[Objective functional monitoring of retinoprotective treatment in diabetic retinopathy]. / Ob"ektivnyi funktsional'nyi kontrol' retinoprotektornogo lecheniya diabeticheskoi retinopatii.

In recent years, there has been a growing interest in the contribution of neuroretinal degeneration to the pathogenesis of diabetic retinopathy (DR). PURPOSE: This study assesses the effect of the drug Retinalamin on the functional state of the retina in patients with DR using the Diopsys NOVA Vision Testing System that utilizes electrophysiological (EP) technology. MATERIAL AND METHODS: The study included patients with type 1 and 2 diabetes mellitus (DM) with DR of any stage without macular edema. Patients underwent standard ophthalmological examination and objective functional examination of the retina using the Diopsys NOVA Vision Testing System. The control group consisted of patients with type 1 and 2 DM with DR who did not receive Retinalamin. RESULTS: Significant changes in pattern electroretinography and flash electroretinography parameters were recorded in patients who received a course of Retinalamin. Two clinical examples are presented, which can be designated as the first experience of objective functional monitoring of treatment of patients with DR with Retinalamin. CONCLUSION: Retinoprotective therapy is necessary already at the early stages of DR. Electroretinography is an objective tool for functional analysis of the earliest changes in retinal cells in DR. It is necessary to use the identified "therapeutic" window for the appointment of retinoprotective agents.

[Retinoprotective effects of Retinalamin studied in an experimental model of photochemical damage to rabbit retinas]. / Issledovanie retinoprotektornykh effektov retinalamina v eksperimental'noi modeli fotokhimicheskogo povrezhdeniya setchatki krolika.

Purpose - to investigate functional and morphological effects of peptide bioregulator (Retinalamin) in modeling of photochemical damage to rabbit retina. MATERIAL AND METHODS: The study was conducted on 36 rabbits (72 eyes) randomized into 4 equal groups: two experimental groups received parabulbar injections of Retinalamin («Geropharm¼, Russia) in each eye in dosages of 0.25 mg/kg in a course of 10 days starting from day 1 and day 10 of the experiment, respectively, and two control groups that received injections of normal solution with the same regimen. To simulate photochemical damage to the retina, exposure to light with a wavelength of 405 nm, a power density of 5 mW/cm2 and daily exposure time of 4 h was performed for 20 days. Multifocal and flicker 30 Hz electroretinogram (mfERG and fERG) were recorded, and histological studies of retina samples with quantitative assessment of retinal cells apoptosis by the TUNEL method were conducted before, as well as 10, 20 and 30 days after the start of light exposure. RESULTS: Ophthalmoscopic signs of light-induced retinal degeneration were revealed 6-10 days after start of exposure in all groups. When registering mfERG and fERG in all groups, there was a significant decrease in the amplitude of N1 and P1 peaks, retinal density of the bioelectric response of the P1 component, as well as the amplitude of fERG on days 10 and 20 after the beginning of light exposure (p<0.001 in comparison with the background values), and a slight increase in the indicators on day 30. Histological examination revealed a significant decrease in the number of cells in the outer nuclear layer and an increase in the proportion of apoptotic cells in the outer and inner nuclear layers on days 10 and 20 of the experiment, with a decrease on day 30 (after cessation of light exposure). Comparison of the groups receiving Retinalamin injections from days 1 or 10 of light exposure between themselves and the control groups revealed no significant differences in any of the studied parameters (p>0.05). CONCLUSION: No significant functional and morphological evidence of neuroprotective effects of Retinalamin were found in the model of photochemical damage to rabbit retinas.

[Investigation of ligand-receptor interaction and biodistribution of a drug containing cattle retinal polypeptides in various administration routes]. / Issledovanie ligand-retseptornogo vzaimodeistviya i bioraspredeleniya pri razlichnykh rezhimakh vvedeniya lekarstvennogo sredstva, soderzhashchego polipeptidy setchatki glaz skota.

