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Infectious keratitis is a rare but potentially severe sight-threatening disease, associated with considerable societal burden, cost and morbidity. This review summarises the most recent evidence for the incidence, risk factors and impact of disease, all of which vary widely according to region, access to health care, socioeconomic and environmental factors, predisposing conditions and causative organisms. The frequency and societal impact of infectious keratitis are significantly higher in low-income countries. In non-viral infectious keratitis, bacterial causes predominate in most regions. Fungi, particularly linked with agricultural trauma, are more frequently associated with infectious keratitis in low-income regions, particularly in India and certain African countries. The disease impact is compounded by poverty and limited access to services and treatment. Early diagnosis, access to appropriate treatment, prophylaxis in ocular trauma, availability of eye protection, awareness of risk factors may be associated with reduced disease severity and vision loss. Evidence for the incidence and burden of disease is lacking in certain regions and well-designed epidemiological studies to identify independent risk factors for the disease and those associated with more severe outcomes may better identify causation and guide resource allocation and preventative strategies., Competing Interests: Declaration of competing interest There are no conflicts of interest declared., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objective: The study aimed to profile and quantify tear metabolites associated with bacterial keratitis using both untargeted and targeted metabolomic platforms., Methods: Untargeted metabolomic analysis using liquid-chromatography-Q Exactive-HF mass-spectrometry explored tear metabolites significantly associated with bacterial keratitis (n = 6) compared to healthy participants (n = 6). Differential statistics and principal component analysis determined meaningful metabolite differences between cases and controls. Purines and nucleosides were further quantified and compared between 15 cases and 15 controls in the targeted metabolomic platform using TSQ quantum access triple quadrupole mass spectrometry. Compound quantification was done by plotting the calibration curves and the difference in the compound levels was evaluated using the Wilcoxon rank-sum test., Results: In the untargeted analysis, 49 tear metabolites (27 upregulated and 22 downregulated) were differentially expressed between cases and controls. The untargeted analysis indicated that the purine metabolism pathway was the most affected by bacterial keratitis. Metabolite quantification in the targeted analysis further confirmed the upregulation of xanthine (P = 0.02) and downregulation of adenine (P < 0.0001), adenosine (P < 0.0001) and cytidine (P < 0.0001) in the tears of participants with bacterial keratitis compared to that of healthy participants., Conclusions: Bacterial keratitis significantly changes the tear metabolite profile, including five major compound classes such as indoles, amino acids, nucleosides, carbohydrates, and steroids. This study also indicates that tear fluids can be used to map the metabolic pathways and uncover metabolic markers associated with bacterial keratitis. Conceivably, the inhibition of nucleoside synthesis may contribute to the pathophysiology of bacterial keratitis because nucleosides are required for maintaining cellular energy homeostasis and immune adaptability., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Determine demographic and clinical characteristics associated with positive culture in suspected microbial keratitis., Methods: Retrospective audit of patients that had corneal scrapings between October 1999-September 2004 at Princess Alexandra Hospital. Clinical information was gathered from medical records, smear and culture results from the local microbiology database. Univariate and multivariate analyses of variables associated with positive cultures and calculation of population attributable risk percentage (PAR)., Results: Univariate analysis showed that positive cultures were associated with patients over 60 years (81% vs 55%; p < 0.001), presenting visual acuity (VA) of 6/24 or worse (74% vs 57%; p = 0.012) or contact lens-related keratitis (CLK 77% vs 62%; p = 0.08). Analysis of patients' clinical presentation showed that positive culture was associated with a central epithelial defect (74% vs 57%; p = 0.012), anterior chamber reaction of 2 + cells or worse (73% vs 56%; p = 0.03), an epithelial defect of 2 mm or more in diameter (71% vs 50%; p = 0.006) or no prior treatment with antibiotics (68% vs 56%; p = 0.053). Multivariate analysis showed the independent variables associated with positive cultures were VA of 6/24 or worse on presentation, contact lens-related keratitis, age greater than 60 years, an anterior chamber reaction of 2 + cells or worse and no prior treatment with antibiotics. The factor with the highest attributable risk (PAR%) for a positive corneal scraping was VA of 6/24 or worse on presentation (21%)., Conclusions: In this series positive cultures were associated with poor presenting VA contact lens keratitis (CLK), older age, anterior chamber reaction and no prior treatment with antibiotics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Staphylococcus aureus, cause a range of ocular diseases in humans, including noninfectious corneal infiltrative events (niCIE), infectious conjunctivitis and sight threatening microbial keratitis (MK). This study aimed to determine the possession of known virulence genes of S. aureus associated with MK and conjunctivitis, in strains isolated from these conditions and niCIE., Methods: Sixty-three S. aureus strains-23 from MK, 26 from conjunctivitis, and 14 from niCIE-were evaluated for possession of genes. Polymerase chain reaction was used for the detection of mecA and 10 known virulence genes involved in MK (clfA, fnbpA, eap, coa, scpA, sspB, sspA, hla, hld, and hlg), 2 associated with conjunctivitis (pvl and seb)., Results: mecA was present in 35% of infections and 7% of niCIE strains (P = 0.05). It was not seen in infection strains from Australia. Adhesion genes were found in all strains except clfA, which was found in 75% of infection and 93% of niCIE strains. Invasion genes were found in higher frequency in infections strains-hlg (100% vs. 85%; P = 0.04) and hld (94% vs. 50%; P = 0.005)-compared with niCIE strains. Evasion genes were common in infection strains except scpA, which was found at a significantly higher frequency in niCIE strains (86%) compared with infection strains (45%; P = 0.001)., Conclusions: The higher rates of hlg and hld in strains isolated from infections than niCIE may have a role in pathogenesis, whereas scpA may be an important virulence factor during niCIEs., Translational Relevance: This study has identified virulence factors involved in the ocular pathogenesis of S. aureus infections and niCIE.

Abstract: Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non-CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CL-related and non-CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Contact Lens Association of Ophthalmologists.)

