Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 212
Filtrar
1.
Methods Mol Biol ; 2858: 159-172, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39433675

RESUMEN

Aqueous humor angiography, or aqueous angiography, is an anterior segment imaging technique capable of visualizing the conventional/trabecular aqueous humor outflow pathways. As a translational technique, it is applicable for in vivo imaging in living subjects and ex vivo imaging using whole-globe preparations or anterior segment perfusion setups. Excellent spatial and temporal resolution has enabled insights into the segmental distribution of aqueous humor outflow in physiological conditions as well as after trabecular bypass surgery. In this chapter, we thoroughly describe aqueous humor angiography in various experimental setups. The necessary materials for different settings and their application for in vivo and ex vivo experiments as well as notes on dye choice, dye sequences, and special considerations on performing aqueous humor angiography during surgery are presented.


Asunto(s)
Humor Acuoso , Humor Acuoso/metabolismo , Humanos , Animales , Angiografía/métodos , Angiografía con Fluoresceína/métodos , Malla Trabecular/diagnóstico por imagen , Malla Trabecular/metabolismo
2.
J Inj Violence Res ; 16(2)2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39427255

RESUMEN

BACKGROUND: Mass shootings represent a persistent public health crisis. Prior studies have linked social determinants of health (SDOH) to the phenomenon of gun violence, but there remain limited analyses on mass shooting events specifically. METHODS: Mass shooting events from 2014-2019 were recorded from the Gun Violence Archive. State-level data regarding population, ATF registered weapons, federal firearm licensees and several SDOHs (poverty, unemployment and educational attainment) were collected from publicly-available US governmental databases. Giffords Law Center rankings were used to assess the relative strictness of each state's gun laws. Gun ownership rates were obtained from the RAND Corporation. Bivariate analyses compared each SDOH, as well as ATF registered weapons, Giffords Center ranking and gun ownership rates, to the death rate, injury rate, and combined injury/death rate from mass shootings in each state. All associations were evaluated via Pearson's Rho. Slope and p-values were analyzed, with a threshold significance value of p less than 0.05. RESULTS: Unadjusted analysis revealed poor mental health, decreased educational attainment and increased unemployment to all be associated with an increased risk of mass shooting-related injury or death. Adjusted analysis revealed fewer firearm regulations, higher gun ownership, lack of handgun magazine restrictions and lack of long-gun registration requirements were associated with an increased risk of mass-shooting death. Similarly, adjusted analysis revealed lack of handgun permit requirements to be associated with both an increased risk of mass shooting-related injury and combined risk of injury/death. CONCLUSIONS: This study revealed associations between multiple SDOH and firearm restrictions with morbidity due to mass shooting events.

3.
bioRxiv ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39386690

RESUMEN

Purpose: To use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration. Methods: Anterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes. Results: Circumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045). Conclusion: High-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.

4.
J Glaucoma ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39283690

RESUMEN

PURPOSE: To characterize the presence of amyloid-beta (Aß) in human glaucoma retina and to test identification of retinal Aß using a novel fluorescent Aß-binding small molecule (AMDX-2011). METHODS: Post-mortem human eyes with (n=4) and without (n=4) glaucoma were acquired from an eye bank. Retinas were dissected, flat-mounted, and fixed. Using the flat-mounts, immunofluorescence was performed against Aß, AMDX-2011 staining was conducted, and images were acquired using fluorescence microscopy. RESULTS: Fluorescence microscopy demonstrated presence of Aß signal that co-localized with AMDX-2011 staining in glaucoma retina. Co-labeled puncta appeared in all quadrants of the retina, including retina temporal to the optic nerve. The puncta were mainly located within the inner layers of the retina. Glaucoma retinas had more co-labeled puncta than control retinas in all locations (P = 0.002-0.02). Co-labeled puncta were also larger in the superior quadrant of glaucoma compared to control retinas (P = 0.02). CONCLUSIONS: Aß was detected in human glaucomatous retina, and its distribution was mapped. AMDX-2011 identification of Aß may lead to future diagnostic tests aimed at detecting Aß in glaucoma patients.

