PURPOSE: To study the efficacy, safety and tolerability of preservative-free fixed combination in the treatment of patients with open-angle glaucoma.

METHODS: The study included 147 patients (289 eyes) divided into 4 groups: Group I included 35 people (69 eyes) who previously received Duotrav (travoprost 0.004% solution, timolol maleate 0.5%, “Novartis”), Group II comprised 38 people (74 eyes) with previous instillations of nonselectiveblockers (timolol maleate 0.5% solution), Group III consisted of 31 people (60 eyes) with prior hypotensive therapy with Taflotan (tafluprost 0.0015% solution, “Santen”) and Group IV — 43 people (86 eyes) who had not previously received any hypotensive therapy. All patients were transferred to a standard mode of Tapticom instillation (0.0015% solution of tafluprost in fixed combination with 0.5% timolol maleate). All patients underwent IOP monitoring, automated computer perimetry, biomicroscopy and drug tolerability assessment according to subjective complaints of the patient.

RESULTS and СONCLUSION: A decrease in IOP level by an average of 37.5% was noted among POAG patients after they changed their current hypotensive drug to a fixed preservative-free combination drug Tapticom (0.0015% solution of tafluprost with 0.5% timolol maleate). Target IOP was reached in 83% of patients, using Tapticom as the starting therapy. In patients who previously instilled betablockers and analogues of prostaglandins, the alteration in hypotensive scheme allowed an additional decrease in intraocular pressure from the initial 22-25%, achieving target IOP in 86-91% of cases. Functional perimetry parameters stabilization was achieved, an increase in the total photosensitivity of the central and peripheral fields was observed, which was expressed in a significant increase in the perimetrical indices of MD and PSD in all study groups by the 3rd month of treatment.

PURPOSE: To determine the precision of selected samples of Polyak measuring scales used in Maklakov tonometry.

METHODS: Twenty two samples of different models of Polyak measuring scales for Maklakov tonometers were assessed. So called “tonometric” intraocular pressure (IOP) scales were appraised. The ideal size of the imprint for each grade of the scale was calculated using the ImbertFick law formula. These calculations were considered a “golden standard” for the purpose of this study. The scales were scanned and saved as JPG-files with resolution 300 or 600 DPI. The following parameters were measured for each sample: the diameter of imprints which can fit in between “16” and “17”, “25” and “26”, “35” and “36”, and “54” and “56” mm Hg, representing low, borderline, high and very high IOP. Measurements were then compared to the “golden standard”, and the conclusions were made regarding the precision of each sample of tonometric measuring scale. Results were compared to three additional IOP measuring scales: 2 models of Nesterov–Egorov measuring scale and 1 model of Nesterov–Vurgaft–Vagin measuring scale.

RESULTS: Twenty two Polyak measuring scales were evaluated according to the precision of “16”, “25”, “35” and “54” mm Hg marks. Three scales were determined as accurate. The study revealed six measuring scales critically underestimating the IOP level (up to 5-16 mm Hg of underestimation).

PURPOSE: To estimate long-term efficiency of the microinvasive nonpenetrating deep sclerectomy (MNPDS) in surgical treatment of primary open-angle glaucoma.

MATERIALS AND METHODS: In our clinical research were analysed the clinical and functional condition of 96 primary open-angle glaucoma (POAG) patients (100 eyes) aged 44-84 years before and after MNPDS. Before the operation and in various terms after the operation all patients underwent ophthalmologic examination: visometry, perimetry, intraocular pressure (IOP) measurement, biomicroscopy, gonioscopy, ophthalmoscopy, ocular ultrasound. Mild glaucoma has been diagnosed in 8 eyes, moderate — in 19 eyes, advanced — in 73 eyes. Baseline IOP on hypotensive treatment varied from 24 to 59 mm Hg. Best corrected visual acuity varied from 20/20 to light perception with projection. Anterior chamber angle according to gonioscopy in all cases was open (Grades 3-4, according to Shaffer system) with various extents of intensive pigmentation of the trabecula. Surgical or laser glaucoma surgery had been carried out on 27 eyes prior to our research.

RESULTS: Our research showed that MNPDS is an effective operation for IOP normalization in the majority of patients. In most cases no postoperative complications were registered, and only 2 patients developed ciliochoroidal detachment that demanded a second operation — posterior sclerotomy. Being microinvasive, this operation allows minimizing operational trauma, reducing excessive postoperative scarring, prolonging the hypotensive effect and maintaining the level of visual functions.

PURPOSE: To evaluate the cytotoxicity of hypotensive instillation containing benzalkonium chloride and the protective effect of StillavitR artificial tears on the corneal limbus primary cell culture.

