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Current Therapy
in Ocular Disease
by Drs. Ron Melton and Randall Thomas
Past recipients of the “Glaucoma Educator of the Year” Award
by the American Academy of Optometry
Authors of Review of Optometry’s annual Clinical Guide to Ophthalmic Drugs



This lecture is 20 hours of COPE-approved continuing education, filled with clinically relevant, “take-to-the-
office” pearls. This sought-after post-graduate education symposium is expertly taught all over North America
by Drs. Ron Melton and Randall Thomas. Join your colleagues for professional enrichment at its best.

September 16-18, 2010

Idaho Optometric Physicians Association Annual Congress
Double Tree Boise-Riverside Hotel
Boise, Idaho
Contact: Larry Benton, Executive Director
Phone: 208-461-0001

October 22-24, 2010

The Windsor Laser Eye Institute
Caesars Windsor Convention Centre
Windsor, Ontario, Canada
Contact: Robin Marentette, CE Coordinator
Phone: 800-391-1613

What your colleagues

ues a
re s
• “The most entertaining and practical lecture
cture I’ve heard in
more than 20 years.”
• “100% relevant to our practice. I feel like Melton & Thomas
are truly interested in making me a better clinician.”
• “They have perfected the tag-team approach with humor, asking each
other questions that we would ask.”
• Very entertaining, and the content is practical, useful, and real.
• If I were to attend only one meeting a year, this would be it.

Visit our website:

000_dg0610_R&Rcourse.indd 49 6/2/10 12:54 PM

Dear Colleagues:
We are grateful to the many colleagues who share with us each year
their appreciation of this Clinical Guide to Ophthalmic Drugs. It is our
honor to be a part of your lifelong learning process.
To all of you consistent, faithful readers, we apologize that every issue
is not completely fresh information (only a very few new drugs come to
market each year). You all are a solid core of attentive, interested clini-
cians, and we value your professionalism. However, many of our col- CONTENTS
leagues, like the authors, have to be exposed to information more than
once before it effects a change in their clinical behavior. Furthermore, Glaucoma .............................. 2A
there are many new O.D.s entering the profession who can benefit from
the core principles of medical management. So, please bear with us as we
do all we can to bring everyone up to speed.
• In 2010, the big news is that Xalatan is scheduled to lose patent
Overview of
protection in March 2011. This will rock the world of glaucoma patient Oral Medicines .................... 10A
care, and hopefully will be of huge benefit to our glaucoma patients.
• Valtrex (valacyclovir) and Famvir (famciclovir) have joined acyclovir
in the generic camp. This also should be of benefit to many patients. The Simplicity of
• A new drug is now available (ganciclovir), marketed as Zirgan by Allergy Management ........... 14A
Sirion, and is approved for treatment of epithelial herpes simplex kerati-
tis. Zirgan is likely to displace trifluoridine (Viroptic) from gold-standard
status. Insights Into
• Yet another antihistamine/mast-cell stabilizer, known as Bepreve Adenoviral Infections .......... 16A
(bepotastine, Ista Pharmaceuticals), has also come to market.
• Erythromycin, and several other ophthalmic ointments, are readily
available again, and this is certainly welcome news.
• For the relatively few glaucoma patients needing an alpha-adrenergic Insights in Antibiotics ......... 20A
agonist to help control their intraocular pressure, brimonidine 0.2% and
0.15% are now generically available. The 0.2% is the least expensive.
• In the even less frequently prescribed class of drugs, the carbonic Combination Drugs ............. 26A
anhydrase inhibitors, dorzolamide (Trusopt) is now available in generic
As always, we hope the information shared herein will help you better Corticosteroids ................... 32A
serve the needs of your patients.

Our very best wishes to each of you,

Clinical Update on the
NSAIDs ................................ 37A

Randall K. Thomas, O.D. Ron Melton, O.D. The Mastery of Dry Eye ....... 42A

For Perspective: Good Chairside Manner is the Best Policy

“Increasing emphasis on patient-centered care, and other recent developments, should make patient expectations increasingly important
... Honesty was not only the most frequently cited expectation among focus group participants as a whole but also the most frequently
expressed expectation area among all subgroups as well.”
“The observation that ophthalmology patients place greater emphasis on communication and interpersonal manner than technical
interventions is consistent with a previous study, which found that patient satisfaction is more closely linked to patients’ perceptions about
whether they received nontechnical interventions, such as education, than technical interventions, such as diagnostic tests.”
Dawn AG, Santiago-Turla C, Lee PP. Patient expectations regarding eye care: focus group results. Arch Ophthalmol. 2003 Jun;121(6):762-8.

001_dg0610_intro.indd 1 6/2/10 1:49 PM

The challenge in glaucoma is to monitor for progression—especially the rate of
progression. Once this is determined, then optimum therapy can be prescribed.
e believe that eye doctors are the easy ones. It is the 55-year-

W continue to miss glau-

coma in wholesale fashion
because they either are inattentive
old patient with a 0.6 to 0.7 cup
with a central corneal thickness of
545µm, an IOP of 20mm Hg, an
to the optic nerve head, or simply older brother who is being watched
fail to act upon their observa- for glaucoma, and a normal to bor-
tions—both of which can carry dire derline retinal nerve fiber layer who
consequences. is the challenge to “assess risk.”
We have no explanation for the Does the patient have sufficient
former; however, the “failure to risk to justify treatment, or is it in
act” scenario can perhaps be ex- the patient’s overall best interest
plained. If the patient has a normal to be followed every six to twelve
intraocular pressure, especially in months?
the afternoon (where IOP tends to Glaucoma is all about assessing risk. At this point in time, everyone
be at its lowest), then the clinician Does this patient have sufficient risk to has an opinion, but no one knows
may simply assume the optic nerve justify treatment, or is it in the patient’s for sure. In fact, many “glaucoma
to be physiologically cupped. It is overall best interest to be followed? suspects” remain suspect for many
these patients who have suspicious years. If after several years of being
optic nerve cupping that merit maneuver in such circumstances followed, there is no evidence of
another investigative step or two. is to measure the central corneal progression, then the patient can
If the patient was examined in the thickness (CCT)! Many patients finally be declared to have physi-
afternoon, we strongly recom- with relatively thin physiological ologically normal cupping. It must
mend another intraocular pressure corneas (an independent risk fac- be stressed here that by definition,
measurement in the early morning tor for glaucoma) have measured glaucoma is a “progressive optic
within a few days or weeks. Many normal intraocular pressure. These neuropathy.” Said another way,
such “normal tension” glaucomas patients can be missed so easily, yet if there is no progression over five
are simply missed hypertensive detected with only very minimal ef- to eight years, then there is most
glaucomas, because the higher fort. Note that a thinned cornea via probably no disease. “Progres-
morning time IOP was never de- refractive surgery does NOT confer sion” is most commonly assessed
tected. upon the patient any additional risk by documented increase in the
Most importantly, one must of glaucoma, only a reduction in C/D ratio, thinning of the retinal
not to be lulled into complacency measured IOP. nerve fiber layer, and/or visual field
when encountering a suspicious Glaucoma, in large part, is all compromise.
optic nerve head in the presence about assessing risk. Some people Regarding visual field progres-
of a normal intraocular pressure. have 0.8 cups with IOPs in the 30s sion, it is imperative that any
The most important diagnostic and have frank glaucoma. These change in perimetry outcome be


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documented as repeatable. This glaucoma evaluation: near emmetropes if they have ever
typically requires repeating the vi- 1. Take a really thorough his- had refractive surgery. Note that
sual field two to four times in order tory, and ask especially about the the CCT reaches stable adult status
to confidently declare that true pro- presence of glaucoma in siblings. by age 10.
gression is occurring. Such repeat Glaucoma does tend to run in fami- 7. Perform gonioscopy. We pre-
testing is done perhaps every six lies. If your patient is deemed to be fer the four-mirror gonioscope, as it
months. Never believe borderline at risk for (or to have) glaucoma, is quick and efficient.
changes in any visual field unless it be sure to encourage him or her 8. Perform binocular indirect
can be reproduced on subsequent to contact siblings to urge them to ophthalmoscopy, just to be thor-
tests. (More on this critical diagnos- have their eyes evaluated for the ough.
tic assessment later.) potential of glaucoma. 9. Do a careful, detailed, high-
The measurement of central 2. Determine the patient’s best magnification stereoscopic evalu-
corneal thickness was shown to be corrected vision. ation of the optic nerve head via
a critical factor in glaucoma assess- 3. Carefully assess pupillary high-convex (90D, etc.) lens-en-
ment via the Ocular Hypertension function, looking especially for a hanced slit lamp ophthalmoscopy.
Treatment Study, as published in subtle afferent pupillary defect. This is the single most important
June 2002.1 This incredible revela- 4. Perform dilated, attentive slit aspect of the entire workup.
tion allowed for a much enhanced lamp biomicroscopy noting any 10. Perform standard automated
assessment of glaucoma and glau- pigment dispersion, iris retroillumi- perimetry (SAP), preferably with
coma risk. Corneal pachymetry has nation defects, pseudoexfoliation, the Humphrey visual field ana-
now become standard of care; yet guttata (which can alter corneal lyzer (HFA-2) using the 24-2 SITA
not all eye doctors have embraced thickness). Also note that topi- standard or SITA Fast algorithm.
this simple and inexpensive technol- cal carbonic anhydrase inhibitors (Matrix is in close second place, but
ogy. might compromise endothelial is not fully gold-standard.)
An example of this disregard of function in the presence of endothe- 11. Scan the nerve fiber layer
pachymetry is the woman in her lial pathology. (using HRT, GDx-VCC or ECC,
30s who reported that her father 5. Measure IOP. Goldmann or OCT). The premier technology
was recently diagnosed and treated applanation tonometry is standard in this category is OCT, because it
for glaucoma. She had healthy, of care, so we urge the use of this can provide both retinal/macular
pink optic nerves with a 0.2 cup technology for such measurements. tissue assessment, as well as nerve
in the central aspect of both optic Always note the time the IOP is fiber layer analysis. While spectral
nerve heads. Her intraocular pres- taken. domain technology is more so-
sure was 26mm Hg in both eyes, 6. Measure CCT. Always ask phisticated, time domain technol-
but she had 640µm corneas! It is
well established that corneal thick- Brimonidine
ness is the most heritable aspect Brimonidine is available in three concentrations: the original 0.2%, which is the least
of the human eye. We have great expensive of the three; 0.15%, which is more expensive than the 0.2% formulation; and
belief that this woman’s father has lastly, 0.1%. Both 0.2% and the 0.15% brimonidine are available
nothing more than corneal thick- generically. The 0.1% concentration is brand-name protected, and
ness-dictated ocular hypertension is the most expensive. It is known as Alphagan P, from Allergan.
and is being treated for a disease he All three strengths are FDA-approved for t.i.d. dosing,
does not have! We strongly urge all which is how they should be dosed as monotherapy. As
optometrists to acquire a corneal an additive drug (usually to a prostaglandin analog),
pachymeter. We believe that of all however, brimonidine is typically prescribed b.i.d.
the glaucoma assessment technolo- Interestingly, all three concentrations perform equiva-
gies currently available, pachymetry lently.
offers the best diagnostic power We urge you to have your staff obtain price
value. quotes on brimonidine and other commonly used
medicines from a few pharmacies near your office.
The Ideal Evaluation You’ll be amazed at the different prices for this and
Before we get into treatment other medicines.
options, let’s describe the ideal


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ogy is amply adequate to provide a glaucoma diagnosis is definitive ate soft, subjective psychometric
clinically meaningful measurements at the initial visit, the challenge is data. Therefore, it is vitally impor-
of the nerve fiber layer. Remem- to monitor for “progression,” and tant not to believe a defective visual
ber that none of these wonderful especially the rate of progression. field result unless it correlates with
technologies “diagnose” glaucoma; Once the rate of progression is your observation of the optic nerve
however, they can be a very helpful determined, then optimum therapy (or NFL analysis). An isolated,
component within the comprehen- can be prescribed. unexplained visual field defect re-
sive glaucoma evaluation. quires re-testing (in days, weeks or
12. Photograph the optic nerve Finer Points of the Exam months) to either confirm (or deny)
head. Any good retinal camera can There are a few common diag- the validity of such a visual field de-
provide either two- or three-dimen- nostic errors we encounter that fect. There is expert consensus that
sional documentation of optic nerve need to be addressed. Most of these it may take two to four additional
head anatomy. Such anatomic com- center around the concept of “mi- visual field tests to accomplish
parisons over time (i.e., years) can cromanagement” of any one of the this. Bottom line: If the visual field
be useful to document change in the various diagnostic entities that we correlates to optic nerve anatomy,
appearance of the optic nerve head. have set forth above. believe the visual field to be true.
Again, glaucoma is a “progres- • Visual fields. These are often If there is any question at all
sive” optic neuropathy. So, unless highly variable because they gener- regarding the validity of the visual

Topical Glaucoma Drugs

Beta Blockers
Betagan, and generic levobunolol hydrochloride Allergan 0.25% 5ml, 10ml
0.5% 5ml, 10ml, 15ml
Betimol timolol hemihydrate Vistakon Pharm. 0.25% 5ml
0.5% 5ml, 10ml, 15ml
Betoptic-S betaxolol hydrochloride Alcon 0.25% 5ml, 10ml, 15ml
Istalol timolol maleate Ista 0.5% 5ml
Timoptic, and generic timolol maleate Aton Pharma, generic 0.25% 5ml, 10ml, 15ml
0.5% 5ml, 10ml, 15ml
Timoptic (preservative-free) timolol maleate Aton Pharma 0.25% unit-dose
0.5% unit-dose
Timoptic-XE, and generic timolol maleate Aton Pharma, generic 0.25% 2.5ml, 5ml
0.5% 2.5ml, 5ml

Prostaglandin Analogs
Lumigan bimatoprost Allergan 0.03% 2.5ml, 5ml, 7.5ml
Travatan Z travoprost Alcon 0.004% 2.5ml, 5ml
Xalatan latanoprost Pfizer 0.005% 2.5ml

Alpha Agonists
Alphagan P, brimonidine Allergan, 0.1%, 5ml, 10ml, 15ml
and generic brimonidine generic 0.15%, 0.2% 5ml, 10ml, 15ml

Carbonic Anhydrase Inhibitors

Azopt brinzolamide Alcon 1% 5ml, 10ml, 15ml
Trusopt, and generic dorzolamide Merck 2% 5ml, 10ml

Combination Glaucoma Medications

Combigan brimonidine/timolol Allergan 0.2%/0.5% 5ml, 10ml
Cosopt dorzolamide/timolol Merck 2%/0.5% 5ml, 10ml


002_dg0610_glaucoma.indd 4 6/2/10 1:12 PM

field, always repeat it, and probably SAP vs. SWAP in the Detection of Glaucomatous Conversion
more than once (unless the previous “Despite its limitations, standard automated perimetry has become a standard in clini-
questionable defect disappears at cal care across the world. Short-wavelength automated perimetry (SWAP), however, has
the next re-test, which is extremely never gained such widespread acceptance … It is possible that SITA-SWAP will prove to
common). A healthy visual field can be useful for early detection of glaucomatous conversion. To date, there is insufficient evi-
generally be believed, but always dence for that. We therefore recommend that clinicians use standard automated perimetry
question the validity of an unex- (SAP) rather than SWAP in their daily practices to detect early glaucomatous conversion in
pected or unexplained visual field patients with ocular hypertension.
defect. We generally conduct visual “Although early SWAP visual field defects have been suggested typically to precede
field testing annually, unless there those in SAP in conversion from ocular hypertension to primary open-angle glaucoma,
is a medically valid reason to do so our prospective, longitudinal follow-up study does not support this suggestion. On the
sooner. contrary, SAP appears to be at least as sensitive to conversion as SWAP in a large majority
• Pachymetry. Forget the conver- of eyes.”
sion tables. Just judge the corneal
thickness as thin, normal or thick. van der Schoot J, Reus NJ, Colen TP, Lemij HG. The ability of short-wavelength automated
Our working ranges are: less than perimetry to predict conversion to glaucoma. Ophthalmology. 2010 Jan;117(1):30-4.
510µm is thin, and over 590µm is
thick. We sometimes use a calcula- we’re able to tell patients something For prostaglandins, we gener-
tion chart to explain to our patients like this: “If you were to present ally have the patient return in three
why they are at greater or lesser to 10 glaucoma experts, probably weeks, because this time period
risk for developing glaucoma, but half of them would treat you and generally gives these relatively
this is for patient orientation and half would simply follow you; I am slower-onset drugs time to achieve
education purposes, not for critical inclined to just follow you for a their full therapeutic effect. For all
clinical management. while”—or whatever scenario is ap- other drug classes, we have patients
• Optic nerve head size. Large plicable to the patient at that point back in two weeks.
optic nerves tend to have physio- in time. Beyond the mechanics of a thera-
logically large cups, and small optic The truth is, knowing the perfect peutic trial, it is important that the
nerves tend to have small cups. time (if ever) to initiate therapy is patient have a meaningful under-
Also, glaucomatous cupping tends based largely on an assessment of standing of why they are taking the
to evolve more rapidly in a small risk. Further, if your patient were eyedrops, and what to expect. We
optic nerve than in a large optic to seek a second opinion, you have always explain that reducing the
nerve. However, we never use the already made it clear to the patient intraocular pressure will not make
slit lamp reticule to exactly measure that knowledgeable glaucoma doc- their eyes feel better or help them
an optic nerve diameter. We simply tors often differ on patient manage- see better.
judge the nerve to be larger than ment decisions. Of course, the deci- By the way, we use so-called
normal or smaller than normal sion becomes clearer and clearer “glaucoma medicines” for many
by ophthalmoscopic observation. as you competently and attentively people who do not have glaucoma.
After a couple of years of clinical follow the glaucoma suspect patient When glaucoma is evident, we
experience, this is a relatively easy over the years. use “IOP-lowering medicines” to
observation. So, how do we appropriately be- actively intervene in a disease pro-
gin therapeutic intervention? While cess. However, a large minority of
Assess Risk the monocular therapeutic trial patients who use these eyedrops are
The prime decision in all glau- is not a foolproof maneuver, we simply modifying a risk factor—el-
coma-related cases is: “When do typically do start therapy in one eye evated IOP.
I initiate therapy?” This simple, and see the patient back about the If a patient has perfectly healthy
five-word question is the Holy same time of day (to attempt to fac- optic nerves, yet has an IOP of
Grail of clinical decision-making tor out any diurnal variation that 32mm Hg (and a corneal thickness
in glaucoma care. This decision is might be present). If several IOP below 560µm, for example) we
occasionally very clear, yet most of measurements are made prior to the could rationally recommend a once-
the time it is fraught with anguish. initiation of therapy, the patient’s daily eyedrop to reduce this risk
Having acquired considerable IOP pattern can be reasonably well factor down to the 25-ish range. If
clinical experience over the years, established. the corneal thickness were 640µm


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in this same patient, we could per- the lay of the land before altering Select Appropriate Therapy
haps more rationally simply follow the landscape. Let’s assume we have decided
the patient every six to 12 months. Lastly, we try to see our treated a patient merits IOP reduction, so
Therapeutic intervention needs to patients as infrequently as practi- what drug do we select?
be based on a comprehensive risk cal to safeguard their vision. Most • Prostaglandins. Most of the
assessment and a thorough discus- patients we see every three to four time, the answer is a prostaglan-
sion with the patient. months, several every six months, din, preferably one of the lower-
Since it would be exceedingly and a few patients—who we know concentration formula-
rare to start a patient on therapy at to be totally trustworthy and whose tions (having less side
the initial visit, we urge all eye doc- disease is well controlled—on an effect potential) such as
tors to move slowly, methodically annual basis. latanoprost 0.005% or
and comprehensively in assessing The main reason to see many/ travoprost 0.004%. All
and treating glaucoma patients. most patients is to encourage them of the prostaglandins
Collect three or four IOP readings to be faithful with their prescribed perform nearly identi-
at different times of the day. Know therapy. cally, so prescribing
decisions are based
Prostaglandin Pearls on side effect profile
• Although Xalatan and Viroptic are stored long-term under refrigeration, once dis- for most patients
pensed to the patient, there is no need to keep these products refrigerated. most of the time.
Regarding Viroptic, however, since herpes simplex keratitis can be recurrent, we (Note that Travatan
instruct our patients that once the keratitis has resolved and the drops are discontinued, is no longer available; although
to place any unused medicine back in the refrigerator to store it (until its expiration date) Travatan Z still is.)
in the event of any recurrence. While these drugs may
Regarding Xalatan, patients whose insurance allows them to get a 90-day supply at perform optimally when
one dispensing are generally instructed to keep the two bottles not currently being used instilled in the evening
in the refrigerator, and to keep the bottle currently in use in a location most conducive to (or before retiring
patient compliance. The prostaglandins should never sit in direct sunlight or be exposed to for those who work
hot temperatures. second- or third-
• Xalatan loses patent protection (i.e., “goes generic”) in March 2011. This will send shift), they perform
a shockwave of financial depression throughout the prostaglandin manufacturers’ world, nearly identically
and equal joy to millions of patients with glaucoma. While we doubt we will see a major when instilled in
drop in the cost of latanoprost right away, we hope to see considerable financial relief for the morning time.
our patients soon thereafter. This will be a significant defining moment in the natural his- So, the
tory of this class of drugs. time of
• There is little to no reason to switch between the prostaglandins. All three perform instilla-
clinically identically. tion should center
While prostaglandins perform optimally when instilled in the evening, these drops per- around when the
form excellently regardless of time of instillation. The best time to dose these medicines, patient finds it to be
then, is when it is most convenient for the individual patient. the most convenient.
• An excellent article in the Journal of Pharmacology and Therapeutics, Vol. 20, No. 4, Remember, compli-
2004, showed that the ocular hypotensive effect of latanoprost dosed once weekly was ance is the weak
“as effective” as when dosed once daily. Based on the evidence gleaned from this study link in the treatment
out of Tel Aviv University Medical Center, it would seem rational and prudent to consider chain, so we need to
q.o.d. or Monday-Wednesday-Friday administration. This would immediately reduce the do whatever we can
cost of therapy by approximately 50%. There is no risk in dosing the medicine in this to make adherence
manner; simply recheck the IOP after a month or two to see if target IOP is maintained. If most achievable for
it is, then the goal of effective (and cost-effective) IOP reduction is achieved. It’s just that each patient.
simple! • Beta blockers. Alternatively,
• Don’t forget that, although exceedingly rare, prostaglandins can cause flu-like symp- if cost is an overriding factor (and
toms and dyspepsia (stomach ache, gastritis). So always listen attentively (or ask proac- cost can compromise compliance),
tive questions) when seeing patients for follow-up. initiate therapy with a non-selective
beta blocker such as timolol or


