Issue 54 - University of Florida

A CONTINUING
MEDICAL
CME
EDUCATION
PUBLICATION
N
DICAL EDU
G ME
CA
UIN
TIO
TIN
CON
APRIL 2015 • ISSUE 54
Ocular
Antiinfectives
TOPICS IN
the spectrum of options
for antibiotic Prophylaxis
in cataract surgery
Rosa M. Braga-Mele, MD,
MEd, FRCSC
Today, cataract surgeons looking for an
antibiotic prophylaxis regimen can chose
from a variety of drugs, formulations,
and routes of administration. The ultimate
decision is, in most cases, left largely to each
surgeon’s discretion. In North America,
intraocular antibiotic injection for
prophylaxis is being increasingly adopted.
The existence of an approved, commercially
prepared, unit-dose antibiotic for injection
would drive this trend.
Postoperative endophthalmitis is
one of the most serious complications of
cataract surgery (Figure 1). Occurring
in 0.04% to 0.2% of cases, its overall
incidence is low.1,2 However, for those
who are affected, the consequences
can be severe: pain and vision loss are
common, and the prognosis is generally
tarGet auDienCe this educational activity is intended
for ophthalmologists and ophthalmologists in residency or
fellowship training.
LearninG oBJeCtiVes upon completion of this activity, participants will be able to:
1. discuss the advantages and disadvantages of current
antiinfective prophylaxis options for cataract surgery.
2. Establish an antiinfective prophylaxis approach in
clinical practice that effectively minimizes cataract
patients’ risk of endophthalmitis.
3. Consider and recognize Demodex infestation in
patients with anterior blepharitis.
4. Formulate a staged treatment strategy for patients
with staphylococcal blepharitis.
grim—even with aggressive treatment,
only about half of the patients with
endophthalmitis achieve 20/40 or better vision.3 Because its outcomes can be
devastating, endophthalmitis merits our
best efforts to minimize its occurrence.
One universally used method for
reducing the risk of postoperative endophthalmitis is antiseptic preparation
of the periorbital skin and ocular surface with povidone-iodine at the time
of surgery, the efficacy of which has
been confirmed in prospective studies.4
Although, there is no consensus with
respect to the ideal concentration of
povidone-iodine for surface prophylaxis;
the generally recommended and most
commonly used solution concentration
is 5%.5
In addition to povidone-iodine,
a variety of prophylactic antibiotic
agents—administered through various
routes—are commonly used before, durEdItORS
nisha aCharYa, mD, is an associate professor of
ophthalmology and epidemiology at the university of
California, San Francisco and director of the uveitis Service
at the F.I. Proctor Foundation.
nataLie aFshari, mD, FaCs, is professor of ophthalmology and chief of cornea and refractive surgery at the Shiley
Eye Center, university of California San diego.
terrY Kim, mD, is a professor of ophthalmology at duke
university Eye Center, where he practices cataract, corneal,
and refractive surgery.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
FiGure 1 Acute endophthalmitis with hypopyon.
ing, and after surgery. Each option has
its own advantages and disadvantages,
and practice patterns vary by location.
topical antibiotics
In the US, topical antibiotics—
typically fourth generation fluoroquinolones—are the drugs most frequently
used for cataract surgery prophylaxis.6,7
Studies have shown that preoperative
application of a third or fourth generation fluoroquinolone decreases ocular
surface flora.8,9 Since patients’ skin and
see insiDe for:
infectious aspects of Blepharitis
by Preeya K. Gupta, MD
Topics in Ocular Antiinfectives is jointly sponsored by
Candeo Clinical/Science Communications, llC, and
the university of Florida College of medicine. this
publication is administered by an independent editorial
board and supported by an unrestricted educational
grant from Bausch + lomb, Inc.
Copyright 2015 Candeo Clinical/Science Communications, llC. All rights reserved. Neither the university of
Florida nor Candeo Clinical/Science Communications,
llC, assume any responsibility for injury or damage to
persons or property arising from the use of information
or ideas contained in this publication.
COuRSE dIRECtOR
anuP KuBaL, mD
university of Florida
Gainesville, Fl, uSA
Topics in
ocular
1
Supported by an unrestricted educational
grant
from anTiinfecTives
Bausch + Lomb, Inc.
conjunctival flora are the primary source
of organisms responsible for postoperative endophthalmitis, a reduction
in bacterial load of the conjunctival sac
should, in theory, reduce patients’ risk
of postoperative infection.4
Despite the popularity of topical
antibiotic prophylaxis, some surgeons
prefer the use of povidone-iodine preparation alone prior to surgery out of the
concern that preoperative use of topical
antibiotic drops may promote bacterial resistance and lessen the efficacy of
postoperative antibiotic drops. Indeed,
application of moxifloxacin 0.5% one
day before surgery has been found to
select for fluoroquinolone-resistant organisms, though a longer course (3-day)
of preoperative moxifloxacin showed no
such effect.10
The bottom line with prophylactic
topical antibiotics is that their efficacy
in preventing endophthalmitis has not
been confirmed by prospective studies.
