Study of Optimal Perimetric Testing In Children (OPTIC): Feasibility, reliability and repeatability of perimetry in children

Purpose: To investigate feasibility, reliability and repeatability of perimetry in children. Methods: A prospective, observational study recruiting 154 children aged 5-15 years, without an ophthalmic condition that affects the visual field (controls), identified consecutively between May 2012 and November 2013 from hospital eye clinics. Perimetry was undertaken in a single sitting, with standardised protocols, in a randomised order using the Humphrey static (SITA 24-2 FAST), Goldmann and Octopus kinetic perimeters. Data collected included test duration, subjective experience and test quality (incorporating examiner ratings on comprehension of instructions, fatigue, response to visual and auditory stimuli, concentration and co-operation) to assess feasibility and reliability. Testing was repeated within 6 months to assess repeatability. Results: Overall feasibility was very high (Goldmann=96.1%, Octopus=89% and Humphrey=100% completed the tests). Examiner rated reliability was ‘good’ in 125 (81.2%) children for Goldmann, 100 (64.9%) for Octopus and 98 (63.6%) for Humphrey perimetry. Goldmann perimetry was the most reliable method in children under 9 years of age. Reliability improved with increasing age (multinomial logistic regression (Goldmann, Octopus and Humphrey), p<0.001). No significant differences were found for any of the three test strategies when examining initial and follow-up data outputs (Bland-Altman plots, n=43), suggesting good test repeatability, although the sample size may preclude detection of a small learning effect. Conclusions: Feasibility and reliability of formal perimetry in children improves with age. By the age of 9 years, all the strategies used here were highly feasible and reliable. Clinical assessment of the visual field is achievable in children as young as 5 years, and should be considered where visual field loss is suspected. Since Goldmann perimetry is the most effective strategy in children aged 5-8 years and this perimeter is no longer available, further research is required on a suitable alternative for this age group

The Clinical Characteristics of Optic Neuritis in Korean Children

To study the clinical characteristics of optic neuritis in Korean children. A retrospective review of the medical charts of 20 patients who were diagnosed with optic neuritis before age 10 was conducted in this study. Data were collected on the demographics, clinical features, use of intravenous corticosteroids, neuroimaging, and diagnosis of multiple sclerosis. The mean age at diagnosis was 6.5 ± 1.8 years (range, 3 to 9 years). Seventeen patients (85%) were female, and 13 patients (65%) exhibited bilateral diseases. Visual acuity had decreased to ≤20 / 200 in 16 of the 20 patients, and recovered to ≥20 / 40 in 16 of the 20 patients. The mean duration between the worst visual acuity and 20 / 40 was 2.30 ± 2.91 months. Intravenous corticosteroid treatment was performed in 15 patients and exerted a beneficial effect on the visual outcomes. Disc swelling was observed in 75.8% of the affected eyes. Multiple sclerosis was diagnosed in five patients with a mean follow-up period of 21.9 ± 20.3 months. The presence of lesions in brain magnetic resonance images was identified as the most significant factor with regards to the occurrence of multiple sclerosis. In children with optic neuritis, a profound decrease in initial visual acuity and rapid recovery of visual acuity were confirmed. Corticosteroid treatment resulted in a beneficial effect on visual outcomes, but had no effect on the risk of multiple sclerosis. © 2011 The Korean Ophthalmological SocietyY

Study of Optimal Perimetric Testing in Children (OPTIC): evaluation of kinetic approaches in childhood neuro-ophthalmic disease

AIMS: We compared feasibility, quality and outcomes of visual field (VF) testing in children with neuro-ophthalmic disease between the discontinued 'gold-standard' Goldmann and Octopus perimeters. METHODS: Children with neuro-ophthalmic disease, attending Great Ormond Street Hospital, London, were assessed using standardised protocols by one examiner in a single sitting, using Goldmann and Octopus kinetic perimetry. Outputs were classified to compare severity of loss and defect type. Test quality was assessed using both qualitative and quantitative methods. RESULTS: Thirty children (40% female) aged 5-15 years participated. Goldmann perimetry was completed in full by 90.0% vs 72.4% for Octopus. Inability to plot the blind spot was the most common reason for not completing testing. Over 75% completed a test in ≤20 min. Duration was similar between perimeters (paired t-test, mean difference: 0.48min (-1.2, 2.2), p=0.559). The lowest quality tests were for Octopus perimetry in children <8 years, without significant differences between perimeters in older children (McNemar's test, χ2=1.0, p=0.317). There was broad agreement between Goldmann and Octopus outputs (good quality, n=21, Bland-Altman, mean difference for isopters I4e (-514.3  deg2 (-817.4, -211.2), p=0.814), I2e (-575.5 deg2 (-900.1, -250.9), p=0.450) and blind spot (20.8 deg2 (5.7, 35.8), p=0.451)). However, VF severity grades and defect type matched in only 57% and 69% of tests, respectively. Octopus perimetry underestimated severe VF defects. CONCLUSIONS: Informative perimetry is feasible in children ≥8 years with neuro-ophthalmic conditions, with either Goldmann or Octopus perimeters. However, meaningful differences exist between the two approaches with implications for consistency in longitudinal assessments

