2016 CLINICAL GUIDE TO
`
`OPHTHALMIC
`DR u Gs 201 ~di~~~rsory
`
`A SU PPLEMENT TO
`
`R~~
`
`Supported by an unrestricted grant from
`Bausch+ Lomb
`
`Randall Thomas, OD, MPH
`
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`

`

`FROM THE AUTHORS
`
`DEAR OPTOMETRIC COLLEAGUES:
`
`Welcome to the 2016 Clinical Guide to Ophthalmic Drugs-the 20th An(cid:173)
`niversary Edition of this publication.
`We are grateful that so many of you who have expressed your appreciation
`for this guide over the years. Our exclusive focus in this annual publication
`is to help practicing optometrists provide the highest level of care to their
`patients. Caring for one another is a high calling, and every effort should
`be made to achieve this laudable goal. Our hope is that the knowledge you
`glean from these contents helps move you closer to perfection in patient care.
`Thank you for taking this journey along with us over these past 20 years.
`Notably, 2016 is projected to bring us a newer glaucoma drug and a new
`drug to help treat dry eye disease. In addition to sharing with you informa(cid:173)
`tion on these new drugs and their use, we also review how and when to use
`tried-and-true ophthalmic medications, many of which are now available
`generically.
`We are especially honored this year to have a guest author, Kathleen F.
`Elliott, OD. The 2014 Oklahoma Optometric Physician of the year and ABO
`Board Certified optometrist brings us up to date on clinical aspects of pediat(cid:173)
`ric eye care. She can be reached at drelliottl 11 l@yahoo.com.
`We want to sincerely thank the awesome team at Review of Optometry
`for painstakingly working with us to publish the Drug Guide over the past
`two decades. Obviously, it is expensive to produce a work of this magnitude
`without corporate support. Without the enduring and consistent educational
`grant support of Bausch+ Lomb (now a Valeant company) each and every
`year, this guide would not be possible. Life is a team sport, and we are, and
`have been, honored to work with both Review of Optometry and Bausch +
`Lomb in this endeavor toward the enhancement of patient care.
`Having the high honor of seeing patients full-time for a combined 70-plus
`years now, we have accumulated considerable experience in patient care.
`We diligently and carefully peruse several journals every month to assure
`ourselves that we remain on the cutting edge of knowledge, but this guide
`remains a clinically practical work. Thus, if a statement is made herein that
`is not referenced, it is to be understood that the statement is based on our ex(cid:173)
`tensive clinical experience. Our hope is that, through reading this Drug Guide
`and taking to heart its contents, you will be better able to provide the highest
`level of care to your patients.
`
`Sincerely,
`
`~:::::.:~;;;:!·.:~
`
`-~ ~;;-dall Thomas, OD, ~ -PH
`
`Ron Melton, OD
`
`Supported by an
`unrestricted grant from
`Bausch+ Lomb
`
`CONTENTS
`
`Allergy Drugs ............................... 3
`
`Antibiotic Agents ..................... 6
`
`Dry Eye Therapy ..................... 13
`
`Nonsteroidal Drugs ............. 20
`
`Corticosteroid Use ............... .26
`
`Pediatric Pearls ........................ 33
`
`Glaucoma Care ....................... 36
`
`Shingles Therapy .................. 44
`
`Clinical Insights ....................... 46
`
`Disclosure: Ors. Melton and Thomas are consultants to, but have no financial
`interests in, the following companies: Bausch+ Lomb/Valeant and lcare.
`
`A PEER-REVIEWED
`SUPPLEMENT
`
`Note: The authors present unapproved and "off-label" uses of specific drugs in this guide.
`
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`

`

`)> DRUGS
`r
`r
`m
`::a
`G'\
`-<
`ALLERGY TREATMENT:
`QUELLING THE ITCH
`' ' D octor, my eyes just
`
`Though the
`condition may
`be the most
`harmless one
`we see, our
`ocular allergy
`patients are
`among our
`most grateful.
`
`itch and burn all
`the time," the pa-
`tient says. How
`many hundreds of
`times have we heard this lament?
`However,
`this common complaint
`brings us front and center to the prover(cid:173)
`bial fork in the road. T he first question is
`basic. Ask the patient, "So, think about
`this: Is the burning or the itching your
`main symptom?" Most patients can give
`a clear answer to this fundamental ques(cid:173)
`tion.