METHODS: Test samples: 1) latanoprost 0.005%, containing benzalkonium chloride (BC) 0.02% as a preservative agent 2) StillavitR, containing sodium hyaluronate 0,16%, chondroitin sulfate sodium of 0.05%, D-panthenol 1% and sodium tetraborate 0,05% acting as preservative. Primary cell culture of the corneal limbus was used for the assessment. At the first stage of the research we estimated the effect of a 100% concentration of latanoprost+BC and Stillavit on the cell culture. At the second stage we analyzed the influence of agents’serial dilution on cytotoxicity indicators. The aim of the third stage was the assessment of cell viability level after their exposure to diluted substances in three various combinations: single latanoprost + BC (30 min exposure); simultaneous and consecutive adding of Stillavit and latanoprost + BC to the culture with a 30 min interval. To evaluate the cell culture viability we carried out MTS test using CellTiter 96R AQueous One Solution Reagent («Promega»). Obtained results underwent additional cytological examination.

RESULTS: Cell viability level after the exposure to a 100% concentration of latanoprost+BC amounted to 13.95Ѓ}4.014%. In cases of exposing the culture to a combination of latanoprost + BC and Stillavit, viability level reached 22.03Ѓ}3.152%. The second stage of the research revealed that the cell culture has a survival rate of 60-80% if the drug (latanoprost + BC) in the sample is diluted 32-fold, and in relation to drug volume amounts to 6.25%. Consequently, in the third stage of the research we evaluated cell viability level exposing them to a 6.25% dilution of the drug. Cell survival rate after single latanoprost + BC exposure equaled 68.49Ѓ}20.61%. Both simultaneous and consecutive adding of Stillavit (30 min prior to the drug) increased cell survival rate: 94.95Ѓ}of 12.52 and 103.8Ѓ}12.45% respectively. The observed difference was statistically significant in both cases (95% reliability level).

PURPOSE: To define morphofunctional criteria for evaluating the state of the optic nerve, depending on the stage of optic neuritis (ON).

METHODS: The study included 42 patients (84 eyes) with different stages of bilateral ON, who were divided into 2 groups according to the stage of the pathological process. The first group consisted of 22 patients (44 eyes) with optic nerve head (ONH) hyperemia and edema; the second group consisted of 20 patients (40 eyes) with ONH ischemia and atrophy. The control group consisted of 5 healthy people (10 eyes) of the same age and sex.

RESULTS: According to the visual evoked potentials (VEP) assessment, mean N75 latency in Group I was significantly increased compared to the control group (p<0.05). In the second group of patients, this index was higher than in Group I (p<0.01). Further VEP analysis showed a significant increase of N75-100 component amplitude in Group I and a significant decrease of the same index in Group II compared to the control group (p <0.05). A significant (p <0.0001) decrease in fractional anisotropy (FA 252.5Ѓ}11.89) was revealed during the analysis of the optic nerve by means of MR-tractography in Group I, compared to the control group (369.2Ѓ}5.6). Statistically significant changes in FA of the optic radiation (OR) have not been identified. In Group II patients showed a significant reduction in FA (148.6Ѓ}7.15) of the optic nerve. There was also an increase of apparent diffusion coefficient — ADC (2184.3Ѓ}63.16) compared to the control group (1438.4Ѓ}58.5). A significant FA decrease and ADC increase was revealed in the optic radiation area. In Group I the tractography 3D map did not find significant changes in the amount and direction of the white matter tracts. Meanwhile, in Group II it showed a marked thinning of OR fiber and features of partial breaks of occipital forceps fibers at the point of their attachment to the OR beam.

CONCLUSION: Significant (p<0.05) differential diagnostic criteria of ON stages include OCT and VEP data. OCT can reveal an increase in RNFL thickness and rim changes during the stage of ONH swelling and ischemia, and a decrease of these parameters in patients with optic atrophy. VEP evaluation of these patients shows an increase in N75 and P100 latency as well as a change in N75-P100 amplitude in all stages of the disease. Changes in FA and ADC in optic nerve and OR areas demonstrate the neurodegenerative process spread to the fourth order neuron in the course of disease progression.

PURPOSE: To increase the efficiency of refractory glaucoma surgical treatment.

METHODS: A retrospective study of 29 patients (29 eyes) with refractory glaucoma, who underwent the original leucosapphire drainage implantation («VIM», SaintPetersburg). Most patients (25 eyes — 86.2%) had primary open-angle glaucoma and have been repeatedly operated previously. 2 patients (6.9%) had traumatic glaucoma, and 2 patients (6.9%) had neovascular glaucoma. The average IOP before surgery was 32.4Ѓ}0.7 mm Hg. All IOP measurements were conducted by means of Maklakov tonometry with 10 g weights. Follow up period varied from 1 to 8 years.

