Allergic Conjunctivitis

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Article initiated by:

A. Paula Grigorian, MD, Adrian Au

All contributors:

Chrysavgi Adamopoulou, MD, Vatinee Y. Bunya, MD, MSCE, Christina Moon, M.D., Colleen Halfpenny, M.D., S. Grace Prakalapakorn, MD, MPH, Donny W. Suh, MD, FAAP, MBA, FACS, Seth Bricel, MD, A. Paula Grigorian, MD, Allison Umfress, MD

Assigned editor:

Allison Umfress, MD, Ravi Patel MD MBA

Review:

Assigned status Update Pending

 by Christina Moon, M.D. on September 4, 2023.

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Contributing Editors:	add

Allergic Conjunctivitis

DiseasesDB

30842

ICD-10

H10.1 H10.4

MedlinePlus

001031

MeSH

D003233

Allergic conjunctivitis is an inflammatory response of the conjunctiva to an allergen. It is part of a larger systemic atopic reaction and is usually seasonal with associated upper respiratory tract symptoms and complaints of redness and swelling of the conjunctiva with severe itching and increased lacrimation. Presence of rhinitis often terms this process as allergic rhinoconjunctivitis.

ICD Codes

ICD 9:
372.0
        372.00 Acute conjunctivitis, unspecified
        372.05 Acute atopic conjunctivitis

372.1 Chronic conjunctivitis
        372.10 Chronic conjunctivitis, unspecificied
        372.13 Vernal conjunctivitis
        372.14 Other chronic allergic conjunctivitis

ICD 10:
H10.1 Acute atopic conjunctivitis
        H10.10 - unspecified eye
        H10.11 - right eye
        H10.12 - left eye
        H10.13 - bilateral

H10.4 Chronic conjunctivitis
        H10.40 Unspecified chronic conjunctivitis
                H10.401 right eye
                H10.402 left eye
                H10.403 bilateral
                H10.409 unspecified eye
        H10.41 Chronic giant papillary conjunctivitis
                H10.411 right eye
                H10.412 left eye
                H10.413 bilateral
                H10.419 unspecified eye
         H10.44 Vernal conjunctivitis
         H10.45 Other chronic allergic conjunctivitis

Disease Entity

Disease

Classification

Allergic Conjunctivitis

• Seasonal Allergic Conjunctivitis - has a more rapid presentation, typically after airborne exposure to pollen
• Perennial Allergic Conjunctivitis - has a milder presentation that can last year round, triggered by various allergens

Other Immune Mediated Conjunctivitis

• Vernal Keratoconjunctivitis
• Atopic Keratoconjunctivitis
• Giant Papillary Conjunctivitis

Epidemiology

Allergic conjunctivitis is one of the most common forms of conjunctivitis. In a report from the National Health and Nutrition Examination Survey studying the epidemiology of allergic conjunctivitis, 6.4% and 29.7% of 20,010 patients reported ocular symptoms and combined ocular and nasal symptoms, respectively. 40% of the population reported experiencing at least 1 occurrence of ocular symptoms in the past 12 months.

Atopic keratoconjunctivitis occurs predominantly between the late teenage years and fifth decade of life. It relapses and remits with no seasonal correlation. Atopic dermatitis is present in 95% of cases and asthma in 87% of cases. 

Vernal keratoconjunctivitis changes with the seasons. Commonly seen in prepubescent males ranging from age 5-20 with a peak incidence at 11-13. Males are twice as often affected than females. More often seen in warm, dry, climates with a decrease in inflammation and symptoms in the winter. 

Risk Factors

Grouping	Type	Risk Factors
Without corneal involvement	Acute	Environmental allergens, particularly if they are known; an example is cat dander.
	Seasonal	Environmental allergens that are often associated with changes in seasons; examples include grass and weed pollens.
	Perennial	Environmental allergens that occur throughout the year; examples include Indoor allergens: dust mites, mold, animal dander.
With corneal involvement	Vernal	Environmental allergens may incite an acute exacerbation. Most commonly present during the springtime with the associated increase in pollen. Increased presence in hot and dry environments with a decrease in inflammation and symptoms during the winter months.
	Atopic	Genetic predisposition to atopic reactions with comorbid asthma and atopic dermatitis commonly present. Increased risk with positive family history. Environmental allergens may cause an acute exacerbation as well. No changes with seasons.
	Giant papillary conjunctivitis (GPC)	Commonly seen in individuals wearing soft contact lens who infrequently replace their lenses, wear their lenses for prolonged periods of time, have poor lens hygiene, have poor contact lens fitting, or are allergic to the various contact lens solution. Similarly, irritation from exposed sutures or prostheses increase the risk for developing GPC.

