The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.

PURPOSE: To study collagen structures of periorbital tissues of patients with primary open-angle glaucoma (POAG). METHODS: During the surgeries of 12 patients aged 55-87, 17 samples of various tissues were taken: 13 eyelid skin samples of 8 patients during blepharoplasty, 3 cartilage samples during eyelid eversion surgery, 1 sample of sclera during nonpenetrating deep sclerotomy. In total, 7 samples were obtained from patients with stages II and III of POAG and 10 samples from patients without glaucoma. We measured the endothermic temperature peak (Td) and enthalpy ΔHd) of denaturation process using differential scanning calorimetry (Phoenix DSC 204, «Netzsch», Germany) to estimate the crosslinking level of the examined tissues. RESULTS: ΔHd and Td medians of eyelid skin samples of patients aged 55-60 (median - 57 years) without POAG were equal to 7.03 J/g of dry weight and 66.600С, respectively. In contrast, patients of an older age group - 72-79 years (median - 75 years) revealed higher values of this parameter: 9.12 J/g of dry weight and 67.25°С. Moreover, the patients of the same age group (median - 74 years) with POAG showed even higher values of these parameters: 9.33 J/g of dry weight and 67.35°С, respectively. Thermomechanical parameters of eyelid cartilage of same age patients (71-78 years) were different in POAG/No POAG cases: 8.26 J/g of dry weight and 66.6°С, and 10.106 J/g of dry weight and 67,1°С respectively. A clinical case of a metabolic disorder of eyelid connective tissue and sclera is presented: a 72-year old patient K. with stage II POAG in OD and stage III POAG in OS and initial cataract of OU. ΔHd and Тd of OD eyelid skin (9.97 J/g of dry weight and 66.3°С) were lower than in OS (13.1 J/g of dry weight and 66.4°С). ΔHd and Тd of the OS sclera were 4.8 J/g of dry weight and 65.9°С. After glaucoma surgery in OS, excessive scarring along newly formed outflow paths was noted. CONCLUSION: A clear age-related rising trend of collagen crosslinking level and collagen content increase in eyelid tissues (skin and cartilage) was revealed. Respective parameters in POAG patients were higher than in patients of the same age group without glaucoma.

PURPOSE: To evaluate the role of optical coherence tomography with angiography (OCT-A) in early glaucoma detection and its monitoring. METHODS: 48 eyes of patients with early stage and 47 eyes of patients with advanced primary open angle glaucoma (POAG) and 42 eyes of age-matched healthy subjects were examined by means of SD-OCT-А (RtVue xR Avanti with the AngioVue software). Retinal Thickness and Angio Flow Density (AFD) were measured. AFD Disc and Peripapillary Flow Density were measured in ONH and 750-pm-wide elliptical annulus extending from the optic disc boundary. AFD retina was evaluated in macula (area bounded by a circle with a 3 mm diameter) including fovea and parafovea regions (superficial and deep) of the inner retinal layers. Retrobulbar blood flow parameters, including ophthalmic artery (OA), central retinal artery (CRA), posterior short ciliary artery (PCA), central retinal vein (CRV) and vortex vein (VV) were measured by CDI. The average thickness of the retinal ganglion cells complex (avg. GCC), retinal nerve fiber layer (avg. RNFL) and choroid (Tx), and the focal loss volume (FLV) and global loss volume (GLV) of GCC were measured using SD-OCT. Visual fields were evaluated using Humphrey Visual Field Analyzer 3 («Carl Zeiss Meditec», Dublin, CA). Corneal-compensated IOP (lOPcc) and corneal hysteresis (CH) were determined using Ocular Response Analyzer (ORA). Mean ocular perfusion pressure (MOPP) was calculated using IOP and mean arterial blood pressure (MAP) measurements, according to the following formula: MOPP = ([2/3 diastolic BP + 1/3 systolic BP] « 2/3 - IOP). Statistical analysis was performed using SPSS version 21 and MASS library of language R. The value of each diagnostic indicator (z-value) was calculated using the Wilcoxon-Mann-Whitney test and the area under the receiver operating characteristic curve (AUC) was used for discrimination of studied groups. RESULTS: Despite the significant decrease of all structural parameters and variables of retrobulbar blood flow in early POAG the following indicators had the largest AUC and diagnostic value (z-value) to discriminate the early glaucoma from normal eyes: AFD Retina Superficial Whole En Face (z=3.86, p<0.0001; AUC 0.8 (0.69-0.90)), and macular thickness in the inferior sector (z=3.86, p <0.0001; AUC 0.8 (0.69-0.91)) and to discriminate the early glaucoma from the advanced stages: AFD Disc Peripapillary Inferior Temporalis (z=5.61, p<0.0001; AUC 0.94 (0.86-1.0)) and the mean flow velocity in the CRA (z=4.16, p<0.0001; AUC 0.81 (0.69-0.92)). CONCLUSION: The present study revealed the important role of OCT-angiography in the early glaucoma detection and its monitoring. Microcirculation in the macular area and its thickness in the inferior sector are of high importance. These results allow understanding the early involvement of macula inner layers in the pathological process in glaucoma.

