Download PDF Edition - Review of Cornea and Contact Lenses

RCCL
REVIEW OF CORNEA
& CONTACT LENSES
SEPTEMBER 2016
The Human
Microbiome
Under THREAT
p. 8
An Antibacterial Q&A
p. 10
Beware the BIOFILM
p. 14
Managing Corneal
INFECTIONS
p. 18
[EARN 1 CE CREDIT]
Antibiotics in Practice:
Use, Don’t ABUSE
p. 24
Have Patients See You
for URGENT CARE
p. 40 & p. 42
Supplement to
Contact Lens Wear and
CORNEAL
INFECTIONS
Also: How Point-of-Care Testing Makes Dry Eye Therapy More Targeted and Timely
001_RCCL0916_Cover-V4.indd 1
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©2016 CooperVision 9033O BC 7/16
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contents
Review of Cornea & Contact Lenses | September 2016
departments
4
News Review
Corneal Nerves Altered by Ortho-K;
Contact Lens Washout Period May
Not Impact Tear Film
6
My Perspective
Understanding the Contact Lens
Prescription Release Legislation
By Joseph P. Shovlin, OD
8
Corneal Consult
Treating the Ocular Surface:
Resistance is Futile
By J. James Thimons, OD
10
Pharma Science & Practice
An Antibacterial Q&A
By Elyse L. Chaglasian, OD, and
Tammy Than, MS, OD
40
Practice Progress
Turning a Negative Into a Positive
By Mile Brujic, OD, and
Jason R. Miller, OD, MBA
42
features
14
18
24
Out of the Box
Keeping Contact Lens Care In-House
Beware the Biofilm
What are practitioners doing to prevent
this common formation and the risk it
poses to contact lens wearers?
By Amy Lagina, OD
Managing Contact LensRelated Bacterial Infections
When a patient at risk presents, how do
you keep them free of problems?
By Anar Maurya, OD
CE — Antibiotics in Practice:
Use, Don’t Abuse
Resistant bacterial
strains challenge
eye doctors to
be judicious in
treatment. Here
are several key
trends to heed
when setting a
regimen.
By Blair Lonsberry, MS, OD, MEd.
By Gary Gerber, OD
32
ON THE COVER
Patient with a resultant corneal scar
eight months following an infection of
Pseudomonas keratitis with hypoyon.
Courtesy of Christine W. Sindt, OD.
Become a Fan on
Facebook
/ReviewofCorneaAndContactLenses
Targeted and Timely:
The New Model of
Dry Eye Care
Point-of-care tests and advanced
diagnostic imaging are helping doctors
tackle it faster and more precisely than
ever before.
By Richard B. Mangan, OD
With contributions by
Scott Schachter, OD,
Scott Hauswirth, OD, and
Whitney Hauser, OD
Follow Us On
Twitter
@RCCLmag
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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News Review
IN BRIEF
■ Pterygium size may impact the rate at
which patients recover corneal sensitivity
(CS) following excision surgery, notes
a study published online in the journal
Cornea.1 Researchers in Spain examined 32
eyes of patients with primary nasal pterygium, recording differences in corneal sensitivity, pterygium corneal area (PCA), tear
osmolarity, tear break-up time, Schirmer’s
test results and ocular symptoms before
and one month after lesion excision.
Ultimately, the researchers concluded, the
only determinant was PCA. “Measures of
CS did not show a relationship, evidencing
an external factor such as the surgical
injury as a determinant of the CS recovery
process. Therefore, it may be advisable to
operate when the lesion is still relatively
small because the CS recovery seems to
be faster.”
1. Julio G, Campos P, Pujol P, et al. Determining
factors for fast corneal sensitivity recovery after pterygium excision. Cornea. 2016. [Epub ahead of print.]
■ Bausch + Lomb recently announced the
offering of a same-day dispensing program for eye care practitioners designed
to offer patients rebate savings of up to
$150 on Bausch + Lomb Ultra and Biotrue
ONEday contact lenses. Biotrue multipurpose and PeroxiClear hydrogen peroxide
solutions will also be featured in several
major retailer in-store promotions as part
of the back-to-school sales period.
■ Re-esterified omega-3 fatty acids are
an effective treatment for dry eye disease,
according to a new study.1 One hundred
and five subjects (54 in the treatment
group, 51 in control group) completed the
study, which assessed oral nutrition as the
primary therapy—specifically with regard
to the effect of oral re-esterified omega-3
fatty acids on tear osmolarity, MMP-9,
ocular durface disease index, tear breakup time, Schirmer’s score, corneal staining
and omega Index. The study claims statistically significant improvement of tear
osmolarity in its primary and secondary
endpoints of six and 12 weeks.
1. Epitropoulos AT, Donnenfeld ED, Zubin SA,
et al. Effect of Oral Re-esterified Omega-3
Nutritional Supplementation on Dry Eyes. Cornea.
2016;35(9):1185-91.
■ A recent study involving patients with
meibomian gland dysfunction (MGD)
and dry eye demonstrates that a single
LipiFlow (TearScience) treatment provides sustained mean improvement in
gland function and symptoms.1 The trial
monitored the effects of a single Lipiflow
treatment through a 12-month period,
during which researchers claim 86% of
subjects required no further prescription
therapy for dry eye symptoms.
1. Blackie CA, Coleman CA, Holland EJ. The
sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian
gland dysfunction and evaporative dry eye. Clin
Ophthal. 2016;10:1385-96.
4
Corneal Nerves Altered by
Orthokeratology Wear
L
ong-term wear of orthokeratology lenses is associated
with a reduction in central
corneal sensitivity and nerve
fiber density, reports a study published online in the journal Eye &
Contact Lens.1 However, the results
from the study are unclear with regards to whether patients are at risk
for issues with their tear films.
Researchers from the University
of New South Wales, Sydney,
Australia conducted a cross-sectional study with 54 patients grouped
into one of three categories, either
non-lens-wearing, soft lens-wearing,
or orthokeratology lens wearing.
Each patient attended the clinic for
a single visit during which corneal
sensitivity measurements and in
vivo corneal confocal microscopy
were conducted on each individual’s
right eye, with corneal sensitivity
measured at the corneal apex and
2.5mm temporal to the apex using
a Cochet-Bonnet esthesiometer.
Corneal nerve morphology, in contrast, was assessed via sampling of a
1mm2 area of the corneal sub-basal
nerve plexus using the Heidelberg
Retinal Tomography with Rostock
Corneal Module at the corneal
apex and 2.5mm temporal to
the apex, and nerve fiber density
was calculated via measurement
of nerve fiber length per square
millimeter.
Ultimately, results indicated a
significant difference in corneal sensitivity between each group, with
central threshold being significantly
higher in the orthokeratology group
than the non-wearer group and
central nerve fiber density being
significantly less in the orthokeratology group than in either the
non-wearer or soft lens-wearer
groups. Interestingly, mid-peripheral nerve fiber density was similar
between all three groups, suggesting
the presence of regional variations
in corneal sensitivity following
orthokeratology lens wear.
“Normal corneal sensitivity is
essential for the health of the ocular
surface,” the researchers note.
“Any reduction in sensitivity can
lessen the ability of the cornea to
detect foreign bodies that could
damage the ocular surface. The
desensitization of the cornea might
also compromise the lacrimal functional unit, leading to a reduction
in aqueous tear film secretion and
subsequently to dry eye.” As such,
further research is necessary to
determine whether alterations to
corneal nerve morphology might
“impact the stability of the precorneal tear film and integrity of
the functional lacrimal unit in an
[orthokeratology] lens-wearing
population.”
RCCL
1. Lum E, Golebiowski B, Swarbrick HA. Reduced
corneal sensitivity and sub-basal nerve density in
long-term orthokeratology lens wear. Eye Contact
Lens. 2016. [Epub ahead of print.]
Gender and Transplants
Patient gender may play a role in corneal
graft rejection rates.1 A study involving
18,000 British patients found that female
transplant receipients were more likely
to have a successful transplant if they
received a woman’s cornea while there
was no gender difference in failure rates
for men receiving corneal tissue from either a man or a woman. Further research
is necessary, to determine whether this
discovery is significant; however, it falls
in line with other research indicating that
gender mismatches have higher rates of
immunological rejection in vascularized
organ transplants.
1. Hopkinson CL, Romano V, Kaye RA, et al. The
Influence of donor and recipient gender incompatibility
on corneal transplantation rejection and failure. Am J
Transplant. 2016 July. [Epub ahead of print.]
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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RCCL
REVIEW OF CORNEA
& CONTACT LENSES
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Telephone (610) 492-1000
Fax (610) 492-1049
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EDITORIAL STAFF
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ASSOCIATE CLINICAL EDITOR
Christine W. Sindt, OD, [email protected]
EXECUTIVE EDITOR
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EDITORIAL REVIEW BOARD
Mark B. Abelson, MD
James V. Aquavella, MD
Edward S. Bennett, OD
Aaron Bronner, OD
Brian Chou, OD
Kenneth Daniels, OD
S. Barry Eiden, OD
Desmond Fonn, Dip Optom M Optom
Gary Gerber, OD
Robert M. Grohe, OD
Susan Gromacki, OD
Patricia Keech, OD
Bruce Koffler, MD
Pete Kollbaum, OD, PhD
Jeffrey Charles Krohn, OD
Kenneth A. Lebow, OD
Jerry Legerton, OD
Kelly Nichols, OD
Robert Ryan, OD
Jack Schaeffer, OD
Charles B. Slonim, MD
Kirk Smick, OD
Mary Jo Stiegemeier, OD
Loretta B. Szczotka, OD
Michael A. Ward, FCLSA
Barry M. Weiner, OD
Barry Weissman, OD
Contact Lens Washout Period
May Not Impact Tear Film
A
washout period may
not be as necessary as
initially believed when
evaluating tear cytokines
following contact lens wear or lens
care product use, reports a study
from the July 2016 issue of Eye &
Contact Lens.1 Certain cytokines
are responsible for promoting the
inflammatory response on the ocular surface and are found in cases
of dry eye, ocular allergy, bacterial
keratitis and both soft and rigid
contact lens wear.2-4
Researchers at the State
University of New York and the
University of New South Wales in
Sydney, Australia investigated the
tear makeup of 10 subjects immediately following contact lens wear
and then after one, two, three, four
and seven days without contact
lens wear, looking for changes in
the concentration levels of IL-1ß,
IL-1Ra, IL-6, IL-10, IL-12 (p70)
and TNF-α. Approximately 20µL to
30µL of pooled basal tears were collected bilaterally from each subject
at each visit, and two custom multiplex assays were used to quantify
the concentration of tear cytokines.
Repeatability and reproducibility
of multiple assays using tears has
previously been reported.5,6
Slit lamp findings at baseline and
seven days after contact lens removal were not significantly different,
though several subjects displayed
epithelial microcysts, corneal neovascularization and significant lid
flakes at different points during the
experiment. Average corneal staining was mild at baseline (4.9±4.3)
and day seven (2.9±2.5). Overall,
there was no significant change in
tear cytokine concentrations, with
alterations over the seven-day time
period as follows: 4.6±2.8 for IL1ß, 4.6±2.8 for IL-1Ra, 14.6±11.2
for IL-6, 7.9±11.2 for IL-10,
39.8±16.8 for IL-12 and 24.9±46.3
for TNF-α.
“This study has confirmed that
the selected tear cytokine concentrations did not change significantly
within one week after discontinuation of contact lens wear. This
indicates that a seven-day washout
period may not significantly affect
the ocular surface inflammatory
state observed with contact lens
use, although a longer period may
be required to return to the levels
to pre-contact lens wear level,” the
researchers noted. Also, “although
the between-kit repeatability was
poor, this study also showed that a
well-trained operator can provide
repeatable and reliable findings
using custom multiplex assays.”
RCCL
1. Chao C, Golebiowski B, Stapleton F, Richdale K.
Changes in tear cytokine concentrations following
discontinuation of soft contact lenses—a pilot study.
Eye Contact Lens. 2016 Jul;42(4):237-43
2. Enriquez-de-Salamanca A, Castellanos E, Stern
ME, et al. Tear cytokine and chemokine analysis
and clinical correlations in evaporative-type dry eye
disease. Mol Vis. 2010;16:862-873.
3. Yamaguchi T, Calvacanti BM, Cruzat A, et al.
Correlation between human tear cytokine levels and
cellular corneal changes in patients with bacterial
keratitis by in vivo confocal microscopy. Invest
Ophthalmol Vis Sci. 2014;55:7457-7466.
4. Thakur A, Willcox MD. Contact lens wear alters
the production of certain inflammatory mediators in
tears. Exp Eye Res. 2000;70:255-259.
5. LaFrance MW, Kehinde LE, Fullard RJ. Multiple
cytokine analysis in human tears: an optimized
procedure for cytometric bead-based assay. Curr
Eye Res. 2008;33:525-544.
6. Benito MJ, Gonzalez-Garcia MJ, Teson M, et al.
Intra- and inter-day variation of cytokines and
chemokines in tears of healthy subjects. Exp Eye
Res. 2014;120:43-49.
Advertiser Index
Alcon.......................Page 7, Cover 3
Bausch + Lomb ..................Page 23
CooperVision.......................Cover 2
Menicon ............................... Cover 4
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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8/25/16 12:43 PM
My Perspective
By Joseph P. Shovlin, OD
Understanding the Contact Lens
Prescription Release Legislation
The next step in a legislative confrontation may mean better protection for lens wearers.
T
hough country singer
Kelly Clarkson’s song
lyrics, What doesn’t
kill you makes you
stronger, are a far cry
from being linked to anything
medical in nature, there are still
two applications she more than
likely did not think of when lifting
that line from Nietzche. First,
her song could actually stand as
the theme song for exposure to
pathogens: inoculations ultimately
make us stronger—if they don’t
kill us first. Second, there is some
relevance attached to the legislation that was recently introduced
by Senator Bill Cassidy, MD. The
Consumer Health Protection Act
(S.2777)—which aims to modify
the 2003 Fairness to Contact Lens
Consumers Act (FCLCA)—at first
glance appeared to be problematic
for us as eye care practitioners;
but now, it may in fact yield some
good with the modifications that
were recently introduced.
A HISTORICAL PERSPECTIVE
In 2003, the FCLCA was introduced to organize the way
in which contact lenses were
dispensed and by whom. The
legislation’s initial intent was to
improve the level of protection
for consumers; it requires practitioners to provide patients with a
copy of their lens prescription so
they might be able to look around
for where they want to purchase
their contact lenses from, if they
so desire. As part of the Act, the
Federal Trade Commission (FTC)
was given the power to enforce
6
the rules on both prescribers and
sellers of contact lenses. Overall,
the Act was implemented with the
goal of reducing barriers for retail
competition.
Unfortunately, the American
Optometric Association revealed
several examples of widespread
abuse of the current FCLCA legislation scope by sellers, prompting the introduction of the more
recent Contact Lens Consumer
Health Protection Act of 2016. Its
aim is to provide new patient safety requirements and accountability
for online retailers. A number of
significant modifications exist,
including an allowance for the
prescriber to email, fax or phone
prescription confirmations to potential sellers depending on which
is more convenient, thus avoiding
the troubling “robo-calls” of the
past. Additionally, this legislation
is expected to help assure that a
prescription is filled exactly as
it is written. The legislation also
establishes a hotline for patient
safety, allowing prescribers to
provide sellers with patient health
information. Fines to sellers who
do not adhere to the rules will be
increased to $40,000 per infraction. The CDC will study the public health impact and direct health
costs to online sales and abuses.
OPPOSING VIEWS
Opponents to the legislation
argue that the bill is anti-consumer and would stifle competition
in terms of securing lens sales.
1-800-Contacts, for example,
argues that the legislation would
in fact have unintended health
consequences to the consumer,
since it is the one that promotes
healthy behaviors to lens wearers.2
Other contact lens retailers have
also begun to report prescribers
who don’t adhere to prescription
expirations originally agreed upon
to the FTC, even though they
have the medical discretion to
do so (i.e., in the case of patients
requiring continuous wear lenses
or following surgery.)
S
o, prescribers must remain
committed to further educating
contact lens wearers on the care
of their contact lenses, including
when to reorder, as we wait for
the legislature to move forward.
Advising patients that these products are in fact medical devices capable of causing sight-threatening
problems when handled improperly can help hammer home the
fact that discussion with a licensed
prescriber is key to maintaining
good contact lens wear. Though
not perfect, the FCLCA did not
kill us in its original form. Could
the removal of known issues make
the revised legislation stronger
than ever?
RCCL
1. Federal Trade Commission. The Contact Lens
Rule: A Guide for Prescribers and Sellers. Available at: www.ftc.gov/tips-advice/business-center/guidance/contact-lens-rule-guide-prescribers-sellers. Accessed July 28, 2016.
2. 1-800-Contacts. Anti-Consumer Legislation
Would Increase Costs for 41 Million Contact Lens
Consumers. Available at: www.1800contacts.
com/connect/press-releases/1-800-contacts-opposes-legislation-introduced-today-gut-fairness-contact-lens-consumers-act. Accessed July
28, 2016.
3. American Optometric Association. FCLCA
Compliance and Contact Lens Safety. Available
at: www.aoa.org/advocacy/federal-advocacy/
regulatory-issues/fclca?ss0=y. Accessed July 28,
2016.
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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A FLEXIBLE LENS-WEARING EXPERIENCE TO
HELP PATIENTS SEE, LOOK AND FEEL THEIR BEST…
DAY OR NIGHT
Scot Morris, OD, FAAO
Optometrist
Eye Consultants of Colorado
Conifer, Colorado
In my 20 years of practicing optometry, I have come across various types of
patients with a multitude of visual and lifestyle needs - busy professionals,
frequent travelers, new mothers, doctors and nurses with unpredictable
work schedules, and even those who live in low-humidity environments like
right here in Conifer, Colorado (elev. 8,200 feet). It is only by listening to
our patients and understanding their needs that we can recommend the
contact lens option that will give them the best contact lens experience.
These patients share one common need—a flexible lens-wearing experience
which will allow them to wake up with comfortable, clear, immediate vision to
perform their best. The one contact lens that immediately springs to my mind for
these patients is AIR OPTIX NIGHT & DAY AQUA contact lenses from Alcon.
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®
In addition to the proprietary SmartShield Surface Technology, which is
featured in the entire AIR OPTIX family, I like that AIR OPTIX NIGHT &
DAY AQUA contact lenses are made of a material (lotrafilcon A) which
has the highest oxygen transmissibility in the market,* and an established
safety profile.
TM
®
4
®
®
5
Unpredictable
Work Schedules
Need immediate
vision waking up
for shift
Busy Professionals
Frequent Travelers
Eyes feel strained
looking at my
mobile devices
Travel too often to
hassle with my
lenses
Moms with
Young Kids
6
AIR OPTIX NIGHT & DAY AQUA contact lenses are the first to be
introduced with these features and the only contact lenses designed to
provide comfort for up to 30 nights of continuous wear. They are the
#1 practitioner-recommended contact lens for people who sleep in
their lenses, and ideal for people who lead busy lives. I also prescribe
these to my patients who not only sleep in their lenses but also face
lens dehydration and discomfort from living in our low-humidity
environment, knowing that lenses from the AIR OPTIX family
maintain lens surface wettability and provide comfort throughout the
wearing period.
®
Can’t see clearly
getting up
throughout the
night
®
7
®
4
I am confident in recommending AIR OPTIX NIGHT & DAY AQUA contact
lenses for extended periods and encourage you to give them a try. The
benefits are quick and easy to communicate, and you can rest assured that
they will give your patients the flexible lens-wearing experience they need
to see, look and feel their best.
