PDT with verteporfin: impact on clinical practice

As treatments for AMD and CNV improve, more training is needed.

Issue: July 1, 2001

ByPaolo Lanzetta, MD

Recently, the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group reported that photodynamic therapy (PDT) with verteporfin can reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) during age-related macular degeneration (AMD).

AMD is the leading cause of severe vision loss in people older than 65 years of age. The prevalence of the disease ranges from 1.6% in subjects between 52 and 64 years of age to 27.9% in patients older than 75 years of age. Although neovascular or wet AMD, characterized by CNV, is present in 20% of cases, it causes approximately 90% of all cases of severe vision loss due to AMD. It is estimated that almost 500,000 new cases of neovascular AMD occur each year in the world. This figure is expected to grow dramatically as the population ages. It is also estimated that by 2020 in the United States as many as 7.5 million people older than 65 years of age may have AMD-related vision loss.

CNV treatment

Until recently, treatment of CNV secondary to AMD has been limited to laser photocoagulation. However, photocoagulation is indicated in only a selected number of cases because it damages the overlying neural retina and results in immediate vision loss when the CNV is subfoveal. There is also a high recurrence rate after laser photocoagulation. Therefore, AMD is a progressive illness with a considerable prevalence and limited possibilities of treatment, and is frequently associated with severe visual impairment. Its impact on the quality of life of the individuals it afflicts is substantial. Studies have shown that patients with AMD were willing to trade 30% of their remaining years of life to obtain 6/6 vision in their better-seeing eye. Those with legal blindness had a reduction in quality of life of 60%.

Verteporfin approvals

Visudyne (verteporfin for injection, Novartis Ophthalmics) is already approved in more than 30 countries for treating AMD. The U.S. Food and Drug Administration (FDA) has recently issued an approvable letter for expanded uses of verteporfin in eye care treatment. The additional indications include pathologic myopia (PM) and ocular histoplasmosis syndrome. The European Medicines Evaluation Agency has recently approved a granting of a Marketing Authorization for verteporfin therapy for CNV in patients with PM. The worldwide incidence of CNV due to PM is estimated to be 50,000 new cases per year, excluding Asia where the incidence is even greater due to the higher prevalence of PM. In Italy the Medicines Evaluation Agency pre-registered verteporfin for the treatment of predominantly classic subfoveal CNV secondary to AMD and subfoveal CNV due to PM, and the regulatory approval has been recently issued.

The TAP Study Group showed that the visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years. In the study, 59% of verteporfin-treated patients versus 31% of placebo-treated patients lost fewer than three lines (P <.001). For subfoveal lesions with some evidence of classic CNV, 53% of verteporfin-treated patients versus 38% of placebo-patients lost fewer than three lines (P <.001).

VIP study group

Data at 24 months show that verteporfin might also benefit AMD patients with occult CNV. The Verteporfin in Photodynamic therapy (VIP) Study Group evaluates patients with less-advanced CNV secondary to AMD than those in the TAP study and in those with subfoveal CNV secondary to PM.

At 24 months in the entire population of AMD patients, mainly patients with occult CNV without classic components plus some patients with a component of classic CNV, a difference of 13% (verteporfin 46% versus placebo 33%) was found between the treatment and the placebo groups with respect to the avoidance of moderate vision loss (P = .023). Further, a 17% difference (verteporfin 70% versus placebo 53%) between treatment groups was found with respect to the avoidance of severe vision loss (P = .001).

In those patients with occult CNV without classic component, who comprised about 75% of patients enrolled in the study, at 24 months a difference of 14% (verteporfin 45% versus placebo 31%) was found with respect to the avoidance of moderate vision loss (P = .032) and a difference of 18% (verte porfin 71% versus placebo 53%) with respect to the avoidance of severe vision loss (P = .004).

Subgroup analyses suggest that a greater benefit of verteporfin therapy is obtained after 24 months in patients presenting with relatively small lesions (< 4 DA) or lower levels of visual acuity (< 20/40). The VIP Study Group also evaluates patients affected with CNV due to PM. In the primary analysis at 12 months, it was found that patients showed a definite benefit from verteporfin therapy. Among the verteporfin-treated patients, 86% lost less than three lines of vision versus 67% of patients receiving placebo (P = .011). The percentage difference dropped during the second year from 20% to 7% in favor of verteporfin (P = .381).

Increased CNV treatments

It is estimated that about 40,000 treatments with verteporfin have been performed so far and the number of patients treated is expected to increase 24% over the first quarter of 2001. Margherio et al in 1999 estimated that for every 1,000 patients with AMD, over 600 verteporfin treatments would be required, an increase of almost sevenfold over laser photocoagulation. There would also be at least a threefold increase in the number of office visits, fluorescein angiograms and grading of fluorescein angiograms.

This increase in treatments for CNV could have a considerable impact on retinal practices. The resources that will be expended are high and it has been suggested that the potential benefit of verteporfin therapy in reducing vision loss will outweigh the costs. In the TAP study, after 2 years of follow-up, PDT with verteporfin in patients with exclusively classic subfoveal CNV was associated with a reduction in relative risk of 68%, a reduction in absolute risk of 50%, and the numbers needed to treat was two.

Training needed

At the beginning of 2001, on a global basis, approximately 1,300 laser systems for use with verteporfin were in place and roughly 2,000 eye care professionals had received training in the use of verteporfin for AMD. Training should be one of the major objectives when a new and effective treatment strategy is developed and popularized. Eye care professionals should be instructed on the importance of a timely diagnosis of CNV, the grading of type and dimensions of the neovascular lesions on fluorescein and indocyanine green angiograms and on how to properly perform PDT with verteporfin.

In the last decades clinical research and research funding have been devoted largely to defining the role of laser photocoagulation in the treatment of CNV. PDT has opened a new era with a dramatic impact on ophthalmology and the visual sciences. Further improvements and refinements in PDT will be made possible by future studies exploring different treatment regimens, other photosensitizers and the combination with other treatments such as anti-angiogenic therapy or transpupillary therapy.

For Your Information:

Paolo Lanzetta, MD, can be reached at Department of Ophthalmology, University of Udine, 33100 Udine, Italy; (39) 0432-239-268; fax: (39) 0432-239-313; e-mail: paolo.lanzetta@dsc.uniud.it. Dr. Lanzetta has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Novartis Ophthalmics, distributor of Visudyne, can be reached at 11460 Johns Creek Pkwy, Duluth, GA 30097; (800) 533-1676; fax: (678) 415-2378. Visudyne is a trademark of Novartis AG.

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