Alpha-Synuclein in Peripheral Tissues as a Possible Marker for Neurological Diseases and Other Medical Conditions.

The possible usefulness of alpha-synuclein (aSyn) determinations in peripheral tissues (blood cells, salivary gland biopsies, olfactory mucosa, digestive tract, skin) and in biological fluids, except for cerebrospinal fluid (serum, plasma, saliva, feces, urine), as a marker of several diseases, has been the subject of numerous publications. This narrative review summarizes data from studies trying to determine the role of total, oligomeric, and phosphorylated aSyn determinations as a marker of various diseases, especially PD and other alpha-synucleinopathies. In summary, the results of studies addressing the determinations of aSyn in its different forms in peripheral tissues (especially in platelets, skin, and digestive tract, but also salivary glands and olfactory mucosa), in combination with other potential biomarkers, could be a useful tool to discriminate PD from controls and from other causes of parkinsonisms, including synucleinopathies.

Diagnostic Ability and Capacity of Optical Coherence Tomography-Angiography to Detect Retinal and Vascular Changes in Patients with Fibromyalgia.

Background: To evaluate the neuroretina and retinal vasculature of fibromyalgia (FM) patients and calculate a linear discriminant function (LDF) to improve retinal parameters' contribution to FM diagnosis. Methods: Fifty FM patients and 232 healthy controls underwent retinal evaluation using swept-source optical coherence tomography (SS-OCT) angiography (Triton plus; Topcon) and spectral domain OCT (SD-OCT) (Spectralis; Heidelberg). The macular (m) and peripapillary (p) retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) were assessed, as was the macular vascular density. A logistic regression analysis was performed, and an LDF was calculated to evaluate OCT's contribution to FM diagnosis. Results: With Triton OCT, the patients presented pRNFL thinning in the temporal sector (p=0.006). Spectralis OCT measurements showed decreased pRNFL in patients in the following sectors: superonasal, p=0.001; nasal, p=0.001; inferonasal, p=0.006; temporal, p=0.001; and inferotemporal, p=0.001. No significant differences were observed in the macular vascular plexus between patients and controls. However, vascular density in the superior sector showed a strong inverse correlation with disease duration (r = -0.978, p=0.022). The LDF calculated for Spectralis OCT yielded an area under the ROC curve of 0.968. Conclusions: FM patients present RNFL thinning observable using SS- and SD-OCT. However, these patients show similar vascular density in the macular area to healthy controls. The LDF that combines several RNFL parameters obtained using Spectralis OCT gives this device a powerful ability to differentiate between healthy individuals and individuals with FM.

Objective Diagnosis of Fibromyalgia Using Neuroretinal Evaluation and Artificial Intelligence.

Background/Objective: This study aims to identify objective biomarkers of fibromyalgia (FM) by applying artificial intelligence algorithms to structural data on the neuroretina obtained using swept-source optical coherence tomography (SS-OCT). Method: The study cohort comprised 29 FM patients and 32 control subjects. The thicknesses of complete retina, 3 retinal layers [ganglion cell layer (GCL+), GCL++ (between the inner limiting membrane and the inner nuclear layer boundaries) and retinal nerve fiber layer (RNFL)] and choroid in 9 areas around the macula were obtained using SS-OCT. Discriminant capacity was evaluated using the area under the curve (AUC) and the Relief algorithm. A diagnostic aid system with an automatic classifier was implemented. Results: No significant difference (p ≥ .660) was found anywhere in the choroid. In the RNFL, a significant difference was found in the inner inferior region (p = .010). In the GCL+, GCL++ layers and complete retina, a significant difference was found in the 4 regions defining the inner ring: temporal, superior, nasal and inferior. Applying an ensemble RUSBoosted tree classifier to the features with greatest discriminant capacity achieved accuracy = .82 and AUC = .82. Conclusions: This study identifies a potential novel objective and non-invasive biomarker of FM based on retina analysis using SS-OCT.

