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56 Current Allergy & Clinical Immunology, June 2006 Vol 19, No.2

ALLERGIC CONJUNCTIVITIS

A Ziskind, FCS(SA)(Ophth), MB BCh, MSc(Eng),BSc(Med)

Department of Ophthalmology, Tygerberg AcademicHospital and Faculty of Health Sciences, University ofStellenbosch, South Africa

Allergic conjunctivitis is an extremely common disor-der. The Allergy Report,1 a survey published by theAmerican Academy of Allergy, Asthma, andImmunology in 2000, found that 35% of families inter-viewed had experienced allergies during the previousyear, of whom over 50% reported associated eyesymptoms. Fortunately the vast majority of these aremild and self-limiting, either not requiring medicalattention at all or being very adequately managed atthe primary care level. A small minority however maybe very difficult to control and may result in chronicsight-threatening complications, caused by secondarycorneal involvement.

All classifications have inherent limitations because ofthe overlap of the classically described conditions.Grouping the allergic conjunctivitides, however, intoacute and chronic subtypes is very commonly used,and has significant clinical value.

The two major acute disorders are seasonal allergicconjunctivitis (SAC) and perennial allergic conjunctivitis(PAC), while atopic keratoconjunctivitis (APC), vernalkeratoconjunctivitis (VKC) and giant papillary conjunc-tivitis (GPC) are recognised as chronic ones. Someauthors feel that GPC is not strictly an allergic condi-tion, containing as it does elements of chronic low-grade trauma, but it is traditionally classified with thechronic allergic conjunctivitides and has several fea-tures in common with these conditions.

The above diagnostic groupings do not however coverthe full spectrum of allergic conjunctival disease. Forexample, topical medications may cause either a toxicor allergic conjunctivitis and it may be important,although not always easy, to distinguish betweenthese responses in order to treat the patient effective-ly. In addition conjunctivitides associated with periph-eral corneal infiltrates may have an allergic aetiology aswell. Understanding the pathophysiology of these con-ditions also impacts on their effective management.

The presence of a type I hypersensitivity reaction isusually considered a defining characteristic of an aller-gic conjunctivitis, distinguishing it from other immune-dependent ocular surface diseases. Within thisdefinition the acute disorders are usually referred to as

being purely type I hypersensitivity reactions while thechronic ones are described as having an additional typeIV component. Although this classification has somevalidity, ongoing research has shown it to be a signifi-cant oversimplification, and the full complexity of therelationship between the clinical and immunologicalpictures remains to be elucidated.

COMMON CLINICAL PRESENTATION

Although each condition has typical distinguishing fea-tures there are several signs and symptoms that arecommon to all types of allergic conjunctivitis. Patientsusually complain of a burning or itching sensation,which is often associated with an irresistible urge torub the eyes. Rubbing however provides only transientrelief and usually aggravates the itchiness leading to an

even greater desire to rub and a consequent perpetu-ally aggravating cycle of itch-rub-itch. Tearing whichmay be severe is very common although this may besomewhat less prominent as chronicity increases,resulting in the complaint of a slightly thicker, less pro-fuse discharge.

The complaint of red and swollen eyes is also commonto all forms of allergic conjunctivitis and this is usuallyfurther exacerbated by the above itch-rub-itch cycle. Adegree of photophobia is also a common symptomalthough the pathophysiology of this symptom is notwell understood. Examination usually confirms theabove with chemosis, hyperaemia, and tearing whichis occasionally associated with a fine papillary reaction(Fig. 1).

ABSTRACT

Allergic conjunctivitis is an extremely common con-dition, occurring in up to 50% of individuals report-ing allergic symptoms. Although most of thedifferent forms of the condition have many symp-toms in common it is important to be able to distin-guish them from one another as this may haveimportant prognostic and management implications.

