Abstract OBJECTIVE: To identify the differences and similar changes in the cytokine profiles during a natural ageing process and in the course of primary open angle glaucoma (POAG) and identify the possible contribution of ageing changes in the pathological process. METHODS: The study included 64 people aged 21 to 74 years. All subjects were divided into 4 groups: group I, «the young control group», consisted of 16 healthy young people (26±5 years); group II, «the senior control group» - included 12 healthy elderly people (69±4 years); group III, 20 glaucoma suspects (68±6 years); group IV consisted of 16 people with the early-stage of POAG (67±5 years). Blood serum (n=64) and tear fluid (Tf, n=64) were used as test samples. The investigation included interleukins (IL-1 ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18); tumor necrosis factors (TNF-α, TNF-ß); interferons (IFN-a, IFN-γ); vascular endothelial growth factor (VEGF-A) and transforming growth factor (TGF-ß1). Investigation of cytokines was performed by a flow cytometer BDFACS Cantoll with the use of BDFACS Diva program, using CBA kits ("BD Biosciences", USA). The data was processed by FCAP Array program ("SoftFlow", USA). Statistical analysis was performed by SPSS 17.0 (SPSS, Inc., Chicago, IL) software, using U-Mann-Whitney test, (p <0.05 was considered statistically significant). RESULTS: A significant increase of the IFN-α, TGF-ß1, IL-6 levels, a significant decrease of IL-1 ß and an insignificant decrease IL-8, IL-17, IFN-γ, VEGF-A were discovered in the blood serum of healthy elderly people compared to younger donors. In glaucoma suspect group a significant increase of IL-1 ß, IFN-α, TNF-α, TNF-ß and an insignificant increase of IL-2, IL-5, IL-4, IL-5, IL-8, IL-17 and IFN-y compared to "age control" were observed. However, there also was a significant decrease of IL-6 and TGF-ß1 and an insignificant decrease VEGF-A. When we compared the serum cytokine in the 2nd ("age control") and 4th (early-stage POAG) groups, we revealed a significant increase in the IL-1 ß, IL-5 levels and a significant decrease in the IL-6, TGF-ß1 levels, as well as an insignificant decrease of IL-10, IL-12, VEGF-A in 4th group. Analysis of the cytokine levels in the Tf showed no significant differences between the two control groups (1st and 2nd group). In the Tf of the glaucoma suspects all cytokine levels except for IL-8, and VEGF-A were significantly increased. Significantly increased levels of cytokines IL-1 ß, IL-5, IL-12p70, IL-18, TNF-a, TNF-ß, VEGF-A, TGF-ß1 were discovered in the Tf in the 4th group (early-stage POAG) as compared to the 2nd ("age control"). CONCLUSION: The specifics of age and pathological changes of local and systemic cytokine levels presented in our study show a significant deviation of the immune system during the development of POAG. This is confirmed by the absence of significant changes in most of the investigated cytokines in the course of a natural aging process and changes in the cytokine levels during the development of POAG. Our data suggest the possibility of searching early markers of the disease in patients at risk, taking into account the characteristics of their immune profile.

