Association of Single Nucleotide Polymorphisms of Interleukins-1β, -6, and -12B with Contact Lens Keratitis Susceptibility and Severity

Carnt, Nicole; Willcox, Mark; Hau, Scott; Garthwaite, Linda; Evans, Victoria; Radford, Cherry; Dart, John; Chakrabarti, Subhabrata; Stapleton, Fiona

doi:10.1016/j.ophtha.2012.01.031

Cited by 38 publications

(35 citation statements)

References 38 publications

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“…And, while the study group has been making steps toward a broader assessment of the many known and presumed risk factors, the ORACL pilot study did not assess all of the known and presumed drivers of CL complications (i.e., genetic predisposition, ocular immune response). [57][58][59] Nevertheless, this study demonstrated that the use of standardized patient surveys and study procedures allowed systematic collection of detailed data that would not otherwise have been available from clinical records and can be used as a model for future studies. 51,52,60 …”

Section: Soft Contact Lens Wearersmentioning

confidence: 99%

Case-Control Pilot Study of Soft Contact Lens Wearers With Corneal Infiltrative Events and Healthy Controls

Richdale

Lam

Wagner

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to assess risk factors associated with soft contact lens (SCL)-related corneal infiltrative events (CIEs).METHODS. This was a single-visit, case-control study conducted at five academic centers in North America. Cases were defined as current SCL wearers with a symptomatic CIE. For each case, three age-and sex-matched controls were enrolled. Subjects completed the Contact Lens Risk Survey (CLRS), a standardized scripted medical interview, supplied a recent health history, and underwent an ocular examination. Microbial culturing of the ocular surface, SCL, and lens storage case was conducted for all cases and one of the three matched controls. Univariate and multivariate logistic regression modeling were used to assess the risk of developing a CIE.RESULTS. Thirty cases and 90 controls 13 to 31 years of age completed the study. Corneal infiltrative event diagnosis included contact lens-associated red eye, infiltrative keratitis, and contact lens peripheral ulcer. Subjects with symptomatic CIEs were more likely to harbor substantial levels of gram-negative bioburden on the ocular surface and contact lens. Significant risk factors for developing a CIE were overnight wear of SCLs, use of multipurpose solution, rinsing SCLs with water, lens storage case older than 6 months, previous ''red eye'' event, use of ocular drops in the past week, and illness during the past week.CONCLUSIONS. This pilot study demonstrated feasibility of enrolling a representative pool of SCL wearers with an untreated, symptomatic CIE and assessing CIE risk factors by using standardized methods. A larger sample size is needed to determine relationships between patient-reported behaviors and exposures, microbial bioburden, and CIE development.Keywords: adverse events, contact lenses, corneal infiltrative events, microbial culturing A recent report from the US Centers for Disease Control and Prevention (CDC) called to light the substantial burden associated with contact lens-related complications.1 The CDC report estimated that contact lens-related keratitis results in nearly 1 million doctor visits each year and carries an associated cost of $175 million.1 This estimate does not include the additional ''costs'' to the patient such as pain or discomfort, missed school or work, and potential for permanent loss of vision.Approximately 37 million people in the United States currently wear contact lenses and, due to the increasing prevalence of myopia, more and younger patients are expected to begin wearing contact lenses to aid in its management. 2,3 Research has demonstrated that adult and pediatric patients can safely wear soft contact lenses (SCLs) within controlled trials, with relatively low rates of complications, especially for daily lens wear. 4,5 However, as with most medical devices, when contact lenses are used by the general population outside of controlled trials, the rate and types of complications increase. 1,[6][7][8] The increased risk of complications is likely caused by poor wear and care beha...

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Section: Soft Contact Lens Wearersmentioning

confidence: 99%

Case-Control Pilot Study of Soft Contact Lens Wearers With Corneal Infiltrative Events and Healthy Controls

Richdale

Lam

Wagner

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…68 Specifically the animal models do not exhibit the severe extracorneal inflammation such as scleritis and chorioretinitis. 40 Keijser et al and Carnt et al have shown that small changes to the genes (single nucleotide polymorphisms, SNPs) of key proinflammatory and defence molecules, interleukin, IL-6, 128 IL-10, 129,130 IL-12b, 128 IL-17 131 and beta defensin 1 132 are associated with the susceptibility and severity of bacterial keratitis in contact lens wearers. These studies have provided proof of concept that the host immune profile plays a role in keratitis and, because of complex interactions of Acanthamoeba with the host defences and the wide spectrum of severity of disease, it is likely that by profiling the host immune profile in Acanthamoeba keratitis will show differences between patients and show associations with disease severity.…”

Section: Understanding Individual Differences In Susceptibilitymentioning

confidence: 99%

Strategies for the prevention of contact lens‐related Acanthamoeba keratitis: a review

