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1.
J Cataract Refract Surg ; 46(2): 228-234, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32126036

RESUMO

PURPOSE: To investigate whether the safety of intracameral moxifloxacin (IC-Mox) was equivalent to subconjunctival antibiotics (SC-Abs) in pediatric lens surgery. SETTING: The Hospital for Sick Children, Toronto, Canada. DESIGN: Retrospective consecutive cohort study. METHODS: This equivalence study compared 95% CI in the difference between the preoperative and postoperative safety variables of best corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT), endothelial cell density (ECD), corneal edema, and anterior chamber (AC) inflammation in IC-Mox with SC-Abs. The zone of clinical equivalence for BCVA was set at ±0.2 logarithm of the minimum angle of resolution, IOP at ±3 mm Hg, CCT at ±30 µm, and ECD at ±400 cells/mm. RESULTS: The charts of 358 patients undergoing lens-related surgeries were reviewed. Of 317 eyes (215 patients) included, 170 eyes received IC-Mox and 147 eyes had SC-Abs. The mean age was 4.9 and 5.1 years with a mean follow-up of 19 and 34.4 months (P < .001) in IC-Mox and SC-Ab groups, respectively. The 95% CIs for the change from preoperative to postoperative safety parameters between IC-Mox and SC-Abs were all in the zones of clinical equivalence (BCVA, P = 0.75; highest IOP in the first 6 weeks postoperatively, P = 0.27; IOP at the last visit, P = 0.74; CCT, P = 0.89; and ECD, P = 0.76). During the first 6 weeks postoperatively, there was no difference in corneal edema (P = .69) and AC flare (P = .4) between IC-Mox and SC-Ab groups, whereas AC cellular activity was significantly higher in the SC-Ab group (P = .028). CONCLUSIONS: IC-Mox prophylaxis in pediatric patients showed equivalent postoperative safety outcomes when compared with SC-Abs. The use of IC-Mox (250 µg) for endophthalmitis prophylaxis appears to be safe in the pediatric population.


Assuntos
Câmara Anterior/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Extração de Catarata , Túnica Conjuntiva/efeitos dos fármacos , Endoftalmite/prevenção & controle , Moxifloxacina/uso terapêutico , Adolescente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Edema da Córnea/patologia , Paquimetria Corneana , Endotélio Corneano/patologia , Feminino , Seguimentos , Humanos , Lactente , Injeções Intraoculares , Pressão Intraocular/fisiologia , Implante de Lente Intraocular , Masculino , Moxifloxacina/efeitos adversos , Soluções Oftálmicas , Estudos Retrospectivos , Acuidade Visual/fisiologia
2.
Proc Natl Acad Sci U S A ; 117(1): 573-583, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31852820

RESUMO

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.


Assuntos
Citocromo P-450 CYP1B1/metabolismo , Adutos de DNA/efeitos da radiação , Dano ao DNA/efeitos da radiação , Estrogênios/metabolismo , Distrofia Endotelial de Fuchs/etiologia , Raios Ultravioleta/efeitos adversos , Acetilcisteína/administração & dosagem , Animais , Humor Aquoso/efeitos dos fármacos , Humor Aquoso/metabolismo , Humor Aquoso/efeitos da radiação , Adutos de DNA/metabolismo , Dano ao DNA/efeitos dos fármacos , DNA Mitocondrial/metabolismo , DNA Mitocondrial/efeitos da radiação , Modelos Animais de Doenças , Endotélio Corneano/efeitos dos fármacos , Endotélio Corneano/patologia , Endotélio Corneano/efeitos da radiação , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Distrofia Endotelial de Fuchs/diagnóstico , Distrofia Endotelial de Fuchs/tratamento farmacológico , Distrofia Endotelial de Fuchs/patologia , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença
3.
Exp Eye Res ; 188: 107808, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31539544