This review first discusses the common symptomcomplex and then divides the allergic conjunctivi-tides into acute and chronic forms. The acute formsdescribed are seasonal allergic conjunctivitis (SAC)and perennial allergic conjunctivitis (PAC), while thechronic conditions detailed are atopic keratocon-junctivitis (AKC) and vernal keratoconjunctivitis(VKC). Giant papillary conjunctivitis (GPC) and con-tact allergic conjunctivitis (CAC), although not pureexamples of allergic conjunctivitis have many fea-tures in common with the group, and are thereforealso described. The review focuses primarily on theclinical presentation of the conditions, but a briefoverview of the pathophysiology and an approach tothe management of each condition is also provided.

Correspondence: Dr A Ziskind, Department of Ophthalmology,Tygerberg Academic Hospital, University of Stellenbosch, PO Box19059, Tygerberg 7505. Tel 021-938-9380, fax 021-938-5511, e-mailaz@sun.ac.za Fig. 1. Acute conjunctival chemosis and hyperaemia.

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THE ACUTE CONDITIONS: SEASONAL

ALLERGIC CONJUNCTIVITIS (SAC) AND

PERENNIAL ALLERGIC CONJUNCTIVITIS

(PAC)

SAC and PAC, the two acute conditions, are both usu-ally bilateral although they may be asymmetrical. They

are almost always self-limiting on removal of the trig-gering allergen. They have an equal gender distributionand there is no particular age or racial distribution. Apersonal or family history of atopy is very common. Thesimultaneous presence of an allergic rhinitis is typical.The rhinitis will also tend to be seasonal in SAC andperennial in PAC, causing patients to report sneezingand a watery rhinorrhea as well as itching of the noseand ears. Both present with similar symptoms of itch-ing, burning, tearing, red eyes on exposure to allergens,while the major difference between them is related tothe variable presence of the sensitising allergens. Bothconditions are extremely common, but the incidence ofSAC in most population groups is considerably greater,reflecting the epidemiology of the triggering allergens.

In SAC the patients are usually completely asympto-

matic when the particular allergen to which they aresensitive is not present in the environment, but someindividuals may be sensitive to both seasonal andperennial allergens and will consequently have year-round symptoms with seasonal exacerbations.Seasonal allergens and their timing may differ in differ-ent parts of the world, with common allergens beingtree and flower pollen in the spring, grass pollen in thelate spring and early summer and ragweed during thelate summer and early autumn.

In PAC the patients are usually symptomatic through-out the year, reflecting the perennial nature of the trig-gering allergens. The most common allergensimplicated in the pathogenesis of PAC are locatedindoors and include animal dander, dust mites andfeathers, but may also include air pollutants and fungalspores in the external environment.

The pathogenesis of both SAC and PAC involves a typeI immune response with the allergens dissolving in thetear film and traversing the conjunctival epithelium toreach the substantia propria. There they bind to the IgEantibodies attached to the mast-cell membranes,resulting in their degranulation and the release of hist-amine and other cytokines and inflammatory media-tors. These result in vasodilatation and increasedvascular permeability which are responsible for all thesymptoms and signs of the condition. This early phaseis typically followed after a few hours by a late phasewith the influx of eosinophils and T lymphocytes. Thefull picture is considerably more complicated than theabove desciption and opinions vary considerably on thefiner detail. A more detailed analysis of the literature onthis subject is beyond the scope of this review and is

discussed elsewhere in this issue.Both SAC and PAC present with the typical allergicsymptoms and signs detailed above, with itching beingvery prominent in this group of patients, resulting in anintense urge to rub the eyes. Rubbing may cause therupture of subepithelial mast cells, causing their furtherdegranulation and aggravation of symptoms. In thisscenario the degree of chemosis may be exaggerated,resulting in conjunctival ballooning. In addition this mayaggravate lid swelling and induce superficial skinchanges. Because of the self-limiting nature of the con-dition, there may be only a few residual signs by thetime medical attention is sought, but mild chemosis onthe bulbar and lower tarsal conjunctiva may persist, andan occasional mild papillary reaction may be noticeablein the lower fornix or upper palpebral conjunctiva.

