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2016 CLINICAL GUIDE TO OPHTHALMIC 20th20thh AAnniversarynniversary EEditiondition

Supported by an unrestricted grant from Ron Melton, OD Randall Thomas, OD, MPH Bausch + Lomb

FC_DG0516.indd 2 5/4/16 6:27 PM FROM THE AUTHORS

DEAR OPTOMETRIC COLLEAGUES: Supported by an Welcome to the 2016 Clinical Guide to Ophthalmic Drugs—the 20th An- unrestricted grant from niversary Edition of this publication. Bausch + Lomb 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 CONTENTS . 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 care. Drugs ...... 3 Thank you for taking this journey along with us over these past 20 years. Notably, 2016 is projected to bring us a newer and a new drug to help treat dry disease. In addition to sharing with you informa- tion on these new drugs and their use, we also review how and when to use Agents...... 6 tried-and-true ophthalmic , many of which are now available generically. We are especially honored this year to have a guest author, Kathleen F. Dry Eye ...... 13 Elliott, OD. The 2014 Oklahoma Optometric of the year and ABO Board Certified optometrist brings us up to date on clinical aspects of pediat- ric eye care. She can be reached at [email protected]. Drugs ...... 20 We want to sincerely thank the awesome team at Review of 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 Use ...... 26 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 + Pediatric Pearls...... 33 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. Glaucoma Care ...... 36 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- Therapy ...... 44 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. Clinical Insights...... 46

Sincerely,

Randall Thomas, OD, MPH Ron Melton, OD

A PEER-REVIEWED : Drs. Melton and Thomas are consultants to, but have no financial SUPPLEMENT interests in, the following companies: Bausch + Lomb/Valeant and Icare.

Note: The authors present unapproved and “off-label” uses of specific drugs in this guide.

002_dg0516_Intro_v3.indd 2 5/4/16 4:17 PM ALLERGY DRUGS

ALLERGY TREATMENT: QUELLING THE

octor, my just Though the itch and burn all the time,” the pa- condition may tient says. How be the most “Dmany hundreds of times have we heard this lament? harmless one However, this common complaint brings us front and center to the prover- we see, our bial fork in the road. The first question is basic. Ask the patient, “So, think about ocular allergy this: Is the burning or the itching your patients are main symptom?” Most patients can give a clear answer to this fundamental ques- among our tion. For the few patients who feel the symp- most grateful. toms of burning and itching are about equal, or who can’t decide which symp- tom is most bothersome, treatment with A woman experiencing a severe ocular a topical corticosteroid will usually quell allergic reaction. both complaints. Don’t forget our time- honored advice in these cases: “When in doubt, use a .” SYMPTOMS ONLY If itching is the predominant symptom, If there are minimal associated signs of our approach to drug selection takes one allergy—such as chemosis, conjunctival of the following two routes. and/or —an anti-

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003_dg0516_Allergy_v3.indd 3 5/4/16 4:24 PM ALLERGY DRUGS

OCULAR ALLERGY BRAND NAME GENERIC NAME MANUFACTURER PEDIATRIC USE BOTTLE SIZE(S) DOSING Acute Care Products Acular LS tromethamine 0.4% Allergan, and generic 3 years 5ml, 10ml QID Alaway (OTC) fumarate 0.025% Bausch + Lomb 3 years 10ml BID Alrex etabonate 0.2% Bausch + Lomb 12 years 5ml, 10ml QID Bepreve bepotastine besilate 1.5% Bausch + Lomb 2 years 5ml, 10ml BID Elestat HCl 0.05% Allergan, and generic 3 years 5ml BID Emadine difumarate 0.05% Alcon 3 years 5ml QID Lastacaft alcaftadine 0.25% Allergan, and generic 2 years 3ml QD Optivar hydrochloride 0.05% Meda, and generic 3 years 6ml BID Pataday hydrochloride 0.2% Alcon 3 years 2.5ml QD Patanol olopatadine hydrochloride 0.1% Alcon, and generic 3 years 5ml BID Pazeo olopatadine hydrochloride 0.7% Alcon 2 years 2.5ml QD Zaditor (OTC) ketotifen fumarate 0.025% Alcon, and generic 3 years 5ml BID

Chronic Care Products Alocril sodium 2% Allergan, and generic 3 years 5ml BID Alomide tromethamine 0.1% Alcon 2 years 10ml QID Crolom cromolyn sodium 4% Bausch + Lomb, 4 years 10ml QID and generic

/ is an • Olopatadine (Patanol/Pataday/ has been available generically and excellent clinical approach. Within Pazeo, Alcon) over the counter. There are several this class, there are six drugs from Notwithstanding fine differences, “brand name” OTC ketotifen prep- which to choose: all the subtype 1 re- arations, such as Alaway (Bausch • Alcaftadine (Lastacaft, Allergan) ceptor blockers nicely suppress ocu- + Lomb), among others. All come • Azelastine (Optivar, Meda Phar- lar itching. Most are dosed initially in 5ml bottles except for Alaway, maceuticals; generic available) BID (except Pataday, Pazeo and which comes in a 10ml bottle. In- • Bepotastine (Bepreve, Bausch + Lastacaft, which are dosed once dai- terestingly, our casual observations Lomb) ly). After two weeks at BID, ask the in a variety of reveal • Epinastine (Elestat, Allergan; patient to try to reduce the drop to that the cost of the 10ml Alaway is generic available) once-daily maintenance therapy. In very near (and occasionally cheaper • Ketotifen (Zaditor, Novartis; our experience, once symptomatic than) the price of its 5ml competi- many generics available. This itching has been brought under con- tors. Thus, OTC Alaway is the most drop is OTC.) trol, it takes less pharmacological cost-effective way to suppress ocular intervention to itch. maintain. How- When a prescription ever, some pa- is preferred, perhaps a 10ml bottle tients may have of Bepreve (using a standard copay) to continue BID would be of greatest value to the pa- therapy. tient, especially with insurance cov- Perhaps the erage or coupons. best news for the consumer is SYMPTOMS PLUS SIGNS the loss of patent The other route of allergy presen- protection for tation is represented by the patient Zaditor. Since who presents with predominant 2007, ketotifen itching along with one or more

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003_dg0516_Allergy_v3.indd 4 5/4/16 4:24 PM ISOLATE PATIENT OCULAR IN YOUR OFFICE A company called ’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 care, nothing is perfect. There is the highly remote possibility of an anaphylactic reaction, so hav- ing an EpiPen in the office is wise. Having available is also advised. That being said, this simple test is highly effective in helping determine what is causing the typically prescribe a steroid Q2H sion of inflammation. Cold com- patient’s ocular allergy reaction. for two days, then QID for one presses can be helpful in most all oc- We encourage our optometric week, followed by BID for one ular surface inflammatory diseases. colleagues to carefully investigate more week. Once the inflamma- In contradistinction, infectious pro- this relatively new diagnostic tory signs are controlled, consider cesses are commonly helped by the technology via the website www. switching the patient to an anti- application of warm soaks. drsallergyformula.com (under histamine/mast cell stabilizer for In summary, if itching is not the construction as of this writing). ongoing symptom control. Long- primary symptom, be sure to con- The company was acquired by term treatment with Alrex once or sider dry eye as the foundational Bausch + Lomb in October 2015, twice daily as maintenance therapy condition, and treat accordingly. and the diagnostic test is being can be done if a steroid is what best If itching is primarily expressed, incorporated into the pharma controls their disease. determine if it is an isolated symp- division’s offerings. According to a conversation we tom or associated with concurrent had with Mark Abelson, MD, a inflammatory signs, and then treat world-renowned ocular allergist at accordingly. Remember: concurrent signs, such as conjuncti- Harvard , there is Symptoms only: Use an antihista- val redness, chemosis and/or eyelid little clinical use for pure mast cell mine/mast cell stabilizer edema. For this particular subset of stabilizing drugs. He says that the Symptoms with signs: Use a patients, we feel a topical cortico- antihistamine/mast cell stabilizer steroid such as Lotemax off-label, steroid such as Alrex (loteprednol drugs more effectively stabilize the Alrex or FML 0.2%, Bausch + Lomb), off-label mast cell membranes than stand- There is no rule in the rulebook that use of Lotemax gel (loteprednol alone mast cell stabilizers such as says you can’t have two problems at 0.5%, Bausch + Lomb) or FML pemirolast (Alamast), nedocromil once. Since dry eye is epidemic, identi- ophthalmic (fluoro- (Alocril) or cromolyn sodium (ge- fy and manage this disease whether or metholone 0.1%, Allergan) is more neric). Based on this expert opinion, not it is concomitant with allergic eye appropriate treatment. we no longer prescribe these pure disease. If, however, the main symp- The only other decision involves mast cell stabilizers. tom is burning, then a thorough dry the frequency of instillation; we Remember, allergy is an expres- eye evaluation is in order. ■

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003_dg0516_Allergy_v3.indd 5 5/4/16 4:24 PM ANTIBIOTIC AGENTS

CHOOSING AND USING WISELY

Success with he medical literature bemoans the egregious overprescrib- antibiotics ing of systemic antibiotics may have and begs and other Thealth care providers to use more to do great restraint in such prescribing. The same admonition may be applied with frequency to the optometric profession regarding topical antibiotics, but for a different rea- of instillation son. The concern with regard to systemic than selection antibiotics centers on the prevention of re- sistance. But the concern with optometric of the drug, so use of topical antibiotics is inaccurate di- agnoses because the vast majority of acute Mucupurulent discharge typical of bacterial it’s important red eyes are inflammatory, not infectious . (with the exception of pediatric patients). to know Generally speaking, infectious diseases trum, and are generally effective against how often produce a discharge whereas inflamma- many common bacterial . We tory diseases do not. This should quickly have found frequency of administration— to prescribe separate the sheep from the goats. We rather than particular drug selection—to opine that such overprescribing is two- be the key determining factor of clinical them. fold: lack of a firm diagnosis and a seem- outcome. Since most (but not all) of the ingly unrelenting reluctance to prescribe currently approved topical antibiotics . possess reasonable antimicrobial abilities, We have seen hundreds of patients who the more frequent the administration of were treated elsewhere with topical anti- these drops, the greater the clinical result. biotics by a wide variety of practitioners However, the frequency of ad- and who were not getting better. They ministration depends almost exclusively presented to us as a “second-opinion” vis- on the severity of the infectious expres- it where we recognized the conditions to sion. be inflammatory, prescribed steroids and When it comes to ocular , the patients were uniformly better within there are two main routes of antibiotic days. It just goes to show: Accurate diag- administration: topical and oral. All topi- nosis and proper therapeutic intervention cal antibiotic drops are , except are great practice builders. (See “The Ef- besifloxacin, which is a suspension. Oral ficient Evaluation,” page 11.) antibiotics are most commonly prescribed Thankfully, most of the commonly as a , or (the latter used antibiotic eye drops are broad spec- used mostly in children).

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006_dg0516_Antibiotics_v3.indd 6 5/4/16 4:54 PM In our practices, we more common- ly prescribe oral antibiotics than topi- cal ones simply because we encounter more patients needing oral antibiotic therapy, such as those with meibo- mian gland disease (doxycycline), ro- sacea (doxycycline) and in- ternal hordeola (cephalexin [Keflex]). On those relatively uncommon acute following eyelid scrubs and/or treat- NEOSPORIN bacterial conjunctivitis cases, we typi- ments at bedtime for a week or two. It While the previous combination of cally prescribe generic Polytrim (trim- can also be used at bedtime to provide besifloxacin and Polysporin pro- ethoprim with polymyxin B), tobra- overnight coverage for moderate to vides a broad spectrum of antibacte- mycin or Besivance (besifloxacin). severe ulcerative . There are rial coverage, perhaps an even better Now, let’s take a more in-depth two key limitations to its clinical use: choice may be the triple-antibiotic of look at this class of medicines. There It is only available in ointment form, neomycin, bacitracin and polymyxin are many antibiotics; however, only a and it has little to no activity against B, commonly known as its original few enjoy—or should enjoy—wide- gram-negative bacteria. brand name: Neosporin. spread use. On those rare occasions when we Interestingly, both bacitracin and encounter a true bacterial corneal Polysporin are available only as oint- BACITRACIN , we prescribe besifloxacin ments, whereas Neosporin is avail- We find this drug to be superbly with Polysporin ophthalmic oint- able both as an ophthalmic bactericidal against most all gram- ment, which contains bacitracin and and an ointment, as the solution con- positive bacterial pathogens, and can polymyxin B, since the polymyxin B tains gramicidin, not bacitracin. We be used to help treat staphylococcal is bactericidal against gram-negative never use the Neosporin in eye drop blepharitis when applied to the pathogens. form, as we prefer generic Polytrim

TOPICAL ANTIBIOTIC DRUGS BRAND NAME GENERIC NAME MANUFACTURER PREPARATION PEDIATRIC USE BOTTLE/TUBE Fluoroquinolones Besivance besifloxacin 0.6% Bausch + Lomb suspension > 1 yr. 5ml Ciloxan 0.3% Alcon, and generic sol./oint. > 1 yr./ > 2 yrs. 5ml, 10ml/3.5g Moxeza 0.5% Alcon solution > 4 mos. 3ml Ocuflox 0.3% Allergan, and generic solution > 1 yr. 5ml, 10ml Vigamox moxifloxacin 0.5% Alcon solution > 1 yr. 3ml Zymaxid gatifloxacin 0.5% Allergan, and generic solution > 1 yr. 2.5ml

Aminoglycosides Tobrex tobramycin 0.3% Alcon, and generic sol./oint. > 2 mos. 5ml/3.5g Garamycin gentamicin 0.3% Perrigo, and generic sol./oint. N/A 5ml/3.5g

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

Other Antibiotics AzaSite 1% Akorn solution > 1 yr. 2.5ml Ilotycin 0.5% Perrigo, and generic ointment > 2 mos. 3.5g Bacitracin bacitracin 500u/g Perrigo ointment N/A 3.5g

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006_dg0516_Antibiotics_v3.indd 7 5/4/16 4:54 PM ANTIBIOTIC AGENTS

(which contains generic trimethoprim it has little or no clinically significant NEOMYCIN with polymyxin B), tobramycin or Be- anti-inflammatory properties; there- Traditional wisdom with regard to sivance, depending on the nature and fore, its use in clinical patient care is this excellent antibiotic focuses more severity of the infectious condition; quite limited. on the negatives than the positives. but we embrace Neosporin ointment Yes, neomycin does possess the abil- without hesitation for those rare oc- BESIFLOXACIN ity to cause an annoying, type IV de- casions when overnight antibiosis is Besifloxacin is a highly unique dual- layed hypersensitivity on rare occa- deemed necessary to enhance a clini- halogenated quinolone that is not sions, but let’s not throw out the baby cal cure. used systemically. Clinical studies with the bathwater. As we have made clear, neomycin is (see “New Benchmarks on Antibi- Neomycin itself is broad-spectrum, a wonderful drug, but can on rare oc- otic Resistance,” page 10) show it to but it does not cover Pseudomonas,

casions cause an annoying type IV de- have low MIC90 values, very similar which is why it is always packaged layed hypersensitivity reaction. Given to those of vancomycin, the gold stan- with polymyxin B or another antibiot- that we have three alternatives (gener- dard in treating known gram-positive ic to cover gram-negative organisms. ic Polytrim, generic tobramycin and pathogens. (Vancomycin is not com- In our experience, type IV delayed Besivance) that are much less prone to mercially available as an ophthalmic hypersensitivity dermatoconjunctivo- causing any sort of allergic response, formulation and has to be prepared keratitis reactions are exceedingly we prefer to follow this simpler path by a compounding pharmacy.) Be- rare when the neomycin combination for most patients most of the time. sifloxacin also has strong coverage is used for no more than a week. against gram-negative organisms, in- The exception is the rare patient MACROLIDES cluding Pseudomonas. This is true of who has been previously exposed to The macrolide antibiotics (i.e., eryth- the aminoglycosides as well. neomycin and already has immuno- romycin, azithromycin and clarithro- Besifloxacin is a 0.6% ophthalmic sensitivity. These patients can react mycin) are widely used systemically suspension (the rest are solutions), to neomycin in just a day or two, but have limited use topically. and it needs to be shaken before each which may also be the result of a Regarding erythromycin, many instillation. It is a thick eye drop, so type 1 hypersensitivity to initial ex- bacteria are increasingly resistant. In the patient should not blink for a few posure. Patient management is simply like manner, topical azithromycin has seconds after instillation to allow the to stop the medication. Again, these been shown to have limited antibiotic drop to spread out across the ocular are non-serious, annoying, superfi- efficacy, and the FDA has stated that surface and remain in the eye. cial responses. In our many years of

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006_dg0516_Antibiotics_v3.indd 8 5/4/16 4:54 PM 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- 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- sions—almost always occurring at or near the limbus—and treatment with a ste- 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- 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 . Either 1% or 5% is typically used to accomplish this purpose. The standard dosage is 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- cent eyelid marginal tissues. (This is distinct from meibomian 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- 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 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 , 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 . 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- tain healthy tissues in our patients. Further, with diminution of Staph. popula- tions, there is a decreased risk of secondary 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.

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006_dg0516_Antibiotics_v3.indd 9 5/4/16 4:54 PM ANTIBIOTIC AGENTS

clinical practice, we have seen only reason they are rarely, if ever, used eye that one would treat with a combi- half a dozen such events, mostly with systemically. Any drug actively or pas- nation drug almost invariably requires neomycin exposure of greater than a sively reserved for only topical use is treatment for no more than a week. week, and often prescribed by prima- relatively protected from resistance, These medicines are highly effective, ry care practitioners. thus enabling it to be a powerful che- cheap, and they remain workhorse When neomycin is packaged (along motherapeutic agent for many decades. drugs in contemporary eye care. with polymyxin B) with a steroid, For example, bacitracin was brought Last, we stress that bacterial infec- such as generic Maxitrol, whatever to market in the 1940s and remains a tions are characterized by a mucopuru- expression of a hypersensitivity reac- superb, exclusively gram-positive anti- lent discharge. Sometimes this is gross- tion that may be occurring typically biotic into the 21st century. ly visible; other times, the discharge is remains subthreshold, or subdued, In summary, neomycin remains an more subtle and is only found via slit courtesy of the concurrent corticoste- excellent antibiotic in combination lamp observation of microparticulate roid suppression. with other antibiotics, such as Neospo- debris in the lacrimal lake. The aminoglycosides, used systemi- rin and/or dexamethasone, and when Both the aqueous humor and lac- cally, can cause ototoxicity. For this used for about a week. The acute red rimal lake should be optically empty.

FROM THE LITERATURE hence some blanks are present. Also, we did not list meth- icillin-sensitive Staphylococcus species because a clinician NEW BENCHMARKS ON does not know the nature (i.e., methicillin sensitive vs. ANTIBIOTIC RESISTANCE methicillin resistant) of the causative at clinical presentation, so we need to treat based on a “most difficult The five-year Antibiotic Resistance Monitoring in Ocular to kill” approach. If we treat a presumed Staphylococcus Microorganisms (ARMOR) study data was recently pub- infection, and in reality it is methicillin sensitive, it will be lished in JAMA (December 2015). This quickly eradicated if we are assuming (and treating for) is reportedly the most robust evaluation of nationwide methicillin-resistant species. antibacterial susceptibility of common ocular pathogens Interestingly, MRSA organisms are more common to date. Thankfully, resistance rates have remained stable among the elderly and those who reside in the southern over the past five years of this study. portions of the United States. Note that the drug of choice About half of Staphylococcus species are methicillin for culture-proven Pseudomonas is ciprofloxacin, although resistant, meaning they are more difficult to kill than the the fluoroquinolones and tobramycin performed quite well. methicillin-sensitive bacterial pathogens. Minimal inhibi- A summary statement says: “Until rapid diagnostic meth- tory concentration–90 (MIC ) represents how effective a 90 ods are available to guide treatment choices, clinicians drug is at eradicating a bacterial species—i.e., the lowest should consider these data to guide the empirical treat- concentration of a drug that will inhibit 90% of bacterial ment of ocular infections.” isolates. To interpret these results: the lower the MIC90, the more effective the drug. Focusing on the most commonly Asbell PA, Sanfilippo CM, Pillar CM, et al. Antibiotic Resistance Among Ocular Pathogens in the United States: Five-Year Results From the prescribed drugs, the findings are as follows: Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) Some drugs were not tested against all pathogens, Surveillance Study. JAMA Ophthalmol. 2015 Dec;133(12):1445-54.

MINIMUM INHIBITORY CONCENTRATIONS (MIC90) FOR SELECTED ORGANISMS MRSA MR Staph Epi.* Strep. Pneumo. Pseudomonas Ciprofloxacin 256 64 1 0.5 Gatifloxacin 16 32 0.25 2 Moxifloxacin 16 32 0.12 4 Besifloxacin 2 4 0.06 4 Azithromycin >512 >512 >128 Tobramycin >256 16 1 Trimethoprim 2 >128 Vancomycin 1 2 * 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.

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0006_dg0516_Antibiotics_v3.indd06_dg0516_Antibiotics_v3.indd 1010 55/4/16/4/16 4:554:55 PMPM Cellular and/or proteinaceous debris KEEP THE EFFICIENT RED EYE EVALUATION in the aqueous humor is exhibited in IN MIND Each of these procedures generally takes about anterior uveitis and debris in the lac- two to three minutes in most cases. rimal lake is typically seen in more subtle cases of acute bacterial ocular • Assess (pinhole if indicated) surface infection. • Note the degree of conjunctival injection Every time you are uncertain of Mild: dry eyes, allergy, chlamydia, mild bacterial infections the diagnosis and are considering pre- Marked: acute viral or non-specific bacterial infection, acute iritis scribing a topical antibiotic, always • Note the degree of conjunctival injection pattern reconsider this low-yield therapeutic Sector injection: corneal infiltrate, , phlyctenule, inflamed approach. At the very least, consider use of a combination antibiotic-steroid Global injection: uniform—bacterial or viral infection, or uveitis with appropriate follow-up care in More pronounced in fornices: bacterial infection two to three days. More pronounced paralimbally: uveitis • Quality and quantity of discharge if any ORAL ANTIBIOTICS Watery: viral Selecting an oral antibiotic for acute Mucoid: dry eyes, allergy, chlamydia internal hordeola is usually straight- Mucopurulent: bacteria forward. We almost exclusively pre- • Preauricular lymphadenopathy (not grossly visible) scribe the first-generation cephalospo- Most commonly, adenoviral rin cephalexin (Keflex) at 500mg BID Less commonly, chlamydial for one week. Rarely, hyperacute conjunctivitis If the condition is severe and/or the If grossly visible: Parinaud’s oculoglandular syndrome (cat-scratch disease) patient is large in size, then 500mg • Follicles vs. papillae: clinically virtually meaningless QID for one week may be indicated. Exception: Giant follicles in the inferior forniceal are highly If the patient has had a true ana- indicative of chlamydial infection phylactic reaction to a penicillin drug, • Character of : Examine without, then with, fluorescein dye to rule we opt for Levaquin (500mg QD) or out herpes keratitis, subtle abrasions, ulceration, through-and-through doxycycline (200mg/day), or Bactrim perforation (Seidel’s sign) or Septra (both common brand names of trimethoprim with sulfamethoxa- • Measure the IOP if no contraindications exist zole) prescribed as two DS (double • Evert the eyelid to rule out conjunctival foreign material or strength) tablets BID for one week. • Examine the anterior chamber for cells/flare This “double strength” is the stan- • Quick to rule out concurrent intraocular disease dard, commonly prescribed dosage.

