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ObjectiveTo evaluate whether a retinal spectral-domain optical coherence tomography (SD-OCT) assessment at baseline is associated with long-term disability worsening in people with multiple sclerosis (PwMS), we performed SD-OCT and Expanded Disability Status Scale (EDSS) assessments among 132 PwMS at baseline and at a median of 10 years later.MethodsIn this prospective, longitudinal study, participants underwent SD-OCT, EDSS, and visual acuity (VA) assessments at baseline and at follow-up. Statistical analyses were performed using generalized linear regression models, adjusted for age, sex, race, multiple sclerosis (MS) subtype, and baseline disability. We defined clinically meaningful EDSS worsening as an increase of ≥2.0 if baseline EDSS score was ResultsA total of 132 PwMS (mean age 43 years; 106 patients with relapsing-remitting MS) were included in analyses. Median duration of follow-up was 10.4 years. In multivariable models excluding eyes with prior optic neuritis, relative to patients with an average baseline ganglion cell + inner plexiform layer (GCIPL) thickness ≥70 µm (the mean GCIPL thickness of all eyes at baseline), an average baseline GCIPL thickness p = 0.02) and an almost 3-fold increased odds of low-contrast VA worsening (adjusted OR 2.93, 95% CI 1.40–6.13; p = 0.04).ConclusionsLower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS. Accordingly, SD-OCT at a single time point may help guide therapeutic decision-making among individual PwMS.Classification of EvidenceThis study provides Class I evidence that lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS.

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.

ObjectiveTo 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 patients with RRMS 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 patients with RRMS and healthy controls (HCs).MethodsIn 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.ResultsDuring the overall follow-up period, rates of GCIPL atrophy were −0.28 ± 0.11 µm/y among rituximab-treated patients with RRMS (n = 35). This was similar to GA-treated (n = 49; −0.33 ± 0.05 µm/y; p = 0.69) and natalizumab-treated patients (n = 88; −0.17 ± 0.10 µm/y; p = 0.13) and faster than HCs (n = 78; −0.15 ± 0.03 µm/y; p = 0.006). Rituximab-treated patients exhibited 0.55 ± 0.23 µm/y 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 ± 0.13 µm/y.ConclusionsRetinal 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 patients with RRMS and HCs. Our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, which should be confirmed by larger studies.Classification of EvidenceThis study provides Class IV evidence on the difference in rate of change of the GCIPL thickness in patients with RRMS comparing rituximab to other disease-modifying therapies.

OBJECTIVE Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing-remitting multiple sclerosis (RRMS). METHODS 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years. RESULTS The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (-0.34 ± 0.09%/yr, p

Background The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes. Methods Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI. Results OD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s, P = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s, P = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar (r = 0.84, P

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 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.

OBJECTIVES: Using optic coherence tomography (OCT), to determine relationships with visual function (VF) and disability in patients with multiple sclerosis (MS) and a) ganglion cell-inner plexiform layer (GCIPL) b) peripapillary retinal nerve fiber layer (pRNFL); and c) Bruch’s membrane opening minimum rim width (BMO-MRW) thicknesses. METHODS: Sixty-eight MS patients and 22 healthy controls (HCs) underwent spectral-domain OCT, and 100%-contrast visual acuity (VA), 2.5%-, and 1.25%-contrast letter-acuity (LA), and Expanded Disability Status Scale (EDSS) testing. Mixed-effects linear regression models, accounting for within-subject, inter-eye correlations, were used to assess relationships. RESULTS: The MS cohort exhibited significantly lower BMO-MRW (p=0.01), pRNFL at 3.7 mm, 4.1 mm, and 4.7 mm diameters surrounding the optic disc (p

Background: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. Objective: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. Methods: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. Results: A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (−0.15% vs −0.81%; p = 0.001) and putaminal (−0.27% vs −0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. Conclusion: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.

PURPOSE: Optical coherence tomography (OCT) is a reliable method used to quantify discrete layers of the retina. Spectralis OCT is a device used for this purpose. Spectralis OCT macular scan imaging acquisition can be obtained either on the horizontal or vertical plane. The vertical protocol has been proposed as favorable, due to postulated reduction in confound of Henle’s fibers on segmentation derived metrics. Yet, agreement of segmentation measures of horizontal and vertical macular scans remains unexplored. Our aim was to determine this agreement. MATERIALS AND METHODS: Horizontal and vertical macular scans on Spectralis OCT were acquired in 20 healthy controls (HCs) and 20 multiple sclerosis (MS) patients. All scans were segmented using Heidelberg software and a Johns Hopkins University (JHU) developed method. Agreement was analyzed using Bland Altman analyses and intra-class correlation coefficients (ICCs). RESULTS: Using both segmentation techniques, mean differences (agreement at the cohort level) in thicknesses of all macular layers derived from both acquisition protocols in MS patients and HCs were narrow (