LOCALIZATION OF LIPOPROTEIN-DELIVERED BENZOPORPHYRIN DERIVATIVE IN THE RABBIT EYE

Purpose. Photodynamic therapy (PDT) using the photosensitizer Benzopor phyrin derivative monoacid (BPD-MA or verteporfin(R)) is currently und er investigation for the treatment of choroidal neovascularization. We investigated the localization of this photosensitizer using fluoresce nce microscopy and quantified its presence in ocular tissues after por phyrin extraction using fluorescence spectroscopy. Methods. Albino rab bits were administered 2mg/kg BPD-MA pre-complexed with low density li poprotein (LDL) intravenously, or given no treatment. The eyes were en ucleated at intervals between 5 minutes and 24 hours after dye injecti on and were studied with light and fluorescence microscopy, or dissect ed for porphyrin extraction. Results. At 5 minutes after dye injection , there was bright fluorescence from the choroid and retinal pigment e pithelium (RPE) with trace retinal outer segment fluorescence. After 2 0 minutes, there was increased photoreceptor outer segment and RPE flu orescence but decreased choroidal fluorescence. By 2 hours no fluoresc ence remained in either the choroid or the photoreceptors and there wa s diminished fluorescence of the RPE. Trace RPE fluorescence was still visible at 24 hours. Fluorescence localization of liposomal BPD (2mg/ kg) at the earliest (5 minutes) time point was indistinguishable from that of the BPD-LDL complex. Using spectrofluorimetry, the highest BPD -MA levels from the eye were measured in the retina/RPE/uvea complex w ith lower levels measured from the sclera and other tissues. Conclusio ns. BPD-MA with LDL rapidly accumulates in the choroid, RPE, and photo receptors after intravenous injection. Future studies of PDT with BPD- MA for the treatment of fundus disorders may need to address the relat ionship between dye localization and photodynamically-mediated injury.