LEARNING METHOD AND MEDIUM This educational activity consists of a case report and four (4) studyquestions. The participant should, in order, read the learning objectivescontained at the beginning of this activity, read the material, answerall questions in the post test, and complete the Activity Evaluation/Credit Request form. To receive credit for this activity, please followthe instructions provided on the post test and Activity Evaluation/Credit Request form. This educational activity should take a maximumof 0.75 hour to complete.

CONTENT SOURCEThis continuing medical education (CME) activity captures contentfrom a roundtable discussion held August 2013.

ACTIVITY DESCRIPTIONEye care providers face multiple challenges in diagnosing allergicconjunctivitis (AC) and achieving patient satisfaction with treatment.Studies show that AC is often underdiagnosed and often not optimallytreated. Recently, a group of experts convened to discuss their insightsand approaches for managing patients with AC. This CME activity bringsyou highlights from these case discussions in a 4-part series.

TARGET AUDIENCEThis educational activity is intended for ophthalmologists.

LEARNING OBJECTIVESUpon completion of this activity, ophthalmologists will be betterable to:• Conduct a thorough differential diagnosis to identify allergicconjunctivitis and any comorbid conditions

• Choose appropriate medications based on disease severity toeffectively control the early-phase and late-phase responses ofocular allergy

• Choose appropriate medications to provide effective maintenancecontrol of ocular allergy

• Counsel patients on preemptive strategies and the role ofpharmacologic and nonpharmacologic interventions for allergy control

• Collaborate with colleagues in other specialty areas to optimizethe management of the patient with ocular allergy

ACCREDITATION STATEMENTThis activity has been planned and implemented inaccordance with the Essential Areas and Policies ofthe Accreditation Council for Continuing MedicalEducation through the joint sponsorship of The New York Eye and Ear Infirmary andMedEdicus LLC. The New York Eye and Ear Infirmaryis accredited by the ACCME to provide continuingmedical education for physicians.

AMA CREDIT DESIGNATION STATEMENTThe New York Eye and Ear Infirmary designates this enduringmaterial for a maximum of 0.75 AMA PRA Category 1 Credit™.Physicians should claim only the credit commensurate with theextent of their participation in the activity.

GRANTOR STATEMENTThis continuing medical education activity is supported through anunrestricted educational grant from Bausch + Lomb Incorporated.

DISCLOSURE POLICY STATEMENTIt is the policy of The New York Eye and Ear Infirmary that thefaculty and anyone in a position to control activity content discloseany real or apparent conflicts of interest relating to the topics of thiseducational activity, and also disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentation(s). The New York Eye and Ear Infirmary has established policies inplace that will identify and resolve all conflicts of interest prior tothis educational activity. Full disclosure of faculty/planners and theircommercial relationships, if any, follows.

DISCLOSURESMichael S. Blaiss, MD, had a financial agreement or affiliationduring the past year with the following commercial interests in theform of Honoraria: Alcon, Inc; Allergan, Inc; and Bausch + LombIncorporated; Consultant/Advisory Board: Allergan, Inc; and Bausch+ Lomb Incorporated.Thomas J. Joly, MD, PhD, has no relevant commercial relationshipsto disclose.

Jai G. Parekh, MD, MBA, had a financial agreement or affiliationduring the past year with the following commercial interests in theform of Consultant/Advisory Board: Alcon, Inc; Bausch + LombIncorporated; and Omeros Corporation; Honoraria for promotional,advertising or non-CME services received directly from commercialinterest or their Agents (eg, Speakers Bureaus): Alcon, Inc; Allergan,Inc; Bausch + Lomb Incorporated; and Merck & Co, Inc.John Sheppard, MD, MMSc, had a financial agreement or affiliationduring the past year with the following commercial interests in the formof Honoraria: Alcon, Inc; Allergan, Inc; Bausch + Lomb Incorporated; andMerck & Co, Inc; Consultant/Advisory Board: Alcon, Inc; Allergan, Inc;Bausch + Lomb Incorporated; and Eleven Biotherapeutics; ContractedResearch: Bausch + Lomb Incorporated; Eleven Biotherapeutics; andRutech; Ownership Interest: Eyegate Pharmaceuticals, Inc; RapidPathogen Screening Inc; and TearLab Corporation.

PEER REVIEW DISCLOSURE Joseph F. Panarelli, MD, has no relevant commercial relationshipsto disclose.