It is important to understand the features of the interaction of drug components with body receptors and obtain data on its distribution in various administration routes in recommended doses in order for its usage in clinical practice to be safe and effective. PURPOSE: To investigate in vitro the interactions of a drug consisting of water-soluble polypeptide fractions produced on animal retina with a wide range of receptor targets, and to assess its biodistribution in the organs of laboratory animals. MATERIAL AND METHODS: The biodistribution of the radioactively marked drug in different organs and tissues of laboratory mice in various routes of administration was studied at the National Research Centre «Kurchatov Institute¼. Evaluation of the ligand-receptor interaction of the drug was carried out in the laboratory at Eurofins Pharma Discovery Services by the method of competitive radioligand binding. RESULTS: A significant effect of the interaction of the polypeptide drug was revealed with different subtypes of glutamate receptors: AMPA, NMDA, and mGluR1. As a result of an in vivo test, we have obtained biodistribution data of the drug for intravenous, intramuscular and parabulbar administration, and the dynamics of drug accumulation in the tissues of the brain and eyes. CONCLUSION: According to the study results, the peptide drug binds to receptors associated with the loss of retinal ganglion cells. Interaction with these receptors potentially provides the test subject with neuroprotective effect. The content dynamics of the studied drug in the blood of animals depends on the route of administration and the amount of drug administered. At the time point of 0.5 hours for intravenous and intramuscular administration in the dose of 1.7 mg/kg, the studied drug has sufficiently high bioavailability in the tissues of the brain and eye. The data suggest that the main route of excretion of the studied drug is through kidneys.

[Effect of retinal protective therapy on optical coherence tomography angiography (pilot study)]. / Vliyanie retinoprotektornoi terapii na pokazateli opticheskoi kogerentnoi tomografii s funktsiei angiografii (pilotnoe issledovanie).

PURPOSE: To assess the influence of the frequency of retinal protective therapy courses on the indicators of regional hemodynamics of the eye. MATERIAL AND METHODS: The study included 17 patients (34 eyes) with a diagnosis of primary open-angle glaucoma (POAG), advanced stage. The patients were divided into 2 groups: the first group received a course of retinal protective therapy with Retinalamin every 3 months, the second group received a course of retinal protective therapy with Retinalamin every 6 months. All patients underwent standard ophthalmological examination including standard automatic perimetry according to the 24-2 program, optical coherence tomography angiography (OCT-A) of the macular area and optic disc. RESULTS: The comparison of hemodynamic parameters of all vascular plexuses of the retina at the beginning and at the end of the study, as well as intergroup comparison did not reveal any statistically significant differences (p>0.05). However, when studying the density and fractal dimension of the vascular bed, multidirectional trends were observed. Specifically, in the peripapillary region, there was a decrease in the length from 19.8 (1/mm) to 19.0 (1/mm) (p=0.37) and the density from 36.6% to 35.7% (p=0.63) of the vascular bed of the peripapillary capillary plexus of the retina in patients of the first group. In the superficial vascular plexus, the trend in the density of the vascular bed in both groups slightly changed (in group 1 - 38.1% and 38.3%, p=0.97; group 2 - 37.8% and 38.7%, p=0.46). The fractal dimension of the vascular bed in the first group tended to increase during treatment from 18.8 (1/mm) to 19.1 (1/mm) (p=0.5), while in the second group, on the contrary, it had tendency to decrease from 18.6 (1/mm) to 17.9 (1/mm) (p=0.63). In the deep vascular plexus, the density of the vascular bed trended to decrease in both groups, but in group 2 (42.5% and 42.4%, p=1.0) it was more pronounced than in the first group (42.5% and 42.6%, p=0.82). However, the fractal dimension of the vascular bed increased in group 1 (21.0 (1/mm) and 21.3 (1/mm), p=0.43) and showed a slight tendency to decrease in group 2 (21.5 (1/mm) and 21.0 (1/mm), p=0.86). CONCLUSION: The general trend of changes in hemodynamic parameters demonstrates a potential positive effect, especially in the data related to the deep vascular plexus.

