TREATMENT OF OCULAR ALLERGY

Abstract

Treatment of ocular hypersensitivity reactions requires a multidisciplinary approach in conjunction with an ophthalmologist and a clinical allergist/immunologist. Mast cell activation plays a central role in ocular allergy. Mast cells are found at a high density in normal conjunctiva (5000 per mm 3 ) 4 and their density increases in the more chronic forms of ocular hypersensitivity disorders. Treatment is directed at the release of preformed and newly formed mediators. Histamine, the prototype of the preformed mediators, has been shown to be elevated in tears of patients with vernal conjunctivitis. 1 Furthermore, these patients have an exaggerated response to histamine challenge compared with nonallergic controls. 15 This hyper-responsiveness of allergic patients to nonspecific stimuli also occurs in asthmatics. 22 Two types of histamine receptors have been delineated: 1 The H 1 receptor causes vasodilatation, increased vascular permeability, and itching. 2 H 2 receptors also cause vasodilatation and itching, and they alone are responsible for the mucous discharge seen in allergic eye disease. Newly synthesized mediators include derivatives of the eicosanoids, which are a class of potent oxygenated lipids that are generated from 20 carbon unsaturated fatty acids, usually arachidonic acid. Arachidonic acid is covalently bound (esterified) to membrane phospholipids. Upon stimulation of mast cells by allergen, arachidonic acid is hydrolyzed from membrane phospholipids and then oxygenated by cyclo-oxygenase (now known to be prostaglandin H synthase) to form prostaglandin H 2 (PGH 2 ). PGH 2 is then in turn the precursor of all prostaglandins, prostacyclins, and thromboxanes. The type of eiconsanoid ultimately synthesized depends on the enzymatic machinery present, and in mast cells, the major prostanoid produced is PGD 2 . Using quantitative gas chromatography and mass spectroscopy, Roberts et al have shown that isolated rat peritoneal and pleural mast cells produce PGD 2 and several other oxygenated products of arachidonic acid. Upon stimulation of these cells by ionophore, PGD 2 synthesis increases 10-fold, with modest increases in prostaglandins F 2 , E 2 , thromboxane B 2 , and a prostacyclin breakdown product (6-keto-prostaglandin F 1a ). 52 Stimulation of human mast cells by anti-IgE antibody also has been shown to lead to histamine release and PGD 2 biosynthesis. 44 PGD 2 has been shown to be elevated in tears of patients with vernal conjunctivitis, 25 and when instilled into human eyes leads to injection, chemosis, and eosinophil influx. 3