Pathophysiology

Seasonal and perennial allergic conjunctivitis

Seasonal and Perennial allergic conjunctivitis are IgE mediated hypersensitivity reactions. The allergen causes cross-linkage of membrane-bound IgE that causes mast cells to degranulate. This causes a release and cascade of allergic and inflammatory mediators, such as histamine.

Vernal keratoconjunctivitis and atopic keratoconjunctivitis

The pathophysiological mechanism of disease is not fully understood. However, evidence suggest the involvement of various cells within the conjunctiva, specifically eosinophils, fibroblasts, epithelial cells, mast cells, and TH2 lymphocytes. Allergens activate these various cells creating an inflammatory response. 

Giant papillary conjunctivitis

This is not a true ocular allergy but rather a repetitive mechanical irritation, often in due to contact lenses, that is aggravated by concomitant allergy. 

Primary prevention

Removal of allergen, such as pollen or stitches.

Diagnosis

The diagnosis is clinical based on history, signs and symptoms, and physical exam findings. An allergy panel for identification of specific allergen can be considered. In addition, confocal microscopy can be used to evaluate some forms of allergic conjunctivitis, such as atopic conjunctivitis.

The American Academy of Ophthalmology's Pathology Atlas contains a virtual microscopy image of Papillary Conjunctivitis.

Signs and Symptoms

Itching is the primary symptom where patients are constantly rubbing their eyes with temporary relief. The eyelids and conjunctiva become edematous and diffusely hyperemic. Presentation is most often bilateral, due to the systemic nature of the disease.

Physical examination

Type of Allergic Conjunctivitis	Physical Exam Findings
Seasonal/Perennial conjunctivitis	Bilateral conjunctival injection, chemosis, watery discharge, and mild mucous discharge.
Vernal keratoconjunctivitis (VKC)	Bilateral bulbar conjunctival injection with associated watery and mucoid discharge. Patients develop a giant papillary hypertrophy of only the superior tarsal conjunctiva, resembling “cobblestones”. Specific findings that help differentiate VKC from AKC are: limbal (Horner-Trantas) dots which are small white-yellow chalky concretions around the corneal limbus; corneal vernal plaques; or shield (Togby’s) shaped ulcers of the cornea. Just as in AKC, patients, if untreated, can develop conjunctival scarring or corneal neovascularization, scarring, or erosions/ulcers.
Atopic keratoconjunctivits (AKC)	Bilateral conjunctival injection with associated eczematoid belpharitis, watery/mucoid discharge, and boggy edema. Papillary hypertrophy of superior or inferior tarsal conjunctival can occur with increased risk for eyelid thickening and scarring. In more severe and untreated cases, patients can develop loss of eyelashes, conjunctival scarring, corneal neovascularization, ulcers or scars, punctate epithelial keratitis and associated keratoconus and/or anterior/posterior subcapsular cataracts.
Giant papillary conjunctivitis (GPC)	The laterality of symptoms is associated with contact lens, suture, or prostheses wear pattern. Most notably, patients will have papillary hypertrophy of the superior tarsal conjunctiva. In long-standing, untreated disease, the papillae will develop white fibrotic centers. In severe cases, patients will have lid swelling and ptosis.

 

Natural History

Allergic conjunctivitis	Natural History	Potential Sequelae
Seasonal/Perennial conjunctivitis	Recur seasonally with the changes in pollens and allergens present.	Minimal or local inflammation that often resolves and remits.
Vernal keratoconjunctivitis (VKC)	The onset of symptomatology begins in childhood and peaks at about 11-13 with acute exacerbations occurring more frequently during the spring and summer months. Commonly patients will “grow out” of the disease with decreased symptoms ranging from 2-30 years of age.	Untreated VKC can lead to eyelid thickening that ultimately leads to ptosis. Severe corneal involvement can cause corneal neovascularization, thinning, ulceration, and infection. This can lead to vision loss or development of keratoconus. Conjunctival scarring can also occur.
Atopic keratoconjunctivitis (AKC)	Similar to VKC, the onset of symptoms occurs during childhood but peaks during young adult and continues into the fifth decade of life. The course remains chronic with periodic acute exacerbations.	The natural sequelae is similar to VKC with eyelid thickening or tightening. Conjunctival scarring can occur and involvement of the cornea can lead to scarring, neovascularization, thinning, ulceration and infection. This can also develop into keratoconus or cause vision loss. There can also be development of concurrent anterior or posterior subcapsular cataracts.
Giant papillary conjunctivitis (GPC)	This disease process is directly correlated with presence of risk factors. Therefore, continued contact lens wear, exposed corneal or scleral sutures, or ocular prosthesis cause worsening or increasing in symptoms.	If left untreated, GPC can cause acquired ptosis.

