Keratitis; Infectious Disease (Manifestation) Clinical Trial
Official title:
Association of Type Three Secretion System (T3SS) of Pseudomonas Aeruginosa With Pathogenesis of Contact Lens-Associated Microbial Keratitis (CLMK)
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.
Subject recruitment
The inclusion criteria includes:
1. age 20-35 years old
2. myopia less than -6.00D and astigmatism less than -1.50D
3. previous soft contact lens wear discontinued for at least 2 weeks.
Exclusion criteria includes:
1. subjects with previous RGP wear
2. any ocular inflammation or infection, proved dry eye syndrome, glaucoma, ocular trauma
or surgery, and topical medication instillation
3. diabetic mellitus
4. pregnancy
5. 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).
At each stage, we will recruit subjects to certain amount (M) each time (M＝N×T , N equals
1,2,3…to 15). M subjects will then be randomized, equally distributed to wear T types of
lenses by the random number method. Until the required case numberis achieved at the first
stage, we will proceed to the second and the third stage with the same stratified
randomization methods.( required case number, ΣM, equals 60, 75 and 45 at stage one, two and
three).
Subjects are fitted with the soft contact lenses and are expected to wear the lenses for at
least 6-8 hour per day. Standardized hand hygiene and lens care regimen are thoroughly
explained to each subject to insert the contact lens. Each subject enrolled will be provided
with the soft contact lenses without charge. After wear each day, the contact lenses must be
returned and collected for material analysis.
;
Observational Model: Cohort, Time Perspective: Retrospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02717871 -
Swiss PACK-CXL Multicenter Trial for the Treatment of Infectious Keratitis
|
Phase 3 |