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Intestinal dysbiosis (changes in the gut commensal microbiome) is related to several ophthalmic diseases. The aim of this study was to verify whether oral specific probiotics can alter the clinical course of chalaziosis and its recurrence. A prospective comparative pilot study involving 26 children suffering from chalaziosis was conducted. Children were randomly divided into two groups. The first group received medical treatment (lid hygiene, warm compression and dexamethasone/tobramycin ointment for at least 20 days), and the second group received medical treatment plus a daily supplementation of oral probiotics (≥ 1 × 10^9 live cells of Streptococcus thermophilus ST10 (DSM 25246), ≥ 1 × 10^9 live cells of Lactococcus lactis LCC02 (DSM 29536) and ≥ 1 × 10^9 live cells of Lactobacillus delbrueckii subsp. bulgaricus (DSM 16606) with maltodextrin as the bulking agent (Probiotical S.p.A., Novara, Italy). All patients were evaluated at 2-week intervals for 3 months. If the lesion had not disappeared or decreased in size to 1 mm or less in diameter at the time of subsequent visits, the same procedure was repeated for another 3-month cycle. There was a significant difference in the time taken for complete resolution of the chalazion between the two groups in favour of the children receiving the probiotics. The treatment was not associated with any significant complications in either group. Trial registration: The trial was registered at clinical trials.gov under NCT04322500 on 25/03/2020 ("retrospectively registered").Conclusions: Modification of the intestinal microbiome with specific probiotics can alter the clinical course of chalaziosis in children by re-establishing intestinal and immune homeostasis. Probiotic supplementation can increase the effectiveness of traditional therapies by prompting the complete resolution of chalaziosis in a shorter amount of time, in an easy and feasible way. What is Known: ⢠The intestinal microbiome plays a crucial role in several inflammatory diseases of the eye and is considered a therapeutic target. ⢠Probiotics play a role in the prevention and treatment of different conditions in children. What is New: ⢠In children probiotic supplementation is safe and effective. ⢠Probiotic supplementation reduced the time required for complete resolution of the chalazion.
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Microbioma Gastrointestinal , Probióticos , Niño , Humanos , Italia , Proyectos Piloto , Probióticos/uso terapéutico , Estudios ProspectivosRESUMEN
BACKGROUND: Recently, many studies have investigated the role of migration on mental health. Nonetheless, only few focused on the consequences of childhood trauma, hopelessness, and resilience on migrants' psychopathology, including psychiatric disorders and symptoms. METHOD: 119 migrants were recruited between May 2017 and April 2018, among those applying for assessment to the Mental Health Operational Unit of the National Institute for Health, Migration and Poverty (NIHMP) in Rome, Italy. Assessment included the following: Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), Connor-Davidson Resilience Scale (CD-RISC), Childhood Trauma Questionnaire (CTQ), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Hopelessness Scale (BHS), Beck's Suicide Intent Scale (SIS), Brief Aggression Questionnaire (BAQ), Deliberate Self-Harm Inventory (DSHI). RESULTS: 53.39% of migrants scored above the PCL-5 cut-off score (mean score was 39.45). SDS scores below the cutoff suggested the presence of depression in 42.37%, while According to SAS scores anxiety levels were low in 38.98% of migrants. During childhood, physical abuse and neglect were reported respectively by 56.78 and 69.49% of migrants. CONCLUSION: We found that Post Traumatic Stress Disorders play the role of mediators for the relation between the childhood traumatic experiences and aggressiveness, anxious and depressive symptomatology, while hopelessness is a mediator between the childhood traumatic experiences and the development of depression in adulthood. Hopelessness seems to influence the strength of the relation between childhood traumatic experiences and the individual's current intensity of suicidal attitudes, plans, and behaviors. Further developments and future perspectives of the research project are to address key gaps in the field of resilience by means of a longitudinal evaluation study in migrants, including a native population control group, acceding to NIHMP.
