Ocular Allergy: Allergic Conjunctivitis and Related Conditions, Brief Review

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Classification of ocular allergy (click to enlarge the image).

Alphabet "soup": SAC, PAC, AKC, VKC, GPC (click to enlarge the image).

Allergic Conjunctivitis


- Atopic Keratoconjunctivitis (AKC), atopic dermatitis-related, lower eyelid
- Vernal Keratoconjunctivitis (VKC), upper eyelid. See Vernal Keratoconjunctivitis - NEJM images, 2012.

Giant Papillary Conjunctivitis (GPC), contact lenses-related, upper eyelid
Contact dermatoconjunctivitis

All ocular allergies are characterized by bilateral involvement. Sensitization is necessary for all ocular allergies except for giant papillary conjunctivitis.

Most common type of ocular allergy is allergic conjunctivitis (80-90% of all cases).

Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.

Allergic conjunctivitis

Allergic conjunctivitis is a relatively benign disease that does not threaten vision. Ocular allergy is estimated to affect 20-25% of the population and the incidence is increasing.

Clinical Manifestations

Allergic conjunctivitis is a disease of young adults (average age of onset 20 years).

As with many allergic diseases, symptoms decrease with age.

50% of patients have a personal or family history of other allergic conditions such as allergic rhinitis, atopic dermatitis, and asthma

Signs and symptoms

Itching, tearing, conjunctival edema, hyperemia, watery discharge, burning, and photophobia, eyelid edema.

Laboratory findings

Allergic conjunctivitis is a clinical diagnosis.

Diagnostic Tests in Allergic Conjunctivitis (of academic interest) (click to enlarge the image).

Some tests of academic interest:

- Conjunctival scrapings show eosinophils in 80%
- Tear film and serum IgE levels are elevated
- Tear film mast cell activity is increased - measured by immunoassay for tryptase (unique to mast cells).

But rubbing by itself can result in a significant increase of tryptase in tears.

Conjunctival provocation test (CPT)

CPT is used to study AC and drug efficacies. Before undergoing a CPT, patients must first be skin tested to determine the appropriate allergen for each patient. The allergen extract is applied bilaterally into the conjunctival sac of the eyes.

At baseline, 2 visits (7 days apart) are used to establish the threshold dose of allergen (visit 1) and reproducibility (visit 2).

CPT is a double-blind, randomized test in which the test drug is applied to one eye and placebo to the other.

Types of allergic conjunctivitis

3 categories

- Acute allergic conjunctivitis (AAC)
- Seasonal allergic conjunctivitis (SAC)
- Perennial allergic conjunctivitis (PAC), less common and less severe than SAC

The main difference between SAC and PAC is the timing of the symptoms. SAC symptoms last a specific season. PAC symptoms last throughout the year.

Acute allergic conjunctivitis (AAC)

Sudden-onset hypersensitivity reaction caused by environmental exposure, for example, such as cat dander.

AAC can be severe and debilitating. However, most cases of AAC are self-limited to 24 hours and do not require long-term treatment.

Seasonal allergic conjunctivitis (SAC)

There are several synonyms for SAC: allergic conjunctivitis, hay-fever conjunctivitis, or allergic rhinoconjunctivitis.

SAC is a milder form of ocular allergy than AAC, typically associated with allergic rhinitis (AR).

SAC is most commonly triggered by ragweed or grass pollens.

SAC has a chronic course that corresponds to pollen seasons: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.

Perennial allergic conjunctivitis (PAC)

PAC is a mild chronic allergic conjunctivitis related to year-round indoor allergens, for example, house dust mite (HDM), animal dander, and molds.

PAC is less common and less severe than SAC.


All 3 types result from type I IgE–mediated hypersensitivity, same as other atopic diseases.

Conjunctival scrapings show 2 phases (early and late) of the allergic response, same as other atopic diseases affecting the skin, nose and lungs.

The immediate response to allergens is mediated by mast cells, which are normally present in high concentrations in the conjunctiva.

Allergen-IgE crosslinking causes mast cells to release chemical mediators.

Histamine is the mediator of the early response.

Late response consists of cell influx (eosinophils, basophils, and neutrophils) which usually takes 6-10 hours after allergen challenge.

Eosinophils release leukotriene C4, eosinophilic peroxidase, eosinophilic cationic protein, and histamine into the tear fluid.


The diagnosis of allergic conjunctivitis is usually clinically apparent in the context of typical history and physical examination findings.

The dominant symptom in AC is itching. The eye appears red. Typically, itch is not reported with dry eye.

Laboratory tests are not usually needed to confirm the clinical diagnosis of AC.

Differential diagnosis

- infectious conjunctivitis
- blepharitis
- dry eye

Allergic conditions are often accompanied by pruritus which is not common in infections.


