Grundlagen allergischer Erkrankungen der Augenoberfläche und aktuelle medikamentöse Therapiekonzepte

 

 Buy Article Permissions and Reprints

Zusammenfassung

Hintergrund: Die okuläre Allergie gehört zu den häufigsten Augenerkrankungen weltweit. Dem klinischen Phänotyp und der Pathogenese nach werden verschiedene Allergieformen unterschieden, die unterschiedliche Behandlungsstrategien erfordern. Der Übersichtsartikel stellt die zentralen immunologischen Pathomechanismen sowie aktuelle Behandlungsmöglichkeiten dar. Methoden: Literatursuche in PubMed und eigene klinische und experimentelle Daten. Ergebnisse: An der Pathogenese der okulären Allergie sind unterschiedliche Immunzellen wie dendritische Zellen, B-Zellen, T-Zellen, Mastzellen, Eosinophile und regulatorische T-Zellen beteiligt. Therapeutische Ansätze fokussieren auf eine Symptomverbesserung mittels Antihistaminika, Mastzellstabilisatoren und Kombinationswirkstoffen. In schweren Fällen werden Steroide und Calcineurin-Inhibitoren eingesetzt. Schlussfolgerungen: Obwohl in der Erforschung der Pathogenese der okulären Allergie in den vergangenen Jahren große Fortschritte gemacht wurden, sind noch Fragen z. B. zum Zusammenhang zwischen Trockenem Auge und okulärer Allergie ungeklärt. Zukünftige Therapieverfahren werden auf kürzlich beschriebene Mechanismen wie die Lymphangiogenese aufbauen und zunehmend kausalere Behandlungsmethoden ermöglichen.

Abstract

Background: Ocular allergy belongs to the most common ocular diseases globally. Following clinical phenotype and immunopathogenesis different forms of allergy are distinguished, which require different forms of therapeutic approach. This manuscript reviews the basic immunological processes involved in the development of ocular allergies and current and future therapeutic approaches. Methods: Results of a literature search in PubMed and our own clinical and experimental experience are presented. Results: In the immunopathogenesis of ocular allergy different immune cells such as dendritic cells, B-cells, T-cells, mast cells, eosinophils and regulatory T-cells are involved. Therapeutic approaches focus on either relief of symptoms using antihistamins or mast cell stabilisers or combinations of both. In severe cases steroids or calcineurin inhibitors are used. Discussion: Despite great progress in the investigation of ocular allergy in the past decade several open questions remain, such as the relation of ocular allergy with dry eye disease. Future therapeutic approaches will likely be based on recently identified new aspects such as lymphangiogenesis and will allow better and potentially causal treatment of ocular allergy.

