Tear 1H Nuclear Magnetic Resonance-Based Metabolomics Application to the Molecular Diagnosis of Aqueous Tear Deficiency and Meibomian Gland Dysfunction.

PURPOSE: Meibomian gland dysfunction (MGD) is a major cause of signs and symptoms related to dry eyes (DE) and eyelid inflammation. We investigated the composition of human tears by metabolomic approaches in patients with aqueous tear deficiency and MGD. METHODS: Participants in this prospective, case-control pilot study were split into patients with aqueous tear deficiency and MGD (DE-MGD [n = 15]) and healthy controls (CG; n = 20). Personal interviews, ocular surface disease index (OSDI), and ophthalmic examinations were performed. Reflex tears collected by capillarity were processed to 1H nuclear magnetic resonance (NMR) spectroscopy and quantitative data analysis to identify molecules by spectra comparison to library entries of purified standards and/or unknown entities. Statistical analyses were made by the SPSS 22.0 program. RESULTS: Chemometric analysis and 1H NMR spectra comparison revealed the presence of 60 metabolites in tears. Differentiating features were evident in the NMR spectra of the 2 clinical groups, characterized by significant upregulation of phenylalanine, glycerol, and isoleucine, and downregulation of glycoproteins, leucine, and -CH3 lipids, as compared to the CG. The 1H NMR metabolomic analyses of human tears confirmed the applicability of this platform with high predictive accuracy/reliability. CONCLUSIONS: Our key distinctive findings support that DE-MGD induces tear metabolomics profile changes. Metabolites contributing to a higher separation from the CG can presumably be used, in the foreseeable future, as DE-MGD biomarkers for better managing the diagnosis and therapy of this disease.

Early post-procedural patients compliance and VAS after UAE through transradial versus transfemoral approach: preliminary results.

PURPOSE: The aim of our study is to verify VAS and patient compliance in the immediate post-procedural time, in patients undergoing UAE through radial approach versus femoral procedure. METHODS: Between January and September 2017, 30 consecutive patients (age range 28-47, average 32 years) were enrolled for the study. UAE was performed by two interventional radiologists with more than 10 years of experience and more than 100 cases of UAE done. Patients were divided into two groups: transfemoral approach (group a, n = 15 patients) and transradial approach (group b, n = 15 patients). After procedure, patients were questioned about the compliance using the questionnaire at 24 h and VAS rating at 6, 12, 18 and 24 h. RESULTS: The average of VAS in group b was lower than in group a in each evaluation at 6 h (p < 0.20), 12 h (p < 0.07), 18 h (p < 0.02) and 24 h (p < 0.22) on the basis of Mann-Whitney U test, however, without a clear scientific evidence. Also the compliance score at 24 h had better results in the group b (average 14.0, range 13.0-16.0) in comparison with group a (average 18.0, range 17.0-21.4) (p < 0.001). CONCLUSION: Transradial approach improves the compliance and VAS of patients undergone to UAE.

A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case-control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-TMCO1, rs4236601-CAV1/CAV2, rs2157719-CDKN2B-AS1 and rs3088440-CDKN2A). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79-4.77) times more likely to have POAG compared with participants in the bottom category (p < 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (p = 0.002) and vitamin E (p = 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.

Genetic polymorphism related to exfoliative glaucoma is also associated with primary open-angle glaucoma risk.

BACKGROUND: To investigate the possible association of the rs2165241 polymorphism (C > T) in LOXL1 gene with the risk of primary open-angle glaucoma in a Mediterranean population. METHODS: The analysis of genetic polymorphisms was performed by standard TaqMan allelic discrimination technique, using a 7900HT Sequence Detection System (Applied Biosystems). RESULTS: In a recessive genetic model, the T allele of the rs2165241 polymorphism was significantly associated with the risk of primary open-angle glaucoma (TT vs. CC: odds ratios = 2.19, 95% confidence interval = [1.33-3.62]). After multivariate logistic regression model adjusted by age and weight, the magnitude of the association decreased but remained statistically significant (TT vs. CC: odds ratios = 2.07, 95% confidence interval = [1.20-3.57]). CONCLUSION: This polymorphism seems to be associated with high risk for primary open-angle glaucoma in a Mediterranean population.

