Корреляционный анализ морфофункциональных и иммунологических параметров у пациентов с продвинутыми стадиями первичной открытоугольной глаукомы

PURPOSE. To study the correlations between the immunological data and the indicators of electroretinography (ERG) and optical coherence tomography (OCT) in patients with advanced stages of primary open-angle glaucoma (POAG).METHODS. Previously, we conducted a multimodal study of patients with advanced stages of glaucoma involving ERG, morphometric and immunological studies. In this new study we performed a correlation analysis of the immunological and morphofunctional data of patients with advanced stages of POAG. The study included 35 patients (35 eyes), among them 19 women and 16 men, who were divided into two groups: group 1 — stage II POAG (12 patients, 12 eyes), and group 2 — stage III POAG (23 patients, 23 eyes). The average age of the subjects was 64.2±6.5 years. Intraocular pressure was compensated in all study patients. The Pearson's correlation coefficient was used to calculate the linear relationship between continuous features.RESULTS. In the subgroup with stage II POAG significant correlations of moderate strength (according to the Chaddock scale) were found between the parameters of pattern ERG (PERG) and photopic negative response (PhNR) and the level of VEGF-A in the blood serum (BS), EGF in the tear fluid (TF) and aqueous humor (AH); strong correlations — for the concentrations of EGF and TGF-β2 in the AH. In group 2, moderate correlations between PERG and PhNR parameters and the level of IL-1RA in the TF were found, as well as moderate correlation of TGF-β2 expression in the AH with PnHR amplitude from the baseline. In patients with stage II glaucoma, the levels of MIP-1β/CCL4 in the TF, IL-1RA in the intraocular fluid correlated with the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (GCL), while the EGF in the TF and AH correlated with RNFL thickness. In the group with stage III POAG, correlations of moderate strength were found for the expression level of TNF-α, IL-8/CXCL8 in the TF and RNFL thickness, and strong correlations — for the level of IP-10/CXCL10, HGF/SF, TGF-β2 in AH and the thickness of RNFL and GCL.CONCLUSION. Comparison of ERG, OCT findings and the level of cytokines of various biological effects in the BS, TF and AH confirmed the high informativeness of PERG and PhNR indicators and immunological data as markers of advanced stages of POAG, and allow EGF to be considered as the most promising pathogenetically oriented immunological marker of II and III stages of glaucoma.ЦЕЛЬ. Изучить корреляционные взаимосвязи между данными иммунологических исследований и показателей электроретинографии (ЭРГ) и оптической когерентной томографии (ОКТ) у пациентов с продвинутыми стадиями первичной открытоугольной глаукомой (ПОУГ).МЕТОДЫ. Ранее нами было выполнено мультимодальное исследование пациентов с продвинутыми стадиями глаукомы, включающее электроретинографию, морфометрические и иммунологические исследования. В настоящей работе проведен корреляционный анализ данных иммунологических и морфофункциональных исследований у больных с продвинутыми стадиями ПОУГ. Проанализированы результаты исследований 35 пациентов (35 глаз), в том числе 19 женщин и 16 мужчин, в двух группах: 1 — с развитой (12 больных, 12 глаз), и 2 — далекозашедшей стадией ПОУГ (23 пациента, 23 глаза). Средний возраст исследуемых составил 64,2±6,5 лет. Внутриглазное давление было компенсировано у всех обследуемых. Для вычисления линейной зависимости между непрерывными признаками использовали коэффициент корреляции Пирсона.РЕЗУЛЬТАТЫ. В подгруппе с развитой глаукомой выявлены достоверные корреляции «заметной» силы (по шкале Чеддока) между параметрами паттерн-ЭРГ (ПЭРГ) и фотопического негативного ответа (ФНО) и уровнем VEGF-A в сыворотке крови (СК), EGF в слезной жидкости (СЖ) и внутриглазной жидкости (ВГЖ); и взаимосвязи «высокой» силы – для концентраций EGF и TGF-β2 в ВГЖ. В группе больных с далекозашедшей ПОУГ выявлены корреляции «умеренной» силы для параметров ПЭРГ и ФНО и содержания IL-1RA в СЖ, и «заметная» корреляция экспрессии TGF-β2 в ВГЖ с амплитудой ФНО от изолинии. У пациентов со развитой стадией глаукомы уровни содержания MIP-1β/CCL4 в СЖ, IL-1RA в ВГЖ коррелируют с толщиной слоя нервных волокон сетчатки (СНВС) и ганглиозных клеток сетчатки (ГКС), а концентрации EGF в СЖ и ВГЖ — с толщиной СНВС. В группе с далекозашедшей ПОУГ обнаружены корреляции «умеренной» силы для уровня экспрессии TNF-α, IL-8/CXCL8 в СЖ и толщины СНВС и «заметной» силы — для содержания  IP-10/CXCL10,  HGF/SF,  TGF-β2  в  ВГЖ  и  толщины СНВС и слоя ГКС.ЗАКЛЮЧЕНИЕ. Сопоставление результатов электроретинографии, ОКТ и уровня цитокинов разнообразного биологического действия в СК, СЖ и ВГЖ подтверждают клинически значимую информативность параметров ПЭРГ и ФНО и показателей иммунологических исследований как маркеров продвинутых стадий ПОУГ и позволяют выделить EGF в качестве наиболее перспективного патогенетически ориентированного иммунологического маркера II и III стадии глаукомы