[The influence of long-term retinal protective therapy on glaucoma progression according to structural and functional tests]. / Vliyanie dlitel'noi retinoprotektornoi terapii na progressirovanie glaukomy po dannym strukturno-funktsional'nykh issledovanii.

PURPOSE: To evaluate the influence of prolonged neuroprotective therapy on disease progression in patients with primary open-angle glaucoma (POAG) with compensated intraocular pressure (IOP). MATERIAL AND METHODS: The study included 147 patients with stages I-II POAG (249 eyes) who were randomized into the main (69 patients, 119 eyes) and control groups (78 patients, 130 eyes). Patients of the main group underwent retinalamin treatment course every 6 months. Patients were examined before enrolling and then every 3 months during the 24-months follow-up including optical coherence tomography (OCT; RNFL - retinal nerve fiber layer, NRR - neuroretinal rim, GCL - ganglion cell layer) and static perimetry (MD - mean deviation, PSD - pattern standard deviation). RESULTS: Visual acuity and refraction did not change in either group (p>0.05). IOP increased in the control group (p=0.033). There was no difference between the groups by the 24th month (p=0.87). No MD changes were noted in the main (p=0.45) and control groups (p=0.27). PSD changed in the main (4.84±3.21 and 6.01±2.584 dB in the beginning and the end, respectively, p=0.0004) and the control groups (3.46±2.23 and 5.86±2.26 dB, respectively; p<0.0001). The groups differed in MD and PSD initially (p=0.15; p=0.02) and became equal by the end (p=0.59; p=0.53). RNFL did not change significantly in the main group (p=0.078) and decreased from 83.5±22.47 to 76.7±20.7 µm in the control group (p=0.001); no differences between the groups were noted in the beginning (p=0.276) or in the end of the study (p=0.524). NRR increased in the main group from 222±88.94 to 231±99.3 (p=0.012), and decreased in the control group from 248±87.09 to 234±96.2 (p=0.0006); no differences were found between groups in the beginning or in the end of the study (p=0.109; p=0.909). GCL thickness did not change either in the main, or in the control group (p=0.211; p=0.16), with no difference between the group noted in the beginning or the end of the study (p=0.44; p=0.51). CONCLUSION: Regular treatment with retinalamin arrests the development of glaucomatous optic neuropathy. Longer-term research is required to study its influence on the visual function and the quality of life.

[Peptide bioregulators: delivery and efficacy]. / Peptidnye bioregulyatory: sposob vvedeniya i effektivnost'.

PURPOSE: To compare the neuroprotective properties of retinalamin administered in different ways among open-angle glaucoma patients with compensated intraocular pressure. MATERIAL AND METHODS: The study included 498 patients (eyes) with initial, moderate and advanced stages of glaucoma. Patients were divided into 3 groups: group I (n=110) received 5 mg intramuscular and 5 mg retrobulbar injections of retinalamin; group II (n=171) received 5 mg retrobulbar injection of retinalamin; group III received 5 mg intramuscular injection of retinalamin. The overall treatment dose contained 50 mg of retinalamin. All the patients underwent tonometry and static perimetry. Patients of group II with initial glaucoma and patients of group III with moderate glaucoma also underwent contrast sensitivity tests. The examinations were conducted before the treatment, and on months 3 and 6. RESULTS: Visual acuity did not change significantly. In group I, after 3 months of treatment total threshold retinal sensitivity increased by 122 dB in patients with initial glaucoma, by 166 dB in moderate and by 124 dB in advanced glaucoma. Positive trend was observed in patients with initial and moderate stages of glaucoma by month 6. In group II, total threshold retinal sensitivity increased by 123 dB in initial glaucoma and by 110 dB in moderate; the result did not change by month 6. No significant changes were observed in patients with advanced glaucoma. In group III, total threshold retinal sensitivity increased by 142 dB in initial glaucoma, by 274 dB in moderate and by 148 dB in advanced glaucoma. Regression began on the sixth month. In group II, patients with initial glaucoma were observed to have decreased sensorimotor reaction times to achromatic stimuli within the studied areas of central visual field. In group III, patients with advanced glaucoma were also observed to have decreased sensorimotor reaction times to achromatic stimuli detected within 1° and 5° areas from the fixation point, but not in the 10° area. CONCLUSION: Retinalamin is most effective in initial and moderate glaucoma stages. Intramuscular, retrobulbar and combined administration methods have comparable efficacy.