Impact of stimulant treatment on refractive errors and pupil diameter in attention deficit hyperactivity disorder.

PURPOSE: The relationship between attention deficit hyperactivity disorder (ADHD) and visual impairment remains poorly understood, and the impact of visual impairment on the development of ADHD is uncertain. The aim of this study was to investigate the refractive profile and ocular biometric characteristics in patients diagnosed with ADHD and compare them with a control group. Additionally, we aimed to explore the potential influence of sex and medication intake. METHODS: A cohort of 100 participants, including 50 individuals with ADHD and 50 age- and sex-matched control subjects, was included in this study. Ocular biometric parameters were measured, and refractive error was assessed using cycloplegic and non-cycloplegic autorefraction. Subgroup analyses were performed within the ADHD group based on sex, medication intake and age to investigate potential associations with the ocular findings. RESULTS: We observed no statistically significant differences in axial length, corneal topography parameters or anterior chamber characteristics between ADHD and control subjects. However, subgroup analysis within the ADHD group revealed that the prevalence of ametropia under cycloplegia was significantly higher in unmedicated (69.6%) compared to medicated (37.5%) (X2(2) = 7.320, p = 0.026) participants. Pupil diameter was significantly larger in medicated (3.91 mm) compared to unmedicated (3.58 mm; p = 0.017) individuals. Males had flatter (p = 0.004) and thicker (p = 0.008) corneas than females. Older ADHD participants had higher refractive error (p = 0.008 for non-cycloplegic and p = 0.0.003 for cycloplegic), axial length (p = 0.002) and corneal astigmatism (p = 0.049). CONCLUSIONS: Our study provides compelling evidence that individuals diagnosed with ADHD exhibit a similar incidence of refractive errors and ocular parameters compared to normal subjects. Nonetheless, the prevalence of refractive errors appears to be higher in unmedicated ADHD patients, suggesting the potential benefit of stimulant treatment. Additionally, stimulant use is associated with an increase in pupil diameter.

Evaluation of the Diagnostic Capability of Spectralis SD-OCT 8 × 8 Posterior Pole Software with the Grid Tilted at 7 Degrees and Horizontalized in Glaucoma.

Background: The goal was to evaluate the diagnostic capability of different parameters obtained with the posterior pole (PP) software in Spectralis SD-OCT with the 8 × 8 grid tilted at 7° and horizontalized in glaucomatous eyes. Methods: A total of 299 eyes were included, comprising 136 healthy eyes and 163 with primary open-angle glaucoma (POAG). The following segmentations were evaluated: complete retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), GCL and inner plexiform layer (GCLIPL), ganglion cell complex (GCC), outer plexiform layer and outer nuclear layer (OPLONL), inner retinal layer (IRL), and outer retinal layer (ORL). Different patterns of macular damage were represented using heatmaps for each studied layer, where the areas under the curve (AUROC) values and a retinal thickness cutoff point were defined to discriminate POAG patients. Results: There was not any difference in the diagnostic capability for detecting glaucoma between the grid tilted at 7° and horizontalized. The macular segmentations that offer the highest diagnostic ability in glaucoma discrimination were, in the following order, RNFL (AUROC = 0.796), GCC (AUROC = 0.785), GCL (AUROC = 0.784), GCLIPL (AUROC = 0.770), IRL (AUROC = 0.755), and the complete retina (AUROC = 0.752). In contrast, ORL and OPLONL do not appear to be helpful for discriminating POAG. Conclusions: Some results of PP software may be useful for discriminating POAG.

Effects of polymorphisms in vitamin E-, vitamin C-, and glutathione peroxidase-related genes on serum biomarkers and associations with glaucoma.

