UPDATED EDITION

PartKeratitis four of an ongoing series

New paradigms in the understanding and management of .

Supported by an Unrestricted Grant from

Presented by

ce ion of Ex llence A Traditi Celebrating Our 120 th Year Serving the Profession

000_ro1111B&L12pg_ac4.indd 1 10/26/11 9:40 AM Dear Colleagues: of keratitis. It also offers a consensus on the most effective Thus far in the 2011 update to our series of mono- ways to address and manage this condition. graphs, we have examined ocular allergy, This series has been made possible because of the gener- and dry eye. As the others in this series did for the afore- ous support of Bausch + Lomb. The next and last install- mentioned ocular surface disease states, this monograph ment in this series will provide an in-depth look at a new will comprehensively review new and existing informa- topic, nutrition, by a fresh panel of doctors. tion as it relates to the understanding and management — The Authors

About the Authors Jimmy D. Bartlett, O.D., D.O.S., Paul M. Karpecki, O.D., Sc.D., is the former Professor and practices at the Koffler Vision Chairman of the Department of Group in Lexington, Ky. in Optometry at the University of Alabama Services and External Disease. He is at Birmingham. also Director of Research.

Ron Melton, O.D., F.A.A.O., is in Randall K. Thomas, O.D., private group practice in Charlotte, M.P.H., F.A.A.O., is in private N.C., an adjunct faculty member group practice in Concord, N.C., at the Salus University College of and co-founder of Educators in Optometry and Indiana University Primary Eye Care, LLC. School of Optometry, and co-founder of Educators in Primary Eye Care, LLC.

Keratitis, or inflammation of lenses, particularly hydro- their effect on tear film struc- the cornea, is the most serious gel lenses, increases carbon ture and physiology is similar of the ocular surface disorders dioxide accumulation and to that found with other types we have explored in this series. decreases oxygen availability of soft lenses.2 As the turn- It can be sight-threatening and under the , which reduces over of the corneal epithelium in severe cases, can even lead the metabolic activity of the slows down with lens wear, to loss of the eye. Both sterile epithelium.1 Through mechani- tear evaporation and thinning and microbial forms of kerati- cal trauma, hypoxia or as-yet- increases, and tear break-up tis have been associated with undiscovered mechanisms, time and lipid layer thickness wear. Other types contact lens wear may, in rare decrease.2 include chemical, phlyctenular cases, also damage the limbal In addition, contact lens and herpetic keratitis. epithelial stem cells. wear interrupts and slows New silicone hydrogel con- down the normal rate of tear Contact Lenses and tact lens materials have signifi- exchange, which is neces- Keratitis cantly reduced or eliminated sary for the removal of debris, Contact lens wear contrib- negative effects on corneal bacteria and antigens from utes to keratitis risk in several homeostasis and lens-induced the ocular surface. Silicone ways. First, wearing contact hypoxia for most wearers, but hydrogel lenses promote better

2 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 2 10/26/11 9:53 AM tear exchange than hydrogel lenses.3,4 Regardless of material, overnight wear of lenses poses Clinical Pearl the greatest risk of complica- As part of your patient education efforts, refer contact tions. Patients who want to lens wearers to this Food and Drug Administration web sleep in their contact lenses site for a teaching video and additional information about lens care: should be wearing lenses made www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ from healthier silicone hydro- HomeHealthandConsumer/ConsumerProducts/ gel materials, but they need ContactLenses/default.htm to be aware that this material does not limit their risk of infection.5 Practitioners should be par- regular replacement as a critical risk of sterile keratitis, per- ticularly cautious about recom- component of good contact haps because greater comfort mending extended wear for lens care. encourages overwear. There patients with other risk factors appear to be significant differ- for microbial keratitis, such as Sterile Keratitis ences among daily disposable ocular surface disease, ocular Marginal infiltrative kerati- brands, with some lens brands trauma, smoking and older tis, also called hypersensitivity increasing risk and others age. Unsupervised or unin- keratitis, contact lens acute decreasing it.14 structed wear, as in the use of (CLARE) or sterile Clinicians may also see a cosmetic contact lenses from infiltrative keratitis, is the most sterile form of keratitis in post- unlicensed vendors or lens common contact lens-related LASIK eyes. Diffuse lamellar sharing among friends, also form of keratitis. Overnight or keratitis (DLK) is an inflamma- increases the risk of infection.6,7 extended wear, poor hygiene, tory condition associated with All contact lens patients—espe- protein buildup, a fit that is epithelial trauma that usually cially those who sleep in lens- too tight and contact lens solu- occurs within a few days after es—should be counseled about tion hypersensitivity may all LASIK surgery. The incidence appropriate lens care and wear. be contributing factors. The of DLK has been declining, The latest evidence also sug- condition is typically not sight- but continued outbreaks asso- gests that microbial contami- threatening, but symptoms ciated with improper equip- nation of contact lens cases may be acute and involve sig- ment sterilization have been is a significant and probably nificant morbidity. identified. underappreciated risk factor in Rather than a direct bacte- contact lens-related keratitis.8–10 rial infection, sterile keratitis is Microbial Keratitis Despite expectations that cases thought to be the result of a When the cornea’s defenses should be cleaned daily, 33% host-immune response to bac- are weakened from contact lens of patients say they only clean terial exotoxins.13 It may also wear or trauma, opportunistic their cases once per month (or be associated with lid disease, bacteria can more easily infect less often) and the majority collagen vascular diseases or the cornea. The infection may expose their lenses to tap water viral eye infections. be followed by stromal inflam- in the process.11 One recent Neither silicone hydrogel mation, which can be as dam- paper suggests digital rubbing, materials nor daily disposable aging as the infectious process rinsing with solution, tissue lens modalities have reduced itself and may result in a per- wiping and air drying as a bet- the overall risk of acute non- manent scar. ter cleaning method.12 In any ulcerative sterile keratitis.14 In In a retrospective review of case, practitioners would do fact, certain silicone hydrogel more than 1 million patient well to emphasize the impor- lenses were recently associ- records, Jeng and colleagues tance of case cleaning and ated with a two-fold increased determined that the rate of