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Psicopatología , Migrantes , Adulto , Ansiedad , Niño , Humanos , Italia , AutoimagenRESUMEN
PURPOSE: To assess the ocular hypotensive effect of 15-keto fluprostenol, the oxidized metabolite of travoprost, on glaucoma patients, through a randomized double-masked placebo-controlled study. METHODS: Twelve patients with ocular normal tension glaucoma (NTG) (intraocular pressure [IOP] < 22 mmHg) were enrolled. In order to ensure patient compliance to treatment, all study subjects were hospitalized. In each patient, the eye to be submitted to the treatments was randomly chosen. After hospital admission (day 1), those patients received for 5 days at 8 P.M. either one drop of 15-keto fluprostenol (35 µg/ml) or one drop of placebo. IOP evaluation was performed within 8 A.M. and 8 P.M. for 6 days. Furthermore, we performed a determination of cardiovascular parameters before and after the treatments. RESULTS: Starting with the first IOP measurement after the first treatment (8 A.M. on day 2), IOP was reduced of about 14% in the eyes treated 15-keto fluprostenol, in comparison with baseline IOP values of 15-keto fluprostenol-treated patients. The IOP reduction in the 15-keto fluprostenol-treated group was significantly compared to placebo group (p < 0.05) starting from day 3 till day 6 of the study. Except for mild hyperemia in one 15-keto fluprostenol-treated eye, no other side effects were observed or reported by the enrolled patients. CONCLUSIONS: The travoprost metabolite 15-keto fluprostenol was effective in decrease IOP and maintained IOP reduction along 5 days of treatment. The 15-keto fluprostenol can be developed as a good candidate for once-a-day NTG patients' treatment.
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Glaucoma/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Prostaglandinas F Sintéticas/administración & dosificación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Glaucoma/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas/administración & dosificación , Proyectos Piloto , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study has been to evaluate the protective effect of a topical antioxidant formulation containing riboflavin, d-α-tocopheryl polyethylene glycol (TPGS vitamin E), proline, glycine, lysine, and leucine against UV-B-induced damage in in vivo rabbit retina. METHODS: Twenty male albino rabbits were used. Animals were divided into four groups of five animals each. Control group did not receive any UV irradiation. The first group (IG) was irradiated with a UV-A lamp for 30 min; the second (IG30) and the third (IG60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with 1 drop (approximately 50 µl) of the antioxidant formulation, every 15 min, starting 1 h before irradiation, until the end of the UC exposure. RESULTS: The retina of IG group showed extensive destruction of the retinal pigment epithelium (RPE) and of the cones and rods layer. The retina of G30 group showed a lesser destruction of both RPE and cones and rods layer. In the G60 group, retina showed an irregular thickening of the RPE, with massive edema of the inner and outer layer immediately adjacent together with a significant reduction of the photoreceptor number. CONCLUSION: Our results demonstrate that a topical application of eye drops containing riboflavin, d-α-tocopheryl polyethylene glycol (TPGS vitamin E), proline, glycine, lysine, and leucine counteracts UV retinal injury in exposed retina rabbits.
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Antioxidantes/administración & dosificación , Retina/efectos de los fármacos , Enfermedades de la Retina/prevención & control , Rayos Ultravioleta/efectos adversos , Animales , Modelos Animales de Enfermedad , Masculino , Soluciones Oftálmicas , Conejos , Retina/diagnóstico por imagen , Retina/efectos de la radiación , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de la radiaciónRESUMEN
Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on the involvement of APN and its receptors in the etiology of different types of cancer.
