Association study of single nucleotide polymorphisms in IL-10 and IL-17 genes with the severity of microbial keratitis

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

Correction to: The Activity of Polyhomoarginine against Acanthamoeba castellanii (Biology, (2022), 11, 12, (1726), 10.3390/biology11121726)

In the original publication [1], there was a mistake in the legend for ** Figure 1—4 **. **Using a two-sample t-test and two-tailed distribution**. The correct legend appears below. **i. Figure 1: Change “(** p < 0.001 using a two-sample t-test and two-tailed distribution).” to “(** p < 0.001 using one way ANOVA).” ii. Figure 2: Change “(** p < 0.001, * p < 0.05 using a two-sample t-test and two-tailed distribution).” to “(** p < 0.001, * p < 0.05 using one way ANOVA).” iii. Figure 3: change “(** p < 0.001, * p < 0.05 using a two-sample t-test and two-tailed distribution).” to “(** p < 0.001, * p < 0.05 using one way ANOVA).” iv. Figure 4: change “(** p < 0.001, * p < 0.05 using a two-sample t-test and two-tailed distribution).” to “(** p < 0.001, * p < 0.05 using one way ANOVA).” ** There was an error in the original publication. **Full name of PHMB missing in Introduction**. A correction has been made to **Introduction**, **Paragraph Number—3**: i. Change “PHMB or chlorhexidine are widely used to treat this infection as monotherapies or in combination” to “Polyhexamethylene biguanide or chlorhexidine are widely used to treat this infection as monotherapies or in combination”. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated

American Academy of Optometry Microbial Keratitis Think Tank

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

Innate and adaptive gene single nucleotide polymorphisms associated with susceptibility of severe inflammatory complications in acanthamoeba keratitis

PURPOSE. Over a third of patients with Acanthamoeba keratitis (AK) experience severe inflammatory complications (SICs). This study aimed to determine if some contact lens (CL) wearers with AK were predisposed to SICs due to variations in key immune genes. METHODS. CL wearers with AK who attended Moorfields Eye Hospital were recruited prospectively between April 2013 and October 2014. SICs were defined as scleritis and/or stromal ring infiltrate. Genomic DNA was processed with an Illumina Low Input Custom Amplicon assay of 58 single nucleotide polymorphism (SNP) targets across 18 genes and tested for association in PLINK. RESULTS. Genomic DNA was obtained and analyzed for 105 cases of AK, 40 (38%) of whom experienced SICs. SNPs in the CXCL8 gene encoding IL-8 was significantly associated with protection from SICs (chr4: Rs1126647, odds ratio [OR] = 0.3, P = 0.005, rs2227543, OR = 0.4, P = 0.007, and rs2227307, OR = 0.4, P = 0.02) after adjusting for age, sex, steroids prediagnosis, and herpes simplex keratitis (HSK) misdiagnosis. Two TLR-4 SNPs were associated with increased risk of SICs (chr9: Rs4986791 and rs4986790, both OR = 6.9, P = 0.01). Th-17 associated SNPs (chr1: IL-23R rs11209026, chr2: IL-1β rs16944, and chr12: IL-22 rs1179251) were also associated with SICs. CONCLUSIONS. The current study identifies biologically relevant genetic variants in patients with AK with SICs; IL-8 is associated with a strong neutrophil response in the cornea in AK, TLR-4 is important in early AK disease, and Th-17 genes are associated with adaptive immune responses to AK in animal models. Genetic screening of patients with AK to predict severity is viable and this would be expected to assist disease management

Investigating domestic shower settings as a risk factor for acanthamoeba keratitis

Acanthamoeba keratitis (AK) is a sight-threatening infection of the cornea, which is caused by soil and the waterborne protist Acanthamoeba spp. AK most commonly occurs during contact lens (CL) wear. Risk factors for AK have been linked to non-optimal lens hygiene practices and Acanthamoeba contamination of domestic water. This study investigated the prevalence of Acanthamoeba species in domestic showers in the greater Sydney region, as well as the perception of water contamination of CL as being a risk factor for AK among previous AK patients and their family and friends. Samples from four locations of 13 participants’ shower areas were cultured and Acanthamoeba 18S rRNA was amplified by PCR, followed by sequencing. Twenty-six responses were received to the online questionnaire. Fifteen water samples (29%, 15/52) contained amoeba that were morphologically classified as Acanthamoeba spp. PCR amplification confirmed the presence of Acanthamoeba spp. in four samples (8%, 4/52). Three isolates belonged to the T4, and one isolate to the T3 genotype. On the questionnaire survey, 96% (25/26) of respondents believed that water contamination was likely to be a risk factor for Acanthamoeba keratitis and 58% rated showering with CL as ‘extremely likely’ to be a risk factor for AK. Acanthamoeba pathogenic genotypes (T3 and T4) in the domestic bathroom water suggest that clinicians should remain vigilant in educating CL wearers about avoiding domestic water contamination of CL