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  • 1. FC_DG0511.indd 3 5/11/11 4:41 PM
  • 2. Current Therapy in Ocular Disease by Drs. Ron Melton and Randall Thomas Past recipients of the “Glaucoma Educator of the Year” Award by the American Academy of Optometry Authors of Review of Optometry’s annual Clinical Guide to Ophthalmic Drugs CONTINUING EDUCATION Our Courses on Your Computer! A team of California optometrists/educators has developed a website, OptSpace.com, to provide optometrists and their staff educational enrichment in the area of medical diagnosis and treatment, and other areas of interest to optometry. OptSpace has partnered with us for several video presentations that can be viewed from any computer or electronic media of your choice. This is a new way of accessing Melton and Thomasʼ lectures. Currently our emphasis is on glaucoma care, with additional topics available in the near future. Our series of lectures will be presented exclusively through the genius of OptSpace. We invite you to visit www.OptSpace.com for more details. Come to China with Us! June 12 - 23, 2012 Bridgitte Shen Lee, O.D., a bilingual and bicultural Chinese-American optometrist, created iTravelCE LLC and put together a truly first-class (and beyond!) enlightening journey into China for COPE-approved optometric CE. She will serve as both course director and tour guide. For the educational component of this exotic voyage, we will provide our comprehensive, 20-hour “Current Therapy in Ocular Disease” course. The itinerary includes: • Beijing, the imperial and modern capital city, rebuilt by Kublai Khan in 1215 and host of the 2008 Olympics • Xiʼan, the cradle of Chinese civilization, the seat of the Emperor for more than 10 dynasties and the start of the Silk Road • Yangtze River, cruise along the longest, most majestic waterway in Asia. We invite you to join us for a trip of a lifetime! For more details, visit www.iTravelCE.com, e-mail info@iTravelCE.com, or call 832-390-1393. Visit our website: www.eyeupdate.com000_dg0511_R&Rcourse.indd 49 5/11/11 4:36 PM
  • 3. A Brief Overview of the Past Twelve Months Supported by an unrestricted grant from Welcome to the 2011 Clinical Guide to Ophthalmic Drugs! This year, we are attempting to answer many of the questions we have received during our lectures over this past year. We have col- lected well over 100 questions, and we are sharing our responses to as many of them as space allows. We encourage you to read this CONTENTS question-and-answer dialogue, as it contains many clinically practical pearls that we trust you will value There have been two significant additions to the therapeutic land- Glaucoma ............................. 2A scape during the past year: Zirgan and generic latanoprost. But there are also numerous “new and improved” remakes and enhanced formulations of medicines already in the marketplace: Beneath the Surface of • an increased concentration of gatifloxacin (Zymaxid, which is a Dry Eye Disease ................. 12A 0.5% formulation) • a decreased concentration of bimatoprost (Lumigan 0.01%) • a decreased concentration of dexamethasone combined with to- Corticosteroids .................. 18A bramycin (TobraDex ST) • another topical antihistamine for once-daily use (Lastacaft) • a reformulation of moxifloxacin (Moxeza) Topical Antibiotics ............. 22A • a newer, lipid-based artificial tear (Systane Balance) • the first once-daily topical NSAID, bromfenac (Bromday) Antiviral Strategies ............ 26A • loteprednol ophthalmic ointment (Lotemax ointment) So, you can see the waters have been stirred! We will try to put these changes, and other relevant topics, into a clinically practical per- Combination Drugs ............ 29A spective for you. It must be absolutely stressed that everything written in this guide is explicitly aimed at enhancing the lives of the patients we all serve. We can never lose sight of why we exist and what our Clinical Update on the mission is. NSAIDs ............................... 32A With all best wishes to our esteemed colleagues, Keeping Allergy Management Simple .......... 34A Overview of Oral Medicines .......................... 36A Ron Melton, O.D. Randall Thomas, O.D., M.P.H. Questions & Answers From the Trenches ............. 40A Note: The clinical views and advice expressed in this publication are those of the authors, and do not necessarily reflect those of the sponsor, Bausch + Lomb, or the publisher, Review of Optometry.001_dg0511_intro.indd 3 5/11/11 3:52 PM
  • 4. Glaucoma New drugs may come and old drugs may go, but the essential question remains: At what point does the patient “convert” to glaucoma? fter 15 years of basking in A the warm sun, the curtain has fallen on the most successful glaucoma drug in the history of the world. Generic latanoprost should radically re-script glaucoma care from a financial perspective. This same fate will soon occur for Lipi- tor. We think, and hope, this will bring financial relief to the masses. Like all of you, we are watching from the bleachers to see how this radical transformation will play out. (See “Latanoprost Goes Generic,” page 3A.) There are other glaucoma medi- cines in research and development, and we anticipate newer and better therapies in the coming years. At what point, clinically, do you begin to inform patients that you are following them But don’t forget that a once-daily as a “glaucoma suspect”? This is an optic nerve that has converted to glaucoma. beta-blocker is an excellent second- Note the inferior erosion of the neuroretinal rim. line drug for monotherapy, or as additive therapy to a prostaglan- discontinuing it? Q: Would you use a prostaglan- din. All others must be used twice A: Studies have shown that the din to manage increased intraocular daily and preferably three times effects of prostaglandins last longer pressure in a steroid responder? a day—but it is rare that patients than the other classes. In our prac- A: Probably not. Most iatro- can perform these complex instilla- tices, we wait a month to recheck genic intraocular pressure increases tions with any significant degree of the intraocular pressure after stop- quickly vanish upon the discontinu- consistency. ping a prostaglandin. We generally ation of the offending corticoste- assess the effect of such “reverse roid, so additional medical therapy Q: When new patients present therapeutic trials” in two to three is usually unwarranted. to our office on multiple glaucoma weeks for the shorter duration-of- If the IOP was high enough to meds, we want to experiment with action drugs such as the alpha ad- warrant therapeutic intervention which meds are optimally effec- renergic agonists, the beta blockers, (perhaps over 35mm Hg to 40mm tive. How long does it usually take and the topical carbonic anhydrase Hg), then we would select a more for a medicine’s effect to stop after inhibitors. rapid onset medicine such as a beta 2A REVIEW OF OPTOMETRY MAY 15, 2011002_dg0511_glaucoma.indd 2 5/11/11 3:12 PM
  • 5. Glaucoma blocker or brimonidine. Prosta- Latanoprost Goes Generic glandins are relatively slow in their The biggest news in glaucoma in 2011 is that Xalatan lost its onset of action, and so are rarely patent protection March 28. This means we now have generic a class of choice when rapid IOP latanoprost. While this is bad news for the drug manufacturers, reduction is desired. it is good news for glaucoma patients. A basic understanding of market dynamics explains why Travatan Z and Lumigan Q: Do you recommend occluding have also reduced their costs (either directly or through rebate the nasolacrimal ducts to prevent programs, etc.) to be competitive with generic latanoprost. systemic effects from glaucoma Generally speaking, and when prudent to do so, we prefer to medicines? prescribe quality brand-name products as opposed to gener- A: As a general rule, glaucoma ics of unknown quality. For this reason, we plan to prescribe medicines are very well tolerated, Travatan Z or Lumigan 0.01% as long as the price points are and therefore there is not a need to similar to the generic latanoprost. undertake unnecessary medication- We encourage you to call around to your local pharmacies modifying procedures. to ascertain the cost of these medications. You will be amazed However, if the medicine was at the differences. At press time, our survey of local pharmacies revealed great disparity truly needed for glaucoma care, and among prostaglandin prices (anywhere from $25 to $85). Overall, it seems that $38 is the patient had a rare side effect generally the going price. This brings great relief to the cost-burden of glaucoma therapy. (such as taste perversion, a cough, Also note that the prostaglandins exert a therapeutic effect well beyond 24 hours. For slight shortness of breath, brady- a few of our indigent patients with non-severe glaucoma, we have reduced dosing to cardia, etc.), then punctal occlusion Monday, Wednesday and Friday. may be wise. Now let’s think about this rationally and apply some common sense: The goal in glau- However, we would try switch- coma management is to achieve and maintain an intraocular pressure within the target ing to another class of drug first, if range deemed to be “safe” for each patient individually. With that in mind, medication possible. In caring for many hun- management becomes very elementary: We simply check the IOP at one month and at dreds of patients with glaucoma, two months after dosage-reduction to see if the IOP remains the same as it did with we have never found the need to once-daily dosing. If that is the case, then we have achieved our IOP goal, and helped the punctally occlude. patient from not only a health standpoint, but a financial one as well. We simply need to be thinking, compassionate and attentive doctors. Q: If a visual field is abnormal, and repeat testing is normal, do you would repeat the field every six to we provide a standard dilated eye retest? Or is one normal visual field 12 months to continue to monitor examination. all you need? for stability or progression. If there is a history of glaucoma A: Clinically significant visual If the next field shows “progres- suspicion in the family, then we field defects are largely predictable, sion,” such “progression” MUST would likely obtain pachymetry and not like a box of chocolates. be confirmed by repeat testing in addition to our always thor- Generally speaking, if the visual (again, in weeks to months based ough study of the optic nerves via field is normal, consider it to be on the overall status of the patient’s biomicroscopic-enabled (90D, etc.) so. If the visual field is defective condition). It is well established ophthalmoscopy. and the catch trials (fixation losses, that the vast majority of “progres- If the optic nerve(s) appear etc.) are reasonably normal, and sion” is artifactitious, and disap- compromised in their structure, we if the optic nerve neuroretinal rim pears upon repeat testing! would then consider accomplishing tissues are intact, then we would nerve fiber layer assessment, and if not believe this defective field to be Q: When you see a family mem- this were to be suspicious, then we a reflection of reality, and therefore ber of a glaucoma suspect patient, would likely obtain a visual field would repeat the field in a few do you perform a full dilated assessment. weeks (or even a few months). comprehensive eye exam? Do you Notice that all subsequent testing However, if there are defects charge them, or is just a quick look is driven by the sequential findings that correspond to alterations in with the indirect ophthalmoscope during the course of the eye exami- the optic nerve head anatomy (such sufficient? nation. We do not do tests that are as polar erosion), then we would A: If it has been over a year since unwarranted, and we always obtain believe that the defect is true, and the patient has seen an eye doctor, exam elements that are rational, REVIEW OF OPTOMETRY MAY 15, 2011 3A002_dg0511_glaucoma.indd 3 5/11/11 3:12 PM
  • 6. Glaucoma prudent, and medically substanti- We charge a professional fee when Q: At a recent glaucoma lecture, ated. Appropriate charges are whatever service or procedure per- the specialist stated that nerve fiber assessed for indicated professional formed is medically prudent. One analysis was pushing back glau- services and diagnostic testing. could code “glaucoma suspect” if, coma diagnosis by 10 years; that Some of these may be accomplished in one’s sound clinical judgment, is, initiating treatment for patients at the initial visit; others may be there is rational justification to in their 50s rather than their 60s. done days or weeks later, depend- conduct such an examination along Bottom line: With no visual field ing on assessed risk, the disease with any rational ancillary testing defect, would you treat based on stage, the patient’s desires, insur- needed to facilitate accurate deci- nerve fiber layer analysis, given the ance coverage, etc. sion making. potential for long-term consequenc- es of using glaucoma medicines? Q: How do you code a claim Q: At what intraocular pressure A: First, glaucoma medicines are for a family member’s glaucoma would you treat the patient on the generally very well tolerated, even examination when the results are same day as the exam? in patients who have ocular surface normal? A: Probably 40mm Hg or disease, so that concern is a mini- A: How does an orthopedic greater, and even at lower IOP if mal player in decision making. The surgeon code for a radiographic there were substantial optic nerve larger question is actually much study if it is normal? The answer: compromise. bigger than structural vs. functional Topical Glaucoma Drugs BRAND NAME GENERIC NAME MANUFACTURER CONCENTRATION BOTTLE SIZE Beta Blockers Betagan, and generic levobunolol hydrochloride Allergan, and generic 0.25% 5ml, 10ml 0.5% 5ml, 10ml, 15ml Betimol timolol hemihydrate Vistakon Pharm. 0.25% 5ml 0.5% 5ml, 10ml, 15ml Betoptic-S betaxolol hydrochloride Alcon 0.25% 5ml, 10ml, 15ml Istalol timolol maleate Ista 0.5% 5ml Timoptic, and generic timolol maleate Aton Pharma, and generic 0.25% 5ml, 10ml, 15ml 0.5% 5ml, 10ml, 15ml Timoptic (preservative-free) timolol maleate Aton Pharma 0.25% unit-dose 0.5% unit-dose Timoptic-XE, and generic timolol maleate Aton Pharma, and generic 0.25% 2.5ml, 5ml 0.5% 2.5ml, 5ml Prostaglandin Analogs Lumigan bimatoprost Allergan 0.01%, 0.03% 2.5ml, 5ml, 7.5ml Travatan Z travoprost Alcon 0.004% 2.5ml, 5ml Xalatan, and generic latanoprost Pfizer, and generic 0.005% 2.5ml Alpha Agonists Alphagan P, brimonidine Allergan, 0.1%, 5ml, 10ml, 15ml and generic brimonidine generic 0.15%, 0.2% 5ml, 10ml, 15ml Carbonic Anhydrase Inhibitors Azopt brinzolamide Alcon 1% 5ml, 10ml, 15ml Trusopt, and generic dorzolamide Merck 2% 5ml, 10ml Combination Glaucoma Medications Combigan brimonidine/timolol Allergan 0.2%/0.5% 5ml, 10ml Cosopt dorzolamide/timolol Merck 2%/0.5% 5ml, 10ml 4A REVIEW OF OPTOMETRY MAY 15, 2011002_dg0511_glaucoma.indd 4 5/11/11 3:12 PM
  • 7. Glaucoma Select Appropriate Therapy Let’s assume we have decided for our black patients, and 0.25% ing frequency a patient merits IOP reduction, for white patients. Furthermore, and compliance. so what drug do we select? numerous studies clearly support In recognition of • Prostaglandins. Most the use of these two non-selective this reality, these of the time, the answer is a beta blockers once daily. It is drugs are general- prostaglandin, preferably one best to have patients instill beta ly prescribed b.i.d. of the lower-concentration blockers shortly upon awakening (approximately formulations (having less for maximum therapeutic effect. every 12 hours). side effect potential) such Understand that these drugs sup- The CAIs are as latanoprost 0.005% or press beta adrenergic tone. Our known by their travoprost 0.004%—and now adrenergic system is active while brand names: bimatoprost 0.01%. All of the we are awake, and physiologi- Trusopt (dorzol- prostaglandins lower IOP near- cally asleep while we are asleep. amide, Merck; and generic) and Azopt ly identically, so prescribing There is little benefit in attempting (brinzolamide, Alcon). Since brimonidine decisions are based on side to pharmacologically suppress a seems to be slightly more effective than effect profile and affordability system that is already physiologi- a topical CAI, we generally try it as our for most patients.1 cally suppressed. This is why it is “Plan B” of choice. The time of instillation important to dose beta blockers • Combinations. What about the should center around when shortly upon awakening. “combination” drugs, such as 0.5% the patient finds it to be the The vast majority of our glauco- timolol with 0.2% dorzolamide (Cosopt most convenient. Remember, ma patients are successfully man- [Merck], which has been generic since compliance is the weak link aged with either a prostaglandin, October 2008) or 0.5% timolol with 0.2% in the treatment chain, so or a beta blocker, or a combination brimonidine (Combigan [Allergan], an we need to do whatever we of the two. This is relatively inex- expensive combination of two relatively can to make adherence most pensive, and requires a drop either inexpensive generic products)? We know achievable for once daily, or if using both, b.i.d. that timolol is only each patient. • Carbonic anhydrase inhibitors and needed once daily, • Beta block- alpha adrenergic agonists. If there is and we know that ers. Alternatively, a need to move beyond a prostaglandin brimonidine and if cost is an over- and/or a non-selective beta blocker, then the CAIs are most riding factor (and do a therapeutic trial of either brimoni- effective at their cost can compro- dine or a topical CAI—brinzolamide or FDA-approved mise compliance), dorzolamide. Both of these drugs are labeling of t.i.d. initiate therapy FDA-approved for t.i.d. therapy, and We suggest try- with a non-selec- when used as monotherapy, will best ing timolol alone, tive beta blocker serve the patient as one drop every and to only “add” such as timolol or eight hours. The problem is that there dorzolamide or levobunolol. They is an inverse relationship between dos- brimonidine if truly are available in needed to achieve 0.25% and 0.5% target IOP. These concentrations, are rare occa- and are readily sions. available for about 1. Parrish RK, Palmberg $4 per 5ml at P, Sheu WP; XLT Study Group. A comparison of many pharmacies. latanoprost, bimatoprost, Since melanin and travoprost in patients with elevated intraocular pigments can bind pressure: a 12-week, some medicines, randomized, masked- evaluator multicenter we use the 0.5% study. concentrations REVIEW OF OPTOMETRY MAY 15, 2011 5A002_dg0511_glaucoma.indd 5 5/11/11 3:13 PM
  • 8. Glaucoma concerns, which is the essence of that can indeed safely use a topical Glaucoma is very similar. With the this question. The decision is just nonselective beta blocker. We have, limits of our current technology, it not so dichotomous! in fact, had the occasion to do such, could well be reasonable to pro- For background, we are currently but only after consultation with the claim a repeatable visual field defect treating hundreds of patients with patient’s primary care or pulmo- as the “Holy Grail” of glaucoma glaucoma medicines who do not nary physician. It has recently been confirmation. However, we have have glaucoma! We obsessively- demonstrated that systemic beta patients with 0.8 cups with no visu- compulsively assess each of our pa- blockers are in fact therapeutic in al field defects, and we confidently tients; for those whom we feel are the setting of COPD for many such tell them that they have glaucoma at considerable risk to develop glau- patients. So, if you have a need to (based on progressive cupping, thin coma, we intervene therapeutically use a beta blocker in a patient with corneas, and/or high IOPs). So, in what we believe will prevent the what you might think are systemic in one sense, the question may be development of glaucoma. Ex- contraindications, consult the pa- more academic and philosophical amples of such patients are younger tient’s physician—it may well be than clinical and firm. people with very high intraocular that your therapeutic need can be pressures; very thin corneas (physi- successfully met. Q: A very similar question: At ologically, not via keratorefractive what point, clinically, do you begin surgery); compromised optic to inform patients that you are nerve head tissues (based on following them as a “glaucoma either stereoscopic ophthalmos- suspect”? copy or a nerve fiber layer scan- A: It depends. If there is a ning device or both, without vi- family history of glaucoma, a sual field defects); a very strong borderline IOP (around 18mm family history; or a combination Hg to 26mm Hg), a 0.4 to 0.6 of the above. These decisions cup, a corneal thickness below are complex and require the as- 510µm, then such patients might similation of a constellation of be considered “suspicious.” parameters. But, these various parameters Lastly, note that doctors of cannot be viewed in a vacuum! equal competence legitimately The entire clinical picture must differ on the decisions of treat- be considered collectively. Only ing vs. attentive monitoring. then can “risk” be rationally The soundness of whichever de- When does the diagnosis change from ocular assessed. cision is made usually becomes hypertension to glaucoma? clear over the ensuing five to 10 Q: When would you discon- years. A patient is rarely a “glau- Q: When does the diagnosis tinue glaucoma therapy started by coma suspect” beyond five to eight change from ocular hypertension another clinician? years, because during this time span to glaucoma? Does the diagnostic A: If, in your clinical opinion, it should become clear whether definition of glaucoma require a and after a thorough examination, they have progressive disease or just visual field defect? you feel the patient may not merit benign risk factors. A: This question is ubiquitous therapy, then a thoughtful “reverse and haunts most glaucoma clini- therapeutic trial” is very reason- Q: Are topical nonselective beta cians. Glaucoma is not like a light able. We would have a long conver- blockers an absolute or a relative switch; either present or absent, but sation with the patient explaining contraindication in patients hav- rather like a light controlled by a how good doctors commonly have ing reactive airway disease and/ rheostat. As you begin to reduce the different approaches to the same or chronic obstructive pulmonary energy flow to the light, the light condition, and that at the least you disease (COPD)? begins to become less bright—but would like to know the patient’s A: Only recently has it become when would the average person say true baseline intraocular pressure. clear to us that the correct answer the luminance goes from “bright” This is something we do commonly, is “relative.” There are patients to “dim”? There is a zone or range especially if the patient has no who have lesser expressed asthma in which this declaration is made. positive family history of glaucoma, 6A REVIEW OF OPTOMETRY MAY 15, 2011002_dg0511_glaucoma.indd 6 5/11/11 3:13 PM