• Literatur

• 1 Johansson SGO, Bieber T, Dahl R et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113: 832-836
  CrossrefPubMedGoogle Scholar
• 2 Bielory L. Allergic and immunologic disorders of the eye. Part II: ocular allergy. J Allergy Clin Immunol 2000; 106: 1019-1032
  CrossrefPubMedGoogle Scholar
• 3 Messmer EM. [Ocular allergies]. Ophthalmologe 2005; 102: 527-543 quiz 544
  CrossrefPubMedGoogle Scholar
• 4 Schopf L, Luccioli S, Bundoc V et al. Differential modulation of allergic eye disease by chronic and acute ascaris infection. Invest Ophthalmol Vis Sci 2005; 46: 2772-2780
  CrossrefPubMedGoogle Scholar
• 5 Forister JF, Forister EF, Yeung KK et al. Prevalence of contact lens-related complications: UCLA contact lens study. Eye Contact Lens 2009; 35: 176-180
  CrossrefPubMedGoogle Scholar
• 6 McGill JI, Holgate ST, Church MK et al. Allergic eye disease mechanisms. Br J Ophthalmol 1998; 82: 1203-1214
  CrossrefPubMedGoogle Scholar
• 7 Saban DR, Calder V, Kuo CH et al. New twists to an old story: novel concepts in the pathogenesis of allergic eye disease. Curr Eye Res 2013; 38: 317-330
  CrossrefPubMedGoogle Scholar
• 8 Lachmann PJ, Peters SK, Rosen FS. Clinical Aspects of Immunology. Oxford: Blackwell Scientific Publications; 1993
  Google Scholar
• 9 Fukuda K, Ohbayashi M, Morohoshi K et al. Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis. J Allergy Clin Immunol 2009; 124: 827.e2-833.e2
  PubMedGoogle Scholar
• 10 Tabbara KF. Immunopathogenesis of chronic allergic conjunctivitis. Int Ophthalmol Clin 2003; 43: 1-7
  CrossrefPubMedGoogle Scholar
• 11 Schlereth S, Lee HS, Khandelwal P et al. Blocking CCR7 at the ocular surface impairs the pathogenic contribution of dendritic cells in allergic conjunctivitis. Am J Pathol 2012; 180: 2351-2360
  CrossrefPubMedGoogle Scholar
• 12 Messmer EM, May CA, Stefani FH et al. Toxic eosinophil granule protein deposition in corneal ulcerations and scars associated with atopic keratoconjunctivitis. Am J Ophthalmol 2002; 134: 816-821
  CrossrefPubMedGoogle Scholar
• 13 Trocme SD, Gleich GJ, Kephart GM et al. Eosinophil granule major basic protein inhibition of corneal epithelial wound healing. Invest Ophthalmol Vis Sci 1994; 35: 3051-3056
  PubMedGoogle Scholar
• 14 Trocme SD, Leiferman KM, George T et al. Neutrophil and eosinophil participation in atopic and vernal keratoconjunctivitis. Curr Eye Res 2003; 26: 319-325
  CrossrefPubMedGoogle Scholar
• 15 Moy JN, Gleich GJ, Thomas LL. Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. J Immunol 1990; 145: 2626-2632
  PubMedGoogle Scholar
• 16 Fukushima A, Ozaki A, Fukata K et al. Ag-specific recognition, activation, and effector function of T cells in the conjunctiva with experimental immune-mediated blepharoconjunctivitis. Invest Ophthalmol Vis Sci 2003; 44: 4366-4374
  CrossrefPubMedGoogle Scholar
• 17 Calder VL, Jolly G, Hingorani M et al. Cytokine production and mRNA expression by conjunctival T-cell lines in chronic allergic eye disease. Clin Exp Allergy 1999; 29: 1214-1222
  CrossrefPubMedGoogle Scholar
• 18 Bundoc VG, Keane-Myers A. IL-10 confers protection from mast cell degranulation in a mouse model of allergic conjunctivitis. Exp Eye Res 2007; 85: 575-579
  CrossrefPubMedGoogle Scholar
• 19 Fukushima A, Sumi T, Fukuda K et al. Modulation of murine experimental allergic conjunctivitis by treatment with alpha-galactosylceramide. Immunol Lett 2006; 107: 32-40
  CrossrefPubMedGoogle Scholar
• 20 Moser M, Murphy KM. Dendritic cell regulation of TH1-TH2 development. Nat Immunol 2000; 1: 199-205
  CrossrefPubMedGoogle Scholar
• 21 Maggi E. The TH1/TH2 paradigm in allergy. Immunotechnology 1998; 3: 233-244
  CrossrefPubMedGoogle Scholar
• 22 Stern ME, Siemasko KF, Niederkorn JY. The Th1/Th2 paradigm in ocular allergy. Curr Opin Allergy Clin Immunol 2005; 5: 446-450
  CrossrefPubMedGoogle Scholar
• 23 Siemasko KF, Gao J, Calder VL et al. In vitro expanded CD4+CD25+Foxp3+ regulatory T cells maintain a normal phenotype and suppress immune-mediated ocular surface inflammation. Invest Ophthalmol Vis Sci 2008; 49: 5434-5440
  CrossrefPubMedGoogle Scholar
• 24 Niederkorn JY. Immune regulatory mechanisms in allergic conjunctivitis: insights from mouse models. Curr Opin Allergy Clin Immunol 2008; 8: 472-476
  CrossrefPubMedGoogle Scholar
• 25 Foster CS, Rice BA, Dutt JE. Immunopathology of atopic keratoconjunctivitis. Ophthalmology 1991; 98: 1190-1196
  CrossrefPubMedGoogle Scholar