`For the few patients who feel the symp(cid:173)
`toms of burning and itching are about
`equal, or who can't decide which symp(cid:173)
`tom is most bothersome, treatment with
`a topical corticosteroid will usually quell
`both complaints. Don't forget our time(cid:173)
`honored advice in these cases: "When in
`doubt, use a steroid."
`If itching is the predominant symptom,
`our approach to drug selection takes one
`of the following tv,o routes.
`
`A woman experiencing a severe ocular
`allergic reaction.
`
`SYMPTOMS ONLY
`If there are minimal associated signs of
`allergy- such as chemosis, conjunctiva!
`injection and/or eyelid edema- an anti-
`
`.,OC,0:,Y..,...
`
`oPTIVAR
`
`1BEPREVE
`(~ooilate
`opiljialri:tolulill)\5'
`..._____.,
`
`REVIEW OF OPTOMETRY MAY 15, 201 6
`
`3
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`ALLERGY DRUGS
`
`OCULAR ALLERGY MEDICINES
`
`BRAND NAME GENERIC NAME
`Acute Care Products
`ketorolac tromethamine 0.4%
`Acular LS
`Alaway (OTC)
`ketotifen fumarate 0.025%
`Alrex
`loteprednol etabonate 0.2%
`Bepreve
`bepotastine besilate 1.5%
`Elestat
`epinastine HCI 0.05%
`Emadine
`emedastine difumarate 0.05%
`Lastacaft
`alcaftadine 0.25%
`Optivar
`azelastine hydrochloride 0.05%
`Pataday
`olopatadine hydrochloride 0.2%
`Patanol
`olopatadine hydrochloride 0.1%
`Pazeo
`olopatadine hydrochloride 0.7%
`Zaditor (OTC)
`ketotifen fumarate 0.025%
`
`Chronic Care Products
`Alocril
`nedocromil sodium 2%
`Alomide
`lodoxamide tromethamine 0.1%
`Crolom
`cromolyn sodium 4%
`
`MANUFACTURER
`
`PEDIATRIC USE BOTTLE SIZE(S) DOSING
`
`Allergan, and generic
`Bausch + Lomb
`Bausch + Lomb
`Bausch + Lomb
`Allergan, and generic
`Alcon
`Allergan, and generic
`Meda, and generic
`Alcon
`Alcon, and generic
`Alcon
`Alcon, and generic
`
`3 years
`3 years
`12 years
`2 years
`3 years
`3 years
`2 years
`3 years
`3 years
`3 years
`2 years
`3 years
`
`Allergan, and generic
`Alcon
`Bausch + Lomb,
`and generic
`
`3 years
`2 years
`4 years
`
`5ml, 10ml
`10ml
`5ml, 10ml
`5ml, 10ml
`5ml
`5ml
`3ml
`6ml
`2.5ml
`5ml
`2.5ml
`5ml
`
`5ml
`10ml
`10ml
`
`QID
`BID
`QID
`BID
`BID
`QID
`OD
`BID
`OD
`BID
`OD
`BID
`
`BID
`QID
`QID
`
`histamine/mast cell stabilizer is an
`excellent clinical approach. Within
`this class, there are six drugs from
`which to choose:
`• Alcaftadine (Lastacaft, Allergan)
`• A.zelastine (Optivar, Meda Phar(cid:173)
`maceuticals; generic available)
`• Bepotastine (Bepreve, Bausch +
`Lomb)
`• Epinastine (Elestat, Allergan;
`generic available)
`• Ketotifen (Zaditor, Novartis;
`many generics available. This
`drop is OTC.)
`
`• Olopatadine (Patanol/Pataday/
`Pazeo, Alcon)
`Notv,ithstanding fine differences,
`all the antihistamine subtype 1 re(cid:173)
`ceptor blockers nicely suppress ocu(cid:173)
`lar itching. Most are dosed initially
`BID (except Pataday, Pazeo and
`Lastacaft, which are dosed once dai(cid:173)
`ly). After tv,o weeks at BID, ask the
`patient to try to reduce the drop to
`once-daily maintenance therapy. In
`our experience, once symptomatic
`itching has been brought under con(cid:173)
`trol, it takes less pharmacological
`intervention
`to
`maintain. How(cid:173)
`ever, some pa(cid:173)
`tients may have
`to continue BID
`therapy.
`the
`Perhaps
`for
`best news
`the consumer is
`the loss of patent
`protection
`for
`Zaditor.
