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RCCL
REVIEW OF CORNEA
& CONTACT LENSES
Supplement to
MAY 2015
EARN 1 CE CREDIT:
• KEEPING THE CORNEA CLEAR
• HOW ANTI-INFLAMMATORY AGENTS WORK
• CYCLOSPORINE — NOT JUST FOR DRY EYE?
• DON’T HOLD BACK: TOPICAL STEROIDS
IN CLINICAL PRACTICE
HOW DOES IT HAPPEN—AND HOW CAN IT BE
STOPPED? EXPERTS EXPLAIN THE SCIENCE AND
PRACTICE OF ANTI-INFLAMATORIES.
Also — Kids Aren’t Short Adults: Tips For Fitting Young Contact Lens Wearers
001_rcl0515_cover.indd 1
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contents
Review of Cornea & Contact Lenses | May 2015
departments
4
News Review
Osmolarity Levels in Eye Drops
Documented; Even Good Compliance May Not Eradicate Fungi
10
features
CE — Keeping the Cornea Clear
6
My Perspective
Is Google Making Us Stupid?
By Joseph P. Shovlin, OD
7
Lens Care Insights
A Different Kind of Colored Lens
By Christine W. Sindt, OD, and
Prashant Parekh, MD
8
Pharma Science & Practice
Cyclosporine — Not Just for Dry Eye
By Elyse L. Chaglasian, OD, and
Tammy P. Than, OD, MS
30
The GP Expert
A ‘Coherent’ Strategy for Fitting
Scleral Lenses
By Stephanie L. Woo, OD
32
Derail Dropouts
’Tis the Season
By Mile Brujic, OD, and
Jason R. Miller, OD, MBA
34
While a complex, remarkable system with a tough line of
defense, the cornea sometimes needs a little help from
practitioners.
By Bhawanjot Minhas, OD
Out of the Box
Band Together
By Gary Gerber, OD
16
22
26
How Anti-Inflammatory
Agents Work
Understanding corticosteroid and NSAID
mechanisms can help you to choose and use
them wisely. An expert explains.
By Bruce E. Onofrey, OD, RPh
Don’t Hold Back: Topical
Steroids in Clinical Practice
With a little extra consideration and care, you
can safely use steroids to treat a range of
ocular conditions.
By Christopher Cakanac, OD
Kids Aren’t Short Adults:
Tips for Fitting Young
Contact Lens Wearers
Prescribing contact lenses to children requires
a vastly different approach compared to
adults. Here are some things to keep in mind.
By Jeffrey J. Walline, OD
Cover design by Matt Egger
©iStock.com/Jobsonhealthcare
/ReviewofCorneaAndContactLenses
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#rcclmag
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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News Review
IN BRIEF
• Patients with floppy lid syndrome
(FES) may have structural changes that
could signal risk for glaucoma development, says a study in the May 2015
Cornea.1 Researchers in Spain performed
a corneal biomechanical evaluation on
208 eyes—72 with FES and 136 without
FES—of 107 patients, measuring corneal
hysteresis (CH), corneal resistance factor
(CRF), central corneal thickness (CCT),
Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated
intraocular pressure (IOPcc). Noncontact
IOP and all corneal biomechanical properties were measured using the Ocular
Response Analyzer (Reichert).
Mean CH was significantly lower in
patients with FES compared with those
without FES (i.e., 9.51 ± 1.56 vs. 11.66 ±
9.11), which may “constitute a risk factor
for glaucoma due to an association with
the response of the corneoscleral shell
and the ocular vasculature to IOPinduced stress,” say the researchers.
Interestingly, mean CH remained statistically significant after adjusting for age
and apnea-hypoapnea index, but mean
CRF and mean IOPcc did not. There was
no statistically significant difference in
Goldmann-correlated IOP and CCT.
1. Royo MM, de Ribot AM, Sanchez-de-la-Torre M, et
al. Corneal biomechanical properties in floppy eyelid
syndrome. Cornea. 2015 May;34(5):521-4.
1. Lee KLY, Nguyen DPA, Edrington TB, and Weissman BA. Calculated in situ tear oxygen tension
under hybrid contact lenses. Eye & Contact Lens.
2015 Mar;41(2):111-116.
4
V
ariations in the osmolarity of topical eye drops
may influence clinical
performance, and this
trait warrants greater attention, reports a study published in the May
2015 Cornea. Documenting a range
of hypo- and hyperosmolarity levels
in 87 prescription and OTC drops,
the researchers call the effort “a first
step in understanding the influence
of osmolarity of ophthalmic formulations on the ocular surface.”1
Hyperosmolar eye drops could
have therapeutic efficacy in treating
corneal edema, they note.
Researchers in Germany evaluated the impact of hypoosmotic
and hyperosmotic conditions on ex
vivo corneal thickness and integrity
(specifically, glucose and lactate
levels) in a rabbit model of induced corneal edema by filling the
anterior chamber with a hypoosmolar solution. After 48 hours,
two hyperosmolar solutions—Omnisorb (preserved with BAK) and
Ocusaline (preservative-free)—were
topically applied every 15 minutes
over the course of one hour.
Both “significantly reduced corneal swelling” on OCT, the authors
found. Omnisorb reduced corneal
thickness by 279µm vs. 258µm for
Ocusaline. The authors say that
this suggests eye drops containing
preservatives may be more beneficial than preservative-free solutions
in some cases, at least initially.
There was no significant difference
in treatment effect at 72 hours.
In the second part of the study,
researchers categorized the osmolarity of 87 commercially available
eye drops using freezing point
osmometry. Forty-three showed an
osmolarity value below a physiological tear osmolarity value of
289mOsm/L, while the other 44
demonstrated a higher osmolarity
value. Overall, however, the majority of the products fell within a
limited range around isoosmolarity,
suggesting further experiments with
application on a corneal model are
necessary.
Regardless, “it is important to
keep in mind that the osmolarity of
eye drops is not an isolated factor; instead, osmolarity is relevant
concerning various product ingredients,” the researchers say. “Another
factor is the viscosity of eye drops
that prolongs their retention time
on the ocular surface. This might
alter the osmotic effects of eye
drops as well.”
RCCL
1. Dutescu RM, Panfil C, Schrage N. Osmolarity of
prevalent eye drops, side effects, and therapeutic
approaches. Cornea. 2015 May;34(5):560-566.
Multifocal Halo Reduction Possible?
A new lens surface modification that smoothes
out surface discontinuities could reduce the halo
effect commonly experienced by patients with
multifocal intraocular or contact lenses, reports
a study in the December 2014 Optics Communications.1 Coauthor Zeev Zalevsky, PhD, of Israel’s
Bar-Ilan University says “the proposed surfacing Untreated IOL
Treated IOL
technique can be very important in significantly
improving [vision], especially the night vision performance of any IOL for presbyopia
correction,” noting that it could in theory be added to any multifocal lens.
Photo: Zeev Zalevsky, PhD
• Hybrid contact lenses with tear
vaults of more than 100μm may be
detrimental to corneal health because
of inadequate surface oxygen supply,
reports a study in the March 2015 Eye &
Contact Lens.1 Slit lamp and OCT evaluations found that fitting hybrids with the
manufacturers’ recommended tear vault
of 100μm or less resulted in acceptable
corneal surface oxygen values, around
100mm Hg, while vaults greater than
100μm created less ideal corneal surface pO2—as low as 0mm Hg.
The researchers had hoped to find
an acceptable way to calculate corneal
surface pO2 under a hybrid lens, but inconsistent results between the slit lamp
and OCT limited reliability. Despite the
study’s limitations, it highlights the need
for a better clinical method for measuring corneal surface pO2—similar to methods used for soft, silicone hydrogel and
rigid contact lenses. Such testing would
help clinicians better fit hybrids. Until
then, the researchers advise fitting hybrid contact lenses with modest vaults
to provide adequate oxygen supply.
Osmolarity Levels in
Eye Drops Documented
1. Limon O, Zalevsky Z. Ophthalmic halo reduced lenses design. Optics Communications. 2014 Dec;342:253-8.
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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RCCL
REVIEW OF CORNEA
& CONTACT LENSES
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EDITORIAL STAFF
EDITOR-IN-CHIEF
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ASSOCIATE EDITOR
Aliza Martin [email protected]
CLINICAL EDITOR
Joseph P. Shovlin, OD, [email protected]
EXECUTIVE EDITOR
Arthur B. Epstein, OD, [email protected]
ASSOCIATE CLINICAL EDITOR
Christine W. Sindt, OD, [email protected]
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EDITORIAL BOARD
Mark B. Abelson, MD
James V. Aquavella, MD
Edward S. Bennett, OD
Aaron Bronner, OD
Brian Chou, OD
S. Barry Eiden, OD
Gary Gerber, OD
Susan Gromacki, OD
Brien Holden, PhD
Bruce Koffler, MD
Pete Kollbaum, OD, PhD
Jeffrey Charles Krohn, OD
Kenneth A. Lebow, OD
Kelly Nichols, OD
Robert Ryan, OD
Jack Schaeffer, OD
Kirk Smick, OD
Barry Weissman, OD
REVIEW BOARD
Kenneth Daniels, OD
Desmond Fonn, Dip Optom M Optom
Robert M. Grohe, OD
Patricia Keech, OD
Jerry Legerton, OD
Charles B. Slonim, MD
Mary Jo Stiegemeier, OD
Loretta B. Szczotka, OD
Michael A. Ward, FCLSA
Barry M. Weiner, OD
Even Good Compliance
May Not Eradicate Fungi
F
ungal contamination of
contact lens cases can
occur despite patient compliance with proper lens
handling, cleaning and replacement
instructions, reports a study in the
March 2015 Eye & Contact Lens.1
Researchers in Greece collected
216 samples of contact lens solution from 117 lens cases of asymptomatic lens wearers; 194 were
collected from two-cup storage
cases (TCSC) filled with non-hydrogen peroxide-containing solutions,
four from TCSCs with a hydrogen
peroxide solution and 36 from
single-cup storage cases (SCSC)
containing hydrogen peroxide
solutions. All subjects were using
monthly disposable hydrogel, low
water content soft lenses on a daily
wear basis and were required to
comply with lens cleaning, handling
and replacement instructions given
by the manufacturer or attending
optometrist in order to participate
in the study.
After culturing the collected lens
solution samples, researchers identified the presence of fungi from 15
cultures obtained from 12 storage
cases. Seven molds (one Fusarium
solani, four Aspergillus niger and
two Aspergillus fumigatus), seven
yeasts (five Candida parapsilosis,
one Candida tropicalis and one
Rhodotorula rubra) and one a mold
in combination with a yeast (F.
solani with Candida guilliermondii)
were discovered. Interestingly, the
peroxide group had a higher rate
of fungal isolation compared with
the multipurpose solution group,
likely due to quick neutralization,
selection of naturally resistant mi-
crobes adapted to survive repeated
peroxide use and biofilm release of
catalase that neutralizes peroxide.
These results are concerning,
say the researchers, because “even
when contact lens users report
compliance with instructions of
contact lens handling cleaning and
replacement, it is still possible to
have microbial contamination of
the stock solutions that may lead
to corneal infection.” They say that
further improvement of contact
lens disinfectant solutions and lens
hygiene education is needed.
Another study suggests topical
amphotericin B (AMB) and natamycin may be particularly effective
against certain fungi—specifically,
the Candida species.2 Researchers
exposed samples of 68 Candida
isolates (37 albicans and 31 nonalbicans) to AMB 0.2%, natamycin
5%, voriconazole 1% and fluconazole 0.2%, examined for growth
after 48 hours and found 100% of
the Candida isolate samples mixed
with AMB 0.2% and natamycin
5% demonstrated growth inhibition, suggesting that both AMB and
natamycin have been shown in this
study to be more effective than the
other agents tested.
RCCL
1. Mela EK, Anastassiou ED, Gartaganis SP,
Christofidou M. Fungal isolation from disinfectant solutions of contact lens storage cases
among asymptomatic users. Eye & Contact
Lens. 2015 Mar;41(2):87-90.
2. Spierer O, Dugar J, Miller D, O’Brien TP.
Comparative antifungal susceptibility analysis of
candida albicans versus non-albicans candida
corneal isolates. Cornea. 2015 May;34(5):576579.
Advertiser Index
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REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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My Perspective
By Joseph P. Shovlin, OD
Is Google Making Us Stupid?
The ubiquity of information online is both a blessing and a curse. How much
knowledge is too much?
N
ot long ago, a
colleague of mine
mentioned an article
she had read in The
Atlantic, published
in 2008 but perhaps even more relevant today. The title—“Is Google
Making Us Stupid?”—lured me
in; ironically, I used Google to find
it. From the long list of comments
other readers had posted, I surmised
it had made them look at how the
online search engine impacts their
daily lives. The perceived omniscience of Google absolves us of the
need to contemplate, discuss and
learn. All answers are just a click
away. And it also made me think:
how often do our patients question
our recommendations or even our
diagnosis after consulting Google?
The torrent of online data that
flows through our days also affects
the ways in which we interact with
it, argues Nicholas Carr, author of
the article, who has written several
books and news columns on the
subjects of technology and culture.
“Over the past few years, I’ve
had an uncomfortable sense that
someone or something has been
tinkering with my brain, remapping
the neural circuitry, reprogramming
the memory … I’m not thinking
the way I used to think,” he writes.
“Now my concentration often starts
to drift after two or three pages.
I get fidgety, lose the thread, start
looking for something else to do. I
feel as if I’m dragging my wayward
brain back to the text.”1
Carr suggests that his inability to
focus may be the result of acclimating to the fast pace at which information streams across his computer
screen. Reading online blogs, news
6
headlines or email requires less concentration than reading a full-length
novel. On the computer, as soon as
my interest wanes, I simply click a
new link and I’m on to something
else.
There have been numerous
books, studies and articles written on this phenomenon, including (ironically) by Google—the
company claims it would like to
turn its search engine into a form
of artificial intelligence that would
know exactly what the user wants,
before the user does (Google Now
is already laying the groundwork).
It’s little wonder then, as we use
the so-called information highway
to educate ourselves and communicate, that we become less
and less accustomed to pondering,
analyzing and connecting pieces
of information as we used to do
when we read them on pages in a
book. Bruce Friedman, a pathologist from University of Michigan
Medical School describes his online
reading habits as being “staccato,”
in that he rapidly glances through
small sections of text from multiple
sources. “I can’t read War and
Peace anymore,” he told Carr in a
telephone interview. “Even a blog
post of three or four paragraphs is
too much to absorb.”
Tara Brabazon, in her book The
University of Google, describes the
challenges of teaching her university
students who seem to have lost the
ability to think deeply.2 She claims
that online lectures entice students
to merely download and read them,
rather than attending lectures in
person. By doing this, she argues,
something is lost when the face-toface contact ceases.
COMPETING WITH GOOGLE
So, how does this affect us as
health care professionals? Well,
your patients are almost certainly
“Googling” information about their
disease. Are they self-diagnosing
based on descriptions from the
Internet? Likely. Are you growing
impatient when having to slow
down to explain something and
undo incorrect assumptions again?
