Early predictors of visual and axonal outcomes after acute optic neuritis.
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ABSTRACT: Background
Predicting long-term visual outcomes and axonal loss following acute optic neuritis (ON) is critical for choosing treatment. Predictive models including all clinical and paraclinical measures of optic nerve dysfunction following ON are lacking.Objectives
Using a prospective study method, to identify 1 and 3 months predictors of 6 and 12 months visual outcome (low contrast letter acuity 2.5%) and axonal loss [retinal nerve fiber layer thickness and multifocal evoked potential (mfVEP) amplitude] following acute ON.Methods
In total, 37 patients of acute ON onset were evaluated within 14 days using between-eye asymmetry of visual acuity, color vision (Ishihara plates), optical coherence tomography, mfVEP, and optic nerve magnetic resonance imaging [magnetic transfer ratio (MTR) and diffusion tensor imaging (DTI)].Results
Visual outcome at 6 and 12 months was best predicted by Ishihara asymmetry at 1 and 3 months following ON onset. Axonal loss at 6 and 12 months was reliably predicted by Ishihara asymmetry at 1 month. Optic nerve MTR and DTI at 3 months post-acute ON could predict axonal loss at 6 and 12 months.Conclusions
Simple Ishihara asymmetry testing 1 month after acute ON onset can best predict visual outcome and axonal loss at 6 and 12 months in a clinical or research setting.
SUBMITTER: Nguyen MNL
PROVIDER: S-EPMC9493016 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Early predictors of visual and axonal outcomes after acute optic neuritis.
Nguyen Minh N L MNL Zhu Chao C Kolbe Scott C SC Butzkueven Helmut H White Owen B OB Fielding Joanne J Kilpatrick Trevor J TJ Egan Gary F GF Klistorner Alexander A van der Walt Anneke A
Frontiers in neurology 20220908
<h4>Background</h4>Predicting long-term visual outcomes and axonal loss following acute optic neuritis (ON) is critical for choosing treatment. Predictive models including all clinical and paraclinical measures of optic nerve dysfunction following ON are lacking.<h4>Objectives</h4>Using a prospective study method, to identify 1 and 3 months predictors of 6 and 12 months visual outcome (low contrast letter acuity 2.5%) and axonal loss [retinal nerve fiber layer thickness and multifocal evoked pot ...[more]
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Project description:IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment × time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.
| S-EPMC4115276 | biostudies-literature
Project description:ObjectiveThe objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab.MethodsRENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint. Interactions between the primary endpoint and prespecified baseline variables (including age, timing of treatment initiation, and visual impairment) using the median as cut-off were evaluated in the per protocol population using analysis of covariance (ANCOVA); subgroups based on preexisting brain T2 lesion volume were also analyzed. Interactions between the primary endpoint and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) and retinal nerve fiber layer (RNFL) thickness were assessed post hoc as was weight gain by treatment.ResultsTreatment benefit of opicinumab (n = 33) over placebo (n = 36) on the primary endpoint was greatest in participants older than the median age at baseline (≥33 years); the difference versus placebo for baseline age ≥33 years was -14.17 msec [P = 0.01] versus -0.89 msec for baseline age <33 years, [P = 0.87]). Post hoc analysis showed that VEP latency recovery was significantly associated with less RGCL/IPL thinning (P = 0.0164), occurring early on.InterpretationAge was the strongest prespecified baseline characteristic associated with a treatment effect of opicinumab. A strong association between VEP latency recovery at week 24 and early RGCL/IPL preservation was observed.
| S-EPMC6186935 | biostudies-literature
Project description:ObjectiveDiffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. The goal of this study was to test whether, following a remote episode of optic neuritis (ON), breakdown of myelin and axons within the optic nerve could be detected by alterations in DTI parameters, and whether these alterations would correlate with visual loss.MethodsSeventy subjects with a history of ON > or =6 months prior underwent DTI of the optic nerves, assessment of visual acuities (VA) and contrast sensitivities (CS), and laboratory measures of visual evoked potentials (VEP) and optical coherence tomography (OCT).ResultsRadial diffusivity (RD) correlated with visual acuity (r = -0.61), Pelli-Robson CS (r = -0.60), 5%CS (r = 0.61), OCT (r = -0.78), VEP latency (r = 0.61), and VEP amplitude (r = -0.46). RD differentiated the unaffected fellow nerves from affected nerves in all visual outcome categories. RD also discriminated nerves with recovery to normal from mild visual impairment, and those with mild impairment from profound visual loss. RD differentiated healthy controls from both clinically affected nerves and unaffected fellow nerves after ON. RD differentiated all categories of 5%CS outcomes, and all categories of Pelli-Robson CS with the exception of normal recovery from mildly affected.ConclusionsIncreased optic nerve radial diffusivity (RD) detected by diffusion tensor imaging (DTI) was associated with a proportional decline in vision after optic neuritis. RD can differentiate healthy control nerves from both affected and unaffected fellow nerves. RD can discriminate among categories of visual recovery within affected eyes. Optic nerve injury as assessed by DTI was corroborated by both optical coherence tomography and visual evoked potentials.