PURPOSE: To study the association of selected polymorphism in genes related to vitamin E, vitamin C, and glutathione peroxidase with these biomarkers and primary open-angle glaucoma (POAG) risk. METHODS: A case-control study matched for age, sex, and bodyweight was undertaken. Two hundred fifty POAG cases and 250 controls were recruited from a Mediterranean population. Plasma concentrations of vitamin C, vitamin E, and glutathione peroxidase (GPx) activity were measured. We analyzed the polymorphisms rs1279683 in the Na(+)-dependent L-ascorbic acid transporter 2 (SLC23A2) gene, rs6994076 in the tocopherol alpha transfer protein (TTPA) gene, rs737723 in the tocopherol-associated protein (SEC14L2/TAP) gene, and rs757228 in the glutathione peroxidase 4 (GPX4) gene. We also analyzed expression of the SLC23A2 gene in a subsample. RESULTS: We found a novel association between the rs737723 polymorphism and POAG risk. Homozygous subjects for the C allele had a higher POAG risk than carriers of the ancestral G allele (adjusted odds ratio 1.73, 95% confidence interval 1.13-2.65, p=0.011). This association remained statistically significant after adjustment for multiple comparisons. We also confirmed the association between the rs1279683 polymorphism and a higher POAG risk in GG homozygous subjects and detected statistically significant differences in SLC23A2 gene expression between POAG cases and controls, even after adjustment for multiple testing. We observed a nominally significant (p<0.05) gene-gene interaction between the SEC14L2/TAP and SLC23A2 polymorphisms in determining POAG risk, increasing POAG risk in those subjects who had both risk genotypes at the same time (p<0.01). This increase was statistically significant even after adjustment for multiple comparisons. We did not detect any association with POAG risk for the rs6994076 or rs757228 polymorphisms. We also found that POAG patients had statistically significant (after correction for multiple testing) lower plasma vitamin E (p<0.001) and vitamin C (p<0.001) concentrations than control subjects. However, we detected a higher plasma GPx activity in POAG cases than in controls (p<0.001). The rs6994076 and rs1279683 polymorphisms were significantly (p<0.001) associated with plasma vitamin E and vitamin C, respectively. However, the rs757228 polymorphism in the GPX4 gene was not associated with plasma GPx activity. CONCLUSIONS: We have described a novel association between the rs737723 polymorphism (SEC14L2/TAP) and higher POAG risk and confirmed the association between rs1279683 (SLC23A2) and POAG. Our results also suggested a gene-gene interaction between both polymorphisms that increases POAG risk.

Normative Database of the Superior-Inferior Thickness Asymmetry for All Inner and Outer Macular Layers of Adults for the Posterior Pole Algorithm of the Spectralis SD-OCT.

BACKGROUND: This study aims to establish a reference for the superior-inferior hemisphere asymmetry in thickness values for all macular layers for the posterior pole algorithm (PPA) available for the Spectralis SD-OCT device. METHODS: We examined 300 eyes of 300 healthy Caucasian volunteers aged 18-84 years using the PPA, composed of a grid of 64 (8 × 8) cells, to analyze the thickness asymmetries of the following automatically segmented macular layers: retinal nerve fiber layer (RNFL); ganglion cell layer (GCL); inner plexiform layer (IPL); inner nuclear layer (INL); outer plexiform layer (OPL); outer nuclear layer (ONL); retinal pigment epithelium (RPE); inner retina; outer retina; complete retina. Mean ± standard deviation and the 2.5th and 97.5th percentiles of the thickness asymmetry values were obtained for all the corresponding cells. RESULTS: All the macular layers had significant superior-inferior thickness asymmetries. GCL, IPL, INL, ONL and RPE showed significantly greater thicknesses in the superior than the inferior hemisphere, whereas RNFL and OPL were thicker in the inferior hemisphere. The largest differences between hemispheres were for RNFL and ONL. CONCLUSIONS: This is the first normative database of macular thickness asymmetries for the PPA and should be considered to distinguish normal from pathological values when interpreting superior-inferior macular asymmetries.

Macular Anatomy Differs in Dyslexic Subjects.

