To develop consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results.
A panel of experienced OCT researchers (including 11 neurologists, 2 ...ophthalmologists, and 2 neuroscientists) discussed requirements for performing and reporting quantitative analyses of retinal morphology and developed a list of initial recommendations based on experience and previous studies. The list of recommendations was subsequently revised during several meetings of the coordinating group.
We provide a 9-point checklist encompassing aspects deemed relevant when reporting quantitative OCT studies. The areas covered are study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition data analysis, recommended nomenclature, and statistical analysis.
The Advised Protocol for OCT Study Terminology and Elements recommendations include core items to standardize and improve quality of reporting in quantitative OCT studies. The recommendations will make reporting of quantitative OCT studies more consistent and in line with existing standards for reporting research in other biomedical areas. The recommendations originated from expert consensus and thus represent Class IV evidence. They will need to be regularly adjusted according to new insights and practices.
Summary Background Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre ...layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. Methods In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. Findings 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5–5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36–3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63–8·91; p=0·002). We did not identify meaningful associations for macular volume. Interpretation Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. Funding Instituto de Salud Carlos III.
Objectives:
The aim of this study was to find, using spectral domain-optical coherence tomography (SD-OCT), retinal imaging biomarkers differentiating neuromyelitis optica spectrum disorder (NMOSD), ...multiple sclerosis (MS) and healthy controls (HCs).
Materials and methods:
The population was composed of patients with NMOSD (n=23) or MS (n=110) and of HCs (n=75). Evaluation criteria were retinal thickness/volume, visual acuity, low contrast vision acuity and Expanded Disability Status Scale score.
Results:
Considering all eyes and after statistical adjustments including the number of optic neuritis (ON) episodes, we found that NMOSD patients did not have significantly more retinal atrophy than MS patients; whereas MS non-optic neuritis (NON) eyes had thinner temporal (p=0.032) and temporo-superior peripapillary retinal nerve fibre layer (pRNFL; p=0.011) thicknesses than NMOSD NON eyes; in addition, NMOSD NON eyes presented significant naso-inferior pRNFL (p=0.024), temporal pRNFL (p=0.039), macular ganglion cell complex (p=0.004) and ganglion cell layer (p=0.002) atrophy vs HC eyes. We identified significant correlations between visual and clinical disability and retinal thicknesses in both diseases.
Conclusion:
OCT may help to differentiate NMOSD and MS by focusing on the NON eyes (temporal pRNFL atrophy more severe in MS). Moreover, we discuss the possibility of a retinal degenerative process independent of ON in NMOSD.
Cerebrovascular ischemic events (CIE) are among the most severe complications of giant cell arteritis (GCA). Heterogeneity between different studies in the definition of GCA-related CIE leads to ...uncertainty regarding their real prevalence. The aim of our study was to evaluate the prevalence and describe the characteristics of GCA-related CIE in a well-phenotyped cohort completed by a meta-analysis of the existing literature.
In this retrospective study performed in the Lille University Hospital, all consecutive patients with GCA according to American College of Rheumatology (ACR) diagnostic criteria were included from January 1, 2010, to December 31, 2020. A systematic review of the literature using MEDLINE and EMBASE was performed. Cohort studies of unselected GCA patients reporting CIE were included in the meta-analysis. We calculated the pooled summary estimate of GCA-related CIE prevalence.
A total of 271 GCA patients (89 males, mean age 72 ± 9 years) were included in the study. Among them, 14 (5.2%) presented with GCA-related CIE including 8 in the vertebrobasilar territory, 5 in the carotid territory, and 1 patient having multifocal ischemic and hemorrhagic strokes related to intra-cranial vasculitis. Fourteen studies were included in the meta-analysis, representing a total population of 3553 patients. The pooled prevalence of GCA-related CIE was 4% (95% CI 3-6, I
= 68%). Lower body mass index (BMI), vertebral artery thrombosis on Doppler US (17% vs 0.8%, p = 0.012), vertebral arteries involvement (50% vs 3.4%, p < 0.001) and intracranial arteries involvement (50% vs 1.8%, p < 0.001) on computed tomography angiography (CTA) and/or magnetic resonance angiography (MRA), and axillary arteries involvement on positron emission computed tomography (PET/CT) (55% vs 20%, p = 0.016) were more frequent in GCA patients with CIE in our population.
The pooled prevalence of GCA-related CIE was 4%. Our cohort identified an association between GCA-related CIE, lower BMI, and vertebral, intracranial, and axillary arteries involvement on various imaging modalities.
Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction ...between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS network found 32 patients receiving rituximab as first-line therapy. Main measures were number of relapse-free patients, changes in the annualized relapse rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO patients were 45 ± 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them had AQP4 antibodies. The median disease duration was 6.5 months (1–410), the mean EDSS was 5.8 ± 2.4 and the mean ARR was 3.8 ± 4.3. After rituximab with a mean follow-up of 28.7 ± 21 months, twenty-seven patients (84.3 %) were relapse free. Patients presented a 97 % decrease of ARR (
p
= 0.00001). EDSS decreased significantly to 3.9 ± 2.6 (
p
= 0.01). No relevant side effect was noted. New retrospective data are presented on RTX use in NMOSD. When used as first-line therapy RTX is highly effective and well tolerated.
Serum antibodies against myelin-oligodendrocyte-glycoprotein (MOG-IgG) are detectable in a proportion of patients with acute or relapsing neuroinflammation. It is unclear, if neuro-axonal damage ...occurs only in an attack-dependent manner or also progressively. Therefore, this study aimed to investigate longitudinally intra-retinal layer changes in eyes without new optic neuritis (ON) in MOG-IgG-seropositive patients.
We included 38 eyes of 24 patients without ON during follow-up (F/U) median years (IQR) 1.9 (1.0-2.2) and 56 eyes of 28 age- and sex-matched healthy controls (HC). The patient group's eyes included 18 eyes without (Eye
) and 20 eyes with history of ON (Eye
). Using spectral domain optical coherence tomography (OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIP), inner nuclear layer (INL), and macular volume (MV). High-contrast visual acuity (VA) was assessed at baseline.
At baseline in Eye
, pRNFL (94.3 ± 15.9 μm, p = 0.36), INL (0.26 ± 0.03 mm
, p = 0.11), and MV (2.34 ± 0.11 mm
, p = 0.29) were not reduced compared to HC; GCIP showed thinning (0.57 ± 0.07 mm
; p = 0.008), and VA was reduced (logMAR 0.05 ± 0.15 vs. - 0.09 ± 0.14, p = 0.008) in comparison to HC. Longitudinally, we observed pRNFL thinning in models including all patient eyes (annual reduction - 2.20 ± 4.29 μm vs. - 0.35 ± 1.17 μm, p = 0.009) in comparison to HC. Twelve Eye
with other than ipsilateral ON attacks ≤ 6 months before baseline showed thicker pRNFL at baseline and more severe pRNFL thinning in comparison to 6 Eye
without other clinical relapses.
We observed pRNFL thinning in patients with MOG-IgG during F/U, which was not accompanied by progressive GCIP reduction. This effect could be caused by a small number of Eye
with other than ipsilateral ON attacks within 6 months before baseline. One possible interpretation could be a reduction of the swelling, which could mean that MOG-IgG patients show immune-related swelling in the CNS also outside of an attack's target area.
Background:
Optic nerve involvement is not considered in dissemination in space (DIS) or time (DIT) of multiple sclerosis (MS) lesions.
Objectives:
To evaluate frequency of optic nerve involvement ...using three-dimensional (3D)-double inversion recovery (DIR) sequence in clinically isolated syndrome (CIS) and to measure its relationship with DIS and DIT (2010 and 2017 McDonald criteria).
Methods:
From November 2013 to August 2016, 57 CIS patients underwent 3T-magnetic resonance imaging (3T-MRI) including 3D-DIR sequence and optical coherence tomography (OCT) at 3 months after CIS. We assessed signal abnormalities of the optic nerves on DIR sequence and collected data for DIS and DIT criteria according to 2010 and 2017 McDonald criteria.
Results:
Among the 57 recruited patients, the presence of ⩾1 DIR hypersignal in optic nerve was observed in 36 (63%; 48 optic nerves) including asymptomatic hypersignal in 22 (38.5%; 25 optic nerves). Optic nerve involvement was significantly associated with DIT (p = 0.006) and MS according to 2010 criteria (p = 0.01) but was not significantly associated with presence of DIS criteria according to 2010 and 2017 McDonald criteria. We identified a significant (p < 0.001) temporal peripapillary retinal nerve fiber layer thinning on eyes with optic nerve involvement versus healthy controls.
Conclusions:
Optic nerve involvement is very frequent at the earliest clinical stage of MS. It is associated with the presence of asymptomatic gadolinium-enhancement and retinal axonal loss and may reflect the inflammatory disease activity level.
Background:
Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS).
Objectives:
To evaluate the time of onset of secondary progressive phase in ...patients with an RRMS treated with NTZ and to investigate predictive factors.
Methods:
TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0.
Results:
770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor.
Conclusion:
In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.
Background
Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve ...disability in patients with progressive MS.
Objective
The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss.
Methods
The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye visual acuity (VA) below 0.5 decimal chart were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed.
Results
Ninety-three patients received MD1003 (
n
= 65) or placebo (
n
= 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (
p
= 0.66) with MD1003 (− 0.061 logMAR, + 3.1 letters) than with placebo (− 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (− 0.058 logMAR) with MD1003 and worsened by − 1.5 letters (+ 0.029 logMAR) with placebo (
p
= 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo.
Conclusions
MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated.
Trial registration
EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244
Funding
MedDay Pharmaceuticals.
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