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Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Neoplasias/metabolismo , Adiponectina/química , Animales , Humanos , Inflamación/metabolismo , Modelos Biológicos , Transducción de SeñalRESUMEN
Mutations in the KCNQ2 gene, encoding for voltage-gated Kv7.2K(+) channel subunits, are responsible for early-onset epileptic diseases with widely-diverging phenotypic presentation, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy. In the present study, Kv7.2 BFNS-causing mutations (W344R, L351F, L351V, Y362C, and R553Q) have been investigated for their ability to interfere with calmodulin (CaM) binding and CaM-induced channel regulation. To this aim, semi-quantitative (Far-Western blotting) and quantitative (Surface Plasmon Resonance and dansylated CaM fluorescence) biochemical assays have been performed to investigate the interaction of CaM with wild-type or mutant Kv7.2 C-terminal fragments encompassing the CaM-binding domain; in parallel, mutation-induced changes in CaM-dependent Kv7.2 or Kv7.2/Kv7.3 current regulation were investigated by patch-clamp recordings in Chinese Hamster Ovary (CHO) cells co-expressing Kv7.2 or Kv7.2/Kv7.3 channels and CaM or CaM1234 (a CaM isoform unable to bind Ca(2+)). The results obtained suggest that each BFNS-causing mutation prompts specific biochemical and/or functional consequences; these range from slight alterations in CaM affinity which did not translate into functional changes (L351V), to a significant reduction in the affinity and functional modulation by CaM (L351F, Y362C or R553Q), to a complete functional loss without significant alteration in CaM affinity (W344R). CaM overexpression increased Kv7.2 and Kv7.2/Kv7.3 current levels, and partially (R553Q) or fully (L351F) restored normal channel function, providing a rationale pathogenetic mechanism for mutation-induced channel dysfunction in BFNS, and highlighting the potentiation of CaM-dependent Kv7.2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies.
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We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15-20 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression.
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Metilación de ADN , Reparación del ADN por Recombinación , Transcripción Genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas de Ciclo Celular/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Roturas del ADN de Doble Cadena , ADN Metiltransferasa 3A , Proteínas Fluorescentes Verdes/genética , Células HeLa , Humanos , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína LigasasRESUMEN
Bcl-2 plays a prominent role in regulating the function of mitochondria during respiration and in determining the threshold of apoptotic sensitivity. Despite its relevance, the mechanism through which these processes are achieved is still unknown. Using surface plasmon resonance technology to monitor Bcl-2 multimerisation we discovered that a simple dimeric model does not fit with experimental data. A molecular model of the experimentally observed Bcl-2 homomeric complex has been developed. Accordingly, using a panel of mutants we identified in the loop a critical region for the process of Bcl-2 multimerisation. Our results indicate that the Bcl-2 loop posttranscriptional changes can modulate its ability to make homo and hetero-complexes, ultimately leading to functional modulation, suggesting an intriguing relationship between the ability of Bcl-2 to form multimeric complexes and its multi-functional role as a membrane channel. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
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Proteínas Proto-Oncogénicas c-bcl-2/química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Humanos , Immunoblotting , Cinética , Modelos Moleculares , Unión Proteica , Multimerización de Proteína , Relación Estructura-Actividad , Resonancia por Plasmón de SuperficieRESUMEN
AIM: To define the possible beneficial impact of probiotics oral supplementation on patients affected by chalazion. METHODS: Prospective comparative pilot study on 20 adults suffering from chalazion randomly divided into two groups. The first group (n=10) received conservative treatment with lid hygiene, warm compression, and dexamethasone/tobramycin ointment for at least 20d. The second group (n=10), in addition to the conservative treatment, received a mixture of probiotic microorganisms of Streptococcus thermophilus ST10 (DSM 25246), Lactococcus lactis LLC02 (DSM 29536) and Lactobacillus delbrueckii (DSM 16606) once a day up to 3mo. Chalazia were classified according to their size into three groups: small (<2 mm), medium (≥2 to <4 mm), or large (≥4 mm). When conservative treatment with and without probiotics supplementation failed to resolve the lesion, invasive methods were used, intralesional steroid injection in medium size chalazion and surgical incision and curettage for the largest ones. RESULTS: Medical treatment with or without probiotics supplementation was effective only on the small size chalazia. There was a significant difference in the time taken for complete resolution of small size chalazia between the two groups in favor of the patients receiving probiotics (38.50±9.04d vs 21.00±7.00d, P=0.039). Medium and large size chalazia did not respond to medical treatment with or without probiotics supplementation over the follow-up period (3mo). The treatment did not induce any complications in both groups and no recurrence of chalaziosis was recorded in both groups. CONCLUSION: The considerable difference in time taken for complete resolution of small chalazia between the two groups in favor of the experimental one confirms the presence of a gut-eye axis.
