0000000000006427
AUTHOR
Maria D Pinazo-duran
Effect of an oral supplementation with a formula containing R-lipoic acid in glaucoma patients
Abstract Objective To analyse the safety and effectiveness of the oral administration of a commercialised supplement containing R-alpha lipoic acid (ALA), taurine, vitamins C and E, lutein, zeaxanthin, zinc, copper and docosahexaenoic acid (DHA), in patients with primary open angle glaucoma (POAG), and in control subjects. Material and methods A prospective study of cases and controls was carried out, including 30 participants of both genders that were divided into: POAG Group (n = 15) and a control group (CG; n = 15), assigned to the oral intake of NuaDHA preparations Vision® (1 pill/day) + NuaDHA 1000 (2 pills/day) for 6 months. Participants were interviewed, ophthalmologically examined, …
New horizons for the treatment of glaucoma. I: Neuroinflammation and inflammasomes
Antioxidant supplementation in diabetic retinopathy
Conventional treatments for diabetic retinopathy (DR) include glycaemic control, laser photocoagulation, vitrectomy, intravitreal triamcinolone, and intravitreal antivascular endothelial growth factor agents. However, these strategies have not been proven capable of halting the progression of this disease in all cases. The mechanisms leading to DR are not fully understood, but there is a growing body of evidence showing that oxidative stress plays a pivotal role in the development of this diabetic complications. Indeed, it has been proposed that oxidative stress is the initial and maintaining event that triggers and provides feedback to the other pathophysiological pathways related to DR. T…
Análisis de la capa de fibras nerviosas usando el GDx en pacientes pseudofáquicos con opacificación capsular posterior
Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma
Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) and experimental tests (enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and Western blot/immunoblotting) directed to evaluate the oxidative stress, inflammation, apoptosis, and neurodegeneration processes, we gather information to build a network of data to perform a computational bioinformatics analysis. Our results sho…
Reduced retinal nerve fibre layer thickness in children with severe obesity
Summary Background Some optic nerve diseases are silent and insidious. Recently, reduced thickness of retinal nerve fibre layer (RNFL) has been associated with increasing body mass index in adults. Objectives To investigate the association of childhood obesity with RNFL measured by optical coherence tomography imaging. Methods Ninety-seven children aged 5–14 years classified according to standard deviation score of body mass index (SDS-BMI) were included. Parameters of metabolic risk, adipocytokines (leptin, adiponectin) and interleukin-6 were analyzed. All subjects underwent a comprehensive ophthalmologic examination with direct ophthalmoscopy. Evaluation of RNFL with optical coherence tom…
Los trastornos oculares del espectro alcohólico fetal
Este artículo se encuentra disponible en la siguiente URL: https://www.elsevier.es/es-revista-archivos-sociedad-espanola-oftalmologia-296-articulo-los-trastornos-oculares-del-espectro-S0365669119303508 Preprint
Oxidative stress and mitochondrial failure in the pathogenesis of glaucoma neurodegeneration
This review focuses on oxidative stress and mitochondrial failure for understanding mechanisms of optic nerve damage in primary open-angle glaucoma. The chapter shows scientific evidence for the role of mitochondrial disbalance and reactive oxygen species in glaucoma neurodegeneration. Mitochondria regulate important cellular functions including reactive oxygen species generation and apoptosis. Mitochondrial alterations result from a wide variety of damaging sources. Reactive oxygen species formed by the mitochondria can act as signaling molecules, inducing lipid peroxidation and/or excitotoxicity with the result of cell lesion and death. Antioxidants may help to counteract oxidative stress…
SLC23A2 Gene Variation, Vitamin C Levels, and Glaucoma
Abstract Primary open-angle glaucoma (POAG) is a multifactorial disease in which both genetic and environmental factors are involved. Among the environmental factors associated with POAG, nutritional factors are particularly important since nutrition is essential for maintaining good health. Researchers can study the interactions between nutrition and genes by means of nutritional genomics, but nutrigenomics studies regarding eye diseases are very scarce. This research group recently published one of the first studies on nutrigenomics in POAG. It was found that the rs1279683 polymorphism in the SLC23A2 gene, which encodes a vitamin C transporter, is associated with a higher risk of POAG. Si…
Sistemas genéticos para un nuevo abordaje del riesgo de progresión de la retinopatía diabética
Resumen Objetivo Evaluar el riesgo de progresion de la retinopatia diabetica (RD) utilizando nuevas estrategias para obtener informacion genetica en diabeticos tipo 2 (DT2) basadas en interferencia por acido ribonucleico (ARN). Material y metodos Estudio multicentrico, prospectivo de casos-controles en 132 participantes divididos en: grupo DT2 (GDT2) con RD (+RD) y sin RD (−RD) (n = 77) y grupo control (GC) (n = 55). Tras entrevista personal y examen oftalmologico, se extrajeron lagrimas para analisis molecular (expresion de micro-ARN [miARN] [miRCURY™ ARN Isolation Kit, Qiagen]). En 18 muestras (GDT2+RD = 6; GDT2–RD = 6; GC = 6) obtuvimos librerias de 137 vs. 140 pares de bases (GeneMapper…
Efficacy and safety study of an eyelid gel after repeated nocturnal application in healthy contact lens users and non-users
