THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH PHOTODYNAMIC THERAPY (TAP) STUDY

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. The severe visual loss that is seen in this disease process is largely secondary to the ingrowth of new vessels from the choriocapillaris. These new vessels are accompanied by eventual cicatricial changes that can destroy central vision over a period of months to years. Conventional thermal laser photocoagulation is a viable treatment option for very few of these patients. In the setting of subfoveal choroidal neovascularization (CNV), such treatment is accompanied by an immediate and significant loss of central vision. While this loss of vision is more likely to remain stable and unchanging over time, as compared to the natural course of the disease, such treatment has never gained widespread acceptance despite the clear recommendations of the Macular Photocoagulation Study (MPS).

The goal of photodynamic therapy is to selectively destroy the abnormal subretinal vessels while limiting the destruction to the overlying retina. It involves giving the patient an intravenous injection of verteporfin, a photosensitizer or light-activated drug. After infusion, the photosensitizer is activated by the light of a lowenergy laser source at a wavelength that corresponds

to the absorption peak of the drug. The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) investigation was initiated in North America and Europe to determine whether verteporfin therapy could reduce the risk of visual loss compared with placebo in people with subfoveal CNV caused by AMD.

Study Design/Treatment Groups

Eligible patients had subfoveal CNV lesions secondary to AMD 5400 µm in size with some evidence of classic CNV, and a best corrected visual acuity of approximately 20/40 to 20/200.

A total of 609 patients were randomized (2:1) to intravenous infusion of verteporfin or placebo. Fifteen minutes following the infusion, all patients were subjected to laser light at 689 nm delivered over 83 seconds, using a spot size with a diameter 1000 µm larger than the greatest linear dimension of the CNV lesions. Subjects were followed up at 3 monthly intervals and retreatment was given with the same treatment regimen if the fluorescein angiogram demonstrated fluorescein leakage.

The primary outcome measure was the proportion of eyes with a loss of fewer than 15 letters (approximately3 lines of visual acuity) compared with the baseline examination at 1 year after study entry. Secondary out-

come measures included the proportion of eyes that lost fewer than 30 letters (approximately 6 lines of visual acuity) compared with the baseline examination, mean changes in visual acuity, mean changes in contrast threshold, and angiographic outcomes.

Summary of Results and Implications for Clinical Practice

There were 351 (87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207 patients in the placebo group who completed the examination at month 24. Visual acuity and contrast sensitivity outcomes were better in the verteporfin-treated eyes than in the placebotreated eyes at every follow-up examination through the 24-month examination. These visual results were supported by the findings on fluorescein angiography, namely, that verteporfin reduced lesion growth, was associated with cessation of leakage from classic CNV, and decreased the progression of classic CNV.

At the 12-month examination, 246 (61%) of 402 eyes assigned to verteporfin compared to 96 (46%) of 207 eyes assigned the placebo had lost fewer than

15 letters of visual acuity from baseline. At the 24-month examination, 213 (53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207 placebo-treated patients lost fewer than 15 letters. Verteporfin-treated patients received an average of 5.6 treatments over the 24 months of their involvement in the study.

Subgroup analysis suggested that the visual acuity benefit of verteporfin therapy was present in only those eyes that demonstrated an area of classic CNV occupying 50% or more of the area of the entire lesion (predominantly classic CNV lesions). Among this group, 94 (59%) of 159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated patients lost fewer

than 15 letters at the 24-month examination. This finding was especially true when the lesions treated were entirely classic CNV lesions. In this group, 65 (70%) of 93 verteporfin-treated patients lost fewer than 15 letters compared with 14 (29%) of 49 placebo-treated patients at the 24-month examination. No statistically significant differences in visual acuity were noted when the area of classic CNV was less than 50% of the area of the entire lesion. Very few ocular or other systemic adverse events were associated with verteporfin infusion.

The benefits of verteporfin therapy for AMD patients with predominantly classic subfoveal CNV are clear, compelling, and safely sustained for 2 years. The TAP study group recommends treatment with verteporfin in this patient population.

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