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To investigate alteration of outer nuclear layer (ONL) and choroidal vascularity index (CVI) in different status of central serous chorioretinopathy (CSC). A retrospective review of 65 CSC eyes with subretinal fluid (manifest CSC) and 40 control eyes was conducted in a single tertiary university hospital. Differences in best-corrected visual acuity (BCVA), ONL, and CVI were compared. CVI was assessed both in the entire choroid (CVI-EC) and around the 1500 µm leakage area (CVI-1500). Measurements were repeated after the subretinal fluid resorption (quiescent CSC), and compared. CSC eyes showed worse BCVA, thinner ONL and greater CVI than controls. Quiescent CSC showed a recovery of ONL compared to the manifest CSC, along with the BCVA improvement. The resolution of the CSC revealed a decrease across all three choroidal areas (total, stromal and luminal), with a more pronounced reduction in the stromal than in the luminal choroidal area, leading to an increase in the CVI. This phenomenon was shown in both CVI-EC and CVI-1500. Conclusively, ONL thickness can be used as a quantitative biomarker for photoreceptor function in CSC. Increased CVI may reflect a disease activity. The stromal choroidal area is particularly sensitive in illustrating leakage from the choroidal vasculature.
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Coriorretinopatía Serosa Central , Coroides , Tomografía de Coherencia Óptica , Agudeza Visual , Coriorretinopatía Serosa Central/patología , Coriorretinopatía Serosa Central/diagnóstico por imagen , Humanos , Coroides/irrigación sanguínea , Coroides/patología , Coroides/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Enfermedad Aguda , Angiografía con FluoresceínaRESUMEN
Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function1. To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts)2, an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+ T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+ T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8+ T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.
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Linfocitos B , Linfocitos T CD8-positivos , Comunicación Celular , Células Dendríticas , Células Epiteliales , Células T Auxiliares Foliculares , Linfocitos T Reguladores , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Comunicación Celular/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Ligandos , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Células T Auxiliares Foliculares/citología , Células T Auxiliares Foliculares/inmunología , Linfocitos B/citología , Linfocitos B/inmunología , Centro Germinal/citología , Análisis de Expresión Génica de una Sola Célula , Células Epiteliales/citología , Células Epiteliales/inmunología , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Virus de la Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/virología , Especificidad de ÓrganosRESUMEN
AIM: To investigate the difference in the initial surgical results between a new monofocal intraocular lens (IOL) with enhanced intermediate vision and the standard monofocal IOL in patients with retinal disease. METHODS: We retrospectively reviewed the medical records of patients with retinal disease who underwent cataract surgery due to accompanying cataracts. Types of retinal diseases were investigated and best-corrected distant visual acuity, distant uncorrected visual acuity (UCVA), intermediate UCVA, near UCVA, and spherical equivalent were recorded at each visit. The surgical results were investigated at 1 day, 1 week, and 1 month after surgery. RESULTS: Seventeen eyes treated with a new monofocal IOL enhanced for intermediate vision (ICB00 group) and 18 eyes treated with the standard monofocal IOL (AAB00 group) were included in this study. There were no significant differences in the baseline characteristics, including the type of underlying retinal disease, between the groups. There were no significant differences between the groups in terms of distant, intermediate, or near UCVA at day 1 and week 1 after surgery. However, at 1 month after surgery, the ICB00 group showed a significantly better intermediate vision improvement than the AAB00 group (p = 0.001). CONCLUSION: Even in patients with cataract accompanied by retinal disease, the use of the ICB00 IOL showed significant improvement in intermediate vision compared to the use of the AAB00 (standard monofocal) IOL. The ICB00 IOL might be a good option for patients with cataract and retinal disease in the era of increased intermediate vision needs in daily life.
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Catarata , Lentes Intraoculares , Facoemulsificación , Enfermedades de la Retina , Humanos , Implantación de Lentes Intraoculares/métodos , Estudios Retrospectivos , Catarata/complicaciones , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/cirugía , Diseño de Prótesis , Facoemulsificación/métodos , Satisfacción del PacienteRESUMEN
PURPOSE: To investigate the association between visual outcomes and choroidal changes in patients with macula-off rhegmatogenous retinal detachment. METHODS: This study retrospectively reviewed 63 eyes of patients with macula-off rhegmatogenous retinal detachment who underwent vitrectomy. Their fellow eyes were analyzed as a control group. The choroidal vascularity index (CVI), ellipsoid zone/external limiting membrane integrity, central foveal thickness, and subfoveal choroidal thickness were documented and analyzed. Linear regression analyses were performed to identify factors affecting the final best-corrected visual acuity. RESULTS: Eyes with rhegmatogenous retinal detachment showed increased CVI (68.8 ± 4.1) compared with the control group (66.1 ± 8.8, P = 0.028). Multivariate linear regression analysis revealed that patients with a poor final best-corrected visual acuity had a longer detachment duration ( P = 0.002), worse baseline best-corrected visual acuity ( P = 0.034), thinner central foveal thickness ( P = 0.005), and greater CVI ( P = 0.001) and were more likely to be tamponated with silicone oil ( P = 0.001). Choroidal vascularity index was particularly increased in eyes with poor ellipsoid zone/external limiting membrane integrity, prolonged detachment duration, thin central foveal thickness, and worse best-corrected visual acuity. CONCLUSION: Increased CVI could indicate poor visual outcomes in patients with macula-off rhegmatogenous retinal detachment. Choroidal remodeling could be associated with the disruption of the ellipsoid zone/external limiting membrane integrity.
