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S Afr Fam Pract
ISSN 2078-6190 EISSN 2078-6204

REVIEW

Definition and Introduction

Allergic conjunctivitis is a condition characterized by conjunctival

inflammation, presenting as acute, intermittent or chronic.1

It results from an airborne allergen and the symptoms of the

condition include itching, excessive lacrimation, ophthalmic

discharge, and conjunctival hyperaemia (pink eye). The diagnosis

of this condition is primarily clinical and the management is

usually through topical antihistamine and mast cell stabilizers.1

Allergic conjunctivitis is estimated to affect at least 20 percent of

the population (in the United States) on an annual basis with the

incidence increasing.2-5 It is primarily a condition of young adults

with an average age of onset of 20 years and the symptoms of

the condition tend to decrease with age. 2-5 Allergic conjunctivitis

has been affiliated with other allergic diseases like allergic

rhinitis, bronchial asthma, atopic dermatitis and other related

comorbidities.6

Pathophysiology

Allergic conjunctivitis results from contact of an allergen or

allergens with the surface of the eye in a person who is allergic

to that specific allergen.1,7 Both histamine 1 and 2 receptors

play a role in ocular allergy.7 It is considered a classic type 1

Immunoglobulin E (IgE)-mediated hypersensitivity reaction,

and shares a similar pathophysiology to other atopic diseases.7,8

Analyses of conjunctival scrapings have shown two phases

of this allergic response which are similar to the early and late

phases of cutaneous, nasal, and pulmonary allergen responses.7

The immediate response to allergens is mediated almost

primarily by mast cells, which are present in high concentrations

in the conjunctival epithelium and increase further in patients

with allergic conjunctivitis.7 The mast cells become activated and

release histamine via exocytosis. Histamine is the main mediator

of this response and causes vasodilatation, vasopermeability,

and itching. 7 Elevated levels have been found in patients with

seasonal allergic conjunctivitis.8

The late phase response to allergens begins with an influx of

other inflammatory cells attracted by cytokines and chemokines

released by the mast cells in the immediate phase. Within

6 to 10 hours after allergen challenge, eosinophils, basophils

and neutrophils appear.9-13 This is followed by lymphocytes

and monocytes.9-13 The eosinophils produce and release

leukotriene C4, eosinophil peroxidase, eosinophil cationic

proteins and histamine into the tear fluid.9 These cells create

continued inflammation. The presence of eosinophils have been

demonstrated in up to 80 percent of conjunctival scrapings in

patients with acute allergic conjunctivitis.14

Types of Allergic Conjunctivitis

There are three different types of allergic conjunctivitis, namely:

acute allergic conjunctivitis,15,16 seasonal allergic conjunctivitis

(SAC)1,6 and perennial allergic conjunctivitis (PAC).1 Table 1

demonstrates the key differences between these types.

Abstract

Allergic conjunctivitis is a condition characterized by conjunctival inflammation caused by airborne allergens. The symptoms
include: itching, excessive lacrimation, discharge, and conjunctival hyperaemia (pink eye). The disease usually affects young
adults and is associated with other allergic conditions like allergic rhinitis, and bronchial asthma for example. There are three
types of allergic conjunctivitis, namely acute allergic conjunctivitis, seasonal allergic conjunctivitis (SAC) and perennial allergic
conjunctivitis (PAC). The diagnosis is primarily clinical and the prevalence is on the increase. Therapeutic modalities include a
combination of topical vasoconstrictor and antihistamine therapies, topical antihistamines with mast cell stabilising properties,
topical mast cell stabilisers, topical glucocorticosteroids and (in some cases) oral antihistamines when necessary.

