Age is a main risk factor for age-related macular degeneration (AMD), a complex multifactorial neurodegenerative retinal disease that is becoming the leading cause of vision loss in people over 55 years in developed countries. The risk of developing and rate of progression of AMD, as well as response to therapy, depend on the interaction of multiple genetic and environmental factors. In advanced stage, AMD is classified into dry atrophic (dry) or neovascular (wet) form. Intravitreal injection of anti-vascular endothelial growth factor agents is currently the first-line therapy for neovascular AMD. Unfortunately, therapy for dry AMD is still challenging, owing to an insufficient knowledge of the exact pathogenetic mechanisms. Considering the heterogeneity of AMD and the complexity of influencing age-dependent physiological processes, aging and immune disorders, the most realistic seems to be the further development of antiangiogenic therapy with an expansion of the range of targets, prolongation of their action and improvement of the delivery system. The neuroprotective potential of exogenous neurotrophins for retinal neurons has been proven; however, in order to develop effective drugs for the dry form of AMD based on them, it is necessary to resolve the issue of ways to effectively deliver them to the retina. In this review we discuss the current data on the AMD pathophysiology with focus on the role of vascular growth factors and neurotrophins.
Visomitin eye drops are the first and, so far, the only drug based on SkQ1 – the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl) decyltriphenylphosphonium, developed in the laboratories of Moscow State University under the leadership of Academician V. P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.
Purpose: to identify the intraretinal hyperreflective foci (HRF), their specific characteristics, localization features and correlations with the duration of the disease, type of course and previous episodes of optic neuritis (ON) in multiple sclerosis (MS) patients using a high-resolution OCT scanning protocol. Materials and methods. The study included 160 patients (318 eyes) divided into 8 groups, i.e. Group 1: 44 eyes (13.84 %) — MS onset without a history of ON; Group 2: 30 eyes (9.43 %) — debut of MS with ON; Group 3: 56 eyes (17.61 %) — relapsing-remitting MS (RRMS) lasting ≤ 10 years without ON; Group 4: 38 eyes (11.95 %) — RRMS lasting ≤ 10 years with ON; Group 5: 49 eyes (15.41 %) — RRMS lasting ˃ 10 years without ON; Group 6: 37 eyes (11.63 %) — RRMS lasting ˃ 10 years with ON; Group 7: 34 eyes (10.69 %) — secondary progressive MS (SPMS) without ON; Group 8: 30 eyes (9.43 %) — SPMS with ON. Results. HRF were identified in all groups, at the levels of both the outer nuclear layer (ONL) and the inner nuclear layer (INL). Their number increased depending on the duration, type of course, and the presence of ON history. The thickness of the inner layers of the retina corresponded to the average normative indicators in the group with the onset of MS without ON. In the SPMS group after ON, a decrease in the total thickness of ganglions retinal cells layer (GCL) and the inner plexiform layer (IPL) was noted, showing minimal values of both avGCL + IPL (65.83 ± 8.27 μm) and avRNFL (76.37 ± 6.94 μm). High inverse correlations were revealed between avGCL + IPL and the amount of GRF at the levels of ONL and INL (-0.82 and -0.85, respectively, p = 0.01). Conclusions. The presence and quantity of HRF can be considered as a prognostic non-invasive biomarker associated with the duration of MS and the history of ON, allowing one to visualize the penetration of microglia activated by immune cells into the unmyelinated part of the central nervous system, helpful in elucidating their role in the pathogenesis and progression of the disease.