OPHTHALMIC MYTHS: INFECTION CARE Myth Fourth-generation fluoroquinolones are the best, most effective medicines for ocular surface infections. Our Take Several recent studies have documented significant and increasing resistance to this class of . Better choices would be an aminoglycoside, trimethoprim with polymyxin B, or Besivance suspension. Myth Pressure patching abrasions is now obsolete. Our Take Patients with large, painful abrasions may be best treated with therapeutic cycloplegia and a well-placed pres- sure patch over an antibiotic ointment, such as Polysporin (bacitracin with polymyxin B), at least initially. Most abrasions are treated with a bandage/therapeutic soft contact lens with topical trimethoprim/polymyxin B (Polytrim) eye drops used four times a day until the abrasion is healed. The generic Polytrim is used because it is minimally toxic to the ocular surface, highly effective and affordable. Myth Don’t touch the dropper tip to the eye, as it could cause an infection. Our Take We all know many patients do this routinely, and we have never seen an eye infection from such a behavior. No doubt this has happened to some unlucky soul, but such a complication would be exceedingly rare. The greater risk is the potential for . Myth Ointments retard re-epithelialization in the setting of corneal abrasion. Our Take This has long been proven to be false.

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Azithromycin, besifloxacin and some of the lipid-based artificial are very viscous eye drops, so it is important to instruct the patient to gently close the eyes and not blink for five to eight seconds after instillation. This allows the thick drop to spread across the ocular surface and have greater retention; oth- erwise, the drop could be quickly expelled out of the eye and onto Classic appearance of giant fornix Perform a thorough sweep of the the eyelid or floor. syndrome, a Staphylococcus aureus superior cul-de-sac. This can help find infection in older patients that is elusive foreign bodies or, in this case, If the patient is truly allergic to both more challenging to treat than typical remove fixed innoculum debris residing penicillin and sulfa, consider oral doxy- bacterial infections. deep in the forniceal conjunctiva. cycline 100mg BID for one week, or the oral fluoroquinolone As a postscript, pharmacy pricing tive drug selected.2 This could parallel 500mg once daily for one week. For issues are maddening, and clinicians our use of doxycycline 50mg/day to perspective, the risk of a cross-sensitiv- are constantly faced with dynamic and treat rosacea blepharitis or meibomian ity reaction of a cephalosporin in a pa- ever-changing pricing structures. Re- gland disease. “Plan B” was minocy- tient truly allergic to penicillin is about garding doxycycline, we have found cline, but since they perform very simi- 0.1%, but why ever take this miniscule in several instances that the 100mg larly, the authors recommended trying risk? Just prescribe an alternate class. units are cheaper than the 50mg units. azithromycin (a different class of anti- biotic). The literature also shows that QUOTABLE azithromycin 500mg three times/week is as effective as doxycycline in treat- ing rosacea, while 500mg/day for two IF THE PATIENT IS TRULY ALLERGIC TO BOTH PENICILLIN AND weeks is effective for cases of intrac- SULFA, THEN CONSIDER ORAL DOXYCYCLINE 100mg BID FOR table rosacea.3,4 However, dermatolo- gists defaulted to minocycline 80% of ONE WEEK, OR THE ORAL FLUOROQUINOLONE LEVOFLOXACIN the time, and azithromycin 20% of the AT 500mg ONCE DAILY FOR ONE WEEK. time. Overall use of azithromycin among Always remember that the aggres- Therefore, we occasionally prescribe dermatologists is about 3%. Perhaps sive use of warm soaks is essential to 100mg doxycycline monohydrate tab- physicians of all stripes struggle with maximize restoration to a normal state lets that can be split in half to provide appropriate drug selection and appro- in acute eyelid infections. our patients cost-effective treatment. priate duration of therapy. ■ For chronic care conditions, such as While both doxycycline hyclate and 1. Kashkouli MB, Fazel AJ, Kiavash V, et al. Oral meibomian gland disease and rosacea doxycycline monohydrate are well- azithromycin versus doxycycline in meibo- blepharitis, prescribe doxycycline at tolerated, the monohydrate form ap- mian gland dysfunction: a randomised double- masked open-label clinical trial. Br J Ophthalmol. 50mg daily for three to six months. pears to be a bit better tolerated. 2015;99(2):199-204. The dichotomous character of doxy- An interesting article in the Journal 2. Nagler AR, Milam EC, Orlow SJ. The use of oral antibiotics before isotretinoin therapy in patients cycline (anti-infective at high dosage, of the American Academy of Derma- with acne. J Am Acad Dermatol. 2016;74(2):273-9. and anti-inflammatory at low dosage) tology (February 2016) pointed out 3. Akhyani M, Ehsani AH, Ghiasi M, Jafari AK. Com- parison of efficacy of azithromycin vs. doxycycline requires different dosing based on two noteworthy observations: If a pa- in the treatment of rosacea: a randomized open clinical intent. Some recent research tient’s acne is not improved by three clinical trial. Int J Dermatol. 2008;47(3):284-288. 4. Kim JH, Oh YS, Choi EH. Oral azithromycin for also suggests a five-day course of oral to four months of doxycycline, then treatment of intractable rosacea. J Korean Med Sci. azithromycin can improve MGD.1 it should be stopped, and an alterna- 2011;26(5):694-696.

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ALL ABOUT DRY EYE

onald Korb, OD, and Caro- We hope line Blackie, OD, PhD, and that some their research team, along with other researchers around intervention Dthe world, have now shown that the “root of all evil” in dry will soon be is dysfunction of the meibomian glands.1 Said differently, if we can find ways to found to help embellish and restore normal meibomian the masses gland function, most dry eye disease likely would resolve or not occur at all. This patient’s lid, imaged with meibography who suffer Following along this foundational technology, displays severe meibomian gland pathophysiologic pathway, it makes sense dysfunction. from dry eye. that a dysfunction of the lipid layer needs to be secondarily addressed. With this cas- ease is comparable. Obviously, the earlier For now, cade of deterioration of the precorneal tear we can intervene in these pathophysiologi- several rational film, hyperosmolarity occurs because of cal processes, the better. Different thera- increased evaporation, which then causes pies are employed at these different stages. approaches, ocular surface inflammation. Such inflam- Until meibography comes into wide- mation has been consistently characterized spread clinical use, which will allow us to properly as the epicenter of the pathogenesis of clin- stratify proper interventions, we will con- ically symptomatic dry eye disease. tinue to encounter patients at secondary applied, can Let’s try a complex analogous compari- and tertiary levels of dry eye expression. help most son of meibomian gland disease (MGD) Interventions could include: inclusion of to : Many factors, such dietary omega-3 essential fatty acids, such patients. as diet, lifestyle and genetics, determine as fish oils or flaxseed oil; use of lipid- one’s risk for hypercholesterolemia. Such based artificial tears to augment the de- pathological blood chemistry leads to ath- ficient lipid layer; and/or a short course eromatous plaquing of the intimal lining of a topical ester-based corticosteroid to of arteries. If subsequent cholesterol levels address the inflammatory component. A are not stabilized, the risk of arterial oc- clear target for intervening at the earliest clusion occurs, which can result in a heart stages of meibomian gland compromise attack or stroke. has yet to be fully elucidated, but it is ob- The cascade of evaporative dry eye dis- vious that supporting meibomian gland

* Loteprednol (Lotemax) therapy for inflammation due to dry eye disease is consid- ered an off-label use. All mentions of such use herein reflects the views of the authors.

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COMMONLY USED LIPID-BASED ARTIFICIAL TEARS

Brand Name Manufacturer Lipid Lubricants Preservative Refresh Optive Allergan castor oil carboxymethylcellulose, glycerin, Purite (stabilized oxychloro Advanced polysorbate 80 complex) Refresh Optive Allergan castor oil carboxymethylcellulose, glycerin, none Advanced polysorbate 80 Preservative Free Retaine MGD OcuSoft glycerol light mineral oil, mineral oil none Soothe XP Bausch + Lomb light mineral oil, polysorbate 80 polyquarternium-1 mineral oil Systane Balance Alcon mineral oil polyquarternium-1

function early on is the key to ulti- symptoms with which patients pres- mate prevention of dry eye disease. ent. Interventions such as LipiFlow Aggressive use of warm compresses and intense pulsed light can be intro- combined with physical expression of duced earlier in the pathway to hope- the meibomian glands can go a long fully obviate the need for downstream way in enhancing proper function. interventions. While these maneuvers are indeed We think that as meibography be- helpful, wouldn’t it be grand if there comes a standard diagnostic tool in were some sort of side effect-free pill the office, and as technology becomes we could give patients to prevent more refined and affordable, meibo- MGD and to maintain a youthful, vi- mian gland disease can be detected brant precorneal tear film? earlier, and preventive or enhance- The current reality is that patients ment techniques can be employed to present to us with the downstream massively decrease the clinical presen- A reduced lacrimal lake and meibomian symptoms of dry, gritty, burning tation of symptomatic dry eye. gland dysfunction, as is seen in this eyes. So, at least for the time being, patient, suggests a poor tear film lipid we are left having to intervene at these CASCADE OF EVENTS layer. more advanced levels of disease. This IN DRY EYE DISEASE is why we commonly use lipid-based We know that dessicatory stress initi- artificial tears and pulse-dosing of ates the cascade of events leading to mented with fish oil and/or punctal loteprednol used off-label, along with dry eye disease. Clinically, therapeu- plugs. punctal plugs to address these dry eye tic intervention is relatively straight- Although treatment is compara- symptoms. forward: Suppress the ocular surface tively basic, the biochemical mecha- We are hopeful that potential FDA inflammation and augment the pre- nism is complex—but here is a simpli- approval of a new drug for dry eye corneal tear film (especially the lipid fied version: disease, lifitegrast, will be helpful layer) with lipid-based artificial tears. Intracellular adhesion molecules in the amelioration of the signs and This latter portion can be further aug- (ICAM) are found on the surface of

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013_dg0516_Dry eye_v3_BK.indd 14 5/4/16 5:48 PM FROM THE LITERATURE Optometry has a unique opportunity to help potential SS patients by being keenly attentive to the history, and care, A LOOK AT SJÖGREN’S SYNDROME of patients with dry eye disease. Quite simply, be sure to Patients with Sjögren’s syndrome (SS) comprise a small query patients, particularly women, about “pain, , subset of the dry eye disease population, yet these patients depressed mood and cognitive symptoms.” often have a more debilitating expression of the disease. Write down the words “Sjogren’s syndrome” for your It is important that we have a contemporary perspective SS-suspect patients, and encourage them to ask their on this condition. An insightful article in Ophthalmology to pursue a diagnostic evalua- (January 2015) made some useful contributions to our tion. Most physicians, especially rheumatologists, are fully knowledge in this area.1 Excerpts are as follows: capable of doing this. It is our duty and responsibility to be • “Sjögren’s syndrome is a multi-system autoimmune dis- especially attentive to this cohort of possible SS patients ease characterized by lymphocytic infiltration of exocrine and provide guidance and encouragement to them. glands in other organs.” There is a new blood test, Sjö, that any optometrist • “Although common, SS is under-recognized in clinical can order, which uses newer, novel biomarkers than are practice, largely as a result of its diverse presentation lead- currently in widespread clinical use. Using this diagnos- ing to a significant delay in diagnosis. This delay is of great tic assay, SS may be detected five years earlier than clinical significance because patients with SS are likely with existing testing. At the very least, encourage your to have reduced quality of life as a result of pain, fatigue, SS-suspect patients to seek care from their PCPs or a rheu- depressed mood, and cognitive symptoms.” matologist as this may be critical to their longevity and • “Lymphoma is one of the most serious complications quality of life. of SS, and the primary source of increased mortality result- In addition, guidelines for management of dry eye asso- ing from this disease. Multiple studies consistently have ciated with SS were published in April 2015 in The Ocular 2 identified SS as an independent risk factor for non-Hodg- Surface..

kin’s lymphoma.” 1. Akpek EK, Mathews P, Hahn S, et. al. Ocular and systemic morbidity in a longitudi- • “We recommend assessing the presence of SS in nal cohort of Sjögren’s syndrome. Ophthalmology. 2015 Jan;122(1):56-61. patients with clinically significant dry eye because dry eye 2. Foulks GN, Forstot SL, Donshik PC, et al. Clinical guidelines for management of dry eye associated with Sjögren disease. Ocul Surf. 2015 Apr;13(2):118-32. precedes the occurrence of these manifestations.”

epithelial cells, and they are over- cells as the to antigen, setting try, then this inflammatory process expressed in the face of dessica- in motion degranulation, release of and its treatment makes perfect sense. tory stress. T-lymphocytes abound and the start to the allergic throughout the body, and their acti- cascade. PROPER DIAGNOSIS vation results in inflammation. When Topical steroids potently inhibit AND TREATMENT T-lymphocyte cells are activated, they this process and subdue the inflam- The genesis of most cases of dry eye release pro-inflammatory cytokines. mation. NSAIDs and Restasis (cyclo- disease lies in the meibomian glands. These cytokines lead to the develop- sporine 0.05%, Allergan) also inhibit Perhaps it is our diets and lifestyles ment of tissue inflammation. On the this process, but in a more attenuated that set the stage for altered meibum surface of T-lymphocytes are recep- manner.3-4 This is why we initiate function; the pathophysiology has not tors called lymphocyte functional as- anti-inflammatory therapy with the been fully elucidated. sociated antigen (LFA). ICAM binds most efficacious suppressor of inflam- Not all meibomian gland disease (ligands) to the LFA, thus activating mation: a topical corticosteroid. As is immediately evident. We can test the T-cell lymphocytes, setting the in- per our algorithm, we use Lotemax* for “non-obvious” meibomian gland flammatory cascade in motion. QID for two weeks, then BID for disease by pressing on the meibomian Investigational data shows that li- two more weeks. Should lifitegrast glands to qualify and quantify their fitegrast blocks recruitment and acti- gain FDA approval, we plan to try secretions. This is a diagnostic maneu- vation of T-lymphocytes to the ocular using this agent concurrently at the ver that needs to be a routine part of surface by binding to LFA on the sur- time we reduce Lotemax to BID. The the comprehensive . face of T-lymphocytes and preventing drug’s Phase III OPUS-1 trial showed Performing meibography could/ LFA from interacting with ICAM on improvement in corneal and conjunc- should be entertained as well. Just the surface of the corneal epithelial tival staining associated with ocular as OCT has revolutionized posterior cells and on other immune cells resid- inflammation.5 pole evaluation, so will meibography ing in the ocular surface tissue.2 When you understand the basic for MGD. Unfortunately, just as with Think of IgE receptors on mast biochemistry and medicinal chemis- asymptomatic glaucoma, it is difficult

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THIS DEVICE IS A REAL TEAR-JERKER 180 days.2 Specific neurological pathways are crucial to It is well said that “necessity is the mother of invention,” maintenance of a healthy ocular surface. Delivery of low and herein we share just how true this is. levels of intranasal neuronal stimulation activates these Most chronic conditions present a management chal- pathways, which stimulates tear production.

lenge. Dry eye is a perfect example. Photo: Allergan The precorneal tear film has three Certainly, we have essential fatty acids sub-layers, and it is yet to be fully deter- to help meibomian gland disease.1 We mined if there is an effect on mucin have good quality lipid-based artifi- and/or lipid layers in addition to aque- cial tears and good anti-inflammatory ous layer enhancement. A 2016 ARVO medicines. While these can be helpful abstract, however, does show con- to many patients, there is always a junctival goblet cell degranulation and need for other beneficial interventions. increased mucin level after ILN.3 Enter a new idea currently in clinical We foresee a definite, but not yet trials called intranasal lacrimal neuro- quantified, role for this device, but we stimulation (ILN). A battery-powered will not know the exact stage of disease device generates a low-grade electri- or optimum frequency of application cal current that stimulates lacrimation until widespread clinical application. We when applied to the interior aspect are excited to see the potential of intra- of the nose—not copious tearing, nasal lacrimal neurostimulation for dry but rather more of a physiological eye treatment. enhancement of natural tear produc- Trials are ongoing. Hopefully, we will tion. This genius concept seems to have more to write on this device truly help many patients suffering from year, pending FDA approval. dry eye disease.

Allergan acquired this technology from the original 1. Malhotra C, Singh S, Chakma P, et al. Effect of oral omega-3 Fatty Acid supplemen- tation on sensitivity in patients with moderate meibomian gland dysfunc- research and development company Oculeve, and plans to tion: a prospective placebo-controlled study. Cornea. 2015 Jun;34(6):637-43. commercialize such a device in the event of FDA approval. 2. Chayet A. Evaluation of the effect of intranasal lacrimal neurostimulation on tear production in subjects with dry eye: nonrandomized open-label study. ASCRS 2016 In one study, this handheld instrument, self-administered paper session 3-A. by patients four times a day, showed increased tear pro- 3. Gumus K, Schuetzle K, Loudin JD, Pflugfelder SC. Randomized, controlled, crossover trial comparing the impact of sham or intranasal neurostimulation on duction and reduced corneal/conjunctival staining out to conjunctival goblet cell degranulation ARVO 2016 abstract 2864.

to get patient cooperation in the treat- not wholly practical at this time. integrity of the epithelial tissue, and ment of asymptomatic dry eye disease. Regarding diagnosis of dry eye measure the tear film breakup time. Success in getting patients to consis- disease, the approach we use is pro- As part of our diagnostic protocol tently use warm soaks, eyelid massage foundly simple: for dry eye disease, these three steps (including LipiFlow, etc.) and fish oil 1. First, take a history of the pa- offer us the information needed to supplementation at these pre-symp- tient’s symptoms make the diagnosis and provide su- tomatic stages of dry eye/meibomian 2. Next, assess the height and vol- perb patient care. gland disease is a challenge. The real- ume of the lacrimal lake When patients do present with ity is, early intervention in meibomian 3. Stain the cornea with fluorescein symptomatic dry eye disease, we have gland disease may be ideal, but it is or lissamine green dye to assess the quite a few options for resolution.

FROM THE LITERATURE genesis, various anti-inflammatory agents were used to treat this syndrome. In particular, there is a type I level of SUPPRESS INFLAMMATION evidence on efficacy. Among these, 0.5% TO TREAT DED loteprednol etabonate was effective in reducing signs and symptoms of dry eye … Modulating the expression of proin- Dry eye is a complex, multifactorial condition of the ocular flammatory and proapoptotic molecules may have a thera- surface whose pathogenesis can be attributed to two dif- peutic potential for the treatment of the corneal epithelial ferent mechanisms, namely reduced tear production and disease that develops in dry eye.” increased tear evaporation, both inducing increased tear

osmolarity and inflammation, according to a recent study in Aragona P, Aguennouz M, Rania L, et al. Matrix metalloproteinase 9 and transgluta- Ophthalmology: minase 2 expression at the ocular surface in patients with different forms of dry eye disease. Ophthalmology. 2015 Jan; 122(1):62-71. “Given the importance of inflammation in dry eye patho-

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013_dg0516_Dry eye_v3_BK.indd 16 5/4/16 5:46 PM FROM THE LITERATURE sures. Topically applied corticosteroids can suppress acute environmentally induced ocular surface inflam- DESSICATORY STRESS AND STEROIDS mation.” A recent study sheds light on the environmental factors • “In conclusion, our study shows that corticosteroids that can impact our dry eye patients. can mitigate the adverse effects of low-humidity envi- • What can treat dry eye in a dry environment? “In this ronmental stress on the ocular surface in individuals study, we found that dry eye signs and symptoms with dry eye disease. This suggests that the increased worsened after exposure to low-humidity environment irritation and ocular surface epithelial disease that when subjects were untreated and also when subjects develops following a desiccating environmental chal- were treated with 2 weeks of artificial tears. However, lenge is attributable to inflammation that can be mod- after 2 weeks of treatment with dexamethasone, ulated by a corticosteroid.” subjects reported decreased eye irritation symptoms Rather than dexamethasone, we would use either compared to their initial evaluation, and they had a Lotemax gel or generic because of the significantly lower increased in HLA-DR expression extended margin of safety. and reduced corneal and conjunctival staining after Moore QL, De Paiva CS, Pflugfelder SC. Effects of dry eye on environ- the low-humidity exposure compared to prior expo- mentally induced ocular surface disease. Am J Ophthalmol. 2015 Jul;160(1):135-42.