Various forms of allergen testing may be of value in dif-ficult cases. Skin-prick testing is the most widely used,but patients will often be aware of the allergens thattrigger their symptoms. Therefore a good history andexamination are all that is indicated in the vast majori-ty of cases. Conjunctival scrapings, looking for thepresence of eosinophils, may be useful in diagnostical-

ly difficult cases, but this is rarely necessary in routineclinical practice.

Although patients may be extremely symptomaticthere is generally no corneal involvement in either SACor PAC and consequently it is extremely rare forpatients to develop sight-threatening complications.

Treatment is initially directed at avoiding or eliminatingthe causative agent if this is possible. Careful attentionto environmental modifications can have a major ame-liorative effect. Patients should also be advised not torub their eyes as this may introduce additional aller-gens into the eyes in addition to the consequencesmentioned above. Artificial tears may provide somerelief by diluting the allergens. Inflammatory mediatorsand cold compresses may provide some relief as well.Topical antihistamines and vasoconstrictors may be of

value in the acute stages and mast-cell stabilisers areof value in the prevention of chronic symptoms. Themajor value of oral antihistamines is in the control ofthe associated systemic symptoms such as rhinitis.

THE CHRONIC CONDITIONS: ATOPIC

KERATOCONJUNCTIVITIS (AKC) AND

VERNAL KERATOCONJUNCTIVITIS (VKC)

In both AKC and VKC the allergic process may result insevere sight-threatening complications. Here, in addi-tion to the type I immune response that is active inSAC and PAC, a type IV immune response is also gen-erated which is responsible for these additional com-plications. VKC is discussed in some detail in aseparate article in this issue and will not be discussedfurther, except in so far as it is important to be able todifferentiate it from AKC.

Once again both AKC and VKC present predominantlyin patients with a personal or family history of atopy.They are chronic and bilateral, although often asym-metrical, conditions. While AKC presents in all agegroups and persists throughout the life of the individ-ual, VKC has its onset in childhood and typicallyresolves spontaneously in the late teens to early twen-ties. While most reviews show that AKC has no partic-ular gender, racial or geographic predilection, VKC isknown to be more common in males and individuals ofAfrican origin. Furthermore while AKC has no particularseasonal predilection, VKC is typically seen in thespring.

The symptoms of AKC are once again those typicallyseen in all allergic patients, and these are oftenincreased if animals are involved. The prominent fea-ture in AKC however is a significant component of peri-ocular skin and lid changes (Fig. 2). These include aprominent dermatitis with scaling and flaking, and thelids may eventually become thickened, resulting in acicatricial ectropion and lagophthalmos. There is oftena chronic meibomitis, keratinisation of the lid marginsand loss of lashes. As opposed to VKC the signs pre-dominantly involve the lower lid. Subepithelial fibrosisof the conjunctiva is a common finding, eventuallyresulting in shallowing of the inferior fornix and occa-sional symblepharon formation. Vision loss is a resultof subsequent corneal involvement, which starts witha superficial punctate keratitis, and may progress to apersistent epithelial defect with secondary infection,scarring and neovascularisation. The association

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between AKC and the early development of cataracts isdifficult to determine, because many of these patientsare placed on chronic steroid therapy, which is an inde-pendent risk factor for cataract formation.

The immune pathophysiology of VKC and AKC is very

complex and incompletely understood. Although thereis a very definite increase in the number and activationof mast cells, the overall immune cell profile involveseosinophils, lymphocytes, fibroblasts and a complexarray of cytokines and immune modulators in a poorlycharacterised combination.

Management of AKC requires a careful history todefine the sensitising allergen so that measures can betaken to decrease exposure. Because of the chronicityof the problem, care should be taken with the long-term use of topical medications, because it is possibleto exacerbate the problem by inducing toxicity. Long-term mast-cell stabilisation is important, and manage-ment of acute exacerbations with topical steroids andsteroid-sparing agents such as cyclosporin both topi-cally and systemically may sometimes be indicated.Management and prevention of lid complications is

necessary and maintenance of an adequate tear filmmay diminish the severity of corneal complications.

