Ulkus kornea ; Review of Ophthalmology® _ Winning the Battle Against Corneal Ulcers

892019 Ulkus kornea Review of Ophthalmologyreg _ Winning the Battle Against Corneal Ulcers

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The location of a corneal ulcer is an important factor in diagntreatment Above left A central corneal ulcer with hypopyonright An aggressive chronic limbal bacterial ulcer (methicillinStaphylococcus epidermidis ) with limbal hypervascularity (Alcourtesy John Sheppard MD MMSc)

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Winning the Battle Against Corneal UlcersFour experts share their knowledge and experience dealing withthese sight-threatening lesionsChristopher Kent Senior Editor

952013

Corneal ulcers are a common problem often encountered by eye-care professionals Unfortunately an ulcer can be difficult todiagnose its cause can be elusive and the consequences of an error in diagnosis or treatment can be severe Knowing what tolook for and common mistakes to avoid can make all th e difference

Common Encounters

ldquoThe most common type of ulcer clinicians are likely to see by far is a bacterial ulcerrdquo says John Sheppard MD MMScpresident of Virginia Eye Consultants professor of ophth almology microbiology and molecular biology director of residencyresearch training and clinical director of the Thomas R Lee Center for Ocular Pharmacology at Eastern Virginia Medical Schoolin Norfolk Va ldquoMany of the organisms that cause bacte rial ulcers h ave extremely potent tissue-destructive mechanisms so itrsquosalways imperative that bacterial keratitis is identified an d treated r apidly Pseudomonas in particular creates proteolyticenzymes like collagenase that rapidly degrade tissues i trsquos known for creating ulcers that lead to perforations

ldquoThe number one risk factor for corneal ulcers in the United States is contact lens userdquo he continues ldquoAnother key risk factor istrauma Corneal ulcers are more common among those in industrial or outdoor occupations and being older increases your risk

mdashparticularly in the case of a very old patient who has chronic blepharitis Diabetics are at greater risk as are patientssuffering from dry eye Latitude is important the warmer the climate the more likely you are to develop an ulcer and the morelikely you are to develop a fungal ul cer In Virg inia we see mo re fungus than in Boston in Florida they see more than we dordquo

ldquoAnother ulcer that clinicians often run into is the peripheral corneal ulcerrdquo says John R Wittpenn Jr MD partner atOphthalmic Consultants of Long Island and associate clinical professor of ophthalmology at the State University of New York atStony Brook ldquoThis isnrsquot so much an ulcer as it is a type of keratitis an inflammatory problem associated with staphylococcus overgrowth in the lid Thindividuals present with the classic peripheral infiltrate

ldquoIf therersquos a defect I recommend treating it as an infectious ulcer until proven otherwiserdquo he continues ldquoBut if the epithelium is fully intact and therersquoin the anterior chamber thatrsquos phlyctenular keratitis an inflammatory problem You should address the lids with something like AzaSite which has grpenetration or a topical ointment applied to the lid margins at bedtime in conjunction with an anti-inflammatory I happen to like loteprednol because igood surface anti-inflammatory with a very low risk of pressure elevation But you could also use a fluorometholone or something similarrdquo

Of course the difficulty of treatment and likelihood of a positive outcome are profoundly affected by how quickly the corneal ulcer is detected and treapatient comes in early even with a virulent organism if the infection is limited to the anterior-most part of the cornea and the patient is treated intensappropriate topical antibiotics he might end up with complete resolution of the infection and just a small anterior corneal scarrdquo notes Thomas John Massociate professor at Loyola University at Chicago ldquoHowever if the patient has a compromised cornea and presents later with a large corneal ulcerbest scenario that can potentially result in a large corneal scarrdquo

Dr Sheppard points out that this issue can be exacerbated by contact lenses ldquoA contact lens may actually mitigate the initial symptoms of an ulcerrdquo hresult the patient may leave the contact lens on to make it feel better thereby delaying presentation to the ophthalmologist or optometristrdquo

Identifying the Organism

Charles Stephen Foster MD FACS FACR clinical professor of ophthalmology at Harvard Medical School and founder and president of the Massachus

Research and Surgery Institution in Cambridge points out that when a patient presents with a corneal ulcer a number of questions should be asked tthe diagnosis and a reasonable first-line treatment

ldquoI donrsquot strongly promote the idea of trying to make a categorical diagnosis on the basisof clinical features but there are a few clues that can helprdquo he says ldquoIs the ulcerperipheral near the limbus or is it more central or paracentral Is it just an infiltrate ora true ulcer If itrsquos infectious is it bacterial viral fungal or parasitic Is the patientrsquoscorneal sensibility intact or diminished Does the patient have normal lid function If not is this an exposure problem Is the patient lying asleep at night with the lids openthe cornea drying out and the epithelium breaking down Is it a neurotrophic problemcaused by nerve damage Testing both corneas for sensation of touch can be veryenlightening in that regard

ldquoIn cases of microbial keratitis and stromal ulceration in addition to culturing theorganism there are certain clinical cues and clues that can be helpfulrdquo he continues

ldquoThese include obvious factors such as a discharge If there is a discharge what are itscharacteristics Is it watery or more like pus What color is it If the dischargeresembles pus does it have an odor Pseudomonas for example often has acharacteristic sweet smell

ldquoWith fungus therersquos an infiltrate and two or three other little white spots not connected to the infiltraterdquo he notes ldquoYou may see a bit of a plaque onendothelium on the inside behind the white infiltrate Itrsquos not always the case that a fungus is present when those signs exist but the index of suspiciheightened if one saw those featuresrdquo

