Global ETD Search

1	The incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand Edwards, Catherine Patrice, Optometry & Vision Science, Faculty of Science, UNSW January 2008 (has links) Microbial keratitis is the most serious, and only potentially blinding complication of contact lens wear. To further understand and reduce the risk of this disease, incidence rates and risk factors have been estimated in numerous studies. Since these studies were conducted, new lens types have been introduced designed to reduce the risk of infection. It was hypothesised that the issues of contact lens related hypoxia and poor lens hygiene could be addressed by the introduction of silicone hydrogel and daily disposable lenses respectively. This thesis describes the incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand. The incidence of infection was determined by capturing all cases of contact lens related presumed microbial keratitis in a 12-month surveillance study, and by estimating the number of lens wearers using a population-based phone survey. Characteristics of the cases and controls were compared to estimate risk factors. In Australia, rates of infection with daily and overnight wear of hydrogel lenses were similar to previously published reports (1.9 [95%CI]:1.8-2.0] and 19.5 [95%CI:14.6-29.5] per 10,000 wearers respectively). Compared to the incidence of infection with hydrogel lenses, silicone hydrogel lenses had a higher rate in daily wear (11.9 [95%CI: 10.0-14.6]), and a similar rate in extended wear (19.5 [95%CI:14.6-29.5]). Daily disposable lenses had a similar rate of infection to daily wear of hydrogel lenses (2.0 [95%CI:1.7-2.4]), but appeared to reduce the incidence of severe or vision loss keratitis (0.5 [95%CI: 0.5-0.6] and 0.0 [95%CI: 0.0-0.0] respectively). Conducting the study in New Zealand confirmed the increase in incidence for overnight use of lenses, irrespective of lens type. Comparison of the incidence rates in New Zealand and Australia show that the rates in the two countries are comparable, bar an unexplained lower rate of infection for extended wear of soft hydrogel lenses in New Zealand. Risk factors for infection were overnight use of lenses, from occasional overnight to extended wear use, poor lens case hygiene, smoking, high socio-economic status and less than 6 months experience in current lens type. Amongst daily wearers, Internet or mail order purchasing of lenses was also associated with a higher risk of infection. This study is unique in terms of the study design and sample size, and the wide scope of risk factors considered. The determination of these incidence rates of infection and identification of risk factors is of extreme value to lens wearers and lens care practitioners around the world, particularly as the strongest and most prevalent risk factors are modifiable. microbial keratitis contact lenses incidence
2	The incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand Edwards, Catherine Patrice, Optometry & Vision Science, Faculty of Science, UNSW January 2008 (has links) Microbial keratitis is the most serious, and only potentially blinding complication of contact lens wear. To further understand and reduce the risk of this disease, incidence rates and risk factors have been estimated in numerous studies. Since these studies were conducted, new lens types have been introduced designed to reduce the risk of infection. It was hypothesised that the issues of contact lens related hypoxia and poor lens hygiene could be addressed by the introduction of silicone hydrogel and daily disposable lenses respectively. This thesis describes the incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand. The incidence of infection was determined by capturing all cases of contact lens related presumed microbial keratitis in a 12-month surveillance study, and by estimating the number of lens wearers using a population-based phone survey. Characteristics of the cases and controls were compared to estimate risk factors. In Australia, rates of infection with daily and overnight wear of hydrogel lenses were similar to previously published reports (1.9 [95%CI]:1.8-2.0] and 19.5 [95%CI:14.6-29.5] per 10,000 wearers respectively). Compared to the incidence of infection with hydrogel lenses, silicone hydrogel lenses had a higher rate in daily wear (11.9 [95%CI: 10.0-14.6]), and a similar rate in extended wear (19.5 [95%CI:14.6-29.5]). Daily disposable lenses had a similar rate of infection to daily wear of hydrogel lenses (2.0 [95%CI:1.7-2.4]), but appeared to reduce the incidence of severe or vision loss keratitis (0.5 [95%CI: 0.5-0.6] and 0.0 [95%CI: 0.0-0.0] respectively). Conducting the study in New Zealand confirmed the increase in incidence for overnight use of lenses, irrespective of lens type. Comparison of the incidence rates in New Zealand and Australia show that the rates in the two countries are comparable, bar an unexplained lower rate of infection for extended wear of soft hydrogel lenses in New Zealand. Risk factors for infection were overnight use of lenses, from occasional overnight to extended wear use, poor lens case hygiene, smoking, high socio-economic status and less than 6 months experience in current lens type. Amongst daily wearers, Internet or mail order purchasing of lenses was also associated with a higher risk of infection. This study is unique in terms of the study design and sample size, and the wide scope of risk factors considered. The determination of these incidence rates of infection and identification of risk factors is of extreme value to lens wearers and lens care practitioners around the world, particularly as the strongest and most prevalent risk factors are modifiable. microbial keratitis contact lenses incidence