  • 9. Glaucoma has a thick cornea (greater than tients,” we assume you mean those shortly upon awakening, regardless 580µm—our subjective cutoff), who have a 0.4 to 0.5 or greater of the actual time of the day. Pros- and/or has healthy-appearing optic cup. If the cup is small and the pres- taglandin efficacy is, by and large, nerve heads. We also get a Consent sure is normal, this is almost always time of instillation-independent. for Release of Records from the pa- a plain ol’ normal patient. But, if While slightly more effective when tient so that we can have the benefit the optic nerve head is suspicious in taken toward the end of a waking of the prior doctor’s observations appearance, there is a 100% chance period, actual time of instillation is and thoughts. we will assess the corneal thickness! not a major issue with the prosta- glandins. So, regardless of the time Q: Do you obtain pachymetry Q: For patients who work second of the patient’s sleep cycle, it is on all of your low-normal tension or third shift, how do you recom- always best to instill beta blockers patients, just to see if the cornea is mend dosing schedules for prosta- shortly upon awakening. While it is thin? glandins and beta blockers? best to instill the prostaglandins just A: By “low-normal tension pa- A: Beta blockers are best instilled prior to retiring, time of dosing is Key Points to Ponder in Glaucoma Management It is well established that there is some diminution in quality of • Visual field test results are extremely variable, and it life when a person is diagnosed with glaucoma, as at that point may take three to five tests over a two to four-year period of their lifestyle is encumbered with medication habituation behav- time to truly know the extent (if any) and/or rate of progres- ior, as well as cost concerns, and perhaps the ultimate concern sion of a visual field defect. The exception to this is if there is a of going blind. Note that we, like you, are attentive physicians, strong clinical correlation. For example, if there is observable infe- and we carefully monitor our patients. If there are any consistent rior erosion of the optic nerve rim, and there is a dense superior signs of accelerated progression, we would institute therapy. Yet field defect, then such a defect can be viewed with certainty, and we have learned over the past 30 years to not be trigger-happy, probably annual retesting is all that is indicated. but rather to be very thoughtful in our management decisions. The much more common finding, however, is a generalized Standard white-on-white perimetry can facilitate diagnosis, as scattering of scotomas, or a nonspecific clustering that does not well as provide guidance regarding progression. correlate with the optic nerve anatomy or a nerve fiber analyzer scan. It is these vague, non-clinically-correlatable visual field • Always initiate therapy with a lesser concentration of defects that must be verified by repeat testing, perhaps three to medication if available. Remember, in therapeutic intervention, five times, in order to know with certainty whether the defect(s) we have a target IOP range in our heads, and our goal should be is a true reflection of optic nerve damage or simply artifacti- to achieve an IOP within this range with the least medical inter- tious noise. A classic mistake is to observe what appears to be a vention possible. change in the visual field and make management decisions based Unfortunately, we have few lower-concentration options in upon “apparent” demise of the visual field. This is almost always glaucoma therapy: 0.25% timolol (or levobunolol), bimatoprost an error in clinical judgment and management. 0.01% and pilocarpine 1%. Being faithful to this concept, our rou- In summary, if the field is normal, believe it to be normal; if it is tine dilating drop only contains 0.25% tropicamide (Paremyd also borderline or questionable, then repeat the testing. contains 1% hydroxyamphetamine hydrobromide). Thankfully, we now have the lesser concentration of bimatoprost (0.01%) and the • It is by and large a myth that short wavelength (blue-on- concentration of BAK has been increased from 0.005% to 0.02% yellow) or frequency doubling perimetry detects glaucoma (the same as is in latanoprost). earlier than standard (white-on-white) automated perimetry. A couple of unsubstantiated thoughts come to mind: Because Furthermore, it truly may not be in the patient’s best interest to BAK enhances drug penetration, it may be that this higher con- be diagnosed “too early” in the setting of early glaucoma. Recent centration of preservative is what enables the 0.01% bimatoprost results from the Ocular Hypertension Treatment Study follow-up to provide the same reduction in IOP as the 0.03%, and that it is showed that delaying IOP reduction for a few years did not result not the BAK potentially causing side effects, but rather the active in any loss of ultimate control. On average, glaucoma progresses drug itself. The manufacturer claims a significant reduction in at about 3% per year. With the excellent medicines available to side effects with the 0.01% rendition of the bimatoprost. So keep us, we can intervene therapeutically in a thoughtful, timely man- in mind that “less is better,” as long as the target IOP goal is ner to gain good control of the intraocular pressure once the need achieved and maintained. for control is clearly indicated. (continued on page 9A) REVIEW OF OPTOMETRY MAY 15, 2011 7A002_dg0511_glaucoma.indd 7 5/11/11 3:15 PM
  • 10. Glaucoma diagnosis. It is well established that a subset of the population has quite marked nocturnal hypotensive epi- sodes. This could cause a pathologi- cally low perfusion pressure to the optic nerve (and brain) during the sleep cycle. For this reason, patients with true low tension glaucoma (and especially patients who have had nonarteritic anterior ischemic optic neuropathy in one eye) should perhaps only take their blood pres- sure medicine near breakfast time and never at bedtime, where this “piling on” effect could play a key role in optic nerve tissue demise. A conversation with the patient’s pre- Confrontational visual field testing as a screening tool is standard-of-care, but is this scribing physician certainly should test really adequate? be accomplished. not a major issue with the prosta- function was treated. I realize it’s a Q: Since breath-holding can glandins. multifactorial disease, but let’s rule increase episcleral venous pressure out the easy options. and therefore intraocular pressure, Q: What is your opinion on A: Thoughtful question. One should we routinely emphasize confrontational visual field testing would think that thyroid disorders “keep breathing normally” during as a screening tool in the context of could have an impact on aqueous tonometry? comprehensive eye examination? production and/or outflow. In all of A: We would suggest that the This is standard-of-care, but is this our exhaustive reading of the world clinician simply be attentive during test really adequate? literature, we have never read of the procedure, and perhaps just en- A: The world’s premier author- any such association with thyroid courage the patient to relax before- ity in neuro-ophthalmology is Neil dysfunction. We can’t explain your hand. It is usually obese, anxious, Miller, M.D., at the Wilmer Eye anecdotal observations, and, as you short-waisted, large upper body- Institute at Johns Hopkins. He rightfully point out, glaucoma is a size patients that often struggle to stated that 90% of all clinically multifactorial disease, so perhaps properly position themselves at the significant neurologically-related other factors are at play that are slit lamp. This is why we all need to visual field defects can be detected not yet fully elucidated. have alternative instruments at the by confrontation examination. He ready to enable more accurate IOP recommended that this assessment Q: Since it is known that some assessments in these patients, such be done as counting-fingers in each low tension glaucoma patients as a handheld (Kowa or Perkins) quadrant, not bringing in a target may be compromised by nocturnal applanation tonometer or an Icare from non-seeing areas into see- systemic hypotension, should these Rebound tonometer. Also, beyond ing areas. We have followed Dr. patients have a sleep study? breath-holding, the blepharospas- Miller’s guidance since the early A: Perhaps. This is an area of tic patients most always do better 1980s, and have found his observa- ongoing research, and in select with handheld devices than those tions to be spot-on. patients, knowing their diastolic mounted at the slit lamp. nocturnal blood pressure profile Q: Why isn’t thyroid function could potentially be very helpful. Q: Do prostaglandins cause or part of the glaucoma workup? Along this same line of thought is increase the risk of recurrent cor- I have seen three patients, and the consideration of the patient’s neal erosions? heard of more, with high IOP that medical treatment for systemic A: This question acknowledges normalized after their thyroid dys- hypertension, if they carry that two clinical realities: 8A REVIEW OF OPTOMETRY MAY 15, 2011002_dg0511_glaucoma.indd 8 5/11/11 3:15 PM
  • 11. Glaucoma (continued from page 7A) • If you have not yet acquired a nerve fiber layer imaging instrument, we encourage you to do so as soon as you can • Do not “micromanage” any single component of the justify the cost of the purchase. Without debate, the technology glaucoma workup. For example, refrain from performing a quan- to acquire is an ocular coherence tomography (OCT) unit. We rec- titative analysis on central corneal thickness: the cornea is simply ommend spectral-domain OCT technology because it can give you thick, thin, or normal. Here are our entirely subjective breakpoints: quantitative information on the retina nerve fiber layer for glauco- thick is >580µm to 590µm, and thin is <500µm to 510µm. ma assistance, and also provide diagnostic help for hydroxychlo- What’s in the middle is essentially normal, and minimally impact- roquine and other screenings, as well as for macular conditions ful to our decision-making process. such as central serous retinopathy, macular edema, etc. By the way, the cornea reaches adult thickness by age 10. We While the Fourier (spectral)-domain platform is the most have already discussed how incredibly subjective visual field data sophisticated technology available, the truth is that a basic OCT are. Even so-called “objective” tests, such as nerve fiber layer is amply adequate to meet the vast majority of the clinical needs analyses, are not precisely objective; they are simply less variable. of practicing eye doctors. We’d much rather see an O.D. have We have seen nerve fiber layers “thicken” a bit year to year, and a time-domain OCT than not have an OCT in his/her diagnostic test to test, but short of retinal edema, nerve fiber layer thickness armamentarium at all. One can always upgrade later. We have stays the same or slowly thins. So we know an “improved” nerve never encountered an O.D. who acquired an OCT who was not fiber layer is just a change relative to a prior test. As with visual thrilled to have it. Do note, though, that the time-domain OCT fields, do not make a management change based on the result of technology is not adequate for hydroxychloroquine screening. This a single test, even those that are supposedly objective. is the most notable shortcoming of the time-domain technology. With IOP, we know it can fluctuate wildly. Thus, if the IOP is up on one visit and down the next, we do not make proclamations • We think there is now a such as “You’re doing great!” or “You’re getting worse;” rather, technology “ready for prime we proclaim that “overall, it appears that your pressure control is time” (it is awaiting FDA- pretty stable,” or some other appropriate statement. We most cer- approval) to allow patients tainly do not know what each individual’s IOP is during sleep. to do self-tonometry. It is It is well established that there is considerable inter- and intra- from Icare, the inventor of observer variability in the numeric assessment of the optic disc the Icare Rebound tonometer anatomy (i.e., the cup-to-disc ratio). It would perhaps be over- (www.Icaretonometer.com). confident to chart “cup has enlarged from 0.3 to 0.4, therefore It uses the same exact will initiate therapy,” etc. One would more likely have to see a 0.2 rebound technology as the change, or perhaps even a 0.3 change in order to state with any standard, handheld unit, but is authority that there has been progressive optic neuropathy. placed in a special handheld frame type device that should allow So, it can be seen that there are several opportunities to most adults to competently obtain a series of measurements become bogged down with minutiae in the global context of the on their own, and outside of typical office hours. This should comprehensive glaucoma evaluation. There are plenty of data be a huge help to learn our glaucoma suspects’ and glaucoma points, plenty of parts, so that a thoughtful doctor should be able patients’ IOP behaviors early in the mornings, late in the evenings, to assimilate these various pieces and arrive at a rational stratifi- and perhaps even mid-sleep, for those patients who habitually cation of risks for, or stage of, glaucoma. awake during the night to use the bathroom. (1) Prostaglandins potentiate the stage for epithelial erosions. glaucoma suspects. I have a large cytoarchitecture remodeling ability While this question is quite intel- geriatric population, but is that of extracellular matrix metallopro- lectual, and obviously has a sound percentage too much? teinases. This is indeed the mecha- scientific basis, we are not aware A: It seems reasonable that your nism of action by which prostaglan- of any studies that point toward percentage is in keeping with the dins enhance uveoscleral outflow. an increased tendency in patients prevalence of glaucoma suspects (2) There is an abundance of to experience recurrent corneal in an aged population. We do matrix metalloproteinases at sites erosions while using prostaglandin know that increased age is a key within the cornea where the epi- eyedrops. risk factor for the development thelium is loosely adherent. These of glaucoma. We commend your destructive enzymes weaken the Q: I’ve carefully studied my keen attention to your patients, and epithelial-basement membrane-an- patients’ optic nerves, and I esti- further commend your focus on the terior stromal complex, setting the mate that 5% to 10% of them are optic nerve, not the IOP. ■ REVIEW OF OPTOMETRY MAY 15, 2011 9A002_dg0511_glaucoma.indd 9 5/11/11 3:15 PM
  • 12. Glaucoma Medical Management of Acute Angle-closure Glaucoma Almost all cases of angle-closure glau- coma can be successfully—and calmly— managed in the office. First, one needs to have on hand all the meds that might be useful in such a rare presentation. These would include acetazolamide tab- lets, either 250mg or 500mg. Do not use the 500mg Diamox Sequels because an extended, time-release of the medicine is not as impactful as the quicker onset of action that one gets from the tablet forms. You also need to have 0.5% nonselec- tive beta blocker, brimonidine, and 2% pilocarpine at the ready. There is little to no value in the use of a prostaglandin in the setting of acute angle-closure glaucoma, as the aforementioned rapid- A gonioscopic image (above) of an counterproductive to opening the angle. onset medications perform very nicely. angle in closure. In a different eye in The 2% seems to be the optimum bal- The prostaglandins’ speed-of-onset is acute angle closure (below), note the ance between effectively stimulating the relatively slow, and is simply not needed fixed, mid-dilated pupil in a red eye. parasympathomimetically innervated (like too many cooks in the kitchen) in this musculature of the iris sphincter, and situation. not creating overall iris volume expan- In the event the patient is vomiting, sion. Keep in mind that the iris sphincter have Compazine (prochlorperazine) sup- becomes very lethargic when the IOP positories stored in the refrigerator. It is exceeds around 60mm Hg, so the pilocar- counterproductive, if not impossible, to pine will be most pharmacologically active get oral acetazolamide tablets into the once the intraocular pressure drops into patient’s system when the patient has the 50s or 40s. uncontrolled vomiting. A single antiemetic This is why the aqueous suppressants suppository quickly calms the storm are used first, and pilocarpine shortly in most cases, and thereby allows the after. Of course, once the IOP is con- appropriate administration of oral medi- trolled, the patient is kept on the 2% pilo- cation. (Note that most patients prefer drops, and then a second drop of brimo- carpine q.i.d. until a YAG photoiridotomy to insert the suppositories themselves; nidine in two to three minutes. Both beta can be performed—which may take a another good reason to keep gloves avail- blockers and alpha adrenergic agonists day or two to schedule, depending upon able in the office.) rapidly decrease aqueous production via the location and availability of this ser- Since all carbonic anhydrase inhibitors separate pharmacologic mechanisms. vice. Of note, there can be considerable contain a sulfa moiety, there is perhaps In 10 minutes or so, instill 2% pilocar- conjunctival injection present as well, and a slight chance of a sulfa allergy even in pine. It is the pilocarpine that will actually if so, then a potent corticosteroid, such these non-sulfonamide medicines. Just to physically open the angle—the other as Lotemax, Durezol or Pred Forte used be thorough, always inquire if there is a three meds simply reduce the IOP by radi- q.i.d., can help the eye look and feel bet- history of severe allergic reaction to sulfa. cally subduing aqueous production. ter, particularly if there is any associated If there is no history of such, then have Why not use 4% pilocarpine? anterior uveal inflammation present. the patient take 500mg of acetazolamide Pilocarpine is an acetylcholinergic agonist In summary, the diagnosis and treat- right away. If there is no asthma, then (parasympathomimetic) and can cause ment plan for the uncommon presentation instill a drop of beta blocker, followed by blood vessel dilation, thus enlarging the of acute angle-closure glaucoma is very a second drop in two to three minutes. mass volume of the iris, and in turn caus- straightforward. The key is to have all the Get in a drop of brimonidine in between ing some anterior-posterior dimensional medications necessary at the ready to the two administrations of beta blocker swelling of the peripheral iris, which is treat the patient quickly and efficiently. 10A REVIEW OF OPTOMETRY MAY 15, 2011002_dg0511_glaucoma.indd 10 5/11/11 3:15 PM
  • 13. Glaucoma Glaucoma Pearls • Even glaucoma subspecialists cannot always judge optic • Childhood glaucoma is very rare. Note that virtually all nerve glaucomatous “progression” from sequential optic cases of childhood glaucoma have significantly increased intra- nerve head photographs. “Interobserver agreement among ocular pressure. glaucoma specialists in judging progressive optic disc change The key in such suspicious cases is to examine the optic from stereophotographs was slight to fair. After masked adju- nerves of parents and/or siblings, to photodocument the optic dication, in 40% of the cases in which the optic disc appeared nerves, and to attentively follow these children every six to 12 to have progressed in glaucoma severity, the photograph of the months until it becomes clear whether these suspicious optic ‘worse’ optic disc was in fact taken at the start of the study. nerves are either a physiological variant, or there is evidence of Caution must be exercised when using disc change on photo- progression. Bear in mind that asymmetry of approximately 0.2 graphs as the “gold standard” for diagnosing open-angle glau- cup-to-disc ratio is a common physiological finding.1 coma or determining its progression.”4 It may take longer than the five to 50 months (median 26 • Central corneal thickness reaches adult status by age months) of analysis performed in this study to accurately discern 10. changes in optic nerve anatomy. Because glaucoma progresses on average at a rate of 3% per year, it may take more like eight • Most patients with ophthalmoscopically visible optic to 10 years to competently and accurately judge progression nerve drusen manifest wide-ranging variations of visual field using optic disc photography. We think sequential nerve fiber defects. If these patients are observed to have high intraocular layer scanning technology may be a more refined manner to pressure, or if there is a documented steady increase in IOP over assess progression. time (years), then it may be prudent to institute IOP-lowering therapy. By and large, visual field and nerve fiber layer scanning • “Objective” technology is not absolutely objective, only data will be relatively useless, and so keeping IOP at physiologi- objective relative to other subjective tests. It is well under- cal levels is likely the wisest course. stood that visual field testing can be highly variable from test to test. We love our nerve fiber layer scanning instruments, and • The single most challenging decision in the care of depend upon them to aid us in the assessment of our glaucoma patients who are glaucoma suspects endures: When should patients, but even these wonderful “objective” tests can vary therapy be initiated? “In the end, the physician is struck with slightly from test to test. the persistent problem of whom to treat and whom to watch… Our advice: Never micromanage any single component of the The endless symposium and debate on how to best manage glaucoma evaluation, but rather look for repeatable trends over with ocular hypertension will probably continue unabated.”2 time (years). This seminal declaration precisely establishes the imprecision Regarding visual field testing, we recommend the Humphrey of decision-making and caring for patients with glaucoma. One 24-2 SITA-Standard or SITA-Fast, using standard white-on-white doctor may judge the best course of care to be watchful waiting, perimetry (standard achromatic perimetry, SAP). Newer research while another may pursue a course of active treatment. In these as shown that there is little or no advantage to using blue-on-yel- unclear cases, one doctor cannot declare the other errant in clini- low (short-wavelength automated perimetry, SWAP) or frequency cal judgment. The truth is, it may require many years of following doubling technologies.5-7 such a patient in order to know with certainty which course con- 1. Beck A. Evaluating and Managing Optic Disc Cupping in Children. Glaucoma Today. fers the greater benefit to the patient. Jan-Feb 2009. We urge the clinician to provide all glaucoma suspects a 2. Sommer A. Treatment of ocular hypertension: Hamlet’s Lament revisited. Arch Ophthal- mol. 2010 Mar;128(3):363-4. state-of-the-art assessment, develop a solid patient care plan, 3. Barkana Y, Dorairaj SK, Gerber Y, et al. Agreement between gonioscopy and ultra- and be confident in that care plan. Do not concern yourself with sound biomicroscopy in detecting iridotrabecular apposition. Arch Ophthalmol. 2007 Oct;125(10):1331-5. the potential for another clinician’s different approach. Above all, 4. Jampel HD, Friedman D, Quigley H, et al. Agreement among glaucoma specialists in carefully, attentively follow the patient.2 assessing progressive disc changes from photographs in open-angle glaucoma patients. Am J Ophthalmol. 2009 Jan;147(1):39-44.e1. 5. van der Schoot J, Reus NJ, Colen TP, Lemij HG. The ability of short-wavelength auto- • The website gonioscopy.org is a magnificent way to mated perimetry to predict conversion to glaucoma. Ophthalmology. 2010 Jan;117(1):30-4. 6. Bengtsson B, Heijl A. Diagnostic sensitivity of fast blue-yellow and standard automated improve your assessment of the iridocorneal angle anatomy. perimetry in early glaucoma: a comparison between different test programs. Ophthalmol- “In routine clinical practice, gonioscopy should be performed in ogy. 2006 Jul;113(7):1092-7. 7. SWAP or DOUBLE? International Glaucoma Review: The Journal for the World Glau- a dark room to avoid misdiagnosis of treatable iridotrabecular coma Association. 2008 Sep; 10-2. Available at: www.e-igr.com/SP/index.php?issue=102 apposition.”3 &supID=7&pageID=146. REVIEW OF OPTOMETRY MAY 15, 2011 11A002_dg0511_glaucoma.indd 11 5/11/11 3:15 PM