General measures:
- do not to rub the eyes. Eye rubbing causes mechanical mast cell degranulation.
- artificial tears several times a day
- allergen avoidance
- topical antihistamine eye drops
- cool compresses
-avoidance of contact lenses use -- allergens adhere to contact lens surfaces

Dry eyes or tear film insufficiency are extremely common.

Signs of tear film insufficiency include superficial punctate-keratopathy, reduced tear break-up time, and decreased production of tears as measured by the Schirmer's test.

Oral antihistamines can exacerbate tear film insufficiency through decreased tear production (anticholinergic effect).

Punctal plugs may be helpful and can be placed quickly and painlessly by an ophthalmologist.

Allergen avoidance

- limit outdoor exposure
- air conditioning
- car and home windows closed

- replacement of old pillows and mattresses
- covers for pillows and mattresses
- frequent washing of beddings
- reducing humidity
- frequent vacuuming and dusting of the home
- remove reservoirs of dust: old carpets, old furniture, old curtains or drapes
- if allergic to animal dander, remove the animal from the home


Immunotherapy is effective for treatment of allergic rhinoconjunctivitis

One meta-analysis included 15 studies of immunotherapy in patients with ocular allergy symptoms - 12 studies showed benefit -- decreased ocular symptoms scores and medication use.

Immunotherapy is useful treating ocular symptoms that coexist with allergic rhinitis or asthma but the its role in treating isolated ocular allergy is less clear.


Medications for Allergic Conjunctivitis (click to enlarge the image).

Medications for AAC

Most cases of AAC are self-limited to 24 hours and do not require long-term treatment.

Over-the-counter topical antihistamine/vasoconstrictor

Over-the-counter topical antihistamine/vasoconstrictor can be used to treat symptoms of short-duration (less than 2 weeks):
- Naphazoline/pheniramine maleate (Naphcon-A®, Opcon-A®, Visine-A®)
- Naphazoline/pheniramine phosphate (Vasocon-A®)

Topical vasoconstrictor (decongestants) work within minutes with a duration of 2 hours. Dosing is QID.

Use for longer than 2 weeks can lead to rebound hyperemia.


Topical antihistamines are faster-acting than oral anthistimines and have little systemic effects.

The combination of a topical antihistamine and a vasoconstrictor works better than either agent alone.

Frequent attacks of AAC (more than 2 days per month) are treated with a dual-action agent (antihistamine/mast cell stabilizer) such as olopatadine.

Pataday® is used qd, Patanol® is used bid for prevention and qid for acute symptoms.

Other topical antihistamines and/or mast cell stabilizers: azelastine (Optivar®), epinastine (Elestat®), pemirolast (Alamast®), and ketotifen (generic).

Ketotifen bid is generic and over-the-counter.

Dual-acting, Antihistamine and Mast Cell–Stabilizing Drugs

These most commonly prescribed eye drops for allergic eye disease: azelastine, olopatadine, and ketotifen.

Medications for SAC and PAC

5 classes of topical drugs:

1. antihistamines
2. mast cell stabilizers, e.g. cromolyn
3. antihistamine/mast cell stabilizer combinations, e.g. olopatadine, ketotifen
4. steroids
5. non-steroidal anti-inflammatory agents (NSAIDs), e.g. ketorolac

Mnemonic for medications for SAC and PAC: MD VANS

Mast cell stabilizers
Dual-acting: antihistamine/mast cell stabilizer

Vasoconstrictors, not recommended
NSAIDs, only ketorolac, not recommended
Steroids, only loteprednol, by opthalmologist

The treatment of choice for AC is dual–acting eye drops (antihistamine/mast cell stabilizer).

Treatment for SAC should be started 2 weeks prior to the onset of season which cases symptoms: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.

Dual-action agents (topical antihistamines with mast cell stabilizing properties):
- olapatadine (Patanol®, Pataday®)
- azelastine HCl (Optivar®)
- epinastine (Elestat®)
- pemirolast (Alamast®)
- ketotifen (generic)

Ocular antihistamines (eye drops) (click to enlarge the image).

Mast cell stabilizers:
- cromolyn (generic, Opticrom®)
- lodoxamide (Alomide®)

The onset of action of mast cell stabilizers is slow (5-14 days) and the dosing is QID (inconvenient). Cromolyn cannot be used for acute symptoms.

One study compared cromolyn (4%, 4 times daily) for 2 weeks prior to allergen challenge to a single drop of ketotifen (0.025 percent) used just before the allergen challenge. The single drop of ketotifen was more effective.

Oral antihistamines

Oral antihistamines are less effective than topical olopatadine or topical ketotifen.

All antihistamines dry the ocular surface due to their atropine-like effect which decreases tear production of the lacrimal glands.