RESUMO

Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) is a novel potential treatment for progressive infectious keratitis. The principle behind this therapy is using Rose Bengal as a photosensitizer that can be activated by green light and results in the production of oxygen free radicals which in turn eradicate the microorganism. Given RB-PDAT's mechanism of action and the potential cytotoxic effects, concerns regarding the safety of this technique have arisen. The purpose of this study was to evaluate the effect of RB-PDAT on keratocytes, while focusing on the safety profile that the photo-chemical reaction has on the limbal stem cell (LSC) niche and endothelial cell layer of the treated cornea. To perform RB-PDAT, Rose Bengal solution (0.1% RB in BSS) was applied to the right cornea of rabbits for 30 min and then irradiated by a custom-made green LED light source (525 nm, 6 mW/cm2) for 15 min (5.4 J/cm2). Three rabbits were sacrificed and enucleated after 24 h for evaluation. TUNEL assay and immunohistochemistry for endothelium and limbal stem cell viability were performed on whole mounts and frozen sections in treated and control eyes. LSC of both eyes were isolated and cultured to perform MTT viability and proliferation, and scratch wound healing assays under time-lapse microscopy. Interestingly, while Rose Bengal dye penetration was superficial, yet associated cellular apoptosis was evidenced in up to 1/3 of the stromal thickness on frozen sections. TUNEL assay on whole mounts showed no endothelial cell death following treatment. Immunohistochemistry on frozen sections of LSC displayed no structural difference between treated and non-treated eyes. There was no difference in LSC proliferation rates and scratch wound healing assay demonstrated adequate cell migration from treated and non-treated eyes. The current study suggests that even though penetration of the RB dye has been shown to be limited, oxidative stress produced by RB-PDAT can reach deeper into the corneal stroma. Nevertheless, our results show that performing RB-PDAT is safe on the corneal endothelium and has no effect on LSC viability or function.


Assuntos
Anti-Infecciosos/farmacologia , Ceratócitos da Córnea/efeitos dos fármacos , Endotélio Corneano/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Fotoquimioterapia , Rosa Bengala/farmacologia , Nicho de Células-Tronco/efeitos dos fármacos , Animais , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Ceratócitos da Córnea/metabolismo , Ceratócitos da Córnea/patologia , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Substância Própria/patologia , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Limbo da Córnea/efeitos dos fármacos , Limbo da Córnea/metabolismo , Limbo da Córnea/patologia , Coelhos
4.
Exp Eye Res ; 161: 106-115, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28619506

RESUMO

In the present study mechanical damage to the corneal endothelium was induced by elevation of intraocular pressure (IOP, 140 mmHg, 60 min) to one eye of rats, delivered either in complete darkness or in the presence of red light (16.5 W/m2, 3000 lx, 625-635 nm). IOP raised in the dark revealed the endothelium to be damaged as staining for the gap junction protein ZO-1 was irregular in appearance with some cells displaced in position or lost to leave gaps or holes. This damage was clearly attenuated when red light was focused through the pupil during the insult of raised IOP. Moreover, staining of endothelium with JC-1 dye showed mitochondria to be activated by both elevated IOP and red light but the activation of mitochondria persisted longer for red light. We interpret this finding to suggest that raised IOP causes apoptosis of endothelial cells and that their mitochondria are activated in the initial stages of the process. In contrast, red light activates mitochondria to induce a protective mechanism to counteract the negative influence of raised IOP on endothelial cells. Evidence is provided to support this notion by the finding that red light stimulates mitochondrial cytochrome oxidase IV (COX IV). Moreover, mitochondria in corneal endothelial cell cultures are activated by red light, revealed by staining with JC-1, that results in an increased rate of proliferation and are also able to counteract toxic insults (sodium azide or cobalt chloride) to the cultures. The present studies therefore show that a non-toxic level of red light attenuates damage to the corneal endothelium both in situ and in vitro through action on COX IV located in mitochondria that results in an enhancement of a cell's survival mechanisms. The study provides proof of principle for the non-invasive use of red-light therapy to attenuate any dysfunctions associated with the corneal endothelium and so preserve maximum visual acuity.


Assuntos
Sobrevivência Celular/fisiologia , Perda de Células Endoteliais da Córnea/terapia , Modelos Animais de Doenças , Raios Infravermelhos , Fototerapia/métodos , Animais , Benzimidazóis/metabolismo , Western Blotting , Carbocianinas/metabolismo , Proliferação de Células/fisiologia , Células Cultivadas , Perda de Células Endoteliais da Córnea/etiologia , Perda de Células Endoteliais da Córnea/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Técnica Indireta de Fluorescência para Anticorpo , Corantes Fluorescentes/metabolismo , Pressão Intraocular , Masculino , Mitocôndrias/enzimologia , Hipertensão Ocular/complicações , Ratos , Ratos Wistar , Proteína da Zônula de Oclusão-1/metabolismo
5.
Cornea ; 35(9): 1250-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27442316

RESUMO

PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.


