CE Monograph Online Testing and Instant Certificate Processing http://tinyurl.com/OcularSurface1 ar Surfac Ocul e W in ell tes ne da ss Up

Part 1: Ocular Allergy

Proceedings From an Expert Roundtable Discussion

faculty Original Release: March 1, 2014 Mile Brujic, OD, FAAO—Program Chair and Moderator Expiration: January 7, 2017 Alan Kabat, OD, FAAO David Kading, OD, FAAO Christine Sindt, OD, FAAO Loretta Szczotka-Flynn, OD, PhD, FAAO This course is COPE approved for 2 hours of CE credit for optometrists. COPE Course ID: 40008-AS

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A supplement to Learning Method and Medium David L. Kading, OD, FAAO, has had a financial This educational activity consists of a case report agreement or affiliation with the following and ten (10) study questions. The participant commercial interests in the form of should, in order, read the Learning Objectives Consultant/Advisory Board/Speaker contained at the beginning of this activity, read the Bureau/Contracted Writing: Alcon, Inc; Allergan, material, answer all questions in the post test, and Inc; Aton Pharma, Inc; Bausch + Lomb complete the Activity Evaluation/Credit Request Incorporated; Bio-Tissue, Inc; Contamac; Ciba form. To receive credit for this activity, please follow Vision; CooperVision; Essilor Laboratories of the instructions provided below in the section titled America; Inspire Pharmaceuticals, Inc; NicOx; To Obtain CE Credit. This educational activity should Valeant Pharmaceuticals Inc; and Valley Contax; faculty take a maximum of 2.0 hours to complete. Contracted Research: Alcon, Inc; Bausch + Lomb Incorporated; Ciba Vision; CooperVision; Content Source SynergEyes; and Valley Contax. Mile Brujic, OD, FAAO This continuing education (CE) activity captures (Program Chair and Moderator) content from a roundtable discussion. Christine Sindt, OD, FAAO, had a financial Premier Vision Group agreement or affiliation during the past year with Bowling Green, Ohio Activity Description the following commercial interests in the form of Eye care providers face multiple challenges in Consultant/Advisory Board: Alcon Vision Care; managing ocular surface disorders including ocular Contracted Research: Alcon Vision Care; allergy and dry eye. Studies show that ocular Alan Kabat, OD, FAAO Ownership Interest: EyePrint Prosthetics. Professor allergies are often underdiagnosed and often not treated optimally. Recently, a group of experts Southern College of Optometry Loretta Szczotka-Flynn, OD, PhD, FAAO, had a convened to discuss their insights and approaches financial agreement or affiliation during the past Memphis, Tennessee for managing patients with ocular allergy including year with the following commercial interests in the special considerations for patients wearing contact form of Consultant/Advisory Board: Alcon, Inc; lenses. This CE activity brings you highlights from David Kading, OD, FAAO Contracted Research: Alcon, Inc; and Johnson & these discussions in a 2-part series: Part 1 focuses Johnson Vision Care, Inc. Specialty Eyecare Group on Ocular Allergy, Part 2 on Dry Eye. Seattle, Washington Disclosure Attestation Target Audience Each of the contributing physicians listed above This educational activity is intended for has attested to the following: optometrists. Christine Sindt, OD, FAAO 1. that the relationships/affiliations noted will not bias or otherwise influence his or her Director, Contact Lens Service Learning Objectives Clinical Associate Professor of Upon completion of this activity, participants will involvement in this activity; be better able to: 2. that practice recommendations given relevant to Ophthalmology and Visual the companies with whom he or she has Sciences • Make a differential diagnosis in patients with ocular allergy relationships/affiliations will be supported by University of Iowa • Select the therapy that is most appropriate the best available evidence or, absent evidence, Carver College of Medicine for the patient’s diagnosis and phase of will be consistent with generally accepted medical practice; and Iowa City, Iowa ocular allergy • Incorporate current approaches to successfully 3. that all reasonable clinical alternatives will be manage contact lens wearing patients who discussed when making practice Loretta Szczotka-Flynn, OD, also have ocular allergy recommendations. PhD, FAAO • Counsel patients on proactive measures for managing ocular allergy Product Usage in Accordance with Labeling Director, Contact Lens Service Please refer to the official prescribing information University Hospitals Case Accreditation Designation Statement for each product for discussion of approved indications, contraindications, and warnings. Medical Center This course is COPE approved for 2 hours of CE credit for optometrists. Professor of Ophthalmology COPE Course ID: 40008-AS Grantor Statement Case Western Reserve University This CE activity is supported through an unrestricted educational grant from Alcon, Inc. School of Medicine Disclosures Mile Brujic, OD, FAAO, had a financial agreement Cleveland, Ohio or affiliation during the past year with the following To Obtain CE Credit commercial interests in the form of Consultant/ We offer instant certificate processing and support Advisory Board: Alcon, Inc; Allergan, Inc; Bio-Tissue, Green CE. Please take this post test and evaluation Inc; NicOx SA; TelScreen; Transitions Optical, Inc; online by going to http://tinyurl.com/OcularSurface1. Valeant Pharmaceuticals International, Inc; and Upon passing, you will receive your certificate Vmax Vision, Inc; Contracted Research: Alcon, Inc; immediately. You must answer 7 out of 10 Honoraria from promotional, advertising or questions correctly in order to pass, and may take non-CME services received directly from the test up to 2 times. Upon registering and commercial interests or their Agents (eg, Speakers successfully completing the post test, your Bureaus): Alcon, Inc; Allergan, Inc; Optovue, Inc; certificate will be made available online and you Paragon, Valley Contax; and Vmax Vision, Inc. can print it or file it. Please make sure you take the online post test and evaluation on a device Alan G. Kabat, OD, FAAO, had a financial that has printing capabilities. There are no fees agreement or affiliation during the past year with for participating in and receiving CE credit for the following commercial interests in the form of this activity. Consultant/Advisory Board: Alcon, Inc; Allergan, Inc; Bio-Tissue, Inc; NicOx SA; TearScience; and Disclaimer Valeant Pharmaceuticals Inc; Honoraria from The views and opinions expressed in this promotional, advertising or non-CME services educational activity are those of the faculty and do received directly from commercial interests or their not necessarily represent the views of the State Agents (eg, Speakers Bureaus): Alcon, Inc; and University of New York College of Optometry, Valeant Pharmaceuticals Inc. MedEdicus LLC, Alcon, Inc, or Review of Optometry.