RESULTS: After the implantation of leucosapphire drainage, IOP level significantly decreased from 32.4Ѓ}0.7 mm Hg to 14.8Ѓ}1.0 mm Hg. In 1 month after drainage implantation mean IOP was 19.3Ѓ}1.0 mm Hg, after 3 months it equaled 19.8Ѓ}0.9 mm Hg, after 6 months — 20.0Ѓ}0.9 mm Hg, one year after surgery — 20.5Ѓ}0.9 mm Hg. IOP was below 26.0 in 89.6% cases, in 37.9% of which no additional medication had been administered. Compensation at the IOP level of ≤22.0 mm Hg was noted in 75.9% of cases. Visual field test was stable in 69.0% of patients. The following postoperative complications were registered in our study: a shallow anterior chamber (17.2%), hypertension episode (20.7%), hyphema (17.2%), ciliochoroidal detachment (17.2%), external filtration (10.3%), uveal reaction (6.9%).

CONCLUSION: Leucosapphire drainage device implantation may be considered an alternative method of effective surgical treatment of patients with refractory forms of glaucoma.

PURPOSE: To evaluate the corneal nerves structure in patients with primary open-angle glaucoma (POAG).

METHODS: The study included 111 patients. The main group comprised 76 patients (148 eyes) aged 36 to 83 years (62.9Ѓ}2.3 years) with I-IV stages of POAG, control group consisted of 35 healthy volunteers (70 eyes) aged 38-76 years (65.3Ѓ}1.4 years) with normal IOP level and no POAG signs. Patient examination included visometry, biomicroscopy, ophthalmoscopy, gonioscopy, contour tonometry (Pascal), OCT (Zeiss Stratus 3000) and corneal confocal microscopy (HRT III, with Rostock Cornea Modul).

RESULTS: The following structural changes in the corneal nerves were revealed in POAG patients: a decreasing number of nerves, nerve fibers thinning and discontinuity. A quantitative assessment of the corneal nerves tortuosity degree was made by calculating the anisotropy coefficient of the corneal nerves directivity (KΔL). Mean KΔL in the control group was 2.78 (2.47; 3.57) (Me (Q1; Q3)), which significantly differed from the glaucoma group (p=0.0014), where mean KΔL was 2.51 (2.07; 3.16) (Me (Q1; Q3)). Significant differences in KΔL were obtained for different stages of glaucoma (p=0.0004), a moderate negative KΔL bond was detected with POAG stage (r=-0.41, p<0.001). Positive, though weak, correlation was established between KΔL and the following OCT parameters: Rim Cross Sectional Area (r=0.27, p=0.001), Rim Area (r=0.25, p=0.0032) (p<0.005), Rim Volume (r=0.23, p=0.01) and Avg. Thickness (r=0.29, p=0.00063) (p<0.001). The interocular asymmetry of the corneal nerves structure in patients with different glaucoma stages in pair eyes has been studied. The KΔL index asymmetry was calculated. It turned out that this index in the glaucoma group was higher than in the control group, with values in both groups showing a significant difference (p=0.00026). KΔL asymmetry index directly correlated with the divergence in POAG stages between the pair eyes.

CONCLUSION: The presence of structural changes in the corneal nerves layer and the increase in the severity of these changes depending on glaucoma stage, indicate that the dystrophic process in the cornea is a local manifestation of glaucomatous neurodegenerative process. This is best seen in the study of interocular asymmetry in patients with different glaucoma stages in pair eyes. This gives us a notion of universality of the neurodegenerative process in patients with POAG, and consequently, suggests that the study of corneal structures may have diagnostic value.

PURPOSE: A theoretical justification of a new method of diagnosing the ciliary body microcirculatory ischemia.

METHODS: Mathematical modeling of high-frequency current distribution in eye tissues during electrical impedance plethysmography (IPG). Mathematical modeling of converting the degree of local short-term globe vacuum compression into the level of intraocular pressure (IOP) elevation.

RESULTS: The possibility to diagnose the ciliary body microcirculatory ischemia has been theoretically substantiated. According to the utility model, original suction ring with rheographic electrodes was applied to perilimbal sclera. Diastolic ocular perfusion pressure (OPP) was determined by means of ocular impedance plethysmography (IPG) in arterioles of the ciliary body microcirculation bed, excluding the contribution of blood circulation in superficial subconjunctival vessels of the anterior eye segment and in intraocular vessels of the posterior eye segment. Determination of perfusion pressure in small vessels of the anterior eye segment was carried out at a lower IOP level. Aqueous humor inflow and outflow was temporarily blocked during the examination to ensure an unchanging eye globe volume. The following formula was used to calculate OPP: , where VAC is the degree of vacuum compression applied and D is the eye globe diameter, coefficient K is determined by specific dimensions of suction ring. The ciliary body microcirculatory ischemia was diagnosed when diastolic OPP was below 35.0 mmHg.