Because almost all dry eye disease is ment is achieved. The omega-3 essen- um-quality fish oil. It is our opinion expressed as a result of meibomian tial fatty acids found in fish (or flax- that a pharmacist should know more gland disease, evidence exists that seed) oil enhance meibomian gland about the nuances of fish oil than there is a lipid-deficient dry eye state; function, and this therapy is likely most clinicians. so we should, at the very least, start enhanced with warm soaks. For patients with a history of dif- the patient on a lipid-based artificial We guide the patient to consult ficulty swallowing large capsules, rec- tear, such as Soothe XP (Bausch + with a pharmacist regarding a premi- ommend either Coromega Omega-3 Lomb) or Systane Balance (Alcon). For those rare patients we encoun- FROM THE LITERATURE ter who need a preservative-free tear, Retaine MGD (OcuSoft) or Refresh Optive Advanced Preservative Free EFFICACY OF LOTEMAX GEL (Allergan) are excellent. Gel formula- FOR EVAPORATIVE DED & MGD tions, such as Systane Gel (Alcon) or In some big news for treatment of patients with evaporative dry eye (EDE) GenTeal Gel (Novartis) can be used disease and meibomian gland dysfunction (MGD), a study presented at a at bedtime if needed, which is not all poster session at the annual American Academy of Optometry meeting in that often. October 2015 on the efficacy of off-label use of loteprednol etabonate oph- If there is concurrent blepharitis, thalmic gel 0.5% for treating evaporative DED and MGD found: warm soaks followed by meticulous • When used twice a day, loteprednol etabonate ophthalmic gel eyelid hygiene can be quite helpful. 0.5% significantly improved the clinical signs associated with EDE Hypochlorous acid in solution is an resulting from MGD. efficient antimicrobial agent, report- • Loteprednol etabonate ophthalmic gel 0.5% showed significant ed to have a >99.99% kill for many reduction in severity of symptoms associated with EDE resulting pathogens.6,7 Anecdotally, it appears from MGD. • Results indicate that loteprednol etabonate gel is a safe and the newer hypochlorus acid scrubs effective treatment option for EDE and MGD. (e.g., NovaBay, Ocusoft, etc.) work In this open-label, prospective, multi-centered study, patients well. The main drawback to these is with meibomian gland dysfunction were treated bilaterally with the necessity for the patient to pur- loteprenol gel 0.5% twice a day for 30 days. After treatment, all chase cotton pads at the pharmacy objective parameters evaluated showed a statistically significant improve- on which to spray the hypochlorus ment, except for Schirmer II and tear osmolarity. Results also showed a sig- acid solution prior to performing lid nificant reduction of patient symptoms as measured by the OSDI and SPEED. scrubs. IOP and visual acuity were unchanged, and no adverse events took place. We start almost all of our patients on 2,000mg of fish oil daily, telling Opitz, DL, Evola C, Paradesi A, et al. (2015, October). Efficacy of loteprednol etabonate ophthalmic gel 0.5% for the treatment of evaporative dry eye and meibomian gland dysfunction. Poster presented at the meeting them that it may be four to six months of the American Academy of Optometry, New Orleans, LA. before the full benefit of the supple-

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Orange Squeeze or Nordic Naturals One non-coded procedure that . The former is flavored as we increasingly perform for our dry KEEP IN MIND orange sherbet; the latter has a mild eye patients involves gently scraping lemon flavor. across the top of the eyelid three to If the patient is moderately symp- five times with a golf club spud. This tomatic at presentation, we don’t hes- inevitably seems to make our patients itate to concurrently initiate Lotemax feel better right away (maybe like a gel QID for two weeks, and then BID back scratch), but its main benefit is for two more weeks. It is well estab- to help open the meibomian gland ori- lished that inflammation is central to fices and smooth the top surface of the symptomatic dry eye disease, so sup- eyelids, further enhancing meibum se- pressing the inflammatory compo- cretion flow into the tear film, thereby Clogged meibomian gland orifices nent is imperative in effecting relief bolstering the lipid layer. restrict lipid secretion and lead to of symptoms. We strongly prefer lote- Patients with persistent photopho- evaporative dry eye. prednol because of its advanced safety bia and discomfort/pain may have profile. Fluorometholone 0.1% oph- keratoneuralgia, a highly complex thalmic suspension can also be used, and not well-understood disease. A PERSPECTIVES AND but it does not enjoy the same level of consult visit with a cornea subspecial- PEARLS ON DRY EYE safety as the ester-based loteprednol ist or with a Though not a part of the scientific (see “Steroids for Dry Eye Disease— would be in order. Centrally acting literature, a recent review article Effective and Safe Long-Term Treat- medicines such as gabapentin can oc- offered some practical tips. ment,” page 27). Lotemax gel does casionally be employed in these un- • Dry eye “is associated with not need to be shaken, whereas fluo- common situations. contact lens use, cigarette , , prolonged rometholone drops must be shaken video display viewing and well prior to each instillation. GETTING CONTROL low-humidity environments.” We generally see our dry eye pa- OF DRY EYE DISEASE • “The two major types of DED tients back in one month to assess their Several pharmacologic options are are aqueous tear deficiency progress. If dry eye symptoms persist available (or may soon be) for main- and evaporative dry eye.” after a month of topical corticoste- taining symptomatic control of dry Regarding distinguishing the roid therapy and use of a lipid-based eye disease, once it has been achieved. two, “The reality is that it’s artificial tear, we certainly consider • Enduring use of Lotemax* gel pretty hard to tell. There’s no punctal plugs. If all of these measures drops once (or twice) daily sure fire test.” fail to bring about relief (which some- • Lifitegrast BID (pending approval) • Because about one in 10 times occurs, but uncommonly), do • Restasis BID patients with DED may have not forget Lacrisert inserts. • Pulse dosing of Lotemax* gel drops Sjögren’s syndrome, “these For a minority of patients whose The last option is likely the best ap- patients often complain of dry symptoms return upon discontinu- proach in our experience, considering mouth, fatigue, and joint pain. ation of the corticosteroid, we try both efficacy and cost. The literature The clinician should always loteprednol BID for another month, fully supports the concept of pulse inquire about these symptoms and then once daily for another cou- dosing. As one example, the Asclepius in assessing dry eye patients.” ple of months, with the goal of trying Panel recommends practitioners begin We fully agree. to find the least amount of drug suffi- early treatment with an anti-inflam- • For moderate to severe cases cient to keep the patient comfortable. matory agent (such as Lotemax) four of dry eye, “start with a ste- We have several patients who require times a day to improve symptoms roid four times a day for two Lotemax gel once (or twice) daily to and to prevent disease progression, weeks then taper to twice a day for two weeks. No more achieve this state. Our patients typi- reducing frequency to twice daily af- than two to four weeks of cally do very well. However, for pa- ter two weeks and supplemented with treatment is recommended.” tients who do not respond well to this Restasis twice a day.3 We might see a • “If you’re going to use punctal therapy, topical cyclosporine (Resta- patient who has achieved good con- plugs, put in the largest plug sis) can provide modest but long-term trol and comfort, but after several possible because it’s more 8 suppression of inflammation. We weeks or months her eyes begin to be likely to stay in.” Agreed. would begin with BID dosing for a symptomatic again. Here’s where she few months, then QD for continued could use Lotemax* gel drops three Karmel M. A Quick Guide to Dry Eye. EyeNet Magazine. 2014 Jun;19(6)40-6. maintenance. or four times a day for four to seven

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013_dg0516_Dry eye_v3_BK.indd 18 5/4/16 5:47 PM FROM THE a steroid eye drop for a month, and LITERATURE subsequently consider punctal plugs if the aforementioned treatments are DEPRESSION AND DRY EYE: IS THERE A LINK? not sufficient. Once there’s clinical improvement, be mindful of the need An important study found that people with dry eye disease are about the three times more likely to have anxiety and/or depression. for long-lasting control. “Perhaps the treatment of dry eye disease, then, would also benefit from Due to cost concerns, try to keep treatment of depression and/or anxiety,” the authors wrote. (This is yet to be on hand coupons for all brand-name determined, but is a plausible concept.) By the same token, perhaps proper eye medicines. This will require the management of dry eye disease could help to some degree with depression optometrist to actively reach out to and/or anxiety. the various drug companies to request that coupons be made available to van der Vaart R, Weaver MA, Lefebvre C, et al. The association between dry eye disease and depression and them for the benefit of their patients. anxiety in a large population-based study. Am J Ophthalmol. 2015 Mar;159(3):470-4. www.GoodRx.com is a resource that can help doctors find the least expen- The importance of sive sources in their areas. ■

monitoring for poten- 1. Nichols KK, Foulks GN, Bron AJ, et al. The interna- tial steroid response, tional workshop on meibomian gland dysfunction: ex- ecutive summary. Invest Ophthalmol Vis Sci. 2011 Mar particularly in those 30;52(4):1922-9. patients who use a topi- 2. Perez V, Pflugfelder S, Zhang S, et al. Lifitegrast, a nov- el integrin antagonist for treatment of dry eye disease. cal corticosteroid regu- Ocul Surf. 2016 Epub Jan 22. larly or on pulse dosing, 3. Donnenfeld E, Sheppard JD, Holland EJ, et al. Pro- spective, multi-center, randomized controlled study on should not go unsaid. the effect of loteprednol etabonate on initiating therapy with cyclosporin A. Presented at the AAO Annual Meet- Patients have a ten- ing. 2007; New Orleans. dency to become “com- 4. Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflam- matory drugs in ophthalmology. Surv Ophthalmol. 2010 fortable” using topical Mar-Apr;55(2):108-33. To debride the lower lid margin, gently wipe a golf club corticosteroids, and a 5. Sheppard JD, Torkildsen GL, Lonsdale JD, D’Ambrosio spud repeatedly across the margin to remove debris. FA, et al. Lifitegrast ophthalmic solution 5.0% for treat- steroid response could ment of dry eye disease: results of the OPUS-1 phase 3 lead to ocular hyperten- study. Ophthalmology. 2014 Feb;121(2):475-83. 6. Wang L, Bassiri M, Najafi R, et al. Hypochlorous acid days; this almost always regains pa- sion in a few cases if patients are not as a potential wound care agent: part I. Stabilized hy- pochlorous acid: a component of the inorganic arma- tient comfort. Most patients need to periodically checked for intraocular mentarium of innate immunity. J Burns Wounds. 2007 pulse dose a couple of times a year. It pressure spikes. Apr;6:e5. 7. Kim HJ, Lee JG, Kang JW, et al. Effects of a low is a steroid-sparing and cost-effective concentration hypochlorous acid nasal irrigation solu- tion on bacteria, fungi, and virus. Laryngoscope. 2008 approach. We are hopeful that lifite- In summary, always inquire of Oct;118(10):1862-7. grast may give us another option at patients about how their eyes feel; 8. Food and Drug Administration. Draft Guidance on Cyclo- sporine. June 2013. Available at: www.fda.gov/ this stage, pending FDA approval and select a lipid-based artificial tear, get downloads/drugs/guidancecomplianceregulatoryinfor- clinical validation. them on fish or flaxseed oil, consider mation/guidances/ ucm358114.pdf.

FROM THE LITERATURE as a problem, the long-term course of the disease is not yet well characterized.” LONG-TERM PERSPECTIVE • “One of the most consistent correlates of worsening ON DRY EYE DISEASE was a record of past severe symptoms. This finding A study following about 700 patients over a decade of is in line with the idea that patients who present with dry eye care suggests that “DED is not necessarily pro- more severe symptoms early in the course of their gressive over the long-term, and most men and women disease are the ones who are most likely to experi- report no change or some level of improvement.” ence a worsening, usually despite therapy.” • “Clinical tests in dry eye disease tend to have We fervently hope that some sort of intervention poor reproducibility, and symptoms and signs will soon be discovered or invented to help the masses may fluctuate. Newer technologies such as in vivo who suffer with DED. In the meantime, there are rational and tear osmolarity also have approaches as outlined in this drug guide, that when limitations.” properly applied, can be of significant help to many.

• “Even with therapy, dry eye disease tends to persist, Lienert JP, Tarko L, Uchino M, et al. Long-term natural history of dry eye disease but despite data supporting the importance of DED from the patient’s perspective. Ophthalmology. 2016 Feb;123(2):425-33.

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013_dg0516_Dry eye_v3_BK.indd 19 5/5/16 12:45 PM NONSTEROIDAL DRUGS

CLINICAL UPDATE ON THE NSAIDs

While oral he field of nonsteroidal anti- OF NSAIDS inflammatory drugs has many Let’s first understand the pharmacology nonsteroidals players. Older drugs have been of NSAIDs. First of all, they don’t directly are heavily reformulated and new drugs reduce inflammation. Rather, they inhibit Thave come to market. The an along the synthetic pathway to used in newest editions, Prolensa ( so- the production of , which dium 0.07%, Bausch + Lomb) and Ilevro are powerful mediators of inflammation. systemic (nepafenac 0.3%, Alcon), are the super- As doctors, it is vital that we have knowl- stars of this class and need to be used only edge of this particular pathway—the ara- medicine, once daily. This should be a blessing to chidonic acid cascade. post-op patients by reducing the As you can see in the diagram (“The topical intensity of their eye drop regimen. Pathway,” page 21), ophthalmic While oral NSAIDs are heavily used the origin substrate for inflammatory in systemic medicine, topical ophthalmic mediators is phospholipids released from NSAIDs have NSAID use within nonsurgical eye care cell membranes as a generic response to is relatively limited. The foundational multiple causes of cellular microtrauma. limited use in perspective on this class of drugs is the Corticosteroids inhibit the conversion of acknowledgement that steroids reign su- these phospholipids to arachidonic acid nonsurgical preme in inflammation control; topical (AA) by inhibiting the catalytic enzyme eye care. NSAIDs are never an appropriate substi- phospholipase A2 early in this synthetic tute when the clinical condition merits a cascade. topical corticosteroid. Once AA is formed, two different en- NSAID use has much more applicabil- zymes convert it to either or ity in perioperative care than in primary . converts AA eye care; however, several clinical circum- to prostaglandins, and lipoxygenase con- stances merit use of such a drug in order verts AA to . The key point to enhance patient care. here is that while NSAIDs inhibit the en-

NONSTEROIDAL ANTI-INFLAMMATORIES BRAND NAME GENERIC NAME MANUFACTURER DOSAGE PEDIATRIC USE BOTTLE SIZE(S) Acular LS ketorolac tromethamine 0.4% Allergan, and generic QID 3 years 5ml Acuvail bromfenac 0.075% Allergan BID N/A unit-dose Bromsite bromfenac 0.075% N/A N/A 5ml Ilevro nepafenac 0.3% Alcon QD 10 years 1.7ml Nevanac nepafenac 0.1% Alcon TID 10 years 3ml Prolensa bromfenac 0.07% Bausch + Lomb QD N/A 1.6ml, 3ml Voltaren sodium 0.1% Novartis, and generic QID N/A 2.5ml, 5ml

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0020_dg0516_NSAIDS_v3.indd20_dg0516_NSAIDS_v3.indd 2200 55/4/16/4/16 5:515:51 PMPM THE ARACHIDONIC ACID PATHWAY

Trauma

Membrane Phospholipids Inhibited by Phospholipase A2 corticosteroids Arachidonic Acid

Inhibited by Cyclo-oxygenase Lipoxygenase NSAIDs

Endoperoxides Hydroperoxides

Thromboxane A2 Prostaglandins Leukotrienes and

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

zymatic activity of cyclooxygenase, oxygenase and lipoxygenase, thus in- frequency). However, this synergy is they have no effect on lipoxygenase, hibiting production of prostaglandins difficult to reconcile based on the dy- thereby allowing the production of and leukotrienes. namics of the AA cascade previously leukotrienes to go unchecked. The AA pathway is more eas- discussed. Perhaps the rapidity of For clinical perspective, remember ily grasped by studying the diagram, onset and/or the degree of enzymatic the early days of photorefractive kera- which illustrates the processes we inhibition may be considerations for tectomy where NSAIDs were initially have just described. Once you have a explanation. used postoperatively? Patients experi- clear understanding of the AA path- Contrarily, we find no literature enced problems with white blood cell way, then you can prescribe with supporting the use of both drug (leukocytic) corneal infiltrates until it enhanced clinical authority and pre- groups in the standard initial treat- was realized that steroids prevented cision. ment of anterior uveitis. A great deal their formation. Why? Because leu- Steroids and NSAIDs are thought remains to be understood in how kotrienes are chemotactic for leuko- to demonstrate some synergy, and these drug classes modify tissue re- cytes, for which NSAIDs do noth- therefore, might be beneficial used sponses. ing—they only inhibit the synthesis concurrently. For example, standard- of prostaglandins and have no activ- of-care treatment of postoperative ROLE OF TOPICAL NSAIDS ity against lipoxygenase-catalyzed cystoid is usually Compared to topical corticosteroids, production of leukotrienes. Because treated with a potent corticosteroid, NSAIDs play a limited role in prima- steroids work higher up in the AA such as Durezol, and a topical NSAID ry eye care. Nonetheless, several situ- synthetic pathway, they inhibit cyclo- (dosed at its FDA-approved dosing ations demonstrate where NSAIDs

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FROM THE LITERATURE NSAIDs significantly reduced the odds of developing cys- toid macular edema, as compared to topical corticosteroids. UPDATE ON NSAIDs FOR CME • Approximately 0% to 6% of non-diabetic subjects Cystoid macular edema, known academically as Irvine-Gass develop visual complaints and suffer from clinically signifi- syndrome, is the most common cause of post-cataract sur- cant macular edema. In contrast, incidence rates of clini- gery . Are topical NSAIDs of clinically sig- cally significant macular edema are up to 56% in diabetic nificant value in managing the small subset of postoperative patients with mild to moderate nonproliferative diabetic patients who develop cystoid macular edema? and no cystoid macular edema preoperatively. A seminal work addressing this issue appeared in • Results of this meta-analysis show that topical NSAIDs Ophthalmology (November 2015).1 Below are excerpts: significantly reduced the odds of developing CME, as com- • Because many cases of CME are mild and resolve spon- pared to topical corticosteroids in non-diabetic and mixed taneously, it remains unknown whether prophylactic NSAID populations. Furthermore, a combination of topical NSAIDs treatment improves long-term visual outcomes. It also and corticosteroids significantly reduced the odds of devel- remains unclear whether prophylactic treatment prevents oping cystoid macular edema in non-diabetic and diabetic the onset of chronic CME (present >six months after sur- patients, as compared to topical corticosteroids in a single gery) or in some way decreases its severity. drug treatment. Based on an indirect treatment comparison, • In conclusion, there is a lack of level I evidence that sup- no difference could be found between topical combination ports the long-term visual benefit of NSAID therapy when treatment and topical NSAIDs in non-diabetic patients. applied solely or in combination with corticosteroid therapy As can be seen from these articles, there is no defini- to prevent vision loss resulting from CME after cataract tive consensus yet on the best therapeutic intervention to . The implication that the combined effect of NSAID diminish or prevent cystoid macular edema. We anticipate and corticosteroid exceeds the additive effect of these that use of NSAIDs and steroids in contemporary cataract drugs is not supported by the literature. Dosing of NSAIDs care will continue unabated for the foreseeable future. before surgery seems to hasten visual recovery after cata- 1. Kim SJ, Schoenberger SD, Thorne JE, et al. Topical nonsteroidal ract surgery, but does not affect long-term visual outcomes. anti-inflammatory drugs and . Ophthalmology. 2015 Another article, from the American Journal of Nov;122(11):2159-68. 2 2. Wielders LHP, Lambermont VA, Schouten J, et al. Prevention of cys- Ophthalmology (November 2015), gave these observations: toid macular edema after cataract surgery in nondiabetic and diabetic • In non-diabetic patients, it was found that topical patients: A systematic review and meta-analysis. Am J Ophthalmol. 2015 Nov;160(5):968-981.

can be beneficial. (See “Consider an what in effect. Systemic NSAIDs are their forté in ocular surface pain ame- NSAID For...,” page 23.) true to their name and do indeed ren- lioration and provide only limited ac- However, be aware that topical der a significant anti-inflammatory tivity against inflammation. and systemic NSAIDs differ some- effect, whereas topical NSAIDs have Diclofenac (Voltaren 0.1%, No- vartis) and ketorolac (Acular LS NEW NSAID APPROVED WITH 0.4%, Allergan) have historically CATARACT SURGERY INDICATION been the standard bearers of topical In early April 2016, the FDA approved BromSite (bromfenac 0.075% oph- NSAID care. Both are used QID and thalmic solution, Sun Pharma), the first NSAID with the specific indication for are largely clinical equivalents. One preventing ocular pain in patients undergoing cataract surgery. Like other study that compared ketorolac and NSAIDs, it’s also indicated for treating postoperative inflammation. diclofenac head to head concluded: BromSite achieves its low 0.075% concentration due to its DuraSite deliv- “The decrease in corneal sensitivity ery vehicle (developed by InSite Vision), which is believed to extend the in normal human is more drug’s residence time on the ocular surface. (Sun Pharma acquired InSite pronounced and longer lasting with 1 Vision in November 2015.) diclofenac than with ketorolac.” In two Phase III clinical trials, a greater number of patients treated with A modification of ketorolac is the BromSite were pain-free at one day post-op (77% and 82%) compared development of a 0.45% concentra- with those given only the vehicle (48% and 62%). Also, more patients given tion: Acuvail (Allergan) comes as a BromSite were free of inflammation at 15 days post-cataract surgery com- preservative-free unit-dose indicated pared with patients given only the vehicle. Sun Pharma expects BromSite to for perioperative use BID one day come to market in the second half of 2016. prior to cataract surgery, and is con- tinued for two weeks postoperatively. InSite Vision Announces FDA Acceptance of NDA Filing for BromSite (0.075% bromfenac). Avail- able at: www.businesswire.com/news/home/20150817006205/en/InSite-Vision-Announces-FDA- The original formulation of oph- Acceptance-NDA-Filing (last accessed April 25, 2016). thalmic ketorolac (Acular) was a 0.5%