Purpose: To explore demographics, disease characteristics, and wear habits in cosmetic contact lens (CL)-related corneal infections in Asia., Design: Prospective multicenter cross-sectional study., Methods: Cases of CL-related corneal infection presenting over a 12-month period were prospectively identified from 11 centers in 8 countries in Asia. Case demographics, clinical features, microbiology, and compliance characteristics were compared between wearers using CLs for cosmetic purposes and those using CLs for the correction of refractive errors., Results: Six hundred and ninety-four CL wearers with corneal infection presented: 204 cosmetic CL (29.4%) and 490 (70.6%) refractive CL wearers. Cosmetic CL infections comprised 7%-54% of cases across the region. Compared with noncosmetic CL wearers, cosmetic CLs wearers were significantly more likely to be female (90% vs 59%), young (aged <25, 68% vs 44%), and to have a shorter period of wear experience. Lenses worn by cosmetic CL wearers were more likely to be hydrogel materials and manufactured with the pigment located on the back surface of the CL. Presenting disease characteristics and visual outcomes were similar in both groups. Causative organisms were similar between the 2 groups; however, there was a higher rate of Acanthamoeba disease (9%) in cosmetic wearers, compared with refractive wearers (1%; P < .005)., Conclusions: Cosmetic CL infections represent a significant proportion of CL-related infections in Asia. Cosmetic CL users with corneal infections are generally young, female, and wearing hydrogel CLs. Internet supply, quality control, and regulation of the sale of these products provide significant challenges in managing this population of vulnerable wearers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Clinical relevance : Keratitis is common and studies of blindness throughout the world have found that corneal disease is the second most common cause of blindness. Background : Microbial keratitis a bacterial, fungal, or protozoan disease of the cornea, characterised by a corneal infiltrate with an overlying epithelial defect and associated anterior chamber reaction. Methods : Patients were identified through the hospital pathology database and a retrospective chart review of all patients with a positive corneal culture between 1999 and 2015 at Princess Alexandra Hospital was carried out. Results : There were 895 records from 779 patients included and additional 107 records excluded. The average age of the included patients was 58.9 years (SD 21.0). Males made up 498 (55.6%) of the included patients. Contact lens microbial keratitis (CLMK) was the most common risk factor for MK and was significantly more common in younger patients. CLMK was significantly associated with cultures positive for Pseudomonas aeruginosa (p < 0.001) while MK secondary to ocular surface disease and prior ocular surgery were more commonly associated with gram-positive organisms (p < 0.001). Monotherapy with a fluoroquinolone was the most common treatment for patients with MK. Good outcomes were seen in 57% of patients. Conclusion : In this patient group, contact lens wear was the most common risk factor for MK. Pseudomonas aeruginosa was the most common isolate.

Significance: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies., Purpose: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting., Methods: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives., Results: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed., Conclusions: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain., Competing Interests: Conflict of Interest Disclosure: All participants were paid by the American Academy of Optometry to participate. The following authors report financial interests, but none of these sponsors provided financial or other support and had no involvement in this report: ECA, Alcon Laboratories, Alcon Research Institute, and Salvat Laboratories; CL, Johnson & Johnson Vision Care, Source One Technical Solutions, Scigofer, and CooperVision; NAC, Alcon, Johnson & Johnson, CooperVision, Specsavers, and Luxottica; DSJ, TECLens, Inc., and Simple Contacts; CEJ, Johnson & Johnson Vision Care, Inc.; CMS, Johnson & Johnson Vision Care; JPS, AbbVie, Aerie Pharmaceuticals, Dompe, LensTech, and Novartis; FS, Alcon Laboratories, Azura Ophthalmics, Nthalmic, Menicon, Novartis, and Sequirus; LBS-F, Johnson & Johnson Vision Care, Alcon, and LensTech; and MDPW, Johnson & Johnson Medical Pty Ltd., Johnson & Johnson Vision Care Inc., CooperVision, Allergan, Alcon Laboratories, and Ophtecs Corp., (Copyright © 2021 American Academy of Optometry.)

Pseudomonas aeruginosa and Staphylococcus aureus are the two dominant Gram-negative and -positive species, respectively, isolated from patients with contact lens-related bacterial keratitis. The clinical features of bacterial keratitis vary, such that timely differential diagnosis can be challenging, which may cause a delay in diagnosis resulting in poorer outcome. This review aims to explore the current understanding of clinical and immunological features associated with contact lens-related P. aeruginosa and S. aureus keratitis based on currently available evidence. Firstly, the review characterises contact lens-related P. aeruginosa and S. aureus keratitis, based on clinical features and prognostic factors. Secondly, the review describes the primary immune response associated with a bacterial infection in in-vivo non-scratch contact lens-wearing animal models, colonised by bacteria on contact lens and topical administration of bacteria on the cornea. Finally, the review discusses the role of macrophage inflammatory protein-2 (MIP-2) and intercellular adhesion molecule (ICAM-1) in neutrophil recruitment based on both in-vivo scratch models of bacterial keratitis and bacterial challenged in cell culture models., (Copyright © 2020 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Microbial keratitis is a rare but potentially severe sight-threatening condition, associated with societal burden, cost and morbidity. Compared with microbial keratitis without lens wear, the disease in contact lens wear is more common, occurs at an earlier age, has lower morbidity and is more often caused by Pseudomonas aeruginosa and Acanthamoeba spp. Resistance to common antibiotics is infrequent in contact lens-related isolates and there is little evidence to suggest increasing bacterial resistance over time. There is some evidence for increased reporting of cases of Acanthamoeba keratitis internationally. The incidence of contact lens-related microbial keratitis has remained stable over time. Rates vary with wear modality, with the lowest risk of severe disease in daily disposable and rigid gas permeable contact lens wear; however, there are limited studies in daily wear silicone hydrogel and in contemporary daily disposable contact lenses. Risk factors for contact lens-related microbial keratitis can be either modifiable or non-modifiable and interventions to reduce the risk of, or severity of disease may be prioritised based on the attributable risk. Key risk factors based on high attributable risk include any overnight wear, failing to wash and dry hands prior to handling lenses and poor storage case hygiene practice. The strong link between microbial keratitis and storage case hygiene and replacement suggests the relevance of microbial contamination of the storage case. Both risk factors and evidence-based strategies for limiting storage case contamination are presented, including storage case cleaning protocols and antimicrobial storage cases; however, it is unclear if such interventions can ultimately limit the rate or severity of microbial keratitis in daily wear. Emerging challenges include understanding and limiting the risk of infection associated with decorative or cosmetic contact lens wear, particularly in Asia, and in understanding the safety of contact lens modalities for myopia control in a paediatric population., (© 2020 Optometry Australia.)

Purpose: This study analyzed the susceptibilities of 17 contact lens (CL)-related keratitis isolates of Pseudomonas aeruginosa from Australia to antibiotics, multipurpose contact lens disinfecting solutions (MPDS), and disinfectants through minimum inhibitory (MIC) and minimum bactericidal concentrations., Methods: Antibiotics included ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin, imipenem, ceftazidime, and polymyxin B. The MPDS OPTI-FREE PureMoist, Complete RevitaLens OcuTec, Biotrue, and Renu Advanced Formula and the constituent disinfectants; alexidine dihydrochloride, polyquaternium-1, polyaminopropyl biguanide, and myristamidopropyl dimethylamine (Aldox) were analyzed. The combined susceptibility of disinfectants based on the MPDS formulation was assessed through fractional inhibitory concentration., Results: All isolates were susceptible to levofloxacin and gentamicin, 2/17 were resistant to ciprofloxacin; 1/17 was resistant to tobramycin, piperacillin, and polymyxin; and 3/17 were resistant to ceftazidime whereas 12/17 were resistant to imipenem. Of the four MPDSs, for Renu Advanced Formula 8/17 strains have an MIC ≤ 11.36 for OPTI-FREE PureMoist 14/17 strains have an MIC ≤ 11.36% for Complete RevitaLens 9/17 strains have an MIC ≤ 11.36, and for Biotrue 5/17 strains have MIC = 11.36. All strains were killed by 100% MPDS. At the concentrations used in the MPDSs, individual disinfectants were not active. From three tested isolates, no synergy was found in dual combinations of disinfectants. However, synergy was found for triple combination of disinfectants for three tested strains., Conclusions: Australian CL-related isolates of P aeruginosa were susceptible to most antibiotics. There was variability in susceptibility to different MPDS. Individual disinfectant excipients had limited activity. The combination of the disinfectants showed synergy, antagonism, and no interaction., Translational Relevance: This study will help to choose better preventive and treatment measures for microbial keratitis., Competing Interests: Disclosure: M. Khan, None; F. Stapleton, None; M.D.P. Willcox, None, (Copyright 2020 The Authors.)