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The microbiota is a dynamic ecosystem that plays a major role in the host health. Numerous studies have reported that alterations in the intestinal microbiota (dysbiosis) may contribute to the pathogenesis of various common diseases such as diabetes, neuropsychiatric diseases, and cancer. However, emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor influencing the onset and progression of multiple ocular diseases, including uveitis, dry eye, macular degeneration, and glaucoma. Currently, supplementation with pre- and probiotics appears is the most feasible and cost-effective approach to restore the gut microbiota to a eubiotic state and prevent eye pathologies. In this review, we discuss the current knowledge on how gut microbiota may be linked to the pathogenesis of common eye diseases, providing therapeutic perspectives for future translational investigations within this promising research field.
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Oftalmopatías , Microbioma Gastrointestinal , Microbiota , Probióticos , Disbiosis , HumanosRESUMEN
Keratitis is a severe condition characterized by inflammation of the cornea following a local trauma. The most common ocular disease is the bacterial one, which requires an antibiotic treatment. The major limitation of this therapy is the resistance of the antibiotic. For this reason, alternative procedures have been developed and consist of antimicrobial molecules. One of the most used is the chlorhexidine gluconate, which has shown activity versus Gram-positive and Gram-negative bacteria and fungi. In addition to its efficiency, chlorhexidine shows low toxicity levels for mammalian cells and is a low-cost molecule. Despite its multiple benefits, chlorhexidine, if used at concentrations higher than 0.02% (w/w), can cause local eye irritation. Additionally, its poor penetrability through the cornea makes necessary frequent instillation of eye drops for a prolonged time. Due to these limitations, alternative drug delivery strategies are required. Here, we report a novel formulation based on the combination of d-alpha-tocopherol polyethylene glycol 1000 succinate with chlorhexidine, which results in higher accumulation of the drug in human corneas measured by liquid chromatography and strong antimicrobial activity. Moreover, this formulation does not cause any toxic effect on human cells and is well tolerated by rabbit eyes. Therefore this novel formulation represents a good candidate for the treatment of keratitis that overcomes the risk of antibiotic resistance.
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Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 µM), with or without homotaurine (100 µM) and vitamin D3 (50 nM). Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37°C for 20 h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant. Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.008, (curcumin 0.5 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0004, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.02, (curcumin 1 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.025, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.009; IL2: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0023, and (curcumin 0.5 µM vs. curcumin 0.5 µM+ homotaurine 100 µM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.006, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment. Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future. Clinical Trial Registration : The trial was registered at clinical trials.gov as NCT04378972 on 06 May 2020 ("retrospectively registered") https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid = S0009UI8&selectaction = Edit&uid = U0003RKC&ts = 2&cx = dstm4o.
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AIMS: Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key features of diabetes mellitus, being both diagnostic parameters and pathogenetic mechanisms. Vascular endothelial growth factor (VEGF) is importantly implicated in the physiology and pathology of blood vessels, including diabetic vascular damage. METHODS: These factors certainly affect endothelial cells, and to evaluate mechanisms involved, we took advantage of telomerase-immortalized human microvascular endothelial (TIME) cells. TIME cells were exposed to different glucose concentrations and to VEGF treatments. Culture conditions also included the use of basement membrane extract, as an in vitro differentiation model. Cell morphology was then evaluated in the different conditions, and cellular proteins were extracted to analyze specific protein products by Western blot. RESULTS: High glucose concentrations and VEGF did substantially affect neither morphology nor growth of cultured TIME cells, while both considerably increased differentiation into "capillary-like" structures when cells were cultured on basement membrane extract. CONCLUSIONS: Under these conditions, high glucose concentration and VEGF also produced a short-term increase in pERK1/2 and p85 proteins, while total and phosphorylated AKT were not affected. These data suggest a direct angiogenetic effect of glucose, affecting intracellular transduction mechanisms with an action similar to that of VEGF. This effect on endothelial cell proliferation and differentiation could be part of pathogenetic mechanisms producing diabetic microvascular alterations.