EDITORIAL SUPPORT DISCLOSURESCheryl Guttman; Cynthia Tornallyay, RD, MBA, CCMEP; Kimberly Corbin, CCMEP; Barbara Aubel; and Barbara Lyon haveno relevant commercial relationships to disclose.

DISCLOSURE ATTESTATION The contributing physicians listed above have attested to the following: 1) that the relationships/affiliations noted will not bias or otherwiseinfluence their involvement in this activity;

2) that practice recommendations given relevant to the companieswith whom they have relationships/affiliations will be supportedby the best available evidence or, absent evidence, will beconsistent with generally accepted medical practice; and

3) that all reasonable clinical alternatives will be discussed whenmaking practice recommendations.

OFF-LABEL DISCUSSIONThis activity includes off-label discussion of the use of loteprednoletabonate, 0.5%, for allergy. Please refer to the official prescribinginformation for discussion of approved indications, contraindications,and warnings.

For Digital EditionsSystem Requirements:When viewing this activity online, please ensure the computer youare using meets the following requirements:• Operating System: Windows or Macintosh• Media Viewing Requirements: Flash Player or Adobe Reader• Supported Browsers: Microsoft Internet Explorer, Firefox, Google Chrome, Safari, and Opera

• A good Internet connection

The New York Eye and Ear Infirmary Privacy & Confidentiality PoliciesCME policies: http://www.nyee.edu/cme-enduring.html Hospital policies: http://www.nyee.edu/website-privacy.html

CME Provider Contact InformationFor questions about this activity, call 212-979-4383.

TO OBTAIN AMA PRA CATEGORY 1 CREDIT™ Online and Instant CertificateTo obtain AMA PRA Category 1 Credit™ for this activity, read thematerial in its entirety and consult referenced sources as necessary.We offer instant certificate processing and support Green CME.Please take this post test and evaluation online by going tohttp://tinyurl.com/eyeonallergycmecase2. Upon passing, you will receive your certificate immediately. You must score 70% orhigher to receive credit for this activity, and may take the test up to 2 times.

DISCLAIMERThe views and opinions expressed in this educational activity arethose of the faculty and do not necessarily represent the views ofThe New York Eye and Ear Infirmary; MedEdicus LLC; Bausch +Lomb Incorporated; or Ophthalmology Management.

Strategies for Improving Ocular AllergyDiagnosis, Treatments, and Outcomes

CME Newsletter Series For Ophthalmologists

With Online Testing and Instant CME Certificate

ORIGINAL RELEASE: JANUARY 2, 2014LAST REVIEW: DECEMBER 14, 2013EXPIRATION: JANUARY 31, 2015

Faculty John Sheppard, MD, MMSc (Chair and Moderator)Professor of Ophthalmology, Microbiology & Molecular BiologyClinical Director, Thomas R. Lee Center for Ocular PharmacologyOphthalmology Residency Research Program DirectorEastern Virginia Medical SchoolPresident, Virginia Eye ConsultantsNorfolk, Virginia

Michael S. Blaiss, MDClinical Professor of Pediatrics and MedicineUniversity of Tennessee Health Sciences CenterAllergy and Asthma CareMemphis, Tennessee

Thomas J. Joly, MD, PhDAssistant ProfessorEastern Virginia Medical SchoolOrbital and Oculoplastic SurgeryVirginia Eye ConsultantsNorfolk, Virginia

Jai G. Parekh, MD, MBAClinical Associate Professor, Cornea Services The New York Eye and Ear InfirmaryNew York, New York Managing Partner Brar-Parekh Eye AssociatesEdison, New Jersey Chief of Cornea & External Diseases and Medical Director The Research Institute of St. Joseph’s Healthcare System Paterson, New Jersey

EYE ON ALLERGY™

CASE 2 in a Series of 4

Distributed with

Jointly sponsored by The New York Eye and Ear Infirmary and MedEdicus LLC.

This continuing medical education activity is supported through an unrestrictededucational grant from Bausch + Lomb Incorporated.

This CME activity is copyrighted to MedEdicus LLC ©2014. All rights reserved.

2

IntroductionSeasonal allergic conjunctivitis (SAC) is the most common form ofallergic eye disease and its incidence is on the increase, along withassociated conditions, including conjunctivochalasis. It also may beassociated with other ocular issues, such as contact lens intolerance,which may be the primary reason some patients with SAC seekophthalmic care. Patients with SAC may have comorbid sinus and nasaldisease as well. This roundtable discussion highlights the importance ofa multidisciplinary approach to the evaluation and management ofpatients with uncontrolled ocular allergy as well as the importance ofadequate preparation for ophthalmic surgery in these patients.

