СТРЕСС-РЕАКЦИИ ПРИ РАЗЛИЧНЫХ МЕТОДАХ АНЕСТЕЗИИ ВО ВРЕМЯ ОФТАЛЬМОХИРУРГИЧЕСКИХ ВМЕШАТЕЛЬСТВ У ДЕТЕЙ

Just like any surgery, a surgical operation pertaining to the eye and its appendages is a common cause of stress that changes the functions of all organs and systems. Numerous previous studies have shown this. The task of anesthesia is to protect a body from stress.The purpose of the study was to estimate the severity of a stress reaction when using different methods of anesthesia during eye surgeries in children.Material and methods. Plasma concentrations of glucose, lactate and cortisol were measured in children aged 4 to 18 years old at three surgical stages. Various methods of anesthesia were used in 5 groups. The patients were distributed at random with 20 children in every group. Results. All estimated values were within the age-specific reference range. Glucose and cortisol levels tended to increase, whereas lactate level was decreasing.Conclusion. The suggested anesthesia types can sufficiently protect patients during eye surgeries and be applied in the practice. Операции на глазном яблоке и придаточном аппарате глаза, как и любое вмешательство, приводит к возникновению стрессовой реакции в организме с изменением функции всех органов и систем в целом, что было показано в многочисленных ранее выполненных исследованиях. Задача анестезии обеспечить защиту организма от переносимого стресса.Цель исследования – оценить выраженность стресс-реакции при различных методах анестезии во время офтальмохирургических вмешательств у детей.Материал и методы. У детей в возрасте от 4 до 18 лет оценивали глюкозу, лактат, кортизол в крови на трех этапах операции в 5 группах с разными методами анестезии. Пациенты были распределены случайным образом по 20 человек.Результаты. Все оцениваемые показатели находились в пределах возрастных референсных значений. При этом глюкоза и кортизол имели тенденцию к повышению, лактат снижался.Заключение. Предложенные варианты анестезии имеют достаточный уровень защиты пациентов при выполнении офтальмохирургических вмешательств и могут быть использованы в практике.

Genetic testing of ocular manifestations of proliferative syndrome to provide pathophysiology-oriented treatment

M.E. Weener1, N.A. Bakunina2,3, J.M. Salmasi4, G.V. Poryadin4, D. Barh1,&nbsp;Yu.D. Kuznetsova2, L.M. Balashova2,4 1LLC "Oftalmic", Moscow, Russian Federation 2Non-profit partnership "International Scientific and Practical Center for the Proliferation of Tis-sues of Russia", Moscow, Russian Federation 3N.I. Pirogov City Clinical Hospital No. 1, Moscow, Russian Federation 4Pirogov Russian National Research Medical University, Moscow, Russian Federation Background: uncontrolled cell proliferation of the ocular blood network is one of the leading causes of blindness and low vision worldwide. We summarize relevant published data and our 5-year experience in searching treatment tools for excessive non-productive proliferation. Aim: to describe genetic patterns in patients with ocular blood network proliferation for predicting disease course and selecting adequate treatment. Patients and Methods: 1210 patients with proliferative ocular disorders, retinopathy of prematurity, and diabetes were enrolled. Patients were divided into three groups: (1) monogenic disorders, (2) proliferative vitreoretinopathy and diabetes mellitus, (3) retinopathy of prematurity. Follow-up was 6 to 36 months. Laboratory, genetic, and relevant clinical tests were pursued in all patients. Results: proprietary approach of bioinformatic analysis of whole exome/whole genome sequencing data allows for specifying the proliferative process’s prognosis and severity given clinical and genetic findings. This approach includes the analysis of gene mutations directly or indirectly involved in angiogenesis and key signaling pathways. The analysis of mutation identified in group 2 revealed 509C&gt;T TGFB1 gene polymorphism in two patients and c.3174G&gt;A IGF1R gene polymorphism in three patients. In group 3, the most common VEGFA gene polymorphisms were +13553C&gt;T, -634G&gt;C, +405G&gt;C (rs2010963), and -460C&gt;T (rs833061). Conclusion: specifying the prognosis of the course and severity of proliferative ocular disorders pathogenically-oriented targeted treatment requires specialized genetic testing using an improved data analysis approach. Keywords: proliferative syndrome, diabetes, retinopathy of prematurity, VEGFA, TGFB1, IGF1R, Stickler syndrome, Wagner syndrome, Wolframe syndrome, Marshall syndrome, Norrie disease, Coats disease, retinoschisis. For citation: Weener M.E., Bakunina N.A., Salmasi J.M. et al. Genetic testing of ocular manifestations of proliferative syndrome to provide pathophysiology-oriented treatment. Russian Journal of Clinical Ophthalmology. 2022;22(1):16–22 (in Russ.). DOI: 10.32364/2311-7729-2022-22-1-16-22. <br

The study of interactome in Russian patients with Usher syndrome to select priority approaches in pathogenetically oriented treatment

