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Purpose: to develop a model of the early stage of retinal neurodegeneration via an intravitreal injection of the dopaminergic neurotoxin. Material and methods. The experiment was carried out on 20 Chinchilla rabbits. The experimental groups received intravitreal injection of 0.1 ml of 6-hydroxydopamine (6-OHDA) in NaCl 0.9 % with 0.5 % ascorbate, containing 0.25 or 0.5 mg 6-OHDA. The control group received injections of 0.1 ml of NaCl-ascorbate solution without neurotoxin. On the 7th and the 14th days after the injection, intraocular pressure (IOP), pupillary light reaction and ocular blood flow were estimated and the fundus was examined. On the 7th day after an injection of 0.25 mg 6-OHDA, we used ELISA to measure dopamine concentration in retinal homogenates, while on the 14th day after an injection of 0.5 mg 6-OHDA, the concentrations of dopamine, norepinephrine, TNF-a and endothelin-1 were measured by the same method. Results. On the 7th day after a 0,25 mg injection of neurotoxine, we revealed a decrease of dopamine in the retina (0.043 ± 0.130 pg/mg protein compared with 0.10 ± 0,03 pg/mg protein in the controls, р < 0.01). On the 14th day, dopamine and norepinephrine levels showed a fourfold increase (р < 0.05). An injection of 0.5 mg of 6-OHDA caused a threefold increase of dopamine (р < 0.05) and a fivefold increase of norepinephrine (р < 0.01) concentration in comparison with the controls. On the 14th day, endotheline-1 level was 65 % higher than in the controls after a 0.25 mg 6-OHDA injection (р < 0.01) and 45 % higher after a 0,5 mg injection (р

It is believed that in degenerative diseases of the retina, photostimulation by fractal dynamics signals activates neuroplasticity, thereby increasing the efficiency of visual rehabilitation. Previously, we showed a positive effect of fractal phototherapy (FF) on the electroretinogram (ERG) of healthy rabbits and demonstrated the safety of long-term photostimulation courses for the retina. The purpose of this work is to study the effect of FF on the functional activity and morphology of the retina in rabbits with a model of retinal pathology. Material and methods. We modelled an atrophy of retinal pigment epithelium (RPE) on both eyes of 50 rabbits. 30 days after the administration of bevacizumab, the animals were divided into two groups of 25 animals each. In the main group, photostimulation was performed using a device for FF, while in the control group incandescent lamps were used that create radiation of constant intensity. In both groups, 20-minute binocular light stimulation sessions were performed daily, five times a week. ERG and optical coherence tomography of the retina were performed before and after courses of treatment which lasted 1 week, 1 and 3 months. Results. Long-term courses of FF were shown to be safe for the morphology of the retina of animals with the RPE atrophy model. In all periods of observation, biochemical studies revealed no statistically significant changes in the content of norepinephrine and dopamine in the tear as compared with baseline values. In the main group, a slight positive effect of FF on rod and cone ERG was found after 5 FF sessions, while a significant increase in the amplitude of the transient and steady-state pattern-ERG (PERG), most pronounced after a 1-month FF course, was observed. Conclusions. A positive effect of FF on the functional activity of retinal ganglion cells (RGC) may suggest that prescribing a course of FF lasting up to 1 month (20 sessions) in diseases accompanied by a pathology of RGC is advisable, whereas for patients with a pathology of the macular region, such as AMD, an effective improvement in the activity of photoreceptors and bipolar cells could probably be achieved through a 1-week course of FF, conducted under the control of electroretinography.