Purpose: To describe the usage patterns of steroids in bacterial keratitis and to analyze the effect of steroids on patients' visual outcomes., Methods: This was a single-center retrospective review of patients with culture-positive bacterial keratitis treated between 1999 and 2015 at Princess Alexandra Hospital (Brisbane, Australia). Patients with culture-positive bacterial keratitis were identified through the Queensland Pathology Database, and clinical information was gathered through a subsequent medical record review. High-dose steroid treatment was classified as 6 or more drops of a steroid a day started within 7 days of corneal scraping. The outcome of a patient's episode of keratitis was classified as good if their final visual acuity was 6/12 or better; poor if it was 6/60 or worse or required a corneal transplant, otherwise it was classified as average. Microbiological and clinical variables' association with outcomes was evaluated in univariate analyses. Variables significant at P < 0.1 were examined in a multivariate ordinal logistic regression analysis created with forward variable selection with forced inclusion of steroid treatment (high, regular, low dose, and none)., Results: A total of 328 patients were included from the 1002 reviewed charts. Of these patients, 164 (50.0%) were treated with steroids. Factors significantly associated with outcomes in the multivariate model were high-dose steroid treatment, visual acuity on presentation, age group, cause of keratitis, infiltrate size, and location. The odds ratio of better outcomes with high-dose steroids was 5.49 (confidence interval, 1.6-19.0, P = 0.007)., Conclusions: High-dose steroid treatment is significantly associated with better visual outcomes in patients with culture-positive bacterial keratitis in this case series.

Contact lens-associated microbial keratitis poses a diagnostic dilemma for optometrists on two fronts. The distinction between sterile inflammation and microbial infection is often blurred. In addition, there is a requirement with nearly 50 per cent of the Australian and New Zealand optometric profession being therapeutically endorsed, to distinguish between cases of infection that can be managed in the community verses those that require escalation to public hospitals that have access to laboratory diagnostic tools and advanced imaging techniques, such as in vivo confocal microscopy. Pattern recognition and incorporation of knowledge of aetiology and risk factors assists optometrists to decide on optimal management strategies. Skilled optometrists will utilise emerging diagnostic and therapeutic technologies to ensure safe management strategies and better outcomes for these cases., (© 2017 Optometry Australia.)

Purpose: This study investigated independent risk factors and causative organisms in microbial keratitis in daily disposable contact lens (CL)-wearers., Methods: A multisite prospective case-control study was undertaken. Cases were daily disposable CL-wearers attending Moorfields Eye Hospital with microbial keratitis and those reported through a one-year surveillance study in Australia and in New Zealand. A population-based telephone survey identified daily disposable CL-wearing controls. Subjects completed a questionnaire describing CL-wear history, hygiene and demographics. The sample used for risk factor analysis was weighted in proportion to the CL-wearing population at each location. Corneal scrape results were accessed. Independent risk factors were determined using multiple binary logistic regression. Causative organisms in different CL-wear modalities were compared using a chi-squared test., Results: 963 daily disposable CL-wearers were identified, from which 67 cases and 374 controls were sampled. Independent risk factors were; wearing CLs every day compared with less frequent use (OR 10.4x; 95% CI 2.9-56.4), any overnight wear (OR 1.8x; 95% CI 1.6-2.1), less frequent hand washing (OR 1.8x; 95% CI 1.6-2.0), and smoking (OR 1.3x; 95% CI 1.1-1.6). Certain daily disposable CLs (OR 0.2x; 95% CI 0.1-0.2) had protective effects. Environmental organisms were less frequently recovered with daily disposable CLs (20%), compared with other modalities (36%; p<0.02)., Conclusion: Overnight wear, increased exposure in daily wear, smoking and poor hand hygiene are significant risk factors for microbial keratitis with daily disposable CLs. Risk varied with daily disposable CL type. The profile of causative organisms is consistent with less severe disease.

A contaminated contact lens case can act as a reservoir for microorganisms that could potentially compromise contact lens wear and lead to sight threatening adverse events. The rate, level and profile of microbial contamination in lens cases, compliance and other risk factors associated with lens case contamination, and the challenges currently faced in this field are discussed. The rate of lens case contamination is commonly over 50%. Coagulase-negative Staphylococcus, Bacillus spp., Pseudomonas aeruginosa and Serratia marcescens are frequently recovered from lens cases. In addition, we provide suggestions regarding how to clean contact lens cases and improve lens wearers' compliance as well as future lens case design for reducing lens case contamination. This review highlights the challenges in reducing the level of microbial contamination which require an industry wide approach., (Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Daily wear of silicone hydrogel (SiHy) lenses using marketed lens care solutions results in varied levels of anterior eye inflammation. There are several pathways that may lead to corneal and conjunctival inflammation that include mechanical, allergic, and pathogen driven stimuli. The hypotheses and evidence for these various models of inflammation will be discussed in the context of SiHy lens designs and materials and lens care solution components.

It was widely anticipated that after the introduction of silicone hydrogel lenses, the risk of microbial keratitis would be lower than with hydrogel lenses because of the reduction in hypoxic effects on the corneal epithelium. Large-scale epidemiological studies have confirmed that the absolute and relative risk of microbial keratitis is unchanged with overnight use of silicone hydrogel materials. The key findings include the following: (1) The risk of infection with 30 nights of silicone hydrogel use is equivalent to 6 nights of hydrogel extended wear; (2) Occasional overnight lens use is associated with a greater risk than daily lens use; (3) The rate of vision loss due to corneal infection with silicone hydrogel contact lenses is similar to that seen in hydrogel lenses; (4) The spectrum of causative organisms is similar to that seen in hydrogel lenses, and the material type does not impact the corneal location of presumed microbial keratitis; and (5) Modifiable risk factors for infection include overnight lens use, the degree of exposure, failing to wash hands before lens handling, and storage case hygiene practice. The lack of change in the absolute risk of disease would suggest that exposure to large number of pathogenic organisms can overcome any advantages obtained from eliminating the hypoxic effects of contact lenses. Epidemiological studies remain important in the assessment of new materials and modalities. Consideration of an early adopter effect with studies involving new materials and modalities and further investigation of the impact of second-generation silicone hydrogel materials is warranted.