`Since
`2007, ketotifen
`
`has been available generically and
`over the counter. T here are several
`"brand name" OT C ketotifen prep(cid:173)
`arations, such as Alaway (Bausch
`+ Lomb), among others. All come
`in 5ml bottles except for Alaway,
`which comes in a 10ml bottle. In(cid:173)
`terestingly, our casual observations
`in a variety of pharmacies reveal
`that the cost of the 10ml Alaway is
`very near (and occasionally cheaper
`than) the price of its 5ml competi(cid:173)
`tors. Thus, OT C Alaway is the most
`cost-effective way to suppress ocular
`itch.
`When a prescription medication
`is preferred, perhaps a 10ml bottle
`of Bepreve (using a standard copay)
`would be of greatest value to the pa(cid:173)
`tient, especially with insurance cov(cid:173)
`erage or coupons.
`
`SYMPTOMS PLUS SIGNS
`T he other route of allergy presen(cid:173)
`tation is represented by the patient
`who presents with predominant
`itching along with one or more
`
`I
`
`"1uscf'HI'~
`
`Alaway .. 11
`
`~·
`I-
`~
`
`4 REVIEW OF OPTOMETRY MAY 15, 2016
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`ISOLATE PATIENT
`OCULAR ALLERGIES
`IN YOUR OFFICE
`A company called Doctor's
`Allergy Formula has developed
`a point-of-care diagnostic test to
`determine specific environmental
`allergen triggers for ocular allergy.
`It is a simple, noninvasive (no
`shots or needles), in-office skin
`test that tests for 60 regionally
`specific allergens. Testing can be
`conducted by the doctor or an
`assistant, and results are available
`in about 15 minutes.
`However, as in contact lens
`care, nothing is perfect. There is
`the highly remote possibility of
`an anaphylactic reaction, so hav(cid:173)
`ing an EpiPen in the office is wise.
`Having diphenhydramine available
`is also advised.
`That being said, this simple
`test is highly effective in helping
`determine what is causing the
`patient's ocular allergy reaction.
`We encourage our optometric
`colleagues to carefully investigate
`this relatively new diagnostic
`technology via the website www.
`drsallergyfonnula.com (under
`construction as of this writing).
`The company was acquired by
`Bausch + Lomb in October 2015,
`and the diagnostic test is being
`incorporated into the pharma
`division's offerings.
`
`concurrent signs, such as conjuncti(cid:173)
`va) redness, chemosis and/or eyelid
`edema. For this particular subset of
`patients, we feel a topical cortico(cid:173)
`steroid such as Alrex {loteprednol
`0.2%, Bausch + Lomb), off-label
`use of Lotemax gel {loteprednol
`0.5%, Bausch + Lomb) or FM L
`ophthalmic
`suspension
`(fluoro(cid:173)
`metholone 0. 1 %, Allergan) is more
`appropriate treatment.
`T he only other decision involves
`the frequency of instillation; we
`
`typically prescribe a steroid Q2H
`for two days, then QID for one
`week, followed by BID for one
`more week. Once the inflamma(cid:173)
`tory signs are controlled, consider
`switching the patient to an anti(cid:173)
`histamine/mast cell stabilizer for
`ongoing symptom control. Long(cid:173)
`term treatment with Alrex once or
`twice daily as maintenance therapy
`can be done if a steroid is what best
`controls their disease.
`According to a conversation we
`had with Mark Abelson, MD, a
`world-renowned ocular allergist at
`Harvard Medical School, there is
`little clinical use for pure mast cell
`stabilizing drugs. He says that the
`antihistamine/mast cell stabilizer
`drugs more effectively stabilize the
`mast cell membranes than stand(cid:173)
`alone mast cell stabilizers such as
`pemirolast (Alamast), nedocromil
`(Alocril) or cromolyn sodium (ge(cid:173)
`neric). Based on this expert opinion,
`we no longer prescribe these pure
`mast cell stabilizers.
`Remember, allergy is an expres-
`
`sion of inflammation. Cold com(cid:173)
`presses can be helpful in most all oc(cid:173)
`ular surface inflammatory diseases.
`In contradistinction, infectious pro(cid:173)
`cesses are commonly helped by the
`application of warm soaks.
`In summary, if itching is not the
`primary symptom, be sure to con(cid:173)
`sider dry eye as the foundational
`condition, and treat accordingly.
