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PURPOSE: We describe three different approaches for lens management in cases of metallic IOFBs involving the posterior segment. METHODS: All consecutive posterior segment metallic IOFB cases from 2012 to 2023 at a single institution were included in this retrospective case series. Surgical outcomes and surgical videos are presented. RESULTS: A total of 25 metallic IOFB cases were included. In 9 cases, there was no significant lens involvement, therefore not requiring lens extraction at the time of IOFB removal. In 8 cases with traumatic cataract, lens extraction sparing the anterior lens capsule was performed with IOFB removal. In 8 cases, both lens extraction and lens capsule removal were required at the time of IOFB removal. CONCLUSION: We demonstrate our algorithm to capsular management in patients who present with IOFB with good visual outcomes in follow-up.
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Purpose: Using previously approved medications for new indications can expedite the lengthy and expensive drug development process. We describe a bioinformatics pipeline that integrates genomics and proteomics platforms to identify already-approved drugs that might be useful to treat diabetic retinopathy (DR). Methods: Proteomics analysis of vitreous humor samples from 12 patients undergoing pars plana vitrectomy for DR and a whole genome dataset (UKBiobank TOPMed-imputed) from 1330 individuals with DR and 395,155 controls were analyzed independently to identify biological pathways associated with DR. Common biological pathways shared between both datasets were further analyzed (STRING and REACTOME analyses) to identify target proteins for probable drug modulation. Curated target proteins were subsequently analyzed by the BindingDB database to identify chemical compounds they interact with. Identified chemical compounds were further curated through the Expasy SwissSimilarity database for already-approved drugs that interact with target proteins. Results: The pathways in each dataset (proteomics and genomics) converged in the upregulation of a previously unknown pathway involved in DR (RUNX2 signaling; constituents MMP-13 and LGALS3), with an emphasis on its role in angiogenesis and blood-retina barrier. Bioinformatics analysis identified U.S. Food and Drug Administration (FDA)-approved medications (raltitrexed, pemetrexed, glyburide, probenecid, clindamycin hydrochloride, and ticagrelor) that, in theory, may modulate this pathway. Conclusions: The bioinformatics pipeline described here identifies FDA-approved drugs that can be used for new alternative indications. These theoretical candidate drugs should be validated with experimental studies. Translational Relevance: Our study suggests possible drugs for DR treatment based on an integrated proteomics and genomics pipeline. This approach can potentially expedite the drug discovery process by identifying already-approved drugs that might be used for new indications.
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Diabetes Mellitus , Retinopatía Diabética , Estados Unidos , Humanos , Proteómica , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/genética , GenómicaRESUMEN
PURPOSE: To report a case of early postoperative scleral buckle slippage because of the dehiscence of scleral belt loop tunnels. METHOD: Case report. RESULTS: A 54-year-old woman presented with painful diplopia after a combination pars plana vitrectomy and scleral buckling procedure. Ocular movements were limited. Forced duction testing was restricted in all directions. Anterior slippage of the silicone band was suggested on computed tomography (CT) scans and was confirmed with surgical exploration. During surgery, it was found that thin-roofed scleral belt loop tunnels were dehisced in three quadrants leading to anterior slippage of the buckle. The displaced buckle was removed. Diplopia and pain resolved, and ocular motility improved immediately afterward. The retina remained attached at six months follow-up. A supplemental video summarizes the surgical findings and postoperative results. CONCLUSION: Spontaneous dehiscence of scleral belt loops may occur in thinly dissected scleral tunnels. Painful eye movement, diplopia, and a positive forced duction test should raise suspicion about a displaced scleral buckle. A CT scan may help with the diagnosis. Early diagnosis and immediate surgical intervention are needed to minimize patient discomfort and to improve long-term ocular motility.