Purpose: The aim of this study was to characterize the clinical signs, symptoms, and ocular and systemic comorbidities in a large case series of contact lens-related microbial keratitis., Methods: Two hundred ninety-seven cases of contact lens-related microbial keratitis, aged between 15 and 64 years were detected through surveillance of hospital and community based ophthalmic practitioners in Australia and New Zealand. Full clinical data were available for 190 cases and 90 were interviewed by telephone. Clinical data included the size, location, and degree of anterior chamber response. Symptom data were available from the practitioner and from participant self-report. Associations between symptoms and disease severity were evaluated. Data on ocular and systemic disease were collected from participants and practitioners. The frequency of comorbidities was compared between the different severities of disease and to population norms., Results: More severe disease was associated with greater symptom severity and pain was the most prevalent symptom reported. Ninety-one percent of cases showed progression of ocular symptoms after lens removal, and symptom progression was associated with all severities of disease. Twenty-five percent of cases reported prior episodes requiring emergency attention. Thyroid disease (p = 0.05) and self-reported poor health (p = 0.001) were more common in cases compared with age-matched population norms., Discussion: Information on the signs, symptoms, and comorbidities associated with contact lens-related microbial keratitis may be useful in patient education and for practitioners involved in the fitting of lenses and management of complications. Although pain was the most common symptom experienced, progression of symptoms despite lens removal was close to universal. Poor general health, particularly respiratory disease and thyroid disease was more common in cases than in the general population, which may prompt practitioners to recommend flexibility in wear schedules when in poor health or the selection of a lower risk wear schedule in at risk patients.

Pseudomonas aeruginosa is one of the common pathogens associated with corneal infection, particularly in contact lens-related keratitis events. The pathogenesis of P. aeruginosa in keratitis is attributed to the production of virulence factors under certain environmental conditions. The aim of this study was to determine differences in the virulence factors of P. aeruginosa isolated from contact lens- and non-contact lens-related keratitis. Associations were assessed between type III secretion toxin-encoding genes, protease profiles, biofilm formation, serotypes and antibiotic-resistance patterns among 27 non-contact lens- and 28 contact lens-related P. aeruginosa keratitis isolates from Australia. Strains with a exoS+/exoU- genotype and a type I protease profile predominated in the non-contact lens-related keratitis isolates, whereas the exoS-/exoU+ and a type II protease profile was associated with contact lens-related isolates (P<0.05). A strong biofilm formation phenotype was found to be associated with the possession of the exoU gene, and serotypes E, I and C. The exoS gene was strongly associated with serotypes G, A and B, while exoU was associated with serotypes E and C. Six out of fifty-five (11 %) clinical isolates were non-susceptible (intermediate-resistant or resistant) to ofloxacin and moxifloxacin. All resistant isolates were from non-contact lens-related keratitis. The results suggest that P. aeruginosa isolates from different infection origins may have different characteristics. A better understanding of these differences may lead to further development of evidence-based clinical guidelines for the management of keratitis.

Background: We examine the referral pathways and treatment for contact lens-related microbial keratitis in Australia and New Zealand., Methods: Cases were reported in May 2003-September 2004; data on presentation, referral and treatment collected from practitioners and via patient interview. Severity was graded, 1-week cure rate estimated, delays in treatment and medications documented. Hospital and private clinic managements were compared., Results: A total of 297 eligible cases were reported; detailed information on treatment and referral pathways was available on a subset of these cases. Presentation was to optometrists (81/200, 41%), general practitioners (GPs) (69/200, 34%) or emergency departments (46/200, 23%). Optometrists referred to private ophthalmologists (47/79, 60%) more often than hospitals (27/79, 34%). GPs initiated treatment (39/68, 57%) but also referred to hospitals (22/68, 32%) and to private ophthalmologists (7/68, 10%). Of all cases, 67% (195/297) were managed in hospitals (29% admitted, 87/297). Hospitalized cases were predominantly managed with fortified aminoglycoside/cephalosporin (66/81, 82%) and others fluoroquinolones (168/195, 86%). Steroids were used in 36% (98/276) commencing on day 5 (median, interquartile range = 3-7). One-week cure rate was 60% (49/82) in private clinics, 72% (62/86) for hospital outpatient cases and 37% (25/67, P < 0.001) for inpatient cases, which were more severe diseases (47%, 52% and 0% mild, respectively). Delays (>/=12 h) receiving therapy were experienced by 33% (55/168) because of initial inappropriate treatment (48/55), time delays (7/55) but not remoteness (P = 0.6)., Conclusions: The majority of treatment is via hospital clinics, but milder disease is managed in private clinics. The referral process via optometrists, GPs and emergency departments is generally efficient; however, one-third of cases experienced some delays before receiving appropriate therapy highlighting the need for timely diagnosis.

Purpose: To assess the response to clinical guidelines based on recent epidemiological studies of contact lens-related microbial keratitis., Methods: Incidence rates for silicone hydrogel extended wear were summarized from recent studies. Risk factors were listed and two key factors identified: overnight wear and poor hygiene accounting for 43% and 33% of risk, respectively. A pre-guidelines, web-based survey was conducted to assess the need for information and level of knowledge on CL-related microbial keratitis (n=162). Comparisons to a post-guidelines survey (n=51) measured whether new information was acquired through an educational brochure posted to the membership., Results: In the pre- and post-guidelines surveys, 52% (85/162) vs. 43% (22/51, p=0.3) indicated they did not have enough information on CL-related microbial keratitis. The importance attached to risk factors was generally reflective of the magnitude of risk and practitioners made appropriate recommendations about low risk modalities. Hygiene practices were rated as highly important in both surveys (>90%) with increased awareness of handwashing (p=0.03). Overnight wear of hydrogel lenses was considered highly important in 94% (201/213). However, despite evidence to the contrary, only 53% in the pre-guidelines and 58% in the post-guidelines surveys indicated that silicone hydrogel overnight wear was a highly important risk factor., Conclusions: Research evidence has been disseminated to the BCLA membership and responses gathered via a web survey. There are some areas of disconnect between practitioner opinion, as gauged in this survey, and the evidence from the research, particularly with regards to increased risk with overnight wear.

Purpose: To evaluate a multi-source surveillance system used in a 12-month study of contact lens related microbial keratitis in Australia and New Zealand., Methods: All practicing ophthalmologists and optometrists were surveyed on 6 occasions over 12 months via post or the Internet. Participation was defined as reporting at least once during the study period and the response rates represented those who responded on all six occasions. Cases were also detected through hospital audit. All ophthalmologists and a sub-group of optometrists were contacted by phone to elicit a response (active surveillance). The utilization and cost-effectiveness of active surveillance were compared to reports received via the post or the Internet. Case ascertainment and cost-effectiveness were compared for different sources of case capture., Results: The rate of participation for ophthalmologists was 95.8% (711/742) and 88.5% (657/742) responded for all reporting periods. Active surveillance was required for 63% (416/661) of responses in Australia (AU) and 73% (59/81) in New Zealand (NZ) at AUD23.14 per practitioner. Internet reporting was more widely used in New Zealand (NZ: 31% vs. AU:17%, p=0.006) and was the most cost effective mode of reporting (AUD1.43 per practitioner). Postal reporting (AUD; AU:3.54,NZ:9.84 per practitioner) was under-utilized (3% of responses). Average start-up costs comprised 50% of study costs followed by active follow-up (42%), postal (6%) and Internet reporting (2%). Ophthalmologists (50.4%, 144/286 of cases) were the most cost-effective source of cases, followed by hospital audit (24.5%, 70/286) and optometry (25.1%, 72/286). Duplicate reporting occurred in 13% (37/286) of cases., Conclusions: High response rates were obtained by substantial resource commitment to active follow-up. Internet reporting was widely used and was cost-effective. Hospital audit and supplementary reporting by optometry were used for the first time in a study of contact lens related microbial keratitis, and contributed significantly to case capture.

