (1) ◽  
pp. 275-287
Author(s):  
Robert C. Sergott ◽  
Annaswamy Raji ◽  
James Kost ◽  
Cyrille Sur ◽  
Saheeda Jackson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Optical Coherence Tomography ◽  
Nerve Fiber ◽  
Retinal Nerve Fiber Layer ◽  
Brain Atrophy ◽  
Retinal Thickness ◽  
Optical Coherence ◽  
Fiber Layer ◽  
Nerve Fiber Layer ◽  
Retinal Nerve Fiber

Background: We performed exploratory analyses of retinal thickness data from a clinical trial of the AβPP cleaving enzyme (BACE) inhibitor verubecestat in patients with Alzheimer’s disease (AD). Objective: To evaluate: 1) possible retinal thickness changes following BACE inhibition; and 2) possible association between retinal thickness and brain atrophy. Methods: Retinal thickness was measured using spectral-domain optical coherence tomography in a 78-week randomized placebo-controlled trial of verubecestat in 1,785 patients with mild-to-moderate AD. Changes from baseline in retinal pigment epithelium, macular grid retinal nerve fiber layer, central subfield retinal thickness, and macular grid volume were evaluated for verubecestat versus placebo. Correlation analyses were performed to investigate the potential association between macular grid retinal nerve fiber layer and central subfield retinal thickness with brain volumetric magnetic resonance imaging (vMRI) data at baseline, as well as correlations for changes from baseline at Week 78 in patients receiving placebo. Results: Verubecestat did not significantly alter retinal thickness during the trial compared with placebo. At baseline, mean macular grid retinal nerve fiber layer and central subfield retinal thickness were weakly but significantly correlated (Pearson’s r values≤0.23, p-values < 0.01) with vMRI of several brain regions including whole brain, hippocampus, and thalamus. At Week 78, correlations between retinal thickness and brain vMRI changes from baseline in the placebo group were small and mostly not statistically significant. Conclusion: BACE inhibition by verubecestat was not associated with adverse effects on retinal thickness in patients with mild-to-moderate AD. Correlations between retinal thickness and brain volume were observed at baseline. Trial registration: Clinicaltrials.gov NCT01739348 (registered December 3, 2012; https://clinicaltrials.gov/ct2/show/NCT01739348).

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study

2008 ◽  
Vol 15 (2) ◽  
pp. 204-211 ◽  
Author(s):  
G Tedeschi ◽  
D Dinacci ◽  
M Comerci ◽  
L Lavorgna ◽  
G Savettieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Lesion Load ◽  
Whole Brain ◽  
Gray Matter Atrophy

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

Hopelessness Ratings in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

2002 ◽  
Vol 32 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Scott B. Patten ◽  
Luanne M. Metz
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Exact Probability ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Trial Participants ◽  
Over Time

Objective: Two recent randomized double-blind placebo controlled clinical trials of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial, evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS). Another, the SPECTRIMS trial, evaluated the same medication in secondary progressive (SP) MS. The objective of this analysis was to compare levels of hopelessness in persons with RRMS and SPMS, and to describe changes over time in the clinical trial participants. Method: Raw data from each clinical trial was obtained from the sponsor of the trials (Serono). Median BHS ratings, and the proportions at or above the BHS cut-point of 10 were calculated over a two (PRISMS) or three (SPECTRIMS) year period. Results: The analysis included n = 532 clinical trial participants. Ratings of hopelessness were higher in SPMS clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness were higher during follow-up than at baseline, in the SPMS group (McNemar's exact probability, p = 0.0015), but not in the RRMS group (McNemar's exact probability, p = 0.65). Depression was strongly associated with hopelessness in both RRMS ( z = 4.13, p < 0.001) and SPMS ( z = 5.24, p < 0.001). Conclusions: Hopelessness is associated with SPMS, and may increase over time in this group. Hopelessness may influence suicide risk in people with MS and may potentially have an impact on coping and quality of life. Additional research is necessary to define the clinical implications of hopelessness in persons with this condition.

scholarly journals Optical coherence tomography segmentation analysis in relapsing remitting versus progressive multiple sclerosis

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0172120 ◽  
Author(s):  
Raed Behbehani ◽  
Abdullah Abu Al-Hassan ◽  
Ali Al-Salahat ◽  
Devarajan Sriraman ◽  
J. D. Oakley ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Progressive Multiple Sclerosis ◽  
Optical Coherence ◽  
Segmentation Analysis ◽  
Relapsing Remitting

scholarly journals Effects of ibudilast on MRI measures in the phase 2 SPRINT-MS study

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011314
Author(s):  
Robert T Naismith ◽  
Robert A Bermel ◽  
Christopher S Coffey ◽  
Andrew D Goodman ◽  
Janel Fedler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Secondary Analysis ◽  
Progressive Multiple Sclerosis ◽  
Whole Brain ◽  
T2 Lesions ◽  
Gray Matter Atrophy ◽  
Inflammatory Processes

OBJECTIVE:For progressive forms of multiple sclerosis, determine whether ibudilast has an effect on brain volume and new lesions.METHODS:A randomized, placebo controlled, blinded study evaluated ibudilast at a dose of up to 100 mg over 96 weeks in primary and secondary progressive multiple sclerosis. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks. Whole brain atrophy measured by SIENA was a sensitivity analysis.RESULTS:129 participants were assigned to ibudilast and 126 to placebo. New or enlarging T2 lesions were observed in 37.2% on ibudilast and 29.0% on placebo (p=0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (p=0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs. placebo (p=0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (p=0.08).CONCLUSIONS:Ibudilast treatment was associated with a reduction in gray matter atrophy. Ibudilast treatment was not associated with a reduction in new or enlarging T2 lesions, or new T1 lesions. An effect on brain volume contributes to prior data that ibudilast appears to impact markers associated with neurodegenerative processes, but not inflammatory processes.Classification of Evidence:This study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions, or new T1 lesions.

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