novel therapeutic regimens in treating cme education ... · as a sponsor accredited by the...

A CME Supplement from an EyeWorld Educational Symposium held at ASCRS•ASOA 2008 in Chicago

CME EDUCATION

Lid margin disease: Incidence,etiology, and diagnosis

by Henry D. Perry, M.D.

There are very few papers thateven suggest the incidenceof blepharitis. The best I’vefound was from Walter Reed:a study showing that 3.1% of

recruits between 18 and 22 years oldhad blepharitis versus 71.1% of thepensioners.1 So obviously this is acondition that increases with age.Lemp’s dry eye study showed that inpatients with dry eye disease, virtual-ly 70% of them have an associatedblepharitis.2

What about the etiology? Lidmargin cultures are positive invirtually 100% of these patients.Pathogenic strains can occurbetween 35 and 95%. It’s important

Supplement to EyeWorld September 2008

Supported by an unrestricted educational grant from Inspire Pharmaceuticals.

Continuing Medical Education

Program chairEric D. Donnenfeld, M.D., is founding partner,Ophthalmic Consultants of Long Island.

FacultyHenry D. Perry, M.D., is senior founding partner,Ophthalmic Consultants of Long Island; medicaldirector, Lions Eye Bank; and chief, CorneaService, Nassau University Medical Center.

Helen K. Wu, M.D., is assistant professor ofophthalmology, Tufts University School ofMedicine, and director, Refractive SurgeryService, New England Eye Center.

Marguerite B. McDonald, M.D., is cornea,refractive, anterior segment specialist,Ophthalmic Consultants; adjunct clinical professor, ophthalmology, Tulane UniversitySchool of Medicine; clinical professor, ophthalmology, New York University; and physician, Island Eye Center.

Edward J. Holland, M.D., is professor of ophthalmology, University of Cincinnati, anddirector of Cornea & External Disease, CincinnatiEye Institute.

Terrence P. O'Brien, M.D., is professor ofophthalmology; Charlotte Breyer RodgersDistinguished Chair in Ophthalmology; and director, Refractive Surgery Service, BascomPalmer Institute of the Palm Beach Gardens.

Kerry D. Solomon, M.D., is Arturo and HollyMelosi Professor of Ophthalmology; director,Cornea, Cataract and Refractive Surgery;medical director, Magill Laser Center; anddirector, Magill Research Center, MedicalUniversity of South Carolina.

Educational ObjectivesOphthalmologists who take part in thiseducational activity will:• Discuss the etiology, diagnosis, and

incidence of ocular surface disease andblepharitis

• Demonstrate an understanding of theimpact of ocular surface conditions oncataract and refractive surgery outcomes

• Discuss therapeutic options for thetreatment of the ocular surface

• Integrate appropriate pre- and post-operative treatment regimens toimprove surgical outcomes and patientsatisfaction

continued on page 2

to remember that bacteria havelipolytic exoenzymes and collagenas-es that degrade the lipid, forming aninflammatory soup that is dumped onthe corneal surface and leads to theproblems we see in our patients.

We also have Demodex folliculo-rum, a mite that lives at the base ofthe lashes and is present in 5% ofnormals and 35% of patients withblepharitis.

Diagnosis and classifyingHow do we make a blepharitisdiagnosis? Symptoms wax andwane. Patients complain of burning,irritation, and foreign body sensation;it especially seems prominent in themorning. Patients say their lids stick,

Here is a patient with several signs of blepharitis: severe neovascularization of the lid margin,the inspissation of some of the glands, and complete obstruction of some of the other glandsand changes associated with the eyelashes themselves

Novel Therapeutic Regimens in TreatingOcular Surface Disease and Blepharitis

continued on page 3

Notice About Off-Label Use PresentationsThis EyeWorld Educational Symposium Supplement may include presentationson drugs or devices or uses of drugs or devices that may not have beenapproved by the Food and Drug Administration (FDA) or have been approved bythe FDA for specific uses only. The FDA has stated that it is the responsibility ofthe physician to determine the FDA clearance status of each drug or devicehe/she wishes to use in clinical practice.

ASCRS is committed to the free exchange of medical education. Inclusion of anypresentation in this program, including presentations of off-label uses, does notimply an endorsement by ASCRS of the uses, products, or techniques presented.

Continuing Medical Education (CME) The American Society of Cataract and Refractive Surgery is accredited by theAccreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education to physicians. ASCRS takes responsibility for the content, quality, and scientific integrity for these activities.

CME CreditsASCRS designates this educational activity for a maximum of 1 AMA PRACategory 1 Credit™. Each physician should claim credit commensurate with theextent of his/her participation in the activity. Please note physicians must checkin at the symposium registration desk onsite to be eligible for credit.

Claiming CME CreditQuestions have been developed for this written supplement about material covered in the EyeWorld Educational Symposium, Novel Therapeutic Regimens inTreating Ocular Surface Disease and Blepharitis, presented on Monday, April 7,2008, in Chicago.

Participants must take the written test once they have completed their review ofall material within this supplement. To receive CME credit, 80% of the questionsmust be answered correctly. The test must be completed individually, andanswers must be based on personal knowledge gained from reviewing the written material.