Assuntos
Edema da Córnea/tratamento farmacológico , Complexo de Proteínas da Cadeia de Transporte de Elétrons/uso terapêutico , Endotélio Corneano/efeitos dos fármacos , Distrofia Endotelial de Fuchs/tratamento farmacológico , Síndrome de Kearns-Sayre/tratamento farmacológico , Ubiquinona/análogos & derivados , Criança , Pré-Escolar , Edema da Córnea/diagnóstico , Endotélio Corneano/patologia , Humanos , Síndrome de Kearns-Sayre/diagnóstico , Masculino , Soluções Oftálmicas , Ubiquinona/uso terapêutico , Acuidade Visual/efeitos dos fármacos
6.
Cornea ; 35(10): 1320-5, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27429081

RESUMO

PURPOSE: To evaluate the corneal endothelial changes in patients with chronic renal failure. METHODS: A total of 128 corneas of 128 subjects were studied, and 3 groups were formed. The first, the dialyzed group, composed of 32 corneas of 32 patients; the second, the nondialyzed group, composed of 34 corneas of 34 patients; and the third, the age-matched control group, composed of 64 corneas of 64 healthy subjects were examined by a specular microscope and the endothelial parameters were compared. The dialyzed group (enhanced level of toxins in the blood) was further analyzed to assess the influence of blood urea, serum creatinine, serum calcium, and serum phosphorus including the duration of dialysis on corneal endothelium. RESULTS: On comparing the 3 groups using analysis of variance and posthoc tests, a significant difference was found in the central corneal thickness (CCT) and endothelial cell density (CD) between the control (CCT: 506 ± 29 µm, CD: 2760 ± 304 cells/mm) and dialyzed groups (CCT: 549 ± 30 µm, CD: 2337 ± 324 cells/mm) [P < 0.001 (CCT); P < 0.001 (CD)]; control and nondialyzed groups (CCT: 524 ± 27 µm, CD: 2574 ± 260 cells/mm) [P = 0.023 (CCT); P = 0.016 (CD)]; and dialyzed and nondialyzed groups [P = 0.002 (CCT); P = 0.007 (CD)]. Using the linear generalized model, a significant correlation was found between the endothelial parameters and blood urea only [P = 0.006 (CCT), 0.002 (coefficient of variation), 0.022 (CD), and 0.026 (percentage of hexagonality)], although the correlation was poorly positive for CCT but poorly negative for the remaining endothelial parameters. CONCLUSIONS: Corneal endothelial alteration is present in patients with chronic renal failure, more marked in patients undergoing hemodialysis and with raised blood urea level.


Assuntos
Doenças da Córnea/etiologia , Endotélio Corneano/patologia , Falência Renal Crônica/complicações , Adulto , Idoso , Cálcio/sangue , Contagem de Células , Doenças da Córnea/sangue , Doenças da Córnea/terapia , Creatinina/sangue , Feminino , Voluntários Saudáveis , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fósforo/sangue , Diálise Renal , Ureia/sangue , Adulto Jovem
7.
J Refract Surg ; 31(3): 146-52, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25751829

RESUMO

PURPOSE: To compare femtosecond laser-assisted cataract surgery without the use of ophthalmic viscosurgical device (OVD) with standard phacoemulsification using OVD. METHODS: This was a prospective, randomized, single-center trial of 37 patients (74 eyes) diagnosed as having significant cataract in both eyes. Randomly, one eye underwent standard phacoemulsification with OVD (the OVD group); this group acted as controls. The other eye was treated with the femtosecond laser; the subsequent manual part of the procedure was performed without OVD (non-OVD group). Time of surgery, amount of fluid used during phacoemulsification, central corneal thickness, intraocular pressure, endothelial cell count, and visual acuity were documented over the 6-month follow-up. RESULTS: There were no major complications and no significant difference in overall surgery time (non-OVD: 375 ± 81 seconds; OVD: 362 ± 43 seconds; P = .713) and in the quantity of fluid passing through the eye (non-OVD: 187 ± 35 mL; OVD: 186 ± 27 mL; P = .952) between groups. Endothelial cell loss after 6 months was not significantly different between groups (non-OVD: -2.4%; OVD: -2.7%; P = .880). Central corneal thickness was not different at 1 week postoperatively between groups (non-OVD: 575 ± 45 µm; OVD: 573 ± 46 µm; P = .820). Three patients in the OVD group and one patient in the non-OVD group experienced intraocular pressure greater than 25 mm Hg at 1 day postoperatively. There were no significant differences in corrected distance visual acuity between groups (logMAR non-OVD: 0.024; OVD: 0.038; P = .461). CONCLUSIONS: Femtosecond laser-assisted treatment allows the cataract surgeon to perform phacoemulsification and intraocular lens implantation without the use of OVD at no additional risk to the corneal endothelium. Furthermore, there was a tendency toward fewer increases in intraocular pressure in patients treated with the femtosecond laser.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Perda de Células Endoteliais da Córnea/diagnóstico , Endotélio Corneano/patologia , Ácido Hialurônico/administração & dosagem , Terapia a Laser , Implante de Lente Intraocular , Facoemulsificação/métodos , Viscossuplementos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Combinação de Medicamentos , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Acuidade Visual/fisiologia
9.
Graefes Arch Clin Exp Ophthalmol ; 253(5): 753-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25572351

