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Photodynamic therapy (PDT) using verteporfin is widely used for treatment of age related macular degeneration (AMD).
Due to non-perfect selectivity of the drug accumulation in the neovasculature some collateral damage to healthy tissue
arises during the treatment. Damage to healthy structures in the eye is always a concern because of a high probability of
reducing visual acuity. Two-photon (2-&ggr;) photodynamic therapy potentially offers much higher treatment selectivity than
its one-photon (1-&ggr;) counterpart. By utilizing focused light for 2-&ggr; excitation, treatment volumes on the order of
microliters can be achieved thus maximizing localized insult to abnormal blood vessels and sparing healthy tissue. We
propose that 2-&ggr; photodynamic therapy will be valuable in the treatment of choroidal neovascularization secondary to
age related macular degeneration as well as other conditions. To ascertain feasibility of 2-&ggr; photodynamic therapy we
measured 2-&ggr; spectrum and cross sections of verteporfin (80 GM at 940 nm, 1 GM = 10-50 cm4s/photon), chlorin e6 (14
GM at 800 nm) and tetrasulfonated aluminum phthalocyanine (140 GM at 900 nm) and investigated their in vitro
efficiency under 2-&ggr; excitation. Only verteporfin demonstrated cell kill under the used irradiation parameters (average
light intensity 9.1 mW, wavelength 850 nm, total light dose 6900 J/cm2). Dorsal skinfold window chamber model in
mouse was used to test efficiency of 2-&ggr; PDT with verteporfin in vivo. Although we were able to induce photodynamic
damage to a blood vessel using 1-&ggr; excitation, 2-&ggr; excitation resulted in no visible damage to irradiated blood vessel. The most probable reason is low efficiency of verteporfin as a 2-&ggr; photosensitizer. We also report 2-&ggr; spectrum of new
photosensitizer, HCC4 (4300 GM at 830 nm), specifically designed for efficient 2-&ggr; excitation.
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