Single-nucleotide polymorphisms (SNPs) can serve as reliable markers in genetic engineering, selection, screening examinations, and other fields of science, medicine, and manufacturing. Whole-genome sequencing and genotyping by sequencing can detect SNPs with high specificity and identify novel variants. Nonetheless, in situations where the interest of researchers is individual specific loci, these methods become redundant, and their cost, the proportion of false positive and false negative results, and labor costs for sample preparation and analysis do not justify their use. Accordingly, accurate and rapid methods for genotyping individual alleles are still in demand, especially for verification of candidate polymorphisms in analyses of association with a given phenotype. One of these techniques is genotyping using TaqMan allele-specific probes (TaqMan dual labeled probes). The method consists of real-time PCR with a pair of primers and two oligonucleotide probes that are complementary to a sequence near a given locus in such a way that one probe is complementary to the wild-type allele, and the other to a mutant one. Advantages of this approach are its specificity, sensitivity, low cost, and quick results. It makes it possible to distinguish alleles in a genome with high accuracy without additional manipulations with DNA samples or PCR products; hence the popularity of this method in genetic association studies in molecular genetics and medicine. Due to advancements in technologies for the synthesis of oligonucleotides and improvements in techniques for designing primers and probes, we can expect expansion of the possibilities of this approach in terms of the diagnosis of hereditary diseases. In this article, we discuss in detail basic principles of the method, the processes that influence the result of genotyping, criteria for selecting optimal primers and probes, and the use of locked nucleic acid modifications in oligonucleotides as well as provide a protocol for the selection of primers and probes and for PCR by means of rs11121704 as an example. We hope that the presented protocol will allow research groups to independently design their own effective assays for testing for polymorphisms of interest.
Increasing evidence on the adverse health impacts of microplastics (MPs) is available, but their associated risks to the well-being of humans and long-term impacts are poorly understood. An indicator of the remote effects of MPs may be their influence on the rate of aging. To assess the effects of MPs on the aging process, we used accelerated senescence OXYS rats that develop a complex of geriatric diseases. We prepared the polyethylene terephthalate MPs (2–6 microns in size) and in OXYS and Wistar (maternal strain) rats assessed the influence of chronic administration of MPs (10 or 100 mg/kg per day from age 1.5 to 3.5 months,) on the hematological and biochemical blood parameters, spatial learning, and memory. In addition, the effects of MPs on the development of cataracts and retinopathy, similar to age-related macular degeneration (AMD), in OXYS rats were assessed. We found that in the absence of significant changes in standard clinical blood parameters, chronic MP administration negatively affected the cognitive functions of both Wistar rats and OXYS rats. Additionally, a dose of 100 mg/kg MPs contributed to cataract and AMD progression in OXYS rats. Our results suggest that MPs may increase the rate of aging and, in the long term, lifespan.
Introduction. Presbyopia is a global problem affecting more than 1.5 billion people worldwide. Projections indicate an increase in the average age of the population to 40 years by 2050, which is associated with an increase in the presbyopia incidence and corresponding economic losses. Despite the widespread prevalence of presbyopia, there are currently no effective methods for early prevention and restoration of dynamic accommodation and a standardized approach to assessing age-related changes in the lens that underlie presbyopia. The purpose: to study the effect of age-related changes in the lens on accommodation and to consider modern pharmacological approaches to the prevention and treatment of presbyopia.Methods. A multicenter prospective study was conducted, including analysis of visual acuity, the nearest point of clear vision and the volume of accommodation in individuals aged 40 to 55 years. Study participants were prescribed pyrenoxine (Catalin) as eye drops three times daily for 4 months. The study included 382 questionnaires collected from 29 ophthalmologists.Results. As a result of the study, the average distance to the nearest point of clear vision decreased slightly, but the reserve of accommodation remained at the same level. This indicates the absence of significant progression of age-related decrease in the reserve of accommodation as one of the manifestations of presbyopia and the possible effectiveness of pyrenoxine in preserving the elastic properties of the lens.Conclusion. The study confirmed the effectiveness of pyrenoxine in the prevention of presbyopia and the preservation of accommodative abilities in middle-aged people. The concept of Dysfunctional Lens Syndrome may be useful for clinical practice by providing opportunities for early diagnosis and treatment of presbyopia. Incorporating this concept into clinical guidelines may improve approaches to the treatment and prevention of age-related lens changes.