RESUMO

To evaluate temporary exposure to hyperthermia for its impact on endothelial cell density of porcine corneas in organ culture medium containing dextran with regards to possible negative influences of high temperatures during the storage and transport of corneal grafts. Four groups of central discs (diameter 8 mm) from the corneas of both eyes in 40 pigs were first organ-cultured (MEM with 6% dextran 500) for 24 h at 32°C. Ten corneas were then exposed to 40°C in group 1, to 42°C in group 2, to 44°C in group 3, and to 50°C in group 4 for 12 h each. The paired corneal discs for all groups were not treated, stored at 32°C and served as controls. After further organ culture of all corneas for 48 h at 32°C to allow regenerative processes, corneal endothelium was stained with Alizarin Red S and examined by light microscopy. The endothelial cell densities were determined on three central images using a system for the automatic estimation of morphometric parameters of corneal endothelium. Exposure for 12 h to 40°C as well as to 42°C induced no endothelial cell loss. Statistical analysis showed no significant difference of the endothelial cell density between corneas exposed to 40°C and 42°C and the control corneas (40°C treatment: 4736 ± 426 cells/mm(2) and control: 4762 ± 344 cells/mm(2), p = 0.74; 42°C treatment: 4240 ± 363 cells/mm(2) and control: 4176 ± 448 cells/mm(2), p = 0.40). Exposure to 44°C and 50°C lead to total necrosis of the endothelial cell layer. Exposure of organ cultured porcine corneas in dextran containing medium up to 42°C for 12 h does not compromise the endothelial cell density in a clinically relevant manner. Temperatures above 42°C, as it might be the case during transports from the cornea bank to the ophthalmic surgeon, must be strictly avoided as they damage the endothelial cell layer.


Assuntos
Endotélio Corneano , Hipertermia Induzida/efeitos adversos , Técnicas de Cultura de Órgãos , Preservação de Órgãos/métodos , Animais , Contagem de Células , Sobrevivência Celular/fisiologia , Meios de Cultura , Endotélio Corneano/patologia , Bancos de Olhos/métodos , Necrose , Suínos
10.
Cornea ; 33(10): 1061-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25119959

RESUMO

PURPOSE: The aim of this study was to evaluate the effect of vitreous surgery on the corneal endothelium. METHODS: A total of 113 eyes undergoing pars plana vitrectomy for variable indications at a tertiary care center were included prospectively. The mean age was 41 years (range, 9-84 years), and 60% were male. The endothelial cell count was measured preoperatively and on postoperative day 1, 30, 90, and 180. The rate of endothelial cell loss was measured and analysis performed based on gauge of surgery, lens status, and vitreous substitute used. RESULTS: About 7.6% of endothelial cells were lost at postoperative day 1. This rate had decreased to 2.5% in the first 30 days, 1.5% between days 30 and 90, and 1.4% between days 90 and 180. Significant difference in endothelial cell loss was noted on day 1 between phakic (7.2%), pseudophakic (6.4%), and aphakic (11.4%) eyes with similar results at 6 months. There was no significant difference between the gauges of surgery (20 G vs. 23 G) or the vitreous substitutes used (air vs. gas vs. silicone oil) on day 1 or at 6 months. CONCLUSIONS: Endothelial decompensation is an important complication of vitreoretinal surgery. Precautions should be taken in aphakics and patients requiring anterior segment manipulation. Although there is immediate cell loss, the rate of cell loss approaches normative values with time.


Assuntos
Afacia Pós-Catarata/fisiopatologia , Perda de Células Endoteliais da Córnea/prevenção & controle , Cristalino/fisiologia , Pseudofacia/fisiopatologia , Vitrectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Criança , Perda de Células Endoteliais da Córnea/fisiopatologia , Endotélio Corneano/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Viscossuplementos
11.
JAMA Ophthalmol ; 132(7): 832-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24789459

RESUMO

IMPORTANCE: Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. Most postkeratoplasty endophthalmitis and keratitis cases are now of a fungal origin. OBJECTIVE: To assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions. DESIGN, SETTING, AND PARTICIPANTS: In vitro laboratory study using 15 pairs of research-grade donor corneas and 20-mL vials of Optisol-GS. INTERVENTIONS: Twenty vials of Optisol-GS were supplemented with either voriconazole at 1×, 10×, 25×, or 50× minimum inhibitory concentration (MIC) or amphotericin B at 0.25×, 0.5×, 1×, or 10× MIC. Known concentrations of Candida albicans and Candida glabrata were each added to a set of vials. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus an antifungal. MAIN OUTCOMES AND MEASURES: Efficacy outcomes were viable fungal colony counts determined from samples taken on days 2, 7, and 14 immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety outcomes included percentage of intact epithelium and endothelial cell density on days 0, 7, and 14, as well as percentage of nonviable endothelial cells by vital dye staining on day 14. RESULTS: Growth of C albicans and C glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B-supplemented vials, except at 0.25× and 0.5× MIC on day 2, when viable counts of C glabrata were reduced by 99% and 96%, respectively. Compared with paired controls, with the exception of Optisol-GS plus amphotericin B at 10× MIC, donor corneas in supplemented Optisol-GS appeared to have no difference in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells. CONCLUSIONS AND RELEVANCE: The addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species, the primary cause of fungal infection after corneal transplantation. This study found significant endothelial toxic effects at the maximal concentration of amphotericin B.