002_dg0610_glaucoma.indd 6 6/2/10 1:12 PM

levobunolol; with rare exception, these are drugs suppress beta adrenergic tone. Our adrenergic
the only beta blockers we use. They are system is active while we are awake, and physiologi-
available in 0.25% and 0.5% concentra- cally asleep while we are asleep. There is little benefit in
tions, and are readily available for about attempting to pharmacologically suppress a system that
$4 per 5ml at many pharmacies. By com- is already physiologically suppressed. This is why it is
parison, prostaglandins cost about $60 to important to dose beta blockers shortly upon awaken-
$80 per 2.5ml. ing.
Since melanin pigments Beta blockers do little to decrease IOP during the
can bind some medicines, sleep cycle, yet seem to adequately preserve visual
we use the 0.5% concentra-
tions for our black patients, Beta Blockers and Asthma Patients
and 0.25% for white Although everyone knows to avoid use of beta blockers in
patients. Furthermore, numerous stud- patients with asthma, we would be remiss not to re-stress this
ies clearly support the use of these two “relative” dogma. Why “relative”? Somewhat surprisingly, beta
non-selective beta blockers once daily. It blockers can be safely and effectively used in some asthma
is best to have patients instill beta block- patients. Yes, you read this correctly. Ask any internist—that’s
ers shortly upon awakening for maximum how we came to learn this. We had a patient who we felt needed
therapeutic effect. Understand that these a beta blocker to achieve target IOP, yet noticed he was on a
systemic beta blocker and had asthma!
Pearls for Beta Blockers This required an explanation. His internist explained that beta
• Non-selective beta blockers are, by far, the most cost- blockers need to be used with caution in patients with asthma,
effective means to lower intraocular pressure. A 5mL bottle sells but were only relatively contraindicated. Since that time—and
for about $5. always with internal medicine consultation—we have success-
• The literature consistently states that non-selective beta fully used topical beta blocker eyedrops in a few select patients
blockers reduce intraocular pressure about 25%; the prostaglan- with asthma when it was necessary to achieve target IOP.
dins, about 30%. Reflect this narrow percentage gap against their Furthermore, Paul Lama, M.D., who trained as both an inter-
cost, and the value difference is staggering. nist and ophthalmologist, published his worldwide review of
• The non-selective beta blockers timolol and levobunolol are beta blocker use in the November 2002 American Journal of
properly dosed once daily, and shortly upon awakening. Since this Ophthalmology. Here is an excerpt from his conclusions:
class of drug suppresses the adrenergic system (which autonomi- “Ophthalmic beta-adrenergic blockers are effective in low-
cally “rests” when we sleep), it exerts is most therapeutic effect ering IOP and have a long history of success and tolerability,
during waking hours, so instillation upon awakening is maximally despite the known contraindications. However, many of the beta-
therapeutic. adrenergic blocker contraindications have been either disproven
• Timolol and levobunolol are the only two non-selective beta or there is no definitive evidence to prove a causal link. In fact, it
blockers that possess a long enough half-life to enable once-daily has been decisively shown that these agents administered sys-
administration, and are the only two beta blocker medicines we temically improve survival in CHF [congestive heart failure]. This
prescribe. review has identified no scientific studies supporting the devel-
• We never prescribe more expensive “gel-forming” formula- opment of worsening claudication, depression, hypoglycemic
tions, since they perform no better than the traditional solution unawareness or prolonged hypoglycemia in NIDDM [noninsulin-
formulations. We never prescribe non-generic beta blocker prod- dependent diabetes mellitus], sexual dysfunction, or impaired
ucts because of the expense. neuromuscular transmission with either systemic or ophthalmic
• Whenever we initiate therapy, we ask the patient to dose the beta-adrenergic blockers. Wide acceptance of such traditionally
medicine every morning for two weeks, but NOT the morning of purported side effects has been largely due to propagation of
the follow-up evaluation. This enables us to assess the therapeu- isolated case reports and short series as well as personal com-
tic effect over a full 24-hour period. munication felt to reflect expert opinion. Based on the published
• Since melanin pigment can absorb some of these medicines, evidence, many more patients are eligible for ophthalmic beta-
we use 0.5% for our black patients, and 0.25% for our white adrenergic blockers than previously presumed.”
patients. For perspective, note that more than 40 million prescriptions
• Because of the once-daily simplicity of use, we try a beta for systemic beta blockers are filled each year in the United
blocker as our “add-on” to a prostaglandin when we need addi- States. Beta blockers must therefore be assumed to be a very
tional IOP-lowering. helpful class of drug, and also quite safe.


002_dg0610_glaucoma.indd 7 6/2/10 1:12 PM

with glaucoma. therapy, will best serve the patient
The vast majority of as one drop every eight hours.
our glaucoma patients The problem is that there is an
are successfully managed inverse relationship between dos-
with either a prostaglan- ing frequency and compliance. In
din, or a beta blocker, recognition of this reality,
or a combination of the these drugs are generally
two. This is relatively in- prescribed b.i.d. (ap-
expensive, and requires proximately every 12
a drop either once daily, hours). Brimonidine is
or if using both, b.i.d. generically available
field. Looking at clinical reality, If there is non-response (or in its original con-
we do not recall an epidemic of minimal response) to one or both centration of 0.2%,
uncontrolled glaucoma between of these medicines, then the clinical in a second rendition
the introduction of timolol in 1978 decision-making becomes quite a of 0.15%, and also
until the introduction of latano- bit more challenging. (by the brand name,
prost in 1996. So, we do not truly • Carbonic anhydrase inhibitors Alphagan P) as a
know what to make of this find- and alpha adrenergic agonists. If 0.1% concentration. We recom-
ing, but perhaps inexplicably, it there is a need to move beyond a mend the 0.15% generic product
does not seem to be a major issue prostaglandin and/or a non-selec- in most patients most of the time,
in glaucoma patient care. Just for tive beta blocker, then do a thera- as this nicely balances cost and side
perspective, all current “combina- peutic trial of either brimonidine effect potential.
tion” glaucoma drugs contain 0.5% or a topical CAI—brinzolamide The CAIs are
timolol. This should be very clear or dorzolamide. Both of these known by their
evidence that beta blockers are drugs are FDA-approved for t.i.d. brand names: Tru-
noble players in the care of patients therapy, and when used as mono- sopt (dorzolamide,
Merck; and generic)
When to Treat? and Azopt (brinzol-
Of course, the most challenging amide, Alcon). Since
decision in glaucoma manage- brimonidine seems
ment is “when” to treat. This to be slightly more ef-
requires a keen intellect, a fective than a topical
thorough clinical evaluation, CAI, we generally try
and the wisdom to know how it as our “Plan B” of
to assimilate the clinical picture choice. There is some thought that
so as to maximally care for the a CAI is a more effec-
patient. Once a decision to treat tive “add to” drug to a
has been made, it now falls to prostaglandin than is
intelligent trial-and-error to find a beta blocker. Even if
the least amount of medicine this is true, addition of a
to achieve and maintain target CAI (or brimonidine)
IOP for each individual patient. requires a patient to
Fortunately, very few people who present in a timely manner ever become symptomatic instill a drop t.i.d., as
to their disease. opposed to just b.i.d.
But, for those people who see the eye doctor every 10 to 20 years (and there are a with a beta blocker—
bunch), undiagnosed glaucoma can be so advanced that the most skilled trabeculecto- we believe “simpler”
mist cannot save the eye from NLP. There is good reason for all people to see an eye here trumps perhaps
doctor every two or three years. “more effective.” Whatever the
By the way, when did you last have your eyes truly examined? We personally know case, the difference is almost invari-
two colleagues who now have very advanced glaucoma because they did not access eye ably clinically insignificant.
care in a timely manner. Please take as good care of yourselves as you do your patients. • Combinations. What about
the “combination” drugs, such as


002_dg0610_glaucoma.indd 8 6/2/10 1:12 PM

0.5% timolol with 0.2% Neuroprotection in Glaucoma Therapy
dorzolamide (Cosopt As there is still some lingering confusion regarding “neuroprotection,” we thought it
[Merck], which has might be helpful to share this information, which was first printed in our Clinical Guide to
been generic since Ophthalmic Drugs in 2002. It is still relevant in 2010.
October 2008) or What About Neuroprotection? Clearly, there are factors beyond IOP that cause glau-
0.5% timolol with comatous optic neuropathy in some patients, particularly where the IOP is never found to
0.2% brimonidine be above the upper limits of normal. Apoptosis (genetically programmed cell death) is the
(Combigan [Aller- centerpiece of neuroprotective research. The causes for apoptotic cell death are the focus
gan], an expensive of intensive investigation. It may well be that in a few years gene therapy will indeed play
combination of two a central role in glaucoma management. For now, as sad a state as it may be, all we can
relatively inexpen- do is decrease IOP. Fortunately, this proves to be sufficiently effective in the vast majority
sive generic products)? of patients with glaucoma.
Let’s become thinking prescribers There is a lot of talk about this concept of neuroprotection and its potential role in glau-
rather than reflex prescribers. We coma. We feel it is important to share the perspectives of several authorities in an effort to
know that timolol is only needed bring objective enlightenment to this concept.
once daily, and we know that • “Some drugs have some very interesting properties in experimental and animal
brimonidine and the CAIs are most models, but I know of no evidence that these results are necessarily relevant to glaucoma.
effective at their FDA-approved I don’t believe we have a drug that has a proven benefit in glaucoma beyond its IOP-
labeling of t.i.d. So, lowering effect.”
does it even make —Robert D. Fechtner, M.D., New Jersey University of Medicine and Dentistry
common sense to Eye World, January 2001
package these two
drugs together? We • “We do not have neuroprotective drugs that we can prescribe. We do not have
urge all clinicians to devices for retarding ganglion cell loss as of yet, with the exception of pressure-lowering
try timolol alone as agents.”
a therapeutic trial, —Evan Dreyer, M.D., Ph.D., Scheie Eye Institute, University of Pennsylvania
and to only “add” Primary Care Optometry News, February 2001
dorzolamide or
brimonidine if truly • “At this time, there is not a drug available to you that has known neuroprotective
needed to achieve features.”
target IOP. These —Harry Quigley, M.D., Wilmer Ophthalmological Institute
are rare occasions. Audio-Digest Ophthalmology, April 1998
Regarding “maximal medical
therapy,” we do feel that a prosta- • “Although the data on neuroprotection with brimonidine in animal models is com-
glandin and one of these combina- pelling, there is not yet any data regarding neuroprotection with Alphagan in glaucoma
tion drugs would represent such, patients.”
and would require instilling a drop —Louis Cantor, M.D., Indiana University School of Medicine
t.i.d. Expert Opinion on Pharmacotherapy, May 2000

In summary, glaucoma can either • “In the field of glaucoma, this past year [1999] was characterized by a lot of hoopla
be easily diagnosed (such as frank and some substance. Leading the hoopla camp is the whole area of neuroprotection …
glaucoma), or it can be very chal- one of the most important questions that needs to be answered has to do with why some
lenging—sometimes requiring one nerves are sensitive, and other nerves are resistant to the damaging effects of intraocular
to follow a glaucoma suspect for pressures.”
many years before circumstances —George Spaeth, M.D., Wills Eye Hospital
evolve to the point where therapeu- Yearbook of Ophthalmology, 2000
tic intervention is deemed appropri-
ate. ■ • “There is currently no solid evidence that any drug that has a blood-flow change or a
neuroprotective aspect has any advantage in the treatment of our glaucoma patients.”
1. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular
Hypertension Treatment Study: baseline factors that predict
—Thom Zimmerman, M.D., Ph.D., University of Louisville
the onset of primary open-angle glaucoma. Arch Ophthalmol. Audio-Digest Ophthalmology, February 2000
2002 Jun;120(6):714-20.


002_dg0610_glaucoma.indd 9 6/2/10 1:12 PM

Overview of
Oral Medicines
There are only a handful of oral medicines germane to eye care. Fortunately, O.D.s
in most states can now prescribe most of these oral medicines.
s optometrists, the mastery of the most frequently prescribed, let’s icillinase. This “combination” drug

A a handful of oral medicines

can be immensely helpful in
effecting a cure for many of the
begin with them.

Oral Antibiotics
is commonly known as Augmentin
(GlaxoSmithKline), and is another
excellent choice in combating most
ocular conditions we see. Having • Penicillins. The prototypic common eye and eyelid infections.
this “extended reach” of oral medi- antibiotics are the penicillins and It is prescribed as 500mg, 875mg,
cines is often necessary to meet the the synthetic penicillins. By and or 1,000mg b.i.d. for one week.
clinical needs of our patients. large, penicillins are rarely used in The 500mg and 875mg strengths
The most common use of oral eye care because most staphylococ- are generically available, while the
medicines is in the treatment of cal species produce penicillinase, an 1,000mg is still brand-name pro-
bacterial infections, most notably enzyme that degrades the clinical tected. The dosage is determined by
of the eyelids. Oral prednisone to efficacy of the penicillins. the severity of the clinical condi-
quell inflammation, and antivirals There are, however, certain tion. For most patients most of the
for the treatment of zoster condi- penicillins that are “penicillinase- time, we prescribe 875mg b.i.d. for
tions, are also oral medicines upon resistant.” The classic one is one week. For those patients with
which we heavily rely. dicloxacillin, which is generic and less severe disease, choose 500mg
There are few oral medicines has been for more than 20 years. b.i.d. For patients with more severe
germane to ophthalmic patient The standard dicloxacillin dosage disease, prescribe 1,000mg b.i.d.
care. The classes most commonly is 250mg q.i.d., and it can be taken for one week.
used are antibiotics, corticosteroids, without regard to meals. There is People with an allergy to penicil-
antivirals, analgesics and carbonic some question as to whether this lin have three choices: a cephalo-
anhydrase inhibitors. Since oral drug can be dosed at 500mg b.i.d.; sporin, a macrolide, or a fluoroqui-
therapy is becoming more widely we have had clinical success with nolone.
embraced by doctors of optometry, this dosage, but our pharmacologi- • Cephalosporins. Cephalospo-
we want to examine the clinical cal colleagues tell us that because of rins are closely related to penicil-
attributes of these medicines in by the drug’s relatively short half-life, lins, so a severe allergy to penicillin
providing an overview of select it is probably best dosed at 250mg precludes the use of these drugs.
drugs from each of these classes, q.i.d. for one week. Internists with whom we have
and some of the specific clinical Amoxicillin is the classic syn- consulted tell us that the selection
entities for which these drugs can thetic penicillin. To be clinically of a cephalosporin is common for
be used to restore health. effective against bacterial species patients who have had a minor
There are numerous drugs in producing penicillinase, it must be adverse reaction to penicillin;
some of these classes; the ones formulated with a chemical known however, if the patient does indeed
we’ve selected to discuss are those as clavulanic acid, which potenti- give a history of life-threatening
most commonly used in eye disease ates the amoxicillin and protects it anaphylaxis, then we would not
management. Since antibiotics are against the degrading effects of pen- prescribe any cephalosporin. Thus,


010_dg0610_orals.indd 10 6/2/10 1:15 PM

Oral Drugs
in most patients with a history of Corticosteroids can be very help-
penicillin anaphylaxis, choose either ful for a wide variety of acute in-
a macrolide or a fluoroquinolone. flammatory eye, orbital and eyelid
When an antibiotic is indicated, conditions. The universal work-
many doctors simply start with a horse of this class is generic pred-
cephalosporin (most commonly nisone, generally dosed at 40mg
cephalexin). Cephalexin is generi- once daily, and tapered over a few
cally available, but is commonly days to two weeks, depending upon
known by its brand name Keflex the severity of the presentation and
(MiddleBrook Pharmaceuticals). Topical therapy is useless for chlamydial the size of the patient. A modicum
The usual dosage is 500mg b.i.d. conjunctivitis. The treatment is simple: of clinical “art” and experience
for one week. one 1,000mg dose of oral azithromycin. is needed for precise prescribing.
There are many cephalospo- Corticosteroids are pregnancy rated
rins; however, cephalexin is a real as cephalosporin), this class is usu- as Category C.
workhorse in clinical practice. Note ally reserved for use when there is Since prednisolone is commonly
that there is a 5% to 10% cross- true penicillin anaphylaxis. available in 10mg tablets, prescrib-
sensitivity with the penicillin, so be While there are several fluoro- ing is made mathematically easy.
attentive with your history prior to quinolones available, we gener- There are also “dosepaks” that can
prescribing any orally administered ally select Levaquin (levofloxacin, be used. The most common dose
medicines. Ortho-McNeil). Levofloxacin is pack contains 4mg tablets, taken
• Macrolides. The macrolides a favorite of our local infectious as six tablets (24mg daily dose)
are represented by erythromycin, disease specialists, and with regard on day one, and then tapered by a
clarithromycin and azithromycin. to nationwide prescribing patterns, reduction of 4mg per day until day
The prototypic representative of is by far the most popular oral drug six, when only a single 4mg tablet
this class is erythromycin. It’s rarely in this class. (Of course, by virtue is taken. However, a starting dose
used for first-line therapy, but is of its popularity, and therefore its of 24mg is often insufficient, so we
very commonly used as a second widespread use, it means this drug rarely prescribe dose packs.
choice. Because of its Class B will eventually succumb to resis- There are also now available
pregnancy rating, erythromycin is tance.) generically 5mg and 10mg “dose-
the darling of obstetrical medicine The usual dosage for levofloxa- paks,” which provide a starting
when an antibiotic is needed. Eryth- cin is 500mg once daily for one dose of 30mg and 60mg respective-
romycin is commonly prescribed at week. In most situations when an ly. These are prepackaged just like
500mg t.i.d. for one week. antibiotic is indicated, and there is the original 4mg pack, and also pro-
Clarithromycin is rarely used in a history of penicillin anaphylaxis, vide a six-day course of treatment.
eye care, whereas azithromycin is we prescribe levofloxacin. We rarely use these dose packs
an excellent agent against chla- because we prefer more control over
mydial infections. Azithromycin is Oral Corticosteroids dosing. For example, in a patient
available in 250mg tablets, 500mg Corticosteroids are often viewed, with pronounced facial and orbital
tablets, 1,000mg oral suspension, or approached, with distinct clinical allergic dermatitis, we would com-
and Zmax (Pfizer), a 2,000mg hesitation. Such hesitation is likely monly dose 60mg for one to two
extended-release oral suspension. borne out of the potential for long- days, then 40mg for two days, then
One dose of either 1,000mg or term side effects from corticoste- 20mg for two days and then stop.
2,000mg azithromycin (in any roids, and the timidity of teaching Such prescribing is highly variable,
form) is chlamydiacidal in most on this class of drugs. depending upon the severity and
cases. Other than in chlamydial However, the clinical wisdom of nature of the clinical condition.
infections and/or in pregnancy, we short-term use of these drugs dem- Some conditions, such as orbital
never use a macrolide as a first-line onstrates their awesome healing pseudotumor, may require higher
antibiotic. powers and their very few tem- initial dosing. We generally divide
• Fluoroquinolones. The fluoro- porary side effects. Of course, for the dose at 60mg and higher, so
quinolones are excellent, broad- maximum patient care, an accurate that 30mg is taken b.i.d., 40mg
spectrum antibiotics. Since less diagnosis is essential, regardless of b.i.d. (if 80mg is prescribed), etc.
expensive drugs are available (such the medicine prescribed. Steroids are best taken with meals


010_dg0610_orals.indd 11 6/2/10 1:15 PM

Oral Drugs
to minimize the possibility of gas- For acyclovir, the dose is 800mg is impaired, there are computer-
trointestinal upset. five times a day for one week; for based algorithms and formulas to
A little perspective: The dosage valacyclovir, the dose is 1,000mg quickly and easily determine the
for acute optic neuritis and giant three times daily for one week; and appropriate dosage. You will need
cell (cranial/temporal) arteritis is for famciclovir, it is 500mg three to contact the patient’s physician
1,000mg of methylprednisolone times daily for one week. or nephrologist/urologist to obtain
(500mg q12 hours) IV daily for Since the herpes simplex virus the glomerular filtration rate and/
three days. By comparison, the dos- (HSV) is less virulent than is the or creatinine clearance rate.
ages we use orally are considerably varicella zoster virus, herpes simplex Once this information is in
more tame. requires less antiviral to achieve vi- hand, your physician partner or
rucidal levels; in fact, it is prescribed pharmacy partner can calculate
Oral Antivirals at exactly half the standard anti- the dosage of the antiviral for you.
The antivirals are routinely em- zoster dosage. Thus, to treat any This is a very standard and routine
ployed in the management of ocular HSV disease, the dosage of acyclo- maneuver. This situation occurs
and dermatologic herpetic disease. vir is 400mg five times daily for one very rarely; however, in the face of
Acyclovir (ACV), valacyclovir week; for valacyclovir, it is 500mg such kidney disease, the dosage is
(Valtrex, GlaxoSmithKline) Famvir three times daily for one week; and reduced. Since the drug is not read-
(famciclovir, Novartis) are now all for famciclovir, it is 250mg three ily excreted through the kidneys,
available generically. Because ACV times daily for one week. All dos- it remains at a chemotherapeutic
has a short half-life, it is dosed five ages are used for seven to 10 days, level for a longer period of time.
times daily (roughly every 3 1/2 most often for one week. It’s simple, Other than this one wrinkle,
hours), whereas valacyclovir and really, but you may want to keep antivirals are safe, highly effective
famciclovir, having longer half- this table handy: medicines for treating all stripes of
lives, are dosed t.i.d. (roughly every
eight hours). They are all relatively To Treat Shingles (VZV), Give Double the Dose Used for HSV
clinically equivalent. Dosing for Dosing for
The special chemistry of all these Antiviral Drug Varicella Zoster Herpes Simplex
medicines confers upon them great Acyclovir 800mg 5x q.d. x 1 week 400mg 5x q.d. x 1 week
clinical safety. Let us explain: All of Valacyclovir 1,000mg t.i.d. x 1 week 500mg t.i.d. x 1 week
these medicines are in fact placebo
Famciclovir 500mg t.i.d. x 1 week 250mg t.i.d. x 1 week
in nature until they are converted
by virally expressed thymidine ki- Acyclovir is available in 200mg herpetic viral disease.
nase into active medicine through a capsules, 400mg and 800mg tab-
process known as phosphorylation. lets, and in a 200mg-per-teaspoon Analgesics
The virally-activated drug now (5ml) banana-flavored oral suspen- Usually, a topical cycloplegic
rapidly, effectively and non-toxi- sion. Valacyclovir comes in 500mg agent and/or a topical NSAID suf-
cally eradicates viral replication, and 1,000mg tablets. Famciclovir ficiently control ocular pain; the
resulting in clinical cure. The drug is available in 125mg, 250mg cycloplegic is used for uveitic condi-
is minimally uptaken into non- and 500mg tablets. All the oral tions, and the NSAID for ocular
virally infected cells, which renders antiviral medicines are Pregnancy surface disorders.
such excellent safety. The dosage is Category B. However, there are times when
fixed, and can therefore be rotely The only precaution for these oral therapy is needed to keep the
memorized. antivirals centers around kidney patient tolerably comfortable. For
One distinction, however, is function, as all of the antiviral perspective, an opioid analgesic (hy-
made between varicella zoster drugs are eliminated via the urine. drocodone/acetaminophen) is, by
(shingles) and herpes simplex dis- So always ask patients, especially far, the most frequently prescribed
ease. Varicella zoster virus infection older patients, about any known oral drug in the United States.1
is the prime target disease of these renal disease. Patients with clini- Fortunately, eye-related pain,
antivirals; therefore, their standard cally significant kidney disease are which can certainly be intense, is in-
prescribing dosages are for the usually aware of such. Should you variably short lived. Corneal abra-
treatment of such varicella infec- encounter an older patient with sions, recurrent erosions, inflamma-
tions, almost exclusively shingles. acute shingles whose renal function tory keratitis, severe iritis and some