PURPOSE: To assess the structural condition of the cornea in patients with newly diagnosed primary open-angle glaucoma at different stages of the disease and levels of IOP, to investigate the «dry eye» syndrome before the appointment of local hypotensive therapy. METHODS: The study included 252 patients aged 40 to 71 years (67.1±3.7 years). The Main group included 202 patients with newly diagnosed primary open-angle glaucoma, the Control group - 50 patients diagnosed with immature cataract with normal IOP. All patients underwent the following examinations: visual acuity, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, autorefractometry, Gonioscopy, Maklakov tonometry, electron tonography, static and kinetic perimetry, the determination of the critical flicker fusion frequency, optic disc retinal imaging (HRT III), confocal biomicroscopy of the cornea (HRT III, with the Rostock Cornea Modul), Schirmer's test and Norn test (tear film stability test). RESULTS: Confocal biomicroscopy revealed typical structural changes in almost all layers of the cornea. A close connection of structural abnormalities in the fibrous tunic of glaucomatous eyes to the disease stage was also established: the degree of corneal and scleral degenerative lesions in POAG depended on the severity of glaucomatous process, which in shows the specificity of detected changes to primary glaucoma. This association was evident in the fellow eyes with different stages of glaucoma in one and the same patient. We revealed for the first time the presence of mild to moderate «dry eye» syndrome in patients with newly diagnosed primary open angle glaucoma before the appointment of local hypotensive therapy, which was confirmed by objective examination methods of the functional state of precorneal tear film and morphological study of the cornea. Using tear substitutes in combination with antihypertensive drugs helped stabilize the development of subjective and objective manifestations of «dry eye» syndrome. CONCLUSION: The presence of degenerative changes in the cornea gives evidence of early involvement of the fibrous tunic in glaucoma process. Degenerative changes of the fibrous tunic in primary open-angle glaucoma could have clinical implications in the form of dry eye, requiring combination treatment for these patients. Glaucomatous nature of these degenerative changes is revealed by both the degree of corneal tissue changes directly correlating with IOP level and glaucoma stage and the presence of interocular asymmetry of structural changes in the cornea of patients with different stages of POAG in fellow eyes.

PURPOSE: To compare the diagnostic efficiency of 6 different computerized perimetric methods in patients with primary open-angle glaucoma (POAG) in an open comparative clinical research. METHODS: The study involved 52 patients (96 eyes) aged from 41 to 76 years old (average age 63 years) with POAG. Patients were divided into three groups depending on the stage of POAG: Group 1 included patients with mild (41 eyes), Group 2 - with moderate (36 eyes)and Group 3 -with advanced stages (19 eyes) of POAG. The control group consisted of 20 healthy persons (40 eyes) aged from 44 to 67 years old (average age 59 years). The patient examination included a standard ophthalmic assessment as well as computerized perimetry (CP) on Humphrey Visual Field Analyzer II (HFA II) 745i (Germany-USA), automated perimeters AP1000 («Tomey», Germany) and Pericom (Russian Federation), Micro-Perimeter MP-1 («Nidek Technologies», Japan), our modifications of Frequency Doubling Technology (FDT) perimetry and investigation of the multifocal Visual Evoked Potentials (mf VEP) as well as optical coherence tomography ОСТ RTVue-100 («Optovue», USA). RESULTS: FDT perimetry data demonstrated the same sensitivity (84%) as the HFA II ones (81%) and the greatest specificity (96%), the lowest variability of repeated results and the minimum testing time of one eye (1.5+0.04 min). Perimeters AP1000 and Pericom had lower levels of sensitivity (76/74%) and specificity (71/88%); the testing was longer (9.1+0.4 and 9.3+0.3 min). Data of MP-1 showed the high sensitivity (88%) and the lowest specificity (54%), the testing took place even longer (13.5+7.1 min.). The results of mf VEP had a quite high sensitivity (78%) and specificity (81%) and the maximum testing time of one eye (20.2+0.7 min.). CONCLUSION: To diagnose glaucoma, determine its stage and progression several methods of CP should be used. If it is impossible, it is necessary to repeat the same perimeter test a few times comparing perimetry data with the condition of the optic nerve head.