Undoubtedly.
These and others are challenges
we all face as technology changes.
This is not to say that the Internet
is evil; our lives are certainly richer
because of the instant access to
information. But let’s slow down
and remember that more often than
not humans still prefer face-to-face
contact. Your patients will thank
you when you look them in the eye,
patiently instruct them with handson methods and answer questions.
Everyone likes to know that they
are valued and worthy of your care
and concern. So, if you have managed to read to the end of this editorial, let me know your thoughts.
But don’t email or text me—pick up
the phone and let’s chat.
And the next time one of your
patients comes in armed with reams
of downloaded information from
the “University of Google” that
might be contrary to your advice,
just carefully listen and smile, as
only another person can. Besides,
we all know it’s probably just making them stupid!
RCCL
1. The Atlantic. Is Google Making us Stupid?
Available at: www.theatlantic.com/magazine/
archive/2008/07/is-google-making-us-stupid/306868/. Accessed April 19, 2015.
2. Brabazon T. The University of Google: Education in a (post) information age. Aldershot:
Ashgate, 2007.
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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Lens Care Insights
By Christine W. Sindt, OD, and Prashant Parekh, MD
A Different Kind of Colored Lens
Some medications can alter the ocular surface environment—and anything therein.
R
oughly three million
people over the age
of 50 in the United
States wear contact
lenses.1 This is also
the age when routine medication
use becomes a way of life for many
patients. So, how do systemic and
topical drugs alter the ocular surface
environment and the contact lens
wearing experience?
CHEMICAL COMPLICATIONS
Silicone hydrogel lenses are known
to interact stronger with lipids but
weaker with proteins compared
with conventional hydrogel lenses.3,4
Within this lens class, however, there
are differences in the absorption
and release rates of biocidal compounds.3
Lens characteristics that affect
drug absorption of a given molecular compound include water content, pore size, hydrophobicity and
ionic charge.2 For example, hypertonic solutions such as sodium sul-
facetamide 10% or pilocarpine 8%
can cause loss of lens water content
and alteration of the lens curvature.3
Application of topical medications
with an acidic pH can lead to lens
dehydration and steepening, while
use of alkaline medications can
cause hydration and flattening.3
Topical suspensions may also cause
lens intolerance due to a particulate
aggregation; this has been observed
with drugs containing salicylates,
which are secreted into the tear film
and can cause ocular irritation.3
PATIENT CARE
When evaluating a soft contact lens
wearer undergoing treatment for
an ocular or systemic condition,
take a careful history first, and pay
particular attention to irritative
symptoms as they relate not only to
lens maintenance and care, but also
to medications. Do the symptoms
improve or become compounded
by the removal of the lenses? This
may suggest lens absorption and/or
release of various agents.
Table 1. Chemicals That Cause Color
Next, perform an exChanges in Hydrogel and Silicone Lenses
amination with the lenses
in place and look for
evidence of steepening or
flattening. Consider your
findings in the context of
the patient’s medication
profile and use this data
to coordinate treatment regimens with the
patient’s other—if any—
health care providers.
Give special consideration to lens material
type and replacement
schedule when patients
are using concomitant
medications. For patients
SPECIAL DELIVERY
Interestingly, soft contact lenses are
being investigated as a vehicle for topical delivery of certain drugs, including
fluoroquinolones, cromolyn sodium,
ketotifen, ketorolac, cyclosporine,
dexamethasone, epidermal growth
factor, timolol and natamycin.4-7
In one study evaluating the use of
extended antibiotic-releasing lenses
to treat ocular infections, researchers
injected a methicillin-resistant strain
of Staphylococcus aureus into the
anterior chamber of rabbits to model
bacterial endophthalmitis.7 Treatment
with a topical fluoroquinolone reduced
the bacterial load from 100,000 in the
untreated group to 10,000; in comparison, immediate treatment with
experimental gatifloxacin-releasing
lenses prevented growth of microorganisms, thus providing an effective
potential treatment of perioperative or
trauma-related infection.7
who wear soft contact lenses, daily
disposable lenses may be the best
option, rather than trying to purge
drugs by soaking lenses overnight in
a contact lens solution. Gas permeable lenses typically will not have
the same absorptive rate as hydrogel
and silicone lenses. Keep in mind,
however, that each material is different, so the adsorption of drugs
cannot always be predicted.
RCCL
1. Swanson M. A Cross-Sectional Analysis of U.S.
Contact Lens User Demographics. Optom Vis Sci.
2012 Jun;89(6):839-48
2. Jones L, Powell CH. Uptake and release phenomena in contact lens care by silicone hydrogel
lenses. Eye Contact Lens. 2013 Jan;39(1):29-36.
3. Croker C. Contact Lens Interaction with Pharmaceutical Products and Cosmetics. www.eyesite.
co.za/magazine/december2004/columns1.asp?
mainbutton=columns&navbutton=columns1 Accessed Apr. 8, 2015.
4. Nichols J. Contact Lenses 2014. Contact Lens
Spectrum. 2015 Jan;30(1):22-27.
5. Hui A, Willcox M, Jones L. In vitro and in vivo
evaluation of novel ciprofloxacin-releasing silicone hydrogel contact lenses. Invest Ophthalmol
Vis Sci. 2014 Jul 15;55(8):4896-904.
6. Peng CC, Chauhan A. Extended cyclosporine
delivery by silicone-hydrogel contact lenses. J
Control Release. 2011 Sep 25;154(3):267-74.
7. Kakisu K, Matsunaga T, Kobayakawa S.
Development and efficacy of a drug-releasing
soft contact lens. Invest Ophthalmol Vis Sci.
2013;54:2551–61.
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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Pharma Science & Practice
By Elyse L. Chaglasian, OD, and Tammy Than, MS, OD
Cyclosporine — Not Just for Dry Eye?
Literature suggests this immunosuppressant may be suited to treat more conditions
than you might think.
C
yclosporine, a nonsteroidal immunomodulator that acts
primarily by inhibiting
T-cell proliferation, is
well known to all eye care practitioners. Formulated as an emulsion in
a concentration of 0.05%, this drug
is FDA-approved to increase tear
production in patients for whom it
is suppressed, presumably due to
ocular inflammation associated with
dry eye syndrome.1
As the theme of this month’s edition focuses on anti-inflammatory
pharmaceuticals, let’s discuss some
nontraditional uses of cyclosporine
and the use of medications off-label.
WHAT IS “OFF-LABEL”?
Before discussing the meaning of
“off-label,” we must first define
the term “on-label.” It describes a
specific use for which a drug has
satisfied safety and efficacy tests
and received FDA approval. It is
expensive and time-consuming for
pharmaceutical companies to obtain
multiple on-label drug indications;
trials can take seven to 10 years and
cost millions of dollars. Additionally, once a drug becomes generic,
motivation to obtain other on-label
indications decreases even further.
Once a drug is FDA-approved,
physicians often prescribe it for
conditions, population segments or
doses other than what it was approved for—all of which constitute
“off-label” use.2 For example, 75%
of prescription drugs have no indications for children, so off-label use
is often necessary. Pregnant women
and nursing mothers are also often
not included in drug studies.
8
Off-label use is generally legal; the
FDA even states, “Once a [pharmaceutical] product has been approved
for marketing, a physician may
prescribe it for uses in treatment
regimes of patient populations that
are not included in the approved
labeling.”3 However, practitioners
should inform themselves about
the drug prior to prescribing. The
acid test is whether the use meets
the “standard of practice” among
eye care practitioners.4 In any case,
regulations prevent manufacturers
from endorsing the off-label use.
KERATOCONUS
Elevated levels of proinflammatory
cytokines and matrix metalloproteinases (MMPs) have been shown
to be present in the tears of patients
with keratoconus. Corneal epithelial cells of keratoconic patients also
demonstrate upregulation of some
of these cytokines.5,6
In one study, keratoconus patients
were separated into a control group
and study group treated with cyclosporine 0.05% twice a day for six
months. Researchers found MMP-9
levels, which had been significantly
elevated at baseline, were reduced
to levels comparable to the negative
controls at the end of the study.
Interestingly, some patients who
received cyclosporine showed corneal topographic changes, including
focal flattening of corneal curvature,
after six months’ use. Others did
not manifest these changes, but
also didn’t show evidence of disease
progression. Researchers concluded
that cyclosporine may be an effective treatment strategy for patients
with keratoconus.7
CONJUNCTIVOCHALASIS
This condition manifests as loose,
redundant, nonedematous bulbar
conjunctival tissue; the presentation
is typically bilateral and usually
inferior. It may also occur nasally
and centrally, but is usually noted
temporally. The mechanism of onset
is thought to be thinning or loss
of Tenon’s capsule. Risk factors
include dry eye and a history of
ocular surgery. Patients with this
condition often present with focal
pain in the affected area that is
exacerbated with eye movement or
lid closure. This pain can often be
reproduced by applying pressure to
the eyelid using a finger. The patient
should then be directed to look up
and down.
Conjunctivochalasis often needs
to be differentiated from dry eye.8
Two recent epidemiological studies
in Chinese populations reported
prevalence rates of 44% and more
than 98%, respectively, in patients
older than the age of 60.9,10 Despite
the large discrepancy in these findings, conjunctivochalasis is common
in the elderly. A separate Chinese
study evaluated the impact this condition has on vision-related quality
of life using several standardized
questionnaires. Patients with conjunctivochalasis had a more significant decrease in tear film stability
compared to those with dry eye.11
Tear MMP-9 levels are elevated
in patients with conjunctivochalasis,
and surgical intervention decreases
inflammation.8 Others have proposed that the degeneration of the
elastic fibers might be worsened by
the presence of pro-inflammatory
cytokines such as IL-1ß, TNF-α,
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Conjunctivochalasis may respond to
topical cyclosporine.
IL-1 and IL-6.12,13 Because of the
presence of these inflammatory
components, conservative treatment of conjunctivochalasis should
include pharmacologic intervention.
In particular, cyclosporine may useful because of its inhibitory effect on
these proinflammatory cytokines.
Topical steroids and NSAIDs have
also been advocated. If meds prove
ineffective, surgical approaches also
exist for managing this condition
when moderate to severe.8
ADENOVIRAL
CONJUNCTIVITIS
Adenoviral conjunctivitis is a common and highly contagious infection. Following a two-day to 14-day
incubation period, initial signs
include conjunctival hyperemia and
edema. Keratitis may develop and,
after a period of two weeks in some
cases, subepithelial infiltrates (SEIs)
may appear. These infiltrates may
affect vision clarity, as they often
appear centrally. Histologically,
SEIs are composed of lymphocytes,
histiocytes and fibroblasts, which
may also disrupt collagen within
Bowman’s layer. These SEIs may
persist for months, or even as long
as a year.14
Three studies demonstrate that
cyclosporine is an effective treatment for SEIs associated with
adenoviral conjunctivitis.15-17 Two
of the studies evaluated a concentration of 1%, which is stronger
than what is commercially available
in the United States; however, this
concentration could be prepared by
a compounding pharmacy. Despite
this wrinkle, the findings from these
studies do warrant consideration of
cyclosporine for treating SEIs.
Note, there have been concerns
about the possibility of promoting
increased viral shedding due to the
use of cyclosporine, but by the time
the SEIs appear, viral shedding has
often ceased, so benefits ultimately
appear to outweigh the risks.18
OTHER POTENTIAL USES
In a small study (n=12), patients
with chronic, recalcitrant follicular
conjunctivitis were treated with
cyclosporine 1%. Researchers observed a reduction in inflammation
after one month of use; however,
because of the small sample size,
further investigation is warranted.19
Another small pilot study (n=20)
evaluated cyclosporine 0.05%
when administered to patients with
ocular prosthetics twice a day for
three months. All patients reported
marked improvement in their symptoms after one month, and Schirmer
tear test objectively improved at the
three-month follow-up.20
In conclusion, using the literature
to help guide the use of cyclosporine for off-label indications can
provide an additional approach to
managing inflammation with a safe
nonsteroidal alternate.
RCCL
1. US FDA. Restasis Highlights of Prescribing
Information. Available at: www.accessdata.fda.gov/
drugsatfda_docs/label/2013/050790s021lbl.pdf.
2. Fugh-Berman A, Melnick D. Off-label promotion,
on-target sales. PLoS Med. 2008 Oct ;28;5(10):e210.
3. Wilkes M, Johns M. Informed consent and
shared decision-making: a requirement to disclose
to patients off-label prescriptions. PLoS Med.
2008;11;5(11):e223.
4. Wilkes M, Johns M. Informed consent and shared
decision-making: a requirement to disclose to patients off-label prescriptions. PLoS Medicine 2008
Nov 11;5(11):e223.
5. Balasubramanian SA, Mohan S, Pye DC, et al.
Proteases, proteolysis and inflammatory molecules
in the tears of people with keratoconus. Acta Ophthalmol. 2012;90:e303–9
6. Lema I, Sobrino T, Duran JA, et al. Subclinical
keratoconus and inflammatory molecules from
tears. Br J Ophthalmol. 2009 Jun;93(6):820–4.
7. Shetty R, Ghosh A, Lim R, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited
by cyclosporine a. Invest Ophthalmol Vis Sci. 2015
Feb3;56(2):738-50.
8. Acera A, Vecino E, Duran J. Tear MMP-9 levels
as a marker of ocular surface inflammation in conjunctivochalasis. Invest Ophthalmol Vis Sci. 2013
Dec;54(13):8285-91.
9. Zhang X, Li Q, Zou H, et al. Assessing the severity of conjunctivochalasis in a senile population: a
community-based epidemiology study in Shanghai,
China. BMC Public Health. 2011 Mar; 11(198).
10. Mimura T, Yamagami S, Usui T, et al. Changes
of conjunctivochalasis with age in a hospital-based
study. Am J Ophthalmol. 2009 Jan;147(1):171-177.
11. Le, Q, Cui X, Xiang J, et al. Impact of conjunctivochalasis on visual quality of life: community
population survey. PLoS One. 2014 Oct 20;9(10).
12. Acera A, Rocha G, Vecino E, et al. Inflammatory
markers in the tears of patients with ocular surface
disease. Ophthalmic Res. 2008 Oct;40(6):315-21.
13. Latkany R. Dry eyes: etiology and management.
Curr Op Ophthalmol. 2008 Jul;19(4):287-91.
14. Yanoff M, Duker JS. Ophthalmology 4th Ed.
2014. Elsevier.
15. Jeng B, Holsclaw D. Cyclosporine A 1% eye
drops for the treatment of subepithelial infiltrates
after adenoviral keratoconjunctivitis. Cornea. 2011
Sept;30(9):958-61.
16. Levinger E, Slomovic A, Sansanayudh W, et al.
Topical treatment with 1% cyclosporine for subepithelial infiltrates secondary to adenoviral keratoconjunctivitis. Cornea. 2010 Jun;29(6):638-40.