Antecedentes/Objetivo: Identificar biomarcadores objetivos de fibromialgia (FM) aplicando inteligencia artificial a datos estructurales de retina obtenidos mediante tomografía de coherencia óptica Swept Source (TCO-SS). Método: Se evaluó una cohorte de 29 pacientes con FM y otra de 32 sujetos control, registrando los espesores de la retina completa, de varias capas de la retina [capa de células ganglionares (CCG+), CCG ampliada (CCG++, entre la membrana limitante interna y los límites de la capa nuclear interna) y capa de fibras nerviosas (CFNR)] y de la coroides, mediante TCO-SS. La capacidad discriminante se evaluó mediante el área bajo la curva ROC (AROC) y el algoritmo Relief. Se implementó un sistema de ayuda al diagnóstico con clasificador automático. Resultados: No se observó diferencia significativa (p ≥ .660) en la coroides, pero sí en el sector inferior del anillo interno de la CFNR (p = .010) y en los cuatro sectores del anillo interno en las capas CCG+, CCG++ y retina completa. Utilizando un árbol de decisión ensemble RUSBoosted como clasificador de las características con mayor capacidad discriminante, se obtuvo una predicción alta (AROC=.820). Conclusiones: Se identifica un potencial biomarcador objetivo y no invasivo para el diagnóstico de FM basado en el análisis de la neurorretina mediante TCO-SS.

Toric intraocular lens implantation vs femtosecond laser-assisted arcuate keratotomy for correction of moderate astigmatism in cataract surgery.

PURPOSE: To compare toric intraocular lens (TIOL) implantation and femtosecond laser-assisted arcuate keratotomy (FSAK) during phacoemulsification surgery in correction of moderate astigmatism. SETTING: Clinical research study. DESIGN: Prospective randomized comparison study. METHODS: Patients with age-related cataract and moderate preoperative corneal astigmatism of 1.25 to 3.0 diopters (D) were randomized into a TIOL implantation group and an FSAK group with symmetrical paired corneal arcuate keratotomies. The preoperative evaluation included corrected distance visual acuity (CDVA), corneal topography, autokeratometry, and ocular biometry. Postoperative examinations were performed at 1 month and 3 months and included CDVA and uncorrected distance visual acuity, manifest refraction, autokeratometry, and corneal topography. Vector analysis of astigmatic changes was performed using the Alpins vector method. RESULTS: This study comprised 75 eyes from 67 patients. The mean residual refractive astigmatism at 3 months was -0.63 ± 0.55 D in the TIOL group and -0.90 ± 0.53 D in the FSAK group ( P = .037) and was ≤1.00 D in 32 eyes (84%) and 25 eyes (64%), respectively. There were no statistically significant differences between the 2 groups in difference vector, angle of error, magnitude error, or correction index in the 3-month follow-up. The index of success was 0.32 ± 0.33 D in the TIOL group and 0.48 ± 0.29 D in the FSAK group ( P = .029). CONCLUSIONS: TIOL implantation showed better results in correcting moderate astigmatism. Despite this, FSAK is shown to be a safe technique for reducing astigmatism.

Association between restless legs syndrome and peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The coexistence of peripheral neuropathy (PN) and restless legs syndrome (RLS) or Willis-Ekbom disease is relatively frequent, but its prevalence has shown a high variability across studies. In addition, several reports have shown data suggesting the presence of PN in patients with idiopathic RLS. METHODS: A search was undertaken using the PubMed, Embase and Web of Science Databases, from 1966 to 6 December 2020, crossing the search term 'restless legs syndrome' with 'neuropathy', 'polyneuropathy' (PNP) and 'peripheral neuropathy', and the references of interest for this topic were identified; a meta-analysis was performed, according to PRISMA guidelines, and a calculation of pooled prevalences, where appropriate, was made using standard methods. RESULTS: Restless legs syndrome has been reported in 5.2%-53.7% of patients with PN (average 21.5%; 95% confidence interval 18.6%-24.5%), and PN has been reported in 0%-87.5% of patients with RLS (average 41.8%; 95% confidence interval 39.9%-43.6%), both being significantly more frequent than in controls. The heterogeneity across studies could be due to differences in the diagnostic criteria used for both RLS and PN. RLS is a frequent clinical complaint in patients with PN of different aetiologies, mainly diabetic PN, uraemic PNP, familial amyloid PNP, Charcot-Marie-Tooth disease and chronic dysimmune inflammatory PNP. Recent neurophysiological findings suggest the presence of small sensory fibre loss in patients diagnosed with idiopathic RLS, but it remains to be determined whether RLS associated with small sensory fibre loss and idiopathic RLS are different clinical entities. CONCLUSIONS: Future studies including clinical and neurophysiological assessment and skin biopsy involving a large series of patients with PN and RLS are needed for a better understanding of the association between these two entities.