Purpose: To evaluate skin biocompatibility of a nighttime hydrating eyelid gel and possible ocular surface effects in contact lens users (CLU) and non-contact lens users (NCLU). The formulation is registered as a medical device as Tridocosahexaenoine-AOX® (TDHA-AOX) (a concentrated DHA triglyceride), containing also hyaluronic acid (HA). Methods: A prospective, randomized, masked clinical trial was performed with 62 participants of both sexes, aged 20–70 years, split into: (1) CLU (n = 30) and (2) NCLU (n = 32). All participants were instructed to apply a single dose of the moisturizing gel (containing TDHA-AOX and HA) nightly to the upper and inner eyelids of their right eye (RE) only, and…
Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders
Maria D Pinazo-Durán,1,* Carmen Galbis-Estrada,1,* Sheila Pons-Vázquez,1 Jorge Cantú-Dibildox,2 Carla Marco-Ramírez,1 Javier Benítez-del-Castillo21Ophthalmic Research Unit Santiago Grisolia, Department of Surgery/Ophthalmology, Faculty of Medicine, University of Valencia, Valencia, Spain; 2Department of Ophthalmology, Hospital of Jerez, Jerez de la Frontera, Spain*These authors contributed equally to this workBackground: Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and …
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. Correlati…
Oxidative stress and its downstream signaling in aging eyes
María Dolores Pinazo-Durán,1,* Roberto Gallego-Pinazo,2,* Jose Javier García-Medina,1,3,* Vicente Zanón-Moreno,1,4 Carlo Nucci,5 Rosa Dolz-Marco,2 Sebastián Martínez-Castillo,2 Carmen Galbis-Estrada,1 Carla Marco-Ramírez,1 Maria Isabel López-Gálvez,6,* David J Galarreta,6,* Manuel Díaz-Llópis4,*1Ophthalmic Research Unit "Santiago Grisolía", Valencia, Spain; 2Department of Ophthalmology, Macula Section, The University and Polytechnic Hospital La Fe, Valencia, Spain; 3Department of Ophthalmology, University Hospital Reina Sofia, Murcia, Spain; 4Faculty of Medicine, University of Valencia, Spain; 5Uni…
Does Posterior Capsule Opacification Affect the Results of Diagnostic Technologies to Evaluate the Retina and the Optic Disc?
The visual outcome obtained after cataract removal may progressively decline because of posterior capsular opacification (PCO). This condition can be treated by creating an opening in the posterior lens capsule by Nd:YAG laser capsulotomy. PCO optical imperfections cause several light reflection, refraction, and diffraction phenomena, which may interfere with the functional and structural tests performed in different ocular locations for the diagnosis and follow-up of ocular disease, like macular and optic nerve diseases. Some parameters measured by visual field examinations, scanning laser polarimetry, and optical coherence tomography (OCT) have changed after PCO removal. Imaging quality a…
Differential Effects of Dry Eye Disorders on Metabolomic Profile by 1H Nuclear Magnetic Resonance Spectroscopy
We used1H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG;n = 55) and (2) healthy subjects (CG;n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22andn = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20–30 μL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at −80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water…
Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements
We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (−DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (−A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best cor…
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 assoc…
Antioxidant Supplements and Diabetic Retinopathy
Abstract Conventional treatments for diabetic retinopathy (DR) includes glycemic control, laser photocoagulation, vitrectomy, intravitreal triamcinolone, and intravitreal anti-vascular endothelial growth factor agents. However these strategies have not proved capable of halting the progression of this disease in all cases. The mechanisms leading to DR are not fully understood, but there is a growing body of evidence showing that oxidative stress plays a pivotal role in the development of this diabetic complication. In fact it has been proposed that oxidative stress is the initial and maintaining event that triggers and provides feedback to the other pathophysiological pathways related to DR…
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 b…
Determinación de mediadores de la respuesta inmune e inflamación en lágrimas: cambios en ojo seco y glaucoma frente a población sana
Resumen Objetivo Determinar el perfil de expresion de las moleculas mediadoras de inflamacion y respuesta inmune (IRI) en lagrimas de pacientes con ojo seco (OS) y pacientes en tratamiento medico por sospecha o diagnostico de glaucoma primario de angulo abierto (GPAA) para compararlos con sujetos sanos. Metodo Estudio prospectivo observacional de cohortes de 107 participantes subdivididos en: pacientes con OS (GOS; n = 30), pacientes con sospecha o diagnostico de GPAA con tratamiento hipotensor ocular (GGPAA; n = 41) y controles sanos (GC; n = 36). Se obtuvieron muestras de lagrimas mediante capilaridad para analizarlas mediante sistema de multiinmunoanalisis basado en citometria de flujo (…
“Super p53” Mice Display Retinal Astroglial Changes
Tumour-suppressor genes, such as the p53 gene, produce proteins that inhibit cell division under adverse conditions, as in the case of DNA damage, radiation, hypoxia, or oxidative stress (OS). The p53 gene can arrest proliferation and trigger death by apoptosis subsequent to several factors. In astrocytes, p53 promotes cell-cycle arrest and is involved in oxidative stress-mediated astrocyte cell death. Increasingly, astrocytic p53 is proving fundamental in orchestrating neurodegenerative disease pathogenesis. In terms of ocular disease, p53 may play a role in hypoxia due to ischaemia and may be involved in the retinal response to oxidative stress (OS). We studied the influence of the p53 ge…
Hypotensive eyedrops: The neverending story. Should we consider more than active principles?
