Modulation of Retinal Atrophy With Rituximab in Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011933
Author(s):  
Jeffrey Lambe ◽  
Hunter Risher ◽  
Angeliki G. Filippatou ◽  
Olwen C. Murphy ◽  
Elias S. Sotirchos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ganglion Cell ◽  
Plexiform Layer ◽  
Rate Of Change ◽  
Uncontrolled Hypertension ◽  
Inner Plexiform Layer ◽  
Disease Modifying Therapy ◽  
Retinal Atrophy ◽  
The Difference

Objective:To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of RRMS patients on rituximab, and compared rates of ganglion cell+inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)- and natalizumab-treated RRMS patients, and healthy controls (HCs).Methods:In this observational study, patients with RRMS treated with a single disease-modifying therapy, and HCs, were followed with serial OCT for a median duration of 2.8 years. Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT, or during follow-up, were excluded. Statistical analyses were performed using linear mixed-effects regression.Results:During the overall follow-up period, rates of GCIPL atrophy were -0.28±0.11µm/yr among rituximab-treated RRMS patients (n=35). This was similar to GA-treated (n=49; -0.33±0.05µm/yr; p=0.69) and natalizumab-treated patients (n=88; -0.17±0.10µm/yr; p=0.13), and faster than HCs (n=78; -0.15±0.03µm/yr; p=0.006). Rituximab-treated patients exhibited 0.55±0.23µm/yr faster rates of GCIPL atrophy during the first 12 months of treatment, relative to afterwards (n=25; p=0.02), during which period GCIPL atrophy rates were -0.14±0.13µm/yr.Conclusions:Retinal atrophy in RRMS is modulated by rituximab. Greater attenuation of retinal atrophy may occur after 12 months of rituximab treatment, following which time GCIPL atrophy rates are similar to those observed among natalizumab-treated RRMS patients and HCs. Our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, though should be confirmed by larger studies.Classification of evidence:This study provides Class IV evidence on the difference in rate of change of the ganglion cell+inner plexiform layer thickness in patients with RRMS, comparing rituximab to other DMTs.

scholarly journals Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis

2020 ◽  
Vol 26 (7) ◽  
pp. 843-854
Author(s):  
Angeliki G Filippatou ◽  
Jeffrey Lambe ◽  
Elias S Sotirchos ◽  
Kathryn C Fitzgerald ◽  
Andrew Aston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Body Mass Index ◽  
Body Mass ◽  
Plexiform Layer ◽  
Normal Weight ◽  
Uncontrolled Hypertension ◽  
Inner Plexiform Layer ◽  
Atrophy Rate ◽  
Spectral Domain Oct ◽  
Retinal Atrophy

Background: Studies evaluating associations between body mass index (BMI) and optical coherence tomography (OCT) measures in multiple sclerosis (MS) are lacking. Objective: To assess whether elevated BMI is associated with accelerated retinal atrophy. Methods: In this observational study, 513 MS patients were followed with serial spectral-domain OCT for a median of 4.4 years. Participants were categorized as normal weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2), and obese (BMI: ⩾30 kg/m2). Participants with diabetes mellitus or uncontrolled hypertension and eyes with optic neuritis (ON) ⩽6 months prior to baseline OCT or during follow-up were excluded. Statistical analyses were performed with mixed-effects linear regression. Results: Obese patients ( n = 146) exhibited accelerated rates of ganglion cell + inner plexiform layer (GCIPL) atrophy relative to normal weight patients ( n = 214; –0.57%/year (95% confidence interval (CI): –0.65% to –0.48%) versus –0.42%/year (95% CI: –0.49% to –0.35%); p = 0.012). GCIPL atrophy rate did not differ between overweight ( n = 153) and normal weight patients (–0.47%/year vs –0.42%/year; p = 0.41). Each 1 kg/m2 higher BMI was associated with accelerated GCIPL (–0.011%/year; 95% CI: –0.019% to –0.004%; p = 0.003) atrophy. Multivariable analyses accounting for age, sex, race, MS subtype, and ON history did not alter the above findings. Conclusions: Elevated BMI, in the absence of overt metabolic comorbidities, may be associated with accelerated GCIPL atrophy. Obesity, a modifiable risk factor, may be associated with accelerated neurodegeneration in MS.

scholarly journals Tracking changes over time in retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in multiple sclerosis

2014 ◽  
Vol 20 (10) ◽  
pp. 1331-1341 ◽  
Author(s):  
Divya Narayanan ◽  
Han Cheng ◽  
Karlie N Bonem ◽  
Roberto Saenz ◽  
Rosa A Tang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ganglion Cell ◽  
Layer Thickness ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Fiber Layer ◽  
Cross Sectional ◽  
Permanent Disability ◽  
Progressive Neurodegeneration