010_dg0610_orals.indd 12 6/2/10 1:15 PM

Oral Drugs
eyelid processes are common causes by far the most prescribed schedule. determine the level of analgesia are
of eye pain that might require sup- Tylenol #3 has historically been the patient’s general threshold for
plemental oral analgesia. The most the workhorse in this class of drugs. pain, the nature of the injury or
straightforward approach is to ask It is a combination of 30mg of condition, and the patient’s percep-
patients what they generally use for codeine and 300mg of acetamino- tion of the pain’s intensity. Generi-
pain. The most common answers phen. Because of its propensity to cally speaking, the greater the pain,
are extra-strength acetaminophen cause nausea, and the realization the more drug is needed to achieve
and ibuprofen, and these usually that hydrocodone is more effective pain control.
carry the patient through. for controlling pain, it has lost con- Common dosing of any of these
Acetaminophen (N-acetyl-para- siderable ground to hydrocodone as narcotic analgesics is one tablet p.o.
aminophenol, or APAP) is indeed the Schedule III favorite. All narcot- every four to six hours p.r.n. for
an excellent analgesic, which also ics can cause nausea, so it is always pain. The quantity of drug pre-
has antipyretic (fever-reducing) best to take them with food. scribed by the doctor is a clinical
properties. It is known commonly
by its original brand name Extra Abuse Alert for Analgesics
Strength Tylenol (McNeil), but Beware of weird histories, weird presentations, and weird patients who know more about
generics are now ubiquitous. Acet- this class of drugs than the doctor. These patients may be “narcotic-seeking.” People
aminophen is synergistic with oral have been known to harm themselves (Munchausen syndrome) in order to extract a pre-
narcotic analgesics and is common- scription from a doctor.
ly found as a component to most
such drugs. Hydrocodone with acetamino- judgment. We typically dispense 10
Non-steroidal anti-inflammatory phen is the most commonly or 12 tablets, and spell out the num-
drugs (NSAIDs), such as ibuprofen, prescribed narcotic analgesic, and ber (i.e., “ten” rather than “10”) to
are likewise very broadly used and one with which we all need to be prevent numeric tampering.
are generically available. Ibupro- familiar and comfortable. While ge- Schedule II narcotics include oxy-
fen is available over-the-counter neric, these are commonly referred codone with APAP. These drugs do
as 200mg tablets or capsules. The to by their original brand names offer a slight increase in analgesia
optimum dosage of ibuprofen is Lortab (UCB Pharma) and Vicodin control. The common players are
1,600mg per day. It is most often (Abbott), but signed as “generic Tylox (Ortho-McNeil) and Perco-
dosed as two 200mg tablets taken substitution permitted” on the cet (Endo Pharmaceuticals). Tylox
every four hours. This dosage is prescription pad: contains 5mg of oxycodone and
generally sufficient and approxi- • Lortab contains 2.5mg hydro- 500mg of APAP. Percocet is most
mates that of a Schedule III opioid. codone with 500mg APAP. commonly prescribed as 5mg of
There is an abundance of oral • Lortab 5 contains 5mg hydro- oxycodone with 325mg APAP.
opioid analgesics. (The best we’ve codone with 500mg APAP. Schedule III drugs can be tele-
read on the topic of pain control is, • Lortab 7.5 contains 7.5mg phoned or faxed to a pharmacy;
“Drugs for Pain,” published in The hydrocodone with 500mg APAP. Schedule II drugs can only be dis-
Medical Letter, Vol. 42, issue 1085, • Lortab 10 contains 10mg hy- pensed with a written prescription.
August 21, 2000, www.themedi- drocodone with 500mg APAP. If you want a quick, • Vicodin contains 5mg hydroco- In summary, the opioid analge-
thorough, and clinically relevant done with 500mg APAP. sics are a safe and effective class of
overview on this topic, we highly • Vicodin ES contains 7.5mg drugs that can help patients with
recommend this article.) Narcotic hydrocodone with 750mg APAP. select conditions gain tissue restora-
prescribing requires state statutory • Vicodin HP contains 10mg tion with minimal discomfort. The
authority (the Optometric Practice hydrocodone with 650mg APAP. risk of addiction occurs with long-
Act), and formal registration with For most patients most of the term use of Schedule II or Schedule
the Drug Enforcement Administra- time, we simply write for Vicodin, III drugs; not for a day or two as in
tion (DEA). and sign over the “generic permis- the treatment of painful eye condi-
Narcotics are available at five sible” line on the prescription pad. tions. ■
scheduled levels. We will focus If you feel your patient needs 7.5mg 1. IMS Health web site. 2009 Top Products by U.S.
mostly on Schedule III drugs, which or 10mg of hydrocodone, then Dispensed Prescriptions. (Accessed
May 31, 2010.)
include codeine and hydrocodone, write accordingly. The factors that


010_dg0610_orals.indd 13 6/2/10 1:15 PM

The Simplicity of
Allergy Management
Allergy management is rather straightforward. Identify the predominant symptoms
—and the signs—then treat accordingly.
or the most part, when a discussed under the dry eye • azelastine (Optivar, Meda

F patient presents with symp-

toms of a dry, scratchy, itchy,
burning and gritty feeling, this is a
On the other hand, if
itching is the predominant
• bepotastine (Bepreve, ISTA
patient suffering from “dry eyes.” symptom, drug selection is • epinastine (Elestat, Allergan)
Even though itching is a component dichotomous: • ketotifen (Zaditor, Novartis;
of the constellation of presenting If there are minimal as- now available generically
symptoms, this subcomponent sociated signs of allergy, such and OTC)
itching is likely an opportunistic as chemosis, conjunctival • olopatadine (Pata-
expression resulting from ocular injection, and/or eyelid edema, nol/Pataday, Alcon).
surface tear film dysfunction, i.e., along with the predominant itch- Notwithstanding fine
dryness. This dry eye-associated ing, then an antihistamine/mast differences, all of these
symptomatic itching is best man- cell stabilizer is an excellent clinical antihistamine subtype 1
aged by treating the underlying approach. Within this class, there receptor blockers nicely
primary dry eye. This is extensively are five drugs: suppress ocular itching.
All are dosed initially
Update on Bepreve b.i.d. (except Pataday, which
Bepreve (bepotastine, ISTA Pharmaceuticals) is the first is dosed once-daily). We
new topical ophthalmic drug for allergic conjunctivitis recommend after two
approved in several years. weeks at b.i.d., try reduc-
Here is The Medical Letter’s summary statement, ing these to once-daily as
from February 8, 2010, regarding Bepreve: “Bepotastine “maintenance” therapy.
besilate 1.5% ophthalmic solution (Bepreve) is likely to be In our experience, once
effective for treatment of ocular itching associated with symptomatic itching has
allergic conjunctivitis. There is no evidence that it offers been brought under con-
any advantage over other ophthalmic H1-antihistamines.” trol, it takes less pharmacological
(The Medical Letter,, is an independent, peer-reviewed, non- intervention to maintain control.
profit publication that offers unbiased critical evaluation of drugs, with special emphasis Perhaps the best news for the
on new drugs. It is completely independent of the pharmaceutical industry.) consumer is the loss of pat-
Furthermore, this same article includes a cost comparison on the antihistamine/mast ent protection for Zaditor.
cell stabilizing drugs. All drugs in this class cost about $100 for a standard size bottle, Ketotifen is now available
except for generic ketotifen (Alaway, Claritin Eye, and Zaditor), which was less than $15. generically and OTC.
Since Bepreve (Rx) and Alaway (OTC) come in 10mL bottles—compared to 5mL for There are several brand-
most other topical allergy drugs—these clearly offer the most value per drop. We should name OTC ketotifen
be mindful of these facts when we place pen to prescription pad. preparations, such as
Alaway (Bausch + Lomb),


014_dg0610_allergy.indd 14 6/2/10 1:18 PM

Allergy Drugs
Claritin Eye (Schering- involves frequency of instillation, ger prescribe these pure mast cell
Plough) and Refresh Eye Itch which could be q2h for two days, stabilizers.
Relief (Allergan). All come then q.i.d. for one week, followed Remember, allergy is an expres-
in 5mL bottles (except for by b.i.d. for one more week. sion of inflammation. Cold com-
Alaway, which comes as a Once the inflammatory signs are presses can be helpful in almost all
10mL bottle.) Interestingly, controlled, then consider switch- ocular surface inflammatory dis-
our casual observations in a ing the patient to an antihistamine/ eases. (Infectious processes, on the
variety of pharmacies reveal mast cell stabilizer for ongoing other hand, are commonly helped
that the cost of 10mL Alaway symptom control. Long-term treat- by the application of warm soaks.)
is very near (and occasionally ment with Alrex b.i.d. as mainte- In summary, if itching is not the
cheaper) than the price of its 5mL nance therapy can be done, if need primary symptom, be sure to con-
competitors. So, it should be clearly be. sider dry eyes as the foundational
evident that OTC Alaway is the According to a conversation we condition and treat accordingly. If
most cost-effective way to suppress had with Mark Abelson, M.D., a itching is primarily expressed, de-
ocular itch. world-renowned ocular allergist termine if it is an isolated symptom
If there are one or more at Harvard Medical School, there or if it is associated with concurrent
concurrent signs of allergy, is little or no clinical use for pure inflammatory signs, and then treat
such as conjunctival red- mast cell stabilizing drugs. He says accordingly.
ness, chemosis, and/or eye- that the antihistamine/mast cell Remember:
lid edema, along with the stabilizer drugs more effectively sta- • Symptoms only—use an anti-
predominant itching, then bilize the mast cell membranes than histamine/mast cell stabilizer.
a topical corticosteroid standalone mast cell stabilizers such • Symptoms with signs—use a
such as Alrex, Lotemax or as pemirolast (Alamast, Vistakon), steroid such as Lotemax, Alrex or
FML ophthalmic suspension would nedocromil (Alocril, Allergan), or FML.
be more appropriate treatment. cromolyn sodium (generic). Based Actually, allergy management is
The only other decision tree on this expert opinion, we no lon- very straightforward. ■

Ocular Allergy Medicine Profile

Acute Care Products
Acular LS ketorolac tromethamine 0.4% Allergan 3 years 5ml, 10ml q.i.d.
Alaway (OTC) ketotifen fumarate 0.025% Bausch + Lomb 3 years 10ml b.i.d.
Alrex loteprednol etabonate 0.2% Bausch + Lomb 12 years 5ml, 10ml q.i.d.
Bepreve bepotastine besilate 1.5% ISTA 2 years 10ml b.i.d.
Claritin Eye (OTC) ketotifen fumarate 0.025% Schering-Plough 3 years 5ml b.i.d.
Elestat epinastine HCl 0.05% Allergan 3 years 5ml b.i.d.
Emadine emedastine difumarate 0.05% Alcon 3 years 5ml q.i.d.
Optivar azelastine hydrochloride 0.05% Meda 3 years 6ml b.i.d.
Pataday olopatadine hydrochloride 0.2% Alcon 3 years 2.5ml q.d.
Patanol olopatadine hydrochloride 0.1% Alcon 3 years 5ml b.i.d.
Refresh (OTC) ketotifen fumarate 0.025% Allergan 3 years 5ml b.i.d.
Zaditor (OTC) ketotifen fumarate 0.025% Novartis 3 years 5ml b.i.d.

Chronic Care Products

Alamast pemirolast potassium 0.1% Vistakon Pharm. 3 years 10ml q.i.d./b.i.d.
Alocril nedocromil sodium 2% Allergan 3 years 5ml b.i.d.
Alomide lodoxamide tromethamine 0.1% Alcon 2 years 10ml q.i.d.
Crolom cromolyn sodium 4% Bausch + Lomb 4 years 10ml q.i.d.
Opticrom cromolyn sodium 4% Allergan 4 years 10ml q.i.d.


014_dg0610_allergy.indd 15 6/2/10 1:18 PM

Insights Into
Adenoviral Infections
A keen understanding of the natural history and pathophysiology of adenoviral infec-
tion is crucial to precise management. To maximize the therapeutic response, initiate
treatment as early as possible.
ollowing are two diametri- “Dear Doctors, you know it infiltrates, smiling, no sunglasses,

F cally opposed statements. You

decide which one is true:
never fails—go to a meeting and
then see the very thing the lec-
turer was discussing. Well, I had
and headed to school! Thanks for
making me look like a genius!”
–E-mail correspondence, Novem-
“Since viruses incorporate a patient with the worst EKC I ber 20, 2009
themselves within host cells and use had ever seen—started in one eye,
host cell machinery for replication, then the other, and now comes in So, how do we reconcile these
they are notoriously hard to treat wearing two pairs of sunglasses and apparently contradictory state-
without unwanted toxic effects. miserable. I gave her the bilateral ments? We probably have to resort
Adenoviruses are no exception, Betadine treatment protocol late to such observations as “the proof
as there are currently no avail- Wednesday afternoon, and the staff is in the pudding,” and just good,
able treatments for these diseases, paid close attention. (You know, old-fashioned common sense.
although most infections typically ‘Does he really know what he is We’re privileged to speak to many
resolve themselves.” doing? – Watch.’) She returned thousands of our colleagues each
Review of Ophthalmology, this morning, less than 48 hours year, and in inquiring of these
March 2010 later, with only trace injection, no highly diverse audiences, we dis-
cover two consistent findings: Very
few O.D.s have performed Betadine
treatment for patients with epidem-
ic keratoconjunctivitis (EKC). And
of those who have, 100% of them
have had excellent success. This,
too, is difficult to reconcile—this
treatment is unbeatable, yet so few
eye doctors use it.
To that end, we set forth the fol-
lowing Betadine protocol for acute
EKC, which we have successfully
used more than 200 times.
In using this Betadine proto-
col, it is important to understand
the natural history of adenoviral
infection. There are approximately
If diagnosis of adenoviral disease is elusive, the RPS Adeno Detector may help. eight days of latency between the


016_dg0610_antivirals.indd 16 6/2/10 1:25 PM

Antiviral Drugs
time of viral acquisition and overt
disease expression. Then, there are
approximately eight days of active
disease, when the eye is injected
and uncomfortable. It’s during this
acute infectious stage that viral
eradication via Betadine 5% Sterile
Ophthalmic Prep Solution (povi-
done-iodone, Alcon) is most ben-
eficial to the patient. Just as with
the oral antivirals in treating herpes
simplex or herpes zoster infections,
the earlier in the acute disease phase
that you can intervene, the more
beneficial the therapeutic effect.
Let’s look at the clinical features
of acute EKC. Patients typically
present with a history of acute
redness starting in one eye, then
spreading to the fellow eye in two This patient presented with severe EKC. He had the classic signs of acute red eye
to three days. A watery discharge (top) and watery discharge (above).
is a constant feature. A palpable
preauricular lymph node is com-
monly detected (if you feel for it) on
the side of the initially infected eye.
In more advanced cases, the bulbar
conjunctiva can demonstrate mul-
tiple petechial hemorrhages, most
commonly seen superiorly.
By contrast, bacterial conjunc-
tivitis can have variably expressed
microvascular injection of the con- Just two days after treatment with our EKC-Betadine protocol, his eyes were white
junctiva and evident mucopurulent and quiet.
discharge. Only in “hyperacute”
bacterial conjunctivitis is there • Because Betadine can cause the 5% Betadine in contact with
evident preauricular lymphade- mild stippling to the corneal epithe- the ocular surface for two minutes
nopathy. lium resulting in marked stinging, (when prepping for intraocular sur-
If diagnostic certainly is elusive, instill a drop or two of a topical gery); however, our experience in
the RPS Adeno Detector (www. NSAID prior to instillation of the the treatment of EKC has been that may be helpful. Betadine. one minute of contact is sufficient.
• Now instill four to six drops of • Just for good measure, instill
The EKC-Betadine Protocol Betadine into the eye(s). another drop or two of the NSAID
When we encounter a patient • Ask the patient to gently close (or even proparacaine if the patient
with moderate to advanced EKC, the eyes and roll them around to has any discomfort).
we generally use the following ensure thorough distribution of the • Add a potent corticosteroid
EKC-Betadine Protocol. Betadine across the ocular surfaces. q.i.d. for four days.
• By history, rule out any allergy • After one minute, lavage out Since using this protocol, we
or sensitivity to iodine, the molecu- the Betadine (to avoid any unneces- have not had a patient to go on to
lar backbone of Betadine. sary toxicity and discoloration of develop the legendary subepithelial
• Instill a drop of 0.5% propara- the tissues) with any sterile oph- infiltrates. We reason that by rapid
caine into the eye(s), since Betadine thalmic irrigating solution. Note: diminution and/or elimination of
can sting upon instillation. The package insert states to leave live virus from the ocular surface,


016_dg0610_antivirals.indd 17 6/2/10 1:25 PM

Antiviral Drugs
‘Off-label’ Use of Ophthalmic Drugs and Devices label,’ or approved, when a sponsor conducts a prospective mul-
“The practice of ophthalmic off-label drug use is neither uncom- ticenter clinical trial to show its safety and efficacy for a particular
mon nor new,” says an editorial in the May 2007 American Journal indication. Often these regulatory trials are of limited value, for
of Ophthalmology. “The prevalence and clinical importance of several reasons. First, often the approved indication is of little
prescribing drugs for unlabeled uses are substantial … thus the value, whereas off-label indications are the primary use,” says
prescribing of drugs for unlabeled use is often necessary for opti- a letter to the editor in the January 2010 American Journal of
mum patient care.”1 Ophthalmology.2
The article also quotes an FDA statement on “off-label” usage: This writer goes on to say, “Manufacturers often take the most
“Good medical practice and the best interest of the patient require direct route to an approval rather than demonstrating the best use
that physicians use legally available drugs according to their best of the product in a clinical trial. For example, topical ophthalmic
knowledge and judgment. If physicians use a product for an indica- antibiotics universally are approved only for the treatment of bac-
tion not in the approved labeling, they have the responsibility to be terial conjunctivitis, a self-limiting condition with little morbidity.
well informed about the product, to base its use on firm scientific However, their greatest value is in the treatment of bacterial kera-
rationale and on sound medical evidence, and to maintain records titis and in prophylaxis after ophthalmic surgery. These applica-
of the products’ use and effects.” tions are proven off-label uses. The use of these agents is entirely
In summary, “Treatment with any drug or therapy is based on a ethical.”2
consensus between a well informed patient and physician. This is A follow-up letter in the same journal states, “In ophthalmol-
no different in the case of the use of off-label ophthalmic medica- ogy, off-label drugs and devices play an enormously important role
tions. The more scientifically sound the information supporting its in our ability to care for patients … Ophthalmology has a strong,
use, the more confidently can the physician and patient assess the proud, and vibrant tradition of practicing off-label.”3
possible value of the proposed unapproved treatment.”1
1. Parrish R 2nd, Sternberg P Jr. Does “off-label” mean off limits for patient care? Am J
“The Ophthalmic Mutual Insurance Company recognizes that Ophthalmol 2007 May;143(5):853-5.
‘off-label’ use of approved medications is a legal and necessary 2. Maloney RK. Off-label use of drugs and devices. [Correspondence]. Am J Ophthalmol.
2010 Jan;149(1):170.
part of the practice of medicine.”1 3. Rosenfeld PJ, Goodman KW. Off-label use of drugs and devices. [Correspondence]. Am
For additional perspective: “A drug or device becomes ‘on- J Ophthalmol. 2010 Jan;149(1):170-1.

there is insufficient time for enough “Topical azithromycin is likely as prophylaxis demonstrated that
viral particles to migrate into the effective for the important causes povidone-iodine was more effective
anterior stromal tissues to incite an of ophthalmia neonatorum as its than the other agents for preventing
immune response. fellow macrolide erythromycin ... infectious conjunctivitis, including
Take note of the safety and effica- A controlled clinical trial compar- chlamydial conjunctivitis ... We
cy of this approach. As an example, ing erythromycin 0.5%, povidone- believe povidone-iodine would be
Betadine is used in just-born infants iodine 2.5%, and silver nitrate a suitable and perhaps preferable
to prevent ophthalmia neonatorum: 1%, for ophthalmia neonatorum alternative to azithromycin for oph-
thalmia neonatorum prophylaxis.”1
Sources for Betadine 5%
We’re often asked, “Where or how can I acquire Stopping Sequelae
5% Betadine?” Now, back to the “rule of
There are probably many sources. Here are a few: eights”: If left untreated, after eight
• or so days of active viral expres-
• sion, a secondary immune response
• is commonly seen, typically clini-
• cally expressed as infiltrative viral
These companies offer a broad array of oph- keratitis, as evidenced by disciform
thalmic products. The 30ml opaque plastic bottle subepithelial keratitis.
of Betadine 5% sells for approximately $16. For perspective, Thygeson’s SPK
Also, if “sampling” becomes an historic event, is an intraepithelial disease process,
one can purchase at minimal cost a wide variety and therefore some fluorescein dye
of generic ophthalmic drops from these same uptake can be seen. However, the
sources to keep in the office for altruistic use for indigent patients, or when seeing emer- subepithelial infiltrates following
gency patients after hours. adenoviral infection are indeed
subepithelial, and therefore do not