Dr Sheppard: This 34-year-old white female is a patent attorney whopresents with recurrent seasonal conjunctivitis, rhinitis, and sinusitis.She reports having chronic headaches, postnasal discharge, and ahistory of nasal polyps, and she complains of persistent ocular foreignbody sensation and dryness. She is using contact lenses to correctmyopic astigmatism, but is struggling with contact lens intoleranceand is interested in LASIK (laser-assisted in situ keratomileusis)because she wants to be glasses-free.

Her ophthalmic examination reveals the following:• Refraction OD -4.26 + 1.50 x 90, OS -5.00 +2.00 x 80 • Best Corrected Visual Acuity 20/20OU • Tear osmolarity OD 295 mOsm/L, OS 310 mOsm/L • Schirmer test >30 mm OU • 1+ inferior punctate epithelial keratopathy OU • 2+ inferior temporal conjunctivochalasis with overlying 2+ lissaminestaining OU

This patient requires multidisciplinary care. She has ocular surfacedisease that is making her contact lens wear intolerable, and thediagnostic evaluation indicates that ocular allergy, rather thanaqueous-deficient or evaporative dry eye, is the cause. Chronic allergyalso likely underlies her conjunctivochalasis and sinus issues, while atleast contributing to her nasal polyps.

Dr Parekh, what are your thoughts about initial management for this patient?

Dr Parekh: I see patients such as the one described in my officefrequently during the spring and fall allergy seasons in northern NewJersey; they can be challenging to treat. Although this patient soughtophthalmic care because she wants refractive surgery, she needsmedical care to restore her ocular surface and control her allergicdisease before surgery can be considered.

Dr Sheppard: What is your agent of choice for managing an acuteexacerbation in patients with recurrent SAC?

Dr Parekh: I use an ophthalmic dual-acting antihistamine/mast cellstabilizer. Ketotifen, .025%, is now available over-the-counter, andthere are several prescription products from which to choose. I think amore frequent administration is helpful for maintaining 24-hourcontrol of allergic symptoms, considering that patients may be exposedto allergens throughout the day and into the evening, and so I usuallyrecommend an agent for twice-daily use. Alcaftadine or olopatadine,0.2%, are indicated for once-daily administration, but bepotastine isrecommend for twice-daily use, so I will often suggest patients use thelatter agent because it is labeled for more frequent administration. A particularly important consideration in this patient who has ocularsurface disease and is likely using oral antihistamines to control herallergic symptoms is to avoid ocular drying. The ophthalmicantihistamines, alcaftadine and bepotastine, are good choices becausethey have high H1 receptor specificity and low muscarinic activity.1

Because the conjunctival injection, neovascularization, andconjunctivochalasis in this patient are signs of more severeinflammation, I would also start treatment with a topicalcorticosteroid. She needs something that is more potent thanfluorometholone, and because the corticosteroid would have to beused for several weeks, I would choose loteprednol etabonate becauseit is less likely to increase intraocular pressure than other potenttopical corticosteroids.2 While the 0.2% formulation of loteprednoletabonate is specifically indicated for treatment of SAC, given theseverity of this patient’s presentation, I feel she needs to useloteprednol, 0.5%. Considering the condition of her ocular surface, thegel—rather than the suspension—formulation would be desirable, inorder to provide a more physiologic pH and demulcents whileminimizing the effects of preservatives.3

When there is eyelid disease, I like to use an ointment. There are only 2 corticosteroid ointments available—fluorometholone andloteprednol. Other corticosteroid ointments are combination productscontaining an antibiotic and are not appropriate for management ofallergic disease. Fluorometholone ointment is less costly thanloteprednol ointment, but may not be potent enough to treatmoderate or more severe inflammation.

This patient also needs to be seen by an allergist to address her nasaland sinus conditions.

CASE 2

Figure. Chronic injection,punctate keratopathy, serousdischarge, and tarsal papillaryresponse. Infero-temporalconjunctivochalasis mostnotable with downgaze, orupward lower lid externalcompression.

Photo Courtesy of John Sheppard, MD, MMSc

3

Dr Sheppard: Dr Joly, do you have any concerns about short-term or long-term useof a topical steroid ointment on the eyelids?

Dr Joly: In general, we want to limit cumulative steroid use from all routes ofadministration, but I think that the amount of systemic exposure from topicalapplication to the lid is relatively small while the benefit patients derive istremendous. An ointment formulation is very helpful on the eyelid skin because itadheres to the tissue and therefore enables penetration of the active ingredient. Inaddition, an ointment provides a physical barrier to protect the keratinizedepithelium against irritation from the slightly acidic tears.

