Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration.

Age-related macular degeneration, especially the neovascular form of the disease, is the leading cause of blindness in elderly people in developed countries. Thermal photocoagulation is still the preferred treatment for choroidal neovascularization that does not involve the fovea, but it is suitable for only a small number of patients and it can lead to immediate loss of visual acuity. Photodynamic therapy with use of photochemical light activation of verteporfin as a photosensitizer (verteporfin therapy) has been shown to be effective in treating vascularized tumors, and its potential to treat other conditions involving neovascularization has also been suggested. Preclinical and clinical studies have indicated that verteporfin therapy can be used to treat choroidal neovascularization secondary to age-related macular degeneration effectively and safely. Selective occlusion of choroidal neovasculature by this therapy causes minimal damage to the neurosensory retina and, therefore, does not induce loss of visual acuity. This benefit allows verteporfin therapy to be used in the large proportion of patients who are not eligible for treatment by laser photocoagulation. The mechanistic aspects of the mode of action of light-activated verteporfin are described in this review.

[1]  B. Miller,et al.  Photodynamic therapy of subretinal neovascularization in the monkey eye. , 1993, Archives of ophthalmology.

[2]  M. Ochsner Photophysical and photobiological processes in the photodynamic therapy of tumours. , 1997, Journal of photochemistry and photobiology. B, Biology.

[3]  MOUSE SKIN PHOTOSENSITIZATION WITH BENZOPORPHYRIN DERIVATIVES AND PHOTOFRIN®: MACROSCOPIC AND MICROSCOPIC EVALUATION , 1991, Photochemistry and photobiology.

[4]  D. Kessel,et al.  Pharmacokinetics of N-aspartyl chlorin e6 in cancer patients. , 1997, Journal of photochemistry and photobiology. B, Biology.

[5]  R. Boyle,et al.  Structure and Biodistribution Relationships of Photodynamic Sensitizers * , 1996, Photochemistry and photobiology.

[6]  M. Tso,et al.  Experimental photocoagulation of the human retina. I. Correlation of physical, clinical, and pathologic data. , 1977, Archives of ophthalmology.

[7]  C. Gomer PRECLINICAL EXAMINATION OF FIRST and SECOND GENERATION PHOTOSENSITIZERS USED IN PHOTODYNAMIC THERAPY , 1991, Photochemistry and photobiology.

[8]  Joan W. Miller,et al.  Photodynamic Therapy of Experimental Choroidal Neovascularization Using Lipoprotein-Delivered Benzoporphyrin , 1995 .

[9]  M. Rodgers,et al.  DEPOLARIZATION OF MOUSE MYELOMA CELL MEMBRANES DURING PHOTODYNAMIC ACTION , 1990, Photochemistry and photobiology.

[10]  S. Bown New techniques in laser therapy , 1998, BMJ.

[11]  B. Khoobehi,et al.  Photodynamic therapy for choriocapillaris using tin ethyl etiopurpurin (SnET2). , 1997, Ophthalmic surgery and lasers.

[12]  U. Schmidt-Erfurth Indocyanine green angiography and retinal sensitivity after photodynamic therapy of subfoveal choroidal neovascularization. , 1999, Seminars in ophthalmology.

[13]  M. Territo,et al.  Lipoprotein Receptors and Endothelial Cells , 1988, Seminars in thrombosis and hemostasis.

[14]  R Birngruber,et al.  Photodynamic therapy of experimental choroidal melanoma using lipoprotein-delivered benzoporphyrin. , 1994, Ophthalmology.

[15]  M. Rodgers On the problems involved in detecting luminescence from singlet oxygen in biological specimens. , 1988, Journal of photochemistry and photobiology. B, Biology.

[16]  U. Schmidt-Erfurth,et al.  Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates. , 1997, British Journal of Cancer.

[17]  R Birngruber,et al.  Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study. , 1999, Archives of ophthalmology.

[18]  C J Gomer,et al.  Photodynamic therapy in the treatment of malignancies. , 1989, Seminars in hematology.

