CROQ - Vol. 1, Number 1, 2016 by MediConcept

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CROQ

Clinical Refractive & Optometry Quebec EDITION

VOLUME 1, NUMBER 1, 2016

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All articles are accredited by the OOQ for Category A UFC credits

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) The Role of Inflammation in Allergic Eye Disease Treatment Options for Seasonal Allergic Conjunctivitis The Role of Ointments in Clinical Practice

See additional safety information on page 39

Clinical

&Refractive Optometry Quebec

Editorial Board • Volume 1, Number 1, 2016 Editor-in-Chief

Associate Editor

Yvon Rhéaume, OD Montreal, Quebec

Richard Maharaj, OD Toronto, Ontario

Contributing Editors Brad Almond, OD Calgary, Alberta

Louis Catania, OD Philadelphia, Pennsylvania

Guy Julien, OD Montreal, Quebec

Rodger Pace, OD Waterloo, Ontario

Jean Bélanger, OD Montreal, Quebec

Paul Dame, OD Calgary, Alberta

Gerald Komarnicky, OD Vancouver, British Columbia

Maynard Pohl, OD Bellevue, Washington

Scott D. Brisbin, OD Edmonton, Alberta

Danielle DeGuise, OD Montreal, Quebec

Bart McRoberts, OD Vancouver, British Columbia

Barbara Robinson, OD Waterloo, Ontario

Lorance Bumgarner, OD Pinehurst, North Carolina

Pierre Forcier, OD Montreal, Quebec

Ron Melton, OD Charlotte, North Carolina

Jacob Sivak, OD, PhD Waterloo, Ontario

Barbara Caffery, OD Toronto, Ontario

John Jantzi, OD Vancouver, British Columbia

Langis Michaud, OD Montreal, Quebec

Randall Thomas, OD Concord, North Carolina

Publication Staff Publisher Lawrence Goldstein

Managing Editor Mary Di Lemme

Senior Medical Editor Evra Taylor

Layout Editor Colin MacPherson

Graphics & Design Mediconcept Inc.

Mission Statement Clinical & Refractive Optometry Quebec is an online, quarterly, peer-reviewed, professional journal dedicated to publishing and distributing clinical and scientific COPE approved articles which have been accredited by the OOQ as Category A, UFC-credit courses. The contents of the journal are composed of articles that will be of particular use and interest to practicing eye care professionals. Test participants who score 50% or more on the UFC test questionnaires will receive a printed UFC-credit certificate by return email.

Why are the UFC-credit articles published in English? Recently the regulations governing continuing education credits in Quebec have been amended so that COPE approved CE-credit articles which have been written by some of the most noted and influential optometric opinion leaders in the US, can now be offered to Quebec ODs as Category A, UFC-credit distance learning courses. In this regard it’s important to note that these articles, which were written in English, require a letter from their authors authorizing both their publication and accreditation. And it would be unrealistic to ask a US doctor to sign off on and approve a paper that has been rewritten in French. For this reason the re-accredited COPE approved articles in this journal are presented here in English.

Clinical

&Refractive Optometry Quebec

Contents • Volume 1, Number 1, 2016 4

PUBLISHER’S PAGE

CE CREDIT ARTICLES

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) Jimmy D. Bartlett, OD; Chris Snyder, OD INTRODUCTION: Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a growing concern that presents implications for both systemic and ophthalmic health. Eyecare and healthcare providers should be familiar with the clinical characteristics of a MRSA infection and with the treatment and management protocols for MRSA. They should be familiar with infection prevention control measures for clinical practice and they should know how to decrease the potential for MRSA infection in their patients through appropriate recommendations and counseling.

The Role of Inflammation in Allergic Eye Disease Paul M. Karpecki, OD INTRODUCTION: Allergy is one of the leading causes of chronic disease in North America, affecting approximately 30% of the population. Furthermore, studies indicate that up to 40% of the population have experienced ocular symptoms at least once in their lifetime. Why is ocular allergy so prevalent?

Treatment Options for Seasonal Allergic Conjunctivitis Michael L. Nordlund, MD ABSTRACT: Allergies affect more than 50 million Americans and may involve multiple organs, including the ears, nose, skin, and lungs. However, allergy sufferers report that ocular symptoms of allergic diseases such as seasonal allergic conjunctivitis (SAC) cause the greatest discomfort and contribute significantly to decreased quality of life and work productivity. Prevalence of allergic diseases is increasing and allergic eye disease is a leading cause of visits to internists, optometrists, and ophthalmologists.

Clinical & Refractive Optometry Quebec is published 4 times per year by Mediconcept. The Journal is made available to all practicing optometrists in Quebec on www.crojournal.com. Advertising insertion orders and copy must be received before the first day of the preceding month for which the advertising is scheduled. While the editorial staff of Clinical & Refractive Optometry Quebec exercises great care to ensure accuracy, we suggest that the reader consult the manufacturer’s instructions before using products mentioned in this publication. The views contained in the Journal are those of the respective authors and not of the Publisher. Please direct all correspondence to: Mediconcept Editorial & Sales Office 2113 St. Regis, Suite 250 Dollard-des-Ormeaux, Quebec Canada H9B 2M9 Tel.: (514) 447-1110 E-mail: info@mediconcept.ca Printed in Canada. All rights reserved. Copyright © 2016 Mediconcept. The contents of the publication may not be mechanically or electronically reproduced in whole or in part without the written permission of the publisher. All drug advertisements have been cleared by the Pharmaceutical Advertising Advisory Board.

The Role of Ointments in Clinical Practice Paul M. Karpecki, OD INTRODUCTION: Ophthalmic ointments have a long history dating back to ancient times and yet are still evolving with recent approvals involving technologies that allow the medication to be preservative-free. The understanding of the use, positive characteristics and side effects has also evolved to better help us position these products to most assist our patients with ocular diseases.

ISSN: 2369-498X; Date of Issue: January/February 2016

Cover Image Atopic keratoconjunctivitis Excerpted from: The Role of Inflammation in Allergic Eye Disease Courtesy of: Dr. Paul M. Karpecki

Clinical

&Refractive Optometry Quebec Volume 1, Number 1, 2016

Publisher’s Page This year, the Order of Optometrists of Quebec (OOQ) officially amended the regulations regarding how optometrists in Quebec can acquire their annual requirement of continuing education credits in order to maintain their optometric licences. More specifically, the OOQ will now accept qualified print articles that are published and distributed through recognized professional journals, for UFC credit. This means that Quebec ODs will now have the choice of either attending UFC accredited meetings and/or successfully completing UFC accredited journal articles for portions of their CE requirement. In response to this change in the regulations, the publisher of CRO (Clinical & Refractive Optometry) Canada’s leading all COPE approved CE-credit journal, has launched a new bimonthly, peer reviewed, UFC accredited journal, entitled CROQ (Clinical & Refractive Optometry Quebec) Online which will be made available online at no charge to all Quebec optometrists. Each issue of CROQ Online will be composed entirely of four OOQ approved, Category A, UFC-Credit articles, as they were written (in English), by some of North America’s leading and most recognized optometric experts. In order to distribute this journal, complimentary subscriptions are being offered to all Quebec ODs so that online issues of CROQ can be forwarded directly to their email accounts. These online issues are fully downloadable for immediate viewing and they can also be saved (either in whole or in part) for later use. Each article in the journal will have an accompanying Category a UFC test questionnaire that can be completed and returned for grading at a cost of $25 per test. Upon successfully completing each test, a UFC-credit certificate of completion will be emailed to each applicant. Please note that an upgraded subscription package for a print version of the journal that includes no charge UFC tests is also available. For more details, please see the Subscription Upgrade Form on the facing page. We hope that you will enjoy reading this inaugural issue of CROQ, and that you will come to rely on this publication as a valued resource for your annual UFC credit requirements. We would also like to hear from you with your thoughts and impressions about this new journal, and most importantly what you would like to see included in future issues. Lawrence Goldstein Publisher lgoldstein@mediconcept.ca

Clinical & Refractive Optometry Quebec 1:1, 2016

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January/February 2016 issue

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Upgrade to a subscription to the Print Edition and you will automatically receive three more consecutive printed issues for the 2016 volume year by direct mail, and each of those 3 issues will contain at least four OOQ approved UFC-credit articles with prepaid UFC test questionnaires. For those of you doing the math, this means that you will receive 300$ worth of Category A UFC-credit tests, for a one-time price of 200$ plus tax.

Subscription Form Clinical & Refractive Optometry Quebec: Print Edition Yes, please enter my subscription for the 2016 Print Edition of Clinical & Refractive Optometry Quebec for 3 consecutive print issues including a total of twelve OOQ approved Category A UFC-credit tests for 230.48$. Registration Information Title ______ First Name ___________________ Last Name _______________________________ Number __________ Street _____________________________________________ Suite ________ City ______________________________________________________ Postal Code ______________ Office Phone (_____) _______________________ E-mail _________________________________ Professional License ________________________________________________________________ Please forward a cheque made payable to Mediconcept Communications, and mail it today to:

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Clinical & Refractive Optometry Quebec is pleased to present this continuing education (CE) article by Dr. Jimmy D. Bartlett, Professor and Chairman at the University of Alabama at Birmingham School of Optometry, Birmingham, AL and Dr. Chris Snyder, Adjunct Professor at the University of Alabama at Birmingham School of Optometry, Birmingham, AL. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optometrists du Québec. In order to obtain your credit, please refer to page 13 for complete instructions.

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) Jimmy D. Bartlett, OD, DOS, ScD Chris Snyder, OD, MS, FAAO

INTRODUCTION Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a growing concern that presents implications for both systemic and ophthalmic health. Eyecare and healthcare providers should be familiar with the clinical characteristics of a MRSA infection and with the treatment and management protocols for MRSA. They should be familiar with infection prevention control measures for clinical practice and they should know how to decrease the potential for MRSA infection in their patients through appropriate recommendations and counseling. Staphylococcus aureus, often referred to simply as “staph,” is a common bacterium that’s colonized on human skin and in the noses of 25% to 30% of the population of healthy people.1 It can affect individuals of any age. Individuals are said to be “colonized” when bacteria are present, but not harming the host or causing symptoms.1,2 Staph is the most common cause of localized skin infections, such as folliculitis, furuncles (boils), pimples and impetigo. Moreover, the endo- and exotoxins from staph on the eyelids can cause inflammatory conditions such as staphylococcal blepharitis, phlyctenular conjunctivitis and infiltrative keratitis. Staph can be a serious pathogen, particularly when associated with a

J.D. Bartlett — Professor and Chairman, Department of Optometry, University of Alabama at Birmingham School of Optometry, Birmingham, Alabama; C. Snyder — Adjunct Professor, University of Alabama at Birmingham School of Optometry, Burningham, Alabama Correspondence to: Dr. Jimmy Bartlett, HPB 121, 1530 3rd Avenue S, Birmingham, AL 35294-0010; E-mail: eyedrug@uab.edu This article is reprinted by permission from a supplement to the February 2010 Contact Lens Spectrum titled Methicillin-resistant Staphylococcus aureus: Challenges and Risks. Contact Lens Spectrum is published by Wolters Kluwer Pharma Solutions Vision Care Group © 2009-2010. All rights reserved. Wolters Kluwer Pharma Solutions Vision Care Group is located at 323 Norristown Road, Suite 200, Ambler, PA 19002 (USA). Please visit www.clspectrum.com for more information.

Clinical & Refractive Optometry Quebec 1:1, 2016

wound to the skin, surgical or otherwise, or in an immunocompromised patient. Most life-threatening staph infections are acquired in a healthcare setting, such as a hospital or nursing home. Colonizing staph can cause serious conditions such as abscesses, osteomyelitis, staphylococcal pneumonia, septicemia, toxic shock syndrome and endocarditis.2 Around and in the eye, infection by Staphylococcus aureus can be the cause of preseptal and orbital cellulitis, lid abscess, conjunctivitis, corneal ulcers, endophthalmitis and blebitis.3

TREATMENT WITH ANTIBIOTICS MSSA Staphylococcus aureus was generally susceptible to the beta-lactam antibiotics when they were introduced in the early 1940s. Beta-lactams are the most widely used group of antibiotics and they include penicillin, penicillin’s synthetic derivatives (methicillin, oxacillin, nafcillin, cloxacillin, dicloxacillin and flucloxacillin) and the cephalosporins (cephalexin, cefadroxil, cefazolin, and others). Staphylococcus aureus microorganisms that demonstrate susceptibility to the antimicrobial effects of penicillin and its synthetic derivatives are referred to as methicillin-susceptible Staphylococcus aureus (MSSA). VSSA Vancomycin is a glycopeptide antibiotic that inhibits cell wall synthesis in Gram-positive bacteria.4 Staphylococcus aureus microorganisms that are susceptible to vancomycin are referred to as vancomycin-susceptible Staphylococcus aureus (VSSA). Vancomycin is often effective in treating Gram-positive bacteria that are unresponsive to beta-lactams. Vancomycin will not pass across the gastrointestinal mucosa and therefore must be administered intravenously for systemic therapy, requiring in-patient care.4

DEVELOPMENT OF RESISTANCE TO ANTIBIOTICS MRSA In 1944, Staphylococcus aureus was found to demonstrate some resistance to penicillin, likely in response to the wide usage of beta-lactam drugs, making it the first

known bacterium to acquire antibiotic resistance.5 Resistance to penicillin became widespread during the 1950s, and increasing resistance to the semi-synthetic penicillinase-resistant antimicrobial agents (such as methicillin, oxacillin, nafcillin) followed in the 1960s.6 The resistance to these semi-synthetic penicillins had become so prevalent by the 1990s that they could no longer be used as first-line empirical therapy for serious staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is the name given to Staphylococcus aureus microorganisms that have become resistant to penicillin and its synthetic derivatives. VRSA While vancomycin has been considered the drug of choice after treatment failure with other antibiotics, bacterial resistance to vancomycin has also developed during the past 20 years. Vancomycin-resistant Staphylococcus aureus (VRSA) is the name given to Staphylococcus aureus microorganisms that have become resistant to vancomycin.

