Article Text
Abstract
Aim: The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined.
Methods: MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01–0.1 μmol/kg, 5–25 J/cm2, and 10–60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025–0.25 μmol/kg, 3.3–20 J/cm2, and 10 minutes, respectively.
Results: In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 μmol/kg was activated by a 20 J/cm2 light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 μmol/kg using light doses from 3.3 to 20 J/cm2.
Conclusion: PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.
- AMD, age related macular degeneration
- CNVM, choroidal neovascular membranes
- EYP, egg yolk phosphatidylcholine
- PDT, photodynamic therapy
- PIAT, post-injection activation time
- RPE, retinal pigment epithelium
- animal model
- age related macular degeneration
- neovascularisation
- laser
- photodynamic therapy
- photosensitiser
- AMD, age related macular degeneration
- CNVM, choroidal neovascular membranes
- EYP, egg yolk phosphatidylcholine
- PDT, photodynamic therapy
- PIAT, post-injection activation time
- RPE, retinal pigment epithelium
- animal model
- age related macular degeneration
- neovascularisation
- laser
- photodynamic therapy
- photosensitiser
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- AMD, age related macular degeneration
- CNVM, choroidal neovascular membranes
- EYP, egg yolk phosphatidylcholine
- PDT, photodynamic therapy
- PIAT, post-injection activation time
- RPE, retinal pigment epithelium
- animal model
- age related macular degeneration
- neovascularisation
- laser
- photodynamic therapy
- photosensitiser
- AMD, age related macular degeneration
- CNVM, choroidal neovascular membranes
- EYP, egg yolk phosphatidylcholine
- PDT, photodynamic therapy
- PIAT, post-injection activation time
- RPE, retinal pigment epithelium
- animal model
- age related macular degeneration
- neovascularisation
- laser
- photodynamic therapy
- photosensitiser
Footnotes
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Supported by National Eye Institute Grant R44 EY11191, Business Innovation Research Program via Miravant Medical Technologies, by a grant from Miravant Medical Technologies Inc, and by an unrestricted grant from Research to Prevent Blindness, Inc, New York. TA Ciulla is a recipient of a Career Development Award from Research to Prevent Blindness, Inc, New York, USA.
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Proprietary interest: Drs Snyder and Small are employees of Miravant Medical Technologies Inc.
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This research investigation was performed at both locations.
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PhotoPoint is a trademark of Miravant Medical Technologies, Santa Barbara, CA, USA.