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2 introduction History Ocular allergy is a common condition associated with Obtaining an accurate medical history from each patient is significant morbidity and economic burden from both direct important to elicit the characteristic signs and symptoms of and indirect costs.1-5 It encompasses a group of type I and allergic conjunctivitis, the causative , the presence of type IV hypersensitivity-mediated ocular surface diseases other allergic disorders, and the use of for that include seasonal allergic conjunctivitis (SAC), perennial controlling allergy signs and symptoms. Considering the high allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), prevalence of SAC and PAC and the opportunity to provide vernal keratoconjunctivitis (VKC), and contact lens–induced preemptive care, clinicians should probe for these conditions papillary conjunctivitis (CLPC; previously known as giant as part of the history in all patients. papillary conjunctivitis). According to various studies, the Itching is the hallmark symptom of allergic conjunctivitis, and overall prevalence of ocular allergy ranges between 15% in patients who present with red, irritated eyes, a chief 1 and 40%. However, SAC and PAC are the most common complaint of itching should direct the diagnostic evaluation forms, accounting for up to 95% of allergic eye disease in toward allergy. However, absence of a report of itching does 2 the United States. not necessarily rule out allergic conjunctivitis since some While SAC and PAC are not generally considered patients experiencing itchy eyes may describe it using other sight-threatening diseases, they can adversely affect visual terms (eg, burning, stinging, or irritated eyes). Other common function, contact lens wear comfort, work productivity, sleep, complaints of patients with allergic conjunctivitis are tearing, and quality of life.3-5 Numerous studies have also shown the redness, and eyelid swelling, while chemosis is seen in severe association between excessive ocular itching and the cases. Most patients will also have nasal symptoms, including nasal itching, congestion, or a runny nose. development of keratoconus.6,7 In addition, ocular allergy has cosmetic sequelae associated with having red, irritated The patient’s medical history should also elicit whether or eyes and the potential for frequent, long-term scratching to not the patient is using any anti-allergy medications at any cause progressive collagenous stress along the eyelid skin. time throughout the year. This information can explain an Despite its many consequences, allergic conjunctivitis is incomplete clinical picture of allergy in a patient with active underdiagnosed and undertreated.1 Optometrists, as disease and identify an underlying cause for problems with primary eye care providers, are positioned to address dry eye or contact lens discomfort. For example, patients these problems. who are using an oral may not have prominent itch, but may be suffering from the ocular Several factors can contribute to the suboptimal drying effects of those medications. In addition, the patient’s management of patients with allergic conjunctivitis. Many medication history can trigger the clinician to inquire about patients self-treat their condition with over-the-counter (OTC) SAC or PAC in patients who are seen when their allergies medications and do not even present for care to health care may not be active. providers. Some patients with allergic conjunctivitis may seek attention for concomitant atopic diseases (ie, asthma, Electronic medical records can help in obtaining the allergic , urticaria, or eczema),8 and the primary care medication history, although the patient’s record may not clinician or dermatologist who is managing those comorbid include a full list of medications and in particular may be conditions may overlook the patient’s ocular manifestations. missing information about OTC products. Asking specifically Due to the periodic nature of reactions in patients with SAC about agents purchased without a prescription is important and PAC, it is likely that even those patients who regularly considering that anti-allergy agents are top-selling OTC see an eye care provider for other reasons may not have medications and because some patients do not consider OTC active allergic symptoms at the time of their visit. Among products as “medications.” patients who present for care because of signs and symptoms of allergic eye disease, the diagnosis may still be Recognizing that patients may have poor recall of medications missed because other common ocular surface conditions they used several months earlier, it is also helpful to routinely with overlapping manifestations—such as dry eye, ask patients to bring in bottles of any medications they have meibomian gland dysfunction (MGD), and contact lens– used since their last visit. Patients who do not bring in their related discomfort—may coexist. medications or are unable to provide product names should be asked about the reason why they were using the The aim of this continuing education activity is to improve medication. This may help the clinician in determining the care for patients with allergic conjunctivitis by raising class of medication that was taken. awareness of its prevalence and burden, presenting If the medication history shows a patient is self-treating for strategies to increase its recognition, and reviewing allergy with an oral antihistamine and does not have active approaches for safe and effective treatment. disease, further questioning is needed to determine whether or not allergic conjunctivitis is a problem. Although most Diagnosis patients with seasonal and perennial allergies suffer with Allergic conjunctivitis is usually a clinical diagnosis based on both nasal and ocular manifestations, it is possible that only the findings from the patient’s history and physical the nose or only the eyes are affected.9 Even if the patient examination. denies ocular allergy symptoms, the optometrist must still

3 consider whether or not the use of an oral antihistamine for Differential Diagnosis may be causing dry eye. Establishing a diagnosis of allergic conjunctivitis can be challenging because it shares signs and symptoms with other Clinical Examination common conditions. The ocular examination of patients with allergic conjunctivitis As itching is not specific to allergic conjunctivitis, it can be reveals chemosis and hyperemia of the palpebral and bulbar helpful to ask patients to demonstrate how they scratch to conjunctiva (Figure 1), and there may also be mild papillae on relieve the itch. Itch associated with allergic conjunctivitis is the palpebral conjunctiva (Figure 2). Patients with allergic typically worst in the nasal canthal region. Itching of the conjunctivitis may also have periocular skin changes, upper eyelid skin suggests dermatitis, and itching along the especially if they have concurrent allergic rhinitis or eyelash margin is more common in blepharitis. Some rhinosinusitis. These signs include a horizontal crease across patients may pull their lower eyelid down and rub or scratch the bridge of the nose that develops from habitual wiping of the conjunctiva in the lower fornix area, demonstrating a a runny nose (“the allergic salute”) and darkened circles mucous fishing syndrome. under the eyes (“allergic shiners”) (Figure 3) from allergic rhinitis-related vascular congestion. Since itching, redness, tearing, and other symptoms of ocular surface irritation are manifestations of both allergic conjunctivitis and dry eye, it may be appropriate to perform a full ocular surface workup to identify whether the patient might have dry eye alone or as a comorbid condition. Dry eye and allergic conjunctivitis commonly coexist,10 and each condition can exacerbate the other. The natural flushing of antigens from the ocular surface by the patients’ tears is reduced in dry eye while patients with allergy may be using medications that dry the ocular surface. In addition, ocular surface irregularities and inflammatory mediators associated with allergic disease can Figure 1. This image shows the typical appearance of the eye in a patient with contribute to the pathophysiology of dry eye. seasonal allergic conjunctivitis. Note the pronounced diffuse hyperemia and eyelid swelling. Ocular itching is also a feature of AKC, VKC, and CLPC, and it is Photo courtesy of Mile Brujic, OD, FAAO important to differentiate these ocular allergies from allergic conjunctivitis because they require different management strategies (Table 1). Furthermore, AKC and VKC are potentially sight-threatening. Compared with SAC and PAC, AKC and VKC are usually associated with more intense itching and a stringy rather than a clear mucoid discharge.8,11 Cobblestone papillae of the superior palpebral conjunctiva, along with lid and cornea involvement, are also features of AKC (Figure 4) and VKC (Figure 5) that are not seen with SAC or PAC.

Table 1. Signs and Symptoms of Allergic Eye8,11

Findings AC VKC AKC CLPC

Itch + ++ ++ ++ Figure 2. A fine, velvety-looking papillary reaction may be seen upon upper eyelid eversion in many patients with allergic conjunctivitis, particularly those Grittiness +/− +/− +/− + who wear contact lenses. Photo courtesy of Alan G. Kabat, OD, FAAO Seasonal + + +/− +/− variation

Chemosis + +/− +/− +/−

Cobblestoning − ++ ++ ++

Discharge Clear Stringy Stringy Stringy mucoid mucoid mucoid mucoid (especially in the morning)

Figure 3. “Allergic shiners” can be seen in patients with allergic Eyelid skin − + + − rhinoconjunctivitis. These dark circles below the eyes appear in association involvement with swollen and congested small blood vessels beneath the skin. AC = allergic conjunctivitis; VKC = vernal keratoconjunctivitis; AKC = atopic keratoconjunctivitis; Photo courtesy of Christine W. Sindt, OD, FAAO CLPC = contact lens–papillary conjunctivitis

4 CLPC is also associated with more severe pruritus than allergic conjunctivitis. Eversion of the upper eyelid allows the clinician to examine for papillary changes in the upper tarsal plate that are pathognomonic of CLPC (Figures 6 and 7) and should be performed in all contact lens wearers, whether or not they are symptomatic. The presence of a velvety appearing tarsal plate in asymptomatic patients is an early sign of CLPC. Detection of this change allows for timely intervention that can prevent progression to the development of frank giant papillae and the unfortunate sequelae of contact lens intolerance.

