2019 CLINICAL GUIDE TO OPHTHALMIC DRUGS 23rd23rd EEditiondition

Expert advice to help you eradicate .

Ron Melton, OD

Randall Thomas, OD, MPH

A Supplement to Patrick Vollmer, OD

Supported by an unrestricted grant from Bausch + Lomb

001_dg0519_Cover.indd 3 5/14/19 3:39 PM FROM THE AUTHORS

DEAR OPTOMETRIC COLLEAGUES: Supported by an Welcome to the 2019 edition of our annual Clinical Guide to Ophthalmic unrestricted grant from Drugs. In these pages, we offer you our collective clinical wisdom, gleaned Bausch + Lomb from over 75 years of combined experience, and the latest information on developments in ocular therapies and care to help you in your daily practice. Though advancements are always welcome, technology is a two-edged CONTENTS sword that can truly cut both ways. For example, refraction can now be performed by any number of scanning devices. And in many parts of the world, automated refraction is the only way to provide people with Thoughts from the Chair .....3 corrective lenses. 3D printers can now produce eyeglasses. Even more strikingly, eye drop technology will soon be available to dampen the onset and degree of . We all know such advances will only continue. What we are getting at here is our strong admonition to begin diversifying Care ...... 5 your practice to embrace more medical eye care services. This is especially important for younger clinicians, since refractive-centric practices are already at risk of being replaced by technology. The time to plan ahead is now. Corticosteroids ...... 14 Turning to the state of advancing therapies, the drug pipeline has been influenced by the patent expiration of Restasis and the advent of numerous generics. Yet another new glaucoma drug was approved, as well as a Antibiotics ...... 23 non-BAK-preserved formulation of . We now have a medicine specifically indicated to help patients with neurotrophic . And a micro-particle delivery system for loteprednol was approved for BID administration, in addition to a newer 0.38% Lotemax SM available for Combination Drugs ...... 28 TID, both of which are indicated for postoperative care. Soothe XP is now offered in preservative-free unit-dose packages, AREDS2 vitamin supplements now come in chewable tablets, and a new supplement Ocular Surface Care ...... 32 containing lutein and zeaxanthin is formulated to help guard against blue light macular phototrauma. This year, as in past years, we will help you to better understand how Allergy Drugs ...... 38 to use available ophthalmic medicines as well as discuss these newer . And we will continue to emphasize the increasingly important role of systemic medications in the care of patients who present to optometrists. Shingles Therapy ...... 42 Medical care may be a science, but it’s also an art. No treatment is foolproof and methods vary among practitioners. We are pleased to share our approaches and their rationales with you each year. As always, our goal Vision Insights ...... 45 is to help you better serve and care for patients. Remember to care for them as you would like to be cared for yourself. Practice Management ...... 48 With our best wishes,

Randall K. Thomas, Ron Melton, Patrick M. Vollmer, OD, MPH, FAAO OD, FAAO OD, FAAO

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

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

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Persistence Pays Off

The need to purchased my practice in October 2016, shortly after completing my residency. diversify your Like most new grads, I was eager to make an immediate impact in my newly practice to Idiscovered community. Patients were include medical going to line up at my door, recommend my services to their family and friends and, eye care is perhaps most importantly, surrounding healthcare professionals would refer me all becoming their complex eye cases. I was going to be swamped in no time. apparent. Here’s But that didn’t happen… at least not how I broke into right away. One month into practice, I real- ized patients were not just going to sponta- the local referral neously show up at my door and I wasn’t going to be seeing emergency cases franti- Dr. Vollmer’s emphasis on emergency care network. cally sent over by other providers. I was helped his practice establish an identity as a new to my community—an outsider—and vital local resource. By Patrick Vollmer, OD, FAAO no one knew me. This was a discovery I met with early frustration. tance of offering these kinds of important Just as a financial advisor will encourage medical services. But I can assure you that you to diversify your investment portfolio, succeeding in medical eye care did not hap- I knew at the outset I had to diversify my pen overnight, even to a recent grad who services. Funding a practice strictly through was both well-trained for and enthusiastic retail alone is not infallible, and I had too about that role. much at stake. Additionally, I had studied The first time I met with the medical extensively under my coauthors, who man- community was at a local Urgent Care. I age high-level acute and chronic ocular dis- waited patiently for the attending physician ease every day, and I understood the impor- to finish examining his patient so I could

THE VIRTUES OF 24/7 EMERGENCY CARE I don’t personally subscribe to the idea that optimum patient care is a 9-to-5 endeav- or. My clinic offers around-the-clock emergency services on nights and weekends. Ironically, about 80% of all these emergency cases are not my existing patients, but rather patients who weren’t able to locate other optometrists during their distress. I’ve found this to be a tremendous practice builder. Patients really appreciate your willingness to extend your hours outside of normative realms. The number of true eye “specialists” is severely diminished outside of regular business hours. By making yourself available, you will be tapping into a market that demands your attentive expertise. At the conclusion of every exam, I say, “If you ever have an eye emergency, let me know first.” This quick comment takes three seconds. Its impact is immeasurable.

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talk with him about the services I could HOW I BECAME A RELUCTANT INTERNET STAR offer. When I met him, my attempts To give you an idea of the inroads one new optometrist can have in a com- to convey my skills and abilities were munity, my recent case—referred to me from a local Urgent Care—went dampened by his condescending re- viral on social media and was marks, including: “Are you old enough covered on news outlets from to be a doctor?” “I thought you guys Newsweek to the Daily Mail. just prescribe glasses.” “Optometrists When I first posted pictures can treat pink eye?” (Ha.) The meeting April 28 of a Pseudomonas finished in my humiliation. ulcer, directly caused by a But I came back to him next week. patient sleeping in contact And the next week. And the week lenses, I had no idea that more after that. I did this at all of the lo- than 30 million people would cal Urgent Care clinics and medical see it in the first three days. But practices, where I continued to be met I’m thrilled the case is raising The patient’s ulcer grew from a “small ucler” with the same initial responses. Despite awareness on this important noted at Urgent Care to this—in just 36 hours. my most sincere efforts to explain my issue and, hopefully, helping potential role within their clinics, I to correct unhealthy patient typically would leave each one feeling behaviors when it comes to contact wear. slightly more admonished than the last. I started the patient on forti- Then one day, I was finishing up fied antibiotic drops around work at my desk, and I got a call. It the clock and recently added was the doctor I met with the first day. steroids to reduce permanent “Yes, I have a patient here who is not scarring. While this patient’s eye getting better on the drops I prescribed. continues to drastically improve Can you see her?” This initial call was from baseline, she will likely followed by others later that week. exhibit some form of residual Around-the-clock fortified antibiotic drops The frequency and complexity of the vision loss even after treatment. and steriods have helped the patient referred cases began to accelerate with This problem is not new. This considerably. But she will likely have each successful outcome. is the fourth case of cultured permanent vision loss of some kind. I was beginning to establish myself Pseudomonas I’ve treated in in the community as a doctor who my clinic—remember, I’ve been practicing would treat ocular emergencies. With for less than three years—and I constantly each case, I would examine the patient hear from patients, “I sleep in my contacts and send a one-page report back to the all the time and I’ve never had a problem.” referring provider detailing my find- Disturbingly, the adoption—and increas- ings with a recommended course of ingly popular overnight use (or misuse)— action. This brief summary showcased of soft extended-wear contact lenses as the wide array of treatments I could a convenient method for correction of provide and brought the referring prac- routine refractive errors has been associ- titioner closure that their patient was in ated with a dramatic increase in cases of microbial keratitis in eyes not otherwise good hands. predisposed to this condition. Now, just over two years later, it’s I never recommend sleeping in soft no longer novel to be providing care contact lenses. The risks outweigh the not only to the patients of these physi- benefits every time. It takes seconds to cians, but also to the physicians’ fami- remove your contacts but risks a poten- lies and to the physicians themselves. I tial lifetime of irreversible damage if you am amicably greeted when I go to visit don’t. them now, and they know they can count on me to take care of their needs. I’m grateful that I wasn’t just handed A MESSAGE FROM DRS. MELTON AND THOMAS this privilege when I first started out. We are most happy to recommend Dr. Vollmer as a lecturer for optometric Professional development, network- continuing medical education programs. He has developed a series of clinical case presentations that perfectly represents the pinnacle of optometric patient ing and reputation-building take time. care. He can be contacted at: [email protected]. This is how it’s supposed to be. ■

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DETECT AND PROTECT THE

With laucoma management has become a hot topic in op- glaucoma, tometry these days with the recent approval of several proper Gnew drugs to reduce IOP. diagnosis and Yet, we shouldn’t lose sight of the ultimate goal when managing glaucoma patients: careful follow- protecting the optic nerve. In fact, critical observation of the optic up are crucial nerve is far more important than measuring IOP. Many patients who have statistically to protecting normal IOPs experience glaucomatous op- against optic tic neuropathy—or perhaps they do have elevated pressures but these episodes occur This optic nerve sustained severe loss of neuropathy. outside of normal office hours. We would neural tissue, thus showing a C/D ratio of 0.8. miss diagnosing these patients if IOP was Be sure to our only driving force to pursue a more detailed glaucoma workup. families. We look at the patient’s overall “look before The final common pathway of all forms health status and medications they are tak- you leap” of glaucoma is optic nerve head atrophy ing. It is important to know that oral beta- as evidenced by progressive cupping with blockers have a slightly protective effect, into medical concurrent thinning of the neuroretinal whereas calcium channel blockers such as rim tissue. Especially in older patients Norvasc (amlodipine besylate, Pfizer) can therapy. with normal-tension glaucoma, such cup- be significantly detrimental. ping can be quite elusive, as in the case of We then measure IOP, corneal thick- a shallow cup with very thin rim tissue. It 2.ness and the retinal nerve fiber layer, takes attentive study of these types of op- followed by a 24-2 SITA fast visual field tic nerve heads to detect subtle advanced and a four-mirror gonioscopic evaluation. cupping. Most importantly, we attentively So, how can eye doctors make sure they 3.study the optic nerve head. This last don’t miss glaucoma? The key is a com- step isn’t as easy as it sounds. A recent re- prehensive patient evaluation. Here is our port found “there is little consistency in the usual workup: way clinicians are taught how to identify We begin with a detailed family the disc and rim margins,” and disc exami- 1.history, especially if there are sib- nation is variable between clinicians.1 The lings with glaucoma. While glaucoma is study found fellowship-trained glaucoma not inherited per se, it does tend to run in specialists show substantial differences in

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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 timolol hemihydrate Akorn 0.25% 5ml 0.5% 5ml, 10ml, 15ml Betoptic-S betaxolol hydrochloride Novartis 0.25% 5ml, 10ml, 15ml Istalol timolol maleate Bausch + Lomb 0.5% 2.5ml, 5ml Timoptic timolol maleate Bausch Health 0.25% 5ml, 10ml, 15ml and generic 0.5% 5ml, 10ml, 15ml Timoptic (preservative-free) timolol maleate Bausch Health 0.25% unit-dose 0.5% unit-dose Timoptic-XE timolol maleate Bausch Health 0.25% 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 travoprost Novartis 0.004% 2.5ml, 5ml Travoprost travoprost generic 0.004% 2.5ml, 5ml Vyzulta latanoprostene bunod Bausch + Lomb 0.024% 2.5ml, 5ml Xalatan latanoprost Pfizer, + generic 0.005% 2.5ml Xelpros latanoprost ophthalmic emulsion Sun Ophthalmics 0.005% 5ml Zioptan Akorn 0.0015% unit-dose

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

Carbonic Anhydrase Inhibitors Azopt brinzolamide suspension Novartis 1% 5ml, 10ml, 15ml Trusopt dorzolamide Merck and generic 2% 5ml, 10ml

Rho Kinase Inhibitors Rhopressa Aerie Pharmaceuticals 0.02% 2.5ml

Combination Glaucoma Medications Combigan brimonidine/timolol Allergan 0.2%/0.5% 5ml, 10ml Cosopt dorzolamide/timolol Akorn and generic 2%/0.5% 5ml, 10ml Cosopt PF dorzolamide/timolol Akorn 2%/0.5% unit-dose Rocklatan netarsudil and latanoprost Aerie Pharmaceuticals 0.02%, 0.005% 2.5ml Simbrinza brinzolamide/brimonidine Novartis 1%/0.2% 8ml suspension their optic nerve head tissue estimates Luckily, numerous tests and clini- explaining the situation to the patient in glaucomatous or at-risk eyes. cal parameters exist to help us follow and thoroughly answer all of their The takeaway here is that critical glaucoma patients, so being a little ir- questions. If we read skepticism on assessment of the micro-neuroanat- regular with a single observation car- the patient’s face (which is very rare), omy of the optic nerve head is truly ries no meaningful impact to quality we suggest getting a second opinion, subjective, and all eye doctors strug- of life concerns. and we recommend several glaucoma gle with detailed assessment. We look Once these steps are complete, we subspecialists in the area. This further back through our own records and can assess risk and decide whether assures the patient that we do, indeed, are dismayed at the inconsistency of to follow the patient, the frequency know what we’re talking about. our quantitative grading and tissue of follow-up and whether to initiate Whether the patient’s IOP is high characterization. It’s oddly reassuring therapy. If therapy is initiated, we al- or normal, the ultimate goal is to re- that such inconsistency occurs at all ways do a monocular therapeutic tri- duce it to a target range you feel is levels of clinical expertise. al. Most importantly, we spend time safe for that individual.

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TODAY’S PERSPECTIVE ON RHO-KINASE INHIBITORS An exhaustive “translational science review” on this topic was published in the November 2018 issue of , with several observations wor- thy of sharing: • Under normal physiological conditions, about 15% of aqueous humor exits via the uveoscleral pathway. Prostaglandins greatly shift aqueous outflow through the uveoscleral tissues. • “Brimonidine may lower IOP, in part, by stimulating prostaglandin THERAPEUTIC TOOLBOX release.” Now, let’s turn our attention to the • “Approximately 40% to 50% of patients require two or more medica- therapeutic armamentarium available tions to adequately lower .” to us to reduce IOP. • Current commonly used glaucoma medications adjunctive to pros- If the patient has established glau- taglandins reduce IOP by 1.5mm Hg to 3mm Hg. In keeping with this coma as evidenced by visual field de- trend, “Netarsudil lowers IOP approximately an additional 2mm Hg when fects that correspond to your observa- added to a prostaglandin […] however, the incidence of adverse events tion of the optic nerve head, the IOP is higher.” needs to be reduced generally into • “Rho-kinase inhibitors have a variety of effects. They can increase blood the low- to mid-teens. Here we usu- flow by causing vascular smooth muscle relaxation leading to vasodila- ally initiate prostaglandin therapy; tion. On the ocular surface, this can lead to conjunctival hyperemia.” our newest option in this category Such action also causes smooth muscle cell relaxation in the trabecular is Vyzulta (latanoprostene bunod meshwork. 0.024% ophthalmic solution, Bausch • Conjunctival hyperemia was observed in about 50% of patients and the + Lomb), which we have found to be “incidence and severity remained stable through the three-month study most effective at reducing IOP. period.” If, on the other hand, the optic • Paralimbal subconjunctival hemorrhages were seen in about 14% of nerve is healthy but the IOP is perhaps patients, and about 10% developed corneal verticillata—neither of which 28mm Hg, and we want to decrease have any clinically significant bearing. These conditions resolved after the IOP into the low 20s, we might drug discontinuation. select a beta-blocker for both efficacy • “It is notable that a large proportion of patients withdrew from clinical and cost; however, in most instances, trials because of adverse events, raising some questions about the ease we simply follow the patient without with which these agents can be used in clinical practice.” therapy every six months and repeat • “Although these agents have been shown to be effective in lowering testing annually. Don’t be in a hurry intraocular pressure, both as monotherapy and adjunctively with beta- to treat. Glaucoma, on average, pro- blockers and prostaglandin analogues, their side effect profile raises seri- gresses at about 3% per year, so no ous concerns about the likelihood of their acceptance by patients.” rush—rather, timely attentiveness As we earnestly strive to share clinical knowledge with our colleagues and follow-up are the keys. to enhance patient care, we also want to share our perspectives. First, if an Daily dosing options. The prosta- adjunctive medicine to a prostaglandin is needed, it is abundantly evident glandins have been the drug that timolol is the drug of choice because of its dosing regimen, cost and of choice for initial therapy efficacy. since 1996, when latano- Perhaps even more importantly, and in acknowledgement of the reality prost first came to market that adding any adjunctive medicine adds further expense and complexity to under the brand name Xa- the regimen, target-range IOP might be achieved by simply switching from a latan (Pfizer). While there standard prostaglandin to Vyzulta, which has been shown to further reduce are now several prosta- IOP. glandins to choose from, Do not let us persuade you here; instead, we invite you to think along with they all work about the us as we ponder how to best serve our patients based on medical literature same, with the exception and our many combined decades of caring for patients with glaucoma. of Vyzulta (see, “Vyzul- Tanna AP, Johnson M. Rho kinase inhibitors as a novel treatment for glaucoma and ocular ta: A One-Two Punch to hypertension. Ophthalmology. 2018;125(11):1741-56. IOP”).

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VYZULTA: A ONE-TWO PUNCH TO IOP the setting of clinically expressed asth- ma. Always inquire about a history of While Vyzulta is primarily a prostaglandin, it has a secondary effect on trabecu- asthma prior to prescribing any topical lar outflow beyond its enhancement of uveoscleral outflow. This is a single mol- ecule that is cleaved by intrinsic esterases to also release nitric oxide, which is beta-blocker. the biochemical stimulant of outflow. Timolol has a long half-life, which is This secondary effect is what separates this medicine from the other prosta- why it can be used once daily. Timolol glandins. Vyzulta reduced IOP anywhere between 7.5mm Hg and 9.1mm Hg in is ineffective during the nocturnal sleep Phase III studies.1-3 In preapproval studies, Vyzulta decreased IOP an average of cycle, so it requires morning adminis- 1.23mm Hg beyond that of latanoprost.1-3 The significance here is that several tration. We use the 0.25% formulation independent studies have established that every millimeter reduction in IOP for patients with lightly pigmented iri- results in a 10% decrease in the risk of glaucoma progression.4-6 des (usually Caucasians) and the 0.5% As a prostaglandin, Vyzulta performs maximally when instilled in the evening for patients with darkly pigmented and, as with latanoprost, is stored under refrigeration at pharmacies. However, irides since melanin pigments tend to Vyzulta can be kept at room temperature for up to two months once it has absorb some of this medicine. been dispensed to the patient. It shares a high tolerability profile with latano- Of our numerous glaucoma pa- prost and its 0.2% benzalkonium chloride preservative. Further distinguishing tients, 80% to 85% use a prostaglan- Vyzulta, it comes in both a 2.5mL and a 5mL bottle. din drop alone, timolol alone or a com- We know that about half of all glaucoma patients end up requiring a second bination of the two. eye drop as they age to further decrease IOP. By using Vyzulta with its dual Another relatively new once-daily effect, our hope is that we can push the need to add a second drop further glaucoma is Rhopressa down the road. Any time we can decrease therapeutic complexity, it enhances (netarsudil 0.02%, Aerie Pharmaceu- adherence and intraocular pressure control. ticals), which works exclusively at the As with all branded products, coupons greatly reduce the cost to the patient. trabecular meshwork to enhance aque- Also, many new drugs require prior authorization, so Bausch + Lomb has con- ous outflow. , a parasym- tracted with a company (parxsolutions.com) to help streamline this encum- pathomimetic, also potentiates aque- brance. ous outflow, but through a different 1. Weinreb RN, Sforzolini S, Vittitow J, Liebmann J. Latanoprostene bunod 0.024% versus timolol mechanism; it causes contraction of maleate 0.5% in subjects with open-angle glaucoma or : The APOLLO study. Oph- thalmology. 2016;123(5):965-73. the longitudinal muscles of the ciliary 2. Medeiros FA, Martin KR, Peace J, et al. Comparison of latanoprostene bunod 0.024% and timolol body, mechanically opening the po- maleate 0.5% in open-angle glaucoma or ocular hypertension: the LUNAR study. Am J Ophthalmol. 2016;168:250-59. rous trabecular tissues. Because of its 3. Kawase K, Vittitow JL, Weinreb RN, et al. Long-term safety and efficacy of latanoprostene bunod QID frequency of administration, ac- 0.024% in Japanese subjects with open-angle glaucoma or ocular hypertension: the JUPITER study. Adv Ther. 2016;33(9):1612-27. commodative spasm, brow ache and 4.Heijl A. Glaucoma Treatment: by the highest level of evidence. Lancet. 2015;385(9975):1264-6. , pilocarpine quickly fell out of 5. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of the treatment. favor once beta-blockers came to mar- Arch Ophthalmol. 2003;121(1):48-56. 6. Bengtsson B, Leske MC, Hyman L, et al. Fluctuation of intraocular pressure and glaucoma progres- ket in 1978. sion in the early manifest glaucoma trial. Ophthalmology. 2007;114(2):205-9. Rhopressa works through a rho-ki- nase (ROCK)–mediated chemical sys- Recently, Xelpros (latanoprost we almost always add a beta-blocker, tem that reduces IOP on average about 0.005% ophthalmic emulsion, Sun usually timolol, for three reasons: (1) 4mm Hg to 5mm Hg and is used once Pharmaceuticals) became our only it is inexpensive, (2) it is administered daily, usually in the evening, as with version of latanoprost not preserved once daily and (3) it has good efficacy. the prostaglandins. The Achilles heel with benzalkonium chloride—it uses Nonselective beta-blockers such as of Rhopressa is its proclivity to cause 0.47% potassium sorbate instead. timolol reduce IOP about 25%, significant conjunctival hyper- No refrigeration is required for long- which is not that much less than emia, which is likely to limit its term storage, and, as with the original the 30% to 35% reduction seen acceptability for many patients. latanoprost, it is dosed once daily in with the prostaglandin class. Rhopressa can cause an amiod- the evening. However, be aware that Systemic beta-blockers are arone-like verticillata deposition you can’t just “prescribe” Xelpros, as always among the top 10 most in the , although this has it’s not available in retail pharmacies. prescribed medicines in the no clinical significance. Fur- This medication can only be ordered United States because they are ther, some patients may expe- through the manufacturer’s two con- prescribed for a wide variety of rience some subtle paralimbal, tracted pharmacies via XelprosXpress. heart conditions. Beta-blockers splotchy and transient subcon- If we are unable to achieve the tar- are quite safe, with the signifi- junctival hemorrhages, also with get range IOP with a prostaglandin, cant exception of their use in no known clinical significant.