PURPOSE:This study evaluated the impact of phacoemulsification cataract surgery (PE) on anatomical and functional parameters, as well as the regimen and frequency of anti-VEGF injections in patients with neovascular age-related macular degeneration (nAMD) over a long-term period (up to 3 years). MATERIAL AND METHODS:The study included 117 patients (117 eyes) diagnosed with nAMD and cataract, graded by LOCS: LOCS I (n=56; 47.9%), LOCS II (n=57; 48.7%), LOCS III (n=4; 3.4%); the average age of the patients was 76.2±5.7 years. All patients received anti-VEGF therapy (aflibercept 2 mg) following the treat-and-extend protocol. PE was performed only with disease activity under control. The observation period included 12 months before PE and 36 months after, with eight checkpoints for standard ophthalmological examination. RESULTS:The average number of injections before PE was 6.85±1.78. In the first year after PE, the injection frequency increased to 7.85±0.83, then decreased to 7.04±1.50 in the second year and 3.85±1.22 in the third, with intervals between injections lengthening (to 13.35±1.84 weeks by the third year). All eyes (100%) demonstrated significant improvement in best-corrected visual acuity (BCVA), with an absolute increase of 0.28 from pre-PE baseline (from 0.22±0.17 to 0.50±0.18 by study end). There was a positive trend in reduction of central retinal thickness (by 138.5 μm or 36.5%) compared to baseline at the start of treatment, as well as reduction in neuroretinal and retinal pigment epithelial detachment over the observation period. Statistically significant correlations were found between BCVA, injection frequency, injection interval, and morphological biomarkers of nAMD activity over time. CONCLUSION:Initiation of antiangiogenic therapy in nAMD patients and the continuation of individualized monitoring and treatment after PE is associated with effective suppression of nAMD activity, improvement in functional and anatomical parameters, and a reduction in the number of intravitreal injections both in the short term and the long term.
Diabetes mellitus (DM) is a major public health problem, with approximately one third having signs of diabetic retinopathy (DR). In such patients, cataracts develop at an earlier age and 2–5 times more frequently. The incidence of macular edema (ME) after phacoemulsification of cataracts (FEC) in patients with diabetes has been shown to increase by 1.80 times and, in the presence of DR by 6.23. The critical period for retinal deterioration is 2 months after FEC, which requires an active therapy and monitoring. For patients with pre-existing diabetic macular edema (DME), If the cataract does not affect daily activities of patients with a pre-existing DME and the optical clarity is adequate, it is preferable to postpone surgical treatment in order to maximize retinal stabilization on OCT at two consecutive visits with a month’s interval between. In the case of severe impairment of lens transparency, FEC with an intravitreal injection of anti-VEGF 28 days or steroids 1 month before surgery under strict monitoring of the retinal condition using OCT is recommended. If macular changes are absent and there is a risk of developing DME, the use of nonsteroid anti-inflammatory drugs is necessary. Prophylactic intravitreal therapy is unacceptable in the absence of MO.
The leading cause of vision loss in older adults is age-related macular degeneration (AMD). AMD is a multifactorial neurodegenerative disease of the retina that is becoming the leading cause of central vision loss in people over 55 years of age. The course of AMD depends on many interacting factors: genetic, environmental, and epigenetic, including changes in microRNA expression patterns. MicroRNAs are a large group of small noncoding regulatory RNA molecules that modulate the expression of target genes by blocking translation through complementary binding of messenger RNAs. The freeze–thaw stability of microRNAs in plasma/serum/urine, efficient recovery, and the availability of quantitative detection methods expand the possibilities of their use as biomarkers as well as potential mediators of physiological and pathological processes. Assessing the circulating pool of miRNAs in various biological fluids, such as blood plasma, is considered a promising approach to diagnosing AMD and assessing the effectiveness of future therapy, which may contribute to early detection of the disease and monitoring of AMD progression. The review summarizes recent studies with a focus on clinical and experimental studies of neovascular AMD, which have established the involvement of various microRNAs in the processes of pathological angiogenesis and the possibility of their use as biomarkers and therapeutic targets.