Cytokine expression in tears of patients with glaucoma or dry eye disease: A prospective, observational cohort study.
Background: The aim of this study was to assess the expression of cytokines/chemokines in tears from patients with non-advanced primary open-angle glaucoma and patients with non-severe dry eye disease versus healthy controls. Methods: This prospective, observational cohort study enrolled patients with confirmed or suspected non-advanced primary open-angle glaucoma who received any prostaglandin analogue monotherapy for longer than 6 months, patients with non-severe dry eye disease, and healthy controls. Expression of interleukin-1β, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, and interleukin-12; tumor necrosis factor α; vascular endothelial gro…
Glaucoma and Antioxidants: Review and Update
Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma.
miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks
Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2077-0383/10/11/2227 En esta investigación también participan: Mar Valero Vello, Silvia M. Sanz González, José E. O'Connor, David Galarreta Mira, María D. Pinazo-Durán y Vicente Zanón Moreno. Este artículo pertenece al número especial "Recent Clinical Research on Glaucoma". 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 landmark…
Identificación de nuevos genes candidatos para la retinopatía en diabéticos tipo 2. Estudio Valencia sobre Retinopatía Diabética (EVRD). Informe n.° 3
Resumen Objetivo Identificar genes implicados en los mecanismos patogenicos de la retinopatia diabetica no proliferante, como estres oxidativo, alteracion de la matriz extracelular y/o apoptosis, para valorar el riesgo de desarrollo de la misma en una poblacion de diabeticos tipo 2 (DM2). Material y metodos Estudio de casos y controles en 81 participantes del Estudio Valencia sobre Retinopatia Diabetica (EVRD), de ambos sexos y con edades comprendidas entre los 25 y 85 anos, clasificados en: 1) grupo DM2 (n = 49), con RD (+RD; n = 14) y sin RD (−RD; n = 35), y 2) grupo control (GC; n = 32). Se realizo entrevista personal, examen oftalmologico estandarizado y extraccion de sangre que se proc…
Thyroid hormone deficiency disrupts rat eye neurodevelopment
Clinical and experimental studies have highlighted the role played by thyroid hormones (TH) in neural and neuro-sensorial development. However, knowledge on TH mechanisms on the developing visual system is still incomplete. To uncover TH actions on the eyes and vision we carried out a microscopical study on the role of TH in the developing retina and optic nerve, in a rat model of controlled TH deficiency (THD). Morphometric and stereological analyses of the retina and optic nerve showed a reduction in the volume of the eye (p<0.001) and optic nerve cross-sectional area (p<0.001), and thinning of the retinal layers (p<0.001). Glial development and myelination was significantly delayed in th…
Preexisting Ocular Motor Palsy and Central Neuroaxial Block
Comparison of Foveal, Macular, and Peripapillary Intraretinal Thicknesses Between Autism Spectrum Disorder and Neurotypical Subjects
Purpose To compare thicknesses of intraretinal layers segmented by spectral-domain optical coherence tomography (SD-OCT) between autism spectrum disorder (ASD) and neurotypical (NT) individuals. Methods We performed 2 scans on 108 eyes from 54 participants (27 high-functioning ASD and 27 age- and sex-matched NT subjects): macular fast volume and peripapillary retinal nerve fiber layer (pRNFL). Macula was automatically segmented. The mean foveal and macular thickness of nine different layers and the thickness of nine pRNFL sectors were considered. Data from the right and left eyes were averaged for each participant. The results were compared between the ASD and NT groups. Associations betwee…
Severe scleral dellen as an early complication of pterygium excision with simple conjunctival closure and review of the literature