Study of Optimal Perimetric Testing In Children (OPTIC): developing consensus and setting research priorities for perimetry in the management of children with glaucoma

BACKGROUND: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research. METHODS: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish 'agreement'. Divergence of opinions was investigated and resolved where possible through further iterations. RESULTS: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75-7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances-from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing. CONCLUSIONS: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals' lifetime, highlighting the need for further research

Retinal nerve fibre layer thinning is associated with worse visual outcome after optic neuritis in children with a relapsing demyelinating syndrome

AIM: Optic neuritis may be monophasic or occur as part of a relapsing demyelinating syndrome (RDS), such as multiple sclerosis, aquaporin-4 antibody (AQP4-Ab) neuromyelitis optical spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. The aims of this study were to test whether clinical, electrophysiological, and microstructural parameters differ in multiple-sclerosis-associated optic neuritis (MS-ON) and antibody-associated optic neuritis (Ab-ON); to identify the clinical and paraclinical characteristics of children suffering worse long-term visual outcome of RDS-optic neuritis; and to explore the relationship between RNFL thickness and clinical parameters in RDS-optic neuritis. METHOD: Forty-two children with optic neuritis were retrospectively studied: 22 with multiple sclerosis (MS-ON) and 20 with antibody-associated demyelination (Ab-ON: MOG-Ab=16 and AQP4-Ab=4). Clinical and paraclinical features were analysed. RESULTS: Complete recovery of visual acuity was reported in 25 out of 42 children; eight out of 38 (21%) suffered moderate or severe visual impairment (logarithm of the minimum angle of resolution [logMAR]>0.5) in their worse eye, including four out of 38 who were blind (logMAR>1.3) in their worse eye (two with multiple sclerosis, two with AQP4-Ab NMOSD). None of the children with MOG-Ab were blind. Recurrence of optic neuritis was more common in the Ab-ON group than the MS-ON group (15 out of 20 vs seven out of 22, p=0.007). Retinal nerve fibre layer (RNFL) thickness at baseline inversely correlated with visual acuity at final follow-up (r=-0.41, p=0.008). There was no significant relationship between the number of episodes of optic neuritis and mean RNFL (r=-0.08, p=0.628), nor any significant relationship between the number of episodes of optic neuritis and visual impairment (r=0.03, p=0.794). INTERPRETATION: In children with RDS, long-term visual impairment inversely correlated with RNFL thickness, but not with the number of relapses of optic neuritis. Optical coherence tomography may have a role in assessing children with optic neuritis to monitor disease activity and inform treatment decisions. WHAT THIS PAPER ADDS: Long-term visual impairment is reported in 40% of children with a relapsing demyelinating syndrome following optic neuritis. Relapse of optic neuritis, occurring more frequently in the non-multiple-sclerosis group. Retinal nerve fibre layer thinning is associated with worse visual outcome. Optical coherence tomography can be used alongside clinical parameters as an objective measure of neuroretinal loss

Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial

BACKGROUND: The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. METHODS: We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel(® )software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). RESULTS: Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. CONCLUSION: The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting

Patients' knowledge and perception on optic neuritis management before and after an information session

<p>Abstract</p> <p>Background</p> <p>Patients' understanding of their condition affect the choice of treatment. The aim of this study is to evaluate patients' understanding and treatment preferences before and after an information session on the treatment of acute optic neuritis.</p> <p>Methods</p> <p>Participants were asked to complete a questionnaire consisting of 14 questions before and after an information session presented by a neuro-ophthalmologist. The information session highlighted the treatment options and the treatment effects based on the Optic Neuritis Treatment Trial in plain patient language. The information session stressed the finding that high dose intravenous steroid therapy accelerated visual recovery but does not change final vision and that treatment with oral prednisone alone resulted in a higher incidence of recurrent optic neuritis.</p> <p>Results</p> <p>Before the information session, 23 (85%) participants knew that there was treatment available for ON and this increased to 27 (100%) after the information session. There were no significantly change in patients knowledge of symptoms of ON and purpose of treatment before and after the information session. Before the information session, 4 (14%) respondents reported they would like to be treated by oral steroid alone in the event of an optic neuritis and 5 (19%) did not respond. After the education session, only 1 patient (4%) indicated they would undergo treatment with oral steroid alone but 25 (92%) indicated they would undergo treatment with intravenous steroid treatment, alone or in combination with oral treatment. Results indicated that there were significant differences in the numbers of participants selecting that they would undergo treatment with a steroid injection (n = 22, p = 0.016).</p> <p>Conclusions</p> <p>In this study, patients have shown good understanding of the symptoms and signs of optic neuritis. The finding that significant increases in the likelihood of patients engaging in best practice can be achieved with an information session is very important. This suggests that patient knowledge of available treatments and outcomes can play an important role in implementing and adopting guideline recommendations.</p

Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis

Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016-April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96-0.99; P = 7.80 × 10 −03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35-4.10; P = 2.60 × 10 −03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10 −02) and African ancestry (Beta: −10.07; P = 1.39 × 10 −03). Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics

Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations

BACKGROUND: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. METHODS: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed. RESULTS: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. CONCLUSION: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS

Differential diagnosis of suspected multiple sclerosis: a consensus approach

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision