A personalized approach to preclinical diagnosis and initial therapy of primary glaucoma based on a comprehensive structural and functional examination. A clinical case

The principles of personalized approach to early diagnosis and monitoring of primary glaucoma are shown by a clinical example. We analyzed the potentials of contemporary electrophysiological tests for preclinically diagnosing glaucoma optic neuropathy and monitoring drug treatment. For the first time, we demonstrated the experience of using a new fixed combination of brinzolamide + brimonidine by a clinical case from our practice. The test results confirm the hypotensive effect of the medication (IOP reduction by 36.2 %) so that it can be recommended for the treatment of patients with glaucomatous optic neuropathy and that combined with vascular pathology.

Comorbidity of NAFLD and GERD as a cardiometabolic phenomenon

The aim of the study was to study the cardiometabolic characteristics in individuals with an associated course of non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) in comparison with isolated cases of diseases.Materials and methods. The study included 120 patients (30 — with GERD, 30 — with NAFLD, 30 — with GERD + NAFLD. Work design — prospective parallel comparative study with 2 stages. Stage I — inclusion in the study, assessment of the main cardiometabolic, cardio vascular rice (CVR) according to the SCORE scale and the Framingham scale. Stage II — follow-up of the participants for 5 years, re-examination and riskmetry.Results. It has been shown that with a combination of NAFLD and GERD, the pathogenetic mechanisms involved in the formation of NAFLD (especially in steatohepatitis) affect the key characteristics of the metabolic profile and the state of the CV system to a greater extent than GERD. The total CVR values in this category of patients were: 4.8 — SCORE; 13.4 — on the Framingham scale. Over 5 years in this group, 10 (33% of the initial) newly diagnosed cases of CVD were verified: 6 — AH, 3 — IHD, 1 — AH + IHD. CVR for the NAFLD and GERD group increased: according to the SCORE scale — from low risk (4.8) to high (8.9), and according to the Framingham scale, the dynamics was even more negative (from 13.4 to 18.6).Conclusion. Kinds of cardiometabolic disorders in persons with comorbidity of NAFLD and GERD have been proven, which can form the prerequisites for structural cardiovascular changes, including the risks of CVD. This can be a rationale for carrying out additional preventive measures for the groups of patients under discussion, especially in the case of their associated course, as measures for the early preclinical diagnosis of CVR factors and for timely correction of the identified disorders.

A Monoiodotyrosine Challenge Test in a Parkinson’s Disease Model

Early (preclinical) diagnosis of Parkinsons disease (PD) is a major challenge in modern neuroscience. The objective of this study was to experimentally evaluate a diagnostic challenge test with monoiodotyrosine (MIT), an endogenous inhibitor of tyrosine hydroxylase. Striatal dopamine was shown to decrease by 34% 2 h after subcutaneous injection of 100 mg/kg MIT to intact mice, with the effect not being amplified by a further increase in the MIT dose. The selected MIT dose caused motor impairment in a neurotoxic mouse model of preclinical PD, but not in the controls. This was because MIT reduced striatal dopamine to the threshold of motor symptoms manifestation only in PD mice. Therefore, using the experimental mouse model of preclinical PD, we have shown that a MIT challenge test may be used to detect latent nigrostriatal dysfunction.

Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis

Background: Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Methods: Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Results: Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Conclusions: Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.

Structural and functional correlations in the pre-perimetric and the initial stages of glaucomatous optic neuropathy

Purpose:to study morphological and functional relationships in the early and preclinical diagnosis of glaucomatous optical neuropathy based on optical coherence tomography (OCT) of the retina and the data of electrophysiological research. Material and methods. Two clinical groups: (I) 35 patients (60 eyes) aged 49–70 (ave. 58.0 ± 5.3 yrs) with suspected glaucoma and (II) 21 patients (30 eyes) aged 46-68 (ave. 61.0 ± 4.8 yrs) with initial primary open-angle glaucoma (POAG), and a comparison group consisting of 36 relativelyhealthy subjects (41 eyes) aged 54–70 (ave. 62.0 ± 4.5 yrs), were subjected to spectral OCT by OСT Spectralis (Heidelberg Engineering, Germany). The thickness of the peripapillary layer of retinal nerve fibers (pRNFL), the minimum rim width (MRW), and the thickness of theretinal layers in the macular region that make up the ganglion cell complex (GCC) were evaluated. Spearman correlation analysis was used to identify correlations between OCT and electroretinography (ERG) data. Results.In patients with suspected glaucoma, changes in the parameters of transient pattern-ERG correlated with RNFL thinning in the macular region, inner plexiform layer (IPL), and ganglion cell layer(GCL) in the parafoveal area. In patients with initial glaucoma, changes in the retinal GCL were detected for the upper, lower, and temporal quadrants, while the nasal and central quadrants remained intact in all three GCC layers (RNFL, GCL, and IPL). In patients with suspected glaucoma, no statistically significant changes in the thickness of the pRNFL as compared with the norm were detected. Yet the MRW differed significantly from the comparison group. The highest number of correlations was found between the parameters of the ERGs and the thickness of the pRNFL. In patients with the initial stage of POAG, there was a significant increase in the thickness of RNFL in the temporal quadrant of the paramacular region. In our opinion, this phenomenon may be associated with the development of reactive gliosis being thereaction of neuroglia in response to changes in vascular and/or dystrophic homeostasis. Conclusion.Specific combinations of changes in the structural parameters of the retina and optic nerve head and the temporal and amplitude indices of the PERG and phototopic negative response have been found, justifying their use as combined markers of early and preclinical diagnosis of POAG.

The role of genetic factors in the pathogenesis of primary open-angle glaucoma. Part 1. Connective tissue

The article presents an analytical review of works devoted to molecular and genetic studies in primary open-angle glaucoma from the perspective of the concept of hereditary inferiority of the connective tissue of the eye (scleral component), and the entire body as a whole, as triggers in the development of the disease. The relationship between the main theories of the pathogenesis of glaucoma optical neuropathy and the determining role of molecular and genetic mechanisms of specific changes in the eye tissue is shown. The clinical features of primary open-angle glaucoma in patients with a family history are analyzed. Potentially new directions for preclinical diagnosis of glaucoma and pathogenetically oriented therapy are proposed.

Gene polymorphisms associated with the remodeling of the connective tissue as markers of preclinical diagnosis of primary open-angle glaucoma in patients with hereditary predisposition

Цель исследования - изучение взаимосвязи полиморфизмов генов, кодирующих структуру регуляторных белков синтеза и деградации экстрацеллюлярного матрикса соединительной ткани, с развитием первичной открытоугольной глаукомы (ПОУГ). Обследовано 144 человека (мужчин - 56, женщин - 88), средний возраст 59,3±6,2, не состоящих в родстве, русской национальности. Группу I составили 40 человек с подозрением на глаукому, в группу II вошли 40 человек с диагнозом ПОУГ I-II стадий на одном или обоих глазах. Пациенты обеих групп имели отягощенный семейный анамнез по глаукоме. Группу контроля составили 64 относительно здоровых человека. Всем пациентам проведены стандартные и специальные офтальмологические, а также молекулярно-генетические исследования. Носительство генотипа GT и аллеля Т полиморфизма rs8136803 (TIMP3), генотипа AG и аллеля A полиморфизма rs652438 (MMP12), генотипа GA и аллеля A полиморфизма rs3825942 (LOXL1) ассоциировано с развитием ПОУГ. Ассоциации полиморфизма rs1048661 гена LOXL1 с развитием ПОУГ не выявлено. Проведенное исследование указывает на необходимость формирования алгоритма обследования пациентов с ПОУГ и подозрением на глаукому с включением молекулярно-генетических исследований. Objective: to study gene polymorphisms associated with the remodeling of the connective tissue of the eye as markers of preclinical diagnosis of primary open-angle glaucoma in patients with hereditary predisposition. Materials and methods: a total of 144 persons (56 men, 88 women), average age 59.3±6.2, were examined, not related, of Russian nationality. Group I consisted of 40 individuals suspected to affected by glaucoma, group II included 40 individuals with a diagnosis of I-II stage POAG in one or both eyes. Patients of both groups had a complicated family history of glaucoma. The control group consisted of 64 relatively healthy individuals. All patients underwent standard and special ophthalmological examination, as well as molecular genetic testing. Results: carriage of GT genotype and T allele of rs8136803 polymorphism (TIMP3), AG genotype and A allele of rs652438 polymorphism (MMP12), GA genotype and A allele of rs3825942 polymorphism (LOXL1) was associated with the development of POAG. The rs1048661 polymorphism of the LOXL1 gene cannot be considered as a marker of POAG development. Conclusion: the study indicates the need to develop a correct algorithm for diagnosing patients with POAG and suspected glaucoma with the inclusion of molecular genetic studies.

A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice

Development of differential and early (preclinical) diagnostics of Parkinson’s disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms (72%, p = 0.049), a decreased level of adrenaline on both sides (ipsilateral—53%, p = 0.004; contralateral—42%, p = 0.02), and an increased α-2-macroglobulin activity on both sides (ipsilateral—53%, p = 0.03; contralateral—56%, p = 0.037) compared to controls. These changes are considered as potential biomarkers for differential diagnosis. Similar changes in the TF were found in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice when modeling clinical and preclinical stages of PD. These data show the adequacy of models to the pathogenesis of PD along the selected metabolic pathways, and also suggest that the found TF changes can be considered as potential biomarkers for preclinical diagnosis of PD. In Parkinsonian mice, the level of catecholamines also changes in the lacrimal glands, which makes it possible to consider them as one of the sources of catecholamines in the TF.