Whether or not topical antibiotic prophylaxis is used is, ultimately, a matter
of surgeon preference.
intracameral injection: the
trend
Besides preparation of the eye with
povidone-iodine, intracameral cefuroxime is the only other method that
has been unequivocally demonstrated
to reduce the rate of postoperative endophthalmitis. The European Society
of Cataract and Refractive Surgery’s
(ESCRS’s) landmark study of intracameral prophylaxis in 2007 showed
a 5-fold decrease in endophthalmitis
after cataract surgery with the use of
intracameral cefuroxime.11 The results
were subsequently corroborated in a
number of other large, prospective
studies by various groups from Europe
and Asia.12,13
Intracameral cefuroxime injection is
now commonly used for cataract surgery
prophylaxis in Europe. A powdered
preparation of cefuroxime that is mixed
with sterile sodium chloride 0.9% solution just before use has recently been
approved in many European countries
for endophthalmitis prophylaxis. In the
US, however, no antibiotic has been
approved for intracameral prophylaxis,
and single-dose preparations are still
unavailable. That fact likely explains,
at least in part, the low adoption rate
of intracameral cefuroxime in the US.
topics in ocular antiinfectives, issue 54
statement oF neeD
Ophthalmologists face numerous challenges in optimizing
their competencies and clinical practices in the realm of
preventing, diagnosing, and treating ocular infections and
their sequelae; these challenges include:
• The widespread “off-label” use of topical ophthalmic antibiotics to prevent and treat serious and sight-threatening
infections—given the reality that the most widely used
topical antibiotics in ophthalmology have FDA approvals
restricted to bacterial conjunctivitis.
• The escalating levels of multi-drug resistance in common
ocular pathogens.1
• The emergence and increasing prevalence of once-atypical
infections that may require diagnostic and treatment
techniques relatively unfamiliar to comprehensive ophthalmologists.2
• The introduction of new and potentially more efficacious
and/or safe ophthalmic antiinfectives.3
• The introduction of new and potentially more accurate
diagnostic techniques for ophthalmic infections.4
• Widespread discussion over the efficacy and safety of novel
or alternative delivery techniques and vehicles for prophylactic ophthalmic antibiotics (including but not limited to
intracameral injection and topical mucoadhesives).5,6
• Increased understanding of the inflammatory damage
caused by ocular infections and the best ways to prevent/
alleviate inflammation without fueling the growth of
pathogenic organisms.
Given the continually evolving challenges described above,
Topics in Ocular Antiinfectives aims to help ophthalmologists
update outdated competencies and narrow gaps between
actual and optimal clinical practices. As an ongoing resource,
this series will support evidence-based and rational antiinfective choices across a range of ophthalmic clinical situations.
reFerenCes
1. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST:
nationwide antimicrobial susceptibility patterns in ocular
isolates. Am J Ophthalmol. 2008 Jun;145(6):951-8.
2. Gower EW, Keay LJ, Oechsler RA, et al. Trends in fungal
keratitis in the United States, 2001 to 2007. Ophthalmology. 2010 Dec;117(12):2263-7.
3. Colin J, Hoh HB, Easty DL, et al. Ganciclovir ophthalmic
gel (Virgan 0.15%) in the treatment of herpes simplex
keratitis. Cornea. 1997;16:393-9.
4. Sambursky R, Tauber S, Schirra F, et al. The RPS adeno
detector for diagnosing adenoviral conjunctivitis. Ophthalmology. 2006;113(10):1758-64.
5. Akpek EK, Vittitow J, Verhoeven RS, et al. Ocular surface
distribution and pharmacokinetics of a novel ophthalmic
1% azithromycin formulation. J Ocul Pharmacol Ther.
2009;25:433-9.
2 Topics in ocular anTiinfecTives
6. Endophthalmitis Study Group, European Society of
Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results
of the ESCRS multicenter study and identification of risk
factors. J Cataract Refract Surg. 2007;33(6):978-88.
oFF-LaBeL use statement This work discusses offlabel uses of antiinfective medications.
GeneraL inFormation This CME activity is
sponsored by the University of Florida College of Medicine
and is supported by an unrestricted educational grant from
Bausch + Lomb, Inc.
Directions: Select one answer to each question in the exam
(questions 1–10) and in the evaluation (questions 11–16).
The University of Florida College of Medicine designates
this activity for a maximum of 1.0 AMA PRA Category 1
Credit™. There is no fee to participate in this activity. In order
to receive CME credit, participants should read the report,
and then take the posttest. A score of 80% is required to qualify
for CME credit. Estimated time to complete the activity is
60 minutes. On completion, tear out or photocopy the answer
sheet and send it to:
University of Florida CME Office
PO Box 100233, Gainesville, FL 32610-0233
phone: 352-733-0064 fax: 352-733-0007
Or you can take the test online at http://cme.ufl.edu/ocular
System requirements for this activity are: For PC users: Windows® 2000, XP, 2003 Server, or Vista; Internet Explorer® 6.0
or newer, or Mozilla® Firefox® 2.0 or newer ( JavaScript™
and Java™ enabled). For Mac® users: Mac OS® X 10.4
(Tiger®) or newer; Safari™ 3.0 or newer, Mozilla® Firefox®
2.0 or newer; ( JavaScript™ and Java™ enabled).
Internet connection required: Cable modem, DSL, or better.
Date oF oriGinaL reLease April 2015. Approved
for a period of 12 months.
aCCreDitation statement This activity has been
planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for
Continuing Medical Education (ACCME) through the
joint sponsorship of the University of Florida College of
Medicine and Candeo Clinical/Science Communications,
LLC. The University of Florida College of Medicine is
accredited by the ACCME to provide continuing medical
education for physicians.
CreDit DesiGnation statement The University
of Florida College of Medicine designates this educational
activity for a maximum of 1.0 AMA PRA Category 1 Credit™.
Physicians should only claim credit commensurate with the
extent of their participation in the activity.
FaCuLtY anD DisCLosure statements
Nisha Acharya, MD (Faculty Advisor), is an associate
professor of ophthalmology and epidemiology at the University of California, San Francisco and director of the Uveitis
Service at the F.I. Proctor Foundation. She states that in the
past 12 months, she has not had a financial relationship with
any commercial organization that produces, markets, re-sells,
or distributes healthcare goods or services consumed by or
used on patients.
Natalie Afshari MD, FACS (Faculty Advisor), is professor
of ophthalmology and chief of cornea and refractive surgery
at the Shiley Eye Center, University of California San Diego.
She states that in the past 12 months, she has not had a
financial relationship with any commercial organization that
produces, markets, re-sells, or distributes healthcare goods or
services consumed by or used on patients.
Terry Kim, MD (Faculty Advisor), is a professor of ophthalmology at Duke University Eye Center, where he practices
cataract, corneal, and refractive surgery. He states that in the
past 12 months he has been a consultant for Alcon, Bausch
+ Lomb, Kala Pharmaceuticals, OSI Pharmaceuticals, Ocular
Systems Inc., Ocular Therapeutix, Omeros, PowerVision,
Inc., Presbyopia Therapies, NovaBay Pharmaceuticals, Shire,
TearScience, and Valeant Pharmaceuticals. Dr. Kim also
states that he has been on the speakers bureau for Alcon
and Bausch + Lomb.
Rosa M. Braga-Mele, MD, MEd, FRCSC, is a professor
of ophthalmology and director of professionalism and biomedical ethics at the department of ophthalmology at the
University of Toronto. Dr. Braga-Mele is also the director of
cataract surgery at the Kensington Eye Institute in Toronto,
Canada. She is a consultant for Alcon Laboratories and
Allergan, Inc.
Preeya K. Gupta, MD, is assistant professor of ophthalmology at Duke Eye Center in Durham, NC and clinical medical
director at the Duke Eye Center at Page Road. She is a
consultant to Shire, Allergan, Biotissue Inc., and TearScience.
DisCLaimer Participants have an implied responsibility
to use the newly acquired information to enhance patient
outcomes and professional development. The information
presented in this activity is not meant to serve as a guideline
for patient care. Procedures, medications, and other courses
of diagnosis and treatment discussed or suggested in this
activity should not be used by clinicians without evaluation
of their patients’ conditions and possible contraindications or
dangers in use, applicable manufacturer’s product information,
and comparison with recommendations of other authorities.
CommerCiaL suPPorters This activity is supported by an unrestricted educational grant from Bausch
+ Lomb, Inc.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
According to the 2007 American Society of Cataract and Refractive Surgery
(ASCRS) survey very few US surgeons
were using intracameral antibiotic, but
many indicated they would do so if a
commercially prepared injectable solution were available.6
Some investigators have reported
using commercially prepared nonpreserved moxifloxacin for intracameral
injection.14-16 Their experience generally supports the safety of intracameral
moxifloxacin, but such usage is off-label,
and its efficacy in preventing endophthalmitis remains to be established.
Another alternative agent for intracameral injection is vancomycin.
There is evidence to support its safety
in intracameral use, but, like intracameral moxifloxacin, no large clinical
trials have assessed its efficacy.17 More
importantly, vancomycin is considered
the agent of choice for Gram-positive
coverage in endophthalmitis treatment
and often the agent of last resort for
treating multidrug-resistant organisms.
Many experts warn against its routine
prophylactic use, lest bacteria develop
resistance to our drug of last resort.