Cataract is one of the leading causes of blindness worldwide; its prevalence increases with age, ranging from 3.9 % among 55–64 years old to 92.6 % among those aged 80 years or more. Intraocular lenses (IOLs) are used in cataract surgery to replace the natural human lens and/or correct refractive errors. In recent years, a wide range of IOLs have been developed for the correction of presbyopia, which have surpassed traditional monofocal intraocular lenses. With an increased life duration and lifestyle changes, an increasing number of patients are not content with excellent distant vision alone but wish to have adequate near- and intermediate-distance vision. The review presents modern approaches to the correction of presbyopia by IOLs produced with the help of various technologies. The mechanisms of presbyopia correction, the general principles of multifocal IOL use, extended depth of focus (EDOF) technology, the advantages and drawbacks of individual IOL categories such as multifocal IOLs, improved monofocal IOLs, and deep focus IOLs are discussed. Special attention is given to terminology. Specifically, the concepts of EDOF and multifocal IOLs are distinguished, which however are not mutually exclusive as bifocal IOL, aspherical monofocal IOL, diffraction or refraction trifocal IOL can have EDOF characteristics (with partial range limitation at near distance in order to minimize dysphotoptic complaints). Taking into account the active marketing strategies of IOL manufacturers, the presented data can be useful in clinical practice, facilitating and structuring the relevant information for the ophthalmologist. Innovative solutions in the development of materials, optical platforms and the design of intraocular lenses for intraocular presbyopia correction provide a differentiated approach to achieving high functional results depending on the individual needs of patients.
The purpose: to compare the results of studies on intraocular lenses (IOLs) with extended depth of focus (EDOF) and trifocal intraocular lenses (THIOLs).Methods. The comparative analysis was conducted based on data from meta-analyses, systematic reviews, and randomized clinical trials. The electronic databases used were PubMed and Elibrary. The most commonly analyzed characteristics were postoperative refraction, visual acuity, optical aberrations, contrast sensitivity, visual quality, and dependence on glasses.Results. THIOL has significant advantages over EDOF in terms of postoperative refraction and visual acuity. This is demonstrated by a significantly lower postoperative residual spherical correction and spherical equivalent. There was no significant difference in postoperative astigmatism between the two groups. The analysis of visual acuity and eyeglass independence shows the advantages of EDOF for medium distances and THIOL for close distances. Some researchers prefer a combination of these two IOL types to achieve maximum results. Published data on optical phenomena indicate a higher number of dysphotopsias in the THIOL group. However, research results are highly contradictory due to their heterogeneity. A significant decrease in contrast sensitivity was observed in all groups for both photopic and mesopic conditions. Nevertheless, EDOF showed an advantage at lower spatial frequencies. In terms of satisfaction with the results obtained after surgery, there were no significant differences between the two groups of intraocular lenses (IOLs), as all patients reported a high level of satisfaction.Conclusion. Binocular implantation of a THIOL can provide greater independence from glasses and good vision at medium and short distances. However, patients should be aware of a possible decrease in contrast sensitivity and visual quality, especially at night, which may be accompanied by discomfort while driving. If more activity is required at intermediate distances in daily life, the choice of an EDOF IOL is crucial, and the patient may not require additional eyeglasses for closerange work if necessary. In clinical practice, knowing the characteristics of an IOL helps meet patient expectations and achieve high levels of satisfaction.
Introduction. Primary open-angle glaucoma (POAG) is the most common among the clinical forms of the disease. The main way to treat POAG is to reduce intraocular pressure (IOP). In most patients, treatment begins with a conservative method of reducing blood pressure by selecting medications for topical use. At the same time, studies show that only about a third of patients fully comply with doctors' prescriptions. In this regard, the concept of compliance is currently becoming relevant – the degree to which patients comply with the prescribed regimen of medicines and other recommendations. Aim. To study the degree of compliance in patients with glaucoma, and identify factors contributing to decreased adherence to treatment. Materials and methods. The study involved 45 patients (24 women (53.3%), 21 men (46.7%), average age 68.2 ± 6.7 years. Distribution by stages of glaucoma: stage I – 14 patients, stage II – 11 patients, stage III – 20 patients. Average duration of glaucoma disease – 6.25 ± 2.33 years. The study of compliance in patients with glaucoma was carried out using a questionnaire on the basis of the ophthalmology department of the State Novosibirsk Regional Clinical Hospital in the period from January 2023 to March 2023. The questionnaire was developed by the authors. Compliance was assessed according to degrees: high – compliance with doctor’s recommendations for at least 29 days a month, average – from 15 to 28 days, low – for less than 15 days. Clinical, medical, social and behavioral factors influencing the level of compliance were analyzed. Results. Among patients with stage III glaucoma, high compliance was detected in 80% of cases; in stages I and II – 50%, which may be due to the fact that this group of patients already has functional disorders that reduce the quality of life and the motivation of such patients is significantly higher than in the initial stages of the disease. In patients with initial and advanced stages of glaucoma, the reasons for low compliance were: presence of side effects (86.4 and 85.4%), complex instillation regimen (32.6 and 30.2%), low awareness of the disease (75 and 70 %) number of instillations per day (42.1 and 40.1%), inconvenient bottle (14.5 and 13.7%). In stage III, the decrease in adherence to treatment was facilitated by: presence of disability (24.3%), other systemic diseases requiring treatment with multiple drugs (85.4%), inconvenient bottle (5.3%), side effects (32.5%). The cost and availability of drugs played an important role in adherence to treatment regimens at all stages of glaucoma. Conclusion. To increase compliance, it is necessary to inform patients about the disease itself, its outcomes, complications, and identify the goals of local antihypertensive therapy for understanding and motivation to comply with the prescribed treatment regimen. It is equally important to involve the patient himself in drawing up a treatment plan and report possible consequences and side effects from the use of drugs.