`If itching is primarily expressed,
`determine if it is an isolated symp(cid:173)
`tom or associated with concurrent
`inflammatory signs, and then treat
`accordingly. Remember:
`Symptoms only: Use an antihista(cid:173)
`mine/mast cell stabilizer
`Symptoms with signs: Use a
`steroid such as Lotemax gel off-label,
`Alrexor FML
`There is no rule in the rulebook that
`says you can't have two problems at
`once. Since dry eye is epidemic, identi(cid:173)
`fy and manage this disease whether or
`not it is concomitant with allergic eye
`disease. If, however, the main symp(cid:173)
`tom is burning, then a thorough dry
`eye evaluation is in order. ■
`
`REVIEW OF OPTOMETRY MAY 15, 201 6
`
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`11 I l I'--,
`
`)> -
`z
`
`Success with
`antibiotics
`may have
`more to do
`with frequency
`of instillation
`than selection
`of the drug, so
`it's important
`to know
`how often
`to prescribe
`them.
`
`-I -UJ -0
`-I -n
`CHOOSING AND USING
`ANTIBIOTICS WISELY
`T he medical literature bemoans
`
`the egregious overprescrib(cid:173)
`ing of systemic antibiotics
`and begs physicians and other
`health care providers to use
`great restraint in such prescribing.
`The same admonition may be applied
`to the optometric profession regarding
`topical antibiotics, but for a different rea(cid:173)
`son. T he concern with regard to systemic
`antibiotics centers on the prevention of re(cid:173)
`sistance. But the concern with optometric
`use of topical antibiotics is inaccurate di(cid:173)
`agnoses because the vast majority of acute
`red eyes are inflammatory, not infectious
`(with the exception of pediatric patients).
`Generally speaking, infectious diseases
`produce a discharge whereas inflamma(cid:173)
`tory diseases do not. T his should quickly
`separate the sheep from the goats. We
`opine that such overprescribing is t\vo(cid:173)
`fold: lack of a firm diagnosis and a seem(cid:173)
`ingly unrelenting reluctance to prescribe
`steroids.
`We have seen hundreds of patients who
`were treated elsewhere with topical anti(cid:173)
`biotics by a wide variety of practitioners
`and who were not getting better. T hey
`presented to us as a "second-opinion" vis(cid:173)
`it where we recognized the conditions to
`be inflammatory, prescribed steroids and
`the patients were uniformly better within
`days. It just goes to show: Accurate diag(cid:173)
`nosis and proper therapeutic intervention
`are great practice builders. (See "The Ef(cid:173)
`ficient Red Eye Evaluation," page 11.)
`Thankfully, most of the commonly
`used antibiotic eye drops are broad spec-
`
`Mucupurulent discharge typical of bacterial
`conjunctivitis.
`
`trum, and are generally effective against
`many common bacterial pathogens. We
`have found frequency of administration(cid:173)
`rather than particular drug selection- to
`be the key determining factor of clinical
`outcome. Since most (but not all) of the
`currently approved topical antibiotics
`possess reasonable antimicrobial abilities,
`the more frequent the administration of
`these drops, the greater the clinical result.
`However, the frequency of eye drop ad(cid:173)
`ministration depends almost exclusively
`on the severity of the infectious expres(cid:173)
`sion.
`When it comes to ocular infections,
`there are two main routes of antibiotic
`administration: topical and oral. All topi(cid:173)
`cal antibiotic drops are solutions, except
`besifloxacin, which is a suspension. Oral
`antibiotics are most commonly prescribed
`as a tablet, capsule or liquid (the latter
`used mostly in children).
`
`8 REVIEW OF OPTOMETRY MAY 15, 2016
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`

`In our practices, we more common(cid:173)
`ly prescribe oral antibiotics than topi(cid:173)
`cal ones simply because we encounter
`more patients needing oral antibiotic
`therapy, such as those with meibo(cid:173)
`mian gland disease (doxycycline), ro(cid:173)
`sacea blepharitis (doxycycline) and in(cid:173)
`ternal hordeola (cephalexin [Keflex]).
`On those relatively uncommon acute
`bacterial conjunctivitis cases, we typi(cid:173)
`cally prescribe generic Polytrim (trim(cid:173)
`ethoprim with polymyxin B), tobra(cid:173)
`mycin or Besivance (besifloxacin).
`Now, let's take a more in-depth
`look at this class of medicines. There
`are many antibiotics; however, only a
`few enjoy-or should enjoy- wide(cid:173)
`spread use.