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Dolor Intratable , Desprendimiento de Retina , Femenino , Humanos , Persona de Mediana Edad , Curvatura de la Esclerótica/efectos adversos , Curvatura de la Esclerótica/métodos , Diplopía/diagnóstico , Diplopía/etiología , Diplopía/cirugía , Dolor Intratable/complicaciones , Dolor Intratable/cirugía , Desprendimiento de Retina/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Vitrectomía/métodosRESUMEN
PURPOSE: To report a case of paracentral acute middle maculopathy in a pediatric patient with sickle cell trait. METHODS: The patient was evaluated with a comprehensive ophthalmic examination, optical coherence tomography (OCT), optical coherence tomography angiography, and fluorescein angiography. RESULTS: Acute loss of vision occurred immediately after an uneventful scleral buckling procedure for retinal detachment in a 16-year-old female. Retinal imaging studies confirmed the occurrence of paracentral acute middle maculopathy (PAMM), an ischemic condition characterized by infarction of the inner nuclear layer of the retina caused by hypoperfusion of the intermediate and deep capillary plexuses. Laboratory evaluation was only remarkable for sickle cell trait. Over a course of 3 months after the loss of vision, visual acuity improved from 20/1000 to 20/20, and OCT lesion resolved to a parafoveal area of inner and middle retinal layer thinning. Paracentral scotoma corresponding to the atrophic area persisted. CONCLUSION: Dehydration due to the presurgical non-per-os (NPO) status and transient increase in intraocular pressure during the buckling surgery may have predisposed this patient with sickle cell trait to a sickling event that caused localized ischemia in the middle retina's end-capillaries. Avoiding long NPO status, being mindful of transient intraocular pressure elevation during scleral buckling procedures, and presurgical hemoglobin electrophoresis in at-risk populations are recommended to prevent sickling attacks during retinal surgeries in individuals with sickle cell trait.
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Postoperative endophthalmitis caused by Rothia mucilaginosa, a gram-positive, coagulase-negative Micrococcaceae of the oropharyngeal flora, is rare and all previously reported intraocular implant-related cases have resulted in evisceration. R. mucilaginosa endophthalmitis has also not been described with any glaucoma implant device. Here, the authors report a case of subacute R. mucilaginosa endophthalmitis after phacoemulsification with implantation of an intraocular lens and the iStent inject (Glaukos). The infection was managed with intravitreal antibiotic injections, pars plana vitrectomy, and intraocular lens and iStent explantations. This was followed by a second pars plana vitrectomy and silicone oil tamponade for a tractional retinal detachment. Nine months after the initial presentation, vision in the affected eye was partially preserved, and the globe remained intact. R. mucilaginosa infections are associated with grave outcomes due to biofilm formation on infected implants, and as such, removal of infected implants is advised.
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Endoftalmitis , Micrococcaceae , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/etiología , Humanos , Presión Intraocular , Vitrectomía/efectos adversosRESUMEN
OBJECTIVE: To study the pattern of ophthalmic emergencies after Hurricane Harvey (HH). DESIGN: A retrospective chart review. SETTING: University of Texas Medical Branch (UTMB) in Galveston, Texas. PARTICIPANTS: Patients who presented to UTMB emergency room (ER) during the month before (47 patients) and the month after (39 patients) HH landfall and were seen by the ophthalmology service. MAIN OUTCOME MEASURES: Ocular injuries before and after hurricane landfall were classified by duration of symptoms (acute, subacute, and chronic), type of injury (hurricane related, traumatic, and infectious), region of injury (corneal/anterior segment, glaucoma, vitreoretinal, orbital-oculoplastic, and neuro-ophthalmologic), and level of involvement of injury (limited to eye, a manifestation of systemic disease, and associated with other bodily injuries). RESULTS: Patient demographics were similar before and after the storm. Three direct hurricane-related injuries from rescue and cleanup activities were identified. Only patients with acute/subacute ophthalmic injuries presented after HH. A trend for more traumatic injuries (from 28 to 41 percent of patients), corneal/anterior segment injuries (from 38 to 46 percent of patients), and vitreoretinal injuries (from 17 to 23 percent of patients) was observed after HH. A greater proportion of patients presented with localized injuries limited to the eye (from 49 to 56 percent of patients). Fewer patients had ocular manifestations of systemic disease (from 38 to 31 percent of patients) after HH. None of the changing trends reached statistical significance. CONCLUSIONS: The low incidence of hurricane-related injuries was likely due to victims' evacuation to surrounding nonimpacted areas and limited access to ER facilities within the affected area. ERs and eye care professionals should be prepared for future environmental disasters.