For years following the ESCRS
study, the adoption rate of intracameral
antibiotics in the US remained low. Up
until 2011, less than 20% of surgeons
used any intracameral antibiotic.7 It is
only recently that we see the tide beginning to turn. The first comparative US
study on intracameral prophylaxis came
out in 2013, showing a remarkable—up
to 10-fold—decline in endophthalmitis
rates with the routine use of intracameral injection of cefuroxime, moxifloxacin,
or vancomycin.18
Recently, the ASCRS again surveyed its members regarding antibiotic
prophylaxis practice patterns and recognized an increasing trend towards
intracameral antibiotics.19 Compared
to 2007, use of intracameral antibiotic
injection has grown from 15% to 36%,
and a total of 47% either have initiated
intracameral antibiotic injections in the
past 2 years or plan to start in the next 6
months. In addition, 75% said it is important to have an approved commercial
intracameral antibiotic, and 69% would
inject a single-use cefuroxime prepara-
tion were one available at a reasonable
cost. This suggests that cost and availability are the factors limiting greater
adoption of intracameral prophylaxis.
a transzonular approach
Recently, a new prophylaxis modality has emerged from an effort to reduce
or eliminate the perioperative and
postoperative use of topical antibiotic
drops in cataract surgery. The procedure
involves transzonular injection into the
anterior vitreous of a single dose of a
pharmacy-compounded antiinf lammatory/antiinfective combination (triamcinolone/moxifloxacin) at the end of
surgery. The same company also offers
a compounded formulation comprising triamcinolone, moxifloxacin, and
vancomycin.
Naturally, errors and risks associated
with pharmacy compounding would be
a concern with the use of these drugs.
And, of course, this an off-label use of
these agents. However, no cases of endophthalmitis or toxic anterior segment
syndrome (TASS) have been reported
so far, but the number of uses is still
relatively small.
The corticosteroid/antibiotic combinations are attractive because, in addition to potentially reducing endophthalmitis risk, a single injection could also
decrease postoperative inf lammation
and potentially even cystoid macular
edema. Reducing or eliminating the
need for topical antibiotic drops would
help eliminate patient compliance as
an issue in cataract surgery. And placing drugs in the vitreous—where they
would have a longer half-life—could,
in theory, prolong their prophylactic
effects.
Performed after IOL implantation
and prior to viscoelastic removal, transzonular injection is an additional step at
the end of surgery. Since the risk of endophthalmitis is already low, some may
question whether the benefits of transzonular injection outweigh such risks as
ciliary body trauma. Clinical experience
with this procedure so far indicates that
the risk of adverse events is quite low.
Surgeons will have to learn how to inject
medications behind the zonules, but the
learning curve is likely short. Once the
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
core concePts
➤ topical povidone-iodine
is universally used for
endophthalmitis prophylaxis.
➤ although its clinical efficacy
in reducing endophthalmitis
is not proven, perioperative
use of topical fluoroquinolone
drops remains a popular
means of antibiotic
prophylaxis in north america.
➤ the use of intracameral
antibiotics is growing in
north america.
➤ among the injectable
intracameral antibiotics
(cefuroxime, moxifloxacin,
vancomycin), only
intracameral cefuroxime
prophylaxis has been shown
effective in prospective
studies.
➤ transzonular injection of
compounded drug is a
potential new modality for
both antiinflammatory and
antiinfective prophylaxis.
➤ Proper wound closure
is essential to reducing
the risk of postoperative
endophthalmitis.
surgeons understand where and how to
inject the compound—and as long as
the compound is safe and affordable for
the patient—the transzonular approach
could offer a viable solution for cataract
surgery prophylaxis.
other methods
Subconjunctival injection of antibiotics, once an important prophylaxis option in cataract surgery, has now largely
fallen by the wayside. The 2007 ASCRS
survey found that only about 10% of the
respondents were using subconjunctival
injections for antibiotic. With increasing
transition to clear corneal incisions and
topical anesthesia, this rate will likely
continue to fall.
A number of surgeons continue to
put prophylactic agents in the irrigating
solution. In the ASCRS surveys, about
15% to 20% respondents reported using
antibiotics such as vancomycin in the
Topics in ocular anTiinfecTives
3
irrigating fluid.6,7 However, there have
been no clinical studies that provide
solid evidence to support the benefits
of this practice.
Considerations
Safety, efficacy, availability, and cost
are the key factors that influence a surgeon’s choice of prophylactic regimen.
The transzonular injection is potentially
advantageous, but patients will, in many
circumstances, have to pay for it out of
pocket. Intracameral antibiotic injection
has proven highly effective in reducing
endophthalmitis rates, but fear of the
small but serious risk of compounding
errors has kept many North American
surgeons from moving forward with
the method.
I personally do not inject intracameral antibiotics. At this point, without
access to a commercially available,
regulatory-agency-approved, premade
solution (like the powder for solution
available in parts of Europe), I believe
that the risks of compounding and dilution, including the possibility of TASS,
outweigh the benefits of intracameral
antibiotic injection.
Instead, I routinely use a fourthgeneration fluoroquinolone drop one day
prior to surgery. On the day of surgery,
the patient receives three antibiotic
drops every 3 to 5 minutes over a period of 15 minutes just prior to surgery
(paired with dilating agents). Then in
the OR, I use a povidone-iodine solution
to wipe the surface of the eyelids and
put drops of povidone-iodine into the
conjunctival fornix allowing them to sit
for 1 to 3 minutes while I scrub. I do not
cut the eyelashes, but I believe it is very
important to drape the patient properly
and get the eyelashes out of the way.