Carnt

Stapleton

2015

Ophthalmic Physiologic Optic

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102

129

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Purpose: Acanthamoeba keratitis is a severe, often sight threatening, corneal infection which in Western countries is predominantly seen in daily wear of contact lenses. This review aims to summarise the pathobiology and epidemiology of contact lens-related Acanthamoeba keratitis, and to present strategies for prevention, particularly with respect to modifiable risk factors in contact lens wear. Recent Findings: The virulence of Acanthamoeba and resistance to treatment in keratitis appears to be linked with the production of a low molecular weight pro-tease MIP133 by the organism, in response to binding to corneal epithelial cells through a mannose binding protein, and to the ability of the organism to convert from the trophozoite to the resistant cyst form. Recent epidemiological studies in contact lens relate disease have confirmed the link between solution topping up and Acanthamoeba keratitis and have reinforced the importance of avoidance of tap water, either as part of the care for the contact lens or storage case, handling lenses with wet hands or showering while wearing lenses. In the most recent analysis from the USA, there were no strong effects for solution type, water source or water disinfection process. Wearer age, lens wear time and history to appear to be linked with Acanthamoeba keratitis. Daily disposable contact lens use would be expected to reduce the prevalence of Acanthamoeba disease although this is unproven. Summary: While Acanthamoeba keratitis remains challenging to diagnose and manage, strategies to limit the disease severity in contact lens wearers should include attention to recently identified risk factors, particularly those related to water contact. Public health awareness measures, the use of daily disposable contact lenses, a better understanding of the contribution of the host immunity and the development of standardised methods for culture of amoeba and testing of contact lens care systems against Acanthamoeba in the licensing process may be of value. Alternative treatments for the future may include those which target the mannose binding protein or the genes which control conversion to the cyst form.

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“…Tear pro-inflammatory cytokines, including interleukin (IL)-1β, 6, 12(p70) and tumor necrosis factor-α (TNF-α) promote the inflammatory response on the ocular surface, and are detected in dry eye 1–4 , ocular allergy, 5 bacterial keratitis, 6 graft versus host disease 7 and contact lens wear. 8–11 Specifically, mature IL-1β is involved in upregulating inflammatory cellular activity and defending the ocular surface against infection. 12–16 IL-6 and TNF-α also regulate inflammatory cells on the ocular surface to defend against pathogens and promote epithelial wound healing.…”

Section: Introductionmentioning

confidence: 99%

Changes in Tear Cytokine Concentrations Following Discontinuation of Soft Contact Lenses—A Pilot Study

Chao

Golebiowski²,

Stapleton³

et al. 2016

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Purpose This study investigated changes in selected tear cytokine concentrations (IL-1β, IL-1Ra, IL-6, IL-10, IL-12(p70) and TNF-α) following a 1-week washout from soft contact lens wear (CLW), and the repeatability of cytokine measurements using custom Multiplex assays. Methods A total of 10 subjects completed this 6-visit (immediately following contact lens removal, and after 1, 2, 3, 4 and 7 (±1) days without CLW) pilot study. Approximately 20–30μl of pooled basal tears were collected from both eyes at each visit. Two custom Multiplex assays were used by 2 operators to quantify the concentration of tear cytokines. Tear samples from subjects 1–6 were analysed using the first kit by operator 1. Tear samples from subject 7–10 plus additional tear samples from subjects 1–5, which were used to determine between-kit/operator repeatability, were analysed using the second kit by operator 2. Linear mixed models were used to determine changes in tear cytokine concentrations over time. Between-kit/operator and within-kit/operator repeatability was assessed using a Bland and Altman analysis. Results There were no significant changes in tear cytokine concentrations over a 1-week washout of CLW. More than 99% of the tear samples had detectable levels of cytokines using custom Multiplex assays. Within-kit/operator repeatability was good, but between-kit/operator repeatability was poor; likely due to protein degradation, differences in operator experience and operating procedures. Conclusion A washout period may not be necessary when evaluating changes in tear cytokines with new contact lenses or lens care products. A well-trained operator using standardized operating procedures can produce repeatable measurements using custom Multiplex assays.

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Association of Single Nucleotide Polymorphisms of Interleukins-1β, -6, and -12B with Contact Lens Keratitis Susceptibility and Severity

Cited by 38 publications

References 38 publications

Case-Control Pilot Study of Soft Contact Lens Wearers With Corneal Infiltrative Events and Healthy Controls

Case-Control Pilot Study of Soft Contact Lens Wearers With Corneal Infiltrative Events and Healthy Controls

Strategies for the prevention of contact lens‐related Acanthamoeba keratitis: a review

Changes in Tear Cytokine Concentrations Following Discontinuation of Soft Contact Lenses—A Pilot Study

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