Contact lens-related keratitis has been the subject of a number of rigorous epidemiologic studies over the past 20 years. This article summarizes data from such studies that address incidence and risk factors for this condition. Estimates of risk and associated predisposing factors have been quite consistent over time, geography and study design.

Purpose: This manuscript reports the design of a multi source surveillance study of contact lens-related microbial keratitis in Australia and New Zealand. It describes and evaluates a new combination of techniques not previously used in ophthalmic epidemiology, intended to deliver a more robust methodology appropriate to detecting cases of contact lens related microbial keratitis in the light of increased community management of this condition., Methods: Ophthalmic practitioners in Australia and New Zealand were surveyed 6 times over a 12 month period to detect cases of contact lens-related microbial keratitis. Case detection involved both active and passive surveillance, Internet reporting to capture whether or not cases had been seen during the reporting period and audit of major ophthalmic centres., Results: Good response rates were obtained and maintained using this approach, with an overall participation rate of 95.8% (711/742) of ophthalmologists. Internet reporting was used by 17% and 31% of practitioners in Australia and New Zealand, respectively. However active follow up was required to elicit responses from 72.5% and 63.1% of practitioners, respectively. Twenty-five percent of cases were captured through hospital audit and 33% of cases were managed exclusively in the community., Conclusions: Active surveillance was essential to maintain response rates. The use of web based reporting and communication via the Internet facilitated data capture. One third of cases were managed exclusively in the community, which supports the surveillance of all ophthalmic practitioners. An additional recommendation to facilitate studies of this type would be the establishment of a national ophthalmic surveillance unit.

While the role of CC chemokines in mononuclear cell trafficking and activation has been well studied, the functional role of CC chemokines in the regulation of polymorphonuclear neutrophil (PMN) recruitment in vivo has not been widely examined. Bacterial infection of the cornea (keratitis) is a relatively common, sometimes sight-threatening disease, which features acute inflammation with ulceration and PMN infiltration. Here, we demonstrate a critical role for the chemokines, CCL2 and CCL3, in the Pseudomonas aeruginosa-induced model of corneal infection in BALB/c mice. Treatment of mice with anti-CCL2 or anti-CCL3 antibodies resulted in a significant reduction in severity of corneal damage and PMN infiltration at 1 and 7 days after infection compared to control antibody-treated eyes, but did not significantly alter the rate of bacterial clearance from the cornea. Our findings provide strong evidence that CCL2 and CCL3 are critical regulators of PMN recruitment, and may lead to therapeutic strategies via targeting of the CC chemokines, CCL2 and CCL3, in the management of P. aeruginosa keratitis.

With estimated numbers of contact lens wearers worldwide exceeding 140 million, even complications with a low incidence will affect a significant number of individuals. Although contact lenses clearly have many advantages for wearers, certain risks have been associated with their use. Differences in risk for different types of contact lenses and wearing patterns have been demonstrated for both rare and common lens related complications. This review particularly focuses on the incidence and etiology of contact lens related corneal infection and inflammation. An understanding of the risks and contributory factors to these conditions is important for practitioners and will enable an informed choice of safer lens wear modalities, wear schedules, and hygiene regimes to be made.

The association between possession of toxin gene-related type III secretory system, protease profiles, O serotypes, and antibiotic resistance patterns was characterized genetically and phenotypically in 46 keratitis isolates of Pseudomonas aeruginosa. There was no significant difference in exoU or exoS prevalence among the keratitis strains. Distinct protease profiles were seen in isolates harboring either exoU or exoS genes. One hundred percent (13/13) of serotype E (O:11) strains contained type III secretion system-associated cytotoxin gene exoU. Multidrug resistance was identified in 4% of Australian and 29% of Indian isolates. None of the Australian isolates was resistant to ciprofloxacin. In general, the rate of multidrug resistance in the exoU positive cytotoxic and serotype E (O:11) strains was significantly higher than in exoS positive invasive strains (p < 0.01). The results suggest that multidrug resistance may be more commonly associated with the corneal isolates of P. aeruginosa having type III secretion system-associated cytotoxin gene exoU and belonging to serotype E (O:11) group.

Purpose: Corneal inflammation in overnight contact lens (CL) wear is not fully understood. We designed a masked study to examine the impact of overnight CL wear on clinical variables in subjects who had previously experienced corneal inflammatory disease., Methods: Forty-four subjects were entered into the study: Nine subjects who had previously experienced CL-associated acute red eye (CLARE) and nine controls; 13 subjects who had previously experienced CL-induced peripheral ulceration (CLPU) and 13 controls, respectively. Controls were matched for age, gender, CL wear experience, and refractive error. Subjects wore bilateral disposable CLs (-3.00 DS). Corneal, conjunctival, and CL fitting variables were assessed prior to sleep, after a single night of CL wear, at 1, 2, and 4 hours after waking by clinicians who were masked to group membership. Retrospective analysis of prewear corneal and conjunctival variables for CLARE subjects and their respective controls was also performed., Results: Contact lens-associated acute red eye subjects consistently showed higher limbal redness (p < 0.05), bulbar redness (p < 0.05), and conjunctival staining (p < 0.005) compared with controls. Lens fitting and corneal variables were not significantly different at any time point for CLARE subjects. Contact lens-induced peripheral ulceration subjects were not different from matched controls for any variable at any time point. Limbal redness varied significantly over time among controls, with highest values measured at eye opening (p < 0.05). Retrospective analysis of prewear variables showed no significant differences between CLARE and control subjects., Conclusions: Wearers who previously experienced CLARE had a greater conjunctival response to CL wear compared with wearers who had no previous inflammatory disease. Clinical observations, however, were not helpful in predicting wearers who were predisposed to CLARE.

Pseudomonas aeruginosa keratitis is one of the most destructive diseases of the cornea. The host response to this infection is critical to the outcome. The cytokine interleukin-10 (IL-10) is thought to play an important role in modulating excessive inflammation and antimicrobial defenses. We have found that in IL-10(-/-) mice there is a significant decrease in bacterial load in corneas at 7 days postchallenge with P. aeruginosa. This decrease was accompanied by a reduction in neutrophil numbers in the cornea and changes in cytokine levels compared to those of wild-type mice. A characteristic increase in neovascularization in the cornea was found in the IL-10(-/-) mice. This increased angiogenesis correlated with an increased expression of KC, whereas the kinetics of macrophage inflammatory peptide 2 expression correlated with neutrophil numbers. This finding suggests that KC may play a role in corneal angiogenesis. The source of IL-10 in mouse corneas was identified as a subpopulation of infiltrating cells and keratocytes. This study demonstrates that IL-10 plays an important role in regulating the balance of inflammatory mediators during P. aeruginosa infection of the cornea.