  • 14. Beneath the Surface of Dry Eye Disease We now understand that most ocular surface dryness is related in one way or another to meibomian gland dysfunction, which affects the tear film lipid layer. rom a disease management F perspective, the single most common clinical challenge we face each day is helping patients who suffer from ocular surface disease, predominantly ocular surface dryness. It is now realized that most ocular surface dryness is related in one way or another to meibomian gland dysfunction.1 This leads to a poorly perform- ing tear film lipid layer. Logical thought would then move us to recommend a lipid-based artificial tear as initial therapy. Dry spots on the corneal surface are associated with reduced tear film break-up time. In addition, we start all of our dry eye patients on 2,000mg of hances meibomian gland function. the ultimate treatment/management fish oil. We urge them to take such This gives more rapid improvement of meibomian gland disease is heat with breakfast. We do not get of patient comfort and simultane- and massage, not medical. hung up on micromanaging this ously buys time for the fish oils With this comprehensive back- oral supplement with regard to the to kick in. (For those few patients ground, we now answer questions debate over triglyceride versus ethyl who cannot swallow these rather regarding dry eye. ester formulations—just fish oil. By large capsules, Nordic Naturals, the way, and just for perspective, Coromega and others make very Q: If a patient were to be allergic cardiologists commonly prescribe palatable liquid formulations.) to doxycycline, what would you Lovaza (GlaxoSmithKline), a puri- A more thorough discussion of recommend for treating meibomian fied omega-3 fish oil supplement of meibomian gland gland dysfunction? an ethyl ester variety. treatment is found A: We have never encountered While fish oil can help with mei- on page 12A, but this; the answer is probably oral bomian gland secretions, it often erythromycin or oral azithromycin. takes four to six months to begin We might even prescribe a 5mg to see an effect. For this reason, we steroid Dosepak, just to potentiate often prescribe 50mg of oral doxy- the mild anti-inflammatory proper- cycline once daily for two to three ties of these two antibiotics. months. From our observations, it more quickly and more potently en- Q: In the setting of dry eye, 12A REVIEW OF OPTOMETRY MAY 15, 2011012_dg0511_dryeye.indd 12 5/11/11 3:25 PM
  • 15. Dry Eye which drop works best with contact lenses? A: We would generally select any artificial tear that is not BAK- preserved, and have the patient use it as often as is needed to achieve and maintain comfort. We like to use punctal plugs to diminish the frequency of, or need for, any artifi- cial tear. Don’t forget to use fish oil supplements as well. We commonly recommend 2,000mg taken every day with breakfast. Q: For dry eye, Leiterspharmacy. com will fill an Rx for 5% albumin Most ocular surface dryness is related in one way or another to meibomian gland drops—any comments? dysfunction. This leads to a poorly performing tear film lipid layer. Logical thought A: We have never used this ap- would then move us to recommend a lipid-based artificial tear as initial therapy. proach with any of our patients, but for those few dry eye patients for whom the “kitchen sink” approach New MGD Device on the Way has not achieved control and relief, While not yet FDA approved, there is an incredibly ingenious device known as the this would likely be worth a try. LipiFlow Thermal Pulsation System (TearScience Inc.), which both heats the eyelid Another approach that is talked (from the tarsal conjunctival side about in these more challenging where adequate heat levels can cases is the use of autologous serum, be achieved), while simultane- which we have each used on rare oc- ously massaging/expressing the casions with success, and think that glands. Both the heat application this more comprehensive source of and compression pressure are ocular nutrition would be superior precisely controlled for optimum to albumin. patient care. We foresee the day when a Q: How do you approach the patient who needs meibomian contact lens-wearing dry eye pa- gland therapy will schedule a tient? follow-up appointment to come A: There are a number of ap- into the office for a “meibomian proaches. Here’s what we usually expression treatment” session do: using the LipiFlow technol- • Quantify the degree of ocular ogy. Such a therapeutic session surface dryness. has the potential to reduce or • Replace “rewetting drops” with eliminate symptoms for six to 12 a top-quality artificial tear. We have months. had excellent success with lipid- Necessity is the mother of based tears. invention, and the LipiFlow tech- • We recommend 2,000mg of fish nology may just be what the doc- oil supplementation every day for tor will soon order. It should come nearly all of our dry eye patients. as no surprise that the inventor Note that it may be three to six of this technology is Donald Korb, months before an effect can be ap- O.D. He has done so much over preciated. Whatever the case, fish oil the years to enhance patient care is a very healthy substance, and is and make our profession proud. likely beneficial to total body health, REVIEW OF OPTOMETRY MAY 15, 2011 13A012_dg0511_dryeye.indd 13 5/11/11 3:25 PM
  • 16. Dry E ye whether it improves tear function subject patients to more office visits of action than omega-3 supplemen- or not. than needed? We never use intra- tation, so for our more symptom- • Try loteprednol 0.5% b.i.d. (a canalicular plugs because of an atic and inflamed dry eye patients drop in the morning a few min- increased risk of canaliculitis, and we often prescribe 100mg (50mg utes prior to lens insertion, and a we like to be able to see the plug at b.i.d.) of generic oral doxycycline second drop after lens removal in the punctum. This way, we—and for a week or two, then decrease to the evening) in the setting of acute our patients—can tell if the plug is 50mg once daily for two to three inflammation. It is exceedingly rare present or not. more months. After having been that an individual has a legitimate on the doxycycline for two reason (laziness is not one of them) months, we often start fish oil to sleep in contact lenses. as well. So, as we finish the • If, after a month of the above course of doxycycline, the fish maneuvers, the patient remains oil should be able to pick right symptomatic, try a punctal plug in up where the doxycycline the lower eyelid of the more symp- leaves off. Both doxycycline tomatic eye, and then evaluate the and fish oil render a benefit results in another month. to meibomian gland func- • Try a different brand of contact tion. The topical steroid helps lenses. to quiet the ocular surface • Try Restasis (cyclosporine, Al- If the patient remains symptomatic after a inflammation, while the doxy- lergan). It may do the trick in some month of usual maneuvers, try a punctal plug in cycline and/or fish oil supple- patients. Like fish oil, it takes three the lower eyelid of the more symptomatic eye. mentation aids meibomian to six months to produce an effect. gland function, which yields • Try a different disinfecting While all punctal plugs work a two-pronged approach in helping system, such as a hydrogen perox- well, we have evolved into using the the dry eye patient. ide system. Odyssey brand because of ease of By attentively and systematically insertion and retention properties. Q: If you do get an increased considering the above interven- We do measure punctal diameter in intraocular pressure while using tions, most patients can be helped an attempt to obtain the most op- Lotemax, what do you suggest? considerably. timum fit. Note that punctal plugs A: It depends on how well the create some beneficial scarring once patient has responded to this ther- Q: Is it safe to use OTC Vase- the plug has resided in the punc- apy, and the degree of intraocular line petroleum jelly directly into tal tissues for several weeks. This pressure increase. If the patient was the lower cul-de-sac at bedtime for explains why many patients do not getting a good response to the cor- chronic nocturnal lagophthalmos? revert to symptomatic status once a ticosteroid, then we would consider The cost is very minimal compared plug has been lost or extruded. switching to the 0.2% loteprednol to a tiny tube of petrolatum jelly/ (Alrex) if the IOP increase was less mineral oil combination. Q: I recently read that flaxseed than 10mm Hg above baseline, and A: It must be safe, because we oil causes inflammation of the monitor the intraocular pressure. have had many, many patients over prostate. Has this influenced your If the IOP increase is greater the years use Vaseline-type products recommendation for the male dry than 10mm Hg, then we would try in their eyes without a problem. eye patient? a topical NSAID or cyclosporine A: Yes, it has. We instead recom- IF the patient had a positive initial Q: Which punctal plug do you mend fish oil (2,000mg per day) for response to anti-inflammatory use for maximum patient comfort all of our dry eye patients. therapy. If there was little initial and efficacy, and do you ever use response to the steroid, we see little dissolvable/temporary plugs? Q: If you are using Lotemax in potential to try other anti-inflam- A: From the outset, we have the setting of managing dry eyes, matory approaches. always used permanent plugs. It is when would you consider add- 1. Green-Church KB, Butovich I, Willcox M, et al. The inter- our clinical impression that well- ing oral doxycycline, and for how national workshop on meibomian gland dysfunction: report of the subcommittee on tear film lipids and lipid-protein trained clinicians can determine the long? interactions in health and disease. Invest Ophthalmol Vis Sci. need for occlusion or not, so why A: Doxycycline has a faster onset 2011 Mar 30;52(4):1979-93. 14A REVIEW OF OPTOMETRY MAY 15, 2011012_dg0511_dryeye.indd 14 5/11/11 3:26 PM
  • 17. Dry Eye A Scientific View on Blepharitis and MGD Recent literature has used the terms posterior blepharitis and meibomian gland dysfunction as if they were synonymous, but these terms are not interchangeable. hanks to the recent report MGD Report Released T from the International Work- shop on Meibomian Gland Dysfunction, organized by the Tear Just as the Dry Eye WorkShop (DEWS) report brought greater understanding of dry eye in 2007, the International Workshop on Meibomian Gland Dysfunction report published in March Film & Ocular Surface Society, 2011 brings greater understanding of meibomian gland dys- we have new and more scientifi- function. All optometrists should read this report, if not in cally proper nomenclature for these its entirety, then at least the “executive summary.” These (mostly) distinct clinical entities. can be viewed via www.tearfilm.org/mgdworkshop. Here is the definition from the Although several critical questions remain unanswered, MGD workshop: this landmark report advances our understanding of “Posterior blepharitis is used to meibomian gland functions and their clinical significance. describe inflammatory conditions Because it is well known that most “dry eye” is underpinned by of the posterior lid margin, includ- meibomian gland dysfunction and disease, it is imperative that all O.D.s acquaint them- ing MGD. Indeed, recent litera- selves with this report. ture has used the terms posterior blepharitis and meibomian gland constitutes the vast majority of “professional” therapeutic modal- dysfunction or MGD as if they afflictions to the posterior tissues ity, and should completely replace were synonymous, but these terms of the eyelids. So, to keep things the older, out-of-date baby sham- are not interchangeable. Distinct simple, blepharitis is an anterior poo approach. from the portion of lid margin ante- infectious/inflammatory condition, There are those patients who do rior to the gray line, which includes while MGD represents the prepon- have clinically significant eyelid the skin and eyelashes, the posterior derance of posterior eyelid disease. erythema and other signs of inflam- lid margin contains the marginal They are managed very differently. mation, such as lash misdirection mucosa, the mucocutaneous junc- and madarosis. These inflammatory tion, the meibomian gland orifices Blepharitis signs are predominantly manifested and associated terminal ductules, Blepharitis (like rheumatoid as a response to staphylococcal and the neighboring keratinized arthritis and dandruff) is a chronic exotoxins. When there is clinically skin. Posterior blepharitis is a term disease, and the absolute mainstay significant eyelid inflammation, used to describe inflammatory con- for control (not cure) is initial and medical therapy is indicated to help ditions of the posterior lid margin, enduring eyelid hygiene. Forget achieve tissue restoration. This can of which MGD is only one cause. baby shampoo; this is obsolete be accomplished in several ways. Other causes include infectious or when compared to commercially One way is the use of combination allergic conjunctivitis and systemic available eyelid scrub products such antibiotic/steroid eye drops q.i.d. conditions such as acne rosacea.”1 as OCuSOFT Eyelid Cleanser or for two to four weeks. Options here It has been our observation that SteriLid (TheraTears). These have include Zylet, generic TobraDex, MGD, with or without rosacea, the appearance and function of a TobraDex ST, or generic Maxitrol. REVIEW OF OPTOMETRY MAY 15, 2011 15A012_dg0511_dryeye.indd 15 5/11/11 3:26 PM
  • 18. Dry E ye (We prefer Zylet purely because which is generic neomycin, poly- ties when compared to a corticoste- of the relative safety of the ester- myxin B and dexamethasone) pos- roid.3 based loteprednol.2 The other three sess excellent anti-staphylococcal If patients can be persistent with products would work equally as properties. Lotemax ophthalmic eyelid hygiene, the role of medi- well, but because they contain the ointment could be used at bedtime cal therapy should be very limited. older ketone-based dexamethasone, for two to four weeks, but we Patients being patients, however, we prefer to treat a chronic disease would suggest either the eyedrop most slack off and therefore may with the safest steroid available.) approach, or the ointment ap- require pulsed medical therapy once If cost is a concern, generic proach, but not both at the same or twice a year. It is this realization Maxitrol is by far the least expen- time. The macrolide azithromycin of the episodic need for a corti- sive drug within this class. Note is suboptimally staphylocidal (as costeroid that leads us to prefer that tobramycin (found in Zylet documented in the Ocular TRUST loteprednol. and TobraDex) and neomycin with data), and, as an antibiotic, it has polymyxin-B (found in Maxitrol, limited anti-inflammatory proper- Meibomian Gland Dysfunction It is now evident that most all Breakthrough Technology in Meibomian Gland Dysfunction cases of dry eye have some com- It is now known that a constantly applied pressure (1.25gm/mm2) for 15 seconds is ponent of lipid layer dysfunction needed to adequately evaluate meibomian gland dysfunction (MGD). New research resulting from suboptimum meibo- out of Ocular Research of Boston has yielded a simple, handheld device known as the mian gland function. Meibomian Gland Evaluator. This device should bring to all physicians a simple, semi- Now the question becomes: How qualitative means to can we restore or enhance these objectively assess for glandular secretions physiologi- MGD in all patients cally? We must first understand presenting with dry eye that dysfunctional glands are symptoms. commonly blocked, so it makes no Doing this cen- sense that any topical eyedrop or trally and nasally on both ointment can render a meaningful lower eyes gives great therapeutic effect. As with blepha- clinical insight as to the ritis, the mainstay of therapy is nature of the dry eye symptoms. After constant pressure with the handheld device for 15 physical/mechanical. There may seconds, just judge the character of the expressed glandular secretions. They should be well be a rational and intellectually clear. The more turbid, cloudy or cheesy the secretions, the more pathology is evident. For prudent reason to prescribe oral a description of the technique, visit www.tearscience.com. doxycycline, because the medicine can gain access to these glands via the systemic circulation (unlike with topical medications), and the benefit of oral medication can be enhanced by warm soaks and/or eyelid expression to help promote more normal secretions. The mainstay therapy of aggres- sive use of warm soaks should be followed by physical massage. This can truly be a challenge, and is time-consuming. First, being cogni- zant that these glands anatomically reside in the posterior portion of the eyelid, it is difficult to achieve a sufficiently high heat level external- ly to “loosen” the glandular con- tents—but it is still worth the effort. Then try to immediately massage 16A REVIEW OF OPTOMETRY MAY 15, 2011012_dg0511_dryeye.indd 16 5/11/11 3:26 PM
  • 19. Dry Eye and express these glands to purge at home. As can be seen, the care of patients their contents with the intent that In summary, blepharitis is essen- with meibomian gland dysfunction newly formed secretions may be tially managed with enduring eyelid is rapidly changing, and we antici- more physiologic. The oral doxycy- hygiene, often jumpstarted with two pate newer paradigms in managing cline and/or fish oils can help foster to four weeks of antibiotic-steroid this disorder in the near future. ■ more normal secretions. or steroid therapy. Treatment of 1. Nelson JD, Shimazaki J, Benitez-Del-Castillo JM, et al. A couple of notes about expres- meibomian gland disease is complex The international workshop on meibomian gland dysfunction: sion: It takes a sustained pressure and involves technically correct ap- report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7. for about 15 seconds to empty the plication of warm soaks, followed 2. Pavesio CE, Decory HH. Treatment of ocular inflammatory glands that are not blocked, and by glandular massage, and may be conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9. these efforts need to focus on the underpinned with a loading dose 3. Asbell PA, Sahm DF, Shedden A. Ocular TRUST 3: Ongo- centrally and nasally located glands. of 50mg of oral doxycycline for a ing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates. Poster presented at American Society of (The volume of the temporal meibo- couple of months, and continued Cataract and Refractive Surgery meeting, April 3-8, 2009; mian glands is not worth the effort with 2,000mg of fish oil thereafter. San Francisco. or time it takes to express them, so spend time on the central and nasal Observations on Meibomian Gland Dysfunction glands.) Next, the globe is a rela- “Overall, CD45 leukocyte infiltration into the meibomian gland acini was significantly tively soft substrate for adequate associated with the severity of the MG expression,” says a recent report in the April 2011 compression, so we recommend the Archives of Ophthalmology. “Additionally, meibomian glands exhibited variable amounts of in-office use of the Mastrota paddle leukocyte infiltration that are significantly correlated with the severity of MG expression.” (OCuSOFT) to help facilitate gland expression. Photo: Katherine Mastrota, M.S., O.D. While this study did not discuss any treatment options, it is widely recognized that corticosteroids are highly effective in leukocytic infiltrative disease states. This is an It takes a sustained pressure for about example where we think a highly effective anti-staph medication combined with a cortico- 15 seconds to empty the glands that are steroid would perhaps be most effective in combating blepharitis as well as MG disease. not blocked. Treatment of both conditions would be enhanced by the use of aggressive warm soaks, eyelid hygiene, and massage. Obviously, it would be maximal- The report adds, “In obstructive MGD, hyperkeratinization of the meibomian gland ly beneficial if all gland expression orifice is thought to lead to cystic ductal dilation and downstream disuse atrophy of the could be done in the office, but at meibomian gland acini.” this time that is simply impractical. This leads us to believe that eye doctors need to intervene as early as practical and So, do attempt to express the glands appropriate in treating MGD with the goal of preventing disuse atrophy. Exactly how this for the patient in the office when is done is yet to be fully elucidated, but use of fish oil supplementation may be beneficial; treatment is initiated to accomplish and we recommend these omega-3 fatty acids for most all of our dry eye patients. some active therapy—but more Nien CJ, Massei S, Lin G, et al. Effects of age and dysfunction on human meibomian glands. Arch Ophthalmol. 2011 importantly, do train the patient so Apr;129(4):462-9. that some therapy can be continued REVIEW OF OPTOMETRY MAY 15, 2011 17A012_dg0511_dryeye.indd 17 5/11/11 3:26 PM
