Retrograde trans-synaptic degeneration of retinal ganglion cell layer (GCL) has been proposed as one of the mechanisms contributing to permanent disability after visual pathway damage. We set out to ...test this mechanism taking advantage of the new methods for imaging the macula with high resolution by optical coherence tomography (OCT) in patients with lesions in the posterior visual pathway. Additionally, we explored the association between thinning of GCL as an imaging marker of visual impairment such as visual field defects.
Retrospective case note review of patients with retrogeniculate lesions studied by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the visual fields.
We analysed 8 patients with either hemianopia or quadrantanopia due to brain lesions (stroke = 5; surgery = 2; infection = 1). We found significant thinning of the GCL in the projecting sector of the retina mapping to the brain lesion. Second, we found strong correlation between the PD of the visual field quadrant and the corresponding macular GCL sector for the right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001).
The mapping between lesions in the posterior visual pathway and their projection in the macula GCL sector corroborates retrograde trans-synaptic neuronal degeneration after brain injury as a mechanism of damage with functional consequences. This finding supports the use of GCL thickness as an imaging marker of trans-synaptic degeneration in the visual pathway after brain lesions.
Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we ...investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study.
Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.
At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients.
Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.
Objective
To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans‐synaptic degeneration in multiple ...sclerosis (MS).
Methods
We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer RNFL thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel‐based morphometry (VBM), multiple linear regressions, and general linear models.
Results
VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (β = +0.601, 95% confidence interval CI = +0.04 to +1.16), N‐acetyl aspartate in visual cortex (β = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (β = −2.551, 95% CI = −3.910 to −1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm3 in visual cortex volume predicts a reduction of 0.6μm in RNFL thickness. This association was also observed after 1 year of follow‐up. Patients with severe prior ON (adjusted difference = −3.01, 95% CI = −5.08 to −0.95) and mild prior ON (adjusted difference = −1.03, 95% CI = −3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON.
Interpretation
Our results suggest the presence of trans‐synaptic degeneration as a contributor to chronic axon damage in MS. ANN NEUROL 2014;75:98–107
Disorders of the visual system are one of the main features of multiple sclerosis (MS), and have a great impact on the quality of life of patients. Although optic neuritis is the most frequent ...manifestation, there are other ophthalmological processes not related to neuritis, a knowledge of which is very useful in the management of patients with MS. These abnormalities are described, grouped into impairments of the afferent pathway, efferent pathway, or upper cerebral areas. Additionally, the main ophthalmological side effects of the drugs currently used in the control of MS are described.
Effective management of multisymptomatic chronic diseases such as multiple sclerosis (MS) requires a multimodal, interdisciplinary approach. At MS clinics, numerous healthcare specialties are ...coordinated to provide patients with quality clinical care for all aspects of their disease. Settings and resource availability may vary between countries. Four specific specialty services from different EU countries are examined in more detail.
The multidisciplinary neurorehabilitation team in Rennes, France, provides specialized consultations (e.g. spasticity, urodynamic unit, devices), inpatient and outpatient intensive rehabilitation programs and therapeutic education. Management approaches are based on a patient's level of impairment as assessed by the Expanded Disability Status Scale. In Girona, Spain, neuropsychologists perform assessments as part of the neurological protocol for all patients with MS. Depending on the level of impairment and patients' characteristics (e.g. working or not working), cognitive deficits may be treated at home or at a neurorehabilitation center. In Barcelona, Spain, neuro-ophthalmologists are involved in the differential diagnosis and follow-up care of MS patients with visual disturbances; particular attention is given to patients' vision-related quality of life. Pain specialists at the Marianne Strauß Klinik in Berg, Germany, have developed a system for classifying MS pain syndromes and differentiating MS-related pain from non MS-related pain. Chronic pain management involves numerous disciplines and requires active engagement by patients in developing treatment plans. Key Messages: MS affects several body systems and patients invariably require specialized interdisciplinary support. Insight into services provided by various specialties and their fit within multidisciplinary care models at MS centers may facilitate the design or refinement of care models in other locations.
Purpose
To characterise the changes of the retinal layers in patients with acute anterior ischaemic optic neuropathy (AION), aiming to identify imaging markers for predicting the residual visual ...function.
Methods
This was a retrospective review of consecutive patients with unilateral AION from January 2010 to December 2013. We analysed affected eyes at baseline and 1 month later, compared to fellow healthy eyes. Utilising novel image analysis software, we conducted algorithmic segmentation in layers and division in early treatment of diabetic retinopathy study (ETDRS) quadrants of optical coherence tomography images of the macula. Pearson product moment regression analysis of retinal layer thickness and best corrected visual acuity (BCVA) in logMAR units and mean deviation of the SITA 24–2 visual field (VF) were carried out at the 1-month time point.