Background: Pseudomonas aeruginosa infection is one of the most destructive diseases of the eye. The host response to this infection is critical to the outcome. Interleukin-6 (IL-6) is implicated in this response; however, the mechanisms by which IL-6 contributes to the host defences in corneal infection remain unclear. Using IL-6-/- mice, we have explored the role of IL-6 in P. aeruginosa keratitis., Methods: The eyes of IL-6 gene knockout and wild-type mice were challenged topically with P. aeruginosa and examined on days 1-7. Keratitis was examined clinically and histologically. Cytokine, chemokine and complement 3 levels were determined by ELISA and ICAM-1 by immunohistochemistry., Results: Clinically, the IL-6-/- mice showed more severe disease than wild-type mice and this was supported by the histological findings. More than 2-fold higher bacterial load was detected in the eyes of the IL-6-/- mice than in those of the wild-type mice. Neutrophil infiltration to the central cornea of the IL-6-/- mice failed to occur in response to infection, although a greater number of neutrophils were present in the whole eye. This may in part be due to the reduced expression of the adhesion molecule ICAM-1 in the cornea, but does not appear to stem from insufficient production of chemokines or complement 3., Conclusions: Our findings indicate that IL-6 is critical to the host defence of the cornea during P. aeruginosa infection. Pharmacological manipulation of the IL-6 response may represent a rational strategy for new interventions., (Copyright 2003 S. Karger AG, Basel)

Since the publication of large-scale population based studies to estimate the risks of contact lens-related microbial keratitis, the lens types and modes of wear have changed considerably, with the introduction of silicone hydrogel contact lenses for continuous wear of up to 30 nights and daily disposable contact lenses. It is time to consider epidemiologic studies to estimate the absolute and relative risk of microbial keratitis associated with these new exposures. This article summarizes current knowledge of the estimates and determinants of risk associated with re-useable hydrogel lenses and discusses study design considerations for future studies. The absolute risk of microbial keratitis to the wearer has been remarkably stable since 1989. Risk factors consistently associated with increased risk have included overnight wear, the duration of continuous overnight wear, lower socioeconomic class, smoking, and lens hygiene practice, specifically in daily wear lenses. Men seem to be at a slightly higher risk compared to women. Factors such as the lens age, duration of wear or wear history, and time since the last aftercare visit do not seem to modulate risk. Outstanding questions include whether the risk has changed over time, whether the risk is modified with daily disposable or silicone hydrogel wear, whether the risk is different for 6 or 30 nights of continuous wear, or whether the severity of the disease or spectrum of causative organisms has been modified with new lens types. Different study designs have been used to derive risk data in contact lens wear, including cohort, surveillance, and case-control designs. An appreciation of the advantages and limitations of each of these approaches will assist in the planning of future studies to address these outstanding questions.

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers whose lenses have become contaminated or who have a history of water exposure, and in those without contact lens wear who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induces the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding risk factors, which includes avoiding water contact, such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK. [ABSTRACT FROM AUTHOR]

Importance: Contact lens microbial keratitis (CLMK) is the most common cause of microbial keratitis in our community. Background: Define the trend in rate of CLMK and define patient demographics/culture results that may have a predictive value in patients with CLMK. Design Retrospective review of clinical records of patients with MK. Participants: All patients with positive corneal scraping between 1999 and 2015 at the Princess Alexandra Hospital, Brisbane, Queensland identified through local microbiology database. Methods: Trend in CLMK tested with chi‐squared test of peak 3 years vs other years and Poisson regression of interrupted time series. Patient characteristics predictive of CLMK were defined by creating a polynomial regression model by stepwise variable selection. Main Outcome Measures: Yearly rate of CLMK. Results: Records of 895 episodes of MK were included. The most common: risk factor was contact lens wear (324, 36.2%), isolated organism was Pseudomonas aeruginosa (P. aeruginosa 181, 55.9%) and treatment was monotherapy with a fluoroquinolone 172, 53%). CLMK was most common between 2009 and 2011 (49.5% vs other years 32%, P < 0.001). Poisson regression of the interrupted time series showed there was a significant decrease in the rate over time after 2010 (P < 0.001). Independent factors predictive of CLMK in multivariate regression were young age (15‐49 years) and corneal culture positive for P. aeruginosa Conclusions and Relevance: The rate of CLMK in our community ranged between 32% and 50% and the rate of disease appears to have peaked during 2009 to 2011 and subsequently declined. [ABSTRACT FROM AUTHOR]

Objective: To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. Design: A prospective, 12-month, population-based, case-control study. Participants: New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners. Case detection was augmented by record audits at major ophthalmic centers. Controls were users of daily wear CLs in the community identified using a national telephone survey. Testing: Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Multiple binary logistic regression was used to determine independent risk factors and univariate population attributable risk percentage (PAR%) was estimated for each risk factor. Main Outcome Measures: Independent risk factors, relative risk (with 95% confidence intervals [CIs]), and PAR%. Results: There were 90 eligible moderate and severe cases related to daily wear of CLs reported during the study period. We identified 1090 community controls using daily wear CLs. Independent risk factors for moderate and severe keratitis while adjusting for age, gender, and lens material type included poor storage case hygiene 6.4× (95% CI, 1.9–21.8; PAR, 49%), infrequent storage case replacement 5.4× (95% CI, 1.5–18.9; PAR, 27%), solution type 7.2× (95% CI, 2.3–22.5; PAR, 35%), occasional overnight lens use (<1 night per week) 6.5× (95% CI, 1.3–31.7; PAR, 23%), high socioeconomic status 4.1× (95% CI, 1.2–14.4; PAR, 31%), and smoking 3.7× (95% CI, 1.1–12.8; PAR, 31%). Conclusions: Moderate and severe microbial keratitis associated with daily use of CLs was independently associated with factors likely to cause contamination of CL storage cases (frequency of storage case replacement, hygiene, and solution type). Other factors included occasional overnight use of CLs, smoking, and socioeconomic class. Disease load may be considerably reduced by attention to modifiable risk factors related to CL storage case practice. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To evaluate associations between disease severity, causative organism, and climatic variation in contact lens-related microbial keratitis in Australia. Design: Prospective, observational case series. Methods: Contact lens wearing patients (n = 236) with presumed microbial keratitis presenting to private and hospital ophthalmologists in Australia between October 1, 2003 and September 30, 2004 were identified prospectively. Clinical details, management information, and microbiology data were collected and cases were graded for severity based on lesion size and location criteria. Causative organisms were assigned to “environmental” or “endogenous” groups. Climate zone and daytime temperature and humidity were determined for the geographic location of each event. The main outcome measures were disease severity, causative organism, and climate zone. Results: Severe contact lens-related microbial keratitis was more likely to occur in warmer, humid regions of the country (P < .001), compared with smaller, increasingly peripheral corneal lesions that were more common in cooler conditions (P < .001). Culture-proven keratitis was predominantly caused by environmental organisms with Pseudomonas aeruginosa being recovered most frequently. Environmental organisms were isolated more commonly from tropical regions of the country and also accounted for nearly all cases of vision loss that occurred during the study period. Humidity did not have a significant effect on causative organism. Conclusions: Climatic conditions play a role in disease severity and causative organism in contact lens-related microbial keratitis and therefore have implications for practitioners involved in contact lens care and contact lens wearers who live in or travel to the tropics. [Copyright &y& Elsevier]