  • 20. Corticosteroids Hit most cases of inflammation hard and heavy initially. Begin to taper only once the inflammation is well controlled. he key to managing most tion to damage ocular structures. A: In our clinical experience, T inflammatory processes is to select an appropriate steroid medicine and use it frequently until This is probably most applicable to intraocular inflammation such as iridocyclitis. Of course, the ultimate if patients are going to have an increased intraocular pressure secondary to steroid use, they usu- the inflammation comes under con- goal is to prescribe with precision, ally do so within a few weeks. Such trol, then conduct an appropriate which requires exquisite steroid responders generally show taper of days to weeks, depending teaching coupled with themselves more quickly upon the nature, severity, and re- clinical seasoning. The with more frequent dos- sponse of the condition. Selecting a more patients one sees, ing, and the ketone ste- potent corticosteroid is essential to the more precise the roids hasten this behavior effecting a clinical cure (or control) clinical care can be. more expressively than in most cases. an ester-based cortico- Generally speaking, using a ste- Q: How often do steroid. roid more than necessary is superi- you check IOP for If we are treating or to under-dosing. It is practically patients on long-term an aggressive anterior impossible to use a topical steroid steroid therapy (for uveitis with diflupred- eye drop too often, but under-treat- example, dry eye or nate or prednisolone, ing can allow unchecked inflamma- chronic iritis)? we would monitor the IOP as part Topical Corticosteroid Drugs BRAND NAME GENERIC NAME MANUFACTURER PREPARATION BOTTLE/TUBE Maximum Strength Steroids Durezol difluprednate 0.05% Alcon emulsion 5ml Lotemax loteprednol etabonate 0.5% Bausch + Lomb suspension 5ml, 10ml, 15ml Lotemax Ointment loteprednol etabonate 0.5% Bausch + Lomb ointment 3.5g Pred Forte, and generic prednisolone acetate 1% Allergan, and generic suspension 5ml, 10ml, 15ml generic prednisolone sodium generic solution 5ml, 10ml, 15ml phosphate 1% Vexol rimexolone 1% Alcon suspension 5ml, 10ml Moderate Strength Steroids Alrex loteprednol etabonate 0.5% Bausch + Lomb suspension 5ml, 10ml Flarex, and generic fluorometholone acetate 0.1% Alcon suspension 5ml, 10ml FML, and generic fluorometholone alcohol 0.1% Allergan suspension 5ml, 10ml, 15ml FML S.O.P. fluorometholone alcohol 0.1% Allergan ointment 3.5g Pred Mild, and generic prednisolone acetate 0.12% Allergan suspension 5ml, 10ml 18A REVIEW OF OPTOMETRY MAY 15, 2011018_dg0511_steroids.indd 18 5/11/11 3:34 PM
  • 21. Corticosteroids of all of our follow-up visits. For chronic care patients using lotepre- dnol, after the first month or two of evaluating the response of the clinical condition and evaluating the IOP at these same visits, if there has been no IOP increase, we then monitor the IOP every four to six months. We do not schedule an “IOP check” visit, but during the course of patient follow-up evaluations, an assessment of the IOP is rou- tinely done. What we have very This contact lens patient has a peripheral, white, corneal lesion that exhibits smaller clearly seen is that if a patient does fluorescein staining than the size of the underlying corneal stromal lesion. not demonstrate an increased IOP with the use of steroids q.i.d. for a etrists alike struggle with clinical than the size of the underlying cor- month, they do not exhibit a steroid decision-making. Clinical condi- neal stromal lesion. The conjuncti- response with once-daily or b.i.d. tions are not profession-specific, val injection pattern is accentuated dosing over months or years. and a more keen understanding in the juxtalesional region of the of the pathophysiology of certain bulbar conjunctiva (the Q: Even the ophthalmologists I epithelial defects enable the rational entire bulbar conjunctiva is work with are hesitant about using and prudent use of steroids. A com- not markedly red), and the steroids on any epithelial defects. mon example would be Thygeson’s anterior chamber is devoid So, how do I justify doing this with SPK. This condition’s recom- of any significant inflam- my patients? mended treatment is indeed matory cells. Such a A: The prime question is: “What topical corticosteroids—in presentation would is the nature of the epithelial this case, a mild one such as represent an inflam- compromise?” Is it a non-healing loteprednol 0.2% or fluoro- matory keratocon- metholone 0.1%. There is junctivitis resulting no need to use any topical from leukocytic ophthalmic antibiotic here. chemotaxis into the A slightly more challeng- anterior stroma of the cornea. ing scenario is the contact This commonly results in some lens wearer who presents overlying epithelial compro- with a peripheral, white, mise, as evidenced by a rela- corneal lesion that exhibits tively small positive fluorescein a smaller fluorescein staining defect staining defect. Thygeson’s superficial punctate Lotemax Ophthalmic Ointment keratopathy (SPK). Lotemax ointment (loteprednol 0.5%, Bausch + Lomb) was just approved by the FDA in April. Its indication is for treatment of postoperative inflammation and pain following ocular corneal abrasion from fingernail surgery; however, we anticipate using it “off-label” in a rational manner for a myriad of trauma, where associated anterior clinical conditions. These might include: inflammatory blepharitis; dry eye; augmentatively stromal inflammation is hindering for severe uveitis, episcleritis and cystoid macular edema; contact blepharodermatitis; epithelialization? Is there an abun- recurrent corneal erosion; and various other conditions where corticosteroid suppression dance of anterior stromal leuko- would help restore tissue normalcy. cytic infiltration that is hindering Because it’s an ester-based formulation with an enhanced safety profile, we anticipate re-epithelialization? A good history this new product to largely replace fluorometholone ophthalmic ointment. It may be mid- and attentive slit lamp examination to late summer before Lotemax ophthalmic ointment will be available for prescribing, will guide sound decision-making. however. (A photo was not available at press time.) Ophthalmologists and optom- REVIEW OF OPTOMETRY MAY 15, 2011 19A018_dg0511_steroids.indd 19 5/11/11 3:34 PM
  • 22. Corticosteroids The Many Uses of The use of the steroid will renormalized to baseline. Corticosteroids quickly suppress the stromal A: This patient is obviously an Topical steroids are essential for the res- inflammation, and thus hasten the exquisitely sensitive steroid re- toration of normal tissues for the follow- restoration of tissues to normal sponder. While topical NSAIDs ing diseases, afflictions and conditions: (which would include re-epitheli- pack very little anti-inflammatory • Iridocyclitis alization). Since contact lens wear punch, such a therapeutic trial is • Ultraviolet keratitis always increases the likelihood of reasonable here (along with gener- • Contact lens overwear bacterial infection, especially when ous artificial tears). Bromfenac • Inadvertent hydrogen peroxide kerato- the contacts are worn overnight, (Bromday, ISTA) would be an conjunctivitis we always encourage conservative excellent choice because of its once- • Thygeson’s superficial punctate kera- wearing schedules, strict adherence daily administration. However, it is topathy to proper lens care technique and very expensive, so perhaps generic • Allergic conjunctivitis replacement schedules, and quar- diclofenac b.i.d. to q.i.d. may be a • Acute angle closure1 terly replacement of the contact more practical approach. • Dry eye syndrome lens case. We wonder if the 0.2% con- • Infiltrative keratitis2 centration of loteprednol (Alrex, • Ulcerative keratitis3 Q: Inflammation is classically Bausch + Lomb) would be sub- • Microcystic edema of the cornea discussed as a vascular or micro- threshold to generate an increased • Vernal conjunctivitis vascular event. However, you have IOP, especially if used perhaps • Atopic conjunctivitis shown how suppressing an in- b.i.d.? • Bacterial conjunctivitis2 flamed anterior stroma can hasten All steroids have the potential to • Glaucomatocyclitic crisis (not prolong) corneal re-epitheliali- raise intraocular pressure, as wit- • Uveitis-associated ocular hypertension zation; yet, the cornea is avascular. nessed in your case. Such responses • Blepharitis2,4 Please comment. are indeed rare, as evidenced by this • Curling iron/burn injury (thermal kera- A: Many biochemical insults to being your first encounter in what toconjunctivitis)2 the cornea can cause chemotactic is a busy therapeutic practice. • Nasolacrimal stenosis2 migration of leukocytes from the • Traumatic hyphema blood vessels into the anterior Q: Poison oak is pretty common • Post foreign body removal2 stroma, where an inflammatory out here. Would triamcinolone be • Acute adenoviral infection5 cascade of events can occur. Steroid the best treatment around the eye • Acute, symptomatic giant papillary eyedrops cause the cellular infil- for a child with poison oak? conjunctivitis trates to disappear from the cornea, A: Yes, but perhaps applied only • Corneal graft rejection and visual clarity returns. If there is b.i.d. for a child, as opposed to • Phlyctenulosis (2, if corneal) an overlying, non-healing epithelial q.i.d. for an adult. And don’t forget • Inflamed pinguecula/pterygia defect, suppressing the corneal stro- cold compresses. • Recurrent corneal erosion6 mal inflammation can enable these • Post anterior stromal micropuncture2 tissues to return to normal, thus Q: Is 0.5% triamcinolone safe to • Herpes simplex viral stromal keratitis7 potentiating re-epithelialization— use around the eye? • Episcleritis not retarding it, as older, traditional A: Probably, but we never use • Acute hordeolum (stye)8 teaching has held. this concentration because we • Superior limbic keratoconjunctivitis have had perfect success in treating • Cyanoacrylate-induced chemical kera- Q: Saw my very first Lotemax contact blepharodermatitis with the titis steroid responder (after being in 0.1% concentration of triamcino- practice for 30 years). This 47-year- lone cream. We always strive to 1 once IOP is controlled old white patient had a baseline use the least amount of medicine to 2 with antibiotic intraocular pressure of 18mm Hg meet our patients’ needs. 3 once active infection is controlled O.D. and 20mm Hg O.S. On To- 4 with eyelid hygiene braDex, IOP in the treated left eye Q: Have you ever had a pa- 5 following 5% Betadine treatment increased to 33mm Hg. A trial with tient have an intraocular pressure 6 with oral doxycycline Lotemax also yielded an increased increase as a result of using triam- 7 with antiviral cover IOP (to 36mm Hg). In both cases, cinolone cream to the eyelids? 8 with warm compresses after stopping the steroid, the IOP A: We have not, but it is perhaps 20A REVIEW OF OPTOMETRY MAY 15, 2011018_dg0511_steroids.indd 20 5/11/11 3:34 PM
  • 23. Corticosteroids A: The scenarios you describe are it is well recognized that ointment almost always steroid-dependent medicines tend to stay local and not conditions, so yes, we would use become systemically absorbed. steroids. We would use either com- It is always good practice to petent punctal occlusion or gentle consult by phone with the patient’s eyelid closure for three minutes if obstetric physician, or at least get using eyedrops. We could consider a letter to the OB/GYN so that the The 0.1% triamcinolone cream is likely using the new Lotemax ointment doctor is fully informed of the pa- more appropriate for use around the eye or FML ophthalmic ointment, since tient’s condition and treatment. ■ than the 0.5% concentration. Is it an Infiltrate or is it an Ulcer? possible. So, when doing your usual Corneal infiltration is still commonly mis- follow-up evaluations, go ahead taken for an ulcerative process. There and check the pressure. are a number of factors to consider in the differential diagnosis between a leukocytic Q: What is an average taper for infiltrate and a bacterial corneal ulcer: steroids, once acute stromal herpes • First, pay attention to the epidemiol- simplex keratopathy has been ogy of these two conditions: infiltrates are controlled? very common; ulcers are very rare. A: The taper is typically done • An anterior chamber reaction (i.e., over several weeks or months; cells and flare) is almost always seen with some patients require a drop a an ulcerative process. While an anterior day, or even every other day, for chamber reaction is usually absent with an life. We only use loteprednol for infiltrate, trace cells are sometimes seen, With an ulcer, the size of the staining such protracted therapy. A typical especially if the condition has been ongo- pattern closely mirrors the size of the example of a steroid taper might be ing for several days. corneal lesion. q.i.d. for a month, then t.i.d. for a • The appearance of the conjunctival month, then b.i.d. for two months, injection pattern can also be very helpful. and then once daily for two or With an infiltrate, sector injection is the three more months. If the inflam- rule; in an ulcerative process, the entire mation rebounds when the dos- bulbar conjunctiva is injected. age is reduced to b.i.d., we titrate • While neither highly sensitive nor back to t.i.d. for two months, and specific, the degree of pain the patient then try again to reduce to b.i.d., describes can be helpful. An ulcer tends to and we plan a longer taper at each evoke much more pain than an infiltrate. phase. Ultimately, we try to get the • Location can also be helpful. As a patient to b.i.d. usage of the 0.2% rule, ulcers are solitary and tend to be loteprednol concentration for a few more central, while infiltrates can be single months, and then try to reduce the or multiple and strongly tend to express With an infiltrate, the size of the drop to once daily. It purely is a themselves at or near the corneal limbus. staining pattern is significantly smaller matter of therapeutic trial, trying • The fluorescein staining pattern of the than the underlying lesion. to find the lowest dosage at which lesion is probably one of the characteristics the eye remains quiet. Not all such we find most helpful in making a definitive paralleling its stromal invasion. An infiltrate stromal herpetic keratitis conditions diagnosis. With an ulcer, the size of the results from the chemotactic attraction of will require such a long, drawn-out fluorescein staining pattern closely mirrors leukocytes from the paralimbal microvas- course of therapy, but some will. the size of the corneal lesion, whereas the culature. The accumulation of white blood staining pattern of an infiltrate is signifi- cells in the anterior stromal tissues results Q: How would you change cantly smaller than the underlying lesion. in some secondary compromise to the treatment if seeing episcleritis or This is because an ulcer begins in the overlying epithelium, which tends to cause corneal leukocytic infiltrates in a epithelium, and expands laterally and in a relatively small defect in the center of the pregnant woman? Would you still depth, creating an epithelial defect closely underlying stromal lesion. use steroids? REVIEW OF OPTOMETRY MAY 15, 2011 21A018_dg0511_steroids.indd 21 5/11/11 3:34 PM
  • 24. Topical Antibiotics The key to clinical success and bacterial eradication is not so much the drug prescribed, but rather the frequency of drug instillation. he “go to” drugs for eyes ological adhesion of the basal T evidencing mucopurulent discharge are: generic Polytrim (trimethoprim epithelium/Bowman’s layer/ anterior stromal complex can occur. This, in theory (and in with Polymyxin B); a clinical practice) breaks the generic aminoglyco- cycle of recurrence, and is side (gentamicin “curative” for most patients. or tobramycin); Corticosteroids also inhibit a chloro-flu- these same enzymes, and oroquinolone work in concert with oral (Besivance [besi- Evident mucupurulent discharge is a red doxycycline. floxacin, Bausch flag for bacterial conjunctivitis. Our general approach is + Lomb]); or to prescribe 50mg of doxy- either gati- cycline p.o. b.i.d. for a week, floxacin 0.5% and then once daily for four (Zymaxid [Al- to six weeks, along with lergan]); or moxifloxacin loteprednol 0.5% q.i.d. for 0.5% (either Vigamox three weeks, and then b.i.d. or Moxeza [Alcon], the for three more weeks (or latter being essentially the some reasonable variation same as the former except thereof). that Moxeza has a xan- Doxycycline should be thum gum vehicle, which taken with meals, and not prolongs ocular surface But not all bacterial infections present within two hours of bed- residency time, and so re- with obvious discharge. Check the lacri- time because of the remote quires less frequent dosing mal lake for microparticulant debris. possibility of esophageal of the drug.) reflux, resulting in epigastritis The key to clinical suc- extracellular matrix metallo- (heartburn). cess is not so much the drug proteinases are present in the prescribed, but rather the fre- corneal areas where epithelial Q: Where do you send your quency of drug instillation. breakdown occurs. These de- cultures? What are some sources grading enzymes are thought to purchase the mini-tip culturettes Q: Please go over what to play a role in setting the you espouse? role doxycycline plays in stage for these breaches in A: There are many dozens of treating recurrent corneal epithelial adhesion. The tetra- general medical supply businesses. erosion and RCE-related cyclines (doxycycline and mi- We recommend you ask your per- abrasions. nocycline) excellently inhibit sonal physician or a local micro- A: It has been shown that these enzymes so that physi- biologic laboratory (usually, it’s a 22A REVIEW OF OPTOMETRY MAY 15, 2011022_dg0511_antibiotics.indd 22 5/11/11 3:42 PM
  • 25. Anti biotics hospital lab). We keep several of rarely cause an allergic reaction. myxin B/dexamethasone). It is these mini-culturettes in our offices. These are not acute anaphylactic quite inexpensive, and we have yet Once we do the culture, one of reactions, but are type 4 delayed to have an issue with it when used our staff drives it over to the local hypersensitivity reactions. While short-term; however, a hypersensi- hospital laboratory for processing. still rare, they are more likely to be tivity response is certainly possible. We get staining results (i.e., gram- seen when neomycin is used in a If it does occur, stop the antibiotic positive or gram-negative) in about combination antibiotic, as opposed and use cold compresses for a day a day, and culture results in three to being used in combination with or two. to four days. Mini-Tip Culturette a corticosteroid. The reason: the is available from multiple sources, steroid is most likely to suppress Q: When prescribing erythro- including the following: the type 4 reaction were it to occur. mycin for blepharitis, is it still • eGeneral Medical, Inc., Ra- The neomycin hypersen- advised to limit its use to leigh, NC (609-848-8890 or www. sitivity reaction is more a maximum of 14 days egeneralmedical.com) of an annoyance or because of the potential • Hardy Diagnostics, Santa Ma- bother, rather than a development of bacterial ria, CA (800-266-2222 or www. significant therapeutic resistance? hardydiagnostics.com) misadventure. A: Yes, this is true. For our patients However, we usually use Q: What about the statement who are indigent or bacitracin or Polysporin years ago that 10% of all patients self-pay, we com- (bacitracin with poly- are allergic to neomycin? monly prescribe myxin B) because the A: It may be more like 5% generic Maxitrol bacitracin more effec- to 8%, but yes, neomycin can (neomycin/poly- tively eradicates Staph. 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, and generic ciprofloxacin 0.3% Alcon, and generic sol./ung. > 1 yr./ > 2 yrs. 5ml, 10ml/3.5g Iquix levofloxacin 1.5% Vistakon Pharm. solution > 6 yr. 5ml Moxeza moxifloxacin 0.5% Alcon solution > 4 mos. 3ml Ocuflox, and generic ofloxacin 0.3% Allergan, and generic solution > 1 yr. 5ml, 10ml Quixin levofloxacin 0.5% Vistakon Pharm. solution > 1 yr. 5ml Vigamox moxifloxacin 0.5% Alcon solution > 1 yr. 3ml Zymar gatifloxacin 0.3% Allergan solution > 1 yr. 5ml Zymaxid gatifloxacin 0.5% Allergan solution > 1 yr. 2.5ml Aminoglycosides Tobrex, and generic tobramycin 0.3% Alcon, and generic sol./ung. > 2 mos. 5ml/3.5g Genoptic, and generic gentamicin 0.3% Allergan, and generic sol./ung. N/A 5ml/3.5g Polymyxin B Combinations Polytrim polymyxin B/trimethoprim Allergan, and generic solution > 2 mos. 10ml Polysporin polymyxin B/bacitracin Monarch, and generic unguent N/A 3.5g Neosporin polymyxin B/neomycin/ Monarch, and generic sol./ung. N/A 10ml/3.5g gramicidin Other Antibiotics AzaSite azithromycin 1% Inspire Pharm. solution > 1 yr. 2.5ml Ilotycin, and generic erythromycin 0.5% Dista, and generic unguent > 2 mos. 3.5g AK-Tracin, and generic bacitracin 500u/g Akorn, and generic unguent N/A 3.5g REVIEW OF OPTOMETRY MAY 15, 2011 23A022_dg0511_antibiotics.indd 23 5/11/11 3:42 PM