Keywords: conjunctivitis, allergic conjunctivitis, seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC)

South African Family Practice 2017; 59(5):5-10

Open Access article distributed under the terms of the
Creative Commons License [CC BY-NC-ND 4.0]
http://creativecommons.org/licenses/by-nc-nd/4.0

Allergic Conjunctivitis
M Vally,* MOE Irhuma

Division of Clinical and Experimental Pharmacology, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences
Faculty of Health Sciences, University of Witwatersrand, Johannesburg

*Corresponding author, email: muhammed.vally@wits.ac.za

S Afr Fam Pract 2017;59(5):5-106

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Clinical Presentation

The prominent symptom of allergic conjunctivitis is ocular

pruritis.1,17,18 The absence of pruritus should prompt the

healthcare practitioner to consider other ocular disorders, for

example bacterial, viral, fungal, autoimmune, and drug-induced

conjunctivitis. Table 2 describes the clinical presentation of

allergic rhinitis in terms of symptoms, clinical history and physical

examination findings.1,17-19

Diagnosis

The diagnosis of this condition is primarily clinical and based on

suggestive signs and symptoms consistent with allergic rhinitis.1

Laboratory testing is not required in order to initiate therapy,

however, testing for allergy to specific substances should be

pursued if the patient does not respond to treatment or in

advanced conditions.1 In such situations it would be preferable

to refer to an ophthalmologist.1,19, 20

Differential Diagnosis

The differential diagnosis for this condition includes: infective

conjunctivitis, more severe forms of ocular allergic diseases,

blepharitis, drug-induced conjunctivitis, and keratoconjunctivitis

sicca. Table 3 illustrates the different features of these conditions

useful for differentiation.

Management of Allergic Conjunctivitis

The management of allergic conjunctivitis should include both

non-pharmacological or pharmacological measures.

Non-pharmacological measures

Basic eye-care should be advised for these patients:17-21

1. Patients should not rub their eyes because rubbing can

cause mechanical mast cell degranulation and worsening of

symptoms.

2. Cool compresses can help reduce eyelid and periorbital

oedema.

Table 1: Key differences between the three types of allergic conjunctivitis1,6,15-17

Acute Allergic Conjunctivitis Seasonal Allergic Conjunctivitis Perennial Allergic Conjunctivitis

1. Sudden onset hypersensitivity reaction that
develops rapidly (within 30 mins)

2. Caused by isolated environmental exposure
3. Resolves promptly when the allergen is

removed (usually within 24 hrs)
4. Characterized by intense episodes of:

a. Itching
b. Hyperaemia
c. Tearing
d. Chemosis
e. Eyelid oedema

1. Progressive onset reaction (compared to
acute allergic conjunctivitis) and occurs
gradually (over days to weeks)

2. Usually corresponds to a specific pollen
season

3. Seasonal allergens include:
a. Tree pollen in spring
b. Grass pollen in summer
c. Wood pollen in late summer or autumn

1. PAC is mild, chronic and has a waxing and
waning quality.

2. It is related to year round environment
exposure.

3. PAC allergens include:
a. Dust mites
b. Animal dander
c. Moulds

Table 2: Clinical presentation of allergic conjunctitivis1,17-20

Symptoms Clinical History Physical Examination Findings

• Ocular pruritus
• Burning sensation in the eye
• Redness is universal
• Eyelid oedema is common
• Usually bilateral, but one eye can be more

affected than another
• Discharge: watery and non-purulent
• Mild photophobia and crusting upon

awakening may occur

• History of atopy, seasonal allergy or
specific allergy is usually present in these
patients.

• All patients should be asked about a
previous history of similar symptoms.

• Conjunctival hyperaemia
• Tearing and clear watery discharge
• Conjunctival oedema
• Injection (redness) in allergic conjunctivitis

is usually diffuse and involves the bulbar
conjunctiva as well as the palpebral and tarsal
conjunctiva

• On eyelid eversion: conjunctival papillae may be
present.

• Papillae vary in size from tiny red dots to
polygonal elevations 1 mm or more in diameter

• Papillae are usually found on the tarsal
conjunctiva

• Cobblestoning and large papillae are usually
indicative of other severe ocular allergic
disorders

• Patients with allergic rhinitis may also present
with:
◦ Allergic shiners
◦ Dennie-morgan lines
◦ A pale hue to the nasal mucosa
◦ Oedema of the nasal turbinates
◦ Clear rhinorrhoea maybe visible
◦ If the nasal passages are obstructed, there

may be clear dripping in the posterior
pharynx

Allergic Conjunctivitis 7

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3. Frequent use of refrigerated artificial tears throughout the day
can help dilute and remove allergens.