РЕОЛОГИЧЕСКИЕ СВОЙСТВА И ТЕРМОСТАБИЛЬНОСТЬ ЛИТЬЕВЫХ КОМПОЗИЦИЙ НА ОСНОВЕ ПОЛИФЕНИЛЕНСУЛЬФИДОВ

The rheological properties of polysulfide (PPS) melts and composite materials based on them were investigated in a wide range of temperatures and concentrations of fillers of different nature. It was established that the introduction of rheological additives into dispersed and hybrid-filled composite materials allows significantly reducing the viscosity and improving the processability of the compositions. Introduction of heat-stabilizing additives into PPS allows expanding the temperature interval of processing the composite materials based on PFC from 320 to 340°С. Complete thermal stability curves for the PPS compositions in a wide temperature range were obtained.Исследованы реологические свойства расплавов полифениленсульфидов (ПФС) и композиционных материалов на их основе в широком интервале температур и концентраций наполнителей разной природы. Установлено, что введение реологических добавок в дисперсно- и гибридно-наполненные полимерные композиционные материалы позволяет существенно уменьшить вязкость и улучшить перерабатываемость композиций. Введение термостабилизирующих добавок позволяет повысить температуру переработки композиционных материалов на основе ПФС с 320 до 340°С. Получены полные кривые термостабильности для ПФС-композиций в широком диапазоне температур

Structural and Functional Disorders in Glaucoma: the Prospects for Preclinical Diagnosis. Part 1. Is the Search for what Comes First Relevant?

The review analyzes the capabilities of modern technologies of structural neuroimaging of the retina, standard perimetry, and studies of ocular blood flow in the early diagnosis and management of glaucoma. The relevance of the search for those structural and functional changes that are primary in the development of glaucomatous optical neuropathy (GON) and the diagnostic method that has the greatest clinical significance is discussed. Progress in understanding the pathogenesis of glaucoma and the expansion of scientific understanding of key risk factors for the development and progression of the disease, including genetic factors, can be crucially important to substantiate new strategies for preclinical diagnosis and the development of radically new approaches to personalized and preventive glaucoma therapy. However, the search for what arises most early with in primary open-angle glaucoma — changes in structure or function — will not have clinical relevance unless you take into account the capabilities of specific methods of structural and functional neuroimaging that represent information at various levels of organization of the visual system. The search for a single primary factor in the pathogenesis of GON can lead to an erroneous exaggeration of the close relationship between the variables being studied, which in reality either does not exist as a causal relationship or is significantly less than what is supposed — the phenomenon called “illusory correlation”. The reliable diagnosis of early changes that occur before the clinical manifestation of glaucoma is most likely to be based on a combination of structural, functional, and hemodynamic indicators, aimed not only to increase the sensitivity of diagnosis in detecting the earliest events in the development of GON, but rather to dramatically improve the understanding and quality of interpretation of those markers that we own

Structural and Functional Disorders in Glaucoma: Prospects for Preclinical Diagnosis. Part 2. Electrophysiological Markers of Early Neuroplastic Events