Objection: To analyse the patient, clinical and microbiological variables associated with poor outcomes from keratitis in patients presenting to a major public hospital in Australia. Methods: A retrospective audit of the records of all patients who had a corneal scraping in 5 years at Princess Alexandra Hospital (Brisbane, Australia) was carried out. The outcome of a patient's episode of keratitis was classified as poor if they had final visual acuity of 6/60 or worse; had vision loss during treatment; or a complication of keratitis; or needed surgical intervention. Results: A final outcome was established in 207 cases during the 5-year period. Final vision of 6/12 or better was found in 48% (100) of cases while a poor outcome was seen in 28% (58). Linear regression showed poor outcomes were directly associated with age ( P < 0.001) and disease severity ( P < 0.001). Univariate analysis indicated that poor outcomes were more likely in patients who had had prior ocular surgery ( P = 0.005) or ocular surface disease ( P = 0.01) and were also associated with presenting visual acuity of worse than 6/60 ( P < 0.001) and isolation of Streptococcus pneumoniae ( P = 0.002). While patients with traumatic keratitis, contact lens-related keratitis or negative corneal cultures ( P = 0.009) were more likely to have good outcomes. Multivariate analysis showed that the relative risk of a patient having a poor outcome was 4.3× (CI 2.0–9.5) if they had severe keratitis, 4.1× (CI 1.8–9.5) if they had keratitis related to ocular surface disease and 3.8× (CI 1.8–8.3) if they were over 50 years old. Conclusions: An outcome of poor vision, vision loss during treatment, surgical intervention or complication of keratitis is more likely in patients with severe keratitis, keratitis related to prior ocular surface disease or older age. [ABSTRACT FROM AUTHOR]

Purpose : During contact lens wear, bacterial contamination of the lens can lead to the development of microbial keratitis (MK) or contact lens induced acute red eye (CLARE). Inflammatory mediators released by the host may heighten the response. We have examined the ability of human corneal epithelial cells and polymorphonuclear leukocytes (PMNs) to release cytokines upon stimulation with bacteria. Methods : Serratia marcescens strains were added to corneal epithelial cells or PMNs. After incubations of up to 20 hours, supernatants were assayed for the presence of inflammatory mediators by ELISA. Results : All strains stimulated PMNs to release IL-8 and LTB 4 . Epithelial cells did not release LTB 4 . IL-8 was released after exposure to most S. marcescens isolates. A sub-group of strains stimulated the release of TNF-α from corneal epithelial cells. Conclusions : S. marcescens can stimulate the release of inflammatory mediators from both PMNs and corneal epithelial cells. This release could be important in the progression and resolution of MK and CLARE. [ABSTRACT FROM AUTHOR]

This study investigated genomic differences in Australian and Indian Pseudomonas aeruginosa isolates from keratitis (infection of the cornea). Overall, the Indian isolates were resistant to more antibiotics, with some of those isolates being multi-drug resistant. Acquired genes were related to resistance to fluoroquinolones, aminoglycosides, beta-lactams, macrolides, sulphonamides, and tetracycline and were more frequent in Indian (96%) than in Australian (35%) isolates (p = 0.02). Indian isolates had large numbers of gene variations (median 50,006, IQR = 26,967–50,600) compared to Australian isolates (median 26,317, IQR = 25,681–33,780). There were a larger number of mutations in the mutL and uvrD genes associated with the mismatch repair (MMR) system in Indian isolates, which may result in strains losing their efficacy for DNA repair. The number of gene variations were greater in isolates carrying MMR system genes or exoU. In the phylogenetic division, the number of core genes were similar in both groups, but Indian isolates had larger numbers of pan genes (median 6518, IQR = 6040–6935). Clones related to three different sequence types—ST308, ST316, and ST491—were found among Indian isolates. Only one clone, ST233, containing two strains was present in Australian isolates. The most striking differences between Australian and Indian isolates were carriage of exoU (that encodes a cytolytic phospholipase) in Indian isolates and exoS (that encodes for GTPase activator activity) in Australian isolates, large number of acquired resistance genes, greater changes to MMR genes, and a larger pan genome as well as increased overall genetic variation in the Indian isolates. [ABSTRACT FROM AUTHOR]

