As you know, age-related macular degeneration (AMD) is the leading cause of severe vision loss in people over age 50. Up to 200,000 new cases of the neovascular, or "wet" type of AMD are diagnosed each year in the United States. Although the number of "dry" AMD cases diagnosed is much greater, wet AMD causes 90% of the severe vision loss resulting from the disease.

Unfortunately, options for treating wet AMD have been limited. Now, however, clinical studies have shown that a new treatment marketed by CIBA Vision -- a form of photodynamic therapy known as Visudyne (verteporfin) therapy -- offers hope to these patients. (For more details, see "Findings from the Treatment of AMD with Photodynamic Therapy [TAP] Study Group" on page 44.)

The drug Visudyne and the lasers (by Zeiss Humphrey and Coherent) used to activate the drug in retinal vessels received an approval letter from the FDA on Feb. 11, laying the groundwork for final approval within the next few months. This article, reflecting insights from leading retinal specialists who advanced Visudyne therapy through FDA trials, offers advice on how incorporate this procedure into your practice routine.

When a patient is eligible for this treatment, Visudyne, a light-activated drug, is administered intravenously. The drug is absorbed by the damaged blood vessels. Exactly 15 minutes after the infusion begins, the affected area on the retina is exposed to a nonthermal laser light that activates the drug. This chemically alters the drug into a complex that stops leakage from choroidal neovascularization (CNV) -- without damaging the patient's retina.

Most patients need to be re-treated at 3-month intervals during the first year -- each time after a diagnostic workup that includes fluorescein angiography. The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Investigation (TAP) showed that 91% of patients treated with Visudyne required re-treatment after 3 months, 79% after 6 months, 70% after 9 months, and 64% after 12 months. Two-year results from TAP are expected later this year.

Studies have shown that, although Visudyne therapy improves vision in a few cases, its main benefit is in arresting the progression of this sight-threatening condition.

Because of the light sensitivity caused by Visudyne, patients must take precautions for several days after treatment to avoid devastating eye or skin damage from bright light or sun exposure. They have to avoid sunlight, halogen lighting, tanning salons, and the kind of lighting used in operating rooms or dental offices, and they must wear special dark sunglasses and long-sleeved shirts. Wristbands are also provided to alert emergency personnel of the precautions.

If you want to offer hope to your AMD patients with Visudyne therapy, careful planning is essential to ensure that you maximize the benefits for your patients and your practice. Ultimately, the specific procedures you implement to support this new therapy will depend on the characteristics of your practice and your personal preferences. (Keep in mind that the recommendations in this article are general recommendations intended to help you establish a starting point.)

Remember that patients treated with Visudyne therapy will need to be re-evaluated -- and probably re-treated -- at 3-month intervals. So, as you treat patients with Visudyne therapy, patient flow in your practice will increase.

If your practice is small, and you begin by treating only a few patients at a time, the impact on your patient flow may not be as significant. But if you have a larger practice and many patients with wet AMD, you may eventually need to hire additional staff, purchase an additional laser or camera, or even expand your hours. If you choose not to perform Visudyne therapy, you should identify other physicians to whom you'd feel comfortable referring patients.

There are a number of aspects of your practice that may be affected by the addition of Visudyne treatment:

• Imaging equipment.
Fluorescein angiography is important for determining which candidates are suitable for Visudyne therapy and whether retreatment is necessary. The fluorescein angiogram is also used to determine the size of the lesion on the retina, and to calculate the appropriate laser beam size required for treatment.
Although conventional film angiography was used in the clinical trials, digital angiography may be used for these patients. Whether you opt for digital or film, be sure your system will fit your future needs as you treat and re-treat AMD patients.
• Laser.
Two lasers have been manufactured for Visudyne therapy -- one marketed by Zeiss and the other by Coherent. If you have more than one office, you'll have to decide whether to lease or purchase more than one laser or to perform all Visudyne treatments at one office only.
• Infusion equipment.
To perform Visudyne therapy, you'll need a syringe pump or an infusion pump to administer the timed infusion of the drug.
Either pump can be used for the procedure, but you'll pay more for an infusion pump. A syringe pump costs about $600; an infusion pump costs $2,000 to $5,000.
You can obtain infusion materials from a number of suppliers. For your convenience, CIBA will offer infusion kits containing all of the components you need for Visudyne infusion for $24.75.
• Space options.
There are a number of ways to fit Visudyne therapy into your physical space:
• Use one space for multiple purposes.
In small practices, you can designate the laser room or an exam room for Visudyne therapy during specific time periods.
• Use a designated room.
If you have space, set aside a room exclusively for Visudyne administration and laser treatment. To make the process easier, you can administer the drug with the patient in front of your slit lamp.
• Use two designated rooms.
As your patient volume increases, you may choose to designate two rooms for Visudyne therapy, so that more than one patient at a time can be treated. If you take this approach, you must be careful not to rush the procedure, which could have serious consequences.
• Safeguard against contamination.
You'll need to maintain sterile technique and prevent air from getting into the infusion. You'll also need to make sure that the drug doesn't stray from the bloodstream, causing extravasation. (The infusion must be stopped if the patient experiences discomfort or if extravasation occurs.)
Although some physicians plan to equip one room for infusion and move the patient to another for laser treatment, this approach isn't recommended. After infusion, you have only 5 minutes to disconnect the IV, walk the patient to another room and set up the patient in front of the laser. If you try to move an elderly patient quickly, he or she will probably end up feeling rushed and uncomfortable. If you don't administer the laser treatment exactly 15 minutes after infusion has begun, you will have wasted an expensive dose of Visudyne.
• Perform the procedure at multiple sites.
In the beginning, even if you have more than one office, you'll probably want to offer Visudyne therapy at only one site. Later, if you choose to offer Visudyne therapy at multiple sites, your nurse can move from site to site for treatment days.
• Drug storage.
Visudyne is stored at room temperature. The amount you keep on hand will depend on how many patients you treat. However, given the expense of the drug (about $1,200 for one treatment), you'll probably want to store it in a locked cabinet.

Although you may eventually require extra staff, when you begin offering Visudyne therapy, you can simply reassign staff from other duties. However, you'll need a registered nurse if you plan to delegate drug mixing or administration.

If you have a small practice, you may be reluctant to hire a nurse. Without a nurse, however, you'll need to mix and administer the drug yourself, which will take you away from other responsibilities. For that reason, you may want to consider hiring a part-time nurse or arrange to share one with another practice. (When hiring nurses, make sure to consider infusion experience; extravasation can be painful.)

If you're in a large practice, consider hiring a coordinator to guide each patient through a required exam before the procedure and, then, through procedure itself. The coordinator can also schedule appointments and answer questions if patients phone after the treatment.

Because an IV drug is being administered, each facility should have an emergency care plan in place.

Once you and your nurse or coordinator are comfortable with the procedure, you can train the rest of your staff. A CIBA Vision training video is available for this purpose. CIBA Vision will also offer training courses throughout this year.

Effective scheduling is a key to success with this novel therapy. Considering the steps involved in administering Visudyne therapy (see box), you may need to allow 3 to 5 hours for a patient to be examined, diagnosed and treated during a single visit. (Follow-up appointments should be shorter, because your patient will be familiar with the process.) When scheduling patients for treatment, you need a time slot that's no shorter than 30 minutes. You may prefer to schedule longer appointments, especially when first offering the treatment.

If the patient is returning for treatment within a week -- rather than being treated on the exam day -- make sure your staff still weighs and measures the patient so that the Visudyne dose can be calculated before the patient returns for treatment, which will expedite therapy. (Remember to wait for the patient's arrival before mixing the actual dose, however, so you don't waste any of this expensive drug.)

How you schedule your patients will be determined by a number of factors, including the availability of nursing staff, your office space and the number of patients you treat each week. There are several scheduling options:

• Same-day treatment.
If your patients have transportation concerns or must travel a long distance, you may want to perform the diagnostic assessment and treatment on the same day. However, some patients may arrive without appropriate protective attire. They may also want more time to weigh the pros and cons of treatment.
To make this situation easier, your staff should ask any patients who might be treated to bring sun protection attire to their appointments. Your staff can also mail these patients educational brochures and informed consent forms so that patients can consider the procedure before coming to your office and signing the consent form. Even when you take these steps, however, patients still may need to wait for a treatment slot.
• Treating within your office's normal schedule.
When you begin offering Visudyne therapy, you'll want to work treatments into your regular schedule, especially if you have only a few treatments each week. However, this may be less efficient if you don't have a designated space, because you'll need additional time to repeatedly set up and take down equipment.
• Block scheduling.
Time slots may be blocked for one doctor or for the nurse, with multiple physicians alternating treatment during the nurse's scheduled time. The latter approach ensures that your nurse will have adequate time to assist you. Scheduling in blocks boosts efficiency because equipment is set up once for a number of patients.
While waiting your turn in time blocks schedules, you can also schedule simultaneous short appointments, after you've become comfortable with the procedure. For example, you can evaluate a follow-up patient while your nurse administers an infusion to another patient. For this approach, the nurse should ask you when he or she can begin the infusion and then give you a 5-minute warning when the infusion is complete.