`
`BACITRACIN
`We find this drug to be superbly
`bactericidal against most all gram(cid:173)
`positive bacterial pathogens, and can
`be used to help treat staphylococcal
`blepharitis when applied to the eyelids
`
`TOPICAL ANTIBIOTIC DRUGS
`BRAND NAME
`GENERIC NAME
`Fluoroquinolones
`Besivance
`Ciloxan
`Moxeza
`Ocuflox
`Vigamox
`Zymaxid
`
`besifloxacin 0.6%
`ciprofloxacin 0.3%
`moxifloxacin 0.5%
`ofloxacin 0.3%
`moxifloxacin 0.5%
`gatifloxacin 0.5%
`
`Aminoglycosides
`Toorex
`Garamycin
`
`tooramycin 0.3%
`gentamicin 0.3%
`
`==---
`
`111.JJ,<W.. 91:nl
`
`flnlll!"'
`
`following eyelid scrubs and/or treat(cid:173)
`ments at bedtime for a week or tv,o. It
`can also be used at bedtime to provide
`overnight coverage for moderate to
`severe ulcerative keratitis. T here are
`two key limitations to its clinical use:
`It is only available in ointment form,
`and it has little to no activity against
`gram-negative bacteria.
`On those rare occasions when we
`encounter a true bacterial corneal
`infection, we prescribe besifloxacin
`with Polysporin ophthalmic oint(cid:173)
`ment, which contains bacitracin and
`polymyxin B, since the polymyxin B
`is bactericidal against gram-negative
`pathogens.
`
`NEOSPORIN
`While the previous combination of
`besifloxacin and Polysporin pro(cid:173)
`vides a broad spectrum of antibacte(cid:173)
`rial coverage, perhaps an even better
`choice may be the triple-antibiotic of
`neomycin, bacitracin and polymyxin
`B, commonly known as its original
`brand name: Neosporin.
`Interestingly, both bacitracin and
`Polysporin are available only as oint(cid:173)
`ments, whereas Neosporin is avail(cid:173)
`able both as an ophthalmic solution
`and an ointment, as the solution con(cid:173)
`tains gramicidin, not bacitracin. We
`never use the Neosporin in eye drop
`form, as we prefer generic Polytrim
`
`MANUFACTURER
`
`PREPARATION PEDIATRIC USE BOTTLE/ TUBE
`
`Bausch + Lomb
`suspension
`Alcon, and generic
`sol./oint.
`solution
`Alcon
`Allergan, and generic solution
`Alcon
`solution
`Allergan, and generic solution
`
`5ml
`> 1 yr.
`?. 1 yr./?. 2 yrs. 5ml, 10ml/3.5g
`3ml
`?. 4 mos.
`5ml, 10ml
`?. 1 yr.
`> 1 yr.
`3ml
`2.5ml
`?. 1 yr.
`
`solj oint.
`Alcon, ana generic
`Perrigo, and generic sol./oint.
`
`?. 2 mos.
`N/A
`
`Sml/3.Sg
`Sml/3.Sg
`
`Polymyxin B Combinations
`polymyxin B1trimethoprim Allergan, and generic solution
`Polytrim
`Polysporin
`polymyxin B/bacitracin
`generic
`ointment
`Neosporin
`polymyxin B1neomyciri/
`generic
`solution
`gramicidin
`polymyxin B/ neomycin/
`bacitracin
`
`ointment
`
`generic
`
`> 2 mos.
`N/A
`N1A
`
`NTA
`
`Other Antibiotics
`AzaSite
`llotycin
`Bacitracin
`
`azitliromycin 1%
`erythromycin 0.5%
`bacitracin soou:;g
`
`solution
`Al<orn
`Perrigo, and generic ointment
`Perrigo
`ointment
`
`?. 1 yr.
`?. 2 mos.
`N1A
`
`10ml
`3.Sg
`10ml
`
`3.Sg
`
`2.5ml
`3.Sg
`3.Sg
`
`REVIEW OF OPTOMETRY MAY 15, 2016
`
`7
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`ANTIBIOTIC AGENTS
`
`(which contains generic trimethoprim
`with polymyxin B), tobramycin or Be(cid:173)
`sivance, depending on the nature and
`severity of the infectious condition;
`but we embrace Neosporin ointment
`without hesitation for those rare oc(cid:173)
`casions when overnight antibiosis is
`deemed necessary to enhance a clini(cid:173)
`cal cure.
`As we have made clear, neomycin is
`a wonderful drug, but can on rare oc(cid:173)
`casions cause an annoying type N de(cid:173)
`layed hypersensitivity reaction. Given
`that we have three alternatives (gener(cid:173)
`ic Polytrim, generic tobramycin and
`Besivance) that are much less prone to
`causing any sort of allergic response,
`we prefer to follow this simpler path
`for most patients most of the time.