17. Okumus S, Coskun E, Tatar M, Kavdu E, et al.
Cyclosporine a 0.05% eye drops for the treatment
of subepithelial infiltrates after epidemic keratoconjunctivitis. BMC Ophthalmol. 2012 Aug;12(42).
18. Romanowski E, Pless P, Yates K, Gordon Y.
Topical cyclosporine A inhibits subepithelial immune infiltrates but also promotes viral shedding
in experimental adenovirus models. Cornea. 2005
Jan;24(1):86-91.
19. Kolomeyer A, Nayak N, Ragam A, et al. Topical
Cyclosporine A 1% for the Treatment of Chronic
Follicular Conjunctivitis. Eye Contact Lens. 2014
Dec 10 [epub ahead of print.]
20. Han J, Yoon J, Jang S. Short-term effects of
topical cyclosporine A 0.05% (Restasis) in longstanding prosthetic eye wearers: a pilot study. Eye.
2014 Oct;28(10):1212-17.
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1 CE
Credit
(COPE Approval
Pending)
KEEPING THE
CORNEA CLEAR
While a complex, remarkable system with a tough line of defense,
the cornea sometimes needs a little help from practitioners.
By Bhawanjot Minhas, OD
T
he body’s efforts to
regulate the immune
status of the ocular
surface, in particular
the cornea, present a
unique challenge not found in other
tissues. Maintenance of corneal
transparency must counterbalance
preservation of corneal integrity.
Defense against microbial, inflammatory and physical assault, including that which results from contact
lens wear, is limited by the deleterious effects inflammatory events may
have on the vulnerable structures of
the eye. A highly ordered extracellular matrix of collagen and proteoglycans free of vasculature and
extraneous cells accomplishes maximal light transmission, and consequently visual function. Changes to
this complex structure can irreversibly harm the function of the cornea
as a primary refractive surface and
structural barrier of the eye.
For clinicians who routinely see
cases of corneal inflammation and
would like to better understand the
complex processes responsible and
how to tailor treatment most appropriately, a refresher on the principles
of corneal immunology can be
enlightening—as well as one more
reminder of the elegance of the eye’s
robust capabilities to defend and
heal itself.
10
INNATE MECHANISMS
The anatomy of the cornea consists of five well-known layers: the
epithelium, Bowman’s layer, stroma,
Descemet’s membrane and endothelium. The cornea is essentially a
thick layer of transparent connective tissue lined with a single layer
of endothelial cells on one side and
a four-to-six-layer-thick stratified,
nonkeratinized squamous epithelium on its outer border.1
The corneal epithelium and
associated intercellular junctional
complexes provide an important
first-line innate defense. Gap junctions allow intercellular communication, while tight junctions and
adherens junctions maintain a vital
epithelial barrier from the external
environment, forcing material to
go through the cells rather than
between them.2
Ocular defensive mechanisms
are comprised of both innate and
adaptive immune responses, which,
while considered separate entities,
are not mutually exclusive.3 The innate defenses of the cornea include:
tears, epithelial cells, keratocytes,
corneal nerves, complement components, neutrophils, eosinophils,
macrophages and natural killer
cells. Tears are the first part of this
nonspecific surveillance system that
an antigen may encounter.
In addition to preventing corneal
desiccation, the tears flush foreign
matter from the ocular surface and
contain antimicrobial proteins and
immunoglobulins.3 Three antimicrobial proteins exist in the tears:
lactoferrin binds iron, lysozyme destroys bacterial cell walls and tearspecific prealbumin (lipocalin) acts
as a bacterial product scavenger.4
Corneal epithelial cells are capable of secreting cytokines to activate
immune defense against microbial
invasion. One such product is the
cytokine interleukin (IL)-1α, which
is stored and released by epithelial
cells in response to cell membrane
damage.5 Consequently, keratocytes
can also secrete IL-1α; however,
only epithelial cells can secrete
a natural antagonist of immune
activity, IL-1α receptor (IL-1RII).6
This instance outlines perfectly
the corneal balance of secreting
inflammatory mediators that cause
immune invasion and neovascularization (IL-1α) vs. a mechanism to
modulate these effects (IL-1RII) by
ABOUT THE AUTHOR
Dr. Minhas is currently
full time faculty at Salus
University in Philadelphia, where she works
with both the traditional
Optometry program and
the Scholars Program.
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suppressing leukocyte infiltration
and potential destruction.7
Part of the cornea’s strategy to
stay clear and act as an adequate
refractive surface is to be void of
inessential cells. Keratocytes are
flattened fibroblasts found in the
stroma that are active in synthesizing stromal collagen and proteoglycans of the ground substance.8
Keratocytes can synthesize IL-6
and defensins under the influence
of IL-1α and tumor necrosis factor (TNF)-α, which is secreted by
natural killer (NK) cells.9,10 IL-6
is produced by Th2-lymphocytes,
monocytes, macrophages and
dendritic cells. It enhances proliferation of B- and T-lymphocytes via
the route of MIP-1a and MIP-2.11,12
Defensins have broad-spectrum
antimicrobial activity against
bacteria, fungi and viruses, can accelerate epithelial healing, and are
chemotactic for T-lymphocytes and
numerous granulocytes.12
Although free of blood vessels,
the cornea has a well-developed
innervation. Corneal nerves not
only relay sensory information from
the cornea to cause reflexive and
protective movements of the eye,
but also cause release of neuropeptides that induce cytokine activity.13,14 Neuropeptides, substance P
and calcitonin gene-related peptide
are released in response to pain by
termini of corneal sensory neurons
and induce IL-8 synthesis, leading
to neutrophil recruitment.13,14
The complement system consists
of the classical, lectin and alternate
pathways. All complement components are more concentrated in the
peripheral cornea rather than the
central cornea. This discrepancy
is likely caused by easy diffusion
of complement components from
the conjunctiva limbal vessels to
peripheral cornea, as opposed to the
avascular central cornea.15
Cells of the innate system consist
of neutrophils, eosinophils, macrophages and NK cells. These cells
are extremely important in protecting the cornea from invasion by
microorganisms and are recruited
in response to foreign antigens;
however, if left unchecked, they
can affect normal function of the
corneal epithelial cells, keratocytes
and endothelial cells.16 This excessive inflammatory response, which
is attributed to neutrophils for the
most part but also macrophages
to a lesser extent, can lead to loss
of corneal integrity and clarity.16
The severity of the inflammation
depends on the type and duration of
the trauma and microbial products.
Neutrophils are found near limbal vasculature, while macrophages
reside in the conjunctiva and in
murine corneal stroma.17 Although
eosinophils are not normally present in the conjunctiva, they are
over-expressed in chronic ocular
allergies, paraneoplastic syndromes
and parasitic infections.18,19 NK cells
are part of the lymphocyte lineage,
which include B- and T- lymphocytes, but are a part of the innate
immune response.7
ADAPTIVE MECHANISMS
Cell-mediated immunity, although
critical in bringing pathogenic
invaders under control, can be out
of proportion to the antigen threat
and can lead to irreversible tissue
destruction and potential permanent vision loss. Much of the adaptive immune response in the cornea
Release Date: May 2015
Expiration Date: May 1, 2018
Goal Statement: This course reviews the
cornea's innate and adaptive mechanisms of
defense and the processes that lead to clinical manifestations of corneal inflammation.
Faculty/Editorial Board:
Bhawanjot Minhas, OD
Credit Statement: COPE approval for 1 hour
is due to Langerhans cells and
cytokines. B- and T-lymphocytes,
along with other antigen presenting
cells, are present in normal human
cornea in small numbers as part
of adaptive immunity.12 Like other
innate immunity cells, these are concentrated in the vascularized limbal
region.12
Many studies focus on the role of
corneal epithelial cells in responding
to threat; however the existence of
Langerhans-like dendritic cells in
the cornea is important and should
not be overlooked. Langerhans
cells are often concentrated in the
corneal periphery, but are expressed
in higher density in the sub-basal
nerve plexus of the epithelium in
contact lens wearers as seen in vivo
by a confocal microscope.20
This finding suggests that an
increase in density of Langerhans’
cells occurs as a heightened immune
status of the cornea in potential
“high risk” corneas.20 Furthermore,
research shows lateral movement
of these cells increases from resting state during injury through
time-lapse imaging.21 This lateral movement and recruitment of
Langerhans cells to an otherwise
quiet central cornea is inhibited by
IL-1RII, which as described above is
secreted by corneal epithelial cells to
help maintain corneal clarity.22
Immature Langerhans cells capture antigens, while mature forms
are able to activate native T-lymphocytes through major histocompatibility complex (MHC) molecules. Sentinel Langerhans cells are
of continuing education credit is pending
for 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.
Disclosure Statement: Dr. Minhas has no
relevant financial disclosures.
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KEEPING THE CORNEA CLEAR
Confocal microscopy of the cornea. Far left: a normal non-inflamed cornea; note the presence of corneal nerves.
Center: a mild dendritic invasion in an allergic cornea. Far right: a network of dendritic cells in viral keratitis.
resident antigen-presenting cells and
are responsible for recognizing, processing and presenting antigens.7,12
Traditionally, Langerhans cells have
been thought to have MHC class II
antigens. However, recent studies
show a class of MHC class II-negative cells in murine models.23
Langerhans cells identify an
antigen as non-self and migrate
to a regional lymph node, process
the antigen, transport and express
it on their cell surface by MHC
molecules.12,24 T- lymphocytes are
activated by the antigen and mature
into effector cells: either CD4+, if
the MHC molecules presenting the
antigen are class II, or CD8+, if the
MHC is class I.24 These activated
CD8+ cytotoxic cells directly kill
the invading microorganism while
the CD4+ helper cells secrete cytokines to recruit effector cells such as
microphages.12,24
TOLL-LIKE RECEPTORS
Toll-like receptors (TLRs) play a
critical role in pathogen recognition.
As such, they are the initial step
in the inflammatory process and
innate response. The TLR family is
a class of membrane-spanning noncatalytic receptors that recognize
a wide variety of exogenous and
endogenous molecules, including
protozoa, bacteria and viruses.16,21
More than 10 TLRs that can recognize pathogenic lipids, proteins or
nucleic acids have been identified
12
in humans.21,25 Of note: TLR4, the
most complex member of the family, acts as a sensor for gram-negative bacteria by recognizing the lipid
A part of lipopolysaccharide.21,25
TLRs are expressed in both
non-immune (epithelial, endothelial
cells) and immune cells (monocytes,
antigen presenting cells, lymphocytes, mast cells, neutrophils, NK
cells and eosinophils).12,16,21,25 Many
of the TLRs have been recognized
as responding to a particular ligand
via the pathogen-associated molecular patterns (PAMPs). These are
conserved structural moieties of the
pathogen essential for its survival
and are excellent markers for the innate immune system to recognize.25
In keratitis, the role of toll-like
receptors begins with the exposure
of the PAMPs to their respective
TLRs; the receptors activate intercellular signals via adaptor molecules, including myeloid differentiation factor 88 (MyD88) and TIR
domain-containing adaptor inducing IFN-α (TRIF).25 The activation
of these adaptor molecules initiates
downstream signaling events that
induce translocation of DNA binding proteins NFα and IRF-3 and
production of proinflammatory
and chemotactic cytokines known
as CXC chemokines. The CXC
chemokines, namely IL-1α, IL-1α,
TNF-α and IL-6, cause macrophage
and neutrophil infiltration into the
central cornea.25
As expected, if this inflammatory
response is severe, there is a serious
loss of corneal clarity due to excessive edema. This potentiates for
permanent vision loss as governed
by the severity and duration of
exposure to the PAMPs.
LYMPHOID TISSUE
No lymphoid cells reside in the
central cornea. As such, the cornea
relies heavily on the conjunctiva as
a major support tissue for moisture, nutrition and defense. The
conjunctiva is separated into six
zones, starting from the lid margin:
marginal, tarsal, orbital, fornical,
bulbar and limbal.26
The ocular surface is thought of
as part of the mucosal immune system and consists of lymphoid tissue
of the lacrimal gland, conjunctivalassociated lymphoid tissue (CALT)
and lacrimal drainage-associated
lymphoid tissue (LDALT).26 Together, these are known as eyeassociated lymphoid tissue (EALT),
which encompasses lymphoid tissue
continuous from the lacrimal gland,
conjunctival zones and lacrimal
drainage system. They are functionally connected by the flow of
tears over these surfaces.26 Inflow
and outflow occurs via specialized
blood vessels and lymph vessels,
respectively. Follicles in CALT and
LDALT allow detection of surface
antigens, which then recruit effector
cells to the ocular surface.26
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The tarso-orbital topographical
zone of EALT has proven to be
extremely important in immunity of
the cornea and corresponds to the
position of the cornea during eye
closure.26 Not only does it act as an
“immunological windscreen-wiper”
during blinking, but it also plays a
role during sleep as an “immunological cushion” of the cornea in a
compromised (closed-eye) state.26
The immunosurveillance provided by the EALT is thought to
correspond to afferent and efferent
function. The afferent immunity
occurs due to the direct contact of
the EALT with the corneal surface.
This suggests that EALT can assist
in detection of corneal antigens and
the appropriate immune response.26
Efferently, EALT can provide innate
and specific antibacterial peptides,
proteins and immunoglobulins,
namely immunoglobulin A. IgA
is not produced by the cornea but
rather by the lacrimal gland and
conjunctiva.26 This is particularly
important in the closed eye model,
where pro-inflammatory factors
from neutrophils are upregulated
to quell microbial growth during
sleep.12,27,28
MODULATED IMMUNITY
Maintaining corneal clarity is critical to visual function, but must not
come at the expense of adequate defense of the ocular surface. As such,
the main function of the innate
and adaptive immune systems is to
balance tolerance against numerous
nonpathogenic antigens while still
protecting the ocular surface from
pathogenic substance. This equilibrium of local immune regulation to
maintain corneal integrity is illustrated by the production of different
types of effector T- lymphocytes
(Th1- or Th2- type helper cells).26
A difference in corneal inflammation is seen in a contact lens-
associated Pseudomonas aeruginosa
infection, for example, where a
Th1 predominant response causes
more extreme damage than a Th2
reponse.26 This shows the difference
that the severity of inflammation
can have on corneal integrity and
clarity. If the generation of immune
tolerance is impaired in extreme
inflammatory cases, uncontrolled
antigen access, excessive cytokine
release and deregulated lymph cell
recruitment can lead to corneal infiltration, edema, severe destruction
and permanent vision loss.
CORNEAL FIBROSIS
Transparency of the extracellular
matrix (ECM) of the stroma is accomplished via specifically regulated
collagen fibril size, growth and
spacing. This precise size and spacing of collagen and proteoglycans
is maintained by resident keratocytes.29 When an incidental trauma
affects the stroma, keratocytes
become hypercellular myofibroblasts that can progress to wound
fibroblasts or myofibroblasts.29
Return to normal stromal structure vs. scar formation is dictated
by which fibroblast predominates.
