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Conjunctival provocation tests and the ocular late phase reaction
X ICER Abstracts
Wednesday, Sep 23, 1992 Palazzo Dei Congressi/A 420
7 LYpP!IOCYTE SUB-SETS Power W J., Collum, -zp----Roval Victoria Eve
IN CONJUNCTTVAL L.!I.T. and Ear Hospital,
ALLEQGIC Dublin,
nIS0QDEQS
MAST CELL STABILIZERS IN VERNAL C. Stephen Foster, M.D. Massachusetts Eye b Ear Infirmary,
Ireland.
PROVOCATION
Department of Ophthalmology,
TI3Sl-S AND THE OCULARL4TEPHASE REACIION
Physiopathological Optics, University of Padova, Italy.
Late phase reactions (LPR) have been suggested to play an important role in chmnic ocular allergic diaordera. The conjunctival provocation test (Cpr) is a clinical tool which can be safely used to study all aspects of the allergic LPR. The conjunctiva is challenged with increasing doses of allergen until the minimal dose which produces a clinically relevant reaction is achieved. With this threshold doac, a clinical L.PR is o&en manifested as a persistent or recurrent clinical reaction. Suprathreshold allergen doses can induce a clinical and/or cytological LPR. A similar phenomenon is observed in an animal model of allergen specitic conjunctival challenge, in which both clinical and histological LPR were induced using high doses of antigen. In the same model, during LPR, 55% of the eyes reacted acutely lo a second specific CPT, 11% hyper-reacted, and none reacted to an aspecific CPT. Ckdcally, in some patients, the threshold for reactivity to a second, specific CPT is lowered during late phase. FurIhcrmom, a hyper-reactivity can be observed during this period to aspecific stimuli such as cdd PBS or a smoky environment. Thus, conjunctiva which has been previously challenged with specific allergenic stimuli may retain a clinically inconspicuous inflammation which renders the tissue more vulnerable, not only to subsequent specitic CPTs, but also lo aspecific challenges.
NEU ADVAKRS IN TIIR TURRAPY OF ALLRRGIC CONJUItCTIVITIS lulli&Deportment of OphtbelmoloRy, Royel Victorie Ear Roepita end Royel CoIloRe of SurReons Irslend, Dublin, Irelend.
Eye in
Boston,
MA 02114,
USA
The advantage of mast cell stabilizers over antihistamines in the treatment of patients with vernal keraroconjunctivitis or atopic kerataconjunctivitis, disorders in which mast cells are prominent Mast cell stabilizers, by inhibiting participants, is obvious. mast cell degranulatio", inhibit the liberation of all of the mast cell contents. Of all of the chemicals (mediators) liberated by mast cells in a" allergic/inflammatory response, histamine may be the one with the most trivial biologic effect. Thus, the development of Disodium Cromoglycate, Nedocromil Sodium, and Lodoxamide represents a major advance in the pharmacologic treatment of allergic eye disease. Cromolyn has been shown. unequivocally, by multiple groups to be both safe and effective in the treatment of seasonal allergic conjunctivitis (SAC) and in the treatment of vernal keratoconjunctivitis (VKC). Additionally, it is the mainstay of ocular therapy (as opposed to systemic therapy) in our care of patients with atopic Nedocromil Sodium has also been keratoconjunctivitis (AKC). shown to be effective in the care of patients with SAC, and current studies in progress are evaluating its efficacy in VKC. the newest of the mast cell stabilizers to reach Lodoxamide, phase 3 clinical trials, is currently under investigation in the therapy of patients with VKC. It is obvious that these mast cell stabilizing agents, and any agent which can effectively prevent mast cell degranulatio", are important components in the therapeutic plan for patients with VKC and AKC, and that they are unquestionably more effective in the long-term care of such patients than are competitive inhibitors of histamine.
Using standard immune-histochemical techniques we looked at conjunctival lymphocvte sub-sets in three nroups of patients. We examined a arow of normal oatients, a qrouv of natients with vernal keratoconjunctivitis and a qrou~ of natients with Siorrren’s disease. The uatients in the Siorrren's g;o;p were subsequently treated with topical'2: four times daily ior six weeks Cyclosporine drops, and their conjunctival lvmphocvte sub-sets were The treatment resulteP in a sicni+icant reassessed. reduction in the number of CD4+ cells (T-helperinducer cells). The results of the study will be presented in detail.
CONJUNCTIVAL
AND ATOPIC KEBATOCONJUNCTIVITIS
end
Beceuee of the difficulty ol ellergic eye dieeeee, edvencee in treatment beve been elor. There a-8 . limited number ol rye in ubtch the treatments can be modtlied, nmly druR tberopy end deseneitiertton uad wblle edvencea heve been l ede In tbo invaettRotion of the cause8 end the 88cbuanln8 of allergy, very low now tberepeutic approecher +ere become precticel. Nor drugs, bowever, .re l lreye being produced end Nsdocromil end Lodoxeatde provtde l lteraetivee to the well eetobliebod lodirr CromolRycete. it is unlikely tbmt w revoluttonory tbsrapj will be l veileble la the short term esd tbe best epproecb ml&t be the dovaEvt vlld rrftnement oi new meet cell @tebtlieore, beomaee d~r8anletion ol the meet call ie tbe meta rcPkiiem involved in the production of nearly a11 of the oonfunctivel end entsrior reRment probleme undar discussion.
s.119
Wednesday, Sep 23, 1992 Palazzo Dei Congressi/A 420
7 LYpP!IOCYTE SUB-SETS Power W J., Collum, -zp----Roval Victoria Eve
IN CONJUNCTTVAL L.!I.T. and Ear Hospital,
ALLEQGIC Dublin,
nIS0QDEQS
MAST CELL STABILIZERS IN VERNAL C. Stephen Foster, M.D. Massachusetts Eye b Ear Infirmary,
Ireland.
