Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration
Purpose To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort st...
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| Veröffentlicht in: | Ophthalmology (Rochester, Minn.) Minn.), 2007-03, Vol.114 (3), p.561-570.e2 |
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| creator | MacLaren, Robert E., DPhil, FRCOphth Uppal, Gurmit S., MRCOphth Balaggan, Kamaljit S., MRCOphth Tufail, Adnan, MD, FRCOphth Munro, Peter M.G., PhD Milliken, Andrew B., FCOptom Ali, Robin R., PhD Rubin, Gary S., PhD Aylward, G. William, MD, FRCOphth da Cruz, Lyndon, PhD, FRCOphth |
| description | Purpose To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort study. Participants Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had |
| doi_str_mv | 10.1016/j.ophtha.2006.06.049 |
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William, MD, FRCOphth ; da Cruz, Lyndon, PhD, FRCOphth</creator><creatorcontrib>MacLaren, Robert E., DPhil, FRCOphth ; Uppal, Gurmit S., MRCOphth ; Balaggan, Kamaljit S., MRCOphth ; Tufail, Adnan, MD, FRCOphth ; Munro, Peter M.G., PhD ; Milliken, Andrew B., FCOptom ; Ali, Robin R., PhD ; Rubin, Gary S., PhD ; Aylward, G. William, MD, FRCOphth ; da Cruz, Lyndon, PhD, FRCOphth</creatorcontrib><description>Purpose To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort study. Participants Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Methods Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch’s membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Main Outcome Measures Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Results Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. Conclusions Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.</description><identifier>ISSN: 0161-6420</identifier><identifier>EISSN: 1549-4713</identifier><identifier>DOI: 10.1016/j.ophtha.2006.06.049</identifier><identifier>PMID: 17324698</identifier><identifier>CODEN: OPHTDG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Animals ; Biological and medical sciences ; Blood Vessels - pathology ; Cataract - complications ; Cataract Extraction ; Choroid - blood supply ; Choroid - transplantation ; Choroidal Neovascularization - complications ; Choroidal Neovascularization - surgery ; Cohort Studies ; Gene Transfer Techniques ; Green Fluorescent Proteins - genetics ; Humans ; In Vitro Techniques ; Macular Degeneration - complications ; Macular Degeneration - surgery ; Medical sciences ; Miscellaneous ; Ophthalmology ; Pigment Epithelium of Eye - transplantation ; Postoperative Complications ; Prospective Studies ; Rats ; Recovery of Function ; Severity of Illness Index ; Transplantation, Autologous ; Vision Disorders - etiology ; Vision Disorders - physiopathology ; Vision, Ocular</subject><ispartof>Ophthalmology (Rochester, Minn.), 2007-03, Vol.114 (3), p.561-570.e2</ispartof><rights>American Academy of Ophthalmology</rights><rights>2007 American Academy of Ophthalmology</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-64e853dcf4a1a0bc6db9e7a0512c473fe636d5c1f65a90770163d58c595c1a0b3</citedby><cites>FETCH-LOGICAL-c445t-64e853dcf4a1a0bc6db9e7a0512c473fe636d5c1f65a90770163d58c595c1a0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ophtha.2006.06.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18565275$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17324698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MacLaren, Robert E., DPhil, FRCOphth</creatorcontrib><creatorcontrib>Uppal, Gurmit S., MRCOphth</creatorcontrib><creatorcontrib>Balaggan, Kamaljit S., MRCOphth</creatorcontrib><creatorcontrib>Tufail, Adnan, MD, FRCOphth</creatorcontrib><creatorcontrib>Munro, Peter M.G., PhD</creatorcontrib><creatorcontrib>Milliken, Andrew B., FCOptom</creatorcontrib><creatorcontrib>Ali, Robin R., PhD</creatorcontrib><creatorcontrib>Rubin, Gary S., PhD</creatorcontrib><creatorcontrib>Aylward, G. William, MD, FRCOphth</creatorcontrib><creatorcontrib>da Cruz, Lyndon, PhD, FRCOphth</creatorcontrib><title>Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration</title><title>Ophthalmology (Rochester, Minn.)</title><addtitle>Ophthalmology</addtitle><description>Purpose To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort study. Participants Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Methods Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch’s membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Main Outcome Measures Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Results Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. Conclusions Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Vessels - pathology</subject><subject>Cataract - complications</subject><subject>Cataract Extraction</subject><subject>Choroid - blood supply</subject><subject>Choroid - transplantation</subject><subject>Choroidal Neovascularization - complications</subject><subject>Choroidal Neovascularization - surgery</subject><subject>Cohort Studies</subject><subject>Gene Transfer Techniques</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Macular Degeneration - complications</subject><subject>Macular Degeneration - surgery</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Ophthalmology</subject><subject>Pigment Epithelium of Eye - transplantation</subject><subject>Postoperative Complications</subject><subject>Prospective Studies</subject><subject>Rats</subject><subject>Recovery of Function</subject><subject>Severity of Illness Index</subject><subject>Transplantation, Autologous</subject><subject>Vision Disorders - etiology</subject><subject>Vision Disorders - physiopathology</subject><subject>Vision, Ocular</subject><issn>0161-6420</issn><issn>1549-4713</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks-KFDEQxhtR3HH1DURy0VuPSXeS7r4Iw7i6C-sf1vEcMkn1TMZM0ibphX0E39r09MCCF6EgUPy-qtRXVRSvCV4STPj7w9IP-7SXywpjvpyCdk-KBWG0K2lD6qfFImOk5LTCF8WLGA84g7ymz4sL0tQV5V27KP6sxuSt3_kxok2QLg5WuiST8Q75HqU9oDtIxkmLvpvdEVxCV4PJaWvGI5JOo_XeB280Mu5EbwLIdOKy_Cv4exnVaGVAqx2Ud2BlAo2-yDn3EXbgIJzavSye9dJGeHV-L4ufn6426-vy9tvnm_XqtlSUspTHgZbVWvVUEom3iuttB43EjFSKNnUPvOaaKdJzJjvcNNmDWrNWsS4ns6C-LN7NdYfgf48QkziaqMDmuSG7IBpcEc5wm0E6gyr4GAP0YgjmKMODIFhMKxAHMa9ATCsQU9Auy96c64_bI-hH0dnzDLw9A9kaafvsujLxkWsZZ1XDMvdh5iC7cW8giKgMOAXaBFBJaG_-95N_CyhrnMk9f8EDxIMfQ95rFETESmDxYzqX6VowxwSzpq3_AtHZvXk</recordid><startdate>20070301</startdate><enddate>20070301</enddate><creator>MacLaren, Robert E., DPhil, FRCOphth</creator><creator>Uppal, Gurmit S., MRCOphth</creator><creator>Balaggan, Kamaljit S., MRCOphth</creator><creator>Tufail, Adnan, MD, FRCOphth</creator><creator>Munro, Peter M.G., PhD</creator><creator>Milliken, Andrew B., FCOptom</creator><creator>Ali, Robin R., PhD</creator><creator>Rubin, Gary S., PhD</creator><creator>Aylward, G. William, MD, FRCOphth</creator><creator>da Cruz, Lyndon, PhD, FRCOphth</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20070301</creationdate><title>Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration</title><author>MacLaren, Robert E., DPhil, FRCOphth ; Uppal, Gurmit S., MRCOphth ; Balaggan, Kamaljit S., MRCOphth ; Tufail, Adnan, MD, FRCOphth ; Munro, Peter M.G., PhD ; Milliken, Andrew B., FCOptom ; Ali, Robin R., PhD ; Rubin, Gary S., PhD ; Aylward, G. William, MD, FRCOphth ; da Cruz, Lyndon, PhD, FRCOphth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-64e853dcf4a1a0bc6db9e7a0512c473fe636d5c1f65a90770163d58c595c1a0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Vessels - pathology</topic><topic>Cataract - complications</topic><topic>Cataract Extraction</topic><topic>Choroid - blood supply</topic><topic>Choroid - transplantation</topic><topic>Choroidal Neovascularization - complications</topic><topic>Choroidal Neovascularization - surgery</topic><topic>Cohort Studies</topic><topic>Gene Transfer Techniques</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Macular Degeneration - complications</topic><topic>Macular Degeneration - surgery</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Ophthalmology</topic><topic>Pigment Epithelium of Eye - transplantation</topic><topic>Postoperative Complications</topic><topic>Prospective Studies</topic><topic>Rats</topic><topic>Recovery of Function</topic><topic>Severity of Illness Index</topic><topic>Transplantation, Autologous</topic><topic>Vision Disorders - etiology</topic><topic>Vision Disorders - physiopathology</topic><topic>Vision, Ocular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MacLaren, Robert E., DPhil, FRCOphth</creatorcontrib><creatorcontrib>Uppal, Gurmit S., MRCOphth</creatorcontrib><creatorcontrib>Balaggan, Kamaljit S., MRCOphth</creatorcontrib><creatorcontrib>Tufail, Adnan, MD, FRCOphth</creatorcontrib><creatorcontrib>Munro, Peter M.G., PhD</creatorcontrib><creatorcontrib>Milliken, Andrew B., FCOptom</creatorcontrib><creatorcontrib>Ali, Robin R., PhD</creatorcontrib><creatorcontrib>Rubin, Gary S., PhD</creatorcontrib><creatorcontrib>Aylward, G. William, MD, FRCOphth</creatorcontrib><creatorcontrib>da Cruz, Lyndon, PhD, FRCOphth</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Ophthalmology (Rochester, Minn.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MacLaren, Robert E., DPhil, FRCOphth</au><au>Uppal, Gurmit S., MRCOphth</au><au>Balaggan, Kamaljit S., MRCOphth</au><au>Tufail, Adnan, MD, FRCOphth</au><au>Munro, Peter M.G., PhD</au><au>Milliken, Andrew B., FCOptom</au><au>Ali, Robin R., PhD</au><au>Rubin, Gary S., PhD</au><au>Aylward, G. William, MD, FRCOphth</au><au>da Cruz, Lyndon, PhD, FRCOphth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration</atitle><jtitle>Ophthalmology (Rochester, Minn.)</jtitle><addtitle>Ophthalmology</addtitle><date>2007-03-01</date><risdate>2007</risdate><volume>114</volume><issue>3</issue><spage>561</spage><epage>570.e2</epage><pages>561-570.e2</pages><issn>0161-6420</issn><eissn>1549-4713</eissn><coden>OPHTDG</coden><abstract>Purpose To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort study. Participants Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Methods Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch’s membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Main Outcome Measures Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Results Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. Conclusions Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17324698</pmid><doi>10.1016/j.ophtha.2006.06.049</doi><tpages>10</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Animals Biological and medical sciences Blood Vessels - pathology Cataract - complications Cataract Extraction Choroid - blood supply Choroid - transplantation Choroidal Neovascularization - complications Choroidal Neovascularization - surgery Cohort Studies Gene Transfer Techniques Green Fluorescent Proteins - genetics Humans In Vitro Techniques Macular Degeneration - complications Macular Degeneration - surgery Medical sciences Miscellaneous Ophthalmology Pigment Epithelium of Eye - transplantation Postoperative Complications Prospective Studies Rats Recovery of Function Severity of Illness Index Transplantation, Autologous Vision Disorders - etiology Vision Disorders - physiopathology Vision, Ocular |
| title | Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration |
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