Ghislaine L. Traber

Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria

Background: Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. Objective: An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials. Methods: A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place. Results: The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed. Conclusion: Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.

Subacute bilateral visual loss in methylmalonic acidemia

A 23-year-old woman known to have methylmalonic acidemia (MMA) since birth suffered bilateral visual loss within 5 days. Multiple sclerosis, Leber hereditary optic neuropathy, vasculitis, infections (in particular treponema), and vitamin deficiency were ruled out. The optic nerve head changed from normal in appearance to atrophic. Treatment attempts with high-dose intravenous steroids and coenzyme Q10 combined with vitamin E were ineffective. The patients underlying disease was metabolically well controlled by strict diet and carnitine supplementation. Toxic damage of both optic nerves due to MMA is the most likely mechanism. MRI showed moderate enhancement of both optic nerves. To our knowledge, this is the first report of a morphological correlate on MRI.

Malignant optic glioma – the spectrum of disease in a case series

PurposeMalignant optic glioma of adulthood is a rare, invasive neoplasm of the anterior visual pathway with 66 cases reported in the literature. It presents as anaplastic astrocytoma (WHO grade III) or glioblastoma (WHO grade IV). The present case series covers the spectrum of disease manifestations, discusses neuroradiological findings, and reviews the current literature.MethodsRetrospective case series of five patients from three tertiary referral centers and literature review.ResultsVisual loss with or without pain was the presenting symptom in all patients (two women, three men). Two patients were initially misdiagnosed as optic neuritis, and one patient as atypical non-arteritic anterior ischemic optic neuropathy (NAION). A neoplastic disease was suspected in the two remaining patients. MRI features were iso- to hypointensity on T1-weighted native images, contrast enhancement, and hyperintensity on T2-weighted images. Biopsy was generally diagnostic; however, one patient required two biopsies for diagnosis. The series includes an exceptional case of intraocular tumor extension and vitreous spread. The disease was lethal within one to two years in all patients.ConclusionsMalignant optic glioma is a diagnostic challenge and remains a devastating and lethal disease. Advances in the understanding of tumor biology have yet failed to translate into effective treatment regimens.

Albino mice as an animal model for infantile nystagmus syndrome.

PURPOSE Individuals with oculocutaneous albinism are predisposed to visual system abnormalities affecting the retina and retinofugal projections, which may lead to reduced visual acuity and Infantile Nystagmus Syndrome (INS). Due to absence of an established mammalian animal model, mechanisms underlying INS remain elusive. In this study, we screened wild-type mice of varying pigmentation for ocular motor abnormalities in order to identify a possible mouse model for INS. METHODS Three albino mouse strains (CD1, BALB/c, DBA/1), and two normally pigmented strains (129S6, C57BL/6) were screened using infrared oculography. Varying visual stimuli (black or white background, stationary pattern, optokinetic, i.e., horizontally rotating pattern) were displayed to the full (fVF) or anterior visual field (aVF) of the restrained mouse. RESULTS We found spontaneous nystagmus, specifically jerks and oscillations, in albino mice under all experimental conditions. Median eye velocity was between 0.8 and 3.4 deg/s, depending on the strain. In contrast, the eyes in pigmented mice were nearly stable with a median absolute eye velocity of below 0.4 deg/s. In albino mice, fVF optokinetic stimuli elicited an optokinetic response (OKR) in the correct direction, albeit with superimposed oscillations. However, aVF optokinetic stimuli evoked reversed OKR in these strains, a well known feature of INS. CONCLUSIONS Based on our results, we endorse the investigated albino mouse strains as new animal models for INS.

Multicenter reliability of semiautomatic retinal layer segmentation using OCT

Objective To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. Methods Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps. Results Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers. Conclusions Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL.