Purpose: to assess the possibility of using thioctic acid and indomethacin tin eyedrops for the therapy of early stages of retinal neurodegeneration.Material and methods. The study was performed on 20 Chinchilla rabbits, including 16 rabbits in whom the neurodegenerative process in the retina was produced by intravitreal installation of 6-hydroxydopamine (6-OHDA), 0.25 mg per eye, and 4 rabbits (8 eyes) served as control. Thioctic acid 0.5% and Indocollir 0.1% were instilled separately and in combination 5 times daily for 7 days after the injection of 6-OHDA. Pupillary light reaction was estimated and eye fundus condition analyzed. Alpha2-macroglobuline ( 2-MG) and SOD activity, dopamine and protein concentrations were measured in retinal homogenates.Results. Instillations of thioctic acid reduced the retinal damage area almost by half as compared to the untreated group (p d 0.005). Indomethacin was less effective, but the combination of the two drugs brought about a maximal reduction of the damage area (p d 0.05 against the untreated group). Both preparations normalized the disturbed pupillary light reaction. The injection of 6-OHDA caused a decrease of dopamine concentration in the retina (0.050 ± 0.009 pg/mg as against 0.095 ± 0.031 pg/mg in healthy controls, р d 0,05). After instillations of indomethacin and thioctic acid, the concentration tended to increase, and it increased significantly after treatment with their combination (0.141 ± 0.037 pg/mg, p d 0.01 as against untreated animals). The activity of 2-MG in retina decreased after a 6-OHDA injection (2.93 ± 0.42 pg/mg as against 5.5 ± 1.2 pg/mg in healthy controls, р < 0 005) just as they increased the decreased SOD (13.30 ± 5.68 U/mg in healthy controls, 5.41 ± 1.50 U/mg in untreated animals, р < 0.05). Both preparations applied separately or in combination caused a significant increase of 2-MG activity (thioctic acid — 4.19 ± 0.91 pg/mg, indomethacin — 6.95 ± 1.09 pg/mg, combination — 7.25 ± 0.63 pg/mg, р < 0.05 as against the untreated animals) and SOD activity (thioctic acid — 8.25 ± 1.27 U/mg, indomethacin — 29.84 ± 6.63 U/mg, combination — 23.99 ± 3.78 U/mg, р < 0.01 as against the untreated animals).Conclusion. The combination of indomethacin and thioctic acid in eyedrops is the most effective for the prevention of eye damage caused by 6-OHDA, which makes this method promising for the treatment of eye diseases accompanied by neurodegeneration.

Retinitis pigmentosa (RP) ranks first in the structure of hereditary retinal diseases. Vasoconstriction is one of the main ophthalmoscopic indications of PR. Laser speckle flowgraphy (LSFG) is a new non-invasive method that allows quantitative assessment of blood flow in the posterior pole of the eye.Purpose: to evaluate changes in blood flow as determined by the LSFG method in the area of the optic nerve head (ONH) and the macular area in PR patients.Material and methods. The study included 16 patients with PR aged 25 to 70 years. The control group consisted of 40 healthy volunteers, comparable in gender and age. Blood flow was determined using an LSFG-RetFlow device (Nidek), the main indicator of blood flow determined was MBR (Mean Blur Rate), which was measured for the entire study area, as well as separately for large vessels, and for the microvasculature. A wide range of pulse wave parameters determined by the tool instrument was also analyzed.Results. This study revealed a significant decrease in blood flow in PR patients compared with healthy individuals in different age groups and at different stages of the disease (p d 0.05). In patients with low visual acuity, the deficit of blood flow in the macular area was found to be more pronounced.Conclusion. LSFG is an effective method for determining ocular blood flow in PR patients. The data may indicate that a decrease in blood flow is an independent pathogenetic factor in the development of PD. In the future, the method can be used to assess the effectiveness of therapy of patients with PR.

Circulatory disorders in eye vessels play an important role in the development of ophthalmic pathologies, in particular socially significant diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal vascular occlusion. Eye hemodynamics features are an important diagnostic criterion for both ocular and systemic diseases. A comprehensive assessment of blood flow in various structures of the eyeball offers additional information on the pathogenesis of the diseases and helps develop new approaches to monitoring the effectiveness of treatment and vascular pathology prognostication. Thanks to the improved technologies, we have today a variety of invasive and non-invasive techniques for examining ocular hemoperfusion, including those intended for retrobulbar blood flow and intraocular blood circulation evaluation. The review article is focused on the state-of-the-art techniques: fluorescein angiography, ultrasound examination involving blood flow assessment by colour Doppler mapping and Dopplerography, optical coherence tomography in the angiographic mode and laser speckle flowgraphy. The role of these techniques in the diagnosis of vascular pathology and their advantages and disadvantages when used in ophthalmological practice is considered.