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Tormentas Ciclónicas , Oftalmología , Servicio de Urgencia en Hospital , Hospitalización , Humanos , Estudios RetrospectivosRESUMEN
The influence of Alzheimer's disease (AD) progression and severity on the structural and functional integrity of the cerebral vasculature is well recognized. The retina is an extension of the brain; thus, changes in retinal vascular features may serve as markers of AD cerebrovascular pathologies. However, differentiating normal aging-versus AD-induced retinal vascular changes is unresolved. Therefore, we compared and quantified changes in superficial (SVP), intermediate (IVP), and deep (DVP) retinal vascular plexuses in young, middle-age, and old triple transgenic mouse model of AD (3xT-AD) to the changes that occur in age-matched controls (C57BL/6j). We used immunostaining combined with a novel tissue optical clearing approach along with a computational tool for quantitative analysis of vascular network alterations (vessel length and density) in SVP, IVP, and DVP. All three layers had comparable structural features and densities in young 3xTg-AD and control animals. In controls, IVP and DVP densities decreased with aging (-14% to -32% change from young to old, p < 0.05), while no changes were observed in SVP. In contrast, vascular parameters in the transgenic group decreased in all three layers with aging (-12% to -49% change from young to old, p < 0.05). Furthermore, in the old group, SVP and DVP vascular parameters were lower in the transgenics compared to age-matched controls (p < 0.05). Our analysis demonstrates that normal aging and progression of AD lead to various degrees of vascular alterations in the retina. Specifically, compared to normal aging, changes in vascular features of SVP and DVP regions of the retina are accelerated during AD progression. Considering recent advances in the field of depth-resolved imaging of retinal capillary network and microangiography, noninvasive quantitative monitoring of changes in retinal vascular network parameters of SVP and DVP may serve as markers for diagnosis and staging of Alzheimer's disease and discriminating AD-induced vascular attenuation from age-related vasculopathy.
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Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Modelos Animales de Enfermedad , Enfermedades de la Retina/fisiopatología , Vasos Retinianos/patología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , Fosforilación , Enfermedades de la Retina/metabolismo , Vasos Retinianos/metabolismo , Proteínas tau/metabolismoRESUMEN
Neuronal and vascular structures of the retina in physiologic and pathologic conditions can be better visualized and characterized by using intact whole retina imaging techniques compared to conventional retinal flat mount preparations and sections. However, immunofluorescent imaging of intact whole retina is hindered by the opaque coatings of the eyeball, i.e., sclera, choroid, and retinal pigment epithelium (RPE) and the light scattering properties of retinal layers that prevent full thickness high resolution optical imaging. Chemical bleaching of the pigmented layers and tissue clearing protocols have been described to address these obstacles; however, currently described methods are not suitable for imaging endogenous fluorescent molecules such as green fluorescent protein (GFP) in intact whole retina. Other approaches bypassed this limitation by surgical removal of pigmented layers and the anterior segment of the eyeball allowing intact eye imaging, though the peripheral retina and hyaloid structures were disrupted. Presented here is an intact whole retina and vitreous immunofluorescent imaging protocol that combines surgical dissection of the sclera/choroid/retina pigment epithelium (RPE) layers with a modified tissue clearing method and light sheet fluorescent microscopy (LSFM). The new approach offers an unprecedented view of unperturbed vascular and neuronal elements of the retina as well as the vitreous and hyaloid vascular system in pathologic conditions.
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Coroides/cirugía , Disección/métodos , Microscopía Fluorescente/métodos , Procedimientos Quirúrgicos Oftalmológicos/métodos , Retina/cirugía , Esclerótica/cirugía , Animales , Receptor 1 de Quimiocinas CX3C/metabolismo , Coroides/diagnóstico por imagen , Coroides/metabolismo , Ratones , Retina/diagnóstico por imagen , Retina/metabolismo , Esclerótica/diagnóstico por imagen , Esclerótica/metabolismoRESUMEN
Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The 'COVID-19 lockdown' was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.