016_dg0610_antivirals.indd 18 6/2/10 1:25 PM

Antiviral Drugs
stain. Antiviral Update on Zirgan
If such sequelae to EKC occur, The eyecare professions have greatly
then a protracted course of cortico- enjoyed the improvement trifluridine
steroid therapy is usually required (Viroptic) gave us over idoxuridine (IDU)
to subdue or clear these inflam- about 30 years ago. Thankfully, pharmaco-
matory subepithelial lesions. We therapy continues to improve. While triflu-
would select loteprednol, because ridine performed well, there always loomed
of the multi-week to multi-month the potential for epithelial toxicity because
therapeutic intervention that may the drug attacked both uninfected as well
be required to clear the cornea. Our as infected cells.
treatment for symptomatic (blurred As of 2010, Sirion Therapeutics has
vision) subepithelial infiltrates is brought us an ophthalmic formulation of
typically Lotemax q.i.d. for one ganciclovir, a systemic antiviral approved by
month, t.i.d. for one month, b.i.d. the FDA in 1989. Oral ganciclovir has been
for one month, and then daily for extensively used to treat cytomegalovirus
one month. infections since it came to market. Like
If the steroid is halted premature- acyclovir, ganciclovir is essentially an inert
ly or is tapered too quickly, the im- compound until it is activated into a chemo-
mune-mediated lesions can reform. therapeutic medicine via phosphorylation by viral enzymes. Because ganciclovir targets
Not until the viral particle antigen only virally-infected cells, it has a greatly expanded therapeutic safety profile.
load is reduced below a biologic Zirgan (ganciclovir 0.15%) is an ophthalmic gel-drop that comes in a 5g tube, and
threshold level capable of inciting is specifically FDA indicated for the treatment of acute herpetic keratitis. Typical dosing
an immune response can corticoste- is five times daily for four to five days, then t.i.d. for three to four more days, depending
roid suppression be stopped. This upon tissue response. We are thrilled with the prospect of having a topical drug that is
is accomplished through biological equally efficacious as trifluridine, yet one with a much enhanced safety profile available
antigenic attrition, and may take for the treatment of epithelial herpes simplex keratitis.
many weeks to months. Until this While truly exciting, keep in mind that the least expensive treatment for epithelial
natural degradation of viral anti- infections is oral acyclovir 400mg five times a day for a week. If/when the generic for
genic load occurs, we attempt to use valacyclovir drops in cost to the level of acyclovir, we will abandon that antiviral with its
the least amount of steroid possible five-times-daily dosing in favor of generic valacyclovir with its three-times-daily dosing
to maintain acceptable vision. Indi- schedule as a result of its longer half-life of therapeutic activity.
vidualization of therapy, as always,
is certainly indicated here.
Bear in mind that when these
subepithelial infiltrates occur, the
eye is usually white and quiet. The
acute infectious phase has passed,
and now the patient presents with
the complaint of blurred vision in a
relatively quiet, comfortable eye.

A keen understanding of the

natural history and pathophysiology
of adenoviral infection is crucial to Patients with EKC typically present with acute redness starting in one eye, then
precise management of the spectrum spreading to the fellow eye in two to three days. A palpable preauricular lymph node
of disease that can be encountered. is commonly detected (if you feel for it) on the side of the initially infected eye.
Again, if you treat EKC early on,
you’ll almost always prevent these Ophthalmic Instruments
secondary immune responses. ■ Looking for curved-tipped forceps to peel away EKC membranes? The online sites
for Storz Ophthalmic Instruments and Bausch + Lomb Instruments are now at
1. Keenan JD, Eckert S, Rutar T. Cost analysis of povidone-
iodine for ophthalmia neonatorum prophylaxis. Arch and
Ophthalmol. 2010 Jan;128(1):136-7.


016_dg0610_antivirals.indd 19 6/2/10 3:23 PM

Insights in Antibiotics
Use antibiotics for active bacterial infection or when there’s significant risk of
opportunistic infection. Otherwise, consider a steroid/antibiotic combo drop.
n addition to the introduction and for how long. We stress the scribe an antibiotic, consider that

I of Besivance last year, there’s

now a higher concentration of
gatifloxacin available as Zymaxid,
limited indication for this class of
drugs: either evidence of an active
bacterial infection, or prophylacti-
an antibiotic/corticosteroid combi-
nation drug has a vastly enhanced
chance of effecting tissue resolution
from Allergan. Thus, we are cally when there is significant risk since ocular surface inflammatory
fortunate to have a wide array of of opportunistic infection, such as processes are much more com-
antibiotics from which to choose. when using a bandage soft contact mon than are bacterial infectious
The key decision regarding this lens to treat a corneal abrasion. processes.
class of drugs is not so much which If the red eye diagnosis is not To give more insight into mi-
antibiotic to use, but how often, certain, rather than blindly pre- crobial resistance and antibiotic

Topical Antibiotic Drugs

Besivance besifloxacin 0.6% Bausch + Lomb suspension > 1 yr. 5ml
Ciloxan, and generic ciprofloxacin 0.3% Alcon, and generic sol./ung. > 1 yr./ > 2 yrs. 5ml, 10ml/3.5g
Iquix levofloxacin 1.5% Vistakon Pharm. solution > 6 yr. 5ml
Ocuflox, and generic ofloxacin 0.3% Allergan, and generic solution > 1 yr. 5ml, 10ml
Quixin levofloxacin 0.5% Vistakon Pharm. solution > 1 yr. 5ml
Vigamox moxifloxacin 0.5% Alcon solution > 1 yr. 3ml
Zymar gatifloxacin 0.3% Allergan solution > 1 yr. 5ml
Zymaxid gatifloxacin 0.5% Allergan solution > 1 yr. 2.5ml

Tobrex, and generic tobramycin 0.3% Alcon, and generic sol./ung. > 2 mos. 5ml/3.5g
Genoptic, and generic gentamicin 0.3% Allergan, and generic sol./ung. N/A 5ml/3.5g

Polymyxin B Combinations
Polytrim polymyxin B/trimethoprim Allergan, and generic solution > 2 mos. 10ml
Polysporin polymyxin B/bacitracin Monarch, and generic unguent N/A 3.5g
Neosporin polymyxin B/neomycin/ Monarch, and generic sol./ung. N/A 10ml/3.5g

Other Antibiotics
AzaSite azithromycin 1% Inspire Pharm. solution > 1 yr. 2.5ml
Ilotycin, and generic erythromycin 0.5% Dista, and generic unguent > 2 mos. 3.5g
AK-Tracin, and generic bacitracin 500u/g Akorn, and generic unguent N/A 3.5g


020_dg0610_antibiotics.indd 20 6/2/10 1:28 PM

Anti biotics
effectiveness, a nationwide system MSSA and MRSA in Ocular TRUST
of study and evaluation of these Methicillin-sensitive Methicillin-resistant
concerns was established in 1996, Staphylococcus aureus (MSSA) Staphylococcus aureus (MRSA)
the year levofloxacin was brought
to market. This system is called
“Tracking Resistance in the United
States Today,” or TRUST. More
recently, in 2005 to 2006, Ocular
TRUST was established, which
looks specifically at ocular bacterial
isolates.2 You’ll be rather amazed at
what has been discovered. Basical-
ly, with regard to MRSA infections,
the fluoroquinolones—levofloxacin,
moxifloxacin and gatifloxacin—all
performed identically and were

effective only about 20% of the
time. In contrast, trimethoprim was
effective against 95% of MRSA
isolates. These fluoroquinolones
were effective against 80% of
McDonnell PJ, Sahm DF. Longitudinal nationwide surveillance of antimicrobial susceptibility in ocular isolates (Ocular
methicillin-sensitive Staphylococcus TRUST 2). Presented at the American Academy of Ophthalmology 2007 annual meeting, New Orleans, November 10-13,
aureus (MSSA) isolates, whereas Poster PO052.
both tobramycin and trimethoprim
were about 100% effective. with antibiotics or a corticosteroid nal supplementation to topical eye
Regarding Streptococcus pneu- is to have the patient use whichever drops in the treatment of bacterial
moniae, these three fluoroquino- drug you prescribe frequently (for corneal ulcer. Bacitracin is generi-
lones were 100% effective. Against example, every two hours) for at cally available.
Haemophilus influenzae, the three least a couple of days before drop-
fluoroquinolones were 100% effec- ping down to q.i.d. for four to six Bacitracin with Polymyxin B
tive and trimethoprim was about more days. It is not particularly the Polymyxin B is excellently
85% effective. antibiotic chosen, but the frequency bactericidal against most gram-
Now, from a clinical practi- of the instillation that determines negative bacterial species.
cal perspective, what does all this the clinical efficacy of most drugs. Its mechanism of action is
mean? To explain, the Ocular Now, let’s take a clinically practi- destruction of the bacterial
TRUST authors state: “Although cal look at each drug: cell membrane. Polymyxin
in vitro activity may be predictive B is not a stand-alone drug,
of efficacy, it is not a guarantee Bacitracin however. It is always found
because a multitude of factors influ- Developed in 1943, in combination products to
ence clinical response.”2 Most all bacitracin is an excellent provide coverage against
of our currently available topical gram-positive bactericidal gram-negative pathogens.
antibiotics, used frequently enough, drug. Its mechanism of The combination with
will eradicate most bacterial infec- action is the destruction bacitracin is known as
tions of the conjunctiva and cornea. of the bacterial cell wall. Polysporin ophthalmic
If you’re not achieving clinical cure It is only available as an ointment, and it is not
with a fluoroquinolone, an ami- ophthalmic ointment, available in the United States in
noglycoside or trimethoprim, then which severely limits its eye drop form. The ointment for-
switch or add one of these other clinical use, because adults mulation is available as a generic
classes/drugs. On rare occasions, do not like to have highly product. OTC (non-ophthalmic)
we add Polysporin or Neosporin viscous ointments in their Polysporin comes as a 15gm tube,
ophthalmic ointment at bedtime. eyes. It has two main uses: for in- contains the same two drugs, and
The general principle of treating fectious blepharitis and for noctur- performs identically.


020_dg0610_antibiotics.indd 21 6/2/10 1:28 PM

Anti biotics
Besifloxacin—A Novel, New Chloro-Fluoroquinolone expression of inflammatory
Besifloxacin, marketed as Besivance (Bausch + Lomb), has several unique features that blepharodermatitis. This
make it an excellent choice when a more advanced antibiotic is indicated. red, weepy skin reaction
• Residency time. Its vehicle is DuraSite, a mucoad- can easily be reversed
hesive agent that provides enhanced ocular surface resi- by drug cessation. Such
dency time, potentially allowing greater concentration of so-called “neomycin
the active drug on the ocular surface. This can be a major reactions” occur in
advantage when treating school-age patients who have 5% to 10% of treated
bacterial eye infections. A drop can be placed in the eye patients, and is nothing
in the morning, then again up to eight hours later when more than an inconve-
school is over, and a third drop can be instilled near nience.
bedtime. This meets the FDA recommendation for t.i.d. This triple antibiotic
therapy, yet can bridge over an eight-hour time period—a is an excellent, broad-spectrum
more patient-convenient dosing schedule. drug that is available generically in
• Reduced resistance. Besivance is not a new gen- both solution and ointment form.
eration fluoroquinolone. Rather, it is a first-in-class chloro-fluoroquinolone. Importantly, Because of solubility issues, grami-
Besivance is specifically designed to be an ophthalmic drug—there is no systemic coun- cidin replaces bacitracin in the
terpart for this antibiotic as there are for the fluoroquinolones. This, along with its rapid solution form. Gramicidin and
kill rate, should minimize any trending toward bacterial resistance. Indeed, it appears to bacitracin are clinical equivalents in
be especially effective against methicillin-resistant Staphylococcus aureus (MRSA).1 The combating gram-positive bacteria.
DuraSite vehicle may even further enhance its therapeutic effect.
• High potency. While there are no large studies in humans (other than the obliga- Trimethoprim with Polymyxin B
tory placebo-controlled phase III studies), in vitro and animal studies demonstrate that Trimethoprim is an excellent,
Besivance’s MIC (minimal inhibitory concentration) potency is at least equal or superior broad-spectrum bacteriostatic
to all other tested drugs.1,2 For these reasons, there is cause to believe that Besivance is antibiotic. Though it inhibits bacte-
a highly potent, clinically effective, new chemotherapeutic agent. rial folic acid synthesis in a manner
Besivance 0.6% ophthalmic suspension comes in a 5mL opaque bottle. On a practical similar to the sulfonamides, it is not
note: two or three vigorous shakes are all that are needed for this unique suspension, a sulfa-related drug.
but the last flick needs to sling the viscous liquid toward the tip of the bottle to facilitate Systemically, trimethoprim
ease of drop instillation. combined with sulfamethoxa-
Like many, many medicines, ophthalmic or systemic, FDA approval is often of a lim- zole, historically marketed
ited indication. For Besivance and the fourth-generation fluoroquinolones, the indication as Bactrim (AR Scientific)
is simply for bacterial conjunctivitis. However, based on all the studies to date, there or Septra (Monarch), is
is every reason to believe that Besivance can be used in a broad array of all types of a drug of choice when
ocular surface bacterial conditions. Most certainly, in one more year we will have even treating systemic soft tis-
more extensive experience with this promising medicine, and a much better feel for its sue infections caused by
therapeutic prowess. MRSA pathogens. As can
We are pleased to have this new, highly efficacious medicine available to us to treat be deduced, trimethoprim
the range of bacterial eye infections. is not active against some
1. Haas W. Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic anaerobic bacteria.
gram-negative bacteria,
Antimicrob Agents Chemother. 2009 Aug;53(8):3552-60. which is why it is combined with
2. Bertino JS, Zhang JZ. Besifloxacin, a new ophthalmic fluoroquinolone for the treatment of bacterial conjunctivitis. Expert
Opin Pharmacother. 2009 Oct;10(15):2545-54.
polymyxin B. Because this combi-
nation drug is particularly effective
Bacitracin, Polymyxin B and exception of Pseudomonas species against Streptococcus pneumoniae
Neomycin (this is why polymyxin B is com- and Haemophilus influenzae, two
Neomycin is an aminoglycoside, monly combined within neomycin). common pathogens in the pediat-
which, like polymyxin, is not found Neomycin is an excellent drug, but ric population, this is the drug of
as a stand-alone drug. It is always it is mostly known for its potential choice in children with bacterial
found in a combination formula- to cause a Type IV delayed hyper- conjunctivitis. Originally known
tion. Neomycin works to inhibit sensitivity reaction, which is mani- by the brand name Polytrim (Al-
protein synthesis and is inherently fested as a low-grade blepharo- lergan), this ophthalmic solution is
broad spectrum, with the notable conjunctivitis, with variable now available generically.


020_dg0610_antibiotics.indd 22 6/2/10 1:28 PM

Anti biotics
Erythromycin able only as an ointment, which Azithromycin
The most common use of eryth- limits its practical application. This more modern rendition of a
romycin is as a nocturnal lubricant Erythromycin is essentially macrolide antibiotic is well known
when a lubricant with antibiotic bacteriostatic against many gram- by its original brand name of
properties is desired. Erythromycin, positive and gram-negative bacte- Zithromax (Pfizer). It is prescribed
topically and systemically, has lim- ria. It exerts its antibacterial action systemically as a Z-Pak, and is
ited use because of its poor resis- through the interruption of protein available in a packet of six 250mg
tance profile. It is hardly ever used synthesis. However, because of its capsules; Tri-Pak, which is available
to actively treat an infection, but systemic use for decades, resistance in a packet of three 500mg cap-
is almost always used in a prophy- (particularly against Staph. species) sules; or as a 1,000mg oral suspen-
lactic role. Just as with bacitracin, has developed and has limited its sion and 2,000mg oral suspension
ophthalmic erythromycin is avail- clinical usefulness. (Zmax).

Blepharitis preferable when treating any chronic condi-

Blepharitis is the most common disease of tion, such as blepharitis, because of the
the eyelids, and appears both anteriorly and well-established enhanced safety profile
posteriorly. of loteprednol. (However, AzaSite is an
• Anterior. The anterior form of blepha- excellent choice for treating children with
ritis is best managed with good eyelid bacterial conjunctivitis. It joins generic trim-
hygiene, but not with baby shampoo. We ethoprim/polymyxin B (Polytrim) as our two
strongly recommend commercially prepared, drugs of choice for this condition.)
unit-dose applicator scrubs. These are easi- • Posterior. For posterior blepharitis, it
er to use, have an excellent broad spectrum must be emphasized that meibomian gland
of activity against common eyelid patho- Manage anterior blepharitis with good dysfunction is the centerpiece of this dis-
gens, and certainly appear more of a medi- eyelid hygiene using applicator scrubs, ease. Expressing these glands in the office
cal therapeutic device than hair shampoo. not baby shampoo. is both diagnostic and therapeutic. Patients
We often prescribe an effective anti-staph need to be shown how to perform glandular
antibiotic combined with an effective, safe corticosteroid, such as expression so they can do this several times a week initially, then
Zylet (loteprednol 0.5%/tobramycin 0.3%, Bausch + Lomb), q.i.d. perhaps twice weekly thereafter. Pre-expression warm soaks for
for a week or two. Patients simply instill the drops as usual, and three or four minutes enhances the efficacy of these glandular
we ask them to gently close the eyes and rub excess along the massages.
eyelid margins. After a week or two, we have them use the drops Beyond this, we commonly prescribe oral doxycycline at 50mg
only once or twice daily for another two to four weeks. This works a day for two to three months. Such therapy has been shown to
well and requires only one 5mL bottle. enhance the fatty acid metabolism within these glands. To our
There is a lot of chatter about the off-label use of azithromycin knowledge, all authoritative medical textbooks recommend only
(AzaSite, Inspire Pharmaceuticals) to treat blepharitis. This may doxycycline for this purpose. We have consulted several derma-
help some patients, but let’s look at this practice in a thoughtful, tologists as to why they prefer doxycycline over azithromycin. Their
scientific way. As clearly demonstrated in the TRUST (Tracking consistent answer: doxycycline has much enhanced anti-inflam-
Resistance in the United States Today) data, tobramycin is much matory properties as compared to azithromycin. We urge you to
more staphylocidal than azithromycin. (It comes as no surprise that query your community’s dermatologists in a like manner.
the phase II clinical trials of AzaSite for the treatment of blepharitis One final point regarding oral doxycycline: it can be, and should
did not show any improvement compared to vehicle, which mirrors be, taken with a meal, and never on an empty stomach near bed-
our own clinical observation. The drug’s primary goal of improv- time. Such practice occasionally results in erosive esophagitis, an
ing eyelid margin hyperemia did not reach statistical significance undesired occurrence when our goal is enhancing quality of life.
compared to vehicle during either the two-week or the four-week Remember, once brought under control, the enduring, consis-
clinical trial.) tent application of hygienic maneuvers will maintain eyelid health.
Secondly, nothing, absolutely nothing, suppresses inflammation For episodic “breakthrough” symptoms, re-pulse with Zylet q.i.d.
more effectively than a corticosteroid. Therefore, based on logical for a week or two, and re-emphasize meticulous eyelid hygiene.
thought and scientific information, a drug containing tobramycin Helping patients with blepharitis involves active therapy on the part
with any steroid is more prudent than using any antibiotic alone. of the doctor and the patient. Enduring control rests with a well
It should be intuitive that an ester-based corticosteroid would be informed and compliant patient.