6.
Transplant Proc ; 56(6): 1378-1384, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39025730

RESUMEN

INTRODUCTION: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. MATERIALS AND METHODS: We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). CONCLUSIONS: A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.


Asunto(s)
Disfunción Cognitiva , Encefalopatía Hepática , Cirrosis Hepática , Medición de Resultados Informados por el Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Estudios Prospectivos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/epidemiología , Trasplante de Hígado , Anciano , Hospitalización , Pruebas Neuropsicológicas , Cognición
7.
bioRxiv ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38826217

RESUMEN

Imaging complex, non-planar anatomies with optical coherence tomography (OCT) is limited by the optical field of view (FOV) in a single volumetric acquisition. Combining linear mechanical translation with OCT extends the FOV but suffers from inflexibility in imaging non-planar anatomies. We report the freeform robotic OCT to fill this gap. To address challenges in volumetric reconstruction associated with the robotic movement accuracy being two orders of magnitudes worse than OCT imaging resolution, we developed a volumetric registration algorithm based on simultaneous localization and mapping (SLAM) to overcome this limitation. We imaged the entire aqueous humor outflow pathway, whose imaging has the potential to customize glaucoma surgeries but is typically constrained by the FOV, circumferentially in mice as a test. We acquired volumetric OCT data at different robotic poses and reconstructed the entire anterior segment of the eye. The reconstructed volumes showed heterogeneous Schlemm's canal (SC) morphology in the reconstructed anterior segment and revealed a segmental nature in the circumferential distribution of collector channels (CC) with spatial features as small as a few micrometers.

8.
Invest Ophthalmol Vis Sci ; 65(5): 32, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38771570

RESUMEN

Purpose: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. Methods: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). Results: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P < 0.001, P < 0.001) and vs. control (P < 0.001, P < 0.001). After 30 days, the VEGF-C combined with 5-FU condition resulted in longer bleb survival compared with 5-FU (P = 0.025), VEGF-C (P < 0.001), and control (P < 0.001). Only the VEGF-C combined with 5-FU condition showed a negative correlation between IOP and time that was statistically significant (r = -0.533; P = 0.034). Anterior segment OCT and histology demonstrated larger blebs for the VEGF-C combined with 5-FU condition. Only conditions including VEGF-C led to increased expression of lymphatic markers (LYVE-1, P < 0.001-0.008 and podoplanin, P = 0.002-0.011). Expression of CD31 was not different between the groups (P = 0.978). Conclusions: Adding VEGF-C lymphoproliferation to standard antimetabolite treatment improved rabbit GFS success and may suggest a future strategy to improve human GFSs.


Asunto(s)
Modelos Animales de Enfermedad , Fluorouracilo , Glaucoma , Presión Intraocular , Trabeculectomía , Factor C de Crecimiento Endotelial Vascular , Animales , Conejos , Fluorouracilo/uso terapéutico , Fluorouracilo/farmacología , Glaucoma/cirugía , Glaucoma/fisiopatología , Glaucoma/tratamiento farmacológico , Factor C de Crecimiento Endotelial Vascular/metabolismo , Trabeculectomía/métodos , Presión Intraocular/fisiología , Antimetabolitos/farmacología , Antimetabolitos/uso terapéutico , Tomografía de Coherencia Óptica , Conjuntiva , ARN Mensajero/genética
9.
Indian J Ophthalmol ; 72(Suppl 4): S553-S560, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38622841

RESUMEN

Aqueous humor outflow (AHO) pathways are the main site of resistance causing elevated intraocular pressure in glaucoma, especially primary open-angle glaucoma patients. With the recently introduced technique of aqueous angiography (AA); functional, real time assessment of AHO from proximal (trabecuar meshwork) to distal pathways under physiological conditions has been made possible. AHO pathways are segmental, and AA can identify high-flow region (increased angiographic signals) and low flow region (decreased angiographic signals) in an individual. With the introduction of canal-based minimally invasive glaucoma surgeries (MIGS), the assessment of AHO can help guide the placement of stents/incisions during MIGS procedures. This can allow individualized and targeted MIGS procedures in glaucoma patients for better results. Based on the density of AHO pathways visualized on AA, surgeons can decide whether to perform MIGS or conventional glaucoma surgery for improved outcomes for the patient. Immediate intraoperative assessment for functionality of the MIGS procedure performed is possible with AA, allowing for surgical adjustments of MIGS procedure in the same sitting, if needed. This review provides a summary of the studies performed with AA to date, with a special focus on Indian patients. It covers the basics and clinical applications of AA for improving surgical outcomes in glaucoma patients.


