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Steffen Schmitz-Valckenberg, Johanna Meyer, Alexander Cunea, Pia Welker, Kai Licha, Dagmar Sonntag-Bensch, Frank Holz; In vivo imaging of a new indocyanine green micelle formulation in an animal model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4887.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate a novel optimized formulation of indocyanine green (ICG/Solutol HS15) in an animal model.
ICG was formulated with the nonionic solubilizer and emulsifying agent Solutol HS15 to create ICG/Solutol HS15 in order to improve the chemical stability and fluorescence efficacy. Using confocal scanning laser ophthalmoscopy (cSLO), in vivo reflectance and fluorescence (excitation 790 nm, emission > 820 nm) imaging were performed in Dark Agouti rats that had undergone argon laser photocoagulation to induce choroidal neovascularisations (CNV). Retinal uptake and fluorescence intensity of both conventional ICG and ICG/Solutol HS15 were compared following intravenous injection of 3 dosages: 0.05; 0.1 and 0.15 mg/kg body weight (b.w.). In vivo imaging was performed at three different time points: day 7, 14 and 21 days following laser treatment.
In vivo imaging before dye application showed ill-defined retinal lesions at day 7. Immediately following intravenous dye injection, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity in the retinal vasculature (for all 3 dosages: day 7: p=0.01; day 14: p=0.01; day 21: p=0.01) and in the background was significantly higher for ICG/Solutol HS15 compared to conventional ICG at 8 minutes after injection for all time points. Also, pixel intensity in the laser lesion at 8 min was higher for 0,1 and 0,15 mg/kg b.w. ICG/Solutol HS15 compared to conventional ICG at day 7 (p=0.01) and day 21 (p=0.02). Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes. No fluorescent signal of either ICG/Solutol HS15 or ICG was detectable one day after application.
The results demonstrate that micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV showing overall stronger signal intensity as compared to conventional ICG for all tested dosages. Its spatio-temporal kinetics can be studied using in vivo cSLO imaging. Upon further investigations in animal models, ICG/Solutol HS15 may be applicable in patients with retinal and choroidal diseases for earlier and more refined diagnosis
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