PURPOSE: To assess correlation between biogeometric parameter - central corneal thickness (CCT) and biomechanical parameters - corneal hysteresis (CH) and corneal resistance factor (CRF); to evaluate the clinical significance of parameters of Ocular Response Analyzer® (ORA): corneal-compensated IOP (ORAcc), Goldmann-correlated IOP (ORAg), CH and CRF in diagnosis and monitoring of various forms of glaucoma. METHODS: 476 healthy subjects and 356 patients with glaucoma were examined. 150 patients (230 eyes) underwent ORA examination in groups: healthy, open-angle glaucoma, angle-closure glaucoma, normal pressure glaucoma. Comparative evaluation of ORA parameters was performed using Student t-test. The dependence on CCT and IOP level, valuated by different applanation tonometers (by Maklakov, Goldmann, Icare®), was assessed with a simple regression analysis with calculation of coefficient of determination (r²). Using single-linkage clustering the closeness of relationship of biomechanical parameters CH and CRF, biogeometric index of CCT and indices of ORAcc and ORAg in norm and in various types of glaucoma were defined. Values, corresponding to p<0.05, were considered statistically significant. RESULTS: «Thin» cornea (<520 pm) occurs 3.5 times more frequently in patients with glaucoma. In Normal Pressure Glaucoma (NPG) CCT is 491.35+21.23 pm. The CCT was associated with IOP by Maklakov (r² = 0.3) and with IOP by Goldmann (r² = 0.38); (dependence in 30% of cases). CCT wasn't associated with IOP by Icare (r² = 0.00024) (correlation CCT - Icare was not found). In healthy subjects and patients with POAG with normalized IOP the ratio ORAcc / ORAg and CH / CRF demonstrate the close relationship and aims at «1». In patients with NPG the ratio IOPcc / IOPg is 1,5+1,04, which indicates the absence of true IOP compensation and imbalance of intraocular hydrodynamics. CONCLUSION: 1. Index CCT <520 pm gives the greatest error in the assessment of the true IOP. 2. The relations ORAcc / ORAg and CH / CRF, equal or appoximate to the value «1», can be regarded as ORA-criteria of normalizing intraocular hydrodynamics. 3. Assessment of correlation ORA parameters (the ratio ORAcc / ORAg and CH / CRF) allow measuring the level of hydrodynamic processes, to specity the diagnosis, to assess the choice of therapy, and, if necessary, making adjustments to the treatment for adequate compensation of IOP and stabilization of glaucomatous process.

PURPOSE: To investigate abnormalities of neurospecific protein S-100 level in patients with ocular ischemic syndrome. METHODS: The material included 28 people aged 59 to 79 years. Control group consisted of 10 volunteers without ophthalmic symptoms, main group (Group 2) consisted of 18 patients with ocular ischemic syndrome. Neurospecific protein level was determined by means of chemiluminescence immunoassay in blood serum and lacrimal fluid by an automatic electrochemiluminescence immunoassay analyzer Cobas e 411 («Roche Diagnostics», Switzerland). The amount of protein in the fluid up to 0.105 mmol/l was considered a normal value. RESULTS: The study established that the levels of S-100 in the control group were 0.0914±0.0012 mmol/l in lacrimal fluid and 0.0712±0.0021 mmol/l in blood serum, which was within normal range. In the main group lacrimal levels of S-100 protein were increased in 18 patients and averaged 5.871±0.027 mmol/l (p<0.005), normal serum levels of S-100 marker were found in 18 patients averaging 0.0821 ±0.0042 mmol/l (p<0.005). There was a significant increase (by 5.9 times) (p<0.005) of neurospecific protein S-100 in the tear fluid in patients of the main group compared to the control. It was established that an increased lacrimal concentration of S-100 in patients with ocular ischemic syndrome allows to determine it as a marker of nerve cell damage. CONCLUSION: Identification and control of S-100 level confirms the presence of nerve tissue damage at an early stage, thus justifying a course of neuroprotective therapy. Increased serum and lacrimal levels of protein S-100 are determined by neurodegenerative processes in the brain and the eye - a fact that was confirmed by MRI and clinical data, as well as ocular ischemic syndrome diagnostics, which helps determine the state of the optical fibers correctly and on time. This, in turn, can help adequately choose treatment tactics and stages.