From an oculoplastic surgery perspective, my focus in this patient would be on themanagement of her conjunctivochalasis. Inflammation can lead to the development ofconjunctivochalasis and then can be perpetuated by it.4 In order to break that viciouscycle, this patient would benefit from undergoing surgery for her conjunctivochalasis,but only after the acute conjunctivitis has been brought under control.

Dr Sheppard: What would be your surgical approach?

Dr Joly: Simple excision is probably all that is needed in this patient, who has justslight redundancy of her temporal conjunctival tissue. The incision will be wellprotected, and as a result of the wound healing process, the conjunctiva will adherewell to the underlying sclera.

Dr Parekh: We should also give some attention to the risk factors forconjunctivochalasis, namely, older age, contact lens wear, and autoimmune thyroiddisease.5-7 As this patient is relatively young, I would particularly consider thyroiddisease and order a thyroid function test.

In the past, I have usually addressed symptomatic and chronic conjunctivochalasiswith a simple cut-down. I have also used silver nitrate as well as cautery. Morerecently, I have been using the dehydrated amniotic membrane allograft as anoverlay to bare sclera after the cut-down.

I think conjunctivochalasis is being underdiagnosed as a cause of foreign bodysensation because clinicians fail to look for it.

Dr Sheppard: I tell patients their eyeball needs a “facelift” and I refer them to theoculoplastic surgeon.

If you look at the prevalence of allergy in the general population, it is increasinglogarithmically. We are also seeing an increase in conjunctivochalasis. Dr Blaiss, doyou think allergy is a contributor?

Dr Blaiss: Yes. Over the past 20 to 30 years in the United States and most developedcountries, the incidence of ocular and systemic allergic disorders has been increasing.The phenomenon may be explained by multiple factors. One prominent theory is the“hygiene hypothesis”, which proposes that a lack of exposure to infectious agentsand endotoxins in early life interferes with the natural development of the immunesystem from a TH2-based tendency to a TH1-based response.8 Climate change alsomay be playing a role by increasing pollen levels, the allergen content of pollen, andthe duration of the pollen seasons.9 Numerous studies have also suggested thatvitamin D insufficiency and reduced infant breastfeeding in the population areassociated with an increased risk of allergy10,11

Dr Sheppard: Dr Joly, should the eye care provider be examining the nasal mucosain patients with recurrent or chronic allergic conjunctivitis?

Strategies for Allergen Avoidance

• Keep doors to the outside and windows shut

• Do not hang laundry outside to dry

• Use air conditioning wherepossible (pollen levels areincreased by window or attic fans)

• Change clothes, shampoo andshower after being outsidewhen pollen counts are high

• Stay indoors during windy weather

• Do not mow the lawn

• Do not rub your eyes: if youmust, wash them first toremove pollen

• Keep your pets out of thebedroom, and off your bed

• Remove all down and featherproducts from your bed:pillows and comforters

• Use an allergy-free pillow case

4

Dr Joly: The condition of the nasal mucosa is something allcomprehensive ophthalmologists should be concerned with whentreating patients with allergy and epiphora because there are definiteassociations between rhinitis, ocular allergy, and the lacrimal drainagesystem. Ophthalmologists who are uncomfortable performing a nasalexamination should refer patients to an oculoplastic surgeon,otolaryngologist, or allergist.

Dr Sheppard: Dr Blaiss, what are the concerns with this patient’s nasalpolyps and what are the considerations for managing her sinusitis?

Dr Blaiss: Her nasal allergies can be a factor in her polyps and sinusitisand therefore also underlie her chronic headaches.12 Aggressivemanagement is indicated. Often, I undertake what I call a “medicalpolypectomy” that involves an oral steroid burst for 5 to 7 days and then an intranasal steroid. Those 2 treatments are the only medicalapproaches that have been shown effective for controlling nasal polyps.13

Of course, she should also undergo allergy testing and, according tothe findings, be given recommendations for strategies to reduceenvironmental exposure to her triggering allergens [See Sidebar, page 3]. Considering the severity of this patient’s allergies with herchronic sinus disease, I think she also is an ideal candidate forimmunotherapy to control her allergies.

Dr Sheppard: Your points reinforce the concept that part of the eyecare provider’s role in managing patients with allergic eye disease isguiding them to appropriate specialists for comprehensive management.

Once the patient’s acute condition is controlled, what are theconsiderations in choosing surgery for refractive correction?