PURPOSE: To evaluate the changes of optic nerve head (ONH) stereometric parameters during drug-induced stressrelief tests in patients with primary open-angle glaucoma. METHODS: 165 people (222 eyes) were examined. 135 patients (186 eyes) had open-angle glaucoma diagnosis of different severity (early, moderate, advanced). Also 30 healthy controls (36 eyes) were included. Patients' mean age was 62±8.2 years. Groups were standardized by sex, age and range of the original corneal-compensated IOP (21-30 mmHg), as well as by length of the anterior-posterior axis of the eye. All people underwent standard ophthalmologic examination including visometry, biomicroscopy, gonioscopy, ophthalmoscopy and and Humphrey visual field assessment. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated IOP (lOPcc), and Goldmann-related IOP (lOPg) were measured using ocular response analyzer (ORA). The length of the anterior-posterior axis of the eye was measured using A-scan ultrasound biometry (Ocuscan RxP, “Alcon" USA). Confocal laser scanning ophthalmoscopy (Heidelberg Retina Tomoghaph) HRT Ill was used to evaluate ONH stereometric parameters. RESULTS: ONH rigidity coefficient (RC) was formulated according to the analysis of changes in ONH stereometric parameters as a result of drug induced stress-relief tests. RC coefficient was calculated according to the following formula: RC = (AIOP/Acup volume) / 100. According to this formula, the coefficient modulus increase indicates growing rigidity of ONH structures. RC value of the healthy control group was 3.0+1.4 mm Hg/mm³. In patients with early glaucoma RC did not differ from the control group and equaled 3.3+1.0 mm Hg/mm³. It may be indicative of maintaining resilience of the structures of the optic nerve head and the surrounding tissue in early glaucoma. Significant changes of ONH stereometric parameters were found in patients with moderate glaucoma during drug-induced stress-relief test; CR increased significantly and amounted to 5.7+1.1 mm Hg/mm³ and showed a positive correlation with disease duration (r=0.4; p=0.006). Advanced glaucoma patients group revealed the highest possible CR value (8.6+3.6 mm Hg/mm³), which may indicate a marked increase in the rigidity of ONH structures and surrounding tissues. CONCLUSION: ONH rigidity coefficient (RC) significantly reflects the degree of IOP reduction effect on ONH cup volume; RC value increase may serve as a risk factor for glaucoma progression. Based on our research results we can recommend including RC calculation into complex examination of primary open-angle glaucoma patients. RC may be a possible prognostic factor for evaluating glaucomatous optic neuropathy progression.

