Comprehensive Treatment of Noninfectious Uveitis Accompanied by Macular Edema with the Use of Autologous Platelet-Rich Plasma

Background. A common cause of visual impairment in patients with non-infectious uveitis is macular edema, developing in 38–84 % of cases. Plasma enriched with platelets is widely used in various branches of medicine, the effectiveness of its use in the treatment of non-infectious uveitis, accompanied by macular edema, has not been sufficiently investigated. Aim: To evaluate the effectiveness of autologous platelet-rich plasma in the complex treatment of non-infectious uveitis accompanied by macular edema.Material and methods. The study was conducted on the basis of the academician S.N. Fyodorov Eye Microsurgery Federal State Institution in the period from 2016 to 2018, which included 123 people (176 eyes) from 18 to 50 years with non-infectious uveitis, accompanied by macular edema: 46 men, 77 women. Patients were divided into 2 groups. The main group consisted of patients receiving autologous platelet-rich plasma and anti-inflammatory treatment; the comparison group consisted of patients receiving anti-inflammatory treatment. The results of visual acuity, intraocular pressure, biomicroophthalmoscopy, optical coherence tomography of the macular zone, microperimetry, ultrasound examination on the side of the affected eye were evaluated. Statistical processing of the data was carried out in the program Statistica 10.Results. Maintenance of autologous platelet-rich plasma contributes to a statistically significant improvement in visual acuity on the 10th day of treatment by 64.2 %, a decrease in the thickness of the retina in fovea by 36.3 % and an increase in retinal photosensitivity by 34.6 % compared to the group of patients receiving only anti-inflammatory treatment. Conclusions. The use of autologous platelet-rich plasma in the complex treatment of non-infectious uveitis allows to accelerate the natural mechanisms of tissue regeneration, contributing to the reduction of macular edema, and improve visual performance

Clinical and diagnostic evaluation of the effectiveness of treatment of optic neuropathy in patients with edematous endocrine ophthalmopathy

The aim: to conduct a clinical and diagnostic evaluation of the effectiveness of the administration of a complex of drugs in the region of hemolymphocirculation in optical neuropathy in patients with edematous form of endocrine ophthalmopathy.Materials and methods. The results of diagnosis and treatment of 31 patients (61 eyes) with optical neuropathy on the background of edematous exophthalmos in endocrine ophthalmopathy were analyzed. To identify hidden forms of optical neuropathy, such studies were prescribed as computer microperimetry on a confocal infrared ophthalmoscope, a complex of electroretinographic studies: registration of maximum ERG, oscillatory potentials. Latent forms of optical neuropathy were detected in 22 cases. In 9 cases, there were obvious forms of optical neuropathy. All patients underwent a 10-day course of intensive complex treatment, consisting of injections into the region of hemolymphocirculation (projection of the pterygoid fossa) No. 6–8 (No. 3–4 on each side) with an interval of 24 hours of a drug mixture, the formulation of which included Lidocaine 20 mg, Dexazone 4 mg, Hemase 3000 UNITS, Dalargin 1 mg.Results. In all patients, there was a pronounced positive dynamics in the form of a significant (from 0.6 to 1.0) increase in visual acuity, a decrease in exophthalmos from (2.0 to 3.0 mm), an increase in color and contrast sensitivity.Conclusions. Due to the violation of venous and lymphatic outflow due to thickening of extraocular muscles and retrobulbar fiber, injections into the hemolymphocirculation region (projection of the pterygoid fossa) of drugs with a wide range of decongestant and metabolic effects are justified, effective and safe

Modern anatomical and physiological bases for maintaining the transparency of the corneal stroma

The article presents a literature review of the modern concept of anatomical and physiological structure and functioning of the cornea. The strict morphological structure and corneal tissue homeostasis ensure its transparency. Studying the mechanisms that regulate the constancy of the corneal tissue internal environment allows us to get closer to understanding the prospects forregenerative therapy for the corneal stroma pathology. The article discusses in detail the role and functional potential of corneal stromal cells, which are capable of reverse cytologic differentiation, which primarily ensures the maintenance of tissue homeostasis and corneal transparency. The functional activity of corneal cells can change for a number of reasons, which may be exogenous, iatrogenic (trauma, infection, etc.) or endogenous. Endogenous causes include: cell autoregulation pathologies (for example, enzyme defects); defects in transport systems leading to tissue hypoxia; disorders of the neuro-humoral regulation of trophism. The physical reason forthe violation of the corneal transparency is an increase in the light scattering. The article presents five main causes of increased light scattering in the opaque cornea, and also provides an overview of the main substances – components and products of cellular synthesis of corneal stromal cells: cytokines and growth factors (complex of the signal molecule and the SDF1/CXCR4 receptor, insulin-like growth factor 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, erythropoietin, neurotrophic factors, etc.). Thus, corneal opacity can be caused by a single pathogenic mechanism or be the result of a complex effect of several factors. The main processes of tissue homeostasis regulation are aimed at maintaining the unique morphological structure of the cornea