• 26 Nguyen NX, Martus P, Seitz B et al. Atopic dermatitis as a risk factor for graft rejection following normal-risk keratoplasty. Graefes Arch Clin Exp Ophthalmol 2009; 247: 573-574
  CrossrefPubMedGoogle Scholar
• 27 Abelson MB, Yamamoto GK, Allansmith MR. Effects of ocular decongestants. Arch Ophthalmol 1980; 98: 856-858
  CrossrefPubMedGoogle Scholar
• 28 Qasem AR, Bucolo C, Baiula M et al. Contribution of alpha4beta1 integrin to the antiallergic effect of levocabastine. Biochem Pharmacol 2008; 76: 751-762
  CrossrefPubMedGoogle Scholar
• 29 Abelson MB, McLaughlin JT, Gomes PJ. Antihistamines in ocular allergy: are they all created equal?. Curr Allergy Asthma Rep 2011; 11: 205-211
  CrossrefPubMedGoogle Scholar
• 30 Leonardi A, Di Stefano A, Vicari C et al. Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis. Allergy 2011; 66: 1360-1366
  CrossrefPubMedGoogle Scholar
• 31 Namdar R, Valdez C. Alcaftadine: a topical antihistamine for use in allergic conjunctivitis. Drugs Today (Barc) 2011; 47: 883-890
  CrossrefPubMedGoogle Scholar
• 32 Abelson MB, Wun PJ, Nevius JM. Mast Cell Stabilizers. In: Abelson MB, ed. Allergic Diseases of the Eye. Philadephia: WB Saunders Co; 2000: 228-234
  Google Scholar
• 33 Bielory L, Chun Y, Bielory BP et al. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis. Allergy 2011; 66: 686-693
  CrossrefPubMedGoogle Scholar
• 34 Kaiser HB, Naclerio RM, Given J et al. Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2007; 119: 1430-1437
  CrossrefPubMedGoogle Scholar
• 35 Baiula M, Sparta A, Bedini A et al. Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. Mol Vis 2011; 17: 3208-3223
  PubMedGoogle Scholar
• 36 Ebihara N, Ohashi Y, Uchio E et al. A large prospective observational study of novel cyclosporine 0.1 % aqueous ophthalmic solution in the treatment of severe allergic conjunctivitis. J Ocul Pharmacol Ther 2009; 25: 365-372
  CrossrefPubMedGoogle Scholar
• 37 Lambiase A, Leonardi A, Sacchetti M et al. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double-masked, controlled 2-year study. J Allergy Clin Immunol 2011; 128: 896.e9-897.e9
  PubMedGoogle Scholar
• 38 Attas-Fox L, Barkana Y, Iskhakov V et al. Topical tacrolimus 0.03 % ointment for intractable allergic conjunctivitis: an open-label pilot study. Curr Eye Res 2008; 33: 545-549
  CrossrefPubMedGoogle Scholar
• 39 Chen SL, Yan J, Wang FS. Two topical calcineurin inhibitors for the treatment of atopic dermatitis in pediatric patients: a meta-analysis of randomized clinical trials. J Dermatolog Treat 2010; 21: 144-156
  CrossrefPubMedGoogle Scholar
• 40 Vichyanond P, Tantimongkolsuk C, Dumrongkigchaiporn P et al. Vernal keratoconjunctivitis: Result of a novel therapy with 0.1 % topical ophthalmic FK-506 ointment. J Allergy Clin Immunol 2004; 113: 355-358
  CrossrefPubMedGoogle Scholar
• 41 Brozek JL, Bousquet J, Baena-Cagnani CE et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010; 126: 466-476
  CrossrefPubMedGoogle Scholar
• 42 Calderon MA, Penagos M, Sheikh A et al. Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis. Clin Exp Allergy 2011; 41: 1263-1272
  CrossrefPubMedGoogle Scholar
• 43 Frolund L, Durham SR, Calderon M et al. Sustained effect of SQ-standardized grass allergy immunotherapy tablet on rhinoconjunctivitis quality of life. Allergy 2010; 65: 753-757
  PubMedGoogle Scholar
• 44 Mahdy RA, Nada WM, Marei AA. Subcutaneous allergen-specific immunotherapy versus topical treatment in vernal keratoconjunctivitis. Cornea 2012; 31: 525-528
  CrossrefPubMedGoogle Scholar
• 45 Ousler GW, Wilcox KA, Gupta G et al. An evaluation of the ocular drying effects of 2 systemic antihistamines: loratadine and cetirizine hydrochloride. Ann Allergy Asthma Immunol 2004; 93: 460-464
  CrossrefPubMedGoogle Scholar
• 46 Bock F, Maruyama K, Regenfuss B et al. Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases. Prog Retin Eye Res 2013; 34: 89-124
  CrossrefPubMedGoogle Scholar
• 47 Flynn TH, Ohbayashi M, Dawson M et al. The effect of perioperative allergic conjunctivitis on corneal lymphangiogenesis after corneal transplantation. Br J Ophthalmol 2011; 95: 1451-1456
  CrossrefPubMedGoogle Scholar
• 48 Beauregard C, Stevens C, Mayhew E et al. Cutting edge: atopy promotes Th2 responses to alloantigens and increases the incidence and tempo of corneal allograft rejection. J Immunol 2005; 174: 6577-6581
  CrossrefPubMedGoogle Scholar
• 49 Reyes NJ, Chen PW, Niederkorn JY. Allergic conjunctivitis renders CD4(+) T cells resistant to t regulatory cells and exacerbates corneal allograft rejection. Am J Transplant 2013; 13: 1181-1192
  CrossrefPubMedGoogle Scholar