TYPES OF MRSA MRSA disease has become a major public health problem.7 Before the 1980s, MRSA was primarily considered to be a nosocomial infection — one that is acquired in a hospital or healthcare setting (such as nursing homes); not present or incubating prior to the patient being admitted to the health care facility, but occurring within 72 hours after admittance to the facility.8 Nosocomial MRSA infections are referred to as “Health Care-Associated Methicillin Resistant Staphylococcus aureus” (HA-MRSA) infections to distinguish them from MRSA infections acquired in the general community outside of the healthcare setting.9,10 These staph infections occur most frequently among persons who have a weakened immune system7 and include surgical wound infections, urinary tract infections, bloodstream infections and pneumonia. Approximately 20% of bloodstream infections in the hospital setting are caused by S. aureus and the proportion of hospital-onset S. aureus infections that were methicillin-resistant reached 64.4% in U.S. intensive care units in 2003.7 Standardized mortality rate (in-hospital deaths) was 6.3 per 100,000.7 Approximately 1% of the population is colonized with MRSA.1 Klevens and colleagues7 reported that invasive MRSA infection is a major public health problem primarily related to health care but no longer confined to healthcare settings. Non-nosocomial MRSA infections are referred to as Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) infections. Individuals with these infections have neither been recently hospitalized (within the prior year) nor had a medical procedure (such as dialysis, surgery, catheterization). CA-MRSA infections typically manifest as skin

infections such as pimples, abscesses and boils, and other pus-filled lesions.9,10 Since 1981, CA-MRSA has become the most frequent cause of skin and soft tissue infections presenting to emergency departments in the United States7,11 and the prevalence of CA-MRSA is rapidly increasing.5 Naseri and colleagues12 reported a significant increase in the prevalence of CA-MRSA head and neck infections in the pediatric population from 2001 through 2006. Blomquist3 reviewed the records of culture-positive MRSA patients in an urban public healthcare system (2000-2004) to identify patients with ocular, orbital and ocular adnexal infection. He found that the most common manifestation of ophthalmic MRSA infection was preseptal cellulitis and/or lid abscess, followed by conjunctivitis. Sightthreatening infections also occurred, including corneal ulcers, endophthalmitis, orbital cellulitis and blebitis. The distinction between HA-MRSA and CA-MRSA is based upon genetic studies that show that isolates causing HA- and CA-MRSA infections are different species, meaning CA-MRSA organisms aren’t HAMRSA organisms that have simply moved into the general community.13 Differences in virulence factors between HA-MRSA and CA-MRSA organisms may allow the community strains to spread more easily or to cause more skin disease compared with the traditional hospital-based MRSA strains.1 HA-MRSA is typically a multidrug-resistant organism, while CA-MRSA isolates are usually susceptible to most nonbeta-lactam antimicrobial agents.13

TRANSMISSION AND CONTROL Clinicians should be familiar with infection prevention control measures for clinical practice, must routinely use measures to prevent the transmission of MRSA, and know how to decrease the potential for MRSA infection through appropriate recommendations and patient counseling. HA-MRSA The most important reservoirs of MRSA in hospitals are infected or colonized patients. Hospital personnel are most commonly identified as the transmission link between patients, mainly via their hands, which may become contaminated by contact with colonized or infected patients, colonized or infected body sites of the personnel themselves, or from contact with devices, items or environmental surfaces contaminated with body fluids containing MRSA.14 HA-MRSA isolates can survive on a variety of inanimate surfaces, sometimes for weeks.15 Infection control is the key to limiting or eradicating MRSA and other health care-associated infectious pathogens in hospitals. Control measures include aggressive hand hygiene programs, interventions to reduce catheter-related bloodstream infections, ventilatorassociated pneumonia, and surgical site infections; and

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) — Bartlett, Snyder

chlorhexidine bathing of ICU patients.16-19 Additional information on infection control in healthcare settings is available from the CDC.20 CA-MRSA Factors known to increase the risk of spreading CA-MRSA skin and soft tissue infections include close skin-to-skin contact, openings in the skin such as cuts or abrasions, poor hygiene, crowded living conditions and contaminated items and surfaces.1 The presence of CA-MRSA isolates on items such as clothing, towels and athletic equipment may contribute to outbreaks. Settings, circumstances and activities that provide close contact conditions include households, schools, day care facilities, dormitories, military barracks, correctional facilities, athletics (particularly contact sports) and IV drug use. Groups in the population that tend to have a higher incidence of CA-MRSA infections include Native Americans, Pacific Islanders and men who have sex with men.15 CA-MRSA disease can even be shared between pets and human handlers, as demonstrated in cases where the pets (dogs, cats, livestock and birds) have been identified as the MRSA carriers.21,22 Advice for prevention of CA-MRSA transmission includes the consistent practice of appropriate personal hygiene, avoidance of an unclean/unsanitary environment and use of barriers to bacterial transmission. Basic prevention advice for all individuals should include the following recommendations16,23: • Practice good personal hygiene: – Keep hands clean by washing with soap and water regularly or by using an alcohol-based hand sanitizer. – Don’t share personal items that come into direct contact with bare skin, such as towels and razors. – Avoid contact with other people’s wounds or bandages. – Keep skin abrasions and cuts covered to prevent them from becoming infected (always use clean, dry bandages until healed). • Keep high-touch surfaces clean: – High-touch surfaces (that are frequently in contact with hands) should be kept clean, and all surfaces that might come into direct contact with people’s skin should be cleaned routinely. • Practice healthy hygiene in exercise and sports: – Barrier-like clothing or a towel should be used between skin and equipment, such as weighttraining benches. – Showering should be done immediately after participating in activities with frequent skin-toskin contact, such as exercise and sports. Basic infection control recommendations for clinicians includes using standard precautions24,25:

Clinical & Refractive Optometry Quebec 1:1, 2016

•

• •

• • •

Perform hand hygiene (proper hand-washing or using alcohol-based hand gel): – after touching blood, body fluids, secretions, excretions and contaminated items, even when gloves are worn – between patients – when moving from a contaminated body site to a clean site on the same patient Wear gloves when managing wounds Wear gown and mask/eye protection or face shield for procedures that are likely to generate splashes or sprays of blood, body fluids, secretions or excretions Clean shared equipment between uses Avoid overcrowding and separate infected patients Clean surfaces of exam rooms with commercial disinfectant or a 1:100 solution of diluted bleach (1 tablespoon bleach in 1 quart water)

Additional information about CA-MRSA for both clinicians and the public is available from the CDC.10,26

INFECTION SURVEILLANCE PROGRAMS The CDC plays a large role in MRSA surveillance by monitoring the incidence of health care-associated infections, the associated risk factors and pathogens by gathering data through the National Healthcare Safety Network (NHSN),27 a voluntary reporting system shared by all U.S. hospitals, long-term care facilities, other healthcare organizations and the CDC. The CDC also participates in MRSA prevention, epidemiologic and laboratory research, and outbreak and laboratory support.27 Another useful program is The Surveillance Network (TSN), which was established in 1994 as an electronic repository of infectious organisms, specimen sources and antimicrobial susceptibility data.28 TSN monitors the patterns of antimicrobial susceptibility of pathogens, such as MRSA, in infections requiring diagnostic testing. While most TSN data are from systemic infections, data from cultured ocular infections have also been captured, demonstrating an increase in the rate of ocular MRSA infections of 12.1% over a 5-year period (from 29.5% in 2000 to 41.6% in 2005) (Fig. 1).28 Asbell and colleagues concluded that MRSA isolates soon may become the dominant phenotype in serious ocular S. aureus infections.28 TSN data also showed that MRSA in ocular infections could be classified as multidrug resistant, including all the fluoroquinolones tested, and that trimethoprim was the most effective agent against MRSA.28 Shortly after the TSN program was launched, the “Tracking Resistance in the U.S. Today” (TRUST) program was initiated in 1996 to assess pathogen susceptibility to fluoroquinolones and other antimicrobials when levofloxacin was first introduced for systemic use.29 The ongoing program allows for

Relative Trends of MSSA Rate (purple) and MRSA rate (blue) in Serious Ocular Infections (2000 to 2005; based on TSN database analysis) 100 90

Percentage of S. aureus Isolates

80 70 60 50 40 30 20 10 0

2000

2001

2003

2002

2004

2005

Year Reproduced from Journal of Cataract & Refractive Surgery, Vol 34/5, PA Asbell, DF Sahm, M Shaw, DC Draghi and NP Brown, Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005, page 5, Copyright 2008, with permission from Elsevier. 28

Fig. 1 Relative trends of MSSA rate (purple bars) and MRSA rate (blue bars) in serious ocular infections from 2000 to 2005, based on TSN database analysis.

monitoring of trends in antibiotic resistance with nationwide susceptibility data. The TRUST program, however, did not systematically track in vitro susceptibility in ocular isolates. To fill this gap, Ocular TRUST began in 2005 as a longitudinal nationwide susceptibility surveillance program, tracking antimicrobial susceptibility patterns of common ocular pathogens. Ocular isolates are tested against a panel of antimicrobials representing six pharmacologic classes: fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin); dihydrofolate reductase inhibitors (trimethoprim); macrolides (azithromycin); aminoglycosides (tobramycin); polypeptides (polymyxin B); and beta-lactams (penicillin).30 Among the results from the third year of Ocular TRUST31 (Fig. 2): • Most antimicrobials, except penicillin and polymyxin B, continue to be highly active against MSSA (azithromycin shows only moderate activity). • With the exception of trimethoprim and tobramycin, less than one-third of MRSA strains are susceptible to ophthalmic antimicrobials. • Susceptibility profiles of the fluoroquinolones remain weak for MRSA.

TREATMENT OF MRSA Clinicians should be aware of the currently recommended therapeutic regimens that incorporate new knowledge regarding the most effective antibiotics administered systemically or topically for both HA-MRSA and CA-MRSA (Table I).

HA-MRSA Since HA-MRSA strains are multidrug-resistant organisms (MDRO), final therapy should be guided by results of susceptibility testing from cultures obtained before the initiation of empirical therapy (Table II).11,13,15,25 For initial empirical antibiotic therapy for HA-MRSA, Grayson25 has suggested vancomycin, linezolid, daptomycin or rifampin plus trimethoprim-sulfamethoxazole. Treatment for severe infection (where the patient appears toxic, vital signs are unstable and a sepsis syndrome is present) would include the following:24 • Intravenous therapy for MRSA is preferred; vancomycin remains a first-line therapy (although, owing to concerns about possible development of vancomycin-resistant bacteria, its use is restricted in most hospitals, and requires approval of the Infectious Disease Unit)4 • Final therapy based on results of culture and susceptibility testing • Consult with infectious disease and critical care specialist CA-MRSA CA-MRSA infections often begin as skin or soft tissue lesions, such as a boil or abscess and/or cellulitis, with patients frequently reporting a lesion that is red, swollen and painful.24 CA-MRSA should be suspected particularly if a patient reports, or presents with, a wound resembling a spider bite, since MRSA strains can cause painful lesions in the absence of previous skin trauma.11 Moran and colleagues11 reported that while more than 80% of patients with skin and soft-tissue infections associated with MRSA received empirical antimicrobial therapy for their infections, 57% of those patients were infected with a MRSA isolate that was resistant to the agent prescribed. Susceptibility testing of MRSA isolates in this study revealed that 100% were susceptible to trimethoprim-sulfamethoxazole, 95% to clindamycin, 92% to tetracycline, and 60% to fluoroquinolones. Similar to their findings regarding susceptibility to trimethoprimsulfamethoxazole, Asbell28 reported that trimethoprim is the most effective topically applied antibiotic against ocular MRSA infection. In treating nonpurulent cellulitis, as in preseptal cellulitis, there is a chance that the infection involves group A streptococcus,31 which is mostly resistant to trimethoprim-sulfamethoxazole.11,15 For coverage of streptococcal infection, clindamycin or a combination of a beta-lactam plus trimethoprim-sulfamethoxazole may be preferable.11 Trimethoprim-sulfamethoxazole and tetracyclines are reasonable choices for cases where CA-MRSA infection is either confirmed or strongly suggested by the presence of purulent material.15

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) — Bartlett, Snyder

Staphylococcus aureus In Vitro Susceptibility Figure 2. Results for Staphylococcus aureus in vitro susceptiblity from Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates

Methicillin-Susceptible S. aureus

100

100 93

98 99 98

Ocular Trust 1 (n=33) Ocular Trust 2 (n=84) Ocular Trust 3 (n=78)

100

94 95 95

Methicillin-Resistant S. aureus

Ocular Trust 1 (n=164) Ocular Trust 2 (n=71) Ocular Trust 3 (n=84)

CIP, Ciprofloxacin GAT, Gatifloxacin LEV, Levofloxacin MOX, Moxifloxacin AZTH, Azithromycin PEN, Penicillin PLX, Polymyxin B TOB, Tobramycin TMP, Trimethoprim

89 85 80

81 81

85 81

80 Percentage of Isolates Susceptible

Percentage of Isolates Susceptible

62 62

60 54

17 13

40 30

20 15 18

6 0

CIP

GAT

LEV

MOX

AZTH

PEN

PLX

TOB

TMP

CIP

GAT

LEV

55 50

MOX

AZTH

PEN

PLX

TOB

TMP

Reproduced with permission from: Asbell P., Sahm D., Shedden A., for the Ocular TRUST Study Group. Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates. Copyright 2009. American Society of Cataract and Refractive Surgery. 30

Fig. 2 Results for Staphylococcus aureus in vitro susceptibility from Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates Table I Systemic antibiotics of interest in the treatment of S. aureus and MRSA infections • • • • • • • •

Trimethoprim-sulfamethoxazole (co-trimoxazole), as a sulfonamide antibacterial combination, is effective against MRSA because it synergistically inhibits successive steps in the folate synthesis pathway, starving the bacteria of the folic acid that is necessary for DNA replication and transcription. Clindamycin (a lincosamide antibiotic) can be effective against MRSA infections because it reduces the production of staph exotoxins and may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis). Doxycycline, as a semi-synthetic tetracycline, is effective against MRSA infections primarily through inhibition of bacterial protein synthesis leading to bacteriostasis. Daptomycin, a cyclic lipopeptide, acts on the bacterial cytoplasmic membrane and is bactericidal against most Gram-positive bacteria, including Staphylococcus aureus. Linezolid, an oxazolidinone, is active against almost all CA-MRSA isolates and group A streptococci. High cost, lack of routine availability, hematologic side effects, and the potential for resistance among Staphylococcus aureus strains are relative contraindications for usage. Rifampin is highly active against susceptible community-associated MRSA isolates but it must be used in combination with trimethoprimsulfamethoxazole or doxycycline due to high frequency of resistance when rifampin is used alone. Fluoroquinolones interrupt bacterial replication by binding to both deoxyribonucleic acid (DNA) gyrase and topoisomerase IV. They should not be used to treat skin and soft-tissue infections caused by CA-MRSA since Staphylococcus aureus resistance develops readily and is already widely prevalent. Augmentin (GlaxoSmithKline) — a combination of amoxicillin, a beta-lactam antibiotic, and clavulanic acid, a beta-lactamase inhibitor — addresses bacterial resistance to beta-lactam with the clavulanic acid antagonizing the beta-lactamase enzyme, binding irreversibly to it and allowing the amoxicillin to attack bacterial cell wall synthesis. Augmentin is effective in treating MSSA infection, but is not effective against MRSA.

Asbell28 suggested that a clinician would be prudent to consider the possibility of methicillin or multidrug resistance with any Staphylococcus aureus ocular infection, even in the absence of recognized risk factors, because of recent increases in the prevalence of MRSA and the inability of clinical or epidemiological risk factors to reliably distinguish between CA-MRSA and MSSA.32 Ideally, cultures should be obtained for suspected MRSA infections, with the susceptibility profile of the organism(s) ultimately guiding the antibiotic treatment.11,24

Clinical & Refractive Optometry Quebec 1:1, 2016

CONTROLLING MRSA The increasing prevalence of MRSA has resulted in a paradigm shift to include this group of organisms in the differential diagnosis of numerous diseases, including those that affect the ocular tissues. The spread of MRSA can be controlled through appropriate steps by individuals, and clinicians must routinely use measures to prevent transmission of these organisms. To treat MRSA infection, clinicians should be aware of the currently recommended therapeutic regimens that incorporate new knowledge

Table II Treatment summary for initial empirical antibiotic therapy • •

For MSSA: penicillinase-resistant penicillin or a first-generation cephalosporin should be used.25 (Note that the penicillins are more effective than vancomycin in treating MSSA.) For MRSA: • Generally: — Avoid beta-lactam antibiotics (e.g., no penicillins or cephalosporins) for MRSA • Based on HA- or CA-MRSA: HA-MRSA: — Vancomycin25; alternatives to vancomycin, particularly to manage VRSA, include linezolid, daptomycin, trimethoprim, or rifampin plus trimethoprim-sulfamethoxazole.6,25,28 Asbell28 has reported that trimethoprim can be as effective as vancomycin in both systemic and ocular MRSA infections CA-MRSA: — Systemically: Trimethoprim-sulfamethoxazole, clindamycin, or a long-acting tetracycline such as doxycycline15,25 • CA-MRSA can cause severe and sometimes fatal invasive disease.7,33 When a CA-MRSA infection is severe, it should be treated in • the same manner as previously described for severe HA-MRSA infection. — Ophthalmically: • While fluoroquinolones are commonly used to treat ocular surface infections, alternatives should be considered.29 Trimethoprim has been reported to be the most effective topically applied antibiotic that is active against MRSA.28-30

regarding the most effective systemic and topical antibiotics for HA-MRSA and CA-MRSA. ❏

REFERENCES 1.

4. 5.

8. 9.