[Structural and functional changes in the retina of patients with primary open-angle glaucoma and compensated intraocular pressure while undergoing retinoprotective therapy]. / Strukturno-funktsional'nye izmeneniia setchatki u patsientov s pervichnoi otkrytougol'noi glaukomoi pri kompensirovannom vnutriglaznom davlenii na fone retinoprotektornoi terapii.

PURPOSE: To evaluate the efficacy and safety of intramuscular Retinalamin for retinoprotection in patients with open-angle glaucoma and normalized intraocular pressure (IOP). MATERIAL AND METHODS: The study included 180 patients (355 eyes) randomized into the main (n=90) and control groups (n=90). The patients of the main group received intramuscular Retinalamin injections; the course was repeated 6 months later. Patient examination was performed at 1, 3, 6, 7, 9 and 12 months. RESULTS: Vision acuity did not change in the main group after the treatment courses (p=0.3732, p=0.6862), nor in the control group (p=0.7751). IOP didn't have significant changes during the whole course of the study neither in the main group (p=0.7632), nor in the control group (p=0.3921). MD index in the main group has increased from -5.52±2.76 to -4.82±2.73 dB (measurements from 6 visits: p=0.0391, p=0.0201, p=0.0302, p=0.3708, p=0.0151, p=0.0353). Control group showed negative MD trend (from -3.51±1.84 to -4.60±2.61 dB; p=0.0012). PSD index has changed from 4.63±1.60 to 4.05±1.43 dB (p=0.0081) in the main group, and from 3.73±1.19 to 4.29±1.53 dB (p=0.0027) in the control group. Average thickness of retinal nerve fiber layer (RNFL) and the volume of neuroretinal rim were stable in both the main (p=0.8039, p=0.9005) and the control groups (p=0.7448, p=0.9620). Ganglion cell complex (GCC) thickness remained stable in the main group (p=0.0377), but has decreased in the control group (p=0.0250). P50 amplitude and latency were stable in the main group (6.54±2.61-6.53±2.64 µV, p=0.0479; 48.39±3.69-50.86±4.09 ms, p=0.0271), while in the control group P50 amplitude has decreased (p=0,0031) and the latency has increased (p=0,0194). In the main group, N95 amplitude has stabilized (p=0.0141) with worsened latency (p=0.0492). N95 amplitude in the control group has worsened (p=0.0195), while latency has stabilized (p=0.3401). CONCLUSION: Systemic use of Retinalamin has significant retinoprotective effect confirmed by the dynamics of morphological and functional parameters in patients with POAG and IOP compensation.

[Structural and functional changes in the retinal layers in patients with primary glaucoma and possible means of retinoprotection]. / Strukturno-funktsional'nye izmeneniia sloev setchatki pri pervichnoi glaukome i vozmozhnye puti retinoprotektsii.