Wound fibroblasts along with
growth factors IGF-I and IGF-II
are responsible for well-organized
ECM, which allows the cornea to
return to transparency. On the other
hand, myofibroblasts and trans-
forming growth factor (TGF-α)
cause the formation of a scar. This
fibroblast differentiation is mediated
by cytokines released during the
inflammatory response.12,29
CONTACT LENSES STRESS
Contact lens wear can cause numerous physiological changes in the
cornea; however, the biggest hindrance to corneal clarity comes in
the form of stromal edema. Oxygen
can only diffuse through the material of a lens or dissolve in the tears
and pass around the edges to the
post-lens space. As a result of this,
hypoxic corneal swelling in contact
lens wears is mainly governed by
oxygen transmission (Dk/t).
An important consequence of
hypoxia is the production of lactate
due to an increase in anaerobic glycolysis by the cornea in a decreased
oxygen state.30,31 Accumulating
negatively charged lactic acid alters
the osmotic gradient; endothelial
pumps cannot maintain a water
gradient from the cornea to the
anterior chamber, which creates
stromal swelling.30,31 Anything that
interferes with pH can also be a
confounding factor. Built-up lactate
or contact lens wear can cause an
increase in carbon dioxide, which
can interfere with the carbonic
anhydrase function of the endothelial pump.30 Furthermore, blebs
may form on the endothelium 20
Left: Subepithelial corneal infiltrates in epidemic keratoconjunctivitis. Right:
a lens-related infiltrate located 10:30 mid-peripheral cornea in a patient with
contact lens-related acute red eye.
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KEEPING THE CORNEA CLEAR
Sodium fluorescein staining of corneal abrasion (far left) and complete
resolution of the cornea without scar formation three days later (center),
outlining modulation of corneal immunity to maintain clarity. Compare this to
the severe visual determent seen in band keratopathy (far right).
to 30 minutes after a contact lens
is placed on the eye.20,30 These are
postulated to occur due to corneal
acidosis and hypoxia and affect
endothelial pumps.31
Contact lenses can trigger and
change the immune response of
the ocular surface. Studies show
that exposure of epithelial cells
to contact lenses in vitro blocks
the upregulation of defensins in
response to P. aeruginosa, leading
to increased susceptibility to the
microbe.32
Other studies with confocal microscopes indicate specific changes
to the anterior eye in vivo. One such
change involves mucin balls, which
are seen often in silicone hydrogel cases and have been shown to
penetrate the full thickness of the
epithelium.20 This can cause activation of keratocytes in the underlying stromal layer and possibly
predispose the cornea to infection.20
Keratocyte apoptosis has been
noted, which explains contact lensinduced stromal thinning. Mechanical stimulation by the lens itself can
cause inflammatory mediators to
be released.20 Finally, an increase
in leukocyte rolling, a hallmark of
inflammation, is seen in limbal vessels in response to low Dk/t lenses,
indicating higher susecptibility.20
With constant exposure to both
pathogenic and non-pathogenic organisms, the ocular defense system
has no other choice but to sustain
14
an elaborate mechanism for protection. Although often overlooked,
this delicate balance of modulate
immunity while maintaining corneal
integrity is key to understanding
pathologies that involve this unassumingly transparent yet elegant
structure.
RCCL
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St. Louis, MO: Mosby, 2008. 203-208.
2. Bron AJ, Tripathi DM, Tripathi BJ. Wolff’s
Anatomy of the Eye and Orbit. London: Chapman
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3. Mannis MJ, Smolin G. Natural defense mechanisms of the ocular surface. In: Pepose JS, Holland
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6. Cubitt CL, Lausch RN, Oakes JE. Synthesis of
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7. Akpek EK, Gottsch JD. Immune defense at the
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9. Cubit CL, Lausch RN, Oakes JE. Differences in
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10. Gottsch JD, Li Q, Ashraf MF, et al. Defensin
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Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci, 2002. 43: 639-646.
24.Unanue ER. Perspective on antigen processing
and presentation. Immunol Rev, 2002. 185: 86-102.
25.Kumar A, Fu-Shin XY. Toll-like receptors and
corneal innate immunity. Curr Mol Med, 2006.
6(3): 327-37.
26.Knop E, Knop N. The role of eye-associated
lymphoid tissue in the corneal immune protection. J. Anat, 2005. 206:271-85.
27.Sack et al. Changes in the diurnal pattern of
the distribution of gelatinases and associated
proteins in normal and pathological tear fluids:
evidence that the PMN cell is a major source of
MMP activity in tear fluid. Adv. Exp. Med, 2002.
506: 539-45.
28.Sack et al. Host-defense mechanism of the
ocular surface. Bioscience Reports, 2001. 21 (4):
463-80.
29.Hassell JF, Birk DE. The molecular basis of
corneal transparency. Experimental Eye Research
91, 2010. 326-35.
30.Bonanno JA. Effects of contact lens-induced
hypoxia on the physiology of the corneal endothelium. Optometry and Vision Science, 2001.
78(11): 783-90.
31.Papas EB. The significance of oxygen during
contact lens wear. Contact Lens & Anterior Eye
37, 2014. 394-404.
32. Maltseva IA. Exposure of human corneal epithelial cells to contact lenses in vitro suppresses
the upregulation of human -defensin-2 in response to antigens of Pseudomonas aeruginosa.
Experimental Eye Research 85, 2007. 142-153.
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CE TEST ~ MAY 2015
EXAMINATION ANSWER SHEET
Keeping the Cornea Clear
1. Corneal properties to keep the visual axis clear include all of the following
except:
a. A lack of blood vasculature.
b. Highly ordered matrix of collagen and proteoglycans.
c. A wide variety and supply of extra cells for protection.
d. Endothelial pumps to minimize corneal edema.
2.
a.
b.
c.
d.
Lactoferrin is found in the tears and acts as an antimicrobial protein by:
Binding iron.
Acting as a scavenger for bacterial byproducts.
Destroying bacterial cell walls.
None of the above.
3. The balance between protecting corneal integrity and maintaining clarity is
exemplified by the interaction between:
a. MIP-1a and MIP-2.
b. IL-1α and IL-1RII.
c. TNF and IL-8.
d. MyD88 and TRIF.
4.
a.
b.
c.
d.
Toll-like receptors are expressed in:
Neutrophils.
Epithelial cells.
Eosinophils.
All of the above.
5. Which zone of eye-associated lymphoid tissue (EALT) has been shown to correspond to the position of the cornea during sleep?
a. Tarsal.
b. Orbital.
c. Limbal.
d. Both (a) and (b).
6. All of the following are involved in restoring corneal transparency following
injury except:
a. Myofibroblasts.
b. IGF-I.
c. Wound fibroblasts.
d. IGF-II.
7.
a.
b.
c.
d.
How long after insertion of a contact lens on the eye may blebs form?
1 hour.
4 days.
20 minutes.
1 week.
8. Substance P and calcitonin are released by corneal nerves in response to pain.
They recruit neutrophils with the help of:
a. IL-2.
b. TNF-α.
c. IL-8.
d. MyD88.
9.
a.
b.
c.
d.
In contact lens wearers, leukocyte rolling has been noted in response to:
Large contact lens diameter.
Steep base curve.
Silicone hydrogel material.
Low Dk/t.
10. Corneal stromal swelling and loss of endothelial pump function has been
shown to be related to all of the following except:
a. Contact lens wear.
b. Presence of lysozyme.
c. Changes in pH.
d. Lactic acid build-up.
Valid for credit through May 1, 2018
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
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Credit: COPE approval for 1 hour of CE credit is pending for this course.
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Processing: There is an eight-to-10 week processing time for this exam.
Answers to CE exam:
A
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B
C
3.
A
B
C
4.
A
B
C
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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
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LESSON 111326, RO-RCCL-0515
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HOW
ANTI-INFLAMMATORY
AGENTS
WORK
I
nflammation—we’ve all
seen this quintessential
part of the body’s defense
network in action,
whether due to a serious
infection or simply a stubbed
toe. The inflammatory process
is an immunovascular response
involving immune cells, blood
vessels and molecular mediators
designed to first eliminate the
initial cause of cell injury, then
remove any necrotic cells or
damaged tissues and initiate
tissue repair. Its effectiveness
requires a delicate balance:
insufficient inflammation can lead
to progressive tissue destruction
by the harmful stimulus (e.g.,
bacteria) and compromise the
survival of the organism, while
chronic inflammation can result
in loss of tissue function, chronic
pain and scarring.
In effect, the concept of inflammation as both a normal, protective physiologic process and as
a pathologic damaging process
embodies what’s known as the
Goldilocks principle: too little and
too much are bad; it must be “just
right.” So, how can we as eye care
practitioners achieve this equilibrium in an environment as complex
as the eye?
16
Understanding corticosteroid and
NSAID mechanisms can help you
to choose and use them wisely.
An expert explains.
By Bruce E. Onofrey, OD, RPh
CORTICOSTEROIDS
Considered the “Swiss army
knives” of inflammation control,
corticosteroids act as palliative
treatment for a host of inflammatory disorders (e.g., uveitis,
episcleritis and scleritis) and
adjunctive therapy for inflammation associated with injury and
infection. Patients suffering from
rheumatoid, arteritic, atopic and
allergic diseases may also benefit
from steroid therapy.
Two primary types of corticosteroids exist: ketones (prednisolone,
dexamethasone, fluorometholone, medrysone and rimexolone)
and esters (loteprednol). Ketone
steroids depend upon liver metabolism to become inactive, while
ester steroids do not; instead, they
are inactivated locally by a single
hydrolytic step. Hydrolysis, from
Greek hydro- (“water”) and lysis
(“separation”), means the cleavage of chemical bonds by the addition of water. Because the rapid
cleavage of ester steroids produces
inactive metabolites, these drugs
are classified as “soft” steroids.
Clinically, this results in a lower
incidence of steroid glaucoma
(10% less with use of loteprednol
0.5%) and a lower incidence of
steroid cataract.
Ultimately, the therapeutic goal
of corticosteroid use is resolution of the inflammatory response
without any adverse ocular or
systemic effects, steroid withdrawal symptoms or effect on normal
production of endogenous glucocorticoids. As such, if the diagnosis, dosage or drug is incorrect,
the use of these potent drugs can
lead to consequences that can be
both life- and sight-threatening.
Additionally, while topical
steroids are effective to treat
superficial or anterior segment
inflammation, systemic treatment
is necessary to treat diseases of
the orbit or posterior segment, as
well as arteritic conditions. Thus,
as the optometrist’s prescriptive
authority expands to include
systemic drugs, one must understand both the physiology of the
endogenous corticosteroids and
pharmacology of their synthetic
analogs in order to fully use these
ABOUT THE AUTHOR
Dr. Onofrey is a clinical professor
and executive director
of continuing education
programs at the University
of Houston. He is also an
internationally recognized
lecturer on pharmaceutical agents
and ocular disease management.
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Phospholipid Membrane
Cyclooxygenase
Thromboxanes
Lipoxygenase
Prostaglandins
Leukotriene B4
Leukotriene C4, D4, E4
Fig. 1. The arachidonic cascade in inflammation.
agents in a successful anti-inflammatory regimen. This understanding must then be applied
when selecting the most effective
product and dosing regimen to
appropriately treat the patient's
condition. The optometrist should
also be able to establish clinical
monitoring parameters to identify
adverse or toxic reactions and
significant drug-to-drug interactions with respect to corticosteroid
therapy.
• Method of Action. Corticosteroids work at all points of the
immune system to inhibit humoral
Table 1. Adverse
Corticosteroid Effects
Extended exposure to high-dose
systemic corticosteroids produces:
Weight gain
Hypercalcemia
Baldness
Anxiety
Truncal obesity
Acne
Impotence
Depression
Hump back
Hirsutism
Amenorrhea
Dry, brittle hair
Moon face
Hyperhidrosis
Psychosis
Skin discoloration
(i.e., antibody production) and
cell-mediated (i.e., late-phase
cellular response) immune responses, as well as the production
of phospholipase A, which leads
to a reduction in the body’s major
inflammatory cytokines, prostaglandins and leukotrienes (Figure
1). For example, in rheumatoid arthritis, the body’s immune system
produces an abnormal form of
the IgM antibody via plasma cells
that attack normal IgG antibodies.
This process eventually results in
the inflammatory tissue damage
that we see in rheumatoid disease
as well as in ocular conditions
like uveitis, scleritis and episcleritis. Steroids inhibit plasma cell
production of IgM, thus inhibiting inflammation. Additionally,
leukotriene production can attract
T-lymphocytes that are responsible, in part, for late-phase chronic
inflammation, so reducing these
cytokines can limit chronic inflammation.
When stress or other neural
stimulation is placed on the
hypothalamus, cortocotropin-
releasing factor (CRF) is released,
which acts on the anterior pituitary gland to stimulate the release
of adrenocorticotropic hormone
(ACTH). ACTH then acts as an
agonist on cells of the adrenal cortex, causing the production of the
glucocorticoid cortisol. As blood
cortisol levels rise, they inhibit
production of CRF by the hypothalamus, thus inhibiting excessive
cortisol production. This is called
the negative feedback loop.
Both endogenous systemic
cortisol and exogenously administered synthetic glucocorticoids will
Table 2. Relative
Steroid Potency
Hydrocortisone 20mg is eqivalent in
potency to:
Betamethasone .............................0.6mg
Dexamethasone ......................... 0.75mg
Paramethasone..................................2mg
Methylprednisolone ........................4mg
Triamcinolone ....................................4mg
Prednisone ..........................................5mg
Prednisolone ......................................5mg
Cortisone .......................................... 25mg
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HOW ANTI-INFLAMMATORY AGENTS WORK
produce adrenal glucocorticoid
suppression; thus, use of corticosteroids for more than a few
weeks can lead to adrenal suppression and adrenal atrophy (i.e., Addison’s disease). Long-term use of
systemic corticosteroids can also
lead to Cushing’s syndrome (Table
1). Topical ophthalmic steroids,
however, do not produce these
adverse effects.
• Glucogorticoid vs. Mineralocorticoid Effect. Cortisol
(hydrocortisone), the primary
glucocorticoid produced by the
adrenal cortex, is responsible for
carbohydrate metabolism. Its
overproduction or pharmacologic
use may result in hyperglycemia or
glucose intolerance. Aldosterone
is the major mineralocorticoid,
and plays a role in the retention of
salt and water to maintain proper
fluid/electrolyte balance and blood
pressure. Synthetic corticosteroids
vary in their relative balance of
mineralocorticoid and glucocorticoid effects; however, because
all synthetic glucocorticoids can
produce some degree of water and
salt retention and hyperglycemia,
they should be used cautiously
in cardiovascular and diabetic
patients.
Most of the common oral synthetic corticosteroids have similar
glucocorticoid/mineralocorticoid
activity, with the main difference
being potency. Dosage is calculated based on steroid equivalents,
with 20mg of cortisol acting as the
baseline dose to which all other
glucocorticoid potency is compared (Table 2).