Biological fluid levels of iron and iron-related proteins in Parkinson's disease: Review and meta-analysis.

BACKGROUND AND PURPOSE: Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD. However, the results on cerebrospinal (CSF) and serum/plasma iron levels in PD patients have been controversial. The aim of this systematic review and meta-analysis was to establish the CSF and serum/plasma levels of iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, and hepcidine) levels, and the urine levels of iron, in patients with PD. METHODS: Four databases (PubMed, EMBASE, MedLine, and Web of Science - Core Collection) were reviewed for studies published from 1966 to October 5, 2020. References of interest were identified. A meta-analysis of eligible studies was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, using the R software package meta. RESULTS: A non-significant trend towards higher CSF iron levels and marginally significantly lower serum/plasma iron levels was observed in patients with PD compared with age- and sex-matched controls. CSF and serum/plasma ferritin and transferrin concentrations, and serum/plasma lactoferrin and haptoglobin concentrations did not differ significantly between PD patients and controls. CONCLUSION: The findings of this study suggest an association between decreased serum/plasma iron levels and, possibly, higher CSF iron levels with risk of PD.

Correlation and regression analysis between residual gradation and uncorrected visual acuity one year after refractive surgery with LASIK, FS-LASIK, PRK, PRK Xtra techniques and the implantation of ICL® posterior chamber phakic lens in myopic correction.

PURPOSE: To analyze the influence of the final spherical equivalent (SE) in LogMAR uncorrected distance visual acuity (UDVA) one year after refractive surgery. We analysed refractive results, their predictability and efficacy, and the safety results of the different methods as secondary outcomes. SETTING: Refractive Surgery Unit of the Institut Català de Retina (ICR) in Barcelona, Spain. DESIGN: Retrospective, analytical observational study. METHODS: Retrospective and observational study of 654 eyes of 327 patients who underwent refractive surgery to treat their myopia or myopic astigmatism using LASIK, FS-LASIK, PRK, PRK Xtra or ICL-type lens implantation surgery were included. RESULTS: The correlation between the SE in absolute value was statistically significant in all techniques utilized, reaching higher values in the FS-LASIK and LASIK techniques, 0.774 and 0.706 respectively, and lesser values in PRK (0.480) and PRK Xtra (0.482). A significant adjustment via a univariate linear regression model could be implemented in all techniques, albeit the R2 coefficient of determination values were higher than those for the FS-LASIK (0.599) and LASIK (0.494) techniques. CONCLUSIONS: There is a positive correlation between post-surgical SE value and post-operative LogMAR UDVA. These regression models can be adjusted to predict the final UDVA according to the final SE. The techniques that are most influenced by the final SE in terms of their visual results are FS-LASIK and LASIK.

Reproducibility of retinal and choroidal measurements using swept-source optical coherence tomography in patients with Parkinson's disease / Reprodutibilidade das medições da retina e da coroideia utilizando a tomografia de coerência ótica Swept-Source em pacientes com a doença de Parkinson

ABSTRACT Purpose: To assess the reproducibility of retinal and choroidal measurements in the macular and peripapillary areas using swept-source optical coherence tomography in patients with Parkinson's disease. Methods: A total of 63 eyes of 63 patients with idiopathic Parkinson's disease were evaluated using a three-dimensional protocol of swept-source optical coherence tomography. The following layers were analyzed: full retinal thickness, retinal nerve fiber layer, ganglion cell layer, and choroid. The coefficient of variation was calculated for every measurement. Results: In the macular area, the mean coefficients of variation of retinal thickness, ganglion cell layer + thickness, and choroidal thickness were 0.40%, 0.84%, and 2.09%, respectively. Regarding the peripapillary area, the mean coefficient of variation of the retinal nerve fiber layer thickness was 2.78. The inferior quadrant showed the highest reproducibility (coefficient of variation= 1.62%), whereas the superonasal sector showed the lowest reproducibility (coefficient of variation= 8.76%). Conclusions: Swept-source optical coherence tomography provides highly reproducible measurements of retinal and choroidal thickness in both the macular and peripapillary areas. The reproducibility is higher in measurements of retinal thickness versus choroidal thickness.