The challenge of the coronavirus pandemic, and the research into the mechanism of development of the symptom complex that appears in patients who had COVID-19 (post-COVID syndrome), is a topical issue of modern medicine. Obviously, as the incidence of COVID increases, the number of patients suffering from the post-COVID syndrome increases, too. According to recent estimates, 10 to 20 % of patients who have experienced an acute symptomatic phase of SARS-CoV-2 suffer from the effects of the disease over 12 weeks from the primary diagnosis. COVID-19 has been shown to have a variety of long-term effects on virtually all body systems, including the eye. The ocular surface can serve as a gateway for the virus to enter the body, so that patients experience nonspecific changes in the conjunctiva, cornea, retina, and eye vessels. Thus, the issues of diagnosis and treatment of the COVID-19 infection itself and, notably, its complications and conditions that have arisen and continue after the disease, are of essential research and clinical interest. SARS-CoV-2 has a negative impact on the state of the vascular wall and contributes to the development of hypercoagulable conditions, which increases the risk of thrombosis and possible complications in the cardiovascular system. The review summarizes the analyses of eye vessels blood flow in patients who have undergone COVID-19.

Disorders of ocular perfusion are associated with huge amout of diseases, including such socially significant as diabetic retinopathy and glaucoma. To date, there is no gold standard for measuring ocular perfusion. An innovative method for two-dimensional assessment of eye blood flow — laser speckle flowgraphy (LSFG) — has been developed recent years and implemented in ophthalmological practice.Purpose: to evaluate the possibilities of LSFG for determining ocular blood flow and to find out the age dependence of the obtained indicators of ocular blood flow.Materials and methods. The study includes 60 healthy volunteers. The examined persons were divided into 3 groups of 20 people depending on their age — 20–40 years old, 41–60 years old, and over 61 years old. All examined persons had high visual acuity and normal blood pressure. The study was carried out on an LSFG-RetFlow device (Nidek). The shape of the pulse wave, its qualitative and quantitative characteristics including the main parameter of LSFG - MBR (Mean Blur Rate) were determined.Results. A significant decrease with age of most studied parameters of blood flow volume was revealed, the changes were significant (p £ 0.05). The highest MBR parameters were noted in the group of 20–40 years old. In the macular area, MBR values decreased more significantly in the group after 60 years age, while for the optic nerve head (ONH), a decrease has been already noted after 40 years age. In average, the decrease was 25–34 % for the ONH area and 33–38 % for the macular area. Changes of the other parameters of the pulse waveform had a similar trend.Conclusion. LSFG is a reliable method for quantifying ocular blood flow. Our data support that LSFG-derived MBR and pulse wave measurements may be useful biomarkers for ocular perfusion changes. The identified age-related blood flow changes should be taken into account during the analysis of patients data.

Purpose: to investigate the changes of electrophysiological activity of healthy rabbit retina occurring in courses of fractal stimulation (FS) of varied duration in order to obtain new scientific data on how fractal visual signals of low intensity, self-similar with respect to time, affect the retina.Material and methods. 12 healthy Chinchilla rabbits (24 eyes), were examined before and after FS courses that lasted 1, 4 or 12 weeks, using electroretinographic (ERG), morphometric (optical coherence tomography) and biochemical methods (detection of dopamine in the tear). For FS of rabbits, a device with an LED emitter was developed, which generates nonlinear brightness fluctuation based on the Weierstrass — Mandelbrot fractal functions. The choice of fractal signal parameters used in the work was substantiated. Pattern ERG and ganzfeld ERG were registered according to ISCEV standards; also, photopic flicker ERG was recorded at 8.3, 10, 12, and 24 Hz.Results. No negative effects of a 12-month FS course on the activity and morphology of the retina, or on dopaminergic processes in the eye of a healthy animal were found, which confirms the safety of using low-intensity FS in the clinic. A statistically significant increase in the amplitude of low-frequency flicker ERGs, a shortening of peak latency, and an increase in the amplitude of the b-wave of the scotopic and photopic ERGs was noted.Conclusion. To assess possible therapeutic effects of FS, we need to continue the investigation on animal models and human patients with retinal pathology. Considering the changes of retinal activity as revealed in the present paper, we recommend the duration of FS courses from 1 week to 1 month for future studies.