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005_dg0519_Glaucoma.indd 8 5/14/19 3:53 PM THE CASE FOR PILOCARPINE A 49-year-old female has long been treated for open-angle ocular hypertension (baseline IOPs in the high 30s) with a prosta- glandin and Combigan. She had 0.5 cups and healthy optic nerves when she became our patient. Her IOPs have been main- tained in the low 20s during these past years. All testing is normal. Now she and her husband are trying in vitro fertilization to have a child. We wanted to see if her glaucoma medicines could be stopped during her anticipated pregnancy, so we per- formed a standard discontinuation trial. The patient returned in about two weeks complaining that her eyes were uncomfort- able, and we found that her non-treated IOPs were in the low 60s. While we needed to avoid a prostaglandin during pregnancy because of the rare possibility of uterine contractions, she des- perately needed something. We consulted three different glaucoma subspecialists, all of whom had nothing to offer and sent the patient back to us. We then telephone consulted with a university medical center glaucoma specialist who had an idea: he recommended we restart the patient on Combigan and try 1% pilocarpine QID, since these three drugs are relatively safe. We also inserted punctal plugs in her lower to further minimize any systemic absorption. This approach brought our patient’s IOPs into the mid to upper 20s during the course of her successful pregnancy, and she tolerated the pilocarpine well. Now at age 51, the patient has a healthy two-year-old and is back on a prostaglandin along with Combigan. Although the pilocarpine was a successful treatment avenue, it required QID dosing, and it is much simpler for her to use the once-daily prostaglandin. Clinicians should also consider pilocarpine for the patient with advanced glaucoma who is on maximum medical therapy (a prostaglandin with one of the four combination drugs). Of the typical glaucoma medication classes, only prostaglandins pro- vide a clinically significant nocturnal effect on IOP reduction. Adding 1% or 2% pilocarpine at bedtime may further reduce IOP during the night, when IOP has been documented to be highest.

Although Rhopressa could be used as KEEP GLAUCOMA PEARLS initial monotherapy, its role as adjunc- IN MIND AND PONDERINGS tive therapy to a prostaglandin remains ill-defined. • Most patients can tolerate an IOP of 30mm Hg for many years and may Rocklatan (Aerie)—a combination never require treatment—although they merit close follow-up. of netarsudil 0.02% and latanoprost • Because early therapeutic intervention only provides modest benefits, not 0.005%—gained approval in March rushing into treatment may be best for most patients. 2019 and is the newest once-daily • Most (but not all) cases of glaucoma progress quite slowly, at about 3% per medication that capitalizes on both the year. trabecular meshwork and uveoscleral • We all lose about 5,000 optic nerve fibers annually as a natural course of outflow pathways to lower IOP. We aging. Since we start with about 1.2 million optic nerve fibers, this is rarely a are strongly philosophically opposed concern. to all combination glaucoma medi- • Never believe an initial visual field result unless it appropriately correlates cines as first-line therapy because IOP with your clinical assessment and a nerve fiber layer analysis study of the may well be achieved with one-agent optic nerve head. If the visual field correlates with the optic nerve anatomy, it drugs. However, to give Rocklatan is likely valid. If any ambiguity exists, simply repeat the field in a few months. its due, clinical trials found that more • Physiological cupping is almost always round, whereas glaucomatous optic than 60% of patients taking the drug neuropathic cupping typically manifests as a somewhat vertically elongated achieved an IOP reduction of 30% cup. This can be quite helpful when trying to appreciate and differentiate or more, a frequency that was nearly whether the cupping of the optic nerve is physiologic or pathologic. twice that achieved by participants • Retinal nerve fiber layer hemorrhages occur in most (if not all) glaucoma taking latanoprost alone.2 patients and are transient. These hemorrhages, when seen, do not alter our But remember that cost is a major therapy. deterrent to patient adherence with • Short-wavelength automated perimetry and frequency-doubling technology their glaucoma medications. We ask (FDT) protocols are no more useful than standard white-on-white visual field testing. We have not found FDT to be superior to standard field testing. all of our colleagues to not immedi- • Nearly 10% of patients with glaucoma or ocular hypertension have no idea ately jump at the possibility of a new why they are taking eye drops. A recent study found “poor communication combination medicine; rather, be pa- and patient disease understanding persists in this setting.”1 tient-centric in your decision-making • Take ample time to converse with glaucoma and glaucoma suspect patients and prescribing. In most cases, we to educate and encourage them. Such conversations greatly enhance patient would first try generic latanoprost to compliance. see if it achieves a target IOP range. If the latanoprost comes close to target 1. Lowry EA, Mansberger SL. Characteristics of patients receiving treatment who deny a diagnosis glaucoma or elevated intraocular pressure in the United States. J Glaucoma. 2018 Nov;27(11):1029-1031 but does not quite reach it, then we

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might try Vyzulta or add timolol. Of FROM THE course, all of this rhetoric could go out LITERATURE the window if manufacturers provided coupons to make these drugs more FAMILY HISTORY IN AN AFRICAN-AMERICAN COHORT cost-effective. We all need to be particularly attentive to our patients with African and Twice-daily dosing options. The Caribbean heritage for myriad reasons. If you have diagnosed your patient two other commonly used classes of with glaucoma and they fall into one of these cohorts, aggressively pur- drugs, alpha-adrenergic receptor ago- sue ocular examinations for the families of these patients, with the ultimate nists and carbonic anhydrase inhibi- goal of catching undiagnosed glaucoma as soon as possible. A study in the tors, do not have once-daily dosing. American Journal of Ophthalmology drives home this point: If we cannot, or choose not to, use • “Multiple epidemiological studies have confirmed that African-Americans one of the once-daily drugs, we gen- are disproportionately affected by primary open-angle glaucoma and erally do a therapeutic trial of bri- present earlier with more severe and rapidly progressive disease.” monidine 0.2%, originally known as • “Siblings of affected patients are at greatest risk of developing primary Alphagan (Allergan) until Alphagan-P open-angle glaucoma, compared to parents or children.” (Allergan), a 0.15% formulation hit • Positive family history in a first-degree relative was associated with a 3.4 the market. This is still significantly times greater risk of developing glaucoma. more expensive than the generic 0.2% O’Brien JM, Salowe RJ, Fertig R, et al. Family history in the primary open-angle African American formulation, and all three concentra- glaucoma genetics study cohort. Am J Ophthalmol. 2018 Aug;192:239-47. tions work similarly. A significant minority of patients will ultimately develop an allergy to brimonidine, as and they generally decrease IOP about KIDS WITH LARGE evidenced by a follicular tarsal con- 15%. Like brimonidine, the topi- OPTIC NERVES junctivitis and, usually, a low-grade cal carbonic anhydrase inhibitors are We all see young people with . These symptoms often require FDA-approved for TID administra- large and impressive optic nerve discontinuation of this class of drugs. tion, but most prescribe twice daily head cupping, and it does give us Brimonidine is FDA-approved for use. While these drugs have some ef- pause. However, juvenile glaucoma TID administration because it has fect overnight, they are not as effective is almost invariably accompanied about eight hours of efficacy. We al- nocturnally as the prostaglandins, and by significantly increased IOP, and most always prescribe brimonidine their modest nocturnal performance most suspicious-appearing optic twice daily, usually to be used shortly precludes them from being top-tier nerves have IOPs within normal after awakening and then again about performers. limits, unless they have thickened eight hours later. Brimonidine does Cosopt (Akorn) is a combination . little or nothing during the sleep cycle of dorzolamide with 0.5% timolol, The key to managing these and should not be used near bedtime. but most simply prescribe a generic patients is examining the parents Patients often struggle to remember dorzolamide-timolol. Clinicians now and other siblings. Anatomic fea- the afternoon drop (of any medicine), have a generic form of the preserva- tures are inherited, and central cor- so suggest that your patients set a cell tive-free, unit-dose Cosopt formula- neal thickness is the most heritable phone timer to remind them. tion to prescribe when a preservative- aspect of ocular anatomy. Thus, Because of cost, we almost always free formulation is necessary. measuring the parents’ corneal prescribe the 0.2% concentration of Azopt is also available in a com- thicknesses can help you under- brimonidine. Combigan (Allergan) is bination but with brimonidine, not a stand the patient’s inherited ocular a combination drop of 0.2% brimoni- beta-blocker, making it a reasonable anatomy. To be safe, also obtain a retinal nerve fiber layer analysis and dine with 0.5% timolol. choice for patients with asthma who take baseline photos on the patient. The last commonly used class of truly need both ingredient drugs. This Once we establish that the young glaucoma medicine is the carbonic brand name-protected combination person likely has large physiological anhydrase inhibitors. Dorzolamide is ophthalmic suspension, Simbrinza cups, we typically follow the child a generic 2% solution, while Azopt (Novartis), is relatively expensive and annually. (brinzolamide, Novartis) comes as can intelligently be prescribed only if a 1% ophthalmic suspension. Since monocular therapeutic trials of each these two drops are clinically equiva- ingredient drug show meaningfully ef- both are relatively inexpensive, the lent, we prefer the generic solution of ficacy, and it is affordable to the pa- patient must wait at least five minutes dorzolamide. Only rarely do either of tient. Otherwise, we must prescribe between each instillation. This is cer- these drops exert a robust response, both individual generic drops. While tainly suboptimal compared with one

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0005_dg0519_Glaucoma.indd05_dg0519_Glaucoma.indd 1100 55/14/19/14/19 3:543:54 PMPM One thing is for sure: there is a huge GLAUCOMA MEDS AND SURGERY: Q&A population of undiagnosed glaucoma. Should patients on anticoagulation medicines who are contemplating The potential is there for an enormous Q.intraocular surgery be advised to stop these medicines during the periop- erative period? public health benefit if optometrists There is no increased risk of associated with anti- are vigilant in diagnostic attentiveness A.platelet therapy. However, newer anticoagulants may decrease the risk of and enthusiastically embrace the clini- bleeding compared with warfarin. cal care of these patients, or send them to an optometric colleague who will. Should patients taking a topical prostaglandin be advised to stop one of Q.these medicines during the perioperative period, since these medicines NORMAL-TENSION GLAUCOMA: have a warning regarding cystoid ? A FRESH PERSPECTIVE Our broad observation of expert behavior shows that cataract surgeons Patients with statistically normal IOPs do not alter patients’ glaucoma therapy based on cataract surgery. A. who still show signs of glaucomatous are more common bottle containing both drugs, but the people are not the best of patients. than you might think. In fact, nor- less expensive two drugs may be es- They often quit taking their eye drops mal-tension glaucoma (NTG) is now sential for cost-sensitive patients. and, on occasion, no-show for sched- thought to account for 20% to 40% uled exams. Clinicians must develop of all open-angle glaucoma patients, THERAPEUTIC TIMING an in-office system to track these pa- and prevalence is considerably higher The actual time of treatment initiation tients so that if they skip follow-ups, in patients of Japanese descent. Based for IOP control is relatively straight- you will know. This should prompt a on the Collaborative Normal-Tension forward; the ultimate challenge, how- telephone call to the patient in an ef- Glaucoma Study (CNTGS), we know ever, is knowing the optimal time to fort to reschedule. Good patient edu- that 80% of treated patients and 60% start therapeutic intervention. Equally cation by the optometrist goes a long of untreated patients progress within good doctors have different thresholds way to ensuring good patient coopera- three years; at five years, 80% and for therapeutic initiation. The good tion and care. 40% do not progress, respectively.3 news is that, with rare exception, glau- coma is a slow pathological process FROM THE and there is rarely a need to rush into LITERATURE therapy. Attentively following patients every four to six months is reasonable PERSPECTIVE ON OCULAR HYPERTENSION and can allow more thoughtful, delib- TREATMENT STUDY erate decision-making when the time A recent journal article enumerated five key take-home points from the land- comes to start treatment. mark OHTS study: We generally see patients every • Approximately 5% of Americans over the age of 40 have ocular hypertension. three months initially and extend • Screening tests include retinal nerve fiber layer assessment and visual field those visits out to every four months testing. as we become comfortable with thera- • One study found the observation group developed POAG in an average of six peutic success and the patient’s under- years compared with 8.7 years in the medication group. standing of their medications and the • “There is little absolute benefit of early treatment in low-risk ocular hyperten- need for timely follow-up. Ultimately, sive patients. Most ocular hypertensive patients fall into this group and prob- in many cases, we end up seeing them ably can be followed less frequently without treatment.” every six months. We generally repeat • The authors identified five factors—age, IOP, central corneal thickness, verti- retinal nerve fiber layer measurement, cal cup-to-disc-ratio and visual fields—that all merit our attention. perform visual field assessments and • We would like to add a sixth “key factor” to this list: measuring the status of the retinal nerve fiber layer. If clinicians are keenly attentive to these six fac- perform a dilated examination annu- tors, it is our opinion that glaucoma would never be missed. Although true ally. Since it is possible to obtain ste- glaucoma is a progressive optic neuropathy, it usually takes a few years for reoscopic biomicroscopic condensing conversion from ocular hypertension to glaucoma. There is rarely a need for lens-enabled views of the optic nerve rushing to therapy; even with traditional therapy, conversion occurs, but it head through a 3mm or larger , does extend the time of conversion by about two-and-a-half to three years. we do a quick ophthalmoscopic as- At that point, therapy must be modified to achieve further IOP reduction. sessment between the annual dilated examinations. Gordon MO, Kass MA. What we have learned from the Ocular Hypertension Treatment Study. Am J Ophthalmol. 2018;189:24-27. But clinicians must remember that

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FROM THE diurnal IOP fluctuations lead to mis- LITERATURE diagnosis of NTG because clinicians miss the peaks of elevated IOP in a large number of patients with progres- OBSERVATIONS FROM THE “KING OF GLAUCOMA” sive primary open-angle glaucoma Dr. Harry Quigley of Johns Hopkins is, in our opinion, the ultimate authority in (POAG).4 One study found 80% of glaucoma, so when he speaks, we listen. From his November/December 2018 medically controlled NTG patients Glaucoma Today article, we share these insights. The publication may be non– had prolonged nocturnal IOP spikes, peer reviewed, but Dr. Quigley is an expert of the highest order: and 96% of NTG patients had more • “For the first two to three years of care, we do not truly know whether the patient’s visual field or OCT is stable or getting worse, so we use an intraocu- IOP variability than healthy patients. lar pressure reduction goal that is individualized for each patient.” This obser- Such a discovery is key for making vation is why we cannot judge progression based on a single visual field. With treatment decisions, considering pro- exceedingly rare exception, glaucoma progresses slowly, such that true pro- gression is strongly associated with 4 gression takes a minimum of two to three years to reliably show itself. IOP amplitude. • Regarding the determination of baseline IOP (on a patient you might inherit The same study found NTG patients from another practitioner), “take the patient briefly off any drop treatment with a baseline IOP of less than 15mm that he or she may have been prescribed for a couple of visits, reassuring the Hg had significantly increased IOP at patient that damage will not progress in a week’s washout.” We often inherit bedtime, and progressing patients with patients from all over the United States who are currently treated for glau- IOPs at target levels had mean peak coma. In most cases, depending on their stage of progression, we ask them IOP well above target at night. The to stop their drops for two weeks, and then we recheck their IOP. researchers concluded that increased Over the decades, we have seen that about a third of these patients are nocturnal IOP could be a risk factor being treated for a disease they do not have. That is, their on-treatment and for progression in NTG.4 off-treatment IOPs are the same. It may be that some of these people do New technology such as 24-hour indeed have glaucomatous optic neuropathy but are on an ineffective treat- monitoring may one day help correct ment, or it may be that they are simply not using the previously prescribed this error by documenting IOP spikes eyedrops as they should be; thus, a heartfelt, person-to-person conversation above target levels. While in-office regarding proper use of any medication may be the most critical aspect of monitoring is impractical, at-home their care. Assuming proper use but non-response to the previous medicine, a IOP-monitoring devices, such as the new treatment regimen can be intelligently attempted as a therapeutic mon- Icare Home tonometer, could be useful ocular trial. tools to measure diurnal IOP and help • “If the patient’s target IOP is 15mm Hg, and IOP at this visit is 18mm Hg, should one change the target or add more drops? Neither. Instead, try to us fine-tune our understanding of the assess whether the patient is adherent with the prescribed treatment. At least patient’s IOP profile. half the time, with improved adherence, the patient regains the target. For For reasons that are not yet un- a patient who is achieving his or her target IOP, and yet is having confirmed derstood, there is agreement that dis- worse visual field, improved adherence is still a likely solution. If it is not, a ruptive blood flow to the optic nerve lower target and closer OCT and visual field follow-up are needed.” describes the pathophysiology.5 Vaso- • “With every patient, a balance must be achieved between the benefits of IOP spasm is thought to play a role in some reduction and the burdens of therapy. Setting a target IOP can help codify patients having disorders such as mi- our best estimate for where this balance lies, but it requires evaluation of mul- graine and Raynaud’s disease. Subnor- tiple factors in addition to IOP and the recognition that the target may have mal nocturnal blood pressure can add to be adjusted based on the clinical course of each patient.” further insult, which is why obstructive • It is our duty to have meaningful conversations with our patients and to form sleep apnea syndrome needs to be ad- a team-based relationship to ensure optimum therapy. dressed in some of these patients. Sleep studies may be key to search for this Sit AJ, Quigley HA. Target IOP: to set or not to set? Glaucoma Today. 2018;16(6):42-45. common comorbid condition. Clini- cians should be careful to prescribe Because the odds of progression are since the CNTGS. For example, recent systemic beta-blockers and especially about 50/50, we need to attentively data suggests about 10% of patients calcium channel blockers for morn- follow these patients and therapeuti- continue to progress, even with ideal ing administration to avoid potentially cally intervene if there is any evidence IOP reduction. In those uncommon damaging an already subnormal de- of progression. cases, we must redouble our efforts to crease in nocturnal blood pressure. Several discoveries have updated aggressively decrease IOP. Research suggests both brimonidine our understanding of this condition In addition, research suggests large and timolol may exhibit some degree

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0005_dg0519_Glaucoma.indd05_dg0519_Glaucoma.indd 1122 55/14/19/14/19 3:543:54 PMPM FROM THE even performing, if your state allows— LITERATURE laser trabeculoplasty, which can re- duce IOP about 20%. Various surgical GLAUCOMA AND EXERCISE procedures may help reach the target IOP if these primary interventions fail.4 Often, patients ask if there is anything they can do to help their glaucoma. We But the best intervention is actually have historically reiterated to these patients, “just be faithful to taking your eye drops!” Although we have known for years that consistent exercise can making the right diagnosis by perform- be helpful in the setting of glaucoma, the degree of benefit demonstrated in a ing diurnal curves and documenting recent study was surprising.1 Still, getting patients to make lifestyle changes is IOP peaks. This will make sure your a formidable challenge—think of discussing weight loss benefits with patients patient truly has NTG and not just with diabetes or idiopathic intracranial hypertension, and the benefit of smok- “missed” higher IOP readings. A de- ing cessation for patients with age-related . vice such as the Icare Home tonometer Whether they take our evidence-based advice or not, we must share this can help to make this determination. knowledge with our patients and do our best to encourage them to modify Once you properly diagnose NTG their lifestyles. and document compelling evidence • Recommend 150 minutes of moderate-intensity aerobic exercise and two of progressive optic neuropathy (as days of resistance exercise each week.2 evidenced by true progression of visual • Such exercise may reduce glaucoma risk by as much as 40% to 50%.2 fields and nerve fiber layer diminu- • Promote that physical activity can help to prevent glaucoma, in addition to tion), then aggressive IOP lowering is other chronic diseases. standard of care. ■ • “The magnitude of a 40% to 50% reduced risk of developing glaucoma by being active and fit is surprising, and may be one of the strongest factors 1. Hong SW, Koenigsmana H, Ren R, et al. Glau- coma Specialist Margin, Rim Margin, 2 in glaucoma prevention, besides aging.” and Rim Width Discordance in Glaucoma and Glaucoma Suspect Eyes. Am J Ophthalmol. 1. Meier NF, Lee DC, Sui X, Blair SN. Physical activity, cardiorespiratory fitness, and incident glaucoma. 2018;192(8):65-76. Med Sci Sports Exerc. 2018;50(11):2253-58. 2. Brubaker J, Teymoorian S, Lewis R, et al. 2. Crist C. Staying fit might cut glaucoma risk. Reuters Health News. www.reuters.com/article/ Once-daily fixed-dose combination of netarsudil us-health-glaucoma-fitness/staying-fit-might-cut-glaucoma-risk-idUSKBN1L21JZ. August 17, 2018. 0.02% and latanoprost 0.005% in ocular hyper- Accessed March 27, 2019. tension/open-angle glaucoma: 12-month data from MERCURY-1. Presented at the 28th Meeting of the American Glaucoma Society, March 1-4, of neuroprotection, but this quantita- so the role of these newer medications 2018; New York, NY. 3. Collaborative Normal-Tension Glaucoma tive component requires further inves- is not yet fully understood. If progres- Study Group. The effectiveness intraocular pres- tigation.5 sion endures, even with a 30% reduc- sure reduction in the treatment of normal-ten- sion glaucoma. Am J Ophthalmol. 1998;126:498- Regarding therapy, the CNTGS tion in IOP, additional topical eye 505. found a prostaglandin combined with drops may be required to drive the 4. Razeghinejad MR, Lee D. Managing Normal- Tension Glaucoma by Lowering the Intraocular timolol was the most effective in low- IOP lower, even into the low teens. For Pressure. Surv Ophthalmol. 2019;64(1):101-16. ering IOP in NTG. But remember, this patients with sufficient angle pigmen- 5. Adeghate J, Rahmatnejad K, Waisbourd M, Katz LJ. Intraocular pressure – independent study was done prior to the availability tation (as determined by attentive go- management of normal-tension glaucoma. Surv of Vyzulta, Rhopressa and Rocklatan, nioscopy), consider referring for—or Ophthalmol. 2019;64(1):101-10.

FROM THE LITERATURE

A FINER POINT OF GLAUCOMA PATIENT CARE In patients with advanced asymmetric cupping, is there anything the patient can do, other than adhere to their medical therapy? Probably. A recent study shows patients’ habitual sleeping positions may be exacerbating their optic neuropa- thies, which potentially impacts IOP.1 When patients sleep with their face pressed into the pillow on one side, IOP can increase on that side from direct physical/mechanical pressure. Even if their eye is not directly pressed into the pillow, just having the more pathologic optic nerve in a downward position can result in increased IOP in that eye compared with the upward facing eye. Wearing a Fox shield during sleep may mitigate the increase induced by direct pillow pressure. Clinicians should educate patients about trying to sleep with their more advanced glaucomatous eye in the upward position; sleeping on their back with their head elevated may offer an advantage as well. These are, admittedly, fine points, but in the setting of advanced or advancing disease, every effort to protect against further progression is worthwhile.

Meurs I, Thepass G, Stuij A, et al. Is a pillow a risk factor in glaucoma. Acta Ophthalmologica. 2018;96(8):795-99.