RESUMO Objetivo: Avaliar a reprodutibilidade das medições da retina e da coroide nas áreas macular e peripapilar utilizando a tomografia de coerência ótica com fonte de varredura pacientes com doença de Parkinson. Métodos: Um total de 63 olhos de 63 pacientes com doença de Parkinson idiopática foram avaliados usando um protocolo 3D de tomografia de coerência ótica de fonte Triton Swept. Foram analisadas as seguintes camadas: espessura retiniana total, camada de fibras nervosas da retina, camada de células ganglionares e coróide. O coeficiente de variação foi calculado para cada medição. Resultados: Na área macular, os coeficientes médios de variação da espessura da retina, da camada de células ganglionares + espessura e da espessura da coróide foram de 0,40%, 0,84% e 2,09%, respectivamente. Em relação à área peripapilar, o coeficiente médio de variação da espessura da camada de fibras nervosas da retina foi de 2,78%. O quadrante inferior apresentou a maior reprodutibilidade (coeficiente de variação= 1,62%), enquanto o setor superonasal apresentou a menor reprodutibilidade (coeficiente de variação= 8,76%). Conclusões: A tomografia de coerência ótica de fonte Triton Swept fornece medições altamente reprodutíveis da espessura da retina e da coroide nas áreas macular e peripapilar. A reprodutibilidade é maior nas medidas da espessura da retina versus a espessura da coróide.

An Update on the Neurochemistry of Essential Tremor.

BACKGROUND: The pathophysiology and neurochemical mechanisms of essential tremor (ET) are not fully understood, because only a few post-mortem studies have been reported, and there is a lack of good experimental model for this disease. OBJECTIVE: The main aim of this review is to update data regarding the neurochemical features of ET. Alterations of certain catecholamine systems, the dopaminergic, serotonergic, GABAergic, noradrenergic, and adrenergic systems have been described, and are the object of this revision. METHODS: For this purpose, we performed a literature review on alterations of the neurotransmitter or neuromodulator systems (catecholamines, gammaaminobutyric acid or GABA, excitatory amino acids, adenosine, T-type calcium channels) in ET patients (both post-mortem or in vivo) or in experimental models resembling ET. RESULTS AND CONCLUSION: The most consistent data regarding neurochemistry of ET are related with the GABAergic and glutamatergic systems, with a lesser contribution of adenosine and dopaminergic and adrenergic systems, while there is not enough evidence of a definite role of other neurotransmitter systems in ET. The improvement of harmaline-induced tremor in rodent models achieved with T-type calcium channel antagonists, cannabinoid 1 receptor, sphingosine-1-phosphate receptor agonists, and gap-junction blockers, suggests a potential role of these structures in the pathogenesis of ET.

The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer.

BACKGROUND: Testicular cancer (TCa) is a malignant tumor with highest incidence and mortality rates in Chile. The genes coding for cytochrome P450, glutathione-S-transferases (GSTs), and UDP glucuronyl transferases (UGT) participate in the biotransformation and detoxification of xenobiotics. Mutations in these genes have been associated with a high incidence of various types of cancer and an increased risk of presenting adverse reactions to drugs. OBJECTIVE: The aim of this study was to relate the presence of genetic polymorphisms in cytochrome P450 1A1 (CYP1A1), CYP3A4, GSTM1, GSTP1, GSTT1, and UGT1A1 genes and nongenetic factors with the risk of developing TCa. METHODS: A total of 276 volunteers from the Chilean general population and 251 Chilean TCa patients were recruited for the study. Genotypic analyses were performed using qPCR and PCR-RFLP. RESULTS: Variant alleles found to increase the risk of developing TCa were CYP1A1*2C (rs1048943), GSTP1 (rs1695), and GSTT1null, especially when in conjunction with a cancer family history and/or a smoking habit. The results of the multivariate analysis showed that the presence of variant alleles of GSTP1 (rs1695) together with a smoking habit and a family history of cancer accounted for a 15.9% risk of developing TCa in the Chilean population. CYP1A1*2C, GSTM1null, GSTT1null, and GSTP1 (rs1695) are statistically related to the risk of appearance of TCa, alone or associated with nongenetic factors. CONCLUSION: Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population.

Neurochemical features of idiopathic restless legs syndrome.