Of course, any patient with prominent
blepharitis should be treated before the
surgery. In the postoperative period, my
patients continue on a topical fourthgeneration fluoroquinolone for 7 days.
role of wound Closure
Even though we now have many
options at our disposal for prophylaxis,
as cataract surgeons we cannot forget
the importance of a well-sealed wound
4 Topics in ocular anTiinfecTives
in the prevention of postoperative endophthalmitis. Patients with a leaky
wound are at greater risk of infection,
regardless of the type of antibiotic
prophylaxis.
The association between clear corneal incision and endophthalmitis remains
controversial. Some early reports suggested a link between the two, but other
studies have found otherwise.20,21 Now
that most surgeons have moved toward
microincision cataract surgery (with a
2.2- to 2.4-mm incision), the risk of
wound leak and infection theoretically
should be negligible as long as the selfsealing incision is properly constructed.
Nonetheless, at the end of each procedure, the incision should be checked
for stability and for leakage with a
fluorescein strip or lint-free cellulose
sponge. If wound leakage is suspected,
the surgeon should consider sealing the
wound with a suture or tissue glue.
Rosa M. Braga-Mele, MD, MEd, FRCSC, is a
professor of ophthalmology and director of professionalism and bio-medical ethics at the department
of ophthalmology at the University of Toronto. Dr.
Braga-Mele is also the director of cataract surgery at
the Kensington Eye Institute in Toronto, Canada.
She is a consultant for Alcon Laboratories and Allergan, Inc. Medical writer Ying Guo, MBBS, PhD,
assisted in the preparation of this article.
REFERENCES
1. Miller JJ, Scott IU, Flynn HW Jr, et al. Acuteonset endophthalmitis after cataract surgery
(2000-2004): incidence, clinical settings, and
visual acuity outcomes after treatment. Am J
Ophthalmol. 2005;139(6):983-7.
2. Packer M, Chang DF, Dewey SH, et al;
ASCRS Cataract Clinical Committee. Prevention, diagnosis, and management of acute
postoperative bacterial endophthalmitis. J
Cataract Refract Surg. 2011;37(9):1699-714.
3. Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study.
A randomized trial of immediate vitrectomy
and of intravenous antibiotics for the treatment
of postoperative bacterial endophthalmitis. Arch
Ophthalmol. 1995; 113:1479-96.
4. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine.
Ophthalmology. 1991; 98:1769-75.
5. Ta CN, Singh K, Egbert PR, et al. Prospective
comparative evaluation of povidone-iodine
(10% for 5 minutes versus 5% for 1 minute) as
prophylaxis for ophthalmic surgery. J Cataract
Refract Surg. 2008;34(1):171-2.
6. Chang DF, Braga-Mele R, Mamalis N, et al.
Prophylaxis of postoperative endophthalmitis
after cataract surgery: results of the 2007 AS-
CRS member survey. J Cataract Refract Surg.
2007; 33:1801-05.
7. Leaming D. 2011 Survey of US ASCRS
Members. Available at www.analeyz.com/
AnaleyzASCRS2011.htm.
8. He L, Ta CN, Hu N, et al. Prospective
randomized comparison of 1-day and 3-day
application of topical 0.5% moxifloxacin in
eliminating preoperative conjunctival bacteria.
J Ocul Pharmacol Ther. 2009; 25:373-8.
9. Mino de Kaspar H, Kreutzer TC, AguirreRomo I, et al. A prospective randomized study
to determine the efficacy of preoperative topical levofloxacin in reducing conjunctival bacterial flora. Am J Ophthalmol. 2008;145:136-42.
10. He L, Ta CN, Min˜o de Kaspar H. One-day
application of topical moxifloxacin 0.5% to
select for fluoroquinolone-resistant coagulasenegative Staphylococcus. J Cataract Refract
Surg. 2009; 35:1715-8.
11. Endophthalmitis Study Group, European
Society of Cataract & Refractive Surgeons.
Prophylaxis of postoperative endophthalmitis
following cataract surgery: results of the ESCRS multicenter study and identification of risk
factors. J Cataract Refract Surg. 2007; 33:978-88.
12. García-Sáenz MC, Arias-Puente A, Rodríguez-Caravaca G, et al. Effectiveness of
intracameral cefuroxime in preventing endophthalmitis after cataract surgery Ten-year
comparative study. J Cataract Refract Surg.
2010;36(2):203-7.
13. Tan CS, Wong HK, Yang FP. Epidemiology
of postoperative endophthalmitis in an Asian
population: 11-year incidence and effect of
intracameral antibiotic agents. J Cataract
Refract Surg. 2012;38(3):425-30.
14. Espiritu CRG, Caparas VL, Bolinao JG. Safety of prophylactic intracameral moxifloxacin
0.5% ophthalmic solution in cataract surgery
patients. J Cataract Refract Surg. 2007;33:63-8.
15. Lane SS, Osher RH, Masket S, et al. Evaluation of the safety of prophylactic intracameral
moxifloxacin in cataract surgery. J Cataract
Refract Surg. 2008; 34:1451-9.
16. Arbisser LB. Safety of intracameral moxifloxacin for prophylaxis of endophthalmitis
after cataract surgery. J Cataract Refract Surg.
2008; 34:1114-20.
