Universität zu Köln

Cursiefen, Claus, Viaud, Eric, Bock, Felix, Geudelin, Bernard, Ferry, Antoine, Kadlecova, Pavla, Levy, Michel, Al Mahmood, Salman, Colin, Sylvie, Thorin, Eric ORCID: 0000-0001-5827-8935, Majo, Francois, Frueh, Beatrice, Wilhelm, Frank, Meyer-Ter-Vehn, Tobias, Geerling, Gerd, Boehringer, Daniel, Reinhard, Thomas, Meller, Daniel, Pleyer, Uwe, Bachmann, Bjoern and Seitz, Berthold ORCID: 0000-0001-9701-8204 (2014). Aganirsen Antisense Oligonucleotide Eye Drops Inhibit Keratitis-Induced Corneal Neovascularization and Reduce Need for Transplantation The I-CAN Study. Ophthalmology, 121 (9). S. 1683 - 1693. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1549-4713

Full text not available from this repository.

Abstract

Objective: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Design: Multicenter, double-masked, randomized, placebo-controlled phase III study. Participants: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 mu g/day/eye) or placebo twice daily for 90 days and were followed up to day 180. Main Outcome Measures: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Results: Although no significant differences in VAscores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20%(P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. Conclusions: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated. (C) 2014 by the American Academy of Ophthalmology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Viaud, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Geudelin, Bernard UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferry, Antoine UNSPECIFIED UNSPECIFIED UNSPECIFIED Kadlecova, Pavla UNSPECIFIED UNSPECIFIED UNSPECIFIED Levy, Michel UNSPECIFIED UNSPECIFIED UNSPECIFIED Al Mahmood, Salman UNSPECIFIED UNSPECIFIED UNSPECIFIED Colin, Sylvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Thorin, Eric UNSPECIFIED orcid.org/0000-0001-5827-8935 UNSPECIFIED Majo, Francois UNSPECIFIED UNSPECIFIED UNSPECIFIED Frueh, Beatrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilhelm, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer-Ter-Vehn, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Geerling, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehringer, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhard, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Meller, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Pleyer, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Bachmann, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Seitz, Berthold UNSPECIFIED orcid.org/0000-0001-9701-8204 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430321
DOI:	10.1016/j.ophtha.2014.03.038
Journal or Publication Title:	Ophthalmology
Volume:	121
Number:	9
Page Range:	S. 1683 - 1693
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1549-4713
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; STROMAL KERATITIS; GRAFT FAILURE; LYMPHANGIOGENESIS; ANGIOGENESIS; RANIBIZUMAB; REJECTION Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43032