title: In vivo imaging of a new indocyanine green micelle formulation in an animal model of laser-induced choroidal neovascularization.
abstract: OBJECTIVE
  We investigated a novel formulation of indocyanine green (ICG/HS 15) in an animal model of laser-induced choroidal neovascularization (CNV).
  
  
  METHODS
  The ICG was formulated with the nonionic solubilizer and emulsifying agent Kolliphor HS 15 to create ICG/HS 15 to improve the chemical stability and fluorescence efficacy. In vivo imaging was performed in rats that had undergone laser photocoagulation. Retinal uptake and fluorescence intensity of ICG and ICG/HS 15 were compared following intravenous injection of 3 dosages (0.05, 0.1, and 0.15 mg/kg body weight) at 7, 14, and 21 days following laser treatment. Postmortem analysis included histology with frozen sections and flat mounts.
  
  
  RESULTS
  Immediately following injection of ICG or ICG/HS 15, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity was higher for ICG/HS 15 compared to conventional ICG at 8 minutes after injection for all different injection days and dosages. Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes to baseline level. Flow cytometry data showed an increased uptake of micellar dye of macrophages and endothelial cells. Histology revealed an accumulation of the micellar dye within the laser lesion.
  
  
  CONCLUSIONS
  Micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis.
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Meyer
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cunea
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Sonntag-Bensch
authors.affiliation: mivenion GmbH, Berlin, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Welker
authors.affiliation: mivenion GmbH, Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmitz-Valckenberg
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000175:diagnosis* / Q000378:metabolism; D004396:Coloring Agents; D004195:Disease Models, Animal; D005434:Flow Cytometry / Q000379:methods; D007150:Immunohistochemistry; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D053685:Laser Therapy / Q000009:adverse effects; D008297:Male; D008823:Micelles; D009887:Ophthalmoscopy / Q000379:methods*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004396:Coloring Agents; D008823:Micelles; D007208:Indocyanine Green
keywords: Kolliphor; in vivo imaging; indocyanine green; laser-induced choroidal neovascularization; micellar formulation; micelles