Glaucoma is one of the most severe forms of ophthalmic pathology which can lead to low vision and blindness. Therapy aimed only at reducing intraocular pressure (IOP) may be insufficient in patients with this disease. PURPOSE: To study the structural and functional changes occurring in the retina and the effect of peptide bioregulator on the state of various retinal layers in patients with primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 62 patients (123 eyes) with POAG. The control group consisted of 25 people (50 eyes) of the same age. After the initial examination, patients of the glaucomatous group were divided into two equal subgroups. Patients of the first subgroup received 10 intramuscular injections of the peptide bioregulator; in the second subgroup, patients did not receive any retinoprotective therapy. The state of the visual analyzer was assessed using spectral optical coherence tomography (SOKT), electrophysiological research methods (ERG, PERG, flicker ERG), photostress test. RESULTS: Patients with POAG were found to have current and developing changes in the thickness and the configuration of various layers of the retina in the macular area as the disease progresses - particularly, in the nerve fiber layer (p=0.02), ganglion cells (p=0.002), inner nuclear layer (p=0.003) and the layer of pigment epithelium (p=0.049). Electrophysiological research methods helped reveal statistically significant changes in the functional parameters reflecting the generation and conduction of nerve impulses in retinal layers in patients with glaucoma. The patients undergoing peptide bioregulator therapy showed statistically significant positive changes in the state of ganglion cells observed as a decrease in the latency of the PERG N-95 wave (p=0.002) and stabilization of the structural indicators of SOCT (RNFL peripapillary zone). CONCLUSION: Patients with POAG exhibit progressive decrease in the thickness of not only the inner, but also the outer layers of the retinal macular area. According to objective structural and functional criteria, retinoprotective therapy leads to stabilization of the glaucomatous process.

[Molecular mechanisms of neuroretinoprotection in primary open-angle glaucoma]. / Molekuliarnye mekhanizmy neiroretinoprotektsii pri pervichnoi otkrytougol'noi glaukome.

PURPOSE: To evaluate the effectiveness of neuroprotective therapy in patients with primary open-angle glaucoma based on specific biochemical markers of neurotrophy and neurodegeneration. MATERIAL AND METHODS: In the course of the study, lacrimal fluid (LF) of 23 patients (46 eyes) with stage I-II primary open angle glaucoma (POAG) aged 66.3±10.8 was examined. The control group consisted of healthy individuals (12 control LF samples). Local antihypertensive therapy was complimented with 10 intramuscular injections of retinalamin (GEROPHARM LLC, St. Petersburg) - a complex of peptides isolated from cattle retinas, administered 5 mg once a day. Enzyme immunoassay (ELISA) method was used to test LF for concentrations of brain-derived neurotrophic factor (BDNF) and neuron specific enolase (NSE) before and after the treatment. RESULTS: In healthy subjects, the content of BDNF was 0.83±0.06 ng/mL, NSE - 0.51±0.06 ng/mL. In patients with POAG, the indices were higher: BDNF was 1.39±0.85 ng/mL (p>0.05), NSE - 4.31±2.02 ng/mL (p<0.05). The patients with stage II-III POAG had a significant increase of BDNF concentration (1.37±0.41 ng/mL and 1.52±0.40 ng/mL respectively in stages II and III) indicating compensatory capabilities at these stages of the disease. The NSE marker was also high in these stages (4.16±2.44 ng/mL and 5.78±2.80 ng/mL, p<0.05), which indicates the degeneration of retinal ganglion cells. After Retinalamin® therapy, patients with stage II POAG had control group levels of marker proteins, while in stage III patients NSE content remained high. CONCLUSION: There is a compensatory increase of BDNF level and a pathological increase of NSE content in LF of POAG patients. The change in the content of neurotrophins in the LF was determined to depend on the stage of POAG. Thus, in stages II and III POAG there is a marked increase of NSE and a compensatory increase of BDNF. After the complex therapy including retinalamin in patients with stage II POAG, a decrease in initially high concentrations of BDNF and NSE in LF down to the control group values was noted. In stage III patients, signs of neurodegeneration persist in the form of high NSE values. Taking into account the positive dynamics of the neuronal marker content in LF in the complex therapy of POAG with Retinalamin®, timely neuroretinoprotection is recommended.