The test is available online at www.eyeworld.org. Go to Online Education for test.Once the test has been completed with a score of 80% or higher, a CME certificate will be available to print using the browser's print function.

Participants who score less than 80% will have the opportunity to review thematerial and take the test again.

ASCRS will keep the earned CME information on file for the required time.

Expiration DateCME credit for this educational activity is valid through December 31, 2008. CME credit will not be awarded after that date.

CME QuestionsPlease contact Laura Johnson with the American Society of Cataract andRefractive Surgery at 703-591-2220, or e-mail her at [email protected] if youhave any questions regarding CME credit for this educational activity.

Financial Interest DisclosureAs a sponsor accredited by the Accreditation Council on Continuing MedicalEducation, ASCRS•ASOA must ensure balance, independence, objectivity, andscientific rigor in all its individually or jointly sponsored activities.

All individuals participating in a sponsored activity must disclose any financialinterest or relationship with the manufacturer(s) of any commercial product(s)and/or provider(s) of commercial services discussed in an educational presenta-tion or lack thereof. Financial interest can include such things as grants orresearch support, employee, consultant, major stockholder, member of speakersbureau, financial relationships held by spouse, etc.

The intent of this disclosure is not to prevent participants with a significant finan-cial or other relationship from presenting, but rather to provide the ProgramCommittee with information so they can design and implement a balanced, inde-pendent, and scientific educational activity. This Financial Interest Index providesinformation to attendees so they can make their own judgment regarding theinterest or relationship and the materials presented.

A complete listing of relationships to disclose and their corresponding codes islisted here.

Category Abbreviation Specific Financial Interest

Product P I earn royalty or derive other financial gain from an ophthalmic product or service.

Investor R I have a significant investment interest in a company that makes/develops/provides ophthalmic products or services.

Consultant A I receive a retainer, ad hoc fees, or other consulting income from a company that makes/develops/provides ophthalmic products or services.

B I am a member of the speaker's bureau of a company that makes/develops/provides ophthalmic products or services.

C I provide practice management or marketing consulting services to ophthalmic practices.

Research D My research is fully or partially funded by a company that makes/develops/provides ophthalmic products or services.

Travel E My travel expenses have been reimbursed, paid in full or subsidized by a company that makes/devel-ops/provides ophthalmic products or services.

Employee Y I am a full-time employee of a company that makes/develops/provides ophthalmic products or services.

Z I am a part-time employee of a company that makes/develops/provides ophthalmic products or services.

Spouse S My spouse has a financial relationship with a company that makes/develops/produces ophthalmic products or services, encompassing either royalties, investment, consulting/speakers bureau, research grants, travel reimbursement or employment.

None N I have no financial relationship with any company that makes/develops/produces ophthalmic products or services.

CME – from page 1

Description of Financial Interests

Eric D. Donnenfeld, M.D.Advanced Medical Optics AAdvanced Vision Research AAlcon Laboratories AAllergan Inc. ABausch & Lomb AEyemaginations AInsite AInspire Pharmaceuticals ATLC Laser Centers ATrueVision AWavetec A

Edward J. Holland, M.D.Advanced Medical Optics AAdvanced Vision Research Inc. AAdvanced Vision Science AAlcon Laboratories AAllergan Inc. ABausch & Lomb AEyemaginations Inc. AInSite Vision Inc. AInspire Pharmaceuticals AOCuSOFT AWaveTec Vision Systems A

Marguerite B. McDonald, M.D.Advanced Medical Optics AAllergan Inc. AEssilor AOASIS Medical Inc. AOcularis Pharma. ASanten A

Terrence P. O'Brien, M.D.Advanced Medical Optics AAlcon Laboratories AAlimera Sciences AAllergan Inc. ABausch & Lomb AInspire Pharmaceuticals AIsta Pharmaceuticals Inc. ASanten A

Henry D. Perry, M.D.None N

Kerry D. Solomon, M.D.Advanced Medical Optics A, DAlcon Laboratories A, DAllergan Inc. A, DBausch & Lomb A, D

Helen K. Wu, M.D.Alcon Laboratories BBecton-Dickenson & Co. ARefractec B

3Novel Therapeutic Regimens in Treating Ocular Surface Disease and Blepharitis

species, and P. acne all have effectson these lipolytic enzymes. These allact together in concert to create anincrease in free fatty acids. Thisincrease is central to the theme ofthe pathology that occurs in this dis-ease. What we’re having is saponifi-cation. The problem that occurs inour patients is that there’s adetergent action to the tear filmwhich leads to a recalcitrant superfi-cial punctate keratopathy.

Therapy is directed at control,not cure. I tell my patients that thedifference between blepharitis andtrue love is that one is forever.

In the acute phase, we try tobring the disease under control. Wethen have the chronic phase oftherapy where we want to maintaincontrol. The key factor is lid hygiene.This is the basic therapy that weshould impress on all of our patients.We also encourage warm salt watersoaks four times daily, and in thisprocess there is a change in theownership of treatment from thephysician to the patient. This helpsthe patient realize that it is not onlythe physician who is responsible forimprovement.

The patients who require topicalantibiotics are those with staph,coagulase-negative staphylocci, andpatients with mixed Staphylococcaland seborrheic disease. Virtually all

patients with chronic blepharitis needantibiotics at least intermittently insome form.