`
`MAC ROLi DES
`T he macrolide antibiotics (i.e., eryth(cid:173)
`romycin, azithromycin and clarithro(cid:173)
`mycin) are widely used systemically
`but have limited use topically.
`Regarding erythromycin, many
`bacteria are increasingly resistant. In
`like manner, topical azithromycin has
`been shown to have limited antibiotic
`efficacy, and the FDA has stated that
`
`it has little or no clinically significant
`anti-inflammatory properties; there(cid:173)
`fore, its use in clinical patient care is
`quite limited.
`
`BESIFLOXACIN
`Besifloxacin is a highly unique dual(cid:173)
`halogenated quinolone that is not
`used systemically. Clinical studies
`(see "New Benchmarks on Antibi(cid:173)
`otic Resistance," page 10) show it to
`have low MIC90 values, very similar
`to those of vancomycin, the gold stan(cid:173)
`dard in treating known gram-positive
`pathogens. (Vancomycin is not com(cid:173)
`mercially available as an ophthalmic
`formulation and has to be prepared
`by a compounding pharmacy.) Be(cid:173)
`sifloxacin also has strong coverage
`against gram-negative organisms, in(cid:173)
`cluding Pseudomonas. This is true of
`the aminoglycosides as well.
`Besifloxacin is a 0.6% ophthalmic
`suspension (the rest are solutions),
`and it needs to be shaken before each
`instillation. It is a thick eye drop, so
`the patient should not blink for a few
`seconds after instillation to allow the
`drop to spread out across the ocular
`surface and remain in the eye.
`
`NEOMYCIN
`T raditional wisdom with regard to
`this excellent antibiotic focuses more
`on the negatives than the positives.
`Yes, neomycin does possess the abil(cid:173)
`ity to cause an annoying, type N de(cid:173)
`layed hypersensitivity on rare occa(cid:173)
`sions, but let's not throw out the baby
`with the bathwater.
`Neomycin itself is broad-spectrum,
`but it does not cover Pseudomonas,
`which is why it is always packaged
`with polymyxin B or another antibiot(cid:173)
`ic to cover gram-negative organisms.
`In our experience, type N delayed
`hypersensitivity dermatoconjunctivo(cid:173)
`keratitis reactions are exceedingly
`rare when the neomycin combination
`is used for no more than a week.
`T he exception is the rare patient
`who has been previously exposed to
`neomycin and already has immuno(cid:173)
`sensitivity. These patients can react
`to neomycin in just a day or t\vo,
`which may also be the result of a
`type 1 hypersensitivity to initial ex(cid:173)
`posure. Patient management is simply
`to stop the medication. Again, these
`are non-serious, annoying, superfi(cid:173)
`cial responses. In our many years of
`
`, -~ =
`~~ •5
`1==-=
`
`• ._
`
`Sil
`
`-- .
`~---., :;
`"!'..l.!'t
`
`t,
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`•.:-::':i.:· ""'
`
`8 REVIEW OF OPTOMETRY MAY 15, 2016
`
`Eye Therapies Exhibit 2050, 8 of 52
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`THERAPEUTIC OPTIONS FOR CORNEAL ULCERS
`Thankfully, infectious corneal ulcers are very rare, but when they do occur, they
`are treated aggressively with topical antibiotic eye drops. For perspective, leu(cid:173)
`kocytic infiltrates also create little white lesions in the anterior stroma that may
`have a relatively small epithelial defect over the center of the white infiltrate.
`These infiltrates are often naively and incorrectly referred to as "ulcers," when in
`fact, they possess no infectious potential. Rather, these are inflammatory expres(cid:173)
`sions-almost always occurring at or near the limbus-and treatment with a ste(cid:173)
`roid (a combination drug such as Zylet, generic Maxitrol or generic TobraDex) is
`required to suppress this pathophysiological process.
`Infectious ulcers come in two varieties: large, central ulcers; and small-to(cid:173)
`large, noncentral ulcers. Central ulcers are most commonly treated with fortified
`tobramycin (for gram-negative coverage) and vancomycin (for gram-positive
`coverage). Most eye reference texts, such as the Wills Eye Manual, can guide you and the compounding pharmacy on how
`to make these preparations. Generally speaking, these medicines are used about every 30 minutes for the first few hours,
`then hourly while awake until obvious healing is occurring; every two hours for another few days; and finally, four times a
`day for a few more days. Rather than have the patients instill these drops around the clock, we prefer the use of Neosporin
`ophthalmic ointment at bedtime. Once good healing has occurred, the nocturnal ointment can be discontinued. Some
`patients are allergic to Neosporin, so alternatives exist (e.g., polysporin and Ciloxan, or even TobraDex ointment).