Asunto(s)
Humor Acuoso , Angiografía con Fluoresceína , Presión Intraocular , Humanos , Humor Acuoso/metabolismo , Presión Intraocular/fisiología , Angiografía con Fluoresceína/métodos , Glaucoma/cirugía , Glaucoma/diagnóstico , Glaucoma/fisiopatología , Fondo de Ojo , Malla Trabecular/diagnóstico por imagen , Malla Trabecular/cirugía
10.
Nat Chem Biol ; 20(10): 1260-1271, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38528120

RESUMEN

Exportin-1 (XPO1/CRM1) plays a central role in the nuclear-to-cytoplasmic transport of hundreds of proteins and contributes to other cellular processes, such as centrosome duplication. Small molecules targeting XPO1 induce cytotoxicity, and selinexor was approved by the Food and Drug Administration in 2019 as a cancer chemotherapy for relapsed multiple myeloma. Here, we describe a cell-type-dependent chromatin-binding function for XPO1 that is essential for the chromatin occupancy of NFAT transcription factors and thus the appropriate activation of T cells. Additionally, we establish a class of XPO1-targeting small molecules capable of disrupting the chromatin binding of XPO1 without perturbing nuclear export or inducing cytotoxicity. This work defines a broad transcription regulatory role for XPO1 that is essential for T cell activation as well as a new class of XPO1 modulators to enable therapeutic targeting of XPO1 beyond oncology including in T cell-driven autoimmune disorders.


Asunto(s)
Cromatina , Proteína Exportina 1 , Carioferinas , Activación de Linfocitos , Factores de Transcripción NFATC , Receptores Citoplasmáticos y Nucleares , Linfocitos T , Humanos , Receptores Citoplasmáticos y Nucleares/metabolismo , Carioferinas/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T/inmunología , Cromatina/metabolismo , Factores de Transcripción NFATC/metabolismo , Activación de Linfocitos/efectos de los fármacos , Células Jurkat , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Animales , Unión Proteica
11.
Transl Vis Sci Technol ; 13(3): 23, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38536170

RESUMEN

Purpose: To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Methods: Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Results: Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Conclusions: Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Translational Relevance: Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.


Asunto(s)
Catarata , Glaucoma , Adulto , Humanos , Niño , Humor Acuoso , Cámara Anterior , Angiografía
12.
Acta Ophthalmol ; 102(5): e797-e804, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38306110

RESUMEN

PURPOSE: Bleb failure is a common complication after glaucoma filtration surgery. Different bleb classification schemes incorporating filtration bleb vascularization have been proposed, but the reported correlation with intraocular pressure (IOP) has been variable, possibly because of subjective vascularization grading. The purpose of the present study was to evaluate bleb vascularization after Preserflo Microshunt (PM) implantation using anterior segment OCT-angiography (AS-OCTA) as a biomarker for bleb failure. METHODS: Twenty-three eyes of twenty-three patients underwent PM implantation. Up to 12 months after surgery PM scleral passage-centred AS-OCTA measurements (PLEX Elite 9000) for bleb-vessel density (BVD) determination were performed and IOP as well as necessity for surgical revisions (needling and open revision) were documented. After multi-step image analysis (region of interest definition, artefact removal, binarization, BVD calculation), the predictive value of early postoperative BVD for surgical revisions was assessed using logistic regression modelling. RESULTS: Baseline IOP (23.57 ± 7.75 mmHg) decreased significantly to 8.30 ± 2.12, 9.17 ± 2.33 and 11.70 ± 4.40 mmHg after 1, 2 and 4 week(s), and 13.48 ± 5.83, 11.87 ± 4.49, 12.30 ± 6.65, 11.87 ± 3.11 and 13.05 ± 4.12 mmHg after 2, 3, 6, 9 and 12 month(s), respectively (p < 0.001). Nine patients (39%) needed surgical revisions after a median time of 2 months. Bleb vessel densities at 2 and 4 weeks were significantly associated with future surgical revisions upon logistic regression analysis (2 W/4 W likelihood-ratio test p-value: 0.0244/0.0098; 2 W/4 W area under the receiver operating characteristics curve: 0.796/0.909). CONCLUSION: Filtration bleb vessel density can be determined using AS-OCTA in the early postoperative period and is predictive for bleb failure after PM implantation.