[19]  J. Sessler,et al.  Lutetium Texaphyrin (PCI‐0123): A Near‐Infrared, Water‐Soluble Photosensitizer , 1996, Photochemistry and photobiology.

[20]  G. Buettner,et al.  Hydrogen peroxide and hydroxyl free radical production by hematoporphyrin derivative, ascorbate and light. , 1985, Cancer letters.

[21]  L. Yannuzzi,et al.  Age-related macular degeneration and choroidal neovascularization. , 1993, American journal of ophthalmology.

[22]  Richard Wise,et al.  Science, medicine, and the future , 1998 .

[23]  N. Oleinick,et al.  The Synthesis, Photophysical and Photobiological Properties and in vitro Structure‐Activity Relationships of a Set of Silicon Phthalocyanine PDT Photosensitizers , 1997, Photochemistry and photobiology.

[24]  Benzoporphyrin-lipoprotein-mediated photodestruction of intraocular tumors. , 1996, Experimental eye research.

[25]  Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. , 2001 .

[26]  R A Miller,et al.  Phototherapy of cancer and atheromatous plaque with texaphyrins. , 1996, Journal of clinical laser medicine & surgery.

[27]  S. Gibson,et al.  Hematoporphyrin derivative-induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230AC mammary adenocarcinomas of rats. , 1984, Cancer research.

[28]  R Birngruber,et al.  Vascular targeting in photodynamic occlusion of subretinal vessels. , 1994, Ophthalmology.

[29]  N. Bressler,et al.  Persistent and recurrent neovascularization after krypton laser kphotocoagualation for neovascular lesions fo age-related macular degenration , 1990 .

[30]  B. Allison,et al.  Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative. , 1994, British Journal of Cancer.

[31]  Julia G. Levy,et al.  Clinical status of benzoporphyrin derivative , 1996, European Conference on Biomedical Optics.

[32]  D. Dolphin,et al.  Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. , 1990, Journal of photochemistry and photobiology. B, Biology.

[33]  T. Hasan,et al.  Role of neovasculature and vascular permeability on the tumor retention of photodynamic agents. , 1992, Cancer research.

[34]  C. Puliafito,et al.  Phthalocyanine photodynamic therapy: New strategy for closure of choroidal neovascularization , 1994, Lasers in surgery and medicine.

[35]  M. Obochi,et al.  Prolonged skin allograft survival after photodynamic therapy associated with modification of donor skin antigenicity. , 1997, Transplantation.

[36]  N. Bressler,et al.  Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples , 1998, Graefe's Archive for Clinical and Experimental Ophthalmology.

[37]  T J Flotte,et al.  Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey. , 1999, Ophthalmology.

[38]  S. Kumar,et al.  Differences in the uptake of modified low density lipoproteins by tissue cultured endothelial cells. , 1985, Journal of cell science.

[39]  P. Rowe Photodynamic therapy begins to shine , 1998, The Lancet.

[40]  J. Duker,et al.  The photodynamic occlusion of choroidal vessels using benzoporphyrin derivative. , 1994, Current eye research.

[41]  M. E. Kenney,et al.  Photoinactivation of amelanotic and melanotic melanoma cells sensitized by axially substituted Si-naphthalocyanines. , 1998, Journal of photochemistry and photobiology. B, Biology.

[42]  Lars O. Svaasand,et al.  On the physical rationale of photodynamic therapy , 1990, Other Conferences.

[43]  J. Levy,et al.  Preferential uptake of benzoporphyrin derivative by leukemic versus normal cells. , 1990, Leukemia research.

[44]  T. Hasan,et al.  PHOTOPHYSICAL AND PHOTOSENSITIZING PROPERTIES OF BENZOPORPHYRIN DERIVATIVE MONOACID RING A (BPD‐MA) * , 1994, Photochemistry and photobiology.

[45]  T. Hasan,et al.  The effects of aggregation, protein binding and cellular incorporation on the photophysical properties of benzoporphyrin derivative monoacid ring A (BPDMA). , 1995, Journal of photochemistry and photobiology. B, Biology.

