title: GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized phase II trial.
abstract: OBJECTIVE
  Pathologic corneal neovascularization not only reduces corneal transparency and visual acuity, but also is one of the most significant preoperative and postoperative risk factors for graft rejection after corneal transplantation. The aim of this study was to test tolerability and efficacy of gene signal (GS)-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1, versus placebo on inhibition of progressive corneal neovascularization.
  
  
  METHODS
  Randomized, double-blind, multicenter, phase II clinical study.
  
  
  METHODS
  Interim analysis on 40 patients with progressive corneal neovascularization resulting from various underlying diseases being nonresponsive to conventional therapy.
  
  
  METHODS
  Four groups of 10 patients were treated for 3 months in this dose-finding study comparing 3 doses of GS-101 (eye drops twice daily; 43, 86, and 172 microg/day total) with placebo (10 patients per group).
  
  
  METHODS
  The primary end point was the area covered by pathologic corneal blood vessels, which was measured morphometrically on digitized slit-lamp pictures using image analysis techniques.
  
  
  RESULTS
  GS-101 eye drops were well tolerated. All serious and 95% of all other adverse events were categorized by the investigators as unrelated. In 3 patients, there was a potentially related side effect of ocular surface discomfort. At a dose of 86 microg/day (43 microg/drop), GS-101 eye drops produced a significant inhibition and regression of corneal neovascularization (-2.04+/-1.57% of total corneal area; P = 0.0047), whereas the low dose tended to stabilize it (0.07+/-2.94%; P = 0.2088) compared with placebo (0.89+/-2.15%), where corneal neovascularization progressed in all patients. There was no apparent benefit to the higher dose (1.60+/-7.63%).
  
  
  CONCLUSIONS
  The interim results of this phase II study suggest that GS-101 eye drops at an optimal dose of 86 microg/day are an effective and noninvasive approach specifically to inhibit and regress active corneal angiogenesis, a major risk factor for corneal graft transplantation and graft rejection. Safety concerns were not detected.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors: Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6, Erlangen, Germany. ccursiefen@yahoo.com
authors: Claus
authors: C
authors: Cursiefen
authors: Felix
authors: F
authors: Bock
authors: Folkert K
authors: FK
authors: Horn
authors: Friedrich E
authors: FE
authors: Kruse
authors: Berthold
authors: B
authors: Seitz
authors: Vincent
authors: V
authors: Borderie
authors: Beatrice
authors: B
authors: Früh
authors: Michael A
authors: MA
authors: Thiel
authors: Frank
authors: F
authors: Wilhelm
authors: Bernard
authors: B
authors: Geudelin
authors: Isabelle
authors: I
authors: Descohand
authors: Klaus-Peter
authors: KP
authors: Steuhl
authors: Angela
authors: A
authors: Hahn
authors: Daniel
authors: D
authors: Meller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; C540750:GS 101; D009841:Oligonucleotides; D009883:Ophthalmic Solutions