First observation of secondary childhood glaucoma in Coffin-Siris syndrome : a case report and literature review

BACKGROUND Severe congenital ophthalmological malformations and glaucoma might be an important occasional feature in patients with Coffin-Siris syndrome (CSS), especially Coffin-Siris syndrome 9 (CSS9, OMIM #615866) caused by SOX11 mutation. Recently, primary (open-angle) glaucoma was described in two children with the most common form of Coffin-Siris syndrome, CSS1 (OMIM #135900) by ARID1B (AT-rich interaction domain-containing protein 1B) gene mutation. In this article, we present the first report of glaucoma with Coffin-Siris syndrome 9 as well as the first report of secondary glaucoma with any form of Coffin-Siris syndrome. These findings indicate that secondary glaucoma is an occasional finding in patients with Coffin-Siris syndrome. CASE PRESENTATION A child with secondary childhood glaucoma and additional ocular manifestations was evaluated and treated at the childhood glaucoma centre in Mainz, Germany. Examination under general anaesthesia revealed ocular anterior segment dysgenesis (ASD) (Peters type iridocorneal dysgenesis) in combination with congenital limbal stem cell deficiency (LSCD), aniridia, and cataract. The patient also had multiple other congenital anomalies and severe developmental delay. To explain his combination of anomalies, molecular genetic analysis from peripheral blood was performed in late 2018 and early 2019. Following normal findings with a panel diagnostic of 18 genes associated with congenital glaucoma, whole exome sequencing was performed and revealed a novel likely pathogenic heterozygous variant c.251G>T, p.(Gly84Val) in the SOX11 gene (SRY-related HMG-box gene 11). The variant had occurred de novo. Thus, the multiple congenital anomalies and developmental delay of the patient represented Coffin-Siris syndrome 9 (CSS9, OMIM #615866). CONCLUSIONS When eye diseases occur in combination with other systemic features, genetic analysis can be seminal. Results indicate that glaucoma is an occasional feature of patients with Coffin-Siris syndrome. As early treatment may improve the visual outcome of patients with glaucoma, we suggest that patients with Coffin-Siris syndrome should receive specific ophthalmological screening

Results of childhood glaucoma surgery over a long-term period

Purpose To evaluate long-term results of glaucoma surgery in newborn and infants with glaucoma. Methods Seventy-nine eyes of 52 children (age: 3 weeks–15.3 years) with primary congenital or secondary glaucoma treated between 2015 and 2017 were included. The median follow-up time was 3.9 years. Conventional probe trabeculotomy, 360° catheter-assisted trabeculotomy, filtering and cyclodestructive surgery were compared. Strict criteria for surgical success were applied: Complete surgical success (IOP below target IOP, no further surgery) and incomplete surgical success (additional surgery allowed) were analyzed, and IOP at baseline and last follow-up was compared. Results Intraocular pressure (IOP) was significantly reduced in primary congenital (preoperative IOP: 27.8 ± 7.5 mmHg vs. postoperative IOP: 14.2 ± 4.5 mmHg) and secondary glaucoma (preoperative IOP: 29.2 ± 9.1 mmHg vs. postoperative IOP: 16.6 ± 4.7 mmHg). 90% of all eyes reached target IOP with or without medication allowing for additional surgeries. As first surgery, 360° catheter-assisted trabeculotomy had a tendency to higher surgical success than other surgical approaches, while cyclodestructive procedures had lowest. Conclusions We found very promising surgical results in our childhood glaucoma patient group. Surgical success in both congenital and secondary glaucoma was high

Results of the Patient-Related Outcomes of Mechanical lead Extraction Techniques (PROMET) study: a multicentre retrospective study on advanced mechanical lead extraction techniques.

