PURPOSE: To study the state of the endothelial vasomotor mediators system (endothelin and nitric oxide), as well as the marker of endothelial damage - von Willebrand factor - in the dynamics of glaucoma modeling in rabbits, to identify ion-calcium regulation of these mediators. METHODS: The research was conducted on 60 rabbits, aged 2-3 years. Glaucoma model was induced by intravenous administration of 0.18% solution of adrenalin hydro- tartrat each week on days 1, 3 and 5. Developed scheme included 40 injections. A single drug dose depended on the weight of the animal and amounted to the following values: 12.5 mcg/kg for the first three injections, 20 mcg/kg from the fourth to the sixth injection and 25 mcg/kg for further injections. Endothelial dysfunction was estimated by blood serum levels of endothelin-1 (ET-1), nitric oxide and von Willebrand factor (EF). ET-1 level was determined by ELISA. The level of nitric oxide in peripheral blood was assessed by the level of its stable metabolite nitrite-ion NO₂ in citrate blood serum by means of The Griess Reagent System. The level of von Willebrand factor was determined by ristomycin reaction. RESULTS: An imbalance of endothelial mediators, marking an endothelial dysfunction was observed in glaucoma rabbit models induced by the introduction of the stress hormone adrenaline. The system of vasomotor mediators - endothelin (ET-1) and nitric oxide (NO) - shifted towards strengthening vasoconstriction. The level of ET-1 was increased by 70%, NO - reduced by 39%, the index of the ability to dilatation (IAD) was reduced by half in long-term modelling of glaucoma. Endothelial dysfunction in experimental glaucoma is the Ca²+-dependent process, so it was corrected with calcium channel blocker verapamil. In the course of its 4-month administration vasoconstrictor response in animals with glaucoma was reduced, the level of ET-1 declined by 58%, IAD increased threefold. CONCLUSION: The endothelium is one of the main target organs in the formation of primary glaucoma, and endothelial dysfunction plays a significant role in its pathogenesis. Directed action on this pathogenesis link can be of significant interest in the development of therapeutic treatment of glaucoma.

PURPOSE: To compare clinical features related to changes in the eye surface caused by long term use of prostaglandin antiglaucoma agents, containing and not containing preservatives, and to perform comparative morphological analysis of the conjunctival biopsies in the study groups. METHODS: The study was performed on 90 patients aged 36 to 89 years (mean age 64.5±11.3 years), including 36 males and 54 females. The first two groups were comprised of the patients with newly diagnosed primary open-angle glaucoma stage 1-3, who were prescribed Taflotan without preservatives produced by «Santen» (tafluprost 0.0015% solution in single use 0.3 ml dripping tubes) (1st group) and 0.005% latanoprost with 0.02% benzalkonium chloride or 0.004% travoprost with 0.015% benzalkonium chloride (2nd group). Mean duration of treatment within the frameworks of the study was 135 days, minimal - 90 days. The control group included patients with age-related cataract of various degree of maturation who did not receive local treatment. In the beginning and the end of the study, all patients underwent assessment of the eye surface condition for Dry Eye Syndrome (DES), including symptom scope according to the OSDI (Ocular Surface Disease Index); assessment of the conjunctival folds degree (LIPCOF); the tear film rapture time (TFRT); the degree of Rose Bengal staining of the eye surface (RB); and Schirmer 1 test. At the end of the study selective biopsies were performed during the surgery. RESULTS: Statistically significant gender differences in DES incidence were revealed: 78% of females (42/54) versus 39% of males (14/36). At the end of the study statistically significant decrease in OSDI score in both groups was revealed, compared to baseline data without differences between the groups, as well as Schirmer 1 test in the second group. Treatment complications (hyperemia, subcompensated intraocular pressure, DES and cataract progression) were noted in 3 eyes in the first group, and 11 eyes in the second group (the difference was statistically significant). Hyperemia was revealed in 6% (2 eyes) and 17% (6 eyes), in the first and second group, respectively. In the second group DES progression was revealed, showing correlation with decreased tear expression during Schirmer 1 test. CONCLUSION: Tafluprost without preservatives is an effective and safe hypotensive agent from the group of prostaglandin analogues. It is better tolerated, causes least complaints during instillation, and less adverse effects in the long term use (hyperemia, advancement of the preexisting Dry Eye Syndrome, etc.) when compared to other medications from the same pharmacologic group containing preservatives, which is confirmed by comparative morphological assessment of conjunctiva biopsies.