PROVOCATION
Department of Ophthalmology,
TI3Sl-S AND THE OCULARL4TEPHASE REACIION
Physiopathological Optics, University of Padova, Italy.
Late phase reactions (LPR) have been suggested to play an important role in chmnic ocular allergic diaordera. The conjunctival provocation test (Cpr) is a clinical tool which can be safely used to study all aspects of the allergic LPR. The conjunctiva is challenged with increasing doses of allergen until the minimal dose which produces a clinically relevant reaction is achieved. With this threshold doac, a clinical L.PR is o&en manifested as a persistent or recurrent clinical reaction. Suprathreshold allergen doses can induce a clinical and/or cytological LPR. A similar phenomenon is observed in an animal model of allergen specitic conjunctival challenge, in which both clinical and histological LPR were induced using high doses of antigen. In the same model, during LPR, 55% of the eyes reacted acutely lo a second specific CPT, 11% hyper-reacted, and none reacted to an aspecific CPT. Ckdcally, in some patients, the threshold for reactivity to a second, specific CPT is lowered during late phase. FurIhcrmom, a hyper-reactivity can be observed during this period to aspecific stimuli such as cdd PBS or a smoky environment. Thus, conjunctiva which has been previously challenged with specific allergenic stimuli may retain a clinically inconspicuous inflammation which renders the tissue more vulnerable, not only to subsequent specitic CPTs, but also lo aspecific challenges.
NEU ADVAKRS IN TIIR TURRAPY OF ALLRRGIC CONJUItCTIVITIS lulli&Deportment of OphtbelmoloRy, Royel Victorie Ear Roepita end Royel CoIloRe of SurReons Irslend, Dublin, Irelend.
Eye in
Boston,
MA 02114,
USA
The advantage of mast cell stabilizers over antihistamines in the treatment of patients with vernal keraroconjunctivitis or atopic kerataconjunctivitis, disorders in which mast cells are prominent Mast cell stabilizers, by inhibiting participants, is obvious. mast cell degranulatio", inhibit the liberation of all of the mast cell contents. Of all of the chemicals (mediators) liberated by mast cells in a" allergic/inflammatory response, histamine may be the one with the most trivial biologic effect. Thus, the development of Disodium Cromoglycate, Nedocromil Sodium, and Lodoxamide represents a major advance in the pharmacologic treatment of allergic eye disease. Cromolyn has been shown. unequivocally, by multiple groups to be both safe and effective in the treatment of seasonal allergic conjunctivitis (SAC) and in the treatment of vernal keratoconjunctivitis (VKC). Additionally, it is the mainstay of ocular therapy (as opposed to systemic therapy) in our care of patients with atopic Nedocromil Sodium has also been keratoconjunctivitis (AKC). shown to be effective in the care of patients with SAC, and current studies in progress are evaluating its efficacy in VKC. the newest of the mast cell stabilizers to reach Lodoxamide, phase 3 clinical trials, is currently under investigation in the therapy of patients with VKC. It is obvious that these mast cell stabilizing agents, and any agent which can effectively prevent mast cell degranulatio", are important components in the therapeutic plan for patients with VKC and AKC, and that they are unquestionably more effective in the long-term care of such patients than are competitive inhibitors of histamine.
Using standard immune-histochemical techniques we looked at conjunctival lymphocvte sub-sets in three nroups of patients. We examined a arow of normal oatients, a qrouv of natients with vernal keratoconjunctivitis and a qrou~ of natients with Siorrren’s disease. The uatients in the Siorrren's g;o;p were subsequently treated with topical'2: four times daily ior six weeks Cyclosporine drops, and their conjunctival lvmphocvte sub-sets were The treatment resulteP in a sicni+icant reassessed. reduction in the number of CD4+ cells (T-helperinducer cells). The results of the study will be presented in detail.
CONJUNCTIVAL
AND ATOPIC KEBATOCONJUNCTIVITIS
end
Beceuee of the difficulty ol ellergic eye dieeeee, edvencee in treatment beve been elor. There a-8 . limited number ol rye in ubtch the treatments can be modtlied, nmly druR tberopy end deseneitiertton uad wblle edvencea heve been l ede In tbo invaettRotion of the cause8 end the 88cbuanln8 of allergy, very low now tberepeutic approecher +ere become precticel. Nor drugs, bowever, .re l lreye being produced end Nsdocromil end Lodoxeatde provtde l lteraetivee to the well eetobliebod lodirr CromolRycete. it is unlikely tbmt w revoluttonory tbsrapj will be l veileble la the short term esd tbe best epproecb ml&t be the dovaEvt vlld rrftnement oi new meet cell @tebtlieore, beomaee d~r8anletion ol the meet call ie tbe meta rcPkiiem involved in the production of nearly a11 of the oonfunctivel end entsrior reRment probleme undar discussion.
s.119