Purpose: Exploratory analysis to assess the association of single nucleotide polymorphisms (SNPs) in the interleukin (IL) 10 and IL-17 genes with severity of contact lens keratitis.Methods: This was a retrospective case control study of 88 contact lens keratitis cases (25 severe) and 185 healthy contact lens wearers recruited from studies conducted at Moorfields Eye Hospital and in Australia-wide during 2003-2005. Buccal swab samples were collected on Whatman FTA cards and mailed by post for DNA extraction and SNP genotyping. IL-10 (rs1800871; rs1800896; rs1800872) and IL-17 (rs1800871; rs1800896; rs1800872) SNPs were screened by pyrosequencing. Genetic association analyses were performed via Cochran-Armitage trend tests and logistic regression models using PLINK software.Results: None of the SNPs tested showed evidence of association with severity of contact lens keratitis at P <  0.05. Nevertheless, minor allele G in SNP rs2397084 of the IL-17F gene was associated with increased risk of severe MK, with OR=2.1 (95% CI=0.9-4.8, P = 0.066).Conclusion: Our study cannot exclude with confidence that genetic variation in the IL-17 F proinflammatory cytokine is associated with more severe outcomes of MK. However, there is general body of information that the IL-17 pathway is important in the mechanisms of MK. Studies with larger power and the expanded array of laboratory tools will elucidate the exact role of IL-17 in MK. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association of single nucleotide polymorphisms (SNPs) of defensin 1B and toll-like receptor 4 with contact lens keratitis susceptibility and severity, and to understand the factors that influence study participation. Design: Retrospective, case-control study. Participants: Ninety cases of keratitis and 185 controls recruited from studies conducted at Moorfields Eye Hospital and throughout Australia from 2003 to 2005 were analyzed for genetic associations. The reasons for participation of a subset of 146 participants from 1 site were also investigated. Methods: Buccal swab samples were collected on Whatman FTA cards and mailed by post for analysis. DEFB1 (rs1799946, −52, rs1800972, −44, and rs11362, −20) and TLR4 (rs4986790, D299G) SNPs were screened by pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis [MK], controls) and severity. Study participation was investigated for age, gender, condition, and phone follow-up also using regression analysis. Main Outcome Measures: Relative risk of developing contact lens–related keratitis and more severe forms of the disease based on genetic profiles. Results: Carriers of risk alleles of DEFB1 −52 and −20 showed a trend toward increased susceptibility to keratitis (−52: odds ratio [OR], 1.45; 95% confidence interval [CI], 0.99–2.11; P = 0.051; −20: OR, 1.37; 95% CI, 0.95–1.98; P = 0.088). A DEFB1 promoter haplotype (G-G-A) had a tendency toward decreased susceptibility of MK (OR, 0.68; 95% CI, 0.45–1.03; P = 0.062) and reduced severity (OR, 0.56; 95% CI, 0.30–1.07; P = 0.066). The TLR4 D299G was not associated with type and severity of keratitis. Older age (OR, 1.07; 95% CI, 1.05–1.08) and follow-up phone call (OR, 2.0; 95% CI, 1.2–3.5) were independent predictors of study participation. Conclusions: Genetic variation in DEFB1 that may lead to decreased protein expression of hBD-1 exhibits a tendency toward increased susceptibility and severity of contact lens–related keratitis. Investigation of these and other hBD genes that play important roles in animal models in a larger sample size is warranted. The approach of requesting samples from retrospective case series was generally feasible, although significant resources, including repeat phone calls, are required. More targeted strategies to recruit younger individuals to participate in genetic studies may be useful. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Design: Retrospective, case control study. Participants: One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003 through 2005. Methods: Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1β (−31), IL-6 (−174, −572, −597), and IL-12B (3′+1158) genotypes were analyzed with pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis, controls) and severity. Statistical significance was set at 0.05. Main Outcome Measures: The relative risk of developing contact lens-related keratitis and more severe forms of the disease based on allele, genotype, and haplotype associations. Results: Carriers of IL-6 SNPs were more likely to experience moderate and severe events compared with those with nonmutated genotypes (−174 heterozygous: odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1–8.3; homozygous: OR, 6.4; 95% CI, 1.4–28.4; −174/−597: OR, 4.1; 95% CI, 1.6–11.0). More severe keratitis and microbial keratitis were less likely to occur in wearers with the nonmutated IL-6 haplotype (severity OR, 0.4 [95% CI, 0.2–0.7]; microbial OR, 0.6 [95% CI, 0.4–0.9]). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR, 9.7; 95% CI, 1.2–76.9) compared with controls. Conclusions: The IL-6 SNPs are known to reduce protein expression of this cytokine and thus ocular immune defense, and carriers of these SNPs were more likely to experience more severe and microbial keratitis, suggesting that IL-6 decreases the severity and susceptibility of contact lens-related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Purpose: To assess the relative risks of acute, nonulcerative complications with recently introduced contact lens (CL) wear modalities (compared with the previously most common soft lens wear schedule), and to identify any other associated factors. Design: A 2-year prospective case-control study commencing in December 2003. Participants: Cases were 877 CL wearers attending Moorfields Eye Hospital with CL-related disorders other than microbial keratitis. Controls were 1069 hospital controls who were CL wearers presenting with a disorder unrelated to CL wear, and 639 population-based controls who were CL wearers randomly selected from the Moorfields catchment area. Hospital patients completed a self-administered questionnaire; population controls were interviewed by telephone. Testing: The relative risks of developing the CL-related disorders with different CL types were evaluated. For the more common disorders, multivariable analysis was undertaken. Main Outcome Measures: The relative risk of developing an acute, nonulcerative, CL-related disorder. Results: Compared with planned replacement soft CL, daily disposable lenses significantly reduced the risk of toxic/hypersensitivity (odds ratios for CL solution disorders and papillary conjunctivitis 0.1 and 0.5; P<0.001 and P = 0.05, respectively) and metabolic disorders (0.4; P = 0.04), but the most commonly used brand was associated with increased risks of sterile keratitis (2.7×; 95% confidence interval [CI], 1.7–4.1; P<0.001), mechanical disorders (2.2×; 95% CI, 1.5–3.2; P<0.001), and a tendency for patients to have lens removal difficulties (P<0.001). Silicone hydrogel CL wear was free from hypoxic complications but associated with an increased risk of sterile keratitis (2.0×; 95% CI, 1.2–3.3; P = 0.005), mechanical disorders (1.8×; 95% CI, 1.1–2.8; P = 0.015), and attendance with any nonulcerative complication (1.9×; 95% CI, 1.5–2.6; P<0.001) when compared with other reusable soft lenses. Significant additional risk factors were identified for sterile keratitis (overnight wear [ON], more days per week of lens wear, poor hand hygiene, smoking, and less CL experience) and mechanical disorders (ON and less CL experience). Conclusions: Neither of the 2 recently introduced CL modalities—daily disposable and silicone hydrogel lenses—reduced the overall risk of acute nonulcerative disorders. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Purpose: To examine predisposing factors, treatment costs, and visual outcome of microbial keratitis in an ophthalmic casualty and inpatient population. Design: Retrospective medical records review. Participants: Fifteen- to 64-year-olds with microbial keratitis treated at the Royal Victorian Eye and Ear Hospital between May 2001 and April 2003 (n = 291). Methods: Risk factors were identified from patient files. Demographic, clinical, and microbiological data; severity; outpatient visits; hospital bed days; and vision loss were examined. Main Outcome Measures: Cost to treat (Australian dollars), vision loss, and factors influencing these outcomes. Results: Ocular trauma (106/291 [36.4%]) and contact lens (CL) wear (98/291 [33.7%]) were the most commonly identified predisposing factors; 18 (6.1%) had multiple predisposing factors; 17 (5.8%), ocular surface disease; 20 (6.9%), herpetic eye disease; 4 (1.4%), systemic associations; 5 (1.7%), other; and 23 (7.9%), unknown cause. Of trauma cases, 90.6% involved males, compared with 44% to 57% for other groups (P<0.001). Contact lens wearers were younger than the other groups—mean age 30 years, compared with 40 to 47 years (P<0.01). Gram-negative organisms were isolated more frequently in CL wearers than trauma cases (18.7% vs. 6.5%, P = 0.01). The number of outpatient visits was 4±1 (median ± interquartile range), and 19.6% (57/291) were hospitalized for 5±2 days. Hospital resource use and vision loss were similar for predisposing factors but differed by causative microorganism. Eighty-eight percent of cases were scraped: acanthamoeba keratitis was the most expensive to treat, followed by fungal and herpetic keratitis and, lastly, culture-proven bacterial keratitis or culture-negative cases (P<0.0001). After treatment, 21.7% exhibited >2 lines of vision loss, and 1.6% of cases had ≥10 lines of vision loss. Vision loss was associated with clinical severity (P = 0.005). Conclusions: Ocular trauma and CL wear are the major predisposing factors for microbial keratitis in this age range. These cases require significant hospital resources during treatment, and the keratitis may result in loss of vision. [Copyright &y& Elsevier]