Dr Parekh: The presence of a compromised ocular surface withinflammatory mediators and an unstable tear film can adversely affectthe outcomes of laser vision correction surgery by affecting theaccuracy of the preoperative evaluation and surgical plan as well as byincreasing the likelihood for complications, including diffuse lamellarkeratitis and dry eye.14,15 Therefore, surgery should not be considereduntil the ocular surface condition is rehabilitated and the patient’sallergies have remained well controlled for many months.

Then, and only if the patient is insisting on surgery, the proceduremust be performed using strategies to control inflammation andoptimize the ocular surface condition, including the use of punctalplugs and topical treatment with cyclosporine, a corticosteroid, andartificial tears. In addition, the informed consent must state veryclearly that the risks for complications and suboptimal refractive andvisual results are increased.

Dr Sheppard: In summary, this case illustrates that longstandingsevere SAC may be associated with a variety of other problems.Affected patients require aggressive intervention to control their acuteocular inflammation. Their long-term outcome, however, also dependson their receiving appropriate multidisciplinary care. Therefore, it isincumbent upon the ophthalmologist to refer patients with severe SACto specialists having the necessary diagnostic and therapeutic skills tomanage their treatment.

References 1. Williams JI, Gow JA, Klier SM, McCue SL, Salapatek AM, McNamara TR.Non-clinical pharmacology, pharmacokinetics, and safety findings for theantihistamine bepotastine besilate. Curr Med Res Opin. 2010;26(10):2329-2338.

2. Comstock TL. Decory HH. Advances in corticosteroid therapy for ocularinflammation: loteprednol etabonate. Int J Inflam. 2012;2012:789623. Epub 2012 Mar 28.

3. Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5%for postoperative pain and inflammation after cataract surgery: results of amulticenter trial. Clin Ophthalmol. 2012;6:1113-1124.

4. Meller D, Tseng SC. Conjunctivochalasis: literature review and possiblepathophysiology. Surv Ophthalmol. 1998;43(3):225-232.

5. Mimura T, Yamagami S, Usui T, et al. Changes of conjunctivochalasis withage in a hospital-based study. Am J Ophthalmol. 2009;147:171-177.

6. Mimura T, Usui T, Yamamoto H, et al. Conjunctivochalasis and contactlenses. Am J Ophthalmol. 2009;148(1):20-25.

7. de Almeida SF, de Sousa LB, Vieira LA, Chiamollera MI, Barros Jde N. Clinic-cytologic study of conjunctivochalasis and its relation to thyroidautoimmune diseases: prospective cohort study. Cornea. 2006;25(7):789-793.

8. Brooks C, Pearce N, Douwes J. The hygiene hypothesis in allergy andasthma: an update. Curr Opin Allergy Clin Immunol. 2013;13(1):70-77.

9. Bielory L, Lyons K, Goldberg R. Climate change and allergic disease. CurrAllergy Asthma Rep. 2012;12(6):485-494.

10. Reinholz M, Ruzicka T, Schauber J. Vitamin D and its role in allergic disease.Clin Exp Allergy. 2012;42(6):817-826.

11. Kull I, Melen E, Alm J, et al. Breast-feeding in relation to asthma, lungfunction, and sensitization in young schoolchildren. J Allergy Clin Immunol.2010;125(5):1013-1019.

12. Chaaban MR, Walsh EM, Woodworth BA. Epidemiology and differentialdiagnosis of nasal polyps. Am J Rhinol Allergy. 2013;27(6):473-478.

13. Schlosser RJ. Soler ZM. Evidence-based treatment of chronic rhinosinusitiswith nasal polyps. Am J Rhinol Allergy. 2013;27(6):461-466.

14. Bielory BP, O’Brien TP. Allergic complications with laser-assisted in-situkeratomileusis. Curr Opin Allergy Clin Immunol. 2011;11(5):483-491.

15. Boorstein SM, Henk HJ. Elner VM. Atopy: a patient-specific risk factor fordiffuse lamellar keratitis. Ophthalmology. 2003;110(1):131-137.

TO OBTAIN AMA PRA CATEGORY 1 CREDIT™ Online and Instant Certificate

To obtain AMA PRA Category 1 Credit™ for this activity, read the material in its entirety and consult referenced sources as necessary. We offer instant certificate processing and support Green CME. Please take this post test and evaluation online by going tohttp://tinyurl.com/eyeonallergycmecase2. Upon passing, you will receive your certificate immediately. You must score 70% or higher to receive credit for this activity, and may take the test up to 2 times.