®
®
When patients express dissatisfaction with their contact lens-wearing
experience, it may stem from their sleeping habits. Around 30% of contact
lens-wearing patients admit that they sleep in their lenses, with a whopping
64% of these patients doing so for at least a week at a time in lenses not
approved for this use. In addition, many patients may not have been
offered contact lenses approved to meet their needs.
1
2,3
Our passion is to help your patients
see, look and feel their best.
*Dk/t = 175 @ -3.00D. Other factors may impact eye health.
®
®
Important information for AIR OPTIX NIGHT & DAY AQUA (lotrafilcon A) contact lenses: Indicated for vision correction for daily wear (worn
only while awake) or extended wear (worn while awake and asleep) for up to 30 nights. Relevant Warnings: A corneal ulcer may develop rapidly and cause eye
pain, redness or blurry vision as it progresses. If left untreated, a scar, and in rare cases loss of vision, may result. The risk of serious problems is greater for extended wear vs. daily wear
and smoking increases this risk. A one-year post-market study found 0.18% (18 out of 10,000) of wearers developed a severe corneal infection, with 0.04% (4 out of 10,000) of wearers experiencing a
permanent reduction in vision by two or more rows of letters on an eye chart. Relevant Precautions: Not everyone can wear for 30 nights. Approximately 80% of wearers can wear the lenses for extended wear. About
two-thirds of wearers achieve the full 30 nights continuous wear. Side Effects: In clinical trials, approximately 3-5% of wearers experience at least one episode of infiltrative keratitis, a localized inflammation of the cornea which may be accompanied
by mild to severe pain and may require the use of antibiotic eye drops for up to one week. Other less serious side effects were conjunctivitis, lid irritation or lens discomfort including dryness, mild burning or stinging. Contraindications: Contact lenses
should not be worn if you have: eye infection or inflammation (redness and/ or swelling); eye disease, injury or dryness that interferes with contact lens wear; systemic disease that may be affected by or impact lens wear; certain allergic conditions
or using certain medications (ex. some eye medications). Additional Information: Lenses should be replaced every month. If removed before then, lenses should be cleaned and disinfected before wearing again. Always follow the eye care
professional’s recommended lens wear, care and replacement schedule. Consult package insert for complete information, available without charge by calling (800) 241-5999 or go to myalcon.com.
References 1. In a survey of 2,115 daily and extended wear contact lens patients. Alcon data on file, 2012. 2. In a survey of 284 daily and extended wear contact lens patients. Alcon data on file, 2012. 3. Alcon data on file, 2012. 4. Eiden
SB, et al. Prospective study of lotrafilcon B lenses comparing 2 versus 4 weeks of wear for objective and subjective measures of health, comfort, and vision. Eye & Contact Lens. 2013; 39:290-294. 5. Based on ratio of lens oxygen transmissibility. Alcon
data on file, 2009, 2010. 6. Schein O, McNally J, Katz J, Chalmers R, et al. The incidence of microbial keratitis among wearers of a 30-day silicone hydrogel extended-wear contact lens. Ophthalmology. 2005;112:2172-2179. 7. In a survey of 310
optometrists in the US; Alcon data on file, 2014.
See product instructions for complete wear, care and safety information.
RCCL0916_Alcon AOND.indd 1
© 2016 Novartis
06/16
US-AND-16-E-2124
Sponsored by
8/23/16 3:51 PM
Corneal Consult
By J. James Thimons, OD
Treating the Ocular Surface:
Resistance is Futile
The human microbiome supports our existence, but it also serves as the source of
infection. Resistance is on the rise, and clinicians have to prescribe carefully.
I
n 2008, the National Institutes
of Health launched the Human
Microbiome Project with the
purpose of identifying the
organisms that live both on
and inside the human species. The
ocular surface was of particular interest, and the project estimated that
over 200 species of bacteria colonize
the human conjunctiva. Among
the most typical species were
Staphylococcus, Streptococcus and
Corynebacterium—all gram-positive. Pseudomonas and Neisseria
were those identified among the
gram-negative organisms.1,2
The purpose of this complex community of organisms is somewhat
difficult to discern. Given that we
mostly live symbiotically with these
microbes, it’s possible they are present to prevent more severe organisms from attacking. As an example,
Clostridium difficile is present in
the intestines but is held in check by
other normal flora until something,
such as overuse of antibiotics, erases
the natural population, providing C.
diff. a window of opportunity.
The ocular surface has similar
complexities. The ocular surface’s
biofilm lifecycle varies from days to
weeks, depending on the organisms
present and is associated, in most
instances, with mucins that have
evolved with us over millennia.
Over the last decade, we have
seen significant erosion of the efficacy of commonly used agents, especially in the gram-positive arena.
The ARMOR study analyzed
3,237 bacterial isolates at 22
sites from 2009-2013. It looked
8
at isolates common to the ocular
surface (Streptococcus pneumonia, Staphylococcus aureus, coagulase-negative Staphylococci,
Pseudomonas aeruginosa and
Haemophilus influenza), as well as
commonly used antibiotics, including fluoroquinolones, aminoglycosides, macrolides, cephalosporins
and penicillins.3
CORNEAL DISEASE
Beginning almost two decades ago
with earlier generations (ofloxacin
and ciprofloxacin), fluoroquinolones evolved into the go to drugs
for the treatment of corneal disease, including microbial keratitis.
Typical treatment protocols varied
from QID to Q 1 hour, depending
on disease severity. As use increased,
the efficacy against gram-positive
isolates (specifically Staph.) began
to erode, and the next generation
agents, gatifloxacin and moxifloxacin, replaced their precursors and
were considered incapable of developing resistance due to the necessity
of a dual, simultaneous mutation.5
Unfortunately, this proved untrue
and today the resistance to both
generations by methicillin-resistant
Staphylococcus aureus (MRSA) is
extremely high; some studies indicate less than 20% efficacy against
these organisms.6
Commonly, clinicians initiate
microbial keratitis treatment with a
fluoroquinolone on a Q 1 hour to
Q 3 hour basis, depending on the
severity of presentation. But data on
methicillin-resistant isolates demonstrates the need for vigilance after
the first 24 to 48 hours of therapy in
patients who have not demonstrated
clinical stabilization or improvement.3 In those cases, the best
alternative is fortified vancomycin
(30mg/ml) in addition to the fluoroquinolone on a Q 1 hour or Q 1/2
hour basis. According to ARMOR,
fluoroquinolones have a low level of
sensitivity to gram-positive MRSA
while maintaining good sensitivity
to other gram-positive isolates as
well as the more typical gram-negative isolates such as Pseudomonas.
So, if treatment fails to improve the
patient’s condition, the most likely
cause is a non-sensitive gram-positive organism. Additionally, the
study demonstrated excellent
MRSA coverage for vancomycin.
Another concern is that the best
agents are not available on patients’
formulary or they cost too much.
Thus, it’s useful to know which
other agents can be used. Data show
that Polytrim (trimethoprim/polymixin B sulfate, Allergan) maintains
good sensitivity to MRSA and that
earlier generation fluoroquinolones
are reasonably similar to the next
generation for initial ulcer treatment
when newer generation agents are
not available at effectively the same
dosage patterns.3,4,6
CONJUNCTIVITIS
AND BLEPHARITIS
When treating common conjunctivitis, the ARMOR study indicates
that typical therapy patterns have
not changed materially other than
the notable decline in the sensitivity
of tobramycin and macrolides.6
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PRESEPTAL DISEASE
With preseptal cellulitis, the organisms typically involved are
similar to those seen in microbial
keratitis rather than Pseudomonas.
Since Staphylococcus and some
Streptococcus primarily populate
lids, selection of an appropriate
agent should be based on the patient’s allergy history and the known
performance of the antibiotic
against Staph.
In the penicillin class, drugs
such as ampicillin and dicloxacillin at 1,000mg to 1,500mg
per day are typically effective.
Many clinicians prefer Augmentin
(GlaxoSmithKline), a combination of ampicillin and clavulanate,
which is a beta lactamase inhibitor
that increases efficacy of therapy
(875mg BID). As for the cephalosporin class, first generation
agents have greater efficacy against
gram-positive organisms than 2nd
or 3rd generation agents. Keflex
(Advancis Pharmaceutical) and
Duricef (Bristol-Myers Squibb) are
both effective and cost efficient for
the majority of patients. The newer
classes of drugs such as macrolides
(clarithromycin) and fluoroquinolones have shown little improvement
in outcomes but do demonstrate
increased side effect profiles at a
higher cost.9
I
n the United States, pathogens
resistant to antibiotics cost us approximately $20 billion a year and
add eight million additional hospital
days. A 2014 WHO update shows
continued erosion of drug efficacy
in all key categories worldwide with
continued loss of efficacy in the FQ
and cephalosporin classes even in
Photo: Joseph P. Shovlin, OD
While these agents may show
success in some patients, if the patient’s condition does not improve,
it is most likely the consequence
of increased resistance, making
selection of an alternative agent,
such as Polytrim, appropriate.
Additionally, clinicians can consider using Neosporin Ophthalmic
Solution (neomycin and polymyxin
B sulfates, and gramicidin, Pfizer)
given the relative increase in sensitivity generated by its absence in the
ophthalmic market.
In the treatment of blepharitis,
several studies show little improved
efficacy in the use of antibiotics
versus lid hygiene in long-term management of these conditions.7 Given
the ARMOR data on the poor
performance of tobramycin, look
for other alternatives. Numerous
new topical regimens for cleaning
the lids and multiple versions of lid
scrubs, allow practitioners to avoid
antibiotic use altogether.
If I must use an antibiotic for
lid-related disease, I select an ointment for night time use and combine it with aggressive lid hygiene.
Agents such as Bacitracin (Pfizer),
Polymyxin (Sagent Pharmaceuticals)
or their combination have excellent
coverage against typical isolates
and have the advantage of being
non-preserved. Several studies have
looked at the treatment of ocular
surface disease related to posterior
lid disease for recurrent chalazia
that involve the long-term use of
re-esterified omega 3 fatty acids at
approximately 3,000mg per day.
This avoids the need for doxycycline, which has the potential for
significant side effects as well the
development of resistance.8
Fourth-generation fluoroquinolones
may be the most effective option
against MRSA, which caused this
patient’s corneal ulcer.
treatment of last resort settings.10 As
eye care practitioners, it is critical
we understand the impact of the
market on our decisions and our
patients. Antibiotic resistance is one
of the biggest health issues, and we
all must work toward changing the
course of its impact on our patients
and ourselves.
RCCL
1. Abelson M, McLaughlin J. Of biomes, biofilm
and the ocular Surface. Review of Ophthalmology.
2012;19(9):52-4.
2. Wilcox MD. Characterization of the normal
microbiota of the ocular surface. Exp Eye Res. 2013
Dec;117:99-105.
3. Asbell PA, Sanfilippo CM, Pillar CM, et al. Antibiotic Resistance Among Ocular Pathogens in the
United States: Five-Year Results From the Antibiotic
Resistance Monitoring in Ocular Microorganisms
(ARMOR) Surveillance Study. JAMA Ophthalmol.
2015 Dec;133(12):1445-54.
4. Asbell PA. ARVO/Healio.com. Opthalmology. May
8, 2015.
5. Scoper SV. Review of the third and fourth generation fluoroquinolones in ophthalmology: in vitro and
in vivo efficacy. Adv Ther. 2008 Oct;25(10):979-94.
6. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST:
nationwide antimicrobial susceptibility patterns in
ocular isolates. Am J Ophthalmol. 2008;145(6):951-8.
7. Lindley E, Matsumura S, Hatef E, Akpek EK. Interventions for chronic blepharitis. Cochrane Database
Syst Rev. 2012 May 16;(5):CD005556.
8. Epitropoulous AT, Donnenfeld ED, Shah ZA, et
al. Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes. Cornea. 2016
Sep;35(9):1185-91.
9. Piccirillo F, Mager DE, Frisse ME, et al. Impact of
first line vs second line antibiotics for the treatment
of acute uncomplicated sinusitis. JAMA. 2001 Oct
17;286(15):1849-56.
10. The World Health Organization. WHO’s first
global report on antibiotic resistance reveals
serious, worldwide threat to public health. News
Release. April 30, 2014. Available at www.who.int/
mediacentre/news/releases/2014/amr-report/en/.
Accessed August 22, 2016.
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Pharma Science & Practice
By Elyse L. Chaglasian, OD, and Tammy Than, MS, OD
An Antibacterial Q&A
New antibiotics are scarce—here’s why, and what’s being done about it.
S
ince treating corneal
infections is the focus of
this edition, it seemed
like a good time to talk
about the new antibiotics. Wait—there aren’t any to talk
about! So, I guess this column will
focus on the status of antibacterial
agents by answering some questions
surrounding this topic.
Just a year later, the WHO issued
its first global report on antibiotic
resistance, further emphasizing that
antimicrobial resistance is a serious
threat that “is no longer a prediction for the future, it is happening
right now in every region of the
world and has the potential to
affect anyone, of any age, in any
country.”4
CAN CURRENT
ANTIBACTERIAL AGENTS
MANAGE TODAY’S
INFECTIONS?
Infectious diseases are still the third
leading cause of deaths in the United
States and the second leading cause
of death worldwide.1 According to
a 2013 report by the Centers for
Disease Control and Prevention
(CDC), more than two million people are infected with resistant strains
annually, and more than 23,000
die from these infections.2 In 2013,
The World Health Organization
(WHO) issued a report on priority
medicines, stating that the lack of
effective antibiotics poses a significant threat to global health and will
require the involvement of many
different organizations to respond.3
IS THERE A SHORTAGE OF
NEW ANTIBIOTICS?
Only four new classes of antibiotics
have been introduced in the past
40 years.5 The US Food and Drug
Administration (FDA) approved
only two antibiotics in the past five
years, which represents a drop off
of 88% in approvals since the mid
1980s.6 Table 1 summarizes the approval of antibacterial agents in the
United States over the past several
decades.5
According to the WHO, antimicrobial resistance is one of the
three greatest threats to human
health.4 Of the drugs in the pipeline today, very few appear beneficial over existing drugs, and few
appear to target the “ESKAPE”
pathogens: Enterococcus faecium,
Staphylococcus aureus, Klebsiella
pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa,
and Enterobacter species. This
acronym was so named after the
organisms currently causing most
of hospital infection in the United
States and because they escape being
managed by currently approved
antibiotics.7
Many of the new drugs coming
out lack a novel mechanism and
are merely a new generation of an
existing antibiotic—in other words,
Table 1. Antibiotics
Approved in the United
States, 1983–20115
Dates
Number of
Antibiotics Approved
1983-1987
16
1988-1992
14
1993-1997
10
1998-2002
7
2003-2007
5
2008-2011
2
a follow-up drug.8 Therefore, even
most drugs that have been developed recently are not significantly
improved or better than what we
already have.
WHY IS THERE A SHORTAGE
OF RESEARCH AND
DEVELOPMENT?
Drug development is costly; pharmaceutical companies spend, on
average, $5 billion in research,
development and clinical trials for
each drug they bring to market.6
Additionally, approximately 80% of
drugs fail to make it through safety
and efficacy studies.6 Therefore,
each drug that makes it to market
needs to be highly profitable to help
recoup these extensive costs.
Economically, the return on
investment (ROI) for antibiotics is
poor for many reasons, including:
1. Antibiotics are typically taken
for a short period of time, and
they typically cure the disease.
Pharmaceutical companies are far
more attracted to the development
of drugs that need to be taken for
chronic conditions such as hypertension, hyperlidemia, etc.
2. The rapid development of
drug resistance shortens the clinical
lifespan.
3. New antibacterial drugs often
have a short patent life.
All of these situations reduce the
ROI for new drugs, making their
development an unattractive financial venture.
Added to the financial concerns,
developing an antibacterial drug
is often more challenging than developing other classes of drugs. An
antibacterial drug has to be effective
against many pathogens, be able to
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treat a variety of infections and have
effectivity at different sites within
the body.9
There are also ethical concerns
about clinical trials that compare
the investigative drug to an existing drug. If there is a high level of
resistance to the comparator drug,
randomizing patients to receive that
therapy is ethically questionable.10,11
While there is still a push for
pharmaceutical companies to develop new antibiotics, at the same time
there is a competing initiative to
limit their use because of increasing
resistance.8 These concerns ultimately highlight the underlying paradox
of antibacterial drug research and
development: as the antimicrobial
resistance increases dramatically,
there is a marked decline in the
number of antibiotics in the development pipeline.
WHAT IS THE STATUS OF THE
ANTIBACTERIAL PIPELINE?
As reported by the CDC in 2011,
only five major pharmaceutical
companies had active antibacterial
discovery programs in place.12 In
a 2009 European report entitled
The Bacterial Challenge: Time to
React, researchers found that only
15 antibiotics out of the 167 being
developed had a new mechanism
of action to potentially address the
multidrug resistance challenge.12
Currently, there are 37 new
antibiotics in the pipeline, and given
that only roughly 60% of drugs that
ever reach Phase 3 trials will receive
FDA approval, the pipeline is not
sufficient for the rising health care
needs.13 Right now, 11 of the 37
drugs are in Phase 1 trials, 13 are in
Phase 2 trials and 13 are in Phase 3
trials. Eleven are expected to have
activity against ESKAPE pathogens
and an additional four possibly may
be effective.2
According to one study, in the
last 40 years only two novel classes
of antibiotics have been brought to
market—and both were discovered
before 1987.14 Today, the greatest
threat is multi-drug resistant gram
negative organisms. Unfortunately,
most large pharmaceutical companies have closed (or greatly reduced)
their antibacterial research units.
Now, a large portion of research in
this field is occurring in academia or
in smaller biotech companies.14
As for the few drugs that are
new, researchers evaluated the
characteristics of the new antibiotics approved from 2010 to 2015.
There were eight approved, with
only one having a new mechanism
of action. Half of the drugs were for
the same condition—acute bacterial
skin infections. Three of the eight
showed activity against the ESKAPE
pathogens. One drug demonstrated
activity against Clostridium difficile,
one of the CDC’s greatest-threat
pathogens. None of the drugs studied demonstrated superior outcomes
on patient survivability over what
is currently available. At the very
least, the data did show that the
FDA is approving new antibiotics
efficiently.15
Antibiotic Stewardship programs.
These stewardship programs pro-
Bacteria:
Up Close and Personal
These “ESKAPE” pathogens
are not managed by currently
approved antibiotics:
Colonial growth pattern displayed
by Providencia alcalifaciens
bacteria, belonging to the family
Enterobacteriaceae. Photo: CDC
A digitally-colorized SEM showing
Klebsiella pneumoniae interacting
with white blood cells (blue). Photo:
David Dorward, PhD; NIAID
Staphylococcus aureus escaping
white blood cells. Photo: Frank DeLeo,
NIAID
WHAT IS BEING DONE TO
ADDRESS THE PROBLEM?
Research suggests 20% to 50%
of antibiotics prescribed in United
States acute care hospitals are not
needed or not appropriate.16 In
2014, the CDC recommended that
all acute care hospitals implement
Pseudomonas aeruginosa. Photo:
Janice Haney Carr; CDC
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mote judicious use of antibacterial
agents, increase the correct prescribing and prophylaxis use of antimicrobials and overall improve patient
safety.16
The increase in resistance to the
antimicrobials available to practitioners has led to numerous initiatives, these stewardship programs
among them. But this alone cannot
fix the problem; researchers need
to develop new drugs.5 To address
the barriers to developing antibiotic
drugs, several efforts are underway,
including: public-private partnerships (PPP), modified regulatory
processes, outside-the-box reimbursement plans, and an increase in
government investment.11
In 2012, President Obama signed
the Generating Antibiotic Incentives
Now (GAIN) Act into law. This
legislation extends the market exclusivity of certain antibiotics that treat
serious or life-threatening diseases.