Dr Foster adds that a herpetic ulcer is another albeit less-common possibility ldquoIf the patient has had herpes in the past even if he comes in with sodoesnrsquot look like a classic dendritic epithelial defect he may nonetheless have herpetic disease rather than a bacterial diseaserdquo he says ldquoSimply testisensation at that point can often tell you a lot If you find tremendously depressed sensation that might indicate a neurotrophic ulcer If it is a neurotrpursuing the wrong coursemdashhammering it with drugs rather than lubrication and maybe a bandage soft contact lensmdashis only going to make it worserdquo



An e arly midperiphera l contac t-lens-relat edcorneal ulcer caused by fluoroquinolone-sensitive Serratia marcescens

A nec rotizing corne al ulcer causPseudomonas

Taking a Culture

ldquoI never empirically treat a true corneal ulcer or a serious-looking infiltrate without harvesting material for diagnosisrdquo says Dr Foster He notes thata microbial ulcer itrsquos important to include the edges and base of the ulcer along with any discharge for smears on glass slides and for plating onto vamedia ldquoI personally like two split plates chocolate and blood agarrdquo he says ldquoYou make streaks on each half of both plates then keep one at room tand put the other in an incubator This is helpful because the one kept at room temperature will be extremely good for growth of fungi Irsquoll also plateSabroudrsquos medium for fungus in addition to something for isolating anaerobic bacteria Whether that is thioglycolate or another blood plate placed in aincubator depends on my location at the time

ldquoIf Irsquom suspicious that therersquos a parasite like acanthamoeba involved the process gets even more comcontinues ldquoIn that situation the material has to be transported in saline and then plated by the microbiculture plate thatrsquos already growing E coli The most important thing is to make this happen in a timelnecessary have the patient meet you at the hospital emergency room and do it there or refer the pateye residency program if therersquos one nearby The resident on call can take care of itrdquo

Dr Sheppard adds that a culture can be taken from the conjunctiva and the cul-de-sac as well ldquoTherechance that the organism growing in the cornea will be found in those locationsrdquo he points out ldquoAlsolens user you may be able to culture the infectious organism from the contact lens case if the patient

Dr Sheppard notes that there are visual and tactile clues that may suggest a particular type of organisscraping a large ulcer ldquoWith a gram positive organism you donrsquot see too much tissue necrosisrdquo he sayou get a kind of sandy consistency to the ulcerated corneal bed On the other hand a gram negativeproduce a necrotic effect with loss of normal tissue and a lot of necrotic debris a soupy appearance afeelrdquo

Dr Foster adds that you should never wait for the test results to begin treatment ldquoStarting treatment before knowing the results of the test is standarsays

Dr Foster notes that clinicians frequently ask whether they should do an anterior chamber tap for a culture when a patient has an ulcer and a hypopybad idea because if the ulcer is bacterial the hypopyon is always sterile 100 percent of the timerdquo he explains ldquoBacteria donrsquot get through an intact chypopyon is a reaction not an infection But in the course of doing a tap one may actually drag bacteria into the anterior chamber inoculating it and

creating a catastrophic endophthalmitis

ldquoThe only instance in which Irsquod consider a tap is where wersquove never isolated the microbe things are not going wellmdashin fact theyrsquore getting worse thefeatures that are making us pretty suspicious of fungus and the process is getting deeper and deeper I will do a tap in that situation because fungusthrough an intact Descemetrsquos membranerdquo

Choosing an Antibiotic

ldquoIn ulcer cases where Irsquom really concerned I want to use a potent broad-spectrum antibiotic in the fluoroquinolone classrdquo says Dr Sheppard ldquoI thinkfluoroquinolone for ulcers right now is besifloxacin because of its high concentration its ability to adhere to the surface and its superior MIC values fovariety of infectious bacterial organisms particularly multi-drug resistant staphylococci rdquo

Dr Wittpennrsquos preferred drug for corneal ulcers at the moment is also besifloxacin ldquoIt has very good coverage from a fluoroquinolone standpointmdashitgram positives and gram negativesmdashand it contains benzalkonium chloriderdquo he explains ldquoCertain fluoroquinolones like besifloxacin or gatifloxacin inwith BAK remain very effective against methicillin-resistant bacteria such as MRSA which wersquore increasingly worried about

ldquoIf a patient comes in with any kind of ulcer that involves an epithelial defect I prescribe besifloxacin every hour for the first dayrdquo he says ldquoIf you cabesifloxacin my second choice would be a fluoroquinolone with BAK such as Zymaxid If the patientrsquos insurance is generic only which a lot of plans o

the third choice would be ofloxacin again because it has BAK mixed in Itrsquos not as good as the other two but may serve if the other options are not pIf an ulcer is advanced most surgeons say theyrsquod treat with multiple antibiotics ldquoWhen treating a microbial ulcer a typical treatment is to choose twoagents and treat aggressivelyrdquo says Dr Foster ldquoBy aggressively I mean perhaps six or eight initial drops one every five minutes followed by a dropantibiotics every hour on the hour with a drop of the other antibiotic every hour on the half hourrdquo