Complex studies on gene polymorphisms of MMP2, MMP3, MMP9 matrix metalloproteinases and TIMP1, TIMP2 tissue inhibitors of metalloproteinases in the patients with primary open-angle glaucoma

Abnormal expression of matrix metalloproteinases (MMP) in watery moisture in patients with glaucoma may affect regulation of intraocular pressure (IOP). MMP activity is regulated by tissue metalloproteinase inhibitors (TIMP). The imbalance between tissue metalloproteinase inhibitors and matrix metalloproteinases may contribute to the development of glaucoma. Genetic factors, including polymorphism of matrix metalloproteinase genes and their inhibitors genes, can regulate the level of their expression, thereby affecting susceptibility to disease. Our aim was to perform comprehensive analysis of the MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) polymorphisms, and TIMP1 (rs4898), TIMP2 (rs8179090) tissue inhibitor genes polymorphisms in the patients with stage II (advanced) primary open-angle glaucoma.99 patients (52 men and 47 women) with a verified diagnosis of stage II primary open-angle glaucoma were examined. The comparison group consisted of 100 age-matched persons (81 women and 19 men) without ophthalmic disorders. The single-nucleotide polymorphisms in promoter regions of MMP2, TIMP1, TIMP2 genes were analyzed by the TaqMan method, the MMP3 and MMP9 genes, by means of restriction fragment length polymorphism technique. Statistical evaluation was carried out using the specialized package of IBM SPSS Statistics 23 programs. The critical level of significance was assumed to be 0.05.The differences in the distribution of MMP2 rs243865 allelotypes with decreased frequency of TT genotype were found in the patient group and, vice versa, increased heterozygosity rates were revealed among them. In addition, the frequency of TIMP1 rs4898 heterozygous genotype was decreased in this group as compared to control sample. Four MMP/TIMP complex genotypes are positively associated with the development of pathology. Two of them were of bilocus type, i.e., MMP2-1306TC:TIMP2-418GG, and MMP3-11715A6A:TIMP1 372CC whereas two three-locus constellations were revealed, i.e., MMP2-1306TC:MMP9-1562CC:TIMP2- 418GG, and MMP3-11715A6A:MMP9-1562CC:TIMP1 372CC. There are nine MMP/TIMP complexes, the frequency of which in patients with glaucoma was significantly reduced when compared with control group.Polymorphism of regulatory regions of MMP2, MMP3, MMP9 genes and distinct gene variants of their inhibitors (TIMP1, TIMP2 genes) can be considered potential markers of the POAG development associated with an imbalance of MMP/TIMP activities

THE ELEMENTS OF INTRAOCULAR FLUID LYMPHATIC OUTFLOW PATHWAYS IN CHOROID IN NORM AND IN GLAUCOMA PATIENTS

Purpose. To detect and study the structure of aqueous humor lymphatic outflow pathways in choroid in normotensive patients and patients with primary open-angle glaucoma (POAG).Material and methods. Choroid fragments of seven human eyes (including two eyes with terminal glaucoma) enucleated on medical indications were studied. The structure of the choroid was investigated using immunohistochemistry and electron microscopy.Results. Lymphatic channels and lymphatic lacunae were revealed in the choroid structure. Lymphatic channels were detected in choriocapillar and vascular layers and were limited by Podoplanin+, Prox-1+, LYVE-1+ endothelium-like cells, fibroblasts and pigment cells. Lymphatic lacunae were located in suprachoroid layer and covered with endothelium-like cells and fibroblasts. Morphometric study showed an increase of the volume density of epithelium, interstitial spaces and choroid vessels related to edema and swelling of the choroidal stroma in the terminal stage of glaucoma.Conclusions. Human choroid contains lymphatic structures that are probably a part of the ocular lymphatic drainage system and participate in the aqueous humor outflow. Choroidal edema and swelling, the increase of the volume density of epithelium, interstitial spaces and choroid vessels in the terminal POAG stage indicate the lymphatic drainage dysfunction beginning from initial stages of glaucoma and lead to an aqueous humor outflow alteration through the protective lymphatic system