PURPOSE: To conduct a personalized analysis of patients with advanced stages of glaucoma in Tyumen region. To show the effectiveness of "Method of selecting strategic directions for improving the quality of eye care for glaucoma patients in the framework of the process approach" software product for dealing with this category of patients. METHODS: A retrospective analysis of 1657 outpatients' case histories with first diagnosed advanced or terminal glaucoma in the period from 2011 to 2015. Clinical and sociological portraits of an advanced glaucoma patient were composed based on the "Register of Tyumen region glaucoma patients" automated system and by means of a sociological survey. Compliance of 680 glaucoma patients was assessed with Moriscos-Green clinical and psychological compliance scale. Screening for identification of patients with inadequate compliance was carried out. The correlation of treatment duration and compliance was studied. The efficacy of "Method of selecting strategic directions for improving the quality of eye care for glaucoma patients in the framework of the process approach" software product was investigated. RESULTS: During 5 years in Tyumen region 4 types of first diagnosed glaucoma (51% - mild, 18% - moderate, 22% - advanced, 9% - terminal) were revealed. Registration includes 9585 patients with glaucoma in Tyumen region. 1 657 patients had advanced stages of glaucoma. The ratio of men and women with advanced stages of glaucoma was 40 and 60%. Advanced stages of glaucoma more frequently occurred in men and women aged 70-85 years. The study revealed that by the end of the 5 year follow-up 15% of patients with advanced glaucoma remained compliant, 52% did not follow doctor's prescription, 33% showed insufficient compliance and composed the risk group for noncompliance. Patients with advanced-stage glaucoma regarded their quality of life as decreasing because of a lifelong treatment (52% patients), 33% - because of the illness itself and 15% patients - because of the glaucoma medicine side effects. CONCLUSION: Reasons of late glaucoma stages detection were analyzed. Reasons of low compliance to treatment in patients with advanced stages of glaucoma were studied. Clinical and sociological portrait of a patient with advanced stages of glaucoma was composed.

PURPOSE: To evaluate the efficacy of latanoprost 0.005% treatment for patients with primary open-angle glaucoma during follow-up from the positions of individual IOP level achievement, eye hemodynamics improvement and visual functions stabilization. METHODS: The study included 186 patients with an initial stage of primary open-angle glaucoma (186 eyes) with pseudoexfoliative syndrome. The average age of the patients was 60.4±0.6 years. RESULTS: Individual IOP level was achieved in 119 patients with initial stage primary open-angle glaucoma (119 eyes) - 64% of cases. After latanoprost 0.005% instillation the average IOP value in patients with glaucoma decreased from 22.4±0.7 mm Hg to 15.1±0.7 mm Hg, totaling a decrease of 7.3 mmHg (32.6%) from baseline IOP and fitting into the tolerable IOP green zone (t=7.4; p=0.001). In 67 patients with glaucoma (67 eyes) required a combined drug treatment to reach a needed IOP level. Ophtalmosphygmography showed a significant improvement of hemodynamic parameters of the eyes after intraocular pressure reduction to tolerable IOP level (p=0.001). CONCLUSION: Ophthalmosphygmography parameters (intraocular vessels elasticity index, eye blood supply adequacy index) can be used as hemodynamic criteria in evaluating the effectiveness of primary open-angle glaucoma patients treatment. Glaucoma process stabilization was observed in 95.8% of patients with initial stage of primary open-angle glaucoma after IOP reduction to the individual tolerance level due to latanoprost 0.005% instillation.

PURPOSE: To study the hypotensive effect of modified non-penetrating deep sclerectomy (NPDS) in patients with primary open-angle glaucoma. METHODS: 91 patients with primary open-angle glaucoma were included in the study. The patients were divided into two groups. The first group consisted of 47 patients (51.6%) who underwent modified NPDS with implanted nylon thread 5/00, the second group included 44 patients (48.4%), who underwent modified NPDS with “Xenoplast" drainage implantation. The modified NPDS technique included using a paralimbal approach to cut the conjunctive and separate it from sclera, followed by cutting a U-shaped scleral flap (3*2 mm) with its free edge facing the limb and base - the equator. A cutting edge was used to form a 3 mm deep scleral tunnel opening into subconjunctive space. After that, we cut a deeper rectangular scleral flap (1/3 of scleral thickness) and excised the peripheral part of corneal tissue in single block with the external surface of the Schlemm's canal, opening its lumen. A 5/00 nylon thread (“Xenoplast" drainage) was implanted into the formed tunnel in an anteroposterior direction, thus dilating it. The operation was finished by covering the filtration area with the superficial scleral flap and suturing the conjunctive. RESULTS: After 18 weeks follow-up, patients of Group I had IOP=19.2±1.9 mm Hg, with IOP compensation in 78.7% of patients; in Group II - 19±1,8 mm Hg and 79.5% respectively. CONCLUSION: This proposed NPDS modification might be considered a treatment of choice in patients with primary open-angle glaucoma, it had high hypotensive efficiency during 18 week postoperative follow-up (79.1% compensation rate); drainages of various materials can be used during this operation to enhance its hypotensive effect.