4. Patients should reduce or stop the use of contact lenses during
their symptomatic periods.

Allergen avoidance or reduction of contact with known allergens
is critical for effective management of allergic conjunctivitis,
especially in more severe cases.17-21 Different advice should be
given on the type of allergic conjunctivitis. This includes17-21:

1. For SAC, patients should be advised to use air conditioning
where possible. They should also be advised to limit outdoor
exposure, and keep car and home windows closed during the
peak pollen seasons.

2. For PAC, patients should be advised to avoid specific allergens
that are the cause of the symptoms in a specific patient. For
example: in patients allergic to dust mites, advice should be
given to replace old pillow cases, blankets and mattresses or
using dust mite allergen impermeable covers.

Pharmacological Measures

The mainstay of therapy for ocular related allergies included the
use of allergic therapeutic treatments such as: antihistamine,
multiple action anti-allergic agents and mast cell stabilizers.17

Topical Treatments

1. Vasoconstrictor/antihistamine combinations (tetryzoline/
antazoline)

These medicines are available as over the counter medicine
with tetryzoline having a similar action to that of naphazoline.22
Tetryzoline, a topical vasoconstrictor, was indicated for

ocular redness and continuous use would result in rebound
hyperaemia.22,23 Antazoline is an antihistamine indicated
topically for the symptomatic relief of allergic conjunctivitis.22
Antazoline may be useful in the case of histamine-induced
itching. Antazoline has local stinging properties and may
cause minor ocular irritation.22 Patients should be advised that
increased eye redness for several days may result when the
combination of tetryzoline/antazoline is stopped.22

2. Antihistamines with mast cell stabilising properties (e.g.
olaptadine, ketotifen, emedastine, epinastine, ketotifen, etc.)

These drugs have two main mechanisms of action. They block
histamine receptors in the conjunctiva and thus inhibit the
action of this mediator.22, 24 Furthermore, they stabilise mast
cells and inhibit mast cell degranulation which in turn limits the
release of histamine, tryptase and prostaglandin D2.

22,25 They
also inhibit leukocyte activity and dampen mediator release
from basophils, eosinophils and neutrophils.22,25 Almost all these
drugs are dosed twice daily,22 but two weeks of therapy should
be allowed in order for the drugs to reach maximal efficacy as a
prophylactic agent. Common adverse effects to expect with use
are burning, stinging and irritation upon installation as well as
headaches or ocular dryness. Patients may consider refrigerating
the drops prior to use to combat these adverse effects or even
consider the use of artificial tears with these medications.
A systematic review and a Cochrane meta-analysis on the use of
topical antihistamines have demonstrated their effectiveness in
the management of both SAC and PAC.18,26

3. Mast Cell Stabilisers (sodium cromoglycate, lodoxamide)

The drugs stabilise mast cells and prevent the release of
histamine. The maximal efficacy of these drugs is only reached

Table 3: Differential diagnosis and feature of these conditions1,17,20

More severe forms of allergic ocular disease:
1. Vernal keratoconjunctivitis: more severe disorder, which usually affects boys living in warm, dry climates. It presents with intense pruritis, string

mucoid discharge and cobblestoning on the upper tarsal conjunctiva and may vary with seasons
2. Giant papillary conjunctivitis: a hypersensitivity reaction to contact lenses, ocular sutures or ocular implants. It presents with itching, foreign body

sensations, giant papillae.
3. Atopic keratoconjunctivitis: chronic and severe disorder that can affect the eyelid, conjunctiva, and cornea. It presents with severe pruritus,

sometimes with seasonal variability. Eyelids can become thickened and lichenified.

Viral Infections
Allergic conjunctivitis is often accompanied by significant ocular pruritus, however this is not the case with infectious eye conditions. Infection is
usually unilateral, although it can be bilateral, whereas allergic conjunctivitis is usually bilateral.

Bacterial Infections
Produce some degree of purulent discharge and are unlikely to be mistaken for allergic conjunctivitis, but viral infections can present more subtly.

Keratoconjunctivitis Sicca
Allergic conjunctivitis principally affects the conjunctiva, whereas the principal target tissue in keratoconjunctivitis sicca is the cornea.

Blepharitis
This principally affects the eyelids or lid margins whereas allergic conjunctivitis affects the conjunctiva. Eyelid involvement is characterised by
vascularisation of lids, changes in meibomian glands, and presence of lid dander.

Angle Closure Glaucoma
Allergic conjunctivitis is usually bilateral, and generally not associated with vision loss or ocular pain. Angle closure glaucoma is usually associated
with unilateral ocular pain, vision loss and corneal oedema. Both allergic conjunctivitis and angle closure glaucoma do present with redness.

Episcleritis/scleritis
Both scleritis and episcleritis are associated with significant pain but the pain of episcleritis may be delayed.

Drug-induced conjunctivitis
Drug-induced cicatrising conjunctivitis is type of ocular toxicity resulting from different chemicals used as preservatives in eye drops. Preservatives
like benzalkonium chloride (BAC) and related ammonium salts have been shown to play an important part as allergens in some patients. Other
ophthalmic medications, for example antimicrobial, antifungal, antiviral, corticosteroid drops may also trigger hypersensitivity reactions in some
patients especially in the first few days of use.

S Afr Fam Pract 2017;59(5):5-108

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between 5–14 days after initiation and thus cannot be used in

the management of acute allergic conjunctivitis.27 The dosing

of these drugs is more frequent than topical antihistamine and

must be dosed four times daily.22,27 For this reason, it should be

reserved as treatment for SAC in patients who cannot tolerate

other therapy. A randomised trial which compared the use of

cromolyn sodium (4 percent, four times daily) for two weeks prior

to allergen challenge with a single drop of ketotifen fumarate

(0.025 percent) given just before allergen challenge, found that

the single drop of ketotifen was superior in controlling itching

and redness at 15 minutes and at 4 hours after challenge.28

An analysis of the economic costs of olaptadine or sodium

cromoglycate concluded that the more expensive olaptadine

resulted in sufficiently fewer return visits than the most cost

effective option of sodium cromoglycate.29

4. Glucorticosteroids (loteprednol, flurometholone)

These drugs should be considered in patients with refractory

symptoms and should be prescribed by an ophthalmologist.

Due to their adverse effect profile (cataract formation, increased

intraocular pressure, glaucoma and secondary infections), these

drugs should only be used as “pulse therapy” for a maximum of

two weeks and only in patients where topical antihistamines and

mast cell stabilisers have been ineffective.22 Soft steroids (e.g.

loteprednol, flurometholone) are preferred to dexamethasone or

prednisolone (1%) as pulse therapy, as they are associated with

the lower risk of increased intraocular pressure.30

Systemic Therapy

Oral antihistamines (cetirizine, loratadine, fexofenadine)

Non-sedating antihistamines are histamine -1- receptor (H1)

antagonists and are dosed once daily. They may be useful in

patients with rhinitis or pruritus.22 Randomised trials have shown

that topical medications are more effective than oral therapies

for ocular symptoms. Specifically, topical olopatadine was

more effective than oral loratadine or fexofenadine, and topical

ketotifen was more effective than oral desloratadine.31-33 Oral

antihistamine can cause drying of the mucosal membranes and

in some patients may cause dry eyes.22,34

Treatment for specific types of allergic conjunctivitis

Rational drug selection of the different therapeutic modalities
for the different types of allergic rhinitis is detailed in Table 4.

Conclusion

Allergic conjunctivitis is a condition characterised by conjunctival
inflammation that may be acute, intermittent or chronic.
There are three types of allergic conjunctivitis: acute allergic
conjunctivitis, SAC and PAC. The prominent symptom of allergic
conjunctivitis is ocular pruritis. Drug therapy should be confined
to topical treatments with topical antihistamine with mast cell
stabilising properties being the drug of choice for SAC and PAC,
while the use of topical vasoconstrictor/antihistamine should be
considered for acute allergic conjunctivitis.

