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Photodynamic Therapy: An Emerging Treatment for Classically Leaky
Neovascularizations by Philip Filner, Ph.D.
Limits of the Established Treatment: Laser Photocoagulation While only about 10 - 15% of cases of Age Related Macular
Degeneration involve leaky neovascularizations forming in the choroid behind the macula, they reportedly account for roughly 90% of the cases of severe and relatively rapid vision
loss attributable to ARMD. Until recently, laser photocoagulation was the only treatment which had been proven in clinical trials to be effective against leaky neovascularizations in
wet Age Related Macular Degeneration. However, laser photocoagulation is not appropriate for all leaky neovascularizations. Also, its effectiveness on those for which it is
appropriate is far from ideal. Effectiveness of laser photocoagulation has only been demonstrable statistically. A benefit is not evident in every treated patient, nor even in a
majority of treated patients. The benefit - slowing or stopping of leakage - was temporary, lasting on the average about a year. The energetic laser used in photocoagulation aimed
at leakage points of neovascularizations behind the retina also kills the cells of the overlying part of the retina which are exposed to the laser beam. At the very center of the
macula is a small zone called the fovea, in which the color-sensing cones are concentrated. The fovea is responsible for far more of our color vision, and ability to see detail, than
its very small size might suggest. Consequently, laser photocoagulation of neovascularizations behind the fovea (subfoveal) or at the edges of the fovea (juxtafoveal), does more
damage to vision than good. Ophthalmologists have been looking for alternatives to laser photocoagulation because it is not suitable for subfoveal or juxtafoveal
"classic" neovascularizations, nor for "occult" extrafoveal neovascularizations. Occult neovascularizations are those which are appreciably less leaky than classic
neovascularizations, so it is harder to define the leakage point with enough precision to aim the point of laser light used in photocoagulation. Roughly one-half of leaky
neovascularizations are subfoveal, juxtafoveal or occult, hence should not be treated by laser photocoagulation. The Proposed New Treatment:
Photodynamic Therapy
The Principle: Some molecules absorb visible light much more effectively than other molecules. These compounds often have relatively intense color. The light energy absorbed by
some types of molecules can be released as light, which we call fluorescence. Other types of molecules release the absorbed light energy by energizing a chemical bond, thereby
enabling it to react with other molecules. Light-excitable molecules are said to be photosensitive. Their reactions are called photoreactions. Photodynamic therapy is being
developed by at least two companies: QLT Phototherapeutics of Vancouver, British Columbia, with the backing of CIBA Vision; and Miravant, with the backing of Upjohn. PDT as performed
in the clinical trial reported on below employs the photoreactivity of a molecule of the porphyrin type, called verteporphin or Visudyne, a product developed by QLT Phototherapeutics
initially for use in PDT to treat skin cancer. The red color of blood is caused by the iron-containing porphyrin called heme. The green color of leaves is caused by the
magnesium-containing porphyrin called chlorophyll. Verteporphin is a man-made derivative of a natural porphyrin. The laser light used to make Visudyne photoreactive is of far lower
intensity than that used in laser photocoagulation, so the laser used in PDT does not severely damage the overlying retinal tissue. Because of this, PDT can be performed on leaky
subfoveal or juxtafoveal neovascularizations. Preliminary Studies In phase I/II studies on humans, designed to gauge safety, and
the range of parameters for effectiveness, it was found that PDT with verteporphin could temporarily stop leakage from subfoveal neovascularizations, the benefit typically lasting
about a month. Leakage resumed in almost all cases by 3 months. This led to the use of multiple treatments in the clinical trial. Multi-Site Clinical Trial The multi-site clinical trial was begun in December, 1996. Twenty-two clinical sites, in Germany, United Kingdom, Switzerland and the U.S.A.,
have been involved. Patients were selected who had subfoveal choroidal neovascularization lesions caused by ARMD and measuring no more than 5.4 mm, with symptoms of classic wet ARMD ,
i.e. relatively heavy leakage rates as visualized by angiography, and best-corrected visual acuity of 20/40 - 20/200. Of the 609 patients in the study, 402 eyes received verteporphin
PDT and 207 eyes received the placebo (glucose injection plus laser). Results At 12 months, 67% of the group treated with verteporphin PDT had lost fewer than 3 lines of visual acuity as judged with an eye
chart, compared to 43% of the group treated with the placebo. Other more objective measures of the effectiveness of verteporphin PDT include: * 18.8% experiencing no
leakage after 1 year of verteporphin PDT, compared to 9.1% of placebo treated group. * Distribution of lesion sizes shifted to smaller sizes in the group treated with
verteporphin PDT, compared to the placebo treated group. Verteporphin PDT did not appear to have a significant beneficial effect on occult neovascularizations, with progression of
occult choroidal neovascularizations in 72% of verteporphin treated occult cases, and in 80% of placebo treated occult cases. Conclusion Verteporphin PDT appears to be an effective
treatment for classically leaky subfoveal neovascularizations in age related macular degeneration. Leakage is stopped or reduced; lesion size increases less rapidly; and progression
of classic CNV is slowed. However, if follow-up angiographies at three-month intervals indicate leakage has resumed, the treatment needs to be repeated. REFERENCE: Neil Bressler, et. al, Photodynamic Therapy
of Subfoveal Choroidal Neovascularizations in Age-related Macular Degeneration with Verteporfin. One-Year Results of 2 Randomized Clinical Trials - TAP Report 1. Archives of
Ophthalmology (1999), 117:1329-1345. October 28, 1999 |
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