The most important traditional hypotheses of the pathogenesis of idiopathic restless legs syndrome (iRLS) involve dopaminergic dysfunction and iron deficiency. However, a possible role of other neurotransmitter or neuromodulators, mainly glutamate, gamma-hydroxybutyric acid (GABA), and adenosine have been suggested in recent reports. Moreover, iron deficiency in experimental models (which causes sensorimotor symptoms resembling those of RLS) is able to induce changes in dopaminergic, glutamatergic and adenosinergic neurotransmission, thus suggesting its crucial role in the pathogenesis of this disease. Relationship between iRLS and opiates, oxidative stress and nitric oxide, and with vitamin D deficiency has also been reported, although data regarding these variables should be considered as preliminary. In this review, we focus on studies relating to neurochemical findings in iRLS.

Association Study Among Candidate Genetic Polymorphisms and Chemotherapy-Related Severe Toxicity in Testicular Cancer Patients.

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan ®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p < 0.2) and clinical conditions in relation to severe (III-IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III-IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p < 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III-IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p < 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy.

Early Changes in Visual Quality and Corneal Structure after DMEK: Does DMEK Approach Optical Quality of a Healthy Cornea?

PURPOSE: To evaluate early changes in visual function and visual quality parameters after Descemet membrane endothelial keratoplasty (DMEK) and to compare the outcomes with healthy controls. METHODS: Thirteen patients who underwent DMEK and 14 controls were evaluated. All subjects underwent visual function evaluation, including visual acuity under photopic and mesopic lighting conditions and contrast sensitivity (CSV) tests CSV 1000 and Pelli-Robson. Corneal parameters were assessed with Oculus Pentacam. Corneal mean keratometry (Km), corneal densitometry values, and low and high order aberrations (LOA and HOA) were recorded. In DMEK patients, all tests were performed before surgery and 1 and 6 months after surgery. RESULTS: In patients who underwent DMEK, photopic visual acuity improved from 0.59 to 0.31 at 1 month (p=0.013) and 0.13 at 6 months (p=0.008); mesopic visual acuity and all contrast sensitivity values (both CSV and Pelli-Robson test) improved significantly in the first month (p < 0.005). A significant decrease was observed in corneal density in the 0-2 mm ring (from 43.83 to 35.60, p=0.043) and mean posterior Km (from -5.84 to -6.80, p=0.005) in the first month. Corneal HOAs and all corneal densities improved at 6 months after DMEK (p < 0.05). All visual function parameters and corneal aberrations remained lower and higher, respectively, compared with healthy controls (p < 0.05). Corneal densities were comparable with controls at 6 months after DMEK (p > 0.05). CONCLUSIONS: Patients undergoing DMEK present visual function improvement and a decrease in corneal density at 1 month after surgery. Decrease in corneal posterior HOAs can be observed at 6 months. However, visual function outcomes and corneal aberrations remained worse compared with healthy controls.

Asthma and allergic rhinitis associate with the rs2229542 variant that induces a p.Lys90Glu mutation and compromises AKR1B1 protein levels.

Asthma and rhinitis are two of the main clinical manifestations of allergy, in which increased reactive oxygen or electrophilic species can play a pathogenic role. Aldose reductase (AKR1B1) is involved in aldehyde detoxification and redox balance. Recent evidence from animal models points to a role of AKR1B1 in asthma and rhinitis, but its involvement in human allergy has not been addressed. Here, the putative association of allergic rhinitis and asthma with AKR1B1 variants has been explored by analysis of single-strand variants on the AKR1B1 gene sequence in 526 healthy subjects and 515 patients with allergic rhinitis, 366 of whom also had asthma. We found that the rs2229542 variant, introducing the p.Lys90Glu mutation, was significantly more frequent in allergic patients than in healthy subjects. Additionally, in cells transfected with expression vectors carrying the wild-type or the p.Lys90Glu variant of AKR1B1, the mutant consistently attained lower protein levels than the wild-type and showed a compromised thermal stability. Taken together, our results show that the rs2229542 variant associates with asthma and rhinitis, and hampers AKR1B1 protein levels and stability. This unveils a connection between the genetic variability of aldose reductase and allergic processes.

Influence of cardiovascular condition on retinal and retinal nerve fiber layer measurements.