Centers for Disease Control and Prevention. Communityassociated MRSA information for clinicians. Available at: cdc.gov/ncidod/dhqp/ar_MRSA_ca_clinicians.html# Last accessed November 2009. Lab Tests Online. Staph wound infections and methicillin resistant Staphylococcus aureus. Available at: labtestsonline.org/understanding/conditions/staph.html. Last accessed November 2009. Blomquist PH. Methicillin-resistant Staphylococcus aureus infections of the eye and orbit (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc 2006; 104: 322-345. The Drug Monitor. Anaizi N. Vancomycin. (2002) Available at: thedrugmonitor.com/vanco.html. Last accessed November 2009. ClinLab Navigator. Methicillin resistant Staphylococcus aureus. Available at: clinlabnavigator.com/Tests/Methicillin ResistantStaphylococcusAureus.html. Last accessed November 2009. Centers for Disease Control and Prevention. Investigation and control of VISA/VRSA. A guide for health departments and infection control personnel. Updated: September 2006. Available at: cdc.gov/ncidod/dhqp/ar_ visavrsa_prevention.html. Last accessed November 2009. Klevens RM, Morrison MA, Nadle J, et al. Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007; 298: 1763-1771. MedicineNet. Definition of nosocomial. Available at: medterms.com/script/main/art.asp?articlekey=4590 Last accessed November 2009. Centers for Disease Control and Prevention. Healthcareassociated methicillin resistant Staphylococcus aureus (HA-MRSA). Available at: cdc.gov/ncidod/dhqp/ar_ mrsa.html. Last accessed November 2009.

10. Centers for Disease Control and Prevention. Communityassociated methicillin resistant Staphylococcus aureus (CA-MRSA). Available at: cdc.gov/ncidod/dhqp/ar_ mrsa_ca.html. Last accessed November 2009. 11. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillinresistant S. aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666-674. 12. Naseri I, Jerris RC, Sobol SE. Nationwide trends in pediatric Staphylococcus aureus head and neck infections. Arch Otolaryngol Head Neck Surg 2009; 135: 14-16. 13. Naimi TS, LeDell KH, Como-Sabetti KM, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003; 290: 2976-2984. 14. Centers for Disease Control and Prevention. Information about MRSA for healthcare personnel. Available at: cdc.gov/ncidod/dhqp/ar_mrsa_healthcareFS.html. Last accessed November 2009. 15. Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med 2007; 357: 380-390. 16. MedlinePlus. National Institute of Allergy and Infectious Diseases. MRSA. Available at: nlm.nih.gov/medlineplus/mrsa.html. Last accessed November 2009. 17. Siegel JD, Rhinehart E, Jackson M, Chiarello L. Healthcare Infection Control Practices Advisory Committee. Management of multidrug-resistant organisms in healthcare settings, 2006. Available at: cdc.gov/ncidod/dhqp/pdf/ ar/mdroGuideline2006.pdf. Last accessed November 2009. 18. Centers for Disease Control and Prevention. Guideline for disinfection and sterilization in healthcare facilities, 2008. Available at: cdc.gov/ncidod/dhqp/pdf/guidelines/ Disinfection_Nov_2008.pdf. Last accessed November 2009. 19. Diekema DJ, Climo M. Preventing MRSA infections: finding it is not enough. JAMA 2008; 299: 1190-1192. 20. Centers for Disease Control and Prevention. Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings 2007. Available at: cdc.gov/ncidod/dhqp/gl_isolation.html. Last accessed November 2009.

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) — Bartlett, Snyder

21. Oehler RL, Velez AP, Mizrachi M, Lamarche J, Gompf S. Bite-related and septic syndromes caused by cats and dogs. Lancet Infect Dis 2009; 9: 439-447. 22. Leonard FC, Markey BK. Methicillin-resistant Staphylococcus aureus in animals: a review. Vet J 2008; 175: 27-36. 23. Centers for Disease Control and Prevention. Methicillinresistant Staphylococcus aureus (MRSA), October 2007 CDC podcast transcript. Available at www2.cdc.gov/podcasts/player.asp?f=6936#transcript. Last accessed November 2009. 24. Centers for Disease Control and Prevention. Disaster recovery fact sheet, methicillin-resistant Staphylococcus aureus (MRSA) information for clinicians. Available at: emergency.cdc.gov/disasters/disease/mrsaclinicians.asp. Last accessed November 2009. 25. Grayson ML. The treatment triangle for staphylococcal infections. N Engl J Med 2006; 355: 724-727. 26. Centers for Disease Control and Prevention. National MRSA education initiative: Preventing MRSA skin infections. Available at: cdc.gov/mrsa/. Last accessed November 2009. 27. Centers for Disease Control and Prevention. What is CDC doing about MRSA? Available at: cdc.gov/ncidod/dhqp/ar_ mrsa_CDCactions.html. Last accessed November 2009.

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28. Asbell PA, Sahm DF, Shaw M, Draghi DC, Brown NP. Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005. J Cataract Refract Surg 2008; 34: 814-818. 29. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol 2008; 145: 951-958. 30. Asbell P, Sahm D, Shedden A, for the Ocular TRUST Study Group. Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates. Available at: ascrs2009.abstractsnet.com/handouts/000229_OT3_ASCRS_PosterUpload-AsSlidesFinal.ppt. Last accessed November 2009. 31. Bernard P, Bedane C, Mounier M, Denis F, Catanzano G, Bonnetblanc JM. Streptococcal cause of erysipelas and cellulitis in adults: a microbiologic study using a direct immunofluorescence technique. Arch Dermatol 1989; 125: 779-782. 32. Miller LG, Perdreau-Remington F, Bayer AS, et al. Clinical and epidemiologic characteristics cannot distinguish community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureus infection: a prospective investigation. Clin Infect Dis 2007; 44: 471-482. 33. Hidron AI, Low CE, Honig EG, Blumberg HM. Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising communityonset pneumonia. Lancet Infect Dis 2009; 9: 384-392.

CATEGORY A UFC C REDIT A PPLICATION F ORM

1:1, 16

INSTRUCTIONS

FOR

1 CATEGORY A, UFC CREDIT

This course has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optométristes du Québec. Please complete and submit this test questionnaire for grading before March 31, 2018. In order to obtain 1 Category A, UFC credit, please follow these steps: • Fill in the identification section and answer the 10 multiple choice questions in this UFC credit application form • Prepare a cheque payable to Mediconcept for $25.00 • Mail your completed UFC credit application form along with your cheque to: CRO Quebec, 3484 Sources Blvd, Suite 518, Dollard-des-Ormeaux, QC H9B 1Z9 Your answers will be graded by Clinical & Refractive Optometry. If you score 50% or more, a UFC Credit Certificate approved by the Ordre des Optométristes du Québec will be issued to you for your records.

CLICK HERE TO PRINT THIS UFC CREDIT TEST AND ARTICLE Name: First______________________________ Last___________________________________ Address:________________________________________________________________________ Street

Number

Suite

_______________________________________________________________________________ City

Office Phone: (

Province

) _____________ Fax: (

Postal Code

) ______________ e-mail: __________________

Registration Number:_____________________________________________________________

QUESTIONNAIRE Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) Jimmy D. Bartlett, OD, DOS, ScD; Chris Snyder, OD, MS, FAAO 1. ❑ ❑ ❑ ❑

According to the paper, in what percentage of healthy people is methicillin-resistant Staphylococcus aureus (MRSA) found? 10% 25% to 30% 35% 40%

2. ❑ ❑ ❑ ❑

Which is the most common of the following localized skin infections? Furuncles (boils) Pimples Staphylococcus aureus Folliculitis

3. ❑ ❑ ❑ ❑

All of the following can be caused by colonizing Staphylococcus aureus, EXCEPT: Toxic shock syndrome Endocarditis Septicemia Myocarditis

Overview of Methicillin-Resistant Staphylococcus aureus (MRSA) — Bartlett, Snyder

1:1, 16

CATEGORY A UFC C REDIT A PPLICATION F ORM 14

4. ❑ ❑ ❑ ❑

Nosocomial MRSA infections include all of the following, EXCEPT: Urinary tract infections Pneumonia Kidney infections Blood stream infections

5. ❑ ❑ ❑ ❑

According to the population, what percentage of the population is colonized with MRSA? 1% 5% 10% 20%

6. ❑ ❑ ❑ ❑

Which of the following is the most common source of transmission of MRSA among hospital personnel? Accidental needle sticks Nasal secretions Hand contact Blood products

7. ❑ ❑ ❑ ❑

Which of the following population groups is likely to have a higher incidence of CA-MRSA infections? African Americans Caucasians Native Americans Asians

8. ❑ ❑ ❑ ❑

According to TSN data, which of the following is the most effective agent against MRSA ocular infections? Vancomycin Trimethoprim Linezolid Daptomycin

9. ❑ ❑ ❑ ❑

All of the following are clinical signs of MRSA, EXCEPT: Cellulitis Boil Abscess Hive-like rash typically appearing on legs

10. ❑ ❑ ❑ ❑

All of the following are ways to help prevent CA-MRSA transmission, EXCEPT: Avoiding contact with other people’s wounds Keeping skin abrasions covered to prevent their becoming infected Limiting sun exposure Keeping high-touch surfaces clean

Clinical & Refractive Optometry Quebec 1:1, 2016

CLICK HERE TO PRINT THIS UFC CREDIT ARTICLE AND TEST

Clinical & Refractive Optometry Quebec is pleased to present this continuing education (CE) article by Dr. Paul M. Karpecki, Clinical Research Director at Koffler Vision Group, Lexington, KY. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des optometrists du Québec. In order to obtain your credit, please refer to page 22 for complete instructions.

The Role of Inflammation in Allergic Eye Disease

INFLAMMATION: A MAJOR FACTOR IN ALLERGIC EYE DISEASE

Paul M. Karpecki, OD, FAAO

As vascularized tissue, the conjunctiva consists of a large number of dendritic cells and macrophages. Dendritic cells are immune cells that process antigen material and preset it on the surface to other cells of the immune system such as T-cells. The most commonly known dendritic cells in the conjunctiva are Langerhans cells. Essentially, dendritic cells, like Langerhans cells, are known as antigen-presenting cells. Once they are activated, they migrate to the lymph nodes where they interact with T-cells and B-cells to initiate the adaptive immune response. At certain stages of the immune process they grow branches or projections, from which their name originates. Marcophages also serve to regulate the innate and adaptive immunity of the conjunctival epithelium and are known as phagocytes. Their role is to digest or engulf cellular debris and pathogens. They are also known to stimulate lymphocytes such as dendritic cells. When dendritic cells present the antigen to memory T-lymphocytes, they produce Th-2 cytokines and, in addition, regulate the production of another cytokine known as IL-12.7 These cytokines further promote the synthesis of IgE from B-cells. IgE binds on mast cells, resulting in a cross-linking of the antibodies. This results in an immediate change of the mast cell membrane permeability and the release of inflammatory mediators. Such inflammatory mediators include histamine, chymase, leukotrienes, prostaglandins, carboxypeptidase A, platelet activating factor (PAF), neutrophils and eosinophils.5 The main issue with chronic allergic eye disease is that the memory T-lymphocytes increase dramatically, with the same basic response each time the allergen presents.8

INTRODUCTION Allergy is one of the leading causes of chronic disease in North America, affecting approximately 30% of the population.1 Furthermore, studies indicate that up to 40% of the population have experienced ocular symptoms at least once in their lifetime.2 Why is ocular allergy so prevalent? The answer is that the ocular surface has no mechanical barrier. Like our skin, it cannot prevent the impact of allergens, such as pollen, on its surface.3 Inflammation plays a key role in this and begins early in the process of allergic conjunctivitis, resulting in itching, tearing, edema and redness. The next phase of allergic conjunctivitis involves inflammatory mediators such as prostaglandins, leukotrienes and thromboxanes that recruit additional inflammatory cells.4 The late phase response involves infiltration of eosinophils, neutrophils and basophils.5 Thus, inflammation is central to every aspect of the allergic eye disease cascade. Furthermore, because of the chronic nature of many allergic diseases such as perennial allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC), patients must be monitored regularly and the use of ester-based steroids may be better options. Loteprednol etabonate is the only steroid that does not have a ketone at the C-20 position. This has been bioengineered to replace the ketone found in older steroids by an ester. Our bodies have esterase enzymes that can break down the metabolites that often result in intraocular pressure (IOP) rise, secondary cataracts and other complications, resulting in a significantly lower rate of complications with the use of ester-based steroids.6

P.M. Karpecki — Cornea Services and Clinical Research Director, Koffler Vision Group, Lexington, Kentucky Correspondence to: Dr. Paul M. Karpecki, Koffler Vision Group, 120 N. Eagle Creek Drive, Suite 431, Lexington, KY 40509; E-mail: paul@karpecki.com This article has been peer-reviewed.

THE EFFECTS OF NOT TREATING AN INFLAMMATORY CONDITION The obvious signs of inflammation include edema and erythema, which are common in allergic eye disease. Longstanding inflammation has long been known to cause permanent damage, structural changes and scarring. For example, patients suffering from chronic inflammatory conditions affecting the conjunctiva, such as allergic eye disease, may result in a loose and redundant conjunctiva

The Role of Inflammation in Allergic Eye Disease — Karpecki

Fig. 1 Seasonal allergic conjunctivitis

Fig. 2 Atopic keratoconjunctivitis

Fig. 3 Vernal keratoconjunctivitis

Fig. 4 Giant papillary conjunctivitis

or conjunctivochalasis.9,10 Patients with longstanding giant papillary conjunctivitis (GPC), which has been shown to be a response to trauma,11 can result in hyperemia and papillae of the upper tarsal plate; many clinicians have observed scarring of these papillae in longstanding conditions. In addition, inflammation is certainly a noted component of conditions such as AKC and VKC.12

to go through remissions and exacerbations, and the ocular symptoms can worsen at any point — winter, for example — but tend to increase in the presence of airborne allergens.13 This most commonly affects patients in their teens and early 20s, when T-cell activation is at its highest. The primary symptom of AKC is burning rather than itching. We most often associate allergic eye disease with symptoms of itching, and although it is the most common symptom of most ocular allergy conditions, this is one example where itching is usually a secondary complaint. One of the keys to diagnosing AKC is to inquire about a history of atopic dermatitis, such as eczema. This is most commonly located on the elbows and in the scalp. A hallmark sign of AKC is the presence of periorbital eczema, which can be observed on patient presentation. The conjunctivitis associated with AKC may be cicatrizing, leading to chronic scarring and hypertrophy. Cytokines derived from Th1 and Th2 cell types and

TYPES OF ALLERGIC EYE DISEASE There are four Type 1 hypersensitivity reactions or allergic eye disease forms. These include seasonal allergic conjunctivitis (SAC), AKC, VKC and GPC (Figs. 1-4). One other that may be a subset is PAC. Although all four forms have inflammation present, some such as AKC and VKC have such levels of inflammation that they can threaten one’s sight.12 AKC is a chronic and potentially severe form of allergic eye disease. It is a perennial condition that tends

Clinical & Refractive Optometry Quebec 1:1, 2016

inflammatory cells such as mast cells and eosinophils are the major mediators of the inflammatory response.12 Other signs include corneal findings such as superficial punctate keratitis and corneal infiltrates, which are once again indicators of an inflammatory process as leukotriene expression results in these types of corneal infiltrative responses.14 There is also a high association with keratoconus and anterior polar cataracts.15 Some experts surmise that keratoconus is secondary to eye rubbing.16 Patients with this form of severe ocular allergy must be treated aggressively. If conjunctivalization is present or vascularization is migrating into the cornea, the patient should be treated aggressively with corticosteroids. Corticosteroids are angiotensive and therefore can prevent further blood vessel growth.17 Medications such as loteprednol long term, as well as cyclosporine 0.05%, appear to be very effective and necessary in the treatment of this condition.4 Patients can also be placed on combination antihistamine medications, which has been shown to work exceptionally well in moderate to severe allergic conjunctivitis,18 and may also work well in this severe form of allergic eye disease. As mentioned, patients with AKC often manifest periorbital eczema and severe blepharitis that must also be treated. Treatment options include corticosteroid ointments such as triamcinolone 0.1% cream. Ophthalmic ointments may be safer should they accidentally penetrate the eye. Loteprednol is a very good treatment option because of the increased contact time, the fact that if it were to get into the eye it would not cause problems, and because it is preservative-free and atopic individuals often react to preservatives. In addition, because of the chronic nature of AKC, therapies are often required long term and preservatives such as benzalkonium chloride (BAK) may build up and exacerbate a reaction.19 In light of the significant inflammation involved in AKC, lid scrubs are contraindicated as they can cause further mechanical trauma. Another form of allergic eye disease is VKC. This typically affects young males between the ages of 7 and 21. It is also a condition that is much more prevalent in warmer climates. The hallmark of VKC is severe, incapacitating itch. One of the major signs is a ropey discharge and often a ptosis is present. Everting the eyelids will typically display giant papillae with significant hyperemia. The papillae are much greater than in other forms of allergic eye disease such as GPC, and are often described as having a cobblestone appearance. Another hallmark is Horner-Trantas Dots, which is an accumulation of eosinophils at the limbus. This is an extremely important area to observe in all children who suffer from allergies so that a diagnosis of VKC will not be missed in a patient who presents with SAC. If patients are not treated, they can often progress to develop shield ulcers.