GIANT PAPILLARY CONJUNCTIVITIS (GPC)

GPC is a non-infectious chronic inflammatory processof the conjunctiva, characterised by giant papillae onthe tarsal conjunctiva of the upper lids, with no definiteage or gender distribution. Strictly speaking it is not anallergic disease but occurs predominantly secondarilyto chronic low-grade mechanical trauma of the con-junctiva. However there is a very definite allergic com-ponent to the disease, which is more difficult to define.There is evidence of an increased number of mast cellsin the conjunctiva and increased levels of IgE in the tearfilm, but the exact role of these and many other inflam-matory mediators is complex and incompletely under-

stood. One of the reasons for its common inclusionwith the allergic conjunctivitides is its superficial simi-larity to VKC, but the classic conditions are very easy todistinguish from one another, especially when history isconsidered.

GPC is most typically associated with soft contact lens(SCL) wear, but has been described with hard contactlens (HCL) wear, as well as gas-permeable lenses.More rarely it has been recognised in patients wearingocular prostheses, where exposed sutures chronicallyirritate the conjunctiva, and with prominent glaucomafiltering blebs. Many different features of contact lenswear have been implicated in its aetiology includinglens coatings, lens chemistry, edge design, surfaceproperties, wearing schedule, cleaning routine, fittingcharacteristics and replacement cycle. As an example,

people who sleep wearing their contact lenses arethree times more likely to develop GPC than patientswho restrict themselves to daily wear only. Althoughpatients wearing HCL and gas-permeable lenses arealso prone to develop the condition, the average dura-tion of contact lens wear before symptoms and signsdevelop with these lenses has been reported to be in

the order of 8 years compared with 8 months for SCLwearers.2

The development of symptoms and signs is usuallyslow and progressive. It is important not to ignore theearly complaints, as appropriate intervention at thisstage is likely to simplify management considerablyand avoid chronicity. Early symptoms include tearingand itching even at night once the contact lenses havebeen removed. A foreign body sensation with increas-ing contact lens intolerance is also common. Patientsmay also complain of the accumulation of mucus at theinner canthus on awakening with adherence of the lids.Blurring of vision is usually due to increased proteincoating of the lens.

Early signs include mild upper tarsal conjunctival hyper-aemia, associated with subtle thickening, and gradually

increasing opacification of the conjunctiva. A mucoiddischarge is a common feature. Giant papillae on theupper lids are however the characteristic feature of thedisease, varying in size from 0.3 mm to over 1.0 mm indiameter (Fig. 3). The appearance and distribution ofthese may vary considerably. For example, it has beennoted that those due to SCL may start superiorly andprogress downward while those due to gas-permeablelenses begin inferiorly.

Treatment involves the removal of the inciting agent,but as the majority of cases are secondary to contactlens wear, and patients are often loath to give up thismode of refractive correction, this complicates themanagement significantly. A period without lens wear

is mandatory, coupled with various topical preparationsincluding mast-cell stabilisers, NSAIDs, antihistaminesand steroids. These may be of value while a careful his-tory of the details of contact lens wear is taken so asto guide modifications of contact lens wear technique.This may include varying cleaning, rinsing and storagesolutions and modifying wearing schedules, as well asultimately changing from SCL to gas-permeable lenses.

CONTACT ALLERGIC CONJUNCTIVITIS

(CAC)

Prolonged use of many topical medications and otherproducts, such as cosmetics, hair-care products andindustrial chemicals may induce toxic effects on theconjunctiva. The pathological effects of these productsmay also be allergic in nature and distinguishing these

Fig. 2. Atopic conjunctivitis with peri-ocular skinchanges.

Fig. 3. Giant papillary conjunctivitis.

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two processes may often be difficult, especially as bothprocesses may be present simultaneously. Often how-ever one or the other process may be predominant;then certain clinical features may be very useful in dis-tinguishing the main culprit.