Descrevemos um paciente com "dellen" escleral agudo (SD) após excisão de pterígio com fechamento conjuntival simples. Uma revisão adicional da literatura médica sobre SD precoce após a cirurgia de pterígio também é realizada. Este caso descreve um homem de 45 anos de idade, que apresentou SD grave, sete dias após a cirurgia de pterígio com cauterização mínima de vasos episclerais e fechamento conjuntival simples. Nenhuma outra terapia adjuvante foi utilizada no intraoperatório. O paciente recusou-se à cobertura de retalho conjuntival da lesão. Portanto, o tratamento médico consistiu em pomada antibiótica, oclusão e acompanhamento diário. Após sete dias, a oclusão foi mudada para a lubrifica…
Ocular Comorbidities and the Relationship between Eye Diseases and Systemic Disorders
Patients with ocular disorders may have additional ophthalmic problems that can have an impact on both morbidity and vision. Ocular comorbidities are commonly associated with vision-related disability and decreased quality of life related to visual impairment. The majority of studies on this topic deal with cataracts, glaucoma, uveitis, and/or retinopathies. It is important to summarize the available evidence to date on the association of one or several ocular diseases and the implications these comorbidities have on prognosis and therapy. The relationship between eye disorders and systemic diseases has recently drawn special interest. The increasing prevalence of neurodegenerative disorder…
Biomarcadores de peroxidación lipídica en el humor acuoso de pacientes con glaucoma primario de ángulo abierto
Resumen Objetivo Investigamos la peroxidacion lipidica (PEROX) en el glaucoma primario de angulo abierto (GPAA) y si este mecanismo puede relacionarse con su progresion. Material y metodos Estudio prospectivo observacional, transversal, analitico no experimental de casos y grupo comparativo, con seleccion de 175 pacientes quirurgicos, distribuidos en: 1) grupo diagnosticado de GPAA (GG; n = 88) y 2) grupo comparativo de pacientes con cataratas (GC; n = 87). Se han obtenido datos demograficos, caracteristicas de los participantes y estilo de vida. Se realizo un examen oftalmologico centrado en GPAA. Se obtuvieron muestras de humor acuoso al principio de la cirugia programada, que fueron proc…
Signature of Circulating Biomarkers in Recurrent Non-Infectious Anterior Uveitis. Immunomodulatory Effects of DHA-Triglyceride. A Pilot Study
The purpose of this study was to identify circulating biomarkers of recurrent non-infectious anterior uveitis (NIAU), and to address the anti-inflammatory effects of triglyceride containing docosahexaenoic acid (DHA-TG). A prospective multicenter study was conducted in 72 participants distributed into: patients diagnosed with recurrent NIAU in the quiescence stage (uveitis group (UG)
What to eat and drink in glaucoma? Evidence from human studies
Glutathione-dependent formaldehyde dehydrogenase (ADH3) and low km mitochondrial aldehyde dehydrogenase (ALDH2). New evidence for differential expression in the rat retina in response to oxidative stress.
Epidemiological and experimental studies support the involvement of lipid peroxidation (LPO) in retinal diseases. In addition to other pathogenic mechanisms not fully understood, the possibility remains that peroxidic aldehydes, acting as cytotoxic chemicals, mediate in the progression of chronic ocular disorders.To test proper mechanisms involved in removing peroxidic aldehydes from the retina, in an attempt to understand long-lasting changes induced by LPO, the oxidative and antioxidant enzymatic activities, as well as the retinal distribution and activity of glutathione-dependent formaldehyde dehydrogenase (ADH3) and low km mitochondrial aldehyde dehydrogenase (ALDH2), were studied and c…
Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?
Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cyt…
Optical Coherence Tomography Angiography of Macula and Optic Nerve in Autism Spectrum Disorder: A Pilot Study
The aim of this study was to compare retinal thicknesses and vascular parameters between autism spectrum disorder (ASD) and neurotypical (NT) individuals. Recruited ASD subjects and age- and sex-matched NT controls underwent 2 optical coherence tomography scans (OCT) (macular cube and optic nerve cube) and 2 OCT angiography (OCTA) scans (macular and optic nerve head (ONH) OCTA) with the device Cirrus 5000 (Zeiss). Concerning OCT, we considered full retina thickness in 9 macular sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) pattern and peripapillary retinal nerve fiber layer (pRNFL) thickness in 4 quadrants and 12 clock-hour sectors. Vessel density and capillary perfusion…
Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids
Carmen Galbis-Estrada,1,* Maria D Pinazo-Dur&aacute;n,1,* Jorge Cant&uacute;-Dibildox,2 Carla Marco-Ram&iacute;rez,1 Manuel D&iacute;az-Ll&oacute;pis,1,3 Javier Ben&iacute;tez-del-Castillo21Ophthalmic Research Unit Santiago Grisolia, Department of Surgery/Ophthalmology, Faculty of Medicine, University of Valencia, Valencia, Spain; 2Department of Ophthalmology, Hospital of Jerez, Jerez de la Frontera, C&aacute;diz, Spain; 3University and Polytechnic Hospital La Fe, Valencia, Spain*These authors contributed equally to this workBackground: Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential …
Identification of new candidate genes for retinopathy in type 2 diabetics. Valencia Study on Diabetic Retinopathy (VSDR). Report number 3
Abstract Objective To identify genes involved in the pathogenic mechanisms of non-proliferative diabetic retinopathy (NPDR), among which include oxidative stress, extracellular matrix changes, and/or apoptosis, in order to evaluate the risk of developing this retinal disease in a type 2 diabetic (DM2) population. Material and methods A case–control study was carried out on 81 participants from the Valencia Study on Diabetic Retinopathy (VSDR) of both genders, with ages 25–85 years. They were classified into: (i) DM2 group (n = 49), with DR (+DR; n = 14) and without DR (−DR; n = 35), and (ii) control group (GC; n = 32). The protocols included a personal interview, standardized ophthalmologic…
Strategies to Reduce Oxidative Stress in Glaucoma Patients
Background Primary open-angle glaucoma (POAG) is a multifactorial pathology involving a variety of pathogenic mechanisms, including oxidative/nitrosative stress. This latter is the consequence of the imbalance between excessive formation and insufficient protection against reactive oxygen/nitrogen species. Objective Our main goal is to gather molecular information to better managing pathologic variants that may determine the individual susceptibility to oxidative/nitrosative stress (OS/NS) and POAG. Method An extensive search of the scientific literature was conducted using PUBMED, the Web of Science, the Cochrane Library, and other references on the topic of POAG and OS/NS from human and a…
<p>A randomized multicenter study comparing seawater washes and carmellose artificial tears eyedrops in the treatment of dry eye syndrome</p>
Purpose To investigate the safety and efficacy of sterile isotonic seawater washes vs standard treatment with carmellose artificial tears in dry eye syndrome (DES). Patients and methods This is a randomized multicenter prospective study with 12 weeks of follow-up. A group of patients with DES (N=60) were treated with seawater spray (Quinton®) five times daily, and another similar group (N=60) were treated with carmellose artificial tears eyedrops (Viscofresh® 0.5%) five times a day. The parameters studied and measured were as follows: Ocular Surface Disease Index questionnaire score, Schirmer I test (without anesthesia) score, tear osmolarity (TearLab®), tear breakup time, tear meniscus hei…
Oxidative stress in diabetic retinopathy
Diabetic retinopathy (DR) is the leading cause of acquired blindness in working adults worldwide. Biochemical changes in DR contribute to both the microscopic structural and functional changes in the retina. All these alterations result in retinal damage that can be assessed by funduscopy, optical coherence tomography (OCT), and angioOCT. Reactive oxygen species (ROS) overproduction in the mitochondria is considered a causal link between elevated glucose and biochemical abnormalities in the pathophysiology of DR. Moreover, oxidative-induced pathways also seem to provide positive feedback to ROS production, resulting in a vicious cycle. ROS can directly damage lipids, proteins, and DNA, lead…
Evaluation of intraocular pressure and other biomechanical parameters to distinguish between subclinical keratoconus and healthy corneas
(1) Purpose: To assess the main corneal response differences between normal and subclinical keratoconus (SCKC) with a Corvis® ST device. (2) Material and Methods: We selected 183 eyes of normal patients, of a mean age of 33 ± 9 years and 16 eyes of patients with SCKC of a similar mean age. We measured best corrected visual acuity (BCVA) and corneal topography with a Pentacam HD device to select the SCKC group. Biomechanical measurements were performed using the Corvis® ST device. We carried out a non-parametric analysis of the data with SPSS software (Wilcoxon signed rank-test). (3) Results: We found statistically significant differences between the control and SCKC groups in some corneal b…
Biomarkers of lipid peroxidation in the aqueous humor of primary open-angle glaucoma patients
Objective To investigate the lipid peroxidation (PEROX) processes in primary open-angle glaucoma (POAG) patients, and whether this mechanism may be related to disease progression. Material and methods A prospective, observational, cross-sectional, non-experimental, and analytical study was conducted on a case and a comparison group, consisting of 175 surgical patients divided into: (1) POAG group (GG; n = 88) and (2) comparison group of patients with cataracts (CG; n = 87). Demographic data, patient characteristics, lifestyle data, as well as ophthalmological examination were registered in an Excel spreadsheet. Biochemical data were obtained by processing the aqueous humor collected at the …
Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma
Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microg…
Lens regeneration in children.
