Allergic Conjunctivitis
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The ocular surface may exhibit a wide variety of immunologic responses resulting in inflammation of the conjunctiva and cornea. In the Gell and Coombs classification system for various immunologic hypersensitivity reactions, 5 types of reactions are recognized. The major type I hypersensitivity reactions involving the conjunctiva are commonly referred to as allergic conjunctivitis and are further subclassified into seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). Far less common are the more severe forms of allergic conjunctivitis, including atopic keratoconjunctivitis (AKC), giant papillary conjunctivitis (GPC), and limbal and tarsal vernal keratoconjunctivitis (VKC).
Diagnosis of allergic conjunctivitis is generally made by thorough history and careful clinical observation (see Clinical). The presence of an antigen triggers the allergic cascade, and, thus, avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis. In other respects, management of allergic conjunctivitis varies somewhat according to the specific subtype. Allergic conjunctivitis can be treated with a variety of drugs, including topical antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, and corticosteroids (see Treatment).
See the following for more information:
Acute Hemorrhagic Conjunctivitis
Emergent Treatment of Acute Conjunctivitis
Giant Papillary Conjunctivitis
Superior Limbic Keratoconjunctivitis
Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells, and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell degranulation.
The mast cell’s degranulation releases various preformed and newly formed mediators of the inflammatory cascade. Most notable of these inflammatory mediators are histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various inflammatory mediators, together with various chemotactic factors, result in an increase in vascular permeability and migration of eosinophils and neutrophils. This type I hypersensitivity reaction is the most common allergic response of the eye. These immune-derived reactions may also be the underlying cause of more rare and serious ocular conditions, such as ocular cicatricial pemphigoid (OCP) and Mooren ulcer.
Type III hypersensitivity reactions result in antigen-antibody immune complexes, which deposit in tissues and cause inflammation. A classic systemic type III reaction is the Arthus reaction, and ocular type III hypersensitivity reactions include Stevens-Johnson syndrome and marginal infiltrates of the cornea. These type III reactions can often induce a corneal immune (Wessely) ring that disintegrates as the inflammatory reaction subsides.
Type IV hypersensitivity reactions, also known as cell-mediated immunity, are facilitated by T lymphocytes, rather than merely antibodies. This inflammatory cell-driven reaction is also referred to as delayed-type hypersensitivity, since its onset is generally after 48 hours, in contrast to the type I reaction, which is an immediate hypersensitivity.
Type IV hypersensitivity reactions imply immunocompetence on the part of the individual since an intact immune system is required to mount the cell-mediated response. Ocular examples of type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection, contact dermatitis, and drug allergies, although drug sensitivities can lead to all four types of hypersensitivity reaction.
Allergic conjunctivitis may be divided into 5 major subcategories.
Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are commonly grouped together.
Vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC) constitute the remaining subtypes of allergic conjunctivitis.
Early diagnosis and treatment will help prevent the rare complications that can occur with this disease.
Since allergic conjunctivitis generally clears up readily, the prognosis is favorable. Complications are very rare, with secondary corneal ulcers or keratoconus occurring rarely. Although SAC, PAC, and GPC commonly reoccur, they rarely cause any visual loss. Conversely, VKC and AKC are frequently associated with significant risk of progressive corneal damage and resultant visual loss.
Patients should make every attempt to identify the allergen causing the problem and to avoid the offending antigen. For patient education information, see the Eye and Vision Center, as well as Pinkeye, Eye Allergies, and How to Instill Your Eyedrops.
Since the conjunctiva is a mucosal surface similar to the nasal mucosa, the same allergens that trigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis. Common airborne antigens, including dust, molds, pollen, grass, and weeds, may provoke the symptoms of acute allergic conjunctivitis, such as ocular itching, redness, burning, and tearing. The main distinction between SAC and PAC, as implied by the names, is the timing of symptoms.
