Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome.

Autosomal recessive Cohen syndrome is a neurodevelopmental disorder characterized by postnatal microcephaly, intellectual disability, and a typical facial gestalt. Genetic variants in VPS13B have been found to cause Cohen syndrome, but have also been linked to autism, retinal disease, primary immunodeficiency, and short stature. While it is well established that loss-of-function mutations of VPS13B cause Cohen syndrome, the relevance of missense variants for the pathomechanism remains unexplained. Here, we investigate their pathogenic effect through a systematic re-evaluation of clinical patient information, comprehensive in silico predictions, and in vitro testing of previously published missense variants. In vitro analysis of 10 subcloned VPS13B missense variants resulted in full-length proteins after transient overexpression. 6/10 VPS13B missense variants show reduced accumulation at the Golgi complex in the steady state. The overexpression of these 6/10 VPS13B missense variants did not rescue the Golgi fragmentation after the RNAi-mediated depletion of endogenous VPS13B. These results thus validate 6/10 missense variants as likely pathogenic according to the classification of the American College of Medical Genetics through the integration of clinical, genetic, in silico, and experimental data. In summary, we state that exact variant classification should be the first step towards elucidating the pathomechanisms of genetically inherited neuronal diseases.

[Orbital Trauma]. / Trauma der Orbita.

Orbital trauma is a common medical emergency with potentially sight-threatening complications. Due to the confined orbital conditions, any direct injury or space-consuming lesion may cause serious tissue damage. Possible complications are orbital fractures, foreign body injuries, development of orbital compartment syndrome and traumatic optic neuropathy. Clinical signs include periorbital hematoma or emphysema, subconjunctival hemorrhage, proptosis, decreased ocular mobility, decreased vision, increased intraocular pressure and relative afferent pupillary defect. Ophthalmic status and low-dose CT-imaging provide key information regarding the therapeutic decision. Treatment options include surgical exploration, reconstruction or decompression or a conservative approach with anti-inflammatory or anti-glaucomatous medication. Rapid interdisciplinary diagnostics and therapy is critical for early detection and prevention of irreversible functional loss respectively. Considering the frequent association with life-threatening comorbidities diagnosis may be complicated.

Selective Laser Trabeculoplasty Versus MIGS: Forgotten Art or First-Step Procedure in Selected Patients with Open-Angle Glaucoma.

INTRODUCTION: To evaluate the long-term effect on intraocular pressure (IOP) and glaucoma medication of selective laser trabeculoplasty (SLT) compared to minimally invasive glaucoma surgery (MIGS) in primary open-angle glaucoma (POAG) and its potential in clinical practice. METHODS: A total of 342 consecutive patients (stand-alone procedures) were included. One hundred and five patients underwent SLT treatment (360° SLT, 95-105 spots, Trabeculas SLT ARCLaser, Nürnberg, DE), 107 patients had an ab interno-derived trabeculotomy (Trabectome®, NeoMedix, Tustin, USA), and 130 patients received iStent inject® implantation (2 implants-Glaukos, CA, USA). IOP and glaucoma therapy were evaluated preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1, 2, and 3 years postoperatively. Statistical analysis was performed using a regression model and propensity matching score (reduced cohort number) using SPSS v20.0. Kaplan-Meier analysis was included using the following six criteria: criterion A (IOP ≤ 21 mmHg with or without medication, qualified success), criterion B (IOP ≤ 18 mmHg with or without medication, qualified success), criterion C (IOP ≤ 21 mmHg without medication, complete success), criterion D (IOP ≤ 18 mmHg without medication, complete success), criterion E (IOP ≤ 21 mmHg and IOP reduction > 20% after therapy), and criterion F (IOP ≤ 18 mmHg and IOP reduction > 20% after therapy). RESULTS: In the matched cohort, the SLT cohort showed an IOP reduction of 31.2% from 19.9 ± 2.3 to 13.7 ± 2.7 mmHg (p < 0.001) 3 years postoperatively; in Trabectome® IOP decreased by 31.4% from 20.5 ± 1.3 to 13.8 ± 2.0 mmHg (p < 0.001) and in iStent inject® by 29.9% from 19.5 ± 2.0 to 13.8 ± 2.7 mmHg (p < 0.001). Trabectome® and iStent inject® could not demonstrate a significant reduction in glaucoma therapy (Trabectome® p = 0.138, iStent inject® p = 0.612); a significant drop was noted in SLT (2.2 ± 1.2 to 1.7 ± 1.2, p = 0.046). SLT and MIGS achieved good to moderate survival rates using criterion A (93.3% SLT, 79.7% Trabectome®, 77.6% iStent inject®) and criterion B (74.5% SLT, 48.0% Trabectome®, 56.2% iStent inject®). As expected, low survival rates were obtained with non-filtering procedures: criterion C 11.1% in SLT, 6.5% in Trabectome®, 7.0% in iStent inject® and criterion D 3.0% in SLT, 4.3% in Trabectome®, 3.7% in iStent inject® in 3-year follow-up. CONCLUSION: The SLT is a low-complication and effective method for reducing pressure in mild to moderate POAG. SLT is suitable as an initial procedure when setting up a step scheme; MIGS is the treatment of choice as a follow-up for mild to moderate forms of glaucoma and accepted topical therapy. Ethic approval had been given by the Ethikkommission Charité - Universitätsmedizin Berlin, EA4/047/20-retrospectively registered.