020_dg0610_antibiotics.indd 23 6/2/10 1:28 PM

Anti biotics
The ophthalmic formulation of than generic Polytrim. the same, except that tobra-
azithromycin, known as AzaSite AzaSite comes in a white, opaque mycin appears to be even
(Inspire Pharmaceuticals), is pro- bottle containing 2.5mL of drug. less likely than gentamicin
duced as a high-viscosity eyedrop It has an easy-to-open safety seal to cause any epitheliotoxic
solution. Because azithromycin has very much like that found on the response. While all amino-
a particularly prolonged intracel- Xalatan bottle. glycosides have the poten-
lular half-life, both in systemic tial to cause ocular surface
and topical form, it is dosed less The Aminoglycosides toxicity, this is not a practi-
frequently than other ophthalmic Aminoglycosides are a class cal concern when used for a
drugs. For AzaSite, the represented by gentamicin, tobra- short time, as they would be
standard dosage is one mycin, and neomycin. The first rationally prescribed in eye
drop every eight to 12 two are the only members of this care (i.e., seven to 10 days), unless
hours for the first two class with broad-spectrum antibi- the ocular surface was already com-
days, then one drop daily otic properties, which allows them promised prior to the institution of
for five more days. to function as standalone drugs. treatment. These drugs are generi-
Its mechanism of The aminoglycosides are not used cally available in 5mL bottles.
action is the inhibition systemically (because they can They are excellent, broad-
of protein synthesis. Be- cause ototoxicity) and there- spectrum antibiotics. Like the
cause of its spectrum of fore, they have not had their fluoroquinolones, their forte is
activity, it, like trime- antibiotic properties compro- in the gram-negative spectrum,
thoprim (with polymyxin mised by widespread primary and the highest MICs are for
B), has its greatest value in treating care use. They exert their streptococcal pathogens. Also
pediatric bacterial eye infections. bactericidal action through like the fluoroquinolones,
Its main advantage is its more the inhibition of bacterial these two drugs should be
patient-friendly dosing frequency. protein synthesis. dosed frequently (every one
Since it is only available by brand Both gentamicin and to two hours initially until
name, it is relatively more expensive tobramycin perform about the infection comes under
control), then the dosing fre-
New Procedure for Blepharitis: Maskin Microprobes quency can be reduced as appropri-
Because so much attention is being given to treating blepharitis, it is especially timely ate for the amount of time deemed
that a new approach has come upon the horizon. Steve Maskin, M.D., has discovered necessary to achieve a clinical cure,
that physically opening clogged inspissated meibomian glands, using tiny wire probe can- usually seven to 10 days.
nulas, can bring rapid relief to most patients
with posterior blepharitis. This simple pro- The Fluoroquinolones
cedure, done at the slit lamp following topi- Like erythromycin, the
cal anesthesia, can be performed quickly oral fluoroquinolones
and efficiently. have enjoyed enormous
Topical 0.5% proparacaine can be used, popularity among pri-
but Akten (lidocaine 3.5%, Akorn) may be mary care physicians.
a better option because of its viscous gel This has begun to cause
formulation. Just place a couple of drops significant resistance
in each eye, and rub the excess over the to this class of drugs.
eyelid margin. Most such “resistance”
Rather than detail this new therapeutic procedure here, we prefer to direct you to a arises from in vitro
couple of websites: and Here, you can view studies and can usually
a video of the procedure as it is done, and gain further details on how to help patients be overcome clinically
with posterior blepharitis gain control of this chronic, persistent condition. because of the huge relative volume
We have not yet performed these maneuvers, and do not know of the virtue of doing of drug-per-surface area achiev-
so, but wanted to make the optometric community aware of this new, potentially promis- able on the ocular surface. While
ing, in-office procedure for blepharitis. there are newer generations of
We have no relationship directly or indirectly with either Dr. Maskin or Rhein Medical. fluoroquinolone (just like newer
generations of oral cephalospo-


020_dg0610_antibiotics.indd 24 6/2/10 1:28 PM

Anti biotics
rins), they are only New Gatifloxin Formulation Approved
marginally superior to In keeping with the trend of increasing the
older ones in clinical concentration of fluoroquinolones, Allergan
performance. Like has reformulated its gatifloxicin from 0.3%
the aminoglycosides, (Zymar) to 0.5% (Zymaxid). This new version
the fluoroquinolones was just approved by the FDA in late May.
are concentration- Because fluoroquinolones and aminoglyco-
dependent in their sides are concentration-dependent antibiotics,
bactericidal proper- this increase in concentration may enhance its
ties. Ciprofloxacin clinical efficacy.
(Ciloxan, Alcon), Zymaxid is indicated for the treatment of
ofloxacin (Ocuflox, Allergan) bacterial conjunctivitis. (It is our strong per-
and gatifloxacin (Zymar, Aller- sonal opinion that Besivance, Vigamox, Zymar
gan) are all available as a 0.3% and now Zymaxid are all well-suited to treat
concentration; levofloxacin bacterial keratitis as well, but the FDA approv-
(Quixin, Vistakon Pharma- al process is so bureaucratically onerous that
ceuticals) and moxi- companies generally pursue the shortest,
floxacin (Vigamox, Alcon) easiest route to approval, having great confidence that learned prescribers will use the
are available as a 0.5% drugs for any infectious process where patient care would be enhanced.)
concentration; the newly Zymaxid is preserved with BAK, is approved down to age 1, and comes in a 2.5mL
FDA-approved besifloxa- opaque multi-use bottle.
cin (Besivance, Bausch +
Lomb) is available as Ophthalmology, compared besifloxacin; and 1.5% levo-
a 0.6% ophthalmic 1% moxifloxacin, fortified floxacin.
suspension; and tobramycin/cephazolin, In children, we use either
levofloxacin (Iquix, and 0.3% ofloxacin in generic trimethoprim/poly-
Vistakon Pharma- treating bacterial kera- myxin B or topical azithro-
ceuticals) is avail- titis.3 The result: they mycin.
able as a 1.5% concentra- all performed equally. The best, general-purpose
tion. The 1.5% levofloxacin This is one example— ophthalmic ointment is a
is FDA approved for bacte- of many—of why it combination of bacitracin
rial keratitis, and other than is so important for with polymyxin B. Only
ofloxacin and ciprofloxacin, O.D.s to consistently in advanced ocular surface
is the only fluoroquinolone read the literature. infection would we use eye
specifically FDA ap- In summary, the drops hourly and an oint-
proved for this purpose. topical antibiotics are grossly ment at bedtime; otherwise oint-
So what does all this overutilized—in optometry, oph- ments are largely limited to blepha-
mean clinically? Not very thalmology, and general medicine. ritis care.
much. When a fluoroqui- Make every effort to pinpoint an We are fortunate to have such an
nolone is deemed the accurate diagnosis (which, in most awesome arsenal of medicines avail-
class of choice cases of acute red eye, is not of bac- able to treat bacterial infections.
for a particu- terial etiology), and then select an Use them wisely, judiciously—and
lar infectious appropriate drug or drug class to aggressively when indicated. ■
condition, it achieve renormalization of tissues.
1. Abelson MB, Heller W, Shapiro AM, et al; AzaSite Clinical
is not par- The frequency of instillation Study Group. Clinical cure of bacterial conjunctivitis with
ticularly the is almost always more important azithromycin 1%: vehicle-controlled, double-masked clinical
trial. Am J Ophthalmol. 2008 Jun;145(6):959-65.
specific drug than the drug selected. 2. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST:
chosen that matters as As best as we can determine, nationwide antimicrobial susceptibility patterns in ocular
isolates. Am J Ophthalmol. 2008 Jun;145(6):951-958. Epub
much as how frequently the four best drugs to combat 2008 Mar 28.
the drug is dosed. For acute bacterial infection in adults 3. Constantinou M, Daniell M, Snibson GR, et al. Clini-
cal efficacy of moxifloxacin in the treatment of bacterial
example, an article in the are: bacitracin/polymyxin B/ keratitis: a randomized clinical trial. Ophthalmology. 2007
September 2007 issue of neomycin; tobramycin; 0.6% Sep;114(9):1622-9.


020_dg0610_antibiotics.indd 25 6/2/10 1:28 PM

Combination Drugs
Perhaps half of all inflamed eyes are best treated with a combination drug, rather
than an antibiotic or steroid alone.
his class of ophthalmic drugs acknowledges two clinical realities: nistic bacterial pathogens. This is

T is highly useful and rivals the

pure topical corticosteroids in
the treatment of the acute red eye.
• The need for topical antibiotics
alone is relatively low.
• Almost all acute red eyes have
because an intact epithelium is itself
a firewall of defense. If there is sig-
nificant epithelial compromise, then
As with most drugs, there are clear a significant inflammatory compo- a combination drug may perfectly
indications and clear contraindica- nent. match the clinical need.
tions, with a gray zone in between. So, how does the astute clinician Remember that the conjunctiva
In order to prescribe a combina- choose between a pure steroid and will be inflamed in any patient
tion drug with clinical precision, a combination drug? The answer presenting with an acute red eye.
one has to have a masterful under- is relatively straightforward, but, Simply put, the eye is red because
standing of both antibiotics and as always, there are exceptions to it is inflamed. Also, the conjunc-
corticosteroids. As many as half of generalizations. The pivotal issue is tiva will be inflamed in almost all
all red eyes that we see are treated the integrity of the corneal epithe- cases in which keratitis is present.
with a combination drug, rather lium. If the corneal epithelium is With either keratitis (with an intact
than either a steroid or antibiotic intact, there is little or no reason epithelium) or non-infectious con-
alone. This observation clearly for prophylaxis against opportu- junctivitis, we almost always use a

Corticosteroid/Antibiotic Combination Drugs

Blephamide * Allergan prednisolone sodium sulfacetamide 10% susp./ung. 5ml, 10ml/3.5g
acetate 0.2%
Cortisporin * Monarch hydrocortisone 1% neomycin 0.35%, suspension 7.5ml
polymyxin B 10,000u/ml
FML-S Allergan fluorometholone 0.1% sodium sulfacetamide 10% suspension 5ml, 10ml
Maxitrol * Alcon dexamethasone 0.1% neomycin 0.35%, susp./ung. 5ml/3.5g
polymyxin B 10,000u/ml
NeoDecadron * Merck dexamethasone 0.1% neomycin 0.35% solution 5ml
Poly-Pred Allergan prednisolone acetate 1% neomycin 0.35%, suspension 5ml, 10ml
polymyxin B 10,000u/ml
Pred-G Allergan prednisolone acetate 1% gentamicin 0.3% susp./ung. 10ml/3.5g
TobraDex * Alcon dexamethasone 0.1% tobramycin 0.3% susp./ung. 5ml/3.5g
Vasocidin * Novartis prednisolone sodium sodium sulfacetamide 10% solution 5ml, 10ml
phosphate 0.25%
Zylet Bausch + Lomb loteprednol 0.5% tobramycin 0.3% suspension 5ml, 10ml

PREGNANCY CATEGORY: All drugs listed above are Category C. * = also available generically.


026_dg0610_combos.indd 26 6/2/10 2:07 PM

Combination Drugs
topical steroid. the nasolacrimal system so that the along with the safety and potency
If the accurate diagnosis of objective slit lamp findings reveal of loteprednol. It is available in 5ml
bacterial conjunctivitis is made, only minimal microparticulant and 10ml bottles.
the decision is whether to prescribe debris in the lacrimal lake; a clear, Now that we have 90% of this
an antibiotic or a combination non-staining cornea; and/or a red topic covered, we need to spend the
drug. The prime determinants are eye. Here is where a combination bulk of this article discussing other
twofold: product is used mainly to address various exceptions and modifica-
1. The severity of the infection. the conjunctival inflammation, tions to this rather simple decision
2. The degree of conjunctival while concurrently eliminating any tree. The best way to teach the
injection. infectious component, even when concepts for drug class choice is
If the infection presents with the cornea is uninvolved. perhaps by looking at a few specific
marked mucopurulence, we When there is significant corneal clinical entities.
would likely treat with a epithelial compro-
pure antibiotic, such as mise, we almost al-
moxifloxacin (and perhaps ways use a combina-
even culture if the infection tion drug. For most
was severe). If the infectious cases, the choice of
expression was only mild drug class is that
to moderate, the degree of simple.
conjunctival injection would The first block-
be the overriding issue in buster, highly ef-
choosing between an antibi- fective combination
otic and a combination drug such antibiotic/corticosteroid
as Zylet (loteprednol/tobramycin, was Maxitrol, contain-
Bausch + Lomb), TobraDex (dexa- ing neomycin, polymyx-
methasone/tobramycin, Alcon), or in B and dexametha-
Maxitrol (dexamethasone/neomy- sone. Maxitrol became
cin/polymyxin B, Alcon). We a real workhorse in pri- A classic presentation of the corneal staining pattern
stress again that bacterial mary eye care. However, of Thygeson’s SPK. (The fellow eye was nearly identi-
infection is uncommon, the occasional neomycin cal.) This is one of the unusual cases of keratitis in
especially relative to the reaction, while not a which a modestly potent corticosteroid, such as Alrex
numerous expressions of major issue, prompted (q.i.d. for one week, then b.i.d. for one to two more
non-infectious conjunc- investigation into a weeks), quickly brings resolution in most cases.
tivitis. “new and improved”
An exception is the combination drug. Thygeson’s Superficial Punctate
patient who presents Thus was born TobraDex, Keratopathy (SPK)
with what appears to which replaced the neomycin and This not-so-uncommon keratitis
be a low grade bacterial polymyxin B with tobramycin. is seen in young to middle-aged
conjunctivitis (i.e., minimal This drug, like Maxitrol, enjoyed patients. The classic symptoms are
discharge), yet with moderate to market dominance, though from foreign body sensation, photopho-
marked conjunctival injection. time to time, and again not a bia and lacrimation. This idiopathic
The patient usually com- major issue, intraocular pressure condition has cycles of exacerba-
plains that the affected eye increases prompted an investiga- tion and remissions over the course
was “stuck together when I tion into a “new and improved” of 10 to 20 years, until it finally
woke up.” Commonly, by combination drug. abates. It is during these exacerba-
the time the patient arrives Thus was born Zylet. Keep- tions when symptoms prompt the
at your office, any excess ing the highly efficacious tobra- patient to seek medical attention.
debris may have been mycin, the dexamethasone was This usually bilateral keratitis
cleaned from the lids and replaced with a newer genera- shows several tiny, usually central,
lashes. Further, blinking tion, ester-based corticosteroid, subtle (but readily seen) stain-
has moved considerable loteprednol. Now with Zylet, ing defects with fluorescein dye.
mucopurulent debris down we have excellent antibiosis (Note that about 20% of cases are


026_dg0610_combos.indd 27 6/2/10 2:07 PM

Combination Drugs
unilateral, so differentiating EKC, subepithelial infiltrates
Thygeson’s from herpes simplex (which do not stain) can
must be done; here is where develop. When these cause
corneal sensitivity testing can symptomatic, visual compro-
be useful. Also, the Thygeson’s mise, a steroid will readily
eye will generally be white, or clear this unique, immune
minimally injected, whereas the keratitis. This generally re-
herpetic eye will generally be quires two to four months of
considerably injected.) tapering therapy. Our routine
If the patient is significantly has been to use Lotemax
symptomatic, a topical cortico- q.i.d. for one month, t.i.d.
steroid readily suppresses the Development of thick membranes can be seen in more for one month, b.i.d. for one
keratitis and its attendant symp- advanced cases of EKC. After instillation of topical month, and then once-daily
toms. If the presenting symp- anesthetic, these membranes (note both superior and for one month. It usually
toms are tolerable, then artificial inferior tarsal) were peeled away with minimal bleed- takes two to four months for
tears and patient education are ing, using these curved-tip forceps. Zylet was then sufficient viral antigen to be
likely all that is needed. How- used q2h for two days, then q.i.d. for four days. physiologically leeched from
ever, the teaching point here stromal residence. So when
is that even though there is some of intense inflammation, and as the steroid taper is completed, any
punctate staining in acute Thy- such, corticosteroid therapy is small infiltrates that might reform
geson’s SPK, all that is needed is a of paramount importance. We should be symptomatically mini-
topical steroid. This is the uniform generally use Lotemax (loteprednol mal, or silent.
recommendation in authoritative 0.5%, Bausch + Lomb) q.i.d. for Of note, antibiotics and combi-
textbooks. a week. By the end of this period, nation drugs have little or no role
While 1% concentrations of natural healing will likely have in treating patients with adenoviral
topical steroids are indicated in occurred and the steroid can be infections because concurrent bacte-
most inflammatory eye conditions, stopped, or tapered to b.i.d. for a rial infection is exceedingly rare.
Thygeson’s is steroid sensitive. few more days. While a combina- For several years now, we have
Therefore, our drug of choice in tion drug, such as Zylet, TobraDex successfully treated symptomatic
these cases is Alrex (loteprednol or generic Maxitrol, could be used patients with acute, grade II or
0.2%, Bausch + Lomb). We gener- here, we almost always use a pure higher EKC with a 60-second treat-
ally treat symptomatic patients topical steroid. Aminoglycoside ment of Betadine 5% Sterile Oph-
q.i.d. for one week, then b.i.d. for toxicity on an already toxic ocular thalmic Prep Solution (povidone/
one to four weeks, until the phase surface is probably not a practical iodine, Alcon) followed by ocular
of exacerbation subsides. Artificial concern, but could be in instances surface lavage. This accomplishes
tears complement virtually all acute in which the patient has concurrent two objectives. First, eradication
ocular surface conditions, but there dry eye. of the bulk of the adenoviral load
is no need for an antibiotic. In many advanced cases of hastens acute symptomatic recov-

Epidemic Keratoconjunctivitis Pearls for Using Combination Drugs

(EKC) • Any time you see any process at or near the limbus, it is inflammatory in nature.
If the EKC is severe, and espe- Herpetic infection can present at this area, but will typically be linear (as opposed to oval)
cially if tarsal conjunctival mem- in morphology.
branes have formed, there can be • In any acute, unilateral red eye with a serous discharge, be sure to rule out herpetic
epithelial compromise. The key keratitis.
here is to physically peel away • Never (or rarely) taper combination drugs below q.i.d. because subtherapeutic levels
these membranes, as they exert of antibiotic set the stage for antibiotic resistance.
toxic and mechanical trauma to the • In the context of a red eye with a mild secondary iritis, instill a short-acting cyclo-
epithelium. Be sure to wear gloves plegic agent, particularly if a pure antibiotic is used. A combination product will generally
when performing this procedure, as eliminate such an iritis without the need for a cycloplegic, though this is a fine clinical
minor bleeding often results. point.
These membranes are a marker


026_dg0610_combos.indd 28 6/2/10 2:07 PM

Combination Drugs
ery. Second, since the virus particles is not needed, unless there is clear
residence time has been consider- evidence of concurrent bacterial
ably truncated, the potential for infection.
viral antigenic (stromal immune) Topical Viroptic (trifluridine,
keratitis is largely pre-empted. (See Monarch Pharmaceutical), perhaps
also “The EKC-Betadine Protocol,” in conjunction with preservative-
page 17A.) free artificial tears, is the only thera-
Note: since Betadine stings, peutic intervention warranted for
always pre-treat the cornea with a herpes simplex epithelial keratitis.
drop of proparacaine. Furthermore, Oral antivirals, such as acyclovir
to diminish any patient discomfort, (400mg five times daily for seven
we generally instill a drop or two days) can be used if there is trifluri- Fungal (fusarium) infection with stromal
of Voltaren (diclofenac sodium, dine resistance, or if the patient has infiltrate.
Novartis Ophthalmics) or Acular LS developed an allergic response to
(ketorolac tromethamine, Allergan) trifluridine. fungal involvement at this point
before, and again after the treat- is unlikely, since fungi are usually
ment. Corneal Abrasions slow growing and would take many
Following the in-office treat- Most such defects heal within more days to proliferate to symp-
ment as described above, we always a day or two, regardless of any tomatic proportions.
prescribe Lotemax, usually q.i.d. therapeutic maneuvers. To our Now, if the patient gives a his-
for four to six days, to dampen or knowledge, no studies have tory of vegetative trauma, and
eliminate any residual inflamma- prospectively followed “no treat- reports that the abrasion initially
tory keratoconjunctivitis. ment” of abrasions, but it would healed over a day or two, but is
be interesting to know the absolute now (perhaps a week later) pre-
Herpes Simplex Keratitis (HSK) need for prophylactic antibiotic use, senting with a hot eye and stromal
Here is another condition that which is standard practice in these infiltrates, consider fungal etiology.
commonly demonstrates consider- situations. We imagine the rate of However, such symptoms are still
able epithelial compromise. infectious keratitis would be very most likely associated with a cell-
Since corticosteroids cause local small. However, since antibiotics mediated immune response to the
immunosuppression, their use is are safe, there is no mandate to take initial trauma rather than a fungal
contraindicated—an exceedingly unnecessary risks. infection. The salient features of a
well-known principle. No authori- Conservative therapy with antibi- fungal keratitis are:
tative textbook recommends the otics has evolved into the standard • History of corneal injury (veg-
use of a prophylactic antibacterial of care for corneal abrasions. There etative matter)
agent in such cases. As clinicians, are, however, circumstances—most • Slowly progressive
we do not know why the herpetic notably delay in seeking care—in • Hypopyon in advanced cases
corneal defect does not invite op- which the abraded eye is consider- • Not very painful (relatively)
portunistic bacterial pathogens; we ably inflamed. While fungal infec- • Feathery border (hyphate-like)
just know that antibacterial therapy tion is always a rare possibility if
the traumatic agent was vegetative,
99.9% of the time fungus is not a
That being said, we have occa-
sionally used a short-acting cy-
cloplegic agent and a combination
drug in “hot” eyes with corneal
abrasions. The steroid component
calms the tissues and thus potenti-
ates corneal re-epithelialization. A These classic, limbally expressed phlyc-
further note for the fungal worri- tenules were treated with Zylet (q2h for
ers out there: if the delay in seek- two days, then q.i.d. for five days) with
Herpes simplex keratitis. ing care is only two to four days, quick resolution.


026_dg0610_combos.indd 29 6/2/10 2:07 PM

Combination Drugs
• Slightly raised, dirty-white which were treated successfully. Phlyctenular Keratoconjunctivi-
infiltration If, however, the traumatic vector tis (PKC)
• Satellite lesions of the corneal abrasion was inor- Most usually seen in young girls,
• Partial or complete ring ganic, and there is marked inflam- this staphylococcal hypersensitiv-
• Secondary anterior uveitis mation, a combination product ity response commonly targets the
For perspective, in our combined could be considered. More conser- limbal tissues as one or two raised,
54 years of intense clinical experi- vatively, use a pure antibiotic a day whitish lesions, which stain lightly
ence, we have seen a grand total or two, then if the traumatic kera- with fluorescein. Nothing else looks
of two cases of fungal infection toconjunctivitis fails to subside or if like a phlyctenule.
following corneal abrasion, both of symptoms worsen, add a steroid. While one would think staphy-

Contact Lens-Associated Keratitis

Confusion abounds in eye care regarding the diagnosis and treat- While this is not an exhaustive list, it gives us some red flags
ment of contact lens-related keratitis, although in most cases, by which we can exercise our clinical judgment, and enhance our
these clinical presentations are rather straightforward. Of course, patient education.
our greatest concern is vision loss from a central bacterial corneal If you truly feel your patient has an infectious lesion, then start
ulcer. The good news is that such ulcers are exceedingly rare. them on a fluoroquinolone such as Vigamox or Zymar every 15
The problem, however, is threefold: 1) corneal infiltrates are quite minutes for three to six hours, then hourly until bedtime. We have
common occurrences; 2) there is a lot of uncertainty among eye our patients instill generic Polysporin (or Neosporin) ointment at
doctors as to the differentiation of corneal lesions; and 3) the bedtime. Follow your patient daily and modify therapy based on
ever-looming concern, “Is this the beginning of a potentially vision- the clinical response.
threatening ulcerative process?” This last point is particularly wor- There is a less intensive approach that can be used if you think
risome when a positive epithelial defect is present. your patient has a leukocytic infiltrate, but are still concerned
Corneal hypoxia is the most common cause of corneal infiltra- about possible infection. Here, use any fluoroquinolone or ami-
tive events, but with the advent of the super oxygen-permeable noglycoside hourly until the patient is seen back the next day
silicone hydrogel lenses, we hope to see a dramatic decrease in to assess the clinical course. In either diagnostic circumstance,
the hypoxic-related keratitis. (bacterial infection or leukocytic infiltration), improvement will most
Hypoxia can result in a cascade of events that result in leuko- always be evident, mainly because lens wear has been discontin-
cytic chemotaxis into the anterior stromal tissues. Once ample leu- ued.
kocytic recruitment occurs, exocytotoxic chemicals can lead to ret- Naïve practitioners who witness such improvement may wrong-
rograde demise of some of the overlying epithelium as evidenced ly deduce that the lesion must have been an infective process, and
by a positive fluorescein staining defect. It is these circumstances be glad they used an antibiotic. Once again, infiltrates are very
that lead many doctors to erroneously assume the worst and start common, and bacterial keratitis is very rare.
the patient on a course of topical antibiotics. While this does no The most appropriate therapeutic response to an immune/
harm, it does no more good than simply discontinuing the use of inflammatory condition (e.g., a leukocytic/sterile infiltrate) is a
the contact lenses, which, of course, is the first step of treatment steroid. Since a small epithelial defect may or may not be present,
for all contact lens-related eye problems. A steroid, in combina- or clinical judgment may be wrong (if the lesion actually is an early
tion with an antibiotic, is perfectly suited to suppress the immune/ infectious disease process), we always prescribe an antibiotic/
inflammatory response, while protecting the cornea against any steroid combination drug, such as Zylet, TobraDex, or generic
opportunistic bacterial infections. Maxitrol to treat these conditions. To this day, tobramycin remains
There are numerous parameters to evaluating the differential an excellent, broad spectrum bacterial antibiotic.
diagnosis of leukocytic infiltration (largely from hypoxia) versus Prescribe the combination drug to be used q2h for two days,
stromal opacification lesions (largely from bacterial infection). (See then q.i.d. for four days (mainly to quiet the inflammation and
“Clinical Perspectives on Corneal Infiltrates,” page 17A.) allow the eye to calm down).
Let’s look at some risk factors for ulcerative keratitis so that we Each doctor must evaluate each patient’s condition carefully
can better quantify the likelihood of such occurrences: and prescribe with as much precision as possible. As stated at
• Poor tear film function the outset, treatment of contact lens-associated keratitis is rather
• Uncontrolled staphylococcal blepharitis straightforward in most cases. In ambiguous cases, treat con-
• Smoking servatively until the diagnosis becomes clear. For perspective,
• Swimming while wearing contacts (esp. in fresh water) we have seen less than a handful of cases of microbial keratitis
• Being under age 22 ± between the two of us.