The high prevalence of primary open-angle glaucoma, its leading role in the structure of visual disability, and insufficient effectiveness of treatment, prevention and rehabilitation measures require new approaches to providing quality care of patients with glaucoma. It is important to analyze the epidemiological situation, human and technological resources in various regions of the Russian Federation. The paper evaluates the compliance of specialized medical care of patients with glaucoma with the approved clinical guidelines CR 96 “Primary open-angle glaucoma” in the regions of the Russian Federation monitored by the Helmholtz National Research Center for Eye Diseases, based on the material of on-site data collection visits. The epidemiological situation relating to glaucoma, the structure and performance indicators of ophthalmological service departments, preventive measures, human and material resources, and the correctness of statistical accounting and reporting were studied. In most regions, the times of examination and treatment correspond to the regional territorial programs covered by state guarantees. The cases when primary specialized care lags behind is associated with staff shortage at the outpatient level. Practically in all regions of the Russian Federation, diagnostic methods and conservative/surgical treatment techniques with proven high efficiency conform to CR 96/1 “Primary open-angle glaucoma”. Some of the regions, however, are insufficiently equipped for early diagnosis of glaucoma and monitoring its course.
Multiple sclerosis (MS) is a chronic autoimmune-inflammatory and neurodegenerative disease. PURPOSE:This study explores the main structural changes in patients with MS and their relationships with the activity and type of disease course. MATERIAL AND METHODS:This prospective study included 159 patients (318 eyes) with an established diagnosis of MS: group (44 eyes; 13.84%) - relapsing-remitting type MS (RRMS) lasting up to 1 year without a history of optic neuritis (ON); group 2 (30 eyes; 9.43%) - RRMS up to 1 year with ON; group 3 (56 eyes; 17.61%) - RRMS lasting from 1 to 10 years without ON; group 4 (38 eyes; 11.95%) - RRMS from 1 to 10 years with ON; group 5 (49 eyes; 15.41%) - RRMS >10 years without ON; group 6 (37 eyes; 11.63%) - RRMS >10 years with ON; group 7 (34 eyes; 10.69%) - secondary progressive multiple sclerosis (SPMS) without ON; group 8 (30 eyes; 9.43%) - SPMS with ON. Patients underwent standard ophthalmological examinations, including optical coherence tomography. RESULTS:A decrease in structural parameters was diagnosed, progressing with the duration of the disease and the presence of ON: the minimum values of mGCL+IPL (65.83±9.14 μm) and mSNFL (76.37±14.77 μm) were detected in the group with SPMS with ON. High inverse correlations of EDSS with mGCL+IPL and mRNFL were demonstrated, with maximum in the group with the longest duration of MS without ON (-0.48 and -0.52 (p=0.01), respectively). CONCLUSION:Changes in the thickness of the structural parameters of the retina, measured by OCT, can be considered as a predictor of the course of MS.