REVIEW OF OPTOMETRY November 2011 3

000_ro1111B&L12pg_ac4.indd 3 10/26/11 9:54 AM ulcerative keratitis is 27.6 per dence of MK by contact lens plant matter), diabetes mellitus, 100,000 person-years, which is type from a one-year prospec- chronic topical medication use higher than previously report- tive study in Australia: and topical steroids. ed.15 The relative risk for con- tact lens wearers vs. non-lens # MK cases wearers is 9.31. per 10,000 Contact Lens Type The leading pathogens impli- 1.9 Hydrogel daily wear cated in microbial keratitis (MK) include Gram-positive 11.9 Silicone hydrogel daily wear Staphylococcus and Streptococcus 2.0 Daily disposable wear species and Gram-negative 19.5 Hydrogel extended wear organisms such as Pseudomonas 25.4 Silicone hydrogel extended wear aeruginosa. Pseudomonas is the most frequently identi- fied pathogen in contact lens- • Recent contact lens- In 2007, an outbreak of related MK, but is unusual in related outbreaks. Pathogens Acanthamoeba contact lens- trauma cases.16-18 The bacteria once considered much less related keratitis was linked colonize soft contact lenses common have become the sub- to another contact lens solu- and often, the lens cases.10,19 ject of increasing concern in tion (Complete MoisturePlus, Pseudomonas and other Gram- the United States contact lens AMO), which was also recalled. negative species can quickly community after two major Patient noncompliance was perforate the cornea, especially outbreaks of contact lens- once again a factor, as was in the presence of an epithelial related keratitis. In 2006, an exposure to non-sterile water basement membrane defect. outbreak of Fusarium keratitis (e.g., tap, lake, pool, etc). In a large retrospective among contact lens wearers was Acanthamoeba is a water- records review, 31.7% of MK linked to the use of a particular borne parasite that has both patients lost more than two contact lens solution (ReNu a cyst and trophozoite form. lines of vision and 1.6% lost with MoistureLoc, Bausch + The cysts are very resistant to 10 or more lines of vision, Lomb) that was subsequently treatment. In this case, compo- with ocular trauma and con- withdrawn from the market by nents of the lens care solution tact lens wear being the major the manufacturer. Lens care may have actually encouraged predisposing factors.20 In compliance was also thought encystment of the organ- recent years, researchers have to have been a factor. Research ism.25 Like Fusarium keratitis, attempted to determine the shows that 50% to 99% of con- Acanthamoeba corneal infec- relative risks of different types tact lens wearers are noncompli- tions often go on to keratoplas- of contact lens wear. In large, ant, with case care compliance ty and poor visual outcomes. prospective, post-market clini- being among the worst.23,24 Years after the recalls, rates cal trials of low-Dk/t extended Prior to this outbreak, fungal of both Acanthamoeba and wear disposable lenses, Holden keratitis (caused by Fusarium, fungal keratitis remain elevated and colleagues21 found an Candida, Aspergillus and other and have not returned to pre- annualized incidence of 57 filamentous or dematiaceous outbreak levels.26,27 These two cases of MK per 10,000 wear- fungi) was considered very rare serious contact lens-related ers—or 1 in 173 wearers per in the United States, account- keratitis outbreaks in the year of lens wear. (This was ing for perhaps only 5% of cor- United States should serve as higher than the rate of keratitis neal infections. It is much more a reminder of the importance seen previously in retrospective common in tropical climates. of educating patients about population studies.) Risk factors for fungal keratitis contact lens wearing schedules, Stapleton and colleagues22 include ocular trauma (especial- hygiene and care. They also published the following inci- ly when associated with soil or highlight the need for ongo-

4 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 4 10/26/11 9:54 AM Courtesy of Paul Karpecki, O.D. ing development of contact rences is poorly understood. lens disinfecting solutions. They have long been thought to Fortunately, as multipurpose be linked to stress, but at least solutions (MPSs) continue to one study foundno evidence of evolve, they are beginning to an association with stress.35 offer better disinfection against Immune stromal keratitis fungi, Acanthamoeba and other (ISK, often called disciform atypical organisms, particularly keratitis in the past), although in combination with new sili- Recurrent corneal erosion. also caused by herpes simplex, cone hydrogel materials. is a stromal immune response • Post-LASIK MK. sloughing of the epithelium in to the prior viral antigen expo- Infectious keratitis is also one or more spots where it fails sure. It does not, therefore, seen as a rare but potentially to adhere properly. It is believed present as an active stromal devastating complication of that damage to superficial squa- infection, but there may be laser refractive surgery. In mous cells of the epithelium due some live virus concurrent with 2001, the American Society of to corneal exposure is respon- the immune keratitis. and Refractive Surgery sible for RCES.29 Herpes zoster ophthalmicus reported the incidence of post- In 20% to 30% of cases, this (HZO) also often leads to cor- LASIK keratitis as about 1 in syndrome is primary, related to neal involvement. HZO forms 3000 cases.28 Cases tend to epithelial basement membrane of keratitis include infectious be clustered in mini-epidem- dystrophy (EBMD) or other epithelial pseudodendrites, neu- ics. When the onset is soon dystrophies.29,30 In the majority rotrophic ulcers or persistent after surgery, the most likely of cases (46% to 71%),30,31 how- epithelial defects and stromal pathogens are Staphylococcus ever, RCES is secondary to cor- immune reaction.36 species. Late-onset cases are neal trauma, such as a fingernail more likely to be caused by scratch or paper cut. It may also Phlyctenular Keratitis fungi, Nocardia or atypical be secondary to ocular infection, Phlyctenular keratitis is Mycobacteria.28 lid pathology or systemic causes. thought to be a delayed For the clinician, it is criti- There is a strong association hypersensitivity response to cal to differentiate sterile from between recurrent erosions and microbial infection, often infectious keratitis and fungal increasing age, as well as with Mycobacterium tuberculosis or from bacterial so that appropri- sleep apnea-related dryness.32 S. aureus. Recently, it has been ate management can be initi- shown that Propionibacterium ated. Inappropriate manage- Herpetic Keratitis acnes is also implicated.37 More ment delays resolution of the Herpes simplex virus (HSV) prevalent in young females, the infection, increases cost and stromal keratitis is a recurrent, condition and its severity are the duration of care and may corneal manifestation of the her- often closely associated with result in vision loss and lasting pes simplex virus and a leading meibomitis.37 ocular damage. cause of corneal opacification.33 Most (95%) ocular herpes infec- Chemical Keratitis Recurrent Corneal tions, other than neonatal cases, Chemical injury rapidly Erosion Syndrome are caused by HSV-1.34 The inci- destroys the epithelium and Recurrent corneal erosion dence has been estimated at 8.4 can cause significant damage to syndrome (RCES) is character- to 13.2 new cases per 100,000 the cornea. Acidic agents cause ized by recurrent episodes of person-years,33 with the elderly more surface damage, while nighttime eye pain or pain upon and immunocompromised more alkali agents tend to penetrate awakening, accompanied by red- likely to suffer from this condi- more aggressively, causing stro- ness and . The sud- tion. Recurrences are common. mal scarring, ectasia and pro- den onset of pain is caused by Exactly what triggers these recur- gressive damage.38

REVIEW OF OPTOMETRY November 2011 5

000_ro1111B&L12pg_ac4.indd 5 10/26/11 9:54 AM Sterile Keratitis eral ulcers, more anterior cham- Sterile peripheral corneal ber reaction and is often accom- infiltrates are commonly seen panied by an overlying epithelial in optometric practice. Upon defect approximating the size of examination, the clinician typi- the stromal infiltrate (see sidebar cally sees grayish-white infiltrates “Differential Diagnosis: Sterile in the peripheral cornea, with a Infiltrative Events vs. Microbial Courtesy of Paul Karpecki, O.D. clear zone separating the infil- Keratitis” on the next page). trates from the limbus. In infectious keratitis, the infiltrate is The typical presentation of The standard of care in the often accompanied by an overlying MK includes a significantly treatment of peripheral infil- epithelial defect approximating the red eye with acute onset. The trates is to treat empirically size of the stromal infiltrate. patient will typically experience with a combination antibiotic/ more pain and discharge from steroid such as tobramycin/ often be sufficient to treat any an infectious ulcer compared to loteprednol etabonate (Zylet, pathogenic bacteria should a sterile infiltrate. Severe pain, Bausch & Lomb). The medica- there be an early infection. while not diagnostic, should tion should be instilled every 2 The risk that the infiltrates raise the clinician’s suspicion hours while awake for the first are infectious and could be of infection. Decreased vision 24 to 48 hours, then reduced worsened by the steroid is very is virtually pathognomic for an to q.i.d. for 3 to 5 more days. low. However, if other risk fac- infectious process. Vision may With this regimen, the com- tors, such as a diffuse red eye, be affected even when the infil- bination therapy can address cells in the anterior chamber or trate is relatively small and not the most likely culprit, sterile severe pain are present, a broad- located on the visual axis. corneal inflammation, and will spectrum fluoroquinolone In examining a patient with should be used as initial thera- suspected MK, look for the py. Patients should be followed characteristic epithelial defect When to Culture closely to ensure improvement overlying the infiltrate. Careful • Infiltrate on or near the with treatment. assessment of the tear film and visual axis Sterile diffuse lamellar kera- discharge is essential. The dis- titis (DLK) may also occur charge may be subtle and micro- • Large infiltrate (>3 mm) post-LASIK or other refractive particulate rather than purulent. • Significant decrease in surgery. Topical corticoste- Clinicians will often see cells and vision roids are appropriate for the some flare in the anterior cham- • Post-surgical eye treatment of DLK, unless the ber, as well. • Monocular patient clinician sees clumping of the Although there is some sug- cells. In the presence of this gestion in the literature that • History of immunocom- promise sign, a corneal melt is possible, Gram-negative infections tend and oral corticosteroid therapy to be more diffuse and “wet- • Ocular steroid use 39 should be added. ter” in appearance, visual • Older patient assessment of the lesion is not • Diabetic patient Microbial Keratitis sufficient to determine whether In contrast to the non- the infectious agent is Gram- • Patient who works in a infectious conditions described negative or Gram-positive. nosocomial or health- care setting. above, MK is characterized by Larger, more centrally located more central, rather than periph- or more aggressive infiltrates