CONCLUSION: The proposed method of determining diastolic OPP in the arterioles of the ciliary body microcirculation bed in case of experimental confirmation could be useful for early detection of intraocular vascular microcirculation disorders not only in patients with glaucoma (including low pressure glaucoma), but also in cases of myopia, diabetic angiopathy, peripheral retinal degeneration, age-related macular degeneration, uveitis, and it could also allow the assessment of the treatment effectiveness after conservative therapy and surgical interventions.

Experimental in vivo glaucoma models allow expanding the knowledge of the glaucomatous optic neuropathy pathogenesis. An important criterion of choosing an experimental animal model is the ability to extrapolate received data to humans. This review covers main models of experimental glaucoma in rodents and its technology, including rodent anatomy and physiology specifics. Using rats in glaucoma modeling offers the advantage of fast disease progression and ease of use. Genetic models are based on congenital impairment of intraocular hydrodynamics due to gene mutation; induced models refer to artificial intraocular pressure (IOP) elevation or initiation of neuropathy without affecting the aqueous outflow. Methods aimed at hydrodynamics alteration lead to IOP increase and thus to glaucomatous optic neuropathy development. These include thermic, mechanical and laser effects on the aqueous humor outflow. Optic neuropathy without affecting IOP can be caused by mechanical impairment of the optic nerve, ischemia followed by reperfusion, excitotoxicity, or intravitreal injection of endothelin-1 or rose bengal with following photostimulation. Genetic glaucoma models include rodents with congenital impairment of eye drainage zone due to gene mutations, such as DBA gene family and α1-subunits of I-type collagen mutation, synthesis of altered myocilin or calcitonin receptorlike receptor expression. The current range of rodent glaucoma modelling methods is a perspective and important part of in vivo studies, related to glaucoma pathogenesis and treatment.

This review focuses on historical aspects of neuroprotection as a therapeutic approach to glaucoma, with the retinal ganglion cell (RGC) layer serving as the main therapeutic target. Adequate control of intraocular pressure (IOP) helps to slow down RGC loss, which is, in itself, neuroprotective. There is now evidence that glaucoma mediated remodelling occurs throughout the cellular and tissue layers of the retina, including photoreceptors, pigment epithelium, bipolar, horizontal and Muller cells, astrocytes and retinal vasculature. Neuroprotection, neuroehancement and neuroregeneration are some of the approaches discussed in the literature. In view of the recent tendencies, we explore the potential of one of these approaches — retinoprotection, which defines a complex of therapeutical measures aimed at preventing structural and functional damage to the retina and optic nerve in glaucoma patients. This is particularly important given that glaucoma is a multifactorial disease and may require a complex approach to treatment.

The review covers some of the physiological mechanisms of ocular blood flow regulation and disorders in the aspect of glaucomatous optic neuropathy development. The ocular perfusion pressure and its relations with intraocular and blood pressure, with emphasis on the role of circadian oscillations, have been studied. The studies have shown that glaucoma is associated with a reduction in the perfusion pressure. The problems of ocular blood flow autoregulation and neurovascular interactions’ role in the ocular blood flow regulation have been considered. Particular attention has been paid to the comparison of retinal and choroidal blood flow with an emphasis on the regulation of these two sources of blood supply to the retina and optic nerve. The fundamental causes of ocular blood flow disorder in glaucoma, such as endothelial dysfunction and primary vascular dysregulation, are discussed as well. The variety of factors involved in maintaining the constant ocular blood flow, making the choice of therapy problematic, has been noted. The main mechanisms that support the constancy of ocular blood flow autoregulation and causes of neurovascular interaction disorders have been describes. Thus, despite the presence of all the classic mechanisms of ocular blood flow regulation, physiology and pathophysiology of the eye hemoperfusion largely unique.

The article presents a review of latest research related to various aspects of age-associated diseases pathogenesis. It describes the modern concepts of natural aging and the disorders of adaptation mechanisms that oppose the involution processes. The chronobiological formation concept of temporary biological structure and the key components of circadian system regulation are reported in detail. Arguments in favor of violations of strong consistency of various physiological processes in glaucoma are recounted. The article emphasizes the role of diurnal IOP amplitude fluctuations as a reliable marker, as well as an important pathogenetic factor of glaucoma development. Other chronobiological factors that may be considered predictors of various age-related neurodegenerative diseases, including glaucoma, are discussed. The review analyzes the mechanisms of system desynchronization development, such as extra-circadian dissemination and the development of primary open-angle glaucoma (POAG). Primary open angle glaucoma is considered to be a desynchronosisrelated, age-associated disease. Moreover, the article presents a hypothesis of POAG being not only a consequence, but also a cause of circadian rhythm disturbance.