Assuntos
Antifúngicos/farmacologia , Candidíase/prevenção & controle , Sulfatos de Condroitina/farmacologia , Córnea , Dextranos/farmacologia , Contaminação de Medicamentos/prevenção & controle , Gentamicinas/farmacologia , Soluções para Preservação de Órgãos/farmacologia , Anfotericina B/efeitos adversos , Anfotericina B/farmacologia , Antifúngicos/efeitos adversos , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Candidíase/microbiologia , Contagem de Células , Sulfatos de Condroitina/efeitos adversos , Contagem de Colônia Microbiana , Misturas Complexas/efeitos adversos , Misturas Complexas/farmacologia , Meios de Cultura Livres de Soro/efeitos adversos , Meios de Cultura Livres de Soro/farmacologia , Dextranos/efeitos adversos , Combinação de Medicamentos , Endotélio Corneano/efeitos dos fármacos , Endotélio Corneano/microbiologia , Endotélio Corneano/patologia , Gentamicinas/efeitos adversos , Humanos , Testes de Sensibilidade Microbiana , Preservação de Órgãos , Soluções para Preservação de Órgãos/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/farmacologia , Doadores de Tecidos , Resultado do Tratamento , Triazóis/efeitos adversos , Triazóis/farmacologia , Voriconazol
12.
J Cataract Refract Surg ; 39(9): 1307-13, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23871112

RESUMO

PURPOSE: To quantify changes in endothelial cell counts and corneal thickness measurements in patients having standard phacoemulsification compared with femtosecond laser-assisted cataract removal. SETTING: Ruhr University Eye Clinic, Bochum, Germany. DESIGN: Prospective randomized intraindividual cohort study. METHODS: One eye of each patient had standard phacoemulsification (control group) and the other eye had femtosecond laser-assisted phacoemulsification (study group), both with intraocular lens implantation. Pulsed ultrasound energy was used for phacoemulsification. Noncontact endothelial cell microscopy and corneal pachymetry were performed preoperatively and 1 day, 3 to 4 days, 7 to 10 days, 50 to 60 days, and 90 to 100 days postoperatively. RESULTS: The mean endothelial cell loss was 7.9% ± 7.8% (SD) 1 week postoperatively and 8.1% ± 8.1% 3 months postoperatively in the study group and 12.1% ± 7.3% and 13.7% ± 8.4%, respectively, in the control group. The mean relative change in corneal thickness from the preoperative values was -0.0% ± 1.9% at 1 day, 2.8% ± 1.8% at 1 week, and 3.3% ± 1.7% at 3 months in the study group and -0.9% ± 2.3%, 2.4% ± 1.5%, and 3.2% ± 1.4%, respectively, in the control group. CONCLUSION: The femtosecond laser did not add to the endothelial damage caused by cataract surgery and might be beneficial in eyes with low preoperative endothelial cell values (eg, cornea guttata cases).


Assuntos
Córnea/patologia , Perda de Células Endoteliais da Córnea/etiologia , Implante de Lente Intraocular , Terapia com Luz de Baixa Intensidade/métodos , Facoemulsificação/métodos , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Estudos de Coortes , Perda de Células Endoteliais da Córnea/patologia , Endotélio Corneano/patologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
13.
Klin Monbl Augenheilkd ; 230(3): 247-54, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23508753

RESUMO

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.


