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Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.
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Infecciones Virales del Ojo , Glaucoma , Uveítis Anterior , Infección por el Virus Zika , Virus Zika , Humanos , Uveítis Anterior/complicaciones , Infecciones Virales del Ojo/complicaciones , Infección por el Virus Zika/complicaciones , Glaucoma/epidemiología , Glaucoma/etiología , Progresión de la EnfermedadRESUMEN
Corneal wound healing is influenced by many factors including transcriptional co-repressors and co-activators. Interactions of co-activators and co-repressors with Smads influence mechanistic loop facilitating transcription of alpha-smooth muscle actin (α-SMA), a key profibrotic gene, in corneal repair. The role of a transcriptional repressor, 5'TG3'-interacting factor (TGIF), in the regulation of α-SMA and myofibroblast formation in the cornea was shown previously by our group. This study tested a hypothesis if TGIF1 gene editing via CRISPR/Cas9 can ease myofibroblast formation in the cornea using an in vitro model. Primary human corneal stromal fibroblasts (hCSFs) generated from donor corneas received gene-editing plasmid facilitating loss (CRISPR/Cas9 knockout) or gain (CRISPR activation) of TGIF function by UltraCruz transfection reagent. Phase-contrast microscopy, immunoblotting, immunocytochemistry and quantitative polymerase chain reaction (qPCR) were used to measure levels of myofibroblast profibrotic genes (α-SMA, fibronectin, Collagen-I, and Collagen-IV) in hCSFs lacking or overexpressing TGIF1 after growing them in± transforming growth factor beta1 (TGF-ß1) under serum-free conditions. The CRISPR-assisted TGIF1 activation (gain of function) in hCSFs demonstrated significantly decreased myofibroblast formation and messenger ribonucleic acid (mRNA) and protein levels of profibrotic genes. Conversely, CRISPR/Cas9-assisted TGIF knockdown (loss of function) in hCSFs demonstrated no significant change in the levels of myofibroblast formation or profibrotic genes under similar conditions. These results suggest that TGIF gene-editing approach can be employed to modulate the transcriptional activity of α-SMA in controlling pathological and promoting physiological wound healing in an injured cornea.
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Enfermedades de la Córnea , Edición Génica , Actinas/genética , Actinas/metabolismo , Sistemas CRISPR-Cas , Diferenciación Celular , Células Cultivadas , Proteínas Co-Represoras/genética , Proteínas Co-Represoras/metabolismo , Colágeno/metabolismo , Enfermedades de la Córnea/patología , Fibroblastos/metabolismo , Fibrosis , Proteínas de Homeodominio , Humanos , Miofibroblastos/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
INTRODUCTION: Despite the rise of micro-invasive glaucoma surgery (MIGS), glaucoma drainage device implantation continues to be a mainstay among glaucoma surgical treatment options. Anterior chamber tube placement, while effective in reducing intraocular pressure (IOP), poses corneal endothelial risks. Ciliary sulcus tube placement shows promise in reduced corneal endothelial cell loss, but proper sulcus placement can be challenging. Our study describes the initial safety and effectiveness results using a novel sulcus tube internal needle guidewire (STING) technique for glaucoma drainage device insertion into the ciliary sulcus. METHODS: We retrospectively reviewed the charts of all consecutive patients who underwent the STING technique using the Ahmed ClearPath, Ahmed Glaucoma Valve, or Baerveldt glaucoma implant with at least 6 months of follow-up. Demographic characteristics, type of glaucoma, previous medical and surgical treatment, pre- and postoperative IOP, pre- and postoperative medications, complications, and success rates were recorded. RESULTS: Out of nine eyes, seven resulted in qualified success (77.8%). Preoperative mean IOP was 23.8 ± 6.3 mmHg, and postoperative IOP decreased significantly to 14.9 ± 3.7 mmHg (p = 0.008). The average number of preoperative medications per patient was 4.4 ± 0.7, while the average number of postoperative medications per patient was reduced significantly to 3.6 ± 1.0 (p = 0.039). CONCLUSION: The STING technique is a novel method for placing a glaucoma drainage device into the ciliary sulcus, leading to IOP lowering with minimal complications. The STING technique is designed to improve surgical ease and increase anatomical precision of sulcus tube placement. Video available for this article.
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Conjunctival fibrosis remains the major impediment to the success of glaucoma filtration surgery. Anti-metabolites remain the gold standard for mitigating post-surgical fibrosis, but they are associated with high complication rates and surgical failure rates. Establishing a more targeted approach to attenuate conjunctival fibrosis may revolutionize the surgical approach to glaucoma. A new strategy is needed to prevent progressive tissue remodeling and formation of a fibrotic scar, subsequently increasing surgical success and reducing the prevalence of glaucoma-related vision loss. Advancements in our understanding of molecular signaling and biomechanical cues in the conjunctival tissue architecture are broadening the horizon for new therapies and biomaterials for the mitigation of fibrosis. This review aims to highlight the strategies and current state of promising future approaches for targeting fibrosis in glaucoma filtration surgery.