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COVID-19/epidemiología , Enfermedades de la Retina/tratamiento farmacológico , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , COVID-19/psicología , Retinopatía Diabética/tratamiento farmacológico , Femenino , Humanos , Edema Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Pandemias/estadística & datos numéricos , Proyectos Piloto , Cuarentena/métodos , Cuarentena/psicología , Oclusión de la Vena Retiniana/tratamiento farmacológico , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Agudeza Visual/efectos de los fármacosRESUMEN
Due to increasing the use of antifungal drugs, the development of resistance in some Candida species and the consumption of the side effects of chemical drugs, use of new resources, especially medicinal plants are very important. The aim of this study was to investigate of anti-Candida and antioxidant activities of hydroalcohlic extract from leaves of Rumex obtusifolius. The Rumex obtusifolius Leaves were extracted using Ethyl acetate; methanol and distilled water (6:3:1) by Sox helet system. The hydroalcoholic extraction of Rumex obtusifolius was evaluated for their antioxidant capacities using in vitro methods; including 1-diphenyl-2-picrylhydrazyl radical scavenging, ß-Carotene bleaching test and reducing power assay. Total free phenolics, total flavonoids content and as well as the antifungal activity were also examined. The components of extract were analyzed via GC-Mass instrument. The extract was screened against 40 isolated pathogenic Candida species such as C. albicans and C. glabrata through agar diffusion method. The hydroalcoholic extract can strongly scavenge DPPH radical and its antioxidant capacities which are high correlated with the total free Phenolics and total flavonoids. Also, the extract had high capability inhibition of linoleic acid oxidation and the reducing ability. This study revealed a higher antioxidant capacity in the leaves of Rumex obtusifolius compared with control groups. The minimum inhibitory concentration values within 24 and 48 hours were 200-250µg/µL for C. albicans and 250µg/µL for C. glabrata. The extract includes high amounts of phenolic compounds and antioxidant activity showing is significant. Also, the results confirmed that leaves extract had a potential in anti-Candida activity and suggesting that it could be utilized as a potential source of herbal medicine drugs and natural antioxidants to prevent diseases associated with free radical, anti-fungal disease and food preservation.
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Antifúngicos/farmacología , Antioxidantes/farmacología , Candida/efectos de los fármacos , Extractos Vegetales/farmacología , Rumex/química , Antifúngicos/química , Antioxidantes/química , Evaluación Preclínica de Medicamentos , Flavonoides/análisis , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/análisis , Extractos Vegetales/química , Hojas de la Planta/química , Polifenoles/análisis , beta Caroteno/químicaRESUMEN
In this study, for the first time polymeric nanocomposite (NC) films of poly(vinyl alcohol)/SiO2@bovine serum albumin (PVA/SiO2@BSA) were synthesized by solution casting method under facile and fast method of sonication. In this regard, SiO2 nanoparticles (NPs) were modified by BSA, at room temperature by using phosphate buffer and ultrasonic-assisted method. Then, PVA/SiO2@BSA NCs were prepared by insertion of variant amount (3, 6 and 9wt%) of SiO2@BSA into the PVA matrix, under ultrasonic irradiation. The morphological traits of the NCs were surveyed by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction and field emission scanning electron microscopy. It was detected that NPs incorporation didn't remarkably affect the crystallinity and morphology of the NCs. TEM images indicated that the inserted NPs have good diffusions in the PVA matrix, and their embedment in the matrix significantly upgraded its thermal, optical and mechanical behaviors. The tensile strength showed more than 2-fold increase and the thermal stability exhibited about 37% enhancement that was higher, in comparison with those of the similar NCs. This showed that the prepared NCs can have potential application in food packaging.∗∗∗.
