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Norbert Lange, Jean-Pierre Ballini, Georges Wagnieres, Hubert van den Bergh; A New Drug-Screening Procedure for Photosensitizing Agents Used in Photodynamic Therapy for CNV. Invest. Ophthalmol. Vis. Sci. 2001;42(1):38-46.
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purpose. Because vascular occlusion has been observed as a consequence of
photodynamic therapy (PDT), this method has been successfully used for
the treatment of choroidal neovascularization (CNV) in age-related
macular degeneration (AMD). However, most conventional
photosensitizers, primarily developed for tumor PDT, lack selectivity
for the targeting of neovascularization. An experimental model has been
developed for drug screening of new photosensitizers for the treatment
of CNV associated with AMD. It consists of intravenous (IV) injection
of photosensitizers and fluorescent dyes into the chick’s
chorioallantoic membrane (CAM), followed by measurement of fluorescence
pharmacokinetics, leakage from the vascular system, and photothrombic
methods. Fertilized chicken eggs were placed under a fluorescence microscope.
After intravenous injection of different dyes, time-dependent
fluorescence angiography was performed. The effect of PDT parameters
was assessed by fluorescence angiography 24 hours after PDT.
results. Although fluorescence of lipophilic benzoporphyrin derivative monoacid
ring A (BPD-MA) remained intravascular during 2 hours, hydrophilic dyes
tended to leak through the fenestrated neovascularization. By variation
of PDT parameters, vascular damage could be directed toward closure of
vessels with a diameter smaller than 10 μm, as measured 24 hours
after PDT. High photosensitizer concentrations and high light doses
resulted in blood flow stasis within 60 minutes, confirmed by
conclusions. Fluorescence angiography and PDT after IV injection into the CAM showed
strong similarities to results obtained in clinical tests of PDT in CNV
associated with AMD. Thus, this model can provide valuable information
about PDT mechanisms and can be used for drug-screening purposes in
development of improved sensitizers for the PDT of
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