  • 26. Anti biotics the eye. It would be nice to see such another four to five days. By that a study, for we think its findings time, the patient should be better. might guide us to stop using antibi- otics unnecessarily; however, now Q: Are there “standard-of-care” that many cataract surgery centers issues with older meds? are using generic antibiotics in their A: We are not aware of any clini- postoperative care, cost is minimal cal or medicolegal issues with using and no harm is done. New indus- older medicines that are effective. try guidelines have brought the As stated above, many cataract “postop kit wars” to an end, and surgical centers now use a generic this has significantly diminished antibiotic (usually tobramycin or Manage blepharitis with good eyelid the financial burden to the patient the combination of trimethoprim hygiene using eyelid scrubs, not baby to purchase expensive medicines in with polymyxin B), a generic cor- shampoo. order for the surgery center to get ticosteroid (usually prednisolone free (or at least cheap) kits. acetate 1%), and generic diclofenac. species than does erythromycin. If If there were such concerns, this there is significant associated eyelid Q: What is the best antibiotic practice would not be embraced. margin inflammation, we would regimen for a mucopurulent con- On a broader note, and from an consider an antibiotic/steroid com- junctivitis in a nursing home envi- oral antibiotic perspective, note that bination drug q.i.d. for two weeks, ronment where methicillin-resistant the CDC/FDA-recommended drugs rubbing the excess drop along the Staphylococcus aureus bacteria is for systemic MRSA infections are: eyelid margin at each instillation. prevalent? (1) trimethoprim/sulfamethoxazole Remember, blepharitis is almost A: Four choices: Besivance q2 (Bactrim or Septra); (2) doxycy- exclusively managed via lifelong hours (the DuraSite vehicle pre- cline; (3) clindamycin. All of these meticulous eyelid hygiene. We only cludes the need for more frequent are “older” medicines that are use medicines to jumpstart the pro- instillation); generic Polytrim q1 generically available. This latter cess for two or three weeks. hour initially; generic tobramy- observation probably best answers We have totally abandoned the cin q1 hour initially; or generic your question. baby shampoo approach, and now Polysporin ophthalmic ointment use commercially available eyelid instilled q3 to q4 hours and q h.s. Q: If vancomycin is effective foam scrubs. Once the lids are calm After using one of these medi- against methicillin-resistant Staphy- and clean, most patients need to cines at the stated frequency of lococcus aureus infection, why isn’t continue with adequate lid scrubs instillation for three or four days, it used to treat all MRSA infec- two to four times a week to main- it should be possible (assuming tions? tain healthy tissues. clinical improvement) to reduce the A: It is virtually impossible to frequency of instillation by half for know the nature of the bacte- Q: In India and Tibet, cataract rial pathogen without Photo: Paul Karpecki, O.D. surgeries are done with minimal an- culturing. Vancomy- tibiotic use, but with good cleaning cin must be sterilely of the surgical area before surgery. compounded, and is not Would you please comment on commercially available, this? so it is not an easily A: There are no scientific studies accessed drug. Also, to our knowledge that support the the aminoglycosides, need for antibiotics in concert with besifloxacin, and trim- modern cataract surgery. To wit, ethoprim with polymyx- these practices from afar clearly in B are quite effective support this, assuming uneventful against MRSA species. outcomes of those surgeries. The With any advanced only proven effective maneuver is For mucopurulent conjunctivitis (including MRSA bacterial infection, any the use of 5% Betadine for two infection), several topical antibiotic options are antibiotic should be minutes prior to surgical entry into currently available. used frequently until 24A REVIEW OF OPTOMETRY MAY 15, 2011022_dg0511_antibiotics.indd 24 5/11/11 3:42 PM
  • 27. Anti biotics the infection is controlled, then In a year or two, it is anticipated dropped to about half that fre- that a physical device to heat and quency for several more days before massage these glands as an in-office stopping treatment. procedure will be approved and this will parallel the advent of antibiot- Q: What is your experience with ics for infectious diseases in the using topical ophthalmic azithro- setting of meibomian gland dys- mycin (AzaSite, Inspire) for meibo- function. (See “New MGD Device mian gland dysfunction? on the Way,” page 13A.) A: A thorough read- ing of the literature Q: Is it okay to have patients use on this topic describes bacitracin OTC for blepharitis? It “plugged, inspissated, says “Not For Ophthalmic Use” on constipated glands.” the OTC tube of bacitracin. Furthermore, the A: Yes, it is okay. An “oph- literature consistently thalmic” ointment generally discusses the therapy comes in a 1/8 ounce tube with a for meibomian gland nozzle-shaped tip. Beyond this, we dysfunction as aggres- typically find that a combination sive warm soaks fol- antibiotic-steroid medication—such lowed by glandular expres- as Zylet, TobraDex, or generic sion—two technically challenging neo-poly-dex (generic Maxitrol) maneuvers. Given these two clinical used q.i.d. for two or three weeks Patients with herpes zoster skin lesions realities, a learned individual would then perhaps b.i.d. for two more may apply Polysporin antibiotic ointment rationally ask how any topical weeks (along with eyelid hygiene to prevent secondary bacterial infection. ophthalmic medication could gain maneuvers)—helps more than a access into these glands in sufficient pure antibiotic. Of course, it is In summary, the topical antibi- concentration to affect a clinically standard procedure to have these otics are grossly overutilized—in meaningful therapeutic response. patients back in three to four weeks optometry, ophthalmology and Still, anecdotal reports and to assess the clinical result and to general medicine. Make every effort at least one clinical study have monitor the intraocular pressure. to pinpoint an accurate diagnosis shown some success with topical (which, in most cases of acute red azithromycin in relieving signs and Q: For patients with herpes zos- eye, is not of bacterial etiology), symptoms and restoring the normal ter, do you ever prescribe antibiotic and then select an appropriate drug lipid properties of meibomian gland ointment to rub over the zoster skin or drug class to achieve renormal- secretion.1 lesions in an attempt to prevent ization of tissues. However, keep in mind that secondary bacterial infection? In our 60 years of experience, we AzaSite is not clinically indicated by A: Yes. Over-the-counter Poly- have found the frequency of instilla- the FDA for meibomian gland dys- sporin ointment applied two to tion is almost always more impor- function, and in its phase II clinical three times a day works well. tant than the drug selected. trials, it did not show any improve- We are fortunate to have such an ment compared to its vehicle in the Q: Could 5% Betadine be help- awesome arsenal of medicines avail- treatment of blepharitis. (Indeed, ful in the setting of acute bacterial able to treat bacterial infections. the FDA recently sent a warning conjunctivitis? (For comparison, Use them wisely, judiciously—and letter to Inspire because AzaSite’s see Betadine discussion in “Antivi- aggressively when indicated. ■ advertising claims it “delivers sig- rals,” page 26A?) 1. Foulks GN, Borchman D, Yappert M, et al. Topical nificant anti-inflammatory effects, A: Probably, but we would em- azithromycin therapy for meibomian gland dysfunction: when this has not been demon- ploy Betadine only if the infection clinical response and lipid alterations. Cornea. 2010 Jul;29(7):781-8. strated by substantial evidence or were rather pronounced. We have 2. Davis CC. Letter to Inspire Pharmaceuticals. 2011 April substantial clinical experience,” the plenty of good topical antibiotics 14. Available at: www.fda.gov/Drugs/GuidanceCompli- anceRegulatoryInformation/EnforcementActivitiesbyFDA/ FDA says.2) In our experience, oral to arrest bacteria, so other ancillary WarningLettersandNoticeofViolationLetterstoPharmaceutical- doxyclycline appears more effective. maneuvers are rarely indicated. Companies/ucm252369.pdf. REVIEW OF OPTOMETRY MAY 15, 2011 25A022_dg0511_antibiotics.indd 25 5/11/11 3:42 PM
  • 28. Antiviral Strategies In addition to the Betadine treatment for epidemic keratoconjuncitivitis (EKC), we now have a ganciclovir gel that is as effective as trifluridine, but much easier to use. s introduced in this drug A guide last year, Zirgan (gan- ciclovir gel, Bausch + Lomb) is a major upgrade to the 30-year- old trifluridine. Its main advantage from the patient’s perspective is the less frequent dosing schedule: only five times a day for four to five days and then three times a day for four to five days—as opposed to Viroptic (trifluridine, Monarch) every two hours for four to five days and then four times a day for An estimated 50,000 new or recurrent cases of herpes simplex keratitis are seen each four to five more days. year in the United States. 1 Here’s one of them now! does not require pharmacy Q: When you leave the Betadine refrigeration, it should be on the ocular surface for one min- more readily available. ute, how do you take it off? Lastly, as a brand name- A: Betadine 5% Sterile Oph- From the doctor’s perspective, protected drug, samples are thalmic Prep Solution (povidone- ganciclovir is viral specific, which available to start therapy imme- iodine, Alcon) is used thousands of means much less potential for diately in the event the pharmacy times each workday to prep human epithelial toxicity, and because it does not have the 5g tube in stock. eyes for cataract surgeries. The package insert states to leave it on Topical Antiviral Options the eye for two minutes for this in- dication. However, we have found Trifluridine Ganciclovir that 60 to 90 seconds of exposure • Old drug • New drug beautifully eliminates active adeno- • Indiscriminate expression • Infected cell-specific viral replication. • Potentially toxic • Minimally toxic We instill three or four drops, • More frequent dosing • Less frequent dosing and ask the patient to roll the eyes • Refrigerate until opened • No refrigeration needed around to distribute the medicine • Thiomersal preserved • BAK preserved thoroughly over the ocular sur- • Solution (7.5ml bottle) • Gel (5g tube) face tissues. (Use good, courteous • Viroptic (Monarch) and generic • Zirgan (Bausch + Lomb) hygienic technique so that any drug overflow does not run down 26A REVIEW OF OPTOMETRY MAY 15, 2011026_dg0511_antivirals.indd 26 5/11/11 3:51 PM
  • 29. Antiviral Drugs the patient’s face and/or stain their ment good to use if the patient has junctivitis, i.e., EKC) is about eight clothing.) After 60 to 90 seconds, had EKC for two or more weeks? days of latency, then about eight we lavage the ocular surface for A: Like the oral antivirals, which days of acute infection and, if not a few seconds with any sterile ir- are maximally effective when used treated, subepithelial infiltrates can rigating saline solution (again using within the first three days of the in- begin to form after approximately thoughtful technique not to have fectious process, they are still some- eight more days. water run down the face, neck, what effective if used up to a week So, two weeks, huh? At this onto clothing, etc). out. The natural history of most stage, the body’s natural defenses virulent adenoviral serotypes (those should have the infectious phase Q: Is the Betadine EKC treat- that cause clinically significant con- pretty well controlled, so the an- The EKC-Betadine Protocol Povidone-Iodine in When we encounter a patient with moderate Perspective to advanced EKC, we generally use the fol- “Because of its spectrum of micro- lowing protocol: biocidal activity, PI [povidone-iodine] is • By history, rule out any allergy or sen- used widely in ophthalmology to prepare sitivity to iodine, the molecular backbone of the eyelids, eyelashes, and conjunctiva Betadine. before intraocular surgery to decrease • Instill a drop of 0.5% proparacaine into the risk of endophthalmitis.”1 the eye(s), since Betadine can sting upon This patient presented with severe EKC. “Povidone … serves as a carrier to instillation. deliver iodine. Povidone is used widely • Because Betadine can cause mild stip- … in many hairsprays, cosmetics, and pling to the corneal epithelium resulting pharmaceuticals.”1 in marked stinging, instill a drop or two of “No cases of anaphylaxis related a topical NSAID prior to instillation of the to ophthalmic use of PI have been Betadine. reported.”1 • Now instill four to six drops of Betadine “Seafood allergy does not equate to an into the eye(s). iodine allergy and is not a contraindica- • Ask the patient to gently close the eyes tion to the use of topical PI.”1 and roll them around to ensure thorough Two days after treatment with Beta- Also note, Betadine is used in just-born distribution of the Betadine across the ocu- dine, his eyes were white and quiet. infants to prevent ophthalmia neonato- lar surfaces. rum: “Topical azithromycin is likely as • After one minute, lavage out the effective for the important causes of Betadine (to avoid any unnecessary toxicity ophthalmia neonatorum as its fellow and discoloration of the tissues) with any macrolide erythromycin ... A controlled sterile ophthalmic irrigating solution. Note: clinical trial comparing erythromycin The package insert states to leave the 5% 0.5%, povidone-iodine 2.5%, and silver Betadine in contact with the ocular surface nitrate 1% for ophthalmia neonatorum for two minutes (when prepping for intra- prophylaxis demonstrated that povidone- ocular surgery); however, our experience iodine was more effective than the other in the treatment of EKC has been that one agents for preventing infectious conjunc- minute of contact is sufficient. tivitis, including chlamydial conjunctivitis • Just for good measure, instill another ... We believe povidone-iodine would drop or two of the NSAID (or even propara- be a suitable and perhaps preferable caine if the patient has any discomfort). alternative to azithromycin for ophthalmia • Add a potent corticosteroid q.i.d. for neonatorum prophylaxis.”2 four days. 1. Wykoff CC, Flynn HW Jr, Han DP. Allergy to Since using this protocol, we have not had a patient to go on to develop the legendary povidone-iodine and cephalosporins: the clinical dilemma in ophthalmic use. Am J Ophthalmol. 2011 subepithelial infiltrates. We reason that by rapid diminution and/or elimination of live virus Jan;151(1):4-6. from the ocular surface, there is insufficient time for enough viral particles to migrate into the 2. Keenan JD, Eckert S, Rutar T. Cost analysis of povidone-iodine for ophthalmia neonatorum prophy- anterior stromal tissues to incite an immune response. laxis. Arch Ophthalmol. 2010 Jan;128(1):136-7. REVIEW OF OPTOMETRY MAY 15, 2011 27A026_dg0511_antivirals.indd 27 5/11/11 3:51 PM
  • 30. Antiviral Drugs What is Zostavax? eradicates the viral infection from the ocular surface, Zostavax vaccine (live zoster virus vaccine, Merck) is the adult there are fewer viral antigen substances to trigger an form of Varivax vaccine (live varicella virus vaccine, Merck). immune response. Thus, subepithelial infiltrates do not Varivax is used to inoculate children at least one year of age for occur. the prevention of chickenpox. Zostavax is used in older adults to So, beyond the overall benefit to a patient for a try to prevent or dampen the quick cure via early, appropriate 5% Betadine treat- expression of recurrent vari- ment, there can be a marked secondary benefit by cella infection (shingles). Zostavax is an intramus- cular injection vaccine of attenuated varicella zoster virus. It is approved for patients over age 50 to diminish the risk of con- tracting shingles. Note the words “diminish the risk,” because this vaccine only reduces the risk of getting While most cases of facial shingles by about 50%; but shingles are first division, here for those older adults who is a more rare second division do contract shingles after expression of shingles. having the vaccine, the clin- ical expression is relatively Herpetic stromal immune keratitis. subdued. Also note that the FDA guideline reduced the approved age for injection of this vaccine from 60 to 50 in March 2011. preempting a delayed immune response. This is true for The question always arises as to whether an adult who has both adenoviral and herpetic infections in that timely had shingles should have the Zostavax vaccination. Keep in mind intervention with antiviral therapy can bring quick the natural history of shingles. Once a person has had shingles, resolution to both herpes simplex epithelial keratitis as the risk of recurrence is somewhere between 2% and 4%. Also well as to virulent strains of adenoviral infection. Rapid bear in mind that having shingles “self-immunizes” the patient, eradication of these virus types can prevent or lessen but immunity wanes with time. So, after a person is out five to the risk of subsequent stromal immune keratitis (in her- ten years from the shingles, then perhaps it might be prudent to petic disease) and subepithelial infiltrates (in adenoviral get the Zostavax vaccine. infections). The downside is the cost; this one-time injection costs between $200 and $300. However, since shingles can be so Q: Is 5% Betadine of any value in the initial treat- debilitating, it seems prudent for optometrists to discuss the ment of herpes simplex keratitis? Zostavax vaccine with their over-50 patient population, or at the A: Maybe, but we feel little need to use Betadine very least encourage your over-50 patients to discuss the vaccine because there are highly effective antiviral medicines with their primary care givers. readily available that have proven efficacy in these situ- ations, such as Zirgan, trifluridine or an oral antiviral. swer is that the 5% Betadine EKC treatment is prob- ably not going to be the best treatment option at this Q: It is evident that 5% Betadine is a jewel for epi- time of presentation. We would recommend instead demic keratoconjunctivitis, but what about for children that a corticosteroid be used q.i.d. for a few days to with pharyngoconjunctival fever (PCF)? quiet down any residual secondary inflammation. A: PCF serotypes generally cause mild, often unilat- Since we have been using the 5% Betadine, none eral conjunctivitis, and are fairly quickly self-limiting. of our EKC patients have developed subepithelial We generally treat these with Alrex (loteprednol 0.2%, infiltrates. Why? The longer a viral infection resides Bausch + Lomb) q.i.d. for four to six days. More on the ocular surface, the greater the likelihood that conservative approaches could be artificial tears and an viral antigenic substances can penetrate down into the OTC vasoconstrictor for a few days. ■ anterior stromal tissues where immune responses can 1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001 occur. Because treatment with the 5% Betadine largely Jan;20(1):1-13. 28A REVIEW OF OPTOMETRY MAY 15, 2011026_dg0511_antivirals.indd 28 5/11/11 3:51 PM
  • 31. Combination Drugs How do you choose when to use a pure steroid vs. a combination drug? If there is significant epithelial compromise, a combination drug will help prevent infection. s many as half of all red eyes generalizations. it is inflamed. Also, the conjunc- A that we see are treated with a combination drug, rather than either a steroid or antibiotic The pivotal issue is the integrity of the corneal epithelium. If the corneal epithelium is intact, there tiva will be inflamed in almost all cases in which keratitis is present. With either keratitis (with an intact alone. This observation clearly is little or no reason for prophy- epithelium) or non-infectious con- acknowledges two clinical realities: laxis against opportunistic bacte- junctivitis, we almost always use a • The need for topical antibiotics rial pathogens. This is because an topical steroid. alone is relatively low. intact epithelium is itself a firewall If the accurate diagnosis of • Almost all acute red eyes have of defense. If there is significant bacterial conjunctivitis is made, a significant inflammatory compo- epithelial compromise, then a com- the decision is whether to prescribe nent. bination drug may perfectly match an antibiotic or a combination So, how does the astute clinician the clinical need. drug. The prime determinants are choose between a pure steroid and Remember that the conjunctiva twofold: a combination drug? The answer will be inflamed in any patient 1. The severity of the infection. is relatively straightforward, but, presenting with an acute red eye. 2. The degree of conjunctival as always, there are exceptions to Simply put, the eye is red because injection. Corticosteroid/Antibiotic Combination Drugs BRAND NAME MANUFACTURER STEROID ANTIBIOTIC PREPARATION BOTTLE/TUBE Blephamide * Allergan prednisolone sodium sulfacetamide 10% susp./ung. 5ml, 10ml/3.5g acetate 0.2% Cortisporin * Monarch hydrocortisone 1% neomycin 0.35%, suspension 7.5ml polymyxin B 10,000u/ml FML-S Allergan fluorometholone 0.1% sodium sulfacetamide 10% suspension 5ml, 10ml Maxitrol * Alcon dexamethasone 0.1% neomycin 0.35%, susp./ung. 5ml/3.5g polymyxin B 10,000u/ml NeoDecadron * Merck dexamethasone 0.1% neomycin 0.35% solution 5ml Poly-Pred Allergan prednisolone acetate 1% neomycin 0.35%, suspension 5ml, 10ml polymyxin B 10,000u/ml Pred-G Allergan prednisolone acetate 1% gentamicin 0.3% susp./ung. 10ml/3.5g TobraDex * Alcon dexamethasone 0.1% tobramycin 0.3% susp./ung. 5ml/3.5g TobraDex ST Alcon dexamethasone 0.05% tobramycin 0.3% suspension 2.5ml, 5ml, 10ml Zylet Bausch + Lomb loteprednol 0.5% tobramycin 0.3% suspension 5ml, 10ml PREGNANCY CATEGORY: All drugs listed above are Category C. * = also available generically. REVIEW OF OPTOMETRY MAY 15, 2011 29A029_dg0511_combos.indd 29 5/11/11 3:58 PM