Communication is critical before and during Visudyne therapy, because your patients will rely on you to help them make good decisions. There are three crucial points to convey:

• Patients must understand the precautions they need to take after treatment to avoid devastating eye or skin damage from bright light or sun exposure.
• They must understand what the procedure can and can't do. They need to realize that the treatment is designed to stabilize or slow vision loss -- not correct it. Although vision may improve in a very small number of cases, it's important that your patients don't count on that.
• Patients need to realize that Visudyne therapy is a long-term maintenance program. In most cases, the vessels need to be re-treated at 3-month intervals. If you take the time to explain this to your patients now, they'll understand that your primary goal is to halt their vision loss, not to simply increase your revenue with re-treatments.

Although you are the patient's primary educator, your staff needs to reinforce what you say to the patient. In particular, after you explain the treatment to your patient, your nurse or technician should cover the informed consent point by point.

Besides the written consent form, you may want to prepare a large-print information sheet detailing what happens on the day of treatment, the day after treatment and at the
3-month follow-up, as well as other instructions and precautions. CIBA has produced a brochure about post-treatment precautions that you'll find helpful for educating patients.

After treatment, take a few minutes to discuss what was done and any necessary precautions the patient must take. A nurse or technician can reinforce the need for these precautions and give the patient dark glasses and written instructions.

Patients should schedule follow-up appointments after treatment and before they leave the office. (Be sure your staff reminds the patient to wear sun-protective attire when coming in for follow-up visits.)

It's also a good idea to have a staff member call your patient 48 to 72 hours after the procedure to check on his status and to answer any questions. (You can also schedule patients for follow-up visits at this time, if you haven't already.) If the patient has a concern, ask him to return for an examination.

It's important not to rush Visudyne treatments. Nevertheless, you'll want to take steps to make sure the procedure is incorporated into your practice as efficiently as possible. Here are some strategies that will help:

• If Visudyne therapy is scheduled in time blocks, it may be possible to mix several vials of the drug in one sitting -- provided that the patients' weights and heights were obtained during the previous visit. However, the drug can be mixed only 4 hours before infusion, and it must be stored in low light conditions.
• A word of caution: If you pre-mix, your staff must be absolutely sure to label each syringe with the patient's name to prevent administration of the wrong dose. You also may want to wait until the patient has signed the informed consent form and arrives for the appointment to begin mixing, to avoid wasting the drug.
• Cluster patients together for as many steps in the sequence as possible, such as follow-up calls and follow-up appointments. Staff members also can group patients two at a time for information sessions. These patients often benefit from sharing experiences while waiting together.
• Nurses can set up and take down the equipment, mix and administer the drug, complete paperwork and counsel patients. A coordinator or another assigned staff member can oversee the process, guiding the patient through each step and handling patient education.
• To shorten preparation times, consider purchasing infusion kits from CIBA Vision or having your staff pack supplies in kits that are ready to go when you need them.
• From the time infusion begins, you can schedule small tasks during the infusion, such as completing charts, making phone calls, dictating notes or performing a short exam. However, your staff must keep a close watch on the time, informing you immediately when the infusion begins and when it's complete.
  (You may not want to adopt this approach until you're experienced with the procedure.)

To grow your practice with Visudyne therapy, you'll need to increase patient awareness of AMD and identify patients who may benefit from this procedure. Naturally, you'll want to address the needs and desires of your current patient base first.

One worthwhile option is mailing informational letters to your AMD patients, explaining that you offer this treatment and explaining specifically what it can and can't do.

You can also opt for indirect marketing, offering educational seminars on general eye health and the need for regular examinations. During these seminars, you can explain what macular degeneration is, the symptoms, the importance of early treatment and the need for everyone over 60 to see a physician for annual eye exams. You can also remind those diagnosed with dry macular degeneration to see their ophthalmologist more often and consult with a retina specialist at the earliest signs of wet macular degeneration.