AIMS: Several large studies have documented the outcome of transvenous lead extraction (TLE), focusing on laser and mechanical methods. To date there has been no large series addressing the results obtained with rotational lead extraction tools. This retrospective multicentre study was designed to investigate the outcomes of mechanical and rotational techniques. METHODS AND RESULTS: Data were collected on a total of 2205 patients (age 66.0 ± 15.7 years) with 3849 leads targeted for extraction in six European lead extraction centres. The commonest indication was infection (46%). The targeted leads included 2879 pacemaker leads (74.8%), 949 implantable cardioverter-defibrillator leads (24.6%), and 21 leads for which details were unknown; 46.6% of leads were passive fixation leads. The median lead dwell time was 74 months [interquartile range (IQR) 41-112]. Clinical success was obtained in 97.0% of procedures, and complete extraction was achieved for 96.5% of leads. Major complications occurred in 22/2205 procedures (1%), with a peri-operative or procedure-related mortality rate of 4/2205 (0.18%). Minor complications occurred in 3.1% of procedures. A total of 1552 leads (in 992 patients) with a median dwell time of 106 months (IQR 66-145) were extracted using the Evolution rotational TLE tool. In this subgroup, complete success was obtained for 95.2% of leads with a procedural mortality rate of 0.4%. CONCLUSION: Patient outcomes in the PROMET study compare favourably with other large TLE trials, underlining the capability of rotational TLE tools and techniques to match laser methods in efficacy and surpass them in safety

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT

Refining Treatment Planning in STereotactic Arrhythmia Radioablation (STAR): Benchmark Results and Consensus Statement from the STOPSTORM.eu Consortium.

BACKGROUND AND PURPOSE STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia (VT). However, clinical data is scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS Planning target volumes (PTV) overlapping extra-cardiac organs-at-risk and/or cardiac substructures were generated for three STAR cases. Participating centers were asked to create single fraction treatment plans with 25 Gy dose prescription based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for ICRU report 91 relevant parameters and crowd dose-volume-histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS Twenty centers submitted 67 treatment plans for this study. In most plans (75%) Intensity Modulated Arc Therapy (IMAT) with 6 MV flattening-filter-free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96-100% (19%). Many participants preferred to spare close extra-cardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged 25.5-34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged 2-80 minutes. For the consensus statements, strong agreement was reached for beam technique planning, dose calculation, prescription methods and trade-offs between target and extra-cardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSION This STOPSTORM multi-center treatment planning benchmark study showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established, however clinical data is urgently needed for actionable guidelines for treatment planning

Refining Critical Structure Contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark Results and Consensus Guidelines from the STOPSTORM.eu Consortium.

BACKGROUND AND PURPOSE In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS Centres within the STOPSTORM consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC=0.96, median MDA=0.1mm and median HD95=1.1mm) and aorta (median DSC=0.90, median MDA=0.1mm and median HD95=1.5mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC=0.83, median MDA=0.2mm and median HD95=0.5mm), valves (median DSC=0.16, median MDA=4.6mm and median HD95=16.0mm), coronary arteries (median DSC=0.4, median MDA=0.7mm and median HD95=8.3mm) and the sinoatrial and atrioventricular nodes (median DSC=0.29, median MDA=4.4mm and median HD95=11.4mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established

Light-Induced Responses of Slow Oscillatory Neurons of the Rat Olivary Pretectal Nucleus

Background: The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes. Methodology: To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX). Conclusions: We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillationpreserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firin

Ultrafast laser micro-nano structuring of transparent materials with high aspect ratio

Ultrafast lasers are ideal tools to process transparent materials because they spatially confine the deposition of laser energy within the material's bulk via nonlinear photoionization processes. Nonlinear propagation and filamentation were initially regarded as deleterious effects. But in the last decade, they turned out to be benefits to control energy deposition over long distances. These effects create very high aspect ratio structures which have found a number of important applications, particularly for glass separation with non-ablative techniques. This chapter reviews the developments of in-volume ultrafast laser processing of transparent materials. We discuss the basic physics of the processes, characterization means, filamentation of Gaussian and Bessel beams and provide an overview of present applications