[46]  G. Kutty,et al.  Light history and age-related changes in retinal light damage. , 1998, Investigative ophthalmology & visual science.

[47]  V. Fingar,et al.  Vascular effects of photodynamic therapy. , 1996, Journal of clinical laser medicine & surgery.

[48]  U. Schmidt-Erfurth,et al.  Photodynamic therapy in ocular vascular disease , 1996 .

[49]  R P Murphy,et al.  Natural course of choroidal neovascular membranes within the foveal avascular zone in senile macular degeneration. , 1982, American journal of ophthalmology.

[50]  E. Reddi,et al.  The role of lipoproteins in the delivery of tumour-targeting photosensitizers. , 1993, The International journal of biochemistry.

[51]  F. Ferris,et al.  Age-related macular degeneration and blindness due to neovascular maculopathy. , 1984, Archives of ophthalmology.

[52]  T. Hasan,et al.  Localization of lipoprotein-delivered benzoporphyrin derivative in the rabbit eye. , 1997, Current eye research.

[53]  A. Jain,et al.  LIPOSOMAL DELIVERY OF A PHOTOSENSITIZER, BENZOPORPHYRIN DERIVATIVE MONOACID RING A (BPD), TO TUMOR TISSUE IN A MOUSE TUMOR MODEL , 1993, Photochemistry and photobiology.

[54]  T. Delaney,et al.  Photodynamic therapy of cancer. , 1988, Comprehensive therapy.

[55]  B. Wilson,et al.  Photodynamic therapy: light delivery and dosage for second-generation photosensitizers. , 2007, Ciba Foundation symposium.

[56]  E. Thomas,et al.  CLOSURE OF EXPERIMENTAL SUBRETINAL NEOVASCULAR VESSELS WITH DIHEMATOPORPHYRIN ETHER AUGMENTED ARGON GREEN LASER PHOTOCOAGULATION , 1987, Photochemistry and photobiology.

[57]  A. Jain,et al.  Photosensitising potency of structural analogues of benzoporphyrin derivative (BPD) in a mouse tumour model. , 1991, British Journal of Cancer.

[58]  S. Pelech,et al.  Stimulation of Stress-activated Protein Kinase and p38 HOG1 Kinase in Murine Keratinocytes following Photodynamic Therapy with Benzoporphyrin Derivative* , 1996, The Journal of Biological Chemistry.

[59]  D. Kessel SITES OF PHOTOSENSITIZATION BY DERIVATIVES OF HEMATOPORPHYRIN , 1986, Photochemistry and photobiology.

[60]  Joan W. Miller,et al.  Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization. , 1996, Archives of ophthalmology.

[61]  T. Dougherty,et al.  HOW DOES PHOTODYNAMIC THERAPY WORK? , 1992, Photochemistry and photobiology.

[62]  J. J. Schuitmaker,et al.  Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results. , 1990, Investigative ophthalmology & visual science.

[63]  G. Peyman,et al.  Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6). , 1999, Ophthalmology.

[64]  D. Dolphin,et al.  Preliminary studies on a more effective phototoxic agent than hematoporphyrin. , 1987, Journal of the National Cancer Institute.

[65]  Photodynamische Therapie experimenteller, intraokularer Tumoren mit Benzoporphyrin-Lipoprotein , 1994 .

[66]  R Birngruber,et al.  Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. , 1999, Archives of ophthalmology.

[67]  T. Miki,et al.  Selective occlusion of choroidal neovascularization by photodynamic therapy with a water‐soluble photosensitizer, ATX‐S10 , 1999, Lasers in surgery and medicine.

[68]  U. Schmidt-Erfurth,et al.  In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in experimental corneal neovascularization , 1995, Lasers in surgery and medicine.

[69]  Joan W. Miller,et al.  Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys. , 1996, Ophthalmology.

[70]  Harvey Lui,et al.  Photodynamic therapy of malignant skin tumors with Benzoporphyrin derivative-monoacid ring A (BPD-MA): preliminary observations , 1993, Photonics West - Lasers and Applications in Science and Engineering.