Allergic conjunctivitis is a common, under-appreciated and largely a benign process. It is rarely vision-threatening but can significantly decrease the quality of life for patients. There are three subtypes of simple allergic conjunctivitis: acute, seasonal and perennial. There is considerable overlap with atopic conjunctivitis (vernal and atopic keratoconjunctivitis) as well as giant papillary conjunctivitis in both treatment and certain aspects of pathophysiology. As such, these are all considered to be ocular allergies. Initial treatment strategies can be similar although outcomes and rates of complications vary.
Simple Allergic Conjunctivitis: Most cases are secondary to simple allergen exposure on the ocular surface.
Vernal Keratoconjunctivitis: Exact etiology is not well understood but some combination of climate and allergen is believed to be responsible.
Atopic Keratoconjunctivitis: Etiology is not clear but appears to be a combination of allergen exposure, atopic dermatitis (more than 90% of cases) and\or genetic predisposition.
Giant Papillary Conjunctivitis: Allergen exposure and subsequent response secondary to the ocular foreign body either harboring allergens on its surface or injuring ocular structures which facilitate allergen infiltration. It can be seen with many different ocular foreign bodies (eg., contact lenses, prostheses, cyanoacrylate glue, sutures).
Simple Allergic Conjunctivitis: It is difficult to estimate how many patients are affected as the symptoms are often under-appreciated, and many patients go without seeking medical care. Simple ocular allergy likely affects between 10% to 30% of the general population. In most cases, onset occurs in patients younger than 20 years old with decreasing prevalence in older populations. Allergic conjunctivitis can be seen as an isolated finding but is often associated with allergic rhinitis, atopic dermatitis, and/or asthma.
Vernal Keratoconjunctivitis: More commonly seen in males (ratio 2:1 to 3:1) in dry, warm climates. Most cases occur in patients younger than ten who often have a history of atopy or asthma. Many patients have complete resolution without the return of symptoms after adolescence.
Atopic Keratoconjunctivitis: Not usually seen before adolescence and peaks from 30 to 50 years of age. Most cases are seen in patients with atopic dermatitis. Like vernal keratoconjunctivitis, there is a male to female predominance (2:1 to 3:1)
Giant Papillary Conjunctivitis: Seen most commonly in teens and young adults, most likely because of a temporal relationship with contact lens use. Most commonly seen in conjunction with soft contact lens use and is present in approximately 5% of that population. Average onset is one to two years after starting soft contact lenses but varies widely with other ocular foreign bodies.
Simple allergic conjunctivitis (acute, seasonal and perennial) is an immunoglobulin E (IgE) mediated hypersensitivity reaction (type I) and resultant mast cell degranulation secondary to direct contact with an allergen to the ocular surface. As such, there is an immediate and delayed phase of the reaction mediated by different inflammatory modulators. The exact mechanism involved in vernal keratoconjunctivitis is not well understood, but it is likely that there is an IgE mediated hypersensitivity as well as T cell involvement in the reaction. Atopic keratoconjunctivitis appears to be a combination of delayed type (type IV) and immediate (type I) hypersensitivity to an ocular allergen exposure. Giant papillary conjunctivitis occurs secondary to direct mechanical irritation/injury and subsequent immune response (type I and type IV). The foreign object may become coated with different allergens or injury epithelial tissue and allow deeper exposure to allergens and provoke an immunological response.
Allergic conjunctivitis frequently accompanies seasonal allergy symptoms, specifically known allergy exposures or a history of atopy. As such, recurrent episodes are commonly seen. Practitioners should elicit a personal history of allergies and atopy, as well as, a history of similar episodes in the past. Practitioners should ask about specific symptoms from the current and any past episodes. Itchiness and diffuse bulbar and tarsal conjunctival injection are the most commonly reported symptoms and are present in all subtypes of allergic conjunctivitis. Other histories and physical exam findings vary with the specific subtype of allergic conjunctivitis.
Simple Allergic Conjunctivitis: Clear, watery discharge is the most commonly seen discharge and is usually bilateral with minimal crusting in the mornings. Pain and decreased visual acuity are not commonly reported in simple allergic conjunctivitis and should prompt the provider to consider another diagnosis. Eyelid edema and chemosis are not uncommon and can be quite marked.
Vernal Keratoconjunctivitis: Symptoms are usually most severe in the spring and include thick mucus discharge, pain, photophobia and blurred vision. Patients will also often complain of foreign body sensation. On examination, corneal ulcers and conjunctival infiltrates can sometimes be found. Giant papillae on the tarsal conjunctiva are universally seen on examination.
Atopic Keratoconjunctivitis: Symptoms are usually perennial and include pain, blurry vision, photophobia and foreign body sensation. Examination reveals findings similar to simple allergic conjunctivitis with the addition of chronic inflammatory changes to the ocular surface (corneal scarring and neovascularization) and varied changes to the eyelids (lower lid more commonly) and peri-orbital skin that range from mild atopy to lichenification.