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FLEX YOUR THERAPEUTIC MUSCLE WITH CORTICOSTEROIDS

When ocular n this 23rd issue of the Clinical Guide rounds steroids, possibly due to uncertain- to Ophthalmic Drugs, our thoughts on ty on the part of the prescriber regarding inflammation the virtues of corticosteroid usage for side effects. These notions must be coun- eye inflammation remain unwavering. tered with accurate findings that demon- is present, IWhen inflammation is present, these strate the overwhelming advantages of drugs continue to be the most powerful these drugs—and the detriment to the pa- only one and effective agents optometrists can pre- tient of not using them expediently when class of drugs scribe in patient care. Their applications indicated. should be well integrated into our clin- For example, we see cases of acute red can provide ics—aggressively prescribing them when eyes weekly. Since up to 80% of conjunc- indicated will prevent further damage. tivitis presentations are viral in nature, unparalleled When dosed properly, steroids work ex- with secondary inflammation, prescrib- pediently and effectively. The three authors ing antibiotic monotherapy for acute red relief for of this guide have collectively encountered eye runs the risk of subjecting the eye to patients. many thousands of patients in our clinics, further damage from prolonged untreated many of whom have presented with ocular inflammation.1 It also increases the anti- Don’t hesitate inflammation. Nearly all were treated with biotic resistance profile for the patient (a steroids, and not one got patient worse on significant concern in medicine). This is to use it. the regimen, to our knowledge. In fact, in all the more inadvisable given that only more than 75 years of combined practice, a minority of patients with acute red eye we have yet to encounter a patient whose will benefit from antibiotics to any degree, inflammation did not drastically improve based on our years of experience. on topical and/or oral corticosteroids. Outside the realm of eye care, patients However, an unfortunate stigma sur- who seek red eye evaluation and treatment

This patient with epidemic was treated succesfully with a betadine wash and Lotemax.

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014_dg0519_Corticosteroids.indd 14 5/14/19 4:26 PM QUOTABLE to treat with topical steroids, having the patient return to you in a timely manner will reveal ineffective treat- “Most cases of acute are nonbacterial ments or misdiagnosed conditions. in origin, and even among those with a bacterial That way you can quickly alter the therapy if necessary. cause, antibiotics have only a modest benefit in If you have nagging concerns from reducing symptom duration. The complications the start, call the patient in a couple of acute conjunctivitis are so rare that there is no of days to check on the patient’s prog- ress. Patients love having their doctors evidence from systematic reviews that antibiotics call to check on them. reduce rates of complications.” As one example, let’s say you ex-

Keen M, Thompson M. Treatment of acute conjunctivitis in the United States and evidence of antibiotic amine a patient with typical lesions overuse: isolated issue or a systematic problem? Ophthalmology. 2017;124(8):1096-8. that could be Thygeson’s superficial punctate keratopathy (SPK) or her- from other medical entities (e.g., ur- make it difficult to diagnose in the ear- petic eye disease. Since most red eyes gent care clinics, emergency depart- ly stages. The use of a corticosteroid— are inflammatory in nature, we are ments, primary care) likely will also even if it is a combination antibiotic/ inclined to initiate therapy with a ste- encounter a reluctance to prescribe steroid—could worsen the condition. roid. However, in the uncertainty of steroids for acute red eye. Since con- In every case of prescribing steroids, the diagnosis, we would tell the pa- junctivitis presents in various forms make sure to see the patient back for tient something like this: “This medi- (viral, allergic, bacterial or nonspecif- timely follow-up to evaluate the prog- cine should help your eye get better ic), the untrained professional might ress of the therapy. quickly but, at this time, the diagnosis not accurately segregate the diseases of your condition is not completely or understand the importance of ste- NEED FOR FOLLOW-UP clear, and there is a chance your eye roids to controlling inflammation in In all cases, proper follow-up is para- could worsen on this drug. It is im- this setting. mount. Patient education and open portant that you let me see you again At the same time, many physi- discussions minimize misconceptions in a couple of days. I will be glad to cians and medical professionals tend and concerns about a given disease or work you in anytime.” As previously to overprescribe antibiotics, given therapy, and strengthen the doctor- mentioned, this truly caring conversa- their well-known safety profiles. This patient trust. This, in turn, reduces the tion is key to optimal patient care and mindset to “play it safe” actually can likelihood of patients seeking unwar- rapport. do more harm than good. Inflamma- ranted second opinions that can lead All of this falls under the heading of tion does not go into clinical remission to a delay in care. “patient management” and goes well with antibiotics alone and habitually Acute conjunctivitis rarely presents beyond mere disease management. delays patient recovery. Thus, in the in textbook fashion. More often than Trying to solely manage disease with- setting of acute red eyes, we unhesi- not, the eye will just show signs of out also managing the patient often tatingly prescribe topical ophthalmic nonspecific inflammation. While this results in frustration for both doctor steroids, either as monotherapy or in shouldn’t discourage your willingness and patient. (This not only applies combination with antibiotics. By the same token, it’s essential to rule out herpetic etiology—the main contrain- THREE REASONS WHY ANTIBIOTICS dication to topical steroids. ARE OVERPRESCRIBED IN EYE CARE To be clear, improper use of cor- During our many years in clinical eye care practice, we have identified the fol- ticosteroids can have unwanted and lowing reasons why some doctors overprescribe antibiotic agents: damaging results for your patient un- 1. Some optometrists neglect to stay informed about the latest research and become therapeutically complacent. der rare circumstances. While there 2. Clinically differentiating between various types of conjunctivitis can be chal- are plenty of indications for the use of lenging. This leads providers to prescribe antibiotics “just in case” there is topical steroids, one contraindication an underlying infection. exists: epithelial herpetic infection. 3. The patient perception that antibiotics are a harmless cure-all for their ail- And when the diagnosis is uncer- ments leads many patients to frequently request prescriptions “to be safe.” tain, you should use caution. For ex- Providers often submit to these unfounded petitions to maintain or improve ample, the clinical presentation of an patient satisfaction. Acanthamoeba or can

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to corticosteroid treatment but also to the management of any eye condi- tion.)

MAXIMUM EFFICACY STEROIDS Another common pitfall by optome- trists is to hesitantly prescribe steroids to “test the waters”—an approach that neither leads to symptomatic re- lief nor expedites disease remission. In our experience, “hammering” inflam- As vital as topical steroids are to clinical practice, optometrists must remember that mation with corticosteroids at initial oral steroids should also be readily used, not feared—at least for short-term use presentation quickly suppresses the (less than a week). Further, after a single week of prednisone therapy, it can just inflammatory cascade, after which an be stopped, not tapered. Take this patient, for example. An office accountant for a appropriate tapering schedule can be fiberglass factory, he would occasionally visit the actual plant. He presented with executed if indicated. these facial and ocular symptoms (at left), showing an obvious allergy to the plant’s Clinically, we have found the two environmental assaults. With 40mg of oral prednisone, his symptoms improved most efficacious topical ophthalmic significantly in three days. He was educated on the need to wear adequate face steroids over the last several years to protection whenever he visits the factory. be Durezol emulsion (difluprednate 0.05%, Novartis) and Pred Forte A NEW TWIST TO LOTEPREDNOL (prednisolone acetate 1%, Allergan). Remember when Patanol (olopatadine, Novartis) went from 0.1% to 0.2%? Durezol. Often employed as a It also switched from twice- to once-daily usage. We find that when a prod- heavyweight of topical corticoste- uct’s concentration doubles, we can use it about half as frequently. roids, Durezol is usually looked upon Kala Pharmaceuticals has doubled the traditional concentration of lotepre- favorably when moderate to severe inflammation needs to be rapidly sup- dnol 0.5% to 1%. And the FDA approved its Inveltys ophthalmic suspension pressed. This drug is manufactured as as a twice-daily drug with a sole indication of treating postoperative inflam- an emulsion and does not need to be mation and pain following ocular surgery. To enable the twice-daily dosing, shaken before use. Kala also uses a micro-particle technology to enhance its ocular surface resi- The drug has a long history of use dency time and potential penetration.8 We envision Inveltys joining Lotemax in severe or non-resolving iritis and SM and Alrex in the care of patients with dry eye disease. is gaining recognition as a popular TOPICAL CORTICOSTEROID DRUGS BRAND NAME GENERIC NAME MANUFACTURER PREPARATION BOTTLE/TUBE Maximum Strength Steroids Durezol difluprednate 0.05% Alcon emulsion 5ml Lotemax SM loteprednol etabonate 0.38% Bausch + Lomb gel drops 5g Lotemax gel loteprednol etabonate 0.5% Bausch + Lomb gel drops 5g Lotemax ointment loteprednol etabonate 0.5% Bausch + Lomb ointment 3.5g Inveltys loteprednol etabonate 1% Kala Pharmaceuticals suspension 5ml Pred Forte prednisolone acetate 1% Allergan and generic suspension 5ml, 10ml, 15ml generic prednisolone prednisolone sodium generic solution 5ml, 10ml, 15ml sodium phosphate phosphate 1% Maxidex dexamethasone 0.1% Novartis suspension 5ml Vexol rimexolone 1% Novartis suspension 5ml, 10ml

Moderate and Lesser Strength Steroids Alrex loteprednol etabonate 0.2% Bausch + Lomb suspension 5ml, 10ml Flarex fluorometholone acetate 0.1% Eyevance Pharmaceuticals suspension 5ml, 10ml FML fluorometholone alcohol 0.1% Allergan and 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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014_dg0519_Corticosteroids.indd 16 5/14/19 4:05 PM postoperative medication. Clinically, MICROHEMANGIOMAS we prefer Durezol over Pred Forte for Also known as iris vascular tufts, these presentations are usually discovered several reasons: We have found it to following spontaneous . They can be unilateral or bilateral, and are be more effective, it does not need to almost always found at the pupillary border. Iris microhemangiomatosis has be shaken prior to instillation and it does not need to be dosed as often, no known systemic associations, but can occasionally present with transiently which increases patient compliance. elevated IOP. The natural course is benign and they often resolve spontane- The glucocorticoid binding affin- ously in about a week; thus, observation is typically the best form of initial ity of Durezol’s active metabolite dif- management.1 If treatment is necessary, and steroids are an luprednate was found to be 56 times option, as is argon laser. 2 stronger than prednisolone. In addi- 1. Williams BK Jr, Di Nicola M, Ferenczy S, et al. Iris microhemangiomatosis: clinical, fluorescein angi- tion, the drug’s structural modifica- ography, and optical coherence tomography angiography features in 14 consecutive patients. Am J Ophthalmol. 2018;196:18-25. tions enable difluprednate, a deriva- tive of prednisolone, to have a more consistent potency than prednisolone. As a general rule, the more effica- cious the drug, the more potential for adverse side effects. Durezol is no ex- ception, as it can be associated with elevated intraocular pressure (IOP). Thus, best practices must be engaged, with frequent follow-ups to monitor This patient presented with a concern that their eye was bleeding. Note the iris the patient’s condition and check IOP. vascular tufts at the pupillary border. Pred Forte. While not as clinically

TIPS FOR TAPERING Ever had a challenge tapering a patient off of a topical corticosteroid? Steroids are wonderful for short-term therapy but carry intrinsic risks when used long-term. Here are a few thoughts: You can usually get a patient’s down to two or three times a day, or even once daily, before a relapse occurs. If a relapse does happen, increase the dosage frequency and try a longer, slower taper. In addition, try adding a topical NSAID such as Prolensa (bromfenac, Bausch + Lomb) once daily, or generic diclofenac or ketorolac QID as you begin the next step-down off the corticosteroid. This may offer enough supplemental anti-inflam- matory support to enable the continuation of the steroid taper. Or, try the oral NSAID route: Celebrex (celecoxib, Pfizer) 100mg per day for a few weeks as needed. In some cases, long-term steroid use can be indicated. Certain patients with corneal transplants, stromal immune cor- neal disease, chronic uveitis or recalcitrant dry eye disease might be kept on low-dose steroids for life. While older ketone-based steroids were frequently used for long-term therapy in the past, we recommend ester-based loteprednol SM 0.38% or 0.5% gel off-label once daily for these protracted dosing schedules. Though ketone-based steroids appear to work well in this low-dose approach, it stands to reason that loteprednol is preferable because of its enhanced safety profile as an ester-based steroid. Some patients require one drop of steroid daily to maintain control of their conditions.

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effective as Durezol, prednisolone KEEP acetate 1% (not to be confused with IN MIND prednisolone sodium phosphate 1%, a solution form of prednisolone) pos- RELATIVE CLINICAL sesses impressive anti-inflammatory EFFICACY OF TOPICAL efficacy. Its widespread use in ocular STEROIDS inflammatory conditions is most no- Here, based on our combined tably embraced postoperatively as clinical experience and compara- well as for anterior uveitis cases. Un- tive information we have avail- like Durezol, this drop is a suspension able, we rate the relative efficacy and must be vigorously shaken before This inflamed pingueculum should be of topical steroids, starting with instillation. treated with a topical steroid. Once the most efficacious: Some pharmacists will dispense ge- the inflammation is under control, neric prednisolone acetate, even when the ocular surface must be kept 1. Difluprednate 0.05% you specifically indicate “dispense as properly lubricated to prevent further 2. Prednisolone acetate 1% written” on the prescription. The ge- inflammatory expression. 3. Loteprednol 0.38% or 0.5% neric options, although less expensive, 4. Rimexolone 1% are considerably less effective.3 When 5. Fluorometholone acetate 0.1% our patient requires maximum effica- phate 1% solution (original brand 6. Dexamethasone 0.1% cy, Durezol is our drug of choice. name Inflamase Forte) and generic 7. Fluorometholone alcohol 0.1% prednisolone acetate 1%. Dexameth- 8. Loteprednol 0.2% HIGH EFFICACY STEROIDS asone, either as a solution or suspen- 9. Prednisolone 0.125% Next in clinical efficacy are Lotemax sion form, is also in this category. Of SM and Lotemax Gel (loteprednol note, we have found that generic pred- 10. Hydrocortisone 1% 0.38% and 0.5%, Bausch + Lomb), nisolone sodium phosphate 1% solu- generic prednisolone sodium phos- tion does not penetrate transcorneally

THE LOTEPREDNOL MOLECULE stromal-immune herpetic keratitis, Thygeson’s SPK, recur- AND ITS NEW ITERATIONS rent corneal erosions, contact dermatitis, to supplement In 1998, the landscape of corticosteroid medicines was steroid eye drop therapy; acute, advanced uveitis or remarkably enhanced with the advent of a novel, retro- ; following Betadine epidemic keratoconjunc- metabolically designed ester-based molecule— lotepred- tivitis treatment and for numerous other inflammatory nol. The initial suspension formulation had numerous clini- conditions. Lotemax ophthalmic ointment is the only cal indications to include the treatment of steroid-respon- preservative-free corticosteroid available. sive inflammatory conditions of the palpebral and bulbar In 2012, Lotemax gel came to market and was formu- , cornea and anterior segment of the , lated as an emulsion with no shaking required. Today, such as , acne, rosacea, superficial we have two improvements to the loteprednol molecule punctate keratitis, herpes zoster keratitis, iritis, cyclitis delivery systems: a 1% ophthalmic suspension (Inveltys, and selected infective conjunctivitides “when the inherent Kala Pharmaceuticals) and a 0.38% Lotemax SM ophthal- hazard of steroid use is accepted to obtain an advisable mic gel drop. All are only indicated to treat postoperative diminution in edema and inflammation.”7 inflammation and pain but widely used off-label for other Since 1998, the loteprednol formulations have seen sev- purposes. eral additions, modifications and enhancements. Alrex is a 0.2% concentration indicated for “the temporary relief Clinicians can use any of these loteprednol formulations of the signs and symptoms of seasonal allergic conjunc- on-label or off-label, as long as they enlist them prudently tivitis.” Of course, the Lotemax 0.5% suspension could and in a scientifically sound manner. For our part, we easily be used for this same clinical condition, as it offers a would use any of these products to treat mild to moder- broad array of indications. ate inflammatory conditions of the ocular surface, most Though Lotemax ophthalmic ointment’s indication is notably dry eye disease. The consensus of peer-reviewed for postoperative inflammation and pain, we have used professional literature supports this patient-centric use. In it extensively for numerous off-label indications. These any and all clinical situations, our prime concern is how to include dry eye, allergy, corneal transplant protection, best care for our patients; frequently, this means employ- , giant papillary conjunctivitis, chronic uveitis, ing off-label applications.

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014_dg0519_Corticosteroids.indd 18 5/14/19 4:05 PM STEROIDS vs. CONTACTS: WHICH IS THE GREATER DANGER TO PUBLIC HEALTH? Anyone who gives this question any thought would have to conclude that contact lenses represent a far greater risk to public health than topical or even oral steroids. To be fair, it might not be the actual lenses but patient misuse of these devices that represent the threat. Nonetheless, to be intellectually honest, the two really cannot be separated. Every year, there are numerous cases of microbial keratitis in the United States, as well as many deaths attributable to opioid abuse and motor vehicle fatalities. Using motor vehicles is a necessity for most of us; however, for the most part, wearing contact lenses is an option. Based on this data alone, a rational argument could be put forward to ban the use of these potentially dangerous devices. In one retrospective cohort and trend study, researchers evaluated the laboratory results and prognostic factors of poor clinical outcomes in microbial keratitis cases over 15 years at Saint Louis University and found that Pseudomonas aeruginosa and other organisms were commonly recovered from microbial keratitis cases with a disproportionately high incidence, and seemed to be related to the number of contact lens-related keratitis cases.1 They wrote, “We hypothesize that we are seeing more contact lens-related cases owing to the presence of a grow- ing population in the St. Louis area that use and abuse contact lenses. An epidemiological analysis of our contact lens- related cases mirrors the findings of a Centers for Disease Control and Prevention report regarding the relative young age and female preponderance of contact lens wearers and their high prevalence of reported misuse of contact lenses, which predisposes them to eye infections.” The purpose of this commentary is not to denigrate contact lenses, which are a wonderful vision correction tech- nology. Rather, we are trying to make the point that any technology has its risks when applied in the wrong manner or subjected to unsafe circumstances. Optometrists don’t hesitate to prescribe contact lenses—so why all the anxiety about steroids? We encourage eye doctors to consider using topical and oral corticosteroids whenever warranted, to take advantage of their potentially significant benefits for patient care.

1. Hsu HY, Ernst B, Schmidt EJ,et al. Laboratory results, epidemiological features, and outcome analysis of microbial keratitis; a fifteen-year review from St Louis. Am J Ophthalmol. 2019;198(2):54-62.

as effectively as the acetate moiety. Lotemax SM and Lotemax gel geson’s SPK, chronic uveitis, inflamed Lotemax SM 0.38% and 0.5% gel are non-settling eye drops that don’t and pterygia. drops. The newest version of lotepre- require shaking before instillation. While we have found that lotepred- dnol uses submicron (SM) particles to Though labeled as gels, once on the nol is not quite as efficacious as pred- enhance drug dissolution in the tears, ocular surface, the drugs become a nisolone and Durezol, its ester-based which doubles penetration transcor- viscous liquid. derivatives correlate to fewer unwant- neally compared with Lotemax 0.5% We often prefer Lotemax SM or ed side effects (e.g., subcapsular cata- gel drops. This variation also enables gel as an off-label treatment for many racts and elevated IOP). In Phase III greater adherence to the ocular sur- of our dry eye patients. We also use studies, for instance, only two out of face. The FDA approved the drug for it to treat a number of chronic, recur- 409 patients on Lotemax gel (0.5%) the treatment of postoperative inflam- rent inflammatory conditions such as had an IOP increase greater than mation and pain following ocular sur- stromal , Thy- 10mm Hg after 18 days of treatment.4 gery, but numerous off-label uses exist for such an enhanced formulation. INJECTABLE STEROIDS FOR POST-OP CARE & BEYOND Neither the original nor latest for- Some injectable drugs have been approved for postoperative use after ocular mulation require shaking due to a surgeries and diabetic . Optometrists involved in surgical coman- gel-to-liquid delivery system. Lotemax agement should be aware of these new agents. SM 0.38% is approved for TID dos- • Yutiq (fluocinolone acetonide intravitreal implant 0.18 mg, EyePoint ing, while the 0.5% version is ap- Pharmaceuticals) treats chronic noninfectious uveitis affecting the poste- proved for QID dosing. Of course, in rior segment of the eye. the setting of more severe ocular in- • Dexycu (dexamethasone 9% intraocular suspension, EyePoint flammation, a more aggressive dosing Pharmaceuticals) is approved as a single-dose, sustained-release steroid schedule would be indicated. Both are injection to treat inflammation associated with cataract surgery. preserved with a very low-dose BAK • Dextenza (dexamethasone ophthalmic intracanalicular insert 0.4mg, (0.003%). For perspective, latano- Ocular Therapeutix) treats postoperative pain up to 30 days as a single prost contains 0.02% BAK, and is treatment. well tolerated.

