World Allergy Forum: Ocular Allergy
Epidemiology and Genetics of Ocular Allergy
Neal P. Barney, M.D.
Ocular Allergic disease is found worldwide with certain areas having a greater predisposition. The most commonly encountered disease entities include: Seasonal Allergic Conjunctivitis (SAC), Perennial Allergic Conjunctivitis (PAC), Atopic Keratoconjunctivitis (AKC), Vernal Keratoconjunctivitis (VKC), and Giant Papillary Conjunctivitis (GPC). The genetics of allergic eye diseases are not specifically studied or reported to date. Information regarding the genetics of allergic eye disease is inferred from studies of other allergic diseases. The epidemiology of allergic eye diseases is reported in eye clinic based studies observing the proportion of all patients seen who have an allergic eye disease. The prevalence of allergic eye disease may also be found in Population based studies of patients who have other forms of allergic disease such as atopic dermatitis or asthma and also report eye findings.
Seasonal and Perennial Allergic Conjunctivitis combine to account for about two thirds of all allergic eye disease cases. The prevalence of SAC and PAC tends to be the same as hay fever or allergic rhinitis. No specific genetic studies of these diseases have been performed. Families with history of allergic disease have been found to increase IgE responsiveness to Derp-p base on certain HLA-D loci. Additionally, increased bronchial hyperesponsiveness in families has been linked to the gene for the FcRI-receptor. Liu et al have shown that in addition to general atopy genes being found in allergic families, genes targeting conjunctival allergies may be found. (1)
Atopic Keratoconjunctivitis (AKC) is a bilateral, severe, allergic inflammation of the conjunctiva found in a subset of patients with Atopic Dermatitis (AD) (Eczema). Atopic Dermatitis occurs in 3% of the population and 15–40% of these will develop AKC. No specific studies of the genetics of AKC have been performed. Skin reactivity to typical allergens is quite high in AKC; i.e. 90% of patients with AKC are skin prick positive for house dust mite and cat dander. Th2 cells are implicated in the pathophysiology of AKC. IL-4 and IL-13 both promote Th2 differentiation. A specific allelic form of the IL-4 receptor alpha was strongly associated with hyper IgE syndrome and atopic dermatitis. (2)
Vernal Keratoconjunctivitis (VKC) is a bilateral, severe, vision threatening allergic inflammation of the conjunctiva. It tends to affect prepubescent boys with allergic predisposition in hot, dry, climates such as the Mediterranean basin, West Africa, and Indian subcontinent. It may be seasonal as implied by the name or perennial. These children have allergic predisposition with 70% having other manifestations of allergic disease along with a strong family history of allergic disease. VKC accounts for 0.5–1.0% of eye disease in most countries. (3) The disease accounts for at least 10% of outpatient visits to an eye clinic in east Jerusalem. (4) Very high levels of IgE are often found in patients with VKC. BCL-6 gene knock out mice showed multiple organ inflammation characterized by eosinophilia and IgE bearing B cells.(5) This may demonstrate a suppressor activity of this gene on the development of Th2 responses which might account for loss of controls on the expression of IgE levels.
Giant Papillary Conjunctivitis (GPC) is a proposed allergic inflammation of usually the upper palpebral conjunctiva associated with prosthetic wear, most commonly contact lens. Estimates are that 1-5% of rigid gas-permeable contact lens wearers and 10-15% of hydrogel (soft) contact lens wearers will develop GPC. (6) Age predilection follows that common to contact lens wear, teenage years to the forties. Allergic association is noted by a somewhat bimodal of spring and fall onset of symptoms. No genetic studies have been performed to date.
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Hershey GK, Freidrich MF, Esswein LA, Thomas ML, Chatila TA. 1997. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N. Engl. J. Med. 337: 1720-25
Beigelman MN. 1950 Vernal Conjunctivitis. Los Angeles: University of Southern California Press
O'Shea JG . 2000 A survey of vernal keratoconjunctivitis and other eosinophil-mediated external eye diseases amongst Palestinians. Ophthalmic Epidemiol 7:149-157
Dent AL, Shaffer AL, Yu X, Allman D, Staudt LM. 1997 Control of inflammation, cytokine expression, and germinal center formation by BCL-6. science 276:589-92
Abelson MB. Allergic Diseases of the Eye. WB Saunders 2000