Giant Papillary Conjunctivitis: Symptoms consistent with simple allergic conjunctivitis often give way to worsening itch and discharge that becomes thick mucus instead of clear and watery. Patients usually report worsening pain and blurry vision with the increased sense of foreign body (contact lenses, sutures). The examination reveals findings consistent with simple allergic conjunctivitis as well as giant papillae covering the tarsal conjunctiva.
The diagnosis is made clinically with a thorough history and classic physical examination findings. If there is any concern based on the history and physical examination, fluorescein staining of the cornea can be used to ensure that there is no corneal abrasion. Laboratory testing is generally not needed, although skin prick or serum allergy testing can be helpful for mitigating the disease process by identifying the offending allergens so that they can be avoided if possible.
Simple allergic conjunctivitis: All patients should be educated about general allergic eye care. They should be discouraged from rubbing their eyes which causes mast cell degranulation and worsening of symptoms. They should be asked to apply artificial tears and cool compresses frequently. If possible, they need to avoid known allergen exposures and remove contact lenses (if applicable). Mild acute forms can be treated with over the counter antihistamines, or antihistamine and vasoconstrictor combination drops for relatively short periods. The patient should be warned against mild rebound conjunctival injection if they use a drop with a vasoconstrictor. Seasonal and perennial allergic conjunctivitis should be given combination antihistamine and mast cell stabilizing drops. Topical nonsteroidal anti-inflammatory drops are more effective than placebo but far less so than antihistamine/mast cell stabilizing drops. For refractory cases, corticosteroid drops can be used in short bursts (less than two weeks) in conjunction with a specialist consultation and follow-up. Systemic antihistamines and steroids also have a limited role in refractory cases and in cases where the patient has systemic, as opposed to isolated ocular, symptoms.
Vernal and Atopic Keratoconjunctivitis: Patients should be given the same education about general allergic eye care (avoid rubbing eyes, use artificial tears and cool compresses, avoid allergen exposure) as simple allergic conjunctivitis. Initial pharmacotherapy is similar to seasonal and perennial allergic conjunctivitis with topical combination antihistamine/mast cell stabilizing drops. Refractory cases should be referred to a specialist who can prescribe topical corticosteroid. If the patient continues to be refractory or cannot be weaned from topical steroid therapy, topical or systemic calcineurin inhibitors can be used.
Giant Papillary Conjunctivitis: First item of management is to remove the mechanical irritant which is most commonly a contact lens. Patients should be educated and begin the same general allergic eye care used in other subtypes of ocular allergy (avoid rubbing eyes, use artificial tears and cool compresses, avoid allergen exposure). Initial pharmacotherapy is similar to other ocular allergies, for example, topical antihistamine or combination antihistamine and mast cell stabilizing drops. In conjunction with a specialist, topical corticosteroid drops are used in refractory cases (similar to vernal and atopic keratoconjunctivitis), but calcineurin inhibitors have no role in treatment.
Patients with allergic conjunctivitis need to avoid the offending antigen, and often this requires a change in lifestyle. Some patients may need to undergo allergy tests to determine the allergen and then make the behavior changes. Often the wearing of contact lenses may not be possible. In all cases, the patient should be educated on humidifying the home, wearing sunglasses when going out, avoiding mascara and makeup, using artificial tears liberally and applying cold compresses to the eye. 
The long-term outcomes of PAC and SAC are good, but a significant number of people are left with eye discomfort and poor ocular cosmesis. Some individuals develop recurrences leading to conjunctivochalasis-which is secondary to ongoing limbal conjunctival chemosis. Other complications that can occur in VKC and AKC include corneal opacification and ulcer formation. Some patients may develop lid involvement leading to difficulty in wearing contact lenses. Overall, the management of allergic conjunctivitis also leads to time off work and an increased cost of care because of frequent visits to the eye specialist and the need to buy prescription eye drops. Finally, drugs used to manage allergic symptoms may also lead to adverse reactions like cataracts. (Level V)