  • 32. Combination Drugs If the infection presents with ings reveal only minimal micro- prompted an investigation into a marked mucopurulence, we would particulant debris in the lacrimal “new and improved” combination likely treat with a pure antibiotic, lake; a clear, non-staining cornea; drug. such as moxifloxacin (and perhaps and/or a red eye. Here is where Thus was born Zylet. even culture if the infection was a combination product is used Keeping the highly ef- severe). If the infectious expres- mainly to address the conjunctival ficacious tobramycin, sion was only mild to moderate, inflammation, while concurrently the dexamethasone was the degree of conjunctival injection eliminating any infectious com- replaced with a newer would be the overriding issue in ponent, even when the cornea is generation, ester-based choosing between an antibiotic and uninvolved. corticosteroid, lotepre- a combination drug such as Zylet When there is significant corneal dnol. Now with Zylet, (loteprednol/tobramycin, Bausch + epithelial compromise, we almost we have excellent Lomb), TobraDex or TobraDex ST always use a combination drug. For antibiosis along with (dexamethasone/tobramycin, Al- most cases, the choice of drug class the safety and potency con), or Maxitrol (dexamethasone/ is that simple. of loteprednol. It is available in 5ml neomycin/polymyxin B, Alcon). We The first blockbuster, highly and 10ml bottles. stress again that bacterial infection effective combination antibiotic/ More recently we have is uncommon, especially relative corticosteroid was Maxitrol, con- TobraDex ST, which to the numerous expressions taining neomycin, polymyxin B contains the same of non-infectious conjuncti- and dexamethasone. Maxitrol concentration of tobra- vitis. became a real workhorse in mycin (0.3%) but half An exception is the patient primary eye care. However, the of the dexamethasone who presents with what occasional neomycin reac- (0.05%) of the origi- appears to be a low grade tion, while not a major issue, nal TobraDex. The bacterial conjunctivitis (i.e., prompted investigation into a vehicle of TobraDex minimal discharge), yet with “new and improved” combi- ST contains xanthan moderate to marked con- nation drug. gum, a thickening junctival injection. The pa- Thus was born agent that allows the lower tient usually complains that TobraDex, which concentration of the medication to the affected eye was “stuck together replaced the neomycin be as effective because it provides when I woke up.” Commonly, by and polymyxin B with a longer residence time on the the time the patient arrives at your tobramycin. This drug, ocular surfce. Indeed, at least one office, any excess debris may have like Maxitrol, enjoyed head-to head study has shown that been cleaned from the lids and market dominance, TobraDex ST has greater in vitro lashes. Further, blinking has moved though from time to bactericidal activity and higher rel- considerable mucopurulent debris time, and again not a ative tissue concentrations for the down the nasolacrimal system so major issue, intraocu- conjunctiva, cornea and aqueous that the objective slit lamp find- lar pressure increases humor compared to TobraDex.1 With these considerations in Pearls for Using Combination Drugs mind, let’s talk about specific oc- • Any time that you see any process at or near the limbus, it is inflammatory in casions when a combination drug nature. Herpetic infection can present at this area, but will typically be linear (as opposed may (or may not) be necessary. to oval) in morphology. • In any acute, unilateral red eye with a serous discharge, be sure to rule out herpetic Q: Is a bandage contact lens ap- keratitis. propriate for thermal (curling iron) • Never (or rarely) taper combination drugs below q.i.d. because subtherapeutic levels keratitis? of antibiotic set the stage for antibiotic resistance. A: It depends on the extent of • In the context of a red eye with a mild secondary iritis, instill a short-acting cyclo- tissue compromise. For deeper epi- plegic agent, particularly if a pure antibiotic is used. A combination product will generally thelial burns where there is much eliminate such an iritis without the need for a cycloplegic, though this is a fine clinical positive fluorescein staining, a point. bandage lens (any silicone hydrogel lens will work fine) along with an 30A REVIEW OF OPTOMETRY MAY 15, 2011029_dg0511_combos.indd 30 5/11/11 3:58 PM
  • 33. Combination Drugs Phlyctenular Keratoconjunctivitis (PKC) Most usually seen in young girls, this staphylococ- cal hypersensitivity response commonly targets the limbal tissues as one or two raised, whitish lesions, which stain lightly with fluorescein. However, in this case (right), the phlyctenule has migrated fully onto the cornea with a leash of fine blood vessels. (A sterile infiltrate has a clear, lucid interval between the lesion and the limbus.) A combination drug per- Curling iron burn (thermal keratitis). fectly treats these peripheral corneal lesions. While one would think staphylococcal blepharitis would always be evident, such is not antibiotic-steroid every two hours empirically the case. Certainly, if blepharitis is present, initiate proper care, but first treat to q.i.d. would be reasonable. the inflammatory keratoconjunctivitis. When there is a staining defect at the corneolim- Bear in mind that this condition bus, a prophylactic antibiotic is counterproductively conservative. is first and foremost an inflam- The key clinical feature is the inflammatory component—the eye is red. Use a combi- matory keratoconjunctivitis, and nation drug every two hours for a day or two, then q.i.d. for four to six days, and stop. the employment of a steroid (in combination with a prophylactic antibiotic) is essential to achieve Staph. Marginal “Ulcers” rapid restoration of these compro- Much more appropriately called “peripheral inflam- mised tissues. matory epithelial defects,” these are uncommon For more superficial burns, we events that have a similar pathophysiology to PKC would just use a combination drug and sterile infiltrates. without a bandage lens. In these cases, the staphylococcal exotoxins begin to erode a section of the peripheral corneal Q: What would happen if a epithelial tissues. The eye is red with accentuation corneal ulcer were treated with an of a sector of bulbar conjunctival inflammation adja- antibiotic-steroid combination? cent to the affected cornea. The foci of compromised epithelium stains brightly with fluo- A: One of many things could oc- rescein dye. There may be a few cells in the anterior chamber. The epithelium is broken cur, assuming we are talking about down as a result of the underlying anterior stromal inflammatory process, thus causing a true bacterial infection of the cor- retrograde compromise to the overlying epithelium. nea and not a sterile peripheral in- Once this subepithelial inflammation is subdued by the corticosteroid component in a filtrate. If the infection was caught combination drug, re-epithelialization is potentiated. early and the causative bacterial An antibiotic alone in this case is almost worthless. While an antibiotic can serve to were susceptible to the antibiotic, protect against opportunistic bacterial potential, it will do nothing to curb the inflamma- and if the drop were instilled every tory process. one to two hours, then the antibi- As with PKC, a combination corticosteroid/antibiotic product is perfectly suited to otic would likely overwhelm the address the inflammatory process while simultaneously guarding the cornea against the pathogen. possibility of bacterial infection. If, on the other hand, the patient Therapeutic management is as described for PKC, above. delayed in seeking care, or if the organism were suboptimally sus- quickly to make your eye better. If do in fact add a steroid q.i.d. to ceptible to the antibiotic, or if the you are not improved in a couple of help diminish corneal scarring. frequency of instillation of drops days, or if your symptoms become In summary, we encourage the was q.i.d., then disaster could be worse, be sure to come back to see reader to limit the prescribing of an in the making. The key here is to me right away.” antibiotic for the gamut of red eyes, make a firm diagnosis, choose an Of course, when treating a true and recognize that most red eyes appropriate antibiotic, and instill it corneal ulcer (which is a rare oc- are inflammatory in nature. ■ frequently. currence), we see the patient daily Finally, we tell each patient we until we are certain the condition is 1. Scoper SV, Kabat AG, Owen GR, et al. Ocular distribution, bactericidal activity and settling characteristics of TOBRADEX medically treat something like controlled. After a few days of suc- ST Ophthalmic Suspension compared with TOBRADEX this: “This medicine should work cessful antibiotic therapy, we often Ophthalmic Suspension. Adv Ther. 2008 Feb;25(2):77-88. REVIEW OF OPTOMETRY MAY 15, 2011 31A029_dg0511_combos.indd 31 5/11/11 3:58 PM
  • 34. NSAIDs Clinical Update on the NSAIDs There are four star players in the field of ‘nonsteroidal anti-inflammatory drugs.’ Older drugs have been reformulated and new drugs have come to market. ompared to topical corti- topical NSAID care over the likely be adequately served with C costeroids, NSAIDs have a limited role in primary eye care. Nonetheless, there are several past decade. Both are used q.i.d. and are largely clinical equivalents. One study com- generic diclofenac, or other less expensive NSAIDs. The original formulation of situations where NSAIDs can be pared ketorolac and di- ophthalmic ketorolac (Acu- beneficial. clofenac head-to-head. Its lar) was a 0.5% solution, but There is a partial disconnect be- conclusion: “The decrease marked stinging upon instilla- tween topical and systemic admin- in corneal sensitivity in tion was its Achilles heel. The istration. Systemic NSAIDs are true normal human corneas drug was reformulated a few to their name and do indeed render is more pronounced and years ago to a 0.4% solution a marked anti-inflammatory effect, longer lasting with diclof- (Acular LS) and is now quite whereas topical NSAIDs have enac than with ketorolac.”1 tolerable—a very nice upgrade. their forte in ocular surface The most recent modification in pain amelioration while ketorolac is the introduction of a providing some limited 0.45% concentration of ketoro- activity against inflamma- lac. Acuvail (Allergan) comes tion. (See “Uses for Topical as a preservative-free unit-dose NSAIDs,” right.) indicated for perioperative use Voltaren (diclofenac b.i.d. one day prior to cataract 0.1%, Novartis) and surgery, and is continued for Acular LS (ketorolac two weeks immediately postop. 0.4%, Allergan) have been However, Acuvail is very the standard bearers of expensive, and patients would Non-Steroidal Anti-Inflammatories BRAND NAME GENERIC NAME MANUFACTURER DOSAGE PEDIATRIC USE BOTTLE SIZE(S) Acular LS ketorolac tromethamine 0.4% Allergan q.i.d. 3 years 5ml Acuvail ketorolac tromethamine 0.45% Allergan b.i.d. N/A unit-dose Bromday bromfenac 0.09% ISTA Pharmaceuticals q.d. N/A 1.7ml Nevanac nepafenac 0.1% Alcon t.i.d. 10 years 3ml Voltaren diclofenac sodium 0.1% Novartis q.i.d. N/A 2.5ml, 5ml 32A REVIEW OF OPTOMETRY MAY 15, 2011032_dg0511_NSAIDs.indd 32 5/11/11 4:00 PM
  • 35. NSAIDs In the recent past, two more NSAIDs have come to market. They are Nevanac (nepafenac 0.1%, Alcon) and Bromday (brom- fenac 0.09%, ISTA), which replaces twice-daily Xibrom (bromfenac 0.09%, ISTA). Nevanac is unique in that it is the first avail- able prodrug. Nevanac is enzymatically con- verted to amfenac sodium, which, like all NSAIDs, inhibits cyclooxygenase. It is dosed three times a day. Bromday is unique in that it is the first approved NSAID that is administered only once An extensive review of the world literature concludes that prevention and treatment of daily, which should cystoid macular edema with NSAIDs is beneficial. likely aid compliance. (Incidentally, ISTA is evaluating a new Q: Which NSAID do you prefer for Uses for Topical NSAIDs formulation and dampening ocular surface pain, and at The most common conditions for which lower concentrations what dosage? topical NSAIDs can play an adjunctive of bromfenac called A: Our preference is Bromday (brom- beneficial role are: Remura for the poten- fenac, ISTA) because it has a long half- • Corneal abrasions tial treatment of dry life, and therefore needs to be dosed only • Just before, and just after, in-office eye, which is now in once daily. However, it is very expensive. Betadine 5% Sterile Ophthalmic Prep Phase III clinical studies.) So, when cost is a concern, we use Solution treatment for highly symp- All these drugs are generally generic diclofenac q.i.d., because it is tomatic EKC approved by the FDA for treating inexpensive and works well. • Post foreign body removal postoperative inflammation, and as • Adapting to GP contact lenses such, will be used much more in a with Pred Forte. • Post anterior stromal puncture proce- surgical context. Ketorolac is also While steroids are often initially dure approved to treat ocular allergy, dosed as frequently as hourly for • Post PKP, or any surface disruptive and there are a number of other a few days, we strongly urge that laser procedure applicable uses for NSAIDs relevant NSAID use not exceed the FDA- • Treating and/or preventing cystoid to primary eye care, as enumerated approved dosing frequency. macular edema above. • Adapting to punctal plugs Because of the rare, but real, In summary, there are several off- • Allergic conjunctivitis potential for corneal toxicity and label uses for NSAIDs within the • Supplemental to steroids in treating melting, these drugs should be used context of primary eye care. Their recalcitrant uveitis cautiously when there is preexisting main use is in the prevention or • Some cases of photophobia corneal epithelial compromise. As treatment of cataract surgery-relat- • Post cataract surgery care a general rule, we never prescribe ed cystoid macular edema concur- • Supplemental to oral NSAIDs in treat- any topical NSAID for use beyond rent with a potent corticosteroid. ■ ing scleritis one week—with the exception of • Treating and/or preventing inflamed 1. Seitz B, Sorken K, LaBree LD, et al. Corneal sensitivity CME, which we treat with a topical and burning sensation. Comparing topical ketorolac and pterygia and pingueculae NSAID for a month, concurrent diclofenac. Arch Ophthalmol. 1996 Aug;114(8):921-4. REVIEW OF OPTOMETRY MAY 15, 2011 33A032_dg0511_NSAIDs.indd 33 5/11/11 4:00 PM
  • 36. Keeping Allergy Management Simple Allergy management can be straightforward. For ocular itching, use OTC ketotifen. If there are also signs, add a steroid to quiet the eye. cular allergy treatment is the enzyme cyclooxygenase (which but we think that one of the later O pretty straightforward: Treat with a topical (preferably OTC) antihistamine/mass cell sta- catalyzes the syntheses of prosta- glandins). So we see no reason why this would not be a class effect. generation antihistamine/ mast cell stabilizers would be an excellent choice to bilizer if the eye is white and quiet, However, inhibiting the synthesis treat any and all types of and symptomatic itching is the of prostaglandins in the setting allergy expressions. chief complaint. If there are signs, of a histamine-mediated clinical such as conjunctival injection with condition is relatively counterintui- Q: Did you say that or without chemosis accompanying tive to the use of a topical antihis- the OTC vs. Rx allergy the itching, then prescribe lotepred- tamine. We long ago abandoned drops work the same? nol either 0.2% or 0.5% depending the use of NSAIDs in favor of the A: There are two main upon the magnitude of the disease antihistamine/mast cell stabilizing types of OTC allergy eye drops: the expression. drugs when treating ocular allergy. antihistamine/vasoconstrictors, Making more of this condition But, to your specific question, the such as Naphcon-A, Opcon- and its treatment is like trying to answer is an untested “yes.” A, etc., and the antihista- make a mountain out of a molehill. mine/mast cell stabilizers We have many topical Q: I was told Emadine (emedas- represented by ketotifen, allergy options to choose tine, Alcon) was the drug of choice of which there are numer- from, and we now add one for pet allergies. What is your ous brand names such as more: Lastacaft (alcaftadine opinion about this? Zaditor (Novartis), Alaway 0.25%, Allergan), which A: Emadine is the only pure oph- (Bausch + Lomb), Claritin has the benefit of once-daily thalmic antihistamine in the United Eye (Schering-Plough), dosing. Alcaftadine is a new States market; all the others also Refresh Allergy (Allergan), etc. chemical entity with an af- have mast cell stabilizing proper- Because the older antihis- finity for H1, a histamine re- ties. The key to suppressing al- tamine/vasoconstrictors are ceptor associated with the early lergy is to block the H1 (hista- short-acting and cause blood phase of allergic conjunctivitis. mine subtype I) receptor. This vessel constriction, rebound Now that we know our options, terminates the cellular processes hyperemia can oc- let’s look at our challenges. that result in itching. Since both cur—similar to the Emadine and all the other anti- chronic use of nasal Q: Can any of the topical histamine eyedrops perform this decongestants such as NSAIDs other than ketorolac task, it is likely advantageous to Afrin—so these are not (Acular LS, Allergan) be used for use a medicine that also stabilizes recommended. Indeed, it treating ocular allergy? the mast cell membranes. Because has been our experience A: All the NSAIDs, both topi- there are no head-to-head studies, that chronic use of these cal and oral, work by inhibiting we cannot say with total certainty, eye drops is a fairly com- 34A REVIEW OF OPTOMETRY MAY 15, 2011034_dg0511_allergy.indd 34 5/11/11 4:05 PM
  • 37. Allergy Drugs mon cause of chronic conjunctivitis. value to the patient. Prescription and not vernal disease. A young Our observation is that most of the bepotastine (Bepreve, ISTA) and child with severe allergy most likely chronic users have primary dry eye, OTC ketotifen (specifically Alaway) also has allergic rhinitis or sinusitis, which leads to secondary low-grade are both available in 10ml bottles so your care may need to be done conjunctival injection, which results (compared to 5ml bottles for the in concert with his/her primary care in the patient behavior of purchas- others), and therefore would offer physician or allergist. We suggest ing OTC “get-the-red-out” type the greatest value to our patients. cold compresses for flare-ups, but eyedrops. These two medicines, and the other medical therapy would have to be Regarding the more contempo- antihistamine/mast cell stabiliz- initiated with loteprednol 0.5%, rary antihistamine/mast cell sta- ers, can be used b.i.d. for a week perhaps as often as every two bilizing drops, their performances or two; after that time, once-daily hours for two or three days to gain are all extremely similar; in our administration can usually main- control, then try q.i.d. for a week. experience, there is no clinically tain absence of itch for virtually Once control is firmly established, significant difference between the all patients. Especially for patients try reducing to the 0.2% concentra- OTC antihistamine/mast cell who are not on a prescription tion of loteprednol (Alrex) q.i.d. for stabilizing drops and those that drug plan, the 10ml Alaway is a week, then b.i.d. for two weeks. If still require a prescription. the most cost-effective topical this holds, then try converting to an Given this, we look to the ophthalmic antihistamine/mast antihistamine/mast cell sta- cost of these medicines, and cell stabilizer. bilizing drug for enduring because ketotifen is OTC and therapy on a p.r.n. basis. very inexpensive, we routine- Q: Comment on treating a We would recommend ly recommend it. Within both child under age 10 with severe OTC ketotifen, because prescription and OTC options, ocular allergy. Steroids? it is the least expensive of bottle size is another consideration A: We will assume you’re speak- the antihistamine/mast cell that has a marked impact on the ing of seasonal/perennial allergy, stabilizing drugs. ■ Ocular Allergy Medicine Profile BRAND NAME GENERIC NAME MANUFACTURER PEDIATRIC USE BOTTLE SIZE(S) DOSING Acute Care Products Acular LS ketorolac tromethamine 0.4% Allergan 3 years 5ml, 10ml q.i.d. Alaway (OTC) ketotifen fumarate 0.025% Bausch + Lomb 3 years 10ml b.i.d. Alrex loteprednol etabonate 0.2% Bausch + Lomb 12 years 5ml, 10ml q.i.d. Bepreve bepotastine besilate 1.5% ISTA 2 years 10ml b.i.d. Claritin Eye (OTC) ketotifen fumarate 0.025% Schering-Plough 3 years 5ml b.i.d. Elestat epinastine HCl 0.05% Allergan 3 years 5ml b.i.d. Emadine emedastine difumarate 0.05% Alcon 3 years 5ml q.i.d. Lastacaft alcaftadine 0.25% Allergan 2 years 3ml q.d. Optivar azelastine hydrochloride 0.05% Meda 3 years 6ml b.i.d. Pataday olopatadine hydrochloride 0.2% Alcon 3 years 2.5ml q.d. Patanol olopatadine hydrochloride 0.1% Alcon 3 years 5ml b.i.d. Refresh (OTC) ketotifen fumarate 0.025% Allergan 3 years 5ml b.i.d. Zaditor (OTC) ketotifen fumarate 0.025% Novartis 3 years 5ml b.i.d. Chronic Care Products Alamast pemirolast potassium 0.1% Vistakon Pharm. 3 years 10ml q.i.d./b.i.d. Alocril nedocromil sodium 2% Allergan 3 years 5ml b.i.d. Alomide lodoxamide tromethamine 0.1% Alcon 2 years 10ml q.i.d. Crolom cromolyn sodium 4% Bausch + Lomb 4 years 10ml q.i.d. Opticrom cromolyn sodium 4% Allergan 4 years 10ml q.i.d. REVIEW OF OPTOMETRY MAY 15, 2011 35A034_dg0511_allergy.indd 35 5/11/11 4:05 PM
  • 38. Overview of Oral Medicines Optometrists in 47 states have at least some authority to prescribe oral drugs. Now, it is our task to prescribe thoughtfully and appropriately. here are few oral medicines T germane to ophthalmic pa- tient care. The classes most commonly used are antibiotics, corticosteroids, antivirals, analge- sics and carbonic anhydrase inhibi- tors. Because oral therapy is becoming more widely embraced by doctors of optometry, we want to examine the clinical attributes of these medi- cines by answering some questions Can oral azithromycin take the place of oral doxycycline for the treatment of we have been asked regarding oral meibomian gland dysfunction? Our dermatologist says to stick with doxy. therapies. Q: The corneal subspecialist we Last, keep in mind that mei- Q: When using doxycycline on work with just came back from a bomian gland dysfunction, like a chronic basis, are you concerned cornea conference where she heard dandruff and arthritis, can be with killing off the “good bacteria” of using azithromycin 250mg b.i.d. managed, but not “cured.” Many in the gut? Do you recommend or t.i.d. for a week, instead of oral chronic disease processes require a probiotic to replace the “good doxycycline for the treatment of daily, weekly or monthly therapeu- bacteria”? lipid (posterior) blepharitis. tic maintenance. A: As a general rule, when A: We have heard of this a time treating an active infection with or two ourselves. So we consulted Q: Let’s say you have a recalci- doxycycline, the dosage is 100mg several dermatologists to learn that trant case of anterior uveitis, where b.i.d. When attempting to improve doxycycline has many more clini- a potent topical steroid and good meibomian gland function, we use cally apparent anti-inflammatory cycloplegia failed to suppress the “sub-antibiotic” levels, such as properties than azithromycin. Of inflammation, and you have to 50mg/day. This should spare, or all medical specialists, dermatology augment your therapy with oral minimally alter, the gut flora. should be the most knowledgeable prednisone to achieve successful For those sensitive patients who about how to positively affect intra- suppression of inflammation. You do encounter GI problems with the epidermal glandular secretions. Ask now begin your oral taper, and oral doxycycline, we would suggest any dermatologist: Doxycycline when you drop below 20mg of oral the patient try an OTC probiotic. reigns supreme in enhancing seba- prednisone, even with the continu- Be sure to instruct the patient to ceous gland function (and meibo- ation on hourly topical steroid eye- take the doxycycline with a meal, mian glands are modified sebaceous drops, the uveitis re-flares. Do you preferably breakfast. glands). have a way to facilitate the taper 36A REVIEW OF OPTOMETRY MAY 15, 2011036_dg0511_orals.indd 36 5/11/11 4:09 PM