Figure 4. Large, irregular macropapillae on the upper tarsus are a common Patients who are contact lens wearers may also develop red, finding in atopic keratoconjunctivis. With chronic disease, inflammation may irritated eyes for a variety of other reasons that are related to lead to scarring. lens fit, lens material and/or design, hygiene, wearing schedule, or a lens-care solution interaction. These problems Photo courtesy of Al Kabat, OD, FAAO may occur in isolation or coexist and exacerbate allergic conjunctivitis. Patients with allergy who also wear contact lenses will often experience greater symptoms of redness, itching, and discomfort than those patients who do not wear contact lenses. Having patients temporarily discontinue contact lens wear can help to rule out a contact lens–related cause, but this idea is often rejected by some patients, especially if they are not highly symptomatic. Determining if the patient’s signs and symptoms of itching and redness worsen after the lenses are inserted in the morning can direct the evaluation toward identifying possible sources of contact lens–related ocular redness and irritation. Infectious causes of conjunctivitis Figure 5. Giant “cobblestone” papillae, seen here upon eversion of the upper (bacterial, viral, chlamydial) should also be considered. lid, are a hallmark of vernal keratoconjunctivitis. Note the polygonal shape and lack of uniformity. Treatment of Allergic Conjunctivitis Photo courtesy of Al Kabat, OD, FAAO Effective treatment of allergic conjunctivitis incorporates nonpharmacologic and pharmacologic interventions. Nonpharmacologic strategies focus primarily on environmental measures to reduce exposure. These strategies include limiting time spent outdoors during periods when allergen levels are high and wearing sunglasses to protect the eyes from additional allergen loads while outside. Showering and washing or rinsing the hair at night before going to bed minimizes the allergen load that may be in the hair. Furthermore, although difficult, avoiding eye rubbing is important as it can mechanically induce mast cell release and also introduce allergens from the skin. Since many patients are allergic to dust mites and because Figure 6. View of the everted upper eyelid in a patient who developed contact lens–induced papillary conjunctivitis due to contact lens overwear. mites accumulate in pillows and bedding, patients may be advised about using hypoallergenic bedding, changing their Photo courtesy of Mile Brujic, OD, FAAO sheets frequently and washing them in hot water, and putting their pillow into a hot dryer for 20 minutes to kill dust mites. Keeping the windows and doors closed at home, taking shoes and outerwear off at the door, removing carpets from floors, and using a high-efficiency particulate absorption filter to remove allergens from the circulating air are all strategies to reduce the indoor allergen burden.

In addition to strategies for allergen avoidance, patients can be advised about topical nonpharmacologic measures to control allergic conjunctivitis. The use of artificial tears, isotonic , or rewetting drops by contact lens wearers can be a helpful strategy to dilute and flush away allergens and inflammatory Figure 7. Contact lens–induced papillary conjunctivitis with large papillae mediators. In general, preservative-free formulations are noted in Zones 2 and 3 of the upper tarsal plate. preferred to avoid any potential for preservative-induced Photo courtesy of Loretta Szczotka-Flynn OD, PhD, FAAO hypersensitivity, and refrigeration of these topical products is

5 Table 2. Over-the-Counter and Prescription Medications for Ocular Allergy12

Generic (brand) name Indication Pediatric use Dosing OTC PRODUCTS

H1-antagonist/

Ketotifen fumaratea, 0.025%, Temporary relief of itchy eyes due to ragweed, pollen, ≥3 years twice a day, (Alaway, Claritin Eye, Eye Itch Relief, Zaditor, grass, animal hair, and dander every 8 to 12 hours Zyrtec Itchy Eye, generic) /antihistamine /pheniramine Temporary relief of minor eye symptoms of itching ≥6 years 1 or 2 drops up to (Naphcon-A, Opcon-A, Visine-A) and redness caused by ragweed, pollen grass, animal 4 times daily dander, and hair

PRESCRIPTION PRODUCTS

Emedastine difumarate, 0.05%, (Emadine) Temporary relief of the signs and symptoms of AC ≥3 years up to 4 times a day

Dual acting antihistamine/mast cell stabilizers

Alcaftadine, 0.25%, (Lastacaft) Prevention of itching associated with AC ≥2 years once a day

Azelastine, 0.05%, (Optivar + generic) Treatment of itching of the eye associated with AC ≥ 3 years twice a day

Bepotastine besilate, 1.5%, (Bepreve) Treatment of itching associated with AC ≥2 years twice a day

Epinastine HCl, 0.05%, (Elestat + generic) Prevention of itching associated with AC ≥2 years twice a day

Olopatadine HCl, 0.1%, (Patanol) Treatment of the signs and symptoms of AC ≥3 years twice a day (at an interval of 6 to 8 hours)

Olopatadine HCl, 0.2%, (Pataday) Treatment of ocular itching associated with AC ≥2 years once a day

Mast cell stabilizers

Cromolyn sodium, 4%, (Crolom, generic) Treatment of VKC, vernal conjunctivitis, ≥4 years 1 to 2 drops 4 to 6 times and vernal keratitis daily

Lodoxamide tromethamine, 0.1%, (Alomide) Treatment of VKC, vernal conjunctivitis, ≥2 years 1 to 2 drops and vernal keratitis 4 times a day for up to 3 months sodium, 2%, (Alocril + generic) Treatment of itching associated with AC ≥3 years 1 to 2 drops up to twice a day

Pemirolast potassium, 0.1%, (Alamast) Prevention of itching of the eye due to AC ≥3 years 1 to 2 drops 4 times a day

Other

Ketorolac tromethamine, 0.5%, (Acular + Temporary relief of ocular itching due to SAC ≥2 years 4 times a day generic) (NSAID)

Loteprednol etabonate, 0.2%, (Alrex) Temporary relief of the signs and symptoms of SAC Safety and effectiveness 4 times a day (Ester ) not established in pediatric patients aThe www.pdr.net drug summary for ketotifen fumarate lists antihistamine for mechanism of action. However, in addition to being a noncompetitive H1-antagonist, ketotifen also has mast cell stabilizing activity.11

AC = allergic conjunctivitis; H1 = histamine1; NSAID = nonsteroidal anti-inflammatory drug; SAC = seasonal allergic conjunctivitis; VKC = vernal keratoconjunctivitis

6 Antigen binds to IgE

Mast cell degranulates

Preformed mediators Newly formed mediators Chemokines & cytokines

Histamine Proteases Heparin Eicosanoids (prostaglandins, Platelet-activating leukotrienes, factor thromboxanes) Itching Chemosis Redness IgE expression Mucus secretion Itching Redness Leukocyte activation Upregulation of Redness Chemosis & migration Tearing adhesion molecules Mucus secretion Nerve stimulation Leukocyte infiltration

Figure 8. Immunology of allergic conjunctivitis. SAC and PAC develop as an immune-mediated response to allergen exposure in a sensitized individual. SAC is caused by tree, grass, and weed pollens while the most common allergens causing PAC are mold spores, dust mites, and animal dander. The allergic reaction begins with mast cell activation that is triggered by allergen binding to IgE antibodies on the surface of conjunctival mast cells. This early phase of the allergic reaction is characterized by mast cell destabilization leading to degranulation with the release of numerous preformed and newly formed chemical mediators, including histamine, leukotrienes, prostaglandins, proteases, and cytokines. The early phase response occurs very quickly after allergen exposure and peaks at about 20 minutes.13 Histamine, the principal mediator of the early phase reaction, binds to histamine receptors, leading to itch, redness, tearing, and swelling. Other mediators released from the mast cells contribute to the signs and symptoms of the early phase reaction through proinflammatory activity and effects on vascular permeability, and some have chemotactic properties, attracting inflammatory cells that mediate the late phase response.13 The late phase response is seen at about 6 hours after allergen exposure and is characterized by upregulation of adhesion molecules and increased infiltration of mast cells along with eosinophils and other inflammatory cells into the conjunctiva.13 The actions of these cells and the mediators they release lead to a prolonged and heightened allergic response. helpful as the cold solution is both soothing and acts to The various medications also differ in their recommended counteract the elevated tissue temperature associated dosing frequency, which is an important issue for any with inflammation. medication as it affects compliance and therefore the likelihood of treatment success. Medications that require Medical Therapy only once- or twice-daily dosing are also highly desirable for The feasibility of nonpharmacologic approaches for ocular contact lens users who would need to remove their lenses at allergy management varies depending on lifestyle issues and least once during the day to use a product that involves more the causative allergen. While they may be sufficient for frequent instillation. patients who are only mildly symptomatic, they are often unsatisfactory as a stand-alone measure. Therefore, medical . Most topical OTC products sold for therapy is the cornerstone for effective management of most treating signs and symptoms of allergic conjunctivitis patients with allergic conjunctivitis. combine a decongestant (eg, naphazoline, tetrahydrozoline) with an antihistamine (eg, pheniramine). OTC products OTC and prescription products available for treating allergic containing only a topical decongestant (eg, naphazoline, conjunctivitis include medications that act as decongestants, tetrahydrozoline, ) are sold to relieve ocular antihistamines, mast cell stabilizers, antihistamine/mast cell redness, burning, irritation, and dryness caused by wind, sun, 12 stabilizers, and anti-inflammatory agents (Table 2). The role of and other minor irritants. these different classes as preventive therapy versus providing acute relief—as well as their effects on specific signs and Topical decongestants are adrenergic agonists that reduce symptoms—can be understood by considering the cellular redness by causing . However, they have a and molecular mediators of the allergic cascade (Figure 8). relatively short duration of action and so require frequent

7 dosing, 1 to 2 drops up to 4 times daily.14 Furthermore, these act on both the early and late phases of the medications often cause burning and stinging.14 In addition, allergic reaction by suppressing mast cell proliferation, inhibiting the chronic use of a topical decongestant can lead to the production of multiple inflammatory mediators, and conjunctival inflammation that can exacerbate the allergic reducing the influx of inflammatory cells.21 There is conflicting reaction and be associated with rebound hyperemia when information about the relative efficacy of corticosteroids versus treatment is stopped.15 Other adverse reactions reported with antihistamine/mast cell stabilizers for relieving itching,22,23 the chronic use of topical decongestants include pupillary although an agent with antihistamine activity would be dilation, corneal opacities, and dry eye.16-18 In addition, expected to provide faster onset of relief. Intraocular pressure topical decongestants are contraindicated in patients with (IOP) monitoring at follow-up visits is important for all patients angle-closure glaucoma and associated with potential safety being treated with a topical corticosteroid. concerns in patients with cardiovascular disease, hyperthyroidism, and diabetes. Nonsteroidal anti-inflammatory drugs act to prevent prostaglandin synthesis and desensitize pain receptors so Antihistamines. Antihistamines provide rapid relief of itching that they decrease inflammation and itching. However, by blocking histamine binding to its receptors. However, they ketorolac tromethamine, 0.5%, is the only topical NSAID do not prevent initiation of the allergic cascade or inhibit the approved by the US Food and Drug Administration (FDA) for activity of any other allergy mediators. Oral antihistamines the management of allergic conjunctivitis, and it is not widely may be helpful for patients with allergic nasal symptoms, but used because of the availability of more effective options and can lead to dry mouth, ocular surface dryness, and sedation. its high potential to cause burning and stinging with These adverse reactions particularly occur with older instillation. According to the prescribing information, up to 19 generation antihistamines. However, sedation can also occur 40% of the patients using ketorolac tromethamine, 0.5%, 19 with cetirizine, and both cetirizine and loratadine have been experienced burning and stinging.24 associated with ocular drying effects.20

Mast cell stabilizers. Mast cell stabilizers act to prevent the Patient Counseling degranulation of mast cells; they are useful to prevent Reviewing the available options with patients helps them to sequelae from future allergen exposure. They do not inhibit understand the rationale for their clinician’s therapeutic the action of any mediators that are already released. recommendations and engages them as partners in care, Therefore, mast cell stabilizers do not provide acute relief which can help to improve compliance. The discussion with from existing signs and symptoms. patients on medications should include information about relative costs, dosing frequency, efficacy, and possible adverse Dual-acting antihistamine/mast cell stabilizers. reactions. It should conclude with a definitive recommendation Medications that provide both antihistamine and mast cell and prescription for what the optometrist considers as the stabilizing properties are the current mainstay for the best option, although still making sure that patients management of allergic conjunctivitis, and many of these understand other modalities can be tried if the first is medications offer activity against the inflammatory cells and cytokines involved in the delayed allergic response. With unsatisfactory. Consider, for example, the situation in which a their multimodal mechanisms, these agents can prevent the patient picks up a prescription and finds it is prohibitively onset of the allergic response if started prior to allergen expensive. Patients who have not been informed about viable exposure as well as provide immediate and ongoing relief in alternatives may be displeased with their doctor and choose patients who have experienced a flare-up. to self-treat with an OTC product and/or see another provider.

Available antihistamine/mast cell stabilizers include 1 agent Although it is important to be sensitive to cost issues, OTC available in OTC products and several prescription products may offer less value than prescription products, at medications. The antihistamine/mast cell stabilizers offer least, in part, because the OTC medications may require convenient dosing schedules of only once or twice a day and more frequent dosing. Providing patients with some are safe. In clinical practice, they have been used on a long- suggestions about OTC products to try also puts the onus on term basis without any serious adverse reactions. The only them to go to the store, decide among a host of agents, and precaution to their use is to avoid in patients with make the purchase. Handing patients a written prescription hypersensitivity to any ingredient in the formulation. reduces reliance on patient follow-through, but still assumes the patient will bring the prescription to the pharmacy. Anti-inflammatory agents. Corticosteroid treatment has a Sending a prescription directly to the pharmacy goes 1 step critical role for managing inflammation associated with the further and also reinforces the optometrist’s authoritative severe forms of ocular allergy, VKC, AKC, and CLPC, and is position. Follow-up visits will verify that patients are using useful as a short-term intervention for controlling a severe their treatment and determine its success. presentation of acute SAC or PAC. In addition, corticosteroid treatment can be useful on a short-term basis for dry eye It is better to have patients schedule the visit before they disease, which may be comorbid with allergy. leave the office than to suggest they call for an appointment.