|||Moote W,Kim H,Ellis AK, Allergen-specific immunotherapy. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018 [PubMed PMID: 30275845]|
|||Small P,Keith PK,Kim H, Allergic rhinitis. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018 [PubMed PMID: 30263033]|
|||Doğan Ü,Ağca S, Investigation of possible risk factors in the development of seasonal allergic conjunctivitis. International journal of ophthalmology. 2018 [PubMed PMID: 30225226]|
|||Ojeda P,Sastre J,Olaguibel JM,Chivato T, Alergólogica 2015: A National Survey on Allergic Diseases in the Adult Spanish Population. Journal of investigational allergology [PubMed PMID: 29939133]|
|||Sen E,Celik S,Inanc M,Elgin U,Ozyurt B,Yılmazbas P, Seasonal distribution of ocular conditions treated at the emergency room: a 1-year prospective study. Arquivos brasileiros de oftalmologia. 2018 Apr [PubMed PMID: 29846426]|
|||Wise SK,Lin SY,Toskala E,Orlandi RR,Akdis CA,Alt JA,Azar A,Baroody FM,Bachert C,Canonica GW,Chacko T,Cingi C,Ciprandi G,Corey J,Cox LS,Creticos PS,Custovic A,Damask C,DeConde A,DelGaudio JM,Ebert CS,Eloy JA,Flanagan CE,Fokkens WJ,Franzese C,Gosepath J,Halderman A,Hamilton RG,Hoffman HJ,Hohlfeld JM,Houser SM,Hwang PH,Incorvaia C,Jarvis D,Khalid AN,Kilpeläinen M,Kingdom TT,Krouse H,Larenas-Linnemann D,Laury AM,Lee SE,Levy JM,Luong AU,Marple BF,McCoul ED,McMains KC,Melén E,Mims JW,Moscato G,Mullol J,Nelson HS,Patadia M,Pawankar R,Pfaar O,Platt MP,Reisacher W,Rondón C,Rudmik L,Ryan M,Sastre J,Schlosser RJ,Settipane RA,Sharma HP,Sheikh A,Smith TL,Tantilipikorn P,Tversky JR,Veling MC,Wang Y,Westman M,Wickman M,Zacharek M, International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. International forum of allergy [PubMed PMID: 29438602]|
|||Jordakieva G,Jensen-Jarolim E, The impact of allergen exposure and specific immunotherapy on circulating blood cells in allergic rhinitis. The World Allergy Organization journal. 2018 [PubMed PMID: 30128065]|
|||Li A,Li S,Ruan F,Jie Y, Atopic keratoconjunctivitis: A diagnostic dilemma-a case report. Medicine. 2018 Apr [PubMed PMID: 29668589]|
|||Arasi S,Corsello G,Villani A,Pajno GB, The future outlook on allergen immunotherapy in children: 2018 and beyond. Italian journal of pediatrics. 2018 Jul 11 [PubMed PMID: 29996875]|
|||Mehta R, Allergy and Asthma: Allergic Rhinitis and Allergic Conjunctivitis. FP essentials. 2018 Sep [PubMed PMID: 30152668]|
|||Takamura E, [GUIDELINES FOR THE CLINICAL MANAGEMENT OF ALLERGIC CONJUNCTIVAL DISEASE THE POINT OF THE MANAGEMENT WITH USING CONVENTIONAL TOOL AND EYE DROPS]. Arerugi = [Allergy]. 2018 [PubMed PMID: 29553108]|
|||Roberts G,Pfaar O,Akdis CA,Ansotegui IJ,Durham SR,Gerth van Wijk R,Halken S,Larenas-Linnemann D,Pawankar R,Pitsios C,Sheikh A,Worm M,Arasi S,Calderon MA,Cingi C,Dhami S,Fauquert JL,Hamelmann E,Hellings P,Jacobsen L,Knol EF,Lin SY,Maggina P,Mösges R,Oude Elberink JNG,Pajno GB,Pastorello EA,Penagos M,Rotiroti G,Schmidt-Weber CB,Timmermans F,Tsilochristou O,Varga EM,Wilkinson JN,Williams A,Zhang L,Agache I,Angier E,Fernandez-Rivas M,Jutel M,Lau S,van Ree R,Ryan D,Sturm GJ,Muraro A, EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy. 2018 Apr [PubMed PMID: 28940458]|
|||Sacchetti M,Abicca I,Bruscolini A,Cavaliere C,Nebbioso M,Lambiase A, Allergic conjunctivitis: current concepts on pathogenesis and management. Journal of biological regulators and homeostatic agents. 2018 Jan-Feb [PubMed PMID: 29552874]|
|||Shaker M,Salcone E, An update on ocular allergy. Current opinion in allergy and clinical immunology. 2016 Oct [PubMed PMID: 27490123]|
|||Sgrulletta R,Bonini S,Lambiase A,Bonini S, Allergy and infections: long-term improvement of vernal keratoconjunctivitis following viral conjunctivitis. European journal of ophthalmology. 2006 May-Jun [PubMed PMID: 16761253]|
|||Passali D,Cingi C,Staffa P,Passali F,Muluk NB,Bellussi ML, The International Study of the Allergic Rhinitis Survey: outcomes from 4 geographical regions. Asia Pacific allergy. 2018 Jan [PubMed PMID: 29423374]|
|||Dhami S,Nurmatov U,Arasi S,Khan T,Asaria M,Zaman H,Agarwal A,Netuveli G,Roberts G,Pfaar O,Muraro A,Ansotegui IJ,Calderon M,Cingi C,Durham S,van Wijk RG,Halken S,Hamelmann E,Hellings P,Jacobsen L,Knol E,Larenas-Linnemann D,Lin S,Maggina P,Mösges R,Oude Elberink H,Pajno G,Panwankar R,Pastorello E,Penagos M,Pitsios C,Rotiroti G,Timmermans F,Tsilochristou O,Varga EM,Schmidt-Weber C,Wilkinson J,Williams A,Worm M,Zhang L,Sheikh A, Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis. Allergy. 2017 Nov [PubMed PMID: 28493631]|