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Kathryn Richdale, Cecilia Chao, Lakshmi Akileswaran, Russell Van Gelder, Jessica Cooke Bailey, Jonathan L Haines, Fiona Stapleton, Carol Lakkis, Mark D P Willcox; Genetic, metagenomic, host response, and environmental factors influences on corneal infiltrative events in soft contact lens wearers: the MERGE pilot study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1743. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To explore feasibility and differences in individual genotype, ocular surface microbiome, tear inflammatory markers, and environmental and behavioral exposures in soft contact lens (SCL) wearers with and without a history of corneal infiltrative events (CIEs).
Nine SCL wearers with a recent CIE (3-15 months prior) and 9 age, sex and SCL material-and modality-matched healthy controls were enrolled. The Contact Lens Risk Survey, slit lamp examination data, basal tears, conjunctival microbial cultures and peripheral blood samples were collected. Tear inflammatory mediator concentrations (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12(p70), IL-13, TNFα) were quantified by MSD multiplex assay. Genomic DNA from swabs were extracted, quantified and analyzed using BRISK/16SrDNA to determine microbial species. Whole exome sequencing (WES) of blood samples was conducted by Illumina® HiSeq 3000 and analysis of single nucleotide polymorphism (SNP) variants were planned for IL-6, IL-12, IL-10, TLR-4 and HLA-DQ.
There were no marked differences in SCL wear or care behaviors or risk exposures of the case and control subjects. Tear IL-6 was higher in CIE subjects than controls (4.9±1.5 vs 4.2±2.9 pg/ml, p=0.02). Predominant organisms detected in cultures from cases and controls included Staphylococcus (23% vs. 40%, NS), and Propionibacteria (24% vs. 31%, NS). High levels of Neisseria (>20% of reads) were found in 3/9 cases but 0/9 control samples. WES was completed on 17 blood samples. Mean target coverage ranged from 64-80 and 91% of sequence captures were ≥20X.
IL-6, a pleiotropic mediator shown to be associated with SCL wear and keratitis, was higher in tears of patients with a history of CIEs. The concentration of IL-6 may also be related to susceptibility to CIE. SNP variants are being analyzed. No significant difference in ocular surface microbiome could be appreciated between groups in this pilot study. This study demonstrated feasibility for measuring multiple internal and external risk factors for CIEs. Further studies in larger populations are needed to understand which factors are most closely related to risk of CIEs and explore relationships between genetic variations, the ocular surface microbiome, inflammatory mediators and environmental exposures.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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