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And loteprednol 0.5% suspension, metholone has less chance of raising Alrex. Another ester-based steroid, when used for postoperative cataract IOP than other ketone steroids, we are Alrex (loteprednol 0.2%) is an excel- surgery inflammation, was shown to not as comfortable using it long-term lent off-label treatment in cases of be nearly as effective as prednisolone as we are using ester-based lotepred- Thygeson’s SPK, ocular allergy and acetate, with less effect on IOP.5 nol. maintenance therapy (if needed) for Prednisolone sodium phosphate Since you should use the lowest DED. Because Alrex is slightly less 1%. Although generic, this drug re- effective dose in all cases, we do not efficacious than its “bigger brothers” mains a viable option when an inex- recommend FML Forte (fluorometho- Lotemax SM 0.38% and Lotemax gel pensive, potent steroid is needed. Un- lone 0.25% ophthalmic suspension) 0.5%, it theoretically has a safer ther- like many other topical steroids, the because the fluorometholone 0.1% apeutic profile for extended use. We drop is prepared as a solution, not a concentration represents the top of often use Alrex for patients presenting suspension, and doesn’t need to be the dose response curve—meaning with allergic eye disease whose itching shaken before instillation. It remains that 0.25% is no more efficacious is accompanied by any signs of con- an excellent choice for older patients than 0.1%. junctival injection, chemosis or with arthropathies that make shak- ing a bottle challenging. It’s also well- LOTEMAX GEL VS. LOTEMAX OINTMENT suited for soft contact lens wearers be- Patients, practitioners and pharmacists may mix up these two medicines, so cause it won’t precipitate on the lens let’s set the record straight. to the same extent as suspensions. • Lotemax SM and Lotemax gel.1 Though Prednisolone acetate 1%. Generic called a gel, this comes in a dropper bottle, like prednisolone acetate suspension is a solution. However, inside the bottle it is indeed relatively inexpensive and is a reason- a highly viscous, semisolid gel formulation. But, able choice for mild to moderate acute through a process called adaptive viscosity, it inflammatory conditions. However, becomes a liquid when squeezed out of the it’s not preferred in the setting of ad- dropper. And upon instillation in the eye (no vanced iritis and episcleritis. Make shaking is necessary), the formulation loses its sure you indicate “brand name nec- gel structure altogether as the polycarbophil essary” when prescribing for clinical polymer interacts with the electrolytes in tears. situations that are potentially vision Still, the drop is rather thick upon instillation and threatening. We recommend just pre- will cause a moment of initial blur until the gel fully converts into a liquid. We advise patients to scribing Durezol to bypass the bu- allow the drop to spread out on the ocular surface for four to five seconds reaucratic hassle of battling with the before blinking, so that the initial blink does not displace the drop onto the pharmacy or insurance company. eyelid. Because of the nature of this unique gel, the steroid does not settle out of MODERATE EFFICACY the vehicle, so it does not require shaking. (It is best to tip the bottle back STEROIDS and forth once to make sure the drug enters the tip of the dropper prior to The two most common topical ste- instillation, but no actual shaking is necessary.) Also, unlike suspensions, this roids in this category are fluorometh- delivery system provides a perfectly uniform dose at every instillation.1 olone 0.1% suspension and Alrex sus- • Lotemax ointment.2 This preparation comes in a 3.5g tube and con- pension (loteprednol 0.2%, Bausch + tains inactive ingredients of white petrolatum and mineral oil. Because it Lomb), both of which must be shaken is an ester-based corticosteroid and also because it is a preservative-free prior to instillation. preparation, it may provide a slight safety advantage over fluorometho- Fluorometholone 0.1%. Two de- lone ointment. Lotemax ointment is rivatives of fluorometholone 0.1% indicated for the treatment of post- suspension are available: alcohol operative inflammation and pain, but (FML, Allergan and generic) and ac- is also applicable in many other cases etate (Flarex, Eyevance Pharmaceuti- in which an ointment is useful for sup- cals and generic). Be advised that the pression of inflammation.2 acetate moiety gives the fluorometho- 1. Marlowe ZT, Davio SR. Dose uniformity of lotepre- lone molecule additional anti-inflam- dnol etabonate ophthalmic gel (0.5%) compared matory effectiveness over the alcohol with branded and generic prednisolone acetate ophthalmic suspension (1%). Clin Ophthalmol. 2014;8:23-9. 6 moiety. Because fluorometholone 2. Comstock TL, Paterno MR, Singh A, et al. Safety and efficacy of loteprednol etabonate ophthalmic alcohol is available generically, it’s ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011;5:177-86. relatively inexpensive. Though fluoro-

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Myth: Never use a topical steroid if a significant epithelial defect is present. Our Take: Corneal infiltrates are common presentations, especially in contact lens wearers. If these leukocytic infil- trates remain in the anterior stroma long enough, the overlying epithelial cells can succumb to inflammatory activity just beneath them. The epithelial defect results from subjacent inflammation. Topical corticosteroid suppression of the stroma (AKA subepithelial inflammation) rapidly enables the corneal epithelium to repopulate. Without use of topical steroids, the epithelial defect would endure for many days until innate resolution occurred. Our consistent observation has been that round or oval defects at or near the limbus are involved in inflammatory processes due to the anatomic proximity of abundant humeral immunity (antibodies) and cellular immunity (leukocytes) at the highly vascularized limbus.

Myth: Steroids can cause IOP to rise. Our Take: While technically true, the application of topical steroids in an appropriate manner can help reduce this potential side effect. As one example, the trabecular tissue can become inflamed as a result of shingles and other anterior segment inflammatory disorders. Rarely is there a need to use anti-hypertensive medications in these situations; rather, a topical steroid often can suppress tissue inflammation, helping the IOP to renormalize.

Myth: Never use a steroid in combination with an antibiotic when treating bacterial conjunctivitis because the steroid will impede bacterial eradication and slow healing. Our Take: This is a purely academic concept that holds no practical application. We almost always treat bacterial con- junctivitis with an antibiotic-steroid combination, since this allows us to do three things: kill the bacteria, suppress the sec- ondary inflammation and get our patients looking and feeling better more quickly.

Myth: Be very careful with steroids; they can be dangerous. Our Take: In all of our years of combined clinical practice, we have never found this to be the case. There are situations in which steroids could potentially worsen a patient’s condition, such as with epithelial herpes simplex disease, but such a condition is nearly impossible to miss with attentive care. To explain further, since herpes simplex viral epithelial keratitis is a unilateral condition, any unilateral red eye must prompt the clinicians to consider the potential diagnosis of herpes simplex keratitis. In every case, instill fluorescein dye to examine the integrity of the corneal epithelium. If it is pristine yet the differential diagnosis remains elusive, then pre- scribe a steroid because most acute red eye cases are inflammatory in nature. It is possible (though exceedingly rare) that herpes viral conjunctivitis could precede corneal disease. So in that case, prescribing a steroid might lead to corneal dendrites. This is not even a serious problem. At this point, simply stop the steroid (no need to taper) and start an oral antiviral medication; the patient will improve. No doctor is perfect, and occasional misadventures do occur; thankfully, they can almost always be remedied fairly eas- ily with a little clinical know-how.

Myth: Never use steroids in the setting of adenoviral infection, as they prolong ultimate healing. Our Take: This might be academically true, but who cares? By using a steroid, the patient is going to feel much better during the course of the disease. Although it might take a few more hours to get better, the patient will be much less mis- erable while the tissues heal.

Myth: If you’re not sure of the diagnosis, use an antibiotic for a few days initially and then see the patient back to reevaluate. Our Take: Our many decades of experience lead us to one simple observation, although it runs contrary to conventional wisdom: “When in doubt, consider a steroid.” If you are concerned or unsure about a particular patient, get the patient’s phone number and call in a day or two to see how the individual is doing. This shows that you care, and you’ll feel better knowing that your patient is feeling better.

swelling. We typically dose Alrex (or roids’ various delivery systems (sus- STEROID OINTMENTS Lotemax) QID for one week, then pensions, solutions, emulsions, gels Ophthalmic ointments enjoy a wide BID for one to four weeks. and ointments) in addition to know- array of clinical indications. Three ste- It’s important to be aware of ste- ing their clinical efficacy. roids meriting frequent clinical use are:

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Lotemax ointment. The only ester-based steroid ointment avail- able, Lotemax ophthalmic ointment (loteprednol 0.5%, Bausch + Lomb) is indicated for postoperative inflamma- tion and pain but has many off-label clinical applications. Some examples are dry eye, allergy, corneal transplant protection, blepharitis, giant papillary conjunc- tivitis, chronic uveitis, stromal immune herpetic keratitis, Thygeson’s SPK, This patient presented with considerable ocular surface inflammation; after four days recurrent corneal erosion, of topical steroid therapy, she has much improved. steroid eye drop therapy augmentation in acute ad- of prednisolone acetate suspensions. J Ocul vanced uveitis or episcle- Corticosteroids are the most essen- Pharmacol Ther. 2007;23(2):182-7. ritis, contact dermatitis tial and highly prescribed medicines in 4. FDA Center for Drug Evaluation and Research. and other inflammatory the treatment of ocular inflammation Deputy Division Director Review for NDA 202-872. 2012 Sep 27. www.accessdata.fda.gov/drugsatfda_ conditions. Lotemax oint- of any stripe. Their widespread use docs/nda/2012/202872Orig1s000MedR.pdf. ment is ideally suited for confirms that ocular inflammation is Accessed March 21, 2019. 5. Lane SS, Holland EJ. Loteprednol etabonate 0.5% patients who complain of sandy and the most common clinical manifesta- versus prednisolone acetate 1.0% for the treatment gritty eyes upon awakening. tion in eye care. It is imperative that of inflammation after cataract surgery. J Cataract Refract Surg. 2013;39(2):168-73. FML ointment. Used similarly to optometrists embrace this reality and 6. Leibowitz HM, Hyndiuk RA, Lindsey C, Rosenthal Lotemax ointment, FML ophthalmic become comfortable using these es- AL. Fluorometholone acetate: clinical evaluation in the treatment of external ocular inflammation. Ann ointment (fluorometholone 0.1%, Al- sential drugs to care for patients with Ophthalmol. 1984;16(12):1110-5. lergan) is indicated for inflammation inflammatory eye disease. ■ 7. Bausch + Lomb announces successful results from phase 3 study of sub-micron loteprednol of the palpebral and bulbar conjunc- etabonate ophthalmic gel, 0.38%. www.prnewswire. tiva, cornea, anterior segment of the 1. Azari AA, Barney NP. Conjunctivitis: A systematic com/news-releases/bausch--lomb-announces- review of diagnosis and treatment. JAMA. successful-results-from-phase-3-study-of-sub- globe as well as the off-label uses men- 2013;310(16):1721-9. miwcron-loteprednol-etabonate-ophthalmic- tioned previously. Just make sure to 2. Donnenfeld ED. Difluprednate for the prevention gel-038-277195951.html. Accessed April 2, 2019. of ocular inflammation postsurgery: an update. Clin 8. Kala Pharmaceuticals. MPP Platform. https:// keep a closer watch for steroid-related Ophthalmol. 2011;5:811-6. kalarx.com/technology/mpp-platform. Accessed adverse effects since it is a ketone for- 3. Roberts CW, Nelson PL. Comparative analysis April 2, 2019. mulation. Triamcinolone 0.1% cream. A der- DO STEROIDS CAUSE GLAUCOMA? matological preparation that works The short answer is “no,” but let us explain. Traditional ketone steroids, well for periocular dermatitis condi- especially dexamethasone, prednisolone and difluprednate, have a propen- tions, triamcinolone 0.1% cream, be- sity to elevate IOP; ester-based steroids much less so. However, increased came generic long ago. It has been our IOP and ocular hypertension are not synonymous with glaucoma. favorite medication for many years Most of us have seen patients whose IOPs increased during the course of to treat contact blepharodermatitis. treatment. This is an uncommon side effect of steroids but one that is well It comes in 15g and 30g tubes, each known. So, how then is glaucoma avoided? We apply the following rules in costing about $10 in most markets. our practice: Be sure to tell the patient that the • First, never prescribe more than one bottle of a steroid drop (at least statement, “Not for Ophthalmic Use” initially) to control the patient’s access and exposure to the drug. is on the side of the tube, but that the • Second, schedule all patients who are prescribed a steroid a follow-up medication is perfectly fine to use as visit in less than a month, or sooner if the optic nerve head of the patient appears glaucomatous. prescribed. We explain to patients that If you determine that a patient is a “steroid responder,” you will need to triamcinolone (Kenalog) is frequently more closely monitor that patient in the future if steroids are prescribed. used by subspecialists for FDA- While such increased IOPs do occur in certain patients, we find that proper approved injection into the eye, so if patient management means they are less common and less elevated when some of the triamcinolone cream gets they do occur. But for ocular hypertension to evolve to glaucoma reflects into the patient’s eyes, it’s nothing to inattentive and poorly managed care. be concerned about.

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PRUDENT PRESCRIBING OF ANTIBIOTICS

Clinicians ntibiotics have been a medical mainstay since the have a robust 1940s. Unfortunately, their utility has led to over-use list of topical Aacross many disciplines and systemic and, thus, growing resistance. Antibiot- ics that were once highly effective are no options to longer providing the same clinical benefit, contributing to as many as two million choose from. bacterial and fungal illnesses, and 23,000 deaths, yearly.1 Given these unprecedented A cat scratch to the eye required treatment Consider these statistics, it’s in the clinician’s best interest with an antibiotic ointment and a pressure to prescribe these medications, both topi- clinical tips patch or bandage contact lens. cal and systemic, with discretion. to help you CONFIRM THE ETIOLOGY While the AdenoPlus (Quidel) point- prescribe them If you are contemplating prescribing an- of-care test can help achieve a definitive tibiotics for acute red eyes, consider this: diagnosis if you suspect an adenoviral eti- judiciously. The epidemiology for conjunctivitis is ology, simply looking closely at the signs viral for more than 80% of documented and symptoms can go a long way toward cases, and it’s usually self-limiting.2 Thus, making the diagnosis. For one, infected only one in five patients at most will ben- eyes have discharge: mucopurulent if it’s efit from an antibiotic. bacterial, serous/watery if it is viral and Even when indicated, topical antibiot- mucoid if it’s chlamydia. If no discharge ics only provide moderate benefit. You are exists, the eye is not externally infected. better off prescribing a topical corticoste- Also, sectoral bulbar conjunctival injec- roid in many cases, as long as you first use tion is almost always inflammatory (think fluorescein dye to rule out herpetic kerati- episcleritis). An exception here is early or tis in a unilateral red eye. moderate bacterial conjunctivitis, in which In fact, when we encounter a red eye the superior tissues are relatively spared and are unsure of its etiology, we always compared with the inferior (gravitational prescribe either a topical steroid or ste- pull leads to increased bacterial popula- roid-antibiotic combination drug, since tions inferiorly). such acute red eyes are almost always inflammatory in nature. Early epidemic TOPICAL OPTIONS keratoconjunctivitis may also be unilateral If we do confirm bacterial conjunctivitis, until it involves the fellow eye. we almost always prescribe an antibiotic-

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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 ciprofloxacin 0.3% Novartis and generic sol./oint. > 1 yr./ > 2 yrs. 5ml, 10ml/3.5g Moxeza moxifloxacin 0.5% Novartis solution > 4 mos. 3ml Ocuflox ofloxacin 0.3% Allergan and generic solution > 1 yr. 5ml, 10ml Vigamox moxifloxacin 0.5% Novartis solution > 1 yr. 3ml Zymaxid gatifloxacin 0.5% Allergan and generic solution > 1 yr. 2.5ml

Aminoglycosides Tobrex tobramycin 0.3% Novartis 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 azithromycin 1% Akorn solution > 1 yr. 2.5ml Ilotycin erythromycin 0.5% Perrigo and generic ointment > 2 mos. 3.5g Bacitracin bacitracin 500u/g Perrigo ointment N/A 3.5g

steroid combination suspension such CHALAZIA UP CLOSE as Zylet (loteprednol 0.5%, tobramy- Remember, chalazia represent noninfectious accumulations of granulomatous cin 0.3%, Bausch + Lomb), Tobradex scar tissue that forms when meibomian gland infections (internal hordeola) (tobramycin/dexamethasone, Novar- are untreated or undertreated. Both acute infections and secondary chalazia tis) or Maxitrol (dexamethasone/neo- can be ameliorated with aggressive use of warm soaks. We advise patients to mycin/polymyxin B, Novartis). Com- apply these for approximately 10 minutes, four to six times a day, and to keep bination therapy accomplishes two the heat level up throughout the treatment. Patients can use any number of goals: it eradicates the bacteria and methods to accomplish this, including rewetting a clean washcloth, using a concurrently suppresses the second- microwave to gently heat a sock filled with dry rice, a warm boiled egg in a ary conjunctival hyperemia. A topical stocking, or any number of commercially available heat application devices. antibiotic alone only addresses one component of the condition: bacterial positive infections) and tobramycin a gram-positive antibiotic often pre- eradication. Although this treatment (for gram-negative infections) is usu- scribed for Staph. blepharitis. After method will ultimately yield a white ally the norm. For less expressed, true applying warm compresses and lid eye, we have found that it takes a few infections (not a sterile infiltrate), and scrubs, bacitracin can be applied to more days to achieve renormalization non-centrally located foci, Besivance the lid margins before bedtime for than with a combination drug. (besifloxacin ophthalmic suspension, four to six days. However, because tis- When the cornea becomes bacteri- Bausch + Lomb) is a good option. For sue inflammation accompanies Staph. ally infected, the bar is set significantly any corneal infection, we always pre- blepharitis, we usually choose an an- higher and a broad-spectrum antibi- scribe either Polysporin or Neosporin tibiotic-steroid combination ointment otic is your best option. The stage or ophthalmic ointment at bedtime. Here such as generic Maxitrol. grade and location dictate one of two is a quick look at all of the topical an- Aminoglycosides. These have fallen options: if central in location, fortifi- tibiotics at your disposal: out of favor since the advent of fluoro- cation with vancomycin (for gram- Bacitracin. This ointment is strictly quinolones. In addition, there is mini-

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0023_dg0519_Antibiotics.indd23_dg0519_Antibiotics.indd 2244 55/14/19/14/19 4:084:08 PMPM MIC90 COMPARISONS FOR ARMOR SURVEILLANCE STUDY ISOLATES S. aureus MRSA CoNS* MRCoNS (n=1,695) (n=621) (n=1,475) (n=717) Besifloxacin 12Besifloxacin 24 Vancomycin 11Vancomycin 22 Trimethoprim 42Clindamycin >2 >16 Clindamycin >2 >2 Oxacillin >2 >2 Oxacillin >2 >4 Gatifloxacin 16 32 Moxifloxacin 416Tobramycin 832 Gatifloxacin 816Chloramphenicol 88 This Pseudomonas ulcer required Chloramphenicol 816 Ofloxacin >8 16 treatment with Besivance and Ofloxacin >8 >8 Moxifloxacin 16 32 cycloplegics. Levofloxacin 32 128 Ciprofloxacin 64 64 Ciprofloxacin 128 256 Levofloxacin 128 128 Tobramycin 128 256 Trimethoprim >128 256 only against gram-negative bacte- Azithromycin >512 >512 Azithromycin >512 >512 ria. Trimethoprim is broad-spectrum *CoNS = coagulase-negative Staph. species, of which the majority are Staph. epidermidis. against many gram-positive and some Thomas RK, et al. Clin Optom. 2019;11:15-26.. gram-negative bacteria. Polysporin combines polymyxin B with bacitracin mal risk of a type IV hypersensitivity Polymyxin B Combinations. These and is only available an ophthalmic reaction. Neomycin, itself is broad- can extend the total antibiotic cover- ointment. spectrum, does not cover Pseudomo- age achieved. Generic Polytrim (poly- The pairing of polymyxin B’s gram- nas and is always packaged with poly- myxin B/trimethoprim) is an effective negative and bacitracin’s gram-pos- myxin B or another antibiotic effective combination antibiotic available in itive action makes this an excellent, against gram-negative organisms. solution form. Polymyxin B is active nontoxic, broad-spectrum antibiotic. Neosporin is a triple-antibiotic of neo- FROM THE mycin, bacitracin and polymyxin B LITERATURE (the solution contains gramicidin, not bacitracin). We rarely use Neosporin ADDITIONAL WARNINGS REGARDING in eye drop form because there are so ORAL FLUOROQUINOLONES many other options. Although these have been in common use for many years now, their full clini- Fluoroquinolones. Besivance is the cal profile continues to change. Here’s the latest from the CDC: only topical ophthalmic antibiotic that • “During the past ten years, the FDA has issued several warnings about comes as a suspension. As with all fluo- potentially disabling adverse effects associated with their use, beginning roquinolones, Besivance provides activ- with tendinopathy and tendon rupture. In July, 2018, the FDA strengthened ity against DNA gyrase and topoisom- its warning that fluoroquinolones can affect glucose homeostasis adversely, erase IV. Its broad-spectrum coverage particularly in elders and patients with diabetes who take oral hypoglycemic combats gram-positive, gram-negative agents.” Pseudomonas • “Now, in its most recent update, the FDA has highlighted another recog- (including ) and anaero- nized, much less common yet more serious adverse effect of fluoroquino- bic organisms, as well as methicillin-re- lones—aortic rupture and tearing. Fluoroquinolones up-regulate cellular sistant Staphylococcus aureus (MRSA) matrix metalloproteinases, resulting in fewer collagen fibrils of types I and and methicillin-resistant Staphylococ- III collagen, which comprise the majority of collagen in both Achilles ten- cus epidermidis (MRSE). Ciprofloxa- dons and the aorta, serving as a likely mechanism for those adverse events. cin, a second-generation fluoroquino- Recently published studies demonstrated similar excess risks for aortic dis- lone, is the drug of choice against the section and Achilles tendon rupture with fluoroquinolones, at about 2.5 to gram-negative Pseudomonas species 3-folded compared with controlled populations.” (About half of these aortic and remains close in efficacy to the ruptures occurred within the first three weeks of fluoroquinolone therapy.) fourth-generation fluoroquinolones.

U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about increased risk A second-generation fluoroquinolone, of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. ofloxacin, is rarely used. However, www.fda.gove/DrugSafety/ucm628753.htm. December 20, 2018. Accessed April 2, 2019. because the drug is generic, it remains

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023_dg0519_Antibiotics.indd 25 5/14/19 4:09 PM ANTIBIOTIC AGENTS

FROM THE Although topical antibiotics have a LITERATURE role in contemporary eye care, when they are needed, clinicians should ANTIBIOTIC USE IN URGENT CARE CENTERS use recent data, such as that from the Over the decades from a public health/patient-centric perspective, we have ARMOR study (see table on adjacent realized that all eye care needs to be provided by an eye doctor. A recent page), to guide prescribing.3 article in JAMA Internal Medicine highlights just how different care can be in, say, an urgent care center.1 Here are some enlightening comments regarding SYSTEMIC OPTIONS the research:2 We prescribe significantly more oral • “Patients with viral upper respiratory infections were treated with unneces- antibiotics than topicals simply be- sary antibiotics almost half the time.” cause we see more eyelid infections • “Despite proven harms of unnecessary antibiotic use, the battle to limit (internal hordeola and ) than unnecessary prescriptions rages on.” bacterial or corneal infections. While • “Likelihood of antibiotic prescription use was uniformly higher in urgent care centers than hospital-associated emergency departments (25%) or medical many oral antibiotics exist, we al- offices (17%).” most always prefer one of three oral • “The booming market in urgent care centers has opened another gigantic options: front in the antibiotic wars.” Cephalosporins. For most acute infectious eyelid presentations, we 1. Palms DL, Hicks LA, Bartoces M, et al. Comparison of antibiotic prescribing in retail clinics, urgent care centers, emergency departments, and traditional ambulatory care settings in the United States. recommend patients use warm soaks JAMA Intern Med. 2018;178(9):1267-69. alone to affect a clinical cure. When 2. Zuger A. Antibiotic misuse is rife in urgent care centers. NEJM Journal Watch. July 26, 2018. www. jwatch.org/na47163/2018/07/26/antibiotic-misuse-rife-urgent-care-centers. Accessed April 2, 2019. the presentation is more advanced, we prescribe an oral antibiotic—al- most always cephalexin (originally a reasonable, inexpensive option for minimizing the potential for a toxic branded as Keflex) 500mg BID for bacterial conjunctivitis. Two popular or allergic response (although such is one week. fourth-generation fluoroquinolones— exceedingly rare). Gatifloxacin, a fairly This first-generation cephalosporin topical moxifloxacin 0.5%, available effective fourth-generation fluoroqui- provides excellent coverage against as Moxeza (Novartis) and Vigamox nolone, is FDA-approved to treat bac- gram-positive organisms, most com- (Novartis)—function similarly. Of terial conjunctivitis. While useful and monly Staph. aureus or Staph. epi- clinical note, Vigamox and Moxeza generically available, all fourth-gener- dermidis. Three advanced-generation are the only preservative-free ophthal- ation fluoroquinolones are exhibiting cephalosporins exist, each of which mic fluoroquinolone antibiotics, thus increasing bacterial resistance. have distinct differences in their mo-

ALLERGIC TO PENICILLIN? received cephalosporins.” Patients giving a history of penicillin allergy usually aren’t • “Even those who have experienced a true allergic reac- truly allergic—the scientific literature has robustly refuted tion [to penicillin] have about an 80% chance of losing the myth that this allergy is commonplace. Another effort their sensitivity to penicillin within ten years.” to temper this myth was published in the November 2018 • “Beta-lactam drugs appear to have benefits not exhib- Journal of the American Medical Association. Here are ited by other antimicrobial classes. They do more than some key takeaways from this article: kill bacteria directly; they are also boosting the activi- • “As few as 10% of people who report they are allergic ties of our body’s immune system.” to the topical antibiotic really are.” (Remember, cepha- • “There is now underway a large national effort to do losporins such as cephalexin share a beta-lactam ring ‘oral challenge’ testing in many primary, and allergists’ structure similar to penicillin, meaning a cross-reactivity offices so that such patients inaccurately reporting a between these two structurally similar antibiotics is penicillin allergy can be accurately determined. This is possible. If a patient has truly had an anaphylactic allowing large numbers of people to be ‘de-labeled’ as reaction to a penicillin, we generally do not prescribe a penicillin-allergic, which in turn allows them to be more cephalosporin. That being said…) appropriately treated when the need arises.” • “In one retrospective study that included more than 65,000 patients with a history of penicillin allergy who Despite our personal widespread use of cephalexin, we received more than 127,000 courses of cephalosporins have never had any untoward experiences prescribing (which are beta-lactam antibodies like penicillin), only it. Oddly enough, its high volume use has yet to result in three cases of anaphylaxis were associated with the increasing resistance. drugs. That was not statistically different from ana- Rubin R. Overdiagnosis of penicillin allergy leads to costly, inappropriate phylaxis rates in non-penicillin-allergic patients who treatment. JAMA. 2018;320(18):1846-48.