PURPOSE: Search and identification of thyroid hormone receptors in the structures of the eye by means of immuno- histochemistry analysis (IHC). METHODS: Enucleated eyes of the patients with terminal painful glaucoma (n=30) were the object of morphological research. The search of thyroid hormone receptors was conducted in the retina and optic nerve, ciliary body and its appendixes, trabecular tissue, vessels of choroidea and optic nerve. Antibodies to thyroid hormone receptor THRalfa monoclonal («Diagnostic BioSystem» company, dilution 1:50) and rabbit polyclonal antibodies Anti-Thyroglobulin («Abcam» company, dilution 1:100) were used as primary antibodies (AT). IHC reaction was estimated as follows: - the absence of specific cell color or the presence of less than 10% of stained cells out of all examined area was considered a negative reaction; - a mild positive reaction was considered in case of 10 to 30% staining (+ cells); - moderate positive reaction was in case of the marker expression in 30-75% (++ cells); - marker expression that exceeded 75% was considered a pronounced reaction (+++); - intensive reaction - 100% stained cells (++++). RESULTS: Intensive (4+) positive IHC was discovered in the nuclei of external and internal granular layers of the retina, in the nuclei of the ganglion cells; mild positive staining (1+) was observed in the internal segments of the photoreceptor cells processes. Granule IHC staining (3+) was revealed in the nuclei of the optic nerve glial elements. In the choroidea endotheliocyte nuclei and nuclei of 20% of stroma cells of vascular membrane were stained. There was a marked IHC reaction in the cytoplasm of pigment epithelium cells. Positive staining was observed in the cytoplasm and the nuclei of trabecular endothelial cells, as well as in the nuclei of fibrocytes forming trabecular stroma. Nuclei staining of 80% smooth muscle cells with intensive 3+ and mild cytoplasmic staining 1+ was noted in the ciliary muscle. Pigment and amelanotic epithelium nuclei as well as the nuclei of vessel endothelium cells were stained intensively (3+) in the ciliary body proccesses. CONCLUSION: Conducted investigations help give a morphological base to eye-thyroid association, as well as explain the possible mechanisms of disthyroid optic neuropathy and ocular hypertension, and open-angle glaucoma prevalence in the population of patients with thyroid dysfunction.

PURPOSE: Intraocular pressure (IOP) lowering generally slows the progression of glaucoma, but does not necessarily stop the continuing vision loss. Growing evidence supports the idea that retinal ganglion cells in glaucomatous eyes are under oxidative stress that is associated with pathogenic mechanisms leading to glaucomatous neurodegeneration. Antioxidant protection plays a key role in the conditions of oxidative stress. Therefore, the antioxidative therapy might be of help in preventing glaucomatous neuron degeneration. Prostaglandin (PG) analogues are currently the treatment of choice for glaucoma, because maximum intraocular pressure reduction is derived by once daily application without any systemic side effect in all types of glaucoma. PG analogues, as well as other ocular hypotensive drugs, have been expected to have an additional effect to protect neurons independently of IOP reduction. Purpose оf this study was to compare the antioxidant activity (AOA) of the most widely used prostaglandin analogues. METHODS: The model of oxidation-induced haemolysis was used to study AOA of Latanoprost 0.005% (“Pfizer”), Travoprost 0.004% (“Alcon”), and Bimatoprost ophthalmic solution 0.03% (“Allergan”). Compounds with antioxidant activity inhibit hemolysis caused by free radicals. The degree of hemolysis was determined by the change in hemoglobin concentration in the incubation medium. RESULTS: Travoprost was found to have the highest AOA (17%). However it decreased upon adding larger quantities of the drug into the model system. In contrast to this, bimatoprost showed an increase in AOA when investigated in larger quantities. Its AOA peaked at 38% in 120 mcl of bimatoprost. АОА in latanoprost was the lowest. Upon reaching 120 mcl, latanoprost exhibited oxidative properties. CONCLUSION: Antioxidant activity in PG analogues differs which must be taken into consideration when choosing them as the agents with IOP independent neuroprotective properties.