The macula, as the central part of the retina, plays an important role in the reading process. However, its morphology has not been previously studied in the context of dyslexia. In this research, we compared the thickness of the fovea, parafovea and perifovea between dyslexic subjects and normal controls, in 11 retinal segmentations obtained by optical coherence tomography (OCT). With this aim, we considered the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and also summarized data from sectors into inner ring subfield (parafovea) and outer ring subfield (perifovea). The thickness in all the four parafoveal sectors was significantly thicker in the complete retina, inner retina and middle retina of both eyes in the dyslexic group, as well as other macular sectors (fovea and perifovea) in the inner nuclear layer (INL), inner plexiform layer (IPL), IPL + INL and outer plexiform layer + outer nuclear layer (OPL + ONL). Additionally, the inner ring subfield (parafovea), but not the outer ring subfield (perifovea), was thicker in the complete retina, inner retina, middle retina (INL + OPL + ONL), OPL + ONL, IPL + INL and INL in the dyslexic group for both eyes. In contrast, no differences were found between the groups in any of the sectors or subfields of the outer retina, retinal nerve fiber layer, ganglion cell layer or ganglion cell complex in any eye. Thus, we conclude from this exploratory research that the macular morphology differs between dyslexic and normal control subjects, as measured by OCT, especially in the parafovea at middle retinal segmentations.

Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients.

Introduction: Glaucoma is a chronic neurodegenerative disease, which is the leading cause of irreversible blindness worldwide. As a response to high intraocular pressure, the clinical and molecular glaucoma biomarkers indicate the biological state of the visual system. Classical and uncovering novel biomarkers of glaucoma development and progression, follow-up, and monitoring the response to treatment are key objectives to improve vision outcomes. While the glaucoma imaging field has successfully validated biomarkers of disease progression, there is still a considerable need for developing new biomarkers of early glaucoma, that is, at the preclinical and initial glaucoma stages. Outstanding clinical trials and animal-model study designs, innovative technology, and analytical approaches in bioinformatics are essential tools to successfully uncover novel glaucoma biomarkers with a high potential for translation into clinical practice. Methods: To better understand the clinical and biochemical-molecular-genetic glaucoma pathogenesis, we conducted an analytical, observational, and case-comparative/control study in 358 primary open-angle glaucoma (POAG) patients and 226 comparative-control individuals (CG) to collect tears, aqueous humor, and blood samples to be processed for identifying POAG biomarkers by exploring several biological pathways, such as inflammation, neurotransmitter/neurotrophin alteration, oxidative stress, gene expression, miRNAs fingerprint and its biological targets, and vascular endothelial dysfunction, Statistics were done by using the IBM SPSS 25.0 program. Differences were considered statistically significant when p ≤ 0.05. Results: Mean age of the POAG patients was 70.03 ± 9.23 years, and 70.62 ± 7.89 years in the CG. Malondialdehyde (MDA), nitric oxide (NO), interleuquin (IL)-6, endothelin-1 (ET-1), and 5 hydroxyindolacetic acid (5-HIAA), displayed significantly higher levels in the POAG patients vs. the CG (p < 0.001). Total antioxidant capacity (TAC), brain derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), solute carrier family 23-nucleobase transporters-member 2 (SLC23A2) gene, and the glutathione peroxidase 4 (GPX4) gene, showed significantly lower levelsin the POAG patients than in the CG (p < 0.001). The miRNAs that differentially expressed in tear samples of the POAG patients respect to the CG were the hsa miR-26b-5p (involved in cell proliferation and apoptosis), hsa miR-152-3p (regulator of cell proliferation, and extracellular matrix expression), hsa miR-30e-5p (regulator of autophagy and apoptosis), and hsa miR-151a-3p (regulator of myoblast proliferation). Discussion: We are incredibly enthusiastic gathering as much information as possible on POAG biomarkers to learn how the above information can be used to better steer the diagnosis and therapy of glaucoma to prevent blindness in the predictable future. In fact, we may suggest that the design and development of blended biomarkers is a more appropriate solution in ophthalmological practice for early diagnosis and to predict therapeutic response in the POAG patients.

