by Dan Roberts
Update September 2005: QLT's preliminary results found that Visudyne in an occult trial did not achieve its primary endpoint after two years.
Photodynamic therapy has been shown to be effective in helping to prevent further loss of sight in people who are afflicted by the classic form of exudative (wet) macular degeneration. Neil M. Bressler, M.D., associate professor of ophthalmology at Johns Hopkins, chaired the multicenter trial, and the chemical Visudyne, used in the therapy, has been approved for use in the United States (see the related press release in the MD Support Library), Canada, Europe, and Japan.
Current laser therapy uses a "hot" laser to coagulate leaking blood vessels, while destroying surrounding healthy tissue. Photodynamic therapy does not use heat, so no damage results, and the procedure can be repeated as many times as necessary on an out-patient basis.
First, a drug called BPD-MA (also known as both verteporfrin and Visudyne) is injected into a vein. The drug is then picked up by lipoproteins in the blood, which are taken up specifically by the abnormal blood vessels in the retina.
Second, a beam of red laser light is aimed into the eye. This cool beam activates the drug, which produces a toxic form of oxygen, causing the leaking to stop.
Photodynamic therapy is not a cure, but it is proving to be an effective and safe treatment for exudative MD. Based upon the study by QLT PhotoTherapeutics Inc. (QLT) and CIBA Vision Corporation (the eye care unit of Novartis AG), patients treated with Visudyne therapy were more likely to have stable vision (defined as a loss of less than 3 lines of vision on a standard eye chart) or improved vision compared to placebo-treated patients.
The wholesale cost of the drug is $1,535.00, and the treatment kit is $30.94. Every doctor sets his own price to perform this surgery, but the average cost of each treatment is around $3,000. The recent data compiled from the clinical trials shows that the average patient needs 5 1/2 treatments over a two-year period. Medicare will cover the cost of the drug only, with the remainder to paid by the patient and his/her insurance company, if applicable.
On February 7, 2001 Novartis Ophthalmics announced top-line results that showed Visudyne therapy reduces the risk of vision loss in patients with occult patterns (i.e. leakage beneath the fovea) of wet age-related macular degeneration (AMD). The results were from a multi-center phase IIIb randomized placebo-controlled study called the VIP (Verteporfin In Photodynamic therapy) trial. The results also confirmed the benefits of Visudyne therapy in the treatment of choroidal neovascularization due to pathologic myopia, and regulatory approval is still pending in North America.
In August 2002 Visudyne therapy was granted marketing authorization from the European Commission (EMEA) for the treatment of occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). This includes all patients with subfoveal occult wet AMD with evidence of recent or ongoing disease progression.
In September 2005 QLT's preliminary results found that Visudyne in an occult trial did not achieve its primary endpoint after two years. According to the copmpany, Visudyne in occult trial was part of a broader series of trials and QLT was conducting more analyses on relevant subgroups.
According to CIBA, some patients have shown the following side effects from the use of Visudyne:
In addition to the above, one early report also warned that activation of the drug Visudyne results in the formation of singlet oxygen and free radicals that can lead to vascular endothelial cellular damage, platelet aggregation, thrombosis, and occlusion of CNV within the treatment area. (Schmidt-Erfurth U, Hasan T, Gragoudas E, et al. "Vascular targeting in photodynamic occlusion of subretinal vessels." Ophthalmology. 1994;101:1953-1961.
The doctor who administers PDT is most likely a vitreoretinal surgeon. Dr. Peter Sonkin offers this advice:
"While general ophthalmologists may offer PDT treatment for wet AMD, there are very very few doing so, and for a good reason. The technical aspects of the treatment are not the issue. The most critical component is proper patient selection and appropriate expectations for both the physician and patient. This requires extensive experience with interpreting fluorescein angiograms and correlation to the clinical examination. Many within ophthalmology feel this is only possible if the physician is fellowship trained in vitreoretinal surgery. This is not to say that there are not perfectly qualified general ophthalmologists, just make sure that the doctor is trained in the procedure and interpreting angiograms."
Following is a quote from the article, "Prepare To Activate Visudyne," written by Chet Scerra and published in the 6/1/2000 issue of Ophthalmology Times.
"It's important to have a person such as a phlebotomist or nurse sit with the patient during the whole infusion," suggested Patricia Nesbitt, research nurse and Visudyne program coordinator at the Wilmer Eye Institute, Baltimore.
"The procedure is very time consuming, so someone should sit with the patient, not only to give encouragement but to keep a close eye to make sure that the drug doesn't extravasate (go under the skin instead of the vein)," she continued. "This can cause a very bad burn.
"It's not always easy to tell when the drug is leaking from the vein," Nesbitt said. "Unlike fluorescein, which stings when it leaks outside of a vein, Visudyne does not sting, so the patient doesn't feel it. As a result, a small amount can accumulate under the skin before being discovered.
"Sometimes extravasation will cause the pump to stop," she continued, "and sometimes you'll see nothing more than a very subtle swelling around the site of the infusion. Additionally, since Visudyne is very dark, you may also see some discoloration in the area of injection.
"I treat all infusions as though they've extravasated, in terms of light protection. You can have a very small extravasation that neither you nor the patient can detect that potentially can result in a very severe burn," Nesbitt continued. "This is another reason to use a vein up in the antecubital area, rather than the hand, so that a shirt can better protect the site from the light.
"If a patient has very poor venous access, it should be a consideration when determining if this is an appropriate treatment option," Nesbitt added. "If a vein in the hand is used, be sure to wrap the hand well to protect it from light. The patient might want to wear a glove for 3 to 5 days subsequent to the procedure to protect the site from the light.
"I use a large darkroom clock," she continued. "I set it to 15 minutes so it's easy for the doctors to see when the laser application must begin. During this 15-minute period, someone is sitting there watching for extravasation. The infusion lasts 10 minutes so you have a 5-minute window in which you flush the line, take the IV out, bandage the patient, put a numbing drop in the eye, and turn the patient around to face the laser.
"It all has to be done in the same location, because there really isn't much time to move the patient around," she said.
FDA information states, "If extravasation does occur, infusion should be stopped immediately and cold compresses applied."
This article in its entirety may be downloaded as a PDF file from www.fda.gov/cder/foi/label/2000/21119lbl.pdf.
For further information about photodynamic therapy, see the MD Support Glossary, or read Photodynamic Therapy - Visudyne Approved in the MD Support Library.
To read personal experiences about PDT, visit the Treatment Archives.
More information may be obtained by calling 1-800-821-2450 or going to the Visudyne Web Site on the Internet.