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Mácula Lútea , Desprendimiento de Retina , Humanos , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual , Mácula Lútea/cirugía , VitrectomíaRESUMEN
This study presents a stacked autoencoder (SAE)-based assessment method which is one of the unsupervised learning schemes for the investigation of bone fracture. Relatively accurate health monitoring of bone fracture requires considering physical interactions among tissue, muscle, wave propagation and boundary conditions inside the human body. Furthermore, the investigation of fracture, crack and healing process without state-of-the-art medical devices such as CT, X-ray and MRI systems is challenging. To address these issues, this study presents the SAE method that incorporates bilateral symmetry of the human legs and low-frequency transverse vibration. To verify the presented method, several examples are employed with plastic pipes, cadaver legs and human legs. Virtual spectrograms, created by applying a short-time Fourier transform to the differences in vibration responses, are employed for image-based training in SAE. The virtual spectrograms are then classified and the fine-tuning is also carried out to increase the accuracy. Moreover, a confusion matrix is employed to evaluate classification accuracy and training validity.
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Fracturas Óseas , Humanos , Fracturas Óseas/diagnóstico por imagen , Cadáver , Músculos , Plásticos , VibraciónRESUMEN
To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.
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Neovascularización Coroidal , Degeneración Macular , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Estudios Retrospectivos , Pronóstico , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/tratamiento farmacológico , Factores de Crecimiento Endotelial Vascular , Tomografía de Coherencia Óptica , Degeneración Macular/tratamiento farmacológico , Inyecciones IntravítreasRESUMEN
Diverse intestinal components (e.g., gut-associated neurons, immune cells, gut microbes, and epithelium) are intimately intertwined with each other to maintain homeostasis in the gut. In a recent issue of Cell, Zhang et al. (2022) and Yang et al. (2022) present complementary studies uncovering interactions between nociceptor neurons, gut epithelium, and the microbiome to protect intestinal tissue from inflammation.
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Microbioma Gastrointestinal , Células Caliciformes , Mucosa Intestinal , Homeostasis , NeuronasRESUMEN
Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.
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Tandem welding is extensively used for welding large structures, such as ships and plants, for increased welding speed and volume. Seam tracking is essential because of a large amount of thermal deformation. However, in tandem welding, arc interference causes current and voltage to vary non-uniformly, leading to difficulties in seam tracking. Therefore, in this study, an optimal signal was identified for seam tracking in tandem welding and evaluated. To select the seam-tracking signal, an algorithm was developed that separates the welding signal into peak, average, and base. Based on the collected data, regression and signal-to-noise ratio analyses were performed to identify a suitable seam-tracking signal. To trace the welding line based on the selected signal, the welding signal was checked by weaving on the V-groove specimen. As a result, the current area difference of the welding signal generated between the left and right parts of the center of the V-groove could be calculated. An algorithm and equipment for seam tracking were constructed using the area difference of the welding current. Finally, the seam tracking system was verified by conducting an actual test using the equipment to which the algorithm was applied.
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Soldadura , OcupacionesRESUMEN
Herein, entecavir-3-palmitate (EV-P), an ester prodrug of entecavir (EV), was employed as a model drug, and the effect of drug particle size on in vivo pharmacokinetic profiles and local inflammatory responses, and those associations were evaluated following intramuscular (IM) injection. EV-P crystals with different median diameters (0.8, 2.3, 6.3, 15.3 and 22.6 µm) were prepared using the anti-solvent crystallization method, with analogous surface charges (-10.7 ~ -4.7 mV), and crystallinity (melting point, 160-170 °C). EV-P particles showed size-dependent in vitro dissolution profiles under sink conditions, exhibiting a high correlation between the median diameter and Hixon-Crowell's release rate constant (r2 = 0.94). Following IM injection in rats (1.44 mg/kg as EV), the pharmacokinetic profile of EV exhibited marked size-dependency; 0.8 µm-sized EV-P particles about 1.6-, 3.6-, and 5.6-folds higher systemic exposure, compared to 6.3, 15.3, and 22.6 µm-sized particles, respectively. This pharmacokinetic pattern, depending on particle size, was also highly associated with histopathological responses in the injected tissue. The smaller EV-P particles (0.8 or 2.3 µm) imparted the larger inflammatory lesion after 3 days, lower infiltration of inflammatory cells, and thinner fibroblastic bands around depots after 4 weeks. Conversely, severe fibrous isolation with increasing particle size augmented the drug remaining at injection site over 4 weeks, impeding the dissolution and systemic exposure. These findings regarding the effects of formulation variable on the in vivo behaviors of long-acting injectable suspension, provide constructive knowledge toward the improved design in poorly water-soluble compounds.