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0020_dg0516_NSAIDS_v3.indd20_dg0516_NSAIDS_v3.indd 2222 55/4/16/4/16 5:515:51 PMPM CONSIDER AN NSAID FOR... KEEP These are most common conditions for which topical IN MIND NSAIDs can play an adjunctive beneficial role. • Corneal abrasions • Just before and just after in-office Betadine 5% sterile ophthalmic prep solution treatment for acute, symptomatic EKC • Post-foreign body removal • Adapting to RGP contact lenses • Post-anterior stromal puncture procedure • Post-PKP, or any surface-disruptive laser procedure solution, but marked stinging upon • Treating and/or preventing cystoid macular edema instillation was its Achilles’ heel. The • Adapting to punctal plugs drug was reformulated several years • ago to a 0.4% solution (Acular LS) • Supplement to steroids in treating recalcitrant uveitis and is now quite tolerable. • Some cases of keratitis-related Following these, two more NSAIDs • Post-cataract surgery care came to market. They were Brom- • Supplemental to oral NSAIDs in treating day (bromfenac ophthalmic solution • Treating and/or preventing inflamed pterygia and pingueculae 0.09%, Bausch + Lomb) and Neva- • Quick ophthalmoscopy to rule out concurrent intraocular disease nac (nepafenac ophthalmic suspension 0.1%, Alcon). Bromday is dosed once daily and is both in 7.5ml bottles. Because Pro- also approved to treat ocular allergy, well tolerated; however, be aware that lensa is a solution and not a suspen- along with a number of other appli- Bromday was discontinued in 2013. sion, shaking the bottle before use is cable uses for NSAIDs relevant to pri- Be aware that any product containing not required. mary eye care, as enumerated above. bromfenac should not be used for a pa- Ilevro (nepafenac 0.3%, Alcon) Because of the rare, but real, poten- tient with a sulfite allergy. achieves once-daily dosing by increas- tial for corneal toxicity and melting, Nevanac, an ophthalmic suspen- ing the concentration from Nevanac use these drugs cautiously when there sion, is the first available NSAID pro- (nepafenac 0.1%). Ilevro comes in is preexisting corneal epithelial com- drug. Upon instillation, nepafenac is a 1.7ml bottle, whereas Nevanac is promise. As a general rule, we never enzymatically converted to dispensed as 3ml in a 4ml bottle. The prescribe any topical NSAID for use sodium, which, like all NSAIDs, inhib- innovative bottle design of Ilevro is beyond two weeks—with the excep- its cyclooxygenase. It is dosed three identical to the bottle used by Tra- tion of cystoid macular edema, which times a day. vatan Z. Because Ilevro is a suspen- we treat with a topical NSAID for a sion, the bottle must be shaken before month concurrently with a potent ste- NEWER NSAIDs the drop is instilled. Its pediatric indi- roid, such as Durezol. While steroids In recent years, newer generations cation is down to age 10. are often initially dosed as frequently of these products came to market. Both these new formulations are Prolensa (bromfenac 0.07%, Bausch FDA-approved to treat pain and in- + Lomb) potentiates penetration of flammation associated with cataract the bromfenac molecule, thereby al- surgery. Both are dosed once daily: lowing for a decreased concentration the day before surgery, the day of (0.07%) while maintaining once-dai- surgery, and for 14 days postsurgical- ly dosing. Prolensa contains 22% less ly. Both are indicated for pregnancy drug than Bromday’s 0.09% concen- category C, preserved with 0.005% tration, and its pH has been lowered BAK and have pHs close to 7. from 8.3 to 7.8. This pH modifica- tion is what enables the lower con- All of these NSAID drugs are gen- centration of Prolensa to clinically erally approved by the FDA for treat- perform as well as Bromday. It has ing postoperative inflammation, and Cystoid macular edema before (top) 0.005% BAK as the preservative and as such, will be used much more in and after (bottom) therapy. comes in two sizes: 1.6ml and 3ml, a surgical context. Ketorolac 0.5% is

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FROM THE LITERATURE reported that concurrent administration of NSAIDs and corti- costeroids results in additive effects. ESSENTIAL LITERATURE ON NSAIDs “At present, there is no evidence to suggest one topical If you want the ultimate review of NSAIDs, we urge NSAID treatment is better than another in controlling post- you to read “Nonsteroidal Anti-inflammatory Drugs in operative inflammation.” Ophthalmology,” by Stephen J. Kim, MD, Allan J. Flach, MD, • “CME remains the most common cause of vision loss and Lee M. Jampol, MD, in Survey of Ophthalmology, March- after cataract surgery. Despite its significance, the patho- April 2010. It is excellent. Some quotes (or in-context para- genesis of this syndrome, and its relationship to and its phrases) from this article, and our commentary (indicated in associations with CME in other diseases, is not completely purple), follow: understood. • “NSAIDs do not inhibit lipoxygenase (LPO) and thus do “Systemic NSAIDs provide insufficient drug levels to not typically prevent generation of leukotrienes. This may inhibit prostaglandin production in the anterior segment, explain, in part, their decreased anti-inflammatory effects especially when compared to topical administration. compared to corticosteroids, which inhibit both LPO and “The true incidence of CME following cataract surgery COX (cyclooxygenase). However, celicoxib (Celebrex) and is not precisely known. Despite this continued uncertainty, diclofenac (Voltaren) are notable exceptions and inhibit recent studies have reported incidences following small-inci- LPO by direct and indirect means, respectively. In addition, sion cataract surgery as high as 9% to 19% using fluorescein NSAIDs appear to have anti-inflammatory and anti-angio- angiography, and 41% as measured by OCT. genic effects independent of their inhibition of COX. Several “It has long been recognized that the natural history of reports suggest that ketorolac is the most potent inhibitor of CME usually includes spontaneous resolution. COX-1, while both bromfenac and amfenac have staked the “Although there is no FDA-approved treatment for the claim as being the most potent inhibitors of COX-2. prevention or treatment of CME following cataract surgery, “The clinical importance of selective COX-1 and COX-2 an extensive review of the world literature … concluded that inhibition for ocular disease remains to be established.” prevention and treatment of CME with NSAIDs is beneficial The prostaglandins produced via COX-1 are physiologic in … Available evidence suggests that topical NSAIDs may pre- their action, whereas the prostaglandins produced from the vent and treat CME when used alone or concurrently with upregulation of COX-2 result in pathologic expression of pain corticosteroids.” and inflammation. This is another example of where the scientific litera- • “There is good evidence that topical NSAIDs may be ture trumps FDA guidelines. “Off-label” use of medicines is used in place of, or in addition to, topical corticosteroids becoming more and more commonplace, so don’t let other after cataract surgery to avoid excessive inflammation considerations override sound, rational and prudent use of a and to improve visual acuity. Although none of the studies helpful drug. reviewed by the FDA used topical NSAIDs more than 24 • “Although no other topical NSAID has been approved hours before cataract surgery, well-designed studies sug- for allergic conjunctivitis besides ketorolac, there are studies gest potential benefit from preoperative dosing regimens of suggesting that 0.1% diclofenac and 0.09% bromfenac may up to three days. Furthermore, several clinical studies have also be effective.

as hourly for a few days, we recom- inducible enzyme, which is primarily appears to be less likely to cause such mend that NSAID use not exceed the activated during inflammatory tissue untoward events. All three of these FDA-approved dosing frequency. assaults. As a result, COX-2 inhibitors drugs were FDA-approved around the created great excitement when they year 2000. NOTES ON ORAL NSAIDs came to market years ago because they We rarely prescribe oral NSAIDs, Cyclooxygenase (COX) is the enzyme were purported to address inflamma- but do occasionally use Celebrex by which arachidonic acid is metabo- tion while sparing the physiological 100mg or 200mg BID to help our lized into prostaglandins. Two sub- prostaglandins, specifically sparing the patients in whom we have difficulty species of cyclooxygenase are: COX- GI tract from NSAID toxicity. tapering off oral when 1 and COX-2. Unfortunately, a couple of these treating orbital pseudotumor, stub- COX-1 is a constitutive enzyme that products, Vioxx () and Bex- born uveitis or scleritis. For example, synthesizes prostaglandins, which reg- tra (), were thought to sig- if the anterior uveitis tends to rebound ulate physiological functions such as nificantly increase the risk of heart when the oral prednisone is tapered in the GI tract, kidneys, and attack and stroke, and were removed below 20mg per day, we have been vascular endothelium. from the market.2 Celebrex () successful using Celebrex along with COX-2, on the other hand, is an is now used more conservatively, but 20mg for a week, then

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0020_dg0516_NSAIDS_v3.indd20_dg0516_NSAIDS_v3.indd 2244 55/4/16/4/16 5:515:51 PMPM “Studies have reported that ketorolac 0.5%, diclofenac prostaglandin analog; however, many patients will require 0.1% and bromfenac 0.09% are all effective in treating vernal discontinuation of the medicine.” conjunctivitis.” • “A recent prospective, randomized, placebo-controlled We use a potent topical corticosteroid to gain full con- trial observed no adverse events or changes in liver chem- trol of the vernal conjunctivitis first, and then perhaps try a istries in a large number of patients treated twice daily for topical NSAID to maintain that control. One could also con- 14 days with topical bromfenac. The off-label use of topical sider an antihistamine-mast cell stabilizer, or continue with NSAIDs for durations longer than this is common, and clini- Lotemax gel once to twice daily to keep the condition sup- cians should be vigilant for potential systemic toxicity. In pressed. addition, because eyelid closure and nasolacrimal occlusion • “Whereas topical corticosteroids are frequently helpful in can decrease systemic of topically applied medi- relieving episcleritis, topical NSAIDs appear to be less effec- cations by almost 70%, explaining these techniques to all tive. Systemic NSAIDs are of value in those unusual cases patients seems prudent.” where topical treatments are ineffective.” • “At present, there is no evidence that one NSAID is less This is an excellent reminder that when significant inflam- toxic than another. mation is present, it is a steroid that is needed—not an infe- “The more than two dozen cases of corneal perforations rior quasi-anti-inflammatory agent. reported with the introduction of topical corticosteroids over • “Regarding scleritis, although topical NSAIDs are not 30 years ago were likely related to improper clinical use and effective, systemic NSAIDs are used as first-line agents. patient follow-up. Thus, many topical medications have the Although many NSAIDs may be effective, indomethacin at potential for toxicity if unmonitored or used inappropriately.” 25mg to 50mg three times daily is most commonly used … A Note that “over 30 years ago,” it was not doctors of recent report indicated that the COX-2 selective NSAID, celi- optometry who performed “improper clinical use and patient coxib, at a daily dosage ranging from 200 to 800mg Q day follow up.” was effective in controlling diffuse anterior scleritis in 92% of • “Corneal perforations and melts have been reported with patients without producing any gastrointestinal effects.” the use of topical NSAIDs. Therefore, the routine use of topi- • “There is also evidence that NSAIDs are useful in the cal NSAIDs in dry eye patients may increase the risk of these treatment of inflamed pingueculae and pterygia.” adverse events.” We always use a topical corticosteroid first to get inflam- However, “a definite link between NSAID use and corneal mation controlled, then consider an NSAID to help keep the melt remains tenuous. Application of topical NSAIDs for rea- condition under control. We typically just maintain Lotemax sonable lengths of time in appropriate patients with proper gel once or twice a daily for most of these patients. monitoring appears safe. There is, however, evidence of the • “One in seven Americans receives a prescription for continued misuse of these medications.” orally administered NSAIDs each year.” As can be seen, there are occasions when a topical NSAID • “The most well known accompanying sys- can be useful; however, these uses are dramatically cast in temic NSAID use relate to the GI and central nervous sys- the shadow of corticosteroids. Always keep in mind that the tem … Often the GI toxicity can be partially ameliorated by rational, scientifically sound use of a drug “off label” may be

adding an H2 antagonist, proton pump inhibitor or in the very best interests of a patient.

10mg for a week or two, while con- (cimetadine) similarly protects the primary eye care. Their main use is in currently using Celebrex for four to gastrointestinal tissues. the prevention or treatment of cata- six weeks to facilitate the discontinu- With most oral NSAIDs, clinicians ract surgery-related cystoid macular ation of the oral prednisone. Aggres- should pay heed to the “black box” edema concurrent with a potent cor- sive use of Durezol and therapeutic warning of cardiovascular risk. The ticosteroid. Topical formulations cycloplegia is foundational to these FDA is strengthening its existing are far more commonly used in oral supplementary therapies. warning in labels eye care than orals, but the latter Risk of peptic ulcer disease is in- and OTC drug facts labels to indicate do play an important role in taper- creased when using both oral pred- that oral NSAIDs can increase the ing patients off oral steroid therapy nisone and an oral NSAID (including chance of a heart attack or stroke. when needed. ■ Celebrex), so we would likely also As well, oral NSAIDs can produce 1. Seitz B, Sorken K, LaBree LD, et al. Corneal sen- prescribe a proton pump inhibitor, hypoglycemia in type 2 diabetics by sitivity and burning sensation: comparing topical ketorolac and diclofenac. Arch Ophthalmol. 1996 such as OTC Prilosec or Prevacid drug interaction and can decrease re- Aug;114(8):921-4. 2. US FDA website. FDA Strengthens Warning of 20mg once daily when we are using nal function in susceptible patients. Heart Attack and Stroke Risk for Non-Steroidal such dual therapy. A histamine H In summary, NSAIDs have several Anti-Inflammatory Drugs. 2015 July 21. Available at: 2 www.fda.gov/ForConsumers/ConsumerUpdates/ receptor blocker such as Tagamet off-label uses within the context of ucm453610.htm (accessed April 7, 2016).

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UNLEASH THE POWER OF CORTICOSTEROIDS

ith more than 70 com- With this enlightened and clinically re- Topical bined years of intensive alistic background, let’s now look at this clinical care under our most helpful class of ophthalmic medicines. steroids are belts, we feel we have the most Wdeveloped a mature understanding of the clinical reality of cor- MAXIMUM EFFICACY essential and ticosteroids. STEROIDS It is distressing, and ultimately coun- The key to success in suppressing inflam- effective terproductive to patient care, that the use mation is to select an appropriate topi- of steroids is sometimes portrayed in the cal steroid medicine and have the patient medicines in classroom, at lectures and in the literature use it frequently until control is achieved, the treatment as “dangerous.” Steroids are highly effec- then tapering can begin as indicated. tive at treating nearly all aspects of ocular of any ocular surface and intraocular inflammation; they are extremely safe when used appropriately KEEP IN MIND inflammation. and, in our clinical experience, rarely cause complications, particularly when used for less than a month. Increased IOP is the RELATIVE CLINICAL most annoying serious , but EFFICACY OF TOPICAL this subsides with taper and cessation of STEROIDS therapy. Here, based on our clinical experi- Of course, there is always the rare pa- ence and the comparative infor- tient who does not respond to therapy as mation we have available, we rate anticipated—and may even worsen. For the relative efficacy of the topical that reason, we always end steroids, starting with the most effi- our patient treatment en- cacious: counters with a statement 1. 0.05% like: “This medicine should 2. 1% help you to be much better in just a couple of days. How- 3. Loteprednol 0.5% ever, if your eye(s) do not 4. 1% improve, or if you experience 5. Dexamethasone 0.1% any worsening, be sure to let 6. 0.1% me see you right away.” We 7. Fluorometholone 0.1% say this with confidence and Treat pingueculae like this one with a topical 8. Loteprednol 0.2% to make sure patients know steroid, then keep the ocular surface properly we have a keen interest in 9. Prednisolone 0.125% lubricated to prevent further inflammation. their well-being. 10. 1%

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026_dg0516_Corticosteroids_v3.indd 26 5/4/16 7:01 PM The two most efficacious topical ophthalmic corticosteroids in our experience are Durezol (difluprednate 0.05%, Alcon) and Pred Forte (prednisolone acetate 1%, Allergan)—but not generic predniso- lone acetate. (More on this below.) • Durezol. This drug is an emul- sion and does not need to be shaken before instillation. We use it as our “big gun” to treat advanced cases of iritis and episcleritis. Durezol’s longer duration of action permits LEFT: There is a large epithelial defect inferiorly. Note that the anterior two thirds of less frequent dosing than with pred- the cornea is heavily infiltrated, which nicely explains why the overlying epithelium is nisolone formulations, and provides secondarily compromised. This is a non-infectious epithelial defect, most likely as a 1 efficacy. So, typically we dose it ev- result of epithelial demise secondary to staphylococcal exotoxins. This defect is near ery two hours initially, rather than the limbus, which is very fertile soil for inflammatory events. The limbal area has an hourly. abundance of blood vessels that carry immune weaponry of both humeral immunity But along with Durezol’s increased (antibodies) and cellular immunity (leukocytes). This explains why most all events efficacy comes an increased risk of at or near the limbus are inflammatory in nature, and therefore why corticosteroid significant IOP elevation, especially suppression is so essential to hasten resolution of tissue compromise. in children.2 So, be sure to monitor IOP at follow-up visits. RIGHT: After just two days of an antibiotic/steroid combination, the epithelial defect • Pred Forte. Prednisolone acetate is healing rapidly. The antibiotic is for the benefit of the doctor; the steroid is for the 1% also has good anti-inflammatory benefit of the patient! It is vital to know why there is epithelial compromise. If such efficacy.3 Pred Forte is a workhorse is a result of anterior stromal inflammation (as evidenced by the rather profound and, like Durezol, is used primarily anterior corneal infiltration as seen in optic section), then a steroid is the drug best to treat significant cases of anterior suited to help restore these tissues. uveitis and episcleritis, and other se- vere ocular inflammatory conditions. expensive, they are also less effec- phosphate 1% solution (original brand Because it is a suspension, instruct tive.4 When the maximum effect is name Inflamase Forte), and generic your patients to shake it well prior to required, nothing surpasses brand- prednisolone acetate 1%. Dexametha- each instillation. name Pred Forte or Durezol. sone, either the solution or suspension Some pharmacists will dispense form, is also in this category. generic prednisolone acetate, even HIGH EFFICACY STEROIDS • Lotemax gel. This non-settling eye when you have specified “Dispense Next in clinical efficacy are Lotemax drop does not require shaking before as Written” on the Rx. Although gel (loteprednol 0.5%, Bausch + instillation. Don’t be confused because the generics are considerably less Lomb), generic prednisolone sodium it’s called a “gel”—when dispensed TOPICAL CORTICOSTEROID DRUGS BRAND NAME GENERIC NAME MANUFACTURER PREPARATION BOTTLE/TUBE Maximum Strength Steroids Durezol difluprednate 0.05% Alcon emulsion 5ml Lotemax gel loteprednol etabonate 0.5% Bausch + Lomb gel-drops 5g Lotemax ointment loteprednol etabonate 0.5% Bausch + Lomb ointment 3.5g Pred Forte prednisolone acetate 1% Allergan + Generic suspension 5ml, 10ml, 15ml generic prednisolone prednisolone sodium generic solution 5ml, 10ml, 15ml sodium phosphate phosphate 1% Vexol rimexolone 1% Alcon suspension 5ml, 10ml

Moderate and Lesser Strength Steroids Alrex loteprednol etabonate 0.2% Bausch + Lomb suspension 5ml, 10ml Flarex fluorometholone acetate 0.1% Alcon suspension 5ml, 10ml FML fluorometholone alcohol 0.1% Allergan + Generic suspension 5ml, 10ml, 15ml FML ointment fluorometholone alcohol 0.1% Allergan ointment 3.5g Pred Mild prednisolone acetate 0.12% Allergan suspension 5ml, 10ml

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from its dropper bottle, it becomes a LOTEMAX GEL VS. LOTEMAX OINTMENT viscous liquid (see “Lotemax Gel vs. Patients, practitioners and pharmacists may mix up these two medicines, so Lotemax Ointment,” left). let’s set the record straight. We regularly often use Lotemax gel • Lotemax gel. Though called a gel, this comes in a dropper as an off-label treatment for our dry bottle, like a solution. However, inside the bottle it is indeed eye patients, but we also use it to treat a highly viscous, semisolid gel formulation. But, through a many other chronic, recurrent, inflam- process called adaptive , it becomes a liquid when matory conditions such as stromal squeezed out of the dropper. And upon instillation in the eye, , Thygeson’s the formulation loses its gel structure altogether as the poly- SPK, uveitis, inflamed pingueculae and carbophil polymer interacts with the electrolytes in tears. pterygia, etc. Still, the drop is rather thick upon instillation, and will cause While loteprednol may not be quite a moment of initial blur until the gel fully converts into a liq- as efficacious as prednisolone and Du- uid. We advise patients to allow the drop to spread out on rezol, it has significantly lower pro- pensity to cause the unwanted side the ocular surface for four to five seconds before blinking, effects of subcapsular and so that the initial blink does not displace the drop onto the increased IOP. In Phase III studies, for eyelid. instance, only two out of 409 patients Because of the nature of this unique gel, the steroid does not settle out of on Lotemax gel had an increase in in- the vehicle, so it does not require shaking. (It is best to tip the bottle back traocular pressure greater than 10mm and forth once to make sure the drug enters the tip of the dropper prior to Hg.5 In addition, loteprednol 0.5% instillation, but no actual shaking is necessary.) Also, unlike suspensions, this suspension was shown to be as effec- 1 delivery system provides a perfectly uniform dose at every instillation. tive as prednisolone acetate for post- • Lotemax ointment.2 This preparation comes in a 3.5g tube and contains op cataract surgery inflammation, and inactive ingredients of white petrolatum and mineral oil. Because it is an with less effect on IOP.6 ester-based corticosteroid and also because it is a preservative-free prepa- • Prednisolone sodium phosphate ration, it may provide a safety advantage over fluorometholone ointment. 1%. This generic steroid is an excel- Lotemax ointment is indicated for the treatment of postoperative inflamma- lent choice when a potent, relatively tion and pain, but is also appli- inexpensive steroid is needed. Because cable in many other cases in this is a solution, it does not require which an ointment is useful for shaking and may be an especially good suppression of inflammation. choice for older people with arthropa- thies for whom shaking a bottle can be 1. Marlowe ZT, Davio SR. Dose uniformity a challenge. It’s also good for soft con- of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and tact lens wearers because it won’t pre- generic prednisolone acetate ophthalmic suspension (1%). Clin Ophthalmol. cipitate on the lens as much as other 2014;8:23-9. drops. 2. Comstock TL, Paterno MR, Singh A, et al. Safety and efficacy of loteprednol • Prednisolone acetate 1%. Generic etabonate ophthalmic ointment 0.5% for prednisolone acetate suspension is a the treatment of inflammation and pain following cataract surgery. Clin Ophthal- reasonable choice for mild to moder- mol. 2011;5:177-86. ate acute inflammatory conditions, especially if cost is a concern—but not

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026_dg0516_Corticosteroids_v3.indd 28 5/4/16 7:02 PM OPHTHALMIC MYTHS: STEROIDS Myth Never use a steroid (even combined with an antibiotic) on a cornea with a staining epithelial defect. Our Take We have encountered numerous epithelial defects over the years that were non-healing until we added a ste- roid that quelled the corneal inflammation preventing re-epithelialization. The nature and cause of the epi- thelial defect must be understood in order to properly select therapeutic intervention. If the epithelial defect is present as a result of subepithelial inflammation, as evidenced by leukocytic anterior stromal disease, then adding a steroid to suppress the underlying inflamma- tory process can promote re-epithelialization. We know that inflammation and superficial punctate keratitis commonly coexist in dry eye disease, yet the proper A mild steroid will suffice for Thygeson’s superficial application of a steroid can help restore and enhance punctate keratopathy. the integrity of the epithelial tissues. Myth Steroids should never be used for more than a month. Our Take There are three conditions in which a is commonly used daily for a lifetime: corneal transplants, chronic uveitis and chronic herpetic stromal disease. We have several patients in whom a drop of 0.5% lotepre- dnol is the least frequent dosage that keeps them comfortable with their dry eye disease. We have never had a single problem with this protracted, low-dose approach. Myth Never use a steroid eye drop on top of a soft contact lens. Our Take There are those stubborn patients who simply will not abandon contact lens wear in the face of symptomatic giant papillary conjunctivitis. We reluctantly, but successfully, have had to use a steroid eye drop (loteprednol is our clear favorite here) four times a day for a week or two, then twice daily for an additional week or two, to properly care for such patients. When Dr. Jimmy Bartlett was doing his famed GPC studies, loteprednol drops were used four times daily right on top of dirty soft contact lenses without incident.1 This does not in any way surprise us. We always try to put the patients in a daily disposable soft contact lens during and after the acute treatment. Myth Use steroids with great caution because they can cause glaucoma and cataracts. Our Take Well, contact lenses can cause corneal ulcers, an extremely serious consequence of lens wear, yet that doesn’t seem to halt the use of these wonderful devices in a wholesale manner in the daily practice of optometry. First, steroids, even ester-based steroids, can increase intraocular pressure (usually by less than 10mm Hg), which reverts to baseline upon discontinuation of the steroid drop. For iatrogenic-increased IOP to be allowed to prog- ress to glaucoma (which we have never seen happen) would be egregious. No doubt, this has occurred through patient, pharmacy or doctor incompetence in appropriate patient management, but it is fully preventable. Regarding posterior subcapsular cataracts, we are unaware of a single case report of cataract formation resulting from the use of loteprednol. Cataract formation would certainly be much more common with the use of older, traditional, ketone-based steroids. We have seen a case of bilateral PSC in a 35-year-old man who used 10 bottles of Tobradex over the span of a year for treatment of allergies, as prescribed by his primary care physician; but a knowledgeable, competent eye doctor would never prescribe in such a manner. The physician, pharmacist and patient were all negligent in this case. The patient should have been asked by his physician or pharmacist about this approach, or perhaps he should have read the package insert himself. Myth Oral prednisone should be used with extreme care, as it can have a multitude of side effects. Our Take This is certainly true for long-term use; however, for short-term use (a few days), this statement is simply false. We have prescribed oral prednisone regularly over our careers with excellent success and no therapeutic “mis- adventures.” The occasional patient might report the prednisone made them jittery or that sleep was difficult, but the index condition was cured. The typical dose is 40mg for three to seven days, then stop. No tapering is needed with such short-term use.

