Association of single nucleotide polymorphisms of interleukins-1ß, -6, and -12B with contact lens keratitis susceptibility and severity.

PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1ß, IL-6, and IL-12ß 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-1ß (-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.

Risk factors for nonulcerative contact lens complications in an ophthalmic accident and emergency department: a case-control study.

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 (2.7x; 95% confidence interval [CI], 1.7-4.1; P<0.001), mechanical disorders (2.2x; 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 (2.0x; 95% CI, 1.2-3.3; P=0.005), mechanical disorders (1.8x; 95% CI, 1.1-2.8; P=0.015), and attendance with any nonulcerative complication (1.9x; 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.

Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors.

BACKGROUND/AIMS: Acanthamoeba keratitis (AK) is a chronic debilitating corneal infection principally affecting contact lens (CL) users. Studies were designed to test claims that the UK incidence may have increased in 2012-2014 and to evaluate potential causes. METHODS: Annualised incidence data were collected from January 1984 to December 2016. Case-control study subjects were recruited between 14 April 2011 and 05 June 2017. Reusable CL users with AK were recruited retrospectively and prospectively. Controls were reusable CL users, recruited prospectively, with any disorder other than AK. Multivariable analysis of questionnaire data measured independent risk factors for AK. RESULTS: The current outbreak of AK started in 2010-2011 with an incidence threefold higher than in 2004-2009. Risk factors for AK were: Oxipol disinfection, CLs made of group IV CL materials, poor CL hygiene, deficient hand hygiene, use of CLs while swimming or bathing, being white British, and for those in social classes 4-9. CONCLUSION: AK is a largely preventable disease. The current outbreak is unlikely to be due to any one of the identified risk factors in isolation. Improving CL and hand hygiene, avoiding CLs contamination with water and use of effective CL disinfection solutions, or daily disposable CLs, will reduce the incidence of AK. In the longer-term, water avoidance publicity for CL users can be expected to reduce the incidence further. Ongoing surveillance of AK numbers will identify changes in incidence earlier. Evaluation of Acanthamoeba contamination in end-user drinking water would contribute to our understanding of regional variations in the risk of exposure.