Oxidative Stress Mediates Epigenetic Modifications and the Expression of miRNAs and Genes Related to Apoptosis in Diabetic Retinopathy Patients.

Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.

Comparison of global indices and test duration between two visual field analyzers: Octopus 300 and Topcon SBP-3000.

PURPOSE: To compare the global indices and test duration as measured by Octopus 300 and Topcon SBP-3000 perimeters. To our knowledge, this is the first study performed in this way. METHODS: Eighty eyes of 40 glaucomatous and ocular hypertensive patients with previous perimetric experience had visual field tests with Octopus 300 (TOP strategy) and TOPCON SBP-3000. All pairs of tests were performed randomly on separate days, but within 1 month of each other. Taking into account reliability factors of both perimetric examinations, 54 eyes of thirty patients were eligible. Only one eye from each patient was considered. Mean sensitivity (MS), mean defect (MD), loss of variance (sLV-Octopus- and LV -Topcon-) and test duration times were considered. RESULTS: A significant difference was found between the global indices and duration times of the Octopus and the Topcon perimeters (p < 0.05; Wilcoxon test). Moderate degrees of correlation were obtained for MS (Spearman's rho = 0.635; p < 0.001) and MD (Spearman's rho = 0.592; p = 0.001) measurements. There was no correlation between sLV and LV (Spearman's rho = 0.181; p = 0.337). Agreements between pairs of global indices were low as measured by concordance correlation coefficient. CONCLUSION: Global indices measured by the Octopus and Topcon perimeters are significantly different, so direct comparison of the measured values is not reliable. Because of the poor association and agreement between values obtained by these two perimeters, indirect comparison is also inadvisable.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: Results from the VISIONARY Study Population in Spain.

Purpose: Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. Methods: An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Results: Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P < 0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. Conclusion: In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.

Impact of Systemic Comorbidities on Ocular Hypertension and Open-Angle Glaucoma, in a Population from Spain and Portugal.

Open-angle glaucoma (OAG), the most prevalent clinical type of glaucoma, is still the main cause of irreversible blindness worldwide. OAG is a neurodegenerative illness for which the most important risk factor is elevated intraocular pressure (IOP). Many questions remain unanswered about OAG, such as whether nutritional or toxic habits, other personal characteristics, and/or systemic diseases influence the course of glaucoma. As such, in this study, we performed a multicenter analytical, observational, case-control study of 412 participants of both sexes, aged 40-80 years, that were classified as having ocular hypertension (OHT) or OAG. Our primary endpoint was to investigate the relationship between specific lifestyle habits; anthropometric and endocrine-metabolic, cardiovascular, and respiratory events; and commonly used psychochemicals, with the presence of OHT or OAG in an ophthalmologic population from Spain and Portugal. Demographic, epidemiological, and ocular/systemic clinical data were recorded from all participants. Data were analyzed using the R Statistics v4.1.2 and RStudio v2021.09.1 programs. The mean age was 62 ± 15 years, with 67-80 years old comprising the largest subgroup sample of participants in both study groups. The central corneal thickness (ultrasound pachymetry)-adjusted IOP (Goldman tonometry) in each eye was 20.46 ± 2.35 and 20.1 ± 2.73 mmHg for the OHT individuals, and 15.8 ± 3.83 and 16.94 ± 3.86 mmHg for the OAG patients, with significant differences between groups (both p = 0.001). The highest prevalence of the surveyed characteristics in both groups was for overweight/obesity and daily coffee consumption, followed by psychochemical drug intake, migraine, and peripheral vasospasm. Our data show that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from OHT to OAG in this Spanish and Portuguese population.

Combined pre- and postnatal ethanol exposure in rats disturbs the myelination of optic axons.