1. Bartlett JD, Howes JF, Ghormley NR, et al. Safety and efficacy of loteprednol etabonate for treatment of papillae in contact lens-associated giant papillary conjunctivitis. Curr Eye Res. 1993 Apr;12(4):313-21.

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FROM THE LITERATURE recent clinical trial was not only to assess the clinical effi- cacy of a three-week fluorometholone 0.1% therapy in DED TOPICAL STEROIDS TREAT patients, but more importantly, to determine if this therapy DRY EYE DISEASE could ameliorate the expected worsening of the ocular In our 2015 Drug Guide, we reported on a study showing surface after exposure to a desiccating stress set in a con- the benefit of topical loteprednol (used off label) in caring trolled environmental laboratory. for patients with dry eye disease (DED). Another study, • Patients randomly received one drop four times daily of published in Ophthalmology (January 2016), found, unsur- either topical 0.1% fluorometholone (FML group) or topical prisingly, a similar effect using fluorometholone 0.1%.1 The polyvinyl alcohol (PA group) for 22 days … Liquifilm Tears following are excerpts from this randomized clinical trial: was selected as the control treatment because it is the • An important factor contributing to the increased vehicle used in fluorometholone. prevalence of DED, and certainly making it a worse prob- • No adverse events or treatment-related adverse reac- lem, is the growing proportion of the population exposed tions were observed throughout the study … In particular, to so-called adverse environments or desiccating stress there were no significant changes in IOP and no signs of conditions. We are currently staying longer within artificially corneal epithelial healing-related problems or secondary created environments, such as office buildings, shopping infections as potential side effects from steroid use. malls, air-conditioned vehicles and even households. These • The FML group, at the end of the study, experienced environments are characterized by low humidity, high significant improvement in high- and low-contrast best- temperatures and draftiness—all conditions that cause tear corrected visual acuity. In contrast, the control group expe- film alterations that usually worsen DED. For many DED rienced no change. patients, these conditions are unbearable. In addition, the • This clinical trial evaluated the efficacy of topical fluoro- number of users of visual display terminals (including tablets metholone 0.1% in preventing the exacerbation of DED signs and smart phones) and the amount and symptoms that patients expe- of time spent using them also have rience when exposed to adverse increased dramatically. These infor- environmental desiccating stress mation technology devices reduce ... Findings confirm the efficacy of blink rate, causing tear film evapora- topical corticosteroids as a short- tion that can worsen DED signs and term (≤4 weeks) DED treatment, as symptoms further. previously shown by other research • Even at low severity level two, groups. anti-inflammatory therapy is indi- • Corticosteroids are among the cated, including topical steroids that most effective agents used to treat have been shown to be effective in noninfectious inflammatory diseases, several studies and clinical trials ... Note the scant tear lake in this patient. especially those mediated by the Consequently, the main goal of the immune system. They reduce cel-

in the setting of advanced iritis and (Flarex and Alcon). The acetate moiety comfortable using it long-term as we episcleritis, as discussed above. gives the fluorometholone molecules are with the ester-based loteprednol. some additional anti-inflammatory ef- FML Forte (fluorometholone 0.25%, MODERATE EFFICACY fectiveness over the alcohol moiety.7 Allergan) is not recommended because CORTICOSTEROIDS Fluorometholone is available ge- fluorometholone 0.1% represents the Moderate efficacy steroids in common nerically and is thus reasonably inex- top of the dose response curve—mean- use are fluorometholone 0.1% suspen- pensive. (However, there have been ing that the 0.25% formulation is no sion and Alrex (loteprednol 0.2%, sporadic reports of fluorometholone more efficacious than the 0.1%. More- Bausch + Lomb) suspension, both of being temporarily unavailable in vari- over, the 0.25% concentration has a which must be shaken prior to instil- ous parts of the country. When pre- greater tendency to raise IOP.8 lation. scribing, be sure to check with your • Alrex. For allergic eye disease, pre- • Fluorometholone 0.1%. There are pharmacy for availability.) While fluo- scribe a steroid when itching is accom- two derivatives of fluorometholone rometholone has less tendency to in- panied by clinical signs of conjunctival 0.1% suspension—the alcohol (FML, crease intraocular pressure than other injection, chemosis or eyelid swell- Allergan and generic) and the acetate ketone steroids, we are not nearly as ing. In these instances, Alrex (or even

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026_dg0516_Corticosteroids_v3.indd 30 5/4/16 7:02 PM lular infiltration, inhibit chemotaxis and exacerbations under desiccat- restore the appropriate vascular per- ing conditions and that tear meability. Corticosteroids also reduce substitutes are not sufficient or suppress capillary dilation, fibroblast to protect the ocular surface in proliferation and collagen deposition. these adverse situations. In con- • The benefit of corticosteroids trast, there were no significant in the treatment of DED and in the adverse changes in the FML improvement of both signs and group after adverse environ- symptoms has been demonstrated ment exposure, confirming the in several studies, and these clinical appropriateness of fluorometh- data are consistent with these reports olone 0.1% 21-day treatment for … Fluorometholone was selected as preserving the ocular surface. the study treatment because it was • In conclusion, the clinical shown previously to be effective in DED therapy. Moreover, trial showed that three-week topical fluorometholone 0.1% 0.1% fluorometholone penetrated the ocular tissues less than was a safe and effective therapy for DED patients to reduce other corticosteroids, which minimizes the potential compli- ocular surface signs after a 21-day treatment. Importantly, cations of the therapy. fluorometholone 0.1% therapy also can prevent ocular sur- • In this study, after 21 days of treatment, fluorometho- face worsening in DED patients exposed to desiccating lone 0.1% reduced corneal and conjunctival staining and stress. Thus, this treatment could be administered occasion- hyperemia, whereas no obvious effects were observed with ally to such patients expecting to undergo adverse environ- polyvinyl alcohol artificial tears. The clinical improvement in ments during their daily life (e.g., office buildings, shopping corneal staining was in concordance with previous studies centers, movie theatres, air-conditioned vehicles, etc.). assessing corticosteroids. These results could explain the As this study shows, the short-term use of a topical cor- increase in BCVA … due to a positive correlation between ticosteroid, such as fluorometholone 0.1% or loteprednol corneal epithelial damage and visual acuity … As reported by 0.5%, can be enormously beneficial to patients with dry eye others, fluorometholone 0.1% decreased conjunctival hyper- disease. emia, which is associated with the degree of inflammation. Once the ocular surface inflammation is controlled, clini- In contrast, polyvinyl alcohol artificial tears had no effect on cians should consider ongoing maintenance of inflammation hyperemia. Both fluorometholone and Liquifilm Tears con- suppression with a drug such as lifitegrast (not yet FDA tain as a preservative. However, the approved), Lotemax gel or fluorometholone, depending negative impact of benzalkonium chloride in terms of corne- upon patient response. al staining can be compensated for by the fluorometholone 1. Pinto-Fraga J, López-Miguel A, González-García MJ, et al. Topical fluoro- 0.1% therapy, as observed in this study. metholone protects the ocular surface of dry eye patients from desic- • The ocular surface deterioration observed in the PA cating stress: a randomized controlled clinical trial. Ophthalmology. 2016 Jan;123(1):141-53. group reinforces the fact that DED patients can experience

Lotemax gel) is our answer. We typi- • Lotemax ointment. The only • FML ointment. FML ophthalmic cally dose Alrex (or Lotemax gel) QID ester-based steroid ointment avail- ointment (fluorometholone 0.1%, for one week, then BID for one month. able is Lotemax ophthalmic ointment Allergan) is used much the same as Beyond awareness of the various de- (loteprednol 0.5%, Bausch + Lomb). It Lotemax ointment. It is indicated for livery systems (suspensions, solutions, is indicated for postoperative inflam- inflammation of the palpebral and bul- , and ointments), know- mation and pain, but also has many bar conjunctiva, cornea and anterior ing the clinical efficacy of these drugs “off-label” clinical uses: dry eye, al- segment of the globe, and any of the is important. lergy, corneal transplant protection, off-label uses mentioned above. The blepharitis, giant papillary conjuncti- only very minor difference is to keep a STEROID OINTMENTS vitis, chronic uveitis, stromal immune little bit closer watch on the patient for The ophthalmic ointments enjoy a herpetic keratitis, Thygeson’s SPK, steroid-related adverse effects since it is wide array of clinical indications. RCE, augmentation of steroid eye a ketone steroid. Three corticosteroid medicines that drop therapy in acute advanced uveitis • 0.1% . This merit frequent clinical use in the oint- or episcleritis, contact and is a dermatologic preparation that ment formulation include: other inflammatory conditions. works well for periocular dermati-

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tis conditions. Triamcinolone 0.1% STEROIDS AND CONTACT LENSES cream, which became generic long Steroids have two well-known side effects: posterior subcapsular cataract ago, has been our favorite medicine development and . Notice we did not use the term “glau- for many years to treat contact blepha- coma,” because that is exceedingly rare. Steroid-induced hypertension is rare rodermatitis. It comes in 15g and 30g enough, and is mostly seen with protracted use of ketone-based steroids, tubes, each costing less than $10 in most notably dexamethasone, prednisolone and difluprednate.1 To allow a most markets. situation in which ocular hypertension occurs and actually proceeds to frank Be sure to tell the patient that on glaucoma is unconscionable. This would only occur if a doctor did not sched- the side of the tube is the statement ule appropriate follow-up or the patient failed to return for scheduled follow- “Not For Ophthalmic Use,” but that up visits in a timely manner (or at all), or a naïve, non-optometric physician re- the medication is perfectly fine to use prescribed a steroid. Thus, to say that topical corticosteroids cause glaucoma as you have prescribed. We explain is an egregious stretch of reality. that triamcinolone, also known by Contact lenses have one common indication: correction of ametropias. the brand name Kenalog, is frequently They are also occasionally used as bandage lenses. In radical contradistinc- used by subspecialists for FDA- tion to corticosteroids, contact lenses can carry many risks: giant papillary conjunctivitis; keratitis; corneal neovascularization; CLARE (contact lens approved injection into the eye. In oth- associated red eye); retained lens fragments in the remote recesses of the er words, if some of the triamcinolone superior cul-de-sac; corneal infiltrates; infectious keratitis; and other condi- cream gets into the patient’s eyes, it’s tions. Patients may suffer unilateral corneal blindness from infectious keratitis, nothing to worry about. yet we prescribe contacts as if they were 100% safe. Of course, the patient is Corticosteroids are the most essen- usually complicit in many of these complications via behaviors such as sleep- tial and highly prescribed medicines in ing in their contacts, or using poor lens hygiene or inconsistent replacement the treatment of ocular inflammation schedules. of any stripe. Their widespread clinical In any event, patients rarely have problems with either contact lens wear or usage confirms that ocular inflamma- use of topical steroids if they are used as prescribed. Proper, timely follow-up tion is the most common clinical mani- and competent optometric oversight typically render both steroid and con- festation seen in eye care. tact lens use safe, effective therapeutic interventions. It is so important that all doctors Overall, we would be willing to bet big money that contact lenses cause of optometry come to terms with this far more problems than do steroids. So, let’s keep a realistic perspective on reality and strive to become very com- the clinical care we provide and not live with an unrealistic fear of the most fortable caring for patients with in- beneficial class of acute care medicines available to help our patients enjoy a flammatory eye disease. ■ greater quality of life.

1. Foster CS, Davanzo R, Flynn TE, et al. Durezol Sheppard JD, Comstock TL, Cavet ME. Impact of the topical ophthalmic corticosteroid loteprednol (Difluprednate Ophthalmic Emulsion 0.05%) com- etabonate on intraocular pressure. Adv Ther. 2016; Mar 17. [Epub ahead of print]. pared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther. 2010 Oct;26(5):475-83. 2. Slabaugh MA, Herlihy E, Ongchin S, van Gelder RN. Efficacy and potential complications of diflu- prednate use for pediatric uveitis. Am J Ophthal- STEROIDS FOR DRY EYE DISEASE mol. 2012 May;153(5):932-8. 3. Leibowitz HM, Ryan WJ Jr, Kupferman A. Com- —EFFECTIVE AND SAFE LONG-TERM TREATMENT parative anti-inflammatory efficacy of topical cor- ticosteroids with low glaucoma-inducing potential. Topical administration of 1% ophthalmic solution for Arch Ophthalmol. 1992 Jan;110(1):118-20. several weeks provides moderate to complete relief of DES symptoms and 4. Roberts CW, Nelson PL. Comparative analysis of reduces corneal fluorescein staining in patients with SS-related DES, sug- prednisolone acetate suspensions. J Ocul Pharma- col Ther. 2007 Apr;23(2):182-7. gests research. Pulse treatment with methylprednisolone for two weeks fol- 5. US Food and Drug Administration. Center for lowed by a taper led to improvement in symptoms starting at two weeks, Drug Evaluation and Research. Deputy Division Director Review for NDA 202-872. 2012 Sep 27. followed by improved TBUT and Schirmer test scores by the end of taper. Available at: www.accessdata.fda. gov/drugsatf- After the first pulse treatment, mean drug-free remission time was 56.6 da_docs/nda/2012/202872Orig1s000MedR.pdf. 6. Lane SS, Holland EJ. Loteprednol etabonate weeks; after the second, it increased to 72.4 weeks. No serious complica- 0.5% versus prednisolone acetate 1.0% for the tions, including IOP elevation and cataract formation, occurred during the treatment of inflammation after cataract surgery. J entire follow-up period. Cataract Refract Surg. 2013 Feb;39(2):168-73. 7. Leibowitz HM, Hyndiuk RA, Lindsey C, Rosenthal Again, short-term use of topical corticosteroids (used off-label) should AL. Fluorometholone acetate: clinical evaluation in the treatment of external ocular inflammation. Ann be standard-of-care in most symptomatic dry eye patients. Ophthalmol. 1984 Dec;16(12):1110-5. 8. Kass M, Cheetham J, Duzman E, Burke PJ. The Hong S, Kim T, Chung S-H, et al. Recurrence after topical nonpreserved methylprednisolone thera- ocular hypertensive effect of 0.25% fluorometho- py for keratoconjunctivitis sicca in Sjögren’s syndrome. J Ocul Pharmacol Ther. 2007;23(1):78-82. lone in corticosteroid responders. Am J Ophthal- mol. 1986 Aug 15;102(2):159-63.

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KID GLOVES: PEARLS FOR PEDIATRIC EYE CARE By Kathleen Foster Elliott, OD

Learn ew doors are opening every day for general optometric some of the practitioners to increase their foundational knowledge and skill set in pro- Nviding pediatric comprehen- and alternative sive care. This article explores ophthalmic indications for pediatric treatment, along pharmacologic with strategies, dosages and side effects. For non-complicated corneal abrasion, strategies erythromycin ophthalmic ointment is frequently used in pediatric ophthalmol- for treating ogy and optometry . Gentle on the cornea, easily accessible, affordable and Drop instillation is challenging in pediatric your pediatric patients; ophthalmic gel administered at a boasting a 50-year track record of broad- lower frequency dose can aid in administration spectrum, gram-positive and chlamydial patients—an in some cases. coverage, the macrolide comes in 0.5% increasingly ointment and is safe for all ages down to newborn. It is also used in neonates for pro- rigation. We educate the parent to lavage important phylaxis against gonococcal ophthalmia several times a day before instillation of the segment of neonatorum. It is essential to cycloplege the medication. Additionally, check for pseu- patient and recommend acetaminophen or domembranes on the initial exam your patient for discomfort. and remove any with a surgical sponge, wet • For pediatric bacterial conjunctivitis, cotton swab, blunt forceps or Alger brush. population. the most commonly prescribed medication • Corneal ulcers need fast, viable ther- is Polytrim (polymyxin B sulfate and trime- apy. Besivance (besifloxacin, Bausch + thoprim ophthalmic solution, Allergan; and Lomb) is a newer fluoroquinolone, avail- generic), active against a variety of aerobic able in 0.6% ophthalmic suspension, that is gram-positive and gram-negative ophthal- highly effective against MRSE and MRSA, mic pathogens. Safety and effectiveness in according to the ARMOR study (although children below the age of two months have topical vancomycin is rapidly becoming the not been established.1 Instill one drop in drug of choice to target MRSA).2,3 the affected eye every three hours (up to six This potent, dual-halogenated chloroflu- doses per day) for seven to 10 days.1 A rea- oroquinolone is also highly effective against sonable response time is three to five days. Pseudomonas aeruginosa.4 Children are at For mucopurulent conjunctivitis, a increased risk for this invasive microbe if preservative-free rinsing solution is rec- they have corneal hypoxia, are immuno- ommended. We use Unisol because the compromised or are diagnosed with diabe- design of the bottle lends itself to easy ir- tes. Pediatric microbial keratitis treatment

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should be coupled with a cycloplegic look for the Hutchison sign—presence acyclovir users with pediatricians so agent, such as 1% BID of a vesicle on the tip of the nose—sig- proper blood tests and drug interac- or homatrapine 5% QD. nifying greater risk of corneal involve- tions can be monitored. Besifloxacin is safe for use in infants ment secondary to herpes zoster. Shin- • Preseptal cellulitis is a common pe- to toddlers one year of age. Dosage gles occasionally manifests in pediatric diatric condition that requires an oral is three times a day, four to 12 hours patients. Treatment options for prima- agent. It is common clinical procedure apart for seven days. Around 2% of ry ocular herpes infection include: to rely on the patient’s pediatrician treated patients will have adverse re- – Oral acyclovir (Zovirax, Glaxo or a pharmacist in determining oral actions (e.g., conjunctival redness, SmithKline) 200mg capsules or antibiotics dosage for children. Close , eye pain, eye irritation, 200mg/5ml (teaspoon) suspension monitoring is crucial to avoid orbital eye pruritus and ).4 No sys- – Ganciclovir ophthalmic gel cellulitis, which requires hospitaliza- temic side effects have been reported 0.15% (Zirgan, Bausch + Lomb): five tion with IV antibiotics. Periorbital with besifloxacin on weight-bearing times daily cellulitis usually is caused by Staphylo- joints, although systemic administra- – Trifluridine 1% ophthalmic solu- coccus aureus, Streptococcus pyogenes tion of some quinolones has been tion (Viroptic, Pfizer): seven to nine or Streptococcus pneumoniae. Hae- shown to cause arthropathy in imma- times daily mophilus influenzae B is becoming a ture animals, according to the Adverse – Vidarabine 3% ophthalmic oint- rare cause because of the prevalence of Event Reporting System study.5 ment: five times daily (must be com- H. influenzae .11 Treatment of pediatric microbial pounded by an ophthalmic specialty Common antibiotic treatments for keratitis involves an initial applica- pharmacy) preseptal cellulitis in include tion of antimicrobial agents followed Oral dosing guidelines for acyclovir Augmentin (amoxicillin clavulanate, by anti-inflammatory agents. Pediatric are as follows: In patients over two GlaxoSmithKline) or . cases are rare but devastating if not years old, 20mg/kg every eight hours Augmentin has good broad-spectrum treated properly or quickly. for five to seven days, not to exceed 1g and gram-negative coverage against • For herpes simplex with skin or PO every eight hours. For older teens Haemophilus influenza. In patients less ocular involvement, oral antiviral ther- of adult size, the adult dose of 400mg than 90 pounds, dosage is 35mg/kg per apy with acyclovir is highly effective— five times daily for 10 days can be ad- day to 40mg/kg per day with three di- more effective than ophthalmic antivi- ministered. vided doses every eight hours for 10 ral agents in treating herpetic corneal With pediatrics, putting anything days. If the patient weighs more than keratitis.6 Oral acyclovir reaches ther- in the eye can be challenging; there- 90 pounds, dose is 250mg to 500mg apeutic levels in aqueous and tears, fore, an ophthalmic gel five times daily every eight hours, or 875mg every 12 virtually eliminating the need for con- makes more sense than drops needed hours, for seven to 10 days. Maximum current use of topical antivirals. It is seven to nine times a day. Compared dosage should not exceed 2g per day. highly effective for treatment and pro- with the standard treatment of triflu- Clindamycin is a broad-spectrum phylaxis of herpes simplex epithelial ridine, ganciclovir is equally effective alternative to the penicillin-allergic keratitis, and immune stromal keratitis but less toxic.8 Ganciclovir ophthal- patient. Adverse effects may include in conjunction with Lotemax, and for mic gel has low corneal toxicity and nausea and vomiting, diarrhea and ab- prevention of recurrent infectious epi- less frequent applications. Trifluridine dominal pain. (Bactrim is also a good thelial keratitis. solution and vidarabine ointment are choice for patients allergic to penicil- Ocular manifestations of herpes also effective in treating HSV kera- lin, although it does not cover Group simplex virus or herpes zoster virus titis; however, epithelial toxicity is a A Streptococcus—a likely etiology typically occur later in life, but dis- frequent adverse effect, especially with of preseptal cellulitis in pediatric pa- ease in pediatric patients is often sys- prolonged use.9 tients.) Clindamycin dosing is as fol- temic and accompanied by more ocu- The Herpetic Eye Disease Study lows: 30mg/kg per day to 40mg/kg per lar inflammation and risk; Group (HEDS) demonstrated in pa- day divided TID or QID for 10 days. quick and effective therapeutic dosing tients 12 years or older that long-term Bactrim dosage is 8mg per day to 12 is imperative.7 Adding a cycloplegic suppressive oral acyclovir therapy at mg per day divided BID for 10 days. agent such as cyclopentolate 1% BID 400mg BID reduces risk of recurrent If the patient is less than one year old, will help heal and debride the corneal HSV epithelial (9% vs. 14%) and stro- parenteral antibiotics and/or - epithelium affected by a dendrite. A mal (14% vs. 28%) keratitis.10 So, for ization is recommended. For patients moistened surgical sponge, cotton patients at risk of developing herpetic allergic to penicillin, the broad mac- swab or Alger brush can help debride eye disease, long-term antiviral therapy rolides azithromycin (10mg/kg per necrotic tissue. is a common approach. In our clinic, day for three days) and clarithromycin When evaluating for zoster disease, we typically comanage these long-term (7.5mg/kg BID) are safe and effective.