It also grants those drugs priority
review status so they can undergo
an expedited FDA approval process.
Under the GAIN act, the FDA must
maintain a list of pathogens that
have the potential to pose a significant public health risk and update it
every five years. The FDA must also
provide clinical trial guidance on
the development of drugs that target
specific bacteria.17
Eight drugs have been approved
since the initiative launched—but
not in areas of greatest need such as
treatment for C. diff. and drug-resistant Neisseria gonorrhoeae.13
Of the 37 antibiotics currently
in development, roughly 24 are
qualified infectious disease products
(QIDPs). All drugs approved since
2014 have been QIDP.13
There are several other legislative
proposals in play that will help with
the drug approval process. For example, the Antibiotic Development
to Advance Patient Treatment
(ADAPT) Act has been referred to
the US House of Representatives,
which, if passed, will speed up the
FDA approval process for antibiotics, antifungals or biological products for the treatment of a serious
infection.13
At the 69th World Health
Assembly this past May, the
WHO announced the formation
of a public-private partnership,
the Global Antibiotic Research
and Development (GARD)
Partnership.18 It was created by
the Drugs for Neglected Diseases
Initiative, in conjunction with
WHO, to develop new antibiotics
to meet the challenges of resistance
and to promote conservation but
equitable access. GARD is now in
the start-up phase and is receiving
seed money from various organizations throughout Europe. Hopefully,
such a partnership will allow the
development of products that the
pharmaceutical industry may pass
on due to lack of profitability.18
In 2010 the Infectious Diseases
Society of America launched the
Bad Bugs No Drugs – 10 x ’20
initiative, which aimed to have 10
new systemic antibacterial drugs developed by 2020.7 An interim report
on the 10 x ’20 initiative suggests
there is progress, but the pace of
research and development needs to
speed up if it is going to reach its
goal by 2020.19
In 2009 a transatlantic task force
was created to focus on bolstering
the antibacterial pipeline, strengthening infection control interventions
and promoting antimicrobial stewardship in human and veterinary
settings.6
W
ith so much global attention
on this antibacterial shortage, hopefully these unified efforts
will garner a sufficient stockpile
of antibacterial agents to manage
the serious infections of today and
tomorrow.
RCCL
1. Conly JM, Johnston BL. Where are all the new antibiotics? The new antibiotic paradox. Can J Infect
Dis Med Microbiol. 2005 May;16(3):159-60.
2. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.
Available at www.cdc.gov/drugresistance/threat-report-2013/. Accessed August 23, 2016.
3. Kaplan W, Wirtz VJ, Mantel-Teeuwisse A, et al.
Priority Medicines for Europe and the World, 2013
Update. The World Health Organization. July 9,
2013. Available at www.who.int/medicines/areas/
priority_medicines/MasterDocJune28_FINAL_Web.
pdf. Accessed August 23, 2016.
4. The World Health Organization. WHO’s first global report on antibiotic resistance reveals serious,
worldwide threat to public health. News Release.
April 30, 2014. Available at www.who.int/mediacentre/news/releases/2014/amr-report/en/. Accessed
August 23, 2016.
5.Cooper MA, Shlaes D. Fix the antibiotic pipeline.
Nature. 2011 Apr;472(7341):32.
6. Krans B. Few New Drugs: Why the Antibiotic
Pipeline Is Running Dry. Healthline.com. 2014 July.
Available at www.healthline.com/health/antibiotics/
why-pipeline-running-dry. Accessed August 23,
2016.
7. Infectious Diseases Society of America. The 10
x ‘20 Initiative: pursuing a global commitment to
develop 10 new antibacterial drugs by 2020. Clin
Infect Dis. 2010 Apr 15;50(8):1081-3.
8. Sukkar E. Why are there so few antibiotics in the
research and development pipeline? The Pharmaceutical Journal. 2013 Nov;13.
9. Piddock L. The crisis of no new antibiotics--what
is the way forward? Lancet Infectious Diseases. 2012
Mar;12(3):249-53.
10. DiNubile MJ. Noninferior antibiotics: when is “not
bad” “good enough”? Open Forum Infect Dis. 2016
May 25;3(3):ofw110.
11. McDonnell A, Rex JH, Goossens H. et al. Efficient
delivery of investigational antibacterial agents via
sustainable clinical trial networks. Clin Infect Dis.
2016 Aug 15;63 Suppl 2:S57-9.
12. Race against time to develop new antibiotics. Bulletin of the World Health Organization.
2011;89:88–9.
13. Drug development critical to combating antibiotic resistance. Healio Infectious Disease News. 2015
June. Available at www.healio.com/infectious-diseases. Accessed August 10, 2016.
14. Zorzet A. Overcoming scientific and structural
bottlenecks in antibacterial discovery and development. Ups J Med Sci. 2014 May;119(2):170-5.
15. Deak D, Outterson K, Powers JH, Kesselheim AS.
Progress in the fight against multidrug-resistant
bacteria? A review of U.S. Food and Drug Administration-approved antibiotics, 2010-2015. Ann Intern
Med. 2016 May 31. doi: 10.7326/M16-0291.
16. Centers for Disease Control and Prevention.
Core Elements of Hospital Antibiotic Stewardship
Programs. Available at www.cdc.gov/getsmart/
healthcare/implementation/core-elements.html.
Accessed August 11, 2016.
17. GAIN: How a New Law is Stimulating the
Development of Antibiotics. The Pew Charitable
Trusts Issue Brief. November 07, 2013. Available
at www.pewtrusts.org/en/research-and-analysis/
issue-briefs/2013/11/07/gain-how-a-new-law-is-stimulating-the-development-of-antibiotics. Accessed
August 25, 2016.
18. Drugs for Neglected Diseases Initiative. Global
Antibiotic Research & Development (Gard) Partnership. Available at www.Dndi.org/diseases-project.
Accessed August 10, 2016.
19. Boucher HW, Talbot GH, Benjamin DK, et al. 10
x ‘20 Progress--development of new drugs active
against gram-negative bacilli: an update from the
Infectious Diseases Society of America. Clin Infect
Dis. 2013 Jun;56(12):1685-94.
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2016
MEETINGS
Up to
12 CE
Credits*
MEETINGS CO-CHAIRS:
MURRAY FINGERET, OD
ROBERT N. WEINREB, MD
CE CONFERENCES
8th Annual
EAST COAST OPTOMETRIC
GLAUCOMA SYMPOSIUM
October 21-22, 2016
Crystal Gateway Marriott
1700 Jefferson Davis Hwy,
ARLINGTON, VIRGINA
Up to
12 CE
Credits*
Partially supported by an
unrestricted educational grant from
Alcon
Up to 12 COPE Credits for $275! www.reviewofoptometry.com/ECOGS2016
Please call the hotel directly at 888-236-2427 and identify yourself as a participant of the East Coast Optometric Glaucoma Symposium.
SOUTHWEST OPTOMETRIC
GLAUCOMA SYMPOSIUM
November 19, 2016
JW Marriott Houston
5150 Westheimer Road
HOUSTON, TEXAS
Up to
6 CE
Credits*
Up to 6 COPE Credits for $125! www.reviewofoptometry.com/SWOGS2016
Please call the hotel directly at 713-961-1500 and identify yourself as a participant of the Southwest Optometric Glaucoma Symposium.
8th Annual
WEST COAST OPTOMETRIC
GLAUCOMA SYMPOSIUM
December 9-10, 2016
Hilton Hotel
21100 Pacific Coast Hwy,
HUNTINGTON BEACH, CALIFORNIA
Up to
12 CE
Credits*
Partially supported by an
unrestricted educational grant from
Alcon
Up to 12 COPE Credits for $275! www.reviewofoptometry.com/WCOGS2016
Please call the hotel directly at 800-822-7873 and identify yourself as a participant of the West Coast Optometric Glaucoma Symposium.
For faculty & more information, go to
www.reviewofoptometry.com/events
call 1-866-658-1772, or email [email protected]
2016_OGS_HouseAd-8x10.75.indd 1
*Approval pending
8/24/16 10:34 AM
the
What are practitioners doing
to prevent this common
formation and the risk it poses
to contact lens wearers?
BIOFILM
By Amy Lagina, OD
A
female patient
presented to the
clinic on a Tuesday
morning after a holiday weekend with a
sudden-onset red and painful right
eye, reporting that she had also
been exhibiting tearing and light
sensitivity for the past day. She was
a current contact lens wearer who
had not visited the office since her
last annual eye examination more
than one year ago. Patient history
included noncompliance with a
monthly lens replacement schedule—the patient reported replacing
her lenses every two months while
also using numerous brands of
multipurpose solution and failing
to replace her contact lens case as
recommended. The patient also acknowledged noncompliance with
proper case cleaning and could not
recall when she began using it; the
case itself was covered with the
dry and crusted remnants of her
contact lens solution.
Following a thorough exam,
the patient was diagnosed with
microbial keratitis, empirically treated with a topical broad
spectrum antibiotic eye drop, and
given information on contact lens
and lens case hygiene. She returned
to the clinic for appropriate follow
up care as recommended. Luckily
for this patient, the location of her
infection was peripheral and did
not permanently affect her vision.
After the infection resolved, she
was re-fit into daily disposable
contact lenses.
Unfortunately, this presentation
is all too commonly seen in contact lens patients who experience
lens-related problems or infections. Though the majority of new
contact lens patients are educated
on the importance of proper care
and replacement, in some cases
they become complacent in their
routine along the way, and these
lapses enable infections to occur.
Photo: CDC/Rodney M. Donlan, PhD; Janice Carr (PHIL #7488), 2005.
“CASE” REPORT
Most patients are not aware of
the danger inadequately managed
contact lens cases in particular can
present; without proper cleaning
and storage procedures, free-floating microbes can easily attach
themselves to the inside of a contact lens case and begin to secrete
proteins that create a protective
outer coating, known as a biofilm.1
This matrix-like structure can
attach to both living and non-living surfaces, and has been found
on other medical devices including
prosthetic heart valves, coronary
stents, prosthetic joints, cochlear
and intraocular lens implants.1
The primary culprits of contact
lens-associated microbial keratitis
that can be found in contact lens
case biofilms are Staphylococcus
aureus, Pseudomonas aeruginosa,
Serratia marcescens, Fusarium solani and Acanthamoeba. Together,
these organisms account for more
than 30,000 cases of microbial
keratitis per year in the United
States.1
ABOUT THE AUTHOR
Staphylococcus aureus biofilm on the surface of a medical device, a common
concern in heath care generally, and among contact lens wearers in particular.
Dr. Lagina is a clinical
assistant professor at the
University of Michigan’s
Kellogg Eye Center and
also practices at the VA Ann
Arbor Health Care System.
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Photos: Donna M. Wicker, OD
A keratoconus patient with Type II diabetes who developed an infection following hybrid contact lens wear.
Though most infections occur following soft contact lens wear, in rare cases improper care of GP and hybrid lenses
can also lead to issues: this patient ran out of his prescribed hydrogen peroxide solution and elected to use a
saline solution instead.
For practitioners to adequately
prevent or reduce biofilm formation, it is necessary to first understand how biofilms occur. Five
stages of biofilm formation and
transferability exist:
Stages 1 & 2. First, the biofilm
begins as a reversible collection of
floating cells in the solution near
the case’s surface (stage 1), then as
an attachment of the cells on the
case (stage 2).
Stages 3 & 4. Next, more cell
layers are constructed (stage 3),
followed by the creation of a protective outer covering (stage 4).
Stage 5. Finally, the microbes detach and disperse into the solution
within the case or onto the contact
lens itself.1
A poorly fitting or potentially
contaminated contact lens may
alter the integrity of the corneal
epithelium, allowing easy access
from possible freeloading microbes
from a biofilm to penetrate the
compromised cornea and cause
an infection.1 Furthermore, the
presence of a contact lens on the
eye can also negatively influence
the antimicrobial action of the
tear layer, causing an increase in
the bacterial load and subsequent
corneal invasion from transported
biofilm microbes.1
Once a layer of cells has attached itself to the case and has
begun to grow and reproduce, it is
significantly more resistant to antimicrobials; as such, it may warrant
further study. Current methods of
attacking a biofilm—e.g., including bactericidal agents in contact
lens solutions and cases, modifying contact lens case hygiene
directions—are only designed to
address the early stages of biofilm
formation.
THERE’S THE RUB
Both multipurpose and hydrogen peroxide-based contact lens
solutions are designed to clean and
disinfect contact lenses. For the
most part, debris, makeup residue,
proteins and mucus all need to be
removed from the lens during the
cleaning process—this must occur
prior to the disinfection process in
which the bacteria is destroyed.2
If the lenses are not thoroughly
cleaned prior to disinfection, the
antimicrobial
Table 1. ISO 14729 Specific Test Microbes
action of the
Pseudomonas aeruginosa
solution is
Bacteria
Serratia marcescens
reduced. This
Staphylococcus aureus
highlights the
Fusarium solani
importance of
Fungi
Candida albicans
mechanically
cleaning, or rubbing, the contact
lenses prior to soaking them in
contact lens solutions for disinfection. Simply rubbing and rinsing
lenses yields a 1-log reduction of
microbes from the lens surface.
Common multipurpose solution disinfectants Polyquad
(polyquaternium-1) and PHMB
(polyhexamethylene biguanide)
are found in different products, depending on the solution’s manufacturer, but the mechanism of action
is the same: the chemical is incorporated into the cell membrane of
the bacteria to cause membrane
permeability and, ultimately, cell
death.2 Hydrogen peroxide-based
solutions, in contrast to multipurpose ones, use the oxidizing activity of the cleaning liquid to disrupt
microbial DNA.
Contact lens solutions must
meet the requirements of
the International Standards
Organization’s (ISO) standard
14729, “Microbial requirements
and test methods for products and
regimens for hygienic management
of contact lenses.” These requirements address the antimicrobial
efficacy against free-floating
(planktonic) and non-attached
cells of the following microbes:
Pseudomonas aeruginosa, Serratia
marcescens, Staphylococcus aureus, Fusarium solani and Candida
albicans (Table 1).3 Recently com-
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BEWARE THE BIOFILM
eugenol, which have a bactericidal
effect on cell membranes and have
been shown capable of detaching
sessile bacteria from a surface.4
One study found that cinnamon
oil combined with a multipurpose
solution had an increased antimicrobial effect greater than that of
cinnamon oil or the multipurpose
solution alone. However, additional study is required to determine
the risk of corneal toxicity, contact
lens material damage or adverse
reactions from mixing cinnamon
oil in a contact lens solution.
ON THE CASE
Most contact lens cases are comprised of a mix of three plastic
polymers: polypropylene, styrene
and polyethylene. During the
production process, the contact
lens solution manufacturer tests
the efficacy of their solutions with
a designated contact lens case; as
such, it is important to remind patients to use the case included with
the solution they purchase to ensure the cleaning and disinfecting
properties of the solution are given
the best possible environment to
work within. In some instances,
use of a specific solution with a
contraindicated case can actually
lessen its effectiveness.
Researchers have attempted
to make special modifications
to the material composition of
the contact lens case to engender
a bactericidal effect, namely by
Photos: Donna M. Wicker, OD
Fusarium infection following contact lens wear. From left to right: (a) initial
presentation and (b) post-corneal transplant treatment.
Photo: Christine W. Sindt, OD
pleted research has demonstrated
that current brands of multipurpose solutions are able to reduce
biofilm formation.
Of course, past events like the
Fusarium outbreak linked to
ReNu with MoistureLoc (Bausch +
Lomb) and the Acanthamoeba outbreak in connection with Complete
MoisturePlus (Abbott) have taught
practitioners that multipurpose
solutions alone cannot be our only
defense mechanism against biofilm
formation. For example, ReNu
with MoistureLoc was found to
have adequate antimicrobial activity against free-floating Fusarium,
but limited activity against a sessile
(i.e., adherent) biofilm; as such, a
Fusarium biofilm in a contact lens
case with this solution was able to
continue to grow, develop further antimicrobial resistance and
subsequently cause an infection.1
Complete MoisturePlus was found
to have limited activity against
Acanthamoeba, allowing cysts to
form, which led to keratitis.1 Both
solutions were eventually voluntarily recalled from the market.
As more attention and interest
is paid to alternative and complementary medicine and organic
therapies, research is also being
completed on the antimicrobial
activity of certain types of plant
oils in combination with contact
lens solutions.4 For example,
cinnamon oil has been found to
contain cinnamic aldehyde and
Serratia marcescens corneal
infection.
adding silver or organoselenium
in an effort to reduce and prevent
biofilm formation. Silver-lined
cases work by slowly releasing
silver ions into the lens solution
during the disinfection process.
Silver is known to have antimicrobial properties: it inhibits bacterial
DNA replication and disrupts the
cell membrane to cause cell death.5
Patients using silver-lined cases
should soak their lenses for at least
24 hours, however, as only minimal antimicrobial effect was found
at six- and 10-hour soaking times.5
Additionally, patient compliance
with cleaning and replacing these
cases is also an issue: over time,
the silver ions are depleted from
the case, limiting the antimicrobial
activity.6
The addition of organoselenium
into the polymer of the contact
lens case was the subject of a
recent study.7 The antimicrobial
action of organoselenium serves as
a catalyst to create superoxide free
radicals that disrupt bacterial cell
membranes. The advantage of the
addition of organoselenium into
the case composition over silver is
that the organoselenium will not
be depleted with time and use of
the case, allowing for additional
antimicrobial activity to occur
despite the age of the case.
BACK TO THE FUTURE
Revisiting disinfection methods
that have been used in the past
may also be an effective means to
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a contact lens case is to rub each
well with a finger, rinse the case
with fresh multipurpose solution,
wipe the case with a clean tissue
and then place it face-down to air
dry.11,12 The Centers for Disease
Control and the Food and Drug
Administration have both updated their consumer safety websites with the new case cleaning
recommendations.13,14
So what does this mean for
practitioners and their patients?
Unfortunately, there does not
seem to be a quick fix for biofilm
prevention or reduction. Research
and development continues to be
ongoing in an effort to create new
solutions with improved antimicrobial efficacy, while other studies
are addressing ways to add antimicrobial compounds into contact
lens cases to limit cell adhesion.
Still, continuing to teach new
contact lens wearers and remind
older ones about the importance of
proper cleaning and replacement
of not only their contact lenses but
also their cases remains a priority.
R
eturning to the patient from
the beginning, she reported that she had forgotten about
cleaning the case, even though she
admitted it looked rather dirty.
She stated she would be compliant
from now on for fear of another
infection. Overall, however, it is
hoped that it does not take an episode of infection for a patient to
realize the importance of adequate
care and replacement of contact
lenses and cases.
RCCL
1. Bispo PJM, Haas W, Gilmore MS. Biofilms in
infections in the eye. Pathogens.2015;4:111-136.
2. Artini M, Cellini A, Scoarughi GL, Papa R, et al.
Evaluation of contact lens multipurpose solutions
on bacterial biofilm development. Eye Contact
Lens. 2015;41:177-182.
3. Chang JML, McCanna DJ, Subbaraman LN,
Jones LW. Efficacy of antimicrobial against
biofilms of Achromobacter and Pseudomonas.
Optom Vis Sci. 2015;92:506-513.
4. Bassyouni RH, Kamel Z, Abdelfatteh MM,
Mostafa E. Cinnamon oil: a possible alternative
for contact lens disinfection. Cont Lens Anterior
Photo: Danielle M. Robertson, OD, PhD
counteract biofilm development.