Dr Sheppard concurs ldquoIn more severe cases Irsquo ll use dual therapy with besifloxacin and gentamicinrdquo he says ldquoGentamicin is not very soluble so whibesifloxacin achieves very high concentrations initially it takes a while for the gentamicin to build up However gentamicin is available in injectable vithe patient is in the office Irsquoll give a subconjunctival loading dose injection of 03 cc gentamicin mixed with 03 cc lidocaine at the time of presentationdrop of besifloxacin (We donrsquot need to give this fluoroquinolone every five minutes to load the patient because of its superior pharmacokinetics) Thatthe patient is immediately under treatment Hopefully the patient will go to the pharmacy right away and pick up the respective drops and then returin that first critical 24-hour period so I can see if hersquos getting betterrdquo

Dr Foster notes that therersquos some debate regarding whether or not to use so-called compounded fortifiedantibiotics typically compounded in the hospital pharmacy ldquoStudies have indicated that the hourly use of a broad-spectrum fluoroquinolone such as gatifloxacin or moxifloxacin is just as good as for example fortified vancomycinand tobramycinrdquo he says

Dr John points out that whether or not the epithelium is compromised makes a difference with regard to topical

antibiotic penetration into the corneal stroma ldquoIf the epithelium is intact topical antibiotics have a hard time gettinginto the corneardquo he says On the other hand if the ulceration has already removed a piece of the epithelium andpart of the stroma you donrsquot have to worry about the epithelial barrierrdquo

He adds that when the epithelium is intact the longer an antibiotic stays on the ocular surface the more likely it isto penetrate into the cornea ldquoSome drugs include an additional component that helps retain the drug on the ocularsurface longer leading to increased contact timerdquo he says ldquoFor example Besivance contains Dura-Sitemdashpolycarbophil edetate disodium dihydrate and sodium chloriderdquo

The Steroid Dilemma

One of the most controversial issues surrounding treatment of corneal ulcers is whenmdashand whethermdashto treat with corticosteroids

ldquoCorticosteroids are a double-edged swordrdquo says Dr John ldquoOnce the infection is controlled steroids can help decrease the scarring that can result frinfectious process However when therersquos an active infection you donrsquot want to use steroids because theyrsquoll frequently have a deleterious effect But tmillion-dollar question How can you be certain the cornea is sterile

ldquoThe SCUT study (Steroids for Corneal Ulcers Trial) a large series involving 500 patients that was published in the Archives of Ophthalmology found

difference in three-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers rdquo he continues ldquoBut I usualsteroids when an infectious process is there I would only use it when I believe the infection is completely under control because yoursquore cutting downhost defenses against the enemy and they can help the organisms proliferaterdquo

Dr Sheppard agrees that corticosteroids can be useful but only in specific circumstances ldquoI believe a classic gram positive infection will benefit from itherapyrdquo he says ldquoRecent data from the Proctor Foundation tells us that there may be an improved visual prognosismdashbut only for central ulcers wheprescribed initiallymdashand that the steroids have no significant unexpected deleterious effects [in this situation] On the other hand if the patient has a f infection giving a steroid is the worst thing you can do No patient with trauma should get a topical steroid because the risk of a fungal infection is mu



A ne urotrophic k eratitis caused by a long-standing herpes simplex virus infection Thiseye is at a high risk for secondary bacterialcolonization and infection

Dr Foster believes that if yoursquore sure a microbe is being effectively treated with the chosen antibiotic a judicious use of steroid to reduce post-inflamresponse damage to the cornea is perfectly acceptable ldquoIn this situation where you have a significant level of comfort that yoursquore on top of this if thesignificant inflammation that yoursquod like to blunt I believe most corneal disease experts would agree that stepping in with a little bit of steroid is reasonsays ldquoIrsquom not saying itrsquos standard of care but itrsquos reasonablerdquo