Unilateral and irreversible optic neuropathy associated to infliximab treatment: 3-year follow-up.
Sir,We have recently read with interest the article by Clemmensen et al. [1] We presented a similar case [2] and we followed it up for more than 3 years. A 54-year-old female presented sudden-onset...
Retinal nerve fibre layer and brain grey substance as early prognostic factors for disability in multiple sclerosis.
We read with interest the article by Bock et al ,1 in which the association between retinal nerve fibre layer (RNFL) and total macular volume (TMV) was analysed by optical coherence tomography (OCT) and contrast sensitivity was measured by functional acuity contrast testing in relapsing-remitting multiple sclerosis (MS) patients. The authors found that the functional contrast vision in MS is influenced by morphological changes in the anterior visual pathway. This work emphasised that contrast sensitivity is reduced in MS, and that RNFL and TMV, as morphological measures of retinal axon loss, are predictors of contrast sensitivity. Ophthalmological examinations were the basis of the Bock et …
Coroideremia: seguimiento durante un año con polarimetría láser
espanolCaso clinico: Presentamos el seguimiento de un caso de coroideremia que fue sometido a tres campos visuales automatizados blanco-blanco y tres polarimetrias laser (PL) con GDx VCC en el transcurso de un ano. Se encontro un deterioro perimetrico en indices y escotomas. En concordancia, los parametros de retardo de la capa de fibras nerviosas de la retina y los mapas cambiaron en un analisis serial avanzado con GDx VCC en los dos ojos. Discusion: El analisis con GDx VCC puede ser un metodo objetivo y cuantitativo para evaluar la progresion de las distrofias coriorretinianas como la coroideremia. EnglishCase report: We report the follow-up of a case of choroideremia who underwent three …
Clinical and Molecular-Genetic Insights into the Role of Oxidative Stress in Diabetic Retinopathy: Antioxidant Strategies and Future Avenues
Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control study was carried out in 480 participants [287 T2DM patients with (+)/without (−) diabetic retinopathy (DR) and 193 healthy controls (CG)], randomly assigned to a daily pill of A/ω3. Periodic evaluation through 38 months allowed to outline patient characteristics, DR features, and classic/OS blood parameters. Statistics were performed by the SPSS 24.0 program. Diabetics displayed significantly h…
Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma.
There is growing interest on the correlation among oxidative stress, inflammation, apoptosis and primary open-angle glaucoma initiation and progression. Reactive oxygen species are formed in the eyes following a wide variety of stressors, and are largely implicated in glaucoma pathogenesis. Immune-inflammatory response mediators have recently become a target of ophthalmologic concern, including glaucoma. Much attention has been derived to the role of specific pro and anti-apoptotic molecules in glaucoma. This article reviews the early evidence suggesting that reactive oxygen species, immune inflammatory response mediators, and apoptogenic molecules are engaged in glaucoma disease. Moreover,…
Retinal neurodegenerative changes in the adult insulin receptor substrate-2 deficient mouse.
Abstract Insulin receptor substrate-2 (Irs2) mediates peripheral insulin action and is essential for retinal health. Previous investigations have reported severe photoreceptor degeneration and abnormal visual function in Irs2-deficient mice. However, molecular changes in the Irs2 − / − mouse retina have not been described. In this study, we examined retinal degenerative changes in neuronal and glial cells of adult (9- and 12-week old) Irs2 − / − mice by immunohistochemistry. 9-week old Irs2 − / − mice showed significant thinning of outer retinal layers, concomitant to Muller and microglial cell activation. Photoreceptor cells displayed different signs of degeneration, such as outer/inner…
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…
¿Qué comer y qué beber en el glaucoma? Evidencias a partir de estudios en humanos
Diabetic Retinopathy and Oxidative Stress
Abstract Diabetic retinopathy (DR) is the leading cause of acquired blindness in working age adults worldwide. Biochemical changes in DR contribute to both the microscopic structural and functional changes in the retina. All these alterations result in macroscopic retinal damage that can be assessed by funduscopy. The overproduction of reactive oxygen species (ROS) in the mitochondria is considered a causal link between elevated glucose and biochemical abnormalities in the pathophysiology of DR. Moreover, oxidatively induced pathways also seem to provide positive feedback to ROS production, resulting in a vicious cycle. ROS can directly damage lipids, proteins and DNA, leading to cell death…
Metabolomics of the aqueous humor in the rat glaucoma model induced by a series of intracamerular sodium hyaluronate injection
Glaucoma models are helpful to study disease characteristics and to design new therapeutic options. Metabolomic profiling approach have been used to elucidating the molecular characteristics of the aqueous humor. Juvenile male Wistar rats experimental (n = 15) and controls (n = 6) were used for these studies. Experimental rats received weekly intracamerular injection of 25 µl of sodium hyaluronate in the left eye and sterile saline solution in the right eye, consecutively for ten weeks. Rats were subjected to anterior/posterior eye segment examinations, intraocular pressure (IOP), and flash electroretinograms (ERG). The aqueous humor was collected at endpoints and analyzed by Nuclear Magnet…
Eclectic Ocular Comorbidities and Systemic Diseases with Eye Involvement: A Review.