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PURPOSE: To determine the median spherical aberration (SA) of the cataractous population, how it relates to biometry, and the theoretical effect of different intraocular lens (IOL) platforms. METHODS: A retrospective chart review of patients undergoing cataract surgery evaluation with a high quality Pentacam (Oculus Optikgeräte GmbH) were included. Age, gender, Q-value, mean total SA, higher order aberration root mean square wavefront error, and equivalent keratometry were collected from the Holladay report and axial length and anterior chamber depth (ACD) from the IOLMaster 700 (Carl Zeiss Meditec AG). RESULTS: Data from 1,725 eyes of 999 patients were collected. SA had a median of 0.37 µm (95% confidence interval: 0.36 to 0.38. Age (r = .136, P < .001), Q-factor (r = .743, P < .001), and higher order aberration root mean square wavefront error (r = .307, P < .001) were positively correlated with SA. Average equivalent keratometry (r = -.310, P < .001) was negatively correlated with SA. Axial length (r = -0.037, P = .120) and ACD (r = .004, P = .856) had no association with SA. Up to 1,499 (86.9%) theoretically had SA moved closer to zero with IOLs that had negative SA. Up to 102 (5.9%) had SA theoretically worsened. CONCLUSIONS: SA is not normally distributed, suggesting that there may be no "average" SA that IOLs should aim to correct. Patients might benefit from tailoring IOL choice to individual SA. Without access to SA data, eyes with steeper average keratometry or younger patients may have less SA, which could influence IOL choice. [J Refract Surg. 2023;39(2):89-94.].
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Extracción de Catarata , Lentes Intraoculares , Humanos , Estudios Retrospectivos , Visión Ocular , Biometría , Refracción OcularRESUMEN
BACKGROUND AND OBJECTIVE: Ophthalmologic telemedicine has emerged during the COVID-19 pandemic. The objective of this study is to assess the accuracy and reproducibility of a smartphone-based home vision monitoring system (Sightbook) and to compare it with existing clinical standards. PATIENTS AND METHODS: Near Snellen visual acuity (VA) was measured with Sightbook and compared with conventional measurements for distance and near VA at an academic medical center ophthalmology clinic in 200 patients with a variety of different specified preexisting ocular conditions. Measurements of contrast sensitivity were also compared by using an existing commercially available chart system in 15 normal patients and 15 patients with age-related macular degeneration. RESULTS: Sightbook VA tests were reproducible (SD = ±0.054 logMAR), and correlation with standard VA methods was significant (R > 0.87 and P < .001). Sightbook contrast sensitivity measurements were reproducible (SD/mean ratio, 0.02 to 0.04), yielding results similar to those of standard tests (R2 > 0.87 and P < .001). CONCLUSIONS: Smartphone-based VA and contrast sensitivity are highly correlated with standard charts and may be useful in augmenting limited inoffice care. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:79-84.].
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COVID-19 , Teléfono Inteligente , Humanos , Pandemias , Reproducibilidad de los Resultados , SARS-CoV-2RESUMEN
PURPOSE: The aim of this study is to evaluate whether trabeculectomy with antimetabolites or glaucoma drainage device (GDD) surgery is more likely to achieve an intraocular pressure (IOP) ≤10 mm Hg. DESIGN: Retrospective, nonrandomized, cohort study of pseudophakic, primary glaucoma patients. METHODS: 53 pseudophakic patients underwent trabeculectomy and 65 received GDD at the University of Florida by one surgeon between 1993 and 2015. The main outcome measures were mean IOP and percentage of patients obtaining an IOP ≤10 mm Hg for up to 5 years postoperatively. A subgroup undergoing a first time glaucoma surgery was also analyzed because there were more redo glaucoma procedures in the GDD group. RESULTS: Over 5 years, the mean annual IOP for the trabeculectomy eyes was between 6.9 and 7.8 mm Hg on an average of 0.2 medications, and that for GDD eyes was between 11.4 and 12.1 mm Hg on a mean of 1.6 to 1.9 medications (Pâ<â0.002). A significantly higher percentage of trabeculectomy eyes than GDD eyes achieved a pressure of ≤10 mm Hg, for years 1 to 4 (Pâ<â0.05). Visual acuity (VA) change was not statistically different between the groups, both for mean logMAR acuity and percentage of patients that lost ≥2 Snellen lines. Complication rates were similar between the groups. Postoperative VA change was similar for eyes achieving low IOP ≤5 mm Hg and those eyes with an IOP ≥10 mm Hg. CONCLUSIONS: Trabeculectomy provided significantly lower IOP for 5 years postoperatively in pseudophakic primary glaucoma patients, and was more likely to achieve an IOP ≤10 mm Hg.