Assuntos
Inibidores da Angiogênese/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Imidazóis/farmacologia , Indazóis/farmacologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/patologia , Inibidores da Angiogênese/efeitos adversos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Axitinibe , Córnea/efeitos dos fármacos , Córnea/patologia , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Corneano/efeitos dos fármacos , Endotélio Corneano/patologia , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Cristalino/efeitos dos fármacos , Cristalino/patologia , Microscopia de Contraste de Fase , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Disco Óptico/efeitos dos fármacos , Disco Óptico/patologia , Técnicas de Cultura de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Sorafenibe , Sulfonamidas/efeitos adversos , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia
14.
Invest Ophthalmol Vis Sci ; 53(10): 6164-70, 2012 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-22899758

RESUMO

PURPOSE: We evaluated whether viscoelastics have protective effects on the corneal endothelial cell damage in a toxic anterior segment syndrome (TASS) animal model depending on the types of viscoelastics. METHODS: A TASS animal model was established with an injection of 0.1 mL o-phthaldehyde solution (0.14%) into the anterior chamber of New Zealand white rabbits. One of two different viscoelastics, 1% sodium hyaluronate (cohesive group) or a 1:3 mixture of 4% chondroitin sulfate and 3% sodium hyaluronate (dispersive group), was injected into the anterior chamber. After five minutes, it was removed using a manual I/A instrument, and then 0.1 mL of o-phthaldehyde solution (0.14%) was injected into the anterior chamber. Damage to corneal endothelial cells was compared between the two groups. RESULTS: The corneal thickness increased quickly in both groups after the disinfectant injection. However, the dispersive group showed relatively mild corneal edema compared to the cohesive group. The mean corneal haze score in the dispersive group also was lower than that of the cohesive group. These partial protective effects of the dispersive viscoelastic were demonstrated by the different findings of a live/dead cell assay, TUNEL staining, and scanning electron microscopy between the two groups. CONCLUSIONS: The TASS animal model seems to be a useful means to evaluate corneal endothelial cell damage caused by toxic substances to find ways to protect or reduce endothelial cell damage. Dispersive viscoelastics were shown to have partial protective effects against corneal endothelial cell damage caused by a toxic disinfectant.


Assuntos
Segmento Anterior do Olho/efeitos dos fármacos , Perda de Células Endoteliais da Córnea/induzido quimicamente , Perda de Células Endoteliais da Córnea/tratamento farmacológico , Endotélio Corneano/efeitos dos fármacos , Substâncias Viscoelásticas/farmacologia , o-Ftalaldeído/toxicidade , Animais , Segmento Anterior do Olho/patologia , Antígeno CD11b/metabolismo , Sulfatos de Condroitina/farmacologia , Edema da Córnea/induzido quimicamente , Edema da Córnea/tratamento farmacológico , Edema da Córnea/patologia , Perda de Células Endoteliais da Córnea/patologia , Modelos Animais de Doenças , Desinfetantes/toxicidade , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Ácido Hialurônico/farmacologia , Soluções Oftálmicas/farmacologia , Coelhos , Viscossuplementos/farmacologia
15.
Ophthalmic Surg Lasers Imaging ; 42(2): 152-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21323271

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the protective effect of different ophthalmic viscosurgical devices (OVDs) on corneal endothelial cells against relatively severe phacoemulsification damage in a rabbit model. MATERIALS AND METHODS: Twenty-four rabbit eyes were randomly assigned to four similar groups: in three groups the aqueous humor was completely replaced by Visiol (TRB CHEMEDICA, München, Germany), Biolon (Bio-Technology General Ltd., Kiryat Malachi, Israel), and Viscoat (Alcon, Puurs, Belgium) and in the control group no OVD was applied. Endothelial cell counts were performed prior to initiating the study. All eyes were exposed to continuous 5 minutes of phacoemulsification. Endothelial cell counts were repeated 4 days postoperatively. RESULTS: Viscoat showed the highest endothelial cell loss (30%), followed by Biolon (25%), Visiol (22%), and the control group (19%). None of the differences between the groups were found to be statistically significant, although they were within each group (P = .028). CONCLUSION: None of the tested OVDs demonstrated protective effect on corneal endothelial cells in comparison to the control group. This model was found to be too aggressive for the demonstration of the protective effect of different OVDs even for hard cataract.


Assuntos
Sulfatos de Condroitina/farmacologia , Citoproteção , Endotélio Corneano/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Facoemulsificação/métodos , Viscossuplementos/farmacologia , Animais , Contagem de Células , Morte Celular/efeitos dos fármacos , Combinação de Medicamentos , Endotélio Corneano/patologia , Coelhos , Fatores de Tempo
16.
J Cataract Refract Surg ; 36(11): 1972-5, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21029907