PURPOSE: To compare immediate and long-term results of two glaucoma surgery technologies in combined surgery of cataract and glaucoma. METHODS: A retrospective randomized analysis of combined surgery results was performed in patients with follow-up over 5 years. Group 1 included patients after phacoemulsification with IOL implantation and microinvasive non-penetrating deep sclerectomy (85 operations in 82 patients). Group 2 included patients after phacoemulsification with IOL implantation and ab interno trabeculotomy (87 operations in 86 patients). RESULTS: Among early postoperative complications hypotony (8 cases - 9%) and early hypertension (16 cases - 19%) occurred significantly more frequently in Group 1. Group 2 was distinguished by a higher percentage of temporary visual acuity decrease due to retrograde blood flow into the anterior chamber from emissaries. Visual acuity didn't change from 1 week after the surgery till the end of the follow-up period. Hypotensive effect 5 years after the operation in Group 1 was achieved in 81% of cases (69 eyes), with the use of hypotensive drops - in 89%. Nevertheless, in 65% of cases (55 eyes) the second step - laser goniopuncture - was required within the next 1 to 72 (22±17) months after the operation. It is necessary to mention that in 15 eyes (18% of cases) IOP increase was noticed at the moment of active examination of patients in the course of this investigation. It means that in these patients' cases goniopuncture could be performed much earlier. In Group 2 hypotensive effect was achieved in 78% of cases (68 eyes), with hypotensive drops - in 92%. CONCLUSION: Comparative analysis showed that longterm results (hypotensive effect and visual acuity) after combined operations including phacoemulsification with microinvasive non-penetrating deep sclerectomy or with ab interno trabeculotomy do not have any statistically significant difference. However in the overwhelming majority of cases (up to 70%) patients after non-penetrating deep sclerectomy require laser goniopuncture for achieving long-term IOP compensation. Failing to conduct the procedure in due time may result in progression of glaucoma.

PURPOSE: The assessment of possibility to add a new indication for the registered pharmaceutical. Evaluation of safety and efficacy of Visomitin® compared to placebo in patients with age-related cataracts. METHODS: A randomized, double-blind, placebo-controlled clinical study of Visomitin® eye drops in patients with age-related cataracts was conducted in accordance with Good Clinical Practice guidance, the Declaration of Helsinki and the Russian regulatory requirements. The study included 80 patients (23 men and 57 women) aged 45 to 75 years with diagnosed age-related cataract. All subjects were randomized into two groups of 40 patients each. In the treatment group patients received Visomitin® eye drops and in the control group, patients were given placebo (vehicle, i.e. eye drops with the same composition as Visomitin® except for the active substance SkQ1) in the form of instillations of one drop per each eye three times daily for six months. The study comprised 7 monthly visits. The following standard ophthalmological examinations were used to evaluate the effectiveness of the therapy: visual acuity measurement, refractometry, biomicroscopy of the eye, ophthalmoscopy, tonometry, computer perimetry, densitometry. At certain visits lacrimal fluid was taken for evaluation of its antioxidant activity. Blood pressure and heart rate were measured as a part of safety evaluation which also included documentation of complaints and adverse events. Concomitant therapies were also documented. RESULTS: Analysis of safety parameters showed Visomitin® to be safe and well tolerated for patients with age-related cataract. Practically no adverse effects were documented during the study. In both groups a decrease of the number of patients with subjective complaints was observed. These complaints included: visual deterioration, dryness, grittiness, burning eyes, eye fatigue. The decrease of the number of complaints in the Visomitin® group was more pronounced than in the placebo group. During the first months of treatment an improvement of visual acuity was observed in both groups. This result can be explained by a protective effect of hypromellose contained in both Visomitin® and placebo. However, between the 4th and the 6th months, the improvement in visual acuity significantly slowed down in the placebo group, while positive dynamics remained the same in the Visomitin® group. At the end of the treatment visual acuity increased by more than 50% in Visomitin® group and remained at the level of 10-15% in the placebo group (statistically significant difference between placebo and Visomitin® groups, p<0.05). Even more pronounced difference was detected for older patients, where placebo did not cause any increase in visual acuity (p<0.001 at the end of the treatment). A tendency for decrease of the mean and maximum density of the lens was found in the group of patients treated with Visomitin®. On the contrary in the placebo group both mean and maximum density of the lens tended to increase. It is reasonable to suggest that these effects of Visomitin® resulted from an increase of antioxidant protection of eye that was verified by the measurement of the antioxidant activity of lacrimal fluid in the study. After 6 months of treatment antioxidant activity of lacrimal fluid significantly increased in the group of patients treated with Visomitin® compared to that in the placebo group. CONCLUSION: Study results support the use of Visomitin® as effective and safe treatment of age-related cataract. Such treatment can be aimed at deceleration of the disease progression in order to delay surgery. The study results allowed adding a new indication for the use of Visomitin® eye drops.