Firework-inflicted ocular trauma in children and adults in an urban German setting.

PURPOSE: To assess firework-inflicted ocular trauma in the German capital during the week around New Year's Eve with regards to patient characteristics and age, severity of injuries, and their management and outcome. METHODS: A retrospective chart review of all patients presenting to the department of ophthalmology of Charité-University Medicine Berlin during a 7-day period around New Year's Eve in the years 2014-2017 was performed. Patients with ocular complaints and injuries caused by fireworks were included. We recorded demographic data, active role, visual acuity at presentation and at last follow-up, the most pertinent clinical findings, management and outcome with regards to visual acuity, and integrity of the eye. RESULTS: A total of 146 patients with 165 injured eyes were included. Median age at presentation was 23 (4-58) years, and 71.2% were male. Fifty-one patients (34.9%) were less than 18 years old. Ninty-seven patients (66.4%) sustained minor, 34 (23.3%) sustained moderate, and 15 (10.3%) sustained severe injuries. Severe trauma was seen in younger patients (median age: 12, range: 4-58 years) than mild and moderate trauma (median age: 23, range: 4-45 years) and resulted in loss of light perception in two eyes and in a visual acuity of only light perception in three eyes. One eye was enucleated. CONCLUSION: Ocular trauma inflicted by fireworks can have serious consequences for ocular morbidity and visual acuity, especially in severe trauma which affected younger patients. To significantly reduce firework-inflicted trauma, a ban of private fireworks in densely populated areas and in the vicinity of children should be considered.

[Benign Neoplasms of the Orbit]. / Benigne Neoplasien der Orbita.

Benign orbital neoplasms comprise a wide spectrum of different entities. The origin of the tumours can be epithelial or mesenchymal. Epithelial neoplasms of the orbit originate from the lacrimal gland. The most important tumour is the pleomorphic adenoma, which should not be biopsied but resected in toto. The most common intraconal neoplasm in adults is the cavernous hemangioma. Symptomatic cavernous hemangiomas should be treated. The treatment of choice for most symptomatic benign neoplasms of the orbit is surgical resection. Suitable surgical approaches are anterior transconjunctival and lateral orbitotomy. Cryoextraction is a minimally invasive technique that is particularly suitable for cavernous hemangiomas.

Three-year results of ab interno trabeculectomy (Trabectome): Berlin study group.

PURPOSE: To assess the long-term outcome of Trabectome surgery in the treatment of primary open angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX): 3-year results. METHODS: Trabectome surgery (NeoMedix, Tustin, CA, USA) was performed in 268 POAG patients (women 57.46%, men 42.54%, age 72.35 ± 9.63 years) and 98 PEX glaucoma patients (women 58.16%, men 41.84%, age 73.42 ± 8.54 years), and uncontrolled intraocular pressure (IOP). Parameters were examined preoperatively, 1 day, 6 weeks, 3, 6, 12, 24 and 36 months post surgery. Kaplan-Meier analysis was performed using Criteria A (IOP ≤ 21 mmHg or ≥20% reduction from preoperative IOP), Criteria B (IOP ≤ 18 mmHg or ≥20% IOP reduction), Criteria C (IOP ≤ 21 mmHg, with or without medication) and D (IOP ≤ 18 mmHg, with or without medication). Complete success was defined as IOP ≤ 21 mmHg (Criteria E) and IOP ≤ 18 mmHg without medication (Criteria F). RESULTS: IOP was reduced from 19.10 ± 4.11 mmHg to 14.27 ± 2.93 mmHg (p < 0.001) and glaucoma medication was decreased from 2.40±0.92 to 1.77±1.00 (p < 0.001) in POAG after 36 months. In PEX, IOP decreased from 22.49±9.40 mmHg to 14.57±5.05 mmHg after 36 months (p < 0.001). Medications dropped from 2.31±1.02 to 1.75±0.91 (p = 0.006). Kaplan-Meier analysis showed a success rate of 80.5% for POAG and 80.8% for PEX using criteria A (p = 0.933) and 62.4% for POAG and 73.7% for PEX using criteria B (p = 0.147) at 36 months postoperatively. Complete success showed a low survival rate (criteria E-13.5% in POAG and 7.9% in PEX, p = 0.070 and criteria F-12.8% in POAG and 5.9% in PEX, p = 0.083). CONCLUSIONS: Trabectome is a safe method to lower IOP in patients with POAG and PEX glaucoma in the long-term period. It is beneficial to inform patients prior to surgery about adjuvant glaucoma medication after the surgery.