This can be secondary to the trauma caused by the upper eyelid cobblestone papillae, but may also arise from proteins that are released by inflammatory mediators related to the pathophysiology of this severe disease.20 The mainstay of treatment for VKC is corticosteroids. Once again, because of the chronic nature of this condition, ester-based steroids are often a better therapy, although in the short term, ketone steroids can be utilized. Combination antihistamine agents should be prescribed to reduce the incapacitating itch. Like AKC, the severity of the itch lends itself to treatment with medications that are known for improving severe allergic itching, such as bepotastine 1.5%; the data reports improvement in severe itching.18 These patients also typically require the use of topical corticosteroids to control the severe inflammation and large papillae.21 Should a shield ulcer develop, the ideal treatment is cyclosporine 0.5% (RestasisÂŽ, Allergan, Markham, ON) which has been shown to effectively treat vernal shield ulcers.22 Patients should also be prophylactically treated with a topical antibiotic whenever the epithelium is compromised, as in shield ulcers. GPC is most commonly related to contact lens wearers, although it can also be caused by any form of long-term irritation or trauma, such as the presence of a loose suture in a penetrating keratoplasty patient or in patients with a prosthetic eye.23 These patients present with giant papillae on the upper tarsal conjunctiva and significant hyperemia. The most common symptoms are contact lens intolerance or decreased wearing time, as well as a clear, ropey mucus discharge. Patients may complain that their contact lens moves on the eye. In addition, slit lamp examination may reveal that a lens is riding high due to being captured by the giant papillae on the underside of the tarsal plate. Anecdotally, the incident of GPC appears to be increasing and may be related to the overuse of silicone hydrogel lenses. These patients appear to develop GPC much later in their contact lens wearing life and the presentation appears to be much more persistent. It can present sectorally at times, with or without hyperemia. The presence of hyperemia is critical to the aggressive treatment of GPC. Many patients, for example, who are aggressively treated with corticosteroids and the removal of contact lenses, have been able to successfully return to contact lens wear. However, examination of the upper tarsal plate six months to a year later often show persistent papillae, but no hyperemia; and the patients are asymptomatic. This condition is usually bilateral, unless it is secondary to a foreign body, ocular prosthesis, retinal buckle or loose suture. Everting the upper tarsal plate will easily help the practitioner arrive at a diagnosis, although it is much easier to recognize the papillae with the installation of sodium fluorescein dye.24 Milder forms of GPC can easily be missed by the clinician if they do not evert and stain the upper eyelids. If there is no hyperemia noted,

The Role of Inflammation in Allergic Eye Disease â&#x20AC;&#x201D; Karpecki

and the patient is asymptomatic, treatment may not be necessary and the patient should be monitored. Other options may be to decrease the wearing time, switch to a daily disposable contact lens, or opt for a hydrogel contact lens material. However, in symptomatic conditions, the ideal therapy would be contact lens removal for two weeks. During that time, loteprednol 0.5% can be prescribed four times a day for two weeks, and then b.i.d. when lens wear resumes at two to four weeks.25 Loteprednol has been the only steroid to date shown to be effective in the management of GPC.25-27 Patients should be instructed to apply the loteprednol 10 minutes prior to contact lens insertion and after removal, b.i.d. Long term one might consider combination allergy medications and, as mentioned, changing to daily disposable lenses, hydrogel lenses or even refractive surgery options. Although anecdotal reports of success with GPC with the use of loteprednol ointment have been exchanged at scientific meetings, clinical studies have yet to confirm its role in GPC. Proper compliance, such as adhering to contact lens wearing schedules and not exceeding two weeks with the same silicone hydrogel lens, are highly advisable. Compliance to proper lens hygiene is also critical and the use of a daily disposable lens may be a sound recommendation. The most common form of ocular allergies in the general population is SAC and PAC, accounting for 95% of all forms of allergic eye disease cases in North America.28 SAC is typically present, as the name dictates, during particular seasons such as spring and fall. It is most commonly due to high counts of pollens, grass, ragweed and molds. In the case of perennial allergies, which tend to be less severe but chronic, the typical causes are allergens that are always present such as dust mites, molds and animal dander. It is very important that in younger patients practitioners are aware of the high association between allergic conjunctivitis and asthma.29 Patients with perennial allergies tend to suffer year around and, of course, tend to be worse indoors. It is not uncommon, however, to have exacerbations when pollen counts are higher.30 One of the most common causes of PAC is dust mites, which are approximately 10 microns in size.31 Therefore, it is practically impossible to eliminate this allergen. In the case of SAC, the most common causes are ragweed, grass pollen, tree pollen and molds. The most typical presentation is a “glassy-eyed look” where patients present with hyperemia, chemosis, clear mucus, watery discharge, and often the presence of lid edema. This can be differentiated from other forms of conjunctivitis, such as bacterial conjunctivitis, which tends to manifest significant injection often described as “meaty” red. Bacterial conjunctivitis also has mucopurulent discharge and is less likely to present with lid edema, unless a preseptal cellulitis or keratitis is also present.

Clinical & Refractive Optometry Quebec 1:1, 2016

Viral conjunctivitis, which has a clear discharge, typically has lymphadenopathy associated with it, along with subepithelial infiltrates and significant follicles. Patients with viral or bacterial conjunctivitis typically have suffered from an upper respiratory infection recently or are aware of family members or friends who have had “pink eye.” Another diagnostic option to help in the differentiation is the adenodetector, which can help make a positive diagnosis for viral conjunctivitis. Although the hallmark symptom of allergic conjunctivitis is itching, other secondary symptoms include tearing, redness, burning, photophobia, foreign body sensation and blurred vision. It is also important to differentiate the symptom of itching in allergic conjunctivitis from that of eyelid conditions, such as blepharitis. The key, besides observing the eyelid margins, is to note where the patient describes the location of the itching. If it is the lid margin, this points to a diagnosis of blepharitis, if concurrent signs are present. The most common location for itching associated with allergic conjunctivitis is the ocular surface, including the canthal region. Treatment of the contact lens wearer who suffers from SAC or PAC begins first by treating the ocular disease. The Nichols Survey in Contact Lens Spectrum suggested that most doctors will first try switching contact lenses or solutions. Neither of these steps will significantly decrease the presence of histamine or any allergic immune mediators, nor get at the root of the patient’s contact lens intolerance. Most patients with mild to moderate allergic conjunctivitis can continue to remain in their contact lenses if they are effectively treated with topical allergy medications, especially those who can be prescribed on a bid or less frequent basis. We all know that most allergy patients tend to use allergy medications PRN even though they may be prescribed b.i.d. or q.d., and should be educated about using their drops prior to contact lens wear and following contact lens removal. Overnight contact lens wear should not be recommended as significant inflammatory markers are often present in patients who suffer from allergic conjunctivitis and corneal edema may develop.32 Patients who suffer from significant allergies may benefit from staying indoors during the peak allergy season, showering before bed, changing their bed sheets and pillows more often, and lowering the speed of the ceiling fan or turning it off so that it will not circulate allergens. Patients should also increase the use of rewetting drops or preservative-free artificial tears to help wash out allergens, and other palliative recommendations such as cool compresses are often found to be beneficial. Many patients treat ocular allergies by taking oral or topical antihistamines. Both of these are not recommended given the better prescription options available. The reason for this is that oral antihistamines have been shown to

cause significant ocular surface drying that may prevent irrigating the allergens present on the ocular surface.33 Likewise, topical vasoconstrictors and antihistamines, such as Naphcon-A® (naphazoline/pheniramine, Alcon, Mississauga, ON) or Visine-A® (pheniramine/naphazoline, Johnson & Johnson, Markham, ON) can result in rebound hyperemia.34 So what is the key in deciding which therapeutics to prescribe for SAC and PAC sufferers? The answer depends on signs and symptoms. If we look at the immediate response in cases of earlier acute allergic conjunctivitis, the primary immunological components include histamine, heparin, chymase and tryptase. Patients with mass cell degranulation that results in significant histamine and other mentioned mediators typically manifest significant symptoms of itching. The presence of chymase has been found to cause the mucin discharge so often present in allergic conjunctivitis. It appears that the most effective medications for symptoms of itching primarily focus around the combination antihistamine/mast cell stabilizer agents. These include Pataday® and Patanol® (olopatadine, Alcon, Mississauga, ON), as well as over-the-counter versions that include ketotifen-based drops like Zaditor® (ketotifen, Alcon, Mississauga, ON). However, patients whose signs, such as chemosis, lid edema and hyperemia, are present with symptoms, which is often the case in longer standing allergic conjunctivitis forms, will typically do better with the use of a topical corticosteroid such as Alrex® (loteprednol 0.2%, Bausch & Lomb, Vaughan, ON) or even Lotemax® (loteprednol 0.5%, Bausch & Lomb, Vaughan, ON). Although the allergic cascade is initiated by the release of histamine, synthesis takes place resulting in the formation of leukotrienes, prostaglandins, cytokines, and PAF. These are all inflammatory mediators and immunological cells that are expressed from the arachidonic acid pathway resulting in leukotrienes and prostaglandins, in particular. Corticosteroids are known to inhibit the arachidonic acid pathway, thus affecting every level of the inflammatory cascade. Because many seasonal and perennial allergy sufferers take oral antihistamine medications, clinicians should select topical medications that are less drying for patients who wear contact lenses. The ideal approach is combination allergy medications that are highly H-1 specific. If they are highly H-1 specific, they are less likely to affect the muscarinic receptors that can cause drying, or the serotonin receptors that can result in drowsiness and drying effects. The future allergy medication, bepotastine besilate 1.5%, is known to be highly H-1 specific.35 When significant signs are noted in the presence of allergic symptoms, the primary treatment is likely a corticosteroid. For SAC, drops such as loteprednol 0.2% have been shown to be effective, with safety results such as IOP

rise similar to that of placebo.36 In one study randomized between 0.2% loteprednol etabonate and vehicle, 0/66 patients in the steroid group had an IOP rise of 10 or more mmHg from baseline, with 0/67 in the vehicle group.37 Patients who have more severe allergies or longer duration allergies tend to have a greater presence of signs over symptoms.

QUALITY OF LIFE Because allergic conjunctivitis is so common to the optometric practice, it may seem less of a debilitating condition and yet patient quality of life surveys show that SAC has a significant effect on the ocular surface and on patients’ daily activities. Studies show that over 70% of patients are not able to comfortably go outdoors during allergy season and that they find that their allergy interferes with reading and productivity.38 Over 60% say that it affects their driving and 58% stated a decrease in the ability to concentrate on daily tasks.38 More than 50% of patients with allergic conjunctivitis mention it interfering with their sleep.39 In light of this, our aggressive treatment of allergic eye disease in all patients is extremely important to their quality of life.

SYSTEMIC INVOLVEMENT In our contact lens wearing patients who suffer from allergies and have significant systemic involvement, such as rhinitis, itchy palette or throat, cough, or sinus congestion, what recommendations should be made? The research around oral medications having significant drying effects on the ocular surface was previously discussed.33 It may be best to treat allergic conjunctivitis topically and hope that there is some systemic benefit as the drops drain through the lacrimal system. The one exception may be a patient who presents with allergic sinusitis. It is not uncommon to see this in an eye care practice as most patients describe the pain as periocular. In these cases, it is unlikely that topical medications will quickly suppress the pain that can be associated with sinus headaches. These patients may be better served by being prescribed an oral antihistamine/decongestant combination, such as Allegra-D® (fexofenadine and pseudoephedrine, Sanofi, St. Laurent, QC), Claritin-D® (loratadine and pseudoephedrine, Schering Plough, Kirkland, QC) or Zyrtec-D® (cetirizine and pseudoephedrine, Pfizer, Kirkland, QC). These are now available over-the-counter. Each contains pseudoephedrine as the decongestant and therefore avoidance in patients with hypertension is advisable.40 If systemic treatment is required, options for these patients include seeing an allergist or perhaps nasal sprays or steroid inhalers. Nasal sprays, such as azelastine (Astelin®, Meda Pharma, Somerset, NJ) are antihistamine-based and work well for many patients. Steroid and inhalers work well but still have risks that include IOP rise, conjunctivitis, potential for glaucoma and posterior subcapsular cataract formation.41,42

The Role of Inflammation in Allergic Eye Disease — Karpecki

Practitioners should educate patients with allergic eye diseases to avoid eye rubbing. Many patients feel that for a brief time they get some relief, but are actually mechanically degranulating the mast cells, which will result in much greater amounts of histamine, other allergic mediator release, inflammation, and likely greater signs and symptoms. Furthermore, they can cause problems in terms of the ocular surface, including the cornea. It might be a good recommendation to refrigerate the eye drops, which can cause a soothing effect, and may help patients become aware that the drops have been instilled in their eyes. It is also important to recommend environmental management tips such as to replace pillows at least every three to five years during perennial allergy season; obtain a latex pillow cover; reduce ceiling fan speed or turn it off during peak allergy seasons; wash bed sheets more often; shower before bed; and particularly, wash their hair more often, where allergens often accumulate. As far as when to discontinue contact lens use in patients who suffer from SAC, the answer really depends on observing the key signs upon eversion of the upper eyelid. If the upper eyelid shows significant papillae, and especially hyperemia, even in cases of SAC or PAC, it is possible that the trauma from the contact lens is contributing to the patient’s symptoms. If this is the case, a short-term hiatus of contact lens wear during aggressive treatment is recommended. However, if the upper tarsal plate shows no hyperemia or significant papillae, it is possible to begin treatment with topical medications before and after contact lens wear, as the lens is not likely contributing to the patient’s symptoms. The diagnosis of the various forms of Type 1 hypersensitivity allergic eye diseases can be challenging as inflammation is present among all forms. It is critically important that eye care clinicians be aggressive in the treatment of allergic eye disease as there are severe and even sight-threatening forms of the disease; and in milder forms, patients still comment on significant quality of life issues. Treatments range from palliative measures and patient education to topical corticosteroids and antihistamines and systemic allergy medications. With the increased prevalence of GPC, it is highly important that clinicians evert the upper eyelid on all of their patients and instill fluorescein dye to help in the assessment of GPC. Aggressive treatment may be warranted in light of the more recent forms of GPC. SAC is one of the most common diseases in North America and it is growing in prevalence secondary to unclean environments, longer warm seasons and less exposure to allergens at a young age so as to build up proper immunity.43 This condition will only continue to increase and play a key role in our clinical practice. Awareness of all of the keys to diagnosis, and aggressive management, are critical to maintaining successful patient responses. ❏

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REFERENCES 1. 2.

3. 4.

7. 8.

10. 11. 12. 13.

14.

15.

16.

17.

18.

19.