PURPOSE: To study the influence of Neuromidin on the glaucomatous process. MATERIALS AND METHODS: 88 patients (176 eyes) with primary glaucoma were surveyed. The patients’ distribution according to the stages was as follows: 70 eyes with moderate stage, 103 eyes with advanced and 3 eyes with the terminal stage of primary open-angle glaucoma (POAG) with compensated intraocular pressure (IOP). Eyes with the terminal stage were not included in the statistical analysis. 30 patients (60 eyes) of the control group received complex therapy (Emoxipine intramuscularly, Piracetam and Mildronate intravenously, Retinalaminum parabulbarly. The main group consisted of 58 patients (113 eyes) whose complex therapy also included Neuromidin 1 ml (15 mg) according to the following scheme: 10 intramuscular injections, then 1 tablet (20 mg) 2 times a day for 25 days as monotherapy against the background hypotensive drops (Timolol, Azopt, Azarga, Fotil, Cosopt, Alphagan-P). A standard set of tests was used in the study (viso- metry, tonometry, tonography, biomicroscopy, pachymetry, direct and inverse ophthalmoscopy, gonioscopy, static and kinetic perimetry) as well as the evaluation of the optic disc stereometric parameters with the use of Heidelberg Retinal Tomograph (HRT III). RESULTS: Expansion of the field of view and reduction of absolute and relative scotomas occurred in both groups, but when treated with Neuromidin, the field of view limits expanded up to 25 degrees further than in the control group. The research revealed an influence of Neuromidin on the state of intraocular fluid, rim volume and the cross-section of the retinal nerve fiber layer in patients with advanced stages of glaucoma. CONCLUSION: The effect can be explained by the fact that the drug stimulates the impulse conduction in nerve fibers and synapses. Cholinesterase inhibition induces the stimulation of the ciliary muscle and activation of the outflow of the intraocular fluid. Considering the decrease of the effect in 6 months, the treatment should be repeated twice a year.

PURPOSE: To research the effect of laser peripheral iridectomy (LPI) on anatomical, topographical and functional indicators in primary angle-closure glaucoma with relative pupillary block. METHODS: We examined 20 patients (34 eyes) with primary angle-closure glaucoma (PACG) and relative pupillary block. Stages of glaucoma: I - 28 eyes, II - 3 eyes and III - 3 eyes. Ophthalmologic examination included viso- metry, biomicroscopy, gonioscopy, tonometry, perimetry, ophthalmoscopy, ultrasound biometry. All patients underwent a single-stage LPI with the use of laser Nd:YAG SYL-9000 Premio (“LightMed”, Taiwan). To investigate the depth and volume of the anterior chamber we used Pentacam HR (“Oculus”, Germany). To investigate anatomic and topographic relationships of anterior chamber angle and iridocilliary zone structures we used ultrasound biomicroscopy (UBM) on UBM Hi-scan (“Optikon”, Italy). Obtained measurements included the anterior chamber depth (ACD), trabecular-iris angle (TIA), trabecular-iris distance at 500 micrometers (TID), trabecular-ciliary process distance (TCPD), iris-ciliary processes distance (ICPD), cross-sectional area posterior chamber. We measured viscoelastic properties of the corneoscleral capsule of the eye and intraocular pressure with Ocular Response Analyzer (“Reichert”, США). RESULTS: LPI in patients with relative pupillary block in PACG leads to an increase in anterior chamber volume by 19.57 mm³ on average and practically doesn’t change its depth. According to UBM an increase in the TIA was noted in all cases after LPI, on average by 17.49° temporally, and 16.52° nasally; TID increased on average by 0.21 microns from the temporal and 0.18 microns from the nasal side; TCPD increased on average by 0.09 microns from the temporal and 0.07 microns from the nasal side; ICPD decreased on average by 0.08 microns from the temporal and 0.12 microns from the nasal side. After LPI posterior chamber cross-sectional area decreased by 0.25 mm² temporally and 0.27 mm² nasally. LPI lead to intraocular pressure lowering of 3.29 mm Hg on average. CONCLUSION: UBM revealed specific anatomic and topographic features of the iridocilliary zone structures, inherent relative pupillary block in PACG, and their change after LPI. Increase of TIA and TID values, decrease of ICPD and the posterior chamber cross-sectional area values explain the increase in anterior chamber volume and the invariance of its depth reference value. LPI carried out in at patients with PACG and relative pupillary block, leads to an improvement of the functional space of the iridocilliary zone structures and a decrease in perfusion pressure.