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0023_dg0519_Antibiotics.indd23_dg0519_Antibiotics.indd 2266 55/14/19/14/19 4:094:09 PMPM PRESCRIBING PEARLS • Some female patients are prone to vaginal yeast infections concurrent with oral antibiotic use; most women know how to treat these, so just have this conversation with them prior to prescribing. • These antibiotics are usually taken with meals, and we encourage our patients to do so to minimize any This three-year-old had a deep corneal This patient was treated with an oral potential gastrointestinal issues. Only abrasion from a metal coat hanger. We fluoroquinolone a few years ago and rarely would patients need to concur- treated with antibiotic ointment and suffered extensive tendon rupture, rently use a probiotic. pressure patch. such that his bicep lifting capacity was • For pregnant patients or children profoundly limited. This is an example of younger than 18, we always consult why clinicians rarely prescribe this class their obstetrician or pediatrician to ways sexually transmitted and can be of oral medicine. gain their advice on drug selection and present with a low-grade red eye and dosing. With children in particular, we a mucoid discharge in the setting of never hesitate to call a pediatrician or giant follicles in the inferior forniceal lecular side chains: cefuroxime (Cef- pharmacist for help to ensure we are conjunctiva. A tedious and often awk- tin), cefpodoxime (Vantin) and cef- prescribing the right antibiotic—at the ward history helps to confirm your dinir (Omnicef).4 These can be used right dose—for each patient. clinical findings, as can a chlamydia on the rare occasion of a true and se- • A quick note on penicillin: Be- culture, which must be refrigerated vere history of penicillin allergy. cause most gram-positive bacteria and discarded and replaced as needed. Trimethoprim with sulfamethoxa- produce penicillinase, which dimin- The drug of choice for these infections zole. Since cephalosporin antibiotics ishes the medication’s efficacy, we is 1,000mg of oral azithromycin taken are closely related to the penicillins, do not prescribe penicillin, unless it is as one single dose with either 250mg we generally avoid their use in pa- Augmentin (GlaxoSmithKline), which or 500mg capsules or tablets. ■ tients who have a history of an ana- contains amoxicillin, a synthetic peni- 1. Centers for Disease Control and Prevention. Anti- phylactic reaction (see “Allergic to cillin, with clavulanic acid. The cla- biotic resistance threats in the United States, 2013. Penicillin?”). In these cases we gener- vulanic acid protects the amoxicillin www.cdc.gov/drugresistance/threat-report-2013. Accessed April 2, 2019. ally default to another drug class al- from the degrading effects of peni- 2. Keen M. Treatment of acute conjunctivitis in the together. cillinase, enabling the amoxicillin to United States and evidence of antibiotic overuse: isolated issue or a systematic problem? Ophthal- Most often, we prescribe trim- effectively eradicate gram-positive mology. 2017;124(8):1096-98. ethoprim with sulfamethoxazole pathogens. The most common dos- 3. Asbell PA, Sanfilippo CM, Pillar CM, et al. Anti- biotic resistance among ocular pathogens in the (brand names of Septra or Bactrim). age is 875mg BID for one week. For united states: five-year results from the antibiotic We write the prescription for either of smaller patients, we consider prescrib- resistance monitoring in ocular microorganisms (ARMOR) surveillance study. JAMA Ophthalmol. the brand names and include “generic ing 500mg BID. While a 1,000mg for- 2015;133(12):1445-54. substitution permitted.” The common mulation exists, we have yet to find a 4. Pichichero ME, Casey JR. Safe use of selected cephalosporins in penicillin-allergic patients: a dosage is two double-strength tablets/ need to prescribe it. meta-analysis. Otolaryngol Head Neck Surg. 2007 capsules taken BID for one week. • Chlamydial infections are most al- Mar;136(3):340-7. If a patient is also allergic to sul- fa drugs, we consider doxycycline 100mg BID for one week. Fluoroquinolones. We avoid pre- scribing any oral fluoroquinolone unless truly it is necessary because of the rare possibility of tendon rupture with this class of drug, which can be devastating when it happens. Luckily, tendon rupture does not occur with use of topical ophthalmic A local MD misdiagnosed this patient’s periorbital bullous impetigo as shingles. fluoroquinolones. Treatment with Augmentin 875mg BID for 10 days did the trick.

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023_dg0519_Antibiotics.indd 27 5/14/19 4:09 PM COMBINATION DRUGS

COMBINATION ANTIBIOTIC-CORTICOSTEROID OPTIONS

Used in the ata show eye doctors are far more likely to prescribe com- right way, bination antibiotic-steroid these drugs therapy for acute conjuncti- Dvitis than those outside of eye pack a care. In one study of acute conjunctivitis, as many as 30% of those who saw an op- clinical one- tometrist, and 23% who saw an ophthal- mologist, filled a combination antibiotic- A classic leukocytic infiltrative response from two punch corticosteroid prescription, compared with an unknown immunogenic stimulus. Use an just 8% of those seen by an urgent care antibiotic/corticosteroid every two hours for to address physician, internist, pediatrician or family two days, then every four hours for four more practitioner.1 specific days to re-normalize the inflamed tissues. Considering most acute red eye is in- conditions. flammatory in nature, we are surprised the rate is no higher than 30%—but it’s times, such discharge may not be grossly informative that optometrists were slightly visible (even at the slit lamp), so a high- more inclined to embrace such therapy magnification look at the lacrimal lake may than ophthalmologists. Non-eye doctors be required to thoroughly search for subtle have been specifically trained to avoid the microparticulant debris. use of these types of medicines and instead This close examination is performed in refer to eye doctors, who should be quite a manner similar to that used when one is comfortable with the safety and enormous evaluating for anterior chamber cells and benefits of corticosteroids. flare: have the room relatively dark, and use high magnification. In addition, use COMBINATION your thumb or finger to raise the lower CONSIDERATIONS eyelid a few millimeters, which raises the There are several factors to consider when lacrimal lake high enough so that the iris contemplating prescribing an antibiotic/ste- (not the bulbar conjunctiva and ) is roid combination medication. Let’s take a the background for your viewing. It is eas- closer look at each: ier to see whitish debris against the darker background of the iris. If no evidence of ac- Is there a need for an antibiotic, or tive infection exists, there is no need for an 1.would steroid monotherapy be more antibiotic. appropriate? An antibiotic is indicated only when there are obvious signs of infection, Is the condition primarily infectious such as mucopurulent discharge. Many 2.with secondary inflammation, or is

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028_dg0519_combination.indd 28 5/14/19 4:23 PM TOPICAL STEROID/ANTIBIOTIC COMBINATION DRUGS BRAND MANUFACTURER STEROID ANTIBIOTIC PREPARATION BOTTLE/TUBE NAME sodium Blephamide* Allergan prednisolone acetate 0.2% susp./ung. 5ml, 10ml, 3.5g sulfacetamide 10% neomycin 0.35% Cortisporin* Monarch hydrocortisone 1% suspension 7.5ml polymyxin B 10,000u/ml neomycin 0.35% Maxitrol* Novartis dexamethasone 0.1% susp./oint. 5ml/3.5g polymyxin B 10,000u/ml

Pred-G Allergan prednisolone acetate 1% gentamicin 0.3% susp./oint. 10ml, 3.5g

TobraDex* Novartis dexamethasone 0.1% tobramycin 0.3% susp./oint. 5ml/3.5g TobraDex ST Novartis dexamethasone 0.05% tobramycin 0.3% suspension 2.5ml, 5ml, 10ml Zylet Bausch + Lomb loteprednol 0.5% tobramycin 0.3% suspension 5ml, 10ml HISTORICAL PREGNANCY CATEGORY: All drugs listed above are “historically” Category C *also available generically

the condition primarily inflammatory Which antibiotic has the high- scribe generic Maxitrol (dexametha- with a perceived, rational need for 4.est probability of being clinically sone, neomycin and polymyxin B) for bacterial prophylaxis? This determi- effective? For this question, we must acute bacterial infections but would nation is almost exclusively predicated know the expected spectrum of anti- never use it for conditions that may re- on the integrity of the corneal epitheli- microbial activity of each drug and the quire more than a week of treatment. um. Superficial punctate keratitis (SPK, likely type of bacterial pathogen. For Why? The neomycin (on very rare oc- also called punctate epithelial erosion) example, the macrolides erythromycin casions) can cause a type IV hypersen- does not require antibiotic protection. and azithromycin have limited effec- sitivity/allergic reaction, and the dexa- We all see patients with SPK practically tiveness when used topically. There is methasone has the greatest propensity every day, but do not prescribe an an- increasing resistance to the fourth-gen- to increase intraocular pressure. tibiotic because these epithelial defects eration fluoroquinolones. However, When indicated, though, generic are not predisposed to opportunistic drugs such as Polytrim (trimethoprim Maxitrol is highly effective and inex- bacterial infection. For the most part, with polymyxin B), besifloxacin, the pensive. Thus, we frequently prescribe if there is no significant breach in epi- aminoglycosides and bacitracin with it, usually with a dosing regimen of ev- thelial integrity, antibiotic prophylaxis polymyxin B all show coverage against ery two hours for two days and then is not needed. However, if significant common bacterial pathogens. Al- QID for four more days. epithelial compromise exists, a pro- though aggressive marketing and com- phylactic antibiotic may be of value. mon practice patterns can confuse the Is the corticosteroid component Most clinically significant bacterial conversation, keeping current with the 6.ketone-based or ester-based? For infections cause substantial second- literature will enable you to separate chronic care of a condition such as ary conjunctival inflammation. This is science from “spin.” staphylococcal blepharitis, we would why we treat most bacterial conjuncti- prescribe Zylet (loteprednol 0.5% and val entities with a combination medi- Is the condition acute or chronic? tobramycin 0.3%, Bausch + Lomb). cine—to kill the bacteria while con- 5.Generally speaking, most condi- Why? The tobramycin is effective currently suppressing the secondary tions that evolve quickly are acute, against gram-positive species, and the inflammation to help normalize tissues while conditions, such as blepharitis, ester-based loteprednol has a much as rapidly as possible. rosacea blepharitis and meibomian enhanced safety profile than ketone- gland disease, are most often chronic based corticosteroids. Does the patient have any known and will require a more protracted use We typically prescribe Zylet QID 3.allergies to medicines? This is of medication. For such chronic condi- for two weeks, then BID for a month, critically important. Always, without tions, we typically prescribe Zylet be- along with eyelid hygiene, of course. exception, inquire about any known cause of the enhanced safety profile of Thankfully, with a coupon, this op- allergies prior to prescribing any medi- loteprednol. timum medicine can be obtained for cation, topically or orally. For example, we commonly pre- about $35 with commercial insurance.

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0028_dg0519_combination.indd28_dg0519_combination.indd 2299 55/14/19/14/19 4:234:23 PMPM COMBINATION DRUGS

DIFFERENTIAL DIAGNOSIS: INFECTIOUS CORNEAL ULCERS vs. STERILE LEUKOCYTIC INFILTRATES Ulcers—Bacterial Corneal Infection Infiltrates—Sterile Leukocytic Infiltration • Rare • Common • Usually painful • Mild pain • Tend to be central • Tend to be • 1:1 staining defect to peripheral lesion ratio • Staining defect size • Cells in anterior is relatively small chamber (compared with • Generalized that of an anterior conjunctival injection stromal infiltrate) • Usually solitary • No (or few) cells • Possible tear lake in the anterior debris chamber • Sector skewed injection pattern TREATMENT: besifloxacin or fortified vancomycin and • Can be multiple lesions tobramycin administered frequently until it is evident • Clear tear lake that the lesion is no longer progressing. We would also use an antibiotic ointment at night such as ophthalmic TREATMENT: antibiotic-steroid combination, usually Neosporin or Polysporin. Once the antibiotic has “turned every two hours (while patient is awake) for two days, the cornea,” we blend in loteprednol in an effort to mini- then QID for four more days. mize any scarring.

1. Shekhawat NS, Shtein RM, Blachley TS, Stein JD. Antibiotic prescription fills for acute conjunctivitis among enrollees in a large United States managed control network. Ophthalmology. 2017;124(8):1099-1107. 2. Abelson MB, Plumer A. Marginal infiltrates: A mysterious malady. Rev Ophthalmol. 2005;12(1):66-8.

We rarely prescribe generic TobraDex these two strengths because of a sting- bination drugs was Maxitrol (Novar- (tobramycin and dexamethasone, No- ing effect. In addition, it is rarely used tis). It contains neomycin, polymyxin vartis) because of its expense. in contemporary eye care because of B and dexamethasone 0.1%. Neomy- sodium sulfacetamide’s poor action cin is itself a broad-spectrum antibi- COMBINATION against many Staph. species and the otic, with the exception of Pseudomo- COMPONENTS relatively low concentration of pred- nas species. But because polymyxin B Now that we’ve established the basic nisolone. is highly anti-pseudomonal, it is used principles of drug selection, let’s turn Hydrocortisone 1%. Years ago, a in many combination products to our attention to the specific combina- combination of neomycin, bacitracin shore up activity in the gram-negative tion drugs available, best discussed (or gramicidin), polymyxin B and hy- spectrum. Dexamethasone 0.1% is a based first on the corticosteroid com- drocortisone 1% was rather popular highly effective suppressor of inflam- ponent. among primary care physicians. The mation—so much so that if a neomy- There are four corticosteroids used antibiotic combination punch was cin sensitivity reaction (again, which in topical combination medicines: awesome, but the hydrocortisone is rare) occurs, the dexamethasone prednisolone, hydrocortisone, dexa- was inadequately therapeutic. In fact, is able to mask it and ensure overall methasone and loteprednol. Let’s the corticosteroid component was so therapeutic success, thereby elevating discuss these in the general order that weak that on the rare occasion of a Maxitrol to superstar status. they came to market. neomycin reaction, it could not mask As we’ve emphasized several times, Prednisolone. Sodium sulfaceta- the type IV hypersensitivity and al- neomycin reactions generally are not mide 10% with 0.2% prednisolone lowed the problematic neomycin reac- a big deal clinically—yet drug de- acetate ophthalmic suspension (the tion to manifest clinically. velopers are always looking for im- ointment is 0.25% prednisolone ace- This four-ingredient combination provement. This undoubtedly was tate) is available generically but is best drug was originally known by the the reason for the birth of TobraDex known by its original brand name, brand name Cortisporin (Pfizer) and (dexamethasone 0.1% and tobramy- Blephamide (Allergan). It comes in included numerous generics, but the cin 0.3%, Novartis), the blockbuster 5ml, 10ml and 15ml. It also comes in drug is rarely used today. combo drug of the 1990s, now limited 15% and 30% concentrations of so- Dexamethasone. Back in the 1970s by its cost. Keep in mind that when the dium sulfacetamide, but we never use and ’80s, the “superstar” of the com- market leader’s patent protection runs

30 REVIEW OF OPTOMETRY MAY 15, 2019

028_dg0519_combination.indd 30 5/14/19 4:23 PM COMMON BRANDED ANTI-INFECTIVE/ roid. The main reasons this occurs ANTI-INFLAMMATORY COMBINATIONS may be because of: (1) uncertainty of the diagnosis and a “shotgun” Prednisone Dexamethasone prescribing approach and (2) the ir- Blephamide Maxitrol rational fear of the expression of op- Pred-G TobraDex portunistic pathogenic bacterial su- TobraDex ST perinfection.

Hydrocortisone Loteprednol Recognizing two characteristics Cortisporin Zylet may help make prescribing more precise: First, a skilled clinician who takes a complete history and per- forms a careful slit lamp examination out and generic drug companies are use of dexamethasone to less than can make highly accurate diagnoses. gearing up to jump on the manufac- two weeks. Second, opportunistic bacterial infec- turing wagon, a “new and improved” Loteprednol. The most recent en- tion is just plain rare. version of the old drug often rolls out. try into the combination category Because corneal infections can be Pred-G and TobraDex. Pred-G solves, or most certainly reduces, the devastating, we come to the defense (prednisolone acetate 1% and gen- possibility of increased intraocular of the “shotgun” approach to cor- tamicin 0.3%, Allergan) came to pressure associated with all classes of neal infiltrates. In our vast clinical market prior to the introduction of corticosteroids. Now with Zylet, we experience, though, we have never TobraDex. But the preparation stung finally have a combination drug that seen a “corneal infiltrate” turn out to so much that when the more comfort- is both effective and safe to extend the be the beginning of an actual bacte- able and tolerable TobraDex arrived, range of clinical use beyond seven to rial ulcer—but surely it can happen the latter quickly gained favor. 10 days. This makes Zylet an ideal (probably depending upon the time of Tobramycin. This stand-alone, choice for treating chronic conditions presentation and virulence of the bac- broad-spectrum antibiotic only causes such as staphylococcal blepharitis. terial species). Thus, we agree with any clinically significant toxic or aller- With the availability of coupons, this the succinct and accurate guidance gic reaction in exceedingly rare cases. state-of-the-art combination drop is of ocular pharmacology expert Mark However, there’s an inherent prob- available for $35 for most commer- Abelson, MD:2 lem with dexamethasone. While a cially insured patients. “Left untreated, marginal infil- good suppressor of inflammation, it trates generally disappear within a possesses significant potential to in- A QUICKER RECOVERY week or two. Ocular steroids have crease intraocular pressure, which Over the decades, we have witnessed been shown to be the best and only limits the duration for which it can be the use of a combination drug when recognized drug therapy for sterile used safely. We always try to restrict all that was needed was a corticoste- marginal infiltrates, and their applica- tion will shorten the course of inflam- mation, regardless of causative origin. For many patients, a quicker recov- ery from symptoms such as redness, tearing, and discomfort is important for improving their quality of life. Steroids are often prescribed in con- junction with an antibiotic in order to decrease the chance of developing a secondary infection or to protect against misdiagnosis.” In closing, the combination agent we prescribe most is generic Maxitrol. This classic presentation of phlyctenular keratoconjunctivitis (PKC) represents This is our choice for two simple rea- a hypersensitivity response to staphylococcal exotoxins (at left). A combination sons: it works well clinically and is in- antibiotic (to reduce staph populations)-steroid (to suppress the secondary expensive. However, when therapeu- inflammatory reaction) is ideal to help restore these ocular tissues. We typically tic intervention is needed beyond two prescribe one drop Q2H for two days, and then QID for four more days. The image on weeks, we prescribe Zylet because of the right is after three days of treatment. the safety profile of loteprednol. ■

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OCULAR SURFACE PEARLS: DRY EYE AND BEYOND

Research and aring for the ocular sur- face, already a complex the latest endeavor, has become Ceven more complex with therapies significant changes to our diagnostic differentials and therapeutic arma- to address mentarium. Commonly prescribed a variety of drugs have lost their patent protec- tion, paving the way for generics. ocular surface New research has brought thinking on omega-3 supplements into ques- conditions tion and improved diagnostics have are constantly raised previously ignored condi- tions to the surface. While no sum- As can be readily seen, this patient has a scant evolving. Read mary can adequately address every lacrimal lake. relevant topic, a brief look at these our take on trends can keep your practice up to date and prepare you to care for any num- and function, all the more important in an what’s new and ber of ocular surface complaints. era when people stare at various digital what hasn’t Let’s first recap highlights of our treat- screens too long and blink insufficiently. ment approach before expanding into oth- Some patients can be managed for a changed. er important ocular surface considerations time with over-the-counter tear supple- that may be overlooked in the diagnostic ments for as-needed symptomatic relief. evaluation. Again recognizing the influence of MGD on symptoms, we tend to prioritize lipid- OUR DRY EYE APPROACH based artificial tears as we have found they We all know that a healthy tear film re- best stabilize the tear film. quires proper functioning of the meibo- But to give patients lasting improve- mian glands, lacrimal glands and conjunc- ment, we need to address the effects of tival goblet cells. Of these, the first group inflammation. We feel a topical steroid, is by far the most impactful. Meibomian most notably loteprednol, is the most gland dysfunction (MGD) is the culprit in clinically effective and cost-effective initial most cases of dry eye disease (DED), steer- approach to suppressing the ocular surface ing us to the eyelids as one of the chief inflammation associated with DED. areas of assessment and intervention. Cli- Loteprednol. Our favorite “wonder nicians have the best chance to institute drug” is now available in six formulations: long-term improvement in their DED pa- • The original 0.5% suspension tients by maintaining proper eyelid health • The 0.5% ointment