34 REVIEW OF OPTOMETRY MAY 15, 2016

0033_dg0516_peds.indd33_dg0516_peds.indd 3344 55/4/16/4/16 6:336:33 PMPM • Treatment of iritis, especially in and optometry to detect of this pos- juvenile idiopathic arthritis (JIA) pa- sible side effect. tients, takes a joint effort between the Visual fields and retinal analysis are optometrist or ophthalmologist, pe- required every three months during diatrician, parent and rheumatologist. drug regimens and three to six months The devastating effects of iritis and after cessation, then at one year. A thor- uveitis on a pediatric eye can lead to ough retina assessment is essential dur- permanent scarring and blindness if ing instillation. To get thorough dila- not aggressively treated. tion, use cyclopentolate 1% along with The systemic form of JIA is one 2.5%. Children with classification, but pauciarticular is the brown irides may need to be instilled most common form of JIA, affecting with the dosage twice. In some chil- the large joints. Girls under age eight To view the posterior pole in infants/ dren, exam under is needed. toddlers, support the patient’s head be- are most likely to develop this type. tween the clinician’s knee and parent’s Ocular diseases such as iritis, uveitis There has never been a better time arm, using gentle pressure to bolster. and glaucoma affect about 20% to for the field of optometry to engage in 30% of children with pauciarticular pediatrics. Arming yourself with facts, JIA. Up to 80% also test positive for • Superglue () is part techniques and information on pre- antinuclear antibodies (ANA) in the of a family of strong, fast-acting ad- scribing for the pediatric patient will blood, and the disease tends to develop hesives with industrial, medical and benefit the patient and profession. ■ at an early age. household uses. Change one molecular 1. Polytrim (polymyxin B sulfate and trimethoprim oph- The third classification of JIA is structure and you have a medical-grade thalmic solution, USP). Available at: http://www.drugs. com/pro/polytrim.html (last accessed April 29, 2016). polyarticular, which occurs in 30% adhesive known as Dermabond (2-oc- 2. Asbell PA, Sanfilippo CM, Pillar CM, et al. Antibiotic Re- sistance Among Ocular Pathogens in the United States: of children with JIA. The small joints, tyl cyanoacrylate, Ethicon), which Five-Year Results From the Antibiotic Resistance Moni- such as those in the hands and feet, are forms a strong bond across apposed toring in Ocular Microorganisms (ARMOR) Surveillance Study. JAMA Ophthalmol. 2015 Dec;133(12):1445-54. most commonly involved, but the dis- wound edges to allow normal healing 3. Tarai B, Das P, Kumar D. Recurrent Challenges for 12 Clinicians: Emergence of Methicillin-Resistant Staphy- ease may affect large joints. Patients to occur below. It is marketed to re- lococcus aureus, Vancomycin Resistance, and Current Treatment Options. J Lab Physicians. 2013 Jul-Dec; 5(2): with this classification who are ANA place sutures 5-0 or smaller in diameter 71-8. 13 4. Besivance (besifloxacin ophthalmic suspension) 0.6% positive, female and pauci-jointed are for incisional or laceration repair. Receives Additional Indications, Including the Treat- at highest risk for iritis. Monitor them Dermabond has become an efficient ment of Bacterial Conjunctivitis Infections Due to Pseu- domonas aeruginosa. Available at: www.bausch.com/ with a slit-lamp exam, observing for way of providing pediatric care for lac- our-company/newsroom/2012-archive/besivance-ad- ditional-indications#.VmW_VSZOKnO (last accessed early cell and flare, every three months erations, especially in the periorbital April 29, 2016). 5. Besivance: Safety Review. Department of Health and during the first year of diagnosis. area. Best-suited for small, superficial Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Pred Forte is my drug of choice. lacerations, it may be used with confi- Office of Surveillance and Epidemiology Available at: (Don’t settle for generics, and shake dence on larger wounds where subcu- www.fda.gov/downloads/AdvisoryCommittees/Com- mitteesMeetingMaterials/PediatricAdvisoryCommittee/ the bottle before usage.) For most iri- taneous sutures are needed. Treatment UCM255067.pdf (last accessed April 29, 2016). 6. Hung SO, Patterson A, Rees PJ. tis cases, dose is every two hours for age ranges vary from newborn to age of oral acyclovir (Zovirax) in the eye. Br J Ophthal- mol.1984;68:192-5. the first one to two days, then QID for 18, depending on the size and depth 7. Myers TM, Wallace DK, Johnson SM, et al. Ophthalmic Medications in Pediatric Patients a week, followed by a taper. Be sure of the laceration. have Compr Ophthalmol Update. 2005;6(2):85-101. to obtain baseline intraocular pres- also been successfully used in treat- 8. Topical antiviral gel treats herpetic keratitis. Healio. September 10, 2010. Available at: www.healio.com/ sure, with IOP check at follow-ups. ment of corneal lacerations or globe ophthalmology/cornea-external-disease/news/print/ 14 ocular-surgery-news/%7Bfa6ae2ad-fe4e-4074-b9f1- Also, topical mydriatic and cycloplegic perforations through the cornea. 13cf91e32637%7D/topical-antiviral-gel-treats-herpetic- keratitis (last accessed April 29, 2016). agents are important to prevent - Alternatives to adhesive manage- 9. Wang JC. Herpes Simplex Keratitis Treatment & lary block. Management. Available at: .medscape.com/ ment include sutures and Steri-Strips. article/1194268-treatment#d1 (last accessed April 29, • For ocular allergy, consider a • For moderate to severe 2016). 10. A controlled trial of oral acyclovir for the prevention once-daily dosage for efficacy and disorder, children are often prescribed of stromal keratitis or iritis in patients with herpes sim- plex virus epithelial keratitis. The Epithelial Keratitis Trial. convenience—because children do not Sabril (vigabatrin, Lundbeck). The The Herpetic Eye Disease Study Group. Arch Ophthal- mol. 1997;115: 703-12. like instillation of eye drops. Two QD most common side effect is permanent 11. Sadovsky R. Distinguishing Periorbital from Orbital options are Pataday (olopatadine) and loss, occurring in one-third Cellulitis Am Fam Physician. 2003;15;67(6):1349-53. 12. Types of Juvenile Idiopathic Arthritis. Available at: Lastacaft (alcaftadine). Pataday com- of patients. Critically, visual field is ir- www.spineuniverse.com/conditions/spinal-arthritis/jra/ types-juvenile-rheumatoid-arthritis (last accessed April bines a mast cell stabilizer with an ocu- reversible even upon discontinuation 29, 2016). 13. Bruns TB, Worthington JM. Using Tissue Adhesive lar antihistamine. Lastacaft is an H1 of the medicine. Children placed on for Wound Repair: A Practical Guide to Dermabond Am Fam Physician. 2000 Mar 1;61(5):1383-18. receptor antagonist inhibiting release Sabril must be comanaged by pediatric 14. Eiferman RA, Snyder JW. Antibacterial effect of cya- of histamine from mast cells. , noacrylate glue. Arch Ophthalmol. 1983;101:958-60.

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THE CARE OF PATIENTS WITH GLAUCOMA laucoma and dry eye dis- • Check central corneal thickness. Of Glaucoma ease are the two most poorly course, one cannot know with certainty if cared for chronic eye diseas- a patient truly has normal or low-tension is not a es, yet both conditions can glaucoma without the benefit of pachyme- disease that Gbe managed rather easily—as try to refine the accuracy of the tonometric long as you first perform careful and thor- reading, as the intraocular pressure with- progresses ough assessment. Here, we review some out pachymetry is relatively meaningless. best practices and reminders for a proper Keep in mind that a physiologically thin quickly, so diagnostic glaucoma evaluation. cornea appears to be an independent risk • Carefully observe the optic nerve factor for glaucomatous , take the head. By far, the most common diagnos- and this needs to be factored into the pa- time to make tic error we see is losing sight of the es- tient assessment of risk. sence of glaucomatous optic neuropathy; •Evaluate the neuroretinal rim. Anoth- a careful that is, critically studying and descriptively er key factor in evaluating the optic nerve characterizing the appearance of the op- head is to relatively ignore the actual cup diagnosis and tic nerve head. We regularly see patients and attentively study the neuroretinal rim whose glaucoma has been missed entirely tissues. Even in a 0.8 to 0.9 cup, the vi- a thoughtful because a “normal” intraocular pressure sual field can look pretty good as long as decision lured the clinician into optic nerve com- there is no focal erosion of the rim tissues. placency. Because a large subset of glau- However, if such erosion is present, it is regarding coma patients have normal-tension glau- most commonly seen at the inferotempo- coma, close observation of the optic nerve initiation of appearance is absolutely critical to estab- lishing this diagnosis. therapy. • Perform tonometry. In addition to failing to study the optic nerve head, an- other common error we see regularly is referral for a glaucoma evaluation for patients who have an intraocular pres- sure in the mid- to upper 20s, with 0.2 or 0.3 central cups and corneal thicknesses of 620µm to 640µm. These patients most commonly have a 100% normal workup. If all optometrists would simply measure the central corneal thickness in these pseu- This optic nerve head, while considerably do-ocular hypertensives, it would be an cupped, honors the ISNT rule, and therefore immense service to the patients and our highly likely physiologically cupping. profession.

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036_dg0516_Glaucoma_v3.indd 36 5/4/16 6:20 PM TOPICAL GLAUCOMA DRUGS BRAND NAME GENERIC NAME MANUFACTURER CONCENTRATION BOTTLE SIZE Beta Blockers Betagan hydrochloride Allergan, and generic 0.25% 5ml, 10ml 0.5% 5ml, 10ml, 15ml Betimol hemihydrate Akorn 0.25% 5ml 0.5% 5ml, 10ml, 15ml Betoptic-S hydrochloride Alcon 0.25% 5ml, 10ml, 15ml Istalol timolol maleate Bausch + Lomb 0.5% 2.5ml, 5ml Timoptic timolol maleate Valeant Ophthalmics, 0.25% 5ml, 10ml, 15ml and generic 0.5% 5ml, 10ml, 15ml Timoptic (preservative-free) timolol maleate Valeant Ophthalmics 0.25% unit-dose 0.5% unit-dose Timoptic-XE timolol maleate Valeant Ophthalmics, 0.25% 2.5ml, 5ml and generic 0.5% 2.5ml, 5ml

Prostaglandin Analogs bimatoprost generic 0.03% 2.5ml, 5ml, 7.5ml Lumigan bimatoprost Allergan 0.01% 2.5ml, 5ml, 7.5ml Travatan Z Alcon 0.004% 2.5ml, 5ml Travoprost travoprost generic 0.004% 2.5ml, 5ml Xalatan Pfizer, + generic 0.005% 2.5ml Zioptan Akorn 0.0015% unit-dose

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

Carbonic Anhydrase Inhibitors Azopt Alcon 1% 5ml, 10ml, 15ml Trusopt Merck, + generic 2% 5ml, 10ml

Combination Glaucoma Medications Combigan brimonidine/timolol Allergan 0.2%/0.5% 5ml, 10ml Cosopt dorzolamide/timolol Akorn, + generic 2%/0.5% 5ml, 10ml Cosopt PF dorzolamide/timolol Akorn 2%/0.5% unit-dose Simbrinza brinzolamide/brimonidine Alcon 1%/0.2% 8ml

ral and/or superotemporal rim tissues. high-risk glaucoma suspect or who sure, which can exacerbate glaucoma- This is because of relatively sparse has the disease, we strongly urge them tous progression.1 We find ourselves glial support tissues in these regions. to recommend to their siblings that more and more often writing letters The ISNT rule (inferior > superior > they seek an optometric glaucoma to primary care physicians explain- nasal > temporal) speaks to this ana- evaluation in the area where they live. ing this relatively new knowledge and tomic reality, in that in a normal optic Such screening has been shown to asking them to consider having pa- nerve head the inferior tissues are usu- have a quite high yield, and to posi- tients take blood pressure medicines ally the thickest, followed by slightly tively impact public health. in the morning time. Once the PCPs less thick superior rim tissues, then • Check blood pressure in-office. have this scientific explanation, good slightly less thick nasal rim, with the Carefully assess the patient’s systemic cooperation is generally the rule. temporal rim being the thinnest. This conditions, especially treatment for Along this same line, many pa- is not a bulletproof concept, but it is a systemic hypertension. It has been tients with can use a topical good general guide. found, particularly in low-tension very successfully. How- • Talk about family history. Be- glaucoma patients, that when blood ever, we never prescribe a topical beta cause glaucoma tends to run in fami- pressure medicines are taken in the blocker for such patients without first lies, we always ask about siblings. evening or at bedtime, they can patho- writing to the primary care physi- When we have a patient who is a logically lower nocturnal blood pres- cian for clearance, and having a let-

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ter (i.e., written documentation) from hydroxychloroquine.) Sending a copy explain progression of glaucoma, that doctor to place in our medical of the EMR is an extremely poor sub- despite achievement of target intra- records attesting to such. We have, stitute for a brief letter. ocular pressure. The small, forearm with proper consultative advice, used The optometric measurement of (radial) devices for measuring blood topical beta blockers for a handful of systemic blood pressure can accom- pressure are inexpensive, simple to patients with asthma without inci- plish two key goals: screening for the use by ancillary personnel and can be dent and successfully obtained target epidemic of uncontrolled (or under- of enormous value to human health intraocular pressure. (As an aside, controlled) systemic hypertension, and to glaucoma assessment. we also find ourselves communicat- and fine-tuning our understanding • Analyze retinal nerve fiber layer, ing more often with rheumatologists, of low-tension glaucoma, as many if available. Additional assessment since many of these specialists have a of these patients have blood pres- with retinal nerve fiber layer analysis proclivity to overdose patients taking sure that is too low, which can often can be extremely helpful in under-

FROM THE LITERATURE • “Our findings indicate that aging in healthy control subjects leads to a significant reduction of neuroreti- AGING ALONE CAN EXACERBATE nal parameters and may explain a large proportion “PROGRESSION” IN GLAUCOMA of the deterioration observed in patients with treated PATIENTS glaucoma. Furthermore, both cross-sectional and longitudinal studies of healthy subjects show pat- It stands to reason that natural quantitative loss of optic terns of regional loss similar to those in patients with nerve fibers over time can contribute to glaucomatous glaucoma, suggesting that age-related regional sus- optic neuropathy. An article in Ophthalmology (December ceptibility may be accelerated in glaucoma. Because 2015) gives important insights into the impact of natural several previous longitudinal studies of structural aging on visual field compromise in the setting of glau- progression of glaucoma lacked a control population, coma progression, per these excerpts: the observed changes were attributed to glaucoma, • “Age-related loss of neuroretinal parameters may perhaps overestimating the rate of change in treated explain a large proportion of the deterioration glaucoma. Therefore, without an understanding of observed in treated patients with glaucoma and the significant normal age-related changes, there should be carefully considered in estimating rates of could be errors in rate estimates and the diagnostic changes.” accuracy of glaucoma-related progression.” • “Because there is accumulating evidence that aging Thankfully, there are many other metrics and param- in otherwise healthy subjects also results in statisti- eters to guide us in clinical decision making than just the cally significant change, often with patterns resem- visual fields. However, this article does serve to make us bling those in glaucoma, the clinical assessment of more analytical in changes in the visual fields. Remember, glaucomatous progression can be challenging.” in order to establish true progression, we would have to • “The effect of IOP variability on ONH parameters is do three or four fields about every six to 12 months. This is probably related to changes in laminar position and why it is so challenging and minimally productive to - prelaminar tissue compression.” manage the visual field component of the comprehensive • “Because mean deviation (MD) is age adjusted, it is glaucoma assessment. likely that the absence of normal aging effects with this parameter allows better estimates of glaucoma- Vianna JR, Danthurebandara VM, Sharpe GP, et. al. Importance of normal related damage than with the neuroretinal param- aging in estimating the rate of glaucomatous neuroretinal rim and retinal nerve fiber layer loss. Ophthalmology; 2015;122(12):2392-8. eters.”

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036_dg0516_Glaucoma_v3.indd 38 5/4/16 6:20 PM standing the microanatomy of the TIMOLOL EYE DROPS FOR MIGRAINE HEADACHE? tissues. Such measurements are in no Acute migraine may be reduced in intensity or way absolutely diagnostic, but can stopped altogether with beta blocker eye drops. While the add information to help the clinician daily use of beta blocker pills has proved effective in refine assessment of the health status preventing chronic migraine headaches, they have been of the optic nerve. unsuccessful in treating acute, sudden-onset migraines. • Perform perimetry (repeat, if Beta-blocker eye drops, however, are absorbed more warranted). Humphrey visual field quickly than pills by tear duct drainage onto the nasal 24-2 SITA Fast testing remains our mucosa, achieving therapeutic plasma levels “within min- visual field assessment of choice. One utes.” test result, especially in a naïve-to- patient, can be con- Migliazzo CV, Hagan JC. Beta-blocker eyedrops for treatment of acute migraine. Missouri Medicine. 2014; 111(4):283-8. fusing unless: (a) it is normal or (b) it is abnormal but corresponds to your assessment of the optic nerve head tis- patible with human biology. can be critically important, especially sues. The problem is that many initial Once a repeatable visual field de- in the setting of increased or increas- (and to some degree, subsequent) vi- fect is present, following the patient ing intraocular pressure. sual field results are just plain “noisy” over time is best done with serial vi- Beyond assessing the patency of the and non-constructive in nature. sual fields. Nerve fiber layer analyz- iridocorneal angle is annotating the If you obtain uncertain visual field ers are more helpful in staging risk pigmentation of the angle tissues. This results, repeat the test in a few weeks or helping to detect early glaucoma, is essential to know when contem- to months, depending on the level of whereas serial visual fields are opti- plating laser trabeculoplasty because risk and/or concern by the doctor and/ mal for following patients with estab- pigments absorb the laser energy, en- or the patient for glaucoma disease. lished visual field defects. abling a positive therapeutic response. Never make a change in medical ther- • Look at the angle. is If there is little or no pigmentation apy based on the results of a single vi- best accomplished via a four-mirror of the trabecular meshwork tissues, sual field test, as it is well-established instrument. The Van Herick assess- there will be little or no therapeutic that repeating visual field testing three ment is highly accurate but not ex- response to laser trabeculoplasty. to six times is necessary before one act, and the occasional plateau Last, as a clinical pearl, laser tra- can confirm true progression of a vi- can be misleading. Gonioscopy can beculoplasty is more effective in sual field. Remember that glaucoma more completely elucidate the micro- phakic eyes than in pseudophakic left untreated tends to progress at ap- anatomy of the angle tissues. Such eyes. This is critical knowledge to proximately a rate of 3% per year.2 assessment is even more important in enable maximum clinical patient Take note: Glaucoma management patients with moderate to high hyper- care. We typically repeat gonioscopy is like sailing—there is no wisdom in opia, especially if progressive nuclear making rapid changes in course. Such sclerotic cataract is further narrowing FROM THE apparent rapid changes are not com- the iridocorneal angle. LITERATURE Most patients with pigment disper- sion syndrome or pseudoexfoliation NEW PERSPECTIVES ON are at higher risk for increased in- TARGET IOP traocular pressure via biologic debris • “Meta-analysis shows mean clogging the trabecular meshwork. IOP reduction with prosta- Screening for pigment dispersion can glandin analogues ranges be accomplished by carefully exam- from 28-33%. Slightly smaller ining the corneal endothelial tissues IOP reduction is typically and retroilluminating the non-dilated achieved with beta-blockers iris to look for radial (or splotchy) iris whereas alpha-agonists and transillumination defects. carbonic anhydrase inhibitors Conversely, pseudoexfoliation can will usually reduce IOP by be easily missed unless the pupil is 15-20%.” pharmacologically dilated. Other- Clement CI, Bhartiya S, Shaarawy T. wise, deposits on the face of the lens New perspectives on target intraocular can be obscured. Qualifying and pressure. Surv Ophthalmol. 2014 Nov- When in doubt, repeat the field. Dec;59(6):615-26. quantifying such debris in the angle