Coexistence of several ocular diseases is more frequent than suspected. In spite of the refractive errors, one or more of the following can be detected simultaneously: glaucoma, cataracts, uveitis, age-related macular degeneration, and dry eyes. In addition, as people age, ocular comorbidities are much more usually seen. Specific diseases are openly acknowledged to affect the eyes and vision, such as diabetes mellitus, hypertension blood pressure, arthritis, hyperthyroidism, neurodegenerative disorders, hematologic malignancies, and/or systemic infections. Recent advances in early diagnosis and therapy of the ophthalmic pathologies have reinforced patient options to prevent visual impairmen…
Micro-RNA regulation of the angiogenic response in the diabetic retina
Regulación por micro RNA de la respuesta angiogénica en la retina diabética
MicroRNAs as potential biomarkers of eye diseases
Superdiluted atropine at 0.01% reduces progression in children and adolescents. A 5 year study of safety and effectiveness
Abstract Objective To confirm the clinical security and effectiveness of the daily application of 0.01% superdiluted atropine eyedrops in the progression of myopia in children. Material and methods A total of 200 children 9–12 years of age were randomized into a treated group and a control without treatment. Refraction under cycloplegia was performed. Results Myopia progression of the treated group was −0.14 ± 0.35 versus −0.65 ± 0.54 in the control group without treatment. Only 2% of patients were forced to stop treatment due to side effects. Conclusion Atropine superdiluted atropine 0.01% eyedrops is effective and well tolerated, and reduced myopia progression by 25%.
Searching for the antioxidant, anti-inflammatory, and neuroprotective potential of natural food and nutritional supplements for ocular health in the mediterranean population.
Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received muc…
Glaucoma surgery and anaesthetic techniques. On editorials, scientific reviews and citation possibilities
Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials
Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, anim…
A two-year follow-up of oral antioxidant supplementation in primary open-angle glaucoma: an open-label, randomized, controlled trial
Purpose To evaluate the effect of oral antioxidant supplementation (OAS) on primary open-angle glaucoma (POAG) over a 2-year follow-up period. Patients and methods In this open-label, randomized controlled trial, 117 eyes of 117 patients with mild or moderate POAG and intraocular pressure under control with topical antiglaucoma medications were recruited and randomly divided into three groups according to supplementation: (1) OAS with (ICAPS R® – Alcon Laboratories, n = 26); (2) OAS without ω-3 fatty acids (OFTAN MACULA® – Laboratorios Esteve, n = 28); and (3) a control group without OAS (n = 63). They all underwent visual field (VF) tests (Humphrey 24-2) and scans using a Fourier-domain op…
The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration
The chapter is a review enclosed in the volume "Glaucoma: A pancitopatia of the retina and beyond." No cure exists for glaucoma. Knowledge on the molecular and cellular alterations underlying glaucoma neurodegeneration (GL-ND) includes innovative and path-breaking research on neuroinflammation and neuroprotection. A series of events involving immune response (IR), oxidative stress and gene expression are occurring during the glaucoma course. Uveitic glaucoma (UG) is a prevalent acute/chronic complication, in the setting of chronic anterior chamber inflammation. Managing the disease requires a team approach to guarantee better results for eyes and vision. Advances in biomedicine/biotechnolog…
Implicaciones del óxido nítrico y otras moléculas con potencial redox en el glaucoma primario de ángulo abierto
espanolObjetivos: El oxido nitrico (ON) y otras moleculas con potencial red-ox estan relacionados con mecanismos de transmision de senales, incluyendo la regulacion de la permeabilidad vascular y la homeostasis. Nos proponemos investigar la presencia de ON y de especies reactivas del oxigeno (EROx) en el humor acuoso y su relacion con los mecanismos patogenicos del glaucoma primario de angulo abierto (GPAA). Metodos: Se ha analizado bioquimicamente el humor acuoso, que fue extraido al comienzo de la cirugia de segmento anterior, de dos grupos de individuos: 1) pacientes programados para trabeculectomia de Watson, por empeoramiento de los parametros de riesgo del glaucoma (GG; n=60) y 2) gru…
Efecto de la suplementación oral con una fórmula que contiene ácido R-lipoico en pacientes con glaucoma
Resumen Objetivo Analizar la seguridad y efectividad de la administracion oral de un suplemento comercializado que contiene acido alfa-R-lipoico, taurina, vitaminas C y E, luteina, zeaxantina, zinc, cobre y acido docosahexaenoico en pacientes con glaucoma primario de angulo abierto (GPAA) y sujetos control. Material y metodos Se realizo un estudio prospectivo de casos y controles que incluyo 30 participantes de ambos sexos, divididos en: pacientes con GPAA (n = 15) y sujetos sanos (GC; n = 15) asignados a tomar durante 6 meses los preparados NuaDHA Vision® (1 comp/dia) + NuaDHA 1000 (2 comps/dia). Los participantes fueron entrevistados, examinados oftalmologicamente, extrayendo sangre perif…