M.E. Ivanova1, D.S. Atarshchikov2, A.M. Demchinsky3, V.V. Strelnikov4, D. Barh5, G.V. Poryadin6, L.M. Balashova7, J.M. Salmasi6 1LLC “Oftalmic”, Moscow, Russian Federation 2Central Clinical Hospital under Presidential Affairs, Moscow, Russian Federation 3Autonomous nonprofit organization “Scientific and industrial laboratory “Sensor technology &nbsp; for deafblind”, Moscow, Russian Federation 4Research Centre for Medical Genetics, Moscow, Russian Federation 5Institute of Integrative Omics and Applied Biotechnology (IIOAB), Bangalore, India 6Pirogov Russian National Research Medical University, Moscow, Russian Federation 7Non-profit partnership International Scientific and Practical Center for the Proliferation of Tissues of Russia, Moscow, Russian Federation Background: Usher syndrome (USH) is a heterogeneous syndrome characterized by hearing loss and vision loss. The prevalence of USH is estimated to 5:100,000. USH is classified into three subtypes (I, II, and III) depending on the specific gene mutation, i.e., MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2 for type 1; USH2A, ADGRV1, DFNB31 for type 2; and CLRN1 for type 3. USH requires genetic studies to confirm the diagnosis, to manage patients, and to develop pathogenetically oriented treatment approaches. Historical aspects and development of molecular diagnosis of the disease, as well as evolution of approaches to the treatment are discussed. Aim: to study mutational spectrum in a cohort of Russian patients with USH and to analyze metabolome and interactome as well as pathogenic pathways of USH development to discover targeted therapies. Patients and Methods: 28 patients with USH were enrolled in the study and underwent examinations (clinical trial protocol No. NCT03319524 ). Comprehensive eye and ENT examination as well genetic studies were performed. The diagnosis was confirmed by MLPA next-generation sequencing and Sanger sequencing. Results: type 1 USH was diagnosed in 53.57% of patients and type 2 USH in 39.2% of patients. 17.85% were not confirmed genetically being in line with world statistics. Mutations in genes MYO7A (72.72%), CDH23 (9.09%), PCDH15 (9.09%), and USH1C (9.09%) were found in 11 patients. 11 mutations were identified in MYO7A gene, 54.54% were pathogenic mutations described for the first time. MYO7A: p.Q18* was the most common (27.27%) mutation associated with early and the most severe clinical manifestations. Two novel mutations (p.E1301* и c.158-?_318+?del) were identified in PCDH15 gene. In 90% of patients with type 2 USH, the diagnosis was confirmed genetically. 11 mutations were identified in USH2A gene, 27% were pathogenic causative mutations described for the first time. The most common mutations in USH2A were p.W3955* (50%), p.E767fs, p.R1653*, and c.8682–9A&gt;G (20% each). Conclusion: detailed in silico analysis of metabolome and interactome as well as pathogenic pathways of USH development in Russian cohort was performed. The most promising treatment strategies including gene therapy are discussed. Keywords: USH, USH2A, MYO7A, mutation, Usher syndrome, congenital deaf-blindness, gene therapy, interactome, modeling. For citation: Ivanova M.E., Atarshchikov D.S., Demchinsky A.M. et al. The study of interactome in Russian patients with Usher syndrome to select priority approaches in pathogenetically oriented treatment. Russian Journal of Clinical Ophthalmology. 2019;19(4):180–188. <br

Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia))

M.E. Ivanova1, V.V. Kadyshev2, D.S. Atarshchikov3, I.V. Zolnikova4, N.P. Akchurina4, N.K. Serova5, F.A. Konovalov6, E.R. Lozier6, E.A. Pomerantseva7, N.V. Vetrova7, D. Barh8, L.M. Balashova9,&nbsp;J.M. Salmasi10 1 LLC “Oftalmic”, Moscow, Russian Federation 2 Research Centre for Medical Genetics, Moscow, Russian Federation 3 Central Clinical Hospital under Presidential Affairs, Moscow, Russian Federation 4 Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russian Federation 5 N.N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation 6 Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation 7 Center for Genetics and Reproductive Medicine “Genetiko”, Moscow, Russian Federation 8 Institute of Integrative Omics and Applied Biotechnology (IIOAB), Bangalore, India 9 Non-profit partnership International Scientific and Practical Center for the Proliferation of Tissues of Russia, Moscow, Russian Federation 10Pirogov Russian National Research Medical University, Moscow, Russian Federation The article describes the clinical case of optic atrophy due to a homozygous mutation in exon 3 of the C19orf12 gene (chr19: 30193863AACAGCCCCCCG&gt; A, rs515726204), the frequency of which in the ExAC control sample is 0.0074. With this mutation, a frameshift occurs at 69-th position (p.Gly69fs, NM_001031726.3), which usually leads to neurodegeneration with the brain iron accumulation (NBIA), type 4 (OMIM: 614298). In described clinical case the main complaint of patient was visual impairment, with magnetic resonance imaging patient revealed only the expansion of the sellar fossa. The vision of 7-year-old boy decreased significantly for 2 years without any apparent reasons, spectacle correction did not give an improvement in vision to 100%. During the examination partial atrophy of the optic nerves was revealed, consultations were conducted with a neurologist, neurophthalmologist. Hyperreflexia, gait changes, and a slight delay in speech development were also revealed. No other clinical neurological symptoms were observed. The article describes a detailed ophthalmic clinical picture, discusses diagnostic and therapeutic tactics. Keywords: optic nerve atrophy, neurodegeneration with the brain iron accumulation, NBIA, mutation, gene, C19orf12. For citation: Ivanova M.E., Kadyshev V.V., Atarshchikov D.S. et al. Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia)). Russian Journal of Clinical Ophthalmology. 2020;20(1):–36. DOI: 10.32364/2311-7729-2020-20-1-33-36. </p