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032_dg0519_OcularSurface.indd 32 5/14/19 4:27 PM • Alrex (0.2% suspension, Bausch tive effects of the supplement for dry + Lomb) eye. The Women’s Health study found IS BAK REALLY THAT BAD? • Lotemax 0.5% gel drops (Bausch each gram of oral long-chain omega-3 Let’s start by gaining some per- + Lomb) essential fatty acids consumed each spective. The original 0.03% • Lotemax SM 0.38% gel drop day led to a 30% reduction in the risk Lumigan (Allergan) was not well- (Bausch + Lomb) of DED.1 A more recent randomized, tolerated until the manufacturer reformulated it to a 0.01% concen- • Inveltys 1% loteprednol suspen- double-masked, placebo-controlled tration. Paradoxically, this nicely sion (Kala) clinical trial found a moderate dose of enhanced reformulation contains For DED in particular and ocular omega-3 fatty acids—about 1,000mg four times the concentration of surface disease generally, we feel all of of EPA and about 500mg of DHA per benzalkonium chloride (BAK). these products perform similarly. In day—can reduce tear osmolarity and Latanoprost also has a relatively addition, all of them, except the origi- increase tear stability in patients with high concentration of BAK (0.2%), 2 nal suspension (which enjoys a litany DED. Ultimately, the study found yet it remains quite tolerable. of indications) and Alrex (approved three interesting things: (1) the ome- Thus, the existence of BAK in for treating signs and symptoms of ga-3s provided significant improve- the formulation may not be the allergic conjunctivitis), are approved ments in tear film stability; (2) onset problem, so much as the amount for postoperative care. For additional of benefits, including hyperemia, hap- the ocular surface is exposed to. details on loteprednol, especially the pened within 30 to 60 days; and (3) If a patient is using a preserved newer formulations Lotemax SM and krill oil appears to be a touch more over-the-counter artificial tear, Inveltys, please see the Corticoste- effective than fish oil. another preserved topical eye drop roids section on page 14. A 2018 literature review of ocular and they have advanced DED as Cyclosporine. Because of the pat- rosacea therapies more specifically evidenced by superficial punctate ent expiration of Restasis (Allergan), cited two well-designed studies that keratopathy, we should consider a several new cyclosporine options are showed improvements in subjec- preservative-free product to avoid now available, including a preser- tive symptoms and objective signs of overly exposing the ocular epithe- vative-free ophthalmic solution at MGD with omega-3 fatty acids. Man- lial tissues to more toxic levels of 0.09% concentration (Cequa, Sun aging both DED and MGD are crucial BAK. Until then, clinicians may not Pharmaceutical) and Klarity-C (Im- factors in ocular rosacea.3 need to worry so much about the primis), a compounded ophthalmic With results like these, it’s no possible effects of BAK. The old adage of “moderation in every- emulsion that contains cyclosporine wonder the DREAM study has us all thing” holds true here as well. 0.1% and chondroitin sulfate. scratching our heads. Ultimately, the Lifitegrast. This anti-inflammatory preponderance of the literature finds (Xiidra, Novartis) selectively targets value in such supplementation, and surgical procedure where the ophthal- certain proteins on the surface of leu- we will continue to use them for our mic division of the trigeminal nerve is kocytes (LFA-1 and ICAM-1) to in- own dry eyes, as well as those of our damaged. terfere with recruitment of T-cells in patients. The epithelium tries to mitotically patients with DED. repopulate these epithelial defects, NEUROTROPHIC but because of complex neurochemi- PERSPECTIVE ON THE KERATITIS cal compromise, non-healing defects DREAM STUDY Because sensory innervation is re- sometimes endure, evident from the For years, most eye doctors have rec- quired to maintain epithelial integrity, classic rolled edges. Remember: bac- ommended omega-3 fatty acids in the any condition or surgical procedure terial ulcers always have subepithe- comprehensive care of patients with that harms trigeminal innervation to lial (anterior stromal) whitish lesions, DED. Then came along the DREAM these tissues can study, which found no benefit beyond cause neurotroph- its olive oil placebo group, which the ic keratopathy. authors firmly claim possesses no The most com- clinically significant activity. None- mon situations theless, the vast majority of ODs still that lead to such support the use of fish or flaxseed oil epithelial compro- in their DED treatment regimen, and mise are herpes with good cause. simplex keratitis, Beyond the DREAM study, other herpes zoster oph- peer-reviewed literature shows posi- thalmicus and any

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non-edematous conjunctival folds, typically in the inferior bul- bar conjunctiva of both eyes over- lying the inferior eyelid margin. The condition often causes irrita- tion and discomfort, commonly in older patients. A complex cascade of disrup- tions lead to CCH, most of which begin with the normal aging pro- cess. Patients’ subconjunctival This is a classic case of neurotrophic keratopathy (at left). The patient had neurosurgery connective tissue erodes as they two days prior, during which her nasociliary nerve was cut. After intensive topical age, predisposing them to re- treatment for several weeks with preservative-free, lipid-based artificial tears by day and duced attachment of the bulbar preservative-free ointment at bedtime, her epithelium finally healed (at right). We certainly conjunctiva to the sclera, and thus hope Oxervate can fast-forward the healing process for other patients with this condition. conjunctival laxity. The resulting chronic mechanical friction dur- ing blinking and eye movements but only the epithelium is involved in ists and cutting-edge optometrists and triggers conjunctival epithelium and neurotrophic keratitis. Traditionally, ophthalmologists. We will have a bet- vascular endothelium inflammatory we have used preservative-free artifi- ter understanding of Oxervate’s clini- responses, which play into the CCH cial tears and therapeutic soft contact cal utility once it has been in use for a pathogenesis by degrading extracellu- lens with gentle antibiotic cover. In year or two, but we are excited that lar matrix via matrix metalloprotein- August 2018, a new medicine, Oxer- there is now a medicine available to ases. This circles back to more con- vate (cenegermin 0.002%, Dompé), help treat patients with this challeng- junctival laxity, beginning a vicious was FDA-approved to help enhance ing corneal pathology. cycle of conjunctival redundancy, re-epithelialization of non-healing friction, inflammation and extracel- epithelial defects, associated with neu- ADD CCH TO YOUR lular matrix degradation. rotrophic keratopathy. Oxervate is a DIFFERENTIALS Further delayed tear clearance can human nerve growth factor solution For decades, superior limbic kerato- exacerbate this entire pathophysiolog- with an intricate formulation and ad- conjunctivitis and chlamydia conjunc- ical process and may be caused by an- ministration protocol. It is instilled six tivitis have been cited as the two most atomical obstruction of the punctum times a day at two-hour intervals for commonly missed anterior segment by redundant conjunctival folds—an- eight weeks.4 In the Phase III studies, conditions. It seems we should add a other cycle characterized by redun- 70% of patients had complete healing third clinical condition to the list: con- dant delayed tear clearance leading to in eight weeks.5 junctivochalasis (CCH).6 ocular surface inflammation and the While this wonderful new medi- This common—yet commonly generation of more matrix metallo- cine is highly welcomed, it will likely missed—chronic clinical condition proteinases, which degrades the con- remain a tool for cornea subspecial- is characterized by loose, redundant, junctival matrix and Tenon’s capsule,

The conjunctival folds and their obliteration of the tear lake are more easily identifiable with dye. Left: no dye; middle: blue fluorescein dye; right: green dye (latter image: Nicholas Leonard).

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032_dg0519_OcularSurface.indd 34 5/14/19 4:27 PM ANTIVIRAL INSIGHT INTO killing time, possibly due to an increase in free iodine, the POVIDONE-IODINE (BETADINE) availability of which peaks around 0.1% to 1%.2,3 Despite While iodine has been recognized as an effective bacte- this, for the ocular surface, research shows the 5% povi- ricide since the 1800s, only since the 1980s has Betadine done-iodine more effectively reduces the bacterial load (povidone-iodine, Avrio Health) come into widespread use compared with the 1% concentration.3 Investigators have as standard of care in preventing follow- realized that organic substances in the operative field can ing intraocular surgery or intravitreal injec- inhibit Betadine’s bactericidal activity; thus, tion. In fact, there is little to nothing to be supplying more total iodine with higher con- gained by using a topical antibiotic above centrations is helpful.4 and beyond that of Betadine for sterilizing In addition, such apparent discrepancies the ocular surface. might be found in comparing in vitro and in Povidone-iodine has a wide spectrum vivo applications. The bottom line is that all of antimicrobial activity, including efficacy common-use concentrations are antimicrobi- against a variety of bacteria, fungi, pro- al in 60 to 90 seconds—an incredibly efficient tozoa and viruses, which is why we have clinical effect. long advocated for its use in treating acute The toxicity of povidone-iodine is related infectious adenoviral conjunctivitis. Because to its concentration and duration of expo- povidone is hydrophilic and adheres to cell sure. We do know that 5% Betadine can membranes, it acts as a carrier to transfer cause considerable short-term stinging, even iodine to the target cell—a crucial event of antimicrobial action.1 At the same time free iodine iodin- with the use of topical proparacaine, so one could consid- ates and oxidizes proteins, enzymes and other molecules er diluting the 5% Betadine at a ratio of 5:1 (to achieve a 1% essential for biological viability, povidone-iodine inacti- concentration) to provide good antimicrobial effect while vates bacterial exo- and endotoxins, tissue-destroying minimizing patient discomfort when treating epidemic enzymes and microbial-induced cytokines. Betadine is also keratoconjunctivitis. bactericidal against drug-resistant bacteria.1 Another approach to maximizing efficacy while minimiz- While 5% Betadine is common for pre-op ocular pro- ing toxicity is frequent application of lower-concentration phylaxis, the surgical staff uses a 10% concentration to Betadine. Researchers are currently investigating a combi- scrub in prior to entering the operating room. Even dilute nation of 0.6% povidone-iodine with 0.1% dexamethasone, solutions, such as 0.1%, have been shown to have a fast which might prove useful (we have never used this strat- egy). Only time will tell how such a drug might play out in OUR OFF-LABEL BETADINE PROTOCOL widespread clinical use. FOR EKC: 1. Koener JC, George MJ, Meyer DR, et al. Povidone-iodine concentration and dosing in • Anesthetize the eye with proparacaine cataract surgery. Surv Ophthalmol. 2018;63(6):862-68. • Instill one or two drops of an NSAID 2. Peden MC, Hammer ME, Suñer IJ. Dilute povidone-iodine prophylaxis maintains • Instill several drops of Betadine 5% and then have safety while improving patient comfort after intravitreal injections. Retina. August 23, the patient close their eye 2018. [Epub ahead of print]. • Swab or rub excess liquid over the eyelid margin 3. Pepose JS, Ahuja A, Liu W, et al. Randomized, controlled, phase 2 trial of povidone- iodine/dexamethasone ophthalmic suspension for treatment of adenoviral conjunctivi- • After one minute, irrigate the eye with sterile saline tis. Am J Ophthalmol. 2018 Oct;194:7-15. • Instill one or two drops of an NSAID 4. Cinal A. Correspondence: Randomized, controlled, phase 2 trial of povidone-iodine/ • Rx steroid QID for four days dexamethasone ophthalmic suspension for treatment of adenoviral conjunctivitis. Am J Ophthalmol. 2019 Jan;197:184.

causing CCH progression. chanical compression of the redun- tion. Some patients may experience Risk factors include increasing age, dant conjunctiva during eyelid blink- subconjunctival hemorrhage, usually Asian descent and hyperopia. Sever- ing. No wonder DED and in the inferior conjunctiva, due to the ity, judged by the number and height symptoms are often seen in conjunc- increased mechanical friction. of folds, also increases with age. tion with CCH. In fact, CCH often Given this presentation, clinicians As for CCH’s clinical presentation, coexists with DED, but also causes should consider CCH in any pa- it is often asymptomatic but can also dry eye symptoms and an unstable tient—especially as they age—with present with symptoms related to tear tear film. DED, in turn, can induce or ocular surface irritation and symp- film instability, delayed tear clearance, exacerbate CCH because of increased toms of DED or lacrimal drainage ocular surface inflammation and me- ocular surface friction and inflamma- obstruction, particularly if the patient

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doesn’t respond to appropriate DED successful in most all cases, as it can ization can help shrink the redundant treatments such as loteprednol and improve tear film function and reduce bulbar and forniceal conjunctival tis- lipid-based artificial tears. The di- mechanical friction and suppress ocu- sues. If this also fails, surgical resec- agnosis is complicated by the condi- lar surface inflammation. However, tion can be performed. tion’s nonspecific symptoms and its we have found that only steroids sup- Although CCH is a common cause preponderance for coexisting with press inflammation. of ocular surface irritation, it is often other ocular surface disorders such as In addition to ocular lubricants, overlooked in clinical practice. Now DED, MGD, floppy eyelid syndrome two drug classes are known to in- that you are armed with more infor- and blepharitis. One diagnostic pearl hibit the extracellular matrix metal- mation about this condition, we hope is that down-gaze during reading or loproteinases involved in the CCH it enhances your patient care. ■ computer usage or vigorous blinking cascade: tetracyclines (doxycycline at 1. Miljanovic B, Trivedi KA, Dana MR, et al. Relation be- may exacerbate CCH symptoms in 50mg per day for three to six months tween dietary n-3 and n-6 fatty acids and clinically particular. is common) and corticosteroids. diagnosed in women. Am J Nutr. 2005;82:887-93. Also, don’t forget about the pos- Loteprednol is a mainstay because 2. Deinema LA, Vingrys AJ, Wong CY, et al. A random- sible presence of a recurrent subcon- of its enhanced safety profile. For ized, double-masked, placebo-controlled clinical trial of two forms of omega-3 supplements for treating dry eye junctival hemorrhage, which may in- CCH, we typically prescribe lotepre- disease. Ophthalmology. 2017 Jan;124(1):43-52. dicate CCH. In addition, patients who dnol four times daily for two weeks, 3. Wladis EJ, Adam AP. Treatment of ocular rosacea. Surv Ophthalmol. 2018;63(3):340-46. present with both DED and epiphora then twice daily for another two to 4. FDA. Oxervate Prescribing Information. may have CCH. Clinicians can use the four weeks. We have found that topi- www.accessdata.fda.gov/drugsatfda_docs/ label/2018/761094s000lbl.pdf. Accessed March 29, slit lamp examination (which will re- cal corticosteroids provide more than 2019. veal redundant conjunctival folds that an 80% subjective and objective im- 5. US Food and Drug Administration. FDA approves first drug for neurotrophic keratitis, a rare eye disease. move with blinking) and vital dye provement and resolution of delayed www.fda.gov/NewsEvents/Newsroom/PressAnnounce- staining to confirm a CCH diagnosis. tear film clearing. ments/ucm618047.htm. Accessed March 29, 2019. 6. Marmalidou A, Kheirkhah A, Dana R. Conjunc- Topical medical management with Should medical therapy not meet tivochalasis: a systematic review. Surv Ophthalmol. lipid-based ocular lubricants may be therapeutic goals, conjunctival cauter- 2018;63(4):554-64.

OUR DRY EYE MANAGEMENT ALGORITHM All therapy—dry eye included—should be individualized to the patient. That said, here is our usual approach to dry eye management.

Two Weeks Four Weeks Indefinitely

Lipid-Based Artificial Tear Lipid-Based Artificial Tear Lipid-Based Artificial Tear Four to six times a day as needed Three to four times a day as needed Two to four times a day as needed

Lotemax SM Gel 0.38%* Lotemax SM Gel 0.38% Discontinue Lotemax SM Gel Four times a day Two times a day If symptoms break through or (Consider punctal plugs if needed) continue, then either pulse dose loteprednol four times a day for one week, or consider loteprednol once daily as needed.

The risk of increased IOP with loteprednol is uncommon at high dosage and rare at low dosage. Our experience has been that if an increase in IOP is going to occur, it will do so at the initial one-month follow up, and not later.

Omega-3 essential fatty acids (derived from fish and/or flaxseed oil) can be initiated at any stage

*Alternatively, instill loteprednol ointment daily at bedtime for three weeks, then M-W-F for three weeks. Loteprednol therapy for inflammation due to dry eye disease is considered an “off-label” use.

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0032_dg0519_OcularSurface.indd32_dg0519_OcularSurface.indd 3636 55/14/19/14/19 4:284:28 PMPM SEPARATE SCIENCE FROM SALESMANSHIP without intervention, simply because the condition itself is The early days of patent medicines were tarnished by now highly variable. It’s easy to falsely read regression to the infamous snake oil salesmen who trumped up ‘evidence’ that mean as efficacy, these authors caution. their homemade remedies worked wonders. The creation Regarding the second explanation, while most of us are of the FDA took a lot of that chicanery out of medicine, but aware of the placebo effect, fewer doctors understand the certainly not all. And it isn’t just patients who are vulnerable underlying mechanisms. Research in low back pain patients to aggressive marketing claims—doctors are too. treated with opioids or placebo shows similar brain activity A recent editorial in Ophthalmology uses dry eye as a cau- changes in both groups, illustrating that the placebo effect tionary tale, imploring doctors to critically evaluate primary has a true biological basis. In addition, the patient’s expec- research themselves and cast a skeptical eye at claims com- tation of improvement directly correlated with the actual ing from companies or consultants with a vested interest.1 amount of improvement with the placebo effect. The authors question how we can trust popular interpreta- The third possibility is of course that the prescribed tions of study data—often repeated at the podium or in mar- therapy did as intended and improved the patient’s physical keting—where researchers “use statistical tricks and multiple circumstances by addressing the cause of the pathophysiol- comparisons” to create an impression of efficacy that may ogy. Too often, the editorial argues, we assume this effect not be borne out by the data. is present because we want to believe it or we have been Even when studies demonstrate apparent statistical sig- conditioned by marketing to think that. We should keep this nificance, this doesn’t always translate to clinical significance. in mind every time we are faced with the decision to incor- The authors point out that the concentrations of 0.05% and porate new drugs into our treatment routines. 0.1% cyclosporin were only minimally superior to placebo The editorial goes on to caution against overzealous pre- and that “there is no clear dose response effect in this out- scribing of expensive drugs, noting that “eye care providers come variable or any of the primary outcome variables in prescribe more brand-name medicines than any other medi- this study.” cal provider.” The authors touch on several key points, including the Our bottom line: doctors are susceptible to slick marketing power of the placebo effect and the ability of “one teaspoon efforts that present weak data in a more favorable light than of olive oil to treat dry eyes.” Such was the placebo used the studies themselves show. To ward off undue influence, in the DREAM study. It can be a challenge to truly under- which speaks poorly of our professionalism, we must engage stand why a patient improves with any given treatment, the in detailed, objective review of the literature, the authors authors explain, noting that it could be attributed to one of state. This is why we implore our colleagues to subscribe to three reasons: regression to the mean, placebo effect or true a variety of professional journals. Ophthalmology, American treatment effect. Journal of Ophthalmology and JAMA-Ophthalmology are all The first possible explanation, regression to the mean, simply means that extreme measurements, when repeated, excellent resources that can protect us from aggressive sales often return to a more conventional level. Patients selected tactics under the guise of education. for dry eye trials because of their higher-than-average symp- 1. Seitzman GD, Lietman TM. Dry Eye Research—Still Regressing? Ophthalmology. tomatic scores can have lower scores when retested, even 2019;126(2):192-94.

AESTHETIC INTERVENTIONS We tend to focus on keeping patients healthy and free of symptoms of discomfort, but many are affected by the cosmetic appearance of their eye and we shouldn’t brush off these concerns as unimportant. Somewhat oddly, two pharmaceutical agents originally used in glaucoma have now been modified and repurposed to help improve the appearance of the eye. Latisse. Initially billed as an enhancer or treat- ment for hypotrichosis, this 0.03% bimatoprost formula- tion (Allergan) product recently lost patent protection. Clinicians may soon have access to new generic rendi- tions that may be useful if significantly less expensive than the branded version. Lumify. This brimonidine 0.025% formulation by Here, just 20 seconds after instilling Lumify, this patient’s Bausch + Lomb is an alpha-2 receptor agonist vasocon- eyes appear whiter. strictor indicated for red eye relief. Launched last year to much fanfare, it competes most directly with Visine, a of the ocular surface, as it does not cause the rebound tetrahydrozoline decongestant. Lumify is more sparing hyperemia associated with tetrahydrozoline.

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RAISE THE BAR ON MANAGING OCULAR ALLERGIES

Asking cular allergies continue to be one of the most com- Itchy Eyes Are Often Dry Eyes the right mon conditions seen in our Most patients with “itchy eyes” (consis- questions offices and clinics. Nearly tent with allergic conjunctivitis) also have Oone-third of the American dry eyes and redness. Specifically, the can prompt population is affected by allergic disease, odds of patients with “itchy eyes” who with an estimated 40% to 80% of these also have dry eyes are 2.11 times that of patients to individuals manifesting ocular involve- patients with non-itchy eyes.1 The odds 1 ment. And while allergic eye disease has of these patients disclose clues been shown to strongly impact a patient’s also experienc- that they are quality of life, paradoxically, many pa- ing redness are tients with allergies fail to report their 7.34 times that ocular symptoms. burdened by of patients with Moreover, allergic eye disease is often non-itchy eyes.1 included as a component of the diagno- this common These results ses of allergic rhinitis or sinusitis, accord- This patient presented suggest that ocular ing to the American Academy of Allergy, with an acute allergic some symp- Asthma and Immunology. As a result, si- response of itching, condition. nus inflammation is routinely diagnosed, tomatic patients conjunctival injection treated and managed, while ocular aller- concomitantly and chemosis. gies are not. have features of So we are left to ask ourselves: How ef- allergic conjunc- fectively are we diagnosing and treating tivitis and dry eye syndrome.

this disease? 1. Hom MM, Nguyen AL, Bielory L. Allergic conjunc- Allergic conjunctivitis begins when the tivitis and dry eye syndrome. Ann Allergy Asthma Immunol. 2012;108(3):163-6. immune system identifies an aeroallergen on the conjunctiva. In response, the im- mune system overreacts and produces flammatory process. antibodies called immunoglobulin E (IgE) Allergic eye disease, an immune-mediat- that quickly bind to mast cells. This in turn ed response (IgE antibodies) and type I hy- releases chemical mediators such as hista- persensitivity reaction, can be subdivided mine that initiate a cascade of local inflam- into three phases: sensitization, an early mation (e.g., itching, redness, tearing)—a phase and a late phase. While the early- process known as mast cell degranulation. phase reaction can be mildly symptomatic, This response to the allergen produces the late phase can yield keratitis, limbal in- local itching and tearing, resulting in eye filtrates and potentially sight-threatening rubbing. Unfortunately, in most instances corneal shield ulcers (e.g., vernal kerato- it only accelerates and aggravates the in- conjunctivitis).