Asunto(s)
Presión Intraocular , Reoperación , Tomografía de Coherencia Óptica , Humanos , Femenino , Masculino , Presión Intraocular/fisiología , Anciano , Tomografía de Coherencia Óptica/métodos , Persona de Mediana Edad , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Glaucoma/cirugía , Glaucoma/fisiopatología , Glaucoma/diagnóstico , Implantes de Drenaje de Glaucoma/efectos adversos , Cirugía Filtrante/métodos , Estudios Prospectivos , Fondo de Ojo , Conjuntiva/irrigación sanguínea , Conjuntiva/cirugía , Densidad Microvascular
13.
Transl Vis Sci Technol ; 13(2): 11, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38359019

RESUMEN

Background: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Methods: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. Results: AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. Conclusions: AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. Translational Relevance: AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.


Asunto(s)
Neuropatías Amiloides Familiares , Placa Amiloide , Humanos , Animales , Porcinos , Anciano , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/tratamiento farmacológico , Neuropatías Amiloides Familiares/genética , Rojo Congo/uso terapéutico , Conjuntiva
14.
J Clin Invest ; 134(5)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38194275

RESUMEN

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.


Asunto(s)
Neoplasias Colorrectales , Trampas Extracelulares , Humanos , Animales , Ratones , Modelos Animales de Enfermedad , Fosfatidilinositol 3-Quinasa Clase I , Combinación de Medicamentos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética
16.
Indian J Ophthalmol ; 72(3): 452-454, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38099380

RESUMEN

Corneal haze, due to edema or opacity, is a major contraindication for performing ab interno angle surgeries such as goniotomy in children with primary congenital glaucoma (PCG), despite otherwise favorable surgical outcomes expected in these patients. In this case series involving patients of PCG with moderate corneal haze, the authors describe a technique for performing goniotomy in cases with compromised visibility by using indocyanine green (ICG) to aid in the visualization of angle structures. The authors used 0.2% ICG intracamerally, which stained the anterior and posterior trabecular meshwork (TM) with different intensities, before proceeding with goniotomy. The junction between the two zones was discernible due to the contrast imparted by ICG staining, despite poor visibility, allowing the surgeon to incise the TM at the correct site. The possibility of performing goniotomy in such patients with the help of ICG can revolutionize our surgical approach to patients with PCG and corneal edema.


Asunto(s)
Opacidad de la Córnea , Glaucoma , Trabeculectomía , Niño , Humanos , Trabeculectomía/métodos , Glaucoma/cirugía , Glaucoma/etiología , Verde de Indocianina , Malla Trabecular/cirugía , Opacidad de la Córnea/cirugía , Córnea/cirugía , Presión Intraocular
17.
Oncoimmunology ; 12(1): 2281179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38126029

RESUMEN

Functional effector T cells in the tumor microenvironment (TME) are critical for successful anti-tumor responses. T cell anti-tumor function is dependent on their ability to differentiate from a naïve state, infiltrate into the tumor site, and exert cytotoxic functions. The factors dictating whether a particular T cell can successfully undergo these processes during tumor challenge are not yet completely understood. Piezo1 is a mechanosensitive cation channel with high expression on both CD4+ and CD8+ T cells. Previous studies have demonstrated that Piezo1 optimizes T cell activation and restrains the CD4+ regulatory T cell (Treg) pool in vitro and under inflammatory conditions in vivo. However, little is known about the role Piezo1 plays on CD4+ and CD8+ T cells in cancer. We hypothesized that disruption of Piezo1 on T cells impairs anti-tumor immunity in vivo by hindering inflammatory T cell responses. We challenged mice with T cell Piezo1 deletion (P1KO) with tumor models dependent on T cells for immune rejection. P1KO mice had the more aggressive tumors, higher tumor growth rates and were unresponsive to immune-mediated therapeutic interventions. We observed a decreased CD4:CD8 ratio in both the secondary lymphoid organs and TME of P1KO mice that correlated inversely with tumor size. Poor CD4+ helper T cell responses underpinned the immunodeficient phenotype of P1KO mice. Wild type CD8+ T cells are sub-optimally activated in vivo with P1KO CD4+ T cells, taking on a CD25loPD-1hi phenotype. Together, our results suggest that Piezo1 optimizes T cell activation in the context of a tumor response.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Ratones , Linfocitos T CD8-positivos , Linfocitos T Reguladores/metabolismo , Microambiente Tumoral , Canales Iónicos/genética , Canales Iónicos/metabolismo
18.
19.
J Glaucoma ; 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37851964