6 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 6 10/26/11 9:54 AM Mini-Tip Culturettes are available from are Gram-negative or Gram- multiple sources, including the following: positive. Medical therapy of MK has • eGeneral Medical, Inc., in Raleigh, N.C., (919) 844-9402 changed dramatically over the or www.egeneralmedical.com last decade or so. Prior to the 1990s, the standard of care was • Hardy Diagnostics in Santa Maria, Calif., (805) 346-2766 or www.hardydiagnostics.com fortified cefazolin or vancomycin for Gram-positive ulcers and must be cultured to guide a deep swab of the infiltrate tobramycin or gentamicin for therapy. is needed, so anesthetic eye Gram-negative ulcers. Many Direct culture plating is drops (ideally non-preserved) corneal specialists still adhere to complex and unlikely to be should be instilled. We recom- that regimen today. But research performed often enough to be mend swabbing the infiltrate data and clinical experience sug- reliable in a primary eye-care itself or around the perimeter gest that smaller, superficial, setting. Pre-packaged mini- of the epithelial defect, rather off-axis lesions can be treated tip culturette kits have been than attempting to culture the empirically with fluoroquinolone shown to be as sensitive and discharge, as discharge does not monotherapy.41 specific as direct plating.40 always contain active bacteria. As with the decision of They are simple and have a rel- A gram stain is also rela- whether or not to culture, the atively long shelf life compared tively simple and can provide size of the defect and the like- to other culturing materials. valuable information about lihood of threatening vision For the most accurate result, whether the causative bacteria must also be taken into account

Differential Diagnosis: Sterile Infiltrative Events vs. Microbial Keratitis

Sterile Corneal Infiltrates Microbial Keratitis Symptoms Minimal pain and photophobia Moderately severe pain and photophobia Conjunctival Injection Minimal, possibly sectoral Moderate to severe, most likely diffuse Lid Edema None or minimal Moderate Visual Acuity Normal Decreased Location Usually mid-peripheral to Random with deeper peripheral, subepithelial involvement, tend to be more central Size Usually 1 to 1.5mm, tend to > 1.5mm, enlarges over remain small 24-36 hours NaFl Staining None or minimal Moderate to extensive Anterior Chamber Reaction None or minimal Moderate Stromal edema None or minimal Moderate Number of Infiltrates Tend to be multiple (>1) Single Clear Zone at Limbus Positive Negative Shape Oval Any Purulent Discharge Negative Positive

REVIEW OF OPTOMETRY November 2011 7

000_ro1111B&L12pg_ac4.indd 7 10/26/11 9:54 AM when deciding between forti- from the besifloxacin-treated have added trimethoprim- fied and commercially avail- eyes than from those treated polymyxin B (Polytrim) q2h able antibiotic therapy. With with gatifloxacin, moxifloxacin, to fluoroquinolone therapy to severe infections, aggressive and or saline (controls). The mini- provide additional protection appropriate initial therapy is key mum inhibitory concentrations against resistant organisms, to avoiding poor outcomes.42 (MICs) for besifloxacin were especially S. aureus. Besifloxacin The Wills Eye Manual chart at least 8-fold lower than those may be able to provide similar on fortified antibiotics and the for the other fluoroquinolones. coverage to these two drugs in chapter on the same subject in Besifloxacin may also have a single medication. In addi- Ophthalmic Drug Facts43 are some anti-inflammatory tion to the evidence from the helpful resources. properties.48 MRSA rabbit studies described The only topical ophthalmic Treatment of suspected MK above,46,47 the Antibiotic antibiotics approved for the with topical fluoroquinolones Resistance Monitoring in treatment of MK are ciprofloxa- should be much more aggres- Ocular MicRoorganisms cin, ofloxacin, and levofloxacin. sive than the typical q.i.d. (ARMOR) study provides On-label does not, however, dosing for postoperative pro- important information about mean effective. Resistance to phylaxis or routine corneal pre- differences in the potency of ciprofloxacin, in particular, has sentations. Achieving compli- commonly used antibiotics been increasing. As standards of ance with some of the dosing against clinical isolates.49,50 care have evolved, newer fluo- recommendations in the medi- For example, according to

roquinolones such as moxifloxa- cation package inserts (every their MIC90 values, besifloxa- cin and gatifloxacin have been 15 minutes for six hours, then cin, vancomycin and imipenem utilized off–label. every 30 minutes for 18 hours, were the most potent against The latest iterations of these for example) is very challeng- S. aureus isolates, while cip- fluoroquinolones, Zymaxid ing. A more realistic schedule rofloxacin, tobramycin and (Allergan) and Moxeza (Alcon) is a loading dose of one drop azithromycin were the least include higher antibiotic con- every minute for five minutes potent. Against MRSA, besi- centrations, but the active given in the office, then drops floxacin maintained potency

ingredients (gatifloxacin and every hour while awake. At with an MIC50/MIC90 of 0.5/1 moxifloxacin, respectively) are bedtime, the patient can apply µg/mL (moxifloxacin: 2/8 µg/ the same. an ointment such as bacitra- mL; ciprofloxacin: 8/256 µg/ The newest fluoroquino- cin or bacitracin-polymyxin B, mL).49 Imipenem, besifloxa- lone, besifloxacin (Besivance, although some clinicians may cin and vancomycin were the Bausch + Lomb), while also prefer for them to awaken for most potent agents against not labeled for keratitis, has drops every 2 hours the first coagulase-negative Staphylococci demonstrated broad-spectrum night. Daytime fluoroqui- (CNS), while levofloxacin, tri- in vitro activity against both nolone treatment should be methoprim and azithromycin Gram-positive and Gram- continued at least hourly, and were the least potent. negative pathogens, including patients should be examined Again, the aggressiveness those resistant to other fluoro- daily until clinical resolution of therapy should be titrated quinolones.44 In recent rabbit has occurred. somewhat to the degree of model studies, besifloxacin has In sight-threatening cases risk, using the same factors one been shown to be very effec- where vision loss is a concern, uses in determining whether tive against Pseudomonas kera- q30-minute dosing may be to culture and whether to use titis and methicillin-resistant required, and topical fluoroqui- fortified antibiotics. Staphylococcus aureus (MRSA) nolones alternated with fortified Eradicating the microbes must keratitis.45–47 After treatment, antibiotics may be desirable. be the first priority; adjunctive significantly fewer colony- With increasing concerns agents can then help to suppress forming units were recovered about MRSA, some clinicians tissue inflammation and reduce

