Allergic conjunctivitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis is inflammation of the conjunctiva (the membrane covering the white part of the eye) due to allergy. Symptoms consist of redness (mainly due to vasodilation of the peripheral small blood vessels), oedema of the conjunctiva, itching and increased lacrimation. If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis.

Allergic conjunctivitis exhibits distinct epidemiological and demographic characteristics based on the populations studied and the presence of comorbidities. Females are more affected and children often have other co-existent allergic diseases. Intermittent episodes are common, with the chronic forms more encountered in clinical practice.

Allergic conjunctivitis is usually a non-progressive condition with a favorable prognosis, and rare but serious complications. Most symptoms are self-limiting, while in some subtypes, a temporal association can be found with the age group and specific triggers. Complications include infections, scarring and can also damage the cornea and eyelids. Long-term prognosis is influenced by the recurrence of the attacks and side-effects of treatment.

Allergic conjunctivitis is frequently characterized by a personal history of allergies and/or atopy and occurrence of similar episodes in the past. Itchiness and diffuse bulbar and tarsal conjunctival injection are the most commonly reported symptoms and almost univerally present in all the subtypes. Other clinical features include eye pain, eye discharge, photophobia and abnormal vision.

Conjunctival hyperemia and discharge are found in the majority of patients on clinical examination. Specific signs include Horner-Tranta’s dots, shield ulcers and cobblestone appearance in VKC, sandpaper like eyelid texture in AKC, and giant conjunctival papillae in GPC.

Conjunctival scrapings from the papillae may yield an inflammatory infiltrate. Tear analysis may show raised levels of inflammatory mediators like histamine and prostaglandins.

Therapeutic interventions for allergic conjunctivitis target one or more points in the inflammatory response cascade. The most common treatment approach is use of a topical pharmacologic medication combined with cold compresses or artificial tears.Moderate to severe symptoms affecting quality of life may warrant more effective and longer-lasting treatment.A key limitation of many topical treatments is the need for multiple daily dosing for maintenance.Surgery is not routinely indicated for treatment of allergic conjunctivitis.Avoidance of the allergens is an important step for preventing allergic conjunctivitis.Early diagnosis and treatment constitute the secondary prevention of allergic conjunctivitis. It involves both pharmacological and non-pharmacological measures.In cost analysis from Turkish data, including direct costs of drugs and physician meetings, lowest treatment cost was established by fluorometholon (US$ 38.94) and followed by ketotifen (US$ 43.41),epinastine (US$ 43.60), olopatadine (US$ 44.05) and emedastine (US$ 44.92), respectively.Compared for incremental cost-effectiveness, emedastine was dominated by ketotifen and itself dominated olopatadine while ketotifen could be compared with fluorometholon and olopatadine.Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

There is no documented history of the discovery and advent of allergic conjunctivitis.

There is no documented history of the discovery and advent of allergic conjunctivitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis can be classified based on the severity and the causative agent(s).

• Seasonal conjunctivitis (SAC)
• Perennial conjunctivitis ((PAC)

• Vernal Keratoconjunctivitis (VKC)
• Atopic Keratoconjunctivitis (AKC)

• Contact lens induced papilloconjunctivitis
• Giant papillary conjunctivitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis is a group of diseases affecting the ocular surface and is usually associated with type 1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) exist, as do three chronic diseases, vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC).

Allergic conjunctivitis is the manifestation of a predominantly IgE-mediated hypersensitivity reaction^[1].

Stimulated mast cells release increased amounts of tryptase, histamine, prostaglandins and leukotrienes in tears. This is the immediate response, which lasts for the initial 20-30 min.

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Degranulation of mast cells activates vascular endothelial cells to express adhesion molecules such as intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and release chemokines like regulated upon activation normal T cells expressed and secreted (RANTES), monocyte chemoattractant protein (MCP), Interleukin (IL)-8, eotaxin, macrophage inflammatory protein (MIP)-1 alpha.

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Triggers the recruitment of inflammatory cells in the conjunctival mucosa, which mediate the ocular late-phase reaction^[2].

• The allergic reaction in VKC is chronic in nature, mediated by Th2-lymphocyte alongside the over-expression of mast cells, eosinophils, neutrophils, Th2-derived cytokines, chemokines, adhesion molecules, growth factors, fibroblasts and lymphocytes. IL-4 and IL-13 are involved in the formation of the giant papillae by inducing extra-cellular matrix production and conjunctival fibroblast proliferation^[3].
• Th1 lymphocytes are one of the primary mediators in AKC^[4].
• Contact allergy, or allergic contact dermatitis, in contrast is a type-IV delayed hypersensitivity response^[5]

Antigen-MHC class II complex interacts with T-lymphocytes → Differentiation of CD4+ T-lymphocyte into memory T-lymphocyte→ Proliferates to release cytokines^[6]. Th1 derived cytokines, such as IL-2, IL-3, IFN-γ, recruit macrophages. Th2 derived cytokines, such as IL-4 and IL-5, mediate the activation and chemotaxis of eosinophils^[7].

