Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone

Multicenter Inter-rater Reliability of Retinal Layer Segmentation Using Spectral-domain OCT

Optical coherence tomography (OCT) measures of different retinal layers correlate with structural and functional markers of disease severity in multiple sclerosis (MS), making intra-retinal layer segmentation of high-resolution OCT scans an increasingly important tool for the assessment of clinical progression in MS patients. While automatic intra-retinal layer segmentation is not yet widely available, semi-automatic segmentation of scans is necessary. The aim of our study was to evaluate reliability of semi-automatic and assisted intra-retinal layer segmentation in a multicentre setting and to identify sources of disagreement

Reliability of Cyclotorsion Measurements using Scanning Laser Ophthalmoscopy Imaging in Healthy Subjects - CySLO study

This prospective methodological study evaluates inter- and intra-rater reliability of objective cyclotorsion measurements obtained in healthy subjects using the Heidelberg Spectralis Spectral Domain - Optical Coherence Tomography (SD-OCT) device

Visual snow syndrome: a review on diagnosis, pathophysiology, and treatment

PURPOSE OF REVIEW Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant bilateral whole-visual field flickering or pixelation. When associated with additional visual symptoms, it is referred to as visual snow syndrome. Its pathophysiology remains elusive. This review highlights the visual snow literature focusing on recent clinical studies that add to our understanding of its clinical picture, pathophysiology, and treatment. RECENT FINDINGS Clinical characterization of visual snow syndrome is evolving, including a suggested modification of diagnostic criteria. Regarding pathophysiology, two recent studies tested the hypothesis of dysfunctional visual processing and occipital cortex hyperexcitability using electrophysiology. Likewise, advanced functional imaging shows promise to allow further insights into disease mechanisms. A retrospective study now provides Class IV evidence for a possible benefit of lamotrigine in a minority of patients. SUMMARY Scientific understanding of visual snow syndrome is growing. Major challenges remain the subjective nature of the disease, its overlap with migraine, and the lack of quantifiable outcome measures, which are necessary for clinical trials. In that context, refined perceptual assessment, objective electrophysiological parameters, as well as advanced functional brain imaging studies, are promising tools in the pipeline

Cyclotorsion Measurement on Scanning Laser Ophthalmoscopy Imaging Compared With Fundus Photography in Patients With Fourth Nerve Palsy and Healthy Controls

Background: The purpose of the study is to evaluate the agreement of the foveopapillary angle (FPA) on conventional fundus photography (c-FPA) with the FPA on scanning laser ophthalmoscopy (SLO) imaging (SLO-FPA) in patients with fourth nerve palsy and healthy controls (HCs). Methods: The FPA was measured in both eyes of 25 patients and 25 HCs in synedra View (c-FPA) and with the integrated algorithm of the Heidelberg Spectralis OCT (SLO-FPA). The primary endpoint was the agreement of both measurements. Furthermore, we evaluated the influence of the eye tracker, the influence of fixation on objective torsion, and the FPA cutoff between patients and HCs.Results: The mean SLO-FPA in patients (6/25 acquired palsies) was 11.3 ± 3.6° and 6.4 ± 2.1° in HCs. The mean c-FPA was 11.4 ± 4.0° and 5.8 ± 2.2°, respectively. The Bland–Altman plot of c-FPA vs SLO-FPA in patients and HCs shows no systematic bias (mean of −0.28°). Limits of agreement were −6.58 and 6.02°. Using the eye tracker had no systematic effect. There was no evidence for an immediate shift of torsion with change of fixation (24/25 patients and 23/25 HCs). Discrimination between patients and HCs by the SLO-FPA is very good with an area under the curve = 0.92 (95% confidence interval: 0.84–0.99). Conclusions: SLO-FPA measurement allows convenient and consistent assessment of objective cyclotorsion. There was no systematic bias in the difference between SLO-FPA and traditional c-FPA; thus, SLO-FPA is a valuable alternative to the commonly used c-FPA. Using the eye tracker is recommended for proper centering of the ring scan

Cyclotorsion Measurement on Scanning Laser Ophthalmoscopy Imaging Compared With Fundus Photography in Patients With Fourth Nerve Palsy and Healthy Controls

Background: The purpose of the study is to evaluate the agreement of the foveopapillary angle (FPA) on conventional fundus photography (c-FPA) with the FPA on scanning laser ophthalmoscopy (SLO) imaging (SLO-FPA) in patients with fourth nerve palsy and healthy controls (HCs). Methods: The FPA was measured in both eyes of 25 patients and 25 HCs in synedra View (c-FPA) and with the integrated algorithm of the Heidelberg Spectralis OCT (SLO-FPA). The primary endpoint was the agreement of both measurements. Furthermore, we evaluated the influence of the eye tracker, the influence of fixation on objective torsion, and the FPA cutoff between patients and HCs.Results: The mean SLO-FPA in patients (6/25 acquired palsies) was 11.3 ± 3.6° and 6.4 ± 2.1° in HCs. The mean c-FPA was 11.4 ± 4.0° and 5.8 ± 2.2°, respectively. The Bland–Altman plot of c-FPA vs SLO-FPA in patients and HCs shows no systematic bias (mean of −0.28°). Limits of agreement were −6.58 and 6.02°. Using the eye tracker had no systematic effect. There was no evidence for an immediate shift of torsion with change of fixation (24/25 patients and 23/25 HCs). Discrimination between patients and HCs by the SLO-FPA is very good with an area under the curve = 0.92 (95% confidence interval: 0.84–0.99). Conclusions: SLO-FPA measurement allows convenient and consistent assessment of objective cyclotorsion. There was no systematic bias in the difference between SLO-FPA and traditional c-FPA; thus, SLO-FPA is a valuable alternative to the commonly used c-FPA. Using the eye tracker is recommended for proper centering of the ring scan