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Tamaño de la Partícula , Animales , Cristalización , Ratas , Solubilidad , Solventes , SuspensionesRESUMEN
Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Obesidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/microbiología , Hemoglobina Glucada , Hawaii/epidemiología , Nativos de Hawái y Otras Islas del Pacífico , Obesidad/epidemiología , Obesidad/microbiologíaRESUMEN
Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural population required for this process has yet to be established. Here, we show that Vgat-expressing neurons in the lateral hypothalamus (LHVgat neurons) are required for diverse thermoregulatory behaviors. The population activity of LHVgat neurons is increased during thermoregulatory behavior and bidirectionally encodes thermal punishment and reward (P&R). Although this population also regulates feeding and caloric reward, inhibition of parabrachial inputs selectively impaired thermoregulatory behaviors and encoding of thermal stimulus by LHVgat neurons. Furthermore, two-photon calcium imaging revealed a subpopulation of LHVgat neurons bidirectionally encoding thermal P&R, which is engaged during thermoregulatory behavior, but is largely distinct from caloric reward-encoding LHVgat neurons. Our data establish LHVgat neurons as a required neural substrate for behavioral thermoregulation and point to the key role of the thermal P&R-encoding LHVgat subpopulation in thermoregulatory behavior.
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Área Hipotalámica Lateral , Prosencéfalo , Regulación de la Temperatura Corporal , Área Hipotalámica Lateral/fisiología , Neuronas/fisiología , RecompensaRESUMEN
To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of 182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.
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Retinopatía Diabética/tratamiento farmacológico , Perdida de Seguimiento , Edema Macular/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/patología , Retinopatía Diabética/fisiopatología , Femenino , Humanos , Edema Macular/epidemiología , Edema Macular/patología , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Agudeza VisualRESUMEN
Reliable fracture diagnosis monitoring and analyzing low-frequency transverse vibration data can be achieved through an in-depth understanding of the physical interactions between wave propagation and boundary conditions. The present study aims to investigate the effects of the boundary conditions on the low-frequency structural vibrations of bones. Time-frequency domain analysis of transverse vibration signals depending on the boundary conditions of bones is analyzed and investigated. These studies reveal that the responses of fractured or non-fractured bones are different and influenced by the displacement and force boundary conditions. These relationships can be considered in the development of a smart fracture diagnosis system considering the posture and boundary condition. To validate the present observations, the experiments with artificial specimens and cadaver are carried.
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Fracturas Óseas , Huesos , Cadáver , Humanos , Fenómenos Mecánicos , VibraciónRESUMEN
Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
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Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Dispositivos Laboratorio en un Chip , Neurogénesis/fisiología , Organoides/crecimiento & desarrollo , Organoides/fisiología , Animales , Encéfalo/citología , Medios de Cultivo , Fenómenos Electrofisiológicos , Matriz Extracelular/fisiología , Estudios de Factibilidad , Perfilación de la Expresión Génica , Humanos , Hidrogeles , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/fisiología , Modelos Anatómicos , Modelos Neurológicos , Neurogénesis/genética , Neuroglía/citología , Neuroglía/fisiología , Técnicas de Cultivo de Órganos/instrumentación , Técnicas de Cultivo de Órganos/métodos , Organoides/citología , PorcinosRESUMEN
BACKGROUND: We investigated the incidence and risk of retinal vein occlusion (RVO) in end-stage renal disease (ESRD) patients on dialysis in Korea. METHODS: In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004-2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve. Whether the dialysis modality affects the development of RVO was also evaluated. RESULTS: In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test). CONCLUSION: This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.
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Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Oclusión de la Vena Retiniana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Oclusión de la Vena Retiniana/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. METHODS: Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the 'persistent SRF (+) group'. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. RESULTS: Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (-) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. CONCLUSIONS: Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.