Glaucomatous Maculopathy: Thickness Differences on Inner and Outer Macular Layers between Ocular Hypertension and Early Primary Open-Angle Glaucoma Using 8 × 8 Posterior Pole Algorithm of SD-OCT
The purpose of this study was to compare the thickness of all inner and outer macular layers between ocular hypertension (OHT) and early primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT) 8 × 8 posterior pole algorithm (8 × 8 PPA). Fifty-seven eyes of 57 OHT individuals and fifty-seven eyes of 57 early POAG patients were included. The thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform and nuclear layer, photoreceptor layer (PRL) and retinal pigment epithelium were obtained in 64 cells for each macular layer and mean thickness of superior and inf…
Ocular Motor Palsy After Spinal Puncture
Abstract Ocular motor palsy is a rare but alarming complication of subarachnoid puncture. In order to better understand this condition, a literature search was performed in English of PubMed articles for cranial nerves III, IV, and VI palsies after spinal puncture. Sixty-five articles (dated 1930–2015) were identified, and 114 cases were obtained for analysis. Subarachnoid anesthesia was the most frequent cause (45.6%), with a higher incidence for females than males. The age of patients was 40.24 ± 13.35 years (age range, 6–71 years). The sixth cranial nerve was the most commonly involved (92.1%), with higher frequency in the right eye. Palsy onset started 7.30 ± 4.09 days after puncture. D…
Optic nerve hypoplasia and internal carotid artery hypoplasia: a new association
The Role of Autophagy in Eye Diseases
Autophagy is a catabolic process that ensures homeostasis in the cells of our organism. It plays a crucial role in protecting eye cells against oxidative damage and external stress factors. Ocular pathologies of high incidence, such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy are of multifactorial origin and are associated with genetic, environmental factors, age, and oxidative stress, among others; the latter factor is one of the most influential in ocular diseases, directly affecting the processes of autophagy activity. Alteration of the normal functioning of autophagy processes can interrupt organelle turnover, leading to the accumulation of cellula…
Determination of inmune response and inflammation mediators in tears: Changes in dry eye and glaucoma as compared to healthy controls
Objective To determine the expression profile of immune response and inflammation (IRI) mediator molecules in tears from patients with dry eye (DE), and those suspected of having or have primary open-angle glaucoma (POAG) under treatment and compare them with healthy controls. Methods A prospective observational cohort study including 107 participants sub-divided into: healthy controls (CG; n = 30), patients with DE (DEG; n = 41) and patients suspected of having or have POAG and on hypotensive treatment (POAG-G; n = 36). Tear samples were collected by capillary to be processed using a multi-immunoassay system based on flow cytometry (Luminex R-200®), in order to determine the interleukins (…
Changes in visual function and retinal structure in the progression of Alzheimer's disease
Background Alzheimer's Disease (AD) can cause degeneration in the retina and optic nerve either directly, as a result of amyloid beta deposits, or secondarily, as a result of the degradation of the visual cortex. These effects raise the possibility that tracking ophthalmologic changes in the retina can be used to assess neurodegeneration in AD. This study aimed to detect retinal changes and associated functional changes in three groups of patients consisting of AD patients with mild disease, AD patients with moderate disease and healthy controls by using non-invasive psychophysical ophthalmological tests and optical coherence tomography (OCT). Methods We included 39 patients with mild AD, 2…
Genetic systems for a new approach to risk of progression of diabetic retinopathy.
OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG-DR=6; CG=6) by performing next-generation sequ…
Tear <sup>1</sup>H Nuclear Magnetic Resonance-Based Metabolomics Application to the Molecular Diagnosis of Aqueous Tear Deficiency and Meibomian Gland Dysfunction
<b><i>Purpose:</i></b> 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. <b><i>Methods:</i></b> Participants in this prospective, case-control pilot study were split into patients with aqueous tear deficiency and MGD (DE-MGD [<i>n</i> = 15]) and healthy controls (CG; <i>n</i> = 20). Personal interviews, ocular surface disease index (OSDI), and ophthalmic examinations were performed. Reflex tears collected by capillarity were pr…