8 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 8 10/26/11 9:54 AM discomfort. A topical cyclople- is underway.52 Oral doxycycline lesions, classically at the lim- gic agent such as homatropine, to minimize the potential for bus with a clear zone, while scopolamine or cyclopentolate collagenase activity may also be an infectious etiology is more given at each office visit dramati- considered.53 likely to produce a single, larg- cally reduces the pain level for With Gram-negative infec- er, and more centrally located the patient. Due to the risk of tions, it is not uncommon for lesion. Other differentiating corneal melts, we avoid topical the infiltrate to appear the same features are described above NSAIDs for pain in MK cases, and the epithelial defect to and in the table on page 7. but oral ibuprofen or opioid appear even larger after the first Contact lens wearers are analgesics can be helpful. day of treatment.54 This some- also at increased risk for devel- Steroids are effective in times mistakenly leads clinicians opment of Acanthamoeba treating inflammation but to change the course of treat- keratitis, particularly follow- must be used wisely. They ment too soon. If culture results ing exposure of contact lenses should not be given until cul- suggest the selected therapy is to contaminated water (e.g., ture results are available and correct, give therapy a little lon- swimming pools, hot tubs, there is a significant response ger to begin to show results. tap water). In the early stages,

to treatment—preferably re- Courtesy of Paul Karpecki, O.D. there is sometimes a gelati- epithelialization. This will nous appearance to the cornea. usually be at least two days Later, one will see perineu- after commencing treatment of ral infiltrates that look very Gram-positive organisms, and similar to linear or dendritic at least three days with Gram- herpetic lesions and often lead negative organisms. Provided to misdiagnosis as herpes sim- one is certain that the etiology plex keratitis. Patients with is not fungal or herpetic, it is usually, prudent and reasonable at that but not always, complain of point to add two to four times Contact lens wearers are also significant pain. Typically, the daily dosing of corticosteroid at increased risk for developing eye appears to be getting bet- anti-inflammatory therapy Acanthamoeba keratitis, particularly ter, then suddenly flares back such as loteprednol etabonate following exposure of lenses to con- up between days 10 and 14. If (Lotemax, Bausch + Lomb) taminated water. In the early stages, MK does not improve after 14 or difluprednate (Durezol, there is sometimes a gelatinous days of treatment, reconsider Alcon) to decrease the poten- appearance to the cornea; in the your diagnosis and treatment. tial for scarring, particularly if later stages, it is commonly misdi- Polyhexamethylene bigu- the lesion is para-central. One agnosed as . anide (PHMB) is generally the very recent study showed no preferred agent for treatment of benefit to using steroids in • Contact lens-associated Acanthamoeba keratitis. Other combination with antibiotic MK. Contact lens wearers are agents, used in combination or therapy in the treatment of at increased risk for both sterile alone, include propamidine and corneal ulcers.51 However, the and microbial keratitis, includ- chlorhexidine. A corneal consult authors also suggested that ing some particularly virulent is recommended. the early addition of steroids or unusual pathogens. In mak- Contact lens-related kera- to the antibiotic treatment of ing the differential diagnosis titis is often seen in patients corneal ulcers does not seem in a contact lens wearer, the who are noncompliant with to be harmful when employed location of the lesion is very lens care and wearing sched- in a closely monitored clini- important. In a sterile event, ules. In particular, we know cal setting. A national study the contact lens wearer typi- that the risk of infiltrates and on the role of steroids in the cally would have smaller and ulcers is highest among those treatment of infectious keratitis more peripherally located who sleep in contact lenses.

REVIEW OF OPTOMETRY November 2011 9

000_ro1111B&L12pg_ac4.indd 9 10/26/11 9:55 AM Unfortunately, such patients Culture scrapings will be brittle Post-Refractive may also be noncompliant with rather than wet. However, Surgery Keratitis medical therapy to treat the all these distinctions are MRSA is the most commonly infection. It is very important subtle ones that may be diffi- cultured pathogen in post-LASIK to emphasize to the noncom- cult to discern. keratitis.61 Although the MRSA pliant lens wearer the potential If a fungal etiology is sus- pathogen is still relatively rare in consequences of not using the pected, a spatula scraping non-institutionalized patients, prescribed drops. They must is preferred over a mini-tip MRSA keratitis following refrac- be made aware of the risk of culturette; however, the lat- tive surgery has been reported in blindness, corneal scars and ter may still isolate the fun- the literature, including a series other long-term sequellae. gal pathogen. Although they of 13 cases in New York.62-64 A compliant patient can be tend to develop more slowly A large national surveillance wearing contact lenses again program, ARMOR, has recently within a week or 10 days of shown that the incidence of full resolution of the infection. MRSA may be on the rise,49,50 When there is chronic noncom- so clinicians should maintain a pliance or poor hygiene, keep- healthy awareness of the poten- ing the patient out of lenses a tial for MRSA and be prepared little longer and working on to treat suspected cases. modification of behaviors or Fungal (Fusarium) infection with Post-refractive surgery kerati- Courtesy of Randall Thomas, O.D. wearing schedules is advisable. stromal infiltrate. tis generally occurs within a few The practitioner may consider days of the laser procedure and a switch to daily wear or daily than typical bacterial keratitis, should be cultured and treated disposable lenses or re-fitting Fusarium and other fungal quickly. In choosing an antibi- with a looser lens. infections are very challeng- otic to treat MRSA, the clinician • Fungal keratitis. This ing to treat. Outcomes and must consider more than just the form of keratitis is exceedingly response to medical therapy drug’s minimum inhibitory con- rare in the United States, but have historically been poor.56,57 centration (MIC) value, which is the possibility of a fungal etiol- The standard approach established for the active ingredi- ogy cannot be ignored, par- to treatment is topically admin- ent and doesn’t necessarily reflect ticularly if there is a history of istered . If the eye the efficacy of a given formulation vegetative abrasions or agricul- doesn’t respond, amphotericin in a clinical setting, when factors tural work. The 2006 Fusarium B, flucytosine, fluconazole or a such as washout and pH come outbreak described earlier also new-generation triazole into play. The clinician should demonstrated that contact lens may be added.57-60 Antifungal consider antimicrobial potency as solutions or lens hygiene may be medications have significant well as tissue penetration of the implicated, even without other side effect profiles, so even if antibiotic selected to treat MRSA. corneal trauma. there is a strong suspicion of The ARMOR data have dem- Fungal keratitis is character- a fungal etiology, the ulcer onstrated that the new fluoro- ized by conjunctival injection should be treated with forti- quinolone besifloxacin, along and gray or yellow-white infil- fied antibiotics until positive with some older antibiotics, trates with irregular, dry, feath- culture results are obtained. remain highly efficacious against ery margins.55 The lesions may Serious consideration should pathogens that have developed be slightly raised above the be given to referring to or resistance to other drugs. When plane of the corneal epitheli- co-managing with a corneal MRSA is diagnosed or suspect- um. Satellite lesions and endo- specialist, given the substantial ed, it is appropriate to add besi- thelial plaque formation may risks of morbidity, visual loss, floxacin and/or trimethoprim be more common in fungal corneal scarring and corneal with polymyxin B to your regi- keratitis than in bacterial cases. perforation. men. In post-operative manage-

