June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
The association of Interleukin 8 gene SNP with severe inflammatory complications in contact lens wearers experiencing Acanthamoeba Keratitis.
Author Affiliations & Notes
  • Nicole Ann Carnt
    School of Optometry and Vision Science, UNSW, Sydney, New South Wales, Australia
    UCL Institute of Ophthalmology, London, London, United Kingdom
  • Ignatius Pang
    UNSW, Sydney, New South Wales, Australia
  • Kathryn P Burdon
    University of Tasmania, Tasmania, Australia
  • Virginia L Calder
    UCL Institute of Ophthalmology, London, London, United Kingdom
  • John Dart
    UCL Institute of Ophthalmology, London, London, United Kingdom
    fields Eye Hospital NHS Foundation Trust, London, United Kingdom
  • Dinesh Subedi
    Monash University, Victoria, Australia
  • Alison J Hardcastle
    UCL Institute of Ophthalmology, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Nicole Carnt, None; Ignatius Pang, None; Kathryn Burdon, None; Virginia Calder, None; John Dart, None; Dinesh Subedi, None; Alison Hardcastle, None
  • Footnotes
    Support  Fight for Sight UK 1465/6
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3998. doi:
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      Nicole Ann Carnt, Ignatius Pang, Kathryn P Burdon, Virginia L Calder, John Dart, Dinesh Subedi, Alison J Hardcastle; The association of Interleukin 8 gene SNP with severe inflammatory complications in contact lens wearers experiencing Acanthamoeba Keratitis.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3998.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Over a third of patients with Acanthamoeba keratitis (AK) experience severe inflammatory complications (SICs) thought to be unrelated to the infective process. 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 attending Moorfields Eye Hospital for diagnosis and/or ongoing treatment were recruited prospectively between April 2013 and October 2014. Clinical data was collected using the REDCap database platform (Vanderbilt University, TN,USA). SICs were defined as scleritis and/or stromal ring infiltrate. Genomic DNA was collected by a cheek swab (FLOQswabs, Copan Diagnostics,CA,USA ) or a sputum kit (DNAGenotek, ON, CA or DNAgard, Biomatricia, CA, USA). DNA was extracted and processed with an Illumina Low Input Custom Amplicon assay (Illumina Corp, CA, USA) of 69 SNP targets across 19 genes using the Illumina MiSeq platform. The MiSeq reporter software generated variant calling files (.vcf) for each sample using BWA-MEM for read alignment and GATK for variant calling. The files were merged in vcftools software suite, accounting for missing values and tested for association analysis in PLINK. Covariates included clinical predictors of SIC: steroids pre-diagnosis and Herpes Simplex Keratitis (HSK) misdiagnosis along with sex and age.

Results : Genomic DNA was obtained and analyzed for 105 cases of AK, 40 (38%) of whom experienced SICs. A SNP in the interleukin 8 (IL-8) gene was significantly associated with protection from SICs (chr4: rs11266474 OR 0.3, p=0.005) after adjusting for age, sex, steroids pre-diagnosis and HSK misdiagnosis. The average age at the time of presentation for all AK cases was 36.9±15.5 years, and there was no difference in age between those with SICs compared to those without (38.7±15.6 compared to 36.0±15.5, p=0.19). Likewise, there was no difference in sex between the two groups (Females: 23/43, 53% vs 42/76, 55%, p=0.85).

Conclusions : The current study identifies a biologically relevant gene variation in AK patients with SICs; IL-8 is associated with a strong neutrophil response in the cornea in AK. Further work is needed but this data confirms that genetically screening patients who present with keratitis to predict severity and assist in the management of the disease, is viable.

This is a 2020 ARVO Annual Meeting abstract.

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