“ Therapy is directed at control,not cure.”Henry D. Perry, M.D.

Example of saponification concomitant with chronic blepharitis

and they have crusting. We are allfamiliar with the numerous signssuch as collarette, scurf, lashchanges, inspissation in meibomianglands, and neovascularization of lidmargins, characteristic inferior super-ficial punctate keratopathy, chalazia,and not infrequently, marginalulceration.

Classifying blepharitis is quitedifficult, but I think McCulley devel-oped the best classification schemeto date. Basically, he divided it upinto Staphylococcal, seborrheic,occurring alone or in combinationwith staph disease, and occurring incombination with primarymeibomitis.3 We see patients withprimary meibomitis most frequently.

If we culture our patients, evennormal patients will tend to haveinvolvement with several bacteria.The most common ones that areseen are coagulase-negativestaphylocci, S. aureus, P. acne, andCorynebacterium species. It’s inter-esting to note that in the patientswith the various forms of blepharitis,these bacteria are present in veryhigh amounts.

Last year, Shaeffer Tsengshowed a group of patients in aretrospective study, six in all, whohad severe blepharitis that wasunresponsive to steroids and sys-temic tetracyclines (various manufac-turers).4 In this group he epilatedtheir lashes, studied the base, andfound heavy Demodex infestations.He treated these with tea tree oil andfound a very good response within asix-week period. These were severepatients who had significant cornealfindings; three were thought to havelimbal stem cell deficiency and theyall responded to this therapy.

Chronic blepharitisIn cases of chronic blepharitis, thepathophysiology leads us to believethere is no single bacteria that’sresponsible. Rather it’s a productionof the bacteria in terms of theirlipolytic effect on the meibum that ispresent and the changes that occurin the lipid at the base of the lashes.Staph aureus, Corynebacterium

continued from page 1

continued on page 5

4 Novel Therapeutic Regimens in Treating Ocular Surface Disease and Blepharitis

The surgical and medical impact of lid margin disease

present with pain, discharge, and anepithelial defect.

The onset of infection afterLASIK helps us determine whatetiology it may be. Early onset infec-tions (in the first week) are moreoften gram-positive. Gram-negativeinfections are rarely found.

Normal eyes don’t develop ulcer-ative keratitis because they have aninnate natural host defense mecha-nism. After LASIK, some of that isbroken down partly due to a relativeneurotrophic keratopathy with dryeye syndrome, an epithelial irregular-ity at the flap edge, and a truepotential space or pocket created,which allows for a stromal abscess inthe cornea.

The risk factors for the patientinclude blepharitis and meibomiangland dysfunction, a dysfunctionaltear state or dry eye, Herpes simplexkeratitis, and collagen vascular dis-ease in those rare individuals.

The procedure itself can providerisk factors: the bandage lens, theepithelial defect, topical anestheticabuse afterwards, chronic use of topi-cal steroids, and other factors such asnot using post-op antibiotics or irregu-lar flap or instrument contamination.

“ Instruct your staff in the principlesof sterile operativetechniques.” Helen Wu, M.D.

between the infiltrate and the limbusand may or may not have an overly-ing epithelial defect. You frequentlysee superficial punctate keratopathy,especially inferiorly. In rare circum-stances, we see infectious keratitis.

The diagnosis of infectiouskeratitis is made by culture and sen-sitivity. We choose our therapy basedon the results of these cultures.

Post-surgical infectionsInfections can be associated withrefractive or cataract surgery.

The incidence of infections afterLASIK ranges from 0.2% to 1.2%,and 5% of these can be bilateral.Several large case series reportabsolutely no infections, however.The symptoms, just as with standardbacterial keratitis, include redness,blurry vision, and photophobia, butthe most common presenting symp-tom is pain.

In a pseudomonas infection, thecorneal infiltrate is typically present.An anterior chamber reaction orepithelial defect may be present.There may be separation of the flap,epithelial ingrowth, or melting of theflap overlying the infiltrate. Gram-positive organisms are more likely to

The overwhelming cause of most LASIK keratitis is gram-positive organisms

by Helen Wu, M.D.

Identifying risk factors canhelp clinicians treat andprevent lid margin disease

Clinicians have to managedry eye concurrently with lidmargin disease. Angularblepharitis is most frequent-ly associated with gram-

positive organisms. Proteolyticenzymes can cause lid marginmaceration. Bacterial conjunctivitis isfrequently associated with blephari-tis. It can be cyclical and lead us tobelieve there’s a viral component.

You may see corneal changesassociated with blepharitis: marginalcorneal infiltrates which are type 4hypersensitivity reaction to theStaphylococcal species. Thesetypically present with a clear space


Helen K. Wu, M.D., is assistant professor ofophthalmology, Tufts University School ofMedicine, and director of the RefractiveSurgery Service, New England Eye Center,Boston, Mass.

Long term, we can still see infec-tions after LASIK due to trauma orepithelial instability.

Prevention of infectionA few years ago more than 50% ofthe organisms that were associatedwith LASIK keratitis included atypicalMycobacteria. Now, 90% of theseare gram-positive organisms. Thesource of these organisms, thebacterial, fungal and parasiticsource, is likely the surface flora.

