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{{Allergic conjunctivitis}} | {{Allergic conjunctivitis}} | ||
==Overview== | |||
Emerging [[therapies]] for [[allergic]] [[conjunctivitis]] include [[immunomodulators]] as well as evaluation of novel [[enzymatic]] targets. | |||
==Future or Investigational [[therapies]]== | |||
===[[Calcineurin]] inhibitors=== | |||
* They are capable of inducing local [[immunosuppression]] by blocking Th2 [[lymphocyte]] proliferation and [[IL-2]] production and reducing [[eosinophils]] via inhibition of [[IL-5]]. | |||
* [[Topical]] <ref name="pmid22378107">{{cite journal| author=Tzu JH, Utine CA, Stern ME, Akpek EK| title=Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis. | journal=Cornea | year= 2012 | volume= 31 | issue= 6 | pages= 649-54 | pmid=22378107 | doi=10.1097/ICO.0b013e31822481c2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22378107 }} </ref> and [[systemic]] [[cyclosporine]] a (CsA) <ref name="pmid20491051">{{cite journal| author=Cornish KS, Gregory ME, Ramaesh K| title=Systemic cyclosporin A in severe atopic keratoconjunctivitis. | journal=Eur J Ophthalmol | year= 2010 | volume= 20 | issue= 5 | pages= 844-51 | pmid=20491051 | doi=10.1177/112067211002000506 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20491051 }} </ref> have been suggested in the treatment of severe [[atopic]] [[keratoconjunctivitis]]. | |||
* Use of [[CsA]] appears to be safe and can eliminate the need/dependence of [[steroids]]. | |||
* Others [[calcineurin]] inhibitors that appears to be well tolerated by patients with severe [[atopic]] [[blepharoconjunctivitis]]<ref name="pmid16965503">{{cite journal| author=Virtanen HM, Reitamo S, Kari M, Kari O| title=Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study. | journal=Acta Ophthalmol Scand | year= 2006 | volume= 84 | issue= 5 | pages= 693-5 | pmid=16965503 | doi=10.1111/j.1600-0420.2006.00699.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16965503 }} </ref> and severe [[atopic]] [[keratoconjunctivitis]] are [[tacrolimus]] and [[pimecrolimus]]<ref name="pmid12464150">{{cite journal| author=Reynolds NJ, Al-Daraji WI| title=Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. | journal=Clin Exp Dermatol | year= 2002 | volume= 27 | issue= 7 | pages= 555-61 | pmid=12464150 | doi=10.1046/j.1365-2230.2002.01148.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12464150 }} </ref>. | |||
===Mapracorat<ref name="pmid22194647">{{cite journal| author=Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW | display-authors=etal| title=Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. | journal=Mol Vis | year= 2011 | volume= 17 | issue= | pages= 3208-23 | pmid=22194647 | doi= | pmc=3244483 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22194647 }} </ref>=== | |||
*Mapracorat is a novel selective [[agonist]] of the [[glucocorticoid]] receptor, resulting in a lower potential for side effect. | |||
*In vitro, it inhibited migration and [[IL-8]] release from [[eosinophils]] and the secretion of [[IL-6]], [[IL-8]], [[CCL5]]/[[RANTES]], and [[TNF-α]] from a human mast [[cell]] line with equal [[potency]] as [[dexamethasone]], but it was less potent in inducing [[annexin]] I and [[CXCR4]] expression on the human [[eosinophils]]. | |||
*Animal model of [[allergic]] [[conjunctivitis]] demonstrated mapracorat was similar to [[dexamethasone]] [[eye]] drops in analogous reduction of [[clinical]] [[symptoms]] and [[conjunctival]] [[eosinophil]]. Hence,studies suggest this compound as a candidate for [[clinical]] trials of [[ocular]] [[allergy]]. | |||
===[[Omalizumab]]=== | |||
*It is a biological engineered molecule, targeting the Cε3 domain of the [[IgE]] molecule. It binds with free [[IgE]] and prevents its attachment to high-affinity receptor (FcεRI) on mast [[cells]], [[basophils]] and [[dendritic]] [[cells]]. An [[IgE]]-anti-[[IgE]] complex is formed, lowering free [[IgE]]<ref name="pmid22053590">{{cite journal| author=Vichyanond P| title=Omalizumab in allergic diseases, a recent review. | journal=Asian Pac J Allergy Immunol | year= 2011 | volume= 29 | issue= 3 | pages= 209-19 | pmid=22053590 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22053590 }} </ref>. | |||
*[[Omalizumab]] has been established for use in [[asthma]]<ref name="pmid19362459">{{cite journal| author=Holgate S, Buhl R, Bousquet J, Smith N, Panahloo Z, Jimenez P| title=The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update. | journal=Respir Med | year= 2009 | volume= 103 | issue= 8 | pages= 1098-113 | pmid=19362459 | doi=10.1016/j.rmed.2009.03.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19362459 }} </ref> ,[[urticaria]] and and [[rhinitis]]<ref name="pmid16387596">{{cite journal| author=Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG | display-authors=etal| title=Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. | journal=J Allergy Clin Immunol | year= 2006 | volume= 117 | issue= 1 | pages= 134-40 | pmid=16387596 | doi=10.1016/j.jaci.2005.09.036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16387596 }} </ref>. | |||
*[[Clinical]] trials are needed to asses its real impact in [[ocular]] [[allergies]]. | |||
===Other developments<ref name="pmid21171952">{{cite journal| author=Mishra GP, Tamboli V, Jwala J, Mitra AK| title=Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. | journal=Recent Pat Inflamm Allergy Drug Discov | year= 2011 | volume= 5 | issue= 1 | pages= 26-36 | pmid=21171952 | doi=10.2174/187221311794474883 | pmc=3164156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21171952 }} </ref>=== | |||
*A novel target [[spleen]] [[tyrosine]] [[kinase]] (Syk) regulates the [[phosphorylation]] of [[phospholipase-C]], [[phosphatidylinositol-3]] [[kinase]] and [[protein]] [[kinase]] which mediate [[histamine]] release. Hence, studies will focus Syk inhibitors. | |||
*[[Janus]] [[protein]] [[kinase]]-3 is involved in the [[activation]] and [[proliferation]] of [[T-cells]]. Thus, novel inhibitors of [[JAK-3]] may be an effective [[therapy]]. | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Latest revision as of 09:42, 30 August 2022
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Overview
Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.