Purpose. To study of the effectiveness of cataract surgery based on the results of a comprehensive evaluation, including the patient's opinion about the state of visual functions, when assessed using a questionnaire before and after surgery.Material and methods. 117 patients (117 eyes) diagnosed with nAMD and cataract (LOCS I — 56 patients, 47.9 %; LOCS II — 57 patients, 48.7 %, LOCS III — 4 patients, 3.4 %), mean age 76.2 ± 5.7 years were included in the study. All patients received angiogenesis inhibitor therapy (aflibercept 2 mg), in Treat&Extend regimen. Cataract surgery was performed if disease activity is controlled. A questionnaire including 10 questions was developed to interview patients, 9 of which were assessed before, 1 and 6 months after cataract surgery, and a 10th question on patient satisfaction with the results of surgery — 1 and 6 months after cataract surgery.Results. There was a significant improvement in functional (increase in BCVA by 0.31 units from the baseline) and anatomical parameters (significant decrease in CRT, height of neuro- and pigment epithelium detachment), as well as in patients' assessment of vision-related quality of life. The most compromised aspect before surgery was the ability to read text in newspapers, books, and magazines. After surgery there was a significant improvement of the indicators characterizing the patient's adaptation to navigation and outside activities. There were minimal changes in central vision loss and metamorphopsia as assessed by patients (on average, by 0.02 b. and 1.21 b.). 99 patients (84.0 %) reported satisfaction with the results of the surgery. The strongest correlations (r = 0.94 and 0.81, p < 0.05) characterized the relationship between patients' evaluation of the effect of surgery and the presence of central vision spotting/loss of central vision, double vision.Conclusion. The results of surgery significantly contribute to the patient's assessment of his/her daily activities requiring clearer vision, primarily in the middle and far distances. Cataract surgery does not worsen the course of nAMD and, on the contrary, cataract surgery and continuation of antiangiogenic therapy contribute to a significant improvement in BCVA and anatomical improvement.
Purpose: to study significant functional and structural changes in the retina and the intraocular section of the optic nerve in multiple sclerosis (MS) patients and analyze how they are interrelated with electrophysiological changes in the visual analyzer.Materials and methods. The study included 44 patients (88 eyes): group 1 (26 eyes) with MS duration ≤ 5 years and no history of optic neuritis (ON); group 2 (30 eyes) with MS duration from 6 to15 years and no history of ON; and group 3 (32 eyes) with MS duration ≤ 15 years with a history of ON. All patients underwent a complete ophthalmological examination and optical coherence tomography and had visually evoked potentials (VEP) and static automated perimetry registered.Results. A decrease in functional and structural parameters progressing with the duration of MS was revealed. In particular, best corrected visual acuity (BCVA) fell to 0.860 ± 0.075, the photosensitivity index MD maximally fell to -3.78 ± 0.95 dB, the strength of the P100 wave amplitude dropped to 7.84 ± 2.98 μV, the latency index of VEP rose to 124.21 ± 1.36 ms, the thickness of GCL + IPL fell to 65.69 ± 7.85 μm, and RNFL thickness averagely fell a low as to 80.25 ± 8.81 μm. When analyzing the topography of GCL + IPL decrease by sectors, the maximum value was revealed in the upper temporal segment (67.63 ± 7.89 μm). Sectoral changes in RNFL arranged in descending order of thickness showed the following sequence: lower upper nasal temporal. As the disease progressed, structural and functional changes were accompanied by an increase in the depth and a decrease in the thickness of the lamina cribrosa, with a maximum value revealed in the group with prior ON (239.00 ± 11.93 μm). Strong correlations were found in all study groups between (1) ave. GCL + IPL and ave. RNFL (r = 0.69; 0.64; 0.88, p < 0.03), (2) ave. GCL+IPL and BCVA (r = 0.86; 0.75; 0.78, p < 0.05), (3) MD and ave GCL + IPL (r = 0.52; 0.69; 0.71, p < 0.03), and (4) MD and ave. RNFL (r = 0.67; 0.61; 0.66, p < 0.05), as well as between the parameters of the lamina cribrosa and the markers under study.Conclusion. Significant functional and structural changes in the retina and the optic nerve were detected, correlating with the duration of the disease and with the clinical features of the course of multiple sclerosis. The presence of ON in history was accompanied by more pronounced changes, which can be considered as an important additional aggravating factor of the disease.
Background: Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response. Methods: Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT). Results: MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5–20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58–122] mkm) and CT (66 [30–105] mkm) carriers compared to the CC genotype (47 [24–68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment. Conclusions: MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.