026_dg0610_combos.indd 30 6/2/10 2:07 PM

Combination Drugs

Is it an ulcer or an infiltrate? At left is a sterile infiltrate. At right is an infectious ulcer. Some rules of thumb: Ulcers are rare;
infiltrates are common. Ulcers are usually painful; infiltrates less so. With an infiltrate, the surface area of fluorescein staining is
smaller than the underlying stromal lesion.

lococcal blepharitis would always stromal inflammatory process, thus SPK, topical steroid and/or Restasis
be evident, such is not empirically causing retrograde compromise to (cyclosporine, Allergan) therapy
the case. Certainly, if blepharitis the overlying epithelium. is often employed (along with
is present, initiate proper care, but Once this subepithelial inflamma- artificial tears, etc.) in the success-
first treat the inflammatory kera- tion is subdued by the corticoste- ful management of KCS. We have
toconjunctivitis. When there is a roid component in a combination never read of an antibiotic role in
staining defect at the corneolimbus, drug, re-epithelialization is potenti- the management of KCS.
a prophylactic antibiotic is counter- ated. In summary, select a pure anti-
productively conservative. An antibiotic alone in this case is biotic when the clinical picture is
The key clinical feature is the in- almost worthless. While an anti- portrayed by evident mucopurulent
flammatory component—the eye is biotic can serve to protect against discharge, or there is evident (or
red. Here, a combination product is opportunistic bacterial potential, it high risk for) corneal infection.
probably wise. Use a combination will do nothing to curb the inflam- Select a combination drug in the
drug every two hours for a day or matory process. absence of the above two findings
two, then q.i.d. for four to six days, As with PKC, a combination when there is mild to moderate epi-
and then stop. corticosteroid/antibiotic product is thelial compromise near the limbus
perfectly suited to address the in- along with considerable conjuncti-
Staph. Marginal “Ulcers” flam- matory process while simulta- val inflammation.
Much more appropriately called neously guarding the cornea against Select a pure steroid if the eye is
“peripheral inflammatory epithe- the possibility of bacterial infection. red and the corneal epithelium is
lial defects,” these are uncommon Therapeutic management is as intact.
events that have a similar patho- described for PKC. We might default to a combina-
physiology to PKC and sterile tion drug if the patient is a contact
infiltrates. Keratoconjunctivitis Sicca (KCS) lens wearer, but it would depend on
In these cases, the staphylococcal We have all seen dry eye patients the individual situation.
exotoxins begin to erode a section with slit lamp-observable, coarse
of the peripheral corneal epithelial SPK. Also known as punctate We have discussed many excep-
tissues. The eye is red with accentu- epithelial erosions, SPK represents tions to these general guidelines.
ation of a sector of bulbar conjunc- a break in epithelial integrity that The primary purpose of this article
tival inflammation adjacent to the theoretically provides a foothold for is to encourage the reader to limit
affected cornea. The foci of com- bacterial adherence and subsequent the prescribing of an antibiotic for
promised epithelium stains brightly penetration. Yet, antibiotic inter- the gamut of red eyes and recognize
with fluorescein dye. There may be vention is rarely, if ever indicated. that most red eyes are inflamma-
a few cells in the anterior chamber. Acknowledging the participation tory in nature.
The epithelium is broken down as of inflammation in the pathogenesis Most importantly, prescribe with
a result of the underlying anterior of many cases of dry eye-related precision! ■


026_dg0610_combos.indd 31 6/2/10 2:07 PM

Inflammation is the most common of ocular conditions. Consequently, corticoste-
roids are the most helpful drugs in eye care.

n acknowledgement of the appropriately focused on the great whereas we possess no “ketonases”

I nature and epidemiologic

expression of the acute red eye,
topical corticosteroids are heralded
virtue of the corticosteroids. Corti-
costeroids are inextricably linked to
clinical success in an extraordinari-
to dampen the adverse side effect
potential of traditional ketone ste-
roids. The virtue of an ester-based
as the most helpful class of drugs ly wide range of ocular conditions. corticosteroid is amplified when it
in eye care. In fact, without these (See “The Many Uses of Corticoste- comes to chronic care conditions
marvelous medicines, we would be roids,” p. 33A.) such as dry eye; Thygeson’s SPK;
virtually disarmed from a chemo- chronic uveitis; blepharitis; stromal
therapeutic perspective. Safety in Steroids HSK; chronic, recurrent, inflamed
Sadly, the teaching focus of While a “rose is a rose,” a pterygia; etc.
these wonderful drugs is often steroid is not always a steroid, The key to managing most of
“side-effect”-centered, rather than exactly. Most steroids are ketone- these inflammatory processes is to
“benefit”-centered. The truth is based in their molecular structure, select an appropriate steroid medi-
that all drugs have the potential to except for loteprednol, which is cine and use it frequently until the
be two-edged swords, so it is im- the only ester-based formulation. inflammation comes under control,
perative that a clear understanding The expanded safety feature of then conduct an appropriate taper
of their dichotomy be proportion- loteprednol takes advantage of the of days to weeks, depending upon
ately understood. physiological existence of abun- the nature, severity, and response
So, let’s start this discussion dant esterases in human tissues, of the condition. Selecting a potent

Topical Corticosteroid Drugs

Maximum Strength Steroids
Durezol difluprednate 0.05% Sirion Therapeutics emulsion 5ml
Lotemax loteprednol etabonate 0.5% Bausch & Lomb suspension 5ml, 10ml, 15ml
Pred Forte, and generic prednisolone acetate 1% Allergan, and generic suspension 5ml, 10ml, 15ml
generic prednisolone sodium generic solution 5ml, 10ml, 15ml
phosphate 1%
Vexol rimexolone 1% Alcon suspension 5ml, 10ml

Moderate Strength Steroids

Flarex, and generic fluorometholone acetate 0.1% Alcon suspension 5ml, 10ml
FML, and generic fluorometholone alcohol 0.1% Allergan suspension 5ml, 10ml, 15ml
FML S.O.P. fluorometholone alcohol 0.1% Allergan ointment 3.5g
Pred Mild, and generic prednisolone acetate 0.12% Allergan suspension 5ml, 10ml


032_dg0610_steroids.indd 32 6/2/10 2:42 PM

The Many Uses of corticosteroid is essential to effect- The historic dominance
Corticosteroids ing a clinical cure (or control) in of Allergan’s Pred Forte
Topical steroids are essential for the res- most cases. is being challenged by
toration of normal tissues for the follow- There are five drugs in this the user-friendly Durezol
ing diseases, afflictions and conditions: category: prednisolone, lotepred- (difluprednate, Sirion)
• Iridocyclitis nol, difluprednate, dexamethasone may work as well with
• Ultraviolet keratitis and rimexolone. Moderate-acting less frequent dosing,
• Contact lens overwear steroids are represented by the fluo- thanks to its unique
• Inadvertent hydrogen peroxide kerato- rometholones, and the less potent emulsion for-
conjunctivitis formulations are represented by the mulation.
• Thygeson’s superficial punctate kera- lower concentrations of predniso- While Pred
topathy lone and loteprednol (discussed in Forte is typically dosed
• Allergic conjunctivitis detail later). hourly (while awake)
• Acute angle closure1 Using a steroid more than neces- for as long as necessary
• Dry eye syndrome sary is superior to under-dosing. to quell the inflamma-
• Infiltrative keratitis2 It is practically impossible to use tion (and this can
• Ulcerative keratitis3 a topical steroid eye drop too sometimes be for a few
• Microcystic edema of the cornea often, but under-treating can allow days), Durezol may
• Vernal conjunctivitis unchecked inflammation to damage achieve the same effect
• Atopic conjunctivitis ocular structures. This is prob- with dosing every two
• Bacterial conjunctivitis2 ably most applicable to intraocular hours. Decreasing
• Glaucomatocyclitic crisis inflammation such as iridocyclitis. dosing frequency can be a
• Uveitis-associated ocular hypertension Of course, the ultimate goal is to significant help to many patients.
• Blepharitis2,4 There are yet no head-to-head stud-
• Curling iron/burn injury (thermal ies to verify this, so it falls to
keratoconjunctivitis2) the clinician to judge the
• Nasolacrimal stenosis2 efficacy of this approach.
• Traumatic hyphema Note that our personal
• Post foreign body removal2 modus operandi is the
• Acute adenoviral infection5 use of one of these
• Acute, symptomatic giant papillary two options for the
conjunctivitis most severe uveitis and
• Corneal graft rejection episcleritis cases, and
• Phlyctenulosis (2, if corneal) to use Lotemax for
• Inflamed pinguecula/pterygia Curling iron corneal epithelial burn most other conditions.
• Recurrent corneal erosion6 There are clinical
• Post anterior stromal micropuncture2 prescribe with precision, which presentations, most
• Herpes simplex viral stromal keratitis7 requires exquisite teaching coupled notably high-grade acute
• Episcleritis with clinical seasoning. The more uveitis and episcleritis, where topi-
• Acute hordeolum (stye)8 patients one sees, the more precise cal therapy may be inadequate to
• Superior limbic keratoconjunctivitis the clinical care can be. control the inflammatory process.
• Cyanoacrylate-induced chemical kera- Most steroids are suspension There are two options that are
titis formulations and need to be shaken commonly employed here: FML
well to effect maximum therapeutic ointment qhs and/or oral predni-
once IOP is controlled benefit. Exceptions to this are two sone. We usually opt to add oral
with antibiotic solution formulations: predniso- prednisone, generally 40mg for
once active infection is controlled lone sodium phosphate (known three days, 20mg for three to six
with eyelid hygiene as Inflamase Forte by its original days, and then 10mg for three to
following 5% Betadine treatment brand name; it is now generic), and six more days. Every clinical pre-
with oral doxycycline dexamethasone sodium phosphate sentation is unique, and individual-
with antiviral cover (known as Decadron by its original ized dosing is essential in treating
with warm compresses brand name; it is also generic). every case.


032_dg0610_steroids.indd 33 6/2/10 2:42 PM

Clinical Perspectives on Corneal Infiltrates
Corneal infiltration is still commonly mistaken for an ulcerative pro- If desired, generic Polysporin ointment at bedtime can be added.
cess. There are a number of factors to consider in the differential If there is little or no improvement, the diagnosis is likely a sterile
diagnosis between a leukocytic infiltrate and a bacterial corneal infiltrate, and Lotemax can be added q.i.d. Reassess progress in
ulcer: a day or two. Always remember that hourly around-the-clock eye
• First, pay attention to the epidemiology of these two conditions: drop instillation is brutal to the patient. A highly efficacious ophthal-
infiltrates are very common; ulcers are very rare. mic ointment such as Polysporin should nicely address the infec-
• An anterior chamber reaction (i.e., cells and flare) is almost tious process during the sleep cycle, if indicated.
always seen with an ulcerative process. While an anterior chamber In closing, consider the following quote from prominent Harvard
reaction is usually absent with an infiltrate, trace cells are some- ophthalmologist Mark B. Abelson, M.D., in the January 2005
times seen, especially if the condition has been ongoing for several Review of Ophthalmology. His advice perfectly mirrors our approach
days. as set forth above:
• The appearance of the conjunctival injection pattern can also “Left untreated, marginal infiltrates generally disappear within a
be very helpful. With an infiltrate, sector injection is the rule; in an week or two. Ocular steroids have been the best and only recog-
ulcerative process, the entire bulbar conjunctiva is injected. nized drug therapy for sterile marginal infiltrates, and their applica-
• While not highly sensitive nor specific, the degree of pain the tion will shorten the course of inflammation, regardless of causative
patient describes can be helpful. An ulcer tends to evoke much origin. For many patients, a quicker recovery from symptoms such
more pain than an infiltrate. as redness, tearing, and discomfort is important for improving their
• Location can also be helpful, but not absolute. As a rule, ulcers quality of life. Steroids are often prescribed in conjunction with an
are solitary and tend to be more central, while infiltrates can be antibiotic in order to decrease the chance of developing a second-
single or multiple and strongly tend to express themselves at or ary infection or corneal ulcer and to protect against misdiagnosis.”
near the corneal limbus.
The fluorescein staining pattern of the lesion is probably one
of the characteristics we find most helpful in making a definitive
diagnosis. With an ulcer, the size of the fluorescein staining pattern
closely mirrors the size of the corneal lesion, whereas the staining
pattern of an infiltrate is significantly smaller than the underly-
ing lesion. This is because an ulcer begins in the epithelium, and
expands laterally and in depth, creating an epithelial defect closely
paralleling its stromal invasion. An infiltrate results from the chemo-
tactic attraction of leukocytes from the paralimbal microvasculature.
The accumulation of white blood cells in the anterior stromal tis-
sues results in some secondary compromise to the overlying epi-
thelium, which tends to cause a relatively small defect in the center
of the underlying stromal lesion. With an ulcer, the size of the fluorescein staining pattern
An attentive clinician should, in most presentations, be able to closely mirrors the size of the corneal lesion.
correctly identify the lesion as either an infiltrate or an infectious
ulcer and treat appropriately; however, there are some cases that
defy a clear, confident diagnosis. Let’s look at diagnostic and thera-
peutic considerations:
1. If the lesion is clearly infectious, a fluoroquinolone hourly while
awake with Polysporin ointment at bedtime may be an excellent
initial approach. If there is no response or suboptimal response, add
generic Polytrim hourly, because if this ulcer is caused by a MRSA
bacterium, the fluoroquinolone may be suboptimal and the trim-
ethoprim should be able to complement eradication of any resistant
2. If it is clearly an infiltrate, use Zylet q2h for two or three days,
and then just q.i.d. for three to more five days.
3. If the diagnosis is problematic, then initiate therapy with a With an infiltrate, the size of the fluorescein staining pattern
fluoroquinolone hourly for a day or two while the patient is awake. is significantly smaller than the underlying lesion.


032_dg0610_steroids.indd 34 6/2/10 2:42 PM

As a rule, we initiate therapy 1. Do you have diabetes? sone. The patient’s blood glucose
with eyedrops only. If, in our clini- 2. Do you have (or have you levels will elevate during the course
cal judgment, the initial presenta- had) peptic ulcer disease? of therapy, but will renormalize
tion is sufficiently pronounced, 3. Do you have tuberculosis or once the oral prednisone is stopped.
we may also add FML ointment have you been in areas where tuber- For the patient who is insulin-de-
concurrently with the eyedrops. culosis is endemic? pendent, he/she will be best served
But if there is not some noticeable 4. Are you, or could you be, by using a “sliding dosing scale” of
improvement in three to four days, pregnant? insulin in an attempt to keep blood
we consider adding oral therapy as Let’s look at these inquiries one glucose levels under control. That
noted above. at a time. Regarding diabetes, our is, having diabetes is not a contrain-
endocrinology colleagues give us dication, but is a circumstance that
Oral Prednisone this perspective: If the patient is does require more attentive care.
Before initiating oral prednisone, non-insulin dependent, just press Regarding the patient afflicted
you need to ask the patient three or on with the prescribed short course with peptic ulcer disease, our
four simple questions: (three to 14 days) of the predni- gastroenterology colleagues advise
having patients take a proton pump
Treating Contact Blepharodermatitis inhibitor (such as Nexium or OTC
Patients with contact blepharoder- Prilosec or Prevacid) during the
matitis are typically female. Most course of therapy and for a few
of these presentations result from days afterward. Again, peptic ulcer
exposure to fingernail polish or other disease is not a contraindication,
(usually undetermined) products only a complicating factor.
such as makeup, shampoos, lotions, Regarding tuberculosis, our
etc. Neomycin can also trigger such pulmonary colleagues recommend
an epidermal response. The treat- a quick chest X-ray (CXR) and a
ment: cold compresses and a topical subcutaneous PPD (purified protein
corticosteroid ointment, lotion or derivative) test. The latter takes a
cream. few days to get the results, so start
There are two drugs to effect a cure: FML ophthalmic ointment, or generic 0.1% therapy guided by the CXR results
triamcinolone (non-ophthalmic) ointment, cream or lotion. By far, the most effective alone. As always, we strongly
and least expensive is the 0.1% triamcinolone. (We discovered triamcinolone years ago recommend telephone consultation
when all manufacturers stopped making dexamethasone ophthalmic ointment.) We with an appropriate physician with
almost always prescribe triamcinolone because FML comes in a 1/8-ounce (tiny) tube such a unique presentation.
for around $30 to $40, whereas the triamcinolone comes in a 15g (large) tube for under Regarding the establishment of
$10. pregnancy, or the possibility of
Do note that on the side of the triamcinolone tube is a statement: “not for ophthalmic pregnancy, a telephone call needs
use.” Be sure and explain to the patient that this is default language (since “ophthal- to be made to the patient’s ob-
mic” ointments come in a 1/8 ounce nozzle-tipped tube) and that it is to be used on stetrician to obtain consultation.
the skin and not directly in the eye. (Even if some of it gets into the eye, it will not In like manner, we always have a
cause harm.) If a patient is new to us or is just plain persnickety (“I want only an FDA- telephone conversation with the
approved ophthalmic medicine”), we might also explain that triamcinolone (Kenalog) is patient’s primary care physician (or
commonly injected into the eye (to treat macular edema). Once patients hear the cost other appropriate provider/special-
difference, almost all prefer being prescribed the triamcinolone. ist), just to ensure we are all “on
How often we prescribe the treatment, and for how long, is mostly a matter of clini- the same page” prior to initiat-
cal judgment. A typical treatment is t.i.d. for two days, b.i.d. for two days, then qhs for ing oral prednisone therapy. We
two to four days. Alternatively, it could be used b.i.d. for three to four days and then should stress at this point that such
stopped. We advise the patient to apply a light application during waking hours and a “encumbering comorbidities” are
more generous application at bedtime. very rare, and that in most circum-
Note that triamcinolone comes in three concentrations of 0.025%, 0.1%, and 0.5%, stances, our use of oral prednisone
and in three different forms: lotion, cream and ointment. We always write for the 0.1 % is extremely straightforward and
cream. completely uneventful. When in
doubt, grab the phone, call the


032_dg0610_steroids.indd 35 6/2/10 2:42 PM

patient’s doctor(s), and put your inflamed human tissues. Fluorometholone ophthalmic
heads together. comes in four varieties:
There are two simple approaches Topical Steroids 0.1% FML suspen-
to prescribing oral prednisone, both Now let’s look at various topical sion, 0.25% FML Forte
of which are generic and cheap: therapies. As stated earlier, there suspension, 0.1% Flarex,
10mg tablets prescribed as desired, are roughly three categories: potent, and FML ointment. The
i.e., “take 4 tabs x 3 days, 2 tabs x moderate strength, and weak. 0.25% concentration is
1 week, and then 1 tab x 1 week;” • Potent. Prednisolone, lotepre- beyond the top of the
or, “take 4 tabs x 3 days and dnol, difluprednate, dexametha- dose-response curve
stop.” For the first scenario, order sone and rimexolone represent the (which is 0.1%) and
“dispense #33”; for the second potent steroid category. All of these because there is no ad-
scenario, order “dispense #12”. drops perform about the same; ditional anti-inflamma-
These numbers represent the actual however, there are some caveats tory effect, it has no role in
number of tablets to be dispensed that separate them. clinical patient care. FML
to the patient . The other option is All are ketone-based with the is generic and thus reason-
the “Dosepak,” which is prepack- exception of loteprednol, which is ably inexpensive. While
aged in 4mg, 5mg or 10mg tablets ester-based. it possesses less tendency
for a six-day supply. The “original All have to be shaken well, to increase intraocular
issue” was the 4mg strength tablets, except that the emulsion Durezol pressure than the other
in which the patient takes six (difluprednate) and the more sus- ketone steroids, we are
tablets the first day (i.e., 24mg), five pendable Vexol (rimexolone) only not nearly as comfort-
tablets the second day, etc., until require minimal shaking. able using it long-term as
the package is depleted. While not a We try to avoid using dexameth- we are with the ester-
critical decision, we prefer the 5mg asone because it has the greatest based loteprednol.
Dosepaks for eye conditions, as this propensity to raise the intraocular • Weak. Lastly are the weaker
dosage seems to be a bit more clini- pressure. corticosteroids of 0.2% or 0.25%
cally effective. • Moderate. The moderate prednisolone, and 0.2% lotepred-
Oral prednisone is usually taken strength corticosteroids are repre- nol (Alrex). These are pretty much
as a single daily dose. Some doc- sented by the fluorometholones. limited to the treatment of allergic
tors divide the dose beginning at There are two subtypes, the alcohol conjunctivitis (where there are
60mg, so that the patient takes, for (FML) and the acetate (Flarex). signs of inflammation accompany-
instance, 30mg with breakfast and The acetate moiety gives the ing symptomatic itch). Another
30mg with the evening meal. It is fluorometholone molecule some excellent use of such low-dose
best to take prednisone with a meal. additional anti-inflammatory ef- steroids is in the care of patients
For perspective, patients with fectiveness over the alcohol moiety. with Thygeson’s SPK. In both cases,
acute optic neuritis or giant cell The fluorometholone molecule is a we prefer loteprednol because of its
arteritis are treated with 1,000mg fluorinated analog of progesterone. safety profile. ■
of methylprednisolone IV for three
days, followed with a high dose Clinical Pearls for Corticosteroids
oral steroid taper. With this per- • Always consider that a unilateral red eye, especially one with a serous discharge,
spective in mind, one can quickly could be herpetic.
see that the dosages commonly used • Hit most cases of inflammation hard and heavy initially. Begin to taper only once
to treat more “everyday” ocular the inflammation is well controlled.
conditions are relatively low. • The more protracted the use of steroids, the more protracted should be the taper.
In summary, oral prednisone • Tapering is optional for many conditions for which therapy is used for only a few
therapy is uncommonly needed in days. Generally, intrinsic conditions such as iridocyclitis require tapering, whereas
eye care, but when it is needed, it with some extrinsic conditions, such as traumatic iridocyclitis, tapering is not always
almost invariably can be used safely required.
and effectively. Ask any primary • Patients with stromal herpetic disease, chronic uveitis, chronic dry eye inflamma-
care physician; most prescribe tion, Thygeson’s SPK and corneal grafts may need to use a drop or two or loteprednol
prednisone every day for one simple daily for many years; perhaps a lifetime.
reason: it helps restore health to