• Ocular Use. The ocular
properties of corticosteroids are
different in some aspect from their
systemic counterparts. The ocular
version must be in an active form,
since it is applied topically and
will not undergo hepatic metabo-
18
Table 3. Ocular Indications
For Corticosteroids
Allergic conjunctivitis/blepharitis
Superior punctate keratitis
GPC/VKC/AKC
Posterior uveitis
Contact dermatitis
Juvenile xanthogranuloma
Immune graft rejection
Sympathetic ophthalmia
Optic neuritis
Ocular burns
Cranial arteritis
Episcleritis/scleritis
Graves disease
Rosacea keratitis
Phlectenular keratoconjunctivitis
Ocular pemphigus
Orbital pseudotumor
Iritis/iridocyclitis
Marginal corneal ulcers
Trabeculitis
Inflammatory complications
Interstitial keratitis of herpetic disease
Retinal vasculitis
Epidemic keratoconjunctivitis
Infiltrative keratitis
lism before reaching site of action.
Additionally, it must be capable
of penetrating corneal tissues and
must possess adequate potency
to significantly reduce the local
inflammatory response.
Table 3 lists many of the most
common ocular conditions that respond to topical and, if necessary,
systemic corticosteroid therapy.
These agents are particularly effective in the palliative treatment of
allergic conjunctivitis or keratoconjunctivitis, and any noninfectious inflammatory condition in
the eye because they are able to
affect the immune system at so
many levels (i.e., inhibition of cytokines, antibody production and
T-cell and eosinophil migration).
If the issue is a result of bacterial infection, which can be
adequately treated with antibiotic
therapy, adjunctive corticosteroid
therapy may be used. Note that
the concomitant use of corticosteroids within an antiviral agent in
the treatment of herpes simplex
keratitis is more controversial
because their use is limited to
disciform keratitis and contraindicated for active dendritic disease
in particular.1 Additionally, corticosteroids should not be used in
fungal infections, since the steroid
may worsen infection.
When inflammation is due to
allergens, the offending stimulus
should first be removed if possible.
Mast-cell inhibitors or antihistamines can be used to prevent
further reaction.
• Sizing Up the Corticosteroid
Options. When choosing a topical steroid, consider which one
has the lowest effective dosage,
longest dosing interval and the
shortest duration of therapy to
prevent adverse effects and allow
for discontinuation without withdrawal symptoms or flare-up of
the disease. However, overall the
specific corticosteroid product and
dosage should be chosen based
on the severity of inflammation
(Table 4).
Prednisolone acetate 1% is the
most active ocular corticosteroid,
and should be the drug of choice
when maximal anti-inflammatory
effect is required: a dosage of one
drop every minute for five minutes each hour has been shown to
decrease ocular inflammation by
72%, as compared to a decrease
of 51% with hourly dosing and
11% with doses every four hours.2
This suggests that cumulative
dose increases activity of the antiinflammatory effect of the agent
when applied topically.
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75% of those receiving prednisone
equivalent to more
than 15mg per day
developed cataracts. None of the
six patients receiving less than 10mg
per day of prednisone and none of
the nine patients
receiving steroids
for less than one
year developed
cataracts.
PSCs resulting
from topical use
Topical steroids are a mainstay therapy for inflammatory
are similar in pre- conditions like iritis.
sentation to those
ers observed a mean IOP increase
caused by systemic drugs. Most
from 16.9mm Hg to 32.1mm Hg
reports of PSC are secondary to
in the 44 patients with primary
topical ocular corticosteroids that
open angle glaucoma and a mean
have been administered for more
increase from 17.1mm Hg to
than six months.
28.3mm Hg in the 32 glaucoma
Corticosteroids have also been
suspects. The 30 normal subjects
shown to increase IOP. A study
had a mean pressure increase
evaluating 14 known corticostefrom 13.6mm Hg to 18.2mm Hg.8
roid responders identified IOP
A second study completed later
increases of 4.4mm Hg to 8.1mm
indicated that IOP increase as a
Hg with fluorometholone 0.25%
reaction to corticosteroids may be
suspension compared to 8.1mm
genetically determined; specificalHg to 11.6mm Hg with dexaly, it is possible that primary open
methasone sodium phosphate
angle glaucoma patients are hosolution 0.1%.7
mozygous carriers of a glaucoma
A separate study compared the
gene, non-glaucoma responders
effects of betamethasone 0.1%
combined with sulfacetamide 10% are heterozygous for the glaucoma
on IOP in three groups of patients gene and non-responders are
homozygous for the normal (i.e.,
treated with a single drop QID
non-glaucoma) gene.9
for up to two months. Research-
Photo: Christine W. Sindt, OD
One of the newer high-potency
topical steroids is difluprednate
0.05% (Durezol, Alcon), which
has been demonstrated to have
an efficacy comparable to that
of prednisolone acetate 1% in
anterior uveitis.3 One benefit of
Durezol is that it does not need
to be shaken, as it is an emulsion;
however, prednisolone acetate is
available in a much lower-cost
generic formulation. Both drugs
raise intraocular pressure (IOP)
and increase the risk of cataract
formation.
• Steroid Complications. In
general, due to high receptor
affinity and rapid inactivation,
the likelihood of steroid-linked
cataract formation and glaucoma
is significantly decreased. Steroid
response to loteprednol is less
than 3%, according to an FDA
comparison of loteprednol 0.2%
(Alrex) and 0.5% (Lotemax, B+L)
to prednisolone acetate 1%. The
study measured the incidence of
an increase in IOP>10mm Hg over
a 28-day period; prednisolone
acetate raised IOP in 7% of tested
patients.4
The use of corticosteroids has
been linked to cataract formation
in patients with rheumatoid arthritis. A study in 1961 at the National Institutes of Health (NIH)
found 17 of 47 patients with
rheumatoid arthritis who received
prednisone for more than one
year developed cataracts, compared with none in the 19 patients
who did not receive the steroids.5
Specifically, posterior subcapsular
cataracts (PSC) were observed in
36% of patients treated with steroids for one to four years and in
69% of patients treated for more
than four years.6 With respect to
different dosages of prednisone,
23% of patients treated with a
dose 10mg to 15mg per day and
Table 4. Relative Topcal Ocular Anti-Inflammatory Steroid Efficacy
(When Corneal Epithelium is Intact)
Drug ...............................................................................................Decrease in Inflammation
Prednisone acetate 1% ......................................................................................................... 51%
Dexamethasone alcohol 0.1% ...........................................................................................40%
Fluorometholone alcohol 0.1% ......................................................................................... 31%
Prednisolone sodium phosphate 1% ............................................................................. 28%
Dexamethasone sodium phosphate ............................................................................... 19%
Dexamethasone sodium phosphate 0.05% oint. ...................................................... 13%
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HOW ANTI-INFLAMMATORY AGENTS WORK
NSAIDS
Nonsteroidal anti-inflammatory
drugs (NSAIDs) also play a very
important role in the management
of ocular disease, despite having an anti-inflammatory efficacy
below that of the corticosteroids.
Both the topical (Table 5) and
systemic NSAIDs are used to
manage mild to moderate pain
and are frequently combined with
opiates like codeine, hydrocodone
and oxycodone to enhance their
analgesic effect. Topical ocular
NSAIDs in particular are used
to manage postoperative pain,
miosis and cystoid macular edema
(CME). It should be noted, however, that all NSAIDs have some
degree of potential to inhibit the
beneficial antiplatelet activity of
aspirin.
Nonselective NSAIDs work by
inhibiting all forms of the enzyme
cyclooxygenase (COX), which is
responsible for the formation of
prostanoids (i.e., prostaglandins,
thromboxanes and prostacyclins) that mediate inflammation,
anaphylaxis and vasoconstriction (Figure 1). Prostaglandins
in particular play a role in the
direct stimulation of pain receptors (nociceptors) and vasodilation
(hyperemia), but do not affect the
lipoxygenase/leukotriene pathway.
Two forms of cyclooxygenase
exist: COX-1 is a constitutive
enzyme that is continuously
produced and is responsible for
the production of prostaglandins
necessary for normal physiologic
functions, including fabrication of
the stomach’s protective coating
(i.e., the gastric mucosal barrier),
adequate renal blood flow and
normal blood clotting. Inhibition
of COX-1 can lead to gastric irritation, peptic ulcers, gastrointestinal bleeding and blood clotting
disorders.
20
COX-2 is an inductive enzyme
that is produced in response to
tissue injury. Inhibition of COX-2
can lead to gastrointestinal irritation and ulceration; drugs specifically designed to impede COX-2
can also increase the risk of heart
attack and stroke.
• Antipyretic Effect. NSAIDs are
also known to reduce fever. When
the body’s healthy state is compromised as a result of malignancy,
infection or the introduction of
certain chemicals, it raises its
internal temperature to increase
overall metabolism, enhancing
its ability to fight invaders. This
elevated temperature may also
inhibit bacterial growth, because
pathogenic bacteria typically only
grow within narrow temperature
ranges.
This process is triggered by the
release of interleukin 1 cytokines,
which stimulates the synthesis of
prostaglandins E1 and prostaglandin F2. The prostaglandins then
reset the hypothalamic thermostat
to a level above the normal 37°C
to raise the body’s temperature.
The NSAIDs are effective at low
doses in reducing this elevated
temperature, but have no such
effect on normal or subnormal
temperature.
• Hemostasis. Arachidonic acid
is a precursor in the synthesis of
the prostaglandin analogs prostacyclin and thromboxane A2.
Thromboxane initiates platelet
aggregation, while prostacyclin
antagonizes aggregation. Under
normal circumstances, the two
analogs are physiological antagonists, and the platelets do not
aggregate. The action of NSAIDs
on the prostaglandin endoperoxide synthetase (or cyclooxygenase)
causes inhibition of platelet aggregation, thus prolonging bleeding
time—an effect that can either be
Table 5. Currently Available
Topical Ocular NSAIDs
Acular (ketorolac 0.5%, Allergan)
Acular LS (ketotolac 0.4%, Allergan)
Ocufen (flurbiprofen 0.03%, Allergan)
Diclofenac 0.1% (generic)
Voltaren (diclofenac 0.1%, Novartis)
Prolensa (bromfenac 0.07%, B+L)
Nevanac (nepafenac 0.1%, Alcon)
Ilevro (nepafenac 0.3%, Alcon)
therapeutic or cause an adverse
reaction.
• Off-Label Use. Some evidence
for the efficacy of topical NSAIDs
in the management of retinal
edema associated with epiretinal
membranes, diabetic macular
edema and retinal vein occlusions
does exist; however, more information is needed before their use
can be recommended.
RCCL
1. Barron BA, Gee L, Hauck WW, et al. Herpetic
Eye Disease Study. A controlled trial of oral
acyclovir for herpes simplex stromal keratitis.
Ophthalmology. 1994 Dec;101(12):1871-82.
2. Leibowitz HM. Management of inflammation
in the cornea and conjunctiva. Ophthalmology.
1980 Aug;87(8):753-8.
3. Foster CS, Davanzo R, Flynn TE, et al. Durezol
(Difluprednate 0.05% ophthalmic emulsion)
compared with Pred Forte 1% Ophthalmic
suspension in the treatment of endogenous
anterior uveitis. J. Oc Pharmacol Ther. 2010 Oct
26 (5). 475-83.
4. Pflugfelder SC, Maskin SL, Anderson B, et al.
A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol
etabonate ophthalmic suspension, 0.5%, and
placebo for treatment of keratoconjunctivitis
sicca in patients with delayed tear clearance.
Am J Ophthalmol. 2004 Sep;138(3):444-57.
5. Oglesby RB, Black RL, von Sallmann L, Bunim
JJ. Cataracts in rheumatoid arthritis patients
treated with corticosteroids. Arch Ophthalmol.
1961 Oct:66:519-23.
6. Black RL, Oglesby RB, von Sallmann L, Bunim
JJ. Posterior Subcapsular Cataracts Induced by
Corticosteroids in Patients with Rheumatoid
Arthritis. JAMA 1960:174(2):166-71.
7. Kass M, Cheetham J, Duzman E, Burke PJ. The
ocular hypertensive effect of 0.25% fluorometholone in corticosteroid responders. Am J
Opthalmol. 1986 Aug 15:102(2):159-63.
8. Becker B, Mills DW. Corticosteroids
and intraocular pressure. Arch Opthalmol
1963:70(4):500-7.
9. Becker B. The effect of topical corticosteroids in secondary glaucomas. Arch Opthalmol.
1964:72(6):769-71.
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4/6/15 11:42 AM
Don't Hold Back:
Topical Steroids in
Clinical Practice
With a little extra consideration and care, you can safely use steroids to treat a
range of ocular conditions.
By Christopher Cakanac, OD
S
teroids have traditionally carried the stigma
of potential serious side
effects outweighing
their benefits more
so than any other class of drugs.
Optometric and medical education
had previously emphasized the
negative consequences of steroid
use, making many practitioners
hesitant to use them unless the
situation is dire.
In reality, the anti-inflammatory
effects of steroids far outweigh
their possible side effects—in fact,
some experts believe withholding
steroids has caused more harm
to patients overall than their
occasional consequences. Research
has also supported using them
earlier and more often, as we now
have a better understanding of
potential side effects and more
drug options tailored to treat
specific conditions.
From the eye care professional’s
perspective, prevention of vision
loss, earlier return to contact
lens wear and a reduction in the
amount of work or school days
missed are all practical benefits to
using topical steroids.
22
UNDERSTANDING AND
MANAGING SIDE EFFECTS
Inflammation is the body’s response to a stimulus (e.g., invasive
organism) it perceives as offensive.
While an effective defense mechanism, the inflammatory process
can cause scarring and damage
to healthy tissues that surround
the infected area. Steroids work
by blocking phospholipase A2,
thereby blocking both arms of the
chemical inflammatory cascade.1
Thus, they not only decrease
vasopermeability and reduce
edema and redness, they have
the added benefit over nonsteroidal anti-inflammatory agents of
keeping polymorphonucleocytes,
leukotrienes and other blood cells
sequestered from the site of inflammation, thereby reducing collateral
damage to surrounding healthy
tissue.2 However, while efficacious
and unique in quelling the deleterious effects of inflammation, they
are not without consequences.
The two common ocular side
effects associated with steroid use
are increased intraocular pressure
(IOP) and cataract formation.
Topical steroids are generally more
associated with an increase in IOP
than causing the classic steroidinduced posterior subcapsular
cataract (Figure 1); in fact, risk of
cataract formation from shortterm topical steroid use is considered small. Cataract formation is
instead more commonly associated
with prolonged use of oral steroids, though advances in modern
cataract surgery techniques have
made this less of a concern than it
was decades ago.
The prevalence of steroid-associated IOP increase ranges between 5% and 33% of the general
population depending on the study
cited and the definition used.4
Generally, topical steroids can be
used for two weeks with minimal
effect on IOP.5 After two weeks,
IOP can unpredictably rise with no
discernable correlation regarding
ABOUT THE AUTHOR
Dr. Cakanac is a partner in a
group optometric practice and
clinical staff of a tertiary care
ophthalmology practice, both
in Pittsburgh, Pennsylvania. He
is also a member of the editorial
review board for Review of
Optometry.