What do we do to minimize this?We can use pre-op measures, aswell as local intra-op control andpost-op prophylaxis.

Instruct your staff in the princi-ples of sterile operative techniques.

It’s very important that patientsnot wear eye makeup. Makeup canharbor very dangerous bacteria. Weuse povidone-iodine 5 to 10% on thelids or lashes to help with that.

Perhaps not as frequent is treat-ing the pre-existing blepharitis usingeye scrubs, warm compresses, andomega-3 supplements. We treatblepharitis patients with AzaSite(azithromycin, InspirePharmaceuticals, Durham, N.C.),which is good against gram-positiveorganisms. It’s very important toremind patients that they shouldn’twear contact lenses for at least 2 to3 days prior to surgery to minimizethe bacterial load on the surface.

EndophthalmitisThere are two types of endoph-thalmitis: endogenous fromhematogenous spread andexogenous from surgery, foreignbodies, or trauma. Endogenousendophthalmitis is the smaller cate-gory of the two, only 2 to 15% of allcases of endophthalmitis. The restare exogenous. Sixty percent ofthese cases occur after surgery; theincidence after cataract surgery is0.06% to 0.3%.

Frequently, you see pain out ofproportion to the clinical signs. Thereis typically a little lid edema, cornealedema, fibrinous membrane in theanterior chamber, and progressiveloss of the red reflex. P. acnes, how-ever, can present in a more indolentfashion.

The causative organisms in post-op endophthalmitis are overwhelm-ingly gram-positive. Prevention issimilar to LASIK associated keratitiswith povidone-iodine 5% prep for theskin and the conjunctival fornices,sterile draping techniques, and verymeticulous treatment of the pre-exist-ing blepharitis and external disease.

We like fourth generation fluoro-quinolones for our prophylaxis. Wegenerally do not favor intracameralantibiotics as do most surgeons untilthey become more standard.

In conclusion, lid margin diseasecan be associated with significant

patient discomfort as well as a spec-trum of clinical findings, which canrange from mild redness and crust-ing to significant infections in the lidsand surrounding ocular structures.Blepharitis is a significant risk factorfor infection after both refractive andintraocular surgery. Appropriatemeasures should be taken pre-op,intra-op, and post-op to minimize therisk of infection after surgery.

Causative organisms in post-op endophthalmitis range from mixed flora (2%) to S. epidermidis (41%)


Which ones should we use? Theones to avoid are erythromycin(various manufacturers) and amino-glycides because of the developmentof resistance. Antibiotic therapy canreduce the colony counts andimprove the patient’s signs andsymptoms. Lid hygiene is essential inany treatment plan. We know thatthere is a definite need for a long-term solution.

REFERENCES1 Fillmore GL, Ward TP, Bower KS, et al.

Ocular complications in the Department ofDefense Smallpox Vaccination Program.Ophthalmology. 2004;111:2086-93.

2 Lemp MA. Report of the National EyeInstitute/Industry workshop on ClinicalTrials in Dry Eyes. CLAO J. 1995;21:221-32.

3 McCulley JP, Dougherty JM, Deneau DG.Classification of chronic blepharitis.Ophthalmology. 1982;89:1173-80.

4 Kheirkhah A, Casas V, Li W, Raju VK, TsengSC. Corneal manifestations of oculardemodex infestation. Am J Ophthalmol.2007;143:743-749. Epub 2007 Mar 21.

Henry D. Perry, M.D., is senior founding partner, Ophthalmic Consultants of LongIsland; medical director, Lions Eye Bank; andchief, Cornea Service, Nassau UniversityMedical Center, East Meadow, N.Y.


The importance of improving theocular surface on surgical outcomes

“ We need to useeverything we have inour bag of tricks tooptimize the ocularsurface pre-op because that willimprove theoutcomes.”Marguerite B. McDonald, M.D.

by Marguerite B. McDonald, M.D.

Creating the healthiestocular surface possible pre-op will help improveoutcomes post-op

Ocular surface disease isincredibly underdiagnosed.There are approximately 55million Americans with dryeye disease, and an esti-

mated 39 million dry eye sufferershave not yet been diagnosed.

We all know the symptoms ofdry eye disease: discomfort, dryness,burning, and stinging. Dry eyes havea huge impact on anterior segmentsurgery. Every patient experiencesdry eye post-op but not all patientsdevelop symptoms. The quality of

vision starts with a healthy ocularsurface. The tear film is by far themost important refracting surface ofthe eye. Dry eye and the co-morbidi-ties of blepharitis and allergic con-junctivitis are the most common andpotentially most devastating compli-cations of anterior segment surgery.

Disruption of the ocular surfaceinduces distortion that’s magnified bya multifocal IOL. Disruption of thetear film magnifies the glare and haloinherent in all multifocal IOLs.Patients with multifocal IOLs andocular surface disease have a hugedifference in the point spreadfunctions and the way they view theworld.

Contributing factorsThere are contributing factors thatcan add to ocular surface abnormali-ties. Among these is a lack of lubri-cation during the surgery or epithelialdefects. For instance, if we’vestretched the lid of an older patient,

that may lead to a flaccid lid for several weeks or months, which then leads to lagophthalmos andexposure keratitis.