Перенести в английский вариант Purpose. To assess the effect of adequate laser coagulation (LC) of peripheral vitreochorioretinal dystrophy (PVCRD) on the clinical and functional state of the retina and the microcirculation of the macular region. Material and methods. Ganzfeld electroretinogram (ERG), multifocal ERG (mfERG), and optical coherent tomography with a function of angiography (OCTA) were performed for the retina of 22 patients (37 eyes), aged 20 to 62, who had been given an adequate volume of LC to treat dangerous types of PVCRD. The tests took place before LC and 1, 3, 6, 9, 12 months after it. To analyze the results, two groups were formed: (1) 27 eyes with LC volume of less than 200 coagulates and (2) 10 eyes with LC volume of more than 200 coagulates. Results. After LC, we observed a moderate decrease in the amplitudes of scotopic ERGs and the a-wavepeak latency lengthening in the maximal ERG. In the 2 ndsubgroup, the amplitude of the second wave of oscillatory potentials (OP2) and the OP index decreased more significantly than in the 1st, subgroup (by 17 and 21 % from the initial values, respectively, p

Diabetic retinopathy (DR) is becoming more and more widespread disease. Investigation of local changes of metabolic pathways in the eye improves our knowledge about diabetic retinopathy pathogenesis and provide perspective for the development of new pathogenetically based and individually focused therapy of this disease.Purpose of the study was to determine the concentrations of angiotensin II (AII), angiotensin-converting enzyme (ACE) and matrix metalloprotease-9 (MMP-9) in tears and serum of patients with diabetic retinopathy, estimate their significance for the evaluation of diabetic retinopathy severity and choice of treatment.Patients and methods. Tear and serum samples from 31 patients with diabetic retinopathy were analysed. Control group consisted of healthy volunteers of the same sex and age. Concentrations of angiotensin II, angiotensin-converting enzyme and matrix metalloprotease-9 were measured using the ELISA kits.Results: in controls angiotensin II concentration was 9.8 ± 5.5 pg/ml, in tears — 11.8 ± 6.6 pg/ml, angiotensin-converting enzyme concentration in serum was 82.6 ± 10.9 ng/ml, in tears it was 40 times lower: 2.5 ± 0.5 ng/ml, matrix metalloprotease-9 concentration in serum was 186.3 ± 8.9 ng/ml while in tears it was 100 times lower: 2.0 ± 0.9 ng/ml. In tears of patients with diabetic retinopathy levels of all 3 substances were significantly higher than in controls. Concentration of angiotensin II was 8 times higher, angiotensin-converting enzyme concentration 5 times higher and matrix metalloprotease-9 level 3 times higher. In serum angiotensin II concentration was increased 9 times, angiotensin-converting enzyme — 2 times. No difference in serum matrix metalloprotease-9 levels was observed. Thus diabetic retinopathy cause a significant activation of local and systemic rennin-angiotensin system. Local changes are more marked than systemic. Estimation of angiotensin II, angiotensin-converting enzyme and matrix metalloprotease-9 concentrations in tears can serve as an objective test for the diabetic retinopathy diagnostic and a pathogenetic rationale for the development of a new method of therapy — topical use of angiotensin-converting enzyme inhibitors.

Purpose: to evaluate the effect of inadequately performed laser coagulation (LC) of peripheral vitreochorioretinal dystrophies (PVCRD) on the microcirculation of the macular region in patients with myopia. Material and methods. The state of the microvascular bed was investigated by OCT angiography (OCT-A), Angio Retina mode, scanning area 6 x 6 mm. The density of the surface vascular plexus was evaluated using a 9-quadrant protocol and an ETDRS grid. The parameters of the foveolar avascular zone (FAS) were determined. OCT-A of the retina was performed in 18 patients with PVCRD who had signs of inadequate retinal LC, such as hypercoagulation, an excessive number of coagulates with minimal changes in the retina, or massive LC in normal fundus eyes documented in their case histories. The research results were compared with the data of OCT-A obtained in 10 patients with myopia without signs of PVCRD (controls 1) and in 75 healthy individuals (controls 2). Results. In all patients with myopia (in the main group and controls 1), blood flow density indices were, respectively, 10–20 and 2–14 % lower than those in controls 2. The maximal decrease in blood flow density was found in the foveal zone in cases of hyper LC (p < 0.05). Also, in the eyes with excessive LC a significant expansion of the FAS and thinning of the retina were revealed. Conclusion. The results of the OCT-A study point to a negative effect of hyper LC of the PVCRD on the state of the microvasculature of the retina in the central zone. The obtained data correlate with our results of electrophysiological studies presented in the first part of this paper [ROJ, 2020; 13 (2): 45–52], which indicate functional changes in the fovea zone after inadequate laser coagulation in the peripheral areas of the retina.

Purpose of our work was to evaluate the effect of inadequate laser coagulation (LC) of peripheral vitreochorioretinal dystrophy (PVCRD) on the clinical and functional state of the retina. Material and methods. Ganzfeld ERG and multifocal ERG (mfERG) were recorded in 18 patients (32 eyes) with PVСRD in which, upon examination of the fundus, signs of inadequate retinal LC were detected and documented, such as hypercoagulation, an excessively large number of coagulates with minimal changes in the retina, or massive LC at the normal fundus. Results. The functional activity of the macular region after massive LC at the periphery of the retina in patients with PVCRD was shown to be reduced. The characteristic signs of reduction of the ganzfeld ERG and mfERG associated with a large volume of LC of the retina in patients without a history of surgical treatment of rhegmatogenous retinal detachment are described. For the first time, a functional method has been proposed to identify the risk of development and progression of macular dysfunction associated with massive LC of the retina, which includes a decrease in the amplitude of the waves of the maximal ERG and / or oscillatory potentials by 30 % or more with a parallel decrease in the density P1 in 1–3 rings of mfERG by 30 % and more as compared to the norm. Conclusion. Electrophysiological markers of macular dysfunction development risk associated with massive LC of the retina are proposed. The use of these markers in the clinic is important for predicting the risk of pathological changes in the macular region involving a decrease in visual functions, the choice of treatment tactics, and expert assessment of the volume of retinal LC redundancy.

The paper presents the evaluation of Retinalamin efficacy administered intramuscularly to 90 patients (180 eyes) aged 47 to 75 (averagely, 65.9 ± 7.18 years) with various stages of dry age-related macular degeneration (AMD) once or twice in 6 months. The data of multifocal electroretinography (MfERG) showed that in 80 % of cases of early and intermediate AMD stages, the functional state of the retina improved after a course of Retinalamin, reaching a peak 2 months after the start of treatment. A second course of Retinalamin, given 3 months later, resulted in a more pronounced improvement of the functional parameters, achieving the maximum in the month 5 of the follow-up period. This is confirmed by a change in the P1 component of Mf ERG, which proved to be the most pronounced in the central ring, corresponding to the foveal area. In more than 70 % of cases with atrophic AMD, a positive dynamics of the functional activity of the macula was noted only after a repeated course of intramuscular injections of Retinalamin, whose curative effect reached the maximum in the month 5 of the follow-up. An increase in the density of the P1 component of MfERG was more noticeable in the last two rings, corresponding to the periphery of macula // Russian Ophthalmological Journal, 2016; 1: 39-46.

The paper analyzes the data of a survey, conducted among the chief ophthalmologists in 34 regions of Russian Federation, on the state of medical care of patients with diabetic retinopathy. The questionnaire of the survey was developed by WHO within the international program "Tool for the Assessment of Diabetic Retinopathy and Diabetes Management System" (TADDS) and adapted to Russia’s conditions. We analyzed the scope of practical use of regulatory documents, the availability of medical care, screening quality, diagnosis, monitoring and treatment of diabetic retinopathy, cooperation of medical facilities, and education of medical staff // Russian Ophthalmological Journal, 2016; 2: 5-10. doi: 10.21516/2072-0076-2016-9-2-5-10.