Purpose: to analyze the levels of cytokines in intraocular fluid (IF) and blood plasma of patients with diabetic macular edema (DME) previously untreated by intravitreal therapy before and after the therapy by angiogenesis inhibitor or a corticosteroid. Material and methods. We examined 90 people — 47 females (52.2 %) and 43 males (47.8 %), mean age 64.54 ± 11.30 years. Of these, 60 had DME, and 30 formed the control group. The levels of 41 cytokines/chemokines in IF were determined by Milliplex® Map Human Cytokine/ Chemokine Panel; while the concentration of IL-18, MCP-1/CCL2, EPO, IL-10, IL-4, IL-6, IL-8, IFNα, VEGF-A in blood plasma was measured by enzyme-linked immunosorbent assay kits (Vector-Best, Russia). Patients with DME received intravitreal injections of an angiogenesis inhibitor (aflibercept. 50 eyes) or a corticosteroid (dexamethasone implant, 30 eyes). Results. Significant differences were revealed in 10 cytokine concentrations between the DME patients and the control group. The concentrations of IL-7, IL-15 and MCP-1/CCL2 levels in IF of DME patients were, respectively, 20.5, 20.3, and 11.02 times higher, than in the control group (р ˂ 0.05). Besides, a pairwise comparison of cytokines concentrations in IF of patients from either treatment group with the controls demonstrated a statistically significant increase in GROα/CXCL1 level. The pairwise comparison also revealed significant differences between the control and the corticosteroid therapy for systemic concentrations of IL-18 (p = 0.017), MCP-1/CCL2 (p = 0.009) and VEGF-A (p = 0.016). Conclusion. A pronounced and significant increase of the levels of a number of cytokines (e.g., IL-7, IL-15. FRACTALKINE/CX3CL1) were only sparsely reported before or remained undetermined at all. Our results on systemic cytokines levels may serve as prerequisite for further research into the role of systemic inflammation in DME pathogenesis. The analysis of associations of our results with those of other clinical biomarkers will contribute to the development of individualized treatment strategies.
Purpose : to analyze intraocular fluid (IOF) cytokine concentrations in patients with diabetic macular edema (DME) after intravitreal therapy with angiogenesis inhibitors or corticosteroids (CS). Materials and methods . 44 patients (45 eyes) were divided in 2 groups depending on the therapy: group 1 (n = 19) received an angiogenesis inhibitor (aflibercept) while group2 (n = 26) received CS (dexamethasone implant). They were tested for IOF cytokine levels by Milliplex® Map Human Cytokine/Chemokine Panel at treatment start and 3 months after either 3 monthly injections of aflibercept or a single dexamethasone implant injection. Results . The concentrations of ten cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, PDGF-AA, GROα/CXCL1, VEGF-A, MIP-1β/CCL4, IL-15, IL-7, IL-6) were found to fall significantly in both groups of therapy. IL-6 and IL-5 levels showed the most significant drop as compared to other cytokines, with a more pronounced decrease in the aflibercept treatment group. In both groups, VEGF-A concentration showed a significant drop, and the share of the eyes that responded to the treatment was 94.7 % in the aflibercept therapy group and 96.2 % in in the dexamethasone implant group. Conclusion . The IOF concentration assessment of a number of pro-inflammatory cytokines/chemokines shows that both the anti-VEGF agent — aflibercept and CS — dexamethasone implant contribute to a decrease of inflammation which is observed 3 months after the start of treatment.
Uveal melanoma is the most common primary intraocular malignant tumor among the adult population, its prevalence is more than 85% in the structure of all melanomas. Worldwide, the annual incidence of uveal melanoma is 6 cases per 1 million people. Despite the ongoing search for an effective treatment for uveal melanoma, there has not been a significant increase in the 5-year survival rate (~80%) in recent years, and approximately 50% of patients develop metastatic disease. The aim of this research was to analyze the clinical case of a female patient with metastatic uveal melanoma diagnosed with a metastatic lesion 28 years after enucleation. Modern possibilities of complex diagnostics using clinical, histopathological, cytogenetic and immunohistochemical markers determine the possibilities of performing polychemotherapy and determine the prognostic criteria for the life expectancy of patients.