`For noncentral ulcers, we use Besivance (besifloxacin 0.6% ophthalmic suspension) every 30 minutes for a few
`hours, then hourly, etc., as outlined in the preceding paragraph concerning use of the fortified eye drops. Neosporin (or
`Polysporin) or TobraDex ointment at bedtime is also used as above.
`We always cycloplege these patients, as they invariably will have a secondary anterior uveitis. Either atropine 1% or
`homatropine 5% is typically used to accomplish this purpose. The standard dosage is cycloplegia two to four times daily,
`depending upon the severity of the clinical condition.
`
`CONQUERING BLEPHARITIS
`Chronic anterior eyelid margin disease is most commonly caused by chronic, low-grade infection of Staphylococcus aureus
`and Staphylococcus epidermidis bacteria. These bacteria produce exotoxins, creating secondary inflammation to the adja(cid:173)
`cent eyelid marginal tissues. (This is distinct from me bomian gland disease, which has a wholly different pathophysiology.)
`Occasionally, these exotoxins can cause inferior corneal epithelial compromise.
`Understanding the cascade of tissue compromise resulting from unchecked Staph. populations residing on the ante(cid:173)
`rior eyelid tissues perfectly provides the rationale for using a good antibiotic/corticosteroid combination drug as the
`treatment of choice for symptomatic blepharitis. No other drug or drug class even approximates the efficacy of such
`therapeutic intervention.
`Any of the available combination drugs would work well short term (less than two weeks), but given that blepharitis is
`a chronic, recurrent disease, the drug we find best suited for treating blepharitis is a combination of tobramycin (excellent
`anti-Staph. action) with loteprednol (excellent, safe, anti-inflammatory action) known by the popular brand name Zylet.
`Initiate treatment with Zylet four times daily for two weeks, depending upon the severity of the clinical disease, then just
`pulse dose four times a day for a week if or when breakthrough symptoms occur. Such pulse dosing is an effective and
`"steroid-sparing" therapeutic approach and one that we embrace for almost any chronic, recurrent ocular surface disease.
`The combination drugs TobraDex and Maxitrol are both generic and relatively inexpensive, but contain dexamethasone,
`which limits their usefulness beyond a couple of weeks. One would rarely ever employ dexamethasone for a chronic
`condition because of its propensity to increase intraocular pressure. All three of these drugs are suspensions and, as such,
`need to be shaken well.
`
`However, blepharitis is not treated exclusively with any eye drop. Concurrent
`use of eyelid scrubs is an essential component to not only help control the
`infectious/ inflammatory disease, but as ongoing hygiene to maintain eyelid
`health. Avenova (hypochlorous acid 0.01%, NovaBay Pharmaceuticals) eyelid
`and eyelash cleanser has become quite popular, and does seem to help main(cid:173)
`tain healthy tissues in our patients. Further, with diminution of Staph. popula(cid:173)
`tions, there is a decreased risk of secondary styes and internal hordeola.
`In summary, the combined use of an effective, safe antibiotic/steroid and
`meticulous eyelid hygiene perfectly embodies rational care for patients with
`anterior eyelid margin disease.
`
`REVIEW OF OPTOMETR Y MAY 15, 2016
`
`9
`
`Eye Therapies Exhibit 2050, 9 of 52
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`ANTIBIOTIC 1\C ·f ~ l S
`
`clinical practice, we have seen only
`half a dozen such events, mostly with
`neomycin exposure of greater than a
`week, and often prescribed by prima(cid:173)
`ry care practitioners.
`When neomycin is packaged (along
`with polymyxin B) with a steroid,
`such as generic Maxitrol, whatever
`expression of a hypersensitivity reac(cid:173)
`tion that may be occurring typically
`remains subthreshold, or subdued,
`courtesy of the concurrent corticoste(cid:173)
`roid suppression.
`The aminoglycosides, used systemi(cid:173)
`cally, can cause ototoxicity. For this
`
`reason they are rarely, if ever, used
`systemically. Any drug actively or pas(cid:173)
`sively reserved for only topical use is
`relatively protected from resistance,
`thus enabling it to be a powerful che(cid:173)
`motherapeutic agent for many decades.