Twenty to 30 years ago, contact
lenses were predominantly cleaned
using a device that plugged into
an electrical circuit to create heat.
The advent and ease of use of
multipurpose solutions caused the
heat system to fall out of favor
with many patients and providers;
however, a recent study found
that using a warming device that
reached a temperature of 140˚F
for three hours with a multipurpose solution was more effective
against biofilm formation than the
multipurpose solution alone.8 As
such, further research is needed
to develop a warming device that
could be easily manufactured and
potentially used by our contact
lens patients.
The habits of noncompliant lens
wearers have been thoroughly
studied; hallmarks include reuse
and topping off of solution, and
not cleaning or replacing the case
or contact lenses regularly. Some
patients do some of these things,
while others do all of them; regardless, not making these actions
a habit can lead to a 4.4-fold
higher risk of microbial keratitis.9
Interestingly, contact lens case
contamination has been found in
58% to 85% of patients without
any symptoms of infection.10 As
such, proper contact lens case hygiene can have a significant impact
on the reduction and removal of
biofilm.
Practitioners should also refrain
from recommending that patients
discard used multipurpose solution
from their lens cases, rinse the
wells of the case with hot water or
fresh multipurpose solution and
let the case air dry, as exposure to
water can place both the case and
contact lenses within in contact
with Acanthamoeba and other microbes. Research has indicated the
most effective method for cleaning
Crystal violet staining of lens
storage cases studied at a university
campus showing correlation
between age and staining severity.
Staining was evident as early as
six months. Those older than nine
months showed dramatic increases
in staining intensity.15
Eye.2016;16:30001-7.
5. Dantam J, Zhu H, Stapleton F. Biocidal efficacy
of silver-impregnated contact lens storage cases
in vitro. Invest Ophthalmol Vis Sci.2011;52:51-57.
6. Wu YT, Zhu H, Willcox M, Stapleton F. Impact
of cleaning regimens in silver-impregnated and
hydrogen peroxide cases. Eye Contact Lens.
2011;37:365-369.
7. Tran PL, Huynh E, Pham P, Lacky B, et al. Organoselenium polymer inhibits biofilm formation in
the polypropylene contact lens case material. Eye
Contact Lens.2016;1:1-6.
8. Willcox MDP, Zhu H, Vijay AK. Effect of a warming device on contact lens case contamination.
Eye Contact Lens. 2012;38:394-399.
9. Uno T, Ohashi Y, Imayasu M. Antimicrobial
efficacy tests of multipurpose contact lens case
solutions simulating poor contact lens hygiene
behaviors. Eye Contact Lens. 2012;38:388-393.
10. Vijay AK, Wilcox M, Zhu H, Stapleton F. Contact
lens storage case hygiene practice and storage
case contamination. Eye Contact Lens. 2015;41:91-7.
11. Wu YT, Zhu H, Wilcox M, Stapleton F. Removal
of biofilm from contact lens storage cases. Invest
Ophthalmol Vis Sci. 2010;51:6329-6333.
12. Wu YT, Zhu H, Wilcox M, Stapleton F. Impact
of air-drying lens cases in various locations and
positions. Optom Vis Sci. 2010;87:465-468.
13. Centers for Disease Control and Prevention.
Contact lens case systems and solutions. Available
at www.cdc.gov/contactlenses/care-systems.html.
Accessed April 25, 2016.
14. U.S. Food and Drug Administration. Focusing
on contact lens safety. Available at www.fda.gov/
ForConsumers/ConsumerUpdates/ucm048893.
htm. Accessed April 25, 2016.
15. Burnham GW, Cavanagh HD, Robertson DM.
The impact of cellular debris on Pseudomonas
aeruginosa adherence to silicone hydrogel contact
lenses and contact lens storage cases. Eye Contact Lens 2012;38:7-15.
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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Managing Contact Lens-Related
Bacterial Infections
When a patient at risk presents, how do you keep them free of problems?
By Anar Maurya, OD
O
nset of bacterial
keratitis secondary to
improper contact lens
wear is a serious condition that may lead
to potential blindness, especially in
the absence of adequate patient care
and education.1 Because contact lens
wear alters the state of the ocular
surface, corneal homeostasis is also
disrupted, compromising the natural
defenses that predispose patients to
bacterial infections and sight-threatening complications.2 As such, eye
care practitioners play a vital role
in providing the best treatment
possible to alleviate corneal compromise and ensure successful visual
outcomes.
The release of daily disposable
contact lenses and high-Dk soft
contact lens materials, as well as
more effective antimicrobial medications, has meant that practitioners
as a whole are seeing a decline in
the severity of patients presenting
with contact lens-related bacterial
infections.3 However, though the
level of infection has decreased, the
number of infections has actually
increased, primarily due to poor
patient hygiene and noncompliance with care regimens and the
overnight wear of contact lenses.4
Adopting more proactive measures
may help prevent these potentially
debilitating infections from occurring; thus, the prompt evaluation
of contact lens-related infections is
critical, as is the timely initiation of
patient treatment.
Extended wear lenses manufac-
tured with conventional hydrogel
technology led many patients to develop corneal hypoxia. In response,
silicone hydrogel lenses with highDk materials were created. These
have since become the mainstay for
patients requiring correction with
soft lenses, though they interact no
differently with the corneal epithelium than their predecessors did,
especially in the case of overnight
wear.5,6
Independent of their level of
oxygen transmissibility, however,
contact lenses in general provide a
surface for microbial adhesion while
also disrupting the normal tear
exchange process for removal of
bacteria and debris from the ocular
surface.7,8 Constant mechanical rubbing of the lens and eyelid against
the corneal epithelium further
disrupts the turnover of epithelial
cells, weakening the cornea’s defense
system against bacteria looking for
an opportunity to enter and infect
the cornea.6
WEIGHING IN
Risk factors that predispose patients
to corneal infections secondary to
contact lens use include immunosuppression, smoking, overnight
lens wear, misuse/overwear of lenses, inadequate disinfection practices
and contamination of lens solutions
and/or lens storage cases. Patients
with diabetes and other uncommon
systemic illnesses should limit contact lens wear as certain conditions
experienced by diabetes patients
can delay wound healing, further
exacerbate onset or progression of
an infection and decrease treatment
efficacy (Table 1).9 Patients of a
younger age, male gender and/or
higher socioeconomic status are also
at an increased risk of an infection
related to contact lens wear.10
Obtaining a detailed history is
instrumental in ensuring proper
management of bacterial infections.
Patients should be asked about the
initial onset of symptoms, type of
contact lenses worn, wearing schedule, frequency of overnight wear,
lens solution used and timing of lens
case replacement. The presence of
pain, redness, discharge or blurred
vision can also provide clues as to
the severity of the patient’s infection.
A review of underlying medical
problems, current systemic medications in use and any previous ocular
history (including other infections,
trauma, dry eye or ocular surgery)
is also necessary to determine an
appropriate care regimen.11
To avert a possible infection, practitioners should train patients on
proper techniques for lens insertion,
removal, cleaning, storage and
disinfection. Furthermore, clinicians
should also counsel lens wearers on
effective hygiene practices, including
handwashing, the use of approved
contact lens solutions, frequent
ABOUT THE AUTHOR
Dr. Maurya specializes in fitting
specialty contact lenses,
managing ocular disease
and handling patients postsurgery at Woodhams Eye
Clinic in Atlanta, GA.
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of restoring visual function. Most
patients are looking to alleviate their
symptoms as quickly and effectively
as possible using the most judicious
treatment plans available; as such, it
is the responsibility of the eye care
practitioner to identify the infection’s severity, determine whether it
is sterile or non-sterile, understand
when to obtain a culture and realize
when a prompt referral to a corneal
specialist is necessary.14 Corneal
devastation can take place rapidly if
left unchecked, so prompt recognition and treatment of the problem is
imperative to prevent visual loss.
CULTURE SHOCK
The majority of cases of bacterial
keratitis reflect the normal flora
of the ocular surface and largely
result from gram-positive organisms like coagulase-negative
Staphylococci, Staphylococcus
aureus and Streptococcus, as well
as the gram-negative organisms
Pseudomonas aeruginosa and
Haemophilus influenzae.15 When
contact lenses are introduced to the
ocular surface, changes in the bacterial flora occur and may vary depending on patient age, sex, genetic
Table 1. Systemic Conditions that Contraindictate
Contact Lens Wear
• Diabetes mellitus
• Gonococcal infection with conjunctivitis
• Debilitating illnesses, especially those that cause
malnourishment or require respirator dependence
• Vitamin A deficiency
• Connective tissue diseases
• Acoustic neuroma or a neurological surgery that causes
damage to the 5th or 7th cranial nerves
• Dermatological/mucous membrane disorders (e.g., StevensJohnson syndrome or ocular cicatricial pemphigoid)
• Graft-versus-host disease
• Immunocompromised status
• Diphtheria
• Atopic dermatitis/blepharoconjunctivitis
• Chronic assisted ventilation
Photos: Christine W. Sindt, OD
replacement of contact lens cases
and avoidance of using tap water
or saliva to lubricate their lenses.12
Additionally, instruct them to never
reuse or “top off” the solution in
their contact lens case. Rubbing the
lens during cleaning also constitutes a vital step in the disinfection
process. The FDA has outlined
specific guidelines regarding proper
patient handling and care of contact
lenses.13 These are reproduced in a
special patient education handout
on page 21.
Visual aids and live demonstrations of proper contact lens
handling methods can be effective
as education tools. Counseling the
patient regarding appropriate lens
wear should occur at all follow-up
examinations. Similarly, try to
advise patients to contact a local
eye care professional immediately
should they experience any redness,
pain, sensitivity or blurred vision
associated with their contact lens
wear.13
Practitioner treatment patterns
during an active infection should
focus on minimizing pain, restoring
corneal integrity and minimizing
scarring, with the ultimate goal
Above, a patient presents with an
Acanthamoeba infection. Below, the
same patient seen one month later
following a treatment regimen of
chlorhexidine, voriconazole, PHMB
and brolene QH; Vigamox (Alcon)
and prednisolone QID; 200mg of oral
fluconazole taken by mouth daily;
and atropine applied once a day.
makeup, climate and geographic
location. P. aeruginosa is the most
common pathogen present in contact lens-related infection cases due
to its triggering of biofilm growth
on both lenses and lens cases, and
its ongoing acquired resistance to
certain contact lens solutions and
cleansers.16,17
In any case of a suspected bacterial infection, prompt identification of
the offending organism causing the
issue is an important step towards
selecting the appropriate treatment.
Since the introduction of fluoroquinolones, the need for culturing
to identify the infection has dropped
off significantly, with the majority of cases of contact lens-related
bacterial keratitis managed without smears or cultures; however,
antibiotic resistance is also increasing, with approximately 80% of
current MRSA strains now resistant
to fluoroquinolones.23 As such,
obtaining a culture with appropriate
culture media will help practitioners
both detect resistant strains and also
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MANAGING CONTACT LENS-RELATED BACTERIAL INFECTIONS
identify specific fungal, herpetic and
Acanthamoeba infections.
Culturing is also warranted in cases when the patient’s cornea exhibits
delayed healing, especially when
a large, deep ulcer may be present
within the visual axis. Culturing
may be the best method to determine the most appropriate antibiotic necessary for treatment and also
to help prevent antibiotic resistance.
Other key reasons to perform a
culture include the presence of vegetative material, corneal thinning,
satellite lesions and/or recent care
received in a hospital environment.24
Patients who present to the clinic in
an immunocompromised state also
require prompt culturing; in general,
if a patient does not respond as
expected to initial therapy, a practitioner should proceed with culturing immediately and also consider
contacting an outside specialist.
FIRST RESPONDERS
Regardless of the causative pathogen, first-line treatment for suspected bacterial infections should
include broad-spectrum coverage
against both gram-positive and
gram-negative organisms.
Over the years, the choice of
treatment for bacterial infections
has changed with the introduction
of fourth generation fluoroquinolones; with today’s array of topical
antibiotic options, many practitioners reach for these medications
with good reason. Fluoroquinolones
provide excellent coverage for both
gram-positive and gram-negative
pathogens, and are readily available
at generic prices with good ocular
penetration and less risk of ocular
toxicity.18 The newest fourth-generation fluoroquinolone, Besivance
(besifloxacin ophthalmic suspension
0.6%, Bausch + Lomb), stays at
high concentration in the tear film
for a longer duration once dosed,
and is available in a suspension
To help instill good habits in patients and proper respect for their
role in the success of lens wear, the FDA created the guidelines
on the adjacent page. Please feel free to photocopy this page and
use it as an educational handout with your contact lens patients.
instead of the more typical solution
form.19
In cases in which a patient’s
bacterial infection does not respond
to fluoroquinolones, older antibiotics like bacitracin, tobramycin
or gentamicin can be used instead.
Additionally, consider the use of
compounding fortified vancomycin
or a combination of a fortified aminoglycoside plus fortified cephalosporine in cases in which methicillin-resistant Staphylococcus aureus
(MRSA) is suspected, as fortified
antibiotics offer more complete
coverage of both gram-positive and
gram-negative organisms. These
generally require access to a compounding pharmacy, however.20,21
Corticosteroids, in contrast, are
primarily reserved for treatment of
sterile, noninfectious infiltrates that
present in the peripheral cornea;
indeed, corneal infiltrates that are
the product of an inflammatory response respond well to both topical
steroids and antibiotic combinations.22 These medications work via
the inhibition of the inflammatory
response to reduce corneal scarring
but can also be damaging to the
eye if applied too liberally, and so
should only be used to treat centrally-located corneal infections that
exhibit significant levels of staining.
When the scope of infection is
beyond a certain level of comfort,
the patient should be referred to
a corneal specialist, where they
will likely appreciate the ability to
consult with an outside source who
is well-equipped to both treat and
manage their condition effectively.25
Patients who continue to experience
a reduction in visual acuity at subsequent visits or an increase in pain
and/or nonresolution of any corneal
defects warrant prompt referral as
well.
Annually scheduled eye examinations offer a great encounter in
which to emphasize and review
proper contact lens care and handling methods with patients. During
these visits, practitioners are also
able to monitor the patient’s ocular
health and overall fit of their contact
lenses in order to gauge their infection risk. Annual exams are also an
appropriate time to switch solutions
or upgrade the patient to a contact
lens design and/or wear schedule
that is more suitable for their individual lifestyle, which may increase
compliance. Consider prescribing
daily disposable lenses for young
patients who have active lifestyles or
poor hygiene, for example. Those
patients who are involved in sports
or who travel frequently may also
enjoy the freedom offered by this
modality, as without the need to
worry about lens disinfection and/
or case maintenance, the risk and
severity of microbial keratitis is
reduced.26
However, do not trust that all
patients will dispose of their lenses
following daily disposable wear and
refrain from using their lenses overnight. Urge all patients to maintain
a pair of spectacles in the event that
an infection occurs, and suggest
that lens prescriptions be updated
annually. A fashionable pair is more
likely to be worn in public, where
it will give the patient’s eyes a rest,
so consider investing in certain
appealing designs. Lastly, above all
patients considered unsuitable for
contact lens wear should be advised
against it completely. Practitioners
should feel at liberty to deny contact
lenses in cases where a patient seems
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How to Avoid
Eye Infection or Injury
Contact lens users run the risk of pink eye
(conjunctivitis), corneal abrasions and eye
irritation. A common result of eye infection
is corneal ulcers, which are open sores in
the outer layer of the cornea (the clear part
of the eye over the pupil). Many of these
complications can be avoided through
everyday care of the eye and contact lenses.
To reduce your chances of infection, the
FDA recommends the following practices:
» In general, if you’re using multipurpose contact lens solution, replace your contact lens
storage case at least every three months or as directed by your eye care provider. If you’re
using contact lens solution that contains hydrogen peroxide, always use the new contact lens
case that comes with each box—and follow all directions that are included on or inside the
packaging.
» Clean and disinfect your lenses properly. When using contact lens solution, read and follow
all instructions on the product label to avoid eye injury. This is particularly important if your
eye care professional has recommended a solution with hydrogen peroxide, as these solutions
require special care.
» Always remove contact lenses before swimming.
» Never reuse any lens solution. Always discard all of the used solution after each use, and add
fresh solution to your lens case.
» Do not use any water (which includes distilled water, tap water, and homemade saline solution)
on your lenses because it can be a source of microorganisms that may cause serious eye
infections. (Contact lens solution is sold in “sterile” containers, which means it is free from
living germs or microorganisms.)
» Never put your lenses in your mouth or put saliva on your lenses. Saliva is not sterile.
» Never transfer contact lens solutions into smaller travel size containers. These containers are
not sterile, and unsterile solution can damage your eyes.
» Do not wear contact lenses overnight unless your eye care provider has prescribed them to
be worn that way. Any lenses worn overnight increase your risk of infection. Wearing contact
lenses overnight can stress the cornea by reducing the amount of oxygen to the eye. They can
also cause microscopic damage to the surface of the cornea, making it more susceptible to
infection.
» Never ignore symptoms of eye irritation or infection that may be associated with wearing
contact lenses. These symptoms include discomfort, excess tearing or other discharge, unusual
sensitivity to light, itching, burning, gritty feelings, unusual redness, blurred vision, swelling, or
pain. If you experience any of these symptoms, remove your lenses immediately and keep them
off. Contact your eye care professional immediately. Keep the lenses, because they may help
your eye care professional determine the cause of your symptoms.
Source: US Food and Drug Administration. Contact
Lens Solutions and Products. Available at: www.fda.gov/
ForConsumers/ConsumerUpdates/ucm048893.htm.
018_RCCL0916_ManagingInfections JP.indd 21
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MANAGING CONTACT LENS-RELATED BACTERIAL INFECTIONS
to be unfit—either physically or
psychologically—even at the cost of
losing the patient from the practice’s
population.
W
ith 41 million contact lens
wearers in the United States
today, practitioners need to remain
ahead of possible infections by
keeping patients aware of potential
contact lens-related complications
and continually reiterating best
practices for contact lens wear and
care at each visit.27 Until a lens is
designed that incorporates an optimum balance of surface wettability,
biocompatibility and resistance
to micro-organisms, practitioners
and patients alike must strive to
maintain a proper contact lens wear
regimen.
RCCL
1. Barlett J, Karpecki P, Melton R, Thomas R. New
paradigms in the understanding and management
of keratitis. Review of Optometry. 2011 Nov; 1-16.
2. Fleiszig SM, Glenn A. Fry award lecture 2005.
The pathogenesis of contact lens-related keratitis.
Optom Vis Sci. 2006 Dec; 8:866-873.
3. Cheng K, Leung S, Hoekman H, et al. Incidence of
contact-lens-associated microbial keratitis and its
related morbidity. Lancet, 1999. 354(9174):181-5.
4. Weissman B, Mondino BJ. Why daily wear is still
better than extended wear. Eye Contact Lens. 2003
Jan;29:145-146.
5. Bruce AS, Brennan NA. Corneal pathophysiology
with contact lens wear. Surv Ophthalmol. 1990
July;35(1):25-58.
6. Stapleton F, Stretton S, Papas E, et al. Silicone
hydrogel contact lenses and the ocular surface.
Ocul Surf. 2006 Jan;4(1):24–43.
7. Lavker RM, Sun TT. Epithelial stem cells: the
eye provides a vision. Eye (Lond). 2003 Nov;
17(8):937–942.
8. Paugh J, Stapleton F, Keay L, Ho A. Tear exchange
under hydrogel lenses: methodological considerations. Invest Ophthalmol Vis Sci. 2001 Nov; 42(10):
2813-2820.
9. AAO Cornea/External Disease Panel, Bacterial
Keratitis. Available at www.aao.org/preferred-practice-pattern/bacterial-keratitis-ppp--2013. Accessed
June 20, 2016.