17. Yoeruek E, Spitzer MS, Saygili O, et al.
Comparison of in vitro safety profiles of
vancomycin and cefuroxime on human corneal endothelial cells for intracameral use. J
Cataract Refract Surg. 2008;34(12):2139-45.
18. Shorstein NH, Winthrop KL, Herrinton LJ.
Decreased postoperative endophthalmitis rate
after institution of intracameral antibiotics
in a Northern California eye department. J
Cataract Refract Surg. 2013; 39:8-14.
19. Chang DF. Results of 2014 ASCRS endophthalmitis antibiotic prophylaxis survey. http://eyeworld.org/article-results-of2014-ascrs-endophthalmitis-antibioticprophylaxis-survey
20. Taban M, Behrens A, Newcomb RL, et al.
Acute endophthalmitis following cataract
surgery: a systematic review of the literature.
Arch Ophthalmol. 2005;123(5):613-20.
21. Wykoff CC, Parrott MB, Flynn HW Jr, et
al. Nosocomial acute-onset postoperative
endophthalmitis at a university teaching
hospital (2002–2009). Am J Ophthalmol. 2010;
150(3):392-8.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
infectious aspects of Blepharitis
Preeya K. Gupta, MD
Bacteria can play a key role in the
pathogenesis of blepharitis, particularly
anterior blepharitis. In many cases,
however, bacterial infection can be the
result of a hidden problem.
Blepharitis is a highly prevalent
ocular disease. Surveys of ophthalmologists and optometrists have found this
chronic inflammatory condition of the
eyelid margin in as many as 37% to 47%
of patients.1 The term blepharitis encompasses a number of conditions, and
the distinction is often made between
posterior blepharitis (which affects the
posterior lid margin and meibomian
glands) and anterior blepharitis (which
affects the anterior lid margin, skin,
and eyelashes.) It is, however, not uncommon for both forms to coexist in
the same patient, albeit with differing
degrees of severity.
FiGure 1 Anterior blepharitis is characterized
by crusting on the eyelid margins, collarettes,
and lid debris.
Unlike posterior blepharitis, which
is primarily an inflammatory condition
characterized by meibomian gland
dysfunction (MGD) that is typically
caused by gland obstruction, anterior
blepharitis is most often associated
with bacterial overgrowth or infection
and is considered a more curable form
of blepharitis.1,2 Clinicians should take
care, however, as there can be another
actor in the play: Demodex, a genus of
parasitic mite that is a normal commensal in human hair follicles, can be an
underlying cause of eyelid inflammation
that appears as a bacterial infection.
signs of infection
Eyelid inflammation typically manifests as erythema and swelling of the
anterior portion of the eyelid margin.
This may be accompanied by ocular
surface symptoms, including burning,
itching, foreign body sensation, and
irritation. Patients with anterior blepharitis have various degrees of crusting
(Figure 1). The presence of collarettes
(circular crusting around the base of
individual eyelashes) is a characteristic
sign of bacterial involvement.
Anterior blepharitis can usually be
distinguished clinically from posterior blepharitis. While inflamed (red,
swollen) eyelid margins can sometimes
occur in posterior blepharitis, these
signs are typically more pronounced
in active anterior blepharitis. Patients
with posterior blepharitis usually exhibit
signs of MGD such as changes in the
appearance of gland orifices, poorly
expressible meibomian glands, and/or
turbid or thickened meibum.
role of Bacteria
In anterior blepharitis, which is
sometimes also called staphylococcal
blepharitis, the eyelid margins are excessively colonized with normal skin bacteria, primarily Staphylococcus epidermidis
and, less often, Staphylococcus aureus. 3
Other species commonly isolated from
blepharitis patients include Propionibacterium acnes and corynebacteria.3-5
Staphylococci such as S. epidermidis and S. aureus can produce lipolytic
exoenzymes (eg, triglyceride lipase, cholesterol esterase, and fatty wax esterase)
that degrade normal tear fi lm lipids.
These altered lipids may in turn stimulate bacterial growth on the eyelid margin and result in heavy colonization.6
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core concePts
➤ anterior blepharitis is
typically a chronic infectious
condition characterized
by excessive bacterial
colonization of the lid margin.
➤ the bacterial species most
commonly involved in
anterior blepharitis are part
of the normal skin flora,
predominantly staphylococcal
species including S.
epidermidis and S. aureus.
➤ Demodex folliculorum is
implicated in causing anterior
blepharitis.
➤ Lid hygiene and topical
antibiotics are effective
treatments for anterior
blepharitis due to bacterial
infestation. For Demodex
blepharitis, tea tree oil lid
scrubs are the best treatment
currently available.