10 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 10 10/26/11 9:55 AM ment of suspected MRSA infec- hypertonic sodium chloride Lotemax q.i.d. for two to four tion, fortified vancomycin may solution (Muro 128 5%, Bausch weeks, then b.i.d. for six weeks; also be considered. + Lomb) used q.i.d., plus the and 20 mg to 50 mg of doxy- same medication in an oint- cycline b.i.d. for two months. Recurrent Corneal ment form at bedtime. Research Anterior stromal puncture, as Erosion Syndrome shows that sodium chloride has pioneered by Rubinfeld, is also Acute, unilateral morning a therapeutic effect beyond just very effective.73 pain and redness are hallmarks lubrication.65 To be effective, Long-term management of RCES. The erosions are usu- however, therapy should be con- demands ongoing lubrication of ally found on the inferior cor- tinued for at least six to eight the eye with artificial tears and nea. Macroform erosions result weeks to draw fluid from the possibly supplementation with in significant symptomatology epithelium, keeping it apposed omega-3 fatty acids. Patients and are usually clearly visible to to Bowman’s membrane and should be counseled to avoid the clinician. Microform ero- thereby promoting adherence. ceiling fans, especially at night. sions, however, dissipate within This allows for normalization of Concomitant should 30 minutes to a few hours and the basal cells, epithelial base- also be treated appropriately to must be diagnosed by history. ment membrane and stromal help prevent recurrences. Clinically, the clinician may see corneal tissue complex. (After negative staining patterns or the first month, clinicians may Herpetic Keratitis poor wetting at the site where substitute a non-hypertonic arti- • Herpes simplex. Herpes the epithelium is breaking down, ficial tear ointment at night). simplex keratitis is seen com- even if the erosion has healed by Bandage contact lens therapy monly in clinical eye-care prac- the time of presentation. for three months or longer is a tice. Most people have been Although often associated viable option for the manage- exposed to the herpes simplex with ocular trauma, such as ment of patients with recurrent virus as children, often without a fingernail scratch, corneal corneal erosion.66,67 A low- ever being diagnosed or treated, erosion can be spontaneous. powered refractive lens, whether as the initial exposure presents as In such cases, look closely for approved as a bandage lens or transient mild fever, malaise and subtle signs of epithelial base- not, serves this purpose quite chills. Primary herpetic disease

ment membrane dystrophy well. Phototherapeutic keratec- Courtesy of Randall Thomas, O.D. (EBMD), such as rapid tear tomy (PTK)68 and autologous film break up in the same spot. serum69 have also been shown to After applying a topical anes- have long-term efficacy in treat- thetic, gently touch the cornea ing this condition. Other pos- (typically the inferior cornea) sible interventions include alco- with a Weck cell sponge. In hol delamination or mechanical eyes with EBMD, the epi- debridement of the epithelium. thelium heaps up like a loose Patching is rarely necessary.70 carpet rather than staying tight For recalcitrant cases, inhibi- Herpes simplex keratitis. as it should. When underlying tion of matrix metalloprotein- Courtesy of Randall Thomas, O.D. EBMD is present, it takes very ase-9, the enzyme responsible for little to cause recurrent epithe- epithelial cleaving, with topical lial problems. steroids plus oral doxycycline RCES is relatively easy to appears to be quite successful.71,72 diagnose, but there are many In such cases, we recommend different approaches to manag- a “cocktail” that includes hyper- ing these patients clinically. The tonic sodium chlorine 5% t.i.d. standard baseline treatment for to q.i.d. daily for two months; RCES is lubrication, ideally with Muro 128 ointment at bedtime; Herpes simplex keratitis.

REVIEW OF OPTOMETRY November 2011 11

000_ro1111B&L12pg_ac4.indd 11 10/26/11 9:55 AM Differential Diagnosis of Herpes Simplex and Herpes Zoster

Herpes Simplex Herpes Zoster

Dermatomal distribution Not applicable Respects the dermatome Pain Mild to moderate Severe Dendrite appearance Larger, more branching, Smaller, less branching, discrete, delicate pattern, coarse, blunted pattern, more central usually peripheral Epithelium Ulcerated Blunted dendrite with slightly raised edges NaFl staining Prominent Dull and irregular End bulbs Present Absent Scarring of skin Rare Common Postherpetic neuralgia Rare Common atrophy Rare Common Recurrence Common Rare

Adapted from Nichols B, Ed. Basic and clinical science course. External disease and the cornea, Section 7, American Academy of , San Francisco CA 1990.

often has ocular manifestations stages, but can be revealed even uniform throughout the cornea such as periocular vesicles or in small lesions with rose bengal and individual rather than over- ulcerative blepharitis. or lissamine green dye. In more lapping or coalesced. Herpes simplex keratitis usu- advanced stages, the lesions may A new antiviral, ganciclovir ally builds up over two to five take on a broader, more geo- ophthalmic gel (Zirgan, Bausch days, rather than presenting graphic appearance. + Lomb) has replaced trifluri- acutely, and is almost always In the differential diagno- dine (Viroptic, Monarch) as the unilateral. Patients typically have sis of HSV keratitis (see table some corneal desensitization, above), one must also rule out little pain and mild photopho- conditions that can mimic it, bia—certainly not the extreme including a rare toxic response photophobia that clinicians see to topical latanoprost74 and with infiltrative ulcers or iritis. Thygeson’s SPK.75 About 20% The classic hallmark of herpes of all Thygeson’s cases are uni-

simplex is the dendritic ulcer. lateral, such as HSV keratitis. Courtesy of Ron Melton, O.D. In the early stages, clinicians However, Thygeson’s typically might see some focal superficial presents with sudden onset, In Thygeson’s SPK, the lesions look punctate keratitis (SPK) without more photophobia and normal quite different from those of herpes the typical dendritic configura- corneal sensitivity. Additionally, simplex keratitis. They are granular, tion. But even early herpetic the lesions look quite different. punctate, and well-defined. lesions will tend to be linear in Thygeson’s lesions are granular, shape, rather than the round or punctate and very well defined. standard of care for herpetic ker- oval shape common to sterile or Occasionally, there may be some atitis. Ganciclovir ophthalmic gel bacterial infiltrates. The terminal anterior chamber reaction to is as effective in treating estab- end bulbs that are also charac- herpes simplex, but never to lished HSV-1 herpetic keratitis teristic of herpes simplex kerati- Thygeson’s. Also, the lesions for in the rabbit as trifluridine76 but tis may not be apparent at early Thygeson’s tend to be relatively is more convenient and tolerable