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about every five years, and sooner if FROM THE there is unexplained increasing intra- LITERATURE ocular pressure. Summarizing the diagnostic evalu- STUDY COMPARES FIRST-LINE MEDICATIONS FOR ation: (1) Expectantly study the optic PRIMARY OPEN-ANGLE GLAUCOMA nerve with slit lamp-enabled ophthal- This article in Ophthalmology (January 2016) definitively confirms what clini- moscopy; (2) note the intraocular cians have witnessed over the last decade: All the prostaglandins work very pressure; (3) check central corneal similarly. Some quotes from this article provide unique insights: thickness. • “The objective of this article is to assess the comparative effectiveness of Beyond these three prime maneu- first-line medical treatments for lowering IOP in patients with POAG or ocular vers, take a careful family history, hypertension through a systematic review and network meta-analysis and to especially of the brothers and sisters; provide relative rankings of these treatments. By using a systematic review obtain nerve fiber layer measure- and network meta-analysis, we estimated the pairwise comparative effective- ments, baseline visual fields and per- ness of 14 first-line IOP-lowering drugs used in patients with POAG or ocular form gonioscopy. Lastly, check blood hypertension.” pressure, especially in the setting of • “Drugs in the prostaglandin class were more efficacious than drugs in low-tension glaucoma. By doing all other classes, although the within-class differences were generally small. these things, missing glaucoma would Bimatoprost 0.01% is no more effective than latanoprost or travoprost in low- be nearly impossible. ering IOP at three months. Brimonidine lowered IOP more than ; and and betaxolol lowered IOP the least.” THERAPEUTIC • “In conclusion, we found that all active first-line drugs are effective com- PERSPECTIVES pared with placebo and that prostaglandins were more efficacious in lowering Knowing when to initiate therapy is IOP at three months than beta-blockers, alpha-agonists, or carbonic anhy- the Holy Grail of patient manage- drase. Bimatoprost, latanoprost, and travoprost are among the most effica- ment. Equally competent doctors cious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including side effects, patient preferences have different thresholds and differ- and cost, should be considered in selecting a drug for a given patient.” ent philosophies. By and large, there This final statement is a clinically practical admonishment. A key factor the is no rush to treat because glaucoma authors failed to mention is frequency of administration. While cost is a pre- is almost always a slowly progres- eminent factor, ease of use is similarly so. We find topical timolol to be cheap, sive neuropathy. The decision to treat simple and safe (in non-asthmatic patients), which is why we often start there requires much care, contemplation in select patients. It is most definitely our go-to second-line drug when target and comprehensive assessment. Also, IOP is not achieved with a prostaglandin. don’t forget that we are not treating a condition or disease; we are treating Tianjing Li, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for pri- mary open-angle glaucoma. Ophthalmology. 2016;123(1):129-40. a human patient, so involving them in the decision-making process is ap- propriate. said, let’s take a look at the various cide which drug is, overall, going to This is a drug guide, not a text- glaucoma medications we have in our best serve the patient. book. We assume a significant level of armamentarium. Generic latanoprost is a commonly knowledge on the part of the reader. prescribed glaucoma drop, and for Remember, there can be exceptions to FIRST-LINE THERAPY many patients most of the time, it is everything said herein, and every pa- Most of our patients are started on ei- often the best initial choice. However, tient has to be cared for in a highly ther a prostaglandin or timolol. These choosing the right medicine is highly individualized manner. That being medicines typically reduce intraocu- complicated by diverse and ever- lar pressure by 30% and 25%, re- changing marketing promotions (e.g., spectively. By far, the least expensive coupons) by the companies manu- glaucoma medicine is generic timo- facturing brand-name products. As a lol, which can be critically important result, there may be situations where since cost is a well-recognized reason a brand-name-protected product, at for patient noncompliance. least initially, can be less expensive. Remember, clinical management To further complicate matters, dif- occurs within the context of patient ferent insurance companies have dif- management, and multiple factors ferent drug formularies. You’re not have to be taken into account to de- entirely on your own to navigate this

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036_dg0516_Glaucoma_v3.indd 40 5/4/16 6:20 PM dynamic and maddening landscape; NEW GLAUCOMA DRUG ANTICIPATED IN 2016 the app/website GoodRx.com can as- It was 1978 when timolol came to market, and 1996 for latanoprost. After sist you in your research as you make two decades of few innovative advances, we may be on the threshold of your way through this convoluted an upgrade in clinical efficacy in the care of our patients with glaucoma. decision-making process. Latanoprostene bunod is a unique, single-entity, nitric oxide-donating prosta- We have found that prostaglandins glandin. Interestingly, it enhances conventional trabecular outflow by relaxing perform best when instilled in the eve- the trabecular meshwork cytoarchitecture and also enhances aqueous out- ning; however, if a patient tells you flow through the uveoscleral tissues. they can better remember to use their “Despite the availability of various treatments to reduce elevated IOP, drop at breakfast, then this is perfect- the most commonly prescribed glaucoma drugs do not target the compro- ly fine. The difference in morning vs. mised function of the trabecular outflow pathway,” investigators recently evening instillation of a prostaglandin wrote.1 “Therapeutic use of nitric oxide has the potential to benefit glaucoma is somewhere in the vicinity of 1mm patients by reducing IOP via targeting the diseased conventional outflow Hg, so good at breakfast is pathway.” much preferred to poorer adherence In early studies, latanoprostene bunod was found to reduce intraocular in the evening. pressure 1.23mm Hg more than latanoprost.2 It is to be used once daily. Like Rarely do patients develop signifi- the prostaglandins, it is well-tolerated and holds promise to become a major cant iris coloration changes, and even player in glaucoma patient care. Latanoprostene bunod is awaiting FDA more rarely do they develop periorbi- approval, which is anticipated in upcoming months. topathy changes linked to reduction in The brand name for latanoprostene bunod ophthalmic solution is not orbital adipose tissues. Basically, pros- known at press time, but will be marketed by Bausch + Lomb.

taglandins are generally well-tolerated 1. Cavet, MP, Vittitow JL, Impagnatiello F, et al. Nitric oxide (NO): an emerging target for the treat- and have minimal side effects. ment of glaucoma. Invest Ophthalmol Vis Sci. 2014 Aug 14;55(8):5005-15. In our patients, the 0.01% for- 2. Weinreb RN, Ong T, Scassellati Sforzolini B, et al. A randomized, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open- mulation of Lumigan is much better angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015;99(6):738-45. tolerated than the 0.03% (which is generically available), yet there is four times as much benzalkonium chloride scribed as initial therapy, worked and a second drop of brimonidine be- (BAK) in the lesser concentrated for- well, yet did not achieve the pro- tween 4pm and 5pm in the afternoon. mula, thus acknowledging that BAK is posed target range of intraocular The use of twice-daily brimonidine not as offensive as is commonly tout- pressure reduction, we would, at that tends to work well for about eight ed. However, for those rare patients juncture, choose a beta blocker as hours, and does very little during the who truly need a preservative-free op- adjunctive therapy. sleep cycle, thus the late afternoon in- tion, Zioptan nicely meets this need. Typically, this total twice-daily eye stillation of the drop rather than in- The main downside to Zioptan is that, drop frequency results in a regimen stillation closer to bedtime. like latanoprost and trifluridine, it has to be stored under refrigeration at the QUOTABLE pharmacy. Another consideration: Though these three medicines are refriger- DO NOT LOSE SIGHT OF THE FACT THAT BETA ated during storage, once dispensed to the patient, ongoing refrigeration BLOCKERS REMAIN AN EXCELLENT CHOICE FOR is not necessary; all three medicines REDUCING INTRAOCULAR PRESSURE. can be kept at room temperature by the patient. However, if a patient is dispensed multiple bottles of these of a drop of timolol within 20 to 30 Brimonidine is an alpha-2 selective medicines, we advise that the bot- minutes after awakening, and instilla- adrenergic medicine that en- tles not being used be refrigerated, tion of a prostaglandin drop at night. hances outflow, and to some degree, and the one being used be kept Most patients can handle this routine aqueous production. In our experi- where it is most convenient for the easily, and such a combined therapy ence, its two main limitations are its patient’s access. achieves target IOP most all the time. twice-daily requirement of adminis- If the patient has asthma, consider tration, and the occasional develop- ADJUNCTIVE THERAPY 0.2% brimonidine as one drop within ment of ocular surface allergic dis- Assuming a prostaglandin was pre- 20 to 30 minutes after awakening, ease. While the 0.2% concentration is

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both of these factors limit their clini- uniqueness is that, unlike Cosopt and cal usefulness. CAIs inhibit aqueous Combigan, it does not contain a beta production. Although they have a sul- blocker. Thus, for a patient with asth- fa side chain, we have observed little ma, or one who is nonresponsive to or no cross-reactivity in those people beta blockers, Simbrinza would likely who have an allergy to sulfonamide be an ideal add-on to a prostaglandin antimicrobials. drug, once individual trials of both This class of drug is represented brinzolamide and brimonidine are by the orange-capped bottles of ge- found to be efficacious. Commonly, neric dorzolamide and Alcon’s Azopt if the prostaglandin brought us close (brinzolamide) suspension. Only Azopt to target intraocular pressure but fell and Simbrinza are glaucoma suspen- short, it is likely that adding generic sions, which have to be shaken before brinzolamide or generic brimonidine each instillation. Brimonidine and dor- alone will get the IOP to target, and zolamide are found in combination using a more expensive combination with 0.5% timolol. drug may not be necessary. Cosopt is unique in that it is ge- more likely to cause allergic disease, it COMBINATION nerically available as a traditional is also less expensive than the generic GLAUCOMA DROPS bottled product and as a brand name- 0.15% and the brand-name-protected Three combination drugs are avail- protected, preservative-free unit dose Alphagan-P. So, it is occurring more able: Cosopt (0.5% timolol with product. The carbonic anhydrase commonly that we must balance cost 0.2% dorzolamide, Akorn), Com- inhibitors reduce intraocular pres- to the patient with —a bigan (0.5% timolol with 0.2% bri- sure by suppressing aqueous produc- highly subjective call. monidine, Allergan) and Simbrinza tion, and do so by only about 15%. Carbonic anhydrase inhibitors (0.2% brimonidine with 1% brinzo- Like brimonidine, they are approved (CAIs) only reduce intraocular pres- lamide suspension, Alcon). as TID products, yet we tend to use sure about 15% in our experience, Simbrinza is the only suspension them twice daily in general clinical and also have to be used twice daily; combination drug. Simbrinza’s main care. Dorzolamide is an ophthalmic

OPHTHALMIC MYTHS: GLAUCOMA Myth Glaucoma is a blinding disease and should be cared for by glaucoma specialists. Our Take Most people with glaucoma do well with the disease throughout their lives. Total blindness from this disease is exceedingly rare; optometrists should not avoid providing glaucoma care as a result of this fear. Most cer- tainly, in glaucoma patients who are adherent to medication and follow-up visits, blindness is vanishingly rare. Obviously, catching the disease early is of paramount importance. Blindness from glaucomatous disease is a common outcome in some developing countries where there is no infrastructure for care. That said, glaucoma surgical subspecialists should be consulted when medical therapy does not achieve target IOP. Myth Never use a topical beta-blocker in a patient with asthma. Our Take With written consultation with the patient’s asthma doctor, we have successfully used topical beta-blockers with several patients having asthma. Obviously, it is absolutely essential that you have the full, written consent of the patient’s asthma physician before you prescribe a beta-blocker.

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036_dg0516_Glaucoma_v3.indd 42 5/4/16 6:21 PM FROM THE LITERATURE

HOW TO SAVE MONEY ON GENERIC LATANOPROST AND OTHER DRUGS An interesting article in the March 2016 American Journal of Ophthalmology is enlightening regarding cost of generic latanoprost. Not every available gener- ic product was tested, but the findings hold practical value. • “At the time of this study, examining the generic latanoprost availabilities in the southeastern United States, Bausch + Lomb appears to be the most economical (based on [average wholesale price] AWP) of available gener- ics in regard of days-of-use per bottle and price. It did not differ significantly from branded latanoprost in regard to number of drops per bottle, days’ use per bottle, or bottles used per year, but was similarly priced to the least expensive option, costing $200 per year.” solution (original brand name Tru- • “If a patient being treated successfully with a PGA is interested in generic sopt), and brinzolamide is an ophthal- options, one potential solution could be to specify a generic manufacturer on mic suspension (original brand name the prescription, as one would typically do for the branded, thus improving Azopt). When we need to prescribe the reliability of duration of use for that specific medication.” one of these, we dose the medication • “Practitioners can better advise patients by being aware of these differ- twice daily: first dose in early morn- ences, and pharmacy managers can use these data to help select generics ing, and the second drop about eight contracted.” hours later (just as we do with brimo- Of course, while this peer-reviewed article grants us an updated perspec- nidine). tive on these various generic options, it also finds: In summary, we typically initiate • “Prescription plan coverage is a source of drug cost variation. It is dif- glaucoma therapy with a prostaglan- ficult to address the true cost-savings/loss for the patient when comparing din, and add timolol 0.25% or 0.5% branded and generic medications owing to the extreme range of coverage once daily (in the morning) if target per medication per insurance plan, including copayments, coupon cards, etc. intraocular pressure is not reached In order to have a consistent comparison, we use average wholesale price.” with the prostaglandin alone. In light of the above variables relative to access to medicines, it is difficult We still regularly initiate glaucoma to know the overall best approach for our patients. Our hope is that this therapy with a beta blocker, particu- article will, at least, give us some foundation to make rational prescription larly when only a 5mm Hg to 6mm choices going forward. Hg reduction in IOP is needed and/or Queen JH, Feldman RM, Lee DA. Variation in number of doses, bottle volume, and calculated yearly when we believe that cost is a critical cost of generic and branded latanoprost for glaucoma. Am J Ophthalmol. 2016;163:70-74. factor in patient compliance. A 5mL bottle of timolol is uniformly avail- able for about $5. Be mindful that we blockers reduce intraocular pressure blockers remain an excellent choice have found prostaglandins generally by about 25%. That’s a separation for reducing intraocular pressure. reduce intraocular pressure by about of only about 1mm Hg to 3mm Hg. Taking this together, it is apparent 30%, whereas nonselective beta Do not lose sight of the fact that beta that initial therapeutic interventions are easy, but if the patient is a prosta- glandin nonresponder and/or has ac- KEEP FINGERNAIL GROWTH, HEADACHE IN MIND tive asthma, establishing a therapeutic AND PROSTAGLANDIN EYE DROPS? plan becomes more like a chess game; According to general correspondence from the American Glaucoma Society, it involves considerable thought and it appears that prostaglandins, particularily bimatoprost, may cause finger- therapeutic trials until target intra- nails to grow a bit faster than normal. This effect might be enhanced with ocular pressure is achieved. ■ direct application of a prostaglandin to the lunula (the crescent) up to the finger. Further, some patients have noticed an attenuation of their migraine 1. Charlson ME, de Moraes CG, Link A, et al. Nocturnal systemic increases the risk of glaucoma headaches. progression. Ophthalmology. 2014 Oct;121(10):2004-12. We have no idea of the widespread clinical validity of these anecdotal 2. Quigley HA. The progression of glaucoma: it isn’t musings, but wanted to lay them out there for general clinical contemplation. what you think. In Peril to the Nerve — Glaucoma and It certainly appears that patients taking timolol and a prostaglandin could Clinical Neuro-Ophthalmology. Kugler Publications; 1998: 3-11. have improvement with their migraine headaches.

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CARE OF THE PATIENT WITH SHINGLES

Antivirals he varicella zoster virus causes patients who have not had sufficient expo- shingles. It only occurs in pa- sure to boost their immunity against it, so work best tients who have had chicken clinicians need to be ready for it. pox, generally during child- It is increasingly important that the eye during the Thood. Fortunately, due to the care community become impeccably skilled early phase advent of the childhood Varivax , and adept at caring for patients with shin- which came to market in 1995, there are gles. The diagnosis is quite straightforward of the now generations of people living who will most of the time. A minority of patients will never have shingles because they will never develop skin pain days or weeks before de- varicella contract chicken pox. veloping the vesicular eruptions associated This, however, is a double-edged sword: with shingles. Zoster disease is most com- zoster virus. prior to the Varivax vaccine, there were al- monly expressed in the trunk area of the ways children among us with chicken pox body; the second most common site is the in various stages of contagion. This allowed first (ophthalmic) division of the trigeminal the adult population to come into contact nerve distribution, which involves the fore- with the virus during the course of daily head and upper eyelid. The globe becomes living, stimulat- involved in about half of these first trigemi- ing our immunity nal nerve expressions, and there is disease against the vari- of both the skin and the eyeball. Let’s look cella zoster virus. at these two case scenarios individually. Since Varivax, that is no longer PERIOCULAR SKIN DISEASE the case. When shingles presents as an uncompli- Keep in mind cated skin disease, as evidenced by pain, that as we age, erythema and vesicular expression, the our immune sys- treatment is an oral antiviral for seven to tems become less 10 days. We find three such medications robust and, in equivalent in their therapeutic effectiveness: these “underex- • Acyclovir 800mg five times daily posed” individu- • Valacyclovir 1,000mg three times daily als, some degree • Famciclovir 500mg three times daily of shingles is even The latter two have enhanced bioavail- more likely to oc- ability, which enables them to be used less cur. Thus, we face frequently. While all three are available ge- another 30 to 50 nerically, acyclovir is the least expensive. years of increased These medicines nicely subdue a varicella occurrence of outbreak in most patients, particularly pa- HZO patient before (left) and after (right) therapy. shingles in those tients who present within the first 72 hours

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044_dg0516_shingles.indd 44 5/4/16 6:22 PM of the outbreak. Antiviral medicines We keep cyclopentolate and atro- The downside of Zostavax is that work best during the early replicative pine in our offices to jump-start the it only provides relative immunity for phase of the infection. This does not cycloplegic progress, since it may take about eight years, so repeat vaccina- mean that after three days, the op- a pharmacy a day to two to get these tion may be wise at that point. Guide- portunity for medical intervention has medicines if they are not in stock. We lines for repeat vaccinations are now passed—just that there is decreasing also tell the patient to “pharmacy- being developed. Since we are older clinical efficacy with each day of delay hop” if their usual drug store does not than 50 ourselves, we have been vac- in seeking care. With more virulent ex- have them in stock. It is important to cinated. No one wants shingles. pressions, especially in older individu- start the topical steroid as soon as pos- Patients commonly ask, “Should I als, concurrent therapy with oral pred- sible. Remember that Durezol, as an get the vaccine if I have already had nisone (usually 40mg to 60mg/day for emulsion, does not have to be shaken. shingles?” There is no definitive an- a week) can be valuable in decreasing On rare occasions, usually when swer. It is known that having shingles the pain and inflammation, and it may the patient has delayed seeking care, powerfully reboots the immune sys- dampen the expression of post-herpet- an episode of subsequent stromal-im- tem. This explains why shingles is ic neuralgia. mune uveitis or keratitis may occur. often a one-and-done event. Because Remember, herpes simplex and These cases present with a “hot” eye: the only reduces the risk herpes zoster viruses are neurotrophic very red, very inflamed, and often with of shingles by about 50%, this would viruses, and shingles may result in increased intraocular pressure. The yield a risk of 1.5% to 2.5%. Like protracted neurological pain in some aggressive use of cycloplegia and Du- many aspects of life, it’s a gamble. It is patients. The key to success in treating rezol is again deployed. No “antiviral our opinion that a patient who devel- all shingles patients is early therapeutic cover” is needed with varicella disease; ops shingles and is older than age 50 intervention, if at all possible. however, if the keratouveitis does not most likely would not benefit from the abate within an expected timeframe, vaccine because having shingles much GLOBAL INVOLVEMENT consider another course of oral antivi- more robustly stimulates our immune The plot thickens if the globe of the ral for 10 to 14 days. system than does the Zostavax vac- eye becomes involved. The old teach- This small subset of patients may cine. ing was that, if the tip of the nose was require many months or years of Oral antivirals are extremely safe involved (Hutchinson’s sign, indicating low-dose topical steroid to keep the and effective. Their only Achilles’ heel involvement of the nasociliary nerve ocular inflammation from flaring up. is that they are metabolized in the kid- which innervates corneal and intraocu- Here, once full control is gained with neys. Thus, if a patient has clinically lar tissues), the eye is too. A much sim- Durezol, we would switch the topical significant renal disease, the antiviral pler and better way to determine globe steroid to Lotemax gel off label; the se- dosage needs to be reduced. Phone involvement is to directly examine the quence would be something like this: consultation with the patient’s primary cornea and the anterior chamber. TID for one month, BID for two to care physician or nephrologist, or both, When the eye does become involved, four months and then once daily for is of utmost importance in determining it is an inflammatory uveitis or an in- several more months—always trying the optimum dosage. Computer pro- flammatory keratitis or both. Uveitic to find the least amount of medical grams and mobile apps can calculate involvement will manifest as inflam- intervention while achieving the goal the proper dosage based on renal func- matory cells in the anterior chamber; of quiescence. A drop of steroid a day tion parameters of creatinine clearance corneal involvement will manifest as for life for these patients is not unusual and glomerular filtration rates, which stromal inflammation. Occasionally, in such circumstances. Note that while the physician will have on hand. We even the trabecular tissues become in- shingles is an infectious process, the have never had to have such a consul- flamed, resulting in increased intraocu- downstream sequelae are expressed tation, but we are certainly prepared to lar pressure. Conjunctival injection, out by inflammation. do so if we encounter such a patient. of varying degree, accompanies these As shingles can be devastatingly inflammatory expressions. SHINGLES VACCINE painful, it is satisfying to provide effec- Ocular involvement of the zoster vi- The recurrence rate is about 2% to 5%. tive acute care to those who are suf- rus requires proper (usually aggressive) Having shingles once is much more ef- fering. The diagnosis is almost always treatment with cycloplegia and topical fective in preventing further outbreaks clearly evident, and the medical inter- steroids. We prescribe homatropine than is the shingles vaccine—Zos- vention is straightforward in almost all 5% for use BID to QID, along with tavax—which only reduces the risk of cases. Treatment of this disease is an Durezol every one to two hours for a having shingles by about 50%. The area in which we should all be experts, few days until the inflammation is well- Zostavax vaccine is highly recommend- as we are all likely to see more cases in controlled. Only then begin a taper. ed for those older than age 60. the coming years. ■

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LESSONS LEARNED FROM A LIFE IN THE CLINIC