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Inductores de la Angiogénesis/metabolismo , Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Glucosa/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Inductores de la Angiogénesis/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Fosforilación/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
PURPOSE: To evaluate custom fast cross-linking (cfCXL) treatment of keratoconus. METHODS: "Custom fast cross-linking" or "cfCXL" is a keratoconus treatment algorithm featuring no epithelial disruption, 15 minutes of corneal presoaking with a riboflavin-vitamin E TPGS solution, and a 370-nm ultraviolet A radiation beam centered on the most highly curved corneal region. Ultraviolet A radiation beam fluence, total energy, and exposure time are significantly less than those in the Dresden protocol. In this study, refraction, spectacle-corrected distance visual acuity, Kmax, and corneal hysteresis were monitored in 81 eyes of 81 patients for 7 years with 100% follow-up. Pretreatment Kmax and patient age averaged 53.01 ± 4.87 D and 25.9 ± 4.7 years, respectively. RESULTS: Average refractive cylinder magnitude was reduced by 26.1% at 1 month postoperatively and by 44.2% at 7 years postoperatively. Logarithm of the minimum angle of resolution average spectacle-corrected distance visual acuity (best spectacle-corrected distance visual acuity) improved from +0.26 ± 0.34 (20/36.4) to +0.15 ± 0.23 (20/28.25), +0.05 ± 0.20 (20/22.4), and +0.06 ± 0.20 (20/22.96) at 1 month, 1 year, and 7 years postoperatively, respectively. Best spectacle-corrected distance visual acuity improved in 54.3%, 74.1%, 84.0%, 87.7%, 84.0%, 84.0%, and 82.7% of patients at postoperative months 1, 3, 6, 12, 24, 48, and 84, respectively. Kmax did not increase in 96.3% of patients at 1 month, 97.5% at 1 year, and 98.8% at 7 years postoperatively, with average corneal apex flattening at 1 month and 7 years of -2.79 ± 1.70 D and -4.00 ± 2.40 D, respectively. CONCLUSIONS: Custom fast cross-linking, epi-on, rapid, narrowed beam apex-centered treatment of keratoconus with riboflavin-vitamin E TPGS produced a significant, rapid, and lasting cone progression stoppage, astigmatism reduction, and visual acuity improvement.
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Colágeno/uso terapéutico , Córnea/diagnóstico por imagen , Paquimetría Corneal/métodos , Topografía de la Córnea/métodos , Reactivos de Enlaces Cruzados/uso terapéutico , Queratocono/tratamiento farmacológico , Fotoquimioterapia/métodos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Queratocono/patología , Masculino , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Refracción Ocular , Riboflavina/uso terapéutico , Terapia Asistida por Computador/métodos , Factores de Tiempo , Rayos Ultravioleta , Agudeza VisualRESUMEN
The aqueous humor (AH) outflow pathways definition is still matter of intense debate. To date, the differentiation between conventional (trabecular meshwork) and unconventional (uveoscleral) pathways is widely accepted, distinguishing the different impact of the intraocular pressure on the AH outflow rate. Although the conventional route is recognized to host the main sites for intraocular pressure regulation, the unconventional pathway, with its great potential for AH resorption, seems to act as a sort of relief valve, especially when the trabecular resistance rises. Recent evidence demonstrates the presence of lymphatic channels in the eye and proposes that they may participate in the overall AH drainage and intraocular pressure regulation, in a presumably adaptive fashion. For this reason, the uveolymphatic route is increasingly thought to play an important role in the ocular hydrodynamic system physiology. As a result of the unconventional pathway characteristics, hydrodynamic disorders do not develop until the adaptive routes cannot successfully counterbalance the increased AH outflow resistance. When their adaptive mechanisms fail, glaucoma occurs. Our review deals with the standard and newly discovered AH outflow routes, with particular attention to the importance they may have in opening new therapeutic strategies in the treatment of ocular hypertension and glaucoma.