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038_dg0519_Allergy.indd 38 5/14/19 4:30 PM OPTOMETRISTS AND ALLERGISTS: An Update on Prevalence A POWERFUL TEAM APPROACH According to published find- In a recent conversation, Phil Lieberman, MD, a clinical professor in the ings from a series of studies Departments of Internal Medicine and Pediatrics, Divisions of Allergy and conducted by the International Immunology, at the University of Tennessee College of Medicine, discussed the Study of Asthma and Allergies profound burden allergic eye disease can have on a patient’s quality of life. in Childhood (ISAAC) starting He noted that the two most prevalent allergens are pollen and animal dan- two decades ago, allergic con- der, which cycle throughout varying seasons. In the spring, grass and tree junctivitis has shown a world- pollen aeroallergens are common; in the fall, ragweed is more predominant. wide trend in increasing preva- Additionally, indoor pets can prompt allergic eye disease. lence.1 This upsurge has been Dr. Lieberman stated, “The symptoms of allergic eye disease are usually attributed to climate changes, three in number: itching (paramount), redness and tearing. Without itching, the pollution, increased pollen and patient probably does not have allergic eye disease.” a heightened immunological Allergists suggest that patients suffering from chronic and cyclical symptoms sensitivity in response to envi- caused by allergic disease be tested to identify the offender(s). Treatment is ronmental changes, among delivered through medicine, environmental control (avoidance), allergy injec- other factors.2 About 40% of tions and sublingual drops. patients who suffer from aller- The next time your patient presents with a longstanding history of allergic gies reportedly experience patterns, consider the role of an allergist to further assist your management. some form of ocular sympto- mology (i.e., itching, chemosis and redness).3 Of equal significance are the “Do Your Eyes Itch or Burn?” cell stabilizers and/or corticosteroids. Perennial allergic conjunctivitis fol- documented negative impacts • Itching: If itching is the lows a more indolent course, often of ocular allergies on patient patient’s primary concern, requiring persistent care by the at- quality of life, confirming the determine if it’s an isolated importance of early therapeutic tending doctor, although treatment symptom or if it’s associated intervention. with parallel signs of inflam- options are essentially the same as for mation, and then treat accord- the seasonal variety. 1. Worldwide variation in prevalence of symp- Itching is the definitive hallmark of toms of asthma, allergic rhinoconjunctivitis, ingly. Remember: and atopic eczema: ISAAC. The International Symptoms only: Use cold, ocular allergy. Always ask your pa- Study of Asthma and Allergies in Childhood tient: “Is itching or burning your main (ISAAC) Steering Committee. Lancet. 1998 tears, and oral or topical an Apr;351(9111):1225-32. antihistamine/mast cell stabi- symptom?” Typically, their response 2. D’Amato G, Holgate ST, Pawankar R, et al. lizer. can guide your next step. If the patient Meteorological conditions, climate change, new emerging factors, and asthma and related Symptoms and signs: Use remarks that itching is the main symp- allergic disorders. A statement of the World the same strategy with the Allergy Organization. World Allergy Organ J. tom, allergic etiology is confirmed. In 2015; 8(1):1-52. addition of a steroid such as cases where your patient is unable 3. Singh K, Axelrod S, Bielory L. The epidemiol- Lotemax, Alrex or FML. ogy of ocular and nasal allergy in the United to decide which symptom distresses States, 1988-1994. World Allergy Organ J. • Burning: If burning is the them the most, consider treating with 2015;8(1):25. main symptom, a full dry eye a topical ester-based steroid drop workup is in order. Be sure to (e.g., Alrex, loteprednol etabonate ing the palpebral and bulbar conjunc- consider dry eye as the foun- 0.2% or Lotemax SM loteprednol tivas. If the anterior segment shows dational condition, and treat etabonate 0.38%), which typically minimal or unremarkable signs of an accordingly. Be aware that both of these solves both complaints. Anytime a allergic conjunctivitis (e.g., conjuncti- symptoms can exist concomi- patient is prescribed topical steroids, val chemosis, conjunctival injection, tantly. Due to the prevalence intraocular pressure should be done at lid edema and/or papillae), treating of dry eye across all ages, rec- the two- to four-week follow-up visit. with a combination antihistamine/ ognize and also treat this dis- If patients report itching as their mast cell stabilizer remains the ideal ease whether or not it is affili- predominant symptom, therapy is di- clinical choice. There are currently sev- ated with allergic eye disease. rected toward one of two paths, dis- en drugs in this class to choose from: cussed below. • Alcaftadine (Lastacaft, Allergan) For seasonal allergic conjunctivitis, • Azelastine (Optivar, Meda Phar- the treatment protocol is straightfor- SYMPTOMS ONLY maceuticals; generic available) ward: cold compresses, lubrication, Ocular allergies can be easily over- • Bepotastine (Bepreve, Bausch + oral and topical antihistamines/mast looked, so begin by carefully evaluat- Lomb)

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addition, all are dosed initially BID, KEEP TYPES OF ALLERGIC with the exception of Pazeo, Pataday IN MIND CONJUNCTIVITIS and Lastacaft, which are dosed QD. After two weeks of BID therapy, 1. Acute Allergic Conjunctivitis: Subcategories are seasonal allergic conjuncti- vitis (allergens include: ragweed, pollen, grass, etc.) and perennial allergic con- consider reducing instillation to QD junctivitis (allergens include: dander, foods, molds, etc.). or as needed dosing for maintenance dosing. As with any treatment, the 2. Giant Papillary Conjunctivitis (GPC): More mechanical in nature than a true lowest effective dose is always de- allergic response. sired. In our experience, once inflam- mation is firmly brought under con- 3. Vernal Keratoconjunctivitis (VKC): Involves type I and IV hypersensitiv- trol, less pharmaceutical intervention ity reactions; presents with severe itching; symptoms are exacerbated in the is needed to maintain control. Then spring. again, some patients still require a second additional drop later in the 4. Atopic Keratoconjunctivitis (AKC): Uncommon; associated with asthma, afternoon. hay fever and eczema. When symptoms cannot be man- aged by the OTC medications listed • Epinastine (Elestat, Allergan; ge- Of these, most are rated the his- above, a 5ml bottle of Alrex and neric available) torical pregnancy category C, except Bepreve should only require $10 • Ketotifen (Zaditor, Alcon; Ala- Lastacaft (category B) and Zerviate, copays for the first Rx and refills way, Bausch + Lomb; many gener- in which “no adequate or well-con- (for most eligible commercially in- ics available. This drop is OTC.) trolled studies” were conducted in sured patients) through the Bausch + • Olopatadine (Pazeo/Pataday/Pa- pregnant women, per the drug’s pre- Lomb Access program at Walgreens tanol, Novartis) and generic 0.1% scribing information. Not withstand- and other participating independent olopatadine ing fine differences, all of the antihis- pharmacies during allergy season • Cetirizine (Zerviate, Eyevance tamine subtype 1 receptor blockers (between March 1, 2019 and Oct. Pharmaceuticals) nicely suppress ocular itching. In 31, 2019). Also consider consulting

OCULAR ALLERGY MEDICINES BRAND NAME GENERIC NAME MANUFACTURER PEDIATRIC USE BOTTLE SIZE(S) DOSING Acute Care Products Acular LS ketorolac tromethamine 0.4% Allergan and generic 3 yrs 5ml, 10ml QID Alaway (OTC) ketotifen fumarate 0.035% Bausch + Lomb 3 yrs 10ml BID Alrex loteprednol etabonate 0.2% Bausch + Lomb 12 yrs 5ml, 10ml QID Bepreve bepotastine besilate 1.5% Bausch + Lomb 2 yrs 5ml, 10ml BID Elestat epinastine HCl 0.05% Allergan and generic 3 yrs 5ml BID Emadine emedastine difumarate 0.05% Novartis and generic 3 yrs 5ml QID Lastacaft alcaftadine 0.25% Allergan and generic 2 yrs 3ml QD Optivar azelastine hydrochloride 0.05% Meda and generic 3 yrs 6ml BID Pataday olopatadine hydrochloride 0.2% Novartis 3 yrs 2.5ml QD Patanol olopatadine hydrochloride 0.1% Novartis and generic 3 yrs 5ml BID Pazeo olopatadine hydrochloride 0.7% Novartis 2 yrs 2.5ml QD Zaditor (OTC) ketotifen fumarate 0.035% Novartis and generic 3 yrs 5ml BID Zerviate cetirizine 0.24% Eyevance Pharmaceuticals 2 yrs 5ml, 10ml BID

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

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0038_dg0519_Allergy.indd38_dg0519_Allergy.indd 4400 55/14/19/14/19 4:304:30 PMPM TOPICAL ANTIHISTAMINE DOSING: throughout the day. However, a subset of patients may TWO ARE BETTER THAN ONE need a second drop later in the afternoon. Which is cor- Prescribing pure mast cell stabilizing drugs is no longer rect? In the end, either is appropriate, as patient care is not considered to be a best practice for treating ocular aller- a one-size-fits-all, but rather a tailored approach to find gies, according to Mark Abelson, MD, a world-renowned symptomatic relief. (Remind your patients that transient ocular allergist at Harvard Medical School. Dr. Abelson told burning and stinging upon instillation is common.) us that pure mast cell stabilizing drugs have little clinical Patients with severe allergy expression will need slightly use, as their lag period and mandatory chronic dosing more involved therapy. In addition to an antihistamine/ severely limits their applicability. Rather, topical combina- mast cell stabilizer BID, we turn to an ester-based cortico- tion antihistamine/mast cell stabilizers offer patients nearly steroid such as Alrex (loteprednol 0.2%, Bausch + Lomb) instantaneous relief due to the rapid onset of action. Also or off-label use of Lotemax SM (loteprednol 0.38%, Bausch compelling is their affordability; the cost of an OTC topical + Lomb) QID initially along with cold compresses. combination antihistamine/mast cell stabilizer is similar to Once the inflammation has settled down, the steroid a pure mast cell stabilizer. may be discontinued, and the patient can remain on the For patients who have symptomatic disease, one antihistamine/mast cell stabilizer once or twice daily as drop in the morning may suffice for lasting improvement needed.

www.goodrx.com to find the best counterparts. (Also note: FML, though increasing prevalence in countries ex- pricing in your area. generic, is often more expensive than periencing sustained growth and de- the varying concentrations of lotepred- veloping urban populations.2 Doctors SYMPTOMS AND SIGNS nol once a Bausch + Lomb coupon has should keep in mind that ocular aller- Whenever possible, therapy for ocu- been applied.) gies, while not life-threatening, yield lar allergies should be prophylactic. The frequency of instillation of ste- persistent, uncomfortable symptoms For patients who encounter the same roidal preparations should be tailored that negatively impact the patient’s allergic complications yearly, therapy to the severity of the patient’s signs and productivity and quality of life. should be initiated prior to symp- symptoms. Typically, we prescribe a Also remember that allergy is an tomatic inflammation, be sufficient steroid drop Q2H for two days, then expression of inflammation. In addi- enough to suppress the patient’s signs QID for one week, followed by BID tion to the therapeutic strategies listed and symptoms, and be continued for a for one more week to manage most above, don’t forget to discuss palliative long enough period to prevent conver- cases. Once the signs of allergic eye dis- options with patients such as daily cold sion into a chronic disease. The basis ease are subdued, consider switching compresses to the inflamed eye. Sug- of treating any allergic eye disease re- your patient to an antihistamine/mast gesting that your patients place their mains the same: quell the inflamma- cell stabilizer for ongoing symptomatic allergy drops in the refrigerator until tion early to help avoid potential late regulation. it’s time to instill the drops can provide complications. added relief. ■ In patients who present with symp- AN EQUAL-OPPORTUNITY toms of allergy as well as classical an- DISEASE 1. Kari O, Saari KM. Diagnostics and new develop- ments in the treatment of ocular allergies. Curr Al- terior segment findings, a topical ester- While originally considered to be a lergy Asthma Rep. 2012;12(3):232-9. based corticosteroid is our preferred “disease of affluence,” allergic con- 2. Gomes PJ. Trends in prevalence and treatment therapeutic option. Don’t hesitate junctivitis is now clearly recognized of ocular allergy. Curr Opin Allergy Clin Immunol. to employ Alrex (loteprednol 0.2%, in many corners of the world, with 2014;14(5):451-6. Bausch + Lomb) or off-label Lotemax SM (loteprednol 0.38%, Bausch + Lomb). Topical prednisolone acetate (Pred Forte and Mild, Allergan) and prednisolone sodium phosphate (In- flamase Forte and Mild, Novartis) are additional options. Also, the ketone-based steroid FML ophthalmic suspension (fluorometho- lone 0.1%, Allergan and generic) is a viable option, though we have found This child’s mosquito bite was mistaken as preseptal cellulitis by Urgent Care. We it has a higher propensity to increase treated him with Benadryl, steroid drops and cold compresses. The right image is IOP compared with its ester-based four days later.

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038_dg0519_Allergy.indd 41 5/14/19 4:30 PM SHINGLES DRUGS

ARM YOURSELF FOR A SHINGLES ONSLAUGHT

Until the adult ne day, shingles—a latent A SKIN AND EYE DISEASE secondary expression of the The diagnosis is usually straightforward. A population is varicella zoster virus—will minority of patients will develop skin pain fully vaccinated be exceedingly rare. The days or weeks before developing the ve- Oadvent of the chickenpox sicular eruptions associated with shingles. against vaccine (Varivax, Merck) is creating gen- Zoster disease is most commonly expressed erations of patients who will never have in the trunk of the body; the second most varicella zoster, shingles because they will never contract common site is the first (ophthalmic) divi- chicken pox. sion of the trigeminal nerve distribution, more patients However, until all children are fully im- which involves the forehead and upper eye- munized with the chickenpox vaccine— lid. The globe becomes involved in about will need our which will take another 20 to 30 years, at half of these first trigeminal nerve expres- help with this least—there will be a significant uptick of sions, and the disease affects both the skin adult shingles. This is because, before the and the globe. condition. vaccine’s release, the spread of childhood When shingles presents as an uncompli- chickenpox within the community passive- cated skin disease, as evidenced by pain, With prompt ly fostered adult immunity through contact erythema and vesicular expression, the with the virus during the course of daily treatment is an oral antiviral for seven to attention, you living. Without these sporadic immunity- 10 days with one of three options: can hasten bolstering experiences, unvaccinated adults • Acyclovir 800mg five times daily are more vulnerable to shingles later in life. • Valacyclovir 1000mg TID recovery from As our population ages, eye doctors need to • Famciclovir 500mg TID be prepared to meet the needs of this com- These drugs nicely subdue a varicella this often ing wave of shingles. outbreak in most patients, particularly painful and distressing experience.

HZO patient before (left) and after treatment.

42 REVIEW OF OPTOMETRY MAY 15, 2019

042_dg0519_shingles.indd 42 5/14/19 4:32 PM treatment with cycloplegia and topical SHINGLES VACCINE UPDATE steroids. We prescribe Having shingles is far more effective in preventing further outbreaks than 5% for use BID to QID, along with the vaccines. Zostavax (live zoster vaccine, Merck)—which only reduces the Durezol (difluprednate ophthalmic disease burden by about 50%—has now been relegated to history with the emulsion, Novartis), prednisolone ace- advent of the newer and much more effective Shingrix. The Zostavax vac- tate or loteprednol until the inflamma- cine is highly recommended for those older than age 60. The downside of tion is well controlled. Only then begin the vaccine is that it only provides relative immunity for about eight years, so a taper. If the patient is older or has repeat vaccination may be necessary. a severe presentation, we commonly Shingrix (recombinant zoster vaccine, GlaxoSmithKline) was FDA approved in 2017 for immunocompetent patients ages 50 and older. Studies demon- prescribe 40mg to 60mg of oral pred- strate it is 97% effective for patients between the ages of 50 and 69 and nisone for five to seven days (without remains effective, at 91%, in those aged 70 or older. In addition, researchers taper) in addition to the steroid drop note Shingrix is more cost-effective than Zostavax. and antiviral to help control the con- Although patients often ask if they should get the vaccine if they have current inflammation and pain. already had a bout of shingles, we have no definitive answer. Some advo- All of the oral antivirals are FDA cate that patients should receive the vaccination, whether or not they have Category B, and clinicians must re- already had shingles, simply because the condition could recur. However, duce the dosage for patients with renal having shingles powerfully boosts the immune system, which is why shingles disease. If your patient has impaired is often a one-and-done event. We believe a patient older than age 50 who kidney function, call their nephrolo- develops shingles likely would not benefit from the vaccine any more than gist or internist to learn the creatinine natural history. Further, cataract surgery can increase the risk of a repeat clearance rate or glomerular filtration bout of shingles, so a patient should generally wait a year or so after having rate. This will help you, a pharmacist shingles to get cataract surgery. or an app calculate the proper dosage. While we have never encountered this Jeng BH. Herpes zoster eye disease: new ways to combat an old foe? Ophthalmology. 2018; unusual circumstance, we are well pre- 125(11):1671-74. pared if we do. For our shingles patients, we occa- patients who present within the first concurrently with the skin, it is com- sionally have a brief chat with the pa- 72 hours of the outbreak. Antiviral monly an inflammatory keratitis, uve- tient’s primary care physician first to medicines work best during the early itis or both. Uveitic involvement will be sure there are no contraindications replicative phase of the infection. This manifest as inflammatory cells in the to any of these medications. Always does not mean that after three days, anterior chamber; corneal involvement remember, excellent patient care often the opportunity for medical interven- will manifest as stromal inflammation. requires a team approach. Never hesi- tion has passed—just that there is de- Occasionally, even the trabecular tis- tate to make a call, but take care of the creasing clinical efficacy with each day sues become inflamed, resulting in patient yourself. of delayed care. With more virulent ex- increased intraocular pressure. Con- pressions, especially in older patients, junctival injection, of varying degree, CLINICAL CHALLENGE concurrent therapy with oral predni- accompanies these inflammatory ex- Diagnosis can be tricky for a patient, sone (usually 40mg to 60mg/day for a pressions. Such ocular involvement often older and Caucasian, who pres- week) can help decrease the pain and requires proper (usually aggressive) ents with new-onset headache and skin inflammation, and it may dampen the expression of post-herpetic neuralgia. QUOTABLE Globe. When the globe is involved

Herpes Zoster Regimen Options: For our shingles patients, we occasionally have a Acyclovir 800mg 5x/day for seven brief chat with the patient’s primary care physician to 10 days first to be sure there are no contraindications to any Valacyclovir 1000mg TID for seven of these medications. Always remember, excellent to 10 days patient care often requires a team approach. Never Famciclovir 500mg TID for seven to hesitate to make a call, but take care of the patient 10 days yourself.

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only if the patient develops dermato- logic vesicles over the next few days. Lab results are often available in a day or two. If the lab results are positive for GCA, we prescribe 80mg to 100mg of oral prednisolone that day and sched- ule the patient to undergo a temporal artery biopsy in the next few days with an oculoplastic subspecialist, general surgeon or otolaryngologist. Be sure to keep the patient’s primary care physi- cian up-to-date on the diagnosis and management using a succinct letter— never just send a copy of the volumi- This patient presented with second-division shingles. In addition to standard oral nous electronic medical record. antiviral treatment, such patients may well benefit from oral prednisone to help As shingles can be devastatingly control inflammation and pain. painful, it is satisfying to provide ef- fective acute care to those who are pain, but no vesicles on the face over rate, C-reactive protein and a com- suffering. The diagnosis is almost al- the distribution of the ophthalmic divi- plete blood count to look for elevated ways clearly evident, and the medical sion of the trigeminal nerve. It could be platelets (thrombocytosis). These three intervention is straightforward in most giant cell arteritis (GCA) or early-onset markers tend to be significantly el- cases. We should be experts in treat- shingles. For this patient, we would evated in the setting of GCA. Then we ing this disease, as we are likely to see order an erythrocyte sedimentation prescribe an oral antiviral to be filled more cases in the coming years. ■

KEEP ORAL ANTIVIRAL IN MIND PRESCRIBING PEARLS

While these drugs are the workhorses in treating herpes simplex viral keratitis and shingles, clinicians should keep these clinically relevant finer points in mind when prescribing antivirals: • For patients who are lactose intolerant, we prescribe valacy- clovir. We all need to think about asking about lactose intol- erance prior to prescribing. • For patients older than age 65, famciclovir is preferred because research shows both acyclovir and valacyclovir have an increased risk of central nervous system reactions such as agitation, hallucinations, confusion and encephalopathy.1 In addition, they pose an increased risk of renal failure for older patients compared with those younger than 65.1 • Since the herpes simplex virus is easier to kill than the herpes zoster (varicella) virus, the dosage for simplex is generally half of that used to treat shingles: acyclovir, 400mg; vala- cyclovir, 500mg; and famciclovir 250mg—all for the same duration. This presentation of HSK was mistaken as an abrasion • Acyclovir has a liquid formulation ideal for children and at the ER. The patient simply needed treatment with patients with dysphagia (difficulty swallowing); this is dosed an oral antiviral only. at 200mg/5mL (5mL is one teaspoon). • Don’t forget that oral antivirals are the drugs of choice to treat epithelial herpes simplex keratitis, not the toxic (and more expensive) topical drugs. • The main side effect of the antivirals is occasional nausea, so patients should take them with meals.

1. White ML, Chodosh J. Herpes simplex virus keratiti: a treatment guideline - 2014. American Academy of Ophthalmology. www.aao.org/clinical-statement/ herpes-simplex-virus-keratitis-treatment-guideline. June 2014. Accessed April 4, 2019.

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042_dg0519_shingles.indd 44 5/14/19 4:33 PM VISION INSIGHTS

PRESERVING VISION ACROSS THE LIFECYCLE

New research oung or old, all of our pa- must for many patients. But what that in- tients may need us to step in tervention looks like is still up for debate. on everything to help preserve their vision Based on our experience and that of our from quality at some point in their colleagues, it appears that low-dose at- Ylives. Two conditions that af- ropine may be the best pharmacological to AMD is fect opposite ends of the lifecycle spectrum therapy. However, researchers continue to have been under the microscope of late, debate the best therapeutic regimen for op- helping us and new data is giving us different strate- timal myopia control with . gies to better help these patients. Let’s take A June 2018 article published in Eye protect our a look at the latest literature on myopia provides robust coverage of the various control and nutrition for retinal health. therapeutic options, and it is worth taking patient’s a close look at its conclusions:1 vision—from LOW-DOSE ATROPINE • “Myopia is the most common eye dis- FOR MYOPIA CONTROL order worldwide, but it is often misregard- birth to 101. Over the decades, researchers and clini- ed as merely a that simply cians alike have tested myriad approaches can be corrected by spectacles, contact to slowing the progression of myopia, yet lenses, or refractive surgery.” none are optimal. While patients need to • “…delaying myopia onset and retard- embrace simple lifestyle adjustments such ing myopia progression in school-aged as increasing time spent outside and reduc- children is potentially the key to reduce ing screen time, clinical intervention is a high myopia later in life.”

QUOTABLE

“It is now thought that because of the rapid increase in the prevalence of myopia in under one generation, environmental factors perhaps played a greater role in its development than our genes. Environmental risk factors include urbanization, higher educational attainment, higher IQ, but more important has been two consistent risk factors: increased near-work activity and reduced outdoor activity.”

Dirani M, Crowston JG, Wong TY. et al. “From reading books to increased smart device screen time.” Br J Ophthalmol. 2019;103(1):1-2.

