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OBJECTIVE: To determine the efficacy and pharmacokinetics of intraocularly delivered non-steroidal anti-inflammatory drugs in an animal model of ocular inflammation. METHODS: Lipopolysaccharide was injected into the vitreous of rabbit eyes to induce inflammation. Treated eyes were injected with 3 mg of ketorolac or 0.3 mg of diclofenac. Twenty-four hours later, total leucocyte concentrations and prostaglandin E2 concentrations were determined. For intraocular pharmacokinetics, 0.1 ml of ketorolac (3 mg) and 0.1 ml of diclofenac (0.3 mg) were injected into rabbit eyes. Reverse-phase high-performance liquid chromatography was used to analyse drug levels within the retina/choroid at 0.25 (15 min), 1, 2, 4, 24, and 48 h after injection. RESULTS: Eyes treated with ketorolac and diclofenac demonstrated reduced aqueous leucocyte concentrations of 62% and 64% respectively, compared with untreated controls (p<0.05). Ketorolac and diclofenac reduced aqueous prostaglandin E2 levels by 85% (p<0.005) and 59% (p<0.005), respectively. Ketorolac and diclofenac achieved a peak vitreous concentration of 234 and 73 microg/ml, respectively. After 48 h, ketorolac was barely detectable (0.06 microg/ml) in the vitreous, and diclofenac was undetectable. The peak concentration of each drug in the retina/choroid was 201 microg/g for ketorolac and 4.1 microg/g for diclofenac. Both drugs were undetectable in the retina/choroid after 48 h. CONCLUSIONS: Both ketorolac and diclofenac have potent anti-inflammatory effects after intraocular injection. Pharmacokinetic analysis demonstrated good penetration into the retina/choroid but rapid clearance by 48 h.
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Antiinflamatorios no Esteroideos/uso terapéutico , Uveítis/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Cromatografía Líquida de Alta Presión , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Diclofenaco/uso terapéutico , Dinoprostona/biosíntesis , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Inyecciones , Ketorolaco/administración & dosificación , Ketorolaco/farmacocinética , Ketorolaco/uso terapéutico , Lipopolisacáridos , Masculino , Conejos , Resultado del Tratamiento , Uveítis/inducido químicamente , Uveítis/metabolismo , Cuerpo Vítreo/metabolismoRESUMEN
Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine-glycine-aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model.
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Neovascularización Coroidal/terapia , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Nanopartículas/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Química Física , Neovascularización Coroidal/etiología , Neovascularización Coroidal/patología , Modelos Animales de Enfermedad , Inyecciones Intravenosas , Rayos Láser , Masculino , Microscopía Confocal , Nanopartículas/química , Oligopéptidos/farmacología , Ratas , Ratas Endogámicas BN , Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Distribución Tisular , Transferrina/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The purpose of this review is to discuss the recently published literature related to corneal endothelial toxicity and safety. We discuss postoperative complications, such as toxic endothelial cell destruction syndrome and toxic anterior segment syndrome, that cause significant injury to the patient and anxiety to the physician. Additionally, we review recent papers related to intraocular medications, preservatives, and devices, including antibiotics, anesthetics, viscoelastics, and enzymatic sterilization detergents, that have potentially toxic effects on the corneal endothelium.
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Enfermedades de la Córnea/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Endotelio Corneal/efectos de los fármacos , Procedimientos Quirúrgicos Oftalmológicos , Humanos , SeguridadRESUMEN
PURPOSE: Gram-negative bacterial infections of the eye can lead to corneal bacterial keratitis, visual impairment, and blindness. Many of these pathologic changes may be mediated by bacterially derived products such as lipopolysaccharide (LPS). In this investigation, it has been established for the first time that human corneal cells are capable of expressing the functional LPS receptor complex proteins, CD14 and Toll-like receptor 4 (TLR4). METHODS: CD14 and TLR4 mRNA expression in human corneal cells was determined by RT-PCR and Northern blot analysis, and cell surface expression of these proteins was measured by flow cytometry. LPS-mediated corneal cell activation was determined by measuring intracellular calcium mobilization. Cellular cytokine and chemokine secretion in response to LPS was measured by ELISA. The expression and localization of CD14 in whole human cornea was determined by immunohistochemistry. RESULTS: Human corneal epithelial, stromal, and endothelial cells expressed CD14 mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a rapid intracellular calcium response and the secretion of multiple proinflammatory cytokines and chemokines. CD14 mRNA expression in corneal epithelial cells was upregulated by LPS. In addition to CD14, corneal epithelial cells expressed the functional LPS receptor-signaling protein TLR4, which was also augmented by LPS. CONCLUSIONS: The cornea expresses functional CD14 and TLR4 LPS receptor proteins. Understanding the function and biology of the corneal LPS receptor complex may lead to novel therapies for the management of ocular Gram-negative bacterial infections.