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Glaucoma/cirugía , Presión Intraocular/fisiología , Seudofaquia/cirugía , Trabeculectomía/métodos , Anciano , Femenino , Glaucoma/fisiopatología , Implantes de Drenaje de Glaucoma , Humanos , Masculino , Persona de Mediana Edad , Seudofaquia/fisiopatología , Estudios Retrospectivos , Agudeza VisualRESUMEN
AIM: To compare the intermediate-term efficacy of a large surface area Baerveldt 350 mm2 glaucoma drainage device (GDD) with medium surface area implants (Baerveldt 250 mm2 and Molteno 3, 230, or 245 mm2). DESIGN: This is a retrospective, nonrandomized comparative trial. MATERIALS AND METHODS: A total of 94 eyes of 94 patients of mixed glaucoma diagnoses without any prior glaucoma surgical procedures and who had undergone a glaucoma drainage implant surgery with either a large Baerveldt 350 mm2 GDD or a medium-sized GDD (Baerveldt 250 mm2 or Molteno 230 or 245 mm2) were reviewed for intraocular pressure (IOP), number of glaucoma medications, and visual acuity (VA) preoperatively, and at 1, 2, and 3 years postprocedure. RESULTS: No significant differences were found in mean IOP, number of glaucoma medications used, and VA at 1, 2, and 3 years postoperatively. The rate of additional glaucoma procedures was similar between the two groups. CONCLUSION: There is no clear evidence that a larger implant surface area beyond 230 to 250 mm2 is advantageous in providing intermediate-term IOP control. CLINICAL SIGNIFICANCE: It may be technically easier to surgically place a GDD that does not need to have its wings placed underneath the recti muscles, and the IOP results are similar. HOW TO CITE THIS ARTICLE: Meyer AM, Rodgers CD, Zou B, Rosenberg NC, Webel AD, Sherwood MB. Retrospective Comparison of Intermediate-term Efficacy of 350 mm2 Glaucoma Drainage Implants and Medium-sized 230-250 mm2 Implants. J Curr Glaucoma Pract 2017;11(1):8-15.
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AIM: To estimate the floor of retinal nerve fibre layer (RNFL) thickness measurements and the corresponding retinal sensitivity loss in glaucoma. METHODS: Visual field (VF), Spectralis RNFL (83 patients and 37 healthy subjects) and RTVue RNFL data obtained separately (56 patients and 36 healthy subjects) were reviewed. Global and quadrant residual layer thicknesses and corresponding VF losses were estimated using two Bayesian change point models. RESULTS: The respective residual thicknesses from change point model 1 (CPM1) on Spectralis and RTVue (respectively) were 49.9 and 70.6â µm globally, 57.1 and 83.7â µm superiorly, 55.2 and 79.0â µm inferiorly, 43.1 and 60.5â µm nasally, and 40.1 and 59.5â µm temporally. Corresponding VF losses ranged between -25.1 and -21.7â dB (Spectralis) and between -21.8 and -3.4â dB (RTVue). From CPM2, RNFL thinning reached horizontal asymptotes at VF losses between -18.0 and -10.7â dB (Spectralis) and between -12.1 and -2.5â dB (RTVue). There were no significant differences between postchange point residual layer thicknesses from CPM1 and CPM2 on Spectralis (37.0-50.8â µm vs 38.3-56.0â µm) and RTVue (60.6-80.5â µm vs 58.4-88.8â µm). CONCLUSIONS: Global RNFL thinning reaches the floor at a smaller VF loss level with Spectralis than with RTVue. The nasal and temporal quadrants retain thinner residual layers than superior and inferior quadrant RNFL. Measuring RNFL below their minimums will not yield useful clinical information.
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Glaucoma de Ángulo Abierto/fisiopatología , Fibras Nerviosas/patología , Enfermedades del Nervio Óptico/fisiopatología , Retina/fisiopatología , Células Ganglionares de la Retina/patología , Anciano , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Gonioscopía , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/diagnóstico , Tomografía de Coherencia Óptica , Tonometría Ocular , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Campos Visuales/fisiologíaRESUMEN
BACKGROUND: We evaluated focused training in lung hilar dissection with a reanimated porcine lung model in the boot camp setting. METHODS: A total of 64 first-year cardiothoracic surgical residents participated in four consecutive hours devoted to training in open hilar dissection as part of the Thoracic Surgical Directors Association boot camps. Each resident participated in two open hilar dissections. Component tasks were assessed on a 5-point rating scale for the first and second dissections. RESULTS: Immediate assessment performed after completion of the session showed improvements in all graded components. The mean total score on a 50-point scale improved significantly between the first and second repetition (36.03 ± 7.03 to 41.16 ± 6.95; p = 0.001). CONCLUSIONS: Focused massed (single-session) practice in the boot camp setting improved the ability of residents to perform hilar dissection on simulators using reanimated porcine lung models. Given these early successes in massed simulation-based surgical education, there is good reason to expect that deliberate and distributed practice on similar simulators would improve resident education in cardiothoracic surgery.
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Competencia Clínica , Simulación por Computador , Pulmón/cirugía , Procedimientos Quirúrgicos Torácicos/educación , Adulto , Animales , Curriculum , Educación de Postgrado en Medicina/métodos , Femenino , Humanos , Internado y Residencia , Masculino , Modelos Animales , Neumonectomía/educación , Porcinos , Análisis y Desempeño de TareasRESUMEN
Genetic studies of lung disease in cystic fibrosis (CF) are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2,061 patients representing the Canadian CF population, 1,137 extreme phenotype patients in the UNC/Case Western study, and 1,323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality-adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power, and avoiding possible distortions. This approach will facilitate large-scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF.