Acute optic neuritis: a clinical paradigm for evaluation of neuroprotective and restorative strategies?
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ABSTRACT:
SUBMITTER: Qureshi SS
PROVIDER: S-EPMC4660751 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
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Acute optic neuritis: a clinical paradigm for evaluation of neuroprotective and restorative strategies?
Qureshi Sara S SS Frohman Elliot M EM
Neural regeneration research 20151001 10
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Project description:Purpose: The Optic Neuritis Treatment Trial showed that an MRI of the brain is a powerful predictor of developing multiple sclerosis (MS). However, surveys of practitioners suggest that the recommended use of imaging is not consistently followed in practice. With this study, we aim to assess the rate at which newly diagnosed optic neuritis (ON) patients receive brain MRIs. Methods: This is a retrospective cohort study using administrative medical claims data from a large, national US insurer. All incident cases from 2000 to 2016 of ON in patients without MS were assessed. The primary outcome was a comparison of patterns of MRI scanning usage following diagnosis of ON. Secondary outcomes evaluated steroid treatment and progression to MS. Results: Of 2865 qualified ON patients, 1755 (61.3%) received a brain MRI. At 1 year follow-up, 629 (30.3%) patients had progressed to MS, a rate that increased slightly to 34.3% (366 patients) within a 3-year period of their initial ON diagnosis. A total of 520 (18.2%) patients received intravenous steroids, and 383 (13.4%) received oral steroids within 30 days of the ON diagnosis. Conclusion: Across the United States, a surprisingly low number of individuals obtain a brain MRI following onset of ON, suggesting that physicians may not be fully assessing the risk of MS.
| S-EPMC6785384 | biostudies-literature
Project description:ImportanceNeuroprotective and remyelinating therapies are required for multiple sclerosis (MS), and acute optic neuritis (AON) is a potential condition to evaluate such treatments.ObjectiveTo comprehensively assess key biological and methodological aspects of AON trials for testing neuroprotection and remyelination in MS.Design, setting, and participantsThe AON-VisualPath prospective cohort study was conducted from February 2011 to November 2018 at the Hospital Clinic of University of Barcelona, Barcelona, Spain. Consecutive patients with AON were prospectively enrolled in the cohort and followed up for 18 months. Data analyses occurred from November 2018 to February 2019.ExposuresParticipants were followed up for 18 months using optical coherence tomography, visual acuity tests, and in a subset of 25 participants, multifocal visual evoked potentials.Main outcomes and measuresDynamic models of retinal changes and nerve conduction and their associations with visual end points; and eligibility criteria, stratification, and sample-size estimation for future trials.ResultsA total of 60 patients (50 women [83%]; median age, 34 years) with AON were included. The patients studied displayed early and intense inner retinal thinning, with a thinning rate of approximately 2.38 μm per week in the ganglion cell plus inner plexiform layer (GCIPL) during the first 4 weeks. Eyes with AON displayed a 6-month change in latency of about 20 milliseconds, while the expected change in the eyes of healthy participants by random variability was 0.13 (95% CI, -0.80 to 1.06) milliseconds. The strongest associations with visual end points were for the 6-month intereye difference in 2.5% low-contrast letter acuity, which was correlated with the peripapillary retinal nerve fiber layer thinning (adjusted R2, 0.57), GCIPL thinning (adjusted R2, 0.50), and changes in mfVEP latency (adjusted R2, 0.26). A 5-letter increment in high-contrast visual acuity at presentation (but not sex or age) was associated with 6-month retinal thinning (1.41 [95% CI, 0.60-2.23] μm less peripapillary retinal nerve fiber layer thinning thinning; P = .001; adjusted R2, 0.20; 0.86 [95% CI, 0.35-1.37] μm less GCIPL thinning; P = .001; adjusted R2, 0.19) but not any change in multifocal visual evoked potential latency. To demonstrate 50% efficacy in GCIPL thinning or change in multifocal visual evoked potential latency, a 6-month, 2-arm, parallel-group trial would need 37 or 50 participants per group to test a neuroprotective or remyelinating drug, respectively (power, 80%; α, .05).Conclusions and relevanceAcute optic neuritis is a suitable condition to test neuroprotective and remyelinating therapies after acute inflammation, providing sensitive markers to assess the effects on both processes and prospective visual recovery within a manageable timeframe and with a relatively small sample size.
| S-EPMC6777247 | biostudies-literature
Project description:ObjectiveThe first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON).MethodsWe included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present.ResultsAccording to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%).InterpretationAccording to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.
| S-EPMC11537134 | biostudies-literature
Project description:BackgroundRetinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined.ObjectivesThe objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON.MethodsThirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression.ResultsFour months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = -0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed.ConclusionsFollowing AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.