Dr Wittpenn however feels that steroids are never a good choice when treating an infectious ulcer ldquoI find that steroids will get you in trouble fasterget you out of troublerdquo he says ldquoThe only time Irsquod use steroids is in a case like a phlyctenular keratitis which is not infectious Steroids have never bdecrease scarring Itrsquos tempting to use them because theyrsquoll help the patient feel better at least transiently and the eye gets white faster However smask a lot of things

ldquoOne patient was referred to me because she got a scratch working in the gardenrdquo he continues ldquoShe was treated by her local eye-care provider whmight be bacterial and treated accordingly however it never got completely better She still had some anterior chamber reaction and the epitheliumfunny appearance where it had partially healed The doctor thought the trauma must have induced a herpetic keratitis so he added an antiviral But hinflammation in the anterior chamber so he also added a steroid

ldquoShe was treated with the steroid and antiviral for about three weeks before she was finally referred to me because the ulcer wasnrsquot getting betterrdquo hthen she had started to develop a fungal ball in the deep stroma and it ultimately broke through into the anterior chamber At that point we did a tapanterior chamber and found that she had Aspergillus niger It was difficult to treat It took months including 17 intracameral injections of an antifungalamphotericin which of course had to be specially prepared She ultimately needed a transplant and cataract surgery In the long run she did wellmdashbutcertainly made the case much more difficult to treat

ldquoSo I tell colleagues if yoursquore dealing with what you believe is an infectious ulcer you have to be very comfortable with what yoursquore doing before yousteroidrdquo he concludes ldquoThatrsquos probably the number one mistake I see clinicians makerdquo

Dr John notes that you should also remember your treatment priorities ldquoSteroids may help to decrease scarringrdquo he says ldquobut if you have a bad corthe number one priority is to try to get rid of the offending organisms and minimize the overall direct and collateral damage to the cornea In the bestscenario steroids might decrease the subsequent scar formation but even if you use them yoursquore often not going to eliminate the scarrdquo

Fungal Ulcers

ldquoFungus is suggested as the cause of an ulcer when the history reveals that the ulcer is not becoming rapidly fulminantrdquo Dr Wittpenn says ldquoItrsquos not ddense infiltrate quickly and itrsquos not responding to antibiotics that are being used appropriately Another clue that fungus may be involved is if the sourabrasion was a scratch from vegetable matter such as branches or plants At least up here on Long Island the vast majority of fungal infections I takhave that history it may be a little different in the south where fungal infections are more commonrdquo

ldquoFungal ulcers are often diagnosed late because unless therersquos an obvious cause we generally begin by assuming that patients have a bacterial keratiSheppard ldquoFungal ulcers tend to be caused by trauma but if the patient has a compromised surface loves gardening already had a corneal transplaforeign body in the eye all bets are off

ldquoYou have to look at the physical appearancerdquo he adds ldquoA fungal ulcer tends to have very fuzzy margins tends to be deeper and tends to present wion the endothelium it may have a delayed onset and may have multiple foci These clues can help us decide where we rank the probability of a fungthe ulcerrdquo

Dr Wittpenn says he uses several approaches to address a fungal ulcer ldquoSuppose a patient comes in with what appears to be a bacterial ulcerrdquo he sbeen treated properly letrsquos say with tobramycin every two hours but itrsquos not getting better or worse The first thing Irsquod do is add a fortified vancomycthe treatment so far hasnrsquot really covered gram positive bacteria that well Irsquod also switch the patient to a fluoroquinolone

ldquoAt this point Irsquod give the patient two or three days to see if he improvesrdquo he says ldquoThe best way tothat is by the reported level of pain dropping and by checking the peripheral cornea which will clearindicate that yoursquore no longer recruiting white cells and thatrsquos usually a sign that yoursquove found the cortreatment You canrsquot judge by the infiltrate because the infiltrate will get denser at first it will begin t

white cells consolidate If therersquos no improvement on the antibiotics after three or four days Irsquoll have tstop the drops for 24 hours and then culture for fungus Occasionally depending how bad the ulcer isitrsquos been there Irsquoll begin to treat with an antifungal like natamycin even pending the fungal culturesrdquo

Dr John notes that even when the patientrsquos history gives you a high index of suspicion that the infectiyou should treat for potential bacterial infection at the outset ldquoTreat with antibacterials and do the cultthat it is fungalrdquo he says ldquoAntifungal treatments can often be toxic to the ocular surface In this scenagoing to treat very intensively so you want to have a definitive diagnosis before you start treating witagentsmdashalthough of course there can be some exceptions depending on the clinical setting Besidesis present you can also have a bacterial presencerdquo

He adds that itrsquos also important to know what kind of fungus yoursquore dealing with ldquoIs it Candida or is itfungi like Fusarium That also can help you decide what type of antifungal treatment to initiaterdquo he says ldquoYou can change your treatment direction orantifungal agents once you have a definitive diagnosis either by smear culture or biopsyrdquo

Monitoring Progress

ldquoOnce you start treatment with antibiotics you have to monitor the corneal infection closelyrdquo says Dr John ldquoWhen you do cultures you get a report i

organism and a report telling you whether the organism is sensitive to the antibiotic or resistant but the single most important factor is the clinical retreatment If yoursquore treating a bad corneal ulcer and you see that the infiltrate size is getting smaller the ulceration is not getting worse and there is ehealing taking place especially in the periphery then of course you want to continue with the same treatment modality On the other hand if yoursquore taggressively with an antibiotic and the ulcer is getting worse you have to change direction or add additional antibioticsrdquo