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Fenómenos Químicos , Nanocompuestos/química , Alcohol Polivinílico/química , Albúmina Sérica Bovina/química , Dióxido de Silicio/química , Sonicación , Animales , Bovinos , Fenómenos Mecánicos , Temperatura , HumectabilidadRESUMEN
A 62-year-old female who was legally blind secondary to retinitis pigmentosa (RP) developed new positive visual phenomena (PVP) ("visual storms") following implantation of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, CA). The potential mechanisms for the exacerbating PVP or hallucinatory release phenomena are proposed. Clinicians should be aware of these visual phenomena in patients with RP and the potential for worsening of or de novo development of PVP in patients considering the Argus II implant. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1022-1025.].
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Implantación de Prótesis/métodos , Retina/cirugía , Retinitis Pigmentosa/complicaciones , Baja Visión/cirugía , Agudeza Visual , Prótesis Visuales , Electrorretinografía , Femenino , Humanos , Persona de Mediana Edad , Oftalmoscopía , Diseño de Prótesis , Retina/diagnóstico por imagen , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/cirugía , Baja Visión/etiología , Baja Visión/fisiopatologíaAsunto(s)
Embolización Terapéutica/efectos adversos , Cuerpos Extraños en el Ojo/etiología , Metales , Arteria Retiniana/patología , Hemorragia Subaracnoidea/terapia , Trastornos de la Visión/etiología , Adulto , Embolización Terapéutica/instrumentación , Cuerpos Extraños en el Ojo/diagnóstico por imagen , Femenino , Angiografía con Fluoresceína , Humanos , Arteria Retiniana/diagnóstico por imagen , Tomografía de Coherencia Óptica , Trastornos de la Visión/diagnósticoRESUMEN
In this work, SiO2 nanoparticles (NPs) were modified with bovine serum albumin (BSA) under ultrasound irradiations as a green and fast route to achieve their good dispersion. Subsequently, different weight percentages of the modified NPs (3, 6, and 9wt%) were incorporated in poly(vinyl chloride) (PVC) as the matrix. Thermogravimetric analysis of the SiO2-BSA NPs indicated that 12wt% of the modifier was loaded on the surface of SiO2 NPs. Encapsulation of the SiO2-BSA resulted in a meaningful improvement in the optical, mechanical and thermal characteristics of the prepared PVC nanocomposites (NCs). X-ray diffraction (XRD) patterns for the PVC/SiO2-BSA NCs showed a crystalline behavior for the NC with 6wt% of the SiO2-BSA originated from the phosphate buffer on the NPs. Water contact angle of the PVC/SiO2-BSA NCs showed that the hydrophilicity enhanced with increasing of the NPs contents.
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Nanocompuestos/química , Nanopartículas/química , Cloruro de Polivinilo/química , Albúmina Sérica Bovina/química , Dióxido de Silicio/química , Ondas Ultrasónicas , Animales , Bovinos , Fenómenos Mecánicos , Fenómenos Ópticos , Agua/químicaRESUMEN
PURPOSE: To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. METHODS: Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. RESULTS: Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. CONCLUSIONS: These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.
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Células Madre Embrionarias/citología , Polímeros , Degeneración Retiniana/patología , Epitelio Pigmentado de la Retina/patología , Trasplante de Células Madre , Animales , Recuento de Células , Supervivencia Celular , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Ratas , Ratas Mutantes , Degeneración Retiniana/cirugía , Epitelio Pigmentado de la Retina/fisiopatología , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To evaluate the outcomes of ruthenium-106 ((106)Ru) brachytherapy in terms of radiation parameters in patients with thick uveal melanomas. MATERIAL AND METHODS: Medical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm) uveal melanoma treated with (106)Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA), and treatment-related complications were assessed. RESULTS: Fifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD). Mean radiation dose to tumor apex and to sclera were 71 (± 19.2) Gy and 1269 (± 168.2) Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14) Gy/h and 6.44 (± 1.50) Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9) mm decreased to 4.5 (± 1.6) mm, 3.4 (± 1.4) mm, and 3.0 (± 1.46) mm at 12, 24, and 48 months after brachytherapy (p = 0.03). Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8%) patients. Mean Log MAR (magnification requirement) visual acuity declined from 0.75 (± 0.63) to 0.94 (± 0.5) (p = 0.04). Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04). Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes. CONCLUSIONS: Thick uveal melanomas are amenable to (106)Ru brachytherapy with less than recommended apex radiation dose and dose rates.