Background: Neurodegeneration plays an important role in permanent disability in multiple sclerosis (MS). Objective: The objective of this paper is to determine whether progressive neurodegeneration occurs in MS eyes without clinically evident inflammation. Methods: Retinal nerve fiver layer thickness (RNFLT) and ganglion cell-inner plexiform layer thickness (GCIPT) were measured using Cirrus optical coherence tomography (OCT) in 133 relapsing–remitting MS (RRMS) patients (149 non-optic neuritis (ON), 97 ON eyes, last ON ≥6 months). Ninety-three patients were scanned at two visits. Percentages of abnormal GCIPT vs RNFLT (<5% of machine norms) in cross-sectional data were compared. Relations between RNFLT/GCIPT and MS duration (cross-sectional) and follow-up time (longitudinal) were assessed. Results: GCIPT was abnormal in more eyes than RNFLT (27% vs 16% p = 0.004 in non-ON, 82% vs 72% p = 0.007 in ON). RNFLT and GCIPT decreased with MS duration by −0.49 µm/yr ( p = 0.0001) and −0.36 ( p = 0.005) for non-ON; −0.52 ( p = 0.003) and −0.41 ( p = 0.007) for ON. RNFLT and GCIPT decreased with follow-up time by −1.49 µm/yr ( p < 0.0001) and −0.53 ( p = 0.004) for non-ON, −1.27 ( p = 0.002) and −0.49 ( p = 0.04) for ON. Conclusions: In RRMS eyes without clinically evident inflammation, progressive loss of RNFLT and GCIPT occurred, supporting the need for neuroprotection in addition to suppression of autoimmune responses and inflammation.

scholarly journals The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients

2017 ◽  
Vol 25 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Anna M Pietroboni ◽  
Laura Dell’Arti ◽  
Michela Caprioli ◽  
Marta Scarioni ◽  
Tiziana Carandini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Gray Matter Volume ◽  
Brain Magnetic Resonance Imaging ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Fiber Layer ◽  
Cortical Regions ◽  
Multiple Sclerosis Patients

Background: The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized. Objectives: To evaluate retinal pathology using optical coherence tomography (OCT) and to investigate possible associations between retinal layers’ thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS. Methods: A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). Results: Compared to controls, patients’ macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced ( p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning ( p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex ( p < 0.005). Conclusion: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.

scholarly journals Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning

2019 ◽  
Vol 26 (11) ◽  
pp. 1360-1371 ◽  
Author(s):  
Elias S Sotirchos ◽  
Angeliki Filippatou ◽  
Kathryn C Fitzgerald ◽  
Sara Salama ◽  
Santiago Pardo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Ganglion Cell ◽  
Plexiform Layer ◽  
Cross Sectional Study ◽  
Aquaporin 4 ◽  
Inner Plexiform Layer ◽  
Cross Sectional ◽  
Visual Outcomes ◽  
Spectral Domain Oct

Background: Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited. Objective: To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON). Methods: In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed. Results: AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (−22.3 ± 3.9 letters; p < 0.001) and MS-ON eyes (−21.7 ± 4.0 letters; p < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (−9.1 ± 2.0 µm; p < 0.001) and MOG-ON (−7.6 ± 2.2 µm; p = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (−16.5 ± 1.5 letters per 10 µm decrease; p < 0.001) and MS-ON eyes (−8.5 ± 2.3 letters per 10 µm decrease; p < 0.001), but not in MOG-ON eyes (−5.2 ± 3.8 letters per 10 µm decrease; p = 0.17), and these relationships differed between the AQP4-ON and other ON groups ( p < 0.01 for interaction). Conclusion: AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.

Macular ganglion cell–inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis

2020 ◽  
pp. 135245852093572 ◽  
Author(s):  
Gabriel Bsteh ◽  
Klaus Berek ◽  
Harald Hegen ◽  
Patrick Altmann ◽  
Sebastian Wurth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ganglion Cell ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Operating Characteristics ◽  
Disability Progression ◽  
Prospective Longitudinal Study ◽  
Increased Risk ◽  
Prospective Longitudinal ◽  
Relapsing Multiple Sclerosis

Background: Macular ganglion cell–inner plexiform layer (mGCIPL) is an emerging biomarker of neuroaxonal degeneration in multiple sclerosis (MS). Objective: We aimed to determine cut-off values of mGCIPL thinning for discriminating between progressing and stable patients in relapsing multiple sclerosis (RMS). Methods: This is a 3-year prospective longitudinal study on 183 RMS patients with annual optical coherence tomography. Best possible cut-off values of baseline mGCIPL and annual loss of macular ganglion cell–inner plexiform layer (aLmGCIPL) for discriminating clinically progressing (physical progression or cognitive decline) from stable patients were defined by receiver operating characteristics analysis and tested using multivariate regression models. Results: Baseline mGCIPL thickness <77 µm was associated with an increased risk (hazard ratio: 2.7, 95% confidence interval (CI): 1.5–4.7, p < 0.001) of disability progression. An aLmGCIPL cut-off ⩾1 µm accurately identified clinically progressing patients (87% sensitivity at 90% specificity) and was a strong predictor of clinical progression (odds ratio: 18.3, 95% CI: 8.8–50.3). Conclusion: We present evidence that cross-sectionally measured mGCIPL thickness and annualized thinning rates of mGCIPL are able to identify clinically progressing RMS with high accuracy.

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