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Humor Acuoso/metabolismo , Glaucoma/metabolismo , Presión Intraocular/fisiología , Hipertensión Ocular/metabolismo , Malla Trabecular/fisiopatología , Animales , Glaucoma/fisiopatología , Humanos , Vasos Linfáticos/diagnóstico por imagen , Vasos Linfáticos/fisiopatología , Hipertensión Ocular/fisiopatología , Malla Trabecular/metabolismoRESUMEN
Aims: To study the neuroprotective effect of oral citicoline (CT) therapy in primary open-angle glaucoma (POAG). Methods: This study included one eye each of 60 POAG patients. Patients were randomly divided into two groups (A and B) of 30 participants each. Only patients of group A were administered with CT therapy. Age, sex, and disease duration were matched between groups. Despite a stable intraocular pressure (IOP), a slow disease progression-assessed by standard automated white-on-white perimetry (SAP) in the previous 3 years-occurred in all patients. All patients underwent a complete eye examination, including IOP measurement, SAP, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness measurements with optical coherence tomography (OCT), before starting CT treatment and at 6, 12, 18, and 24 months' follow-up. Parameter differences between groups were evaluated at each eye check. Results: After 18 months, mean values of SAP mean deviation (MD) of group A were significantly (p = 0.039) higher (-7.25 db) than those of group B (-8.64 db). Moreover, they appeared stable in the following visits, whereas in group B, mean MD values continued to significantly (p < 0.001) decrease (-9.28 db) over time. Mean RNFL and GCC thickness in group A were significantly (p < 0.01) higher (70.39 and 71.19 µm, respectively) than in group B (64.91 and 65.60 µm, respectively) after 12 months of CT therapy. Furthermore, they appeared to be stable over the later visits, whereas they thinned significantly (p < 0.001) over time in group B. Conclusion: These findings suggest that CT therapy seems to be effective in slowing POAG progression. Further studies on a larger population and with a longer follow-up are needed to confirm this pilot investigation.
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Introduction: Intravitreal anti-VEGF is the most effective therapy for wet AMD, although systemic effects on the endothelium cannot be excluded. Areas covered: The purpose of this review was to evaluate risk of thromboembolic events associated with intravitreal anti-VEGF. Expert opinion: Current data are insufficient to confirm the safety of these compounds, due to the paucity of specific studies. Thus, pharmacovigilance for all anti-VEGF should be improved to verify the true role of anti-VEGF in the occurrence of systemic adverse events.
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Inhibidores de la Angiogénesis/efectos adversos , Tromboembolia/inducido químicamente , Degeneración Macular Húmeda/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Humanos , Inyecciones Intravítreas , Farmacovigilancia , Tromboembolia/epidemiología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Central serous chorioretinopathy (CSC) is a common retina disease and has a relative high recurrence rate, etiology, and pathogenesis of which remains largely ambiguous. The effects on the retina are usually self-limited, although some people are left with permanent vision loss due to progressive and irreversible photoreceptor damage or retinal pigment epithelium atrophy. There have been a number of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), intravitreal injection of anti-vascular endothelial growth factor agents, and subthreshold lasers. It is not clear whether there is a clinically important benefit to treating acute CSC, which often resolves spontaneously as part of its natural history. Of the interventions studied to date, PDT and micropulse laser treatment appear the most promising. .
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Melatonin, an indoleamine secreted mainly by the pineal gland, is known to modulate a wide range of circadian functions. However, this neurohormone is also synthesized within the eye and acts directly on ocular structures to mediate a variety of physiological processes. This review is focused on the role and therapeutic potential of melatonin in ocular diseases. We summarize data indicating that melatonin may represent a powerful tool to counteract ocular dysfunctions such as uveitis, glaucoma, age-related macular degeneration, and diabetic retinopathy. A search strategy was conducted to identify studies in PubMed (January 1990 to September 2017). In particular, we included experimental studies, clinical trials, and reviews to provide suitable insights and elucidations regarding the action of melatonin on age-related ocular disorders. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. Additionally, melatonin appears to be safe and well-tolerated, even at high doses, and no adverse/side effects were reported. Although this topic remains under intense investigation, we can conclude that melatonin, as a single agent or in combination with other drugs, is an attractive pharmacological candidate for age-related ocular diseases.