Contemporary AMD Management Strategies, Part II
BY LEO SEMES, OD, FAAO
Age-related macular degeneration (AMD) is either dry (non-neovascular) or wet (neovascular). Think of AMD as a continuum from macular pigmentary changes to choroidal neovascular membrane
membrane formation. Evidence, especially with respect to drusen formation, accumulated over the past 20 years suggests that this is the case. Approximately 15 to 20 percent of patients in the non-neovascular category will convert to the neovascular form.
My last column (October 2002) considered potential treatment strategies for non-neovascular AMD. I will devote this month's column to the graver form, neovascular AMD.
Verteporfin Shows Promise
The Macular Photocoagulation Study showed that only a limited number of neovascular AMD patients benefited from the study treatment. As a result, alternative treatments were developed.
The most significant is photodynamic therapy with verteporfin (Visudyne, Novartis Ophthal-mics). One-year results from the 1999 treatment of age-related macular degeneration with photodynamic therapy (TAP) group study, which included VA and fluorescein angiography results, suggested that selected patients overall would benefit at the one-year point. Two-year TAP outcomes were equally encouraging.
Alternative treatments for neovascular AMD are being investigated. These include submacular surgery, external beam irradiation (which has recently been shown ineffective), intravitreal angiostatic steroids and intravitreal anti-vascular endothelial growth factor (VEGF). The anti-angiostatic approaches seem the most exciting.
The agent(s) responsible for initiating neovascularization have been sought for at least 30 years. Only recently have reports on anecortave acetate (1% solution, Alcon) shown the promise of its angiostatic properties. Although only mouse data is available, intracameral injection of highly vascularized anterior-segment tumors and cases of retinopathy of prematurity have shown regression.
The angiostatic steroid, triamcinolone acetonide, has shown to have similar effects on choroidal neovascularization in pigs. Studies of induced choroidal neovascular membranes (CNVM) in rats show they have responded similarly, and one pilot study in humans with AMD indicates the promise of this approach.
Finally, intravitreal VEGF has re-emerged in the CNVM treatment paradigm. Studies on rhuFab (anti-VEGF monoclonal antibody fragment, Genentech) are showing promise. In one study on monkeys, one eye served as the control and the fellow eye of one-half the group had CNVM induction with laser photocoagulation (established arm). All subjects were then injected with rhuFab, and the other half of the group had CNVM induced (prevention arm). Both groups were administered rhuFab (intravitreal) and exhibited statistically significant angiographic evidence of decreased CNVM formation.
A selection paradigm for approved treatment (photodynamic therapy with verteporfin) of neovascular AMD (even subfoveal) is emerging. Patients who have VA poorer than 20/50 but relatively confined areas of involvement are the best candidates. As experience with the therapy is gained, more refined treatment protocols, including re-treatment guidance, will become even more defined.
Current research suggests that additional treatment strategies are promising. With AMD's increasing prevalence, these treatment strategies will become more important. As we gain experience treating other disorders that result in neovascularization, such as degenerative myopia, effective treatments may emerge.
Dr. Semes is an associate professor at the University of Alabama at Birmingham School of Optometry.