As we move into the 21st century, it's exciting to realize how far our ability to treat vision problems has come -- and how far it may go in the years ahead.

This is only one of the first steps on that journey. But it's an exciting step, and it heralds a bright future for your patients -- and for you.

CIBA's new treatment is one of the first of a series of anticipated breakthroughs for treating AMD. Some of those waiting in the wings:

• Targeting individual blood vessels.
As you know, part of the problem in treating AMD has been the difficulty of isolating and treating microscopic individual feeder blood vessels. Now the Glaser Murphy Retina Treatment Center in Chevy Chase, Md., has announced a new technique for treating wet AMD that uses a process known as Phi-motion Angiography. A high-speed scanning laser is used to acquire rapid sequence images, which are capable of illustrating individual blood vessels underlying the retina. Doctors can then use microlasers to seal individual leaking feeder vessels as small as 50 microns.
According to a spokesperson for the Glaser Center, CIBA's new Visudyne treatment is primarily directed at a specific type of blood vessels (classic vessels) that predominate in about 13% of patients with AMD. Phi-motion Angiography may make it possible to treat many of the 87% of patients who have occult vessels, the other type of abnormal blood vessel.
The Center reports that more than 300 patients have already been treated, and many have experienced markedly improved vision.
• Treatment for dry AMD.
Iridex Corporation has reported positive results treating both types of AMD using Iridex's Iris Medical OcuLight Slx 810 laser (currently awaiting FDA approval) to perform transpupillary thermotherapy (TTT). In this procedure, the laser delivers heat to the back of the eye, creating localized hyperthermia that closes the choroidal vessels.
Joseph Olk, M.D., director of the Retina Center of St. Louis, Mo., did a pilot study of 229 eyes with dry AMD. One group was treated with the OcuLight laser; the other group was simply observed. Two-year results showed drusen resulting from early dry AMD were reduced or eliminated in 68% of the treated eyes, vs. 3% of the observed eyes. Visual acuity improved in most treated patients.
Studies using this procedure to treat wet AMD have also shown promising results. A retrospective study of 16 eyes with subfoveal occult wet AMD at the New England Eye Center in Boston, Mass., found that TTT improved vision by two or more Snellen lines in 19% of treated eyes, and stabilized vision in 56%. Fifteen eyes (94%) showed a reduction in subretinal fluid.
Similarly, researchers at Kings College in London, England, used TTT to treat 42 eyes with occult and classic subfoveal choroidal neovascularization (CNV). The 22 eyes with occult CNV showed the best results. CNV resolved in 16 eyes (71%), persisted in five eyes (23%) and recurred in one eye (5%). Visual acuity stabilized at two lines in 19 eyes (86%) and showed a mild loss (2.5 lines) in three eyes. No eyes suffered a severe loss of acuity.
• Other photodynamic therapy options.
Miravant Medical Technologies, working with Pharmacia and Upjohn, has developed the PhotoPoint system, currently in Phase III clinical trials for treatment of wet AMD.
This system, like the Visudyne system, uses a non-thermal laser to activate an injected drug. While it's too early to report any conclusive data from the clinical trials, a spokesperson for Miravant said that early results have been very promising.
The PhotoPoint system is also intended to be useful for treating other types of diseased tissue, such as cancer.

Two multi-center clinical trials studied Visudyne therapy in 609 patients with subfoveal choroidal neovascularization (CNV) caused by AMD. These patients had classic CNV and best-corrected visual acuities ranging from 20/40 to 20/200.

Researchers determined that for patients treated with Visudyne therapy, visual acuity and contrast sensitivity were better than in those treated with placebo, at 12 months. The greatest treatment benefit was found for patients with predominantly classic CNV. At 1 year, 67% of eyes lost less than three lines of vision (i.e., they were stable), vs. 39% of eyes receiving placebo. On average, eyes that were treated lost two lines of vision, compared with four lines in those patients receiving placebo. However, the TAP study group found that not all eyes treated with Visudyne lost vision; 8% gained one to three lines, and 5% gained three lines at 1 year.

Reported adverse events associated with the treatment have included:

• effects occurring at the injection site, including pain, edema, hemorrhage, inflammation, and others, as well as allergic reactions
• back pain
• transient visual disturbances
• photosensitivity.

Also, remember that extravasation is an avoidable complication that may occur during treatment; it requires follow-up care. Perform laser treatment exactly 15 minutes after the start of the Visudyne infusion. (Laser treatment lasts 83 seconds.)