Individuals with SAC typically have symptoms of acute allergic conjunctivitis for a defined period of time, that is, in spring, when the predominant airborne allergen is tree pollen; in summer, when the predominant allergen is grass pollen; or in fall, when the predominant allergen is weed pollen. Typically, persons with SAC are symptom-free during the winter months in cooler climates because of the decreased airborne transmission of these allergens. Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. One study found that outside the pollen season, allergic inflammation did not cause permanent tear film instability. [1]
In contrast, individuals with PAC may have symptoms that last the year round; thus, PAC may not be caused exclusively by seasonal allergens, although they may play a role. Other common household allergens, such as dust mite, cockroach dust, cigarette smoke, airborne allergens, molds, and pet dander, may be responsible for the symptoms of PAC.
VKC is a chronic bilateral inflammation of the conjunctiva, commonly associated with a personal and/or family history of atopy. More than 90% of patients with VKC exhibit one or more atopic conditions, such as asthma, eczema, or seasonal allergic rhinitis. Corneal complications and conjunctival scarring frequently occur, particularly in more severe cases and in patients whose VKC onsets at a very young age.
AKC is a bilateral inflammation of conjunctiva and eyelids, which has a strong association with atopic dermatitis. It is also a type I hypersensitivity disorder with many similarities to VKC, yet AKC is distinct in a number of ways.
In 1953, Hogan first described the association between atopic dermatitis and conjunctival inflammation. [2] He reported 5 cases of conjunctival inflammation in male patients with atopic dermatitis. [2] Atopic dermatitis is a common hereditary disorder that usually first appears childhood; symptoms may regress with advancing age. Approximately 3% of the population is afflicted with atopic dermatitis, and, of these, approximately 25% have ocular involvement. Again, more advanced cases may result in significant conjunctival cicatrization, severe dry eye, and loss of corneal clarity through chronic or acute keratitis.
GPC is an immune-mediated inflammatory disorder of the superior tarsal conjunctiva. As the name implies, the primary finding is the presence of “giant” tarsal papillae, which are typically greater than 0.3 mm in diameter.
A combination of type I and type IV hypersensitivity reactions may be responsible for the pathogenesis of GPC. It is believed that an antigen is present, in predisposed individuals, which stimulates the immunological reaction and the development of GPC.
Prolonged mechanical irritation to the superior tarsal conjunctiva, of the upper lid, from any of a variety of foreign bodies may also be a contributing factor in GPC. Although contact lenses (hard and soft) are the most common irritant, ocular prostheses, extruded scleral buckles, elevated glaucoma shunts or filtering blebs, scleral shells, and exposed sutures following previous surgical intervention may also precipitate GPC.
Allergic conjunctivitis occurs very frequently and is seen most commonly in areas with high seasonal allergen and pollen counts. VKC occurs predominantly in areas with tropical and temperate climates, such as the Mediterranean, the Middle East, and Africa. The limbal form of VKC commonly occurs in dark-skinned individuals from Africa and India.
VKC has a significant male preponderance, typically affecting young males. The onset of VKC generally occurs in the first decade and persists throughout the first 2 decades. Symptoms usually peak prior to the onset of puberty and then subside.
In general, the prognosis of SAC and PAC is good despite significant discomfort and undesirable cosmetic consequences. Occasionally, individuals with chronic recurrences develop significant conjunctivochalasis or, less commonly, a corneal Dellen secondary to persistent limbal conjunctival chemosis. Conversely, AKC and VKC may lead to significant corneal complications such as ulceration and opacification, leading to permanent visual loss. Furthermore, significant chronic ocular surface disease places these patients at high risk for corneal transplantation complications and rejection. Lid involvement from any type of allergic conjunctivitis, particularly GPC, can significantly compromise contact lens tolerance. Medications used for allergic disease may lead to complications such as preservative toxicity and steroid-induced intraocular pressure (IOP) elevations or steroid-related cataract.
Kosina-Hagyó K, Veres A, Fodor E, Mezei G, Csákány B, Németh J. Tear film function in patients with seasonal allergic conjunctivitis outside the pollen season. Int Arch Allergy Immunol. 2012. 157(1):81-8. [Medline].
Hogan MJ. Atopic keratoconjunctivitis. Am J Ophthalmol. 1953. 36:937-947.