Dr John points out that bacterial organisms are very adaptable ldquoThey become resistant to antibioticsrdquo he says ldquoItrsquos a constant battle to keep aheadyou have to monitor very closely to see if your ocular antibiotic choices are working from a clinical standpointrdquo

If medical treatment fails to work surgery may become necessary ldquoYou donrsquot want to wait too long for surgical intervention when there is an expandmedical therapeutic failurerdquo notes Dr John adding that the clinical response is dependent partly upon the location of the ulcer ldquoFor instance if you hPseudomonas ulcer that is paracentral and is expanding rapidly despite medical treatment and moving towards the limbus you may have to considerintervention such as a therapeutic keratoplasty If that infection spreads from the cornea to the sclera resulting in Pseudomonas aeruginosa keratosclthe odds of saving the eye as a whole can rapidly diminish Even in cases where evisceration or enucleation are not necessary the visual prognosis uremains poorrdquo

On the other hand if the treatment is working the clinician has to decide when to taper the medications ldquoIf the infiltrate is decreasing the pain is decredness is decreasing and the epithelial defect is improving then I know that the patient is responding to therapyrdquo says Dr Sheppard ldquoOnce all of thare gone and the epithelium is completely resurfaced I feel safe in concluding that wersquove eliminated the bacteria and we can begin to rapidly wean tthe antimicrobial therapy Sometimes because of the toxicity that comes with any potent antibiotic given frequently we cut back on the dosage frequsee improvementmdashassuming that the information from the cultures also indicated that the current therapeutic regimen is the right one Finally we watpatient for about a week after we stop the antibiotics to make sure the cornea remains clear without therapyrdquo

Clinical Pearls

These strategies can help you avoid common mistakes that might undercut the effectiveness of your treatment

bull Donrsquot confuse an infiltrate with an ulcer Dr Foster notes that an infiltrate by itself is not synonymous with a corneal ulcer ldquoA corneal infilt



Make Sure Your Staff Is Prepared In the struggle to preserve vision in the face of a corneal ulcer your staff are the first line

defense their actions can make or break a positive outcome bull Make sure staff members know when a call might be about a developing corn

ulcer Itrsquos often a staff member who fields a patient inquiry related to a corneal ulcer not theprovider ldquoThe OMIC malpractice insurance company states that the third leading cause of mallawsuits against ophthalmologists is triage by staff membersrdquo says John Sheppard MD MMScprofessor of ophthalmology microbiology and molecular biology at Eastern Virginia Medical ScNorfolk Va ldquoThis means that triage personnel have to be really tuned in to which phone callsimportant and what constitutes a potentially blinding condition

ldquoIn a large percentage of these phone ca lls itrsquos red eye that wersquore concerned aboutrdquo he nothe red eye is of long duration with no risk factors no pain or purulent discharge or loss of visithatrsquos one thing thatrsquos quite common But whenever the patientrsquos comments indicate a risk factbacterial keratitis such as pain and photophobia in addition to the red eye especially in conjunwith contact lens wear or trauma the triage person has to get the patient into the office right aThe last thing you want to do is delay the presentation of an ulcerrdquo

bull Tell your staff If a patient might have an ulcer donrsquot put drops in his eyes ldquoAsdiluting the flora most of the eye drops we use to reduce pain check IOP or dilate the pupils cpreservativerdquo explains Dr Sheppard ldquoThe preservative may significantly reduce our chance ofan organism from the eye which ultimately guides our therapymdashparticularly in difficult cases Ewersquoll use preservative-free tetracaine to culture and debride the corneardquo

bull Make sure your staff knows that red eye might also indicate adenoviruskeratoconjunctivitis ldquoThese patients can have symptoms similar to those of an ulcer but thextremely contagiousrdquo notes Dr Sheppard ldquoFortunately the AdenoPlus pathogen screener frodistributed by NiCox allows us to confirm whether or not a patient has this condition within abminutes with very high sensitivity and specificityrdquo

that some white blood cells have migrated into the corneal stroma but that doesnrsquot mean an ulcer is presentrdquo he explains ldquoIn a true ulcer therersquos a lwith stroma digested by enzymes The result is a divot just like an ulcer in the lining of the stomach An infiltrate is of concern because it can eventuatissuemdashhence an ulcermdashbut itrsquos important to make the distinction

ldquoIf you have a peripheral infiltrate in a contact lens wearer with no loss of stroma no real ulceration and an intact epithelium stop the contact lens ustopical combination of antibiotic and steroid and see the patient frequentlyrdquo he continues ldquoIrsquod see the patient the next day and if he looks good seelater then four days later and so forthrdquo

bull Beware of undertreating a contact lens-related ulcer ldquoSometimes a contact lens patient comes in so early that you donrsquot even see a big innotes Dr Wittpenn ldquoI always warn people about a patient who says lsquoI think I scratched my eye when I took out my contact lens last night becausethis morning and it was real sore and bothering mersquo All you see is a corneal defectmdashno infiltrate In this situation you need to be alert for any cells inchamber and any kind of haze at all