Our combined ■ The attentive study of the optic nerve head is of paramount importance in the 70 years as diagnosis and management of glaucoma. IOP is secondarily important, and relative- optometric ly meaningless in the absence of pachym- physicians etry. A pharmacologically dilated pupil greatly enhances such attentive study and have yielded is essential for viewing the nerve in stereo. IOP, OCT, fields and pachymetry are all these wide- adjunct tests that will confirm your diag- ranging clinical nosis. observations ■ Use only a modest amount of fluores- cein dye when evaluating the precorneal that can hone tear film. Too much dye can mask the nu- ances of certain epithelial conditions. Also, This patient presented with an acute allergic your response unexplained subtle vision loss can result reaction to an unknown chemical. He was to numerous from epithelial basement membrane dys- given lavage, cold compresses and topical trophy in the visual axis, which can only steroid eye drops. conditions (or best) be seen with fluorescein dye. for improved ■ Many patients with dry eye disease matory drugs (NSAIDs), the , will benefit from fish oil supplementa- azithromycin, cyclosporine all have mod- patient care tion—usually about 2,000mg per day. Let est anti-inflammatory effects (and as-yet- and outcomes. them know it takes four to six months to unapproved lifitegrast is expected to) but gain the therapeutic effect as evidenced do not come close to the efficacy of a ste- by decreasing need to use artificial tears. roid. Don’t hesitate with inflammation; Further, not all people can swallow these properly suppress it. rather larger capsules; for this subset of patients, liquid supplementation will be ■ OCT technology is one of the most helpful. We recommend either Coromega helpful ancillary instruments available to Omega-3 Orange Squeeze or Nordic Nat- analyze and document retinal and nerve urals Omega 3 Liquid. changes. It is fast becoming standard of care, if it isn’t already. It can be espe- ■ When inflammation is a significant cially helpful for assessing retinal nerve component of any anterior segment dis- fiber layer thickness in glaucoma evalua- ease, always consider prescribing a topical tions, and retinal evaluations in cases of corticosteroid. Nonsteroidal anti-inflam- unexplained vision loss. Subtle epiretinal

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046_dg0516_Clinical insights_v3.indd 46 5/4/16 6:43 PM membranes and early defects such as Plaquenil Update,” below.) less steel tray with appropriate liquid macular holes, or central serous reti- chemical disinfection. As can be seen nopathy that may be difficult to see ■ Two technologies to consider: in our sidebar on handheld instru- clinically can be more easily revealed Just as OCT revolutionized retinal ments (page 48), these can vastly ex- with OCT. (and to some degree, anterior seg- pand your ability to care for a host of ■ Hydroxychloroquine (Plaquenil) ment) tissue evaluation, we predict patient presentations. screening is best accomplished with meibography will be the next major a functional assessment (10-2 visual wave of advanced diagnostic technol- ■ Be available to your patients field) and a structural assessment ogy. The discovery that meibomian 24/7. Develop call groups where six (HD-OCT). At-risk patients are those gland disease is at the heart of the or so optometrists work together to with , short stature, i.e., a small pathogenesis of most cases of dry eye take turns being on-call, usually for a body. The greater a person’s body disease makes assessment a diagnostic week at a time. Optometric patients weight is over 135 pounds, the lower imperative. should never have to subject them- the risk of paramacular toxicity. The selves to the inconvenience, expense easiest way to calculate the lean body ■ Air puff tonometry is a barbaric, and relative incompetence of emer- is as follows: For women, start at 100 unpleasant and dreaded procedure for gency departments. Whenever opto- pounds at five feet tall, and add five most patients. Goldmann applanation metric patients call their optometrist’s pounds for every additional inch of tonometry is still the gold standard. office after hours, they should always height. For example, a woman who is Another option is the Icare tonome- get an answering machine/answering 5’5” has an ideal body weight of 125 ter, a simple, handheld device that re- service guiding them to an optom- pounds, and should not be taking the quires no eye drops, and is minimally etrist. It’s simply the right thing to do. usual dosage of 400mg/day. For men, felt, if felt at all. Patient acceptance is start at five feet with 110 pounds, excellent, and it greatly enhances the ■ In the strongest of admonitions, and add five pounds for every addi- ambience of the optometric practice. we recommend all optometrists sub- tional inch of height. These general scribe to one or two ophthalmology guidelines can help stage the degree ■ Keep on hand a nice array of journals. We generally recommend of risk Plaquenil patients. (See “2016 clinical hand instruments in a stain- American Journal of Ophthalmology

FROM THE LITERATURE considered reasonable care. • No testing occurred in 25% of Plaquenil patients. 2016 PLAQUENIL UPDATE testing is of no value in HCQ testing, yet was A major article in the American Journal of Ophthalmology done on 40% of subjects. (September 2015) on hydroxychloroquine (HCQ) merits Retinal and comprehensive ophthalmologists see the highlighting. Key findings from this review of patient care majority of subjects for HCQ screening, but are appropri- at a large, tertiary medical center were eye opening; from ately screening subjects less than half the time. these, we provide some clinical point- ers (in italics). The import of all the recent literature • Based on “ideal body weight indicates that we are failing to pro- calculations,” 50% of patients were vide subjects proper HCQ screening, overdosed at the typical dosage of which is of particular concern given 400mg/day. the rising detection rate of toxicity. • At initial screening visits, about It is our opinion that evaluating the 50% of patients received a 10-2 plus an patient’s “ideal body weight,” per- objective test—usually a HD-OCT. forming the appropriate testing, and This should be a standard baseline communicating with the Plaquenil work-up for 100% of subjects taking prescriber perfectly meets the stan- Plaquenil. dard of excellence in clinical care. If • Diagnostic testing was underper- you do not have the requisite diag- formed. Only a 10-2 or only an objec- nostic instrumentation, then send your patients to an optometrist in tive test (OCT, FAF or mf ERG) was This is a classic presentation of “bull’s your area who does. accomplished in about 30% of subjects. eye” maculopathy—a very sad, and very At least one subjective test (usu- preventable, expression of permanent Au A, Parikh V, Modi YS, et al. Hydroxychloroquine ally at 10-2 with white target) and one screening practice patterns within a large multispe- vision loss from HCQ toxicity. cialty ophthalmic practice. Am J Ophthalmol. 2015 objective test (usually a HD-OCT) is Sep;160(3):561-568.

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and Ophthalmology. Better yet, form month to share and discuss pertinent cies where such “journal club” mem- groups of four to six optometrists articles. This is vastly superior to at- bers can receive continuing education where journal subscription costs are tending any lecture (including ours!). credit for such scholarly endeavors. shared, and meet for two hours once a We urge state boards to create poli- An easy portal to engage such sub- All instruments pictured are made by Storz Ophthalmic Instruments/Bausch + Lomb Instruments HANDHELD INSTRUMENTS IN • Kimura spatula. Our instrument of loose or irregular epithelial tissue, PRIMARY EYE CARE choice in obtaining corneal tissue remove erosive conjunctival concre- associated with bacterial keratitis for tions and perform eyelash epilation. Having a variety of essential hand gram/giemsa staining, and material This tool is especially helpful in epi- instruments in your examination/ for bacterial cultures. lating tiny, short, blond lashes. treatment rooms can greatly expand your ability to care for a wider array of patient care needs. Some examples are: removing corneal foreign bodies, scraping along the • Iris scissors. These are perfectly • Curved-tip serrated forceps. This eyelid margin to enhance meibum suited for destruction of symptom- can be used in a wide variety of flow into the tear film, removing atic bulbar conjunctival lymphan- applications, but works especially erosive concretions from the tar- giectatic cysts. Three or four good well at removing ticks and crab lice sal conjunctiva, epilating trichiatic slices across and through these from the lid tissues. lashes, debriding irregular epithelium cysts will not only instantaneously associated with corneal abrasions, deflate them, but this utter destruc- performing anterior stromal micro- tion prevents them from reforming. puncture, destroying symptomatic The same can be accomplished by lymphangectatic bulbar conjuncti- using a sterile needle to deflate the val cysts, removing crab lice from cyst, but without destruction of the • Epilation forceps. This instrument infested eyelashes, dilating punctal cyst, reformation commonly occurs. is obviously intended for removing orifices for punctal plug insertion, Beyond topical anesthesia with pro- trichiatic lashes, and do indeed work irrigating the nasolacrimal system, paracaine, we also instill 2.5% phen- well for this purpose. However, for using an eyelid retractor to enable ylephrine to minimize any some of the stubby, maldeveloped double eversion, incorporating a since these conjunctival cysts often lashes, jeweler’s forceps often work metal spatula to accomplish bac- have blood vessels, because they better. terial culturing, corneal rust ring are simply outpocketings of con- Wide-tipped: removal, scleral depression, and so junctival tissue. on. The following is a more detailed description of some instruments we find useful in everyday practie. Narrow-tipped: • Golf club spud. This instrument is one of the most versatile and widely used tools in all of eye care. • Shahinian cannula. This blunt- Its forté is enabling the removal of tipped cannula is perfect for irrigat- corneal foreign bodies; however, ing the nasolacrimal ducts when more recently, Korb and associates evaluating associated with • Stromal puncture needle. This is have shown it can be used to gently nasolacrimal stenosis or obstruction. a short, 25-gauge needle that has scrape along the lower eyelid mar- been precisely bent to perform gin to enhance meibum flow poste- safe application of corneal micro- riorly into the pre-corneal tear film puncture to treat focal (not diffuse) enhancing tear film function.1 Lastly, corneal erosions. If there is a large it is the instrument of choice in area of loosely adherent epithelium, removing transconjunctival erosion debridement and diamond burr of calcium concretion bodies from • Jeweler’s forceps. This highly ver- buffing or polishing of the debrided the tarsal conjunctiva. satile instrument provides multifac- surface tissue may best serve the eted utility. It can be used to remove patient. Placement of a bandage/ corneal foreign bodies, debride therapeutic soft contact lens after

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046_dg0516_Clinical insights_v3.indd 48 5/4/16 6:43 PM scriptions is www.ophsource.com. mology, and Journal Watch – General matous disease, and put the patient at Beyond the two journals mentioned Medicine, a newsletter that helps us increased risk of stroke. Such ocular above, consider subscribing to JAMA keep up with key clinical insights in TIAs generally last a few seconds to a Ophthalmology, Survey of Ophthal- general medicine. couple of minutes, whereas occipital vasospasm (ocular migraine) episodes ■ either of these procedures is typically Rarely refer patients out; rather, usually last from 10 to 60 minutes. done for three to four days along with do phone consults when appropriate. Always write a brief letter to the pa- antibiotic eye drops QID. These proce- You learn little or nothing through tient’s primary physician advising her dures are generally curative, which is a referral, but can grow your clinical or him of these findings, and send a major blessing for these patients suffer- skills and comfort level by obtaining copy of the ultrasound report as well. ing from corneal erosions. verbal guidance and then managing the patient yourself. This is power- ■ In any patient who presents with ful guidance, and holds enormous a retinal occlusion, diabetic reti- potential for optometric growth. By nopathy, , the way, when you do refer, strongly anterior ischemic optic neuropathy, consider sending to fellow ODs in etc., be sure to check his or her blood your area (or out of your area). We pressure. Undiagnosed or suboptimal- should be a family, a team working ly controlled hypertension is common • Punctal dilator. It is best to try to together for the common good of our and potentially serious. Checking insert the largest punctal plug possible patients and our profession. your patient’s blood pressure (espe- to enable retention, so adequate punctal cially in those over age 40) could be dilation should be done to accomplish ■ There are several default maneu- life-saving. this. Punctal sizing gauge devices are vers we recommend in patient care. available from many punctal plug manu- When pondering what to do in any facturers and are highly recommended KEEP number of circumstances, consider FISH OIL & to facilitate proper size selection. IN MIND these when debating: EPA–DHA • See patients (when they call with Fish oils come in different quali- a problem) ties and their essential fatty acid • Check , then dilate constituents of eicosapentaenoic • Make a phone call (to get advice) • Desmarres lid retractor. Some foreign acid (EPA) and (docosahexaenoic • Do a visual field bodies are elusive and can only be seen acid) DHA can vary. As a general with “double eversion” of the upper eye- • Evert the eye lid guideline, the milligram contents lid. The Desmarres #2 (15mm) retractor • Revisit and expand upon the case of these compounds must add works very well for this purpose, and history up to roughly 850mg to have a while not a frequent-use instrument, it • Try a corticosteroid can be very helpful when a retro-tarsal meaningful effect. These two com- conjunctival search is needed. ■ For the overall benefit of our pounds are concentrated in the profession, join the American Opto- outer layers of the photoreceptors metric Association (AOA), and con- and are thought to absorb harmful tribute to your state political action wavelengths of blue light. Because committee and the AOA PAC. Espe- lutein and zeaxanthin are supple- Other instruments are certainly avail- cially for the under-60 crowd, con- ments, you would need to know able, but these are the ones we use sider becoming board-certified by the the dietary and nutritional intake of most often, and wanted to share with American Board of Optometry; we each patient to properly quantify our readers. Having such varied and are. It is likely that such certification the precise amount of supple- versatile handheld instruments at the will become increasingly important. mentation necessary. This reality ready can powerfully arm optometrists to serve our patients’ needs in a much is often lost in the conversation ■ For any patient with a history of enhanced, comprehensive manner. regarding appropriate supplemen- transient unilateral visual phenom- tal recommendations. 1. Korb DR, Blackie CA. Debridement-scaling: a new pro- ena/loss (often those over age 50), or- cedure that increases meibomian gland function and re- der a carotid ultrasound study within Pizzimenti J, Capogna L. Choroid Chronicles. Talk duces dry eye symptoms. Cornea. 2013 Dec;32(12):1554-7. presented at the Optometric Retina Society Eye- a day or two. Such episodes most Ski Conference. Park City, UT. Feb 23, 2015. commonly represent carotid athero-

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HOW TO HELP PATIENTS PAY LESS FOR PRESCRIPTIONS are already here and become more re- fined every year. Those ODs steeped The expense of medicines today and the various tiers on formularies are in medical eye care will be doing well great frustrations for the patient and doctor alike. Fortunately, most pharma- if “refract-and-refer” practitioners are ceutical companies have developed coupons that enable patients to obtain ever replaced or eliminated. There is forbiddingly expensive medicines at a lower cost. Examples include Durezol, an entire universe of medically orient- Lotemax gel and Zylet; Alcon, Allergan and Bausch + Lomb now have cou- ed patient care in need. Just ponder pons that allow the patient to “pay no more than” $35 for many of these these things, and plan for the future. excellent, state-of-the-art medications. A fly in the ointment, though, is that these coupons are not valid if the ■ Regarding treating ocular allergy, patient is on or one of many other third-party government pro- if there are any signs accompanying grams. You may need to explain to the patient they may be told the coupon symptomatic itching, start with a top- is not valid with their insurance, upon presenting one of these coupons to a ical corticosteroid, and over a couple pharmacy. One way many doctors suggest these patients work around this of weeks, switch to an antihistamine/ obstacle is to tell the pharmacist they wish to pay cash and to “forego the mast cell stabilizing agent, if needed. insurance.” This works well in many circumstances, but sometimes the phar- macy will not allow the patient to pay out-of-pocket. We always try to keep a ■ When a patient has foreign body variety of these coupons on hand, and then coach patients on how to get the sensation but you find nothing, con- most benefit from them. sider “sweeping” the superior cul- You will need to contact the various pharmaceutical representatives of de-sac. Use proparacaine first, then the associated drug companies in order to obtain these coupons for your grease the sterile cotton swab with patients. You might also try searching for the coupons online, as many of any ointment and sweep the recess- them are available electronically. es of the upper fornix three to four times. It feels strange to the patient, ■ Preservative-free formulations If we don’t embrace glaucoma, nurse but can make you a hero. A few years are rarely needed. Most people with practitioners and physician assistants ago, our state’s largest newspaper re- a relatively normal tear film are not are waiting in the wings to take our ported the story of a woman who had affected by preservatives. The dry eye place. A note to most optometrists: consulted 11 different eye doctors (of patient on more than one preserved Refractive services are performed all stripes) over a two-year period. An eye drop may benefit from preser- by talented high school graduates in optometrist finally thought to sweep vative-free options, but for most pa- most ophthalmology practices, and her superior cul-de-sac, and out came tients, preserved formulations do just these practices are bursting at the a folded soft contact lens. There is a fine. Generally speaking, “preserva- seams. Computer-driven reason for everything: Find it. ■ tive-free” is a marketing tool, not a clinical imperative. PATIENT “MANAGEMENT” IS NOT SYNONYMOUS WITH PATIENT “TREATMENT” ■ Regarding pupillary abnormali- ties (), if there is no Treating a clinical condition is usually straightforward, but patient management or no extraocular muscle dysfunction, is fraught with many challenges: How can we ensure that the patient: then it is a benign finding. Looking • Gets your prescribed medicine and uses it as prescribed? at older photographs can be helpful • Can adequately instill the eye drop? in cases that do not resolve in a few • Adequately shakes a suspension medicine prior to instillation? days, such as accidental contact with • Returns for scheduled follow-up visits? an compound such as If you are treating a condition that you are a bit nervous about or unsure of, a patch. get the patient’s phone number and call them in a day or two to see if there are any questions or concerns, and find out how things are going. Patients love it ■ Glaucoma is a disease process when their doctors call to check on them, and doctors can sleep better at night looking for attentive optometrists. knowing their patients are doing well. Taking charge of your patient care is the Our practices are 40% to 50% glau- best way to enhance clinical outcomes, patient satisfaction and all-around posi- coma, and we thoroughly enjoy get- tive patient care experiences. ting to know these patients over the Last, always properly document all patient encounters and activities legibly in years. Relationships are established, your patient’s . Patient “management” is a reflection of compre- referrals are an annuity and our pro- hensive patient oversight; it is not simply prescribing a medicine in a vacuum. fessional services are fully enhanced.

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0046_dg0516_Clinical46_dg0516_Clinical iinsights_v3.inddnsights_v3.indd 5050 55/4/16/4/16 6:446:44 PMPM KEEP WHEN THE PHARMACY OR Plan B: Default to brimonidine 0.2% and dorzolamide IN MIND PATIENT REJECTS YOUR Rx 2% to be used first thing in the morning (be sure to Too often, we get calls from phar- instruct the patient to always wait a few minutes between macies to inform us that Drug Y prescribed for a patient instillation of the two drops), and then second instilla- is not on the insurance formulary, and they recommend tions around 4pm to 5pm. Of note, while brinzolamide Drug Z be substituted. At other times, the medicine that is in Simbrinza, when prescribing an individual carbonic would best serve the patient’s needs is quite expensive, so anhydrase inhibitor, we default to the generic dorzol- the patient rejects the prescription at the pharmacy due amide because it is less expensive and is a solution, thus it to the cost, which prompts yet another call back to the requires no shaking before instillation. prescribing doctor. We, and no doubt you, are sick of this Problem: You prescribe Lotemax gel drops off label for absurd interference in the care of our patients. a patient with dry eye disease, only to be told that it is Here is an example of the maddening scenario we all either too expensive or not on the formulary. encounter with growing frequency: We recently saw a Plan B: Try coupons, or default to generic fluorometho- young woman with chronic, recurrent, bilateral anterior lone 0.1%. While this medicine is relatively safe, it is not as uveitis whose condition was concurrently managed by her safe as loteprednol. Be sure to advise the patient that the rheumatologist, who had placed her on increasingly high fluorometholone must be shaken before each instillation. doses of methotrexate because we were unable to subdue Problem: You prescribe Zylet or generic TobraDex for the uveitis with topical steroids. We prescribed Durezol, Staphylococcal blepharitis, only to be told that it is too the best drug for her, only to get pushback from the phar- expensive or not on the patient’s formulary. macy informing us that Durezol was not on her formulary. Plan B: Offer coupons if they are available, or default to They recommended generic prednisolone acetate. generic Maxitrol if it will be used for less than two weeks. We had no choice but to acquiesce, even though in Be aware that there is a slight potential for prednisone our clinical experience, the substitute drug would likely allergic reaction, or increased intraocular pressure from require a longer time to gain control of the condition. the dexamethasone, which may occasionally be bother- After weeks of chronic recurrence, we finally provided her some. Zylet, generic TobraDex and generic Maxitrol are all with samples of Durezol and, as we expected, this quickly suspensions, and must be shaken before each use. suppressed her uveitis. Once controlled, we had to switch Problem: You prescribe prednisolone acetate for an her back to the generic prednisolone acetate because we episcleritis, but the patient is dismayed by its high price. had no more samples available for her. Plan B: Consider generic Maxitrol, ignoring the antibiot- Since we don’t seem to have leverage to remove all ic component; it is a cheap way to get access to a decent this “red tape,” here are some “Plan Bs” that we use to steroid when push comes to shove. Another option is maneuver through and around some of this bureaucracy generic prednisolone sodium phosphate, which works well to provide optimum care for our patients: for ocular surface conditions and requires no shaking. Problem: When a brand-name prostaglandin is pre- Problem: You Rx Lotemax ointment or FML ophthalmic scribed and denied, and generic latanoprost is recom- ointment, but the expense is a concern for the patient. mended: For most patients, this would be fine, but we Plan B: Try generic Blephamide ointment or Maxitrol have anecdotally found some generic varieties of latano- ointment, ignoring the antibiotic components of these two prost to perform less well than others. drugs. If you are treating contact blepharodermatitis, just Plan B: Keep and offer coupons for brand-name, pre- go with triamcinolone 0.1% cream, proactively explaining ferred drugs. These can be helpful to some patients, to the patient that the tube will state “not for ophthal- though not all. mic use,” but that it is safe to use the drug, as this is a Problem: You prescribe Combigan only to be told it bureaucratic statement, not a clinically relevant one. Note: is not on the patient’s formulary, or the patient is paying Kenalog (triamcinolone) is commonly injected intravitreal- cash for the medicine and the cost is prohibitive. ly and we have never seen a problem with use of triam- Plan B: In either case, a viable option is to prescribe the cinolone cream, even if some happens to get in the eyes. two generic ingredient drugs. In this instance, we would prescribe timolol 0.25% or 0.5% q.a.m., and brimonidine Prescribing has never been so fraught with barriers and 0.2% q.a.m. Clearly instruct the patient to wait 10 minutes inconveniences. It’s like playing chess: One must be fully between the use of these two drops. We prescribe a sec- aware of all potential moves of the adversary (in this case, ond drop of brimonidine 0.2% to be used around 4pm to the insurance companies) at all times, and be ready with 5pm. (Brimonidine only works for about eight hours, thus an effective countermove. This often requires thinking the need for the second, late-afternoon drop.) Optimally, outside the box, and you must have a comprehensive timolol is used only once daily in the morning. knowledge of all available drugs. Sometimes, after a point- Problem: You prescribe Simbrinza ophthalmic suspen- counterpoint with a pharmacist, we finally just say, “Tell sion, and are told it is not on the patient’s formulary, or me what you have,” and work from there to find a medi- that the patient can’t afford the cost. cine that is either affordable or on the patient’s formulary.

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