Dry eye disease overlaps withmeibomian gland disease. More thana third of the dry eye patients havemeibomian gland disease and 13%also have allergies.

The prevalence of post-op dryeye has been exhaustively studied.Most of the peer-reviewed literatureconcerns LASIK and PRK, but thereare articles about post-cataract dryeye. The incidence of dry eye ismuch higher in post-cataract patientsthan in post-LVC patients. Roberts1

found the incidence to be as high as87%. Li2 looked at 37 patients/ 50eyes. They found post-op dry eye incataract patients peaked at onemonth and persisted for at leastthree months. Visual function may benegatively impacted if the dry eyesymptoms persist. Li and his co-authors concluded that symptoms of

On the left, a multifocal IOL view from a patient without ocular surface disease; on the right,the same visual scenario, only this time from a patient with ocular surface disease and a multifocal IOL


dry eye will inevitably emerge inmost patients, and misuse of eyedrops was a major pathogenic factor.

Corneal epithelial integrityCorneal sensation is vital for main-taining corneal epithelial integrity.With cataract surgery, the incisionand limbal relaxing incisions (LRIs)transect the nerves responsible forcorneal innervation. With LASIK,we’re creating a 270-degree flap thatcuts nerves, and the ablation ampu-tates a few more. We should alsoremember 10% of refractive IOLpatients will have both cataract sur-gery and laser vision correction.

LASIK pre-op risk factors are thedegree of myopia, the depth of thelaser treatment, female sex, dryeyes, previous contact lens use,eyelid disorders and anomalies, anddiabetes. Pre-op, it’s important torecognize and treat these conditionsso our patients will sail through thepost-op period and have betteroutcomes.

Lid anatomy and function shouldbe assessed, as well as the blinkrate, the tear film volume and quality,the tear breakup time and ocularsurface staining with lissamine greenor rose bengal.

Candidate choiceIf dry eye symptoms have no effecton vision, the patient is a good can-didate for LASIK. If there is concomi-tant dry eye and fluctuating vision,the patient is a moderate to poorcandidate. If the dry eye symptomsand decreased vision are due toocular surface disease, the patientshould be a non-candidate until thesurface can be improved with treat-ment.

Look for supravital conjunctivalstaining. If none exists, the patient isprobably a good candidate.Supravital conjunctival staining with

no corneal staining is a moderatecandidate. If the patient presentswith supravital conjunctival stainingwith central fluorescein cornealstaining, he is probably not acandidate at all.

Topical corticosteroids, whenused appropriately with andwithout cyclosporine, can be helpfulin both the treatment of dry eye andblepharitis.

We need to use everything wehave in our bag of tricks to optimizethe ocular surface pre-op becausethat will improve the outcomes. Therewill be decreased post-op dry eyeand faster visual recovery. With IOLsyou get a more reliable keratometryand improved IOL power accuracy. Ifthe patient needs LASIK in a biopticsprocedure, you’ll get improved wave-front evaluation.

In summary, recent advances intechnology and the evolution of

Dry eye symptoms peaked at one month and persisted for at least three months, longer forpatients with pre-existing dry eye

cataract and refractive surgery reallyraise the bar for successful out-comes. As clinicians, we need totreat aggressively. Presume visualfluctuation is dry eye until provenotherwise. This all requires a coordi-nated, premeditated, perioperativeregimen.

REFERENCES1 Roberts CW, Elie ER. Dry eye symptoms

following cataract surgery. Insight.2007;32:14-21.

2 Li Xm, Hu L, Hu J, Wang W. Investigationof dry eye disease and analysis of the path-ogenic factors in patients after cataract sur-gery. Cornea. 2007;26(9 Suppl 1):S16-20.

Marguerite B. McDonald, M.D., is cornea,refractive, anterior segment specialist,Ophthalmic Consultants of Long Island, N.Y.;adjunct clinical professor of ophthalmology,Tulane University School of Medicine, NewOrleans, La.; and clinical professor of ophthalmology, New York University, N.Y.


Conventional therapeuticapproach to lid margin diseases

“ I recommend lidhygiene in all patients,nutritional substitutesas a second choice,and tetracycline use asthe third option.”Edward J. Holland, M.D

by Edward J. Holland, M.D.

Lid scrubs, warm compress-es, and corticosteroidsshould be considered as theprimary treatment options

Ten years ago, not many clinicians were interested indry eye or blepharitis. Dryeye really came to the fore-front with refractive surgery

patients. We began talking abouthow to properly diagnose and treatit. In the next 3 to 4 years, thesediscussions will become even moreprevalent as cataract and refractivesurgeons realize that one of theleading causes of decreased visionin our patients is the health of theocular surface. This is extremely

important for our multifocal IOLpatients. Posterior lid margin diseaseis probably the most common misdi-agnosed and prevalent condition thataffects our patients’ visual acuity.

It is critical to differentiate thefindings of the ocular surface,whether it’s aqueous tear deficiency,blepharitis, or both. The majority ofthe patients with blepharitis will haveanterior or posterior meibomiangland disease. Patients with posteriorlid margin disease have chronic com-plaints. We look for inspissation ofglands, erythema and telangiectasiaaround the glands, the pouting of oil,and the rapid tear break up time.That really identifies the unstabletear film and why these patients havefluctuation in vision.