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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Photo: Christine W. Sindt, OD
Fig. 1. Topical steroid use is typically more closely associated with causing an
increase in IOP than a posterior subcapsular cataract, shown here.
amount or time frame. Thus, the
goal of acute topical steroid use is
to aggressively eliminate inflammation within the two-week period
and then discontinue the drug. If
IOP spikes with short-term steroid
use, pressure generally returns to
baseline two to four weeks after
the drug is discontinued.6 With
chronic use, the steroid response
can occur months to even years
later, so patients on long-term steroid therapy—even just one drop
per day—should have their IOP
checked every three months until
the drug is discontinued.
Should IOP increase to the point
that treatment is required, glaucoma drugs can treat the problem.
Note, healthy discs can tolerate
IOP in the high twenties to low
thirties for a few weeks without
significant compromise. Steroidinduced glaucoma is attributable to
increased resistance to outflow at
the trabecular meshwork, possibly
due to an accumulation of glycos-
aminoglycans and other substances
in this area.7 This decrease in aqueous outflow means that drugs that
reduce aqueous production make
sense for treating steroid-induced
glaucoma.8
Topical beta-blockers such as
timolol, levobunolol and metipranolol have long been used to
blunt a steroid-associated increase.
Topical carbonic anhydrase inhibitors such as Trusopt (dorzolamide
2%, Merck) and Azopt (brinzolamide 1%, Alcon) have been
demonstrated to decrease aqueous
production and so work well for
treating steroid-induced glaucoma.
Alpha agonists such as Alphagan
P (brimonidine 1%, Allergan) also
decrease aqueous production while
simultaneously increasing uveoscleral outflow.
Additionally, combination drugs
such as Combigan (brimonidine
0.2% and timolol 0.5%, Allergan)
and Simbrinza (brinzolamide 1%
and brimonidine 0.2%, Alcon)
work well for steroid-induced glaucoma and provide the convenience
of less drop instillation. Prostaglandins are also known to lower
IOP in steroid-induced glaucoma
by increasing uveoscleral outflow;
however, they also carry a small
possibility of increasing ocular
inflammation.9
Another concern regarding topical steroids is that their suppression
of the ocular immune system may
increase risk of infection (Figure 2).
Topical antibiotics have improved
tremendously as well over the
years. Topical fourth-generation
fluoroquinolones like Zymaxid
(gatifloxacin 0.5%, Allergan) Moxeza (moxifloxacin 0.5%, Alcon)
and Besivance (besifloxacin 0.6%,
Bausch + Lomb) are well-equipped
to provide broad-spectrum coverage against many kinds of bacteria
and should be used concurrently
with steroids for prophylaxis if
potential infection is a concern.
PICKING THE RIGHT DRUG
As a result of recent research, we
practitioners now have more drug
options available to us than ever
before. Prednisolone acetate 1%
(Pred Forte, Allergan; Econopred,
Alcon) remains the gold standard
to which all other topical steroid
preparations are compared. It is a
good a choice for moderate to severe inflammation and it continues
to be used postoperatively in many
ocular surgical procedures.
So-called soft steroids offer an
extra margin of safety for longterm topical steroid use or for
patients with a known risk of
steroid response. A “soft” drug
is a biologically active compound
with a predictable inactivation to
a nontoxic substance after achieving its therapeutic role.10 Lotemax
(loteprednol 0.5%, Bausch +
Lomb) is structurally similar to
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DON'T HOLD BACK: TOPICAL STEROIDS IN CLINCAL PRACTICE
prednisolone but rapidly undergoes
hydrolysis in the anterior chamber
to an inactive derivative. While its
efficacy may be a little less than
prednisolone acetate 1%, it is less
likely to increase IOP.11
A weaker version of loteprednol
in a 0.2% formulation (Alrex,
Bausch + Lomb) is available for
treating seasonal allergic conjunc-
mild ocular surface inflammation,
while fluorometholone acetate
0.1% (Flarex, Alcon) has better
ocular penetration and is appropriate for moderate inflammation.5
Durezol (difluprednate 0.05%,
Alcon) is currently the most potent
steroid available.13 Originally developed in Japan as a dermatologic
preparation, it has been reformu-
Photo: Christine W. Sindt, OD
Fig. 2. Topical steroids may increase risk of infection due to their suppression
of the occular immune system, but can be safely combined with antibiotics.
tivitis. Vexol (rimexolone 1%,
Alcon) is another soft steroid with
efficacy approaching prednisolone
acetate 1% but with a lower steroid response rate.12 It has a higher
steroid receptor binding affinity
and is rapidly degraded to inactive
metabolites.
If out-of-pocket cost to the patient is a concern, note that many
fluorometholone-based steroids are
now available generically. These
agents also have reduced steroidinduced IOP elevation response.
Fluorometholone alcohol 0.1%
(FML, Allergan) is effective for
24
lated as an ophthalmic emulsion.
The molecule is specially designed
to offer both better penetration
and higher anti-inflammatory
activity, giving it the same anti-inflammatory ability as prednisolone
acetate 1% at half the dosing. With
its tremendous anti-inflammatory
properties, however, have come
some reports of significant IOP
response.14
STEROIDS AND OCULAR
CONDITIONS
Topical steroids aren’t just for
uveitis any more. The development
of safer drugs with new formulations has led to a reevaluation of
the appropriateness of a steroid for
many ocular conditions where they
were once contraindicated. For example, steroids are now considered
appropriate to alleviate symptoms
of dry eye on a short-term basis,
and are commonly used as immediate discomfort relief while waiting
for longer-term treatments like
Restasis (cyclosporine ophthalmic
emulsion, Allergan), punctal plugs
and advanced lubricants to work.15
Topical steroids can also be used
in cases when a patient’s symptoms
may be temporarily exacerbated.
A soft steroid with a lower incidence of steroid response such as
Lotemax gel BID to QID (depending on severity) can be used to
reduce symptoms during the initial
one-month startup of Restasis, or
BID to QID for a week or two if
symptoms particularly flare up.
Steroids are also considered
beneficial when treating conditions
that involve lid inflammation, such
as posterior blepharitis. This is
because while topical antibiotics
help reduce associated bacteria,
the patient typically does not feel
improvement until lid inflammation is controlled.16 Zylet (Bausch +
Lomb), which combines the antibiotic tobramycin with loteprednol,
is a good choice for this condition.
Tobradex ST (Alcon), which combines tobramycin and dexamethasone with xanthum gum, is another
good choice because this unique
formulation leads to longer surface
contact time between the medication and the lids.
Once considered an absolute
contraindication, topical steroids
have now also been studied in the
treatment of corneal ulcers. The
Steroids for Corneal Ulcer Trial
(SCUT) randomized patients to
receive prednisolone sodium phos-
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"STEROIDS CAN BE USED FOR
TWO WEEKS WITH MINIMAL
EFFECT ON IOP."
phate 1% or placebo in addition to
moxifloxacin.17 The primary endpoint measured was best spectaclecorrected visual acuity at three
months after enrollment. Results
at this time indicated that while
the steroid had no significant effect
on overall acuity outcome, there
was no apparent increased risk of
corneal perforation and no major
safety concerns were identified.
Further analysis of their subgroups
revealed a slight improvement in
visual acuity outcome for large
central ulcers with steroid treatment, and led to the recommendation that steroids should be
avoided for Nocardia, Mycobacterium and fungal infection.
Interestingly, additional data collected at 12 months demonstrated
further reduction in scar density in
a small number of patients enrolled
in SCUT. This continued corneal
remodeling was accompanied by
an improvement in visual acuity,
suggesting steroid use earlier in the
course of the bacterial ulcer may in
fact contribute to eventual improvement in corneal opacity.18
PEARLS FOR USE
We practitioners are fortunate
to have so many topical steroids
available now. So, don’t rely on
one “go-to” drug for all presenting
conditions. Pick your drug based
on the amount of inflammation
you’re treating: mild, moderate or
severe. Mild surface inflammation
is easily treated with less penetrating drugs such as Alrex or FML,
which typically help avoid the steroid response. Moderate inflammation is handled well with Lotemax
or Vexol, while Pred Forte or
Durezol should be reserved as
treatment for severe inflammation.
Many generic topical steroids are
also now available for patients
with financial concerns.
Next, be sure to consider the
potential for steroid response. For
a treatment period of two weeks
or less, the risk of complications is
considered minimal for most available drugs. If treating long term,
however, consider using drugs with
a reduced steroid response, such as
Lotemax, Alrex, Vexol or fluorometholone alcohol or acetate.
If IOP rises during a course of
steroid therapy, again bear in mind
that otherwise unaffected optic
discs can withstand IOP in the high
20s or low 30s for a few weeks
without significant damage to
structure or function. If IOP does
become a concern, however, first
consider discontinuing the steroid
if possible. In cases where inflammation is still present, substituting a soft steroid can help. If the
patient's IOP level remains unacceptable, add concurrent glaucoma
medications as needed until the
steroid is discontinued. Remember,
IOP usually returns to baseline
two to four weeks after the steroid
is discontinued for short-term
therapy.
With a contemporary knowledge
of our topical steroids, there is no
reason to hold back on their use.
Our newer formulations are safer,
and recent studies have made their
side effects more predictable and
manageable. Research also supports using them earlier and more
often in many ocular conditions.
Your patients will thank you.
RCCL
1. Jaanus S and Lesher G. Anti-Inflammatory
Drugs. In: Bartlett J and Jaanus S (eds) Clinical
Ocular Pharmacology. Boston: Butterworth
Heinemann 1995: 308-18.
2. Skorin L. Uses and effects of ocular steroids.
Review of Optometry 2002 May:139(5) 85-92.
3. Renfro L, Snow J. Ocular effects of topical
and systemic steroids. Dermatol Clin 1992
Jul;10(3):505-12.
4. Sihota R et al. Long-term evaluation of
steroid-induced glaucoma due to systemic
and ocular steroids. Las Vegas: AAO APO joint
meeting 2006: Nov 11-14.
5. Leibowitz H, Kupperman A. Uses of corticosteroids in the treatment of corneal inflammation. In: Leibowitz H (ed) Corneal disorders:
clinical diagnosis and management. Philadelphia: WB Saunders 1984; 286-307.
6. Tripathi R et al. Corticosteroids and glaucoma risk. Drugs and Aging 1999, 15(6) 439-50.
7. Sherwood M and Richardson T. Evidence for
in vivo phagocytosis by trabecular endothelial
cells. Invest Ophthalmol 1958: 59,216.
8. Sowka J and Kabat A. A potent new steroid.
Review of Optometry website. 2010: July 15.
9. Scherer Wand Hauber F. Effect of
latanoprost on intraoculoar pressure in
steroid-induced glaucoma. J Glaucoma 2000
Apr,9(2):179-82.
10. Howes J. Development of soft drugs for
ophthalmic use. In: Ocular therapeutic and
drug delivery: a multidisciplinary approach.
Lancaster: Technomic Publishing, 1996 Aug
122(2):171-82.
11. Whitcup S and Ferris F, Hew corticosteroids
for the treatment of ocular inflammation. Am J
Ophthalmol 1999 May:127(5) 597-5.
12. Foster S. Topical steroid treatment of
ocular inflammation. In: Advances in ocular
pharmacology. Ophthalmology Clinics of North
America 1997 Sept: 10(3) 389-403.
13. Ngoei E. What’s ahead: controlling inflammation. Eyeworld website 2015: March 11.
14. Birnbaum A et al. Elevation of Intraocular
Pressure in Patients with Uveitis Treated With
Topical Difluprednate. JAMA Ophthalmology
website 2011: May 9.
15. Bowing E and Russell G. Topical steroids
and the treatment of dry eye. Review of Cornea and Contact Lens website 2011: Mar 17.
16. Jackson W and Bruce M, “Management
of Dysfunctional Tear Syndrome: A Canadian
Consensus.” Canadian Journal of Ophthalmology 2009 44(4) 386.
17. Srinivasan M et al. Corticosteroids for
bacterial keratitis: the steroids for corneal
ulcers trial (SCUT). Arch Ophthalmol 2012 Feb;
130(2) 143-50.
18. McClintic SM, Srinivasan M, Mascarenhas
J, et al. Improvement in corneal scarring following bacterial keratitis. Eye (Lond). 2013
Mar;27(3):443-6.
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KIDS AREN'T
Short Adults:
Prescribing contact lenses
to children requires a vastly
different approach compared
to adults. Here are some
things to keep in mind.
Tips for Fitting Young
Contact Lens Wearers
By Jeffrey J. Walline, OD
C
hildren who become
myopic typically do
so around age eight
years, requiring
some form of vision
correction.1,2 However, for those
children that are active, glasses are
considered an impediment during
recreational activities.3,4 Contact
lenses are an alternative vision
correction option that can easily
be updated as the prescription
changes. Research shows children
are capable of wearing both
gas permeable and soft contact
lenses, and thus far there have
been no documented long-term
consequences of fitting children
with contact lenses.5 Interestingly,
children who wear contact lenses
exhibit a boost in self-perception
of physical appearance, athletic
competence and social acceptance,
compared with spectacle wearers.4
Young contact lens wearers who
did not like wearing their glasses
even report feeling smarter than
spectacle wearers.4
The purpose of this article is to
illustrate differences between fitting
children and adults with contact
lenses to provide readers confidence when fitting children.
26
PHYSICAL BENEFITS
In addition to improving selfperception, contact lenses offer
other benefits to children that
adults may not recognize, such as
myopia control. Controlled studies
and randomized clinical trials show
that corneal reshaping contact
lenses can slow the progression of
myopia in children.6-11 Soft bifocal contact lenses have a similar
effect.12-15 Maintaining a lower
level of myopia ultimately provides
myopic patients with more options
for vision correction and more predictable refractive surgery results,
better quality of life, and possibly
a lower risk of sight-threatening
issues such as cataract, glaucoma,
choroidal atrophy and retinal
detachment.16-28 Children are also
less likely than college students to
experience ocular health problems
and corneal infiltrative events associated with contact lens wear.29-31
Despite the benefits of contact
lens wear for children and the
lower risks of contact lens complications, only approximately 10%
of optometrists agree that eight to
nine years is an appropriate age to
introduce contact lenses, although
approximately one-third of doctors
said they now fit kids at a younger
age than they did one year ago due
to the availability of daily disposable lenses and improved lens materials, as well as specific requests
from the parent or child.32
FIRST TIME CORRECTION
Many optometrists will not fit a
child with contact lenses when
they first become myopic, instead
telling them that it is an option if
the child proves capable of responsible spectacle wear for one year.
However, there is very little about
responsible spectacle care that
prepares a child for independent
contact lens wear (other than providing additional time to mature),
effectively negating the intention
to train the child. So, practitioners
should provide children with the
option of contact lens wear at
myopia onset, and monitor their
ABOUT THE AUTHOR
Dr. Walline is an associate professor
at the Ohio State University
College of Optometry and
the Study Chair of the Bifocal
Lenses In Nearsighted Kids
(BLINK) Study, a randomized
clinical trial sponsored by the
National Eye Institute.