PURPOSE: To study long-term results of refractory glaucoma surgical treatment carried out with the use of an original metallic glaucoma drainage device. METHODS: Between 2007 and 2012, we observed 21 patients with refractive glaucoma who underwent an operation with an implantation of a metallic glaucoma drainage device into the anterior chamber angle. In 9 of these cases (43%), the surgery was performed as an organ-saving procedure. There were 11 cases of glaucoma with ocular pain (52%). Intraocular pressure (IOP) was considered a primary outcome measure. Secondary outcome measures were the following: need for additional hypotensive therapy, second surgical intervention, complications, relief from ocular pain, successful organ-preserving operation, filtration bleb characteristics and the position of drainage device in the anterior chamber angle. Complete success was considered when IOP after surgery ranged between 14 to 25 mm Hg as measured by Maklakov’s method without any hypotensive therapy, partial success - with additional hypotensive therapy. IOP>5 mm Hg or <14 mm Hg and second surgery were considered a failure. Follow-up period was up to 3 years. RESULTS: Complete success after surgery was achieved in 57% of cases (12/21), partial - in 24% (5/21), failure - in 19% (4/21) cases. Mean IOP decreased from 34±5.8 to 20.7±3.9 mm Hg (p=0.0000001), which accounted for a 67.5% IOP drop from baseline. Use of mean number of hypotensive medications decreased from 2.6±0.5 to 1.1±0.3 (p=0.0002). Main reason for surgery failure was tissue fibrosis at the operation site. A repeated surgery with an implantation of another drainage device at another site was required to lower IOP to the desirable level in all failure cases. Postoperatively, hyphema was observed in 1/21 case (5%) only. 82% of patients (9/11) received relief from pain. Preservation of the eye as an anatomic organ was achieved in all planned cases. Diffuse blebs were observed in 48% of cases (10/21), cystic- in 24% (5/21), low - in 28% (6/21). Throughout postoperative follow-up period the device remained in position in all but one case, where device eroded through conjunctiva after 2.5 years of follow-up. The device was explanted and a penetrating glaucoma procedure was performed in this case. CONCLUSION: Implantation of an original metallic glaucoma drainage device into the anterior chamber angle in long terms effectively decreases IOP in patients with refractory glaucoma, relieves patients of pain and can serve as an alternative to enucleation or evisceration of the eye ball.

PURPOSE: To analyze the prevalence and incidence of glaucoma in the Altai region during the period of 2003-2012 and model an incidence forecast for 5 - and 10-year periods. METHODS: The analyzed data was based on annual statistics of glaucoma among the adult population for the said period gathered in medical institutions of Russia and Altai region. Glaucoma prevalence and incidence were calculated using classical formulas per 100 000 population. Predictions of possible changes in incidence rates were calculated using mathematical modeling and forecasting methods. RESULTS: Altai region had the highest glaucoma incidence rate among adult population during the entire study period. Out of 83 subjects of the Russian Federation, Altai region ranks 11th in absolute glaucoma prevalence (absolute number of patients with glaucoma) and 12th in prevalence per 100 000 population. In the Siberian Federal District, Altai region ranks first in the absolute number of patients with glaucoma and second after the Omsk region in incidence per 100 000 population. During the study period from 2003 to 2012 glaucoma prevalence increased by 60.6% and incidence - by 17.8%. Forecasts modeled for 2017 and 2022 predict a further increase in glaucoma incidence and prevalence. CONCLUSION: Analysis of glaucoma prevalence, dynamics as well as incidence and prevalence forecasts for the adult population of the Altai Region show negative trends.