Corneal specialists seecomplications of chronic blepharo-conjunctivitis. These patients are inchronic discomfort. We do seecorneal involvement with scarringand neovascularization and signifi-cant loss of vision in some patients.

Treatment optionsAnterior blepharitis, while not verycommon in my practice, is certainly

due to Staph disease. Treatmentoptions are lid hygiene with hot com-presses and commercial lid scrubs.We do use antibiotic ointments;corticosteroids are rarely indicated.Sometimes in anterior lid margindisease we’ll have an associatedconjunctivitis and discomfort.

For those who present withposterior lid margin disease, patienteducation is vitally important. Thesepatients have chronic discomfort,chronic red eyes, and waxing/waningvision. They are looking for a cureand there isn’t any. But we do haveways to make these patients morecomfortable and improve their visualacuity. Again, lid hygiene and warmcompresses are the cornerstone fortreatment. Patients prefer commer-cial lid scrubs to trying to mix upsome kind of solution on their own. Ioften tell them to use hot compress-es in the shower and make it simple,typically twice a day. Patients are justnot compliant beyond twice daily.

We used to recommend rotatingan antibiotic to reduce the colonycounts of bacteria on lid surfaces,but I have not been that impressed

An example of meibomian gland disease. Note the intense eyelid involvement (left)

continued on page 11


Anti-infective and anti-inflammatoryeffects of azithromycin

“ Azithromycin gives us a high therapeutic index byachieving very highconcentrations in the ocular surfacetissues.”Terrence P. O’Brien, M.D

by Terrence P. O’Brien, M.D.

Pharmacodynamics makeazithromycin particularlysuitable for ocular infections

The first principle in treatingocular infectious diseases isto know the enemy beforeengaging in battle. Thatimplies an understanding of

the epidemiology of the patterns ofocular infectious disease as well asthe susceptibility patterns of theagents that cause the disease.

The second principle is torespect the enemy because we areclearly outnumbered. Ocularpathogens will change course toadapt quickly to our efforts at elimi-nating them. They represent the ulti-mate opportunists and survivalists.

We know there is an emergenceand spread of antimicrobial resist-ance. It’s an increasing global con-cern. Mutations happen, leading tonew resistant bacteria. We alwaysfelt immune to the problem of resist-

ance in ophthalmology because wecan apply our agents topically. Yetdata from the Campbell lab andothers have shown recently thatthere is an alarming increased resist-ance among isolates causing ocularinfections, including keratitis,endophthalmitis, conjunctivitis, andblepharitis.1-3

The next principle is to know theagents. If we could pick the idealagent, it would be broad spectrum,bactericidal in action, biocompatible,meaning non-cytotoxic, andbioavailable, having favorable pharmacodynamics.

Antibiotic parametersBacitracin (various manufacturers)has been around for awhile and isused frequently to treat blepharitis.But it’s insoluble and only available inointment form, having a negativeeffect on vision. Erythromycin(various manufacturers) is usedwidely, but it, too, is insoluble and isonly available as an ointment.

The real problem with these,though, is a considerable resistance,especially among Staphylococci.

Aminoglycosides are mainly gram-negative acting agents: They arevery toxic and rapidly createkeratopathy, and they inhibit woundhealing. Interestingly, chlorampheni-col (various manufacturers) is themost widely used anti-infectiveglobally because of its relativeinexpensiveness. However, it cancause a rare but devastating bonemarrow idiosyncratic toxicity thatcould be fatal.

Sulfacetamide (various manufac-turers), our old friend from the1940s, is still used occasionally. Ithas reasonable effect but can causea hypersensitivity.

We now have some very potent8-methoxy fluoroquinolones thathave improved spectrum of activityagainst Streptococci and other gram

A full therapeutic course of AzaSite requires 60 to 75% fewer doses than leading fluoroquinolones



“ Basically we’re talking about standardizing what we are doing for lidmargin disease, in theexact same way aswe’ve standardized for dry eye.”Kerry D. Solomon, M.D.

Advanced treatment of blepharitis and expert panel recommendations

by Kerry D. Solomon, M.D.

Optimizing the ocularsurface will improve surgical outcomes

Quality of vision is going tobe most important for all

your cataract patients, especially your refractivecataract patients, premium IOL patients, LASIK and

PRK patients. We need to rememberthe refractive surface of the eye isthe tear film, not the cornea or lens.

Dry eye syndrome and blepharitisare two of the most common dis-eases we deal with. Blepharitis reallyis a type of dry eye, an evaporativedry eye. We’ve been trained for yearsthat when we evaluate cataracts, we

put the slit lamp right back to the lensand we bypass the lid.

If the ocular surface is nothealthy, visual distortions will followLASIK, PRK, and multifocal IOLsurgeries.

Dry eye, as we typically thinkabout it, is auto-immune related.Most clinicians use corticosteroids,like Lotemax (loteprednol etabonate0.5%, Bausch & Lomb, Rochester,N.Y.), or Restasis (cyclosporineophthalmic emulsion, Allergan,Irvine, Calif.). Clinicians should applythe same methods used to treataqueous insufficiency to lid margindisease and blepharitis.