8 who have year-round exposure to triggering allergens may be Why Samples Are Not Always maintained on an antihistamine/mast cell stabilizer indefinitely. Again, medications with mast cell stabilizing a Good Thing activity alone might be considered instead for maintenance, Sometimes optometrists think they are doing patients but their more frequent dosing schedule can present a a service by handing out medication samples. compliance issue, and they would not control symptoms if However, similar to seeing a mint left on a hotel pillow mast cell degranulation occurs. at night, patients may consider the sample a nice Patients with comorbid allergic disorders may be referred to gesture, but assign little value to it because it is free. an allergist for further evaluation and optimal management of The end result is that they may be unlikely to use the their nonocular symptoms. product or even to remember its name. In contrast, when patients are given a prescription for Allergic Conjunctivitis in a medication along with an explanation of why that Patients Wearing Contact Lenses specific product was chosen, they are more likely to regard it as important and be compliant with the Lens Selection and Care instructions for use. Allergic conjunctivitis is an important contributor to contact lens intolerance as demonstrated by the results of a study showing that 75% of the patients with allergic Treatment Selection rhinoconjunctivitis reported partial or absolute intolerance of their lenses.30 Although contact lenses can act as a barrier to Decisions on medical treatment for SAC or PAC depend on airborne allergens, they can also serve as a vehicle for whether the patient needs relief from an acute flare-up or is increasing allergen exposure by trapping environmental being treated to prevent an allergic reaction. allergens and binding antigens from the tear film, ocular An antihistamine/mast cell stabilizer is usually sufficient by surface, lids, and lens care solutions. Considering that itself for treating active disease in patients who have mild to bacteria and bacterial products are well-recognized to be moderate signs and symptoms of SAC or PAC. antigenic in patients with atopic dermatitis and allergic airway disease,31 it is plausible that microbial bioburden on An ophthalmic antihistamine/mast cell stabilizer can also the lens surface may also be a trigger for allergic reactions. 25-27 improve nasal rhinitis, although patients with more than This potential relationship is important considering the mild allergic rhinitis may need additional therapy. The use of ubiquitous opportunities for microorganisms to accumulate a systemic antihistamine that will produce some ocular on the lens surface. drying effects is generally best avoided in patients with allergic conjunctivitis. Alternatives include intranasal Ideally, patients might be furloughed from contact lens wear antihistamines and corticosteroids. when they are experiencing significant problems with allergic conjunctivitis. However, most patients will resist this idea, and Patients with a moderate-to-severe flare of AC or PAC may be it is impractical for others, such as patients with keratoconus started simultaneously on a topical corticosteroid that is then whose visual function depends on gas permeable (GP) tapered off when signs of inflammation improve. Anecdotally, contact lens wear. Concern about the buildup of antigens most patients achieve an adequate response after only 1 or on the contact lens surface provides a rationale for 2 weeks of corticosteroid treatment. Scheduling a follow-up recommending daily disposable lenses to soft contact lens visit 5 to 7 days after corticosteroid initiation will allow the clinician to evaluate its benefit and safety. Although all wearers who are suffering with allergic conjunctivitis, and corticosteroids can be used to control ocular inflammation, there is clinical trial evidence showing the efficacy of this 32 loteprednol etabonate, 0.2%, is indicated specifically for relief strategy for improving patient comfort. Daily disposable of the signs and symptoms of SAC, and has a good safety lenses provide the benefits of placing a new, clean lens on profile with respect to risk of IOP elevation.28,29 the eye at the beginning of every day. Thus, any deposition that may have occurred on the lens the prior day is not an Patients with SAC may begin using an antihistamine/mast exacerbating issue. Furthermore, the use of daily disposable cell stabilizer prior to the start of allergy season and continue lenses eliminates exposing the eye to lens care solution using the medication while allergen levels remain elevated. ingredients that can themselves precipitate allergic reactions. Although a mast cell stabilizer could also theoretically be prescribed for this purpose, it rarely is because it usually As technologies have advanced with 2-week and monthly requires more frequent dosing and does not provide disposable lenses, there has also been a significant evolution antihistamine activity that will help patients when challenged in the daily disposable lens modality. Several product options with allergens. A similar preventive approach using an are currently available in the daily disposable lens category antihistamine/mast cell stabilizer can be recommended to that represent 3 different material types: hydrogel, silicone patients with PAC who are able to anticipate allergen hydrogel, and water gradient technology. In addition, new exposure (eg, a patient who is allergic to horse dander and wetting agents are being added to lenses in an attempt to will encounter the animals on vacation). Patients with PAC improve the lens wearing experience.

