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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY007768-07A1
Application #
2161702
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1988-08-01
Project End
1999-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Zeimer, R; Goldberg, M F (2001) Novel ophthalmic therapeutic modalities based on noninvasive light-targeted drug delivery to the posterior pole of the eye. Adv Drug Deliv Rev 52:49-61
Asrani, S; Zou, S; D'Anna, S et al. (1997) Feasibility of laser-targeted photoocclusion of the choriocapillary layer in rats. Invest Ophthalmol Vis Sci 38:2702-10
Asrani, S; Zou, S; D'Anna, S et al. (1996) Selective visualization of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 37:1642-50
Asrani, S; Zou, S; D'Anna, S et al. (1996) Noninvasive visualization of blood flow in the choriocapillaris of the rat. Invest Ophthalmol Vis Sci 37:312-7
Asrani, S; Zeimer, R (1995) Feasibility of laser targeted photo-occlusion of ocular vessels. Br J Ophthalmol 79:766-70
Kiryu, J; Asrani, S; Shahidi, M et al. (1995) Local response of the primate retinal microcirculation to increased metabolic demand induced by flicker. Invest Ophthalmol Vis Sci 36:1240-6
Asrani, S; D'Anna, S; Alkan-Onyuksel, H et al. (1995) Systemic toxicology and laser safety of laser targeted angiography with heat sensitive liposomes. J Ocul Pharmacol Ther 11:575-84
Kiryu, J; Shahidi, M; Mori, M T et al. (1994) Noninvasive visualization of the choriocapillaris and its dynamic filling. Invest Ophthalmol Vis Sci 35:3724-31
Ogura, Y; Guran, T; Takahashi, K et al. (1993) Occlusion of retinal vessels using targeted delivery of a platelet aggregating agent. Br J Ophthalmol 77:233-7

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