The review presents various aspects of structural and functional disorders of the visual system in humans and experimental animals associated with physiological involution and the development of glaucoma, which are organized by visual structures and types of change. Particular attention is given to alterations of retinal ganglion cells (RGC). Age-related changes in the RGCs and their central projections are compared with changes occurring in glaucoma. Literature data on the sequence of events occurring in RGC death, including changes in the inner plexiform layer of the retina (the dendritic and synaptic plasticity, reduction of the complexity of dendritic branching and degeneration of the processes), dysfunction and degeneration, a change in the morphology and apoptosis of RGC soma are discussed in the review. The problem of the sensitivity of axons and dendrites of the RGC for a variety of cell types (belonging to parvocellular and magnocellular systems) and their subclasses (on-, off- and on-off-cells) is analyzed. A comparative analysis of the possibilities of modern technologies in perimetry, structural imaging of the retina and electrophysio-logical studies in the diagnostics of primary glaucoma and their prospects in the context is presented. The necessity to standardize a set of parameters of functional and morphological examinations to identify early stages of RGC death in glaucoma patients and patients with suspected POAG is substantiated. Such a set of parameters would allow an adequate assessment changes in dendritic processes, axon dysfunction and degeneration as well as soma death, facilitating a timely and adequate choice of targeted therapy.

Spectral domain OCT (SD-OCT) is the most promising approach in the early glaucoma detection (especially in pre-perimetric stage of the disease), and in the monitoring of glaucoma patients. In recent years, evidence has accumulated that both the thickness of the retinal nerve fiber layer (RNFL) and internal macular layers have important diagnostic value. According to the latest data, thickness of the retinal ganglion cells complex (GCC) is also as informative as the optic nerve head (ONH) parameters produced by SD-OCT. The new options, such as a global (GLV) and focal loss volume (FLV) of ganglion cells complex, are important as well. Today, a minimum rim width (MRW) and a minimum rim area (MRA) are considered among the most relevant parameters of the ONH. This review also presents study of the thickness of lamina cribrosa and choroid - the least studied aspect of glaucoma diagnostics. It also discusses the new developments in optical coherence tomography, which are of great interest for future research, but have not yet been introduced in clinical use.

Ophthalmic viscosurgical devices (OVDs) entered clinical practice at the end of 20th century. OVDs are pharmacologically inactive, clear, highly viscous and elastic fluids that have both the properties of gels and solids. Their properties depend on molecular weight and concentration which are the determinants of OVD behavior in surgery. OVDs are classified based upon their behavior in surgery. The first classification distinguished dispersives (with lower viscosity) and cohesives (higher viscosity). 1 million Daltons have been used as a dividing line between a cohesive and dispersive agent. The subsequent development of viscoadaptives (Healon5) and higher viscosity dispersives (DisCoVisc) required the classification to be revised. This novel classification includes Cohesion-Dispersion Index (CDI). The paper reviews current OVD classification and the properties of different OVDs. OVDs are primarily used in cataract surgery to protect corneal endothelium from the direct contact with lens fragments and irrigation fluid, to maintain a deep anterior chamber and to keep iris lens diaphragm backward, to dilate the pupil, to prevent anterior capsule flap from curling, to dissect anterior and posterior synechias, to separate lens nucleus from the cortex and capsule (i.e., to perform viscodissection), to facilitate nuclear rotation in the capsular bag, to fill anterior chamber and capsular bag, and to flatten capsular bag. Beginning from 1980, OVDs are used in glaucoma surgery to maintain anterior chamber depth following trabeculectomy, thus lowering the incidence of hypotony, anterior chamber shallowing, and choroidal detachment. In addition, OVDs are used in choroidal detachment surgery. Most papers describe the injection of sodium hyaluronate. Finally, OVDs are used to dilate Schlemm's canal in the course of viscocanalostomy, to perform viscogoniosynechiolysis in anterior chamber angle closure, and to protect corneal endothelium when applying cytostatic agent at the surgical site.