032_dg0610_steroids.indd 36 6/2/10 2:42 PM

Clinical Update on the
There are four star players in the field of ‘nonsteroidal anti-inflammatory drugs.’
Older drugs have been reformulated and new drugs have come to market.
hile oral NSAIDs are of all, they have no direct anti- convert it ultimately to either

W heavily used in systemic

medicine, topical oph-
thalmic NSAIDs use is relatively
inflammatory properties. They
simply inhibit an enzyme along the
synthetic pathway to the produc-
prostaglandin formation or leukot-
riene formation. Cyclooxygenase
converts AA to prostaglandins,
limited. The foundational perspec- tion of prostaglandins, which are and lipoxygenase converts AA to
tive on this class of drugs is the powerful mediators of inflamma- leukotrienes.
acknowledgement that steroids tion. As doctors, it is vital that we The key point here is that while
reign supreme in inflammation have knowledge of this particular NSAIDs inhibit the enzymatic ac-
control. Topical NSAIDs are never pathway. It is known as the arachi- tivity of cyclooxygenase, they have
an appropriate substitute when the donic acid cascade. no effect on lipoxygenase; thereby
clinical condition merits a topical As you can see in the diagram, allowing the production of leukot-
corticosteroid. The Arachidonic Acid Pathway rienes to go unchecked.
NSAID use has much more (right), the origin substrate is For clinical perspective, remem-
applicability in perioperative care phospholipids released from cell ber the early days of photorefrac-
than in primary eye care; however, membranes as a generic response to tive keratectomy when NSAIDs
there are several clinical circum- multiple causes of cellular micro- were initially used postoperatively?
stances in which patient care can be trauma. Corticosteroids inhibit the Patients experienced problems with
enhanced through the use of such conversion of these phospholipids white blood cell corneal infiltrates,
a drug. to arachidonic acid by inhibiting until it was realized that steroids
the catalytic enzyme phospholipase prevented their formation. Why?
Pharmacology of NSAIDs A early in this synthetic cascade. Leukotrienes are chemotactic for
Let’s first understand the Once arachidonic acid (AA) is leukocytes for which NSAIDs do
pharmacology of NSAIDs. First formed, two different enzymes nothing, since they only inhibit the

Non-Steroidal Anti-Inflammatories

Acular LS ketorolac tromethamine 0.4% Allergan q.i.d. 3 years 5ml
Acuvail ketorolac tromethamine 0.45% Allergan b.i.d. N/A unit-dose
Nevanac nepafenac 0.1% Alcon t.i.d. 10 years 3ml
Voltaren diclofenac sodium 0.1% Novartis q.i.d. N/A 2.5ml, 5ml
Xibrom bromfenac 0.09% ISTA Pharmaceuticals b.i.d. N/A 5ml


037_dg0610_NSAIDs.indd 37 6/2/10 2:49 PM

The Arachidonic Acid Pathway


Membrane Phospholipids

Phospholipase A2 Inhibited by
Arachidonic Acid

Inhibited by
Cyclo-oxygenase Lipoxygenase

Endoperoxides Hydroperoxides

Thromboxane A2 Prostaglandins Prostacyclin Leukotrienes and

(PGE2, PFG2a, PGD2) (PGI2) related compounds

synthesis of prostaglandins and leukotrienes. authority and precision.

have no activity against lipoxy- All this may sound like gibberish It is generally thought that
genase-catalyzed production of to some. The AA pathway is more steroids and NSAIDs may demon-
leukotrienes. easily grasped by studying the dia- strate some synergy, and therefore
Since steroids work higher up gram, which illustrates the process- might be beneficial used concur-
in the AA synthetic pathway, they es we have just described. Once you rently. For example, standard-of-
inhibit both cyclooxygenase and have a clear understanding of the care treatment of postoperative
lipoxygenase, thus inhibiting pro- AA pathway, then you can begin cystoid macular edema is usu-
duction of both prostaglandins and to prescribe with enhanced clinical ally treated with Pred Forte (1%

Note on Oral NSAIDs

Cyclooxygenase (COX) is the enzyme by which arachidonic acid ard events. All three of these drugs were FDA-approved around the
is metabolized into prostaglandins. There are two subspecies of year 2000.
cyclooxygenase; COX-1 and COX-2. We rarely prescribe oral NSAIDs, but do occasionally use
COX-1 is a constitutive enzyme that synthesizes prostaglandins, Celebrex (100mg or 200mg b.i.d.) to help our patients in whom
which regulate physiological functions such as in the GI tract, kid- we have difficulty tapering off oral prednisone when treating
neys, platelets and vascular endothelium. orbital pseudotumor, stubborn uveitis or when treating scleritis.
COX-2, on the other hand, is an inducible enzyme, which is pri- For example, if the anterior uveitis tends to rebound when the oral
marily activated during inflammatory tissue assaults. This is why prednisone is tapered below 20mg per day, we have been suc-
there was great excitement years ago when COX-2 inhibitors came cessful using Celebrex along with prednisolone 20mg for a week,
to market. These purportedly would address inflammation while then 10mg for a week or two, while concurrently using Celebrex
sparing the physiological prostaglandins, specifically sparing the GI for four to six weeks to facilitate the discontinuation of the oral
tract from NSAID toxicity. prednisone. Aggressive use of Pred Forte and therapeutic cyclople-
Unfortunately, a couple of these products, Vioxx (rofecoxib, gia is foundational to these oral supplementary therapies.
Merck) and Bextra (valdecoxib, Pfizer) were thought to significantly There is increased risk of peptic ulcer disease when using both
increase the risk for heart attack and stroke, and were removed oral prednisone and an oral NSAID (including Celebrex), so we
from the market. Celebrex (celecoxib, Pfizer) is now used more would likely use a proton pump inhibitor such as OTC Prilosec or
conservatively, but appears to be less likely to cause such untow- Prevacid 20mg once daily when we are using such dual therapy.


037_dg0610_NSAIDs.indd 38 6/2/10 2:49 PM

Uses for Topical NSAIDs topical and systemic administra- very expensive, and patients would
The most common conditions for which tion. Systemic NSAIDs are true to likely be adequately served with
topical NSAIDs can play an adjunctive their name and do indeed render a generic diclofenac, or other less
beneficial role are: marked anti-inflammatory effect, expensive NSAIDs.
• Corneal abrasions whereas topical NSAIDs have their The original formulation of oph-
• Just before, and just after, in-office forte in ocular surface pain amelio- thalmic ketorolac (Acular) was a
Betadine 5% Sterile Ophthalmic Prep ration while providing some limited 0.5% solution, but marked stinging
Solution treatment for highly symp- activity against inflamma- upon instillation was its Achilles
tomatic EKC tion. (See “Uses for Topi- heel. The drug was reformulated
• Post foreign body removal cal NSAIDs,” right.) a few years ago to a 0.4% solu-
• Adapting to GP contact lenses Voltaren (diclofenac tion (Acular LS) and is now quite
• Post anterior stromal puncture proce- 0.1%, Novartis) and tolerable—a very nice upgrade.
dure Acular LS (ketorolac In the recent past, two
• Post PKP, or any surface disruptive 0.4%, Allergan) have more NSAIDs have come
laser procedure been the standard to market. They are
• Treating and/or preventing cystoid bearers of topical Xibrom (bromfenac
macular edema NSAID care over the 0.09%, Ista) and Neva-
• Adapting to punctal plugs past decade. Both nac (nepafenac 0.1%,
• Allergic conjunctivitis are used q.i.d. and Alcon).
• Supplemental to steroids in treating are largely clinical Xibrom’s unique-
recalcitrant uveitis equivalents. One study compared ness is that it is dosed
• Some cases of photophobia ketorolac and diclofenac twice daily, and is
• Post cataract surgery care head-to-head. Its con- well tolerated.
• Supplemental to oral NSAIDs in treat- clusion: “The decrease Nevanac is unique
ing scleritis in corneal sensitiv- in that it is the first
• Treating and/or preventing inflamed ity in normal human available prodrug. Nevanac is
pterygia and pingueculae corneas is more enzymatically converted to amfenac
pronounced and sodium, which, like all NSAIDs,
prednisolone acetate, Allergan) longer lasting with inhibits cyclooxygenase. It is dosed
and a topical NSAID (dosed at its diclofenac than with three times a day.
FDA-approved dosing frequency). ketorolac.”1 All these drugs are
This synergy is difficult to reconcile The most recent generally approved by
based on the dynamics of the AA modification in the FDA for treating
previously discussed. Perhaps the ketorolac is the introduction of a postoperative inflam-
rapidity of onset and/or the degree 0.45% concentration of ketoro- mation, and as such,
of enzymatic inhibition may be lac. Acuvail (Allergan) comes as a will be used much
considerations for explanation. preservative-free unit-dose indicated more in a surgical
Contrarily, we find no literature for perioperative use b.i.d. one day context. Ketorolac
supporting the use of both drug prior to cataract surgery, and is is also approved to
groups in the standard initial treat- continued for two weeks immedi- treat ocular al-
ment of anterior uveitis. There ately postop. However, Acuvail is lergy, and there are
is still a lot to be learned in how a number of other
these drug classes modify tissue applicable uses for
responses. NSAIDs relevant to primary eye
care, as enumerated above.
The Role of Topical NSAIDs Because of the rare, but real,
Compared to topical corticoste- potential for corneal toxicity and
roids, NSAIDs have a limited role melting, these drugs should be used
in primary eye care. Nonetheless, cautiously when there is preexisting
there are several situations where corneal epithelial compromise. As
NSAIDs can be beneficial. There a general rule, we never prescribe
is a partial disconnect between any topical NSAID for use beyond


037_dg0610_NSAIDs.indd 39 6/2/10 3:52 PM

Latest Literature on NSAIDs
If you want the ultimate review of NSAIDs, we urge
you to read: “Nonsteroidal Anti-inflammatory Drugs
in Ophthalmology,” by Stephen J. Kim, M.D., Allan J.
Flach, M.D., and Lee M. Jampol, M.D., in Survey of
Ophthalmology, March-April, 2010. It is excellent.
Some quotes (or in-context paraphrases) from this
article, and our commentary (indicated in blue), follow:

• “NSAIDs do not inhibit lipooxygenase (LPO) and thus

do not typically prevent generation of leukotrienes. This
may explain, in part, their decreased anti-inflammatory
effects compared to corticosteroids, which inhibit both LPO
and COX (cyclooxygenase). However, celecoxib and diclof-
enac are notable exceptions and inhibit LPO by direct and
indirect means, respectively. In addition, NSAIDs appear to
have anti-inflammatory and anti-angiogenic effects inde-
pendent of their inhibition of COX. Several reports suggest
that ketorolac is the most potent inhibitor of COX-1, while An extensive review of the world literature concludes that prevention
both bromfenac and amfenac have staked the claim as and treatment of cystoid macular edema with NSAIDs is beneficial.
being the most potent inhibitors of COX-2.
“The clinical importance of selective COX-1 and COX-2 inhibi- cataract surgery. Despite its significance, the pathogenesis of this
tion for ocular disease remains to be established.” syndrome, and its relationship to and its associations with CME in
The prostaglandins produced via COX1 are physiologic in their other diseases, is not completely understood.
action, whereas the prostaglandins produced from the upregula- “Systemic NSAIDs provide insufficient drug levels to inhibit
tion of COX2 result in pathologic expression, i.e., pain + inflam- prostaglandin production in the anterior segment, especially when
mation. compared to topical administration.
“The true incidence of CME following cataract surgery is not
• “There is good evidence that topical NSAIDs may be used precisely known. Despite this continued uncertainty, recent stud-
in place of, or in addition to, topical corticosteroids after cataract ies have reported incidences following small-incision cataract sur-
surgery to avoid excessive inflammation and to improve visual gery as high as 9-19% using fluorescein angiography, and 41%
acuity. Although none of the studies reviewed by the FDA used as measured by OCT.
topical NSAIDs more than 24 hours before cataract surgery, “It has long been recognized that the natural history of CME
well-designed studies suggest potential benefit from preoperative usually includes spontaneous resolution.
dosing regimens of up to three days. Furthermore, several clinical “Although there is no FDA-approved treatment for the preven-
studies have reported that concurrent administration of NSAIDs tion or treatment of CME following cataract surgery, an extensive
and corticosteroids results in additive effects. review of the world literature… concluded that prevention and
“Therefore at present, there is no evidence to suggest one treatment of CME with NSAIDs is beneficial.”
topical NSAID treatment is better than another in controlling post- This is just another example of where the scientific literature
operative inflammation.” trumps FDA guidelines. “Off-label” use of medicines is becom-
• “CME remains the most common cause of vision loss after ing more and more commonplace; so don’t let a governmental

one week—with the exception of Our favorite brand-name NSAID label uses for NSAIDs within the
CME, which we treat with a topical is Xibrom, purely because of its context of primary eye care. Their
NSAID for a month, concurrent simple b.i.d. dosing. Because of its main use is in the prevention or
with Pred Forte. cost, however, on the rare occa- treatment of cataract surgery-relat-
While steroids are often initially sions when we do write for a topi- ed cystoid macular edema concur-
dosed as frequently as hourly for cal NSAID, we generally prescribe rent with a potent corticosteroid. ■
a few days, we strongly urge that generic diclofenac.
1. Seitz B, Sorken K, LaBree LD, et al. Corneal sensitivity
NSAID use not exceed the FDA- and burning sensation. Comparing topical ketorolac and
approved dosing frequency. In summary, there are several off- diclofenac. Arch Ophthalmol. 1996 Aug;114(8):921-4.


037_dg0610_NSAIDs.indd 40 6/2/10 2:50 PM

bureaucracy override sound, ratio- tion under control. We typically just
nal and prudent use of a helpful maintain Lotemax once- or twice-
drug. daily for most of these patients.

• “Although there is no FDA- • “Corneal perforations and melts

approved therapy for the preven- have been reported with the use
tion and treatment of CME fol- of topical NSAIDs. Therefore, the
lowing cataract surgery, available routine use of topical NSAIDs in dry
evidence suggests that topical eye patients may increase the risk of
NSAIDs may prevent and treat CME these adverse events.”
when used alone or concurrently • “One in seven Americans
with corticosteroids. receives a prescription for orally
“Given the relatively low inci- administered NSAIDs each year.”
dence of clinically significant CME, Although we would use a topical corticosteroid first, • “The most well known side
the cost/benefit of routine prophy- evidence shows that NSAIDs are useful for treating effects accompanying systemic
lactic use of NSAIDs in cataract inflamed pingueculae and pterygia. NSAID use relate to the GI and cen-
surgery is a matter of ongoing tral nervous system.
debate.” “Often the GI toxicity can be partially ameliorated by adding an
• “Although no other topical NSAID has been approved for aller- H2-receptor antagonist, proton pump inhibitor, or prostaglandin
gic conjunctivitis besides ketorolac, there are studies suggesting analog; however, many patients will require discontinuation of the
that 0.1% diclofenac and 0.09% bromfenac may also be effective. medicine.”
“Studies have reported that ketorolac 0.5%, diclofenac 0.1%, • “A recent prospective, randomized placebo-controlled trial
and bromfenac 0.09% are all effective in treating vernal conjunc- observed no adverse events or changes in liver chemistries in a
tivitis.” large number of patients treated twice daily for fourteen days with
We would use a potent topical corticosteroid to gain full control topical bromfenac. The off-label use of topical NSAIDs for dura-
of the vernal conjunctivitis first, and then perhaps try a topical tions longer than this is common, and clinicians should be vigilant
NSAID to maintain that control. One could also consider antihis- for potential systemic toxicity. In addition, because eyelid closure
tamine/mast cell stabilizer, or continue with loteprednol once to and nasolacrimal occlusion can decrease systemic absorption of
twice daily—whatever it takes to keep the condition under control. topically applied medications by almost 70%, explaining these
techniques to all patients seems prudent.”
• “Whereas topical corticosteroids are frequently helpful in • “At present there is no evidence that one NSAID is less toxic
relieving episcleritis, topical NSAIDs appear to be less effective. than another.”
Systemic NSAIDs are of value in those unusual cases where topi- • “The over two dozen cases of corneal perforations reported
cal treatments are ineffective.” with the introduction of topical corticosteroids over 30 years ago
This is an excellent example that, when significant inflam- were likely related to improper clinical use and patient follow-up.
mation is present, it is a steroid that is needed—not an inferior Thus, many topical medications have the potential for toxicity if
quasi-anti-inflammatory agent. unmonitored or used inappropriately.”
Note that “over 30 years ago,” it was not doctors of optometry
• “Regarding scleritis, although topical NSAIDs are not effec- who performed “improper clinical use and patient follow up.”
tive, systemic NSAIDs are used as first-line agents. Although
many NSAIDs may be effective, indomethacin at 25-50mg three • “A definite link between NSAID use and corneal melt remains
times daily is most commonly used. Side effects include gastric tenuous. Application of topical NSAIDs for reasonable lengths of
upset that may require concurrent use of an H2-blocker or proton time in appropriate patients with proper monitoring appears safe.
pump inhibitor. A recent report indicated that the COX-2 selective There is, however, evidence of the continued misuse of these
NSAID, celecoxib, at a daily dosage ranging from 200 to 800mg q medications.”
day was effective in controlling diffuse anterior scleritis in 92% of As can be seen, there are occasions when a topical NSAID can
patients without producing any gastrointestinal effects.” be useful; however, these uses are dramatically overshadowed by
• “There is also evidence that NSAIDs are useful in the treat- the use of corticosteroids. Always keep in mind that the rational,
ment of inflamed pingueculae and pterygia.” scientifically sound use of a drug “off-label” may be in the very
We would always use a topical corticosteroid to first get inflam- best interests of a patient.
mation controlled, then consider an NSAID to help keep the condi-


037_dg0610_NSAIDs.indd 41 6/2/10 2:50 PM

The Mastery of
Dry Eye
Most dry eyes can be ameliorated with the use of a multifaceted approach to reduce
inflammation and renormalize the tear film.
aining control of ocular

G surface dryness can signifi-

cantly improve quality of life
for our patients. There are basically
four interventional maneuvers we
can employ:
• Artificial tears
• Anti-inflammatory therapy
• Oral doxycycline—or fish oil
• Punctal plugs
Judicious, thoughtful use of these
interventions, either singly or ad-
ditively, can be of enormous benefit
to patients with dry eye disease.
There is a lot of marketing spin
regarding the medical treatment of
dry eye. We propose to set forth a
rational, scientifically sound and Moderate rose bengal staining of the conjunctiva and minimal rose bengal staining of
clinically successful, literature- the cornea in a patient with moderate dry eye.
based protocol for truly helping
patients who suffer from ocular of Louisville, in Kentucky. He is ability of the treatment to mimic
surface dryness. editor-in-chief of the authoritative the lipid layer of the tears.”
Bear with us as we set the journal, The Ocular Surface (www. • “One drop containing Resto-
foundation for our clinical ap-, a journal we ryl, the active ingredient of Soothe
proach. Two of the most respected highly recommend to all practicing XP [Bausch + Lomb], more than
clinicians in this field of study eye doctors. doubled lipid layer thickness.”
are Michael A. Lemp, M.D., and Here are some pertinent quotes • “Restoryl has been shown to
Gary N. Foulks, M.D. Dr. Lemp is from these clinicians/scientists from replenish the aqueous layer of the
widely regarded as one of the pio- the peer-reviewed literature. In the tear film. When applied to the eye,
neers in dry eye research and has July-August 2007 issue of Survey of Restoryl differentiates into neutral
been with the Georgetown Univer- Ophthalmology, Dr. Foulks states:1 oils (helping to rebuild the lipid lay-
sity School of Medicine for many • “Increasing the thickness of er), interfacial molecules (stabilizing
years. Dr. Foulks has chaired the the tear lipid layer improves the the interface between the lipid and
cornea service at Duke University stability of the tear film, suggesting aqueous layers, and supporting the
and the University of Pittsburgh, that in selecting a dry eye therapy, mucin layer), and water (helping to
and is currently at the University an important feature would be the restore the aqueous layer).”