Staphylococcal species can also release
toxic products into the tear fi lm that
incite production of proinflammatory
cytokines and recruitment of inflammatory cells. These, in turn, generate
the characteristic signs and symptoms
of staphylococcal blepharitis.7
By contrast, bacteria are not a
primary pathogenetic factor in posterior blepharitis. However, bacteria may
contribute to MGD patients’ symptoms,
as bacterial lipases can break down the
meibum into free fatty acids and other
products that can irritate the eye and
disrupt the tear film.8
Demodex: a Diagnostic
Challenge
Demodex infestation is usually
asymptomatic and is very common. Its
prevalence increases with age—by age
60, 84% of people have Demodex, and by
70 virtually everyone carries the mite.9
Topics in ocular anTiinfecTives
5
Just two Demodex species, however, have
been implicated in the pathogenesis of
blepharitis: Demodex folliculorum, which
is involved in the pathogenesis of anterior blepharitis, and Demodex brevis,
which can cause posterior blepharitis
with MGD and keratoconjunctivitis.10
Demodex can elicit eyelid margin
inf lammation that masquerades as
staphylococcal blepharitis. The mite can
also cause direct damage to the eyelash
follicles, allowing bacteria (including
streptococci and staphylococci) into the
host; by releasing proteins from within
themselves, these bacteria can trigger a
host immune reaction that may disrupt
the eyelid’s normal bacterial homeostasis.10
Because many clinicians do not recognize its potential role in blepharitis,
Demodex infestation is often neglected
in the diagnosis of blepharitis. However,
determining the mite’s presence normally requires only careful examination.
Cylindrical dandruff (“sleeves”) that
cuff the lashes, the product of Demodex
folliculorum, is a typical clinical sign of
Demodex infestation. Slit lamp examination can often reveal D. folliculorum
mites at the base of the eyelashes; or
epilated eyelashes (particularly those
with sleeves) can be examined under a
microscope.
antimicrobial treatment
Once the diagnosis of staphylococcal
blepharitis is established, a short course
of antibiotic therapy is warranted. I
prescribe empirical antibiotics to any
patients with signif icant crusting,
6 Topics in ocular anTiinfecTives
erythema, and swelling of the eyelid
margin. I find antibacterial ophthalmic
ointments, such as bacitracin to be helpful, as well as azithromycin ophthalmic
solution 1% rubbed into the eyelid,
though it is an off-label use of the topical
antibiotic drop.
For patients with a prominent
inflammatory response, mild doses of
topical corticosteroids may be beneficial.
In such cases, I usually use an antibiotic
corticosteroid combination agent to control both the infectious and the inflammatory processes. If the treatment has
been effective, significant improvement
should be seen within 7 to 10 days.
Maintaining the hygiene and health
of the eyelid is essential to managing
blepharitis. Whether using commercially available lid scrubs or baby shampoo diluted in warm water, lid hygiene
can help reduce bacterial colonization
and remove accumulated secretions.
There is also a new eyelid cleanser made
with hypochlorous acid that has broad
spectrum activity against many bacteria
and Demodex. Patients apply this to the
eyelids once or twice daily.
Control of Demodex infestation can
be an important component of blepharitis treatment, especially in cases where
conventional treatments including
topical antibiotics have failed. The adult
Demodex folliculorum mite is resistant
to many common antiseptic solutions
including 75% alcohol, but tea tree oil
treatment has been found to be effective
in eradicating the mites and reducing
ocular surface inflammation.10 Commercial products with tea tree oil include
a 50% tea tree oil weekly lid scrub and
a 5% cream for lids and periocular skin.
One recently developed eyelid wipe
contains the active constituent of tea
tree oil with fewer of the irritating ones
and is better-tolerated. In cases where
infestation is treatment-resistant, oral
antiparasitic drugs such as ivermectin
may be helpful.
Preeya K. Gupta, MD, is assistant professor of ophthalmology at Duke Eye Center in Durham, NC,
and clinical medical director at the Duke Eye Center
at Page Road. She is a consultant to Shire, Allergan,
Biotissue Inc., and TearScience. Medical writer
Ying Guo, MBBS, PhD, assisted in the preparation
of this article.
REFERENCES
1. Lemp MA, Nichols KK. Blepharitis in the
United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf.
2009;7(2 Suppl):S1-S14.
2. Jackson WB. Blepharitis: current strategies for
diagnosis and management. Can J Ophthalmol.
2008;43(2):170-9.
3. Groden LR, Murphy B, Rodnite J, et al. Lid
flora in blepharitis. Cornea. 1991;10(1):50-3.
4. Dougherty JM, McCulley JP. Comparative
bacteriology of chronic blepharitis. Br J Ophthalmol. 1984;68:524-8.
5. McCulley JP, Dougherty JM. Bacterial aspects of chronic blepharitis. Trans Ophthalmol
Soc U K .1986;105 (Pt 3):314-8.
6. Bron AJ, Sci FM, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul
Surf. 2004;2:149-65.
7. O’Brien TP. The role of bacteria in blepharitis.
Ocul Surf. 2009;7(2 Suppl):S21-2.
8. McCulley JP, Shine WE. Meibomian gland
function and the tear lipid layer. Ocul Surf.
2003;1(3):97-106.
9. Post CF, Juhlin E. Demodex folliculorum and
blepharitis. Arch Dermatol. 1963;88:298-302.
10. Liu J, Sheha H, Tseng SCG. Pathogenic role
of Demodex mites in blepharitis. Curr Opin
Allerg Clin Immunol. 2010;10:505-510.