RESUMEN

PRECIS: Trabecular meshwork pigmentation is not correlated with angiographically determined aqueous humor outflow in an ex-vivo perfusion model using human eyes. PURPOSE: To evaluate whether segmental trabecular meshwork (TM) pigmentation is correlated to segmental aqueous humor outflow (AHO) in human eyes. METHODS: Post-mortem human eyes were acquired, and anterior segments were dissected. TM pigmentation was photographed 360-degrees around the eye. The anterior segments were then mounted onto a perfusion apparatus and perfused with DPBS until a stabile baseline outflow facility was achieved. Aqueous angiography (AHO angiography) was performed using fluorescein (2%), and segmental AHO was documented around the limbus using an angiographic camera (Spectralis HRA+OCT). Circumferential and nasal TM pigmentation were compared to respective angiographic outflow imaging using a Pearson's correlation analysis. RESULTS: Segmental TM pigment distribution and segmental AHO were seen. TM pigment was statistically greatest in the inferior quadrant. AHO angiographic outflow was numerically greatest in the nasal quadrant, but this was not statistically significant. No statistically significant correlation was observed (r=-0.083, P=0.06) between segmental TM pigmentation and segmental AHO angiographic signal. Analyzing just the nasal quadrant, a significant weak negative correlation was found (r=-0.296, P=0.001). DISCUSSION: Segmental TM pigmentation circumferentially around the eye is not a good proxy for segmental AHO circumferentially around the eye and should not be used to guide trabecular minimally invasive glaucoma surgeries.

20.
Br J Ophthalmol ; 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798075

RESUMEN

AIM: To perform an independent validation of deep learning (DL) algorithms for automated scleral spur detection and measurement of scleral spur-based biometric parameters in anterior segment optical coherence tomography (AS-OCT) images. METHODS: Patients receiving routine eye care underwent AS-OCT imaging using the ANTERION OCT system (Heidelberg Engineering, Heidelberg, Germany). Scleral spur locations were marked by three human graders (reference, expert and novice) and predicted using DL algorithms developed by Heidelberg Engineering that prioritise a false positive rate <4% (FPR4) or true positive rate >95% (TPR95). Performance of human graders and DL algorithms were evaluated based on agreement of scleral spur locations and biometric measurements with the reference grader. RESULTS: 1308 AS-OCT images were obtained from 117 participants. Median differences in scleral spur locations from reference locations were significantly smaller (p<0.001) for the FPR4 (52.6±48.6 µm) and TPR95 (55.5±50.6 µm) algorithms compared with the expert (61.1±65.7 µm) and novice (79.4±74.9 µm) graders. Intergrader reproducibility of biometric measurements was excellent overall for all four (intraclass correlation coefficient range 0.918-0.997). Intergrader reproducibility of the expert grader (0.567-0.965) and DL algorithms (0.746-0.979) exceeded that of the novice grader (0.146-0.929) for images with narrow angles defined by OCT measurement of angle opening distance 500 µm anterior to the scleral spur (AOD500)<150 µm. CONCLUSIONS: DL algorithms on the ANTERION approximate expert-level measurement of scleral spur-based biometric parameters in an independent patient population. These algorithms could enhance clinical utility of AS-OCT imaging, especially for evaluating patients with angle closure and performing intraocular lens calculations.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA