Drugs

, Volume 65, Issue 2, pp 215–228

Efficacy and Tolerability of Newer Antihistamines in the Treatment of Allergic Conjunctivitis

  • Leonard Bielory
  • Kenneth W. Lien
  • Steve Bigelsen
Review Article

Abstract

Treatment for allergic conjunctivitis has markedly expanded in recent years, providing opportunities for more focused therapy, but often leaving both physicians and patients confused over the variety of options. As monotherapy, oral antihistamines are an excellent choice when attempting to control multiple earlyphase, and some late-phase, allergic symptoms in the eyes, nose and pharynx. Unfortunately, despite their efficacy in relief of allergic symptoms, systemic antihistamines may result in unwanted adverse effects, such as drowsiness and dry mouth. Newer second-generation antihistamines (cetirizine, fexofenadine, loratadine and desloratadine) are preferred over older first-generation antihistamines in order to avoid the sedative and anticholinergic effects that are associated with first-generation agents. When the allergic symptom or complaint, such as ocular pruritus, is isolated, focused therapy with topical (ophthalmic) antihistamines is often efficacious and clearly superior to systemic antihistamines, either as monotherapy or in conjunction with an oral or intranasal agent.

Topical antihistaminic agents not only provide faster and superior relief than systemic antihistamines, but they may also possess a longer duration of action than other classes including vasoconstrictors, pure mast cell stabilisers, NSAIDs and corticosteroids. Many antihistamines have anti-inflammatory properties as well. Some of this anti-inflammatory effect seen with ‘pure’ antihistamines (levocabastine and emedastine) may be directly attributed to the blocking of the histamine receptor that has been shown to downregulate intercellular adhesion molecule-1 expression and, in turn, limit chemotaxis of inflammatory cells. Some topical multiple-action histamine H1-receptor antagonists (olopatadine, ketotifen, azelastine and epinastine) have been shown to prevent activation of neutrophils, eosinophils and macrophages, or inhibit release of leukotrienes, platelet-activating factors and other inflammatory mediators. Topical vasoconstrictor agents provide rapid relief, especially for redness; however, the relief is often short-lived, and overuse of vasoconstrictors may lead to rebound hyperaemia and irritation. Another class of topical agents, mast cell stabilisers (sodium cromoglicate [cromolyn sodium], nedocromil and lodoxamide), may be considered; however, they generally have a much slower onset of action. The efficacy of mast cell stabilisers may be attributed to anti-inflammatory properties in addition to mast cell stabilisation. In the class of topical NSAIDs, ketorolac has been promoted for ocular itching but has been found to be inferior for relief of allergic conjunctivitis when compared with olopatadine and emedastine. Lastly, topical corticosteroids may be considered for severe seasonal ocular allergy symptoms, although long-term use should be avoided because of risks of ocular adverse effects, including glaucoma and cataract formation.

References

  1. 1.
    Buscaglia S, Paolieri F, Catrullo A, et al. Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro. Clin Exp Allergy 1996 Oct; 26(10): 1188–96PubMedCrossRefGoogle Scholar
  2. 2.
    Woodward DF, Hawley SB, Williams LS, et al. Studies on the ocular pharmacology of prostaglandin D 2. Invest Ophthalmol Vis Sci 1990 Jan; 31(1): 138–46PubMedGoogle Scholar
  3. 3.
    Katelaris CH. Ocular allergy: implications for the clinical immunologist. Ann Allergy Asthma Immunol 2003 Jun; 90 (6 Suppl. 3): 23–7PubMedCrossRefGoogle Scholar
  4. 4.
    Bielory L. Allergic and immunologic disorders of the eye. Part I: immunology of the eye. J Allergy Clin Immunol 2000; 106(5): 805–16Google Scholar
  5. 5.
    Tsubota K, Takamura E, Hasegawa T, et al. Detection by brush cytology of mast cells and eosinophils in allergic and vernal conjunctivitis. Cornea 1991 Nov; 10(6): 525–31PubMedCrossRefGoogle Scholar
  6. 6.
    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 Mar; 91(3): 783–92PubMedCrossRefGoogle Scholar
  7. 7.
    Ciprandi G, Tosca MA, Cosentino C, et al. Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules. J Allergy Clin Immunol 2003 Oct; 112 (4 Suppl.): S78–82PubMedCrossRefGoogle Scholar
  8. 8.
    Paolieri F, Battifora M, Riccio AM, et al. Terfenadine and fexofenadine reduce in vitro ICAM-1 expression on human continuous cell lines. Ann Allergy Asthma Immunol 1998 Dec; 81(6): 601–7PubMedCrossRefGoogle Scholar
  9. 9.
    Abelson MB, Udell IJ. H2-receptors in the human ocular surface. Arch Ophthalmol 1981 Feb; 99(2): 302–4PubMedCrossRefGoogle Scholar
  10. 10.
    Sharif NA, Su SX, Yanni JM. 36Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies. J Ocul Pharmacol 1994; 10(4): 653–64PubMedCrossRefGoogle Scholar
  11. 11.
    Kakiuchi M, Ohashi T, Musoh K, et al. Studies on the novel antiallergic agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor. Jpn J Pharmacol 1997 Apr; 73(4): 291–8PubMedCrossRefGoogle Scholar
  12. 12.
    Ellis J, Seidenberg M. Desloratadine exhibits high affinity to-ward muscarinic acetylcholine receptors in binding and functional studies [abstract]. FASEB J 2001; 15(4): A557Google Scholar
  13. 13.
    Gillard M, Van der Perren C, Massingham R, et al. Binding characteristics of [3H]levocetirizine to cloned human H1-histamine-receptors expressed in CHO cells. Inflamm Res 2002 Apr; 51 Suppl. 1: S77–8PubMedGoogle Scholar
  14. 14.
    Evangelista S, Boni P, Castellucci A, et al. Antihistaminic and antiallergic properties of dextro-mequitamium iodide in upper and lower guinea pig airways: comparison with azelastine. Gen Pharmacol 1998 Apr; 30(4): 513–9PubMedCrossRefGoogle Scholar
  15. 15.
    Azelastine (Optivar™) product monograph. Tewksbury (MA): Muro Pharmaceuticals, Inc., 2000 Jun: 8Google Scholar
  16. 16.
    Fugner A, Bechtel WD, Kuhn FJ, et al. In vitro and in vivo studies of the non-sedating antihistamine epinastine. Arzneimittelforschung 1988 Oct; 38(10): 1446–53PubMedGoogle Scholar
  17. 17.
    Kubo N, Shirakawa O, Kuno T, et al. Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay. Jpn J Pharmacol 1987 Mar; 43(3): 277–82PubMedCrossRefGoogle Scholar
  18. 18.
    Sharif NA, Xu SX, Miller ST, et al. Characterisation of the ocular antiallergic and antihistaminic effects of olopatadine (AL-4943A), a novel drug for treating ocular allergic diseases. J Pharmacol Exp Ther 1996 Sep; 278(3): 1252–61PubMedGoogle Scholar
  19. 19.
    Ahn HS, Barnett A. Selective displacement of [3H]mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine. Eur J Pharmacol 1986 Aug 7; 127(1–2): 153–5PubMedCrossRefGoogle Scholar
  20. 20.
    Simons FE. Comparative pharmacology of H1 antihistamines: clinical relevance. Am J Med 2002 Dec 16; 113 Suppl. 9A: 38S–46SPubMedCrossRefGoogle Scholar
  21. 21.
    Zyrtec®: prescribing information [online]. Available from URL: http://www.zyrtec.com [Accessed 2004 Nov 4]
  22. 22.
    Allegra®: prescribing information [online]. Available from URL: http://www.allegra.com/seasonal-allergy-site.jsp [Accessed 2004 Nov 4]
  23. 23.
    Claritin®: prescribing information. Kenilworth (NJ): Schering-Plough Corp., 2004Google Scholar
  24. 24.
    Clarinex®: prescribing information [online]. Available from URL: http://www.sch-plough.com/schering_plough/pc/allergy_respiratory.jsp [Accessed 2004 Nov 4]
  25. 25.
    Schoeneich M, Pecoud AR. Effect of cetirizine in a conjunctival provocation test with allergens. Clin Exp Allergy 1990 Mar; 20(2): 171–4PubMedCrossRefGoogle Scholar
  26. 26.
    Tosca M, Ciprandi G, Passalacqua G, et al. Cetirizine reduces conjunctival nonspecific hyperreactivity in children with mite allergy. J Investig Allergol Clin Immunol 1998 Jan–Feb; 8(1): 23–6PubMedGoogle Scholar
  27. 27.
    Ciprandi G, Buscaglia S, Pesce G, et al. Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early- and late-phase reactions after allergen-specific challenge. J Allergy Clin Immunol 1995 Feb; 95(2): 612–21PubMedCrossRefGoogle Scholar
  28. 28.
    Grumetto L, Cennamo G, Del Prete A, et al. Pharmacokinetics of cetirizine in tear fluid after a single oral dose. Clin Pharmacokinet 2002; 41(7): 525–31PubMedCrossRefGoogle Scholar
  29. 29.
    Spencer CM, Faulds D, Peters DH. Cetirizine: a reappraisal of its pharmacological properties and therapeutic use in selected allergic disorders. Drugs 1993 Dec; 46(6): 1055–80PubMedCrossRefGoogle Scholar
  30. 30.
    Ciprandi G, Tosca MA, Cosentino C, et al. Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules. J Allergy Clin Immunol 2003 Oct; 112 (4 Suppl.): S78–82PubMedCrossRefGoogle Scholar
  31. 31.
    Bronsky EA, Falliers CJ, Kaiser HB, et al. Effectiveness and safety of fexofenadine, a new nonsedating H1-receptor antagonist in the treatment of fall allergies. Allergy Asthma Proc 1998; 19: 135–41PubMedCrossRefGoogle Scholar
  32. 32.
    Russell T, Stoltz M, Weir S. Pharmacokinetics, pharmacodynamics, and tolerance of single and multiple-dose fexofenadine in healthy male volunteers. Clin Pharmacol Ther 1998; 64: 612–21PubMedCrossRefGoogle Scholar
  33. 33.
    Bernstein D, Schoenwetter W, Nathan R, et al. Efficacy and safety of fexofenadine hydrochloride for treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 1997; 79: 443–8PubMedCrossRefGoogle Scholar
  34. 34.
    Casale TB, Andrade C, Qu R. Safety and efficacy of once daily fexofenadine HCl in the treatment of autumn seasonal allergic rhinitis. Allergy Asthma Proc 1999; 20: 193–8PubMedCrossRefGoogle Scholar
  35. 35.
    Wahn U, Meltzer EO, Finn Jr AF, et al. Fexofenadine is efficacious and safe in children (aged 6–11 years) with seasonal allergic rhinitis. J Allergy Clin Immunol 2003 Apr; 111(4): 763–9PubMedCrossRefGoogle Scholar
  36. 36.
    Van Cauwenberge P, Juniper EF. Comparison of the efficacy, safety, and quality of life provided by fexofenadine 120mg, loratadine 10mg, and placebo administered once daily for the treatment of seasonal allergic rhinitis: Star Study Investigating Group. Clin Exp Allergy 2000; 30: 891–9PubMedCrossRefGoogle Scholar
  37. 37.
    Howarth P, Stern M, Roi L, et al. Double-blind, placebo controlled study comparing the efficacy and safety of fexofenadine hydrochloride (120 and 180mg once daily) and cetirizine in seasonal allergic rhinitis. J Allergy Clin Immunol 1999; 104: 927–33PubMedCrossRefGoogle Scholar
  38. 38.
    Sussman GL, Mason J, Compton D, et al. The efficacy and safety of fexofenadine HCl and pseudoephedrine, alone and in combination, in seasonal allergic rhinitis. J Allergy Clin Immunol 1999 Jul; 104(1): 100–6PubMedCrossRefGoogle Scholar
  39. 39.
    Ridout F, Shamsi Z, Meadows R, et al. A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180mg alone and with alcohol, with hydroxyzine hydrochloride 50mg as a positive internal control, on aspects of cognitive and psychomotor function related to driving a car. Clin Ther 2003 May; 25(5): 1518–38PubMedCrossRefGoogle Scholar
  40. 40.
    Mansfield L, Mendoza C, Flores J, et al. Effects of fexofenadine, diphenhydramine, and placebo on performance of the test of variables of attention (TOVA). Ann Allergy Asthma Immunol 2003 May; 90(5): 554–9PubMedCrossRefGoogle Scholar
  41. 41.
    Ridout F, Hindmarch I. The effects of acute doses of fexofenadine, promethazine, and placebo on cognitive and psychomotor function in healthy Japanese volunteers. Ann Allergy Asthma Immunol 2003 Apr; 90(4): 404–10PubMedCrossRefGoogle Scholar
  42. 42.
    Bower EA, Moore JL, Moss M, et al. The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel. Aviat Space Environ Med 2003 Feb; 74(2): 145–52PubMedGoogle Scholar
  43. 43.
    Hindmarch I, Shamsi Z, Kimber S. An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers. Clin Exp Allergy 2002 Jan; 32(1): 133–9PubMedCrossRefGoogle Scholar
  44. 44.
    Ciprandi G, Buscaglia S, Pesce GP, et al. Protective effect of loratadine on specific conjunctival provocation test. Int Arch Allergy Appl Immunol 1991; 96: 344–7PubMedCrossRefGoogle Scholar
  45. 45.
    Ciprandi G, Buscaglia S, Marchesi E, et al. Protective effect of loratadine in late phase reaction induced by conjunctival provocation test. Int Arch Allergy Appl Immunol 1993; 100: 185–9CrossRefGoogle Scholar
  46. 46.
    Moinuddin R, de Tineo M, Maleckar B, et al. Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2004 Jan; 92(1): 73–9PubMedCrossRefGoogle Scholar
  47. 47.
    Frolund L. Efficacy of an oral antihistamine, loratadine, as compared with a nasal steroid spray, beclomethasone dipropionate, in seasonal allergic rhinitis. Clin Otolaryngol 1991 Dec; 16(6): 527–31PubMedCrossRefGoogle Scholar
  48. 48.
    Welch D, Ousler III GW, Nally LA, et al. Ocular drying associated with oral antihistamines (loratadine) in the normal population-an evaluation of exaggerated dose effect. Adv Exp Med Biol 2002; 506 (Pt B): 1051–5PubMedCrossRefGoogle Scholar
  49. 49.
    Nevius JM, Abelson MB, Welch D. The ocular drying effect of oral antihistamines (loratadine) in the normal population: an evaluation [abstract]. Invest Ophthal Vis Sci 1999; 40 Suppl.: 2898Google Scholar
  50. 50.
    Simons FE, Prenner BM, Finn Jr A. Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis: Desloratadine Study Group. J Allergy Clin Immunol 2003 Mar; 111(3): 617–22PubMedCrossRefGoogle Scholar
  51. 51.
    Meltzer EO, Prenner BM, Nayak A, et al. Efficacy and tolerability of once-daily 5mg desloratadine, an H1-receptor antagonist, in patients with seasonal allergic rhinitis. Clin Drug Invest 2001; 21(1): 25–32CrossRefGoogle Scholar
  52. 52.
    Crampton HJ. Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and active-controlled trial. Clin Ther 2003 Jul; 25(7): 1975–87PubMedCrossRefGoogle Scholar
  53. 53.
    Levostin®: prescribing information [online]. Available from URL: http://www.us.novartisophthalmics.com/hcp/products/livostin-hcp.jsp?checked=y [Accessed 2004 Nov 4]
  54. 54.
    Patanol®: prescribing information [online]. Available from URL: http://www.alconlabs.com/us/aj/products/RxTher/A23_PatanolInfo.jhtml [Accessed 2004 Nov 4]
  55. 55.
    Zaditor™: prescribing information [online]. Available from URL: http://www.novartisophthalmics.ca/e/products/zaditor.shtml [Accessed 2004 Nov 4]
  56. 56.
    Optivar®: prescribing information [online]. Available from URL: http://www.optivar.com/prescribinginfo.html [Accessed 2004 Nov 4]
  57. 57.
    Elestat™: prescribing information [online]. Available from URL: http://www.elestat.com/practitioners [Accessed 2004 Nov 4]
  58. 58.
    Spector SL, Raizman MB. Conjunctivitis medicamentosa. J Allergy Clin Immunol 1994 Jul; 94(1): 134–6PubMedCrossRefGoogle Scholar
  59. 59.
    Pipkorn U, Bende M, Hedner J, et al. A double-blind evaluation of topical levocabastine, a new specific H1 antagonist in patients with allergic conjunctivitis. Allergy 1985 Oct; 40(7): 491–6PubMedCrossRefGoogle Scholar
  60. 60.
    Ahluwalia P, Anderson DF, Wilson SJ, et al. Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms. J Allergy Clin Immunol 2001 Sep; 108(3): 449–54PubMedCrossRefGoogle Scholar
  61. 61.
    Azevedo M, Castel-Branco MG, Oliveira JF, et al. Double-blind comparison of levocabastine eye drops with sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy 1991; 21: 689–94PubMedCrossRefGoogle Scholar
  62. 62.
    Davies BH, Mullins J. Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis. Allergy 1993; 48: 519–24PubMedCrossRefGoogle Scholar
  63. 63.
    Richard C, Trinquand C, Bloch-Michel E. Comparison of topical 0.05% levocabastine and 0.1% lodoxamide in patients with allergic conjunctivitis. Study Group. Eur J Ophthalmol 1998 Oct–Dec; 8(4): 207–16Google Scholar
  64. 64.
    Abelson MB, George MA, Smith LM. Evaluation of 0.05% levocabastine versus 4% sodium cromolyn in the allergen challenge model. Ophthalmology 1995 Feb; 102(2): 310–6PubMedGoogle Scholar
  65. 65.
    Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Swedish GP Allergy Team. Allergy 1994 Sep; 49(8): 611–5CrossRefGoogle Scholar
  66. 66.
    Zuber P, Pecoud A. Effect of levocabastine, a new H1 antagonist, in a conjunctival provocation test with allergens. J Allergy Clin Immunol 1988 Oct; 82(4): 590–4PubMedCrossRefGoogle Scholar
  67. 67.
    Abelson MB. Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model. Ann Allergy Asthma Immunol 1998 Sep; 81(3): 211–8PubMedCrossRefGoogle Scholar
  68. 68.
    Butrus S, Greiner JV, Discepola M, et al. Comparison of the clinical efficacy and comfort of olopatadine hydrochloride 0.1% ophthalmic solution and nedocromil sodium 2% ophthalmic solution in the human conjunctival allergen challenge model. Clin Ther 2000 Dec; 22(12): 1462–72PubMedCrossRefGoogle Scholar
  69. 69.
    Abelson MB, Welch DL. An evaluation of onset and duration of action of patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin (loratadine 10mg) tablets in acute allergic conjunctivitis in the conjunctival allergen challenge model. Acta Ophthalmol Scand Suppl 2000; 230: 60–3PubMedCrossRefGoogle Scholar
  70. 70.
    Leonardi A, Abelson MB. Double-masked, randomized, placebo-controlled clinical study of the mast cell-stabilizing effects of treatment with olopatadine in the conjunctival allergen challenge model in humans. Clin Ther 2003 Oct; 25(10): 2539–52PubMedCrossRefGoogle Scholar
  71. 71.
    Cook EB, Stahl JL, Barney NP, et al. Olopatadine inhibits TNFalpha release from human conjunctival mast cells. Ann Allergy Asthma Immunol 2000 May; 84(5): 504–8PubMedCrossRefGoogle Scholar
  72. 72.
    Cook EB, Stahl JL, Barney NP, et al. Olopatadine inhibits anti-immunoglobulin E-stimulated conjunctival mast cell upregulation of ICAM-1 expression on conjunctival epithelial cells. Ann Allergy Asthma Immunol 2001 Nov; 87(5): 424–9PubMedCrossRefGoogle Scholar
  73. 73.
    Lanier BQ, Abelson MB, Berger WE, et al. Comparison of the efficacy of combined fluticasone propionate and olopatadine versus combined fluticasone propionate and fexofenadine for the treatment of allergic rhinoconjunctivitis induced by conjunctival allergen challenge. Clin Ther 2002 Jul; 24(7): 1161–74PubMedCrossRefGoogle Scholar
  74. 74.
    Yamada Y, Sannohe S, Saito N, et al. Effect of ketotifen on the production of reactive oxygen species from human eosinophils primed by eotaxin. Pharmacology 2003 Nov; 69(3): 138–41PubMedCrossRefGoogle Scholar
  75. 75.
    Woerly G, Loiseau S, Loyens M, et al. Inhibitory effects of ketotifen on eotaxin-dependent activation of eosinophils: consequences for allergic eye diseases. Allergy 2003 May; 58(5): 397–406PubMedCrossRefGoogle Scholar
  76. 76.
    Abelson MB, Chapin MJ, Kapik BM, et al. Efficacy of ketotifen fumarate 0.025% ophthalmic solution compared with placebo in the conjunctival allergen challenge model. Arch Ophthalmol 2003 May; 121(5): 626–30PubMedCrossRefGoogle Scholar
  77. 77.
    Greiner JV, Michaelson C, McWhirter CL, et al. Single dose of ketotifen fumarate.025% vs 2 weeks of cromolyn sodium 4% for allergic conjunctivitis. Adv Ther 2002 Jul–Aug; 19(4): 185–93PubMedCrossRefGoogle Scholar
  78. 78.
    Ganz M, Koll E, Gausche J, et al. Ketotifen fumarate and olopatadine hydrochloride in the treatment of allergic conjunctivitis: a real-world comparison of efficacy and ocular comfort. Adv Ther 2003 Mar–Apr; 20(2): 79–91PubMedCrossRefGoogle Scholar
  79. 79.
    Aguilar AJ. Comparative study of clinical efficacy and tolerance in seasonal allergic conjunctivitis management with 0.1% olopatadine hydrochloride versus 0.05% ketotifen fumarate. Acta Ophthalmol Scand Suppl 2000; 230: 52–5PubMedCrossRefGoogle Scholar
  80. 80.
    Abelson MB, Chapin MJ, Kapik BM, et al. Ocular tolerability and safety of ketotifen fumarate ophthalmic solution. Adv Ther 2002 Jul–Aug; 19(4): 161–9PubMedCrossRefGoogle Scholar
  81. 81.
    Giede C, Metzenauer P, Petzold U, et al. Comparison of azelastine eye drops with levocabastine eye drops in the treatment of seasonal allergic conjunctivitis. Curr Med Res Opin 2000; 16(3): 153–63PubMedGoogle Scholar
  82. 82.
    James IG, Campbell LM, Harrison JM, et al. Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis. Curr Med Res Opin 2003; 19(4): 313–20PubMedCrossRefGoogle Scholar
  83. 83.
    Giede-Tuch C, Westhoff M, Zarth A. Azelastine eye-drops in seasonal allergic conjunctivitis or rhinoconjunctivitis: a double-blind, randomized, placebo-controlled study. Allergy 1998 Sep; 53(9): 857–62PubMedCrossRefGoogle Scholar
  84. 84.
    Canonica GW, Ciprandi G, Petzold U, et al. Topical azelastine in perennial allergic conjunctivitis. Curr Med Res Opin 2003; 19(4): 321–9PubMedCrossRefGoogle Scholar
  85. 85.
    Kempuraj D, Huang M, Kandere-Grzybowska K, et al. Azelastine inhibits secretion of IL-6, TNF-alpha and IL-8 as well as NF-kappaB activation and intracellular calcium ion levels in normal human mast cells. Int Arch Allergy Immunol 2003 Nov; 132(3): 231–9PubMedCrossRefGoogle Scholar
  86. 86.
    Kempuraj D, Huang M, Kandere K, et al. Azelastine is more potent than olopatadine n inhibiting interleukin-6 and tryptase release from human umbilical cord blood-derived cultured mast cells. Ann Allergy Asthma Immunol 2002 May; 88(5): 501–6PubMedCrossRefGoogle Scholar
  87. 87.
    Ciprandi G, Buscaglia S, Catrullo A, et al. Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti-allergic activity. Clin Exp Allergy 1997 Feb; 27(2): 182–91PubMedCrossRefGoogle Scholar
  88. 88.
    el-Shazly AE, Masuyama K, Samejima Y, et al. Inhibition of human eosinophil chemotaxis in vitro by the anti-allergic agent emedastine difumarate. Immunopharmacol Immunotoxicol 1996 Nov; 18(4): 587–95PubMedCrossRefGoogle Scholar
  89. 89.
    Saito H, Yamamoto N, Tomita S, et al. Effect of emedastine difumarate on CC chemokine-elicited eosinophil migration. Int Arch Allergy Immunol 2001; 125 Suppl. 1: 22–8PubMedCrossRefGoogle Scholar
  90. 90.
    Netland PA, Leahy C, Krenzer KL. Emedastine ophthalmic solution 0.05% versus levocabastine ophthalmic suspension 0.05% in the treatment of allergic conjunctivitis using the conjunctival allergen challenge model. Am J Ophthalmol 2000 Dec; 130(6): 717–23PubMedCrossRefGoogle Scholar
  91. 91.
    Verin P, Easty DL, Secchi A, et al. Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis. Am J Ophthalmol 2001 Jun; 131(6): 691–8PubMedCrossRefGoogle Scholar
  92. 92.
    Secchi A, Leonardi A, Discepola M, et al. An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Emadine Study Group. Acta Ophthalmol Scand Suppl 2000; 230: 48–51CrossRefGoogle Scholar
  93. 93.
    Orfeo V, Vardaro A, Lena P, et al. Comparison of emedastine 0.05% or nedocromil sodium 2% eye drops and placebo in controlling local reactions in subjects with allergic conjunctivitis. Eur J Ophthalmol 2002 Jul–Aug; 12(4): 262–6PubMedGoogle Scholar
  94. 94.
    Discepola M, Deschenes J, Abelson M. Comparison of the topical ocular antiallergic efficacy of emedastine 0.05% ophthalmic solution to ketorolac 0.5% ophthalmic solution in a clinical model of allergic conjunctivitis. Acta Ophthalmol Scand Suppl 1999; 228: 43–6PubMedGoogle Scholar
  95. 95.
    Abelson MB, Kaplan AP. A randomized, double-blind, placebo-controlled comparison of emedastine 0.05% ophthalmic solution with loratadine 10mg and their combination in the human conjunctival allergen challenge model. Clin Ther 2002 Mar; 24(3): 445–56PubMedCrossRefGoogle Scholar
  96. 96.
    Abelson MB, Gomes P, Crampton HJ, et al. Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis. Clin Ther 2004 Jan; 26(1): 35–47PubMedCrossRefGoogle Scholar
  97. 97.
    Whitcup SM, Bradford R, Lue J, et al. Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis. Clin Ther 2004 Jan; 26(1): 29–34PubMedCrossRefGoogle Scholar
  98. 98.
    Abelson MB, Ghosh P, Bradford R, et al. Safety and efficacy of ophthalmic epinastine in patients with allergic conjunctivitis [abstract]. 60th Anniversary Meeting of the American Academy of Allergy, Asthma and Immunology; 2003 Mar 7–12; DenverGoogle Scholar
  99. 99.
    Friedlander M, Schachar R, Breschears D, et al. Objective evaluation of allergic reactions in the eye [abstract]. 2004 meeting of the American Society of Cataract and Refractive Surgeons (ASCRS); 2004 May 1–4; San DiegoGoogle Scholar
  100. 100.
    Spangler DL, Abelson MB, Ober A, et al. Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models. Clin Ther 2003 Aug; 25(8): 2245–67PubMedCrossRefGoogle Scholar
  101. 101.
    Abelson MB, Lanier RQ. The added benefit of local Patanol therapy when combined with systemic Claritin for the inhibition of ocular itching in the conjunctival antigen challenge model. Acta Ophthalmol Scand Suppl 1999; 228: 53–6PubMedGoogle Scholar
  102. 102.
    Alexander M, Patel P, Allegro S, et al. Supplementation of fexofenadine therapy with nedocromil sodium 2% ophthalmic solution to treat ocular symptoms of seasonal allergic conjunctivitis. Clin Exp Ophthal 2003; 31: 206–12CrossRefGoogle Scholar
  103. 103.
    Chung KF. Effects of nedocromil sodium on airway neurogenic mechanisms. J Allergy Clin Immunol 1996 Nov; 98 (5 Pt 2): S112–6PubMedCrossRefGoogle Scholar
  104. 104.
    Yaylali V, Demirlenk I, Tatlipinar S, et al. Comparative study of 0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine in the treatment of seasonal allergic conjunctivitis. Acta Ophthalmol Scand 2003 Aug; 81(4): 378–82PubMedCrossRefGoogle Scholar
  105. 105.
    Akpek EK, Dart JK, Watson S, et al. A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis. Ophthalmology 2004 Mar; 111(3): 476–82PubMedCrossRefGoogle Scholar
  106. 106.
    Kosrirukvongs P, Vichyanond P, Wongsawad W. Vernal keratoconjunctivitis in Thailand. Asian Pac J Allergy Immunol 2003 Mar; 21(1): 25–30PubMedGoogle Scholar
  107. 107.
    Pucci N, Novembre E, Cianferoni A, et al. Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol 2002 Sep; 89(3): 298–303PubMedCrossRefGoogle Scholar
  108. 108.
    Gupta V, Sahu PK. Topical cyclosporin A in the management of vernal keratoconjunctivitis. Eye 2001 Feb; 15 (Pt 1): 39–41PubMedCrossRefGoogle Scholar
  109. 109.
    Hingorani M, Moodaley L, Calder VL, et al. A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis. Ophthalmology 1998 Sep; 105(9): 1715–20PubMedCrossRefGoogle Scholar
  110. 110.
    Whitcup SM, Chan CC, Kozhich AT, et al. Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis. Clin Immunol 1999 Nov; 93(2): 107–13PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Leonard Bielory
    • 1
  • Kenneth W. Lien
    • 1
  • Steve Bigelsen
    • 1
  1. 1.Department of Medicine, Pediatrics and Ophthalmology, Division of Allergy, Immunology and Rheumatology, Director, Immuno-Ophthalmology ServiceUMDNJ-New Jersey Medical SchoolNewarkUSA

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