References:
1. Roat, MI. Allergic Conjuncitivis. The Merck Manual Online professional

version.2016 [accessed August 2017]. Available from: http://www.msdmanuals.
c o m / p r o f e s s i o n a l / e y e - d i s o r d e r s / c o n j u n c t i v a l - a n d - s c l e r a l - d i s o r d e r s /
allergic-conjunctivitis)

2. Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the
United States, 1988-1994. J Allergy Clin Immunol. 2010;126:778.

3. Wang HY, Pizzichini MM, Becker AB, et al. Disparate geographic prevalences of
asthma, allergic rhinoconjunctivitis and atopic eczema among adolescents in
five Canadian cities. Pediatr Allergy Immunol. 2010;21:867.

4. Kusunoki T, Morimoto T, Nishikomori R, et al. Changing prevalence and severity
of childhood allergic diseases in Kyoto, Japan, from 1996 to 2006. Allergol Int.
2009;58:543.

5. Rosario N, Bielory L. Epidemiology of allergic conjunctivitis. Curr Opin Allergy
Clin Immunol. 2011;11:471.

6. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma
(ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)
LEN and AllerGen). Allergy. 2008;63(86)Suppl:8.

7. Tsubota K, Takamura E, Hasegawa T, Kobayashi T. Detection by brush cytology
of mast cells and eosinophils in allergic and vernal conjunctivitis. Cornea.
1991;10:525.

8. Ehlers WH, Donshik PC. Allergic ocular disorders: a spectrum of diseases. CLAO
J. 1992;18:117.

9. Bonini S, Bonini S, Berruto A, et al. Conjunctival provocation test as a model for
the study of allergy and inflammation in humans. Int Arch Allergy Appl Immunol
1989;88:144.

10. Cohan VL, Massey WA, Gittlin SD, et al. The heterogeneity of human histamine
containing cells. In: Mast cell and basophil differentiation and function in health
and disease. Galli SJ, Austen KF (Eds). Raven Press, New York 1989.

11. Bonini S, Centofanti M, Schiavone M, et al. The pattern of the ocular late phase
reaction induced by allergen challenge in hay fever conjunctivitis. Ocul Immunol
Inflamm. 1994;2:191.

12. Abelson MB, Madiwale N, Weston JH. Conjunctival eosinophils in allergic ocular
disease. Arch Ophthalmol. 1983;101:555.

13. Bonini S, Centofanti M, Schiavone M. Passive transfer of the ocular late-phase
reaction. Ocul Immunol Inflamm. 1993;4:323.

14. Abelson MB, Udell IJ, Weston JH. Conjunctival eosinophils in compound 48/80
rabbit model. Arch Ophthalmol. 1983;101:631.

15. Rodier F, Gautrin D, Ghezzo H, Malo JL. Incidence of occupational
rhinoconjunctivitis and risk factors in animal-health apprentices. J Allergy Clin
Immunol. 2003;112:1105.

16. Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and
prospects for future treatment. J Allergy Clin Immunol. 2005;115:118.

17. La Rosa M, Lionetti E, Reibaldi M, et al. Allergic conjunctivitis: a comprehensive
review of the literature. Ital J Pediatr. 2013;39:18. doi: 10.1186/1824-7288-39-18.

18. Owen CG, Shah A, Henshaw K, Smeeth L, Sheikh A. Topical treatments for
seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy
and effectiveness. Br J Gen Pract.2004;54(503):451-6.