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Córnea/efectos de los fármacos , Proteínas de Drosophila , Receptores de Lipopolisacáridos/genética , Lipopolisacáridos/farmacología , Glicoproteínas de Membrana/genética , Pseudomonas aeruginosa , Receptores de Superficie Celular/genética , Secuencia de Bases , Northern Blotting , Calcio/metabolismo , Córnea/citología , Córnea/metabolismo , Citocinas/metabolismo , Cartilla de ADN/química , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Receptores de Lipopolisacáridos/metabolismo , Glicoproteínas de Membrana/metabolismo , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Receptores de Superficie Celular/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor Toll-Like 4 , Receptores Toll-Like , Regulación hacia ArribaRESUMEN
Exciting new treatments are being developed for retinal degenerations and posterior segment eye disease. The successful treatment of these visually devastating diseases will likely require delivering effective doses of pharmacologic agents to the posterior segment, possibly in conjunction with surgical or genetic interventions. Currently, the treatment of diseases affecting the posterior segment is limited by the difficulty in delivering effective doses of drugs to target tissues in the posterior vitreous, retina or choroid. This review summarizes recent laboratory and clinical studies that indicate that transscleral delivery of therapeutic solutes might be an effective means of achieving therapeutic concentrations of these agents in the posterior eye.
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Sistemas de Liberación de Medicamentos , Oftalmopatías/tratamiento farmacológico , Esclerótica/metabolismo , Animales , Preparaciones de Acción Retardada , Humanos , Permeabilidad , Esclerótica/químicaRESUMEN
Surgeons must decide on the type of anesthesia to use when performing cataract surgery. These "viewpoints" articles provide a well-balanced discussion offering the pros and cons of both topical anesthesia and retrobulbar/peribulbar injection. Dr. Dutton gives an overview of both techniques, focusing on relevant orbital anatomy. Drs. Hassan, Edelhauser and Kim, review the various types of topical anesthesia currently in use, and Drs. Spriggs and Broocker examine retrobulbar and peribulbar injections. Both techniques are associated with advantages and risks, so each surgeon must decide which technique is best suited for his or her own practice.
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Anestesia Local/métodos , Extracción de Catarata , Ojo/anatomía & histología , Órbita/anatomía & histología , HumanosRESUMEN
PURPOSE: To evaluate the 2-year effects of intrastromal corneal ring segments (INTACS) on the corneal endothelium. METHODS: Non-contact specular microscopy was performed as a subgroup test in a Phase III clinical trial. Endothelial cell images were collected before surgery and at 6, 12, and 24 months after surgery at the central and peripheral (6 and 10 o'clock) regions. Images were recorded and analyzed later by a central reading center. Cell density, coefficient of variation, and percent hexagonal cells were determined. RESULTS: There were no clinically significant changes in the endothelial cell structure at 6, 12, and 24 months (102 eyes). There was a gain of 5 cells/mm2 (6 months) and 3 cells/mm2 (12 months) at the central region of the cornea and a loss of 28 cells/mm2 at 24 months. At the 6 o'clock region of the cornea, there was a loss of 0, 24, and 92 cells/mm2 at 6, 12, and 24 months. At the 10 o'clock region of the cornea, there was a loss of 14, 30, and 94 cells/mm2 at 6, 12, and 24 months. INTACS did not statistically affect the central cell density at 6 and 12 months, however, there was a slight loss centrally at 24 months. At 24 months, all corneal regions had a slight decrease in cell density. In all eyes, mean central and peripheral endothelial cell counts remained above 2495 cells/mm2. Coefficient of variation improved and percent hexagonal cells remained unchanged. CONCLUSION: Endothelial cell density changes at 2 years after INTACS implantation were not clinically significant and endothelial cell remodeling was present.
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Sustancia Propia/cirugía , Endotelio Corneal/patología , Miopía/cirugía , Implantación de Prótesis , Adulto , Recuento de Células , Estudios de Seguimiento , Humanos , Polimetil Metacrilato , Complicaciones Posoperatorias , Prótesis e Implantes , Refracción Ocular , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: To report the acute effects of laser in situ keratomileusis (LASIK) on the corneal endothelium. METHODS: Twenty eyes of 10 consecutive patients (mean age, 38.1 +/- 10.84 years) underwent bilateral simultaneous LASIK for myopic astigmatism (spherical equivalent ranging from -1.75 to -7.13 diopters) without any complications. Each eye was evaluated by slit-lamp biomicroscopy and noncontact specular microscopy preoperatively, within 15 minutes after LASIK and 1 day after surgery. Specular microscopy images were then analyzed to calculate endothelial cell density (ECD), coefficient of variation (CV) of cell size, and percentage of hexagonal cells. RESULTS: All corneas demonstrated marked alterations in endothelial cell morphology by slit-lamp biomicroscopy within 15 minutes after surgery that resolved by the first postoperative day. Central corneal endothelial analysis by noncontact specular microscopy confirmed pleomorphism with definite loss of hexagonality. Mean ECD was calculated to be 2,816.3 +/- 286.02 cells/mm(2) preoperatively, 2,750.85 +/- 327.95 cells/mm(2) on day 0 (p = 0.395), and 2,810.55 +/- 218.48 cells/mm(2) on day 1 (p = 0.461). Mean CV was 32.65 +/- 7.29 preoperatively, 34.4 +/- 6.19 on day 0 (p = 0.412), and 30.9 +/- 5.54 on day 1 (p = 0.067). Mean percentage of hexagonal cells was 63.35 +/- 10.76 preoperatively, 47.55 +/- 9.69 on day 0 (p = 0.000009), and 60 +/- 9.3 on day 1 (p = 0.00003). CONCLUSION: Qualitative and quantitative changes in endothelial cell morphology (i.e., decreased endothelial cell hexagonality) demonstrate that LASIK does induce an acute effect on the corneal endothelium that may represent transient endothelial cell edema.
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Astigmatismo/cirugía , Endotelio Corneal/patología , Queratomileusis por Láser In Situ/efectos adversos , Miopía/cirugía , Complicaciones Posoperatorias/patología , Enfermedad Aguda , Adulto , Astigmatismo/patología , Recuento de Células , Edema Corneal/etiología , Edema Corneal/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía/patología , Estudios ProspectivosRESUMEN
AIMS: Corneal perfusion chambers are important tools in the development and assessment of ophthalmic drugs. The aim of this study was to design and test a modified perfusion chamber suitable for topical application of drugs to isolated corneoscleral preparations, and which allowed continuous monitoring of endothelial cell function. METHODS: A polycarbonate and stainless steel perfusion chamber was designed to clamp corneas in a horizontal plane suitable for topical drug delivery. Endothelial cell function was assessed by ultrasonic pachymetry and specular microscopy during perfusion. Epithelial barrier function was assessed by penetration of fluorescein. Leakage was examined by measuring penetration of a large protein, IgG. Tissue architecture after perfusion was examined by conventional histology. RESULTS: Corneas maintained a functionally and morphologically intact endothelial monolayer during perfusion periods of up to 14 hours. The epithelial barrier function was well preserved. The tissue clamp sealed the preparation effectively against leakage of macromolecules. CONCLUSION: The new chamber device forms a reliable tool for in vitro drug penetration and toxicity studies in isolated perfused corneoscleral tissue.
