Transcript Journal Club Slides - JAMA Ophthalmology

JAMA Ophthalmology Journal Club Slides:
Effects of Azithromycin in Patients With
Meibomian Gland Disease
Zhang L, Su Z, Zhang Z, Lin J, Li D-Q, Pflugfelder SC.
Effects of azithromycin on gene expression profiles of
proinflammatory and anti-inflammatory mediators in the
eyelid margin and conjunctiva of patients with meibomian
gland disease. JAMA Ophthalmol. Published online July
23, 2015. doi:10.1001/jamaophthalmol.2015.2326.
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Introduction
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Meibomian gland disease (MGD) is the most prevalent type of blepharitis,
but the etiology of most cases of MGD remains to be determined.
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Azithromycin has been shown to have anti-inflammatory properties.
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Using impression cytology to obtain cells from the surface of the eyelid
margin and conjunctiva, this study characterized the gene expression
profiles of proinflammatory and anti-inflammatory mediators in samples
from patients with MGD and further evaluated the anti-inflammatory
properties of topical azithromycin application on the expression of these
mediators in the eyelid margin and conjunctiva as well as its effects on tear
matrix metalloproteinase 9 (MMP-9) activity.
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Objective
– To explore the effects of azithromycin therapy on expression of
proinflammatory and anti-inflammatory mediators in MGD.
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Methods
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Case-control study performed in a clinic setting in 2010.
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Sixteen patients with posterior blepharitis and conjunctival inflammation
due to MGD were enrolled and followed up over time, and their findings
were compared with a 1-time measurement in healthy participants.
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The patients were treated with azithromycin, 1%, drops for 4 weeks.
Impression cytology of the lower eyelid margin and tarsal conjunctiva as
well as tear collection were performed once in healthy participants and 5
times in patients (every 2 weeks for 8 weeks), before, during, and after
azithromycin treatment.
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Methods
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Cytokine expression was measured in the eyelid margin and conjunctiva
by quantitative real-time polymerase chain reaction, and MMP-9 activity
was measured in tears.
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One-way analysis of variance was used to make comparisons among 3
or more groups, followed by Dunnett post hoc test, and t test was used
to compare differences between 2 groups.
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Results
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Compared with a 1-time measurement in healthy participants, the mean
fold change of messenger RNA (mRNA) expression of proinflammatory
mediators interleukin 1β (IL-1β), IL-8, and MMP-9 increased to 13.26,
9.38, and 13.49, respectively, in conjunctival cells and to 11.75, 9.31,
and 11.52, respectively, in the eyelid margin of patients with MGD.
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The mean fold change of expression of transforming growth factor β1
(TGF-β1) mRNA decreased to 0.58 and 0.63 in conjunctival and eyelid
margin cells, respectively, of patients with MGD.
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Results
Cytokine Expression Profiles in MGD by Quantitative
Real-Time Polymerase Chain Reaction
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Results
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After 4 weeks of azithromycin treatment, mean mRNA expression of
IL-1β, IL-8, and MMP-9 in conjunctival cells decreased to 2.88, 2.82,
and 4.44 fold, respectively, while that of TGF-β1 increased to 1.16
fold.
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Four weeks after azithromycin withdrawal, expression of IL-1β, IL-8,
and MMP-9 slightly rebounded but was still lower than the
pretreatment levels; expression of TGF-β1 decreased slightly but
remained at levels similar to the healthy controls.
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The expression pattern of IL-1β, IL-8, MMP-9, and TGF-β1 by eyelid
margin cells showed a similar response to azithromycin.
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Results
Effects of Azithromycin on
Cytokine Profiles in MGD
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Results
Tear MMP-9 Activity
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Mean tear MMP-9 activity
decreased from 30.1 ng/mL to 9.4
and 6.1 ng/mL after azithromycin
treatment for 2 to 4 weeks,
respectively, and remained 70%
lower than pretreatment levels for
up to 4 weeks after cessation of
azithromycin.
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Comment
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Topical azithromycin suppressed mRNA expression of proinflammatory
mediators IL-1β, IL-8, and MMP-9 and increased expression of TGF-β1.
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Increased levels TGF-β1 may contribute to the anti-inflammatory activity of
azithromycin in ocular surface inflammatory diseases.
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Limitations: the study did not control for potential confounding factors over
time independent of the intervention that may have contributed to the
results.
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Contact Information
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If you have questions, please contact the corresponding author:
– Stephen C. Pflugfelder, MD, Ocular Surface Center, Cullen Eye
Institute, Department of Ophthalmology, Baylor College of Medicine,
6565 Fannin St, NC-505, Houston, TX 77030 ([email protected]).
Funding/Support
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This work was supported in part by grant EY011915 from the National Eye
Institute (Dr Pflugfelder) and by Inspire, Inc, Research to Prevent Blindness,
the Oshman Foundation, and the William Stamps Farish Fund.
Conflict of Interest Disclosures
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None reported.
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