12 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 12 10/26/11 10:17 AM for patients than other options77, 78 (See “Topical Antiviral Topical Antiviral Options Options”). Zirgan is dosed five Trifluridine Ganciclovir times a day until the ulcer is • Old drug • New drug healed, followed by three times • Nonselective toxicity • Infected cell-specific a day for seven days. • Potentially toxic • Very low toxicity • More frequent dosing • Less frequent dosing It is important to emphasize • Refrigerate until opened • No refrigeration needed to patients that there is a 40% • Thimerosal preserved • BAK preserved to 50% chance of recurrence • Solution (7.5 ml bottle) • Gel (5 gram tube) • Viroptic and generic • Zirgan by B+L with HSV keratitis. Adjunctive, • Samples not available • Samples available prophylactic oral antivirals can reduce the chance of re-activa- tion.79 Landmark clinical trials titis is that the steroid treatment to one study, 45% of all cases recommend ongoing prophylac- must usually be continued over of herpes zoster have signifi- tic use of acyclovir 400 mg b.i.d. several months, with a long, cant iritis, while 36% also go or valacyclovir 500 mg once slow taper. Some people may on to develop within daily to prevent future recur- even need once-daily steroid a 10-year period of time,84 so rences.80,81 Additionally, anyone therapy for life. Loteprednol is it is very important to evaluate with a history of herpes simplex ideal for these cases because of for . keratitis should be prophylacti- its reduced propensity to elevate If uveitis or significant stromal cally treated with oral antivirals IOP or cause . disease is present, aggressive before and after undergoing cor- Both forms have a tendency topical corticosteroid inflam- neal surgery. The adult dosage to recur and may be reactivated matory suppression is needed. of acyclovir is easy to remember: by ultraviolet exposure, trauma Clinicians may see a secondary 400 mg (half that for herpes and possibly stress. The triggers sharp increase in IOP, but rather zoster) five times daily for a are difficult to determine and are than stopping the steroid, treat week. Oral antivirals may also be highly variable. the IOP spike by getting the a good first-line choice for chil- • Herpes zoster ophthal- inflammation under control. dren or others who have trouble micus. Ocular involvement with eye drops.82 Permanent is common with first division Phlyctenular Keratitis punctal occlusion by thermal trigeminal herpes zoster oph- Phlyctenular keratitis is seen cautery with topical cyclospo- thalmicus (HZO). The ocular most often in younger children, rine has also been suggested to involvement is typically inflam- especially girls. The position of reduce recurrences of stromal matory keratitis or uveitis, but the lesion—straddling or perpen- HSV keratitis.83 occasionally . In dicular to the limbus—can help The management of ISK milder cases without uveitic to distinguish phlyctenular kerati- can be more challenging. involvement, oral antivirals tis from a marginal infiltrate. The Corticosteroids will quickly alone may be used to treat lesion will have a raised appear- resolve the stromal edema. HZO keratitis. But according ance, and if the lesion is on the

However, steroid therapy may at Courtesy of Paul Karpecki, O.D. cornea, one can usually see a the same time activate or exac- leash of blood vessels continu- erbate the epithelial disease, so ous with the phlyctenule, which a concomitant topical antiviral, is quite different from a clear or dosed q.i.d., is needed. As the lucid interval in the setting of a steroid is tapered, the antiviral peripheral infiltrate. The patient can be reduced or eliminated. may report significant foreign Additionally, a key difference body sensation if the phlyctenule in the treatment of ISK com- migrates onto the cornea. pared to epithelial herpetic kera- Herpes zoster. There is often associated

REVIEW OF OPTOMETRY November 2011 13

000_ro1111B&L12pg_ac4.indd 13 10/26/11 9:55 AM blepharitis, given that phlyc- must be avoided in children pH, significant blanching or tenular keratitis is usually the under 12 years of age. limbal ischemia, the eye may result of staphylococcal hyper- require . sensitivity. However, it may Chemical Consultation with a cornea spe- also be caused by tuberculo- cialist is recommended. sis (TB). Though rare in the With chemical keratitis, which In less severe cases, non- United States, TB exposure typically involves the conjunc- preserved artificial tears are the can occur unnoticed in health- tiva as well, the patient has first line of therapy, but the cli- care settings, foreign travel, or often been pre-treated in an nician should also consider anti- on Native American reserva- emergent care setting. For the biotic and/or steroid therapy. tions. Patients with phlycte- eye-care provider, it is impor- Treat with a topical antibiotic nular keratitis and no obvious tant to know the nature of the alone if there’s a fair amount blepharitis should be referred agent and any pre-treatment of epithelial compromise, or a for a TB test to rule out a that has occurred. Then, after combination antibiotic/steroid, determining the extent of the depending on the nature of injury, the immediate goals the corneal presentation, the are to minimize ulceration and offending agent and the inflam- inflammation and promote re- matory response. A cycloplegic epithelialization. is also very helpful for control- Ocular exposure to cyanoacry- ling ocular pain. late (fingernail glue) is common and can be very frightening for Conclusion Courtesy of Randall Thomas, O.D. the patient but is actually mini- Primary eyecare providers The position of the lesion— mally toxic and fairly benign. routinely see sterile corneal infil- straddling or perpendicular to the Using a wet gauze pad and light trates, herpetic keratitis and other limbus—can help to distinguish pressure pads, keep the area wet forms of corneal inflammation phlyctenular keratitis from a for 24 hours before peeling off and infection, and should be marginal infiltrate. the dried glue. able to recognize and treat rarer, Aminoglycosides, particularly but potentially more devastating tubercular etiology, particularly gentamicin, have been known to forms of keratitis as well. This if they have been in an area cause chemical keratitis, as have monograph is intended to serve where TB is active. proparacaine and tetracaine. as a guide to differential diagno- Phlyctenular keratitis should Contact lens solutions, hydro- sis and management of various be treated with topical steroids, gen peroxide and facial lotions corneal disorders. given every 2 hours for two can also cause chemical injury to REFERENCES or three days, then tapered to the eye. Lavage the eye to flush 1. Bruce AS, Brennan NA. Corneal pathophysiol- ogy with contact lens wear. Surv Ophthalmol. q.i.d. for a week. The patient out any remaining chemicals. 1990;35(1):25-58. 2. Stapleton F, Stretton S, Papas E, et al. Silicone should see improvement within A litmus test strip can be hydrogel contact lenses and the ocular surface. Ocul Surf. 2006;4(1):24-43. just a day or two. If there is sig- helpful for those cases when 3. Paugh J, Stapleton F, Keay L, Ho A. Tear exchange under hydrogel lenses: methodological considerations. nificant epithelial compromise, the exact source of chemical Invest Ophthalmol Vis Sci. 2001;42(12):2813-2820. 4. Miller KL, Lin MC, Radke CJ, et al. Tear mix- with its attendant risk of super- injury is not known. If there ing under soft contact lenses, in Sweeney DF (ed). Silicone hydrogels: continuous wear contact lenses. ficial infection, the clinician can is no known accidental cause, Oxford, Butterworth Heinemann, 2004:57-89. use an antibiotic/steroid com- stop any topical medications. 5. Schein O, McNally JJ, Katz J, et al. The inci- dence of microbial keratitis among wearers of a bination agent such as Zylet. If the chemical agent is highly 30-day silicone hydrogel extended-wear contact lens. Ophthalmol. 2005:112(12):2172-2179. Doxycycline can be used to alkali, use aggressive lavage and 6. Steinemann TL, Pinninti U, Szczotka LB, et al. Ocular complications associated with the use of cos- treat the associated lid disease check the pH again after flush- metic contact lenses from unlicensed vendors. Eye Contact Lens. 2003;29(4):196-200. and improve meibomian gland ing out the eye. If the pH has 7. Sauer A, Bourcier T, French Study Group for Contact Lenses Related Microbial Keratitis. Microbial functioning to prevent recur- normalized, the eye may be keratitis as a foreseeable complication of cosmetic contact lenses: a prospective study. Acta Ophthalmol. rences. This drug, however, fine, but with continued high 2011;89(5):e439-442.