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Evaluación Preclínica de Medicamentos/instrumentación , Soluciones Oftálmicas/farmacocinética , Animales , Bicarbonatos , Cámaras de Difusión de Cultivos , Endotelio Corneal/efectos de los fármacos , Endotelio Corneal/fisiología , Diseño de Equipo , Fluoresceína/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Perfusión/instrumentación , Acero Inoxidable , PorcinosRESUMEN
PURPOSE: To investigate the effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively. METHODS: Patients who were subjects of a previous prospective study (Am J Ophthalmol 125:465-471, (April) 1998) were contacted for a follow-up analysis of the central corneal endothelium. Noncontact specular microscopy was performed 35 to 37 months after LASIK on 52 eyes of 27 patients of the original cohort of 98 eyes of 65 patients and six eyes of three patients who were previously lost to follow-up after their initial post-LASIK evaluation. Patient age ranged from 29 to 66 years at the time of the original LASIK procedure. Attempted corrections ranged from 2.25 to 14.5 diopters of myopia, giving theoretical ablation depths of 182 to 332 microm below the corneal surface. Forty-eight eyes (83%) had a history of preoperative contact lens use (3 to 33 years). Central endothelial cell density, coefficient of variation of cell size, and percent of hexagonal cells were analyzed using 72 to 152 cells from each image. Multivariate analysis was used to search for factors that might predict changes in cell density, coefficient of variation, and percent of hexagonal cells. RESULTS: The mean +/- SD preoperative cell density was 2,498 +/- 354 cells per mm(2), the mean coefficient of variation was 0.36 +/- 0.07, and the percent of hexagonal cells was 58 +/- 6. Three years after surgery there was no statistically significant change in the mean endothelial cell density (2,489 +/- 335 cells per mm(2); P = 0.88, paired t test) or the percent of hexagonal cells (60 +/- 7; P = 0.14, paired t test). The mean coefficient of variation was significantly lower postoperatively (0.32 +/- 0.04; P = 0.0006, paired t test); a repeated measures analysis showed that this significant improvement could not be explained by cessation of contact lens wear after LASIK (P = 0.34). Multivariate analysis did not identify any factors that were predictive of change in cell density, coefficient of variation, and percent of hexagonal cells. CONCLUSIONS: Laser in situ keratomileusis for the correction of 2.25 to 14.5 diopters of myopia had no significant effect on central corneal endothelial cell density or the percent of hexagonal cells 3 years after surgery. The coefficient of variation of cell size improved significantly 3 years after surgery.
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Endotelio Corneal/citología , Queratomileusis por Láser In Situ , Miopía/cirugía , Adulto , Anciano , Recuento de Células , Tamaño de la Célula , Técnicas de Diagnóstico Oftalmológico , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Microscopía , Persona de Mediana Edad , Cuidados PosoperatoriosRESUMEN
PURPOSE: The goal of this study was to characterize the morphology of the mucinous layer on rabbit, bovine, owl, and human corneal endothelial cells. METHODS: Corneoscleral buttons were fixed using cetylpyridinium chloride to stabilize "mucus" and the tissue was prepared for transmission electron microscopy. Photomicrographs were measured to determine the thickness of the endothelial and epithelial mucinous layer in the central cornea. RESULTS: The endothelial mucinous layer was seen as a nearly uniform electrodense region on the apical aspect of the endothelium. It was found to be 0.9 microm, 0.9 microm, 0.9 microm, and 0.5 microm thick in rabbit, bovine, owl, and human, respectively. The owl endothelium had an additional less electrodense layer with a granular appearance and a thickness of about 200 microm. The mucinous layer on the epithelium was similar in appearance to that on the endothelium and across species. CONCLUSIONS: The morphologic similarity of the endothelial and epithelial mucinous layers is a serendipitous finding that should prove valuable in experimental design. Ultimately, it is hoped that studies of the posterior corneal surface will deepen our knowledge of endothelial protection.
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Endotelio Corneal/metabolismo , Mucinas/metabolismo , Adulto , Animales , Bovinos , Endotelio Corneal/citología , Endotelio Corneal/ultraestructura , Humanos , Microscopía Electrónica , Mucinas/ultraestructura , Conejos , Coloración y Etiquetado , EstrigiformesRESUMEN
BACKGROUND: Toxic endothelial cell destruction (TECD) syndrome after intraocular ophthalmic surgery is rare and can result from exposure to a variety of toxins. During January 8 to 14, 1998, 6 patients developed TECD with corneal edema associated with unreactive or dilated pupils at Hospital A. METHODS: A case patient was any Hospital A patient with TECD within 24 hours after surgery during January 5 to 14, 1998 (epidemic period). A control was any hospital A ophthalmic surgery patient without TECD during the epidemic period. The medical records of hospital A ophthalmology surgery patients during the pre-epidemic (ie, September 1, 1997-January 4, 1998) and epidemic periods were reviewed. Inductively coupled plasma atomic emission spectrometry was used to detect trace inorganic elements on sterilized surgical instruments. Cannulated surgical instruments and laboratory rinsates were perfused directly to the corneal endothelium of isolated rabbit and human corneas. Corneal endothelial ultrastructure and swelling were assessed. RESULTS: The rate of TECD at hospital A was higher during the epidemic than pre-epidemic period (6/12 vs 0/118, P<.001). The only change during the periods was the introduction, on November 5, 1997, of a new sterilization method, AbTox Plazlyte, for sterilization of ophthalmic surgery instruments. Findings from spectrometry revealed that copper and zinc residues were higher in instruments sterilized with Plazlyte than in those sterilized with ethylene oxide (median copper value, 7.64 mg/L vs 0.14 mg/L, respectively, P =.02; median zinc value, 5.90 mg/L vs 1.35 mg/L, respectively, P =.2). Corneal endothelial perfusion of Plazlyte sterilized-instrument rinsates or laboratory solution with copper and zinc produced irreversible damage, similar to toxic corneal endothelial destruction, to rabbit and human corneas. CONCLUSION: A new sterilization method degraded brass to copper and zinc on cannulated surgical instruments resulting in TECD of the cornea. Arch Ophthalmol. 2000;118:1167-1176
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Cobre/efectos adversos , Edema Corneal/inducido químicamente , Edema Corneal/epidemiología , Brotes de Enfermedades , Endotelio Corneal/efectos de los fármacos , Contaminación de Equipos , Facoemulsificación/instrumentación , Esterilización/métodos , Zinc/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Edema Corneal/patología , Endotelio Corneal/patología , Endotelio Corneal/ultraestructura , Femenino , Georgia/epidemiología , Humanos , Implantación de Lentes Intraoculares , Masculino , Persona de Mediana Edad , ConejosRESUMEN
PURPOSE: Ten cases of unexpected corneal endothelial cell decompensation occurring after routine intraocular surgery using instruments sterilized with a new plasma gas protocol are described. DESIGN: A retrospective observational case series with 1 year of follow-up was conducted. RESULTS: All patients had corneal decompensation and nonreactive pupils after surgery. Six patients required penetrating keratoplasty. Three patients partially recovered pupillary function. Visual acuity at 1 year ranged from 20/20 to hand motion (HM). One patient with an anterior chamber intraocular lens (ACIOL) experienced optic atrophy and HM vision despite resolution of corneal edema. CONCLUSIONS: Toxic corneal endothelial cell destruction syndrome was associated with the introduction of plasma gas sterilization protocols.
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Cobre/efectos adversos , Edema Corneal/inducido químicamente , Endotelio Corneal/efectos de los fármacos , Contaminación de Equipos , Esterilización , Zinc/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Edema Corneal/patología , Endotelio Corneal/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Facoemulsificación/instrumentación , Trastornos de la Pupila/inducido químicamente , Trastornos de la Pupila/patología , Estudios Retrospectivos , Esterilización/instrumentación , Esterilización/métodos , Síndrome , Agudeza VisualRESUMEN
PURPOSE: To describe stress factors (phenylephrine and contact lenses) from the corneal epithelium that can affect the corneal endothelium, and to describe the effects of refractive and intraocular surgery on the corneal endothelial structure and function. METHODS: Significant clinical and experimental publications are reviewed and recent experiments conducted in the author's laboratory to describe the corneal endothelial stresses. RESULTS: The corneal epithelium serves as a barrier to topical phenylephrine (2.5-10%). In a compromised epithelium, topical phenylephrine will cause drug-induced stromal edema and endothelial vacuolization. Contact lenses are capable of stimulating the epithelial arachidonic acid cascade to release 12(R)hydroxyeicosatetraenoic acid (12(R)HETE) and 8(R)hydroxy-hexadecatrienoic acid (8(R)HHDTrE) to cause endothelial Na+/K+ adenosine triphosphatase (ATPase)-inhibition and polymegethism. Specular microscopy of the corneal endothelial cells after refractive surgery (photorefractive keratectomy [PRK], laser in situ keratomileusis [LASIK], intrastromal rings [INTACs]) has shown that there is minimal effect. However, laser ablation of the stroma within 200 microm of the corneal endothelium will result in endothelial cell structural changes and the formation of the amorphous substance deposited onto Descemet's membrane. Phacoemulsification with a high flow of the irrigation solution can alter the endothelial surface glycoprotein layer. Lidocaine hydrochloride (1%) used as intracameral anesthesia readily diffuses through the corneal endothelium, resulting in stromal uptake and endothelial cell swelling. With phacoemulsification, however, the washout of lidocaine from the cornea (T1/2, 5 minutes) and iris (T1/2, 9 minutes) occurs quickly. Corneal endothelial wound healing after keratoplasty occurs in the following sequence: migration of endothelial cells, development of tight junctions, and the formation of Na+/K+ ATPase pump sites. CONCLUSIONS: Corneal endothelial resiliency is due to the increased peripheral endothelial cell number for migration, the ability of endothelial cells to form tight junctions to maintain the endothelial barrier, the increase in endothelial Na+/K+ ATPase pump sites under stress, and the ability of the corneal endothelial cells to shift their metabolism of glucose to the hexose monophosphate shunt for the production of nicotinamide adenine dinucleotide phosphate (NADPH) and membrane repair. All of these factors are important, along with the aqueous humor sodium concentration, which establishes the osmotic gradient for corneal deturgescence and transparency.
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Extracción de Catarata , Endotelio Corneal/fisiología , Procedimientos Quirúrgicos Refractivos , Agonistas alfa-Adrenérgicos/farmacología , Animales , Lentes de Contacto , Trasplante de Córnea , Endotelio Corneal/citología , Endotelio Corneal/efectos de los fármacos , Glucosa/metabolismo , Humanos , Queratomileusis por Láser In Situ , Láseres de Excímeros , NADP/metabolismo , Fenilefrina/farmacología , Queratectomía Fotorrefractiva , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Uniones EstrechasRESUMEN
PURPOSE: The purpose of this study was to evaluate the effects of intraocular pressure on the permeability of human and rabbit sclera to water, dexamethasone, and carboxyfluorescein. METHODS: Scleral sections excised from moist-chamber-stored human globes or eyes obtained from euthanatized New Zealand White rabbits were mounted in a perfusion chamber that can create a transscleral pressure that simulates an intraocular pressure. A small depot of drug (100 microl) was added to the episcleral surface while perfusing an irrigating solution slowly across the choroidal side. The perfusate was collected and scleral permeability calculated. Experiments were performed at 0, 15, 30, and 60 mm Hg for each compound in human and rabbit tissue. RESULTS: Analysis of variance showed a significant effect of intraocular pressure on both human and rabbit scleral permeability. Human scleral permeability was decreased by as much as a factor of two for water (P = 0.0004), dexamethasone (P<0.0001), and carboxyfluorescein (P = 0.0064) at elevated intraocular pressures. Rabbit scleral permeability was similarly affected by elevated intraocular pressure for water (P = 0.0039), dexamethasone (P = 0.0001), and carboxyfluorescein (P = 0.0016). CONCLUSIONS: This study shows that simulated intraocular pressure ranging from 15 to 60 mm Hg can decrease scleral permeability to small molecules by one half when compared with the sclera with no pressure applied.
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Dexametasona/metabolismo , Fluoresceínas/metabolismo , Presión Intraocular/fisiología , Esclerótica/metabolismo , Agua/metabolismo , Animales , Humanos , Persona de Mediana Edad , Permeabilidad , ConejosRESUMEN
Intraocular medications, solutions, and instruments are an integral component of intraocular surgery. The ionic composition, pH, and osmolality should approximate aqueous humor to prevent damage to the corneal endothelium. Intraocular medications should be evaluated for their intrinsic properties and presence of vehicles or preservatives. Many new cleaning procedures and promising new intraocular drugs are likely to be introduced in the future. The responsibility of ocular surgeons is to protect their patients from drug-, solution-, or instrument-related toxicity.
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Oftalmopatías/inducido químicamente , Ojo/efectos de los fármacos , Soluciones Oftálmicas/efectos adversos , Soluciones/efectos adversos , Ojo/patología , Oftalmopatías/patología , Humanos , Procedimientos Quirúrgicos Oftalmológicos , Irrigación TerapéuticaRESUMEN
PURPOSE: To determine whether intracameral bupivacaine hydrochloride 0.5% is as effective as lidocaine hydrochloride 1.0% in controlling discomfort of patients during phacoemulsification and posterior chamber intraocular lens implantation. In rabbits, corneal endothelial cell function, ultrastructure, and viability were evaluated after in vitro perfusion of bupivacaine 0.5%. METHODS: In a double-masked, controlled trial, 48 eyes of 48 patients with uncomplicated age-related cataract were randomly assigned to receive bupivacaine 0.5% or lidocaine 1.0% intracamerally before phacoemulsification with a posterior chamber intraocular lens. Outcome measures such as pain, visual acuity, amount of sedation, length of surgery, pupil size, intraocular pressure, corneal clarity, and anterior chamber reaction were compared. In laboratory studies, paired rabbit corneas were evaluated by endothelial cell perfusion with either bupivacaine 0.5%, bupivacaine 0.5% and glutathione bicarbonate Ringer solution in a 1:1 ratio or bupivacaine 0.5% buffered to a pH of 7.0. The paired control corneas were perfused with glutathione bicarbonate Ringer solution and rates of corneal swelling were determined. Cell ultrastructure and viability were also evaluated. RESULTS: In the randomized trial, there was no significant difference in the pain patients had during surgery or in the early or late postoperative period. No statistically significant difference was seen between the two groups in terms of pupil size, intraocular pressure, corneal edema, anterior chamber reaction, or visual acuity immediately after the operation or on postoperative day 1. Paired rabbit corneas perfused with bupivacaine 0.5% and bupivacaine 0.5% buffered to a pH of 7.0 swelled significantly (P<.001, P = .009, respectively), and had corneal endothelial cell damage. Dilution of the bupivacaine 1:1 with glutathione bicarbonate Ringer solution prevented corneal edema and damage to the corneal endothelium. Endothelial cell viability was also decreased after perfusion of bupivacaine 0.5% (P<.001). CONCLUSIONS: Clinically, bupivacaine 0.5% is as effective as lidocaine 1.0% for anesthesia during phacoemulsification and posterior chamber intraocular lens implantation. However, in vitro perfusion of bupivacaine 0.5% damaged the corneal endothelium of rabbits except when the drug was diluted 1:1 with glutathione bicarbonate Ringer solution. Surgeons who use 0.2 to 0.5 ml of intracameral bupivacaine 0.5% should be aware of its potential to cause endothelial cell damage because of its lipid solubility. The bupivacaine 0.5% should be diluted at least 1:1 with balanced salt solution before intracameral injection, followed immediately by phacoemulsification. The surgeon should ensure that the bupivacaine 0.5% is nonpreserved and packaged in single-use vials or flip-top containers.
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Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Cámara Anterior/efectos de los fármacos , Bupivacaína/administración & dosificación , Lidocaína/administración & dosificación , Anciano , Anciano de 80 o más Años , Anestésicos Locales/efectos adversos , Animales , Bupivacaína/efectos adversos , Catarata/complicaciones , Recuento de Células , Edema Corneal/inducido químicamente , Edema Corneal/patología , Método Doble Ciego , Endotelio Corneal/efectos de los fármacos , Endotelio Corneal/ultraestructura , Femenino , Humanos , Presión Intraocular/fisiología , Implantación de Lentes Intraoculares , Lidocaína/efectos adversos , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Facoemulsificación , Conservadores Farmacéuticos , Estudios Prospectivos , Pupila/fisiología , Conejos , Seguridad , Agudeza Visual/fisiologíaRESUMEN
OBJECTIVES: To characterize the uptake, washout, and metabolism of lidocaine hydrochloride in the iris/ciliary body and cornea. METHODS: Iris/ciliary body uptake of lidocaine hydrochloride was measured by incubating human and rabbit irides in radiolabeled carbon 14-1% lidocaine hydrochloride for 2 to 60 minutes. Washout was determined by incubating the iris in 14C-1% lidocaine hydrochloride for 5 minutes and transferring the iris to a series of wells. The wells contained a common intraocular irrigating solution of essential ions, glucose, and glutathione buffered with bicarbonate (an enriched balanced salt solution [BSS PLUS]), which is similar to aqueous humor. Corneal uptake was measured by exposing the endothelial surface to 14C-1% lidocaine hydrochloride for 5 or 15 minutes. Corneal washout was performed after 5-minute exposure to 14C-1% lidocaine hydrochloride using a 2-chambered diffusion apparatus. Samples of the iris, cornea, and BSS PLUS washout solution were analyzed by high-performance liquid chromatography and liquid scintillation spectrometry. RESULTS: In vitro iris/ciliary body uptake of 14C-1% lidocaine hydrochloride follows a logarithmic curve, with 50% to 60% of maximum lidocaine hydrochloride uptake present at 5 minutes. There was no difference in uptake between human, albino rabbit, and pigmented rabbit irides. Washout of lidocaine from the iris occurs with a halflife of 8 to 9 minutes. Corneal uptake of lidocaine was greater after incubation for 15 vs. 5 minutes. The washout of lidocaine from the cornea had a half-life of 5 minutes. Results of high-performance liquid chromatography confirmed that there were no metabolites or breakdown products in the iris, cornea, or washout solution. CONCLUSIONS: Lidocaine is taken up quickly by the iris/ ciliary body and cornea and rapidly removed from these tissues after BSS PLUS washout. Irrigation during phacoemulsification seems to limit lidocaine exposure to the ocular tissues, resulting in a short duration of anesthesia. Lidocaine is not metabolized or broken down by the iris or cornea during this short period.
Asunto(s)
Anestesia Local , Anestésicos Locales/farmacocinética , Cuerpo Ciliar/metabolismo , Córnea/metabolismo , Iris/metabolismo , Lidocaína/farmacocinética , Anestésicos Locales/metabolismo , Animales , Cámara Anterior/metabolismo , Cromatografía Líquida de Alta Presión , Semivida , Humanos , Lidocaína/metabolismo , Persona de Mediana Edad , ConejosRESUMEN
PURPOSE: To evaluate the hydration, and the levels of free, total and bound sodium in fresh rabbit corneal stromas and also those preserved for up to 21 days in Optisol-GS. The effect of epithelial removal on stromal sodium and hydration parameters was also evaluated. Trends in stromal hydration and sodium environment were compared to results we previously obtained using human eyes stored under identical conditions. METHODS: Stromal hydration was evaluated thermogravimetrically. A sodium-specific electrode and an atomic absorption spectrophotometer were used to determine the amounts of free and total stromal sodium, respectively. In one cornea of each pair, the epithelium was removed prior to placement in the storage media. After 3, 7, 14 or 21 days at 4 degrees C, corneas were removed from the Optisol-GS, at which time sodium and hydration measurements were obtained. RESULTS: With an intact epithelium, the hydration of the rabbit stromas was elevated significantly at each day of storage compared to fresh corneas. Free and total sodium levels of rabbit stromas did not differ statistically from fresh values, however the bound sodium values did increase during storage. In the absence of the epithelium, the stromal hydration and sodium content (free, total and bound) were significantly elevated and the increase was much greater than in corneas stored with an intact epithelium. These findings differ from those we measured previously using human tissue. CONCLUSIONS: Rabbit corneas responded differently from human corneas to storage in Optisol-GS. The hydration levels increased to a greater level in rabbit than human corneas under both storage conditions. The trends in amounts of both free and total sodium were similar between the species, although the absolute amounts differed. The largest discrepancy was observed in the amount of bound sodium, with the rabbit corneas experiencing large increases not documented in the human tissue. These results suggest that direct comparisons of stromal hydration and ionic environment between the species should be approached with caution.