042_dg0610_dryeye.indd 42 6/2/10 3:02 PM

Dry Eye
Time to Face the Mucin Foulks explains. Dr. Lemp explains dnol. Human systems do not pos-
that the (hyper) osmotic tear film sess “ketonases,” but have an abun-
as the prime cause of ocular surface dance of esterases. It is this reality
inflammation. We believe these two that sets loteprednol apart as a very
foundational cornerstones establish safe and very effective molecule.
Soothe XP as a key element in help- In fact, the loteprednol molecule is
ing patients with dry eye. nearly identical to the prednisolone
Dr. Lemp continues: “Although molecule except that a ketone moi-
the exact place of inflammation ety is replaced with an ester moiety.
in the stream of events leading to So, for a dozen years, the world
ocular surface distress is not clear, has had extensive experience with
its role is unmistakable.” He goes loteprednol and it is authoritatively
on to say, “In the use of cyclospo- established as a highly effective,
rine (Restasis) to modulate immune yet very safe, anti-inflammatory
activity and to suppress inflamma- medicine. Obviously this makes
tion in dry eye, there is increasing loteprednol an excellent choice in
evidence that the use of topical cor- the management of ocular surface
ticosteroids as temporary or pulsed inflammation. We would never be
Soothe Xtra Hydration (Bausch + Lomb) therapy can be useful in reducing comfortable using a protracted regi-
is new as of May 2010. We have not the damaging effect of inflamma- men of traditional ketone steroids,
used this new product and can, at this tion.” but the unique ester-based chem-
time, only share the following informa- Furthermore, the istry of loteprednol makes
tion from the company: “New Soothe Report of the Inter- such a therapeutic approach
Xtra Hydration, for aqueous-deficient dry national Dry Eye safe, clinically effective, and
eye therapy, moisturizes and restores WorkShop (DEWS), cost-effective.
the deficient aqueous and mucin layers published in 2007, Now, the stage is set so
of the tear film to provide lasting hydra- clearly established we can care for our dry eye
tion and comfort.” that “corticoste- patients in an enlightened
Until we can gain clinical experience roids are an effec- manner. We have had the most
with this newer product, we will con- tive anti-inflam- success with the following pro-
tinue to use Soothe XP as our workhorse matory therapy in tocol, and urge you to consider
in the care of our patients with ocular dry eye disease.”3 it as you care for your patients
surface dryness. Now, let’s talk about the with ocular surface dryness:
use of the steroids in ocular surface First, we do a therapeutic trial
• “Overall, decades of research inflammatory disease. Steroids
have shown a strong correlation continue to suffer from the myth Steroids and IOP Increase
between dry eye symptoms and the that they are dangerous. Steroids What about the rare IOP increases that
state of the tear film lipid layer, as have the potential to cause harm, can accompany loteprednol use? In our
well as a clear connection between but many thousands of people are experience, a steroid responder is almost
the status of the lipid layer and the helped by steroids every day. It is always revealed at the time of the one-
osmolarity of the tear film.” so important to keep the enormous month follow-up evaluation. If the patient
In the September 2008 American beneficial attributes of steroids in shows no increase in IOP after a month
Journal of Ophthalmology, Dr. focus. As intensely busy clinicians, of q.i.d. steroid therapy, it is highly
Lemp states: “Tear osmolarity is we have been able to help thou- unlikely that there will be a subsequent
considered ‘the central mechanism sands of patients over the decades, IOP increase. Plus, by this point along the
causing ocular surface inflamma- and we cannot recall a single thera- therapeutic pathway, we are stepping
tion, damage and symptoms, and peutic misadventure with cortico- down the Lotemax to b.i.d., thus reduc-
the initiation of compensatory steroids. ing further the highly remote possibility
events in dry eye’.”2 There are two types of steroid of untoward side effects. The more you
So, Soothe XP stabilizes the lipid molecules: ketone-based, such as utilize corticosteroid therapy, you will see
layer, protecting the tear layer from prednisolone and dexamethasone; how true this is.
becoming hyperosmotic, as Dr. and one that is ester-based, lotepre-


042_dg0610_dryeye.indd 43 6/2/10 3:02 PM

Dry Eye
with Soothe XP for a month. We
encourage our patients to use the
drops as often as they would like,
but at least four times a day. De-
pending on patient symptoms and
clinical signs, we commonly pre-
scribe Lotemax (loteprednol 0.5%,
Bausch + Lomb) to be used concur-
rently q.i.d., instructing the patient
to wait 20 to 30 minutes between
the use of these two eyedrops. Rose bengal and lissamine green staining of the conjunctiva and cornea in a patient
At the one-month follow-up visit, with Sjögren’s syndrome.
we assess the therapeutic success,
and then modify our therapy as reduce the frequency of instillation that Drs. Lemp and Foulks describe
needed. We stress here that of Soothe XP. tear osmolarity as “the central
Soothe XP, being a mineral At the two-month mechanism causing ocular surface
oil emulsion, is radically dif- follow-up (assuming we inflammation.” So, via Soothe
ferent from other artificial have a satisfied patient, XP, we have bolstered the
tears and cannot be described which is typically the lipid layer, thus reducing tear
as “just another artificial case), we are at another osmolarity and, with Lotemax,
tear” due to its completely decision tree. By this we have addressed what-
different molecular chemistry. time, most patients are ever hyperosmolarity-induced
Assuming clinical success, using Soothe XP two to inflammation preexisted. At
we now decrease the Lotemax three times a day, and this juncture, there should be
to b.i.d. for two more months we can try to stop the little or no clinically significant
and allow the patient to try to Lotemax. Remember ocular surface inflammation.

Melton and Thomas Soothe XP/Lotemax Dry Eye Management Protocol


042_dg0610_dryeye.indd 44 6/2/10 3:02 PM

Dry Eye
Perspective on Cyclosporine
We are often asked about Restasis (cyclosporine 0.05%, Allergan) and its role in managing
dry eye disease. The main reason we are infrequent prescribers of Restasis is because
we have experienced firsthand less-than-optimum clinical responses from many of our
patients. It was these “necessity being the mother of invention” patient encounters that
motivated us to try to find a more effective, and less costly, approach to dry eye manage-
ment than Restasis provided. Thus was born our discovery of the beneficial effects of
loteprednol to control ocular surface
An excellent article (supported by
85 references), “Advancements in
Anti-Inflammatory Therapy for Dry Eye
Syndrome,” by Erin McCabe, O.D., Filaments on the cornea in a patient
and Srihari Narayanan, O.D., which with moderate to severe dry eye.
appeared in the October 2009 issue of
Optometry, supports our clinical experi- Now, back to the decision tree:
ence in the management of patients Following the two to three-month
with dry eyes. “inflammation suppression” phase,
In their peer-reviewed article, Drs. McCabe and Narayanan state: we stress the importance of consis-
• “Within the last decade, advancements in the understanding of the pathophysiol- tent ocular surface lubrication to
ogy of dry eye syndrome have underscored inflammation as a common thread linking help prevent any reestablishment
most presenting cases of dry eye. Inflammation often plays a key role in propagating of inflammation, and we generally
and sustaining the disorder regardless of the cause of the ocular surface disease. These stop the Lotemax. Keep in mind
discoveries have triggered the development of a new line of successful anti-inflammatory that we prescribed it q.i.d. for a
treatments.” month and b.i.d. for two months,
• “Several studies have found that topical corticosteroids effectively treat dry eye. which is ample time to suppress
These drugs inhibit cytokine and chemokine production, decrease the synthesis of matrix any ocular surface inflammation.
metalloproteinases and arachidonic acid derivatives, suppress the expression of cell adhe- Now, we are in a “maintenance
sion molecules, and induce lymphocyte apoptosis. Corticosteroid treatment has provided phase,” using only artificial tears.
significant evidence of the involvement of inflammation in the pathogenesis of dry eye Some doctors continue the Lotemax
syndrome.” once daily for a few more months,
• In a study utilizing 1% nonpreserved methylprednisone t.i.d. to q.i.d. for two weeks, and while we have no issue with
“All patients reported symptomatic improvement after the initial two weeks of therapy. this, we do not feel it is necessary in
Corneal fluorescein staining scores decreased in all patients. Many patients noted dimin- most cases.
ished ocular irritation weeks to months after cessation of treatment, which suggests that One question that is commonly
corticosteroids may treat causative factors of dry eye, instead of merely alleviating symp- asked is: “What about using Alrex
toms.” (loteprednol 0.2%, Bausch +
• “One study found that only 3.9% of patients who instilled 0.05% CsA [cyclosporine] Lomb) instead of Lotemax, since
twice daily for a course of at least six weeks enjoyed a disease-free state for a year or a lower concentration would be
more afterward.” even safer?” There are no studies
• “Topical corticosteroids have been mainstays in the eye care field, more so than the regarding this; however, our advice
newer agent, Restasis, and less potent corticosteroid formulations with few side effects is to use Lotemax q.i.d. for at least
are now available. Pulse therapy of corticosteroids has been shown to stave off dry eye two weeks to rapidly suppress the
symptoms for several months, and patients were more likely to notice the beneficial ocular surface inflammation, then
effects of corticosteroids earlier than with Restasis.” b.i.d. until the 5ml bottle is empty.
We urge every optometrist to read this non-industry-supported, comprehensive article. At that point, it would be reason-
With these observations in mind, we urge you to carefully consider your therapeutic able to try the use of Alrex b.i.d. for
options in caring for your patients with dry eye disease. a month or two, and then once-a-
day for another month or two.
McCabe E, Narayanan S. Advancements in anti-inflammatory therapy for dry eye syndrome. Optometry. 2009
After this course of therapy,
use your clinical judgment as to
whether to stop the Alrex, continue


042_dg0610_dryeye.indd 45 6/2/10 3:02 PM

Dry Eye
Fluramene: The ‘No Strip’ Stain
From the research laboratories of Donald Korb, O.D., and
associates, comes the first combination diagnostic drug con-
taining fluorescein sodium 1% and lissamine green 0.5%. This
pharmacologic duo is preserved with ascorbic acid.
Fluramene easily enables the enhanced qualification and
quantification of tissue compromise in the setting of any
ocular surface disease, particularly ocular surface dryness.
Fluramene ophthalmic solution comes in an opaque 5mL
multi-use bottle.
For further information, visit

it once or twice a day, or whether tion early on in the treatment with

to prescribe Lotemax to be used the goal of using the least amount
as pulsed therapy. (See “When Pa- of topical eyedrops to maintain
tients Slack Off, Put Pulse-Dosing comfort. (For more information, Ropy discharge seen in a patient with
Into Play,” below.) In our clinical see “The Slippery Facts About Fish moderate dry eye that stains with lis-
experience, patients can use lotepre- Oil,” by Larry Alexander, O.D., samine green.
dnol safely and effectively once Review of Optometry May 2010,
or twice a day indefinitely when p. 35.) we can find no authoritative basis
circumstances indicate. It’s been our clinical experience support for this.)
Remember, every patient is that oral doxycycline more po- Any antibiotic can cause gas-
different, and you will need to tently and more quickly enhances trointestinal upset and, in women,
exercise your clinical wisdom to meibomian gland function than the vaginal candidiasis can be problem-
find the least therapeutic interven- omega-3s, so we often prescribe atic, so discuss these issues proac-
tion required to keep your patient 40mg to 50mg per day for three to tively. Doxycycline can be taken
comfortable. To that end, we four months and then replace the with food, and doing so generally
offer the following perspectives: doxycycline with one of the ome- solves any GI issue.
it is well established that omega-3 ga-3 products for enduring use. (It (Unless there is moderate to
supplementation can be helpful in may be that 20mg of doxycycline advanced posterior blepharitis, we
cardiovascular disease, rheumato- each day of would be effective, but would bypass the doxycycline and
logic disease, and meibomian gland
dysfunction. Indeed, most adults When Patients Slack Off, Put Pulse-Dosing Into Play
might be well served to take such To continue anti-inflammatory therapy for months or years with either loteprednol or
supplementation. cyclosporine seems counterintuitive. Plus, the clinical reality is that human beings are
Regardless, generally poor patients. They don’t come in for follow-up as consistently as they should;
neither the op- they don’t use their eyedrops optimally; they stop taking their omega-3 supplements;
timum amount plugs become extruded; etc.
nor the ratio of So, how do we keep these less-than-compliant patients with dry eye disease relatively
DHA to EPA has comfortable? One thing we can do is have straightforward conversations with these
been established patients regarding the natural history and proper care of their chronic disease. Sharing
in prospective knowledge and concern for their wellbeing can help promote compliance.
clinical trials. Even so, often these patients slack off their therapy and experience “breakthrough”
And, even if such symptoms. In these situations, we often use pulse-dosed Lotemax or Alrex (pulse dos-
data existed, one ing = q.i.d. for one to two weeks) to regain control of the inflammatory symptoms, and
would still have we always encourage them again to consistently use their artificial tears. Our clinical
to treat each pa- experience is that a single 5ml bottle of Lotemax lasts most patients an entire year! This
tient on an indi- excellently demonstrates the cost-effectiveness of Lotemax as compared to other ongoing
vidualized basis. anti-inflammatory therapies. The explanation for this is that pulse-dosing of loteprednol
Our approach is commonly keeps symptoms at bay for several weeks to a few months at a time.
generally to suggest supplementa-


042_dg0610_dryeye.indd 46 6/2/10 3:02 PM

Dry Eye
simply urge the taking of 2,000mg There is some discussion about more beneficial clinical effect than
of fish oil each morning right before using azithromycin (either topically azithromycin in this setting. We
breakfast. The triglyceride formu- or orally) in place of oral doxy- encourage you to have a similar
lations are advocated by some as cycline. Remember, doxycycline conversation with dermatologists in
being more desirable than the ester is being used at sub-antimicrobial your community.
formulations, but there is no firm dosages to reduce meibomian Punctal plugs can be very
consensus on which form is overall gland inflammation and to enhance beneficial once any ocular surface
more beneficial to human health. the fatty acid metabolism within inflammation has been controlled.
As more truly scientific research the meibomian glands. We have To “plug first and steroid later”
evolves, there may well be more ob- consulted several dermatologists can actually exacerbate ocular sur-
jective clarity regarding the benefits and all of them have unequivocally face inflammation initially. In our
of one type of fish oil over another.) stated that doxycycline has a vastly opinion, it is senseless to monkey
around with dissolvable collagen
New Insights Into Punctal Plugs plugs “to see if the patient is helped
Have you noticed that many patients who benefitted from punctal occlusion can return temporarily.”
after several months and still be doing well, yet the plug(s) has vanished? If punctal We believe the need, or lack
occlusion initially helped patient symptoms, then why would the patient not return to thereof, of punctal occlusion should
baseline symptomatology when the plug(s) was absent? be profoundly evident to a seasoned
The answer to this puzzle is found in the December 2008 American Journal of clinician. “Just do it”, if in your
Ophthalmology: “Stenosis of the punctum and proximal canaliculus are reported to be a judgment the patient can benefit.
frequent observation after spontaneous loss of punctal plugs … While stenosis is com- Whether you chose to plug the
monly found at the punctum, it is more commonly found within the vertical portion of the more symptomatic eye as a trial (to
canaliculus … The abrasion of the canalicular inner wall caused by the plug is theorized see how much relief is obtained), or
to be the main cause of stenosis.” plug both lower puncta simultane-
Another theory is that “Mechanical stress on the mucosa might lead to a mild chronic ously is a judgment call.
inflammation, causing a stenosis.” We always employ “punctal”
The authors add, “It appears that plug size is not a major determinant of stenosis, but plugs, and never use intracana-
larger plugs are thought to be more likely to do so than smaller plugs.” One might won- licular devices. This is mainly so
der: how long must the plug reside within the punctocanalicular tissues to evoke such an we—and our patients—can moni-
unplanned iatrogenic stenotic response? Interestingly, such stenosis “seemed to develop tor whether the plug is still there
independently from the time of insertion. In summary, it seems that the stenosis acts like or not. (See “New Insights Into
an occlusion with a punctal plug.” Punctal Plugs,” left, on why replug-
We found this to be a particularly enlightening article that provides a rational anatomic ging is often unnecessary should the
explanation for the enduring relief from dry eye symptoms, even when the plug is long initial plug become extruded and
gone. lost.)
Boldin I, Klein A, Haller-Schober EM, Horwath-Winter J. Long-term follow-up of punctal and proximal canalicular stenoses
after silicone punctal plug treatment in dry eye patients. Am J Ophthalmol. 2008 Dec;146(6):968-72.e1. Epub 2008 Aug 23. Dry eye disease can be subdued
in almost all patients with use of a
multifaceted approach. Soothe XP,
loteprednol, and omega-3 supple-
mentation, with or without punctal
plugs, can be immensely helpful in
providing symptomatic control of
dry eye disease. ■
1. Foulks GN. The correlation between the tear film lipid
layer and dry eye disease. Surv Ophthalmol. 2007 Jul-
Aug;52(4):369-74. Review.
2. Lemp MA. Advances in understanding and managing dry
eye disease. Am J Ophthalmol. 2008 Sep;146(3):350-356.
Epub 2008 Jul 2. Review.
3. Management and therapy of dry eye disease: report of the
Punctal plugs are an underutilized modality in the care of patients with
Management and Therapy Subcommittee of the International
insufficient tear volume. Patients may benefit even after the plug is long gone. Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):171.


042_dg0610_dryeye.indd 47 6/2/10 3:03 PM

Dry Eye
Medical Therapy for Superior Limbic Keratoconjunctivitis (SLK)
SLK is an uncommon, chronic, remitting and exacerbating disor- We generally instill a drop or two of NSAID to ameliorate any
der affecting the superior limbus and corneolimbus. It is bilateral, discomfort following this procedure. Have the patient instill Soothe
asymmetric and can be associated with dry eyes and dysthyroid- XP q2h for two days, and p.r.n. thereafter.
ism. Like chlamydial conjunctivitis, SLK is often missed—or misdi- This pharmacy-formulated ophthalmic solution needs to be
agnosed—initially. It is usually the second, third or fourth physician refrigerated for the duration of its 30-day shelf-life. To be sensitive
who finally makes the diagnosis in both conditions. This does not to cost-efficient therapy, we have the patient return in one month
compliment either optometrists or ophthalmologists. to repeat the therapeutic process a second time prior to discarding
Most SLK patients present with the chief complaint of “irritated” the solution.
eyes. The condition can cause considerable misery, sometimes This therapeutic approach often gives several weeks (occasion-
to the point of even causing the sufferer to miss days from work. ally months) of symptomatic relief. The duration of relief can be
The typical patient is a middle-aged otherwise healthy woman, influenced by the remission/exacerbation cycle, and by the overall
as women are more commonly afflicted than men. Because these stage of the disease process—i.e., whether the symptoms are of
patients often have concurrent dry eye syndrome, they are com- recent onset, or the patient has carried this diagnosis for a decade
monly diagnosed and treated for such, with minimal resolution of or so.
symptoms. Since SLK runs a 10 to 20-year course of spontaneous These AgNO3 treatments can safely be repeated numerous
exacerbations and remissions (like Thygeson’s SPK), the periods of times; however, if the relief from treatment is minimal or if the
remission can lure the naïve clinician into thinking the artificial tear temporal period of relief is short, then it may be in the patient’s
therapy is responsible. best interest to have a corneal/external disease consultation.
Conjunctival resection is the time-honored definitive procedure.
Diagnosis However, liquid nitrogen cryotherapy is a simple, in-office topical
The diagnosis is extremely straightforward, however, when one procedure that might be helpful.1
simply thinks to look for the classic injection pattern at the superior 1. Fraunfelder FW. Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis. Am
juxtalimbal bulbar conjunctiva. If any doubt remains, simply stain J Ophthalmol. 2009 Feb;147(2):234-238
the eyes—the involved tissues will stain substantially.

There is no FDA-approved medicine for SLK. However,
the off-label use of 0.5% silver nitrate ophthalmic solution
is a time-honored therapeutic approach that can be very
helpful in most cases. Any hospital-grade compounding
pharmacy can readily formulate a sterile ophthalmic solu-
tion. We usually write a prescription for exactly what we
want, then have the patient take it to a pharmacy known
to do specialty compounding. We see the patient back
in the office in a few days with the 0.5% AgNO3 in hand.
Here’s how the procedure goes: Classic presentation of superior limbal keratoconjunctivitis.
• Instill a topical anesthetic O.U.
• Dip a sterile cotton swab into the solution, or drop
several drops onto the cotton swab, to saturate it.
• Use a brisk wrist action to sling off any excess (drip-
py) solution (away from the patient, of course).
• Evert the lid of one eye and, with the patient looking
down, roll (as with a paint roller) the cotton swab back
and forth over the tarsal conjunctiva for about 20 sec-
onds. Then do the same to the affected superior bulbar
conjunctival tissues for about 20 seconds.
• Rinse these tissues with a stream of sterile eye
irrigating solution sufficient to dilute and wash away any
excess AgNO3, then return the upper eyelid to its normal Note the perfectly normal inferior limbal tissues in the same patient in
position. up-gaze.
• Repeat for the fellow eye.


042_dg0610_dryeye.indd 48 6/2/10 3:03 PM

Dear Doctor of Optometry: please feel free to remove this sheet, copy it to your letterhead and
distribute it to your dry eye & contact lens-wearing patients to whom you recommend Soothe XP.

Soothe XP
(available over-the-counter)

Your doctor has recommended a product known as Soothe XP

to help you with your dry, burning, sandy, gritty-feeling eyes.

Soothe XP is a premium quality, state-of-the-art “artificial tear”

that comes in a 15mL bottle. It is a special “oily emulsion”
type of eyedrop and not just another watery, re-wetting tear
product. Because of its special mineral oil formulation, it will
cause foggy, cloudy vision for 20 to 30 seconds each time you
place the drops in your eyes. After a few seconds, your vision
will completely clear and you should have 1 to 4 hours of relief
from your symptoms.

Soothe XP is completely safe and therefore you can put these

drops in your eyes as often as you would like to help keep
them comfortable. Most patients get good relief using Soothe
XP 2 to 4 times a day. Be sure to shake the bottle once or twice
before each use. Note that there is a similar sounding product
known simply as Soothe. It is NOT the same as Soothe XP,
so do not be confused.

For contact lens wearers: Soothe XP is an excellent

lubricating and re-wetting eye drop for both soft and rigid
contacts. A statement on the side of the box reads, “remove
contact lenses before use;” however, this statement is not
accurate. It is not necessary to remove your contacts before
using Soothe XP. In fact, this product was specifically
formulated for use with contact lenses and patients are
routinely using Soothe XP successfully with their contacts to
enhance comfort and prolong wearing time.

Soothe XP is equally effective for patients who wear contact

lenses and for those who do not. Because it can be safely
used by almost anyone, it was not tested as a “for contact lens
use only” product, and therefore is not FDA-approved as such.

ibc_dg0610_Soothe.indd 49 6/2/10 12:57 PM

Drugguide_cover.indd 2 6/2/10 12:48 PM