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due to outliers: twice as many teenagers require less than 20 minutes
to learn insertion and removal
compared with children, and some
children require multiple visits to
master contact lens insertion. The
median difference between children and teenagers is in fact only
five minutes.33 Children typically
remember contact lens care instructions as well as teenagers following
initial instruction, but remember
less than teenagers at longer intervals. Therefore, each time a child
returns for a follow-up, ask them
how they care for their lenses,
and correct any misconceptions to
ensure proper care (Figure 2).
Fig. 1. Teaching children insertion, removal and care of contact lenses requires
only a few additional minutes of training, compared with teenagers.
progress at follow-up appointments. Of course, contact lens
wearers should still have a pair of
spectacles to wear in case of issues.
ANXIETY
Compared with adults, children
don't have as much experience seeing a practitioner, and often have
an exaggerated response to pain
and other negative physical stimuli.
Thus, many believe that anything
placed in the eye will feel like the
standard dilating eye drop. There
are two ways—opposite in nature,
but equally successful—to confront
this issue: either, when inserting
contact lenses, explain every detail
of what you are doing in a soothing, empathetic tone to help alleviate anxiety; or prepare the contact
lens for insertion without allowing
the child to notice, distract them
and insert the lens before they
realize what’s coming. Depending
on your personality, the empathetic
parent or the crazy uncle routine
will help make the fitting process
as easy as possible (Figure 1).
MOTIVATION
Doctors often say that a child’s
motivation is the most important
key for success, but that is not
entirely true. Many children believe
that anything inserted into the
eye will hurt, so they are initially
unmotivated to even try contact
lenses. In fact, more often than not,
it may be the parent’s idea for their
child to try contact lenses. Thus, it
is important to assess motivation
after you insert the lens—children
will frequently change their minds
once they realize contact lenses
improve vision without causing
pain, and will thus be more likely
to continue wearing them. Conversely, adults simply won’t ask
about contact lens wear unless they
are motivated, so assess motivation
during the initial conversation.
INSERTION AND REMOVAL
Children require, on average,
about 11 minutes more than
teenagers to learn proper insertion
and removal techniques for contact
lenses. Most of this difference is
IRRESPONSIBILITY
Optometrists and parents often
agree that children who frequently
lose or break spectacles are poor
candidates for contact lens wear.
In fact, children who lose or break
their spectacles may be the best
candidates. Children rarely remove
their glasses because they prefer
blurry vision—instead, most cases
of lost or broken spectacles happen
when the child is not actively wearing them for appearance reasons
or during recreational activities
and the glasses are forgotten or
crushed. Contact lenses provide
clear vision without altering
appearance, limiting peripheral
vision, falling off or fogging up
during sports.34,35 Children also reported better quality of life scores
while handling contact lenses than
when handling spectacles.3 This is
presumably because glasses are removed throughout the day for different reasons, but contact lenses
are only handled in the morning
and prior to bedtime.
Less overall manipulation of
lenses results in higher handling
quality of life than spectacles, even
though it is more difficult to insert
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KIDS AREN’T SHORT ADULTS: TIPS FOR FITTING YOUNG CONTACT LENS WEARERS
and remove contact lenses than it is
to put on and take off glasses.
COMPLIANCE
Children are often more compliant
with contact lens care than older
patients, possibly because they are
more used to following instructions
from teachers and adults. However, children are also more likely
to forget these messages if they
deviate from their routine—for
example, if they spend the night at
a friend’s house. If a child is sleeping elsewhere for the night, parents
should instruct hosts to remind the
child to remove their contact lenses
before bedtime.
One exception to this might be
corneal reshaping contact lenses.
Because children typically have
lower prescriptions and corneal
epithelium that responds more effectively to corneal reshaping lens
wear than adults, they often experience uncorrected visual benefits
of corneal reshaping lens wear for
a longer period than adults.36 This
means they may be able to wear
their lenses only every other night,
instead of every night. So when
they spend the night at a friend’s
house, they don’t necessarily have
to remember to insert their lenses.
SWIMMING
Since children swim more frequently than adults, and contact lenses
are known to harbor bacteria and
other potential pathogens, it is
important to educate children and
their guardians about contact lens
care while swimming.37-42 Research
shows use of swimming goggles
can reduce the bacterial contamination of contact lenses, but no
evidence-based recommendations
exist regarding what to do with
the lenses if goggles are not worn.
Potential options include removing
lenses during swimming or dispos-
28
ing of or disinfecting lenses immediately after swimming. Regardless
of your recommendation, make
sure your staff relays the same message to all patients.
CORNEAL RESHAPING
CONTACT LENSES
Children are excellent candidates
for corneal reshaping contact
lenses. These specialty lenses slow
the progression of myopia, and
are worn at home in a controlled
environment. Typically, the corneas
of children are easier to correct
during the initial adaptation phase
because glasses provide appropriate correction later in the day as
the cornea begins to return to the
baseline curvature.
However, because myopia progresses until age 15 or 16 years,
children are less likely than adults
to gain full myopic correction from
their spectacles.43,44 As the child’s
cornea returns to normal curvature during the initial adaptation,
the glasses don’t over-correct the
increasing myopia as much as they
would in an adult with a stable,
full myopic prescription in glasses.
Children also adapt more easily
to overcome the over-minused
condition, so soft contact lenses
with half of the baseline prescription are less necessary for children
compared with adults. Children
also do not drive, meaning they
lodge far fewer complaints than
adults of haloes around lights at
night. However, children are just
as at risk for microbial keratitis as
adults, especially since the contact
lenses are worn during sleep, so
they should be educated about
symptoms of corneal infections.45-47
BIFOCAL CONTACT LENSES
Children are increasingly being fit
with soft bifocal contact lenses for
myopia control. However, fitting
a child with soft bifocal contact
lenses is nothing like fitting a presbyopic adult; in fact, fitting a child
with soft bifocal contact lenses for
myopia control is more like fitting
a child with single vision contact
lenses, primarily because they accommodate even while wearing
bifocal lenses. Even the highest add
powers rarely result in complaints
from children, presumably because
they typically accommodate better
than adults, even when wearing
a soft bifocal lens. Young convergence excess patients may even
benefit from soft bifocal lens wear,
presumably because they accommodate less with soft bifocal lenses.
This may be because human body
is adept at adjusting to uncomfortable situations, and these children
may learn to relax accommodation
to alleviate symptoms caused by
convergence excess.48,49
CONCLUSION
Children experience a range of
visual and non-visual benefits from
contact lens wear beyond those
experienced by adults, without increased risks due to adverse physiological effects or irresponsibility.
With additional considerations towards alleviating a child’s anxiety
and making the fitting process as
fun as possible, children are as easy
to fit with contact lenses as teenagers and adults.
Many practitioners love the additional challenge and free advertising that children bring to the
practice. Children are extremely
social beings; they participate in
sports and recreational activities
and hang out with their friends.
Because they are not yet completely
independent, parents often congregate around them, opening up the
possibility for a discussion between
adults regarding a child’s sudden
independence from glasses. In some
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Fig. 2. Children are very capable of independent contact lens insertion,
removal and care.
cases, such a discussion may result
in a referral, benefiting both the
new patient and the practice. So,
don’t be afraid to offer contact
lenses to your young patients!
RCCL
1. Goss DA, Cox VD. Trends in the change of clinical refractive error in myopes. J Am Optom Assoc
1985;56:608-13.
2.Rahi JS, Cumberland PM, Peckham CS. Myopia
over the lifecourse: prevalence and early life influences in the 1958 British birth cohort. Ophthalmology 2011;118:797-804.
3.Rah MJ, Walline JJ, Jones-Jordan LA, et al.
Vision specific quality of life of pediatric contact
lens wearers. Optom Vis Sci 2010;87:560-6.
4.Walline JJ, Jones LA, Sinnott L, et al. Randomized trial of the effect of contact lens wear
on self-perception in children. Optom Vis Sci
2009;86:222-32.
5.Walline JJ, Lorenz KO, Nichols JJ. Long-term
contact lens wear of children and teens. Eye
Contact Lens 2013;39:283-9.
6.Charm J, Cho P. High Myopia-Partial Reduction
Ortho-k: A 2-Year Randomized Study. Optom Vis
Sci 2013;90:530-9.
7.Chen C, Cheung SW, Cho P. Myopia control using toric orthokeratology (TO-SEE study). Invest
Ophthalmol Vis Sci 2013;54:6510-7.
8.Cho P, Cheung SW. Retardation of Myopia in
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9.Cho P, Cheung SW, Edwards M. The longitudinal
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Hong Kong: a pilot study on refractive changes
and myopic control. Curr Eye Res 2005;30:71-80.
10.Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, et al. Myopia Control with Orthokeratology
Contact Lenses in Spain (MCOS): Refractive and
Biometric Changes. Invest Ophthalmol Vis Sci
2012.
11.Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia progression. Br J Ophthalmol 2009;93:1181-5.
12.Anstice NS, Phillips JR. Effect of dual-focus soft
contact lens wear on axial myopia progression in
children. Ophthalmology 2011;118:1152-61.
13.Lam CS, Tang WC, Tse DY, et al. Defocus Incor-
porated Soft Contact (DISC) lens slows myopia
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14.Sankaridurg P, Holden B, Smith E, 3rd, et al. Decrease in rate of myopia progression with a contact lens designed to reduce relative peripheral
hyperopia: one-year results. Invest Ophthalmol
Vis Sci 2011;52:9362-7.
15.Walline JJ, Greiner KL, McVey ME, et al. Multifocal contact lens myopia control. Optom Vis Sci
2013;90:1207-14.
16.Bailey MD, Mitchell GL, Dhaliwal DK, et al.
Patient satisfaction and visual symptoms after
laser in situ keratomileusis. Ophthalmology
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17.Reviglio VE, Luna JD, Rodriguez ML, et al. Laser
in situ keratomileusis using the LaserSight 200
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18.Rose K, Harper R, Tromans C, et al. Quality of
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19.Eye Disease Case-Control Study Group. Risk
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20.Hyams SW, Neumann E. Peripheral retina
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21.Saw SM, Gazzard G, Shih-Yen EC, et al. Myopia
and associated pathological complications. Ophthalmic Physiol Opt 2005;25:381-91.
22.Casson RJ, Gupta A, Newland HS, et al. Risk
factors for primary open-angle glaucoma in a
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23.Lee YA, Shih YF, Lin LL, et al. Association
Between High Myopia and Progression of Visual
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24.Omoti AE, Edema OT. A review of the risk factors in primary open angle glaucoma. Niger J Clin
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25.Giuffre G, Dardanoni G, Lodato G. A
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26.Lim R, Mitchell P, Cumming RG. Refractive associations with cataract: the Blue Mountains Eye
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27.McCarty CA. Cataract in the 21st Century: lessons from previous epidemiological research. Clin
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28.Mukesh BN, Le A, Dimitrov PN, et al. Development of cataract and associated risk factors:
the Visual Impairment Project. Arch Ophthalmol
2006;124:79-85.
29.Chalmers RL, Wagner H, Mitchell GL, et al. Age
and other risk factors for corneal infiltrative and
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2011;52:6690-6.
30.Wagner H, Chalmers RL, Mitchell GL, et al.
Risk Factors for Interruption to Soft Contact Lens
Wear in Children and Young Adults. Optom Vis
Sci 2011;88:973-80.
31.Wagner H, Richdale K, Mitchell GL, et al. Age,
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2014;91:252-61.
32.Sindt CW, Riley CM. Practitioner attitudes
on children and contact lenses. Optometry
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33.Walline JJ, Jones LA, Rah MJ, et al. Contact
Lenses in Pediatrics (CLIP) Study: chair time and
ocular health. Optom Vis Sci 2007;84:896-902.
34.Walline JJ, Bailey MD, Zadnik K. Vision-specific
quality of life and modes of refractive error correction. Optom Vis Sci 2000;77:648-52.
35.Walline JJ, Gaume A, Jones LA, et al. Benefits
of Contact Lens Wear for Children and Teens. Eye
Contact Lens 2007;33:317-21.
36.Kang P, Swarbrick H. Time course of the effects of orthokeratology on peripheral refraction
and corneal topography. Ophthalmic Physiol Opt
2013.
37.Choo J, Vuu K, Bergenske P, et al. Bacterial
populations on silicone hydrogel and hydrogel
contact lenses after swimming in a chlorinated
pool. Optom Vis Sci 2005;82:134-7.
38.Kaji Y, Hu B, Kawana K, et al. Swimming with
soft contact lenses: danger of acanthamoeba
keratitis. Lancet Infect Dis 2005;5:392.
39.Lam J, Tan G, Tan DT, et al. Demographics and
behaviour of patients with contact lens-related
infectious keratitis in singapore. Ann Acad Med
Singapore 2013;42:499-506.
40.Rabinovitch J, Cohen EJ, Genvert GI, et al.
Seasonal variation in contact lens-associated
corneal ulcers. Can J Ophthalmol 1987;22:155-6.
41.Vesaluoma M, Kalso S, Jokipii L, et al. Microbiological quality in Finnish public swimming
pools and whirlpools with special reference to
free living amoebae: a risk factor for contact lens
wearers? Br J Ophthalmol 1995;79:178-81.
42.Wu YT, Tran J, Truong M, et al. Do swimming
goggles limit microbial contamination of contact
lenses? Optom Vis Sci 2011;88:456-60.
43.Goss DA. Cessation age of childhood myopia
progression. Ophthalmic Physiol Opt 1987;7:195-7.
44.Thorn F, Gwiazda J, Held R. Myopia progression is specified by a double exponential growth
function. Optom Vis Sci 2005;82:286-97.
45.Bullimore MA, Sinnott LT, Jones-Jordan
LA. The risk of microbial keratitis with overnight corneal reshaping lenses. Optom Vis Sci
2013;90:937-44.
46.Watt K, Swarbrick HA. Microbial keratitis in
overnight orthokeratology: review of the first 50
cases. Eye Contact Lens 2005;31:201-8.
47.Watt KG, Swarbrick HA. Trends in microbial
keratitis associated with orthokeratology. Eye
Contact Lens 2007;33:373-7; discussion 82.
48.Libassi DP, Barron CL, London R. Soft bifocal
contact lenses for patients with nearpoint asthenopia. J Am Optom Assoc 1985;56:866-70.
49.Shainberg MJ. Nonsurgical treatment of teenagers with high AC/A ratio esotropia. Am Orthopt
J 2014;64:32-6.
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The GP Expert
By Stephanie L. Woo, OD
A ‘Coherent’ Strategy for
Fitting Scleral Lenses
OCT: it’s not just for retina anymore!
I
Fig. 1. OCT
measurement
of central lens
clearance.