Bielory L. Update on ocular allergy treatment. Expert Opin Pharmacother 2002; 3(5): 541-553. Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol 2010; 126(4): 778-783.e6. Bielory L. Allergic conjunctivitis: the evolution of therapeutic options. Allergy Asthma Proc 2012; 33(2): 129-139. Mishra GP, Tamboli V, Jwala J, et al. Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. Recent Pat Inflamm Allergy Drug Discov 2011; 5(1): 26-36. Metz DP, Bacon AS, Holgate S, Lightman SL. Phenotypic characterization of T cells infiltrating the conjunctiva in chronic allergic eye disease. J Allergy Clin Immunol 1996; 98: 686-696. Amon M, Busin M. Loteprednol etabonate ophthalmic suspension 0.5%: efficacy and safety for postoperative antiinflammatory use. Int Ophthalmol 2012; 32(5): 507-517. Leonardi A. Pathophysiology of allergic conjunctivitis. Acta Ophthalmol Scand 1999; 228: 21-23. McGill JI, Holgate ST, Church MK, et al. Allergic eye disease mechanisms. Br J Ophthalmol 1998; 82(10): 1203-1214. Acera A, Rocha G, Vecino E, et al. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res 2008; 40(6): 315-321. Epub 2008 Aug 7. Heidemann DG, Dunn SP, Siegal MJ. Unusual causes of giant papillary conjunctivitis. Cornea 1993; 12(1): 78-80. Katelaris CH. Giant papillary conjunctivitis—a review. Acta Ophthalmol Scand Suppl 1999; 228: 17-20. Chigbu DI. The pathophysiology of ocular allergy: A review. Cont Lens Anterior Eye 2009; 32: 3-15; quiz 43-44. Nivenius E, Van der Ploeg I, Gafvenlin G, et al. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis. Clin Exp Allergy 2012; 42(1): 58-65. doi: 10.1111/j.1365-2222.2011.03858.x. Epub 2011 Sep 20. Hu Y, Matsumoto Y, Dogru M, et al. The differences of tear function and ocular surface findings in patients with atopic keratoconjunctivitis and vernal keratoconjunctivitis. Allergy 2007; 62(8): 917-925. Tuft SJ, Kemeny DM, Dart JK, et al. Clinical features of atopic keratoconjunctivitis Ophthalmology 1991; 98(2): 150-188. Jain V, Nair AG, Jain-Mhatre K, et al. Pellucid marginal corneal disease in a case of atopic keratoconjunctivitis. Ocul Immunol Inflamm 2010 ; 18(3): 187-189. Alzaga Fernandez AG, Demirci H, Darnley-Fisch DA, et al. Interstitial keratitis secondary to severe hidradenitis suppurativa: a case report and literature review. Cornea 2010; 29(10): 1189-1191. Abelson MB, Torkildsen GL, Williams JI. Time to onset and duration of action of the antihistamine bepotastine besilate ophthalmic solutions 1.0% and 1.5% in allergic conjunctivitis: a phase III, single-center, prospective, randomized, double-masked, placebo-controlled, conjunctival allergen challenge assessment in adults and children. Clin Ther 2009; 31(9): 1908-1921. Wijnmaalen AL, van Zuuren EJ, de Keizer RJ, et al. Cutaneous allergy testing in patients suspected of an allergic reaction to eye medications. Ophthalmic Res 2009; 41(4): 225-229. Epub 2009 May 15.

20. Singh S, Pal V, Dhull CS. Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis. Indian J Ophthalmol 2001; 49(4): 241-245. 21. Mantelli F, Santos MS, Petitti T. Systematic review and meta-analysis of randomized clinical trials on topical treatments for vernal keratoconjunctivitis. Br J Ophthalmol 2007; 91(12): 1656-1661. Epub 2007 Jun 22. 22. Cetinkaya A, Akova YA, Dursun D. Topical cyclosporine in the management of shield ulcers. Cornea 2004; 23(2): 194-200. 23. Bozkurt B, Akyurek N, Irkec M. Immunohistochemical findings in prosthesis-associated giant papillary conjunctivitis. Clin Experiment Ophthalmol 2007; 35(6): 535-540. 24. Doughty MJ, Potvin R. Pritchard N. Evaluation of the range of areas of the fluorescein staining patterns of the tarsal conjunctiva in man. Doc Ophthalmol 1995; 89(4): 355-371. 25. Howes JF. Loteprednol etabonate: a review of ophthalmic clinical studies. Pharmazie 2000; 55(3): 178-183. 26. Bartlett JD, Howes JF, Ghormely NR. Safety and efficacy of loteprednol etabonate for treatment of papillae in contact lens-associated giant papillary conjunctivitis. Curr Eye Res 1993; 12(4): 313-321. 27. Asbell P, Howes J. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. CLAO J 1997; 23(1): 31-36. 28. Butrus S, Portela R. Ocular allergy: diagnosis and treatment. Ophthalmol Clin North Am 2005; 18(4): 485-492. 29. Austin JB, Kaur B, Anderson HR. Hay fever, eczema, and wheeze: a nationwide UK study (ISAAC, international study of asthma and allergies in childhood). Arch Dis Child 1999; 81(3): 225-230. 30. Rowe MS, Bailey J, Ownby DR. Evaluation of the cause of nasal and ocular symptoms associated with lawn mowing. J Allergy Clin Immunol 1986; 77(5): 714-719. 31. Platts-Mills TA, Heymann PW, Longbottom JL, et al. Airborne allergens associated with asthma: particle sizes carrying dust mite and rat allergens measured with a cascade impactor. J Allergy Clin Immunol 1986; 77(6): 850-857.

32. Bucci FA Jr, Myers PJ, Evans RE. Clinical and overnight corneal swell comparison of the 1-Day Acuvue lens versus the Medalist, Surevue, Biomedics, and Acuvue lenses. CLAO J 1997; 23(2): 103-112. 33. Welch D, Ousler GW, Nally LA. Ocular drying associated with oral antihistamines (loratadine) in the normal population-an evaluation of exaggerated dose effect. Adv Exp Med Biol 2002; 506(Pt B): 1051-1055. 34. Bielory L, Lien KW, Bigelsen S. Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis. Drugs 2005; 65(2): 215-228. 35. Kida T, Fujii A, Sakai O. Bepotastine besilate, a highly selective histamine H-1 receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models. Exp Eye Res 2010; 91(1): 85-91. Epub 2010 Apr 20. 36. Illyas H, Slonim CB, Braswell GR. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye Contact Lens 2004; 30(1): 10-13. 37. Dell SJ, et al. J Allergy Clin Immun 1998; 102(2): 251-255. 38. Juniper EF. Rhinitis management: the patientâ&#x20AC;&#x2122;s perspective. Clin Exp Allergy 1998; 28(Suppl 6): 34-38. 39. Ellis AK, Day JH, Lundie MJ. Impact on quality of life during an allergen challenge research trial. Ann Allergy Asthma Immunol 1999; 83(1): 33-39. 40. Gordon RD, Ballantine DM, Bachmann AW. Effects of repeated doses of pseudoephedrine on blood pressure and plasma catecholamines in normal subjects and in patients with phaeochromocytoma. Clin Exp Pharmacol Physiol 1992; 19(5): 287-290. 41. Steroid inhalers and glaucoma. J Am Dent Assoc 1997; 128(5): 554, 558. 42. Bui CM, Chen H, Shyr Y, et al. Discontinuing nasal steroids might lower intraocular pressure in glaucoma J Allergy Clin Immunol 2005; 116(5): 1042-1047. Epub 2005 Oct 3. 43. Rook GA, Brunet LR. Give us this day our daily germs. Biologist (London) 2002; 49(4): 145-149.

The Role of Inflammation in Allergic Eye Disease â&#x20AC;&#x201D; Karpecki

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QUESTIONNAIRE The Role of Inflammation in Allergic Eye Disease Paul M. Karpecki, OD, FAAO 1. ❑ ❑ ❑ ❑

Which of the following is a potential complication of longstanding allergic eye disease? Conjunctival melts Conjunctivochalasis Conjunctival concretions Pinguecula

2. ❑ ❑ ❑ ❑

Which of the following is the most likely cause of GPC? Chronic seasonal allergic conjunctivitis Contact lens solutions A response to continuous trauma from various causes ranging from contact lenses to prosthetic eyes or sutures Mucin secretions

3. ❑ ❑ ❑ ❑

What is typically the primary symptom of atopic keratoconjunctivitis (AKC)? Burning Mucin discharge Headaches Itching as itching is the primary symptom in ALL allergic eye disease

Clinical & Refractive Optometry Quebec 1:1, 2016

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4. ❑ ❑ ❑ ❑

Which of the following is a hallmark sign of atopic keratoconjunctivitis (AKC)? Cobblestone papillae on the upper tarsal plate Limbal elevations of eosinophils Small papillae on the upper tarsal plate Periorbital eczema

5. ❑ ❑ ❑ ❑

What medication must be prescribed once an AKC patient starts to manifest signs of corneal neovascularization? Corticosteroids Antihistamines Mast cell stabilizers No medication can slow down neovascularization in AKC patients

6. ❑ ❑ ❑ ❑

One of the most effective treatments for a shield ulcer associated with VKC is: Cyclosporine 0.5% Antihistamines Mast cell stabilizers Triamcinolone cream 0.1%

7. ❑ ❑ ❑ ❑

Which of the following is TRUE about perennial allergic conjunctivitis? Symptoms are typically more severe than seasonal allergic conjunctivitis Children with perennial allergic conjunctivitis have a relatively high incidence of asthma It is most often caused by tree pollen It is often associated with large cobblestone papillae

8. ❑ ❑ ❑ ❑

A way that allergic conjunctivitis can be differentiated from bacterial conjunctivitis is by: Allergic conjunctivitis tends to show more injection than bacterial conjunctivitis Allergic conjunctivitis has a watery discharge whereas bacterial conjunctivitis has a mucopurulent discharge Allergic conjunctivitis tends to show less chemosis than bacterial conjunctivitis Allergic conjunctivitis often presents with a pre-auricular lymph adenopathy

9. ❑ ❑ ❑ ❑

Patients suffering from seasonal allergic conjunctivitis tend to manifest itching in which location? On the eyelid margins On the outside eyelid corners On the conjunctiva, particularly in the canthal region There is typically no itching in seasonal allergic conjunctivitis

10. ❑ ❑ ❑ ❑

Steroids should typically be prescribed in treating allergic eye disease when: Symptoms have not yet developed so as to prevent them? Signs are very apparent along with symptoms The patient has symptoms but no signs In all cases of allergic eye disease except vernal keratoconjunctivitis because it involves children

The Role of Inflammation in Allergic Eye Disease — Karpecki

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Treatment Options for Seasonal Allergic Conjunctivitis Michael L. Nordlund, MD, PhD

ABSTRACT Allergies affect more than 50 million Americans and may involve multiple organs, including the ears, nose, skin, and lungs.1,2 However, allergy sufferers report that ocular symptoms of allergic diseases such as seasonal allergic conjunctivitis (SAC) cause the greatest discomfort and contribute significantly to decreased quality of life and work productivity.2 Prevalence of allergic diseases is increasing and allergic eye disease is a leading cause of visits to internists, optometrists, and ophthalmologists.3 The number of prescriptions for ocular allergy medications has been on the rise and is projected to continue to increase at a rate of greater than 20% annually.2 To illustrate these treatment options, two Case Reports by Drs. Thomas and Melton have been included herein. The first involving a young man presenting with severe allergy distress of unknown origin. The second Case Report describes a middle-aged woman experiencing increasingly severe allergy symptoms.

INTRODUCTION Ocular allergic diseases include seasonal and perennial allergic conjunctivitis, giant papillary conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. Most allergic conjunctivitis cases are seasonal or intermittent and typically peak with increases in pollen levels during the spring and autumn. Seasonal

M.L. Nordlund — Ophthalmic Surgeon and Medical Director, Cincinnati Eye Institute, Cincinnati, OH Correspondence to: Dr. Michael L. Nordlund, Cincinnati Eye Institute, 1945 CEI Drive, Cincinnati, OH, 45242; E-mail: mnordlund@cincinnatieye.com Dr. Nordlund is a member of the advisory group for Bausch & Lomb and is on speakers’ bureaus for Bausch & Lomb, ISTA Pharmaceuticals, and Allergan, Inc. This article has been peer-reviewed.

Clinical & Refractive Optometry Quebec 1:1, 2016

allergy patients may experience a variety of symptoms, including mild to severe ocular itching, redness, swelling, foreign body sensation, tearing, and presence of a stringy, watery discharge.4 Although the conditions of allergic conjunctivitis and rhinitis often coexist, the ocular symptoms are often as or more severe than nasal symptoms. Half of patients with allergic conjunctivitis report that watering and red or itching eyes were moderately to extremely bothersome.5 SAC Pathophysiology The early phase of allergic conjunctivitis is a mast cell-mediated, self-limited inflammatory response that peaks within 20 minutes of allergen exposure. In sensitized individuals, allergen contact triggers mast cell degranulation and release of histamine prostaglandins, leukotrienes, and other preformed pro-inflammatory mediators.6,7 This immediate reaction to allergen exposure increases vasopermeability, vasodilation, and ocular itching, the hallmark symptom of SAC. Allergen-induced mast cell activation also initiates an inflammatory signal transduction cascade that ultimately results in recruitment and activation of other inflammatory cells, including eosinophils, basophils, neutrophils, and T cells. This influx of inflammatory cells into the conjunctiva constitutes the late phase of the allergic response, which is the dominant phase of a patient’s “allergy season.” The cytokines, chemokines, arachidonic acid metabolites, and thromboxanes produced during the late phase of the allergic response are responsible for the majority of long-term SAC symptoms, including ocular redness, swelling, pain, and itching. Because of the multi-factorial nature of the late-phase allergic response, a broadly acting anti-inflammatory agent such as a corticosteroid can be an important therapeutic tool that may help regain normal tissue homeostasis and temporarily relieve SAC signs and symptoms when they are refractive to other therapies, severe, or persistent. Diagnosis of SAC Seasonal allergic conjunctivitis can often be diagnosed by obtaining a complete and accurate patient history, and laboratory testing is not typically required. The hallmark symptom of SAC is ocular itching, without which the diagnosis cannot be ocular allergy.6 Patients will typically complain of recurrent and persistent episodes of itching,

Table I Topical ocular treatment options for seasonal allergic conjunctivitis4 Ocular Surface Lubricating Agents • Facilitate allergen removal and limit allergen exposure Topical Antihistamines* • Antagonists of the histamine receptor, block histamine action • Reduce histamine-induced signs and symptoms of SAC, such as itching Mast Cell Stabilizers • Prevent mast cell degranulation and release of inflammatory mediators • Decrease redness, hyperemia, itching, and ocular irritation NSAIDs • Inhibit activation of cyclooxygenases and prostaglandin production • Reduce itching Corticosteroids • Broad-spectrum anti-inflammatory activity • Inhibit activation of multiple types of inflammatory cells and production and cellular responses to pro-inflammatory mediators • Reduce most ocular signs and symptoms of SAC *May also stabilize mast cells.

tearing, and burning. Discharge in the form of stringy mucus and/or crusting of the eyelashes is also common. A classic presenting sign of allergic conjunctivitis is bilateral eyelid and conjunctival erythema and swelling.6,8 The eyes may also appear glassy due to a reduction in mucin levels at the ocular surface and patients can present with accompanying chemosis, which may be observed during a slit-lamp exam. The extent of the signs and symptoms usually correlates with the amount of allergen exposure and are exacerbated by eye rubbing, which mechanically causes mast cells to degranulate. In most cases, neither the cornea nor patient vision is affected.8 Differential diagnoses include dry eye, blepharitis, and infectious conjunctivitis. Itching is less common with infection and dry eye, and corneal changes such as staining and neovascularization are more common in dry eye, blepharitis, and with infection.