Analysis of the literature on the problem of structural and functional relationships in the development and progression of glaucomatous optical neuropathy (GON) shows that the search for a single primary factor may lead to an erroneous exaggeration of its role in the pathogenesis of GON. A more promising approach may be to search for clinically significant combinations of current markers of changes in structure, function, and ocular blood flow, and to expand our fundamental understanding of the processes underlying these changes, designed to improve their interpretation radically. The discussed in this review data of recent studies showed that the earliest event in the development of GON is the weakening and loss of synapses, even with the preserved dendritic branching. We assume that the loss of synapses on dendrites and axon terminals, being a manifestation of synaptic plasticity, may occur simultaneously with the change in anterograde transport in axons of retinal ganglion cells (RGC), or, ahead of it. Early changes in the discharge timing of the RGCs associated with a decrease in the strength of synaptic contacts and the elimination of synapses on dendrites can be a target for neuroprotective therapy. The review analyzes the tests of modern electroretinography, which can serve as markers of early events in the development of GON, including plastic changes in the retina at the preclinical stage of glaucoma, and provides physiological rationales for their selective possibilities for clinical practice

Sedative-hypnotic and muscle relaxant activities of propoxazepam in animal models and investigation on possible mechanisms

Analgesic (for both neuropathic and nociceptive pain) and anticonvulsant action of 7-bromo-5-(o-chlorophenyl)-3- propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) make it perspective for further studying. Objectives: Propoxazepam was evaluated for sedative-hypnotic-like activity in mice and involved mechanisms in a battery of tests: acute oral toxicity, motor coordination and muscle relaxation studies. Materials and Methods: Acute toxicity (rats) and thiopental-induced sleeping (mice) were determined as motor coordination and muscle relaxation. Results: As relatively nontoxic substance (LD50>5000 mg/kg) propoxazepam belong to fifth category according to GHS toxicity classification. At high doses (700, 1100 and 1300 mg/kg, i.p.) a delay in the righting reflex was observed but not a total loss. The results indicated that substance induces hypnotic effects. Because propoxazepam produces any effect on rotarod test, seems that its effects on sleeping time and sleep latency are mediated by affecting motor movement. Conclusion: Based on previous results and present data, it should be presumed that GABAergic mechanisms may be involved in the potentiating effect of propoxazepam on thiopental-induced sleeping time and sleep latency in mice. Propoxazepam potentiates sleep induced by hypnotics like thiopental, but can not induce hypnosis by itself

Blood Flow and Functional Changes in the Retina and the Optic Nerve Due to Blunt Eye Trauma

To assess the damaged regional blood flow and functional activity of the retina and the optic nerve, 96 patients (96 eyes) with a blunt eye trauma (BET) were observed, of which 62 patients (62 eyes) had mild BET (group I), and 34 patients (34 eyes) had moderate BET (group II). Using Ultrasound Doppler techniques, we revealed a statistically significant increase (p < 0.05) of the peak systolic velocity (Vsyst) in the ophthalmic artery (OA), and a decrease of Vsyst and the final diastolic velocity (Vdiast) in the central retinal artery (CRA) (p < 0.05) during the first three days after the trauma in both groups. The recorded photopic negative response (PhNR) in the cone ERG and visual evoked potentials (VEP) showed an inhibited electrical activity of the inner retinal neurons and the visual cortex and a delayed VEP latency. The degree of these changes depended on the severity of post-contusion effects. In patients of group II, a greater inhibition of VEP into small patterns, and a smaller PhNR amplitude in ERG in response to low and high stimulus intensities was observed. All patients displayed changes in the vascular and neuronal systems of the retina in the early post-contusion period, which almost fully disappeared after one month following a 1st degree trauma but remained in the 2nd degree trauma // Russian Ophthalmological Journal, 2016; 1: 32-38

The Effectiveness of Retinalamin® Administered by Various Intramuscular Injection Timings in the Treatment of Patients with the Dry Form of Age- Related Macular Degeneration

The paper presents the evaluation of Retinalamin efficacy administered intramuscularly to 90 patients (180 eyes) aged 47 to 75 (averagely, 65.9 ± 7.18 years) with various stages of dry age-related macular degeneration (AMD) once or twice in 6 months. The data of multifocal electroretinography (MfERG) showed that in 80 % of cases of early and intermediate AMD stages, the functional state of the retina improved after a course of Retinalamin, reaching a peak 2 months after the start of treatment. A second course of Retinalamin, given 3 months later, resulted in a more pronounced improvement of the functional parameters, achieving the maximum in the month 5 of the follow-up period. This is confirmed by a change in the P1 component of Mf ERG, which proved to be the most pronounced in the central ring, corresponding to the foveal area. In more than 70 % of cases with atrophic AMD, a positive dynamics of the functional activity of the macula was noted only after a repeated course of intramuscular injections of Retinalamin, whose curative effect reached the maximum in the month 5 of the follow-up. An increase in the density of the P1 component of MfERG was more noticeable in the last two rings, corresponding to the periphery of macula // Russian Ophthalmological Journal, 2016; 1: 39-46