14 November 2011 REVIEW OF OPTOMETRY

000_ro1111B&L12pg_ac4.indd 14 10/26/11 9:55 AM 8. Hall BJ, Jones L. Contact lens cases: the miss- Surv Ophthalmol. 2009;54(2):226-234. tis. Cornea. 2008;27(9):1077-1079. ing link in contact lens safety? Eye Contact Lens. 34. Pavan-Langston D. In RA Swartz (ed): Herpes 59. Lalitha P, Shapiro BL, Srinivasan M, et 2010;36(2):101-105. Simplex of the Ocular Anterior Segment. Malden,MA, al.Antimicrobial susceptibility of fusarium, aspergil- 9. Szczotka-Flynn LB, Pearlman E, Ghannoum M. Blackwell Science, Inc. 2000. lus, and other filamentous fungi isolated from kerati- Microbial contamination of contact lenses, lens care 35. Herpetic Study Group. Psychological tis. Arch Ophthalmol. 2007;125(6):789-793. solutions, and their accessories: a literature review. stress and other potential triggers for recurrences of 60. Hirose H, Terasaki H, Awaya S, Yasuma Eye Contact Lens. 2010;36(2):116-129. herpes simplex virus eye infections. Arch Ophthalmol. T. Treatment of fungal corneal ulcers with 10. Ogushi Y, Eguchi H, Kuwahara T, et al. 2000;118(12):1617-1625. amphotericin B ointment. Am J Ophthalmol. Molecular genetic investigations of contami- 36. Pavan-Langston D. Clinical manifestations 1997;124(6):836-838. nated contact lens storage cases as reservoirs of and therapy of herpes zoster ophthalmicus. Comp 61. ASCRS Survey 2002-2008: Infectious keratitis Pseudomonas aeruginosa keratitis. Jpn J Ophthalmol. Ophthalmol Update. 2002;3:217-225. after LASIK. Unpublished data from the annual 2010;54(6):550-554. 37. Suzuki T, Mitsuishi Y, Sano Y, et al. Phlycten-ular ASCRS meeting. 11. Hickson-Curran S, Chalmers RL, Riley C. Patient keratitis associated with meibomitis in young patients. 62. Nomi N, Morishige N, Yamada N, et al. attitudes and behavior regarding hygiene and replace- Am J Ophthalmol. 2005;140(1):77-82. Two cases of methicillin-resistant Staphylococcus ment of soft contact lenses and storage cases. Cont 38. Wagoner MD. Chemical injuries of the eye: aureus keratitis after Epi-LASIK. Jpn J Ophthalmol. Lens Anterior Eye. 2011;34(5):207-215. Current concepts in pathophysiology and therapy. 2008;52(6):440-443. 12. Wu YT, Teng YJ, Nicholas M, et al. Surv Ophthalmol. 1997;41(4):275-313. 63. Solomon R, Donnenfeld ED, Perry HD, et al. Impact of lens case hygiene guidelines on con- 39. MacRae SM, Rich LF, Macaluso DC. Treatment Methicillin-resistant Staphylococcus aureus infec- tact lens case contamination. Optom Vis Sci. of interface keratitis with oral corticosteroids. J tious keratitis following refractive surgery. Am J 2011;88(10):E1180-1187. Cataract Refract Surg. 2002;28(3):454-461. Ophthalmol. 2007;143(4):629-634. 13. Smay JC. CE Course: Sterile corneal infiltrates: 40. McLeod SD, Kumar A, Cevallos V, et al. 64. Woodward M, Randleman JB. Bilateral methi- Differential diagnosis and clinical management. Reliability of transport medium in the laboratory cillin-resistant Staphylococcus aureus keratitis after Optometry Today. March, 1998:54-66. evaluation of corneal ulcers. Am J Ophthalmol. photorefractive keratectomy. J Cataract Refract Surg. 14. Radford CF, Minassian D, Dart JKG, et al. Risk 2005;140(6):1027-1031. 2007;33(2):316-319. factors for nonulcerative contact lens complications in 41. McLeod SD, Kolahdouz-Isfahani A, Rostamian K, 65. Brown N, Bron A. Recurrent erosion of the cor- an ophthalmic accident and emergency department. et al. The role of smears, cultures and antibiotic sen- nea. Br J Ophthalmol. 1976;60(2):84-96. Ophthalmology. 2009;116(3):385-392. sitivity testing in the management of suspected infec- 66. Fraunfelder FW, Cabezas M. Treatment of recur- 15. Jeng BH, Gritz DC, Kumar AB, et al. Epidemiol- tious keratitis. Ophthalmology. 1996;103:23-28. rent corneal erosion by extended-wear bandage con- ogy of ulcerative keratitis in Northern California. Arch 42. McLeod SD, LaBree LD, Tayyanipour R, tact lens. Cornea. 2011;30(2):164-166. Ophthalmol. 2010;128(8):1022-1028. et al. The importance of initial management in 67. Moutray TN, Frazer DG, Jackson AJ. Recurrent 16. Green M, Apel A, Stapleton F. Risk factors and the treatment of severe infectious corneal ulcers. erosion syndrome—the patient’s perspective. Cont causative organisms in microbial keratitis. Cornea. Ophthalmology. 1995;102(12):1943-1948. Lens Anterior Eye. 2011;34(3):139-143. 2008;27(1):22-27. 43. Bartlett JD, ed. Ophthalmic drug facts. St. Louis. 68. Baryla J, Pan YI, Hodge WG. Long-term efficacy 17. Sirikul T, Prabriputaloong T, Smathivat A, et al. Wolters Kluwer Health. 2011; Chap. 15, 431-439. of phototherapeutic keratectomy on recurrent corneal Predisposing factors and etiologic diagnosis of ulcer- 44. Haas W, Pillar CM, Zurenko GE, et al. erosion syndrome. Cornea. 2006;25(10):1150-1152. ative keratitis. Cornea. 2008;27(3):283-287. Besifloxacin, a novel fluoroquinolone, has broad- 69. Ziakas NG, Boboridis KG, Terzidou C, et al. 18. Mah-Sadorra JH, Yavuz SG, Najjar DM, et al. spectrum in vitro activity against aerobic and Long-term follow up of autologous serum treatment Trends in contact lens-related corneal ulcers. Cornea. anaerobic bacteria. Antimicrob Agents Chemother. for recurrent corneal erosions. Clin Exp Ophthalmol. 2005; 24(1):51-58. 2009;53(8):3552-3560. 2010;38(7):683-687. 19. Sankaridurg PR, Sharma S, Willcox M, et al. 45. Sanders ME, Moore QC 3rd, Norcross EW, et al. 70. Arbour JD, Brunette I, Boisjoly HM, et al. Bacterial colonization of disposable soft contact lenses Comparison of besifloxacin, gatifloxacin, and moxi- Should we patch corneal erosions? Arch Ophthalmol. is greater during corneal infiltrative events than during floxacin against strains of pseudomonas aeruginosa 1997;115(3):313-317. asymptomatic extended lens wear. J Clin Microbiol. with different quinolone susceptibility patterns in a 71. Wang L, Tsang H, Coroneo M. Treatment of 2000;38(12):4420-4424. rabbit model of keratitis. Cornea. 2011;30(1):83-90. recurrent corneal erosion syndrome using the combi- 20. Keay L, Edwards K, Naduvilath T, et al. Microbial 46. Sanders ME, Moore QC 3rd, Norcross EW, et al. nation of oral doxycycline and topical corticosteroid. keratitis: Predisposing factors and morbidity. Efficacy of besifloxacin in an early treatment model of Clin Exp Ophthalmol. 2008;36:8-12. Ophthalmology. 