10. Edwards K, Keay L, Naduvilath T, et al. Characteristics of and risk factors for contact lens-related
microbial keratitis in a tertiary referral hospital. Eye.
2007 Aug;23:153-160.
11. Wilhemus KR. Review of clinical experience with
microbial keratitis associated with contact lenses.
CLAO. 1987 July; 13(4):211-214.
12. Centers for Disease Control. Healthy Contact
Lens Wear and Care. Available at www.cdc.gov/
contactlenses. Accessed June 20, 2016.
13. US Food and Drug Administration. Contact Lens
Solutions and Products. Available at www.fda.gov/
ForConsumers/ConsumerUpdates/ucm048893.
htm. Accessed June 20, 2016.
14. Silbert JA. Corneal infiltrative complications
associated with contact lens wear. Rev Optom 2004
Apr;141(4):95-102.
15. Wozniak R, Aquavella J. Considering keratitis:
critical questions in disease management. RCCL.
2015 Oct; 28-31.
16. McLaughlin-Borlace L, Stapleton F, Matheson M,
Dart JKG. Bacterial biofilm on contact lenses and
lens storage cases in wearers with microbial keratitis. J Appl Microbiol. 1998 May;84(5):827–838.
17. Lakkis C, Fleiszig SMJ. Resistance of Pseudomonas aeruginosa isolates to hydrogel contact lens
disinfection correlates with cytotoxic activity. J Clin
Microbiol. 2001 Apr;39:1477–1486.
18. Baum JL. Initial therapy of suspected microbial
corneal ulcers. I. Broad antibiotic therapy based on
prevalence of organisms. Surv Ophthalmol. 1979
Sep-Oct;24(2):97–105.
19. Haas W, Pillar CM, Zurenko GE, et al. Besifloxacin,
a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria.
Antimicrob Agents Chemother. 2009 Aug;53(8):
3552-3560.
20. Lin CP, Boehnke M. Effect of fortified antibiotic
solutions on corneal epithelial wound healing. Cornea 2000 Mar;19(2):204-6.
21. Bowe BE, Snyder JW, Eiferman RA. An in vitro
study of the potency and stability of fortified ophthalmic antibiotic preparations. Am J Ophthalmol.
1991 Jun;111(6):686–689.
22. Srinivasa M, et al. Corticosteroids for bacterial
keratitis: the steroids for corneal ulcers trial (SCUT).
Arch Ophthalmol. 2012 Feb;130(2):143-150.
23. McLeod SD, Kolahdouz-Isfahani A, Rosta-mian
K, et al. The role of smears, cultures, and antibiotic
sensitivity testing in the management of suspected infectious keratitis. Ophthalmology. 1996
Jan;103(1):23-8.
24. Rodman RC, Spisak S, Sugar A, et al. The utility
of culturing corneal ulcers in a tertiary referral
center versus a general ophthalmology clinic. Ophthalmology. 1997 Nov;104: 1897-1901.
25. Kent C. Winning the battle against corneal
ulcers. Rev Ophthalmol. 2013;16(9):20-31.
26. Dumbleton KA, Richter D, Woods CA, et al. A
multi-country assessment of compliance with daily
disposable contact lens wear. Cont Lens Anterior
Eye. 2013 Dec;36:304-312.
27. Nichols J. Annual Contact Lenses Report 2015.
Contact Lens Spectrum. 2016 Jan;31:18-23.
OVERNIGHT SENSATION
A 27-year-old male presented to the clinic with an acute red eye following wear of
his soft contact lenses overnight. His initial
symptoms consisted of a red eye with intense pain, photophobia and blurred vision.
The patient’s visual acuity was reduced five
lines and a slit lamp examination revealed
an excavated corneal defect 2mm in diameter located at six o’clock (see photos at
right) on the right eye. The anterior chamber
presented with trace cells, minimal flare and
no hypopyon. The patient was directed to
begin around-the-clock moxifloxacin, one
drop administered every hour, and was also
advised to discontinue wear of his contact
lenses immediately.
During the next day follow-up, an improvement of two lines in the patient’s visual
acuity was noted, while the patient’s level
of comfort had improved considerably with
a reduction in both pain and photophobia.
Daily follow-up examinations continued to
The patient presented with a 2mm inferior corneal defect.
demonstrate remarkable improvement in
physical signs with a healing corneal defect
and quiet anterior chamber. The antibiotic
was tapered on day three to every other
hour and then to QID by day five.
At the 10-day follow-up appointment, the
patient presented with an intact cornea and
scarring in place of the presumed infectious
ulcer. Visual acuity restored and the patient
resumed contact lens wear in a daily disposable modality, with the recommendation
that he limit lens wear and discontinue overnight wear. Refractive surgery options were
also reviewed.
22 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
018_RCCL0916_ManagingInfections JP.indd 22
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© Bausch & Lomb Incorporated. ®/™ are trademarks of Bausch & Lomb Incorporated or its affiliates. BNL.0028.USA.16
RCCL0916_BL Specialty.indd 1
8/23/16 3:54 PM
1 CE
Credit
(COPE Approval
Pending)
Antibiotics in Practice:
USE, DON’T ABUSE
Resistant bacterial strains challenge eye doctors to be judicious in treatment.
Here are several key trends to heed when setting a regimen.
By Blair Lonsberry, MS, OD, MEd.
T
opical and oral antibiotics are the stock-in-trade
of most health care professionals—workhorse
drugs likely prescribed
every day. For the most part, eye
care practitioners traditionally
prescribe topical forms, though
systemic drugs are increasingly
used in eye care. The release of
new products and the ever-evolving
resistance patterns of the microorganisms responsible for infections
also mean that prescribing habits
continue to change. Pick up any
public health magazine and you’ll
notice that one of the top concerns
is the increase in resistance to our
current armament of antibiotics, as
well as the continuing absence of
new drugs to counter this ever-present threat. These trends compel us
to remain up-to-date on each drug’s
properties, interactions, resistance
patterns and clinical impact.
RESISTANCE AND R&D
The US Centers for Disease Control
and Prevention continues to track
reports of systemic methicillin-resistant Staphylococcus aureus
(MRSA), noting that 72,000
patients in this country required
treatment for a related infection in
2014.1 Most individuals acquired
their condition through the healthcare system, though the number of
cases with community-associated
infections—i.e., those in which the
patient had no inpatient contact
with a medical facility prior to
infection—is also on the rise.1
Data from the recent Antibiotic
Resistance Monitoring in Ocular
Microorganisms (ARMOR) study
reveals that methicillin-resistant
organisms continue to remain common in ocular isolates and, when
resistance is found, most organisms
are discovered to be multidrug-resistant.2 Interestingly, however,
nationwide antibiotic resistance
rates have not increased in the last
five years and have in fact decreased
in the case of some combinations of
antibiotics and pathogens. The first
case of a patient with a strain of E.
coli resistant to the powerful antibiotics administered in the United
States was reported in May 2016.3
Antibiotic resistance is a big
concern, particularly in light of the
relatively few new drugs released in
recent years.
Microorganisms have several
ways to develop resistance to a
drug, including the production of
enzymes that render the antibiotic
ineffective and the alteration or
elimination of the antibiotic target
site so that there is less affinity. The
presence of microorganisms can
also decrease antibiotic uptake and/
or increase efflux of the drug, and
lead to the development of bypass
pathways around target sites,
further rendering the administered
drug ineffective. Furthermore,
during the development of the
bacteria’s resistance characteristics,
the inappropriate use of antibiotics
(e.g., if they are prescribed for viral
infections, or if the wrong one is
given in a case of misdiagnosis) in
both human and veterinary medicine can have a negative effect, as
does the widespread use of these
drugs in the agricultural industry.4
As of May 2016, there were 33
antibiotics in clinical trials being
studied.5 The majority seem to be
variations of existing meds or additional members of already-existing
group of drugs with few, if any,
recently added classes of antibiotics.
Overall, the success rate for
clinical drug development is low,
with many failing stringent clinical
trials. With the expected return for
a company to cover the post-trial
development and market launch of
a new antibiotic unlikely to exceed
initial development costs, many
companies have shut down their
antibiotic research efforts entirely.5
KICKING KERATITIS
Considered an ocular emergency,
microbial keratitis is of particular
concern in contact lens wearers.
Staph. aureus is a leading cause of
keratitis worldwide, possessing a
multitude of characteristics that
enhance its adhesion to host tissues,
evasion of the human immune system and destruction of host cells.6
ABOUT THE AUTHOR
Dr. Lonsberry is a professor at
Pacific University College of
Optometry in Oregon and a
diplomate of the American
Board of Optometry. He is
also a fellow of the American
Academy of Optometry, the
Optometric Retinal Society, the
Optometric Glaucoma Society and
the Ocular Surface Society of Optometry.
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Patients who wear contact lenses
and those who have suffered ocular
trauma with damage to the corneal epithelium have an increased
chance of developing ulceration as a
result of infection by this organism,
necessitating antibiotic therapy for
adequate resolution.7
One study, in which isolates
were found to be susceptible to
vancomycin and polytrim, but also
resistant to the second-generation
fluoroquinolones ciprofloxacin and
ofloxacin, identified approximately
31% of isolates taken from keratitis
patients as MRSA.8 There was also
an increase in the resistance of both
MRSA and methicillin-susceptible
Staphylococcus aureus (MSSA) to
fourth-generation fluoroquinolones
detected during the study period
from 1993 to 2012.8
The latest ARMOR report noted
the global prevalence of MRSA at
42% from Staphylococcus isolates,
with the most effective treatment
option being vancomycin.2 With
respect to minimum inhibitory concentrations (MICs), large
differences were still identified
among the fluoroquinolone class
of antibiotics—namely, the newer
fluoroquinolones in the group had
a lower MIC compared with the
older ones.2 Additionally, the chlorofluoroquinolone Besivance (besifloxacin, Bausch + Lomb) exhibited
the lowest MIC for gram-positive
isolates and was as effective as
moxifloxacin in treating bacterial
conjunctivitis; it was also more
effective than the same at eliminating bacteria from the ocular surface
prior to cataract surgery.2,9
Besivance contains besifloxacin
and the delivery vehicle DuraSite
(Insite Vision), a mucoadhesive
polymer designed to increase drug
retention time on the ocular surface
to 4.7 hours.9 This agent’s extended
retention time and high concentration on the ocular surface, com-
Current antibiotics may not be enough to treat corneal infections such as this
alpha-hemolytic Streptococcus presentation.
bined with the low associated MIC
values for MRSA, may mark it as a
possible first-line choice for patients
suspected of having MRSA-related
conjunctivitis or keratitis.
The ARMOR report also
mentioned other commonly seen
infectious isolates: Pseudomonas
aeruginosa, Streptococcus pneumoniae and Haemophilus influenzae.2
Almost all S. pneumoniae isolates
were susceptible to both chloramphenicol and the fluoroquinolones
tested, with Besivance having the
lowest MIC among all of latter
considered.2 With respect to the P.
aeruginosa isolates, their rates of
resistance remained rather low in
the face of the antibiotics tested,
with good susceptibility to both
fluoroquinolones and tobramycin.
Additionally, the H. influenzae
isolates proved susceptible to all anRelease Date: September 2016
Expiration Date: September 1, 2019
Goal Statement: This course examines the
use of current and emerging antibiotics in
the treatment and management of ocular
related infections.
tibiotics administered, while azithromycin showed the most resistance
against it, with 42% of MSSA and
93% of MRSA isolates remaining
unaffected.2 The ARMOR report
noted that if an isolate was identified as MRSA, there was also a
strong likelihood that it exhibited
multidrug resistance.
Interestingly, the isolates in the
study, regardless of origin, exhibited susceptibility to vancomycin. In
this respect, if a clinician is treating
a suspected MRSA-related infection—either the patient with the
infection is in a hospital or personal
care home, or the infection itself is
not responding to initial antibiotic
therapy—25mg/ml to 50mg/ml of
topical fortified vancomycin is the
recommended treatment to ensure
appropriate coverage.2 This medication would have to be obtained
this course. Check with your state
licensing board to see if this counts toward
your CE requirements for relicensure.
Joint-Sponsorship Statement: This
continuing education course is joint-sponsored by the Pennsylvania College of
Optometry.
Faculty/Editorial Board:
Blair Lonsberry, MS, OD, MEd.
Disclosure Statement: Dr. Lonsberry
has received honoraria from Alcon
Credit Statement: COPE approval for 1 hour and is a consultant to Optovue, Shire
of continuing education credit is pending for Pharmaceuticals and Bausch + Lomb
REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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ANTIBIOTICS IN PRACTICE: USE, DON’T ABUSE
from a compounding pharmacy, where the pharmacist would
reconstitute 500mg of vancomycin
powder with 10ml sterile water
sans-preservative. Alternatively,
they can also use 10ml of artificial
tears as a compounding ingredient,
which would yield a concentration of 50mg/ml. This formulation
should be dosed every hour for the
first 24 hours with a re-evaluation
and a decrease in dosage frequency if improvement is noted. The
compounded vancomycin should
be stored in the refrigerator for
an additional four days before
expiration.10
MRSA infections are of particu-
lar concern when considering their
relation to the periorbital tissues
and adnexa. With Staphylococcus
sp. being the most prevalent
bacteria on the skin, there is also
a higher risk of developing an
external MRSA-related infection.
A study reviewing the records of
patients diagnosed with an ocu-
MRSA Makes Its Mark
A 50-year-old white male presented complaining of
near vision issues. His medical history was unremarkable except for a possible mosquito or spider bite on
the back of his neck. He reported going for a hike the
day before and noticing a bump that had begun to
form later that evening (Figure 1). He admitted taking two of three pills of oral ciprofloxacin “left over”
from a previous Rx and the remaining pill the morning of the current exam. The patient reported no other serious skin conditions or infections, except that
three years prior, he had been visiting a friend in the
hospital and later developed an infection on his arm.
Testing revealed it was MRSA, and the lesion was surgically drained and treated.
At the present exam, he reported some minor discomfort with the lesion and noted that it had a solid
feel to it, much like a knot. It was recommended that
he contact his primary care physician to have the lesion assessed, especially since he had had a previous
MRSA infection.
Two weeks later, the patient returned to the clinic
with an update: he had contacted his PCP and scheduled an appointment for the day after the exam;
however, as the day proceeded, he had noticed an
increase in pain and discomfort and decided to visit an urgent care clinic, where he was given Bactrim
(trimethoprim-sulfamethoxazole, AR Scientific) to be
taken as a single double-strength pill every 12 hours
and also Vicodin (acetaminophen and hydrocodone,
Abbott) for the pain. The patient was informed that
what he initially believed to be a bite instead now appeared to be several pimples “combined” to form a
super pimple.
The day after the urgent care consultation, the patient noted that the lesion in question was becoming
increasingly larger and the level of pain was still rising despite his taking the medication as prescribed.
Unable to wait for his scheduled PCP appointment,
the patient instead went to the emergency room,
where a physician attempted to drain the lesion. A
Fig. 1. The patient reported noticing the appearance of a
bite or wound following a hiking trip.
Fig. 3. The infection was determined to be secondary
to MRSA.
Fig. 2. The surgeon placed gauze into the wound in
order to help it drain.
Fig. 4. The site of the lesion following healing of
the wound.
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lar-centric MRSA infection over a
four-year period at a busy hospital practice found that preseptal
cellulitis was the most prevalent.11
Additional conditions that should
also be looked for, however, included dacrocystitis, canaliculitis
and other periobital lesions and/or
abscesses.11
cotton wedge was ultimately
left in the wound in an attempt
to help it drain further, and the
patient was directed to continue
taking the Bactrim and Vicodin
(Figure 2).
The following day, however, the
patient indicated that the pain
had increased to a point where
it was affecting his sleep, and so
he elected to return to the urgent
care clinic and then ultimately
the ER, where his lesion was debrided and he was given Ancef
(cefazolin, GlaxoSmithKline), a
cephalosporin antibiotic given
intravenously to treat severe
soft tissue and skin infections
secondary to MSSA. He was told
to continue taking the Bactrim,
was given oxycodone and told
to return the next day for a follow-up appointment.
At this visit, it was found that
his infection was secondary
to MRSA, so he was switched
from the Bactrim to doxycycline 100mg BID (Figure 3), a
course of action confirmed as
valid by susceptibility testing on
the MRSA isolate. The patient
continued to self-administer the
doxycycline for 10 days, at which
point the lesion finally healed
(Figure 4).
Though this case doesn’t discuss an ocular infection, it highlights the importance of keeping
MRSA as a differential when assessing a possible skin issue.
SKIN AND SOFT
TISSUE INFECTIONS
High antibiotic tissue concentrations are achieved via frequent dosing and direct access to the affected
tissue when treating ocular surface
infections. However, when treating
skin infections like preseptal cellulitis, systemic antibiotics must travel
through the circulatory system to
enter into the tissue, reducing their
local concentration.6 As such, the
use of topical antibiotics is unlikely
to cause systemic antibiotic resistance, though the overuse of systemic antibiotics has contributed to
systemic and also possibly topical
antibiotic resistance.6
Healthcare-associated methicillin-resistant Staphylococcus aureus
(HA-MRSA) is especially correlated with severe, invasive disease in
hospitalized patients, while community-associated methicillin-resistant
S. aureus (CA-MRSA) is more often
linked to young, healthy individuals exhibiting a skin or soft tissue
infection with no recent exposure
to the healthcare system.1 Athletes,
daycare and school students, military personnel living in barracks
and those who recently received inpatient medical care are at a higher
chance for developing this condition; Additional risk factors for
CA-MRSA infection include skin
trauma (i.e., lacerations, abrasions,
tattoos and injection drug use),
cosmetic body shaving, incarceration, HIV infection and sharing
of uncleaned equipment between
multiple users.1
Two of the newest antibiotics
for acute bacterial skin and skin
structure infections (ABSSSI), a
category that includes MRSA, are
Dalvance (dalbavancin, Allergan)
and Sivextro (tedizolid, Merck).
The former inhibits cell wall synthesis and is delivered to the patient via
intravenous infusion, typically as a
single dose of 1500mg or a two-
dose regimen of 1000mg initially
followed by a 500mg dose one
week later. Dalvance is supplied in
500mg vials at an approximate cost
of $1,788 per vial.12 Sivextro, in
contrast, inhibits protein synthesis,
with its use as treatment for ABSSSI
conditions being 200mg daily for
six days administered either orally
(priced at $2,230) or intravenously
($2,961).13
Preseptal cellulitis is the most
likely periorbital infection an
optometrist would treat. This
infection involves the eyelid and/or
surrounding tissue anterior to the
orbital septum. Signs and symptoms include tenderness, swelling,
unusual warmth, redness and/or
discoloration of the eyelid and fever,
in some cases.14 Common causes of
preseptal cellulitis include hordeolum/chalazion, sinusitis, upper
respiratory infection and trauma.
