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F.F. Behar-Cohen, M. Berdugo, R.A. Bejjani, F. Valamanesh, M. Savoldelli, L. Jonet, A. Scherz, Y. Salomon; Toxicological Evaluation of a New Water-Soluble Photo-Sensitizer for PDT, in the Rabbit Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4947.
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Purpose: Photodynamic therapy (PDT) is efficient to induce a transitory occlusion of the choriocapillaries and more prolonged occlusion of choroidal neovessels. Lesions to normal surrounding tissues may have deleterious effects on the final visual outcome, particularly if they are cumulative with repeated treatment. To evaluate the potential toxicity of a new photosensitizer (WST11, Steba Biotech, France) for PDT on normal rabbits. WST11 is a novel generation of photosensitizer, water-soluble bacteriochlorophyll derivative with a near infrared light absorption. Because of its very quick elimination and its exclusive localisation in the vascular compartment with no extravasation in the tissues, a reduced toxicity to normal tissues was hypothesized. Material and methods: Pigmented 3Kgs rabbits received PDT with WST11 at either 1, 2.5, or 5 mg/kg, and illumination of 25, 50, 100 J/cm2 (753nm), and a drug time interval of either 1, 5, 10 or 15 minutes. Animals (n=4) were followed by fluorescein angiogramms and retinophotographies at 1, 2, 8, 15, 30, 45 days after treatment. They were sacrificed at day 1, 8, 15, 30 and 45 and the eyes were processed for either semi-thin, ultrathin microscopy or TUNEL. Results: Focal choroidal occlusion was observed in the angiogramms for 50J/cm2, 5mg/kg, 1min and 5min; and for 25J/cm2, 5mg/kg 1 min, until one week. Weaker parameters did not induce choriocapillaries occlusions and did not induce any lesions in the outer nuclear layers (ONL). Some abnormalities could be observed in the RPE layers, but n o cell loss was detected. Under conditions that created an occlusion of the choriocapillaries, RPE suffering, loss of less than 20% nuclei in the ONL and thrombus of the gross choroidal vessels was observed. Interestingly, even in those cases, choriocapillaries were occluded but no destruction of endothelial cells could be noticed. Conclusions: WST11 induces under defined conditions, a transient occlusion of the choriocapillaries without any endothelial death. This may explain its reduced toxicity to surrounding tissues because the WST11 remains confined in the vascular bed. Its efficacy on neovessels remains to be demonstrated in a relevant model of choroidal angiogenesis.
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