OBJECTIVE: To assess changes in the retinal nerve fiber layer (RNFL) and macula in subjects with cardiovascular risk factors or subclinical ischemia. DESIGN: Prospective and observational study. METHODS: A total of 152 healthy men underwent cardiovascular examination, including quantification of subclinical atheroma plaques by artery ultrasound scans, blood analysis, and a complete ophthalmic evaluation, including spectral-domain optical coherence tomography. The variables registered in cardiovascular examination were quantification of classic major risk factors, subclinical atheroma plaques by artery ultrasound scans, and analytical records. The ophthalmic evaluation registered RNFL and macular thickness. RESULTS: Mean subject age was 51.27±3.71 years. The 40 subjects without classic cardiovascular risk factors did not show differences in RNFL and macular thicknesses compared with the 112 subjects with at least one risk factor (except in sector 9 that showed higher thicknesses in subjects with ≥1 risk factor). Comparison between the group of subjects with and without atheroma plaques revealed no differences in RNFL and macular thicknesses. The sub-analysis of subjects with subclinical atheroma plaques in the common carotid artery revealed a significant reduction in central macular thickness in the left eye compared with the right eye (p = 0.016), RNFL in the superior quadrant (p = 0.007), and the 11 o'clock sector (p = 0.020). Comparison between smokers and nonsmokers revealed that smokers had significant thinning of the central macular thickness (p = 0.034), the nasal RNFL quadrant (p = 0.006), and the 3 and 5 o'clock sectors (p = 0.016 and 0.009). CONCLUSIONS: Classic cardiovascular risk factors do not cause RNFL or macular thickness reduction, but tobacco smoking habit reduces nasal RNFL thickness. Subclinical atherosclerosis in the common carotid artery associates a reduction in central macular and nasal RNFL quadrant thicknesses in the left eye compared with the right eye.

Study of association between pre-senile cataracts and rs11615 of ERCC1, rs13181 of ERCC2, and rs25487 of XRCC1 polymorphisms in a Spanish population.

BACKGROUND: The purpose of this study was to attempt to determine if the presence of certain polymorphisms in the DNA repair genes (ERCC1, ERCC2, and XRCC1) is associated with pre-senile cataract development. MATERIALS AND METHODS: We performed a retrospective study over three groups of patients. The first group with pre-senile cataract was formed by 72 patients younger than 55 years with cataract surgery. The second group with senile cataract was formed by 101 patients older than 55 years with cataract surgery. And the third group, without cataract, was formed by 42 subjects older than 55 years without lens opacities. We analyzed the presence of SNP rs11615 from ERCC1, rs13181 from ERCC2, and rs25487 from XRCC1 and the relationship between risk factors such as smoking, alcohol intake, hypertension, and diabetes. RESULTS: The comparison of the genotype distribution in ERCC1 and ERCC2 did not show any statistically significant association in any of our analyses (p > 0.05). The comparison of the genotype distribution in XRCC1 within the different groups did not show any statistically significant associations (p > 0.05), except for the comparison between the pre-senile cataract group and the group without cataract, where an increased risk of developing pre-senile cataract for the genotype Gln/Gln (p = 0.029; OR = 1.02-40.67) in recessive inheritance models was observed when adjusting for risk factors. CONCLUSIONS: Allelic variants in ERCC1 and ERCC2 are not associated with an increased risk of developing pre-senile cataract. The presence of Gln/Gln in XRCC1 in the pre-senile cataract group with regard to the group without cataract is associated with a major risk of developing pre-senile cataract.

Pharmacogenomics of Prostaglandin and Leukotriene Receptors.

Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning.