RESUMO

PURPOSE: To evaluate the protective effect of different ophthalmic viscosurgical devices on corneal endothelial cells during phacoemulsification in a rabbit model. SETTING: Harlan Biotech Israel and Ophthalmology Department, Kaplan Medical Center, Rehovot, Israel. DESIGN: Experimental study. METHODS: Rabbit eyes were randomly assigned to 3 equally sized groups. Endothelial cell counts were performed in all eyes before initiation of the study. The aqueous humor was completely replaced by Biolon (sodium hyaluronate 1.0%) in Group A, by a combination of Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) and Provisc (sodium chondroitin sulfate 1.0%) using the soft-shell technique in Group B, and by a combination of Visiol (sodium hyaluronate 2.0%-mannitol 0.5%) and Biolon using the soft-shell technique in Group C. The eyes were exposed to alternating 10 seconds of phacoemulsification and a 10-second pause until a total exposure time of 2.5 minutes elapsed. Endothelial cell counts were repeated 3 days after surgery. RESULTS: The study used 18 rabbit eyes, 6 in each group. Group A had the highest endothelial cell loss (13%) followed by Group B (7%), and Group C (4%). The difference in cell loss between Group C and Group A was statistically significant (P = .037). CONCLUSION: The study showed the efficiency and advantages of the soft-shell technique using the combination of Visiol and Biolon over Biolon alone.


Assuntos
Perda de Células Endoteliais da Córnea/prevenção & controle , Endotélio Corneano/efeitos dos fármacos , Soluções Oftálmicas/farmacologia , Facoemulsificação , Viscossuplementos/farmacologia , Animais , Contagem de Células , Sulfatos de Condroitina/farmacologia , Perda de Células Endoteliais da Córnea/patologia , Combinação de Medicamentos , Endotélio Corneano/patologia , Ácido Hialurônico/farmacologia , Modelos Animais , Coelhos
17.
Chin J Physiol ; 53(3): 190-5, 2010 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-21793328

RESUMO

Cornea absorbs most of daily ultraviolet (UV) light. An excess of UV damages results in not only keratopathy and cataract but also maculopathy. It has been reported that thymosin beta-4 (Tbeta4) promotes wound healing, decreases inflammatory response and prevents apoptosis of corneal epithelial cells. However, it is not clear whether Tbeta4 protects UVB-induced corneal injury, particularly in corneal endothelial cells because of its non-proliferation in nature. The purpose of this study is to compare the protective effects of Tbeta4 on bovine corneal endothelial (BCE) cells from low- and high-dose UVB damage. In this study, 1 microg/ml of Tbeta4 was added to BCE cells 2 h before low (12.5 mj/cm2) or high dosage (100 mj/cm2) UVB exposure. Using a fluorogenic substrate cleavage assay, we found that Tbeta4 diminished the reactive oxygen species level in BCE cells elicited by UVB. However, the protection of viability by Tbeta4 could only be detected under low-dose UVB exposure. Moreover, both caspase-9 activity and annexin V/propidium iodine staining demonstrated that Tbeta4 only protected BCE cells from low-dose UVB-induced apoptosis but not high-dose UVB-induced necrosis. Together, Tbeta4 protected corneal endothelial cells from UVB-induced oxidative stress and apoptosis after low-dose UVB exposure. The results support further investigation towards topical use or anterior chamber injection of this small hydrophilic peptide in treating and preventing UVB-induced corneal endothelial damage.


Assuntos
Apoptose/efeitos da radiação , Perda de Células Endoteliais da Córnea/prevenção & controle , Endotélio Corneano/patologia , Endotélio Corneano/efeitos da radiação , Timosina/uso terapêutico , Raios Ultravioleta/efeitos adversos , Animais , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Bovinos , Células Cultivadas , Perda de Células Endoteliais da Córnea/metabolismo , Perda de Células Endoteliais da Córnea/patologia , Relação Dose-Resposta à Radiação , Endotélio Corneano/efeitos dos fármacos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Timosina/farmacologia
18.
Oftalmologia ; 52(1): 84-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18714496

RESUMO

PURPOSE: To compare the ability of different ophthalmic viscoelastic devices to protect the corneal endothelium following in-the-bag phacoemulsification with posterior chamber intraocular lens (IOL) implantation. MATERIAL & METHODS: We studied 50 patients with soft to moderately dense (Grade 1-3) cataract and corneal endothelial cell density of >2000 cells/mm2. The corneal response to surgery was evaluated by measuring the endothelial cell loss, the variation in the mean cell area of the endothelial cells (CV), and the central corneal thickness, all that by using a TOPCON SP 2000P noncontact, specular microscope. Data were recorded preoperatively and postoperatively. RESULTS: Preoperatively no statistical significant difference was observed in cell count, CV or pachymetry among groups. Postoperatively, all the groups had a statistically significant decrease (p < 0.001) in endothelial cell count. There was an equal and significant (p < 0.001) increase in visual acuity. Between groups there was no statistically significant difference (p > 0.17) in any of the parameters we studied. CONCLUSIONS: Between the OVDs we used, either DisCoVisc or ProVisc & VisCoat, there was no statistical significant difference neither in surgical outcome nor in endothelial layer aspect and function. DisCoVisc protected better the endothelium cells even if it was not statistically significant, and is the one that can be used for the entire surgical procedure.


Assuntos
Adjuvantes Imunológicos/farmacologia , Condroitina/farmacologia , Endotélio Corneano/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Facoemulsificação/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Extração de Catarata/métodos , Contagem de Células , Sulfatos de Condroitina , Combinação de Medicamentos , Endotélio Corneano/patologia , Feminino , Humanos , Implante de Lente Intraocular/métodos , Masculino , Pessoa de Meia-Idade , Facoemulsificação/métodos , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Resultado do Tratamento , Acuidade Visual
19.
J Cataract Refract Surg ; 34(9): 1451-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18721703

RESUMO

PURPOSE: To evaluate posterior and anterior segment safety of an intracameral injection of moxifloxacin 0.5% ophthalmic solution as prophylaxis for endophthalmitis in patients having cataract surgery. SETTING: Three private practices, the University of Minnesota School of Medicine, Stillwater, Minnesota, and the University of Cincinnati, Cincinnati, Ohio, USA. METHODS: In this prospective randomized combined-center open-label trial, 57 eyes of 47 patients were treated with intracameral moxifloxacin (250 mug/0.050 mL) or an equal volume of balanced salt solution at the conclusion of cataract surgery with intraocular lens implantation. Safety parameters, including visual acuity, intraocular pressure, endothelial cell counts, corneal pachymetry, corneal clarity and edema, and anterior chamber cells and flare, were evaluated preoperatively and for 3 months postoperatively. RESULTS: Optical coherence tomography results showed no statistically significant differences between the 2 treatment groups preoperatively or at 3 months. There were also no statistically significant differences between the 2 treatment groups in all other parameters preoperatively or at 1 day, 2 to 4 weeks, or 3 months. No study-related adverse events occurred. CONCLUSION: There was no increased safety risk associated with a 250 mug/0.050 mL intracameral injection of moxifloxacin, which appears to be safe in the prophylaxis of endophthalmitis after cataract surgery.


Assuntos
Câmara Anterior/efeitos dos fármacos , Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Compostos Aza/uso terapêutico , Endoftalmite/prevenção & controle , Facoemulsificação , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Compostos Aza/administração & dosagem , Contagem de Células , Endoftalmite/microbiologia , Endotélio Corneano/patologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/prevenção & controle , Feminino , Fluoroquinolonas , Humanos , Pressão Intraocular , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Estudos Prospectivos , Quinolinas/administração & dosagem , Tomografia de Coerência Óptica , Acuidade Visual
20.
Cornea ; 27(6): 679-85, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18580260

RESUMO

PURPOSE: To evaluate best-corrected visual acuity (BCVA), refractive outcome, corneal topography, optical coherence tomography, and endothelial cell density 12 months after femtosecond laser-assisted inverted mushroom keratoplasty. METHODS: We performed a prospective study of a surgical case series of 5 patients undergoing femtosecond laser-assisted inverted mushroom keratoplasty for pseudophakic bullous keratopathy or pre-Descemet X-linked ichthyosis. The femtosecond laser was used to create a top-hat configuration in the donor cornea and recipient cornea. Laser parameters were as follows: energy, 4.0 (anterior inner vertical side cut and horizontal lamellar cut) and 7.0 microJ (posterior outer vertical side cut); spiral pattern with a firing rate of 15 kHz. The size of the anterior inner diameter was 7.4 mm in the donor cornea and 7.0 mm in the recipient cornea. The posterior outer diameter was 9.0 mm in all eyes. RESULTS: At 6 and 12 months after surgery, all corneal grafts were clear and showed an excellent adaptation of the lamellar donor and recipient wound surfaces. At 12 months postoperatively, BCVA averaged 20/32 (range, 20/60-20/20), refractive cylinder averaged -3.20 +/- 2.0 D, topographical cylinder averaged 3.26 +/- 2.1 D, and the mean endothelial cell density was 1793 +/- 491 cells/mm2 (range, 954-2237 cells/mm2). The mean central corneal thickness and thickness of the posterior shelf was 517 +/- 3 and 175 +/- 8 microm, respectively. CONCLUSIONS: The femtosecond laser-assisted inverted mushroom keratoplasty shows good promise in surgical treatment of corneal diseases. The multiplanar fit between the donor and recipient cornea allows early suture removal and visual rehabilitation.


Assuntos
Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Ictiose Ligada ao Cromossomo X/cirurgia , Lasers Semicondutores/uso terapêutico , Adulto , Idoso , Contagem de Células , Topografia da Córnea , Endotélio Corneano/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Refração Ocular/fisiologia , Técnicas de Sutura , Tomografia de Coerência Óptica , Transtornos da Visão/reabilitação , Acuidade Visual/fisiologia , Cicatrização
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