9 There are no conclusive clinical trial data or other evidence well for patients with keratoconus, the challenge of ocular on which to base recommendations for choosing any allergies can make lens wear much more difficult for this particular daily disposable product or material class. Different population. Edge awareness is especially problematic in lenses within the same class may have unique chemical allergic patients because they have a compromised and characteristics. inflamed ocular surface. Large diameter GP lenses, such as scleral lenses, minimizes the lens edge interaction and A new category of water gradient technology lenses made of provides an alternative for those patients experiencing deleficon A is the latest addition to the daily disposable significant comfort issues wearing small diameter lenses. market. This lens has a high dK silicone hydrogel core with an outer layer (~10% of the lens thickness) made of a nonsilicone hydrophilic polymer. The water content of the Medication Use With Contact Lens Wear lens varies from 33% for the silicone hydrogel core to >80% Effective treatment of allergic conjunctivitis using topical on average for the outer layer in which the water content antihistamine/mast cell stabilizing agents can improve transitions to reach almost 100% at the surface. The lens comfort in contact lens wearing patients.36,37 However, surface is also unique in its level of lubricity33; it was shown because soft contact lenses can absorb medications and act to have less impact on the prelens tear film surface quality as a platform for sustained drug delivery,38 patients wearing than a daily disposable hydrogel lens made of nelficon A.34 soft contact lenses must be counseled not to use these With its moisture rich surface characteristics, the water allergy medications while wearing their lenses and to wait gradient technology lens is a logical consideration in the 10 to 15 minutes after instilling drops before inserting their challenging population of patients with ocular allergy. lenses. Considering the risks associated with corticosteroid treatment (ie, IOP elevation, cataract formation, and When a daily disposable contact lens is not a viable option secondary infection), it is best to discontinue wearing contact for a patient with ocular allergies who wears soft contact lens while patients are being treated with a corticosteroid. lenses, other strategies need to be put into place to optimize contact lens wear. This process begins with patient education Gas permeable lens materials do not absorb medications, and reinforcing the importance of thorough cleaning and and medication that adheres to the lens surface can be other aspects of good lens hygiene practices. Making sure effectively removed with proper cleaning. Patients with patients are rubbing and rinsing their lenses is critical in this keratoconus and others dependent on their GP lens may be population. In addition, clinicians should ascertain that allowed to continue wearing their contact lenses while being patients have not strayed from using the lens care systems treated with a topical corticosteroid. However, the recommended to them. importance of meticulous lens cleaning, as well as For soft lenses, surfactant cleaners may be needed in rare instructions about not dosing the medication with the lens in instances, in addition to the multipurpose disinfecting solution the eye and waiting after medication dosing to insert the that a patient may be using, as the surfactant cleaner assists in lens, must be reinforced. removing additional antigens from the lens surface of heavily depositing ocular allergy sufferers. The use of a peroxide- conclusion based system for cleaning and disinfection should also be Allergic conjunctivitis can have a significant impact on the considered for these patients as it will minimize chemical exposure on the eye while effectively cleaning the lenses. quality of life for all individuals and poses particular problems for contact lens wearers. Establishing the diagnosis An alcohol-based surfactant cleaner is also effective for of allergic conjunctivitis by conducting an appropriate cleaning GP lenses. To help reduce allergen exposure, patients medical history and a thorough clinical examination of the with GP lenses should be instructed to rinse the lens well with patient is the first step to providing effective care. preservative-free saline before lens insertion. A peroxide-based Optometrists must recognize the importance of being cleaning and disinfection system is approved for use by the proactive in their efforts to identify allergy sufferers. Medical FDA with both soft and GP contact lenses, and should be therapy can effectively relieve distress from the signs and considered in GP lens wearers with significant ocular allergies. symptoms of allergic conjunctivitis and, combined with Among contact lens wearers, the prevalence of allergy is allergen avoidance strategies, can limit allergic episodes in particularly high in patients with keratoconus.35 Patients with most patients. For optimal care, some patients may be best keratoconus require aggressive management of allergic referred to an allergist, and for those who wear contact conjunctivitis to limit eye rubbing that can contribute to their lenses, modern contact lens technology, good lens hygiene, disease progression as well as allow them to maintain and careful selection of care systems can facilitate continued contact lens wear. Although small diameter GP lenses work comfortable wear.

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To Obtain COPE Credit Online and Instant Certificate To obtain COPE CE Credit for this activity, read the material in its entirety and consult referenced sources as necessary. We offer instant certificate processing and support Green CE. Please take this post test and evaluation online by going to http://tinyurl.com/OcularSurface1. 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.

Look for the second CE module of Ocular Surface Wellness—Dry Eye in a coming issue. ar Surfac Ocul e W in ell tes ne da ss Up

Part 1: Ocular Allergy