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We investigated the spatial variation of vitreous oxygen consumption in enucleated porcine eyes. A custom made oxygen source was fabricated that could be localized to either the mid or posterior vitreous cavity and steady state vitreous oxygen tension was measured as a function of distance from the source using a commercially available probe. The reaction rate constant of ascorbate oxidation was estimated ex vivo by measuring the change in oxygen tension over time using vitreous harvested from porcine eyes. Vitreous ascorbate from mid and posterior vitreous was measured spectrophotometrically. When the oxygen source was placed in either the mid-vitreous (N = 6) or the posterior vitreous (N = 6), we measured a statistically significant decrease in vitreous oxygen tension as a function of distance from the oxygen source when compared to control experiments without an oxygen source; (p<0.005 for mid-vitreous and p<0.018 for posterior vitreous at all distances). The mid-vitreous oxygen tension change was significantly different from the posterior vitreous oxygen tension change at 2 and 3mm distances from the respective oxygen source (p<0.001). We also found a statistically significant lower concentration of ascorbate in the mid-vitreous as compared to posterior vitreous (p = 0.02). We determined the reaction rate constant, k = 1.61 M(-1) s(-1) ± 0.708 M(-1) s(-1) (SE), of the oxidation of ascorbate which was modeled following a second order rate equation. Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid-vitreous. We also show spatial variations in vitreous ascorbate concentration.
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Consumo de Oxígeno , Oxígeno/metabolismo , Cuerpo Vítreo/metabolismo , Animales , Ácido Ascórbico/análisis , Ácido Ascórbico/metabolismo , Cinética , Oxígeno/análisis , PorcinosRESUMEN
Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial-mesenchymal transition (EMT) of retinal pigment epithelium cells. αB-crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of αB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in αB-crystallin knockout mice compared with wild-type mice. αB-crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of αB-crystallin induced EMT, whereas suppression of αB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-ß2-induced EMT was further enhanced by overexpression of αB-crystallin but was inhibited by suppression of αB-crystallin. Silencing of αB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 up-regulated αB-crystallin, and its EMT induction was inhibited by knockdown of αB-crystallin. Furthermore, inhibition of αB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of αB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, αB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration.
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Neovascularización Coroidal/metabolismo , Transición Epitelial-Mesenquimal/genética , Fibrosis/metabolismo , Degeneración Macular/patología , Epitelio Pigmentado de la Retina/metabolismo , Cadena B de alfa-Cristalina/metabolismo , Animales , Neovascularización Coroidal/genética , Fibronectinas/metabolismo , Humanos , Degeneración Macular/genética , Masculino , Ratones Noqueados , Epitelio Pigmentado de la Retina/patología , Cadena B de alfa-Cristalina/genéticaRESUMEN
Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and ocular trauma, and its recurrence may lead to irreversible vision loss. Epithelial to mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a critical step in the pathogenesis of PVR, which is characterized by fibrotic membrane formation and traction retinal detachment. In this study, we investigated the potential impact of resveratrol (RESV) on EMT and the fibrotic process in cultured RPE cells and further examined the preventive effect of RESV on PVR development using a rabbit model of PVR. We found that RESV induces mesenchymal to epithelial transition (MET) and inhibits transforming growth factor-ß2(TGF-ß2)-induced EMT of RPE cells by deacetylating SMAD4. The effect of RESV on MET was dependent on sirtuin1 activation. RESV suppressed proliferation, migration and fibronectin synthesis induced by platelet-derived growth factor-BB or TGF-ß2. In vivo, RESV inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that RESV reduced fibrotic membrane formation and decreased α-SMA expression in the epiretinal membranes. These results suggest the potential use of RESV as a therapeutic agent to prevent the development of PVR by targeting EMT of RPE.