`For example, bacitracin was brought
`to market in the 1940s and remains a
`superb, exclusively gram-positive anti(cid:173)
`biotic into the 21st century.
`In summary, neomycin remains an
`excellent antibiotic in combination
`with other antibiotics, such as Neospo(cid:173)
`rin and/or dexamethasone, and when
`used for about a week. The acute red
`
`eye that one would treat with a combi(cid:173)
`nation drug almost invariably requires
`treatment for no more than a week.
`T hese medicines are highly effective,
`cheap, and they remain workhorse
`drugs in contemporary eye care.
`last, we stress that bacterial infec(cid:173)
`tions are characterized by a mucopuru(cid:173)
`lent discharge. Sometimes this is gross(cid:173)
`ly visible; other times, the discharge is
`more subtle and is only found via slit
`lamp observation of microparticulate
`debris in the lacrimal lake.
`Both the aqueous humor and lac(cid:173)
`rimal lake should be optically empty.
`
`j~ j FROM THE
`~ LITERATURE
`
`NEW BENCHMARKS ON
`ANTIBIOTIC RESISTANCE
`The five-year Antibiotic Resistance Monitoring in Ocular
`Microorganisms (ARMOR) study data was recently pub(cid:173)
`lished in JAMA Ophthalmology (December 2015). This
`is reportedly the most robust evaluation of nationwide
`antibacterial susceptibility of common ocular pathogens
`to date. Thankfully, resistance rates have remained stable
`over the past five years of this study.
`About half of Staphylococcus species are methicillin
`resistant, meaning they are more difficult to kill than the
`methicillin-sensitive bacterial pathogens. Minimal inhibi(cid:173)
`tory concentration-90 (MIC90) represents how effective a
`drug is at eradicating a bacterial species-Le., the lowest
`concentration of a drug that will inhibit 90% of bacterial
`isolates. To interpret these results: the lower the MIC90, the
`more effective the drug. Focusing on the most commonly
`prescribed drugs, the findings are as follows:
`Some drugs were not tested against all pathogens,
`
`hence some blanks are present. Also, we did not list meth(cid:173)
`icillin-sensitive Staphylococcus species because a clinician
`does not know the nature (i.e., methicillin sensitive vs.
`methicillin resistant) of the causative pathogen at clinical
`presentation, so we need to treat based on a "most difficult
`to kill" approach. If we treat a presumed Staphylococcus
`infection, and in reality it is methicillin sensitive, it will be
`quickly eradicated if we are assuming (and treating for)
`methicillin-resistant species.
`Interestingly, MRSA organisms are more common
`among the elderly and those who reside in the southern
`portions of the United States. Note that the drug of choice
`for culture-proven Pseudomonas is ciprofloxacin, although
`the fluoroquinolones and tobramycin performed quite well.
`A summary statement says: "Until rapid diagnostic meth(cid:173)
`ods are available to guide treatment choices, clinicians
`should consider these data to guide the empirical treat(cid:173)
`ment of ocular infections."
`
`Asbell PA, Sanfilippo CM, Pillar CM, et al. Antibiotic Resistance Among
`Ocular Pathogens in the United States: Five-Year Results From the
`Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR)
`Surveillance Study. JAMA Ophthalmol. 2015 Dec:133(12):1445-54.
`
`) FOR SELECTED ORGANISMS
`MINIMUM INHIBITORY CONCENTRATIONS (MIC90
`MR Staph Epi. •
`Strep. Pneumo.
`MRSA
`256
`64
`1
`16
`32
`0.25
`16
`32
`0.12
`2
`0.06
`4
`>512
`>512
`>128
`>256
`16
`2
`>128
`2
`
`Ciprofloxacin
`Gatifloxacin
`Moxifloxacin
`Besifloxacin
`Azithromycin
`Tobramycin
`Trimethoprim
`Vancomycin
`
`Pseudomonas
`0.5
`2
`4
`4
`
`• There are many organisms which are are "coagulase-negative" but Staph. epidermidis is by far the most numerous, and therefore we
`have chosen to use Staph. epi. as synonymous with the coagulase-negative Staph.
`
`Note that besifloxacin and vancomycin share superb MIC90 levels, which would portend high clinical efficiacy.
`
`10 REVIEW OF OPTOMETRY MAY 15, 2016
`
`Eye Therapies Exhibit 2050, 10 of 52
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`