Age-related macular degeneration is by far the most prevalent cause of legal blindness in developed countries. While NIH-funded trials have demonstrated that laser photocoagulation can help some patients, the number helped is few. One of the major limitations of conventional fluorescein angiography is the """"""""noise"""""""" from the multiple surrounding sources of hyperfluorescence and the relatively weak """"""""signal"""""""" from """"""""occult"""""""" choroidal neovascular membranes, which are increasingly recognized as a cause of laser failure. The investigator's concept of laser targeted angiography would theoretically improve this signal to noise ratio. Preliminary data from rats substantiate this theoretical advantage. If this proves true in further studies in rats, in cynomologous monkeys, and eventually in human subjects, this technique could greatly facilitate conventional photocoagulation of age-related macular degeneration. The second arm of the study deals with improved methods of laser treatment. They hope to deliver high concentrations of the photosensitizing agent aluminum phthalocyanine tetrasulfonate (AlPcS4) to the target CNVM by the same strategy of laser triggered thermal lysis of liposomes. They present theoretical evidence that the laser burst will release the photosensitizing agent only in the choroidal neovascular membrane and adjacent choriocapillaris and not in the overlying retinal capillaries. Furthermore, the rapid blood flow through the choriocapillaris will allow the photosensitizer to linger in the choroidal neovascular membrane after it flushes out of the choriocapillaris. Preliminary data in the iris of albino rat shows that sub-toxic doses of diode laser plus AlPcS4 can bring about occlusion of blood vessels by a photodynamic (opposed to photothermal) mechanism. The investigators present a detailed plan for upgrading his instrumentation. He also presents detailed plans for moving both arms of the study (laser-targeted angiography and laser-targeted photo-occlusion) through further studies in a rat model of CNVM to toxicity and CNVM-model studies in cynomologous monkeys. This will be followed by Phase I studies will be done in ARMD patients (plus healthy volunteers) and then Phase II studies in 70 patients with ARMD.
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