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Degeneración Macular , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Estudios Retrospectivos , Líquido Subretiniano , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológicoRESUMEN
PURPOSE: To examine the incidence and risk of retinal artery occlusion (RAO) in patients who have undergone dialysis in Korea. METHODS: A nationwide, population-based study using South Korean national health insurance data from 2004 to 2013 was used for analysis. All patients who began dialysis between 2004 and 2013 and the same number of control subjects were selected via propensity score matching. The incidence of RAO in the dialysis and control cohorts was calculated for 2004 to 2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to evaluate the risk of developing RAO in dialysis patients. Cumulative RAO incidence curves were generated using the Kaplan-Meier method. Whether dialysis modalities influenced the incidence of RAO was also evaluated. RESULTS: Seventy-six thousand seven hundred and eighty-two end-stage renal disease patients on dialysis were included in the dialysis cohort, and 76,782 individuals were included in the control cohort. During the study period, 293 patients in the dialysis cohort and 99 patients in the control cohort developed RAO. The person-years incidence of RAO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 1.1/1,000 person-years; control = 0.3/1,000 person-years; P < 0.001). The incidence of RAO was not significantly different between the two methods of dialysis (hemodialysis vs. peritoneal dialysis; P = 0.25, log-rank test). CONCLUSION: The current study provided epidemiological evidence that undergoing dialysis for end-stage renal disease was associated with an increased risk of developing RAO. The incidence of RAO rapidly increased as the duration of dialysis increased. These results strengthen the significant role of the renal function in retinal vascular disease.
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Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Oclusión de la Arteria Retiniana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Oclusión de la Arteria Retiniana/fisiopatología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Oral montelukast (MTK) is prescribed to treat asthma or rhinitis, and is clinically investigated as new medication in the treatment of Alzheimer's dementia. Herein, in order to better patient's compliance, microsuspensions (MSs)-based oral liquid preparations of montelukast (MTK) were formulated with polymeric suspending agents including hypromellose (HPMC), and those drug-polymer interaction, physicochemical stability, dissolution, and in vivo pharmacokinetic profile was evaluated. When amorphous MTK particle was suspended in aqueous vehicle, it was readily converted into crystalline form and grown into aggregates, drastically lowering dissolution rate. However, the addition of HPMC polymer markedly suppressed the crystal growth, providing both improved drug stability and profound dissolution profile. Raman spectrometry denoted the inter-molecular hydrogen boding between MTK particle and HPMC polymer. The crystal growth or dissolution profile of MSs was markedly affected by pharmaceutical additives (sucrose or simethicone) in the preparations or storage temperature. The optimized HPMC-based MS exhibited over 80% higher bioavailability, compared to marketed granule (Singulair®) in rats. Therefore, novel MTK-loaded MS can be a promising liquid preparation, bettering oral absorption and patient's compliance.
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Acetatos/administración & dosificación , Ciclopropanos/administración & dosificación , Derivados de la Hipromelosa/química , Quinolinas/administración & dosificación , Sulfuros/administración & dosificación , Acetatos/química , Acetatos/farmacocinética , Administración Oral , Animales , Cristalización , Ciclopropanos/química , Ciclopropanos/farmacocinética , Liberación de Fármacos , Estabilidad de Medicamentos , Enlace de Hidrógeno , Masculino , Quinolinas/química , Quinolinas/farmacocinética , Ratas , Solubilidad , Sulfuros/química , Sulfuros/farmacocinética , SuspensionesRESUMEN
BACKGROUND: To analyze the microbiological causes of infectious endophthalmitis on an isolated island over ten years. METHODS: A retrospective review of the medical records of 49 eyes clinically diagnosed with infectious endophthalmitis between January 2009 and December 2018 was done. The subjects were recruited from a single tertiary referral center on Jeju Island. The baseline characteristics of all subjects were investigated, and a culture examination was performed. The isolated pathogens were analyzed to determine how their microbiological features differed from those in regions with different geographical conditions. RESULTS: Of the 49 eyes, causative microorganisms were identified in 27 eyes (55.1%). Bacteria were found in 24 cases and fungi in 3 cases. Among the exogenous causes, Staphylococcus species (Staphylococcus aureus, S. epidermidis, and S. hominis) were the most common pathogens (7 cases). Achromobacter xylosoxidans was the second most common causative pathogen (4 cases) followed by Moraxella species (3 cases). The most frequent endogenous origin was due to Klebsiella pneumoniae (6 cases). The subjects were divided into two groups according to the treatment results and analyzed for predisposing factors related to visual outcomes. The presence of diabetes mellitus (P = 0.038) and initial visual acuity (P ≤ 0.001) were significant predisposing factors for visual outcomes. CONCLUSION: The causative microorganisms of endogenous endophthalmitis on Jeju Island were not different from those reported previously. However, isolated exogenous microorganisms were different from those reported in other studies from inland areas. A high incidence and atypical clinical features of Achromobacter xylosoxidans and Moraxella in exogenous endophthalmitis were observed, reflective of the distinct climatic features of Jeju Island: high humidity and temperature. Therefore, considering the causative microorganisms of exogenous endophthalmitis, it may be assumed that the causative microorganisms of exogenous endophthalmitis and its clinical manifestations differ according to the region.