ldquoMy advice to most clinicians is Any corneal defect in the setting of contact lens use is a corneal ulcer until proven otherwiserdquo he continues ldquoThe big

clinicians make in this situation is prescribing an antibiotic twice or four times a day When you hit the ulcer with a low dose like thatmdashparticularly if yone of the very popular antibiotics like tobramycin or gentamicinmdashtreatment might be effective but those drugs have gaps in their coverage Three darea still isnrsquot really healed in itrsquos more inflamed and now yoursquore not sure if yoursquore dealing with an unusual fungal ulcer or something else Doctors ethese patients to me to rule out fungus when in fact itrsquos an undertreated bacterial ulcer that just needs to be hit hard with topical antibiotics

ldquoA central contact-lens-associated ulcer can have devastating effects on vision and develop very quickly within 24 hoursrdquo he adds ldquoThatrsquos why anyassociated with a contact lens should be treated aggressively If it really is nothing but a defect nothing is lost If itrsquos the start of an infection you mapatientrsquos visionrdquo

bull When choosing an antibiotic always consider avoiding those the patient may have used previously ldquoIf the patient has had a partiantibiotic such as azithromycin or Ocuflox in the past because of cataract surgery or a bout of conjunctivitis you may not want to treat the ulcer with tmedicationsmdashparticularly if the patient may have abused them by not using them for the full course of therapyrdquo observes Dr Sheppard ldquoInstead if tserious pick a very potent broad-spectrum antibiotic especially if yoursquore selecting monotherapy If yoursquore using multiple drugs select a strategy thatthe broadest range of potential pathogensrdquo

bull Be alert for a shield ulcer ldquoOne form of ulcer thatrsquos been a little more prevalent recently is a shield ulcer which is associated with severe allergconjunctivitis commonly seen in teenage males though it can also be seen in young adult malesrdquo says Dr Wittpenn ldquoThey get such a severe allergiinflammation under their upper lids that the epithelium of the cornea breaks down in response to the inflammatory papillae that form which become bcan cause an ulcer The real problem occurs if that ulcer becomes secondarily infected

ldquoPatients in this situation need to be managedcarefullyrdquo he continues ldquoThey often need to betreated with a topical steroid in conjunction withan antibiotic Unless yoursquore comfortable handlingthis type of ulcer because yoursquove taken care of alot of them you really should send this patient toa specialist These patients can get into troublequickly particularly if they get an infectious ulcercentrally suddenly yoursquore dealing with a bad scarand a patient who might be fairly young but needsa corneal transplantrdquo

bull Warn patients about secondary fungalinfections ldquoMany times you treat a bacterialinfection with antibiotics and the bacterial infectiongets betterrdquo says Dr Sheppard ldquoThen the patientis running around in the garden or working in thebasement or attic or playing with a pet and gets afungus in the eye Fungus will grow more rapidlyin an eye with antibiotics on board becausesuppressing the bacterial growth allows fungi togrow faster As a result wersquove often seensecondary fungal infections Itrsquos worth mentioningthis to the patientrdquo

bull Tell contact lens patients that they needto have a pair of spectacles in reserve

ldquoContact lens wearers often reject this ideardquo notes Dr Wittpenn ldquoThey say lsquoI wear my lensesall the timersquo I tell them that they have tounderstand that if a contact lens starts to botherthem they have to be able to remove it and wear glasses until the problem is resolved Irsquove seen people get themselves in trouble because they hadto fall back onrdquo

bull Be careful about diagnosing an infection as being herpes-based ldquoItrsquos possible to misdiagnose an infection as a herpes infection leading tusing antiviral agentsrdquo says Dr John ldquoIn fact that early dendrite-like lesion that you see may be a radial keratoneuritis or an early epithelial ridge-li

secondary to Acanthamoeba keratitis That misdiagnosis could delay the treatment of Acanthamoeba and have a deleterious effect on the patientrsquos vis

bull Donrsquot be afraid to hospitalize a patient ldquoYou have to consider the possibility that compliance is an issue especially if the ulcer is getting worsyour having prescribed what you think is the state-of-the-art treatment for the given problemrdquo says Dr John ldquoPutting the patient in the hospital mayalternative if the patient is noncompliant because time is of the essence especially if yoursquore dealing with an organism like Pseudomonas You can tellthat he wonrsquot be in the hospital for too long hersquoll be discharged as soon as the ulcer begins to get better and he can manage the treatment at homerdquo