The most likely causative agent is
S. aureus, with a recommended
treatment of an oral antibiotic that
covers the most common pathogens
the cause sinusitis.14
More specifically, the Infectious
Disease Society of America (IDSA)
advocates the use of amoxicillin-clavulante 500mg every eight
hours (or 875mg every 12 hours)
in the treatment of uncomplicated
sinusitis, but not the use of amoxicillin alone secondary to increased
resistance.4,14 An alternative treatment is cephalexin 500mg every
six hours; cephalosporin antibiotics
have excellent soft tissue penetration and should be considered as
first-line treatments for periorbital
infections.14 The IDSA also recommends that treatment for uncomplicated infections in adults be administered for a period no longer than
seven days, while in children it can
be extended from 12 to 14 days.4 In
unresponsive cases, MRSA should
be considered and an antibiotic that
has coverage for MRSA should be
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ANTIBIOTICS IN PRACTICE: USE, DON’T ABUSE
initiated for a seven- to 14-day
period.4
Bactrim/Septra is a combination
of sulfamethoxazole and trimethoprim available in two concentrations: either sulfamethoxazole
400mg and trimethoprim 80mg or
a “double strength” (DS) dose of
sulfamethoxazole 800mg and trimethoprim 160mg. One DS tablet
taken twice daily for seven to 14
days is recommended for the treatment of skin and soft tissue infections due to MRSA. Monotherapy
with DS trimethoprim-sulfamethoxazole for the treatment of an
uncomplicated skin infection may
be reasonable in relatively young
patients in the absence of systemic
manifestations or comorbid conditions. As this medication contains
sulfamethoxazole, it is contraindicated for patients with a known
allergy to sulfonamide.15
Another medication option, clindamycin, is a protein synthesis inhibitor that has been demonstrated to have good activity against
MRSA that can be administered at
dosages of 300mg to 450mg every
six to eight hours for seven to 14
days. Clindamycin exhibits excellent tissue penetration, particularly
with respect to entering bone and
abscesses; however, the drug also
has an FDA black box warning,
as it has been linked to onset of
severe colitis, which may be fatal.
Thus, it is reserved for serious
infections for which less toxic
antimicrobial agents are inappropriate. Furthermore, clindamycin
is also not suitable for use in patients with nonbacterial infections,
including most upper respiratory
tract conditions.16
Doxycycline is another protein
synthesis inhibitor option that
binds to a different ribosomal
subunit than clindamycin. Its
recommended dose of 100mg
twice daily for seven to 14 days is
a treatment option for
MRSA, but only following performance of
susceptibility testing. It
should not be started
empirically in suspected MRSA infections.17
Additionally, doxycycline is a pregnancy
category D medication
and is not suitable
At-risk patients may also include those with
for use in pregnant or Pseudomonas infections.
nursing women, or in
the lack of effectiveness of topical
children under the age of eight.
aminoglycosides as prophylactic
Advise patients who are using this
agents.20 In addition to the pomedication to take it more than
two hours before going to bed,
tential reduction in endophthalwith food but without calcium,
mitis, the use of dropless cataract
antacids or dairy products.
surgery may have the potential
to increase patient compliance of
POST-SURGICAL
medication use post-surgery and
PROPHYLAXIS
also lead to cost savings.21
Topical antibiotics are routinely
The use of intravitreal injecused following cataract surgery
tions has increased dramatically
and/or intravitreal injections as
secondary to the beneficial effects
a means to prevent endophthalof steroids and anti-VEGF medimitis.18,19 The latest significant
cations in patients with conditions
development to date is so-called
such as exudative macular degendropless cataract surgery, which
eration and diabetic retinopathy.
incorporates an intracameral or
Traditionally, a topical antibiotic
transzonular intravitreal injection
is used after (and sometimes prior
at the time of the procedure to
to) the injection itself to prevent
administer the antibiotic drug. The the development of endophthalmiintravitreal transzonular procedure tis, as previously mentioned. One
involves the delivery of TriMoxi
study that compared a 28-month
(Imprimis Pharmaceuticals), a
period in which topical antibiotics
combination of triamcinolone
were prescribed following in3mg and moxifloxacin 0.2mg,
travitreal injections with a nineor TriMoxiVanc, which includes
month period in which they were
the aforementioned agents plus
not found that the incidence of
vancomycin.
endophthalmitis after intravitreal
A retrospective chart review
injection was low and that the use
of endophthalmitis development
of postinjection topical antibiotic
drops did not reduce the risk; in
post-cataract surgery comparing
fact, it was associated with a trend
administration of antibiotics intowards higher incidence of the
tracamerally with topically found
condition.19
there was a 42% reduction in
risk associated with intracameral
use; additionally, an approximate
ORAL ANTIBIOTICS
doubling of risk in the 4.5% of
FOR OSD/MGD
eyes with no evidence of antibiotic Ocular surface disease (OSD) is
prophylaxis was noted, as was
one of the most common reasons
28 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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why patients seek care from an eye
care professional, resulting from
an unstable or insufficient tear film
layer and often leading to ocular
irritation, discomfort and visual
disturbances.21 Meibomian gland
dysfunction (MGD) is an often-underlying cause for the disruption
to the tear film, with multiple
therapies available including warm
compresses, topical lubrication
and immunomodulation, omega-3
supplementation, oral antibiotics,
laser- and light-based therapies
and surgical interventions.21
Oral antibiotic use has also become a mainstay therapy for many
patients suffering from MGD:
oral doxycycline and azithromycin have both been used as part
of treatment for MGD, as the
condition is thought to occur in
part due to increased production
of inflammatory mediators such
as matrix metalloproteinases and
activated B-cells.22 The use of doxycycline and azithromycin is believed to act as anti-inflammatory
medications, reducing the production of these inflammatory mediators to soothe the ocular surface.
Recommended doxycycline dosages for MGD vary in the literature
from 20mg to 100mg QD to BID,
and for varying lengths of time
with results including improved
patient comfort, tear film breakup time, inflammatory signs and
staining scores.22 Azithromycin,
in contrast, is typically prescribed
at 500mg/day for three days per
week for three to four weeks, with
expected improvements in tear
film break-up time, patient comfort and staining scores.22
Interestingly, a recent publication from the American Academy
of Ophthalmology on the use of
oral antibiotics for the treatment
of MGD-related OSD indicated
that although oral antibiotics are
commonly used in the manage-
ment of OSD, there is no Level I
evidence (defined as three or more
randomized clinical trials demonstrating similar results) to support
their use in this fashion.22 As such,
in reviewing the literature, the
report further noted that there are
few clinically meaningful studies
that demonstrate the benefits of
oral antibiotics in the treatment
of MGD-associated ocular surface
disease; however, the studies that
do exist indicate their use may
be effective. More randomized
controlled trials are required in
this area to further confirm this
hypothesis, however.22
A
n increase in therapeutic
privileges for optometrists
necessitates that they continue to
educate themselves regarding the
latest topical and oral treatments
available for their patients. In particular, the increased presence of
MRSA-related infections requires
heightened vigilance in keeping
track of the signs and symptoms
of possible cases, as well as what
options are available for resolution.
RCCL
1. CDC. Active Bacterial Core Surveillance
(ABCs) Report Emerging Infections Program
Network Methicillin-Resistant Staphylococcus
aureus, 2014. Available at: www.cdc.gov/abcs/reports-findings/survreports/mrsa14.pdf. Accessed
June 21, 2016.
2. Ophthalmology Times. Antibiotic resistance levels shift among ocular pathogens
in 2014 ARMOR data. Available at: www.
ophthalmologytimes.modernmedicine.com/
ophthalmologytimes/news/antibiotic-resistance-levels-shift-among-ocular-pathogens-2014-armor-data?page=0,0. Accessed June
21, 2016.
3. Pittsburgh Post-Gazette. Wolf confirms
antibiotic-resistant E. coli strain found in Pa.
woman. Available at: www.post-gazette.com/
news/state/2016/05/26/Gov-Wolf-administration-confirms-antibiotic-resistant-E-coli-strain-found-in-Pennsylvania-woman/stories/201605260206. Accessed June 21, 2016.
4. Barlam TF, Cosgrove SE, Abbo LM, et al.
Executive Summary: Implementing an Antibiotic Stewardship Program: Guidelines by the
Infectious Diseases Society of America and the
Society for Healthcare Epidemiology of America.
Clin Infect Dis. 2016 May;62(10):1197-202.
5. PEW Charitable Trusts. Antibiotics Currently
in Clinical Development. Available at: www.
pewtrusts.org/~/media/assets/2016/05/antibiotics-currently-in-clinical-development.pdf?la=en.
Accessed June 21, 2016.
6. Mangan RB. Incidence of MRSA infections of the eye, adnexa increases. Available at: www.healio.com/optometry/
cornea-external-disease/news/print/primary-care-optometry-news/%7B0b922672b9f3-436e-a09d-0663410e2ce0%7D/
incidence-of-mrsa-infections-of-the-eye-adnexa-increases. Accessed July 1, 2016.
7. Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA.
2013 Oct;310(16):1721-9.
8. Chang VS, Dhaliwal DK, Raju L, Kowalski RP.
Antibiotic resistance in the treatment of staphylococcus aureus keratitis: a 20-year review. Cornea.
2015 Jun;34(6):698-703.
9. Deschenes J, Blondeau J. Besifloxacin in the
management of bacterial infections of the ocular
surface. Can J Ophthalmol. 2015 Jun;50(3):184-91.
10. Duane TD, Tasman W, Jaeger EA. Chapter 26:
Antibiotic Use in Ophthalmology. Ed. Baum, JL.
Duane’s Ophthalmology. Philadelphia: Lippincott
Williams & Wilkins; 2006.
11. Blomquist PH. Methicillin-resistant staphylococcus aureus infections of the eye and orbid (an
American Ophthalmological Society thesis). Trans
Am Ophthalmol Soc. 2006 Dec;104:322-45.
12. UptoDate. Dalbavancin: Drug information.
Available at: www.uptodate.com/contents/dalbavancin-drug-information. Accessed July 2, 2016.
13. UpToDate. Tedizolid: Drug information. Available at: www.uptodate.com/contents/tedizolid-drug-information. Accessed July 2, 2016.
14. Gappy C, Archer S, Barza M. Preseptal cellulitis. Available at: www.uptodate.com/contents/
preseptal-cellulitis. Accessed July 2, 2016.
15. UpToDate. Trimethoprim-sulfamethoxazole
(co-trimoxazole): Drug information. Available at:
www.uptodate.com/contents/trimethoprim-sulfamethoxazole-co-trimoxazole-drug-information.
Accessed July 2, 2016.
16. UpToDate. Clindamycin (systemic): Drug
information. Available at: www.uptodate.com/
contents/clindamycin-systemic-drug-information.
Accessed July 2, 2016.
17. UpToDate. Doxycycline: Drug information.
Available at: www.uptodate.com/contents/doxycycline-drug-information. Accessed July 2, 2016.
18. Herrinton LJ, Shorstein NH, Paschal JF, et al.
Comparative effectiveness of antibiotic prophylaxis in cataract surgery. Ophthalmology. 2016
Feb;123(2):287-94.
19. Storey P, Dollin M, Pitcher J, et al. The role of
topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection. Ophthalmology. 2014 Jan;121(1):283-9.
20. Qiao J, Yan X. Emerging treatment options for
meibomian gland dysfunction. Clin Ophthalmol.
2013;7:1797-803.
21. Liegner J. A case for dropless cataract surgery: A single prophylactic injection is gaining
growing support. Ophthalmology Management.
Available at: www.ophthalmologymanagement.
com/articleviewer.aspx?articleID=111160. Accessed
July 2, 2016.
22. Wladis EJ, Bradley EA, Bilyk JR, et al. Oral
antibiotics for meibomian gland-related ocular
surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2016
Mar;123(3):492-6.
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ANTIBIOTICS IN PRACTICE: USE, DON’T ABUSE
CE TEST ~ SEPTEMBER 2016
1. In May 2016, the first case of a patient with a strain of which organism
resistant to powerful antibiotics administered was reported?
a. Escherichia coli.
b. Mycobacterium tuberculosis.
c. Norovirus.
d. Morganella morganii.
2. Which of the following is not an effect of the presence of antibioticresistant microorganisms?
a. Decreased antibiotic uptake.
b. Production of enzymes that increase the antibiotic’s effectiveness.
c. Increased efflux of the antibiotic drug.
d. Development of bypass pathways around target sites.
3. The latest ARMOR report noted the global prevalence of methicillinsusceptible Staphylococcus aureus at what percentage?
a. 35%.
b. 80%.
c. 27%.
d. 42%.
4. Which organism is most often linked to young, healthy individuals
exhibiting a skin or soft tissue infection that is not responding to initial
treatment with no recent exposure to the healthcare system?
a. CA-MRSA.
b. CA-MSSA.
c. HA-MRSA.
d. HA-MSSA.
5. Which of the following is a new antibiotic for treatment of acute bacterial
skin and skin structure infections?
a. Voriconazole.
b. Doxycycline.
c. Dalbavancin.
d. Gentamicin.
EXAMINATION ANSWER SHEET
Antibiotics in Practice: Use, Don’t Abuse
Valid for credit through September 1, 2019
Online: This exam can also be taken online at www.reviewofcontactlenses.com.
Upon passing the exam, you can view your results immediately. You can also
view your test history at any time from the website.
Directions: Select one answer for each question in the exam and completely
darken the appropriate circle. A minimum score of 70% is required to earn credit.
Mail to: Jobson Optometric CE, Canal Street Station, PO Box 488 New York, NY 10013
Payment: Remit $20 with this exam. Make check payable to Jobson Medical
Information LLC.
Credit: COPE approval for 1 hour of CE credit is pending for this course.
Sponsorship: Joint-sponsored by the Pennsylvania College of Optometry
Processing: There is an eight-to-10 week processing time for this exam.
Answers to CE exam:
A
B
C
1.
A
B
C
2.
A
B
C
3.
A
B
C
4.
A
B
C
5.
6.
7.
8.
9.
10.
D
D
D
D
D
A
B
C
D
A
B
C
D
A
B
C
D
A
B
C
D
A
B
C
D
Evaluation questions (1 = Excellent, 2 = Very Good, 3 = Good, 4 = Fair, 5 = Poor)
Rate the effectiveness of how well the activity:
1
2
3
4
5
11. Met the goal statement:
12. Related to your practice needs:
1
2
3
4
5
13. Will help improve patient care:
1
2
3
4
5
1
2
3
4
5
14. Avoided commercial bias/influence:
15. How do you rate the overall quality of the material? 1
2
3
4
5
16. Your knowledge of the subject increased: Greatly
Somewhat
Little
17. The difficulty of the course was:
Complex
Appropriate Basic
18. How long did it take to complete this course? _________________________
19. Comments on this course: _________________________________________
6. Hordeolumn/chalazion, sinusitis, upper respiratory infection and trauma
are all common causes of which condition?
a. Blepharitis.
b. Preseptal cellulitis.
c. Dacryocystitis.
d. Canaliculitis.
___________________________________________________________________
20. Suggested topics for future CE articles: ______________________________
___________________________________________________________________
Identifying information (please print clearly):
7. Which of the following is not recommended as a treatment for skin and soft
tissue infections attributed to MRSA?
a. Augmentin.
b. Clindamycin.
c. Doxycycline.
d. Sulfamethoxazole and trimethoprim.
8. Which of the following is the most prevalent organism on the skin?
a. Pseudomonas aeruginosa.
b. Streptococcus pneumonia.
c. Staphylococcus sp.
d. Fusarium.
9. Which of the following oral antibiotics are most commonly used to treat
MGD?
a. Tobramycin and ofloxacin.
b. Ciprofloxacin and vancomycin.
c. Besifloxacin and gatifloxacin.
d. Doxycycline and azithromycin.
10. Topical antibiotics are prescribed following cataract surgery and/or
intravitreal injections as a means to prevent which of the following?
a. Corneal edema.
b. Endophthalmitis.
c. Vitreous hemorrhage.
d. Retinal detachment.
First Name
Last Name
Email
The following is your:
Home Address
Business Address
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Address
City
State
ZIP
Telephone #
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Fax #
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By submitting this answer sheet, I certify that I have read the lesson in its entirety
and completed the self-assessment exam personally based on the material presented. I have not obtained the answers to this exam by fraudulent or improper means.
Signature: ________________________________________ Date: _____________
Please retain a copy for your records.
LESSON 113383, RO-RCCL-0916
30 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
024_RCCL0916_AntibioticTrendsCE.indd 30
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Up to
19 CE*
Credits
w Tech
Ne
n
REVIEW OF OPTOMETRY®
s
ogie and
ol
N T
& T
ments
eat
Tr
Philadelphia
EDUCATIONAL MEETINGS OF CLINICAL EXCELLENCE
IN VISION CARE
OCTOBER 7-9, 2016
2016
Superior Education with 4 Interactive Workshops
Philadelphia Marriott Downtown
1201 Market Street
|
Philadelphia, PA
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(215) 625-2900
Discounted room rate: $169/Standard Room
Program Chair: Paul Karpecki, OD
FACULTY
Douglas Devries, OD
Kelly Malloy, OD
Robert Wooldridge, OD
REGISTER NOW!
REGISTRATION COST: $495 • THREE WAYS TO REGISTER
www.ReviewofOptometry.com/PhiladelphiaNTT2016
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Alcon
8/24/16 10:24 AM
Targeted and Timely:
The New Model of Dry Eye Care
By Richard B. Mangan, OD
Point-of-care tests and advanced diagnostic imaging are helping
doctors tackle it faster and more precisely than ever before.
A
s the emphasis in
healthcare continues
to shift toward prevention and early detection of disease, eye
care practitioners have seen technological innovations emerge that
are designed to streamline diagnosis
and patient management. Real-time
data collection during the patient
encounter, called point-of-care testing (POCT), is performed near or at
the site of a patient visit, with results
available quickly enough to influence the course of care right at the
outset, allowing for faster clinical
decision-making. Empowering providers to make decisions chairside
may have a huge impact in quality
of care while also reducing costs to
patients and payers.
Ocular surface disease (OSD) is
one area of eye care that has recently seen a boom in point-of-care
diagnostics. Noting the comorbidity
associated with OSD, the prevalence data is extremely telling: an
estimated 20.7 million Americans
exhibit clinically significant signs
or symptoms of dry eye, with more
recent studies on the prevalence
of meibomian gland dysfunction
(MGD) suggesting this number may
in fact be significantly higher.1
When one accounts for patients
with other forms of ocular surface
compromise, the need for greater vigilance for OSD grows even
more. Fifty million Americans have
allergies, with three million of those
individuals suffering from seasonal forms.2 An estimated 38 to 40
million contact lens wearers exist
in the United States, while 700,000
individuals undergo LASIK annually
across the country.
Data from a 2015 report notes
that 68% of US adults own a smartphone and 45% also own a tablet
computer; both of these devices
have been shown to decrease blink
rate and increase the risk of MGD
and evaporative dry eye. Symptoms
consistent with dry eye are increasing among individuals under the
age of 40, who spend on average
about two hours per day more
on their digital devices than their
over-40 counterparts.3 Additionally,
Sjögren’s syndrome, a systemic autoimmune disease in which immune
cells attach and destroy host exocrine glands that produce tears and
saliva, affects about four million
people in the United States.
Given this huge potential population base, it can be said that the eye
care profession has seen remarkable
advancements in POCT over the last
decade that have given practitioners
the ability to better differentially diagnose underlying causes of ocular
surface disease, and therefore make
treatments more targeted, timely
and cost effective. In this article, several experts on dry eye and ocular
surface disease will discuss point-ofcare testing and its impact on their
dry eye practices.
MY FAVORITE THINGS
Our panelists begin by sharing their
impressions of the POC tests for dry
eye they find most essential.
Richard Mangan, OD,
Moderator. We have come a long
way in recent years in our understanding of the underlying cause of
both aqueous-deficient and evaporative dry eye, as well as the allergic,
infectious and environmental factors
that can influence the ocular surface
in other ways. The addition of certain point-of-care tests to the subspecialty of ocular surface disease
has only broadened our understanding of this multifactorial disease;
however, before we get into how
POCT has personally impacted your
practice, I would like to ask each of
ABOUT THE AUTHORS
Dr. Mangan is a consultative
optometrist at Bennett
& Bloom Eye Centers in
Louisville, KY.