Results
Twenty eyes from 20 patients were included and compared to 20 healthy fellow eyes. At baseline, we found a significantly increased mean thickness of the retinal nerve fibre layer (RNFL) of 42.2 μm (±6.7SD) in AION eyes compared to 37.9 μm (±4.2 SD) in healthy eyes (p = 0.002). The outer nuclear layer (ONL) was also significantly thickened at 96.6 μm (±7.2 SD) compared to 90.8 μm (±5.7 SD) in the fellow eye (p < 0.001). After 1 month, the RNFL and the ganglion cell layer (GCL) were thinned 17.7 % to 31.2 μm (±6.4 SD), p < 0.001 and 19.3 % to 66.5 μm (±7.0 SD), p < 0.001 compared to the contralateral eye. Additionally, the ONL remained thickened at 96.7 μm (±7.0 SD, p < 0.001). At baseline, we found a significant correlation between the ONL thickness and the VF (r = −0.482, p = 0.005) and the BCVA at discharge (r = 0.552, p < 0.001), indicating that a thicker ONL correlates with poorer visual function. The GCL thickness also correlates with the BCVA at discharge (r = 0.411, p = 0.02), where a thinner GCL predicts worse BCVA. At the 1-month time point, the GCL thinning was correlated with both the VF (r = 0.471, p = 0.005) and the BCVA (r = −0.456, p = 0.007), indicating worse visual function.
Conclusions
Changes in the thickness of different layers of the retina occur early in the course of AION and evolve over time, resulting in the atrophy of the GCL and RNFL. ONL thickening at baseline is associated with visual dysfunction. Thinning of the GCL after 1 month correlates with poorer VF and BCVA at 1 month after acute AION.
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 ...protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice.
We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM).
Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli.
Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3.
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•SCA3 patients display macular and GCL thinning directly correlated with disease severity.•SCA3 patients show late response of cones, rods and inner retinal cells directly correlated with disease duration or severity.•SCA3 mouse retinas replicate the human structural and functional phenotypes and further reveal progressive ATXN3 aggregation•Retinas of SCA3 transgenic mice show loss of cones, thickening of OPL and RPE, and longer apical microvilli•Progressive retinal alterations constitute a hallmark of SCA3 disease and ATXN3 aggregation
Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
To characterize a homogenous AAV ...cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated.
This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase MPO-ANCA and 2.6% proteinase 3 PR3-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients.
The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
Objective
We set out to assess the dynamics of retinal injury after acute optic neuritis (ON) and their association with clinical visual outcomes.
Methods
Thirty‐one consecutive patients with acute ...ON were prospectively analyzed over a 6‐month follow‐up period. Each month, we used optical coherence tomography (OCT) to assess the thickness of peripapillary retinal nerve fiber layer (pRNFL) and segmented macular layers, as well as high‐contrast visual acuity, low‐contrast visual acuity (LCVA), color visual acuity (CVA), and visual fields (VF).
Results
In this prospective study, we found that 6 months after clinical onset, ON eyes suffered a reduction in pRNFL (−45.3 μm) and macular thickness (−17.3 μm). Macular atrophy was due to the decrease of macular RNFL thickness (−7.8 μm) and that of the ganglion cell layer and inner plexiform layer (GCIP, −11.3 μm), whereas the thickness of the outer retinal layers increased slightly. The macular RNFL and GCIP thickness decreased in parallel, yet it always occurred more rapidly and more severely for the GCIP. The change in the GCIP thickness in the first month predicted the visual impairment by month 6; a decrease ≥ of 4.5 μm predicted poor LCVA (sensitivity of 93% and specificity of 88%), and a decrease of ≥ 7 μm predicted poor VF and CVA (sensitivity of 78% and 100% and specificity of 63% and 66%, respectively).
Interpretation
Retinal axonal and neuronal damage develops quickly after ON onset. Assessment of ganglion cell layer thickness by OCT after ON onset can be used as an imaging marker of persistent visual disability. Ann Neurol 2015;77:517–528
Aim:
To evaluate compliance rate to pterygium postoperative treatment with two different protocols.
Methods:
Review of clinical data of patients submitted to pterygium excision and conjunctival ...autografting in a single centre (and a single surgeon) in Barcelona between March 2014 and December 2017. Initial postoperative protocol (protocol 1) consisted of 4 months of topical steroids in a tapering fashion. Protocol 2 consisted of topical steroids tapered over 5 weeks. Compliance rate, complications and clinical outcomes were evaluated, and statistical comparisons were made.
Results:
120 surgeries were performed in 99 patients. Protocol 1 was applied in 63 cases and the next 57 followed protocol 2. Compliance with protocol 1 (57.6%) was lower than with protocol 2 (84.9%) (p = 0.002). Intraoperative complications (graft tear, corneal thinning, corneal perforation and bleeding) were found in 10 cases of protocol 1 and three cases of protocol 2, p = 0.08. Postoperative complications (graft dislocation, graft haematoma, ocular hypertension and recurrence) were found in 31 cases of protocol 1 (46.2%) and eight cases of protocol 2 (14%), p = 0.001. Six weeks after surgery, ocular hypertension was detected in eight cases corresponding to protocol 1 (13.6%) and two cases of protocol 2 (3.8%), p = 0.099. Recurrence rate during first year was higher in protocol 1 (26.3%) compared to protocol 2 (7.6%), p = 0.011. No cases of visual acuity worsening or infection were registered.
Conclusion:
Protocol 2 has shown to have higher compliance rate than protocol 1 and less postoperative complications, proving to be a safe and effective postoperative treatment after pterygium surgery.
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