Dr Foster agrees ldquoIf the patient has a microbial ulceration that needs aggressive treatment in my experience the vast majority of patients cannot beget it donerdquo he says ldquoBy far the best solution is to let the nurses do it Put the patient in the hospital No insurance company would ever argue abouta patient for an infectious corneal ulcerrdquo He adds that this is especially important if the ulcer is central or paracentral

bull Donrsquot assume that ongoing corneal opacity means your treatment isnrsquot working Dr John notes that clinicians may be fooled into ovean ongoing corneal opacity ldquoA treated ulcer may be under control but the clinician is concerned about the ongoing corneal opacityrdquo he explains ldquoThibe the result of the scarring process rather than the infection but the clinician keeps treating This can lead to surface issues such as toxicity from thecorneal surface breakdown The clinician should be tapering the medication because the infectious process is under control

ldquoSigns that your treatment is working despite the opacity include healed corneal epithelium that was initially broken down decreasing corneal stromasurrounding the area of initial dense infiltrate and blurry infiltrate margins becoming more distinctrdquo he adds

bull Consider using cyanoacrylate glue to forestall a perforation ldquoA perforation is a pretty scary eventrdquo notes Dr Sheppard ldquoWe may put cyglue on a cornea thatrsquos thinning and a small perforation can be glued A large perforation unfortunately is going to require an emergency transplant

When Should You Refer

ldquoAny time yoursquore dealing with a type of ulcer you seldom treat such as a shield ulcer you should consider referring the patientrdquo says Dr Wittpenn ldquoyou have to be very comfortable discerning whether an ulcer is infectious or noninfectious Also any ulcer that isnrsquot doing what you expect it to do shreferred Clinicians have a tendency to say lsquoWell this isnrsquot terrible but it isnrsquot getting better Maybe if I just give it a little steroid helliprsquo Whenever you get



reach for a steroid because you think it will help the eye heal faster I urge you to resist Thatrsquos the main choice that gets clinicians into troublerdquo

ldquoIf you donrsquot actually enjoy managing these kinds of cases donrsquot try to manage themrdquo adds Dr Foster ldquoJust refer the case out to someone who doestype of case or to the local residency programrdquo REVIEW

Dr John is a consultant and speaker for Bausch + Lomb Dr Wittpenn has been on the speakers bureau at B+L and Allergan and has received reseafrom Allergan Dr Sheppard is a consultant for RPS NiCox Alcon Merck Allergan and B+L

Search on This Topic Back to Issue

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Copyrightcopy 2000 - 2015 Jobson Medical Information LLC unless otherwise noted All rights reserved Reproduction in whole or in part without permission is prohibited



An e arly midperiphera l contac t-lens-relat edcorneal ulcer caused by fluoroquinolone-sensitive Serratia marcescens

A nec rotizing corne al ulcer causPseudomonas

Taking a Culture

ldquoI never empirically treat a true corneal ulcer or a serious-looking infiltrate without harvesting material for diagnosisrdquo says Dr Foster He notes thata microbial ulcer itrsquos important to include the edges and base of the ulcer along with any discharge for smears on glass slides and for plating onto vamedia ldquoI personally like two split plates chocolate and blood agarrdquo he says ldquoYou make streaks on each half of both plates then keep one at room tand put the other in an incubator This is helpful because the one kept at room temperature will be extremely good for growth of fungi Irsquoll also plateSabroudrsquos medium for fungus in addition to something for isolating anaerobic bacteria Whether that is thioglycolate or another blood plate placed in aincubator depends on my location at the time

ldquoIf Irsquom suspicious that therersquos a parasite like acanthamoeba involved the process gets even more comcontinues ldquoIn that situation the material has to be transported in saline and then plated by the microbiculture plate thatrsquos already growing E coli The most important thing is to make this happen in a timelnecessary have the patient meet you at the hospital emergency room and do it there or refer the pateye residency program if therersquos one nearby The resident on call can take care of itrdquo

Dr Sheppard adds that a culture can be taken from the conjunctiva and the cul-de-sac as well ldquoTherechance that the organism growing in the cornea will be found in those locationsrdquo he points out ldquoAlsolens user you may be able to culture the infectious organism from the contact lens case if the patient

Dr Sheppard notes that there are visual and tactile clues that may suggest a particular type of organisscraping a large ulcer ldquoWith a gram positive organism you donrsquot see too much tissue necrosisrdquo he sayou get a kind of sandy consistency to the ulcerated corneal bed On the other hand a gram negativeproduce a necrotic effect with loss of normal tissue and a lot of necrotic debris a soupy appearance afeelrdquo

Dr Foster adds that you should never wait for the test results to begin treatment ldquoStarting treatment before knowing the results of the test is standarsays

Dr Foster notes that clinicians frequently ask whether they should do an anterior chamber tap for a culture when a patient has an ulcer and a hypopybad idea because if the ulcer is bacterial the hypopyon is always sterile 100 percent of the timerdquo he explains ldquoBacteria donrsquot get through an intact chypopyon is a reaction not an infection But in the course of doing a tap one may actually drag bacteria into the anterior chamber inoculating it and

creating a catastrophic endophthalmitis

ldquoThe only instance in which Irsquod consider a tap is where wersquove never isolated the microbe things are not going wellmdashin fact theyrsquore getting worse thefeatures that are making us pretty suspicious of fungus and the process is getting deeper and deeper I will do a tap in that situation because fungusthrough an intact Descemetrsquos membranerdquo