Differential diagnosis

• Infectious conjunctivitis
• Blepharitis
• Dry Eyes Syndrome
• Toxic conjunctivitis
• Ocular rosacea
• Keratitis
• Episcleritis/scleritis
• Angle Closure glaucoma
• Phlyctenular conjunctivitis

Management

Seasonal/Perennial Allergic Conjunctivitis

Topical drops for allergic conjunctivitis come in many different forms. Here we outline a general overview/suggestions of the different options. Of note, chronic use of vasoconstrictive agents can lead to rebound vasodilation when discontinued.

1. First line: Over-the-counter antihistamine/vasoconstrictor agent. Vasoconstrictors: Inexpensive over-the counter are first line. Many brands are available containing antazoline phosphate 0.05%, naphazoline HCl 0.05%, oxymetazoline HCl, tetrahydrozoline HCl 0.05%, or phenylephrine 0.12%.
2. Second line: Second-generation topical histamine H1-receptor antagonist. H-1 receptor antagonists: More effective than the vasoconstrictors, but much more expensive. The three principal choices are pheniramine maleate 0.3% (Naphcon), emedastine (Emadine), and levocabastine HCl 0.05% (Livostin)
3. Third line: recurrent/persistent - mast-cell stabilizers can be used. Mast cell stabilizers: cromolyn sodium 4% (Crolom), nedocromil 2% (Alocril), pemirolast 0.1% (Alamast), and lodoxamide tromethamine 0.1% (Alomide). These are FDA-approved only for a specifically vernal conjunctivitis. Use only if other classes of medications have failed.
4. Combined medications can also be used: Combined H-1 receptor antagonist and mast cell stabilizers: olopatadine hydrochloride 0.1% (Patanol), olopatadine hydrochloride 0.2% (Pataday), optivar, ketotifen fumarate (Zaditor, Alaway), and Elestat. These agents are more effective than the mast cell stabilizers alone.
5. If symptoms are not adequately controlled: Brief course of low-potency and low-frequency topical corticosteroids. NSAID such as ketorolac has been approved by FDA for use of seasonal allergic conjunctivitis but are generally used as adjunctive agents. Nonsteroidal anti-inflammatory agents: ketorolac tromethamine 0.5% (Acular).
6. Oral antihistamines, such as Xyzal (levocetirizine), Zyrtec (cetirizine), Allegra (fexofenadine), Clarinex (desloratadine) and Clarinex (loratadine), can be used, especially if the patient is experiencing additional systemic effects.
7. Some additional measures can be used as adjunctive measures to improve symptom management are as follows:
   • Artificial tears to dilute allergens
   • Cool compresses / ice packs
   • Avoid Allergens
   • Frequent clothes washing and bathing/showering before bedtime
   • Refer/consult allergy or dermatology for those who are not adequately controlled with topical medications and oral antihistamines

Vernal/Atopic Keratoconjunctivitis

Although the disease process is more advanced in both VKC and AKC, the general treatment strategies remain similar to management of seasonal or perennial allergic conjunctivitis. If, however, an acute exacerbation occurs, topical corticosteroids are often added to reduce inflammation. Another adjunctive therapy is addition of topical cyclosporin 2%. If the VKC or AKC is not responsive to topical therapy, supratarsal injection of corticosteroid can be considered.

Giant Papillary Conjunctivitis

The most important management in GPC is modifying the causative entity. This generally includes removal or replacement of sutures, rotating the knots, or using a therapeutic contact lens.

Additional Resources

• Boyd K, Huffman JM, Turbert D. Conjunctivitis: What Is Pink Eye? American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/pink-eye-conjunctivitis Accessed May 27, 2022.
• Boyd K, Mendoza O. Giant Papillary Conjunctivitis American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/what-is-giant-papillary-conjunctivitis Accessed May 27, 2022.
• Turbert D, Mendoza O. What Are Eye Allergies? American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/allergies Accessed May 27, 2022.