Clinical Trial: Pseudomonal Type Three Secretion System and Contact Lens Associated Microbial Keratitis
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Observational
Official Title: Association of Type Three Secretion System (T3SS) of Pseudomonas Aeruginosa With Pathogenesis of Contact Lens-Associated Microbial Keratitis (CLMK)
Brief Summary:
Microbial infection of the cornea, also known as microbial keratitis, causes severe corneal inflammation that could result in permanent visual loss. Contact lens wear is the strongest risk factor related to microbial keratitis in developed countries. The most commonly isolated pathogen of contact lens associated microbial keratitis (CLMK) is Pseudomonas aeruginosa, which accounts for over one third of the cases. Among the various virulence factors involved in the pathogenesis of pseudomonal keratitis, a secretion system known as type three secretion system (T3SS) secretes toxins that damage the host cells. ExoS is a bifunctional exotoxin with GTPase-activating protein (GAP) activity and ADP ribosyl transferase (ADPRT) activity. It results in an invasive phenotype of P. aeruginosa causing a relatively slower host cell death with intracellular invasion and possibly proliferation of bacterium. In contrast, ExoU expressing strains carries a cytotoxic phenotype that causes rapid host cell lysis due to its phospholipase activity. Previously, cytotoxic strains were reported to be more commonly found in patients with pseudomonal keratitis and were highly correlated with multidrug resistance.
In order to understand the pathogenesis of CLMK, especially pseudomonal related CLMK, we proposed to recruit 180 volunteers who will wear different contact lens materials. We then collect the used contact lens and analyze 1) the microbiota on the used contact lens; 2) the bacterial-contact lens adhesion of wild strains, pscC mutant strains (T3SS needle-comples mutant), cytotoxic strain, and invasive strain P. aeruginosa; 3) the effect of shearing forces on bacterial-contact lens adhesion; 4) the bacteriocidal effect of multipurpose solution on different strains of P. aeruginosa.
Detailed Summary:
Subject recruitment
The inclusion criteria includes:
- age 20-35 years old
- myopia less than -6.00D and astigmatism less than -1.50D
- previous soft contact lens wear discontinued for at least 2 weeks.
Exclusion criteria includes:
- subjects with previous RGP wear
- any ocular inflammation or infection, proved dry eye syndrome, glaucoma, ocular trauma or surgery, and topical medication instillation
- diabetic mellitus
- pregnancy
- status post corneal refractive surgery
The aim and purpose of this study will be thoroughly explained to the potential participants. Informed consent will be obtained from all enrolled subjects. This study will be approved by our Institutional Review Board and adheres to the tenets of the Declaration of the Helsinki. A minimal of 12 subjects per group is required to show a difference in the microbiota for one classification level or more at a significance level of 0.05 and a power of 90%. Thus, the goal is to recruit 15 volunteers to wear each type of contact lens and 180 subjects totally for this study.
The recruitment will be divided into three stages. At the first stage, we will test 4 types of silicone hydrogel contact lenses, followed by testing 5 types of color-tinted hydrogel lenses at the second stage and 3 types of hydrogel lenses at the third stage. (T = types of lenses, which equals 4,5 and 3 at stage one, two and three)
Sponsor: National Taiwan University Hospital
Current Primary Outcome: bacterial adhesion assay [ Time Frame: after co-culture for two hours ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Identification of bacterial colonization to worn contact lenses [ Time Frame: after the CL been worn for 6 hours ]
Original Secondary Outcome: Same as current
Information By: National Taiwan University Hospital
Dates:
Date Received: August 16, 2013
Date Started: January 2013
Date Completion: July 2015
Last Updated: April 14, 2014
Last Verified: April 2014