| S-EPMC2882214 | biostudies-literature
Project description:BackgroundBiomarkers are urgently required for predicting the likely progression of multiple sclerosis (MS) at the earliest stages of the disease to aid in personalised therapy.ObjectiveWe aimed to examine early brain volumetric and microstructural changes and retinal nerve fibre layer thinning as predictors of longer term MS severity in patients with clinically isolated syndromes (CIS).MethodsLesion metrics, brain and regional atrophy, diffusion fractional anisotropy and retinal nerve fibre layer thickness were prospectively assessed in 36 patients with CIS over the first 12 months after presentation and compared with clinical outcomes at longer term follow-up [median (IQR) = 8.5 (7.8-8.9) years].ResultsIn total, 25 (69%) patients converted to MS and had greater baseline lesion volume (p = 0.008) and number (p = 0.03)than CIS patients. Over the initial 12 months, new lesions (p = 0.0001), retinal nerve fibre layer thinning (p = 0.04) and ventricular enlargement (p = 0.03) were greater in MS than CIS patients. In MS patients, final Expanded Disability Status Scale score correlated with retinal nerve fibre layer thinning over the first 12 months (ρ = -0.67, p = 0.001).ConclusionsAdditional to lesion metrics, early measurements of fractional anisotropy and retinal nerve fibre layer thinning are informative about longer term clinical outcomes in CIS.
| S-EPMC6651676 | biostudies-literature
Project description:ImportanceOptic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis.ObjectiveTo prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively.Design, setting, and participantsThis nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON.Main outcomes and measuresPrimary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein.ResultsA total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA.Conclusions and relevanceThe study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.
| S-EPMC7563662 | biostudies-literature
Project description:BackgroundMultifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies.ObjectiveMF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants.MethodsThis exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24.ResultsA trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively].ConclusionResults from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment.RegistrationClinicalTrials.gov identifier NCT01721161.
| S-EPMC6280853 | 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:PurposeAcute optic neuritis (ON) is variably treated with glucocorticoids. We aimed to describe factors associated with glucocorticoid use.MethodsIn this retrospective, longitudinal cohort study of insured patients in the United States (2005-2019), adults 18-50 years old with one inpatient or ≥2 outpatient diagnoses of ON within 90 days were included. Glucocorticoid use was classified as none, any dose, and high-dose (>100 mg prednisone equivalent ≥1 days). The primary outcome was glucocorticoid receipt within 90 days of the first ON diagnosis. Multivariable logistic regression models assessed the relationship between glucocorticoid use and sociodemographics, comorbidities, clinician specialty, visit number, and year.ResultsOf 3026 people with ON, 65.8% were women (n = 1991), median age (interquartile range) was 38 years (31,44), and 68.6% were white (n = 2075). Glucocorticoids were received by 46% (n = 1385); 54.6% (n = 760/1385) of whom received high-dose. The odds of receiving glucocorticoids were higher among patients with multiple sclerosis (OR 1.61 [95%CI 1.28-2.04]; P < .001), MRI (OR 1.75 [95%CI 1.09-2.80]; P = .02), 3 (OR 1.80 [95%CI 1.46-2.22]; P < .001) or more (OR 4.08 [95%CI 3.37-4.95]; P < .001) outpatient ON visits, and in certain regions. Compared to ophthalmologists, patients diagnosed by neurologists (OR 1.36 [95%CI: 1.10-1.69], p = .005), emergency medicine (OR 3.97 [95%CI: 2.66-5.94]; P < .001) or inpatient clinicians (OR 2.94 [95%CI: 2.22-3.90]; P < .001) had higher odds of receiving glucocorticoids. Use increased 1.1% annually (P < .001).ConclusionsDemyelinating disease, care intensity, setting, region, and clinician type were associated with glucocorticoid use for ON. To optimize care, future studies should explore reasons for ON care variation, and patient/clinician preferences.
| S-EPMC9378755 | 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:PurposeTo compare the evolvement of visual field (VF) defect in neuromyelitis optica spectrum disorder-optic neuritis (NMOSD-ON) and idiopathic optic neuritis (IDON).MethodsThis prospective study involved 104 optic neuritis (ON) patients followed up for ≥ 6 months (33 patients with NMOSD-ON and 71 patients with IDON). The pattern and recovery pattern of VF defect, mean defect (MD) and pattern standard deviation (PSD) of VF, as well as BCVA at onset, 1 month (1 m), 3 months (3 m), and ≥ 6 months (6 m) after onset were compared between two groups. Analysis of these indicators in first episode patients was also done.ResultsDiffuse abnormalities and nerve fiber bundle abnormalities were the two most common patterns in both groups. The percentage of neurologic abnormality of VF defect in NMOSD-ON was higher than that of IDON. Compared with the IDON group, the MD and PSD of NMOSD-ON group were significantly worse at each follow-up. While a positive correlation in BCVA was found between 1 m and ≥ 6 m in the NMOSD-ON group only, a positive correlation was found between 1 m and ≥ 6 m in MD and PSD of both groups. A positive correlation was found between 3 m and ≥ 6 m in MD, PSD and BCVA of both groups. The quadrant recovery pattern was the most common pattern in both groups (57.1% in NMOSD-ON and 57.4% in IDON). The analysis of the first episode subgroup further confirmed the observation above.ConclusionsThe NMOSD-ON patients tended to suffer more severe VF damage, VF irregularity and worse prognosis than that of IDON patients. Diffuse abnormalities and nerve fiber bundle abnormalities were the two most common types in both groups, while neurologic abnormality more common in NMOSD-ON and central scotoma more common in IDON. The visual functions of 1 m in NMOSD-ON and 3 m in IDON were related to its prognosis.
| S-EPMC9361552 | biostudies-literature