Oral antihistamines reach a peak serum levels in 0.5-3 hours depending on the drug but a full effects is after several days of use (similar to cromolyn). Oral antihistamines act much slower than topical antihistamines.

Cetirizine may cause sedation in a subset of patients, despite its categorization as non-sedating.

Topical NSAIDs

In theory, NSAIDs block the cyclooxygenase and inhibit the conversion of arachidonic acid to prostaglandins and thromboxanes.

In practice, NSAIDs are less effective than antihistanmines but more effective than placebo. NSAIDs are not recommended for treatment of allergic conjunctivitis.

Ketorolac is the only topical NSAID approved for itching due to AC.

Patients with AR and AC

Olopatadine can be combined with an intranasal steroid (INS). Fluticasone furoate nasal spray is the only intranasal corticosteroid to reduce the ocular symptoms of seasonal allergic rhinitis consistently, JACI, 2010.

When to refer to an ophthalmologist?

If there is no response to 2-3 weeks of an antihistamine/mast cell stabilizer (olopatadine).


Only one topical steroid is currently approved for use in ocular allergy—loteprednol.

Loteprednol 0.2% is Alrex.
Loteprednol 0.5% is Lotemax.

Topical steroids may be considered in refractory patients. Topical steroids can cause serious ocular side effects and should only be used for short "pulse therapy."

Side effects of topical steroids can lead to blindness:
- cataract formation
- elevated intraocular pressure (IOP) and glaucoma
- secondary infections

5% of people respond to steroid eye drop with increased intraocular pressure. Of those with a family history of glaucoma, 20-30% respond with elevated intraocular pressure.

Prednisolone acetate (1 %) and dexamethasone phosphate (0.1 %) have the greatest risk of raising IOP.

"Soft" topical steroids have a much llower risk of increased IOP becase they are inactivated after corneal penetration: Lotemax® (loteprednol), Pred Mild® (prednisolone), FML® (fluorometholone), HMS® (medrysone), and Vexol® (rimexolone).

Atopic Keratoconjunctivitis (AKC)

AKC is a chronic ocular inflammation involving the lower tarsal conjunctiva. VKC affects the upper tarsal conjunctiva. See Vernal Keratoconjunctivitis - NEJM images, 2012.

Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.

The association between atopic dermatitis and AKC was first described in 1953.

Almost all patients with AKC have atopic dermatitis, and many have asthma. Peak incidence of AKC is 20–50 years of age.

3% of the population is affected by atopic dermatitis. 25% of people with atopic dermatitis have ocular involvement.

Secondary staphylococcal blepharitis is common because of eyelid induration and maceration. Herpetic keratitis occurs in 14-18% of patients.

Keratoconus (noninflammatory progressive thinning of the cornea) occurs in 7-16% of patients.

Treatment of Atopic Keratoconjunctivitis

AKC is a sight-threatening disease.

Topical vasoconstrictor-antihistamine combination may bring transient relief. Dual-acting and mast cell–stabilizing drugs are also recommended.

Topical steroids 8 times per day for 7-10 days are needed to control the symptoms and often lead to an excellent response. Steroid use is transient.

Trichiasis (misdirected eyelashes) must be corrected surgically.

Staphylococcal-associated blepharitis and herpes simplex keratitis requires specific treatments.

Vernal Keratoconjunctivitis (VKC)

VKC is a severe bilateral chronic inflammation of the upper tarsal conjunctiva.

Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.

VKC is not IgE mediated but occurs most frequently in children with seasonal allergies, asthma, or atopic dermatitis. Males predominate 3:1.

"Vernal" means occurring in spring.

VKC onset is generally before 10 years of age. Without treatment, VKC lasts 2-10 years and usually resolves during puberty. Young men in dry, hot climates (Mediterranean, West Africa) are primarily affected.

VKC signs:

- Giant papillae occur on the upper tarsal plate and are described as cobblestoning.
- yellow-white points in the limbus (Trantas dots)
- yellow-white points on the conjunctiva (Horner points)
- corneal “shield” ulcers
- Dennie lines (Dennie-Morgan folds)

Shield ulcers are sterile ulcers which occur where cobblestone papillae are rubbing on cornea.

Children with VKC have measurably longer eyelashes (reaction to ocular inflammation).

VKC is chronic and sight-threatening.

Treatment of Vernal Keratoconjunctivitis

VKC is a sight-threatening disease.

Topical steroids 8 times per day for 7-10 days usually relieves symptoms.

High-dose aspirin therapy has been shown effective (2.4 gm daily)

Topical cyclosporin A (Restasis) has also been used in VKC: Cyclosporine eye drops prevent seasonal recurrences of vernal keratoconjunctivitis in a 2-year study (JACI, 2011).

