Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty
Purpose Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasin...
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Veröffentlicht in: | Acta ophthalmologica (Oxford, England) England), 2016-10, Vol.94 (S256), p.n/a |
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creator | Crouzet, E. He, Z. Perrache, C. Basset, T. Delavenne, X. Peoc'h, M. Gain, P. Thuret, G. |
description | Purpose
Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasing dexamethasone (SCIRD) in a rabbit model of PK.
Methods
7.5 mm PK were performed in NZW rabbits. After randomisation they received either a SCIRD (Ozurdex, Allergan) (n = 8), dexamethasone eyedrops (1 mg/ml, Dexafree, Thea) 3 times a day (n = 6), or 0.9% NaCl (n = 6). The running suture was left in place to stimulate angiogenesis. Weekly follow‐up by digital slit lamp and anterior segment OCT. Images were analysed blind to the treatment for transparency, neovessels, and central corneal thickness (CCT). After 5 or 6 weeks, animals were killed and corneas were processed for standard histology.
Results
Placebo group: constant early neovascularization growing to neovessels penetrating the graft on >270° after 5 weeks + rejection (opaque graft, 360° neovessels, CCT > 500 μm) in 50% of cases. Eye drops and implants groups: similar evolution, without rejection after 6 weeks and normal CCT. Moderate neovascularization occurred in 5/6 rabbits treated with eyedrops and 6/8 treated with the implant. Histology confirmed clinical diagnosis in all cases. The implants disappeared after 3–5 weeks. No adverse effect.
Conclusions
Despite a severe rejection model, a SCIRD was not less efficient than eye drops to prevent rejection during the first 6 weeks. These findings highlight the potential benefit of subconjunctival implants of steroids after corneal graft. |
doi_str_mv | 10.1111/j.1755-3768.2016.0458 |
format | Article |
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Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasing dexamethasone (SCIRD) in a rabbit model of PK.
Methods
7.5 mm PK were performed in NZW rabbits. After randomisation they received either a SCIRD (Ozurdex, Allergan) (n = 8), dexamethasone eyedrops (1 mg/ml, Dexafree, Thea) 3 times a day (n = 6), or 0.9% NaCl (n = 6). The running suture was left in place to stimulate angiogenesis. Weekly follow‐up by digital slit lamp and anterior segment OCT. Images were analysed blind to the treatment for transparency, neovessels, and central corneal thickness (CCT). After 5 or 6 weeks, animals were killed and corneas were processed for standard histology.
Results
Placebo group: constant early neovascularization growing to neovessels penetrating the graft on >270° after 5 weeks + rejection (opaque graft, 360° neovessels, CCT > 500 μm) in 50% of cases. Eye drops and implants groups: similar evolution, without rejection after 6 weeks and normal CCT. Moderate neovascularization occurred in 5/6 rabbits treated with eyedrops and 6/8 treated with the implant. Histology confirmed clinical diagnosis in all cases. The implants disappeared after 3–5 weeks. No adverse effect.
Conclusions
Despite a severe rejection model, a SCIRD was not less efficient than eye drops to prevent rejection during the first 6 weeks. These findings highlight the potential benefit of subconjunctival implants of steroids after corneal graft.</description><identifier>ISSN: 1755-375X</identifier><identifier>EISSN: 1755-3768</identifier><identifier>DOI: 10.1111/j.1755-3768.2016.0458</identifier><language>eng</language><publisher>Malden: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; Cornea ; Corneal transplantation ; Dexamethasone ; Digital imaging ; Eye ; Graft rejection ; Grafting ; Histology ; Immunosuppression ; Ophthalmology ; Sodium chloride ; Steroid hormones ; Steroids ; Transparency ; Transplants & implants ; Vascularization</subject><ispartof>Acta ophthalmologica (Oxford, England), 2016-10, Vol.94 (S256), p.n/a</ispartof><rights>Copyright © 2016 Acta Ophthalmologica Scandinavica Foundation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1755-3768.2016.0458$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45551,46808</link.rule.ids></links><search><creatorcontrib>Crouzet, E.</creatorcontrib><creatorcontrib>He, Z.</creatorcontrib><creatorcontrib>Perrache, C.</creatorcontrib><creatorcontrib>Basset, T.</creatorcontrib><creatorcontrib>Delavenne, X.</creatorcontrib><creatorcontrib>Peoc'h, M.</creatorcontrib><creatorcontrib>Gain, P.</creatorcontrib><creatorcontrib>Thuret, G.</creatorcontrib><title>Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty</title><title>Acta ophthalmologica (Oxford, England)</title><description>Purpose
Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasing dexamethasone (SCIRD) in a rabbit model of PK.
Methods
7.5 mm PK were performed in NZW rabbits. After randomisation they received either a SCIRD (Ozurdex, Allergan) (n = 8), dexamethasone eyedrops (1 mg/ml, Dexafree, Thea) 3 times a day (n = 6), or 0.9% NaCl (n = 6). The running suture was left in place to stimulate angiogenesis. Weekly follow‐up by digital slit lamp and anterior segment OCT. Images were analysed blind to the treatment for transparency, neovessels, and central corneal thickness (CCT). After 5 or 6 weeks, animals were killed and corneas were processed for standard histology.
Results
Placebo group: constant early neovascularization growing to neovessels penetrating the graft on >270° after 5 weeks + rejection (opaque graft, 360° neovessels, CCT > 500 μm) in 50% of cases. Eye drops and implants groups: similar evolution, without rejection after 6 weeks and normal CCT. Moderate neovascularization occurred in 5/6 rabbits treated with eyedrops and 6/8 treated with the implant. Histology confirmed clinical diagnosis in all cases. The implants disappeared after 3–5 weeks. No adverse effect.