PURPOSE: To conduct a meta-analysis of randomized clinical trials of efficiency and safety of glaucomatous optic neuropathy neuroprotective therapy with water-soluble polypeptide retinal fractions complex conducted in Russia. METHODS: Clinical trials published results were searched by a single investigator using the "Scientific electronic library" (elibrary.ru). Meta-analysis included all clinical trials of Retinalamin efficacy, where its route of administration and dosage corresponded with the guidelines for medical use of Retinalamin in patients with primary open-angle glaucoma and normal intraocular pressure (IOP). RESULTS: Primary search found 302 publications mentioning Retinalamin. 9 of these publications presented the results of randomized clinical trials that met the criteria and were included into our analysis. Meta-analysis revealed a statistically significant vision acuity increase, mostly in early disease stages, a tendency towards IOP decrease regardless of optical neuropathy stage, perimetrical positive dynamics in scotomas size and total field of view, retinal nerve fiber layer thickness increase measured on different timepoints after the therapy. We noted a dissimilarity between application modes and dosages, some of which differed from official recommendations, a lack of a standard diagnostic algorithm and a follow-up timeframe, as well as an inadequate statistical analysis scope, all of which complicates defining Retinalamin indications field and substantiates conducting a multicenter randomized clinical trial. RESULTS: The analyzed data gives evidence of positive dynamics in primary open-angle glaucoma patients after a course of treatment with Retinalamin: a statistically significant visual acuity increase, perimetry parameters improvement, a tendency towards IOP reduction and retinal nerve fiber layer thickness increase.

Glaucoma is a socially significant disease, which is consistently ranked first or second among causes of visual impairment and blindness. Difficulties with diagnosis verification, treatment algorithms, monitoring, patient compliance to treatment regimens that occur at a certain stage of therapy, as well as medication prescriptions inefficiency lead to progressive vision loss. Numerous surgical techniques often have limited effectiveness. Drainage use is aimed at reducing excessive scarring in filtration area and creating one or more paths of intraocular fluid resorption. The review presents currently existing approaches to refractory glaucoma drainage surgery. Different implant groups are described in details, including those reducing excessive scarring, intracameral drainages and Schlemm's canal implants. Current perceptions of viscocanalostomy and canaloplasty effectiveness in glaucoma surgery are recounted. The advantages of implants, designed to maintain the Schlemm's canal volume, are specified. NiTi is a promising new material for use in glaucoma drainage surgery. Technical characteristics of biocompatibility, possibilities of modern engineering and technical lasers for processing NiTi allow to use this material on microstructural level.

This article presents a review of terminology, history of appearance, legislative regulation, pharmacokinetics and pharmacodynamics of cannabinoids, as well as the research results of cannabis use in the treatment of oncologic patients, reducing chemotherapy symptoms (intensive pain syndrome, nausea) and neurologic pathology (disseminated sclerosis, Alzheimer's disease, schizophrenia). The research results of systemic cannabis administration for reducing intraocular pressure in healthy population and patients with different forms of glaucoma are discussed. The review reports on the latest research of the interrelation of the endocannabinoid system with the intraocular fluid flow regulation, as well as its vasodilating and neuroprotective effects. It sums up with recounting the official standpoint of international ophthalmology associations, who do not recommend the use of cannabis in glaucoma treatment due to its short-term hypotensive effect and poor system safety level.