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Photodynamic Therapy with Verteporfin in Age-related Macular Degeneration

US Sensory Disorders Review, 2006:7-12 DOI:
Received: January 10, 2011 Accepted: January 10, 2011

AMD is generally categorized as nonneovascular (dry) or neovascular (wet). Clinical findings of non-neovascular AMD include drusen, pigmentary changes, and atrophy of the retinal pigment epithelium with resultant gradual visual decline. Neovascular AMD occurs when choroidal neovascularization (CNV) penetrates through compromised areas of Bruch’s membrane and into the potential space between the retina and retinal pigment epithelium. Neovascularization can present with subretinal and intra-retinal edema, exudation, hemorrhage, and eventually a fibrovascular scar resulting in profound loss of central visual acuity. The vast majority of AMD related visual loss is caused by the neovascular form.2 With the aging US population, clinicians can expect to see an exponential increase in neovascular AMD over the next twenty years; in fact, it is estimated that one million individuals will develop neovascular AMD in the next five years in the US alone.3

Prior to 2000, patients with neovascular AMD had limited treatment options for subfoveal CNV. The Macular Photocoagulation Study (MPS) Group had proposed thermal laser for the treatment of subfoveal lesions.4 Although thermal laser was shown to reduce the risk of severe vision loss (≥6 lines from baseline), damage to central vision from the treatment itself was immediate, permanent, and difficult for patients to comprehend.This led to a search for alternative treatments such as photodynamic therapy (PDT), submacular surgery, and anti-angiogenesis drugs. PDT with verteporfin was the first of these new modalities to be shown to be effective in randomized controlled clinical trials and was approved by the US Food and Drug Administration (FDA) in 2000.

Verteporfin is a benzoporphyrin derivative that is administered via intravenous infusion over a ten-minute period at a concentration of 6mg/m2 of body surface area.Verteporfin is rapidly distributed throughout the body, bound to low-density lipoproteins (LDLs). Since neovascular tissue is rich in LDL receptors, verteporfin- LDL complexes preferentially accumulate in choroidal neovascular membranes.5,6 Fifteen minutes after administration, verteporfin is then activated in vivo with the application of 689nm non-thermal laser at an intensity of 600mW/cm2 for 83 seconds directly over the choroidal neovascular complex.Activation results in the formation of cytotoxic, free radicals that cause selective vasoconstriction, platelet aggregation, and fibrin clot formation in choroidal neovascular tissue resulting in vessel closure.5,6

The clinical efficacy of PDT with verteporfin for AMD has been evaluated in four large, randomized, double-blind, placebo-controlled studies. The treatment of AMD with photodynamic therapy (TAP) study showed a significant reduction in the risk of vision loss with PDT with verteporfin in patients with classic or classic plus occult subfoveal CNV. After 24 months, 53% of PDT recipients achieved the primary endpoint (<15 letters vision loss) versus 38% of those receiving placebo (p<0.001).

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