VEGF and eNOS genes polymorphism features in patients with diabetes mellitus with and without initial non-proliferative diabetic retinopathy

The endothelial NO synthase (eNOS) and vascular endothelial growth factor (VEGF) imbalance and the polymorphism of these genes may be the predisposition for diabetic retinopathy (DR) development and progression.The aim: to analyze VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes polymorphism and their combinations in patients with type 2 diabetes mellitus (DM2) with and without initial non-proliferative DR.Materials and methods. The study included 200 patients with type 2 diabetes (155 women and 45 men, age – 43–70 years): 111 people without and 89 people with DR. The polymorphism of the regulatory regions of VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes was studied using restriction fragment length polymorphism analysis and TaqMan Real-Time PCR by. Statistical processing was carried out using the software packages Statistica 10.0, SPSS Statistics 23 and the package of original programs for volumetric processing of bioinformation.Results. The VEGF-2578 heterozygosity and two complex genotypes – VEGF-2578CA:VEGF+936CC and NOS3-786CT:VEGF-2578CA:VEGF+936CC – signifi cantly decreased in patients with DR. The predisposition to early DR development to minor genotype of eNOS gene in the NOS3-786CC:VEGF+936CT complex and signifi cantly decreased the homozygous wild-type eNOS genotype in DM2 patients with ophthalmopathology were shown. NOS3-86TT:VEGF2578AA genotype signifi cantly decreased in group with retinopathy developing and the glycated hemoglobin high level.Conclusion. Along with the clinical risk factors for the development of DR in DM2, the genetic polymorphism of the regulatory regions of the genes analyzed by us has a signifi cant weight. When analyzing potential genetic markers, it is important to consider possible joint epistatic/hypostatic effects. The complex analysis of polymorphic gene can help early prognosis of the DR development

POLYMORPHISMS OF EXTRACELLULAR CONNECTIVE TISSUE REMODELING PROTEINASES AND <i>MMP2, MMP3, MMP9</i> GENES, AND NEOANGIGENESIS <i>VEGF</i> GENE IN RETINAL MICROANGIOPATHY IN THE PATIENTS WITH TYPE 2 DIABETES MELLITUS

The aim of our study was to perform an association analysis between MMP2, MMP3, MMP9, VEGF gene polymorphisms and development of non-proliferative diabetic retinopathy (DR) in the type 2 diabetic patients (DM).201 DM patients: 90 cases of DR and 111 subjects without DR features were included into the study. Polymorphic variants of MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), and VEGF (rs699947 and rs3025039) genes were assayed. The genetic typing was carried out by restriction fragment length polymorphism and TaqMan methods.The analysis of complex genotypes at the five polymorphic positions has revealed some significant findings in positive and negatively incorporated complexes. Increased frequencies of MMP2-1306 CC genotype in the group of patients with “early” development of complication, and more frequent combination of high-level HbA1c with MMP2-1306CC and MMP9-1562CT genotypes were shown in DR patients. Computerassisted modelling with visual reconstruction of network interactions between the genotypes involved into the destruction events and angiogenesis, as well as altered HbA1с levels (an integral parameter of glycemia), has revealed some differences in structural and functional organization of gene-gene and gene- protein interactions between the groups of patients with DR versus those without this disorder. Сonclusion. A design of interactome biological networks based on transcription regulation and metabolic pathways, as well as their topological analysis allows to build and study interactions of genes and proteins, with reference to pathogenetic studies of DM2 complications aiming for development of approaches to personalized prevention and therapy in future times

EFFECT OF COMPLEX TREATMENT USING PLATELET AUTOPLASMA ON CLINICAL AND LABORATORY PARAMETERS OF PATIENTS WITH ENDOGENOUS UVEITIS AND MACULAR EDEMA