• IL-17-producing T cells (Th-17 cells) and regulatory T cells (Treg cells) have also been found to be contributing to the pathogenesis. However, their role has not yet been clearly elucidated^[8].
• In GPC, the conjunctival tissues do not contain mast cells, basophils, or eosinophils, to the extent of an allergic reaction. No increase in IgE or histaimine has been found in the tears of GPC patients. It appears that protein deposits on the surface of the contact lens become antigenic and stimulate the production of IgE; mechanical trauma and chronic irritation can also drive the release of some mediators (CXCL8 and TNF-α) from the injured conjunctival epithelium^[9].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis can be attributed to a variety of causative agents, both natural and artificial.

Transitory allergens:

• Tree pollen
• Grass pollen

Indoor allergens

• House dust mites
• Animal dander
• Mold spores
• Cockroach
• Rodents

The smaller allergens, being more easily volatile, are more potent.

There is usually a history of asthma, systemic atopic disease or eczema. It is perennial in nature with worsening in the winter months.

The incidence peaks during spring when exposure to tree grass pollens increases^[3].

It is predominantly iatrogenic, triggered by foreign bodies in the eye such as contact lenses, prostheses, or protruding corneal sutures, all of which may precipitate and perpetuate an inflammatory response^[4].

This is usually precipitated by exposure to an iatrogenic allergen, such as eye cosmetics or ocular therapeutic preparations, whose withdrawal leads to clinical improvement^[5].

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The differential diagnoses of allergic conjunctivitis include:

• Infective conjunctivitis : Bacterial and viral conjunctivitis are the most important clinical entities to differentiate from allergic conjunctivitis. They present with classical systemic symptoms of infection long with some characteristic ocular features
• Autoimmune eye disease: Characterised by episcleritis, scleritis from a wide range of diseases including rheumatoid arthritis, ankylosing spondylitis etc.
• Acne rosacea: Manifests as facial papules and pustules with flushing and photosensitivity.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis exhibits distinct epidemiological and demographic characteristics based on the populations studied and the presence of comorbid conditions. Females are more affected and children often have other co-existent allergic diseases. Intermittent episodes are common, with the chronic forms more encountered in clinical practice.

• A prevalence of 15-20% is seen in studies performed on older population, but more recent studies estimate rates as high as 40%^[1].
• The age-sex adjusted prevalence was as high as 70.5% in a study conducted in Saudi Arabia, which did not show any variation of risk of the disease with age group. However, females were affected more frequently than males^[2].
• Most children with allergic conjunctivitis also suffer from allergic rhinitis. Ocular allergies may even supersede the primary complaints of nasal congestion^[1].
• Although seasonal allergic conjunctivitis is the most frequent form, the chronic forms, such as vernal and atopic keratoconjunctivitis, are the ones more commonly encountered by ophthalmologists^[3].
• Most of the patients with allergic conjunctivitis suffer few mild ,intermittent episodes on an annual basis. However, 30% of patients experience intense and persistent symptoms^[3].
• Treatment is frequently inappropriate^[3].

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Numerous established and probable risk factors have been elucidated in the pathogenesis of allergic conjunctivitis.

• Changing climates^[1]
• Increasing pollution^[1]
• Genetics^[1]
• Cigarette pollutants^[1]
• Allergic disease in early childhood^[1]
• Mixed pollen, thresher dust, raw cotton^[2]
• Prenatal maternal paracetamol intake^[3]
• Insufficient vitamin D supplementation in the postnatal period^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

Allergic conjunctivitis is usually a non-progressive condition with a favorable prognosis, and rare but serious complications. Most symptoms are self-limiting, while in some subtypes, a temporal association can be found with the age group and specific triggers. Complications include infections, scarring and can also damage the cornea and eyelids. Long-term prognosis is influenced by the recurrence of the attacks and side-effects of treatment.

Symptoms are often neglected, and resolve in many patients without medical care.

Complete resolution without the return of symptoms after adolescence is observed in a majority of patients.

Uncommon before adolescence and peaks from 30 to 50 years of age. Most cases coexist with atopic dermatitis.

• A temporal relationship with contact lens use may explain the predominance of this variety in teens and young adults.
• It manifests usually after one to two years of wearing soft contact lenses but varies widely with other ocular foreign bodies^[1].

In most cases, allergic conjunctivitis is a benign condition. Complications although rare,can be serious and include:

• Scarring of the eye in severe cases.
• Progression to infective conjunctivitis, leading to serious secondary infections.
• Corneal opacification and ulceration in VKC and [[AKC]^[2]]
• Difficulty in wearing contact lenses due to significant eyelid involvement^[2]

• PAC and SAC demonstrate favorable long-term outcomes but, significant eye discomfort and poor ocular cosmesis may persist as long-term sequelae in many people.
• Recurrences result in conjunctivochalasis, which is a result of ongoing limba conjunctival chemosis.
• The medications may cause adverse reactions like cataracts.

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