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• “To date, atropine is the only med- THE CONNECTION BETWEEN OPTOMETRY AND UROLOGY ication that has been demonstrated to Eye doctors and urologists generally have little in common, and you can judge be consistently effective in slowing my- whether that’s a good thing. However, a new drug has just been approved for opic progression. Once myopia has de- the treatment of adult patients with locally advanced or metastatic urothelial veloped in a child, the rate of progres- carcinoma. sion is estimated to be around -1D per Balversa (erdafitinib) tablets carry serious ocular side effects including year in East Asians and around -0.5D inflamed eyes, inflamed cornea and disorders of the retina such as central serous per year in Caucasians. […] Therefore, retinopathy/retinal pigmented epithelial detachment.1 It is recommended that intervention to prevent myopia pro- these patients have monthly eye examinations during the first four months of gression early on in myopic children is treatment, every three months afterwards and at any time for visual symptoms. urgent and important.” Beyond a vision assessment and dilated fundus examination, always perform • “Starting treatment with the low- optical coherence tomography imaging at each visit. est concentration, such as 0.01% atro- Here is an opportunity for optometrists to establish a pine, would be preferable as this is as- relationship with area urologists and perhaps oncologists sociated with the least side effects. The to let them know you are available to consult with them dosing frequency is once daily at bed- on Balversa. This is similar to our relationship with rheu- time […] During the period of atropine matologists regarding Plaquenil (hydroxychloroquine) treatment, the appropriate distance screenings.

glasses should be prescribed if the child 1. FDA approves first targeted therapy for metastatic bladder cancer. www. has difficulty in far vision...” fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635906.htm. April 12, 2019. Accessed April 16, 2019. • “For optimal results, the motiva- tion of parent[s] and children is im- portant, and long-term compliance Another, more recent study evalu- • “The anti-myopia mechanisms of and adherence with atropine treatment ated three concentrations of atro- atropine are not fully understood.” cannot be over-emphasized.” pine—0.05%, 0.025% and 0.01%— These two groups of researchers The author notes that rigorous stud- and provides more details on the come to slightly different conclusions, ies comparing different concentrations benefits of these differing atropine perfectly reflecting the embryonic of atropine have found the 0.01% is treatment regimens:2 state of pharmacological dampening most effective with minimal rebound • “After 1 year, there was a reduc- of myopia progression. We think the upon treatment completion. While tion of 67%, 43%, and 27% in the key to widespread use of this yet-to-be- is the most frequent side mean SE [spherical equivalent] pro- perfected approach is to partner with effect in higher concentrations (i.e., gression and 51%, 29%, and 12% a clinician well-versed in using this 1% and 0.5%), participants using in AL [axial length] elongation in the therapeutic approach. 0.1% and 0.01% rarely complained of 0.05%, 0.025%, and 0.01% atropine While these study results are prom- photophobia. This rarity also held true groups, respectively, when compared ising, getting parents and children on- for the development of atropine al- with the placebo group. Of note, board—and keeping them onboard for lergy in these lower concentrations. In the difference in axial elongation be- several years—may be the limiting fac- the 0.01% group, only 2% of patients tween the 0.01% atropine and pla- tor in the ultimate success of low-dose stopped treatment due to side effects.1 cebo groups was not significant. All 3 atropine. We urge you to identify and The researchers also recommend pa- concentrations of atropine were well communicate with pediatric experts tients remove their myopia-correction tolerated by the children in pupil di- before embarking on this pharmaco- eyeglasses during near tasks or wear lation, loss, near vi- logical approach to myopia control. multifocal glasses, along with gener- sion, and best-corrected distant vision. ous outdoor activities. During those There was no reported treatment-re- NUTRITION AND THE RETINA: outdoor activities, they can wear a hat, lated adverse event.” STAVING OFF AMD photochromic glasses or sunglasses to • “Although we confirmed that at- The ravages of age are inevitable for alleviate symptoms of photophobia.1 ropine 0.05% is better than 0.025% many of our senior patients, especially Although the optimal length of over a 1-year period, it is important to those who have not taken reasonable treatment is unknown, some recom- compare their efficacies after 2 years care of themselves. One of the more mend halting treatment for one year to to determine the long-term optimal prevalent ravages is age-related mac- assess the rate of progression after the concentration. […] There is also the ular degeneration (AMD). A recent initial two years of treatment. Those question of whether atropine could population-based study, published in who progress after stopping treatment be discontinued once the myopia pro- the February 2019 issue of American can restart the therapy.1 gression was under control.” Journal of Ophthalmology, highlights

46 REVIEW OF OPTOMETRY MAY 15, 2019

045_dg0519_VisionInsights.indd 46 5/14/19 4:36 PM about the benefits of a healthy overall lifestyle that includes a healthy diet, regular exercise and no smoking. The problem with this recommen- dation, however well-intentioned, is that humans, by and large, make lousy patients. We are often undisciplined ABC and tend to make poor decisions. To help our patients maintain central vi- (A) Large confluent soft drusen represent advanced dry degenerative changes. sion, despite themselves, we common- Hopefully this and the subsequent events could be prevented, delayed or minimized ly recommend oral supplementation of with appropriate vitamin-mineral supplementation. (B) Large disciform scar after vitamins and minerals with either the resorption of blood resulting from hemorrhagic (wet) AMD. (C) A fresh sub-RPE and traditional AREDS2 product or the sub-sensory retinal hemorrhage. new chewable form. ■

many nutritional changes patients can are important components of macular 1. Wu P-C, Chuang M-N, Choi J, et al. Update in myo- pia and treatment strategy of atropine use in myo- 3 take to help ward off retinal changes. pigment and help to maintain the ret- pia control. Eye. 2019;33:3-13. For one, research shows lutein, zea- ina’s integrity. Lutein and zeaxanthin 2. Yam JC, Jiang Y, Tang SM, et al. Low-concentra- tion atropine for myopia progression (LAMP) study. xanthin, zinc, vitamins C and E, and concentrate in the macula and can fil- Ophthalmology. 2019;126(1):113-24. the polyunsaturated omega-3 fatty ter blue light, halt reactive oxygen spe- 3. de Koning-Backus APM, Buitendijk GHS, Kiefte-de acids, can all reduce the risk of de- cies, and reduce light-induced oxida- Jong JC, et al. Intake of vegetables, fruit, and fish is beneficial for age-related macular degeneration. Am veloping AMD. Trials that evaluate tive damage and inflammation. They J Ophthalmol. 2019;198(2):70-79. high-dose supplementation of these can also protect neural membranes. nutrients, as well as reports on dietary Despite this, the study found no signif- intake provide significant evidence of icant association with incident AMD KEEP FISH OIL & their beneficial effects. Patients who for the food categories of vegetables IN MIND EPA–DHA adhere to a diet that combines many of and fruit. these beneficial nutrients may be more The researchers concluded that no Fish oils come in different quali- protected against AMD than patients clear evidence existed that the dietary ties and their essential fatty acid who do not. “A possible explanation intake of lutein and zeaxanthin low- constituents of eicosapentaenoic is that the bioavailability and nutri- ered the risk of AMD. Dietary intake acid (EPA) and (docosahexaeno- tional value of a nutrient depends on of beta-carotene, however, showed a ic acid) DHA can vary. As a gen- the concomitant uptake of other nutri- reduced risk of AMD, especially for eral guideline, the milligram con- 3 ents,” according to the study authors. those with high genetic risk. tents of these compounds must Countries that have established di- At the end of the day, the study con- add up to roughly 850mg to etary guidelines generally recommend firmed what other researchers have have a meaningful effect. These one to two portions of fish per week, already reported: a diet that combines two compounds are concen- 200g to 250g of veg- various food groups influences trated in the outer layers of the etables each day and the bioavailability and nu- photoreceptors and are thought 200g of fruit daily. tritional value of each indi- to absorb harmful wavelengths The study found this vidual nutrient. Combining of blue light. Because lutein and diet provided a 42% foods led to better per- zeaxanthin are supplements, you reduction in the risk formance than each food would need to know the dietary of AMD. Just eating group individually. and nutritional intake of each particularly fatty fish Clinicians can be confi- patient to properly quantify the twice a week reduced dent that the literature sup- precise amount of supplemen- the risk by 24%.3 ports a recommended diet tation necessary. This reality is When it comes to that consists of a large vari- often lost in the conversation nutrition and AMD, ety of vegetables, fruit and regarding appropriate supple- the carotenoids lutein fish will benefit patients at mental recommendations. and zeaxanthin are risk for AMD. The study Pizzimenti J, Capogna L. often the first to come author concluded that cli- Chronicles. Talk presented at the Optometric Retina Society EyeSki to mind for clinicians, nicians should counsel all Conference. Park City, UT. Feb 23, 2015. mostly because they patients at risk of AMD

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045_dg0519_VisionInsights.indd 47 5/14/19 4:36 PM PRACTICE MANAGEMENT

A NEW WORLD OF OPTOMETRY

Optometrists rogression of technology can lic health–oriented stakeholders should cut like a two-edged sword. find such approaches deplorable. must accept We have all seen the rapid Ironically, while some retail-based the reality of evolution of autorefractors; optometrists are refraction-centric prac- Pthey have achieved remark- titioners, they tend to not be AOA mem- encroaching ably excellent accuracy. Now this diag- bers. Why is this ironic? Because the nostic technology is available online in AOA is our profession’s frontline advo- threats a rudimentary form and will likely only cate, and we all need to become mem- become more sophisticated. It’s conceiv- bers. This is especially true of younger from online able that the day will soon be upon us optometrists who perform refraction as refractive when refraction can be achieved via the the centerpiece of their practices. camera function on a phone or tablet, or In addition to the threat from online services and even in a mall kiosk! refractive technology, numerous online Though we would all agree that re- retail sites are offering eyeglasses, and technology fraction is best handled by a well-trained 3-D printers can now print eyeglasses eye doctor, many patients are satisfied from a “phantom model.” advancements with a good-enough refraction online. A study published in the May 16, and find ways Many “consumer advocates” are sure to 2018, issue of Clinical and Experimental enthusiastically embrace these cheap and Optometry noted the ability of 3-D to expand— workable online technologies, while pub- printing technology to fabricate and

and diversify— THE ‘MODEL’ MISNOMER their eye care The term “medical model” is ill-conceived and poorly reflects the modus operandi of comprehensive optometric care. Perhaps this term is intended to indicate an interest practices. in expanding one’s practice to begin to more aggressively manage medically oriented patient presentations. However, in our eyes, this simply reflects the need to become more comprehensive and refer less—not a monumental shift, and certainly not one meriting a special moniker. A more accurate name might be “comprehensive optometry,” signifying that the com- prehensive optometrist provides all of the care needed for the vast majority of patients who present. This, of course, would include medical eye care in addition to contact lens care, low vision, orthodox orthoptics, refractive correction services and more. Medical eye care for most ODs, especially those in rural areas, is and probably always has been a significant part of daily practice. Comprehensive care includes all aspects of medical eye care, but to attempt to isolate a mode of practice as a medical model actually misrepresents what progressive, contemporary optometrists do every day. Enough said.

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0048_dg0519_practiceManagement.indd48_dg0519_practiceManagement.indd 4848 55/14/19/14/19 4:384:38 PMPM KEEP WHEN THE PHARMACY OR 2% to be used first thing in the morning (be sure to IN MIND PATIENT REJECTS YOUR Rx instruct the patient to always wait a few minutes between instillation of the two drops) and then second instilla- Too often, we get calls from pharmacies to inform us that tions around 4pm to 5pm. Of note, while brinzolamide Drug Y prescribed for a patient is not on the insurance is in Simbrinza, when prescribing an individual carbonic formulary, and they recommend Drug Z be substituted. anhydrase inhibitor, we default to the generic dorzol- At other times, the medicine that would best serve the amide because it is less expensive and is a solution, thus it patient’s needs is quite expensive, so the patient rejects requires no shaking before instillation. the prescription at the pharmacy due to the cost, which Problem: You prescribe Lotemax SM drops off label for prompts yet another call back to the prescribing doctor. a patient with dry eye disease, only to be told that it is We, and no doubt you, are sick of this absurd interference either too expensive or not on the formulary. in the care of our patients. Plan B: Try coupons, or default to generic fluorometho- Here is an example of the maddening scenario we all lone 0.1%. While this medicine is relatively safe, it is not as encounter with growing frequency: We saw a young safe as loteprednol. Be sure to advise the patient that the woman with chronic, recurrent, bilateral anterior uveitis fluorometholone must be shaken before each instillation. whose condition was concurrently managed by her rheu- Problem: You prescribe Zylet or generic TobraDex for matologist, who had placed her on increasingly high doses staphylococcal blepharitis, only to be told that it is too of methotrexate because we were unable to subdue the expensive or not on the patient’s formulary. uveitis with topical steroids. We prescribed Durezol, the Plan B: Offer coupons if they are available, or default to best drug for her, only to get pushback from the pharmacy generic Maxitrol if it will be used for less than two weeks. informing us that Durezol wasn’t on her formulary. They Be aware that there is a slight potential for neomycin recommended generic prednisolone acetate. We had no choice but to acquiesce, even though in allergic reaction or increased intraocular pressure from our clinical experience, the substitute drug would likely the dexamethasone, which may occasionally be bother- require a longer time to gain control of the condition. some. Zylet, generic TobraDex and generic Maxitrol are all After weeks of chronic recurrence, we finally provided her suspensions and must be shaken before each use. with samples of Durezol and, as we expected, this quickly Problem: You prescribe prednisolone acetate for an suppressed her uveitis. Once controlled, we had to switch episcleritis, but the patient is dismayed by its high price. her back to the generic prednisolone acetate because we Plan B: Consider generic Maxitrol, ignoring the antibiot- had no more samples available for her. ic component; it is a cheap way to get access to a decent Since we don’t seem to have leverage to remove all steroid when push comes to shove. Another option is this “red tape,” here are some “Plan Bs” that we use to generic prednisolone sodium phosphate, which works well maneuver through and around some of this bureaucracy for ocular surface conditions and requires no shaking. to provide optimum care for our patients: Problem: You Rx Lotemax ointment or FML ophthalmic Problem: When a brand-name prostaglandin is pre- ointment, but the expense is a concern for the patient. scribed and denied and generic latanoprost is recom- Plan B: Try generic Blephamide ointment or Maxitrol mended: For most patients, this would be fine, but we ointment, ignoring the antibiotic components of these have anecdotally found some generic varieties of latano- drugs. If you’re treating contact blepharodermatitis, go prost to perform less well than others. with triamcinolone 0.1% cream, proactively explaining to Plan B: Keep and offer coupons for brand-name, pre- the patient that the tube will state “not for ophthalmic ferred drugs. These can be helpful to some patients. use,” but that it’s completely safe to use the drug, as Problem: You prescribe Combigan only to be told it this is a bureaucratic statement, not a clinically relevant is not on the patient’s formulary, or the patient is paying one. Note: Kenalog (triamcinolone) is commonly injected cash for the medicine and the cost is prohibitive. intravitreally, and we’ve never seen a problem with use of Plan B: In either case, a viable option is to prescribe the triamcinolone cream, even if some gets in the eyes. two generic ingredient drugs. In this instance, we would prescribe timolol 0.25% or 0.5% QAM, and brimonidine 0.2% QAM. Clearly instruct the patient to wait 10 minutes Prescribing has never been so fraught with barriers and between the use of these two drops. We prescribe a sec- inconveniences. It’s like playing chess: One must be fully ond drop of brimonidine 0.2% to be used around 4pm to aware of all potential moves of the adversary (in this case, 5pm. (Brimonidine only works for about eight hours, thus the insurance companies) at all times and be ready with the need for the second, late-afternoon drop.) Optimally, an effective countermove. This often requires thinking timolol is used only once daily in the morning. outside the box, and you must have a comprehensive Problem: You prescribe Simbrinza ophthalmic suspen- knowledge of all available drugs. Sometimes, after a point- sion and are told it is not on the patient’s formulary, or counterpoint with a pharmacist, we finally just say, “tell that the patient can’t afford the cost. me what you have,” and work from there to find a medi- Plan B: Default to brimonidine 0.2% and dorzolamide cine that is either affordable or on the patient’s formulary.

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ONE OPHTHALMOLOGIST’S FDA DRUG APPROVAL & OFF-LABEL USE TAKE ON EYE CARE’S We are noticing that newly approved antibiotics have a sole indication for bac- FUTURE terial conjunctivitis and that new steroids have a sole indication for postopera- In this Q&A, excerpted from tive care. Why is this? Getting drugs approved is an expensive, bureaucratic a July 2018 interview in The exercise, so drug companies have a financial incentive to find the shortest, Ophthalmologist, Bonnie An least expensive way to get their product to market. This process has little to Henderson, MD, partner at nothing to do with the product’s ultimate clinical use. This partly explains why Ophthalmic Consultants of Boston a lot of what we do in clinical practice is “off-label.” and clinical professor at Tufts What we need is a team of experts to objectively assess all drugs guided University School of Medicine by rigorous scientific standards. This would provide all clinicians with vastly Boston, discussed the future of enhanced guidance on the proper, intelligent use of medicines in the care of ophthalmology. our patients. Until such a dream becomes reality, we will all have to become How do you think ophthal- more and more comfortable prescribing “off-label,” which is an extremely com- Q.mology will change in the mon, routine practice. coming years? “Technological advances A.seem to evolve more rap- manufacture eye glasses weighing idly in ophthalmology than in 7 grams (25 ounces) in 14 hours at TECHNOLOGY TO other industries…Hopefully, future a cost of $113.90.1 The researchers AID YOUR PRACTICE advances will allow patients to be wrote, “The 3-D printed spectacles Services such as CoverMyMeds and less dependent on eyedrops for fitted precisely onto the face and PARx Solutions partner with elec- glaucoma, less dependent on cor- were considered to provide a tronic health records (EHRs), health rective spectacles, and medical superior outcome compared with care providers, payers and pharma- therapies will decrease visual mor- conventional spectacles. Optical cies to initiate, transmit and track bidity from age-related diseases alignment, good comfort and the status of electronic prior autho- and endocrine disorders.” acceptable cosmesis were achieved. rization (PA) requests within the What’s exciting you right One month after fitting, the 3-D clinical workflow, helping patients Q.now? printed spectacles did not require to more quickly receive the medica- “The focus on presbyopia further changes.” We all know this tions they need for therapy. A.correction. Not only because technology is only going to improve. of the explosion of new IOLs, but And in the medical realm, eye void where optometry could (and also the new medical develop- drops are in development that might should) become the main provider of ments to prevent lens hardening. potentially delay presbyopia for medical eye care. This field is in its infancy and will years. Such medical advances are From a public health perspective continue to grow over the next only going to continue. and for professional survival, we need few decades.” While online refraction is here to to begin today to stop needless referrals Attentive ODs should be keenly stay, we all know such a service fails to surgeons for medical care that we aware of the changing landscape to screen for glaucoma and other po- can provide. If you do not provide, for of eye care delivery. Those who tentially vision-threatening, asymp- example, glaucoma care, then have an embrace the vast majority of tomatic eye conditions. Regardless optometric colleague care for these pa- patient presentations (and cease of how this online evaluation and tients. As a profession, we refer out un- senseless referrals) are poised told millions of dollars each year that to do well in the face of these other technological/clinical develop- changes. On the other hand, ments play out, it’s vital that optom- should be staying in our offices. Finan- refraction-centric practices will be etrists continue to evolve as broad- cial advisors urge portfolio diversifica- significantly adversely affected. based, comprehensive medical eye tion, and we urge you in like manner doctors. Not only is this crucial to to diversify your patient base. We think Year of the Woman. Sitting Down With… meeting an underserved segment of this is absolutely critical for enhanced Bonnie An Henderson, Partner at Ophthalmic Consultants of Boston, and Clinical Professor patient need, but technology cannot medical care of our patients and for the at Tufts University School of Medicine ■ Boston, MA, USA. Excerpted from The replace sound clinical reasoning and viability of our profession. Ophthalmologist. https://theophthalmologist. judgment. In addition, the decrease com/subspecialties/year-of-the-woman. July 1. Ayyildiz O. Customised spectacles us- 25, 2018. Accessed April 3, 2019. in matriculating ophthalmologists ing 3-D printing technology. Clin Exp Optom. from residencies each year leaves a 2018;101(6).747-51.

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0048_dg0519_practiceManagement.indd48_dg0519_practiceManagement.indd 5050 55/14/19/14/19 4:384:38 PMPM EQUIPPING THE EXAMINATION ROOM To provide high-quality comprehensive care, optometrists need to equip the exam room with the right tools. We catalogued our medical inventory and determined most of the following items to be absolutely essential and highly recommended for the office. (Note that we do not list slit lamps, trial lenses or the basic instrumentation all offices have.) Dilating drops: • Paremyd; 1% and 0.5% ; 2.5% and 10% Anesthetics: • 0.5% proparacaine, and a combination of 0.25% sodium fluorescein with a topical anesthetic (e.g., Fluress) Cycloplegics: • 1%, and homatropine 5% Ointments: • A combination antibiotic/steroid, such as generic Maxitrol, and an antibiotic, such as Polysporin or a generic equivalent Medications: • Acetazolamide (Diamox) 250mg tablets (for acute angle closure) • Pilocarpine 2% (for acute angle closure) • Timolol, brimonidine and prostaglandin samples • Lipid-based artificial tear samples • Steroid and antibiotic samples • Betadine 5% ophthalmic prep solution (for treating acute EKC) Supplies: • Fluorescein and lissamine green strips • Sterile irrigating solution • Bandage-therapeutic soft contact lenses • Oval eye patches • One-inch hypoallergenic surgical tape for patching (e.g., Micropore) • Sterile and non-sterile cotton swabs • Mini-tip culturette swab kits (to collect for bacterial culturing) • Alger brush and 25-gauge, 5/8-inch needles (for foreign body removal and/or rust ring fragmentation) • Alcohol prep pads • Post-mydriatic sunglasses (adult and child sizes) with temples and drop-in • Anterior stromal puncture needles with syringe handles • Syringe barrels (two or three of these universal plastic barrels for use as holders for straight or ASP needles) Instruments: • AdenoPlus (EKC in-office detector) • Blood glucose monitor • Humphrey field analyzer • Optical coherence tomography device • Meibography device • Icare tonometer (and Icare Home tonometer) • Stainless-steel instrument tray containing: sharp-tipped jewelers forceps; golf club spud; Shahinian cannula for lacrimal irrigation; #2 Desmarres lid retractor to facilitate double eversion; Simpson lacrimal dilator; sharp-tipped small iris scissors; epilation forceps; curved, toothed forceps; EOS 28 needles (e.g., Bausch + Lomb) and gouge spud (for foreign body and concretion removal) • 4-mirror and 3-mirror gonio lenses • Plano and convex handheld mirror • Exophthalmometer • BIO 20D or similar condensing lens • Scleral depressor (e.g., Wilder), mainly to facilitate eyelid eversion • 90D (or equivalent) condensing lens to enable slit-lamp ophthalmoscopy • Magnifying loupes for inserting punctal plugs and other procedures • Stethoscope • Sphygmomanometer and/or wrist cuff automatic blood pressure device • Assorted patient education materials

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