Global pachymetry features
have given us the ability to measure the thickness of the cornea,
which is great for monitoring
the progression of diseases like
keratoconus and pellucid marginal
degeneration. Additionally, the
“angle” feature allows us to view
the iris configuration and angle
measurement in degrees, helping
us determine if a patient may be
at greater risk for narrow angle
glaucoma. Now, OCT can also
assist with specialty contact lens
fittings.
AUGMENTING
THE SLIT LAMP
When fitting scleral contact lenses,
it is of utmost importance to
obtain proper corneal and limbal
30
clearance. This can be assessed
with a slit lamp and sodium
fluorescein by comparing lens
thickness to the tear layer thickness. If you only have access to a
slit lamp, this is a completely acceptable method of fitting scleral
lenses—but what if you could
compare your slit lamp findings
with your OCT scans? This could
lead to better overall assessment
of scleral lenses and is a great way
to improve confidence (for both
you and the patient) when fitting
scleral lenses.
It is advisable to first insert the
scleral lens and immediately evaluate it with the slit lamp. If the
amount of clearance looks acceptable, let the lens settle for at least
20 to 30 minutes before reevaluation. Keep in mind the central
clearance will decrease around
100µm during this time. Then, use
the anterior segment feature of
your OCT to measure the amount
of central, limbal and edge clearance. You can do this either before
or after your reevaluation of the
lens under the slit lamp.
First, check the amount of
central clearance by centering the
Fig. 2. OCT measurement of edge.
OCT image over the pupil (Figure
1). Then, use the ruler application to measure from the posterior
portion of the scleral lens to the
anterior portion of the cornea to
determine the amount of central
clearance in microns. You can
then compare your findings with
the slit lamp to see how accurate
you are.
Photo: Jeffrey Sonsino, OD
f you are new to scleral
contact lens fittings and
own an optical coherence
tomography (OCT) device,
you have an amazing tool at
your fingertips that can help make
your job significantly easier. OCT
has long been used to assess the
posterior segment of the eye and
has more recently gained popularity for anterior segment uses as
well.
Fig. 3. OCT image
of hybrid contact
lens on-eye fitting
characteristics.
If you know which area of the
cornea has the highest elevation,
you can also center the OCT image over that portion of the lens
and measure the amount of clearance in that location. To check
limbal clearance, center the OCT
image over the limbus. Clearance
here should be significantly less
than central clearance in most
scleral lens designs.
Edge alignment can also be
viewed using an OCT. Have the
patient look to the left and the
right to capture images of the edge
of the scleral lens (Figure 2). You
can also check the alignment of
the conjunctiva with the scleral
lens edge to see if there is any
compression. OCT imaging can
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also be useful when fitting hybrid
lenses—you can view both the
soft skirt and GP lens junction, as
well as the lens-to-cornea fitting
relationship (Figure 3).
Fig. 4. Distortion of posterior lens
surface.
CASE #1
A 28-year-old female was refit
into scleral lenses due to her high
-10.00D OU Rx. She was fit in a
design for conventionally shaped
corneas and had been wearing
the scleral lenses successfully
for about two weeks. She stated
that insertion and removal were
becoming easier each day and that
comfort and wear time were excellent. However, she noted appearance of a strange glare in her right
eye only and reported that her
vision wasn’t as sharp in the right
eye as it was in the left eye.
Visual acuity was 20/30 OD
and 20/20 OS. There was no
significant spherocylinder overrefraction. Lens fit in both eyes
was good: the central and limbal
clearance of both lenses appeared
appropriate, as well as the lens
edge. Both lens surfaces appeared
to be wetting well with no deposits or scratches. Upon OCT
evaluation, the posterior surface
of the right lens appeared slightly
distorted, and it was determined
the lens was defective: the lathe
had not properly cut the posterior
lens surface, leading to an uneven
surface. This was causing the
patient symptoms of poor vision
and glare (Figure 4). The laboratory refabricated the OD lens and,
upon dispensing, the patient reported 20/20 vision and no glare.
CASE #2
A 40-year-old white female was
fit into scleral lenses for treatment
of dry eye disease. She had been
wearing the lenses successfully for
about one month, but complained
of decreased wear time, stinging
upon removal and increasing eye
redness throughout the day. She
also noticed a compression ring
upon removal. While wearing
the lenses, she could see 20/20
OD and 20/20 OS. There was no
significant spherocylinder overrefraction.
Slit lamp evaluation showed
central clearance of about 200µm
in each eye, but limbal clearance
was difficult to assess. The edges
did show some blanching at 360
degrees. Evaluation of the edges
with the OCT showed minimal
IS OCT BILLABLE FOR
SCLERAL LENS FITTING?
Currently, I roll topography, specular microscopy and any OCT evaluations into my specialty lens fitting
fee. The pricing reflects a bundled
service, and I do not bill each
procedure separately. Hopefully, in
the future, CPT codes will be able
to be billed to insurance during
specialty contact lens fittings.
Fig. 5. OCT before (top) and after
(bottom) lens modifications.
limbal clearance and poor edge
alignment.
With lenses removed, there was
limbal staining OU, indicating
inadequate clearance. To remedy the poor lens fit, the limbal
vault was increased and the edge
design was flattened slightly to
help with the limbal staining and
edge compression, respectively
(Figure 5). She has now worn the
lenses successfully for six months
with no corneal staining or edge
compression.
As optometrists, we typically
think of OCT imaging for the posterior segment, but we should also
remember there are some excellent
anterior segment applications.
OCT imaging definitely helped
me become more confident with
fitting scleral contact lenses when
I was first learning about this
special lens design. Keep in mind
that you do not need an OCT
to successfully fit scleral lenses,
but if you do have this device on
hand, the information it can give
you can be very valuable for your
scleral lens fittings.
RCCL
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Derail Dropouts
By Mile Brujic, OD, and Jason Miller, OD, MBA
’Tis the Season
Managing occasional allergy symptoms is just as important as alleviating persistent
problems in preventing contact lens dropout.
M
any contact lens
wearers experience perennial symptoms of
ocular allergy that
can eventually lead to dropout if
not addressed, but some patients
are only affected during certain
times of the year and thus may
not be symptomatic when they
come in for their exam. These
patients often neglect to mention
their symptoms or use of over-thecounter treatments when reviewing their eye history with you. In
cases like these, it is important to
ask the right questions—you may
be surprised what you hear.
CASE #1
A 31-year-old male patient presented for a comprehensive eye
exam and update of his contact
lens prescription. He did not
have any comfort complaints, but
was having some trouble focusing while using the computer
throughout the day. He was wearing monthly disposable contact
Fig. 1. Mild limbal injection was
observed in a contact lens patient
who complained of difficulty
focusing while using a computer.
32
lenses and replacing
them as prescribed.
He also reported using the same multipurpose solution he
had been using for
several years and
denied any other
ocular or medical
changes since his last
eye exam.
I (Dr. Miller) performed a refraction
on this patient to
see if we had overFig. 2. Significant staining was observed following
minused him during use of fluorescein.
his last appointment,
but found no such issues. With
gradually tapered the Visine, and
slit lamp evaluation, I observed
he was able to safely return to
some mild limbal injection in
contact lens wear with no further
both eyes (Figure 1). I instilled
issues after a couple weeks. I did
fluorescein and, upon observation refit him into daily disposable
of significant staining (Figure 2),
contact lenses, which eased daily
asked him the following quesirritation due to long hours on the
tions:
computer.
• Do you have seasonal allergies?
CASE #2
• Do you ever use OTC eye
An 18-year-old female patient
drops?
presented with ocular discomfort
• How often do your eyes itch,
and itching, which she reported
water or turn red?
increased in severity after taking
• Do your contact lenses ever
her contact lenses out each night.
become more difficult to wear or
To alleviate this discomfort, she
less comfortable during certain
had taken to wearing her daily
times of the year or in your work
lenses overnight. Her symptoms
environment?
started approximately one month
The patient admitted to using
ago and she stated that she had
self-prescribed OTC Visine eye
not been using any eye drops.
drops every few hours per day
Her slit lamp exam demonfor approximately the last six
strated a moderate amount of
months with his contact lenses in. conjunctival injection and edema
He did not think anything was
(Figure 3), and her inferior palpewrong with his regimen; in fact,
bral conjunctiva revealed diffuse
he believed it was helping to clear G3 papillae throughout (Figure
up the redness in his eyes. We
4), suggesting the presence of
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TREATMENT OPTIONS
Allergies are a common cause of contact lens discomfort. If the allergic response is seasonal and paitents know
when their allergy symptoms typically begin, consider starting them on an antihistamine/mast-cell stabilizer a
week or two prior to that time. I prefer to use a prescription (instead of an OTC) product because it can be challenging to ensure the patient will purchase the correct OTC product.
Types of antihistamine/mast-cell stabilizer combination drops include: Astelin (azelastine hydrochloride ophthalmic solution 0.05%, Optivar); Elestat (epinastine hydrochloride ophthalmic solution 0.05%, Allergan); Zaditor
(ketotifen fumarate ophthalmic solution 0.025%, Novartis); ketotifen fumarate (Alaway, Bausch + Lomb); Patanol (olopatadine hydrochloride ophthalmic solution 0.1%, Alcon); and Bepreve (bepotastine besilate ophthalmic
solution 1.5%, Bausch + Lomb). All should be used twice daily. Pataday (olopatadine hydrochloride ophthalmic
solution 0.2%, Alcon), Lastacaft (alcaftadine, Allergan) and the new Pazeo (olopatadine hydrochloride ophthalmic
solution 0.7%, Alcon) are all used once daily.
Topical steroids may also be an option for patients requiring topical medical treatment for their ocular allergy
symptoms in more severe cases or those who are not responding to treatment with the antihistamine/mast-cell
stabilizer. Alrex (loteprednol etabonate ophthalmic suspension 0.2%, Bausch + Lomb) and Lotemax (loteprednol
etabonate ophthalmic suspension 0.5%, Bausch + Lomb) are two commonly prescribed steroid drops for allergic
conjunctivitis. Topical steroids are often used for a pulse during a short period of time (one to two weeks), followed by use of an antihistamine/mast-cell stabilizer for sustained maintenance over a longer period of time.
allergic conjunctivitis. I discontinued her contact lens wear so that
I could get her allergic conjunctivitis under control, first using an
ophthalmic steroid and later an
antihistamine/mast-cell stabilizer
for maintenance. She was able to
return to using her daily dispos-
able contact lenses and is no longer sleeping in them overnight.
Asking the right questions and
treating patients appropriately
can often help you to more easily
manage common cases like these.
By identifying those contact lens
wearers who experience intermit-
Fig. 3. A slit lamp exam revealed moderate conjunctival
injection and edema.
tent—rather than constant—visual or symptomatic discomfort,
you can proactively help improve
all of your patients’ experiences
with contact lenses, thus reducing
the potential for dropouts and improving the profitability of your
practice.
RCCL
Fig. 4. Observation of diffuse G3 papillae, suggesting
allergic conjunctivitis.
REVIEW OF CORNEA & CONTACT LENSES | MAY 2015
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Out of the Box
By Gary Gerber, OD
Band Together
Here’s how an everyday rubber band will make your patients better contact lens
wearers—and increase practice profits.
T
he disposable contact
lens market has come
a long way since 1987,
when the first disposables intended for one
week of continuous wear were
introduced. Sold in a plastic clamshell box, the lenses came in lots of
six. This meant that patients would
need more than eight boxes per eye
to allow them to wear these lenses
as prescribed without interruption
for one year. At the time, we were
less concerned with a patient’s
yearly lens supply and more apprehensive about sticking our toes
back into the previously problemfilled waters of extended wear.
The next lens on the market,
which also had six lenses per box,
was intended to be prescribed for
two weeks of continuous wear,
meaning a yearly supply consisted
of less than five boxes per eye. It
was at that time the “yearly supply” lightbulb went off for most of
us and we started to recognize the
patient (i.e., compliance) and practice (i.e., economic and logistic)
benefits of prescribing and dispensing annual supplies of lenses.
Yet, for many of us, dispensing a
year’s supply of lenses is still a challenge. The most common reason is
that patients balk at the up-front
cost. Much has been written about
how to overcome this objection
and various techniques have been
developed to increase the rate of
annual supply purchase, including
informing the patient they have
been pre-approved for a year’s supply and offering them a tiered price
structure with a discount based on
number of boxes purchased. Lens
34
manufacturers also offer rebates in
an effort to stimulate the frequency
of annual supply purchase. While
collectively some of these techniques may be moderately effective,
they are all largely unnecessary.
The easier solution? A rubber
band. That’s the secret.
DON’T SHORTCHANGE
YOUR PATIENTS
What would have happened if the
first box of disposable one-week
lenses had had seven
lenses in it? What if it
had had 11, 14 or 23?
My guess is that doctors’ heads would have
exploded, or they would
have dispensed one,
possibly two, boxes for
each eye and waited for patients to
call for more lenses, same as they
did for the six-lens boxes. Similarly,
what if the first box had 365 daily
disposable lenses in it? The same
thing would have happened, except
that the patient would have called
for replacements at a much later
date. Manufacturers I’ve spoken
to agree that putting more lenses
into a single box helps with annual
supply concerns and they agree
that 365 daily lenses in a box is a
great solution. But they also believe
that many doctors would shy away
from such a lens supply out of fear
of price rejection from patients.
That’s where they and I disagree,
and the rubber band comes in.
I guarantee that no one reading
this dispenses just the right lens
and tells the patient to try it out for
a few days before coming back to
get the left eye fitted. The reason
you fit both eyes at the same time,
without even considering why, is
because it’s perfectly logical to do
so and rather silly not to. Plus,
many of us would never consider
doing otherwise because we’ve always done it this way and it works.
So, how about the following
logical and successful way to
dispense more annual supplies
without memorizing scripts, explaining rebates or trying to master
tiered-pricing plans? Until the day
“NO APOLOGY
NECESSARY, NO
EXCUSES NEEDED.”
comes when a manufacturer puts
365 daily disposable lenses into
the box, simply put a rubber band
around the appropriate number
of boxes and present the annual
supply of lenses as the default way
that you dispense lenses in your
practice. No apology necessary, no
excuses needed. Just do it. Nine
times out of 10, your patients will
accept this as standard practice
without argument.
It’s better for patients, since it
eliminates their incentive to stretch
the lens replacement cycle beyond
what you prescribed. It’s also more
convenient for them than having to
keep ordering more lenses throughout the year. And just like fitting
both eyes at the same visit, once
you get in the habit of always doing it this way, you’ll wonder why
you never reached for the rubber
band sooner.
RCCL
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fit-boston.com
Educational materials at your fingertips
The Boston website offers a variety of educational materials and videos
for the specialty lens fitting practice. Bookmark fit-boston.com and
make it your “go to” resource for specialty GP lens information.
“Correction of Keratoconus with GP Lenses”
A Guide to Scleral Lens Fitting
Scleral Lens Fitting Videos
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© 2015 Bausch & Lomb Incorporated. Boston and Bausch + Lomb are trademarks of Bausch & Lomb or its affiliates. US/BNL/14/0012b
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