by What is it?
Verteporfin (trade name Visudyne) is a light activated drug used in photodynamic therapy (PDT) to treat wet age-related macular degeneration (AMD). It was the first drug approved by the FDA in 2000 for the treatment of this leading cause of vision loss.
How Does it Work?
Verteporfin is a light sensitive drug that is activated by low energy red light delivered by a laser. It consists of a light absorbing porphyrin molecule attached to a benzoporphyrin derivative. When injected into the bloodstream, Visudyne accumulates selectively in new abnormal blood vessels in the eye affected by wet AMD. A non-thermal laser is then used to deliver red light at 689 nm wavelength to the retina where the drug has accumulated. This causes the Visudyne to produce a reactive form of oxygen that destroys the abnormal blood vessels without damaging surrounding tissues. By closing off these leaky blood vessels, PDT with Visudyne can help prevent further leakage of fluid and blood into the retina which causes vision loss in wet AMD.
Clinical Studies of Visudyne Therapy
The efficacy of Visudyne for PDT was demonstrated in two large randomized clinical trials, the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and the Visudyne in Photodynamic Therapy (VIP) Study. Together these studies enrolled over 1800 patients with predominantly classic subfoveal choroidal neovascularization from wet AMD.
In the TAP study, treatment with Visudyne PDT plus best supportive care resulted in 40% less severe vision loss compared to patients receiving sham treatment plus best supportive care after 24 months. At 3 years, patients given Visudyne PDT were 28% less likely to have lost 15 or more letters of vision compared to those not receiving active treatment.
The VIP study compared Visudyne PDT to no treatment in patients with subfoveal choroidal neovascularization. At 12 months, those receiving PDT had experienced 24% less severe vision loss on average than the untreated group. Moreover, nearly twice as many patients gained 15 or more letters of vision improvement with Visudyne PDT versus no treatment.
Long-Term Outcomes and Retreatment
While initial studies showed verteporfin PDT could significantly reduce vision loss from wet AMD compared to no treatment or placebo, long-term follow up revealed its benefits lessened over time. Recurrence of choroidal neovascularization at the original treatment site or growth of new blood vessels nearby often required repeat Visudyne PDT sessions, known as retreating. Retreatment guidelines recommended additional PDT if new retinal fluid, recent vision loss, or increased lesion size was evident based on clinical exam and fluorescein angiography findings within 24 weeks of initial treatment.
A 5-year analysis of the TAP study found the benefit of Visudyne PDT decreased with longer follow up but still conferred significantly better visual outcomes than placebo. On average, patients received 3 retreatments over the 5 years. At 2 years in a separate study, retreatment extended the vision gains achieved with initial Visudyne PDT by 14%. However, multiple retreatments did not prevent gradual worsening of vision long-term for most patients as choroidal neovascularization frequently recurred.
Combination Therapy with Anti-VEGF Drugs
The development of anti-VEGF medications like ranibizumab (Lucentis) and aflibercept (Eylea) revolutionized wet AMD treatment in the 2000s. When used alone, injections of anti-VEGF drugs every 4-6 weeks provide substantially better long-term vision outcomes than Visudyne PDT monotherapy. However, Visudyne remains an option for some patients unsuitable or unresponsive to frequent anti-VEGF injections due to cost, access or treatment adherence issues.
Studies explored combining Visudyne PDT with anti-VEGF drugs to leverage their complementary mechanisms of action. One trial found initial combination therapy with ranibizumab and Visudyne PDT led to greater vision improvement versus Visudyne alone at 12 months. Another reported combination with aflibercept led to less need for future retreatments versus Visudyne monotherapy over 1 year. However, anti-VEGFs given alone remains the preferred first-line treatment for wet AMD currently in most cases due to their significantly better long-term efficacy compared to Visudyne -based regimens.
Safety of Verteporfin Therapy
In clinical trials, Visudyne PDT was generally well tolerated with mild side effects. The most common adverse reactions reported were vision abnormalities like photopsia (flashing lights) which typically resolved within 1 hour. Rare serious adverse events included gastrointestinal issues and injection site skin reactions. No damage to retinal or other ocular tissues occurred from the low energy light activation itself in studies. The risk of systemic side effects from Visudyne is also very low due to its selective accumulation in abnormal retinal blood vessels following intravenous injection.
Verteporfin was the first drug approved to treat the neovascular form of AMD and slow vision loss through a targeted photodynamic approach. While large randomized trials initially proved its benefit over sham treatment or no intervention, Visudyne monotherapy often required multiple retreatments long-term as choroidal neovascularization recurred. Today, anti-VEGF injections have become preferred first-line therapy due to significantly better outcomes they provide
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