Clinical and functional state of the retina after inadequate laser coagulation of peripheral vitreochorioretinal dystrophies. Part 1. Electroretinography

Purpose of our work was to evaluate the effect of inadequate laser coagulation (LC) of peripheral vitreochorioretinal dystrophy (PVCRD) on the clinical and functional state of the retina. Material and methods. Ganzfeld ERG and multifocal ERG (mfERG) were recorded in 18 patients (32 eyes) with PVСRD in which, upon examination of the fundus, signs of inadequate retinal LC were detected and documented, such as hypercoagulation, an excessively large number of coagulates with minimal changes in the retina, or massive LC at the normal fundus. Results. The functional activity of the macular region after massive LC at the periphery of the retina in patients with PVCRD was shown to be reduced. The characteristic signs of reduction of the ganzfeld ERG and mfERG associated with a large volume of LC of the retina in patients without a history of surgical treatment of rhegmatogenous retinal detachment are described. For the first time, a functional method has been proposed to identify the risk of development and progression of macular dysfunction associated with massive LC of the retina, which includes a decrease in the amplitude of the waves of the maximal ERG and / or oscillatory potentials by 30 % or more with a parallel decrease in the density P1 in 1–3 rings of mfERG by 30 % and more as compared to the norm. Conclusion. Electrophysiological markers of macular dysfunction development risk associated with massive LC of the retina are proposed. The use of these markers in the clinic is important for predicting the risk of pathological changes in the macular region involving a decrease in visual functions, the choice of treatment tactics, and expert assessment of the volume of retinal LC redundancy

RHEOLOGICAL PROPERTIES AND THERMAL STABILITY OF CAST COMPOSITIONS BASED ON POLYPHENYLENESULPHIDES

The rheological properties of polysulfide (PPS) melts and composite materials based on them were investigated in a wide range of temperatures and concentrations of fillers of different nature. It was established that the introduction of rheological additives into dispersed and hybrid-filled composite materials allows significantly reducing the viscosity and improving the processability of the compositions. Introduction of heat-stabilizing additives into PPS allows expanding the temperature interval of processing the composite materials based on PFC from 320 to 340°С. Complete thermal stability curves for the PPS compositions in a wide temperature range were obtained

Fractal Phototherapy in Neuroprotection of Glaucoma

Purpose: to study the effect of low-intensity fractal light stimulation on the sensitivity in the visual field in patients with suspected glaucoma (SG) and primary open-angle glaucoma (POAG). Material and Methods. The study involved 146 people, including 98 patients of the main group (No. 1) and 49 people from the control group “placebo”-therapy (No. 2). Standard automatic perimetry was performed (SITA-Standard, Humphrey, CarlZeissMeditec, 24-2). The dynamics of the perimetry indices MD and PSD were evaluated before and after the course of a ten 10-minute session of fractal phototherapy or after a 10-day course of relaxation consisting in watching a particular training video twice a day. The maximum brightness of the flashes on the cornea during phototherapy was 10–12 lux, the fractal dimension of the optical signal was D = 1.4. Results. A two-week course of low-intensity stimulation with fractal optical signals reliably improved the MD reflected the common defect in the visual field, in all patients with SG and POAG. The expositions to videos with a relaxation program did not have a statistically significant effect on MD and PSD indices. The pronounced effect of fractal stimulation revealed in eyes with POAG III (a reduction of MD on average by 4.39 dB) suggests that even in advanced stages of glaucoma in the general population of retinal ganglion cells there is a significant percentage of cells that are still at the plastic stage of reversible functional changes and can respond positively to therapy. The results substantiate the feasibility of application neuroprotective therapy to patients with any stage of glaucoma, including the advanced stage. Conclusion. In this study, we first used the technology of fractal optical stimulation for the treatment of glaucoma. The first evidence of the neuroprotective effect of fractal phototherapy for POAG at different stages has been obtained. Fractal stimulation can be considered as a new non-pharmacological (physiotherapeutic) approach to neuroprotective therapy, whose potential and mechanisms need to be studied in future studies