19. National Department of Health, South Africa. Allergic Conjunctivitis
Management Guidelines 2015 [cited 30 August 2017]. Adapted from: Standard

Table 4: Rational drugs use of the different therapeutic modalities for
the different types of allergic rhinitis22-34

Type of allergic
conjunctivitis

First line agent Second line agent

Acute Allergic
Conjunctivitis

Considered a self-limiting
condition
Consider the use of
topical vasoconstrictor/
antihistamine preparation for
two weeks

Topical antihistamine
with mast cell stabilising
properties

SAC Topical antihistamine
with mast cell stabilising
properties twice daily
Drugs should be initiated
two to four weeks prior
to anticipated onset of
symptoms

Topical mast cell
stabilisers four times
daily

PAC Topical antihistamine
with mast cell stabilising
properties twice daily

Topical mast cell
stabilisers four times
daily

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Treatment Guidelines and Essential Drugs List PHC (2014) Available from: http://
www.kznhealth.gov.za/pharmacy/edlphc2014a.pdf

20. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Well BG, Posey LM, eds.
Pharmacotherapy A pathophysiologic approach. 9th ed. New York: McGraw-Hill;
2014

21. Bilkhu PS, Wolffsohn JS, Naroo SA, et al. Effectiveness of nonpharmacologic
treatments for acute seasonal allergic conjunctivitis. Ophthalmology.
2014;121:72.

22. Rossiter D, Blockman M, Barnes KI, Cohen K, Decloedt E, Irhuma M, Maartens
G, Pandie M, Sinxadi PZ, et al. eds. South African Medicines Formulary. 12th
Edition. Cape Town: South African Medical Association Health and Publishing
Group;2016.

23. Spector SL, Raizman MB. Conjunctivitis medicamentosa. J Allergy Clin Immunol.
1994;94:134.

24. Stiehm ER, Ochs HD, Winkelstein JA. Immunodeficiency disorders: General
considerations. In: Immunologic disorders in infants and children. Stiehm ER,
Ochs HD, Winkelstein JA (Eds). Elsevier Saunders, Philadelphia 2004. p.423.

25. Berdy GJ, Smith LM, George MA. The effects of disodium cromoglycate in the
human model of acute allergic conjunctivitis. Invest Ophthalmol Vis Sci. 1989;30
Suppl:503.

26. Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A. Topical
antihistamines and mast cell stabilisers for treating seasonal and perennial
allergic conjunctivitis. Cochrane Database Syst Rev. 1 Jun 2015;(6):CD009566.
doi:10.1002/14651858.CD009566.pub2.Review

27. Nizami RM. Treatment of ragweed allergic conjunctivitis with 2% cromolyn
solution in unit doses. Ann Allergy. 1981 47:5.

28. Greiner JV, Michaelson C, McWhirter CL, Shams NB. Single dose of ketotifen
fumarate .025% vs 2 weeks of cromolyn sodium 4% for allergic conjunctivitis.
Adv Ther. 2002;19:185.

29. Guest JF, Clegg JP, Smith AF. Health economic impact of olopatadine compared
to branded and generic sodium cromoglycate in the treatment of seasonal
allergic conjunctivitis in the UK. Curr Med Res Opin. 2006;22:1777.

30. Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprednol
etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991;10:933.

31. Abelson MB, Welch DL. An evaluation of onset and duration of action of patanol
(olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin
(loratadine 10 mg) tablets in acute allergic conjunctivitis in the conjunctival
allergen challenge model. Acta Ophthalmol Scand Suppl. 2000;60.

32. Spangler DL, Abelson MB, Ober A, Gotnes PJ. Randomized, double-masked
comparison of olopatadine ophthalmic solution, mometasone furoate
monohydrate nasal spray, and fexofenadine hydrochloride tablets using the
conjunctival and nasal allergen challenge models. Clin Ther. 2003;25:2245.

33. Crampton HJ. Comparison of ketotifen fumarate ophthalmic solution alone,
desloratadine alone, and their combination for inhibition of the signs and
symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen
challenge model: a double-masked, placebo- and active-controlled trial. Clin
Ther. 2003;25:1975.

34. Ousler GW 3rd, Workman DA, Torkildsen GL. An open-label, investigator-masked,
crossover study of the ocular drying effects of two antihistamines, topical
epinastine and systemic loratadine, in adult volunteers with seasonal allergic
conjunctivitis. Clin Ther. 2007;29:611.