The Purpose of this work was to determine microvascular changes in the macular zone with diabetes mellitus (DM) and with different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCT-A). Materials and methods. 60 patients were inspected (109 eyes) between the ages 58.20 ± 3.27 with DM (patients without clinical DR and with different stages of DR). The control group consisted of 75 healthy subjects (150 eyes) and was compared by gender and age to the DR group. OCT-A was performed with the help of the instrument RTVue XR Avanti (Optovue Inc, USA) in the Angio Retina settings with the scanning field dimensions 3 x 3 mm and 6 x 6 mm. The density of the top vascular plexus in the capillary network was evaluated in 9 quadrants, in the foveal and parafoveal zones, and in the foveal avascular zone (FAZ). Results. In patients with D, all groups were observed to have a significantly decreased density in blood flow in the top capillary network and a widened FAZ in comparison with the control group. The decrease density of blood flow was more evident in groups with preproliferative diabetic retinopathy (prePDR) and with proliferative DR (PDR), averaging at 16.6 % / 13.6 % and 15.5 % / 7.5 % in scanning fields of 3 x 3 mm / 6 x 6 mm, respectively. The FAZ field with DM and DR was at 38.5 %, with nonproliferated DR - at 26.9 %, with prePDR - at 65.4 %, and with PDR at 30.8 % higher than the control group. Conclusion. OCT-A allowed the identity of microvascular changes within the macular zone with DM in even the most early stages of the disease, when there were no manifestations of DR at the eye’s fundus. Early indicators of changes in the microcirculatory path of the retina with DM were qualitative and quantitative changes. These changes were within the FAZ and in the decreased density of the surfacevascular plexus in the capillary network within the scanning fields of 3 x 3 mm Russian ophthalmological journal. 2017; 10 (2): 40-5. (in Russian). doi: 10.21516/2072-0076-2017-10-2-40-45.

OCT angiography, an innovative noninvasive technique, allows a comprehensive assessment of eye vessels, separately for the choroidal and the retinal vasculature. Purpose: to assess microcirculation changes in the macular and peripapillary areas of the retina in retinitis pigmentosa (RP) by OCT angiography in comparison with electrogenesis parameters of the macular area of the retina and the cone system. Material and methods. The results of microcirculation studies of the fovea and the optic disk were analyzed for 14 patients with RP aged 5 to 76 (mean age 26.9 ± 17.6 years). OCT angiography was performed with Optovue RX Avanti (Optovue, USA). Рarafoveal vessel density, blood flow index, blood flow area, the size of the foveal avascular zone (FAZ) in the superficial and deep capillary plexuses and the flow area in retinal peripapillary capillaries (RPC) were assessed. All patients were tested by electroretinography using the MBN electroretinograph (Russia), including the general electroretingram (ERG), the maximal ERG, 30 Hz flicker ERG, and the macular ERG (MERG). Results. Blood flow deficit in superficial and deep capillary plexuses and in peripapillary capillaries (decreased parafoveal vessel density, vascular index, flow area) was associated with the reduction of a- and b-wave amplitudes of MERG and the increase of the implicit time. The enlargement of FAZ found in the deep capillary plexus (DCP) (p < 0.0001).and the normal size of FAZ in superficial capillary plexus (SCP) may be due to the difference in their structures. Conclusion. The blood flow deficit, which is more pronounced in DCP than in SCP in the macula of RP patients, is associated with the reduction of a- and b-wave amplitudes of MERG and the increase of the implicit time Russian ophthalmological journal. 2017; 10 (3): 22-28. doi: 10.21516/2072-0076-2017-10-3-22-28 // (in Russian). For citations: Zolnikova I.V., Levina D.V., Okhotsimskaya T.D., et al. Electroretinography and OCT angiography of the retina and optic nerve in retinitis pigmentosa. Russian ophthalmological journal. 2017; 10 (3): 22-28. doi: 10.21516/2072-0076-2017-10-3-22-28 (in Russian).

Aflibercept is a hybrid protein-imitation of VEGF receptor with a prolonged activity. The review describes the structural properties of the Aflibercept molecule, the impact of the medication on the pathogenesis of retinal diseases, and the results of clinical studies into the safety and effectiveness of Aflibercept in the therapy of age related macular degeneration (VIEW1, VIEW2), diabetic macular oedema (VISTA, VIVID), macular oedema caused by the occlusion of the central retinal vein (GALILEO, COPERNICUS) or its branches (VIBRANT), and myopic choroidal neovascularization (MYRROR) Russian ophthalmological journal. 2017; 10 (2): 103-11. (in Russian). doi: 10.21516/2072-0076-2017-10-2-103-111.