Natural history of primary paediatric optic nerve sheath meningioma: case series and review

Purpose To study the natural history, clinical and radiological characteristics of primary paediatric optic nerve sheath meningioma (PPONSM). Methods Retrospective study of eight paediatric patients who were treated between 1994 and 2016 at the University Hospital Zurich, Switzerland and the Royal Adelaide Hospital, Australia. Clinical records and imaging studies were reviewed. Results The mean age at presentation was 11 years (range: 6–17 years). There were six female patients and two male patients. 2/8 patients had associated neurofibromatosis type 2. Patients were followed up for 71–297 months (mean 156±70 months). 6/8 patients were observed through the course of their disease and 2/8 patients were treated with radiotherapy. 2/8 patients who were observed had minimal change in vision and did not experience tumour growth after long-term follow-up. Conclusions This is the largest PPONSM case series with long-term data on patients treated conservatively. We highlight that a small subset of these tumours are indolent and can be managed using observation alone.

Reliability of Cyclotorsion measurements using Scanning Laser Ophthalmoscopy imaging in healthy subjects: the CySLO study

Background/aims To evaluate inter-rater and intra-rater reliability of objective cyclotorsion measurements obtained in healthy subjects using the Heidelberg Spectralis spectral domain—optical coherence tomography (SD-OCT) device. Methods In this prospective methodological study, 32 healthy subjects (14 men, 18 women; aged 21–64 years) were enrolled, 31 right eyes were examined and their foveo-papillary angles (FPAs) were measured. The retinal nerve fibre layer (RNFL) programme by Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) was used to measure cyclotorsion based on the in-built algorithm for the measurement of the FPA on the scanning laser ophthalmoscopy (SLO) image. Repeated scans of the fixating and non-fixating right eye without and with eye tracker each were obtained by three different examiners. Results The mean FPA measured overall by all three examiners was 6.6°±2.8°. The inter-rater reliability of the measured FPAs using the linear mixed effects model is estimated as rhointer=0.8803. The intra-rater reliability is estimated as rhointra=0.9589. Conclusions Repeatability of objective cyclotorsion measurements within and between observers using the Heidelberg Spectralis OCT is very high. SD-OCT/SLO imaging is a reliable imaging technique to measure and study cyclotorsion. Clinical trial number NCT02631369, Results.

Amiodarone-associated Optic Neuropathy—A Clinical Criteria–based Diagnosis?

ABSTRACT Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with possible impact on vital cardiac therapy decisions. This retrospective case series aims for application of distinguishing features of AAON versus non-arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and systemic toxic effects. Applying these criteria to patients with disc swelling under amiodarone, the authors identified four unilateral disc swellings, one with NAION-typical features only and three with one or more NAION-atypical features. All three sequential and six bilateral cases showed one or more NAION-atypical features. The 12 cases highlight the persisting diagnostic dilemma arising from diversity of presentation, lack of plausible pathomechanism, and controversial existence of the entity itself.

Inter-Rater Reliability of Cyclotorsion Measurements Using Fundus Photography

BACKGROUND The foveo-papillary angle (FPA) on fundus photographs is the accepted standard for the measurement of ocular cyclotorsion. We assessed the inter-rater reliability of this method in healthy subjects and in patients with trochlear nerve palsies. PATIENTS AND METHODS In this methodological study, fundus photographs of healthy subjects and of patients with trochlear nerve palsies were made with a fundus camera (Zeiss Fundus Camera FF 450 plus, Jena, Germany). Three independent observers measured the FPA on the fundus photographs of all subjects in synedra View (synedra View 16, Version 16.0.0.11, Innsbruck, Austria). RESULTS One hundred and four eyes of 52 subjects (26 healthy controls and 26 patients) were assessed. The mean FPA of the healthy controls was 5.80 degrees (°) [± 0.44 standard error of the mean (SEM)] compared to 11.55° (± 0.80 SEM) for patients with trochlear nerve palsies. The inter-rater reliability of all measured FPAs showed an intraclass correlation coefficient (ICC) of 0.98 (95% CI 0.97 - 0.98). CONCLUSIONS The inter-rater reliability of objective cyclotorsion measurements using fundus photographs was very high.

Mystery Case: Don't fall for pseudo-INO!

A 31-year-old woman with a 4-day history of diplopia showed slow adducting saccades in the left eye (pseudo–internuclear ophthalmoplegia [P-INO]1,2; see video 1 at Neurology.org), left inferior rectus muscle weakness, and upper limb fatigability. Edrophonium testing with transient resolution of P-INO led to a diagnosis of myasthenia gravis (MG) (see video 2), which was later confirmed by positive acetylcholine receptor antibodies.