Choosing an Antibiotic

ldquoIn ulcer cases where Irsquom really concerned I want to use a potent broad-spectrum antibiotic in the fluoroquinolone classrdquo says Dr Sheppard ldquoI thinkfluoroquinolone for ulcers right now is besifloxacin because of its high concentration its ability to adhere to the surface and its superior MIC values fovariety of infectious bacterial organisms particularly multi-drug resistant staphylococci rdquo

Dr Wittpennrsquos preferred drug for corneal ulcers at the moment is also besifloxacin ldquoIt has very good coverage from a fluoroquinolone standpointmdashitgram positives and gram negativesmdashand it contains benzalkonium chloriderdquo he explains ldquoCertain fluoroquinolones like besifloxacin or gatifloxacin inwith BAK remain very effective against methicillin-resistant bacteria such as MRSA which wersquore increasingly worried about

ldquoIf a patient comes in with any kind of ulcer that involves an epithelial defect I prescribe besifloxacin every hour for the first dayrdquo he says ldquoIf you cabesifloxacin my second choice would be a fluoroquinolone with BAK such as Zymaxid If the patientrsquos insurance is generic only which a lot of plans o

the third choice would be ofloxacin again because it has BAK mixed in Itrsquos not as good as the other two but may serve if the other options are not pIf an ulcer is advanced most surgeons say theyrsquod treat with multiple antibiotics ldquoWhen treating a microbial ulcer a typical treatment is to choose twoagents and treat aggressivelyrdquo says Dr Foster ldquoBy aggressively I mean perhaps six or eight initial drops one every five minutes followed by a dropantibiotics every hour on the hour with a drop of the other antibiotic every hour on the half hourrdquo

Dr Sheppard concurs ldquoIn more severe cases Irsquo ll use dual therapy with besifloxacin and gentamicinrdquo he says ldquoGentamicin is not very soluble so whibesifloxacin achieves very high concentrations initially it takes a while for the gentamicin to build up However gentamicin is available in injectable vithe patient is in the office Irsquoll give a subconjunctival loading dose injection of 03 cc gentamicin mixed with 03 cc lidocaine at the time of presentationdrop of besifloxacin (We donrsquot need to give this fluoroquinolone every five minutes to load the patient because of its superior pharmacokinetics) Thatthe patient is immediately under treatment Hopefully the patient will go to the pharmacy right away and pick up the respective drops and then returin that first critical 24-hour period so I can see if hersquos getting betterrdquo

Dr Foster notes that therersquos some debate regarding whether or not to use so-called compounded fortifiedantibiotics typically compounded in the hospital pharmacy ldquoStudies have indicated that the hourly use of a broad-spectrum fluoroquinolone such as gatifloxacin or moxifloxacin is just as good as for example fortified vancomycinand tobramycinrdquo he says

Dr John points out that whether or not the epithelium is compromised makes a difference with regard to topical

antibiotic penetration into the corneal stroma ldquoIf the epithelium is intact topical antibiotics have a hard time gettinginto the corneardquo he says On the other hand if the ulceration has already removed a piece of the epithelium andpart of the stroma you donrsquot have to worry about the epithelial barrierrdquo

He adds that when the epithelium is intact the longer an antibiotic stays on the ocular surface the more likely it isto penetrate into the cornea ldquoSome drugs include an additional component that helps retain the drug on the ocularsurface longer leading to increased contact timerdquo he says ldquoFor example Besivance contains Dura-Sitemdashpolycarbophil edetate disodium dihydrate and sodium chloriderdquo

The Steroid Dilemma

One of the most controversial issues surrounding treatment of corneal ulcers is whenmdashand whethermdashto treat with corticosteroids

ldquoCorticosteroids are a double-edged swordrdquo says Dr John ldquoOnce the infection is controlled steroids can help decrease the scarring that can result frinfectious process However when therersquos an active infection you donrsquot want to use steroids because theyrsquoll frequently have a deleterious effect But tmillion-dollar question How can you be certain the cornea is sterile

ldquoThe SCUT study (Steroids for Corneal Ulcers Trial) a large series involving 500 patients that was published in the Archives of Ophthalmology found

difference in three-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers rdquo he continues ldquoBut I usualsteroids when an infectious process is there I would only use it when I believe the infection is completely under control because yoursquore cutting downhost defenses against the enemy and they can help the organisms proliferaterdquo

Dr Sheppard agrees that corticosteroids can be useful but only in specific circumstances ldquoI believe a classic gram positive infection will benefit from itherapyrdquo he says ldquoRecent data from the Proctor Foundation tells us that there may be an improved visual prognosismdashbut only for central ulcers wheprescribed initiallymdashand that the steroids have no significant unexpected deleterious effects [in this situation] On the other hand if the patient has a f infection giving a steroid is the worst thing you can do No patient with trauma should get a topical steroid because the risk of a fungal infection is mu










Fungal Ulcers









Monitoring Progress






Clinical Pearls

















































Fungal Ulcers









Monitoring Progress






Clinical Pearls








































Ulkus kornea ; Review of Ophthalmology® _ Winning the Battle Against Corneal Ulcers

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Transcript of Ulkus kornea ; Review of Ophthalmology® _ Winning the Battle Against Corneal Ulcers