DISCUSSION Available Treatments for Symptoms of SAC Many SAC patients attempt to treat symptoms with home remedies such as the application of cold compresses or over-the-counter therapies such as chilled artificial tears and topical and/or oral antihistamines before consulting a clinician. While oral antihistamines can be effective, they are often better at alleviating nasal rather than ocular symptoms.4 Application of treatment directly to the eye is the most effective manner by which to manage SAC and has been shown to provide rapid symptom relief, as well as the benefits of added ocular hydration.9 Antihistamines, mast cell stabilizers, dual-action

antihistamine/mast cell stabilizers, nonsteroidal antiinflammatory drugs (NSAIDs), and steroids, including loteprednol etabonate (LE) suspension 0.2%, are all available in eye drop form, and have demonstrated efficacy in the temporary relief of SAC signs and symptoms (Table I). Antihistamines, mast cell stabilizers, NSAIDs, and steroids act by different mechanisms to affect the allergic inflammatory response.4 Antihistamines block the effects of released histamine through competitive inhibition of histamine receptors and work quickly to reduce itching. Mast cell stabilizers help to prevent degranulation of mast cells and thus are most effective when used prior to allergen exposure. Dual-mechanism agents offer the advantages of both immediate symptom relief and prolonged resistance to mast cell degranulation. NSAIDs block activation of cyclooxygenase and production of prostaglandins and can help to alleviate itching and pain associated with the late-phase allergic response. Palliative measures, over-the-counter remedies, prescription antihistamines, mast cell stabilizers, and NSAIDs are effective therapies for many patients. However, many patients with moderate to severe SAC experience persistent symptoms despite use of one or more of these therapies. Steroid-based therapies offer broad relief of allergy symptoms because they act to inhibit multiple components of both the early and late phase of the allergic response, including mast cell degranulation, production of proinflammatory mediators such as prostaglandins and leukotrienes, and activation and recruitment of inflammatory cells (Fig. 1).10 Steroids exert their actions through the glucocorticoid receptor, a transcription factor that controls expression of many genes involved in regulation of the inflammatory response and primarily act by modification of protein synthesis. Corticosteroids also inhibit inflammation by DNA-independent mechanisms involving interactions with cellular membranes.4 Topical corticosteroids have traditionally been reserved for the most severe or persistent cases of ocular allergy due to concerns about adverse events (AEs) such as elevations in intraocular pressure (IOP), glaucoma, and cataract formation, particularly with prolonged use.11 Loteprednol etabonate is derived from the corticosteroid prednisolone, but possesses a key structural modification. A single ketone group in the carbon-20 (C-20) position was replaced with an ester moiety, which makes the molecule susceptible to hydrolysis by endogenous esterases found in most eye tissues.4 Like all steroids, LE exerts its effects through activation of the glucocorticoid receptor. However, unbound LE is rapidly hydrolyzed into inactive metabolites, thus lowering active molecule levels. This has been shown to reduce the risk for elevated IOP, associated with prolonged steroid exposure.12

Treatment Options for Seasonal Allergic Conjunctivitis — Nordlund

Fig. 1 Mode of action of loteprednol etabonate 0.2%: Decreases the production of inflammatory proteins, stabilizes mast cell membranes, and suppresses inflammatory cell infiltration. GM-CSF=granulocyte-macrophage colony-stimulating factor; Ig=immunoglobulin; IL=interleukin; PAF=platelet-activating factor; VCAM=vascular cell adhesion molecule. (Adapted from Gelfand EW et al.10)

Loteprednol etabonate was developed specifically for ocular applications and was designed to minimize risks for AEs associated with corticosteroid use. Individual results and occurrence of AEs vary by patient. An ester-based corticosteroid, LE 0.2% is the only corticosteroid specifically developed, tested, and approved by the FDA and Health Canada for the treatment of SAC signs and symptoms.13 Clinical Studies with LE 0.2% The efficacy of LE ophthalmic suspension 0.2% was assessed in 2 separate randomized, double-masked vehicle-controlled clinical studies of patients presenting with signs and symptoms of SAC. In studies conducted by Dell and colleagues and Shulman and colleagues, participants with signs and symptoms of SAC were given either LE 0.2% or vehicle 4 times daily in both eyes for 42 days (n=133 and n=135, respectively).14,15 The primary sign evaluated in both studies was bulbar conjunctival injection, and the primary symptom was itching.14,15 Both trials demonstrate that LE 0.2% significantly relieved the severity of bulbar injection and itching compared to vehicle after 14 days of treatment. In the Dell trial, complete resolution of injection was observed in 31% of LE-treated vs 9% of vehicle-treated patients, and resolution of itching was observed in 54% of LE-treated

Clinical & Refractive Optometry Quebec 1:1, 2016

vs 38% of vehicle-treated patients by day 14.14 Similarly, more patients in the LE 0.2% treatment group experienced complete relief of signs and symptoms over the placebo group patients at day 14 (36% and 15%; 58% and 38%, for injection and itching vs vehicle, respectively) in the Shulman trial.15 Secondary endpoints, which included discomfort, foreign body sensation, burning, stinging, photophobia, palpebral conjunctival injection, chemosis, and erythema, were also shown to be reduced after 2 weeks of treatment in both studies.14,15 Clinical Safety Profile In the study by Shulman and colleagues, one patient in each treatment group experienced elevated IOP levels over the 6-week trial duration.15 However, LE 0.2% had a safety profile comparable to placebo in both the Dell and Shulman clinical trials.14,15 Novack and colleagues have shown the incidence of significant IOP elevations (â&#x2030;Ľ10 mm Hg) with the use of LE 0.2% was only 0.8%, with long-term (â&#x2030;Ľ28 days) treatment, which is comparable to the rate of the vehicle-treated group.16 Conversely, the incidence of significant IOP elevations was 6.7% for prednisolone acetate 1%. The favorable efficacy and safety profiles of LE makes it a viable option for moderate to severe SAC indications, in which long-term or repeated pulse therapy is often necessary.

CASE REPORTS Case 1 SAC symptoms alleviated by loteprednol etabonate ophthalmic suspension 0.2% by Randall Thomas, OD, MPH, FAAO and Ron Melton, OD FAAO

Fig. A Severe ocular redness triggered by an unknown allergen, and diagnosed as seasonal allergic conjunctivitis.

An 18-year-old man experienced severe allergy distress over a

period of 2 weeks, triggered by an unknown allergen.17 His eyes were unbearably itchy, red, and photophobic (Fig. A), preventing him from wearing soft contact lenses. He tried using overthe-counter oral and ocular antihistamines, but sought care from an eye doctor when neither provided complete symptom relief. A slit-lamp examination determined that while his corneas were clear and non-staining, he had conjunctival injection and stringy, excess mucus in the tear film. He was diagnosed as having

seasonal allergic conjunctivitis and began using Alrex® (loteprednol etabonate ophthalmic suspension 0.2%, Bausch & Lomb, Vaughan, ON). At his follow-up exam, he reported that after 4 days of treatment with loteprednol etabonate ophthalmic suspension 0.2%, eye itching had ceased, his other ocular symptoms had dramatically improved, and he was again able to wear contacts. After 1 week of loteprednol etabonate ophthalmic suspension 0.2% administration, his ocular allergy symptoms were relieved.

Case 2 Severe SAC symptoms unimproved with antihistamines but relieved by loteprednol etabonate ophthalmic suspension 0.2% by Randall Thomas, OD, MPH, FAAO and Ron Melton, OD FAAO

Fig. B Increasingly severe itchiness and puffiness in the left eye, subsequently diagnosed as seasonal allergic conjunctivitis.

A middle-aged woman was experiencing moderate ocular itching over several months, which became increasingly severe.18 Her left eye was itchy, puffy, watery, and mildly photophobic (Fig. B). Her right eye was also very itchy and watery. She tried over-the-counter eye drops with a topical antihistamine but her symptoms persisted. The slit-lamp eye examination performed by her

CONCLUSION Seasonal allergic conjunctivitis is a common disorder with a significant impact on patient quality of life. Modern antihistamines, mast cell stabilizers, NSAIDs, and steroids are effective in managing ocular allergy symptoms for many patients. For patients who experience incomplete relief of moderate to severe or persistent SAC signs and symptoms, LE 0.2% can offer the powerful anti-inflammatory activity of steroids and has shown a

doctor revealed she had a zone of sectorial chemosis. Her cornea was clear and nonstaining. The patient was diagnosed as having seasonal allergic conjunctivitis. Her optometrist prescribed loteprednol etabonate ophthalmic suspension 0.2% dosed at 1 drop 4 times per day. At her follow-up exam 4 days later, the patient’s ocular symptoms had cleared.

low incidence of increased IOP. Loteprednol etabonate 0.2% inhibits multiple aspects of the inflammatory response to suppress a broad range of SAC signs and symptoms, including ocular itching, redness, burning/stinging, discomfort, tearing, photophobia, foreign body sensation, discharge, chemosis, and erythema. Eye care professionals can consider LE 0.2% a viable option for treating the signs and symptoms associated with SAC.

Treatment Options for Seasonal Allergic Conjunctivitis — Nordlund

REFERENCES 1.

Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol 2010; 126(4): 778-783.e6. 2. Bielory L. Update on ocular allergy treatment. Exp Opin Pharmacother 2002; 3(5): 541-553. 3. Bielory L, Katelaris CH, Lightman S, Naclerio RM. Treating the ocular component of allergic rhinoconjunctivitis and related eye disorders. MedGenMed 2007; 9(3):35. 4. Bielory BP, Oâ&#x20AC;&#x2122;Brien TP, Bielory L. Management of seasonal allergic conjunctivitis: guide to therapy. Acta Ophthalmologica 2011. 5. Rosario N, Bielory L. Epidemiology of allergic conjunctivitis. Curr Opin Allergy Clin Immunol 2011; 11(5): 471-476. 6. Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 2005; 115(1): 118-122. 7. Slonim CB, Boone R. The ocular allergic response: a pharmacotherapeutic review. Formulary 2004; 39: 213-222. 8. Ilyas H, Slonim CB, Braswell GR, Favetta JR, Schulman M. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye & Contact Lens 2004; 30(1): 10-13. 9. del Cuvillo A, Sastre J, Montoro J, et al. Allergic conjunctivitis and H1 antihistamines. J Invest Allergol Clin Immunol 2009; 19(suppl 1): 11-18. 10. Gelfand EW, Appajosyula S, Meeves S. Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research. Curr Med Res Opin 2004; 20(1): 73-81.

Clinical & Refractive Optometry Quebec 1:1, 2016

11. Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol 2008; 92(4): 455-459. 12. Manabe S, Bucala R, Cerami A. Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts. J Clin Invest 1984; 74(5): 1803-1810. 13. Bodor N, Buchwald P. Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and chemical delivery systems. AAPS J 2005; 7(4): E820-833. 14. Dell SJ, Lowry GM, Northcutt JA, Howes J, Novack GD, Hart K. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol 1998; 102(2): 251-255. 15. Shulman DG, Lothringer LL, Rubin JM, et al. A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis. Ophthalmology 1999; 106(2): 362-369. 16. Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma 1998; 7(4): 266-269. 17. Thomas R, Melton R. SAC symptoms alleviated by loteprednol etabonate ophthalmic suspension 0.2%. Bausch & Lomb, Data on file. 18. Thomas R, Melton R. Severe SAC symptoms unimproved with antihistamines but relieved by loteprednol etabonate ophthalmic suspension 0.2%. Bausch & Lomb, Data on file.

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QUESTIONNAIRE Treatment Options for Seasonal Allergic Conjunctivitis Michael L. Nordlund, MD, PhD 1. ❑ ❑ ❑ ❑

All of the following statements about seasonal allergic conjunctivitis (SAC) are true, EXCEPT: Most cases peak during the spring and autumn The majority of patients are in their fifties 50% of patients report watering and red or itches eye s as being moderately to extremely bothersome Most cases are seasonal or intermittent

2. ❑ ❑ ❑ ❑

The patient in Case 1 presented with all of the following signs and symptoms, EXCEPT: Extreme ocular redness Photophobia Foreign body sensation Extreme ocular itching

3. ❑ ❑ ❑ ❑

Symptoms of SAC include all of the following, EXCEPT: Ocular itching Foreign body sensation Tearing Difficulty blinking

Treatment Options for Seasonal Allergic Conjunctivitis — Nordlund

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4. ❑ ❑ ❑ ❑

All of the following statements describe the patient in Case 2, EXCEPT: Her symptoms included left eye itchiness and mild photophobia Slit-lamp examination revealed a zone of sectorial chemosis After a two-week trial, topical antihistamines were unsuccessful in providing relief Her left-eye cornea was clear and non-staining

5. ❑ ❑ ❑ ❑

In which phase of the allergic response do most long-term SAC symptoms appear? Early Late Middle Varies from case to case

6. ❑ ❑ ❑ ❑

Which of the following is the hallmark symptom which defines SAC? Ocular swelling Ocular discharge Ocular itching Ocular burning

7. ❑ ❑ ❑ ❑

Differential diagnoses for SAC include of the following, EXCEPT: Sjögren’s syndrome Blepharitis Infectious conjunctivitis Dry eye

8. ❑ ❑ ❑ ❑

All of the following statements about loteprednol etabonate are true, EXCEPT: It minimizes the risk of adverse events typically associated with corticosteroids It was less effective than vehicle in relieving secondary endpoints It has been shown to reduce the risk for elevated IOP Studies have demonstrated its efficacy after 14 days of treatment

9. ❑ ❑ ❑ ❑

Which of the following has broad-spectrum anti-inflammatory activity? Topical antihistamines Mast cell stabilizers NSAIDs Corticosteroids

10. ❑ ❑ ❑ ❑

All of the following statements about the prevalence of SAC are true, EXCEPT: It is stable It is increasing It is increasing most notably in the elderly It is decreasing

Clinical & Refractive Optometry Quebec 1:1, 2016

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The Role of Ointments in Clinical Practice Paul M. Karpecki, OD, FAAO

INTRODUCTION Ophthalmic ointments have a long history dating back to ancient times and yet are still evolving with recent approvals involving technologies that allow the medication to be preservative-free. The understanding of the use, positive characteristics and side effects has also evolved to better help us position these products to most assist our patients with ocular diseases. New products of the future, may further change how ophthalmic ointments are utilized and help in treating some of the most common as well as most severe ocular pathologies we face.

THE HISTORY OF OPHTHALMIC OINTMENTS In Egypt in 1500 BC, the first notations of something that might resemble an ophthalmic ointment was noted. A thick eye paste consisting of antimony or the soot from incense and oil applied to the brow and lid margins was used to protect the eye from sun glare and infections.1 Castor seeds or ricinus communis, were found in Egyptian tombs dating back to 4000 BC so ointments could have gone back even further, but there is no specific evidence the oils were used for the eye. They were likely also used in India since they are indigenous to that location. Even natural made ointments (from plants for example) were documented in Egypt in ancient times. Collyrium, which means eyewash, is found in Hippocratic books dating back about 2000 years. Romans specifically documented the term collyriums that involved the use of eye salves,

P. M. Karpecki — Cornea Services and Clinical Research Director, Koffler Vision Group, Lexington, Kentucky Correspondence to: Dr. Paul M. Karpecki, Koffler Vision Group, 120 N. Eagle Creek Drive, Suite 431, Lexington, KY 40509; E-mail: paul@karpecki.com Dr. Karpecki is a consultant to Bausch & Lomb, Allergan, Alcon, AMO, OcuSoft, Shire, Akorn, Focus Laboratories. This article has been peer-reviewed.

pastes and ointments from 31 BC to 312 AD.1 Although they may have used the word collyrium to refer to the vehicles that held the ointments that today may be considered the bottle or droppers. Petroleum jelly, the precursor to most ointments used today, was first patented in 1872 (U.S. Patent 127,568). But it was not until the early 1900’s that tear substitutes like sodium chloride were introduced to make eye ointments and drops more similar to our natural tears.2 And in the 1930’s viscosity agents like gelatin and methylcellulose were introduced.2 Today, ophthalmic ointments are a mainstay and a key vehicle for the management of various ocular conditions.

ADVANTAGES AND DISADVANTAGES OF OINTMENTS Benefits of ointments include an increased contact time and the potential to provide an added barrier or protection to the ocular surface. Increased contact time allows for the drug to reside longer in the vehicle and be available for absorption.3 Studies have shown a higher concentration of fluoromethalone in the anterior chamber when an ointment vehicle is used compared to that of the same drug in a suspension.4 Another advantage is that ointments are easier for patients to apply compared to instilling drops. In one particular study involving post-cataract surgery patients not only was patient satisfaction higher with a ‘bandage ointment’ (meaning a thick ointment coverage of the eye) over drops, but patients described significantly less postoperative pain and discomfort — especially in the first 10 hours after the procedure.5 Studies have also found ophthalmic ointments to be as good or superior to pressure patching when comfort and healing was measured in patients with traumatic corneal abrasions.6 In one particular study comparing relatively similar abrasion sizes, the group receiving ophthalmic ointments had significantly less pain and faster epithelial healing than the pressure patched group at all time points measured.7 Disadvantages of ointments include blurred vision and tear film instability. In a study involving the use of day time artificial tears for dry eye sufferers, patients using artificial tear ointments had a much lower level of

The Role of Ointments in Clinical Practice — Karpecki

Fig. 1 Exposure keratopathy in a 52-year-old patient with an incomplete blink secondary to Bellâ&#x20AC;&#x2122;s palsy.