Dr. Schachter works in a private
practice, with an emphasis
in ocular surface disease,
in Pismo Beach, CA. He
consults for Allergan,
Biotissue, Blephex,
ScienceBased Health and
TearScience.
Dr. Hauswirth is part of the
full-time staff at Minnesota
Eye Consultants, where he
specializes in patients with
advanced ocular surface
disease and corneal issues.
In addition to clinical
practice, he is an active
participant in ophthalmic
research.
Dr. Hauser is an assistant
professor at Southern College
of Optometry, a clinical
development consultant at
TearWell and also serves
on the boards of TearLab,
RySurg, Paragon BioTeck,
Science Based Health and
1800DOCTORS.
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you the following question: of the
available point-of-care diagnostic
tests used in ocular surface disease,
if you could only pick one to use
in your clinical practice, which one
would it be and why?
Scott Schachter, OD. InflammaDry
(Rapid Pathogen Screening) is the
POC test I rely on and use the most,
for several reasons. It measures matrix metalloproteinase 9, or MMP9, a nonspecific biomarker for
inflammation. Studies have shown
that desiccating stress, which most
all of our patients are exposed to
through device use, causes corneal
epithelial cells to produce MMP-9.4
Other studies demonstrate a strong
correlation between certain levels
of MMP-9 and dry eye symptoms,
low contrast visual acuity and tear
film break-up time.5 MMP-9 is a
gelatinase, which weakens epithelial
barrier function. If it is present in
large enough quantities, the patient
essentially has a toxic tear film.
We screen all our patients using
the SPEED questionnaire (Standard
Patient Evaluation of Eye Dryness),
and if they score seven or higher,
the staff at the clinic automatically
knows to perform this test during
pretesting. They write the patient’s
initials on the test, and the time that
the sample was taken. The test is
quick and easy to administer, is reimbursed by most insurers and has
results ready in 10 minutes. If positive, I know to start anti-inflammatory therapy; however, if negative,
inflammation related to elevated
MMP-9 cannot necessarily be ruled
out, as false negatives can still occur
with this test. If the clinical signs
and symptoms suggest a high probability for inflammation, having the
patient back another day to repeat
the test may be a good idea.
Regarding the test itself, sensitivity is estimated at 81% to 85%
and specificity is 94% to 98%.13
According to another study, other
common tests exhibited either poorer sensitivity (i.e., corneal staining at
54%, conjunctival staining at 60%
and meibomian gland grading at
61%) or poorer specificity (tear film
break-up time at 45% and Schirmer
test at 51%) in contrast to this test.6
It’s a single-use test that requires no
capital outlay and no volume-based
contract, and requires that the
tear sample be absorbed from the
palpebral conjunctiva, rather than
scraped, which can cause additional inflammation or irritation.
Practitioners should also keep in
mind that test results can take
Moderate to strong positive MMP9 results on a patient with dry eye
disease and conjunctivochalasis.
longer than 10 minutes to achieve.
Typically, a negative test should
be checked again right before the
patient leaves the office, just in case
it simply has not developed yet.
Scott Hauswirth, OD. I agree
with Dr. Schachter. Given the choice
of only one, InflammaDry is also
my selection for the reasons he
has already listed. Though it does
not give a complete picture of the
inflammatory process, it is probably
the most useful tool regarding the
Table 1. Biomarkers Measured in the Sjö Test Diagnostic Panel
Courtesy Bausch + Lomb
Novel, proprietary
Traditional
Biomarker
Diagnostic Characteristics
Salivary protein-1 (SP-1, IgA, IgC,
IgM)
Provides high specificity and sensitivity for early Sjögren’s
syndrome.
Carbonic anhydrase (CA-6, IgA,
IgC, IgM)
Offers additional sensitivity for an early diagnosis.
Parotic secretory protein (PSP, IgA,
IgC, IgM)
Expressed early in disease course.
SS-A (Ro)
Expressed in about 70% of patients; typically appears later
than the novel biomarkers.
SS-B (La)
Less frequently expressed than Ro; typically appears later
than novel biomarkers.
Antinuclear antibody (ANA) by
HEp-2
Expressed in about 60% of Sjögren’s syndrome patients.
Rheumatoid factor (RF) levels (IgA,
IgC, IgM)
Found in many rheumatic conditions—not unique to
Sjögren’s syndrome.
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TARGETED AND TIMELY: THE NEW MODEL OF DRY EYE CARE
Photos: Chandra Mickles, OD
Scalloped lid margins are indicative
of the inflammation patterns
associated with MGD onset.
Obstructed meibomian glands with
telangiectasia also indicate the
possible presence of MGD.
guidance of treatment and management. Where I think it has been
most helpful is in identification of
our more chronic dry eye patients’
MMP-9 levels, which—when taken
as an indicator for the overall level
of inflammation present on the
ocular surface—is often much more
elevated than what we may initially think. This helps practitioners
determine the success of both the
acute control of inflammation with
an initial anti-inflammatory pulse
and our ongoing maintenance and
protective treatments, and allows us
the ability to tailor our treatments
to gain control of the disease more
efficiently and effectively.
Whitney Hauser, OD. Obtaining
an osmolarity measurement is my
go-to choice. It’s been well-established that tear film osmolarity is
accurate for both the diagnosis and
classification of dry eye disease;
however, research has also shown
that its utility goes beyond a conventional dry eye POC diagnostic.6
In contact lens wear, osmolarity
can be influenced by the lenses
themselves as well as the specific
type of solution used.7 Interestingly,
scleral contact lenses, often used to
treat some of the most symptomatic
dry eye patents, can also cause a
statistically significant increase in
osmolarity after one month of wear;
in a study, tear osmolarity measurements were found to increase at a
statistically significant level after one
month of scleral contact lens wear.8
Reduced basal tear production and
the disruption of the tear film layer
is believed to contribute to this
increase in tear osmolarity.
From a practice management
perspective, osmolarity is billable
(CPT 83861, Microfluidic analysis
utilizing an integrated collection
and analysis device) and data can be
gathered by a trained staff member.
Dr. Mangan. I have quite a bit
of experience using both the RPS
InflammaDry test and the Tearlab
osmolarity system. Both have been
true POC tests for me in that results
have influenced my decision on
whether to treat using anti-inflammatories. While a negative test does
not rule out the presence of inflammatory dry eye disease, it does make
me pause and explore other potential causes for their symptoms.
In accordance with what Dr.
Hauser offered, there is compelling
data and a number of clinical studies to support the idea of using a
product like Tearlab, not only in our
dry eye clinics, but during the course
of a routine examination with our
contact lens wearers, as well as our
cataract and refractive patients.9-11
A study presented by R. Doyle
Stulting, MD, at the 2014 ESCRS
meeting in London suggests a strong
correlation between a hyperosmolar
tear film and the risk of refractive
surprise due to more variable keratometry readings. According to the
published research, 17% of hyperosmolar eyes exhibited more than
1D of change in K cylinder between
the first and second preoperative
visits.10 This is just one more study
to support the idea that surface optimization is important with respect
to surgical outcomes and postoperative satisfaction scores.
One condition that we know
can lead to severe inflammatory
dry eye is Sjögren’s syndrome (SS).
According to the DEWS report, SS
is a chronic systemic inflammatory
disorder characterized by lymphocytic infiltration of exocrine glands.
This often results in xerophthalmia
(dry eyes), and xerostomia (dry
mouth), and parotid gland enlargement. Primary Sjögren’s syndrome
occurs in the absence of another underlying rheumatic disorder, whereas secondary Sjögren’s syndrome is
associated with another underlying
rheumatic disease, such as systemic
lupus erythematosus (SLE), rheumatoid arthritis (RA) or scleroderma.
Traditionally, clinicians adhere
to one of a number of classification
systems in attempting to diagnose SS
in the absence of biopsy results (see
“Classification Systems for Sjögren’s
Syndrome,” p. 37). Serology is
ordered looking for inflammatory
markers like anti-nuclear antibody
(ANA) with instructions for the lab
to run an SS-A (Ro) and SS-B (La)
if the patient’s ANA was elevated.
Rheumatoid factor levels should
also be measured. Note, research
indicates that ANA is expressed in
only 60% of patients with Sjögren’s
syndrome, and the disease process
can be active for years before traditional biomarkers like Ro and La
become evident or positive.1,12
Dr. Hauswirth. The Sjö test
(Bausch + Lomb) has been an extremely useful addition to our tool
chest. First, the potential implications of hastening the diagnosis and
early intervention of a life-altering
34 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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Photo: Ben Gaddie, OD
Photo: Paul M. Karpecki, OD
Entrance acuities of 20/40 and
20/50, respectively, were recorded,
while a slit lamp exam revealed 3+
PEK with filaments, scant tear film
and rapid TBUT OU. Treatment
was modified to include insertion of
Freeman-style punctal plugs in the
lower lids OU and use of preservative-free artificial tears QID OU,
Restasis BID OU and FML (fluorometholone) QID OU. Additionally,
a Sjö test was ordered and the
patient was directed to return in one
month for follow-up.
Upon return, the patient reported
that her symptoms were still present, yet improved. BCVA was 20/30
and 20/50, respectively. Slit lamp
exam demonstrated a 2+ central
PEK OD, 3+ OS but no filaments.
Treatment was once again modified
to include same-day punctal occlusion of the upper lids and she was
switched from FML to Lotemax
gel (loteprednol etabonate 0.5%,
Bausch + Lomb) QID OU. Sjö was
performed and it was revealed that
both traditional and novel biomarkers were abnormal, suggesting this
patient had Sjögren’s syndrome. A
rheumatology consult was scheduled, and the patient was formally
diagnosed with primary Sjögren’s
based on the reported symptoms,
physical signs and Sjö test findings.
She was given patient education
materials on SS and advised to discuss resuming Restasis, as it could
preserve remaining lacrimal glands
from further destruction. A recommendation of Biotene products for
the dryness of mouth was made, as
the symptom was not severe enough
to warrant treatment with cholinergic drugs like Evoxac (cevimeline
hydrochloride, Daiichi-Sankyo).
She was informed that patients with
Sjögren’s are at high risk of having
lymphoma and asked to undergo
labs at the time and six months
later. She was advised to inform her
doctor is she develops any fever,
Photo: Michelle Hessen, OD
disease are tremendous. Use of
this test to identify patients with
Sjögren’s syndrome earlier on in
their disease state and help them
begin to establish relationships with
rheumatology is critical in staying
ahead of the condition’s progression. In my own practice, we have
been able to identify many individuals as early-stage Sjögren’s patients
who are now collaborating with
rheumatology in their care.
This has potentially life-altering
implications, as the 15-year risk
for a Sjögren’s patient to develop
non-Hodgkin’s B-cell lymphoma is
nearly 10%, and the site of lymphoma is often the marginal zone
histological type, and aggregate to
the mucosa-associated lymphoid
tissue where Sjögren’s inflammation
is most active.13 This in addition to
the extraglandular involvement of
organ systems found in 75% of primary SS patients.14 I think this justifies our efforts to identify the disease
as early as possible, and allows our
colleagues in rheumatology and
other subspecialties to collaborate to
our patient’s benefit.
The following case helps to
demonstrate the value of incorporating Sjö into an eye care practice:
A 36-year-old Caucasian female
presented via referral for symptoms
of dry eye following laser vision
correction more than two years
ago. She reported a positive family
history of rheumatoid arthritis.
After attempting compliance with
treatments including warm compresses, artificial tears PRN, Restasis
(cyclosporine 0.05%, Allergan) BID
and Lastacaft (alcaftadine 0.25%,
Allergan) QD OU, she presented
with the feeling that her eyes are
worsening, with significant burning, pain and visual fluctuation.
Additionally, though the patient reports no joint or back pain, she does
note that her mouth has been drier
than normal during the last year.
Signs and symptoms for dry eye
diagnosis. Top to bottom: (a)
conjunctival staining with lissamine
green in a dry eye patient; (b)
staining with lissamine green on the
inferior cornea; and (c) presence of
minimal tear meniscus indicates a
reduction in tear film quantity.
chills or night sweats, or if she
notices any enlarged lymph nodes.
She was also informed that patients
with +SSA/SSB have a 1% chance of
having a child with congenital heart
block, so cardiac monitoring with
weekly fetal echocardiogram is warranted during any future pregnancy.
Dr. Hauser. Sjögren’s is a frequently misdiagnosed and underdiagnosed disease. Just over one
million people in the United States
are diagnosed with it, and it’s estimated that as many as four million
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TARGETED AND TIMELY: THE NEW MODEL OF DRY EYE CARE
individuals are suffering from it.15
Considering that ocular surface
complaints are extremely common
and may be some of the earliest and
most compelling signs and symptoms to present, eye care providers
have a distinct opportunity to act
as the gatekeepers for this elusive
autoimmune disease. As such, the
Sjö test acts as an ideal screener. As
Dr. Hauswirth said, working closely
with rheumatology is critical.
The American-European
Consensus Criteria for Sjögren’s
Syndrome found only one sign and
one symptom commonly associated
with dry eye disease in combination
with oral signs and symptoms warrants additional investigation. As
such, histological and antibody testing for anti-SSA (Ro) anti-SSB (La)
or both are essential for completing
the diagnosis.16 While convention
relies on the traditional biomarkers,
these often fall short in early diagnosis, as Dr. Mangan recognized.
The Sjö test includes three traditional biomarkers and four novel ones,
which may be expressed earlier in
the disease process (Table 1).17
LOOKING AT THE GLANDS
Moving on to pathophysiology evaluation, panelists consider the role
of the relevant ocular anatomy and
how to evaluate it noninvasively.
Dr. Mangan. I would like to
now turn our attention to meibomian gland dysfunction (MGD).
According to the executive summary from the International Workshop
on Meibomian Gland Dysfunction,
MGD is a chronic, diffuse abnormality of the meibomian glands
that is commonly characterized
by terminal duct obstruction and/
or qualitative/quantitative changes
in the glandular secretion. It may
result in alteration of the tear film,
symptoms of eye irritation, clinically
apparent inflammation and ocular
surface disease. The MGD work-
shop additionally proposed that
MGD may well be the leading cause
of dry eye throughout the world.18
Like aqueous-deficient dry eye,
MGD is a multifactorial disease. To
date, epidemiology and prevalence
data is inconsistent, with possible
risk factors still being researched.
With that being said, we know that
MGD can affect a wide range of age
groups. We are seeing more reports
of how excessive use of digital
devices is adversely affecting blink
rate and lid mechanics, secondarily
causing meibomian gland dropout
and evaporative dry eye symptoms
at a much earlier age.
Given all of this information, how
has meibography influenced your
approach to managing MGD?
Dr. Schachter. Meibography has
had a significant impact on how we
diagnose and treat MGD. As we
have looked more, we have found
more. This has led us to image
younger and younger patients. Teens
and young adults spend the majority
of their day looking at electronic
devices, and most of us believe that
this is leading to meibomian gland
atrophy. In fact, in my practice we
are approaching a “screen everyone” protocol for the lower glands
only, and we can now intervene
sooner as we find atrophy sooner.
The new Lipiscan (TearScience)
should allow us to image quickly.
Imaging technology is also an excellent patient education tool, as we
can now show patients their ocular
anatomy and also any meibomian
gland dropout. This helps to drive
patient compliance with our recommendations, which typically include
some combination of blink exercises, warm compresses, debriding,
Lipiflow, nutraceuticals, artificial
tears, lid hygiene and Blephex.
Dr. Hauser. Considering that 86%
of dry eye disease is evaporative in
nature, evaluation of the glands in
an essential diagnostic procedure.19
While I enjoy the use of both the
LipiView and Oculus Keratograph
technology in my office, performing
a simple transillumination of the
meibomian glands offers a more
basic view as well. Determining
the structure, number and level
of atrophy is valuable in creating
a treatment plan and setting the
patient’s expectations. Many eye
care providers recommend the use
of warm compresses without ever
visualizing the glands. However, a
patient with virtually no glands will
be disappointed by their failure to
significantly improve from warm
compresses. On the other hand,
however, while the majority of
patients have evaporative dry eye
disease, a patient with ideal meibography and lipid layer thickness may
suggest another etiology.
Dr. Hauswirth. Meibography has
been an incredible asset, though
we are still in the early stages of
knowing exactly what the causative
factors are regarding several aspects
to alterations in meibomian gland
morphology. Still, it is an incredibly
helpful tool from a prognostic and
diagnostic standpoint—being able
to capture images and display them
for patients to illustrate their pathophysiology is a powerful thing. No
other test we perform commands
a patient’s attention as well as
an image of their own glands. In
our practice, we have the Oculus
Keratograph, Lipiview II and
LipiScan. I think all are excellent in
performing meibography, although
I find the images in the TearScience
technology platforms to be sharper.
Dr. Mangan. I currently use the
Oculus Keratograph in one of my
primary offices, and I find it very
useful in both diagnosis of MGD
and in determining the location
and severity of gland atrophy in
my evaporative dry eye patients.
We now know that the location of
gland atrophy is very important due
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to the work of Blackie and Korb, as
well as Pflugfelder et al. and other
teams.20,21 The glands that offer the
greatest amount of meibum secretion are the nasal ones, which are
responsible for 70% of total secretory volume. Thus, it stands to reason
that if there is significant gland
fallout nasally, patients are more apt
to have more significant disease.
I agree with Dr. Hauser that lid
transillumination works well when
advanced meibography systems are
not available. Transillumination of
the lids is part of my general workup regardless. I find that I can predict the Keratograph results through
transillumination. Still, Keratograph
images do allow me to hammer the
point home when educating my
patients about their condition.
FUTURE ADVANCES
In this rapidly evolving category of
eye care, where might the technology be heading?
Dr. Mangan. Next question:
Where would you most like to see
POC testing improve or advance in
the field of ocular surface disease?
Dr. Schachter. Though MMP-9
is very useful when looking for
inflammation, there are also other
mediators and biomarkers. While a
positive result means inflammation
of some kind is likely present, a negative result doesn’t necessarily rule
it out, as MMP-9 is a non-specific
biomarker. Interestingly, it would be
helpful if we could take a tear sample and test for other inflammatory
biomarkers, such as IFN-gamma—
however, we can’t at this time.
Osmolarity is also meaningful and
can help direct treatment, allowing
us to monitor for efficacy. The problem is, however, that osmolarity can
vary over the surface of the eye.
Also, InflammaDry and TearLab
require some level of skill in sample
collection. InflammaDry test results
can be difficult to interpret when
MMP-9 levels are just above the
cutoff for a positive test, 40ng/ml.
Sample collection is also difficult
on patients who are very dry.
Regardless, as new tests are developed, high sensitivity and specificity
are critical, in addition to positive
and negative predictive values.
Dr. Hauswirth. I believe the direction we’re heading—toward broader spectrum panels of inflammatory markers, as well as improved
Classification Systems for Sjögren’s Syndrome
American-European Consensus Group. These criteria
allow for a diagnosis in patients without sicca symptoms or who have not undergone biopsy.2,22 Diagnosis
of primary Sjögren’s requires at least one of the four
criteria below to be present and either criterion #5 or
#6 must also be included. Sjögren’s can be diagnosed
in patients who have no sicca symptoms if three of the
four objective criteria are fulfilled. These criteria are:
1. Ocular symptoms, specifically dry eye present for
more than three months, foreign body sensation and/
or use of artificial tears more than three times daily.
2. Oral symptoms, including dry mouth, reoccurring
swelling of the salivary glands and/or frequent use of
liquids to aid in swallowing.
3. Ocular signs, specifically results from the Schirmer
test performed without anesthesia less than 5mm in
five minutes and/or positive vital dye staining results.