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
To obtain CME credit for this activity, go to http://cme.ufl.edu/ocular
Topics in ocular anTiinfecTives
7
examination Questions
Topics in Ocular Antiinfectives, Issue 54
This CME program is sponsored by the University of Florida College of Medicine and supported by an
unrestricted educational grant from Bausch + Lomb, Inc. Directions: Select the one best answer to each
question in the exam (Questions 1–10) and in the evaluation (Questions 11–16) below by circling one letter
for each answer. Participants must score at least 80% on the questions and complete the entire Evaluation
section on the form below. The University of Florida College of Medicine designates this activity for a
maximum of 1.0 AMA PRA Category 1 Credit™. There is no fee to participate in this activity. You can take
the test online at http://cme.ufl.edu/ocular.
1. Which of the following
statements about Demodex is
correct?
A. Demodex is a normal
commensal in humans
B. Demodex is
predominantly found in
younger populations
C. Demodex brevis is
implicated in causing
anterior blepharitis
D. Thickened meibum is
a typical sign of Demodex
infestation
2. Routine prophylactic
use of vancomycin is not
recommended because of
concern for?
A. Cost
B. Availability
C. Safety
D. Bacterial resistance
3. Which of the following is
an appropriate treatment for
anterior blepharitis?
A. Compounded
vancomycin ointment
B. Thermal pulsation
C. Ganciclovir gel
D. Antibiotic/
corticosteroid
combination
4. Which of the
following statements
about postoperative
endophthalmitis is NOT
true?
A. It occurs in 0.04 to
0.2% cases
B. Visual prognosis is
poor, even with aggressive
treatment
C. Endophthalmitis is
unrelated to wound leak
D. Endophthalmitis
rates can be reduced
by preoperative use of
povidone-iodine
5. Which of the following
statements about
prophylactic topical
fluoroquinolone drops is
NOT true?
A. They reduce
conjunctival flora
B. They are proven to
prevent postoperative
endophthalmitis
C. They may select for
resistant organisms when
used preoperatively
D. They are the favored
mode of antibiotic
prophylaxis in the US
examination Answer Sheet
This CME activity is jointly sponsored by the University of Florida and Candeo Clinical/Science Communications, LLC, and supported by an unrestricted
educational grant from Bausch + Lomb, Inc. Mail to:
University of Florida CME Office, PO Box 100233,
Gainesville, FL 32610-0233. Directions: Select
the one best answer for each question in the exam
above (Questions 1–10). Participants must score at
least 80% on the questions and complete the entire
Evaluation (Questions 11–16) to receive CME credit.
CME exam expires March 31, 2016.
6. Which one of the following
endophthalmitis prophylaxis
measures has been proven
effective?
A. Intracameral
cefuroxime injection
B. Perioperative topical
antibiotic application
C. Intracameral povidoneiodine
D. Transzonular antibiotic
injection
7. Which bacterial species is
not commonly isolated from
patients with blepharitis?
A. S. epidermidis
B. S. aureus
C. P. acnes
D. E. coli
8. Transzonular injection of
a single-use moxifloxacin/
triamcinolone combination
A. Is fully reimbursable in
the US
B. Uses drug prepared by
compounding pharmacies
C. Is widely used in
Europe and Asia
D. Has been proven
effective in large-scale
clinical trials
1.A B C D
evaluation:
1=Poor 2=Fair 3=Satisfactory 4=Good 5=Outstanding
2.A B C D 7.A B C D
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12.Rate the overall effectiveness of how the activity:
Related to my practice: 1 2 3 4 5
________________________________________________________________
organization/institute
________________________________________________________________
First Name last name
degree
Will influence how I practice: 1 2 3 4 5
Will help me improve patient care: 1 2 3 4 5
Overall met my expectations: 1 2 3 4 5
Avoided commercial bias/influence:12345
13.Will the information presented cause you to make
any changes in your practice? Yes No
3.A B C D
8.A B C D
4.A B C D
9.A B C D
________________________________________________
5.A B C D
10.A B C D
15.How committed are you to making these changes?
12345
8 Topics in ocular antiinfectives
If you wish to receive credit for this activity, please fill in the
following information. Retain a copy­for your records.
11.Extent to which the activity met the identified:
Objective 1: 1 2 3 4 5
Objective 2: 1 2 3 4 5
Objective 3: 1 2 3 4 5
Objective 4: 1 2 3 4 5
Overall quality of material: 1 2 3 4 5
6.A B C D
10. Which of these findings
suggests the presence of
staphylococcal blepharitis?
A. Collarettes
B. Blocked meibomian
gland orifices
C. Prolonged tear film
breakup time
D. All of the above
Topics in Ocular Antiinfectives, Issue 54
Stimulated my intellectual curiosity: 1 2 3 4 5
ANSWERS:
9.Demodex has been found to
be sensitive to which of the
following agents?
A. 75% alcohol
B. Tea tree oil
C. Povidone-iodine
D. Baby shampoo
14.If yes, please describe: __________________________
16.Are future activities on this topic important to you?
Yes No
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