Fig. 2 A patient with significant scarring secondary to longstanding nocturnal lagophthalmos being treated with ointments overnight.

compliance than those using artificial tears in the drop formulation.8 This is likely due to blurring of vision that may occur with more viscous ointments.9 For that reason many clinicians recommend artificial tear ointments at night in less severe ocular surface disease conditions. That provides greater coverage during sleep and may serve a protective role in patients with lagophthalmos.10 Patients may report that ointments can be messy if too much is applied and may get on their pillows or in their hair, so appropriate instructions as to the proper amount of ointment to be applied is imperative. Patients should apply the ointment into the lower fornix not overfill the fornix. Typically about a 1/4 inch strip or one line of ointment from the dispenser is recommended into the lower fornix and sometimes a 1/2 inch strip for more significant ocular diseases. Also the use of ophthalmic ointments will not work well in patients wearing contact lenses such as with a bandage lens as it may coat the lens or dislodge it.11 Ointments, because of the increased contact time, could result in an allergic or toxic reaction, especially for those preserved with benzalkonium chloride when used longterm.12 And long-term use of steroid ointments can lead to thinning of the epidermis of the skin tissue.13 Finally ointments should not be injected into the anterior segment after a surgical procedure for example, as the vehicle may result in toxic anterior segment syndrome.14 As an example, ophthalmic ointments can cover or protect the cornea in cases of exposure keratopathy/ lagophthalmos, trauma, infection, eyelid tumors, incomplete blink or a whole host of other contributing conditions (Fig. 1).15,16 Ointments have been particularly effective for patients suffering from nocturnal lagophthalmos because of their residence time in protecting the inferior cornea during sleep (Fig. 2).15

Ophthalmic ointments are routinely used after various surgical procedures,17 and in neonatal applications.18 The most common surgical procedure that involve ophthalmic ointments are typically those performed by oculoplastic surgeons, such as a blepharoplasty. The ointments, which are more typically antibiotic ointments like erythromycin, but may include OTC ointments like lacrilube, help in lubricating the skin tissues and may decrease the irritation and dryness surrounding the incisions. The antibiotic ointments of course serve a prophylactic role in preventing an infection. Neonatal applications of ophthalmic ointments date back to a need that was discovered in the late 1800s. Although antibiotics were not invented until the mid1900â&#x20AC;&#x2122;s, the incidence of ophthalmic neonatorum (ON) was about 10% at that time resulting in corneal damage to 20% of those infected and blindness to 3%.19 The cause of ON was found to be the bacteria, nisseria gonorrhea. At that time silver nitrate 2% was introduced to prevent ON and turned out to be effective against gonorrhea resulting in a significant decrease in the incidence of ON.19,20 Topical tetracycline ointment was also used extensively in other parts of the world with good efficacy.20 However currently Chlamydia is the most common cause of ON and was resistant to silver nitrate. With the invention of antibiotics in the mid 1900â&#x20AC;&#x2122;s, erythryomycin ointment became the traditional method of prophylaxis at birth. It had advantages in that it prevented ON from chlamydia and was not as toxic or uncomfortable as silver nitrate.21 It is still used today on almost every birth in Canada and the US. Perhaps one of the most common uses of ophthalmic ointment is for lid diseases such as blepharitis.22 Blepharitis can be divided into anterior and posterior forms. Although ophthalmic ointments may work for both

Clinical & Refractive Optometry Quebec 1:1, 2016

Fig. 3 Anterior Staphylococcal blepharitis.

Fig. 4 Demodex blepharitis.

forms, it can also cause blurring of vision if used in the eye such as for posterior blepharitis or meibomian gland dysfunction (MGD). Thus for anterior blepharitis, it holds numerous advantages including effectiveness, contact time and benefits against multiple forms of the disease. The most common cause of blepharitis is from staphylococcus (Fig. 3) and many ointments including bacitracin, tobramycin and erythromycin are effective against gram positive pathogens. Although clinicians should be cognizant of multi-resistant staphylococcus such as MRSA/MRSE as an occasional culprit and thus culturing non-responsive cases may be prudent.23 In these cases none of the aforementioned antibiotics would likely treat the condition.24 Compounded vancomycin or polytrim or other medications known to be effective against MRSA and MRSE would be required. One particular study in 2007 showed that of 915 ocular disease cases involving Staphylococcus aureus isolates, that 88 were MRSA. Of this group the most common ocular condition was blepharoconjunctivitis with 78% of the group that had MRSA, manifesting this ocular condition involving blepharitis.25 Also combination agents such as tobramycin dexamethasone ointment have been shown to be effective in blepharitis.26 In one study on 148 patients randomized to tobramycin dexamethasone ointment versus placebo, the group actively treated had a statistically significant improvement in both signs and symptoms even though both groups used warm compresses, mechanical washing of the eyelids and artificial tears. However it is important to note that the group treated with tobramycin dexamethasone had a significant elevation in IOP was 3.7% compared to 1.5% in the placebo group.26 Patients known to have significant demodex (Fig. 4) have a very high association with blepharitis.27 Although this condition often requires tea tree oil to achieve an effective cure,

there is some thought that ointment can play a secondary role in suffocation of the nits associated with the disease. Likewise although even more rare, pediculosis caused by pubic lice on the eyelashes requires a bland ointment to assist in suffocating the eggs that are present.28 Other areas of application may include allergic eye diseases including giant papillary conjunctivitis,29 vernal keratoconjunctivitis,30 atopic keratoconjunctivitis,31 and even more severe forms of seasonal allergic conjunctivitis.32 Finally corneal conditions (Fig. 5) are a major area of treatment given the contact time and protection of ointments. Conditions where ointments have been shown to be effective include filamentary keratitis,33 keratoconjunctivitis sicca,34 corneal staining and corneal abrasions.35

MOST COMMON USES OF OPHTHALMIC OINTMENTS AND POTENTIAL APPLICATIONS One of the most common applications for ophthalmic ointments is that of blepharitis, although new understanding and research in the field of lid margin disease is now changing our treatment paradigms. For acute cases of blepharitis, often presenting as blepharoconjunctivitis, a pure antibiotic ointment is often sufficient to treat most bacterial pathogens. Variance of this include angular blepharitis and once again were effectively treated with an antibiotic ointment. Combination ointments were primarily used in conditions that involved both an infectious process combined with inflammation. This was often prescribed for conditions such as anterior blepharitis. But overuse and greater contact times could lead to bacterial resistance.36 As new understanding has developed in the role of meibomian gland dysfunction or posterior blepharitis and the role of inflammation, a shift to steroid only â&#x20AC;&#x201D; monotherapy ointments is occurring. For example,

The Role of Ointments in Clinical Practice â&#x20AC;&#x201D; Karpecki

Fig. 5 Severe exposure keratopathy resulting in epithelial erosion.

Fig. 6 Peripheral synechia in a patient with anterior uveitis secondary to Crohnâ&#x20AC;&#x2122;s Disease.

patients with morning symptoms and a diagnosis of MGD tend to find their symptoms improve significantly with an overnight steroid ointment. Other novel application include the use of steroid ointments for the treatment of noninfectious anterior uveitis. In the past, steroid drops were primarily used aggressively, with dosing of Q2H or Q1H being typical, but then no treatment was administered overnight. The corollary to anterior uveitis on the infectious side would be a keratitis/corneal ulcer. As clinicians we always consider overnight drops or ointments in the management of a bacterial ulcer. Likewise it makes sense to apply an ointment overnight combined with steroid drops Q1H or Q2H during the day in the management of anterior uveitis. Since incorporating this into my clinic, which has a large uveitis population, I have seen a dramatic improvement in the resolutions of anterior chamber cell and flare as well as breaking of synechiae over the last 3 to 4 years (Fig. 6). Future study is warranted but the improved treatment results of the addition of a steroid ointment are unmistakable.

treated patients than vehicle treated patients had complete resolution of ACI and zero pain at day 8 (p<0.0001 for both). Fewer Lotemax patients had ocular adverse events (p<0.0001) and fewer required rescue medications compared to the placebo group. The most common adverse events included anterior chamber inflammation, photophobia, corneal edema, conjunctival hyperemia, eye pain and iritis. Four patients had an increase in IOP more than 10 mmHg of which three of the patients were in the LE-ointment group and one was in the placebo group. Perhaps the reason for such a low IOP rise in over 400 patients may be due to the fact that loteprednol is an ester based steroid. Ester-based steroids (loteprednol) unlike ketone-based steroids (prednisolone, fluoromethalone, dexamethasone), can have their metabolites broken down by the naturally occurring esterases.37 I think this is established because these metabolites do not remain, they are less likely to reach receptors that could result in increased intraocular pressure or be likely to create a Schiff base that could result in posterior sub capsular cataract development.38 Studies comparing ester based steroids to ketone based steroids showed half the incidence of significant IOL elevation.39 Another study comparing healthy adults showed a 7.48% incidence of IOP rise greater than 10 mmHg for patients on dexamethasone, compared to 1.95% for patients on loteprednol, but yet the efficacy of each drug in controlling inflammation was found to be the same.40 A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. LE-ointment has also shown a very favorable safety profile consistent with previous studies on loteprednol suspension. It has

NEW DEVELOPMENTS IN OPHTHALMIC OINTMENTS Just recently LotemaxÂŽ ointment (Bausch + Lomb, Vaughan, ON) was approved in Canada, which is the first new ophthalmic ointment approved in over a decade. Safety and efficacy was conducted comparing loteprednol etabonate ophthalmic ointment 0.5% (LE ointment) to the vehicle for the treatment of inflammation and pain following cataract surgery in 805 patients. Efficacy outcomes included the proportion of patients with complete resolution of anterior chamber inflammation and the proportion of patients with no (grade 0) pain at postoperative day 8. Safety outcomes looked at adverse events, ocular symptoms, intraocular pressure changes and visual acuity (VA). Significantly more LE ointment

Clinical & Refractive Optometry Quebec 1:1, 2016

Table I Ocular conditions and their recommended treatment agents Acute blepharoconjunctivits: Antibiotic ung applied to eyelid and eyelashes QHS or BID for 10-14 days. Chronic blepharitis: Antibiotic/steroid combination ointment applied to eyelid/eyelash area QHS or BID x 10-14 days, if further treatment is required for inflammation, consider a steroid ung QHS. Nocturnal lagophthalmos: Bland ointment QHS (Ocunox as an effective preservative-free example) with or without eyelid taping indefinitely. Anterior non-infectious uveitis: Prednisolone Forte Q1H or Q2H during the day + cycloplegia + overnight steroid ointment (Lotemax ung preferred) QHS. Taper slowly as improvement in anterior chamber cell and flare or breaking of synechiae occurs. Severe MGD/meibomitis: Commercial warm compress QD x 10 minutes, lid hygiene QD, combination drops BID and steroid ung QHS x 10-14 days then taper steroid options and maintain warm compresses and lid hygiene + artificial tears.

been shown to be effective and well tolerated by patients for the treatment of ocular inflammation following cataract surgery.41

phosphorous-free which can be especially important in post-traumatic cases such as post-surgical dry eye where calcium has been shown sometimes be released. Insoluble crystals can be formed due to the reaction of phosphorous with calcium and may impair your vision. This can also be applied to the eyelid margins if conditions such as seborrheic blepharitis where dry or chaffing skin is present.

CONCLUSION Although it is critically important for eye care practitioners to be aware of the various therapeutic agents available to them, it is also equally important to understand the vehicle that the drug resides in (Table I). It is important to have a protocol for knowing when to use drops versus ointments depending on the condition and how to best educate patients. Being aware of new ointments, understanding their advantages and disadvantages, can assist in making good clinical decisions. â??

REFERENCES 1. 2.

PRESERVATIVE-FREE INNOVATIONS Lotemax ointment is noted as being preservative-free even though it is not in a unit dose vial. This is possible because non-aqueous formulations cannot support microbial growth. A certain level of water, based on a ratio of vapor pressure of water in product to vapor pressure of pure water at the same temperature (known as aw) must be present for microorganisms to grow.25 Lotemax ointment does not reach that ratio. Microorganisms have been categorized with respect to their capacity to grow and produce metabolites in various conditions based on the aw ratio.25 Bausch + Lomb also conducted its own safety study were several lots of lotemax ointment were inoculated with various microorganisms including staphylococcus aureus, pseudomonas aeruginosa, e-coli, fusarium solani, serratia marcescens, stenotrophomonas maltophilia and bipolaris australiensis.42 The units were stared at 20-25 C and samples were tested at 7, 14 and 28 days post-inoculation by plating serial dilutions of sample aliquots on appropriate growth media and counting colony forming units (CFUs) following incubation. Results showed that growth of the microorganisms was not supported in any of the Lotemax ointment lots tested during all three time periods.26 Another innovation in preservative-free ointments is that of OcunoxTM (CandorVision, Montreal, QC). This product is meant for dry eye disease management as an overnight treatment. The formulation contains retinol palmitate or vitamin A, a natural component of tears that allows for better integration with a patients existing tear film. It also comes in a tube, not a vial, and was also created preservative-free. Furthermore, the formulation is

3. 4. 5.

6. 7. 8. 9. 10. 11.

12. 13.

Hirschberg, J. (1982). The History of Ophthalmology, Vol. 1: Antiquity. Bonn: Verlag J. P. Wayenborgh Caffery B. The history of dry eye diagnosis and management. Contact Lens Spectrum. January 1, 2000. Available at: http://www.clspectrum.com/printarticle.aspx?articleID= 11752. Accessed January 3, 2015 Scruggs J, Wallace T, Hanna C. et al. Route of absorption of drug and ointment after application to the eye. Ann Ophthalmol 1978; 10(3): 267-271. Sieg JW, Robinson JR. Vehicle effects on ocular drug bioavailability i: evaluation of fluorometholone. J Pharm Sci 1975; 64(6): 931-936. Sipos E1, Stifter E, Menapace R. Patient satisfaction and postoperative pain with different postoperative therapy regimens after standardized cataract surgery: a randomized intraindividual comparison. Int Ophthalmol 2011; 31(6): 453-460. Menghini M, Knecht PB, Kaufmann C. Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study. Ophthalmic Res 2013; 50(1): 13-18. Le Sage N, Verreault R, Rochette L. Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical trial. Ann Emerg Med 2001; 38(2): 129-134. Swanson M. Compliance with and typical usage of artificial tears in dry eye conditions. J Am Optom Assoc 1998; 69(10): 649-655. Hiraoka T, Yamamoto T, Okamoto F et al. Tie course of changes in ocular wavefront aberration after administration of eye ointment. Eye 2012; 26(10): 1310-1317. Pereira MV, Gloria AL. Lagophthalmos. Semin Ophthalmol 2010; 25(3): 72-78. Donnenfeld ED1, Selkin BA, Perry HD et al. Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti-inflammatory drug in treating traumatic corneal abrasions. Ophthalmology 1995; 102(6): 979-984. Tu EY. Balancing antimicrobial efficacy and toxicity of currently available topical ophthalmic preservatives. Saudi J Ophthalmol 2014; 28(3): 182-187. Shlivko IL, Kamensky VA, Donchenko EV, Agrba P. Morphological changes in skin of different phototypes under the action of topical corticosteroid therapy and tacrolimus. Skin Res Technol 2014; 20(2): 136-140.