With allergy, repeated exposure and adequate sensiti-sation time are needed, which may vary from days to

years, while toxicity usually occurs on first exposure.Although papillary reactions may occur in both allergicand toxic reactions, papillary reactions are more com-mon with allergy while a follicular response, which iscommon with toxic reactions, is very rarely seen withallergy. Hyperaemia secondary to toxicity is usuallymore pronounced in the inferior conjunctiva, while anevenly distributed hyperaemia is more typical of allergy.A mucoid discharge is a feature of an allergic response,while toxicity is often associated with a more muco-purulent one. The cornea is not usually involved in aller-gic reactions while a range of corneal signs may bepresent with toxicity.

It might also be possible to distinguish between toxici-ty and allergy with skin testing or analysis of conjuncti-val scrapings, but this is rarely necessary in clinical

practice.Topical medications that have been reported to induceallergic responses include gentamycin, neomycin,atropine and idoxuridine. Preservatives such as benzal-conuim chloride, used in commercial eyedrops, arealso frequently responsible for CAC.

CONCLUSION

There are other inflammatory conditions which involvethe conjunctiva, including certain diseases of theperipheral cornea, Stevens Johnson syndrome andocular cicatricial pemphigoid which have clinical fea-tures suggestive of an allergic aetiology, however IgEand type I hypersensitivity do not appear to play a rolein these immune conditions and they are therefore notincluded in this grouping.

Allergic conjunctivitis is a widespread and commoncondition and although it only results in significant visu-al morbidity in a very small minority of affectedpatients, its symptoms may cause significant discom-fort and limit the day-to-day activity of a far greaternumber, resulting in absenteeism from work and

school. It may require major lifestyle adjustments.Although reasonably effective medications exist formanaging the acute forms of the condition, the man-agement of the chronic forms remains a major clinicalchallenge.

Although much of the complex immune pathophysiolo-gy remains unclear, significant progress has been

made in defining the cellular and molecular processesinvolved in the allergic conjunctivitides. It is to be hopedthat this knowledge will soon be translated into moreeffective therapies, especially for the more chronicforms of the disease.

Declaration of conflict of interest

The author has no conflict of interest.

FIGURE CREDITSFigs 1, 2 & 3. Reproduced from Spalton DJ, Hitchings RA, Hunter P.Atlas of Clinical Ophthalmology, 3rd ed. Philadelphia: Elsevier Mosby,2005: pp 118, 119 & 123 respectively.

REFERENCES

1. American Academy of Allergy, Asthma, and Immunology. TheAllergy Report, vol. 1. Milwaukee, WI: American Academy ofAllergy, Asthma, and Immunology, 2000. http://www.theallergyre-port.com .

2. Dunn SP, Heidemann DG. Giant papillary conjunctivitis. KrachmerJH, Mannis MJ, Holland EJ, eds. Cornea, 2nd ed, vol.1.Philadelphia: Elsevier Mosby, 2005: 675-681.

FURTHER READINGBarney NP. Vernal and atopic aeratoconjunctivitis. In: Krachmer JH,Mannis MJ, Holland EJ, eds. Cornea, 2nd ed, vol.1. Philadelphia:Elsevier Mosby, 2005: 667-674.

Chambless SL, Stefan T. Developments in ocular allergy. Curr OpinAllergy Clin Immunol 2004; 4: 431-434.

Ono SJ, Abelson MB. Allergic conjunctivitis: Update on pathophysiolo-gy and prospects for future treatment. J Allergy Clin Immunol 2005;115 (1):118-122

Reilly CD, Mannis MJ, Chang SD. Toxic conjunctivitis. In: Krachmer JH,

Mannis MJ, Holland EJ, eds. Cornea, 2nd ed, vol.1. Philadelphia:Elsevier Mosby, 2005: 703-711.

Rothman JS, Raizman MB, Friedlander MH. Seasonal and perennialallergic conjunctivitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds.Cornea, 2nd ed, vol.1. Philadelphia: Elsevier Mosby, 2005: 661-666

Stahl JL, Barney NP. Ocular allergic disease. Curr Opin Allergy ClinImmunol2004; 4: 455-459.