  • 39. Oral Drugs Acute internal hordeolum being For an internal hordeolum, very warm When an oral antibiotic is necessary for decompressed via gentle pressure by a soaks with a moist washcloth are usually an infectious hordeolum, we generally cotton swab. all the treatment needed. prescribe Keflex 500mg b.i.d. for a week. and ultimate discontinuation of the pharmacist to have them aid us in fluoroquinolone, such as Levaquin oral prednisone? determining the pediatric dosage. (levofloxacin) 500mg once daily, A: That’s a complex, really chal- We also might choose a liquid as or trimethoprim/sulfamethoxazole lenging case! Here’s what we would opposed to a pill if the child cannot (Bactrim or Septra) 1 or 2 (Double- do: As you taper the prednisone to swallow pills easily. All the above Strength) tablets b.i.d for one the point that you reach the 20mg mentioned drugs are also available week. dose, then add Celebrex (celecoxib, in liquid form. Pfizer) 100mg or 200mg/day or Q: If a patient has a history of an ibuprofen 1,600mg/day. Then we Q: What oral medicine do you anaphylactic reaction to aspirin, is have been successful in tapering generally use, if any, for acute eye- the use of another NSAID contrain- off and stopping the oral steroid. lid infections? dicated? We keep up the oral NSAID for A: In our clinical experience, A: Yes! Aspirin is the prototypic another two weeks as we methodi- about 25% of patients presenting NSAID, and they all share similar cally taper down the topical drops. with acute hordeola (or styes) re- antigenic properties. All NSAIDs Obviously, this is a scientific quire oral antibiotic therapy in ad- work by inhibiting the enzyme “guessing game” of just how to do dition to the aggressive use of warm cyclooxygenase, which catalyzes the this, and must be guided by each soaks—warm soaks constitute production of prostaglandins from individual patient’s response, but the foundational underpinning of arachidonic acid. the general concept should be clear. therapy for any infectious process Patients who are this difficult to involving the eyelids. Penicillin and Cephalosporin treat successfully should have a We urge patients to apply a Cross-sensitivity rather exhaustive systemic workup. very warm, moist washcloth to the • Both penicillins and cephalosporins infected lid (or lids) five to 10 min- possess a beta-lactam ring. Q: What do you prescribe for utes at a time, and to repeat this • “Cephalosporins are first-line treat- children with a hordeolum, and at every couple of hours, as able. We ments for many infections and are used what dosage? stress that about every 30 seconds, widely in ophthalmology.” A: Most acute meibomian gland the cloth will need to be quickly • “More than 90% of patients who infections can be managed with reheated and reapplied to the eyelid report a history of penicillin allergy lack properly administered warm soaks. to keep the heat level at a therapeu- penicillin-specific IgE and can tolerate If the eyelid has been worsening, tically sufficient level. the antibiotic safely.” and if it is particularly tender, then When an oral antibiotic is • Penicillin allergy “should not prevent we recommend either erythromy- deemed appropriate, we gener- the use of second- and third-generation cin, Keflex (cephalexin), or trim- ally prescribe Keflex (cephalexin) cephalosporins with distinct side chains.” ethoprim with sulfamethoxazole. 500mg b.i.d. for a week. This is These are cefuroxime, cefprozil, ceftazi- The dosage can vary depending almost always successful. dime and cefpodoxime. upon the severity of the condition If the patient is truly allergic to Wykoff CC, Flynn HW Jr, Han DP. Allergy to povidone- and the age of the child. penicillin (which shares a slight [5 iodine and cephalosporins: the clinical dilemma in We always consult with a to 8%] potential cross-allergenic- ophthalmic use. Am J Ophthalmol. 2011 Jan;151(1):4-6. pediatrician, family physician or ity), we might prescribe an oral REVIEW OF OPTOMETRY MAY 15, 2011 37A036_dg0511_orals.indd 37 5/12/11 10:14 AM
  • 40. Oral Drugs A: Zoster tends to have accompa- strength of the oral antiviral—acy- nying skin pain, whereas simplex is clovir 800mg taken 5qd, valacy- relatively painless. The skin lesions clovir 1,000mg t.i.d. or famciclovir of simplex tend to cluster around 500mg t.i.d. Regardless of the drug the eyelid skin, whereas zoster le- you choose, it should be taken for sions are larger and tend to be more one week. Any of these medicines distributed throughout the targeted will nicely treat either herpes sim- dermatome. plex or herpes zoster infection. If you are unsure about the diag- However, if you are confident nosis, just use the varicella zoster the infection is simplex (and the dis- Primary herpes simplex periorbital dermatitis. To Treat Shingles (VZV), Give Double the Dose Used for HSV Dosing for Dosing for Q: What most helps you dis- Antiviral Drug Varicella Zoster Herpes Simplex tinguish between herpes simplex Acyclovir 800mg 5x q.d. x 1 week 400mg 5x q.d. x 1 week dermatitis and varicella zoster Valacyclovir 1,000mg t.i.d. x 1 week 500mg t.i.d. x 1 week dermatitis in a patient who is 40 Famciclovir 500mg t.i.d. x 1 week 250mg t.i.d. x 1 week years old? Perspective on Nutritional Supplements smokers, it is being replaced in some supplements. Also, lutein Face it: Many Americans have suboptimum lifestyles. Have you and zeaxanthin have been shown to increase macular pigment ever pondered how many billions of health care dollars could be optical density, which can improve visual function, flare recovery saved each year if we all would collectively improve our health- and contrast sensitively. From all we can read, fish oils (preferably related lifestyles? It is well-established that cigarette smoking is the triglyceride form) are clearly beneficial to health, and particu- only second to increased age as a risk factor for macular degener- larly to eye health. These fish oils contain therapeutic levels of EPA ation; one is modifiable, one is not! The acknowledgement of this and DHA, which have been shown to be helpful in both macular reality is why we daily encourage our smoking patients to have function as well as enhancing meibo- a sincere conversation with their primary care provider regarding mian gland function. programs and medicines to help them stop. We all need to redou- It will be interesting to see the ble our “encouragement” conversations with our smoking patients. results of the AREDS 2 study when Smoking is also known to be a risk factor for ulcerative keratitis. it concludes around 2013. From a Since we are not experts in nutrition—and extremely few physi- consensus of the literature, the com- cians are—we are not going to attempt to discuss the molecular bination of vitamins C and E, some basis of nutrition here. We will succinctly discuss the clinically- zinc, the carotenoids lutein and zea- relevant issues at hand. Realizing the exceedingly poor yield on xanthin, and the long-chain essential impacting lifestyle changes, we should still encourage patients to fatty acids EPA and DHA may have a try to be attentive to what they eat and how they live. keenly therapeutic impact on both the Being realists, we find that many people do indeed have a keen prevention and treatment of AMD. For interest in “buying health.” For example, we had a patient recently appropriate patients, it seems rational who said he can now enjoy his cheeseburgers since he’s on a to recommend a supplement contain- statin drug! This is the mindset we are talking about. ing these ingredients, until further Perhaps this partially explains the public’s embrace of nutri- research reveals perhaps even more tional supplements. This topic can be immensely complex. We effective interventions. don’t do complex. Here’s a consensus of what is known regarding As with any supplements taken by nutrition and the eye. Oxidative stress appears to be the underpin- mouth, it is good practice to make ning of tissue demise. Therefore antioxidants, such as vitamins C the patient’s primary care provider and E, the carotenoids lutein, zeaxanthin, along with some zinc, aware of the specifics of any supple- and the essential fatty acid constituents, eicosapentaenoic acid ment we are asking our patients to (EPA) and docosahexaenoic acid (DHA), seem to share the lime- take. light in the articles we read. Since beta-carotene seems relatively suboptimum to lutein/zeaxanthin in its antioxidant properties, and because of its association with increased risk of lung cancer in 38A REVIEW OF OPTOMETRY MAY 15, 2011036_dg0511_orals.indd 38 5/12/11 10:16 AM
  • 41. Oral Drugs tinction is usually straightforward), then use one-half Vitamin D Protects Against AMD in Women the zoster dose as set forth above. “Among women younger than 75 years, intake of vitamin D from foods and supplements was related to decreased odds of early Q: Is herpes zos- AMD in multivariate models; no relationship was observed with ter contagious? self-reported time spent in direct sunlight. A: Only if a “Conclusion: High serum 25(OH)D concentrations may protect person has never against early AMD in women younger than 75 years.” had chickenpox Millen AE, Voland R, Sondel SA, et al; for the CAREDS Study Group. Vitamin D status or the Varivax and early age-related macular degeneration in postmenopausal women. Arch Ophthal- vaccine (varicella mol. 2011;129(4):481-489. zoster live vac- cine, Merck) is there any risk to Healthy Lifestyles Reduce Risk for Early AMD contract the virus. Shingles (i.e., herpes zoster) is not Even in these “at usually contagious. risk” persons, the risk is very slight, and even then only if there is direct skin-to-skin contact with open lesions. Q: I had a patient with chlamydial conjunctivitis, and I am convinced it wasn’t sexually transmitted. She recalled handling feral kittens with goopy eyes a few weeks previously. Could the chlamydia have been transmitted by handling those kittens? A: It’s possible. Cats can become infected with a form of chlamydia, and in rare instances it can be “A combination of healthy lifestyle behaviors that includes healthy transferred to humans. Perhaps the best way to find out diet, physical activity, and not smoking was associated with is to treat with a single 1gm dose of oral azithromycin, markedly lowered prevalence of early AMD an average of six and if the patient is much improved in about three years later in postmenopausal women. Adopting these healthy days, your etiologic suspicion will be substantiated. If habits may markedly lower the prevalence of early AMD, the she gets a recurrence weeks to months later, there had number of people who develop advanced AMD in their lifetime, better be a wild cat to blame! and health care costs associated with treatment for this condition. Lastly, parakeets also commonly carry chlamydial “These results also serve to remind us that risk for AMD is organisms that can cause a conjunctivitis identical to passed to subsequent generations not only through genes but that seen with sexually transmitted disease, so always also possibly through the lifestyle habits we model and encour- be sure to inquire about parakeet exposure in your age. Specifically, we believe that these results, together with history. ■ current scientific evidence for chronic disease prevention, support recommendations to exercise (move at least at a low intensity for one to two hours per day; outside when possible), avoid smok- ing, and follow a healthy diet pattern that meets the following criteria: (1) is abundant in plant foods (vegetables [including dark leafy green and orange vegetables], fruits and whole grains); (2) contains daily protein sources in moderation and variety (beans, nuts, fish, dairy, eggs, meat and poultry); and (3) limits food high in sugar, fat, alcohol, refined starches and oils. “Conclusion: Modifying lifestyles might reduce risk for early AMD as much as three-fold, lowering the risk for advanced AMD in a person’s lifetime and the social and economic costs of AMD to society.” Mares JA, Voland RP, Sondel SA, et al. Healthy lifestyles related to subsequent preva- A patient with chlamydial conjunctivitis. Could a stray cat be to lence of age-related macular degeneration. Arch Ophthalmol. 2011 Apr;129(4):470-80. blame? Or perhaps a parakeet? REVIEW OF OPTOMETRY MAY 15, 2011 39A036_dg0511_orals.indd 39 5/12/11 10:14 AM
  • 42. Questions and Answers From the Trenches There are only a handful of oral medicines germane to eye care. Fortunately, O.D.s in most states can now prescribe most of these oral medicines. n our roles as optometrists and I educators, we receive many interesting questions by letter, by e-mail, and from our colleagues at our lectures. We have selected numerous questions to answer here that we believe will benefit other clinicians who are in “the trenches” caring for patients every day. Q: I seem to get a lot of calls from patients about the cost of pharmaceuticals. Do you see this in your practice, and do you often call in substitute meds? A: We try to be cost-conscious Iris synechia as seen in acute anterior uveitis. when prescribing. There are times when we reluctantly allow a generic alternate a very inexpensive generic We would specifically prescribe switch by the pharmacist. We say (trimethoprim with polymyxin B) an ester-based corticosteroid (i.e., “reluctantly” because we have along with a fluoroquinolone, and loteprednol) because there is no already exercised clinical judgment have the patient use the fluoroqui- other steroid with which we are when initially prescribing, so had nolone drop every two hours, and comfortable with patients using we felt a generic (or an alternate the trimethoprim with polymyxin for perhaps two to three months. medicine) would be permissible, we B every two hours. In this man- The key to many aspects of patient would have written for it in the first ner, the patient is instilling a drop care, including the cost issues, is place. Still, as clinicians, we need every hour. This gives maximum adequate communication with the to be aware of the cost of various antibiotic firepower while using patient. medicines, so that we can counsel two different medicines with two patients about the costs before they different mechanisms of action…in Q: What cycloplegic do you present to the pharmacy. When the event of resistance to one or the generally prefer for patients whose treating a serious external infection, other. Such aggressive prescribing is uveitis is accompanied by aggres- for example, we might prescribe rarely indicated, though. sive posterior synechiae? Besivance, Zymaxid or Vigamox, Another example of cost-control A: We tend to use 1% atropine and would not want a potentially vs. efficacy is in the initial control q.i.d., along with Durezol q2 hours. less effective substitute. of ocular surface inflammation At follow-up visits, we may instill But in some cases, we might associated with dry eye disease. a drop or two of 10% or 2.5% 40A REVIEW OF OPTOMETRY MAY 15, 2011040_dg0511_Q&A.indd 40 5/11/11 4:26 PM
  • 43. Q&A phenylephrine, just to do our best to break the synechiae. Almost invariably, once the steroid and the anticholinergic drops are used aggressively as outlined above, the synechiae resolve. Q: Do you use homatropine 2% in juvenile patients instead of the 5% concentration when therapeutic cycloplegia is indicated? A: Rather than use the 2% concentration q.i.d., we would typi- cally go with the 5% concentration b.i.d. This is close to being clinically equivalent with a more patient- friendly dosing schedule. Source: Duszak RS, Duszak R Jr. Malpractice payments by optometrists: an analysis We would build upon this of the national practitioner databank over 18 years. Optometry. 2011 Jan;82(1):32-7. question by pondering the steroid dosing in a juvenile with anterior The main reason optometrists are successfully sued is “failure to diagnose,” not for uveitis. We would still use a potent actively providing medical care. steroid such as Durezol, Lotemax or brand name Pred Forte fre- and care must be individualized for A: Simply hold the foreign body quently (q2 hours for Lotemax or each of our patients. The majority removal instrument at the ocular Pred Forte, or q.i.d. for Durezol, of eye care patients have excellent surface near the foreign body, since its emulsion formulation clinical outcomes when established and as the patient’s eye saccades allows for a longer ocular surface standards-of-care are followed. But around, the foreign body will even- residence time) until the inflamma- even in the best of hands, patients tually hit the instrument and pop tion is brought under control, then occasionally do poorly. Such is life. out… Just kidding! taper off as indicated. The typical Our duty is to provide the best care We find such situations as stress- decision regarding frequency of possible. If this standard is hon- ful as anyone else. What we do is instillation lies in the severity of the ored, successful litigation is rare. repeatedly urge and encourage the condition, more than the age of the For perspective, it is well es- patient to look at a fixation point— patient. tablished that the main reason the overhead light, the top of our optometrists are successfully sued ear, or any suitable target. During Q: Regarding clinical care, how is “failure to diagnose,” not for the brief moment of steady gaze, we do we know that doing the “right actively providing medical care. Ex- act quickly to dislodge the foreign thing” is right in a climate where amples include not diagnosing giant body. there are so many lawyers and cell (temporal) arteritis, missing a Once the foreign body is re- people sue at the drop of a hat? retinal tear in the setting of an acute moved, we enthusiastically pro- A: This is a common question symptomatic posterior vitreous claim that the offending object is that is asked across the health pro- detachment, missing glaucoma, etc. now out, the worst is over, and fessions. The basic answer is that Our advice? Know your stuff; now we are going to clean out a it is our duty and responsibility to focus on helping the patient; keep little bit of the rust, and that will be provide our patients with state-of- good, legible patient records; and it. Just like in primary care medi- the-art, competent care. Contem- don’t waste time looking over your cine, a good part of what we do porary reference texts, such as the shoulder. involves a lot of psychology. Wills Eye Manual or the Mas- sachusetts Eye and Ear Infirmary Q: What is the best technique for Q: How do you tell papillae from Illustrated Manual of Ophthal- removing a corneal foreign body follicles, and which one is present in mology, can provide this general when a patient cannot keep the eye bacterial, viral and allergic conjunc- foundation. Medical care is an art, steady? tivitis? REVIEW OF OPTOMETRY MAY 15, 2011 41A040_dg0511_Q&A.indd 41 5/11/11 4:26 PM
  • 44. Q&A A: Technically, papillae have a single vessel in the center, whereas follicles have micro-fine telangiec- tatic vessels that course over the mound of tissue. In clinical prac- tice, such distinction is minimally relevant because so many other features characterize the condition. The only exception to this is in chlamydial infection, in which giant follicles in the inferior forniceal conjunctiva pathognomonically seal the diagnosis, as the giant-sized bumps seen with this condition are Here are two classic phlyctenules that straddle the limbal border. more useful than the histological morphology. such as levofloxacin (Levaquin), for Q: What characteristically differ- one week. entiates a corneal phlyctenule from Q: How do you differentiate a peripheral marginal ulcer? contact dermatitis from preseptal Q: How do you distinguish an A: The corneal phlyctenular cellulitis? intraepithelial infiltrate from a lesion will have a leash of blood A: Contact dermatitis itches, and subepithelial infiltrate? vessels associated with it, whereas one can commonly see subtle or A: Generally speaking, intraepi- there is a clear, lucid interval obvious flaking of the epidermis thelial lesions will stain (usually between the sterile peripheral ulcer of the eyelid skin. In the setting of lightly) with vital dyes, in contrast and the limbus. cellulitis, the area is tender (often to subepithelial lesions, which do hurts), and does hurt with percus- not stain at all. Examples: the sub- Q: There are many techniques; sion. Cellulitis is an active bacterial epithelial infiltrates associated with how do you apply a pressure patch? infection, thus the skin feels hot. epidemic keratoconjunctivitis do A: We use the small sized It generally starts out more focal not stain; the intraepithelial lesions Johnson & Johnson eye pads (as and then spreads as the infection seen during the active phase of Thy- opposed to the large size). We use spreads. geson’s SPK will stain lightly. two pads; the first we fold in half like a taco and use it to fill in the Q: Can Thygeson’s SPK be con- ocular sulcus (with the patient’s fused with contact lens overwear? eyes fully closed). Then we place an Or is there a contact lens cause of unfolded pad on top of the folded Thygeson’s? pad, and tape them firmly (but not A: Yes, and no. Thygeson’s is too tightly) using four 5-inch strips bilateral 80% of the time, whereas of 1-inch-wide 3M or similar tape. acute overwear (CLARE) is almost Make sure the eyelid is completely Contact dermatitis itches, and shows always unilateral. However, there closed before affixing the tape. flaking of the eyelid skin. are those problematic contact lens When we do patch, which is rare, wearers who present with bilat- we always do so with an antibiotic Contact blepharodermatitis is eral, semi-diffuse, enduring SPK. ointment instilled into the eye first. treated with topical or oral corti- Consider a different contact lens While patching fell out of common costeroids and cold compresses, material for these patients, change use in the 1990s (because it was whereas cellulitis is treated with to a hydrogen peroxide system, discovered that most corneal abra- warm soaks and oral antibi- reduce wearing time, and rule sions heal just as well without the otic, such as cephalexin (Keflex), out a subnormal tear film. Do a time, trouble and aggravation of a amoxicillin with clavulanic acid trial with 0.2% loteprednol. If it is patch), we still patch most of our (Augmentin), trimethoprim with Thygeson’s, the cornea will clear in larger and more painful abrasions, sulfamethoxazole (Bactrim or just a few days; that will answer the usually over erythromycin or Poly- Septra), or an oral fluoroquinolone etiologic question. sporin ophthalmic ointment. 42A REVIEW OF OPTOMETRY MAY 15, 2011040_dg0511_Q&A.indd 42 5/11/11 4:26 PM