Purpose: to study the clinical and laboratory efficacy of the platelet autoplasma use in the complex treatment of endogenous uveitis associated with systemic diseases accompanied by macular edema. Material and methods. The study included 46 people (72 eyes) with endogenous uveitis and macular edema. The diagnosis was made on the basis of the ophthalmological examination, including visometry, tonometry, biomicroscopy, ophthalmoscopy, perimetry, B-scan, optical coherence tomography of the macular zone, photoregistration of the anterior, posterior segment of the eye. The examination was carried out on the 1st and 10th day of treatment. The main group consisted of 22 people (36 eyes) who underwent anti-inflammatory therapy and the introduction of platelet plasma in the region of the pterygopalatine fossa. The control group consisted of 24 people (36 eyes) receiving only anti-inflammatory therapy (diprospan 0.5 paraequatorially №1, dexazone 4 mg intravenously №5, intravenous lasix 2.0 ml №5, electrophoresis with prednisolone № 7). All patients underwent the definition of IL-4, IL-6, IL-8, IL-17 in tear fluid before the study and on the 10th day. Results. The significant increase in the concentrations of pro-inflammatory cytokines (IL-17A and IL-8) and IL-4 and IL-6 involved in the development of autoimmune response and chronic inflammation was found in the patients with endogenous uveitis and macular edema. The use in the treatment of endogenous uveitis with macular edema of platelet autoplasma leads to more pronounced improvement of clinico-ophthalmological parameters (improvement in visual acuity, retinal photosensitivity, and retinal thickness reduction) relating to the comparison group. A decrease in the activity of the inflammatory process was noted in the main group after treatment, which is manifested by a significant decrease in the concentrations of IL-17A, IL-8, IL-4, IL-6, relating to the data obtained in the comparison group. The proposed scheme of complex treatment allows reducing the frequency of relapses of the pathological process

Особенности содержания матриксных металлопротеиназ 2, 3, 9 и тканевых ингибиторов матриксных металлопротеиназ 1, 2, 3, 4 во внутриглазной жидкости пациентов с первичной открытоугольной глаукомой

Aim. To study the content of matrix metalloproteinase (MMP)-2, -3, -9 and tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3, -4 in the aqueous humor of patients with moderate primary open-angle glaucoma (POAG).Materials and methods. The experimental group included 47 patients with verified moderate primary open-angle glaucoma. The control group consisted of 26 patients with uncomplicated cataract. The levels of MMP-2, -3, -9 were determined with Luminex Performance Human MMP Magnetic Panel 3-plex kit (R&amp;D Systems, USA), the concentration of TIMPs-1, -2, -3, - 4 was determined with the Human TIMP Magnetic Luminex Performance Assay 4-plex kit (R&amp;D Systems, USA). The study was carried out using flow-through field fluorometry on a Bio-Plex 200 double-beam laser analyzer (Bio-Rad, USA).Results. The study showed a statistically significant increase in the levels of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with moderate POAG compared with patients with uncomplicated cataract.Conclusion. The obtained data on high concentrations and imbalance in the levels of matrix metalloproteinases and their tissue inhibitors in the aqueous humor of patients with moderate POAG confirm the role of local inflammation, as well as impairments in the structure of the extracellular matrix and its remodeling in the mechanisms of development of this pathology. Цель – изучить содержание матриксных металлопротеиназ (МMP) 2, 3, 9 и тканевых ингибиторов матриксных металлопротеиназ (TIMP) 1, 2, 3, 4 во внутриглазной жидкости пациентов с развитой стадией первичной открытоугольной глаукомы.Материалы и методы. Обследованы 47 пациентов с верифицированным, на основании офтальмологического обследования, диагнозом развитой стадии первичной открытоугольной глаукомы, которые составили основную группу. Контрольную группу составили 26 пациентов с диагнозом «неосложненная катаракта». Концентрацию MMP-2, MMP-3, MMP-9 определяли с использованием набора Luminex Performance Human MMP Magnetic Panel (3-Plex) (R&amp;D Systems, США), определение концентрации TIMP-1, TIMP-2, TIMP-3, TIMP-4 проводили с помощью набора Human TIMP Magnetic Luminex Performance Assay 4-plex (R&amp;D Systems, США). Исследование проводилось методом проточной флуориметрии на двухлучевом лазерном анализаторе Bio-Plex 200 (Bio-Rad, США).Результаты. Установлена статистически значимо высокая концентрация матриксной металлопротеиназы-2 и тканевых ингибиторов матриксных металлопротеиназ 1, 2, 3, 4 во внутриглазной жидкости пациентов с развитой стадией первичной открытоугольной глаукомы относительно данных, полученных при исследовании внутриглазной жидкости лиц с неосложненной катарактой.Заключение. Полученные в исследовании данные о высоких концентрациях и нарушении баланса содержания матриксных металлопротеиназ и их тканевых ингибиторов в внутриглазной жидкости пациентов с развитой стадией первичной открытоугольной глаукомы подтверждают роль местного воспалительного процесса, а также нарушений структуры внеклеточного матрикса и его ремоделирования в механизмах развития патологического процесса.