2006;113(1):109-116. methicillin-resistant Staphylococcus aureus keratitis. J 72. Dursun D, Kim MC, Solomon A, Pflugfelder 21. Holden BA, Sankaridurg PR, Sweeney DF, et al. Ocul Pharmacol Ther. 2010;26(2):193-198. SC. Treatment of recalcitrant recurrent corneal ero- Microbial keratitis in prospective studies of extended 47. Sanders ME, Norcross EW, Moore QC 3rd, et al. sions with inhibitors of matrix metalloproteinase-9, wear with disposable hydrogel contact lenses. Cornea. Efficacy of besifloxacin in a rabbit model of methicil- doxycycline and corticosteroids. Am J Ophthalmol. 2005; 24(2):156-161. lin-resistant Staphylococcus aureus keratitis. Cornea. 2001;132(1):8-13. 22. Stapleton F, Keay L, Edwards K,et al. The inci- 2009;28(9):1055-1060. 73. Rubinfeld RS, Laibson PR, Cohen EJ, et dence of contact lens-related microbial keratitis in 48. Zhang JZ, Cavet ME, Ward KW. al. Anterior stromal puncture for recurrent Australia. Ophthalmology. 2008;115(10):1655-1662. Antiinflammatory effects of besifloxacin, a novel fluo- erosion:further experience and new instrumentation. 23. Donshik PC, Ehlers WH, Anderson LD, Suchecki roquinolone, in primary human corneal epithelial cells. Ophthalmic Surg. 1990;21(5):318-326. JK. Strategies to better engage, educate, and empower Curr Eye Res. 2008;33(11):923-932. 74. Sudesh S, Cohen EJ, Rapuano CJ, Wilson RP. patient compliance and safe lens wear: Compliance: 49. Haas W, Pillar CM, Morris TW, Sahm DF. Corneal toxicity associated with latanoprost. Arch What we know, what we do not know, and what Antibiotic resistance trends in ocular pathogens – An Ophthalmol. 1999;117(4):539-540. we need to know. Eye Contact Lens. 2007;33(6 Pt update from the ARMOR 2009 and ARMOR 2010 75. Nagra PK, Rapuano CJ, Cohen EJ, Laibson PR. 2):430-434. surveillance studies. Poster presentation, Association Thygeson’s superficial punctate keratitis: Ten years’ 24. Yung AM, Boost MV, Cho P, Yap M. The effect for Research in Vision and Ophthalmology, 2011, Ft. experience. Ophthalmology. 2004;111(1):34-37. of a compliance enhancement strategy (self-review) on Lauderdale, Fla. 76. Varnell ED, Kauffman HE. Comparison of the level of lens care compliance and contamination 50. Haas W, Pillar CM, Torres M, et al. Monitoring ganciclovir ophthalmic gel and trifluridine drops for of contact lenses and lens care accessories. Clin Exp antibiotic resistance in ocular microorganisms: Results treatment of experimental herpetic keratitis. ARVO Optom. 2007;90(3):190-202. from the antibiotic resistance monitoring in ocular Meeting Abstracts April 11, 2008 49:2491. 25. Kilvington S, Heaselgrave W, Lally JM, et al. micro-organisms (ARMOR) 2009 surveillance study. 77. Croxtall JD. Ganciclovir ophthalmic gel 0.15%: Encystment of Acanthamoeba during incubation Am J Ophthalmol. 2011;152(4):567-574. in acute herpetic keratitis (dendritic ulcers). Drugs. in multipurpose contact lens disinfectant solutions 51. Blair J, Hodge W, Al-Ghamdi S, et al. comparison 2011;71(5):603-610. and experimental formulations. Eye Contact Lens. of antibiotic-only and antibiotic-steroid combina- 78. Tabbara KF, Al Balushi N. Topical ganciclovir 2008;34(3):133-139. tion treatment in patients: double- in the treatment of acute herpetic keratitis. Clin 26. Tu EY, Joslin CE. Recent outbreaks of atypical blinded randomized clinical trial. Can J Ophthalmol. Ophthalmol. 2010;4:905-912. contact lens-related keratitis: What have we learned? 2011;46(1):40-45. 79. Young RC, Hodge DO, Liesegang TJ, Baratz Am J Ophthalmol. 2010;150(5):602-608. 52. Hindman HB, Patel SB, Jun AS. Rationale for KH. Incidence, recurrence, and outcomes of her- 27. Yildiz EH, Abdall YF, Elsahn AF, et al. Update adjunctive topical corticosteroids in bacterial keratitis. pes simplex virus eye disease in Olmsted County, on fungal keratitis from 1999 to 2008. Cornea. Arch Ophthalmol 2009;127(1):97-102. Minnesota, 1976-2007: the effect of oral antiviral 2010;29(12):1406-1411. 53. Perry HD, Hodes LW, Seedor JA, et al. Effect prophylaxis. Arch Ophthalmol. 2010;128(9):1178- 28. Donnenfeld ED, Kim T, Holland EJ, et al. of doxycycline hyclate on corneal epithelial wound 1183. ASCRS White Paper: Management of infectious kera- healing in the rabbit alkali-burn model. Cornea. 80. Herpetic Eye Disease Study Group. Oral acy- titis following laser in situ keratomileusis. J Cataract 1993;12(5):379-382. clovir for herpes simplex virus eye disease: Effect on Refract Surg. 2005;31(10):2008-2011. 54. Tuli SS, Schultz GS, Downer DM. Science and prevention of epithelial keratitis and stromal keratitis. 29. Das S, Seitz B. Recurrent corneal erosion syn- strategy for preventing and managing corneal ulcer- Arch Ophthalmol. 2000;118(8):1030-1036. drome. Surv Ophthalmol. 2008;53(1):3-15. ation. The Ocular Surf 2007;5(1):23-39. 81. Herpetic Eye Disease Study Group. Acyclovir for 30. Hykin PG, Foss AE, Pavesio C, et al. The 55. Rosa RH, Miller D, Alfonso EC. The chang- the prevention of recurrent herpes simplex virus eye natural history and management of recurrent cor- ing spectrum of fungal keratitis in South Florida. disease. N Engl J Med. 1998;339(5):300-306. neal erosion:A prospective randomized trial. Eye. Ophthalmology. 1994;101(6):1005-1013. 82. Schwartz GS, Holland EJ. Oral acyclovir for the 1994;8(Pt1):35-40. 56. Lalitha P, Prajna NV, Kabra A, et al. Risk fac- management of herpes simplex virus keratitis in chil- 31. Reidy JJ, Paulus MP, Gona S. Recurrent erosions tors for treatment outcome in fungal keratitis. dren. Ophthalmology. 2000;107(2):278-282. of the cornea: Epidemiology and treatment. Cornea. Ophthalmology. 2006;113(4):526-530. 83. Sheppard JD, Wertheimer ML, Scoper 2000;19:767-71. 57. Hariprasad SM, Mieler WF, Lin TK, et al. SV.Modalities to decrease stromal herpes simplex 32. Mojon D. [Eye diseases in sleep apnea syndrome.] Voriconazole in the treatment of fungal eye infec- keratitis reactivation rates. Arch Ophthalmol. Ther Umsch. 2001;58(1):57-60 (German). tions: a review of current literature. Br J Ophthalmol. 2009;127(7):852-856. 33. Knickelbein JE, Hendricks RL, 2008;92(7):871-878. 84. Nigam P, Kumar A, Kapoor KK, et al. Clinical Charukamnoetkanok P. Management of herpes sim- 58. Ford JG, Agee S, Greenhaw ST. Successful medi- profile of herpes zoster ophthalmicus. J Indian Med plex virus stromal keratitis: An evidence-based review. cal treatment of a case of Paecilomyces lilacinus kerati- Assoc. 1991;89(5):117-119.

REVIEW OF OPTOMETRY November 2011 15

000_ro1111B&L12pg_ac4.indd 15 10/26/11 9:56 AM The opinions expressed in this supplement to Review of Optometry® do not necessarily reflect the views, or imply endorsement, of the editor or publisher. Copyright 2011, Review of Optometry®. All rights reserved.

000_ro1111B&L12pg_ac4.indd 16 10/26/11 9:41 AM