OBJECTIVE: To investigate whether fibromyalgia induces axonal damage in the optic nerve that can be detected using optical coherence tomography (OCT), as the retinal nerve fiber layer (RNFL) is atrophied in patients with fibromyalgia compared with controls. METHODS: Fibromyalgia patients (n = 116) and age-matched healthy controls (n = 144) were included in this observational and prospective cohort study. All subjects underwent visual acuity measurement and structural analysis of the RNFL using two OCT devices (Cirrus and Spectralis). Fibromyalgia patients were evaluated according to Giesecke's fibromyalgia subgroups, the Fibromyalgia Impact Questionnaire (FIQ), and the European Quality of Life-5 Dimensions (EQ5D) scale. We compared the differences between fibromyalgia patients and controls, and analyzed the correlations between OCT measurements, disease duration, fibromyalgia subgroups, severity, and quality of life. The impact on quality of life in fibromyalgia subgroups and in patients with different disease severity was also analyzed. RESULTS: A significant decrease in the RNFL was detected in fibromyalgia patients compared with controls using the two OCT devices: Cirrus OCT ganglion cell layer analysis registered a significant decrease in the minimum thickness of the inner plexiform layer (74.99±16.63 vs 79.36±3.38 µm, respectively; p = 0.023), nasal inferior, temporal inferior and temporal superior sectors (p = 0.040; 0.011 and 0.046 respectively). The Glaucoma application of the Spectralis OCT revealed thinning in the nasal, temporal inferior and temporal superior sectors (p = 0.009, 0.006, and 0.002 respectively) of fibromyalgia patients and the Axonal application in all sectors, except the nasal superior and temporal sectors. The odds ratio (OR) to estimate the size effect of FM in RNFL thickness was 1.39. RNFL atrophy was detected in patients with FIQ scores <60 (patients in early disease stages) compared with controls in the temporal inferior sector (78.74±17.75 vs 81.65±3.61; p = 0.020) and the temporal superior sector (78.20±14.50 vs 80.74±3.88; p = 0.039) with Cirrus OCT; in the temporal inferior sector (145.85±24.32 vs 150.18±19.71; p = 0.012) and temporal superior sector (131.54±20.53 vs 138.13±16.67; p = 0.002) with the Glaucoma application of the Spectralis OCT; and in all sectors, except the average, nasal superior, and temporal sectors, and parameters with the Axonal application of the Spectralis OCT. Temporal inferior RNFL thickness was significantly reduced in patients with severe fibromyalgia (FIQ≥60) compared with patients with mild fibromyalgia (FIQ<60; 145.85±24.32 vs 138.99±18.09 µm, respectively; 145.43±13.21 vs 139.85±13.09 µm, p = 0.032 with the Glaucoma application and p = 0.021 with the Axonal application). The subgroup with biologic fibromyalgia exhibited significant thinning in the temporal inferior and superior sectors (115.17±20.82 µm and 117.05±24.19 µm, respectively) compared with the depressive (130.83±22.97 µm and 127.71±26.10 µm, respectively) and atypical (128.60±26.54 µm and 125.55±23.65 µm, respectively) subgroups (p = 0.005 and 0.001 respectively). CONCLUSIONS: Fibromyalgia causes subclinical axonal damage in the RNFL that can be detected using innocuous and non-invasive OCT, even in the early disease stages. The impact on the RNFL in the temporal sectors is greater in patients with biologic fibromyalgia, suggesting the presence of neurodegenerative processes in this subgroup of patients with fibromyalgia.

Study of Association between Pre-Senile Cataracts and the Polymorphisms rs2228000 in XPC and rs1042522 in p53 in Spanish Population.

PURPOSE: To determine if the presence of certain polymorphisms in the DNA repair gene XPC and the apoptosis inductor gene p53 is associated with pre-senile cataract development. METHODS: We have performed a retrospective study over three groups of patients. The group with pre-senile cataract formed by 72 patients younger than 55 with cataract surgery. The group with senile cataract formed by 101 patients older than 55 with cataract surgery. The group without cataract was formed by 42 subjects older than 55 without lens opacities. We analyzed the presence of SNP rs2228000 from XPC and rs1042522 from p53; and the relationship between risk factors such as smoking, alcohol intake, hypertension or diabetes. RESULTS: The comparison of the genotype distribution in XPC, within the different groups, did not show any statistically significant association in any of our analysis (p>0,05). The comparison of the genotype distribution in p53 within the different groups did not show any statistically significant association (p>0,05); except for the comparison between the pre-senile cataract group and the group with senile cataract where the genotype Pro/Pro (C/C) in the recessive inheritance model showed a higher risk for developing pre-senile cataract (p = 0,031; OR = 1.04-15.97). This association decreased when we performed the analysis adjusting by the studied risk factors (p = 0.056). CONCLUSIONS: Allelic variants in the gene XPC are not associated with an increased risk for developing pre-senile cataract. The presence of the genotype Pro/Pro in p53 might be associated with a major risk for developing pre-senile cataract.