| S-EPMC4724567 | biostudies-literature
Project description:IntroductionOptic neuritis (ON) is a common neuro-ophthalmological condition and remains a significant indicator of inflammatory conditions affecting the central nervous system. Varying etiologies exist for ON including multiple sclerosis, NMOSD, and MOGAD. Differential diagnosis is achieved using both radiological and serological testing. MRI characteristics of MOG-ON include T2 hypersensitive lesions, nerve swelling, and gadolinium enhancement of the affected optic nerve. While acute MOG-ON usually presents with optic nerve enhancement, recognizing atypical presentations is critical in accurate diagnosis and effective management.Case presentationWe herein present a case of a 67-year-old woman presenting with sudden decrease in vision in the right eye. The patient underwent a 3T MRI of the orbits and brain 5 days post vision loss which returned normal right optic nerve appearance at presentation (no edema, enhancement or increased T2 signal). Further serological testing of the MOG antibody returned positive (1:100) while APQ4 antibodies were negative. This yielded a diagnosis of MOG-IgG-ON. Subsequently, the patient was treated with IV methylprednisolone 1 g daily for 5 days followed by prednisone 1 mg/kg, resulting in marked improvement in vision.ConclusionThis case highlights the complexity involved in diagnosing ON, especially in the context of MOGAD. Absence of optic nerve enhancement in this patient calls attention to the possibility of subclinical inflammation and/or detectable enhancement later in clinical course. Our findings, along with existing literature, highlight the need for clinicians to consider atypical MRI presentations in MOG-ON cases. Recognizing that normal MRI does not exclude MOG-ON is important for optimizing diagnostic accuracy and effective treatment interventions.
| S-EPMC11703545 | biostudies-literature
Project description:Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function.
| S-EPMC4414747 | biostudies-literature
Project description:AIMS: The aim of this study is to provide a clinical update on optic neuritis (ON), its association with multiple sclerosis (MS), and neuromyelitis optica (NMO). METHODS: This study included a PubMed review of the literature written in the English language. RESULTS: ON in adults is typically idiopathic or demyelinating, and is characterised by unilateral, subacute, painful loss of vision that is not associated with any systemic or other neurological symptoms. Demyelinating ON is associated with MS, and we review the key studies of ON including the ON treatment trial and several other MS treatment trials and NMO. CONCLUSION: Acute demyelinating ON can occur in isolation or be associated with MS. Typical ON does not require additional evaluation other than cranial magnetic resonance imaging. NMO is likely a separate disorder from MS and the ON in NMO has a different treatment and prognosis. METHODOLOGY: The authors conducted an English language search using Pubmed from the years 1964 to 2010 using the search terms 'ON', 'MS' and 'NMO'. The authors included original articles, review articles, and case reports, which revealed new aspects as far as epidemiology, histopathology, clinical manifestations, imaging, genetics, and treatment of ON. Titles were reviewed for topicality and full references were obtained. Letters to the editor, unpublished work, and abstracts were not included in this review.
| S-EPMC3178158 | biostudies-other
Project description:BackgroundAcute optic neuritis (AON) is a common optic nerve disease leading to retrograde degeneration of optic nerve axons, reflected by thinning of the inner retinal layers on optical coherence tomography. On the contrary, acute macular neuroretinopathy (AMN) type 2 is a rare outer retinal disorder that leads to thinning of the outer nuclear layers and is diagnosed by multimodal imaging. The aim of this study was to report a new association between these two diseases.MethodsPatients with a first episode of optic neuritis were invited to participate in a study that involved optical coherence tomography evaluation at baseline and the following 1, 3, 6 and 12 months. All the study patients underwent ophthalmologic evaluation that comprised of visual acuity, visual field and multimodal imaging as well as orbital and brain Magnetic Resonance Imaging. A diagnosis of multiple sclerosis was made according to the 2010 McDonald criteria.ResultsSix of the 114 patients with acute optic neuritis also had acute macular neuroretinopathy, of whom three were positive for myelin oligodendrocyte glycoprotein antibodies (MOG-Abs), two had relapsing-remitting multiple sclerosis and one had clinical isolated syndrome.ConclusionOur study suggests that it is imperative to check for associated AMN in cases of AON, especially those associated with MOG-Abs.
| S-EPMC6798266 | biostudies-literature
Project description:Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.
| S-EPMC4983385 | biostudies-literature
Project description:PURPOSE: To document the etiology, clinical presentation, and visual prognosis of optic neuritis in Taiwanese children. METHODS: Retrospectively reviewed children younger than 18 years old with optic neuritis in Chang Gung Memorial Hospital and Chang Gung Children's Hospital from 1998 to 2009. RESULTS: There were 24 children (38 eyes) with optic neuritis in that period. Overall, 14 patients (58.3%) were female and 10 patients (41.7%) were male. In total, 14 patients (58.3%) had bilateral involvement, and 10 patients (41.7%) had unilateral involvement. Out of 38 eyes, 24 (63.2%) had disc swelling. Out of 24 patients, 21 (87.5%) underwent intravenous steroid therapy (10 to 30 mg/kg/day) for 3-5 days, and followed by an oral taper. Out of 24 patients, 20 (83.3%) achieved final visual acuity (VA) of 20/40 or better. However, a poor visual outcome (four patients) (VA<20/40) was correlated with pale disc at presentation (P=0.002, Pearson χ (2)-test) and age older than 10 years (P=0.012, Fisher's exact test). Five patients were diagnosed with acute disseminated encephalomyelitis (ADEM) (21%), and three patients were diagnosed with multiple sclerosis (MS) (12.5%). Patients with ADEM did not have a better visual outcome than patients with MS (P=0.643, Fisher's exact test). CONCLUSIONS: Visual recovery from optic neuritis was favorable in Taiwanese children. A poor visual outcome was correlated with pale disc at presentation and patients' age older than 10 years. ADEM is the most common associated systemic disease; MS is relatively rare.
| S-EPMC3213655 | biostudies-other