Conjunctival allergen challenge: Models in the investigation of ocular allergy

Mark B. Abelson1, Oliver P Loeffler1
1Ophthalmic Research Associates, North Andover, USA

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Abelson MB, Chapin MJ: Current and future topical treatments for ocular allergy. Comp Ophthalmol Update 2000, 1:303–317.

Abelson MB, Allansmith MR: Histamine and the eye. In Immunology and Immunopathology of the Eye. Edited by Silverstein AM, O’Connor GF. New York: Masson; 1979:362–363.

Abelson MB, Smith LM. Levocabastine: evaluation in the histamine and compound 48/80 models of ocular allergy in humans. Ophthalmology 1988, 95:1494–1497.

Abelson MB, Leonardi AA, Smith LM, et al.: Histaminase activity in patients with vernal keratoconjunctivitis. Ophthalmology 1995, 102:1958–1963.

Abelson MB, Allansmith MR: Histamine and the eye. In Immunology and Immunopathology of the Eye. Edited by Silverstein AM, O’Connor GF. New York: Masson; 1979:363–364.

Leonardi A, Abelson M: Mast cell stabilizing effects of olopatadine following allergen challenge in humans [abstract]. ARVO. 2003, in press. This is the first study correlating clinical effects and the indices of mast cell stabilizing properties, including decreased histamine levels, for a therapeutic agent with multiple actions in ocular allergic subjects.

George MA, Smith LM, Berdy GL, et al.: Platelet activating factor induced inflammation following topical ocular challenge [abstract]. Invest Ophthalmol Vis Sci 1990, 31(Suppl):63.

Abelson MB, Madiwale NA, Weston JH: The role of prostaglandin D2 in allergic ocular disease. In Third International Symposium of the Immunology and Immunopathology of the Eye. Edited by O’Connor GR, Chandler JW. New York: Masson; 1985:163–166.

Weston JH, Abelson MB: Leukotriene C4 in rabbit and human eyes [abstract]. Invest Ophthalmol Vis Sci 1981, 26(Suppl):191.

Butrus SI, Ochsner KI, Abelson MB, Schwartz LB: The level of tryptase in human tears: an indicator of activation of conjunctival mast cells. Ophthalmology 1990, 97:1678–1683.

Proud D, Sweet J, Stein P, et al.: Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen. J Allergy Clin Immunol 1990, 85:896–905.

Bisgaard H, Ford-Hutchinson AW, Charleson S, et al.: Production of leukotrienes in human skin and conjunctival mucosa after specific allergen challenge. Allergy 1985,40:417–423.

Horak F, Toth J, Hirschwehr R, et al.: Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients. Allergy 1998, 53:68–72.

Abelson MB, Leonardi AA, Smith LM, et al.: Histaminase activity in patients with vernal keratoconjunctivitis. Ophthalmology 1995, 102:1958–1963.

Ciprandi G, Buscaglia S, Pesce G, et al.: Allergic subjects express intercellular adhesion molecule-1 (ICAM-1 or CD54) on epithelial cells of conjunctiva after allergen challenge. J Allergy Clin Immunol 1993, 91:783–792.

Bonini S, Bonini S, Vecchione A, et al.: Inflammatory changes in conjunctival scrapings after allergen provocation in humans. J Allergy Clin Immunol 1988, 82:462–469.

Anderson DF, Macleod JDA, Baddeley SM, et al.: Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers in the absence of leukocyte infiltration. Clin Exp Allergy 1997, 27:1060–1066. Results of this study show that infiltrate of eosinophils and neutrophils was not seen in more than 50% of subjects with seasonal allergic conjunctivitis. This suggested the absence of a clinically relevant late-phase reaction in the eyes of most patients.

Abelson MB, Madiwale N, Weston JH: Conjunctival eosinophils in allergic ocular disease. Arch Ophthalmol 1983, 101:555–556.

Leonardi A, Papa V, Milazzo G, Secchi AG: Efficacy and safety of desonide phosphate for the treatment of allergic conjunctivitis. Cornea 2002, 21:476–481.

Bacon A, Ahluwalia P, Irani A, et al.: Tear and conjunctival changes during the allergen-induced early- and late-phase responses. J Allergy Clin Immunol 2000, 106:948–954. This study shows an evident influx of cells into the conjunctiva following a high dose of allergen. The lack of a peak of tryptase during the 6-h examination following challenge indicates that mast cells might not be degranulating during this time.

Leonardi A, Fregona IA, Gismondi M, et al.: Correlation between conjunctival provocation (CPT) and systemic allergometric tests in allergic conjunctivitis. Eye 1990, 4:760–764.

Rosner S, Gomes P, Abelseon M: Effect of absolute versus relative pollen counts on individual’s ocular itching severity scores in six different geographic locations [abstract]. ARVO 2003, in press.

Davies B, Mullins J: Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis. Allergy 1993, 48:519–524.

Lindsay-Miller A: Group comparative trial of 2% sodium cromoglycate (Opticrom) with placebo in the treatment of seasonal allergic conjunctivitis. Clin Allergy 1979, 9:271–275.

Abelson MB, Smith LM: Levocabastine: evaluation in the histamine and compound 48/80 models of ocular allergy in humans. Ophthalmology 1988, 95:1494–1497.

Abelson MB, Yamamoto GK, Allansmith MR: Effects of ocular decongestants. Arch Ophthalmol 1980, 98:856–858.

Abelson MB, Chembers WA, Smith LM: Conjunctival allergen challenge: a clinical approach to studying allergic conjunctivitis. Arch Opthalmol 1990, 108:84–88.

Abelson MB: Comparison of the conjunctival allergen challenge model with the environmental model of allergic conjunctivitis. Acta Opthalmologica Scandinavica Suppl 1999, 228:38–42. A review paper evaluating the challenge model versus environmental designs.

Abelson MB, George MA, Schaefer K, Smith LM: Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis. J Allergy Clin Immunol 1994, 94:458–464.

Abelson MB: Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model. Ann Allergy Asthma Immunol 1998, 81:211–218.

Abelson MB, Spitalny L: Combined analysis of two studies using the conjunctival allergen challenge model to evaluate olopatadine, a new ophthalmic antiallergic agent with dual activity. Am J Ophthalmol 1998, 125:797–804. This study evaluated the efficacy of olopatadine in the challenge model. The importance is that the model was used to evaluate a drug that has been very successful in treating ocular allergy. This study supported FDA approval.

Berdy GJ, Spangler DL, Bensch G, et al.: A comparison of the relative efficacy and clinical performance of olopatadine hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the conjunctival antigen challenge model. Clin Ther 2000, 22:826–833.

Arienzo P, Leonardi A, Bensch G: Randomized, double-masked, placebo-controlled comparison of the efficacy of emedastine difumarate 0.05% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the human conjunctival allergen challenge model. Clin Ther 2002, 24:409–416.

Spangler DL, Bensch G, Berdy G: Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model. Clin Ther 2001, 23:1272–1280. This study demonstrates the sensitivity of the conjunctival allergen challenge model in evaluating a drug versus an active control.

Abelson MB, Berdy GJ, Mundorf T, et al.: Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis: a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies. J Ocular Pharm Ther 2002, 18:475–488. This study was the first published study utilizing a combined challenge/environmental design. At 17 weeks of dosing during the environmental phase, to our knowledge, it was also the longest environmental ocular allergy study published.

Abelson MB, Turner FD, Amin D: Patanol is effective in the treatment of the signs and symptoms of allergic conjunctivitis and allergic rhinoconjunctivitis [abstract]. Invest Ophthalmol Vis Sci 2000, 41(Suppl):4922. This study shows that in a modified environmental model, topical allergy drops instilled in the eye can have significant effects on nasal symptoms.

Crampton HJ: A comparison of the relative clinical efficacy of a single dose of ketotifen fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge model. Clin Ther 2002, 24:1800–1808. This study demonstrates that the conjunctival allergen challenge induces significant signs of allergic rhinitis and that a topical allergy eyedrop, instilled in the eye, can have effect on these nasal symptoms.