Dry eye and surgeryDry eye is the most common compli-cation we see – one in four patientswill have dry eye symptoms or com-plaints. We’ve learned that the quali-ty of the tear film and health of thecorneal epithelium are extremelyimportant in obtaining good out-comes.

To do this, clinicians must treatthe underlying problem pre-op,protect during surgery, and manageappropriately after surgery.1 Cataractsurgery is likely to induce dry eye orexacerbate pre-existing dry eye in asignificant portion of patients.2

We are familiar with the signsand symptoms of blepharitis, as wellas the sequelae, both anterior andposterior lid margin disease. Much ofthe dry eye we see is related toblepharitis by itself or in combinationwith aqueous insufficiency.

Conventional managementincludes warm compresses and lidscrubs. The ideal mechanism in myopinion for AzaSite (azithromycin,Inspire Pharmaceuticals, Durham,N.C.) is not bacterial conjunctivitisbut blepharitis. One drop gives 100-fold concentration that will last for avery long time on the eyelid.

Left uncontrolled, dry eye disease can lead to sterile melting (on left) or bacterial keratitis (on right)



BETA panel recommendationsBasically we’re talking about stan-dardizing what we are doing for lidmargin disease, in the exact sameway as we’ve standardized for dryeye.

The panel recommends lidhygiene with commercial scrub b.i.d.for two days, then QD for one month.My preference is to use SteriLid(Advanced Vision Research,Woburn, Mass.). Conversely, I do notbelieve baby shampoo is nearly aseffective. This standardized routinewith AzaSite is easy for patients tofollow. I tell patients to take it atnight. It’s got a good lubricant and iswell tolerated.

When recommending nutritionalsupplements to your patients,remember omega-3s are effective.

Even with low-dose tetracyclines(various manufacturers), supplement

once again with topical loteprednolas needed.

For anterior blepharitis, our treat-ment recommendations are AzaSiteb.i.d. for two days, then once daily fora month. For lid hygiene it’s thesame, lid hyperthermia and nutrition-al supplements.

For posterior blepharitis, treat-ment recommendations are verysimilar. Therapeutically, we recom-mend AzaSite twice a day for twodays, then adding oral doxycycline(various manufacturers) as asecond-line treatment. If the condi-tion is still not resolved, third-linetreatment should be the addition ofanti-inflammatory corticosteroidsand/or cyclosporine.

In conclusion, the appropriatemanagement of the ocular surfacewill improve a clinician’s surgical out-comes and patient satisfaction.

Further, a stable tear film is essentialfor good functional visual acuity.

REFERENCES1 Albietz JM, Lenton LM, McLennan SG.

Chronic dry eye and regression after laserin situ keratomileusis for myopia. JCataract Refract Surg. 2004;30:675-84.

2 Roberts, CS, Elie ER. Dry eye symptomsfollowing cataract surgery. Insight.2007;32:14-23.

Kerry D. Solomon, M.D., is Arturo and HollyMelosi Professor of Ophthalmology; director,Cornea, Cataract and Refractive Surgery; andmedical director, Magill Laser Center,Charleston, South Carolina. He is also director, Magill Research Center, MedicalUniversity of South Carolina.

with the results. Patients don’t likeantibiotic ointments, as they don’treally penetrate the lid very well. Asimilar problem occurs with the cur-rent fluoroquinolones. I’ve given thisstep up altogether in my practice.Tetracyclines (various manufacturers)are very effective, but make sureyou’re prescribing a sub-antibioticdose. In my practice, I’ve founddoxycycline (various manufacturers)20 mg/b.i.d. is very effective. Youalmost eliminate the GI upset andthe photosensitivity, and you retainthe efficacy at that dosing.Doxycycline and minocycline (vari-ous manufacturers) should be usedbut in a low dose and you’ll have thesame effect.

About 20% of the patients withposterior lid margin disease will havefacial rosacea, which impacts signifi-cantly on the quality of life.Recommendations here are fortetracycline and metronidazole, or adermatological referral. MetroGel

(metronidazole, GaldermaLaboratories, Fort Worth, Texas) tothe face is effective twice a day.Patients started applying it to their lidmargins and it’s very well tolerated.

Steroids and supplementsTopical steroids are very important inthe management of posterior lidmargin disease. Any patient withcorneal involvement, from an inflam-matory aspect, should be placed ona course of corticosteroids. Inpatients with chronic neovasculariza-tion scarring, Lotemax (loteprednoletabonate 0.5%, Bausch & Lomb,Rochester, N.Y.) should be usedbecause it’s effective and has a verygood safety profile. It’s also one ofthe most effective treatments for thechronic discomfort of posterior lidmargin disease. Patients may haveconjunctivitis associated with chronicpain, and corticosteroids are veryeffective for that.

The omega-3 nutritional supple-ments are very effective in the

management of posterior lid margindisease and dry eye. The combina-tion of flaxseed oil and fish oiltogether are synergistic and I do rec-ommend that. In my practice, we areputting this in front of tetracycline.

SummaryI recommend lid hygiene in allpatients, nutritional substitutes as asecond choice, and tetracycline useas the third option. If there’s conjunc-tival and corneal involvement, con-sider corticosteroids. No one treat-ment is effective for all patients. Youhave to find out what works for thepatient. Continued patient educationwill get him or her to buy into thetreatment. Although we have somegood standard treatments, we havepatients that don’t respond to every-thing that I’ve mentioned here.