4. Oral signs, including abnormal salivary scintigraphy,
abnormal parotid sialography, abnormal sialometry
(i.e., unstimulated salivary flow <1.5mL in 15 min).
5. Positive minor salivary gland biopsy findings.
6. Positive anti-SSA or anti-SSB antibody results.
Secondary Sjögren’s syndrome is diagnosed when
symptoms of oral or ocular dryness exist in addition to
criterion three, four or five above in the presence of a
connective-tissue disease. Application of these criteria
has yielded a sensitivity of 97.2% and a specificity of
48.6% for the diagnosis of primary Sjögren’s syndrome,
while in the case of secondary Sjögren’s syndrome, the
specificity is 97.2% and the sensitivity is 64.7%.23
American College of Rheumatology. The ACR
classification criteria were developed to improve the
specificity of the criteria used for entry into clinical
trials, especially following the emergence of biologic
agents as potential treatments for Sjögren’s syndrome
and their associated comorbidities. This high specificity
makes the ACR criteria more suitable for application in
situations in which misclassification can pose a risk to
the patient’s health. These guidelines were accepted by
the ACR as a provisional criteria set in 2012.24
According to the ACR criteria, the diagnosis of
Sjögren’s syndrome requires presence of at least two of
the following three findings:
• positive serum anti-SSA and/or anti-SSB antibodies,
or positive rheumatoid factor and antinuclear antibody titer of at least 1:320;
• ocular staining score of at least three; and
• the presence of focal lymphocytic sialadenitis with
a focus score of at least one focus/4mm2 in labial
salivary gland biopsy samples.
Compared with commonly used AECG criteria, the
ACR criteria is based entirely on a combination of objective tests that assess the three main components of
Sjögren’s syndrome (serologic, ocular and salivary) and
do not include criteria based on subjective symptoms of
ocular and oral dryness. The application of these criteria
has yielded a sensitivity of 93% and a specificity of 95%
for the diagnosis of Sjögren’s syndrome; however, they
cannot be used to distinguish between the primary and
secondary forms of the disease.
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TARGETED AND TIMELY: THE NEW MODEL OF DRY EYE CARE
Photos: Ben Gaddie, OD
Fluorescein staining of a patient
with severe punctate epithelial
keratopathy secondary to dry eye
that is associated with Sjögren’s
syndrome and exposure keratopathy.
imaging of the glands and other
important ocular surface structures
down to the cellular level—can help
us become more accurate in setting
treatment strategies. We are in what
I call the Model T phase of diagnostic technology for dry eye: benefiting
greatly from its existence while
recognizing limitations this early in
its development. However, understanding those limitations allows
us to remodel and refine our tools,
making them increasingly helpful
and clinically relevant.
Another tool that I believe can be
quite helpful is the confocal microscope, which allows us to image
through corneal and conjunctival
tissue to view active dendritic cells
in the cornea, activated keratocytes
and corneal nerve morphology,
which gives us an image on the
actual mechanics of disease in vivo.
This is not necessarily practical to
implement in a standard eye care
practice yet, but the technology is
improving, and it has great potential
for diagnosis and management.
Dr. Hauser. The greatest potential
in POC testing, in my opinion, is
the use of multiple tests in concert.
We have several useful, but often
underused, tests available today.
Ideally in the future, practitioners
will be able to perform multiple
objective tests to better address the
multifactorial nature of the condition and to objectively monitor
improvement or progression.
Dr. Mangan. Thank you. I think
we can all agree that each POCT
mentioned in this article brings
some amount of value and information to the overall picture of patient
ocular surface health. With that in
mind, however, each of these tests
also has certain limitations regarding the information it can reveal.
I personally have had patients
who were diagnosed with primary Sjögren’s display a normal
osmolarity reading in both eyes.
Another patient tested negative in
the InflammaDry test during one
visit but positive a month later,
without any change in how they
were being treated in between the
two visits. As such, I definitely agree
with Dr. Hauswirth that we are only
in the beginning stages of where
POCT may eventually progress to.
However, the POCT tests discussed
here may provide some information
that can influence chairside treatment decisions in today’s practices.
I
n closing, I would like to thank
the panel for sharing their
thoughts regarding how they use
point-of-care technology in their dry
eye clinics. I, for one, am encouraged by the industry’s continuing
interest in this area and am excited
to see it progress. I hope that eye
care practitioners across the country
understand not only the need but
also the opportunity that is available
to them to become more focused in
the diagnosis and management of
ocular surface disease.
RCCL
1. Harmon D. Market Scope, LLC. 2008 Comprehensive Report on the Global Dry Eye Market. Available
at: http://dev.market-scope.com/market_reports/2008/07/2008-comprehensive-report-on-t.
html. Accessed July 7, 2009.
2. American Academy of Allergy, Asthma & Immunology (AAAAI). Diseases 101: Asthma and Allergy
Statistics. Available at: www.aaaai.org/patients/gallery/prevention.asp?item=1a. Accessed July 7, 2009.
3. Harthan J, O’Dell L, Kwan JT, et al. Dry Eye Symptoms and Visual Function with Digital Device Use.
ARVO 2016; abstract #2843-A0052.
4. Corrales RM, Stern ME, De Paiva CS, et al.
Desiccating stress stimulates expression of matrix
metalloproteinases by the corneal epithelium. Invest
Ophthalmol Vis Sci. 2006 Aug;47(8):3293–302.
5. Kaufman HE. The practical detection of mmp-9
diagnoses ocular surface disease and may help prevent its complications. Cornea. 2013 Feb;32(2):211-6.
6. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye
disease. Am J Ophthalmol. 2011 May;151(5):792-8.
7. Karkkainen TR, Smith MK, Wood JR. The effect
contact lens solution osmolarity has on tear
film toxicity. Invest Ophthalmol Vis Sci. 2002
Dec;32(13):3090.
8. Lau J, Gao C, Chaglasian E. The effect of scleral
lens wear on tear osmolarity. Poster. American
Academy of Optometry 2015.
9. Iskeleli G, Karakoc Y, Aydin O, Yetik H, Uslu H,
Kizikaya M. Comparison of tear-film osmolarity in
different types of contact lenses. CLAO J. 2002
Oct;28(4):174-6.
10. Epitropoulos AT, Matossian C, Berdy GJ, Malhotra RP, Potvin R. Effect of tear osmolarity on repeatability of keratometry for cataract surgery planning.
J Cataract Refract Surg. 2015;41:1672-7.
11. Giancarlo M. Modification of the tear film osmolarity with the use of contact lenses in omafilcon A
and methafilcon A materials. BCLA poster presentation. 2010.
12. Clinical Laboratory International Online. Sjögren’s
syndrome: an under-diagnosed disorder. Available
at www.cli-online.com/fileadmin/pdf/pdf_general/
sj%F6gren’s-syndrome-an-underdiagnosed-disorder.pdf. Accessed July 7, 2016.
13. Solans-Laque R, Lopez-Hernandez A, Bosch-Gill
JA, et al. Risk, predictors, and clinical characteristics
of lymphoma development in primary Sjogren’s
syndrome. Semin Arthritis Rheum. 2011;41(3):415-23.
14. Baldini C, Pepe P, Quartuccio L, et al. Primary
Sjogren’s syndrome as a multi-organ disease:
impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian
patients. Rheumatology. 2014;53(5):839-44.
15. Dysautonomia International. Underlying Causes
of Dysautonomia. Available at: www.dysautonomiainternational.org/page.php?ID=150. Accessed July
7, 2016.
16. John Hopkins Medicine. American-European Consensus Criteria for Sjögren’s Syndrome.
Available at www.hopkinssjogrens.org/disease-information/diagnosis-sjogrens-syndrome/americaneuropean-consensus-criteria-sjgrens-syndrome/.
Accessed July 7, 2016.
17. Kent C. Using today’s dry eye diagnostic tools.
Rev Ophthalmol. 2015 Oct; 22(10):22-34.
18. Nichols KK, Foulks GN, Bron AJ, et al. The
International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis
Sci. 2011 Mar;52(4):1922-9.
19. Lemp MA, Crews LA, Bron AJ. Distribution of
aqueous-deficient and evaporative dry eye in a
clinic-based patient cohort: a retrospective study.
Cornea. 2012 May;31(5):472-8.
20. Blackie CA, Korb DR, Knop E, et al. Nonobvious
obstructive meibomian gland dysfunction. Cornea.
2010 Dec;29(12):133-45.
21. Pflugfelder SC, Tseng S, Sanabria O, et al.
Evaluation of subjective assessments and objective
diagnostic tests for diagnosing tear-film disorders
known to cause ocular irritation. Cornea. 1998
Jan;17(1):38–56.
22. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome.
Arch Intern Med. 2004;164:1275-84.
23. American Academy of Allergy, Asthma & Immunology (AAAAI). Diseases 101: Asthma and Allergy
Statistics. Available at www.aaaai.org/patients/gallery/prevention.asp?item=1a. Accessed July 7, 2009.
24. American College of Rheumatology. American
College of Rheumatology Classification Criteria
for Sjögren’s Syndrome: A Data-Driven, Expert
Consensus Approach in the Sjögren’s International
Collaborative Clinical Alliance Cohort. Available at
www.rheumatology.org/Portals/0/Files/2012%20
ACR%20Sjogrens%20Classification%20Criteria%20v.pdf. Accessed July 23, 2016.
38 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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Practice Progress
By Mile Brujic, OD, and Jason Miller, OD, MBA
Turning a Negative into a Positive
Knowing your contact lens infections and how to keep patients happy is key to keeping
them in the practice.
C
ontact lens wear is not
without its dangers.
Individuals who present to the clinic with a
case of a red, swollen
or otherwise compromised ocular
surface are capable of developing
an infection from poor lens hygiene,
lens overwear, ingress of foreign
material or one of any number of
other compliance issues. However,
aggressive treatment of the issue can
turn this negative situation around,
regardless of whether it’s possible to
identify the underlying cause. Doing
so successfully can improve your
practice’s standing in the eyes of
patients, as most, if not a majority,
of them are unaware that the eye
care practice is the first place to
go when faced with contact lens
irritation, rather than the primary
care physician, emergency room or
urgent care center.
Even more concerning is the
realization that many patients who
go elsewhere for conjunctival or
corneal infections often receive
incorrect treatment, resulting in
either more healing time, recurrence
of the problem or even increased
adverse effects such as the loss of
visual clarity following resolution.
As such, these scenarios represent a
chance to build your medical model
business and provide patients with
targeted treatments their general
PCP may not have the expertise or
means to give them, increasing the
patient’s trust and loyalty to the
practice. But, how does one pass
the message on to them?
UNDERSTANDING THE CAUSE
Educating the patient on the
practice’s abilities is key, either
during the patient exam or with
other in-office marketing efforts.
Consider incorporating a recording
that plays on a loop in the reception area or when the patient is on
hold on the phone to remind them
that the practice they’re calling or
visiting is their primary eye care
provider and thus the place to go if
they have any contact lens–related
issues. Additionally, consider mentioning in the practice’s voicemail
recording that infections associated
with contact lens wear are also handled at the practice, and to contact
the practice’s staff immediately if
any concerns arise.
Depending on the problem that
the patient presents to the clinic
with, different origins are likely and
so must be addressed differently
with each patient to prevent reoccurrence of the same issue. Here are
some possible problems that a contact lens patient may present with
and how to handle them so as not
to lose the patient to lens dropout:
Bacterial conjunctivitis (Figure
1a). Lens hygiene may be to blame
for this infection if present in
association with contact lens wear.
Though rare in comparison to
other types of conjunctivitis, this
issue needs to be addressed as soon
as possible. In addition to treatment, patients must be re-educated
on proper lens care and cleaning
habits to prevent reoccurrence. In
the case of bacterial conjunctivitis,
generally there is no visible corneal
involvement, though discharge, lash
matting and contact lens irritation
are often present.
Following resolution of the
infection, patients should dispose of
their current pair of contact lenses
to reduce risk of further problems.
Custom specialty lenses, however,
may need to be kept out of cost
concerns, and must be disinfected
well. Bacterial conjunctivitis is typically treated with topical antibiotic
therapy, and patients should abstain
Fig. 1. Conjunctivitis can be a common concern in contact lens patients. Here are, from left to right, (a) bacterial, (b)
viral and (c) allergic cases.
40 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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from contact lens wear until the
infection has been cleared and they
have finished the entire course of
prescribed medication.
Viral conjunctivitis (Figure
1b). This form of conjunctivitis is
commonly confused with bacterial
conjunctivitis at presentation; in
fact, research shows that eye care
practitioners only diagnose this
problem correctly approximately
50% of the time due to the many
overlapping signs and symptoms
between it and bacterial conjunctivitis.1 As such, in the case of a
suspected viral conjunctival infection, it is important to evaluate the
patient for traces of upper respiratory infection or lymphadenopathy,
the latter of which is most closely
related to viral origins. Other signs
to look for include differences in the
types of discharge present (watery
indicates viral while mucous or purulent typically indicates bacterial),
or the hallmark presence of follicles.
Allergic conjunctivitis (Figure
1c). Though non-infectious in
origin (in that it is caused by pollen,
pet dander or dust mites rather
than a pathogen), this condition
is still often misdiagnosed by both
primary care providers and urgent
care facilities. Allergic conjunctivitis can make contact lens wear
more difficult due to the presence
of irritating foreign material on the
ocular surface, so consider recommending daily disposable contact
lens wear to the patient. Signs and
symptoms of allergic conjunctivitis
include burning and itching and can
be treated using topical anti-histamine/mast-cell stabilizer drug
combinations.
Giant papillary conjunctivitis
(Figure 2). A more chronic form of
allergic response strongly correlated
with contact lens wear, giant papillary conjunctivitis (GPC) is similarly
non-infectious. Large papillae—the
hallmark sign—are located on the
superior tarsal plate, so evert the
upper eyelid to ascertain whether
GPC is indeed the patient’s diagnosis. GPC itself is sometimes treated
using topical corticosteroids; temporary discontinuation of contact
lens wear during treatment helps
with resolution.
Infiltrative keratitis (Figure 3).
Contact lens-associated corneal
infiltrates can occur from either
noninfectious or infectious processes. The former appears as multiple
infiltrates located across the surface
of the cornea with minimal or no
fluorescein staining, and the latter
appears as a single larger infiltrate
that stains positively with fluorescein.2 Noninfectious corneal infiltrates
may be associated with contact
lens non-compliance, extended lens
wear and/or wear of silicone hydrogel contact lenses versus other lens
materials. In the case of infectious
infiltrates, the bacterial organism
invades the corneal tissue through
a single area.3-5 Treatment in both
cases involves the removal of the
patient’s contact lenses and the use
of either topical corticosteroids or
topical antibiotics.
A
ccurately diagnosing and
treating a variety of contact
lens-related complications—the
ones above and others unmentioned—is key to getting patients
back into their contact lenses
Fig. 2. Large papillae on the
underside of the eyelid are hallmark
signs of giant papillary conjunctivitis.
Fig. 3. Infectious infiltrates are
generally more painful than their
noninfectious counterparts.
safely and keeping them coming to
the practice. Proactively discussing
potential concerns of noncompliance and hygiene are integral in
preventing complications, as is
ensuring that patients understand
they can contact the office should
any of these conditions occur.
RCCL
1. O’Brien TP, Jeng BH, McDonald M, Raizman MB.
Acute conjunctivitis: truth and misconceptions. Curr
Med Res Opin. 2009 Aug;25(8):1953-61.
2. Baum J, Dabezies OH Jr. Pathogenesis and treatment of “sterile” midperipheral corneal infiltrates
associated with soft contact lens use. Cornea. 2000
Nov;19(6):777-81.
3. Stapleton F, Keay L, Jalbert I, Cole N. The epidemiology of contact lens related infiltrates. Optom
Vis Sci. 2007 Apr;84(4):257-72.
4. Chalmers RL, Keay L, McNally J, Kern J. Multicenter case-control study of the role of lens
materials and care products on the development of corneal infiltrates. Optom Vis Sci. 2012
Mar;89(3):316-25.
5. Diagnostic and Treatment Algorithms for Ocular
Surface Disease States; Supplement. Rev Optom.
2009 Oct.
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Out of the Box
By Gary Gerber, OD
Keeping Contact Lens Care In-House
There’s no substitute for your clinical expertise—so don’t let patients find one. Make
sure they know to contact you any time questions arise.
D
uring a recent trip to
the pharmacy to pick
up some medication
for my daughter, I
overheard an interesting conversation between the
person in line in front of me and
the pharmacy technician behind the
counter:
Do you know if I can use this
drop with my contact lenses?, the
patient asked the technician.
It should say so right on the
bottle, the technician responded.
Grabbing the bottle, she took a
closer look and added, No, you
can’t—it says right here. Go over to
aisle four instead, that’s where all
the contact lens stuff is. You should
be able to find something for your
needs there. What do you need it
for, anyway?
My right contact lens has been
bothering me for the last few days,
the patient admitted.
Oh. Aisle four should have
something for that, the technician
directed.
SILENT PARTNERS
Though only two are present in this
chapter, this story in fact has four
main characters: the patient, the
pharmacy technician, the patient’s
doctor and the doctor’s staff.
Assuming for a moment that there
actually is something wrong with
the previous exchange, the question to ask is: Which of the four
participants is most at fault for the
problem?
Most individuals may agree
that it is not the patient. Though
the pharmacy technician possibly
overstepped her boundaries in a
few areas, she is also not the culprit.
She deserves points for instructing
the patient to read the label, but she
really should not have recommended a drop to decrease the patient’s
problem, or at least she should have
added that if the patient experienced further problems, then he
should contact his doctor.
Considering the patient’s doctor and the doctor’s staff, the first
thought is possibly to blame the
presumed lack of patient education:
that is, if someone at the practice
had told the patient that if his
contact lenses ever bothered him,
he should remove them and call
the practice immediately to avert
the need to visit the pharmacy for
eye drops entirely. However, based
on the data from consultations
conducted for hundreds of practices, nearly all practices out there
mention this as part of their general
contact lens fitting appointment. So,
then, why didn’t this patient call his
eye care provider?
MAKING AN IMPRESSION
First and foremost, it may be that
stating to the patient that he should
call you if he ever has a problem
with his lenses is not a strong
enough method to stick in the patient’s mind long-term.
Consider instead what would
happen if you called each of your
patients every day and reinforced
the message that they should
contact you if they have a problem.
Nonsensical though it may be, it
would drive the point home and indicate that some amount of repetition can ensure each patient knows
what directions to follow and how
to combat a problem.
However, it’s more than likely
that the patient also didn’t call for
another reason. Assuming that he
was already in the pharmacy to
pick up something else, it’s more
convenient to pick up something
to use for his issue right then and
there, rather than first calling the
practice to see if it’s even a good
idea to do so in the first place.
CHANGING THE
THOUGHT PROCESS
After instituting some form of
repetitive education at the practice
for contact lens care, informing patients that the practice has resources
available for other aspects of lens
wear—including ways to satisfy
interest in other lens designs, alleviate concerns regarding infections
or clear up confusion with regards
to the selection of lens solution—is
also a good idea.
Stress to them that they are more
than welcome to call, email, text
or visit the practice’s website to
look for information at any time;
however, also make sure you have
the information readily available,
accurate and up-to-date for when
they do come looking. Additionally,
make sure that the practice’s staff is
capable of quickly and accurately
addressing any questions or concerns they may receive.
Finally, keep in mind that,
unfortunately, convenience will
probably trump loyalty every time.
But, knowing this, we should still
educate patients regarding clinical
concerns and also that the practice
is available to help them however
they need.
RCCL
42 REVIEW OF CORNEA & CONTACT LENSES | SEPTEMBER 2016
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8/25/16 12:19 PM
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