Allansmith MR, Korb DR, Greiner JV, Henriquez AS, Simon MA, Finnemore VM. Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol. 1977 May. 83(5):697-708. [Medline].
Calderon MA, Penagos M, Sheikh A, Canonica GW, Durham S. Sublingual immunotherapy for treating allergic conjunctivitis. Cochrane Database Syst Rev. 2011 Jul 6. CD007685. [Medline].
Wahn U, Klimek L, Ploszczuk A, Adelt T, Sandner B, Trebas-Pietras E, et al. High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: A double-blind, placebo-controlled study. J Allergy Clin Immunol. 2012 Aug 29. [Medline].
Aswad MI, Tauber J, Baum J. Plasmapheresis treatment in patients with severe atopic keratoconjunctivitis. Ophthalmology. 1988 Apr. 95(4):444-7. [Medline].
Abelson MB, Gomes PJ, Vogelson CT, Pasquine TA, Turner FD, Wells DT, et al. Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis. Curr Med Res Opin. 2005 May. 21(5):683-91. [Medline].
Abelson MB, Greiner JV. Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model. Curr Med Res Opin. 2004 Dec. 20(12):1953-8. [Medline].
Williams PB, Sheppard JD Jr. Omalizumab: a future innovation for treatment of severe ocular allergy?. Expert Opin Biol Ther. 2005 Dec. 5 (12):1603-9. [Medline].
Williams PB, Crandall E, Sheppard JD. Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis. Clin Ophthalmol. 2010 Sep 7. 4:993-1001. [Medline].
Characteristics
VKC
AKC
Age at onset
Generally presents at a younger age than AKC’ first decade
Second to third decade
Sex
Males are affected preferentially.
No sex predilection
Seasonal variation
Typically occurs during spring months
Generally perennial
Discharge
Thick mucoid discharge
Watery and clear discharge
Conjunctival scarring
Moderate incidence of conjunctival scarring
Higher incidence of conjunctival scarring
Horner-Trantas dots
Horner-Trantas dots and shield ulcers are commonly seen.
Presence of Horner-Trantas dots is rare.
Corneal neovascularization
Not present, unless secondary to infectious keratitis
Deep corneal neovascularization tends to develop
Presence of eosinophils in conjunctival scraping
Conjunctival scraping reveals eosinophils to a greater degree in VKC than in AKC
Presence of eosinophils is less likely
Mark Ventocilla, OD, FAAO Adjunct Clinical Professor, Michigan College of Optometry; Editor, American Optometric Association Ocular Surface Society Newsletter; Chief Executive Officer, Elder Eye Care Group, PLC; Chief Executive Officer, Mark Ventocilla, OD, Inc; President, California Eye Wear, Oakwood Optical
Mark Ventocilla, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Optometric Association
Disclosure: Nothing to disclose.
Marc R Bloomenstein, OD, FAAO Director of Optometric Services, Schwartz Laser Eye Center; Adjunct Assistant Professor, Arizona College of Optometry; Adjunct Assistant Professor, Southern California College of Optometry
Marc R Bloomenstein, OD, FAAO is a member of the following medical societies: International Society of Refractive Surgery, American Academy of Optometry, American Optometric Association, Arizona Optometric Association
Disclosure: Nothing to disclose.
Parag A Majmudar, MD Fellowship Co-Director, Assistant Professor, Department of Ophthalmology, Cornea and Refractive Surgery Service, Rush-Presbyterian-St Luke’s Medical Center
Parag A Majmudar, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, International Society of Refractive Surgery, Phi Beta Kappa
Disclosure: Received consulting fee from Allergan for consulting; Received consulting fee from Alcon for consulting; Received consulting fee from Bausch + Lomb for consulting; Received consulting fee from Tear Science for consulting.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center
Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society
Disclosure: Nothing to disclose.
Jerre Freeman, MD Founder and Chairman, Memphis Eye and Cataract Associates; Clinical Professor, Department of Ophthalmology, University of Tennessee Health Science Center College of Medicine
Jerre Freeman, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Cataract and Refractive Surgery, and Tennessee Medical Association
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; EyeGate Pharma Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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