The Role of Ointments in Clinical Practice â&#x20AC;&#x201D; Karpecki

14. Werner L, Sher JH, Taylor JR et al. Toxic anterior segment syndrome and possible association with ointment in the anterior chamber following cataract surgery. J Cataract Refract Surg 2006; 32(2): 227-235. 15. Katz J, Kaufman HE. Corneal exposure during sleep (nocturnal lagophthalmos). Arch Ophthalmol 1977; 95(3): 449-453. 16. Smith MF, Goode RL. Eye protection in the paralyzed face. Laryngoscope 1979; 89(3): 435-442. 17. Trussler AP, Rohrich RJ. Blepharoplasty. Plast Reconstr Surg. MOC-PSSM CME article: 2008; 121(1 Suppl): 1-10. 18. Faucher MA, Jackson G. Pharmaceutical preparations. A review of drugs commonly used during the neonatal period. J Nurse Midwifery 1992; 37(2 Suppl): 74S-86S. 19. Klauss V, Schwartz EC. Other conditions of the outer eye. In: Johnson GJ, Minassian DC, Weale R, eds. The epidemiology of eye disease. London, Chapman & Hall, 1998. 20. Laga M, Meheus A, Piot P. Epidemiology and control of gonococcal ophthalmia neonatorum. Bull World Health Organ 1989; 67(5): 471-477. 21. Darling EK, McDonald H. A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and chlamydial ophthalmia neonatorum. J Midwifery Womens Health 2010; 55(4): 319-327. 22. Remitz A, Virtanen HM, Reitamo S, Kari O. Tacrolimus ointment in atopic blepharoconjunctivitis does not seem to elevate intraocular pressure. Acta Ophthalmol 2010. Jan 8 23. Khan JA, Hoover D, Ide CH. Methicillin-resistant Staphylococcus epidermidis blepharitis. Am J Ophthalmol 1984; 98(5): 562-565. 24. Kejela T1, Bacha K. Prevalence and antibiotic susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) among primary school children and prisoners in Jimma Town, Southwest Ethiopia. Ann Clin Microbiol Antimicrob 2013; 12: 11. 25. Freidlin JL, Acharya N, Lietman TM. et al. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol 2007; 144(2): 313-315. 26. Yan XM1, Sun XG, Xie et al. Effects of tobramycin dexamethasone eye ointment for blepharitis: multi-center clinical trial. Zhonghua Yan Ke Za Zhi. 2013; 49(1): 16-21. 27. Zhao YE1, Wu LP, Hu L. Association of blepharitis with Demodex: a meta-analysis. Ophthalmic Epidemiol 2012; 19(2): 95-102.

Clinical & Refractive Optometry Quebec 1:1, 2016

28. Couch JM, Green WR, Hirst LW, de la Cruz ZC. Diagnosing and treating Phthirus pubis palpebrarum. Surv Ophthalmol 1982; 26(4): 219-225. 29. Kymionis GD, Goldman D, Ide T et al. Tacrolimus ointment 0.03% in the eye for treatment of giant papillary conjunctivitis. 30. Vichyanond P, tantimongkolsuk C, Dumrongkigchaiporn P. Vernal keratoconjunctivitis: Result of a novel therapy with 0.1% topical ophthalmic FK-506 ointment. J Allergy Clin Immunol 2004; 113(2): 355-358. 31. Nivenius E, van der Ploeg I, Jung K et al. Tacrolimus ointment vs steroid ointment for eyelid dermatitis in patients with atopic keratoconjunctivitis. Eye (Lond) 2007; 21(7): 968-975. Epub 2006 May 5. 32. Kari O, Saari KM. Updates in the treatment of ocular allergies. J Asthma Allergy 2010; 24; 3: 149-158. 33. Diller R, Sant S. A case report and review of filamentary keratitis. Optometry 2005; 76(1): 30-36. 34. Williams DL. A comparative approach to topical cyclosporine therapy. Eye (Lond) 1997; 11(Pt 4): 453-464. 35. Comstock TL, Paterno MR, Singh A. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol 2011; 5: 177-186. Epub 2011 Feb 10. 36. Noah S. A primer on topical antibiotics for the skin and eyes. J Drugs Dermatol 2008; 7(4): 409-415. 37. Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res 1991; 10(10): 933-937. 38. Comstock TL, Decory HH. Advances in corticosteroid therapy for ocular inflammation: loteprednol etabonate. Int J Inflam. 2012; 2012: 789623. Epub 2012 Mar 28 39. Chen M, Gong L, Sun X et al. A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin 2012; 28(3): 385-394. 40. Holland EJ, Bartlett JD, Paterno MR, Effects of loteprednol/ tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. Cornea 2008; 27(1): 50-55. 41. Troller JA. Trends in research related to the influence of â&#x20AC;&#x153;water activityâ&#x20AC;? on microorganisms in food. Adv Exp Med Biol 1991; 302: 305-313. 42. Bausch & Lomb Inc. protocol #7066-R0498-LSG-041911-A

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QUESTIONNAIRE The Role of Ointments in Clinical Practice Paul M. Karpecki, OD, FAAO 1. ❑ ❑ ❑ ❑

All of the following are advantages of ointments, EXCEPT: Added barrier of protection to the ocular surface Increased contact time Cost savings to patient Higher concentration of fluoromethalone in the anterior chamber

2. ❑ ❑ ❑ ❑

All of the following are disadvantages of ointment, EXCEPT: Blurred vision Lack of proven efficacy Tear film instability Inconvenience of application

3. ❑ ❑ ❑ ❑

All of the following statements about ointments are true, EXCEPT: They are particularly effective for patients with nocturnal lagophthalmos They are commonly used in blepharoplasty They can protect or cover the cornea in cases of incomplete blink They have shown a high level of efficacy with bandage lenses

The Role of Ointments in Clinical Practice — Karpecki

1:1,16

CATEGORY A UFC C REDIT A PPLICATION F ORM 38

4. ❑ ❑ ❑ ❑

Conditions where ointments have been shown to be effective include all of the following, EXCEPT: Filamentary keratitis Corneal staining Corneal abrasions Cataracts

5. ❑ ❑ ❑ ❑

In clinical studies, ester-based steroids showed what percentage of IP elevation versus ketone-based steroids? 20% 30% 40% 50%

6. ❑ ❑ ❑ ❑

All of the following statements about ophthalmic ointments are true, EXCEPT: They are a treatment of choice as they rarely result in an allergic or toxic reaction Long-term use of steroid ointments can lead to thinning of the epidermis of the skin tissue Many clinicians recommend artificial tear ointments at night in less severe ocular surface disease conditions They may be as good or superior to pressure patching in patients with traumatic corneal abrasions

7. ❑ ❑ ❑ ❑

All of the following statements about the neonatal population and use of ointments are true, EXCEPT: Ointments are rarely used in neonatal settings because of potential toxicity among newborns Chlamydia is the most common cause of ophthalmic neonatorum (ON) Erythromycin ointment is less toxic than silver nitrate Erythromycin ointment is the traditional method of prophylaxis of ophthalmic neonatorum

8. ❑ ❑ ❑ ❑

Ointments may be used in all of the following conditions, EXCEPT: Blepharoconjunctivitis Infectious uveitis Meibomian gland dysfunction Angular blepharitis

9. ❑ ❑ ❑ ❑

For which of the following conditions is this treatment regimen used: Prednisolone Forte Q1H or Q2H during the day plus cycloplegia plus overnight steroid ointment (Lotemax® ung preferred) QHS? Chronic blepharitis Severe MGD/meibomitis Acute blepharoconjunctivitis Anterior non-infectious uveitis

10. ❑ ❑ ❑ ❑

All of the following statements about treatment regimens with ointments is true, EXCEPT: The shift to steroid-only monotherapy is increasing The trend toward combination therapy is increasing Overnight ointments combined with daytime steroid drops is a common regimen In acute cases of blepharitis, a pure antibiotic ointment is often sufficient

Clinical & Refractive Optometry Quebec 1:1, 2016

Administration Suspension ophtalmique de bésifloxacine à 0,6 %

Résumé des renseignements posologiques Critères de sélection des patients CLASSE THÉRAPEUTIQUE Antibactérien (ophtalmique) INDICATIONS ET USAGE CLINIQUE BESIVANCEMD est indiqué chez les patients âgés d’un an et plus atteints d’une conjonctivite bactérienne causée par une souche sensible des microorganismes suivants : Aérobies Gram positif • Bactéries corynéformes du groupe G de la classification du Centre de contrôle et de prévention des maladies infectieuses • Staphylococcus aureus • Staphylococcus epidermidis • Streptococcus mitis • Streptococcus oralis • Streptococcus pneumoniæ Aérobies Gram négatif • Hæmophilus influenzæ CONTRE-INDICATIONS BESIVANCEMD est contre-indiqué chez les patients ayant une hypersensibilité connue au médicament, à d’autres quinolones ou à l’un des ingrédients de la préparation ou des composants du contenant. Populations particulières Personnes âgées (> 60 ans) : On n’a observé aucune différence globale sur le plan de l’innocuité et de l’efficacité entre les patients âgés et les patients plus jeunes. Enfants (< 1 an) : L’innocuité et l’efficacité de BESIVANCEMD n’ont pas été établies chez les enfants de moins d’un an. Femmes enceintes : BESIVANCEMD ne doit être utilisé durant la grossesse que si les bienfaits escomptés justifient le risque pour le fœtus. Femmes qui allaitent : Il faut user de prudence lorsque l’on administre BESIVANCEMD à une femme qui allaite.

Instillez une goutte dans l’œil ou les yeux atteint(s), 3 fois par jour pendant 7 jours. Si une dose de ce médicament a été oubliée, elle doit être prise le plus tôt possible. Cependant, s’il est presque temps d’administrer la dose suivante, omettez la dose oubliée et revenez à votre horaire de traitement habituel. Il ne faut pas doubler les doses. Il faut indiquer aux patients de se laver les mains soigneusement avant d’utiliser BESIVANCEMD. Il faut indiquer aux patients d’éviter de contaminer la pointe de l’applicateur par contact avec les yeux, les doigts ou d’autres sources. Il faut indiquer aux patients de tourner le flacon fermé à l’envers et de l’agiter une fois avant l’utilisation. Puis, il convient de retirer le bouchon en maintenant le flacon en position retournée, de pencher la tête vers l’arrière et, avec le flacon toujours à l’envers, de presser doucement le flacon afin d’instiller une goutte dans l’œil ou les yeux à traiter.

RENSEIGNEMENTS SUPPLÉMENTAIRES SUR LE PRODUIT MISES EN GARDE ET PRÉCAUTIONS Système immunitaire Anaphylaxie et hypersensibilité : La bésifloxacine n’est disponible sur le marché que pour administration ophtalmique topique. Bien qu’aucune réaction anaphylactique ou d’hypersensibilité n’ait été observée avec l’administration ophtalmique topique de la bésifloxacine chez les humains, l’éventualité de telles réactions doit tout de même être prise en compte puisque aucun patient présentant une hypersensibilité connue aux fluoroquinolones n’a été inclus dans les études cliniques. Des réactions d’hypersensibilité graves (anaphylactiques) et, dans certains cas, mortelles ont été signalées chez des patients recevant une quinolone par voie générale. Celles-ci peuvent survenir dès la première dose. Certaines réactions ont été accompagnées d’un collapsus cardiovasculaire, d’une perte de conscience, d’un œdème de Quincke (y compris un œdème laryngé, pharyngé ou facial), d’une obstruction des voies respiratoires, d’une dyspnée, d’une urticaire et de démangeaisons. En présence d’une réaction allergique, on doit cesser le traitement par BESIVANCE MD, et un traitement approprié doit être administré selon le tableau clinique. Études sur la conjonctivite bactérienne Le tableau 1 présente les taux des effets indésirables oculaires apparus en cours de traitement par BESIVANCE MD qui ont été le plus fréquemment signalés dans les trois études cliniques sur la conjonctivite bactérienne, sans égard à la cause. Tableau 1 – Fréquence (%) des effets indésirables apparus en cours de traitement chez ≥ 1 % des yeux étudiés/patients recevant BESIVANCE MD ou l’excipient dans les études sur la conjonctivite bactérienne, sans égard à la cause (Population : innocuité1)

Renseignements relatifs à l'innocuité Effets indésirables

MISES EN GARDE ET PRÉCAUTIONS Généralités NE PAS INJECTER DANS L’ŒIL. DESTINÉ À UN USAGE OPHTALMIQUE TOPIQUE UNIQUEMENT. BESIVANCEMD est une suspension stérile pour usage ophtalmique topique seulement et ne doit pas être injecté sous la conjonctive ni être appliqué directement dans la chambre antérieure de l’œil. Il n’existe aucune donnée à ce jour appuyant l’utilisation de BESIVANCEMD chez les patients présentant une lésion de la cornée concomitante. Lentilles cornéennes : Il faut indiquer aux patients de ne pas porter de lentilles cornéennes en présence de signes et de symptômes de conjonctivite bactérienne ou au cours d’un traitement par BESIVANCEMD. Croissance de micro-organismes résistants associée à une utilisation prolongée : Comme dans le cas d’autres anti-infectieux, l’utilisation prolongée de BESIVANCEMD peut entraîner une prolifération de microorganismes non sensibles, y compris des champignons. Il est recommandé de cesser l’utilisation du produit en présence d’une surinfection et d’instaurer un autre traitement. Lorsque le clinicien le juge nécessaire, le patient devrait subir un examen ophtalmologique avec grossissement, par exemple au moyen d’une lampe à fente et, si nécessaire, avec coloration à la fluorescéine. Carcinogenèse et mutagenèse : Aucune étude n’a été menée à long terme chez les animaux pour déterminer le potentiel cancérogène de la bésifloxacine. RÉACTIONS DÉFAVORABLES Aperçu des réactions indésirables du médicament Dans le cadre de trois études sur l’innocuité et l’efficacité auxquelles 2 377 patients ont participé, aucun effet indésirable grave lié à BESIVANCEMD n’a été signalé. Les effets oculaires indésirables apparus en cours du traitement ayant été signalés le plus fréquemment dans l’œil étudié ont été la vision trouble (2,1 %), la douleur oculaire (1,9 %) et l’irritation oculaire (1,4 %). Pour signaler un effet indésirable, communiquez avec votre centre régional de surveillance des réactions indésirables, au 1-866-234-2345, ou avec Bausch & Lomb, au 1-888-459-5000.

Bésifloxacine n = 1 187 ( %)

Excipient n = 614 ( %)

Troubles oculaires Vision trouble

25 (2,1 %)

24 (3,9 %)

Irritation oculaire

17 (1,4 %)

18 (2,9 %)

Douleur oculaire

22 (1,9 %)

11 (1,8 %)

Conjonctivite

14 (1,2 %)

15 (2,4 %)

Prurit oculaire

13 (1,1 %)

10 (1,6 %)

Conjonctivite bactérienne

7 (0,6 %)

9 (1,5 %)

21 (1,8 %)

11 (1,8 %)

Troubles du système nerveux Céphalées

1 La population retenue pour l’analyse de l’innocuité a inclus les sujets des trois études sur l’innocuité et l’efficacité qui ont reçu un traitement contre la conjonctivite bactérienne, qui ont été répartis aléatoirement et qui ont reçu au moins une dose du médicament à l’étude. BESIVANCE MD a été évalué dans les trois études, alors que l’excipient a été évalué dans seulement deux des études. Réactions indésirables moins courantes dans les études cliniques (< 1 %) Les effets indésirables (possiblement, probablement ou assurément) liés au traitement signalés chez 0,1 % à 1,0 % des patients traités par BESIVANCE MD comprenaient les troubles suivants : Troubles oculaires : Prurit oculaire, sécheresse oculaire, conjonctivite, conjonctivite bactérienne, kératite ponctuée, œdème conjonctival, écoulement oculaire, infiltrats cornéens, coloration cornéenne, formation de croûtes sur le bord de la paupière, kérato-conjonctivite sèche, sensation d’un corps étranger dans les yeux, follicules conjonctivaux, peau sèche, trouble oculaire, douleur au point d’instillation, photophobie et perturbations de la vue. Troubles du système nerveux : Céphalées SYMPTÔMES ET TRAITEMENT D’UN SURDOSAGE On ne dispose d’aucun renseignement sur le surdosage par BESIVANCE MD. En cas de surdosage topique par BESIVANCE MD, rincer l’œil ou les yeux atteint(s) avec de l’eau tiède du robinet. Monographie complète de produit à la disposition des professionnels de la santé sur : www.bausch.ca

Bausch & Lomb Canada Inc., Vaughan (ON) L4K 4B4 MD/MC désignent des marques de commerce de Bausch & Lomb Incorporated © Bausch & Lomb Incorporated

Voyez le résumé des renseignements posologiques à la page 40