Future or Investigational therapies
Calcineurin inhibitors
- They are capable of inducing local immunosuppression by blocking Th2 lymphocyte proliferation and IL-2 production and reducing eosinophils via inhibition of IL-5.
- Topical [1] and systemic cyclosporine a (CsA) [2] have been suggested in the treatment of severe atopic keratoconjunctivitis.
- Use of CsA appears to be safe and can eliminate the need/dependence of steroids.
- Others calcineurin inhibitors that appears to be well tolerated by patients with severe atopic blepharoconjunctivitis[3] and severe atopic keratoconjunctivitis are tacrolimus and pimecrolimus[4].
Mapracorat[5]
- Mapracorat is a novel selective agonist of the glucocorticoid receptor, resulting in a lower potential for side effect.
- In vitro, it inhibited migration and IL-8 release from eosinophils and the secretion of IL-6, IL-8, CCL5/RANTES, and TNF-α from a human mast cell line with equal potency as dexamethasone, but it was less potent in inducing annexin I and CXCR4 expression on the human eosinophils.
- Animal model of allergic conjunctivitis demonstrated mapracorat was similar to dexamethasone eye drops in analogous reduction of clinical symptoms and conjunctival eosinophil. Hence,studies suggest this compound as a candidate for clinical trials of ocular allergy.
Omalizumab
- It is a biological engineered molecule, targeting the Cε3 domain of the IgE molecule. It binds with free IgE and prevents its attachment to high-affinity receptor (FcεRI) on mast cells, basophils and dendritic cells. An IgE-anti-IgE complex is formed, lowering free IgE[6].
- Omalizumab has been established for use in asthma[7] ,urticaria and and rhinitis[8].
- Clinical trials are needed to asses its real impact in ocular allergies.
Other developments[9]
- A novel target spleen tyrosine kinase (Syk) regulates the phosphorylation of phospholipase-C, phosphatidylinositol-3 kinase and protein kinase which mediate histamine release. Hence, studies will focus Syk inhibitors.
- Janus protein kinase-3 is involved in the activation and proliferation of T-cells. Thus, novel inhibitors of JAK-3 may be an effective therapy.
References
- ↑ Tzu JH, Utine CA, Stern ME, Akpek EK (2012). "Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis". Cornea. 31 (6): 649–54. doi:10.1097/ICO.0b013e31822481c2. PMID 22378107.
- ↑ Cornish KS, Gregory ME, Ramaesh K (2010). "Systemic cyclosporin A in severe atopic keratoconjunctivitis". Eur J Ophthalmol. 20 (5): 844–51. doi:10.1177/112067211002000506. PMID 20491051.
- ↑ Virtanen HM, Reitamo S, Kari M, Kari O (2006). "Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study". Acta Ophthalmol Scand. 84 (5): 693–5. doi:10.1111/j.1600-0420.2006.00699.x. PMID 16965503.
- ↑ Reynolds NJ, Al-Daraji WI (2002). "Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology". Clin Exp Dermatol. 27 (7): 555–61. doi:10.1046/j.1365-2230.2002.01148.x. PMID 12464150.
- ↑ Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW; et al. (2011). "Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist". Mol Vis. 17: 3208–23. PMC 3244483. PMID 22194647.
- ↑ Vichyanond P (2011). "Omalizumab in allergic diseases, a recent review". Asian Pac J Allergy Immunol. 29 (3): 209–19. PMID 22053590.
- ↑ Holgate S, Buhl R, Bousquet J, Smith N, Panahloo Z, Jimenez P (2009). "The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update". Respir Med. 103 (8): 1098–113. doi:10.1016/j.rmed.2009.03.008. PMID 19362459.
- ↑ Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG; et al. (2006). "Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis". J Allergy Clin Immunol. 117 (1): 134–40. doi:10.1016/j.jaci.2005.09.036. PMID 16387596.
- ↑ Mishra GP, Tamboli V, Jwala J, Mitra AK (2011). "Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis". Recent Pat Inflamm Allergy Drug Discov. 5 (1): 26–36. doi:10.2174/187221311794474883. PMC 3164156. PMID 21171952.