AIMS: To analyse myelination and outgrowth of the optic axons in relation to the neuro-ophthalmological manifestations of ethanol (EtOH) abuse during pregnancy. METHODS: An experimental model of chronic EtOH exposure was developed in rats and their offspring by subjecting the dams to a liquid diet (35% of the daily total calories as either EtOH or maltose-dextrose nutritional controls (Con). Eyeballs and optic nerves were obtained at key developmental stages and processed for morphologic, immunocytochemical and immunoblotting procedures, using alternatively antibodies against myelin basic protein (MBP) or neurofilament (NF) protein, and image analysing. RESULTS: A significant delay in onset of optic axons myelination, as well as a significant reduction in optic nerve size (P < 0.001), optic axons number (P < 0.001), myelinated axons density (P < 0.001), number of myelin lamellae linked to axon diameter (P < 0.001) and optic axon cross-sectional area (P < 0.001) were detected in the global morphometric assessment of the EtOH nerves with respect to the Con. Expression of MBP and NF was noticeably reduced in the EtOH optic nerves when compared with the Con. CONCLUSION: Disturbed myelination of optic axons, caused by EtOH abuse, strongly disrupts the optic nerve development and the establishment of definitive retinal and optic nerve targets, and subsequently the visual patterns.

Updates in Clinical and Translational Glaucoma Research.

Glaucoma is a sight-threatening disease and the primum mobile of irreversible blindness worldwide [...].

Macular Structure-Function Relationships of All Retinal Layers in Primary Open-Angle Glaucoma Assessed by Microperimetry and 8 × 8 Posterior Pole Analysis of OCT.

Purpose: The aim of this study is too correlate the sensitivity and thickness values of intraretinal layers at macula in healthy eyes and primary open-angle glaucoma (POAG) eyes. Methods: The thickness of different intraretinal segmentations was estimated by means of optical coherence tomography (OCT) Spectralis (Heidelberg, Engineering, Inc., Heidelberg, Germany) with the posterior pole analysis program 8 × 8 in 91 eyes from 91 patients (60 with glaucoma and 31 healthy patients). Macular sensitivity was also measured with an MP-1 microperimeter (Nidek Instruments, Inc Padova, Italy) with a customized, 36-stimulus pattern adjusted to an anatomical correspondence with the OCT grid. Correlations were calculated by using Spearman's rho and the results were represented in color maps. Results: Significant structure-function correlations were much more frequent in the glaucoma group than in control group. In general terms, associations were positive for inner retinal layers but negative correlations were also found for the inner nuclear layer and outer retinal layer in glaucoma. Conclusions: In general terms, significant structure-function correlations for different intraretinal layers are higher and wider in POAG eyes than in healthy eyes. Inner and outer retinal layers behave differently in terms of the structure-function relationship in POAG as assessed by microperimetry and OCT.

Stent graft deployment in haemodialysis fistula: patency rates in partially thrombosed aneurysm and residual thrombi.

BACKGROUND: Current evidence is insufficient to determine the contribution of stent grafts as treatment in partially thrombosed aneurysms or residual wall-adherent thrombi in arteriovenous fistulae (AVFs) for haemodialysis. The overall purpose of this study was to analyse patency rates of post-interventional covered stent deployment in those cases. We also assessed if patency rates differed when fistulas were punctured through the stent during dialysis sessions. METHODS: We conducted a retrospective study between 2006 and 2014 analysing post-intervention primary patency rates using the Kaplan-Meier log-rank test. Multivariate Cox proportional regression models were performed to determine if cannulation within the stent graft area was a potential risk factor for occlusion, by adjusted hazard ratio (HR). RESULTS: A total of 27 procedures were included in the study. Primary patency rates (%) after stent deployment at 3, 6, 12, 24, 36 and 72 months were, respectively: total 59, 32, 32, 21, 11 and 5; stent puncture 53, 21, 21, 16, 5 and 0; and no stent puncture 80, 80, 80, 40, 40 and 40. Cannulation through the stent graft was not significantly associated with increased risk of obstruction in multivariate analysis (HR = 3.01; P = 0.286). CONCLUSION: Stent graft treatment may be a feasible procedure in partially thrombosed aneurysms and residual thrombi in AVF. Although fistulas punctured through the stent presented lower patency rates, this practice was not associated with a higher risk of obstruction. Giving the impossibility of comparing with similar approaches, further studies are needed to confirm or refute the advantages of this procedure.

miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks.

Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18-22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.