3	Antibiotic functionalised polymers reduce bacterial biofilm and bioburden in a simulated infection of the cornea Doroshenko, N., Rimmer, Stephen, Hoskins, Richard, Garg, P., Swift, Thomas, Spencer, Hannah L.M., Lord, Rianne M., Katsikogianni, Maria G., Pownall, D., MacNeil, S., Douglas, C.W.I., Shepherd, J. 04 June 2018 (has links) Yes / Microbial keratitis can arise from penetrating injuries to the cornea. Corneal trauma promotes bacterial attachment and biofilm growth, which decrease the effectiveness of antimicrobials against microbial keratitis. Improved therapeutic efficacy can be achieved by reducing microbial burden prior to antimicrobial therapy. This paper assesses a highly-branched poly(N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van), for reducing bacterial attachment and biofilm formation. The polymer lacked antimicrobial activity against Staphylococcus aureus, but significantly inhibited biofilm formation (p = 0.0008) on plastic. Furthermore, pre-incubation of S. aureus cells with HB-PNIPAM-van reduced cell attachment by 50% and application of HB-PNIPAM-van to infected ex vivo rabbit corneas caused a 1-log reduction in bacterial recovery, compared to controls (p = 0.002). In conclusion, HB-PNIPAM-van may be a useful adjunct to antimicrobial therapy in the treatment of corneal infections. / Medical Research Council and the Department of Biotechnology, India under grant number, MR/N50188/2. Microbial keratitis Cornea Corneal trauma Antimicrobial therapy
4	Ex vivo rabbit and human corneas as models for bacterial and fungal keratitis Pinnock, A., Shivshetty, N., Roy, S., Rimmer, Stephen, Douglas, I., MacNeil, S., Gary, P. 14 November 2016 (has links) Yes / In the study of microbial keratitis, in vivo animal models often require a large number of animals, and in vitro monolayer cell culture does not maintain the three-dimensional structure of the tissues or cell-to-cell communication of in vivo models. Here, we propose reproducible ex vivo models of single- and dual-infection keratitis as an alternative to in vivo and in vitro models. / Wellcome Trust
5	Development of a novel micro-bead force spectroscopy approach to measure the ability of a thermo-active polymer to remove bacteria from a corneal model Pattem, J., Swift, Thomas, Rimmer, Stephen, Holmes, T., MacNeil, S., Shepherd, J. 25 March 2022 (has links) Yes / Microbial keratitis occurs from the infection of the cornea by fungi and or bacteria. It remains one of the most common global causes of irreversible blindness accounting for 3.5% (36 million) of blind people as of 2015. This paper looks at the use of a bacteria binding polymer designed to bind Staphylococcus aureus and remove it from the corneal surface. Mechanical unbinding measurements were used to probe the interactions of a thermo-active bacteria-binding polymer, highly-branched poly(N-isopropyl acrylamide), functionalised with modified vancomycin end groups (HB-PNIPAM-Van) to bacteria placed on rabbit corneal surfaces studied ex-vivo. This was conducted during sequential temperature phase transitions of HB-PNIPAM-Van-S. aureus below, above and below the lower critical solution temperature (LCST) in 3 stages, in-vitro, using a novel micro-bead force spectroscopy (MBFS) approach via atomic force microscopy (AFM). The effect of temperature on the functionality of HB-PNIPAM-Van-S. aureus showed that the polymer-bacteria complex reduced the work done in removing bacterial aggregates at T > LCST (p < 0.05), exhibiting reversibility at T < LCST (p < 0.05). At T < LCST, the breaking force, number of unbinding events, percentage fitted segments in the short and long range, and the percentage of unbinding events occurring in the long range (> 2.5 µm) increased (p < 0.05). Furthermore, the LCST phase transition temperature showed 100 × more unbinding events in the long-range z-length (> 2.5 µm) compared to S. aureus aggregates only. Here, we present the first study using AFM to assess the reversible mechanical impact of a thermo-active polymer-binding bacteria on a natural corneal surface. / This work was funded by the Medical Research Council (MRC-DBT 'UKICAT-minimising antibiotic use', MR/N501888). Microbial keratitis Thermo‑active polymer Bacteria Cornea Bacteria binding polymer
6	Public health impact of contact lens related microbial keratitis Keay, Lisa Jane, Optometry & Vision Science, Faculty of Science, UNSW January 2006 (has links) This thesis describes the impact of contact lens-related microbial keratitis in terms of incidence and severity. Disease outcome is defined by visual outcome, costs to the healthcare system, costs to the individual and duration of disease. A successful 12-month surveillance study was conducted of the populations of Australia and New Zealand to detect all cases of contact lens-related microbial keratitis. A random telephone survey of 32,000 households in Australia and 7,500 in New Zealand accurately determined the level of use of various contact lenses in the community. The impact of new contact lens types: silicone hydrogels and daily disposables were investigated. Increased risk persisted in overnight wear with silicone hydrogel materials. Microbial keratitis associated with silicone hydrogel materials had slightly shorter disease duration however other factors had a stronger influence on severity. Rigid gas permeable and frequent replacement soft lenses when used for daily wear constitute the lowest risk. Cost analysis was developed in a hospital case series of microbial keratitis. This analysis was applied in the surveillance study including cases managed in the private health care sector. Disease duration and associated costs are novel indices of severity for contact lens-related disease. The most dramatic effects on disease severity were seen with the type of organism involved. Keratitis attributed to environmental organisms (Gram-negative bacteria, Acanthamoeba, fungi and Nocardia species) were 10x more likely to cause loss of visual acuity, had longer duration of symptoms and incurred higher costs. Importantly, delays in receiving treatment increased disease duration and associated costs. Greater awareness of the need for specialist healthcare is indicated amongst health care providers and contact lens wearers. The hypothesis that overnight wear in silicone hydrogel lenses would not increase the risk of infection has been disproven. This information is of value to practitioners who are responsible for informing contact lens wearers about the risk of contact lens-related infections and should be weighed against the benefits of continuous wear. The identification of factors which contribute to the outcomes of disease will be used in education campaigns amongst health care providers and contact lens wearers to minimise the impact of disease. microbial keratitis cost analysis vision loss silicone hydrogel incidence contact lens
7	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology
8	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology

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