Giant Papillary Conjunctivitis (GPC)

GPC is linked to chronic exposure to foreign bodies, such as contact lenses. GPC is considered an iatrogenic form of allergic eye disease.

Sensitization not necessary in GCP but is required in all other forms of ocular allergy.

GPC is a chronic inflammation that produces giant papillae (1 mm or greater) on the tarsal conjunctiva of the upper eyelids.

Causes of GPC:
- mechanical trauma secondary to contact lenses
- buildup of protein on the surface of the contact lens causes an allergic reaction

Treatment of Giant Papillary Conjunctivitis

Reduction in the wearing time of contact lenses or total discontinuation is required.

“Artificial tears” help to wash away environmental allergens and lens debris ("protein deposits").

Topical mast cell stabilizers are effective in the treatment of GPC and dual-acting drugs may be the best therapy.

Topical steroids are very effective but should be used only for a short period of time, e.g. 4 times per day for 2-4 days.

Contact lens can be resumed but it often requires a change in the type or material of the contact lenses.

Contact dermatoconjunctivitis

Contact dermatoconjunctivitis is a delayed cell-mediated hypersensitivity reaction (type IV), not an IgE antibody–mediated process.

Contact dermatitis involves the eyelids but can also involve the conjunctivae. Contact dermatitis may be caused by contact lens solutions but a multitude of irritants and allergens have been implicated, for example:

- eye drops, anesthetics, antiviral agents, pilocarpine, timolol
- preservatives in ophthalmic solutions (thiomersal, benzalkonium chloride, chlorhexidine, EDTA)
- cosmetics (eye glosses)
- perfumes
- sunscreens
- adhesives (false eyelashes)

Patch testing is the most useful diagnostic tool for contact dermatoconjunctivitis.

The best treatment is avoidance of the offending agent.

Immunologic Diseases of the Eye

Ocular cicatricial pemphigoid
Peripheral ulcerative keratitis

List of optometric abbrevations

OU, oculus utro (each eye)
OS, oculus sinister (left eye)
OD, oculus dexter (right eye)
SPK, Superficial punctate keratitis


Allergic conjunctivitis. M Reza Dana, MD, MPH, MSc, UpToDate, 16.2, 8/2008.
Chapter 88 – Allergic and Immunologic Diseases of the Eye. Neal P. Barney, Frank M. Graziano. Adkinson: Middleton's Allergy: Principles and Practice, 6th ed.
Allergic Conjunctivitis. Presentation Materials. World Allergy Organization.
Pediatric Ocular Inflammation. Immunology and Allergy Clinic of North America. Volume 28, Issue 1, Pages 169-188 (February 2008).
Chapter 146 – Ocular Allergies. Mark Boguniewicz Donald Y.M. Leung. Kliegman: Nelson Textbook of Pediatrics, 18th ed.
Ocular Allergies. Ask the Expert. AAAAI.
Allergic Conjunctivitis. Ask the Expert. AAAAI.
Allergic conjunctivitis. Handbook of Ocular Disease Management.
Ocular Allergy. Curr Opin Allergy Clin Immunol. 2007; 7(5):424-428. Medscape. Medscape
The Pathophysiology of Ocular Allergy: Current Thinking. C Stephen Foster. Allergy, Volume 50 Issue s21, Pages 6 - 9, 2007.
Online Continuing Education: Ocular Allergy. University of Indiana.
Conjunctivitis, Allergic. Parag A Majmudar, MD. eMedicine.
Allergic rhinoconjunctivitis and differential diagnosis of the red eye. Granet, David. Allergy and Asthma Proceedings, Volume 29, Number 6, 11/12 2008 , pp. 565-574(10).
Updates in the treatment of ocular allergies. Journal of Asthma and Allergy, November 2010, Volume 2010:3 Pages 149 - 158 DOI 10.2147/JAA.S13705 (free PDF).

PowerPoint Presentations

Ocular allergy. V. Dimov, M.D., 09/2008.

Allergic Conjunctivitis. World Allergy Congress.
Allergic Conjunctivitis. MCFP.
Eye diseases and the internist. ACP.


Review Questions: Pediatric Allergy: Principles & Practices, Chapter 56: Allergic and Immunologic Eye Disease.

Patient information

Patient information: Eye Allergies. WebMD.
Ocular Allergies. Clifford W. Bassett, MD, FAAAAI. Allergy & Asthma Advocate: Summer 2007.

Related reading

Allergy season is here :\ on Flickr
Japanese guideline for allergic conjunctival diseases. Allergol Int. 2011 Mar;60(2):191-203.
Vernal Keratoconjunctivitis - NEJM images, 2012.
Eye Drops for allergic conjunctivitis - why would AAAAI include a homeopathic medications in this list? http://buff.ly/1kPCOgn

Published: 09/25/2008
Updated: 02/02/2012

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