Edward J. Holland, M.D., is professor of ophthalmology, University of Cincinnati, anddirector of Cornea & External Disease,Cincinnati Eye Institute, Ohio.




The CME test is available online at www.eyeworld.org. Go to Online Education for test.Please contact Laura Johnson with the American Society of Cataract and

Refractive Surgery at 703-591-2220, or e-mail her at [email protected] if you haveany questions regarding CME credit for this educational activity.


positives. These have a place yetthere is increasing resistance, espe-cially among Staphylococcus aureus,most notably methicillin-resistantStaph that can also be resistant tothe fluoroquinolones.

MacrolidesThe exciting group is the macrolides.Erythromycin (various manufactur-ers) was the first, discovered in1954. Now we have macrolides withgreater tissue pharmacokinetics andsustainability in ocular tissues.

Azithromycin is really the firstazalide antibiotic. This is well suitedfor ophthalmic use because of thebroad spectrum of activity as well asthe tissue pharmacokinetics. Thesework by inhibiting bacterial proteinsynthesis by inhibiting the 50Sribosomal protein synthesis. So themacrolides suppress RNA-depend-ent protein synthesis. Typically, thesemay be bacteriostatic, yet macrolidescan be bactericidal especially at veryhigh concentrations against verysusceptible organisms. It’s a timedependent activity, so high concen-trations over an extended period oftime equal a very effective agent.

They are not immune to resist-ance. The two main mechanisms ofresistance are an active efflux andaltered target sites. If this occurs,there’s cross-resistance among all ofthe macrolides. At Bascom Palmer,we found that for Staph aureus therewas a relatively comparable effect,comparing azithromycins to fluoro-quinolones. For H. influenzae thesusceptibility was exactly identical.

With AzaSite (InspirePharmaceuticals, Durham, N.C.),

azithromycin is solubilized withDuraSite (InSite Vision, Alameda,Calif.), which contains polycarbophil.This allows for a stable formulation,and increases the bioavailability.Azithromycin gives us a high thera-peutic index by achieving very highconcentrations in the ocular surfacetissues. This allows us to use fewerdoses for treating our diseases. Thefull therapeutic course is quite a bitless than the other leading eyedrops– nine drops as compared to 21 ormore for other commonly usedagents.

Tissue penetrationIn a rabbit study we did, after asingle dose of AzaSite orazithromycin 1% alone, there was ahuge amount of the azithromycin inthe conjunctival tissue for theAzaSite eyes compared to theazithromycin 1% alone. In a multipledose study, we found a sustainedeffect in the tissue for a week ormore after dosing was stopped,which may have clinical relevance forblepharitis.

Moving to single dose humanconcentration studies, we evaluat-ed AzaSite 1% and moxifloxacin(Vigamox, Alcon, Fort Worth,Texas) in 41 healthy conjunctiva.There was a much larger concen-tration of azithromycin compared tomoxifloxacin.

Systemically administeredazithromycin, even at sub-therapeu-tic doses, has significant anti-inflam-matory and immunomodulatorybenefits in subjects with chronicrespiratory diseases, such as cysticfibrosis.4-6

In summary, we need to knowthe enemy and the possible agentsthat are available. Be aware of sus-ceptibility data and the patterns ofresistance. Try to integrate the phar-macokinetics with the microbiology.Analyze data carefully and objective-ly. I think we’re meeting our needsbetter with azithromycin to treatthese challenging conditions.

REFERENCES1 Mah FS. New antibiotics for bacterial infec-

tions. Ophthalmol Clin North Am.2003;16:11-27.

2 Marangon FB, et al. Annual Meeting of theAssociation for Research in Vision andOphthalmology; May 5, 2002; Ft.Lauderdale, Fla. Abstract.

3 Ritterband DC, et al. Annual Meeting of theAssociation for Research in Vision andOphthalmology; May 6, 2002; Ft.Lauderdale, Fla. Abstract.

4 Amsden GW. Anti-inflammatory effects ofmacrolides—an underappreciated benefit inthe treatment of community-acquired respi-ratory tract infections and chronic inflam-matory pulmonary conditions? JAntimicrob Chemother. 2005;55:10-21.Epub 2004 Dec 8. Review.

5 Ianaro A, Ialenti A, Maffia P et al. Anti-inflammatory activity of marcolide antibi-otics. J Pharmacol Exp Ther.2000;292:156-63.

6 Shinkai M, Rubin BK. Macrolides and airwayinflammation in children. Paediatr RespirRev. 2005;6:227-35. Review.

Terrence P. O’Brien, M.D., is professor of ophthalmology; Charlotte Breyer RodgersDistinguished Chair in Ophthalmology; director, Refractive Surgery Service, Bascom Palmer Institute of the Palm BeachGardens, Fla.

This supplement was produced by EyeWorld under an educational grant from Inspire Pharmaceuticals.

Copyright 2008 ASCRS Ophthalmic Corporation. All rights reserved. The views expressed here do not necessarily reflect those of the editor, editorialboard, or the publisher and in no way imply endorsement by EyeWorld or ASCRS.

novel therapeutic regimens in treating cme education ... · as a sponsor accredited by the...

Documents