Conclusions
Despite a severe rejection model, a SCIRD was not less efficient than eye drops to prevent rejection during the first 6 weeks. These findings highlight the potential benefit of subconjunctival implants of steroids after corneal graft.</description><subject>Angiogenesis</subject><subject>Cornea</subject><subject>Corneal transplantation</subject><subject>Dexamethasone</subject><subject>Digital imaging</subject><subject>Eye</subject><subject>Graft rejection</subject><subject>Grafting</subject><subject>Histology</subject><subject>Immunosuppression</subject><subject>Ophthalmology</subject><subject>Sodium chloride</subject><subject>Steroid hormones</subject><subject>Steroids</subject><subject>Transparency</subject><subject>Transplants & implants</subject><subject>Vascularization</subject><issn>1755-375X</issn><issn>1755-3768</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkU1LxDAQhoso-PkThIDn1mTbpKk3WfwCwYMK3kKSTjW1TWqS7rr_3tYVj-JcZgjPM4F5k-SU4IxMdd5mpKQ0zUvGswUmLMMF5TvJwe_r7u9MX_aTwxBajBlhrDhIVnd9P1oXxmHwEIJxFq1NfEMShVFpZ9vR6mhWskOmHzppI_LQgQzGvqIaPmUP8U0GZwEZO0leKmUi6l0NHXINGsBC9DLO-DtMg5uWhLg5TvYa2QU4-elHyfP11dPyNr1_uLlbXt6neoExTwmvGk7rguBiobHWBOqGKVwpxXKZK1C0okzlbKKrUpcF0ZxKVpRAGqyrssmPkrPt3sG7jxFCFK0bvZ2-FKQinGPOKv4nxUmFS8wpnii6pbR3IXhoxOBNL_1GECzmIEQr5jOL-eRiDkLMQUzexdZbmw42_5PE5cPjt_wFafiPKg</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Crouzet, E.</creator><creator>He, Z.</creator><creator>Perrache, C.</creator><creator>Basset, T.</creator><creator>Delavenne, X.</creator><creator>Peoc'h, M.</creator><creator>Gain, P.</creator><creator>Thuret, G.</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>201610</creationdate><title>Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty</title><author>Crouzet, E. ; He, Z. ; Perrache, C. ; Basset, T. ; Delavenne, X. ; Peoc'h, M. ; Gain, P. ; Thuret, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2008-189f85d41042c0cc1edf6b09bb63a3beb5956b36c2097c741c85a647e1f0c97f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Angiogenesis</topic><topic>Cornea</topic><topic>Corneal transplantation</topic><topic>Dexamethasone</topic><topic>Digital imaging</topic><topic>Eye</topic><topic>Graft rejection</topic><topic>Grafting</topic><topic>Histology</topic><topic>Immunosuppression</topic><topic>Ophthalmology</topic><topic>Sodium chloride</topic><topic>Steroid hormones</topic><topic>Steroids</topic><topic>Transparency</topic><topic>Transplants & implants</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crouzet, E.</creatorcontrib><creatorcontrib>He, Z.</creatorcontrib><creatorcontrib>Perrache, C.</creatorcontrib><creatorcontrib>Basset, T.</creatorcontrib><creatorcontrib>Delavenne, X.</creatorcontrib><creatorcontrib>Peoc'h, M.</creatorcontrib><creatorcontrib>Gain, P.</creatorcontrib><creatorcontrib>Thuret, G.</creatorcontrib><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Acta ophthalmologica (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crouzet, E.</au><au>He, Z.</au><au>Perrache, C.</au><au>Basset, T.</au><au>Delavenne, X.</au><au>Peoc'h, M.</au><au>Gain, P.</au><au>Thuret, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty</atitle><jtitle>Acta ophthalmologica (Oxford, England)</jtitle><date>2016-10</date><risdate>2016</risdate><volume>94</volume><issue>S256</issue><epage>n/a</epage><issn>1755-375X</issn><eissn>1755-3768</eissn><abstract>Purpose
Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasing dexamethasone (SCIRD) in a rabbit model of PK.
Methods
7.5 mm PK were performed in NZW rabbits. After randomisation they received either a SCIRD (Ozurdex, Allergan) (n = 8), dexamethasone eyedrops (1 mg/ml, Dexafree, Thea) 3 times a day (n = 6), or 0.9% NaCl (n = 6). The running suture was left in place to stimulate angiogenesis. Weekly follow‐up by digital slit lamp and anterior segment OCT. Images were analysed blind to the treatment for transparency, neovessels, and central corneal thickness (CCT). After 5 or 6 weeks, animals were killed and corneas were processed for standard histology.
Results
Placebo group: constant early neovascularization growing to neovessels penetrating the graft on >270° after 5 weeks + rejection (opaque graft, 360° neovessels, CCT > 500 μm) in 50% of cases. Eye drops and implants groups: similar evolution, without rejection after 6 weeks and normal CCT. Moderate neovascularization occurred in 5/6 rabbits treated with eyedrops and 6/8 treated with the implant. Histology confirmed clinical diagnosis in all cases. The implants disappeared after 3–5 weeks. No adverse effect.
Conclusions
Despite a severe rejection model, a SCIRD was not less efficient than eye drops to prevent rejection during the first 6 weeks. These findings highlight the potential benefit of subconjunctival implants of steroids after corneal graft.</abstract><cop>Malden</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1111/j.1755-3768.2016.0458</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiogenesis Cornea Corneal transplantation Dexamethasone Digital imaging Eye Graft rejection Grafting Histology Immunosuppression Ophthalmology Sodium chloride Steroid hormones Steroids Transparency Transplants & implants Vascularization |
title | Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty |
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