  • 45. Q&A Q: What instruments do you use for corneal debride- ment? A: Corneal debridement is usually performed in association with a fresh corneal abrasion when there are sheets of torn epithelium, or very irregular flaps of epithelium at the lesion margin. We grab these rough edges, or sheets, with jewelers’ forceps and tear them circumferentially (in an arc pattern) and in toward the center of the abrasion. This cleaning of the abrasion margins prepares the surrounding intact epithelium for maximum re-epithelialization and healing. We use sterile cotton swabs, or Weck cell sponge devices when broader, more extensive debridement (such as for a deep epithelial thermal burn or multiple small foreign How do you apply a pressure patch? First, instill an antibiotic bodies) is indicated. A #15 Beaver blade could be used ointment into the eye. Then, take a large-size eye pad, fold it in as well. half like a taco, and use it to fill in the ocular sulcus (with the patient’s eyes fully closed). Q: Do you run into problems with local pharmacies not stocking your favorite meds? No pharmacy in my area stocks dicloxacillin anymore—it’s all special order. A: The most common shortcoming we have expe- rienced over the years has been trifluoridine’s (Virop- tic) availability. Such antivirals are not “high-need” medicines, and the requirement for refrigeration may be another reason why it is not always available. (We anticipate this problem will be obsolete with the advent of non-refrigerated Zirgan.) It is always nice to have samples of medicines on hand that can bridge the ther- apeutic gap for 24 hours—the time it takes for most any pharmacy to get most any drug. Note that there are samples available only for brand-name protected medicines, not generics. Next, place an unfolded pad on top of the folded pad. Regarding your specific question: dicloxacillin is a perfectly noble antibiotic, but has been generic for two decades, and most physicians may well be unfamiliar with this medicine—thus is it not often prescribed. What we do is try to prescribe medicines that are more commonly used, as these are readily available. In lieu of prescribing dicloxacillin 250mg q.i.d., we would prescribe cephalexin (Keflex) 500mg b.i.d. for one week. Cephalexin has a nearly identical spectrum of activity, a less frequent dosing administration, and is also very inexpensive. This is an example of where one’s favorite drug may need to be put aside for a medicine that is simply more readily available. Q: Prior to punctal irrigation, what drops or oint- ment would you recommend for chronic epiphora? A: We have learned over the years that a combina- Last, tape the pads firmly (but not too tightly) using four 5-inch tion antibiotic-steroid q.i.d. for a week or two resolves strips of 1-inch-wide 3M or similar tape. Make sure the eyelid about half of such cases. If after seven to 14 days of is completely closed before affixing the tape. medical treatment, the condition persists, then nasolac- REVIEW OF OPTOMETRY MAY 15, 2011 43A040_dg0511_Q&A.indd 43 5/11/11 4:26 PM
  • 46. Q&A A highly magnified view if the needle tip used to perform ASP. Acute recurrent corneal erosion, as in a patient with epithelial basement membrane dystrophy (EBMD), is treated with anterior stromal micropuncture (ASP). The corneal surface post-ASP. rimal irrigation is indicated. This a bandage/therapeutic soft contact and the clinical circumstances, we can be accomplished by the optom- lens, and prescribe an antibiotic would either perform ASP that day, etrist, a general ophthalmologist or such as generic tobramycin or tri- or just treat the acute abrasion in an oculoplastics subspecialist. methoprim/polymyxin B q.i.d. for standard manner with 50mg of oral When doing nasolacrimal irriga- three or four days. doxycycline for a month and con- tion, we would not pre-medicate We see the patient back in three currently prescribe Lotemax q.i.d. because the drops would just get to four days, at which time we gen- for a month. washed away. However, after the erally remove the soft contact lens Both the procedural technique procedure, we commonly prescribe and keep the eye lubricated with a (ASP) and the medical approach an antibiotic-steroid drop q.i.d. for lipid-based artificial tear during the (as outlined above) are largely a week. day, and a lubricant eye gel at bed- curative, and bring great relief to time, for two to four weeks. ASP is patients. The ASP is a quicker fix, Q: Can anterior stromal mi- generally curative. but as long as the patient tolerates cropuncture (ASP) be performed the doxycycline well, the medical when there is an acute occurrence Q: When do you decide to approach is perfectly prudent. Only of recurrent corneal erosion, as in actively treat a recurrent corneal under very unusual circumstances a patient with epithelial basement erosion? And, how do you decide would we ever do both. membrane dystrophy (EBMD)? on performing ASP vs. treating Because most cases of recurrent A: Yes. Regardless of the origin medically with oral doxycycline corneal erosion heal with conserva- (old traumatic abrasion, EBMD or and loteprednol? tive approaches, such as lubricating spontaneously idiopathic), ASP can A: If a patient has had a previ- eyedrops by day and either GenTeal be applied at the time of the acute ous injury from a fingernail, paper gel or a lubricating ointment at presentation. If there is even a day’s cut or other sharp object (as sharp bedtime for six weeks (the typical delay, the epithelium can heal, and objects tend to penetrate through healing time for basement mem- therefore be a real challenge to Bowman’s membrane, which then brane tissues), we only initiate know exactly where to apply the predisposes to RCEs), and the active therapy when we think the anterior stromal micropunctures. patient has a history of recurrent patient is at high risk (such as in When we perform this elemen- episodes, and presents to one of the instance of a severe fingernail tary procedure, we complete the us as a new patient with an acute abrasion near the inferior third of treatment process with instillation event, we act aggressively to try to the cornea, where most erosions of a topical NSAID, a drop of 1% halt these painful episodes. Depend- occur), or the patient has a history cyclopentolate, then placement of ing on the disposition of the patient of multiple recurrences. ■ 44A REVIEW OF OPTOMETRY MAY 15, 2011040_dg0511_Q&A.indd 44 5/11/11 4:29 PM
  • 47. Q&A How to Conquer Excess Mucus A verbatim e-mail exchange. Dear Drs. Melton and Thomas: having a few I have a post-penetrating kerato- more problems plasty (PKP) O.U. patient in bitoric with the mucus RGPs who is plagued with 2+ giant during the day. papillary conjunctivitis (GPC). To I told him to take him out of his RGPs entirely increase the incapacitates him. Pataday and acetylcysteine to Alrex have been ineffective. I have Lotemax q.i.d. for two weeks, right t.i.d. and see if that helped. read your protocol of Lotemax with the RGP. During the initial I have another question. I have every two hours for two days and studies on GPC and Lotemax, this run across some other patients who then four times a day for five days drop was instilled right on top of would benefit from this regimen. with no contact lens wear. He will soft contact lenses, so it should One of the patients is already tak- not be able to do this. only be even safer for RGPs. We ing oral Mucomyst daily. She still Another huge problem for him would also recommend the frequent has fogging/coating problems. Is is the mucus that his irritated eyes use of a lipid-based artificial tear. there any problem to adding this produce and the interference with With any two different eye drops, regimen on to her oral dose? contact lens wear. He is at the point we would have him wait about 20 of considering repeat PKPs. If I minutes between use of the first and Our response: could reduce the mucus problem, second medications. Dear Doctor: he would be overjoyed. He can If you do these things, you We are pleased that your patient physically handle the contact lens should have a pretty satisfied pa- has been helped with the Mucomyst wear with GPC. I don’t know how tient. Please let us know how this and loteprednol. Your last ques- effective Lotemax t.i.d. with con- works. tion related to one of your patients tinued contact lens use will be. Can using topical as well as systemic you make any recommendations? The writer responds: Mucomyst. We would see no prob- Thank you for your help. Thank you for your suggestion! lem with a patient using topical eye I’ve not run across this treatment drops while at the same time taking Our response: plan. Because his complaints seem oral Mucomyst. Dear Doctor: to be focused on the mucus pro- Thank you for your thought- duction and not lens irritation, I The writer responds: ful inquiry. Have a compounding am thrilled to have something that My patient currently taking Mu- pharmacist take either 10% or additionally addresses the mucus comyst said that her problem isn’t 20% Mucomyst (acetylcysteine, buildup. It’s also nice to know that that bad, but it’s good to have this Bristol-Myers Squibb) and dilute it he can leave the RGPs in and still in my pocket if needed. to a 5% ophthalmic solution. Have get a good effect from the Lotemax. This has been “life changing” for your patient instill this q.i.d. for a I will let you know how this works! my one patient, not having to take week or two. Then once control Thanks again! lenses out to clean three to four is achieved, taper use to perhaps …and later writes: times a day. This would be a huge b.i.d. as maintenance therapy. The Thank you so much for your pearl for other doctors in your next acetylcysteine is an excellent muco- recommendations! I just spoke with drug guide! lytic, and is heavily used in treating the patient. The two weeks he was excess mucus in the pulmonary on the acetylcysteine and Lotemax Our response: system. q.i.d. was the best he’s been in a As you can see, doctor, your sug- We would also have him use the year! Now that he’s b.i.d., he is gestion has been taken to heart! ■ REVIEW OF OPTOMETRY MAY 15, 2011 45A040_dg0511_Q&A.indd 45 5/11/11 4:29 PM
  • 48. Q&A New Insights into Plaquenil Retinotoxicity New, as of 2011, is the addition of one or more objective assessments, such as spectral-domain OCT, to evaluate early retinal damage. Two new articles further refine our understanding of the retinotoxic risks of Plaquenil (hydroxychlo- roquine, Sanofi-Aventis) usage, and also provide new insights into patient evaluation and follow-up care.1,2 It is well understood that hy- droxychloroquine (HCQ) has the potential to cause irreversible cen- tral vision loss. A baseline retinal evaluation is standard-of-care for patients being treated with HCQ, within a few months of initiation of The gold standard for evaluation of Plaquenil retinotoxicity has been, and continues to therapy. be, a central 10-degree visual field test to look for repeatable central and paracentral Because there is no known means scotomas. As with all types of visual field tests, there can be much variability. This available to diagnose toxic damage HCQ patient demonstrated apparent paracentral defects at baseline... before some minor permanent dam- age has occurred, it is critical to as- sess risk factors for HCQ toxicity, thoroughly educate our patients, and perform appropriate screening measures in a timely manner. Known risk factors are: • Daily dosage of HCQ exceed- ing 6.5mg/kg (that is, a daily dos- age not to exceed 400mg in patients having a lean body weight of less than 135 lbs.) • Obesity. We stress here that HCQ is not absorbed into adipose tissue. This means that an obese But, when retested three months later, the patient revealed normal results. Use sound person who weighs 160 lbs may clinical judgment when interpreting any subjective data! be considered within the “safe” zone, but their lean body weight information known to us, so that five years. It is now more firmly may be only 120 lbs, which poses we can more accurately assess the established that duration of expo- an increased relative risk. We have risk for retinotoxicity. If you want sure (i.e., cumulative dose) portends communicated this critical issue of to calculate it yourself, the formula more retinotoxic risk than daily lean body weight to our referring for women (the vast preponderant intake. In fact, prevalence of toxic rheumatologists and dermatolo- gender prescribed HCQ) is: 1.07 x expression is quite limited within gists, and have asked them to assess weight – 1.48 x (wt2/100 x height the first five years of use, and the the lean body weight of each of in meters2). risk “increased sharply after five to their HCQ patients and make this • Duration of use longer than seven years to approximately 1%.” 46A REVIEW OF OPTOMETRY MAY 15, 2011040_dg0511_Q&A.indd 46 5/11/11 4:29 PM
  • 49. Q&A So, it appears that initial screening accessible is the SD-OCT, and it during the first five years of therapy is our recommended instrumenta- can be rationally relaxed in those tion. These spectral-domain scans patients not having significant risk can reveal localized thinning in the factors. But beginning about Year parafoveal region. (Time-domain 5, as dosage accumulates, more OCT instruments do not have the frequent (usually annually) assess- resolution to enable meaningful ments should be performed. quantification of these crucial reti- • Renal or hepatic functional New recommendations aim to catch nal tissues.) It is thought that these impairment. Compromised kidney Plaquenil retinotoxicity long before this objective assessments may even be a and/or liver function can lead to classic bullseye maculopathy appears. bit more sensitive to tissue compro- increased accumulation of HCQ in mise than the 10-2 visual field test. the tissues, so that the health status this is probably true for almost of these organs should be assessed all patients, there may be a few In summary, it is of paramount by the prescribing physician. patients who are indeed properly importance to inform HCQ patients • Older age. “Patients older than dosed yet, because of individual of the remote (<1%) chance of a 60 years, and with a duration of idiosyncrasies and variability, they problem. Furthermore, it should treatment greater than five years, still develop toxicity. be stressed that it is in detecting appear to be at greater risk for the earliest possible expression of retinal toxicity.” Assessing the Damage damage that further, irreversible • Preexisting retinal disease. It So how do we evaluate patients vision loss can be prevented. The stands to reason that any clinically for early toxic effects? Unfortunate- patient should understand that risk significant retinomacular tissue ly, no mechanism exists to detect is extremely low during the first compromise could place these deli- ocular damage from HCQ before five years of HCQ therapy, but that cate tissues at increased risk from it occurs. We can only try to detect continued use beyond five to seven HCQ exposure. Such patients may such damage at its earliest mani- years confers an increasing risk (up have a contraindication to HCQ festation. Functional compromise to about 1%) for retinomacular use, or at least a lower dose should occurs before any ophthalmoscop- tissue damage. be tried. ically-visible changes can be seen. Bottom line: Assess vision, The gold standard has been, and baseline macular abnormalities, Toxicity Buildup continues to be, a central 10-de- 10-2 visual field testing with a Most physicians, in our experi- gree visual field test to look for white target, and if at all possible, ence, prescribe the usual 400mg/ repeatable central and paracentral try to obtain a paramacular scan day dosage. However, because of scotomas. with an SD-OCT. Then follow this drug’s long residence time in As with any other visual field these patients probably annually, the blood and tissues, the clinical test, one must bear in mind that particularly after five years of drug effects build up slowly. This unique there can be a lot of subjective vari- exposure. ■ pharmacology allows for intermedi- ability; thus if there are any suspi- 1. Michaelides M, Stover NB, Francis PJ, Weleber RG. ate dosing, which is easily achieved cious defects, a second visual field Retinal toxicity associated with hydroxychloroquine and by varying the daily dosage. “For test should be performed within a chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol. 2011 Jan;129(1):30- example, 300mg daily results from few weeks to determine if the same 9. taking 200mg and 400mg on alter- defects are still present. The Amsler 2. Marmor MF, Kellner U, Lai TY, et al; American Academy of Ophthalmology. Revised recommendations on screening for nate days.” grid is supra-threshold, and is of no chloroquine and hydroxychloroquine retinopathy. Ophthal- A 2002 article stated: “These value in the setting of HCQ screen- mology. 2011 Feb;118(2):415-22. 3. Marmor MF, Carr RE, Easterbrook M, et al; American drugs are typically prescribed by ing. Use the 10-2 visual field test for Academy of Ophthalmology. Recommendations on screening internists, rheumatologists and all HCQ patient evaluations. for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmol- dermatologists who may not be New, as of 2011, is the addition ogy. 2002 Jul;109(7):1377-82. fully aware of the ophthalmic im- of one or more objective assess- 4. Browning DJ. Hydroxychloroquine and chloroquine retinopathy: screening for drug toxicity. Am J Ophthalmol. plications.”3 Another 2002 article ments, such as spectral-domain 2002 May;133(5):649-56. stated: “Under circumstances of OCT, multifocal electroretinogram proper dosing, screening could be and fundus autofluorescence. Of Next page: a hydroxychloroquine rationally discontinued.”4 While these, the most practical and most (Plaquenil) referral form. REVIEW OF OPTOMETRY MAY 15, 2011 47A040_dg0511_Q&A.indd 47 5/11/11 4:29 PM
  • 50. Doctor, please feel free to remove this sheet, copy it to your letterhead and use it for referrals. Hydroxychloroquine (Plaquenil) Evaluation Patient Name D.O.B. Referring Physician Consultant Optometrist Date / / Plaquenil dose mg Number of years taking HCQ Acuity Right 20/_____ Left 20/_____ Patient’s Weight lbs. Estimated Lean Weight lbs. Fundus exam Normal Other Macular Visual Field Testing (10-2) Normal Other Additional Testing Recheck Annually Other Comments: Thank you very much for entrusting us with the eye care of your patient.040_dg0511_Q&A.indd 48 5/11/11 4:30 PM
  • 51. Doctor, please feel free to remove this sheet, copy it to your letterhead and distribute it to your patients. UNDERSTANDING AMBLYOPIA Probably the single most important factor in the The two-step care and safeguarding of children’s eyesight is a treatment of thorough eye examination between 3 and 4 years amblyopia is of age. Many parents assume little can be accom- usually very plished at such an early age; however, this is not the straightforward. case. In fact, much critical information can be rather easily determined even in babies. First, perfect eyeglasses are A common condition known as amblyopia (lazy prescribed to eye) is one of the key problems that can only be fully correct prevented if its underlying cause is diagnosed and each eye. This treated early. The main causes of amblyopia are 1) provides clear, crisp images focused on the retina at one eye being more farsighted than the other (the the back of the eye. These sharp images are then children will not be aware of this at all because the transmitted to the optic nerves to reach the occipi- more normal of the two eyes will simply take over), tal cortex where special vision cells are sufficiently and 2) one eye being turned in or out relative to the stimulated so that they can develop to their fullest straight eye. Family members often detect crossed potential. or deviated eyes; however, there is no way to detect the status of farsightedness by casual observation. The second step in treating amblyopia is to selec- Such a diagnosis can only be made with a thorough tively patch the “good” (stronger) eye. This forces examination by an eye doctor. the “bad” (weaker or amblyopic) eye to begin to be used more. This forced use of the amblyopic eye Amblyopia, and the conditions that lead to amblyo- is what stimulates the specialized vision cells in the pia, are unilateral in nature—this means only one brain to develop properly, thereby allowing good eye is affected. Sadly, and far too often, children vision development in both eyes. Usually, special with amblyopia are not brought into the eye doc- dilating eyedrops are used by the doctor to deter- tor’s office until they realize they see poorly out mine the exact eyeglass prescription for the child. of one eye. If the child is older than 7 or 8, there Of course, every patient with amblyopia is unique, may be little that can be done to improve his or her so the frequency, duration and outcome of patching vision. While most people with amblyopia function therapy will vary, depending on the visual status of well in life, their depth perception is decreased and each patient. this may restrict their choice of occupation to some degree. (A person with good eyesight in only one Here are some behaviors that might be observed in eye should always wear impact-resistant eyeglasses young children with potential vision problems: to protect the good eye. This is true even if there is • Frequent eye rubbing no prescription in the lenses.) • Excessive blinking • Squinting Why is it so important to diagnose the conditions • Covering or closing one eye that can lead to amblyopia by the age 3 or 4? The • Stumbling over small objects central nervous system (specifically the occipital cortex tissues in the back of the brain) can be stimu- Any of these activities should prompt a visit to the lated and enhanced in children until they are about eye doctor; however, even if no such behaviors are 6 to 8 years old, and thus their vision can more seen, every child should have his or her eyes exam- likely be improved. ined by age 3 or 4.040_dg0511_Q&A.indd 49 5/11/11 4:30 PM
  • 52. FC_DG0511.indd 2 5/12/11 9:18 AM