PURPOSE: To define changes of immunoglobulins A, M, G in the tear fluid of patients with primary open-angle glaucoma (POAG). METHODS: We investigated the content of serum immunoglobulins and secretory immunoglobulin A in the tear fluid of patients with POAG and people with risk of its development. RESULTS: The level of IgG, which is the main immunoglobulin of the secondary immune response, was slightly elevated. Investigation of IgA concentration in the serum of patients with POAG showed an increase. Serum IgA concentration in the risk group almost did not differ from the control group. CONCLUSION: The study of immunoglobulin G, M and A in the serum of patients with POAG showed a slight increase Conflicts of Interest and Source of Funding: none declared. in their concentrations, indicating the activation of humoral mechanisms of immunopathogenesis in patients with POAG. Concentrations of secretory immunoglobulin A (sIgA) in the tear fluid was increased both in patients with POAG and in the risk group. It gives reason to consider the local humoral mechanisms an important link in the development of immune inflammation in primary open-angle glaucoma. Selective accumulation of sIgA in the tear fluid indicates an increase in the protective function of the mucous in response to any antigen, toxin, autoantigen, and the aim to limit the development of the pathological process.

This literature review depicts various tonometry methods (Maklakov, elastotonometry, Goldmann tonometry, tonometry by means of Ocular Response Analyzer (ORA) and ICare). The efficacy and accuracy characteristics of different intraocular pressure measuring methods are presented. The article sums up current research on the interdependence of the intraocular pressure and central cornea thickness, the influence of visco-elastic characteristics of the fibrous membrane of the eye on results of some tonometry methods, the correlation of biomechanical indices and interrelation of corneal hysteresis, corneal resistance factor and intraocular pressure. The review describes various tests used in early diagnostics of glaucoma: stress tests (mydriatic test, Wurgaft compression tonometry test, Heims position test, Krasnov orthoclinostatic test, corticosteroid provocative testing by B. Becker, W. Mills etc.).

This review presents ROCK inhibitors - a new family of hypotensive drugs that lower intraocular pressure by enhancing trabecular outflow. It mentions a crutial role of the actin- myosin contractile system in resisting the aqueous humor outflow, and describes the effect that selective Rho-kinase inhibitors have on trabecular system contraction, laxation and, consequently, on the outflow volume. The article also enumerates several Rho-kinase inhibitors that are currently in the pipeline, such as Rhopressa™ (Phase III, “Aerie Pharmaceuticals”, USA), Roclatan™, Ar-12286 (Phase II, “Aerie Pharmaceuticals”, USA), K-115 (Phase III, “Kowa Pharmaceutical”, Japan), AMA0076 (Phase II, “Amakem Therapeutics”, Belgium). The review provides a short description of their mechanisms of action, such as the relaxation of trabecular meshwork that leads to increased outflow, mediated decrease in fluid production and lowering of episcleral venous pressure. It also describes the transient moderate adverse reactions, and gives a brief recount of conducted clinical trials of the new drugs.

The first part of the article describes various factors increasing the risk for angle closure glaucoma, such as older age, female sex, being Asian, having blood relatives with glaucoma, having smaller eyes (far-sightedness) and individual features of the eye. It emphasizes that angle closure glaucoma is more a disease of higher than normal eye pressure than is open angle glaucoma. The author explicates in comprehensible anatomic details the process, mechanism and first means of treatment of angle closure, specifics of hyperopic eyes, the nature of pupil block. In the next part of the article the author answers the most pressing question for all glaucoma patients: will I be blind? He explains that though glaucoma presents a real threat to the vision of anyone who develops it, if a person continues to follow the standard care instructions, there is a good chance that he will preserve much of his sight until the end of his life. At the same time the author emphasizes the irreversibility of the vision loss and the importance of adhering with the treatment program, describes several characteristic signs and symptoms of glaucoma, and gives a brief account of the anatomical reasons behind them. Vision loss statistics is also presented. The next section forms of definitive treatment for glaucoma are discussed. Today restoring the lost vision still remains a future hope, however, present treatments can slow the process so much that no meaningful loss might occur in the person’s lifetime. Successful glaucoma surgery can lower eye pressure to a safe level, but it is important to keep having doctor’s exams regularly even when successful surgery has been done. The other kind of successful treatment for most persons with glaucoma is to take daily eye drops indefinitely. Several hypothetic ways of prolonging the effect of glaucoma medicine are discussed, such as long-lasting drugs and virus particles carriers. Current neuroprotection therapy research and the initial steps of nerve cell replacement are also mentioned. The last part of the article gives an account of genetic background of glaucoma and present research of genetic risk factors, and underlines the importance of intrafamilial information sharing and regular glaucoma check-ups.